FINAL REPORT – January 2014 

 

i 

BISPHENOL A ALTERNATIVES IN THERMAL PAPER 

FINAL REPORT

January 2014
FINAL REPORT – January 2014 

Executive Summary 

This report provides information on bisphenol A (BPA), its use in thermal paper, and possible 

substitutes for this use. The report was developed by the U.S. Environmental Protection Agency 

(EPA) with input from stakeholders from business, government, academia, and environmental 

organizations. Based on conversations with technical experts, including stakeholders, we 

identified nineteen alternatives that are potential functional substitutes for inclusion and 

assessment. In addition to information on potential hazards of BPA and possible substitutes, 

information on the trade-offs associated with each alternative is presented for consideration in 

substitution decision-making. 

Background 

In March 2010, EPA released a chemical action plan for BPA. BPA is a high production volume 

(HPV) chemical that is used in manufacturing most polycarbonate plastics, the majority of epoxy 

resins, and other uses subject to regulation under the Toxic Substances Control Act. The action 

plan summarizes hazard, exposure, and use information, and identifies actions to address BPA 

in the environment based on concerns for potential effects on aquatic species.1 BPA is also a 

commonly used developer in a number of thermal paper applications, such as point-of-sale 

(POS) receipts. The developer is a component of a chemically reactive layer of thermal paper, 

which reacts in the presence of heat to create the printed image. When used in thermal paper, 

BPA is present as “free” (i.e., discrete, non-polymerized) BPA, which is likely to be more 

available for exposure than BPA polymerized into a resin or plastic (U.S. EPA 2010). 

One component of the action plan tasked the EPA Design for the Environment (DfE) Branch to 

conduct an alternatives assessment for BPA in thermal paper. Thermal paper was selected for 

evaluation based on concern for potential exposures to consumers and workers, releases to the 

environment, and stakeholder interest. DfE’s Alternatives Assessment Program provides a basis 

for informed decision-making by developing a semi-quantitative, screening-level comparison of 

the potential human health and environmental impacts of chemical alternatives. DfE Alternatives 

Assessments provide information on functional use class, intrinsic hazard, exposure properties, 

and environmental fate for chemical alternatives. Information from DfE Alternatives 

Assessments can support the selection of safer alternatives when combined with other 

information not addressed in DfE Alternatives Assessments, such as performance, cost, and 

life-cycle impacts. 

Goal of the Alternatives Assessment and Report Overview

In July 2010, DfE convened a multi-stakeholder effort to assess the human health and 

environmental effects of BPA and its alternatives as developers in thermal paper. This informal 

partnership includes a diverse array of stakeholders, such as thermal paper manufacturers, 

thermal paper converters, chemical manufacturers, POS equipment manufacturers, retailers, 

trade associations, non-governmental organizations (NGOs), green chemistry and technical 

experts, and international governmental organizations. The outcome of this effort is presented in 

this report. The report provides information that will help decision-makers consider 

1 The U.S. Food and Drug Administration (FDA) is expected to take the lead on assessing potential human health 

impacts associated with exposure to BPA. See www.fda.gov/ForConsumers/ConsumerUpdates/ucm297954.htm. 

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FINAL REPORT – January 2014 

environmental and human health profiles for all evaluated chemicals so that they can choose 

safer functional alternatives and take into account potential hazard trade-offs that may exist. 

Chapter 1of this report provides background information on BPA and defines the report’s 

purpose and scope. Chapter 2 discusses information on BPA and its use in thermal paper as a 

developer. Chapter 3 offers background information on the thermal paper printing system and 

how developers interact with other components in the system to create a printed product. Chapter 

4 explains the hazard evaluation methodology and includes the hazard profiles for BPA and the 

alternatives. Chapter 5 provides exposure information and life-cycle considerations for BPA. 

Chapter 6 discusses considerations for selecting thermal paper developers and provides relevant 

resources for moving towards a substitution decision. 

Hazard Evaluation of BPA and Alternatives 

Given that the project scope is limited to BPA’s use as a developer in thermal paper, this 

alternatives assessment does not consider alternatives to BPA for other uses. In addition to 

BPA, 19 potential chemical alternatives were identified for evaluation, which were considered 

by stakeholders likely to be functional in thermal paper. The assessment evaluated three 

general attributes to inform decision-making on chemical alternatives: (1) human health 

effects, (2) ecotoxicity, and (3) environmental fate. The evaluation was conducted according to 

the DfE Alternatives Assessment Criteria for Hazard Evaluation, which is a transparent tool for 

evaluating and differentiating among chemicals based on their human health and environmental 

hazards. For most endpoints, the criteria define “High,” “Moderate,” and “Low” concern. Very 

few chemicals had measured data for all endpoints; therefore, estimation methods were applied 

to fill data gaps. Since estimation methods come with a lower degree of confidence, this 

circumstance may be an important consideration for decision-making. No clearly safer 

alternatives to BPA were identified in this report – most alternatives have Moderate or High 

hazard designations for human health or aquatic toxicity endpoints. Persistence and 

bioaccumulation potential were not distinguishing for this group of alternatives. 

The human health effects endpoints evaluated in DfE Alternatives Assessments include acute 

toxicity, carcinogenicity, genotoxicity, reproductive toxicity, developmental toxicity, 

neurotoxicity, repeated dose toxicity, skin sensitization, respiratory sensitization, eye irritation, 

and dermal irritation. Qualitative discussions on available endocrine activity and immunotoxicity 

data were included, where relevant. All chemicals (including BPA) had Low designations for 

acute mammalian toxicity. Nine chemicals had High designations for developmental toxicity. 

For repeated dose toxicity, five chemicals had a High designation. Thirteen chemicals had 

Moderate, High, or Very High designations for at least one of the irritation and sensitization 

endpoints. All chemicals were assigned Moderate concern for carcinogenicity. Six chemicals 

were assigned Moderate concern for genotoxicity, with the remaining chemicals being of Low 

concern for this endpoint. 

The ecotoxicity endpoints evaluated in DfE Alternatives Assessments include acute and chronic 

aquatic toxicity. Ecotoxicity data for terrestrial species is limited. Most of the alternatives had 

High designations for aquatic toxicity (acute and chronic). 

Environmental fate of BPA and the 19 alternatives were also evaluated. Three of the 

20 chemicals had Low or Very Low persistence values; 11 had High or Very High persistence 

values. Only two chemicals had a High bioaccumulation potential. 

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FINAL REPORT – January 2014 

For a screening-level summary of the hazard evaluations for alternatives (including BPA), see 

Table ES-1 below. 

General Exposure and Life-Cycle Factors

Environmental exposure to BPA or alternatives may occur during manufacture, conversion, or 

use of thermal paper, at its end-of-life (i.e., recycling, landfilling, or incineration), or during 

manufacture of recycled paper products. Understanding the factors that affect exposure to BPA 

and alternative developers across their life-cycles provides additional context to the alternative 

selection process. There is a potential for occupational exposure during chemical and product 

manufacturing and product end-of-life. Additionally, there may be exposures to workers and 

consumers while thermal paper is being used and to the general population and the environment 

from releases during product manufacturing, use, and end-of-life.

Considerations for Selecting Thermal Paper Developers

Along with presenting information on hazard to inform substitution decisions, the report 

discusses considerations for selecting thermal paper developers, including opportunities for 

innovation and design challenges. Options that may be considered for substitution include the 

development of new chemicals that have a preferable hazard profile while still meeting the 

performance considerations required by particular applications. Another option would be to 

re-design thermal paper to eliminate the need for chemical developers. In addition to 

reconfiguring thermal printing systems, decision-makers may wish to consider alternative 

printing systems. These systems should be evaluated and compared to thermal printing to better 

understand relative performance, cost, and hazard. Finally, another option would be the use of ereceipts. A full examination of the relative merits of thermal paper versus e-receipts would 

require the consideration of life-cycle impacts, which is beyond the scope of this study. 

How to Use This Report 

The intended audience for the report includes, but is not limited to, chemical manufacturers, 

product manufacturers, retailers, consumers, NGOs, consultants, and state and federal regulators. 

Four possible uses of this report include: (1) identification of potential substitutes, (2) selection 

of alternative chemicals based on comparative hazard assessment, (3) incorporation of hazard 

information for further analysis and decision-making, and (4) as a baseline for the development 

of new and safer chemical substitutes. 

This report allows stakeholders interested in chemical substitution to identify functional 

substitutes for BPA in thermal paper. The list of potential alternatives introduced in Chapter 3 

includes chemicals identified by stakeholders as likely to be viable, functional alternatives as 

well as chemicals that are not considered functional alternatives, which were subsequently 

removed from consideration. The inclusion of a chemical in this assessment does not indicate 

environmental- or health-based preferability. By identifying potential functional alternatives, this 

report assists manufacturers in selecting chemicals for additional performance testing. 

Chapter 4 contains human health and environmental profiles for each chemical. Decision-makers

can use this information to understand and compare the hazard concerns associated with 

potential alternatives, and it may help businesses avoid the cost of repeated substitution. Some 

alternatives may be associated with hazard concerns similar to those of BPA, while others may 

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FINAL REPORT – January 2014 

be associated with different hazard concerns. The profiles in Chapter 4 can help decision-makers 

understand which potential alternatives may come under scrutiny in the future. 

In addition to reading the hazard summary table (ES-1), decision-makers should review the full 

hazard assessments for each chemical available in Section 4.2 of the report. The hazard 

assessments provide more information on hazard criteria, data interpretation, and information 

used to assign hazard values in each category. Decision-makers should consider this information 

to ensure a complete understanding of the hazard profiles of each alternative. 

The information in this report can be used to inform further analyses on preferred alternative 

chemicals, such as risk assessments or life-cycle assessments. For example, a decision-maker 

could identify several preferred functional alternatives and conduct product-specific risk 

assessments based on exposure expectations along the product’s life-cycle. This type of 

supplementary information may be helpful in guiding product-specific decision-making. The 

criteria used to develop the hazard assessments in this report can also be used to inform green 

chemistry design, if availability of safer alternatives is limited.

Many of the chemicals have significant data gaps; while estimation methods can be used to 

address these data gaps, access to high quality, relevant toxicological and environmental fate 

data is preferred as it provides more robust assessments. Chemicals used at high volumes, or 

likely to be used at high volumes in the future, should be of high priority for further testing. The 

full hazard assessments for each chemical, available in Chapter 4, may inform whether additional 

assessment or testing is needed.

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FINAL REPORT – January 2014 

ES-1 Screening Level Toxicology Hazard Summary for BPA and Alternatives

This table only contains information regarding the inherent hazards of the chemicals evaluated. Evaluation of risk considers both the hazard and exposure. 

The caveats listed in the legend and footnote sections must be taken into account when interpreting the hazard information in the table below.

VL = Very Low hazard L = Low hazard M = Moderate hazard H = High hazard VH = Very High hazard  Endpoints in colored text (VL, L, M, H, and VH) 

were assigned based on empirical data. Endpoints in black italics (VL, L, M, H, and VH) were assigned using values from estimation software and professional judgment.

§ Based on analogy to experimental data for a structurally similar compound.

Structure

Chemical

(for TSCA inventory name and 

relevant trade names see the 

individual profiles in Section 4.8) CASRN

Human Health Effects

Aquatic 

Toxicity

Environmental 

Fate

Acute ToxicityCarcinogenicity Genotoxicity ReproductiveDevelopmentalNeurological Repeated DoseSkin SensitizationRespiratory SensitizationEye IrritationDermal IrritationAcuteChronicPersistenceBioaccumulation

Bisphenol A and Phenolic Alternatives

Bisphenol A

2,2-bis(p-hydroxyphenyl)propane 80-05-7 L M L M H M M M M M H H VL L

Bisphenol F

Bis(4-hydroxyphenyl)methane 620-92-8 L M L M § H§ M H L VH M§ M H L L

Bisphenol C

2,2’-Bis(4-hydroxy-3-

methylphenyl)propane

79-97-0 L§ M M M § H§ M M§ M§ H§ M§ H H M M 

MBHA

Methyl bis(4-hydroxyphenyl)acetate 5129-00-0 L§ M L§ M § H§ M M§ L M§ M§ H H M L 

BisOPP-A

4,4’-Isopropyllidenebis(2-

phenylphenol)

24038-68-

4 L§ M L§ M § H§ M M§ M§ M§ M§ L H H M 

Bisphenol AP

4,4’-(1-Phenylethylidene)bisphenol 1571-75-1 L§ M L§ M § H§ M M§ M§ M§ M§ H H H M 

Substituted phenolic compound, 

PROPRIETARY #1 L§ M L M § H§ M M§ M§ M§ M§ H M M L 

Substituted phenolic compound, 

PROPRIETARY #2 L§ M L§ M § H§ M M§ M§ M§ M§ H H H H 

PHBB

Benzyl 4-hydroxybenzoate 94-18-8 L M M L M M L M§ VL VL H H L§ L 

OH OH

OH OH

OH OH

O O

OH

OH

OH OH

OH

O

O

OH OH

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FINAL REPORT – January 2014 

ES-1 Screening Level Toxicology Hazard Summary for BPA and Alternatives (Continued)

This table only contains information regarding the inherent hazards of the chemicals evaluated. Evaluation of risk considers both the hazard and exposure. 

The caveats listed in the legend and footnote sections must be taken into account when interpreting the hazard information in the table below.

VL = Very Low hazard L = Low hazard M = Moderate hazard H = High hazard VH = Very High hazard  Endpoints in colored text (VL, L, M, H, and VH) 

were assigned based on empirical data. Endpoints in black italics (VL, L, M, H, and VH) were assigned using values from estimation software and professional judgment.

§ Based on analogy to experimental data for a structurally similar compound.

Structure

Chemical

(for TSCA inventory name and 

relevant trade names see the 

individual profiles in Section 4.8) CASRN

Human Health Effects

Aquatic 

Toxicity

Environmental 

Fate

Acute ToxicityCarcinogenicity Genotoxicity ReproductiveDevelopmentalNeurological Repeated DoseSkin SensitizationRespiratory SensitizationEye IrritationDermal IrritationAcuteChronicPersistenceBioaccumulation

Hydroxyphenyl Sulfone Alternatives

Bisphenol S

4-Hydroxyphenyl sulfone 80-09-1 L M M M M M H L L L M M M L

2,4-BPS

2,4’-Bis(hydroxyphenyl)sulfone 5397-34-2 L§ M M M§ M§ M H§ L§ L§ L§ M H M L

TGSA

Bis-(3-allyl-4-hydroxyphenyl) 

sulfone

41481-66-7 L M L M§ M§ M H M M L VL H M H L 

BPS-MAE 

Phenol,4-[[4-(2-propen-1-

yloxy)phenyl]sulfonyl]-

97042-18-7 L M§ M M§ M§ M L L M L VL H H H L 

BPS-MPE

4-Hydroxy-4’-

benzyloxydiphenylsulfone

63134-33-8 L M M§ M§ M§ M H§ L L L VH H H M

D-8

4-Hydroxyphenyl 

4-isoprooxyphenylsulfone

95235-30-6 L M L M§ M§ M M L§ L§ L§ H H M M

OH

S

O O OH

S

O

O

OH OH

S

O

O

OH O

S

O

O

O OH

S

O

O

O OH

S

O

O

HO OH

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FINAL REPORT – January 2014 

ES-1 Screening Level Toxicology Hazard Summary for BPA and Alternatives (Continued)

This table only contains information regarding the inherent hazards of the chemicals evaluated. Evaluation of risk considers both the hazard and exposure.

The caveats listed in the legend and footnote sections must be taken into account when interpreting the hazard information in the table below.

VL = Very Low hazard L = Low hazard M = Moderate hazard H = High hazard VH = Very High hazard  Endpoints in colored text (VL, L, M, H, and VH) were 

assigned based on empirical data. Endpoints in black italics (VL, L, M, H, and VH) were assigned using values from estimation software and professional judgment.

◊ The highest hazard designation of a representative component of the oligomeric mixture with MWs <1,000. 

‡ The highest hazard designation of any of the oligomers with MW <1,000

§ Based on analogy to experimental data for a structurally similar compound.

Structure

Chemical

(for TSCA inventory name and 

relevant trade names see the 

individual profiles in Section 4.8) CASRN

Human Health Effects

Aquatic 

Toxicity

Environmental 

Fate

Acute ToxicityCarcinogenicity GenotoxicityReproductiveDevelopmentalNeurological Repeated DoseSkin SensitizationRespiratory SensitizationEye IrritationDermal IrritationAcuteChronicPersistenceBioaccumulation

Oligomeric and Polymeric Alternatives

D-90 

Phenol, 4,4’-sulfonylbis-, polymer 

with 1,1’-oxybis[2-chloroethane] 

191680-83-8 L M L L L M L L M VL L‡ L‡ VH‡ H‡

DD-70

1,7-bis(4-Hydroxyphenylthio)-3,5-

dioxaheptane

93589-69-6 L M L M M§ M M§ M§ H§ M§ H H H L 

Pergafast 201

N-(p-Toluenesulfonyl)-N'-(3-ptoluenesulfonyloxyphenyl)urea232938-43-1 L M L M H L M L L VL H H VH L

BTUM

4,4'-bis(N-carbamoyl-4-

methylbenzenesulfomide)diphenylme

thane

151882-81-4 L M L L L L M L L L H H H L 

UU 

Urea Urethane Compound 321860-75-7 L M L L L L L L L L L L◊ VH L

OH

S O O S

OH

N

H O

N

H S

O

O

3CH

O S

O

O

CH3

N N

O

S

O O

N N

O

S

O O

S

O

O

HO O O O S

O

O

O

n

H

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FINAL REPORT – January 2014 

Table of Contents

Executive Summary ...................................................................................................................... ii

1. Introduction ........................................................................................................................ 1-1

1.1 Purpose of the BPA in Thermal Paper Alternatives Assessment ................................ 1-2

1.2 Scope of the BPA in Thermal Paper Alternatives Assessment.................................... 1-3

1.3 DfE Alternatives Assessment as a Risk Management Tool......................................... 1-3

2. Products and Materials: BPA in Thermal Paper ........................................................... 2-1

2.1 BPA as a Developer in Thermal Paper ........................................................................ 2-1

2.2 Thermal Paper Uses ..................................................................................................... 2-2

3. Background on Thermal Printing Technology ................................................................ 3-1

3.1 Components of Thermal Paper .................................................................................... 3-1

3.1.1 Paper ............................................................................................................ 3-1

3.1.2 Printing Chemistry ....................................................................................... 3-2

3.2 Thermal Printing Equipment and Process.................................................................... 3-5

3.3 Advantages and Disadvantages of Thermal Printing Technology ............................... 3-6

3.4 Alternatives Included in this Assessment .................................................................... 3-7

3.5 Alternatives Not Included in this Assessment ........................................................... 3-11

4. Hazard Evaluation of Bisphenol A (BPA) and Alternatives .......................................... 4-1

4.1 Toxicological and Environmental Endpoints............................................................... 4-1

4.1.1 Definitions of Each Endpoint Evaluated Against Criteria ........................... 4-1

4.1.2 Criteria ......................................................................................................... 4-4

4.1.3 Endpoints Characterized but Not Evaluated ................................................ 4-7

4.2 Data Sources and Assessment Methodology ............................................................... 4-8

4.2.1 Identifying and Reviewing Measured Data ................................................. 4-8

4.3 Importance of Physical and Chemical Properties, Environmental Transport, 

and Biodegradation .................................................................................................... 4-11

4.4 Evaluating Human Health Endpoints......................................................................... 4-18

4.4.1 Endpoints Characterized and Evaluated Against Criteria Based on 

Measured Data ........................................................................................... 4-18

4.4.2 SAR – Application of SAR and Expert Judgment to Endpoint Criteria .... 4-19

4.5 Evaluating Environmental Endpoints ........................................................................ 4-20

4.5.1 Ecotoxicity ................................................................................................. 4-20

4.5.2 Bioaccumulation ........................................................................................ 4-21

4.5.3 Environmental Persistence ......................................................................... 4-22

4.6 Endocrine Activity ..................................................................................................... 4-25

4.7 Hazard Summary Table ............................................................................................... 4-1

4.8 Hazard Profiles............................................................................................................. 4-4

Bisphenol A ................................................................................................................. 4-4

Bisphenol F................................................................................................................ 4-54

Bisphenol C ............................................................................................................... 4-87

MBHA ..................................................................................................................... 4-114

BisOPP-A ................................................................................................................ 4-136

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FINAL REPORT – January 2014 

Bisphenol AP ........................................................................................................... 4-158

Substituted Phenolic Compound #1 ........................................................................ 4-182

Substituted Phenolic Compound #2 ........................................................................ 4-202

PHBB....................................................................................................................... 4-227

Bisphenol S.............................................................................................................. 4-250

2,4-BPS.................................................................................................................... 4-275

TGSA....................................................................................................................... 4-289

BPS-MAE ................................................................................................................ 4-307

BPS-MPE ................................................................................................................ 4-321

D-8 ........................................................................................................................... 4-337

D-90 ......................................................................................................................... 4-353

DD-70 ...................................................................................................................... 4-367

Pergafast 201 ........................................................................................................... 4-378

BTUM ..................................................................................................................... 4-395

UU ........................................................................................................................... 4-406

5. General Exposure and Life-cycle Information ................................................................ 5-1

5.1 Potential Exposure Pathways and Routes (General) .................................................... 5-2

5.1.1 Inhalation Exposures .................................................................................... 5-2

5.1.2 Dermal Exposures ........................................................................................ 5-3

5.1.3 Ingestion Exposures ..................................................................................... 5-3

5.1.4 Environmental and General Population Exposures ..................................... 5-3

5.1.5 Exposures to Susceptible Populations ......................................................... 5-4

5.1.6 Physical/Chemical Properties for that May Impact Exposure to 

BPA and Alternatives .................................................................................. 5-5

5.2 Potential Sources of Exposure in the Life-cycle of Thermal Paper ............................. 5-7

5.2.1 Manufacture of Developers.......................................................................... 5-7

5.2.2 Manufacture of Thermal Paper .................................................................... 5-8

5.2.3 Conversion of Thermal Paper .................................................................... 5-10

5.2.4 Use of Thermal Paper ................................................................................ 5-10

5.2.5 End-of-Life ................................................................................................ 5-11

5.2.6 Manufacture of Recycled Paper Products .................................................. 5-11

5.3 Available Data on Occupational, Consumer, and Environmental Exposures 

to BPA, Thermal Paper Life-cycle ............................................................................. 5-12

5.3.1 BPA in Receipts ......................................................................................... 5-12

5.3.2 Bisphenol S (BPS) in Receipts .................................................................. 5-13

5.3.3 BPA Transfer to Skin and Potential for Dermal Absorption ..................... 5-13

5.3.4 Occupational Exposure .............................................................................. 5-13

5.3.5 Consumer and General Population Exposure ............................................ 5-14

5.3.6 Environmental Exposure ............................................................................ 5-15

6. Considerations for Selecting Thermal Paper Developers ............................................... 6-1

6.1 Human Health and Environmental Considerations...................................................... 6-1

6.1.1 Human Health Hazard.................................................................................. 6-1

6.1.2 Ecotoxicity ................................................................................................... 6-2

6.1.3 Persistence.................................................................................................... 6-2

6.1.4 Bioaccumulation Potential ........................................................................... 6-2

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6.1.5 Exposure Considerations ............................................................................. 6-3

6.2 Considerations for Poorly or Incompletely Characterized Chemicals and 

Variable Amounts of Data ........................................................................................... 6-3

6.3 Performance Considerations ........................................................................................ 6-4

6.4 Economic Considerations ............................................................................................ 6-5

6.5 Social Considerations................................................................................................... 6-6

6.6 Trade-offs and Interim Risk Mitigation ....................................................................... 6-8

6.7 Innovation and Design Challenges .............................................................................. 6-9

6.8 Relevant Resources .................................................................................................... 6-10

6.8.1 Resources for State and Local Authorities................................................. 6-10

6.8.2 Federal Agency Resources ......................................................................... 6-11

6.8.3 Resources for Global Regulations ............................................................. 6-11

6.8.4 GreenScreenTM for Safer Chemicals .......................................................... 6-12

6.9 Related Assessments .................................................................................................. 6-12

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List of Acronyms and Abbreviations

AIM Analog Identification Methodology 

ACR Acute to Chronic Ratio 

ADME Absorption, Distribution, Metabolism, and Excretion

AIST Advanced Industrial Science and Technology 

ASTM American Society for Testing and Materials

BAF Bioaccumulation Factor 

BCF Bioconcentration Factor 

BMD Benchmark Dose 

BMDL Benchmark Dose Lower-confidence Limit

BPA Bisphenol A 

BPS Bisphenol S 

BOD Biochemical Oxygen Demand

CASRN Chemical Abstracts Service Registry Number 

CDC Centers for Disease Control and Prevention 

CHO Chinese Hamster Ovary Cells

ChV Chronic Value 

CPSC Consumer Product Safety Commission

CVL Crystal Violet Lactone

DfE Design for the Environment 

DOC Dissolved Organic Carbon 

dpi Dots per inch 

EC50 Half Maximal Effective Concentration

ECHA European Chemicals Agency 

ECOSAR Ecological Structure Activity Relationships

EDSP Endocrine Disruptor Screening Program 

EEC European Economic Community 

Eh Redox potential 

EKG Electrocardiogram

EPA U.S. Environmental Protection Agency 

EPCRA Emergency Planning and Community Right-to-Know Act

EPI Estimations Program Interface

ERMA Environmental Risk Management Authority 

EU European Union 

EWG Environmental Working Group 

FDA U.S. Food and Drug Administration 

GHS Globally Harmonized System of Classification and Labeling of Chemicals

GLP Good Laboratory Practice 

HGPRT Hypoxanthine-Guanine Phosphoribosyl-Transferase

HIPAA Health Insurance Portability and Accountability Act of 1996 

HPLC High Performance Liquid Chromatography 

HPV High Production Volume 

HSDB Hazardous Substances Data Bank

IARC International Agency for Research on Cancer

IR Infrared

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FINAL REPORT – January 2014 

IRIS Integrated Risk Information System 

IUCLID International Uniform Chemical Information Database

Koc Soil adsorption coefficient

Kow Octanol/water partition coefficient

LC50 Median Lethal Concentration 

LCA Life-cycle Assessment

LD50 Median Lethal Dose

LD Lactation Day

LFL Lower Limit of Flammability

LOAEL Lowest Observed Adverse Effect Level

LOEC Lowest Observed Effective Concentration

MDI Mean Daily Intake

MF Molecular Formula

MITI Japanese Ministry of International Trade and Industry 

MW Molecular Weight

MSDS Material Safety Data Sheet

NAICS North American Industry Classification System

NES No Effects at Saturation

NGO Non-Governmental Organization 

NHANES National Health and Nutrition Examination Survey 

NICNAS National Industrial Chemicals Notification and Assessment Scheme

NIOSH National Institute for Occupational Safety and Health

NIR Near Infrared

NOAEL No Observed Adverse Effect Level

NOEC No Observed Effect Concentration 

NOEL No Observed Effect Level

NTP National Toxicology Program 

OECD Organisation for Economic Cooperation and Development 

OPPT Office of Pollution Prevention and Toxics 

P2 Pollution Prevention

PBB Poly-Brominated Biphenyls

PBDE Polybrominated Diphenyl Ether

PBT Profiler Persistent, Bioaccumulative, and Toxic (PBT) Chemical Profiler

PMN Premanufacture Notice

PNEC Predicted No Effect Concentration

POS Point-of-sale

ppb parts per billion

ppm parts per million

PVC Polyvinyl Chloride 

REACH Registration, Evaluation, Authorisation and Restriction of Chemical substances

RoHS Restriction of Hazardous Substances 

SAR Structure Activity Relationship

SCAS Semi-Continuous Activated Sludge 

SF Sustainable Futures 

SMILES Simplified Molecular-Input Line-Entry System

SPARC Sparc Performs Automated Reasoning in Chemistry

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TDI Total Daily Intake

TOC Total Organic Carbon

TRI Toxics Release Inventory

TSCA Toxic Substances Control Act

QSAR Quantitative Structure Activity Relationships

UFL Upper Limit of Flammability

USGS U.S. Geological Survey

WHO World Health Organization

WWTP Wastewater Treatment Plant

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FINAL REPORT – January 2014 

1. Introduction

As part of its effort to enhance the Agency’s current chemicals management program, the 

U.S. Environmental Protection Agency (EPA) has taken steps to identify chemicals that may 

pose environmental and health concerns. In 2009-2011, EPA developed action plans to 

investigate potential regulatory and voluntary actions. In March 2010, EPA released a chemical 

action plan that summarizes hazard, exposure, and use information on bisphenol A (BPA) and 

identifies actions EPA is considering.1 Under this action plan, EPA’s Design for the 

Environment (DfE) Branch initiated this alternatives assessment: BPA Alternatives in Thermal 

Paper. Thermal paper was selected for evaluation based on concern for potential exposures to 

consumers and workers, releases to the environment, and stakeholder interest. DfE’s Alternatives 

Assessment Program helps industries choose safer chemicals and provides a basis for informed 

decision-making by developing a screening-level comparison of potential human health and 

environmental impacts of chemical alternatives. Representatives from industry, academia, 

government, and non-governmental organizations (NGOs) provided input which DfE considered 

to select and evaluate alternatives to BPA in thermal paper2

 and develop this report. Although 

the purpose of DfE Alternatives Assessments is to provide information that will enable selection

of safer alternatives, in some projects, clearly safer alternatives are not available. Hazard tradeoffs complicate the interpretation of results. Nonetheless, the report contains helpful risk 

management information for thermal paper companies who are considering alternative 

chemicals. 

BPA is a high production volume (HPV) chemical with U.S. production volume estimated at 

2.4 billion pounds in 2007, with an estimated value of almost $2 billion (U.S. EPA 2010). It is a 

monomer used in manufacturing most polycarbonate plastics, the majority of epoxy resins, and 

other chemical products such as flame retardants. Recently, there has been heightened public 

attention around exposures to BPA and its potential effects as an environmental pollutant. 

Because BPA is a reproductive, developmental, and systemic toxicant in animal studies and 

interacts with estrogen receptors, there are questions about its potential impact, particularly on 

children’s health and ecosystems. Several government entities have published reports 

examining potential human health and environmental hazards associated with BPA exposure. 

Such entities include a number of regulatory agencies in the European Union (EU), Health 

Canada and Environment Canada, Japan’s National Institute of Advanced Industrial Science and 

Technology (AIST), the U.S. Food and Drug Administration (FDA), and the U.S. National 

Institute of Environmental Health Sciences National Toxicology Program (NTP). Additional 

research is underway, particularly concerning whether BPA may cause effects at low doses 

(U.S. EPA 2010). 

Approximately 94% of BPA is used as a monomer to make polycarbonate plastic and epoxy 

resins (U.S. EPA 2010). Although most human exposure to BPA is believed to come from food 

and beverage packaging made from these materials, less than 5% of the BPA produced is used in 

food contact applications (U.S. EPA 2010). Apart from food-related uses, BPA-based materials 

are used in automotive and other transportation equipment, optical media such as DVDs, 

1 The BPA action plan is available online at 

http://www.epa.gov/opptintr/existingchemicals/pubs/actionplans/bpa_action_plan.pdf. 2 The term “thermal paper” used in this report refers to paper used in direct thermal transfer machines.

1-1 

 
FINAL REPORT – January 2014 

electrical/electronics equipment, construction, linings inside drinking water pipes, thermal paper 

coatings, foundry casting, and elsewhere.

BPA is a commonly used developer in a number of thermal paper applications, such as 

point-of-sale (POS) receipts, but may also be used in other thermal paper applications such as 

airline tickets, event and cinema tickets, and labels. When used in thermal paper, BPA is present 

as “free” (i.e., discrete, non-polymerized) BPA, which is likely to be more available for exposure 

than BPA polymerized into a resin or plastic (U.S. EPA 2010). Upon handling, BPA in thermal 

paper can be transferred to skin, and there is some concern that residues on hands could be 

ingested through incidental hand-to-mouth contact (Zalko, Jacques et al. 2011). Furthermore, 

some studies suggest that dermal absorption may contribute some small fraction to the overall 

human exposure (Biedermann, Tschudin et al. 2010; Zalko, Jacques et al. 2011). European data 

indicate that the use of BPA in paper may also contribute to the presence of BPA in the stream of 

recycled paper and in landfills (JRC-IHCP 2010). Although there are currently no estimates for 

the amount of BPA used in thermal paper in the United States, in Western Europe, the volume of 

BPA reported to be used in thermal paper in 2005/2006 was 1,890 tonnes per year, while total 

production was estimated at 1,150,000 tonnes per year (JRC-IHCP 2010), which accounts for 

roughly 0.2% of the annual use of BPA. 

As described in the action plan, EPA’s DfE Branch initiated this multi-stakeholder effort 

alternatives assessment: BPA Alternatives in Thermal Paper.

3 DfE’s Alternatives Assessment 

Program provides a basis for informed decision-making by developing a screening-level

comparison of potential human health and environmental impacts of chemical alternatives. The 

BPA Alternatives in Thermal Paper Partnership was formed in July 2010 and includes a diverse 

array of stakeholders, such as thermal paper manufacturers, thermal paper converters, chemical 

manufacturers, POS equipment manufacturers, retailers, trade associations, NGOs, green 

chemistry and technical experts, and international governmental organizations. Partners engaged 

with DfE to identify and evaluate potential alternatives to BPA in thermal paper and develop this 

report. 

This alternatives assessment evaluated the alternatives that were judged by stakeholders as most 

likely to be functional in thermal printing applications. Selection of a chemical for evaluation in 

the report does not denote environmental preferability. Rather, the report provides information 

that will help decision-makers consider environmental and human health profiles for all 

evaluated chemicals, so that they can choose the safest possible functional alternative. This 

report also presents general information on exposures to thermal paper, life-cycle considerations, 

and some considerations for weighing human health and environmental information with other 

factors, such as cost and performance.

1.1 Purpose of the BPA in Thermal Paper Alternatives Assessment

The purpose of the BPA in Thermal Paper Alternatives Assessment is to inform substitution by 

evaluating the hazards associated with likely functional alternatives to BPA, and make this

information available to decision-makers and the public. Information generated from this effort 

will contribute to more informed decisions concerning the selection and use of developers in 

thermal paper technologies and the disposal and recycling of thermal paper. 

3 For more information on the DfE Program’s Alternatives Assessments, see 

www.epa.gov/dfe/alternative_assessments.html. 

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1.2 Scope of the BPA in Thermal Paper Alternatives Assessment

The BPA in Thermal Paper Alternatives Assessment is an evaluation of potential hazards 

associated with thermal paper developers that are likely to be functional alternatives to BPA. 

Thermal paper systems include a developer and other components such as dyes and sensitizers. 

EPA recognizes that a change in the developer may require additional adjustments to the system. 

An assessment of process chemicals (i.e., those used in the manufacture of BPA) and other 

chemicals used in the manufacture of thermal paper is beyond the scope of this assessment. 

Similarly, assessments of technologies that could replace thermal paper applications altogether, 

such as alternative printing technologies or electronic receipts, are also outside the scope of this 

assessment. Selected alternative technologies are briefly discussed in Chapter 6. 

This report summarizes the outcomes of the alternatives assessment, and aims to improve 

understanding of the potential environmental and human health hazards of BPA and alternative 

developers in thermal paper throughout their life-cycles. It is intended to provide information 

that will inform industry and other stakeholders on the selection of alternative developers for use 

in thermal paper. This report does not provide a ranking of alternatives or provide guidance on 

the appropriate use of BPA or other alternatives; rather the information provided in this 

alternatives assessment is meant to assist decision makers in better understanding BPA and its 

potential chemical alternatives in thermal paper.

This report is organized as follows: 

•

•

•

•

•

•

Chapter 1 (Introduction): provides background on the BPA Alternatives in Thermal Paper 

Partnership, including the purpose and scope of the assessment.

Chapter 2 (Products and Materials: BPA in Thermal Paper): provides information on BPA 

and its use in thermal paper as a developer.

Chapter 3 (Background on Thermal Printing Technology): describes the thermal paper 

printing system and how developers interact with other components in the system to create a 

printed product. 

Chapter 4 (Hazard Evaluation of Bisphenol A (BPA) and Alternatives): provides the results 

of the hazard assessment of BPA and the 19 alternatives identified for inclusion. This chapter 

also discusses how the alternatives were identified. 

Chapter 5 (General Exposure and Life-cycle Information): details the human health and 

environmental exposure pathways of developers from thermal paper and other life-cycle 

considerations. 

Chapter 6 (Considerations for Selecting Thermal Paper Developers): describes 

considerations involved with selecting an alternative developer to BPA in thermal paper. 

This chapter also discusses green chemistry options and alternative technologies that could 

be used in place of thermal paper applications.

1.3 DfE Alternatives Assessment as a Risk Management Tool 

Among other actions, the Agency included an alternatives assessment for BPA in thermal paper 

as a suitable risk management tool in the BPA action plan. The Agency chose this tool to inform 

the chemical substitution that may occur as an outcome of other activities described in the action 

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FINAL REPORT – January 2014 

plan. The intent was to compare the intrinsic properties of chemical alternatives that may be 

substituted for BPA in thermal paper, based on a consistent and comprehensive set of endpoints. 

DfE Alternatives Assessments provide an opportunity to learn more about chemicals used in 

specific applications. This approach often complements other EPA activities, such as research or 

regulatory programs. 

Alternatives assessments may include a comparison of the chemical of interest with design or 

process changes, alternative materials, or chemical substitutes. DfE Alternatives Assessments 

focus on the hazard characteristics of chemical alternatives, providing information on the 

environmental and human health profiles of each chemical included. In addition, DfE 

Alternatives Assessments describe intrinsic properties that inform our understanding of the 

potential for exposure and hazard. These properties include concerns associated with chemical 

structure, absorption potential, persistence and bioaccumulation. Industry and other stakeholders 

can use this information, in combination with an analysis of cost, performance, and other factors, 

to choose alternatives. DfE Alternatives Assessments can also identify the characteristics of safer 

alternatives and guide innovation and product development, especially when clearly preferable 

alternatives are not available. 

Under this approach the health and environmental profiles in the alternatives assessments 

become the key variable and source of distinguishing characteristics. The potential impact of 

exposure attributes, including significant differences in environmental fate and transport based 

on persistence, bioaccumulation, and physical properties, are discussed in Chapters 4 and 5. 

Alternatives assessments, life-cycle assessments (LCAs), and risk assessments are all tools that 

can be used to improve the sustainability profiles of chemicals and products. These tools, which 

can be complementary, should be selected according to the risk management need and other 

regulatory and policy considerations. DfE Alternatives Assessments establish a foundation upon 

which other tools, such as risk assessments and LCAs, can build. 

Risk assessment and alternatives assessment are both based on the premise that risk is a function 

of hazard and exposure. Risk assessment characterizes the nature and magnitude of hazard and

exposure from chemical contaminants and other stressors. DfE’s “functional use” approach to 

alternatives assessment orients chemical evaluations within a given product type and 

functionality. Under this approach, factors related to exposure scenarios, such as the amount 

used, physical form, and route of exposure, can be quite similar within a given functional use, 

allowing for a focus on hazard reduction. When less hazardous alternatives have different 

physical/chemical profiles or require different use levels, it may be appropriate to also conduct 

an exposure assessment.

The substitutes evaluated in some DfE alternatives assessments include chemical alternatives 

that are of low concern for human health and environmental health hazards, while in other 

alternatives assessments, the chemical alternatives exhibit significant hazard trade-offs. When 

trade-offs are a concern, other approaches may be needed. For example, it may be necessary to 

gather additional information on exposure scenarios and the potential for control or mitigation of 

risks, such as design changes, alternative materials, or, when necessary, exposure controls. The 

National Institute for Occupational Safety and Health (NIOSH) Hierarchy of Controls illustrates 

the order of preference of potential control solutions (NIOSH 2011). 

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FINAL REPORT – January 2014 

DfE Alternatives Assessment Furthers the Goals of Green Chemistry

The DfE Alternatives Assessment approach is aligned with green chemistry principles.4 The 

relationship to two of those principles is especially noteworthy: 

•

•

Principle 4: Designing safer chemicals -- “Design chemical products to affect their desired 

function while minimizing their toxicity,” and

Principle 10: Design for degradation -- “Design chemical products so they break down into 

innocuous products that do not persist in the environment.” 

DfE incorporates these two green chemistry principles in its criteria and applies them in its 

assessment of chemical hazard and fate in the environment. This approach can enable 

identification of safer substitutes that emphasize greener chemistry and point the way to 

innovation in safer chemical design, where hazard becomes a part of a performance evaluation.

4 http://www.epa.gov/sciencematters/june2011/principles.htm

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FINAL REPORT – January 2014 

References

Biedermann, S., P. Tschudin, et al. (2010). "Transfer of bisphenol A from thermal printer paper 

to the skin." Anal Bioanal Chem 398: 571-576. 

Joint Research Centre-Institute for Health and Consumer Protection (JRC-IHCP) (2010). 

European Union Risk Assessment Report, 4,4'-Isopropylidenediphenol (Bisphenol-A).

NIOSH. (2011). "Workplace Safety & Health Topics." from 

http://www.cdc.gov/niosh/topics/ctrlbanding/ctrlbandingfaq.html. 

U.S. Environmental Protection Agency (U.S. EPA) (2010). Bisphenol A Action Plan. 

Zalko, D., C. Jacques, et al. (2011). "Viable skin efficiently absorbs and metabolizes bisphenol 

A." Chemosphere 82(3): 424-430.

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FINAL REPORT – January 2014

2. Products and Materials: BPA in Thermal Paper

Bisphenol A (BPA) is one of the highest production volume chemicals in the world. Global 

production capacity of BPA was about 5,160 kilotons in 2008 (Chemical Weekly 2009). The 

U.S. alone had a production capacity of 1,226 kilotons of BPA in 2008. In 2008, Europe’s

estimated annual production capacity was 1,438 kilotons (Chemical Weekly 2009), up from 

1,150 kilotons/year in 2005/2006 (JRC-IHCP 2010). 

BPA is found in a diverse array of products in addition to thermal paper. One of the main uses of 

BPA is in polycarbonate plastics and in epoxy resins. Applications of polycarbonates include 

reusable food and drink containers such as plastic bottles, optical media such as CDs and DVDs, 

automotive and other transport equipment, sports safety equipment, glazing, and polycarbonate 

blends in the electronics industry (OECD 2002; Polycarbonate/BPA Global Group 2011). 

Applications of epoxy resins containing BPA include lacquers in protective coatings in food cans 

and water pipes, structural composites, electrical laminates such as for printed circuit boards, 

composites, electrical applications, as well as paints, adhesives, and other protective coatings 

such as dental sealants (OECD 2002; Polycarbonate/BPA Global Group 2011). BPA is used in 

the production of polyester resins, polysulfone resins, polyacrylate resins, and flame retardants 

(NTP-CERHR 2008). It is also contained in polyvinyl chloride (PVC) plastics and foundry 

castings (U.S. EPA 2010).

BPA is synthesized by the condensation of phenol and acetone in the presence of an acid catalyst 

(e.g., hydrogen chloride) and a promoter (e.g., methyl mercaptan). This condensation reaction 

yields two grades of BPA, both of which may be used in the manufacture of thermal paper (ICIS 

2011; S. MacNeil, personal communication, November 28, 2011).

This chapter describes BPA’s use as a developer, as well as the thermal paper applications in 

which BPA is often used. Thermal printing technology is described in Chapter 3.

2.1 BPA as a Developer in Thermal Paper

BPA is widely used as a developer in thermal paper because it is efficacious, available, and 

affordable (Mendum, Stoler et al. 2011). Although there are currently no estimates for the 

amount of BPA used in thermal paper in the U.S., the amount of BPA used in Europe in 

2005/2006 in thermal paper amounted to 1.89 kilotons (JRC-IHCP 2010). This accounts for 

roughly 0.2 percent of total European BPA consumption (JRC-IHCP 2010).

In a sample of ten twelve-inch blank cash register receipts from businesses in suburban Boston, 

Mendum et al. (2011) found that eight receipts had quantifiable concentrations of BPA (level of 

quantification 26 μg/g); detectable BPA varied from 3 to 19 mg per 12-inch receipt. Mendum et 

al. identified three categories for the amount of BPA in thermal paper: full BPA content (9-

19mg/12 inches), low BPA content (1-3 mg/12 inches), and BPA-free paper (below the detection 

limit) (2011). 

In a larger study, 103 thermal receipt papers from 58 locations in the U.S., Japan, Korea, and 

Vietnam were tested (Liao and Kannan 2011). BPA was found in 94 percent of the receipts, 

ranging from below the level of quantification (1 ng/g in this study) to 13.9 mg/g (geometric 

mean: 0.211 mg/g). Some receipt papers claimed to be “BPA-free,” as specifically printed on 

the receipt paper, but all of these receipt papers contained hundreds of μg/g levels of BPA 

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FINAL REPORT – January 2014 

(geometric mean: 217μg/g). Of the receipt papers collected in the U.S., 100 percent of them 

contained BPA. BPA was not detected in any of the six samples from Japan, likely due to the 

2001 Japanese phase-out of BPA in thermal paper. 

2.2 Thermal Paper Uses

Thermal paper has extensive applications, with the most common uses including: point-of-sale

(POS) receipts, labels, tickets, and print-outs from recording devices. POS receipts include sales 

receipts from cash registers, ATMs, and banks. Labels printed on thermal paper include labels on 

prescriptions, industrial barcodes, packaged items such as supermarket foods (e.g., deli meats, 

cheese, bulk items) and retail shelf labels. Tickets for transportation (e.g., airlines, trains), 

entertainment (e.g., cinema, theatre, gaming, sporting events, amusement parks, arenas, and 

museums), parking tickets, and tickets from kiosks are all common applications of thermal paper 

(Nashua Corporation 2008). Ultrasound, electrocardiogram (EKG), and printouts from other 

laboratory recorders are also common examples of thermal printing (JPI Healthcare n.d.). 

Testing of thermal paper used in medical applications, such as EKG printouts, indicates that it is 

made with bisphenol S (J. Warner, personal communication, March 1, 2011). 

According to European estimates, POS receipts account for only half of thermal paper sold. 

Nearly one-third of thermal paper is used in self-adhesive labels in applications such as deli 

trays, shipping labels, luggage tags, etc. Lottery tickets account for 10 percent of thermal paper 

applications and another 10 percent for fax paper (JRC-IHCP 2010). 

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References

Chemical Weekly (2009). Bisphenol-A: A Techno-Commercial Profile. September 1, 2009: 

205-211.

ICIS (2011). Bisphenol A (BPA) Production and Manufacturing Information.

Joint Research Centre-Institute for Health and Consumer Protection (JRC-IHCP) (2010). 

European Union Risk Assessment Report, 4,4'-Isopropylidenediphenol (Bisphenol-A).

JPI Healthcare. (n.d.). "Ultrasound Paper." from http://www.jpihealthcare.com/ultrasound-paper.

Liao, C. and K. Kannan (2011). "Widespread Occurence of Bisphenol A in Paper and Paper 

Products: Implications for Human Exposure." Environ. Sci. Technol. 45: 9372-9379. 

Mendum, T., E. Stoler, et al. (2011). "Concentration of bisphenol A in thermal paper." Green 

Chemistry Letters and Reviews 4(1): 81-86. 

Nashua Corporation. (2008). "Label Products." from 

http://nashua.com/prodandservices/labelproducts.aspx?selected=labeltrans.

National Toxicology Program-Center for the Evaluation of Risks to Human Reproduction (NTPCERHR) (2008). NTP-CERHR Monograph on the Potential Human Reproductive and 

Developmental Effects of Bisphenol A. U.S. Department of Health and Human Services.

Organisation for Economic Co-operation and Development (OECD) (2002). "SIDS Initial 

Assessment Profile." Existing Chemicals Database SIAM 14: 26-28. 

Polycarbonate/BPA Global Group. (2011). "Bisphenol A." from http://bisphenol-a.org/.

U.S. Environmental Protection Agency (U.S. EPA) (2010). Bisphenol A Action Plan.

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3. Background on Thermal Printing Technology

Thermal printing is a rapid and inexpensive printing technology widely used in commercial 

applications such as point-of-sale (POS) receipts, luggage tags, faxes, and labels (Mendum, 

Stoler et al. 2011). Direct thermal printing produces an image when specific chemicals within the 

coating of thermal paper are heated.1 Thermal printing technology was first developed in the late 

1960s, and its popularity grew in the 1980s and 1990s as it became more cost-effective and 

versatile. This chapter describes the components of the thermal paper system, its associated 

equipment, process, and applications, as well as the alternative chemicals analyzed and 

considered in the alternatives assessment.

3.1 Components of Thermal Paper

Thermal paper is a highly engineered product, in which paper is coated with a thermal sensitive 

layer that reacts in the presence of heat to create the printed image. The following sections 

describe the key components of thermal paper development, including chemistry and 

manufacture. This information was useful in evaluating potential alternatives in this application. 

3.1.1 Paper

Thermal paper is a standard paper grade that has been coated with a thermal sensitive layer, also 

known as a thermal reactive layer (see Figure 3 1). A pre-coat, or base coat, is applied to the base 

paper and allows for high resolution by preventing the heat transfer through all of the paper’s 

layers, and for smoothness. Applied to the pre-coat is a thermal layer that contains the necessary 

reactive components (see Section 3.1.2). Additionally, thermal paper may contain a protective 

top coat and/or back coat. Top coats may be used for some applications to protect thermal paper 

from mechanical stress or chemical reactions. Similarly, back coats may be used to provide 

additional protection during lamination, printing, or other mechanical processes (Koehler 

Thermal Papers n.d.). Thermal paper used for receipts typically lacks the top and back coats. 

Figure 3-1: Cross-Section of Thermal Paper

Thermal paper manufacturers produce the thermal paper in “jumbo rolls,” which is considered a 

semi-finished product. Paper converters print the paper, cut the product to the appropriate size 

for use, rewind the paper onto a specific core (called “slit rolls”), and package the paper for sale 

to distributors. There are three major categories of thermal paper depending on basis weight, or 

density (typically g/m2 or pounds per ream): (1) fax and POS grades, with an average basis 

weight of 58 grams, (2) label and ticket grades, with an average basis weight of 80 grams, and 

(3) heavy ticket grades, with an average basis weight of 120 grams (USITC 2007). Thermal 

paper is generally not made from recycled material, as post-consumer content can lack the 

1 Note: Other types of thermal printing include thermal transfer printing or dye sublimation. Direct thermal printing 

is the focus of the DfE Alternatives Assessment, and thus of this report.

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FINAL REPORT – January 2014 

consistency required for this highly engineered product. Limited quantities of recycled thermal 

paper are available, often including up to 50 percent post-consumer content. Thermal paper can 

be printed in both single-sided and double-sided formats. 

3.1.2 Printing Chemistry

The thermal layer includes three key compounds (see Figure 3 2): a dye (also referred to as a 

colorformer), a developer (also referred to as a coreactant), and in some systems, a sensitizer 

(also referred to as a modifier). A binder, such as polyvinyl alcohol or latex, helps these coatings 

adhere to the paper. The materials are slurried and applied as an aqueous emulsion to the paper. 

The combination of these materials and their properties determines the image color, scanning 

characteristics and durability. 

Figure 3-2: Elements of the Thermal Reactive Layer

3-2 

Dye

The colorant typically used in thermal paper is a leuco dye, which is colorless at room 

temperature (Biedermann, Tschudin et al. 2010). Leuco dyes used in thermal paper undergo a 

structural change when protonated in the presence of heat and a proton donor (i.e., developer). 

The structural change results in the production of color. During printing, the thermal head of the 

printing unit pulses heat to the paper, which causes the components to melt, triggering the 

transfer of the proton from the developer to the dye, causing the leuco dye molecule to change 

structure to form a visible color (Biedermann, Tschudin et al. 2010). When used, the sensitizer 

has a lower melting point, thus acting as a solvent, promoting the interaction of the developer 

with the dye.

The dyes are often spirolactone compounds, with Black 305 and ODB2 among the most 

common. Some dyes extend the wavelength resulting in direct transfer systems that can scan in 

the near infrared (NIR) and infrared (IR) wavelengths (ETAC and NIR Black 78, respectively). 

Based on discussions with stakeholders, Design for the Environment (DfE) compiled a list that 

illustrates a variety of dyes that can be used in direct thermal printing (see Table 3 1). Each of 

these dyes shares the property that they are colorless until developed following heat activation. 
FINAL REPORT – January 2014 

Table 3-1: Example of Dyes Used in Thermal Paper

Chemical Names and Synonyms CASRN Color

Spiro[isobenzofuran-1(3H),9'-[9H]xanthen]-3-one, 6'-

(dibutylamino)-3'-methyl-2'-(phenylamino)-; 2-

Anilino-6-dibutylamino-3-methylfluoran; ODB-2, 

Black 400

89331-94-2 black

Spiro[isobenzofuran-1(3H),9'-[9H]xanthen]-3-one, 6'-

(dipentylamino)-3'-methyl-2'-(phenylamino)-; Black 

305

129473-78-5 black

Furo[3,4-b]pyridin-5(7H)-one, 7,7-bis[4-

(diethylamino)-2-ethoxyphenyl]-; 3,3-Bis (4-

diethylamino-2-ethoxyphenyl)-4-azaphthalide

GN-2

132467-74-4 green

Spiro[isobenzofuran-1(3H),9'-

[9H]xanthen]-3-one, 6'- 

(diethylamino)-3'-methyl-2'- 

(phenylamino)-; N-102 (ODB)

29512-49-0 black

Spiro[isobenzofuran-1(3H),9'-[9H]xanthen]-3-one,6'-

[ethyl(4-methylphenyl)amino]-3'-methyl-2'-

(phenylamino)-; ODB-250, ETAC

59129-79-2 black

Spiro[isobenzofuran-1(3H),9'-[9H]xanthen]-3-one,6'-

(diethylamino)-3'-methyl-2'-[(3-methylphenyl)amino]-; 

ODB-7

151019-95-3 black

Spiro[12H-benzo[a]xanthene-12,1'(3'H)-

isobenzofuran]-3'-one,9-[ethyl(3-methylbutyl)amino]-; 

Red 500

115392-27-3 red

Spiro[isobenzofuran-1(3H),9'-[9H]xanthen]-3-one,6'-

[ethyl(4-methylphenyl)amino]-2'-methyl-; Red 520

42228-32-0 red

1(3H)-Isobenzofuranone,6-(dimethylamino)-3,3-bis[4-

(dimethylamino)phenyl]-; Crystal violet lactone; CVL

1552-42-7 blue

Spiro[isobenzofuran-1(3H),9'-[9H]xanthen]-3-one,6'-

[ethyl(3-methylbutyl)amino]-3'-methyl-2'-

(phenylamino)-; S-205

70516-41-5 black

1(3H)-Isobenzofuranone,

4,5,6,7-tetrachloro-3,3-bis[2-[4- 

(dimethylamino)phenyl]-2-(4- 

methoxyphenyl)ethenyl]-; NIR Black 78

113915-68-7 black

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FINAL REPORT – January 2014 

Chemical Names and Synonyms CASRN Color

3-(4-Diethylamino-2-methylphenyl)-3-(1-ethyl-2-

methyl-1H-indol-3-yl)-4-azaphthalide; Blue 220

114090-18-5 blue

7-[4-(diethylamino)-2-hexoxyphenyl]-7-(1-ethyl-2-

methylindol-3-yl)furo[3,4-b]pyridin-5-one; Blue 203

98660-18-5 blue

Spiro[isobenzofuran-1(3H),9'-[9H]xanthen]-3-one,6'-

[ethyl(4-methylphenyl)amino]-2'-

(methylphenylamino)-; ATP

42530-35-8 green

Spiro[isobenzofuran-1(3H),9'-[9H]xanthen]-3-one,6'-

[(3-ethoxypropyl)ethylamino]-3'-methyl-2'-

(phenylamino)-(93071-94-4); Black 500

93071-94-4 black

Developer

The purpose of the developer, also referred to as a coreactant, which is weakly acidic, is to 

transfer protons to the dye, triggering color formation. In selecting a developer, its solubility, 

pKa, melting point, color, odor, purity, and vapor pressure are key properties. Performance 

characteristics of effective developers include:

•

•

•

•

•

•

•

Acidity such that it produces no background imaging, 

Ability to fully react with the colorformer when heated, 

Reaction at the temperature of the specific printer, 

Stable at end use temperatures, 

Appropriate permanence for the application, 

Appropriate performance vs. cost balance, and

Feasible in large-scale production. 

See Section 3.4 for a list of alternative developers considered in this alternatives assessment.

Sensitizer

Sensitizers, also referred to as modifiers, can facilitate the dye coloration process by lowering the 

melting point of the dye/developer, and/or by acting as a type of solvent in which a dye and 

developer dissolve below their melting point. Sensitizers typically have a melting point between 

45-65oC (Mendum, Stoler et al. 2011). The sensitizer helps to provide the optimal conditions for 

the developer to transfer protons upon heating, which enables color formation and can increase 

printing speed, or make a product suitable for low-energy printers. A variety of sensitizers are 

used in direct thermal printing (see Table 3 2).

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FINAL REPORT – January 2014 

Table 3-2: Examples of Sensitizers Used in Thermal Printing

Chemical Names and Synonyms CASRN

Ethanedioic acid,1,2-bis[(4-chlorophenyl)methyl] ester; Di-

(P-Chlorobenzyl) oxalate

19829-42-6

Ethanedioic acid,1,2-bis[(4-methylphenyl)methyl] ester; Di-

(P-Menthylbenzyl) oxalate

18241-31-1

Ethanedioic acid,1,2-bis(phenylmethyl) ester; Dibenzyl 

oxalate

7579-36-4

Naphthalene, 2-(phenylmethoxyl)-; 2-Benzyloxynapthalene 613-62-7

1,4-diphenylbutane-1,4-dione; 1,4-Diphenoxybutanes 495-71-6

1-phenyl-4-(phenylmethyl)benzene; 4-Benzylbiphenyl 613-42-3

1,4-Benzenedicarboxylicacid,1,4-dimethylester; Dimethyl 

terephthalate

120-61-6

Benzene, 1,1’-[1,2-ethanediylbis(oxy)]bis-; (2-

Phenoxyethoxy)benzene; 1,2-Diphenoxyethane

104-66-5

Benzene,1,1'-[1,2-ethanediylbis(oxy)]bis[3-methyl-; 1,2-

Bis(3-methoxyphenoxy) ethane

54914-85-1

1,1'-Sulfonylbisbenzene; Diphenyl sulfone 127-63-9

Octadecanamide; Stearamide (waxy) 124-26-5

Hexanedioic acid, polymer with 1,4-butanediol and 1,2-

ethanediol; Oligoethylene butylene glycol adipate, 

Hexanedioic acid; Kemamide S ( waxy)

26570-73-0

Octadecanamide,N,N'-1,2-ethylenebis-; Ethylene bis 

stearamide

110-30-5

Octadecanamide, N-phenyl; N-phenylstearamide; 637-54-7

N-(2-methylphenyl)-3-oxobutanamide; oAcetoacetotoluidide93-68-5

3.2 Thermal Printing Equipment and Process

Direct thermal printing produces an image by selectively heating specific areas of thermal paper

(Mendum, Stoler et al. 2011). At room temperature, the dye is in its neutral, unprotenated state, 

which is colorless. When the dye/developer/ sensitizer system is heated above the melting point 

of the sensitizer, the developer (commonly bisphenol A (BPA)) donates a proton. In the case of 

the CVL dye (Table 3 1), this causes the lactone ring to open and increases the conjugation of the 

system, resulting in color formation (Mendum, Stoler et al. 2011). The chemicals then solidify to 

create a relatively stable image.

As Figure 3 3 illustrates, a thermal printing system consists of three basic components: a printer 

head, thermal paper, and a platen (i.e., backing roll). The printer head contains miniature heating 

units along the length of the printer head that electronically transfers the required amount of heat 

to the paper. As the thermal paper is driven by the platen, it is heated by the unit’s thermal head 

causing the dye and the developer in the coating of the paper to melt and react, which 

subsequently produces an image on the paper (Koehler Thermal Papers n.d.). 

3-5 
FINAL REPORT – January 2014 

Figure 3-3: Overview of Thermal Printing Process 

(based on Koehler Thermal Paper n.d. and Charters Paper Pty Ltd 2006) 

3-6 

 

To ensure optimal printing results, it is important to consider the characteristics of the type of 

thermal paper and printer used. Different grades of thermal paper have certain characteristics that 

render them more applicable to certain uses. One important characteristic is dynamic sensitivity, 

which pertains to the length of time the paper is exposed to heat. The faster a printer operates, the 

less time the paper is exposed to the unit’s heating element. Thermal paper with a higher 

dynamic sensitivity is most appropriate for higher-speed or lower-energy printing. If thermal 

paper with low dynamic sensitivity is used instead, insufficient heat will be applied to the paper 

resulting in a reduced long-term stability of the finished product (Koehler Thermal Papers n.d.). 

Static sensitivity is another important characteristic of thermal paper. Static sensitivity defines 

the temperature at which the dye and the developer begin to melt. The static sensitivity value is 

important for thermally-sensitive applications, such as for parking tickets or environments with 

high temperatures (e.g., pizza boxes, coffee cup labels) (Koehler Thermal Papers n.d.). Different 

grades of thermal paper exhibiting varying degrees of thicknesses and sensitivities affect the 

lifespan of the print job. If the appropriate paper and printer combination is used, and proper 

storage conditions are met, an image printed on thermal paper typically lasts between five to ten 

years (Koehler Thermal Papers 2011). 

3.3 Advantages and Disadvantages of Thermal Printing Technology 

Direct thermal printing offers several advantages in commercial environments, including not 

requiring any additional inks or chemicals to form the printer image. The only consumable item 

needed for direct thermal paper printing is the paper. Unlike thermal transfer printing, the direct 

thermal paper technology obviates the need for ink or ribbon maintenance and replacement.2

Thermal printing systems also have few moving parts, making them reliable and relatively 

durable. In addition, direct thermal printing systems are quiet, have appropriate edge definition 

(up to 400 dpi, or dots per inch), can be manufactured to be small and lightweight, and can print 

quickly (up to 406 mm per second) (Charters Paper Pty Ltd 2006). Such advantages make direct 

2 The use of ribbons, which contain a mirror image of anything printed, raise privacy and security concerns; ribbons 

used in the printing of medical information must be destroyed in accordance with the Health Insurance Portability 

and Accountability Act of 1996 (HIPAA). 
FINAL REPORT – January 2014 

thermal printing systems a useful tool for market segments like retailers, laboratories with 

recorders, transportation, and hospitality, which tend to value an economical and fast printing 

system. Stakeholders noted that direct transfer print systems can be made portable, which is a 

highly valued attribute. 

Thermal paper rolls exposed to heat may turn black, necessitating appropriate storage conditions. 

POS thermal paper is generally very thin and may be damaged by prolonged exposure to 

sunlight, water, or chemicals (e.g., solvents, plasticizers) and to friction. In general, POS thermal 

printing is best suited for short-term printing needs more so than longer term data storage. 

However, some thermal printing is estimated to last five to 12 years (Koehler Thermal 

Papers n.d.). 

3.4 Alternatives Included in this Assessment

Potential alternatives to BPA for use in thermal paper were initially identified through internet 

searches, and focused on chemicals of similar structure and physical/chemical properties. 

Stakeholders also suggested specific chemicals for inclusion. With the assistance of stakeholders, 

the U.S. Environmental Protection Agency (EPA) identified 19 alternatives to BPA in thermal 

paper (see Table 3 3 below). These alternatives were selected because they have the potential to 

be functional substitutes to BPA based on their physical and chemical properties and/or because 

they are already in commercial use. Current commercial use was not a requirement for inclusion. 

A hazard assessment was conducted on BPA and these 19 alternatives; the findings are discussed 

in Chapter 4.

Chemical Alternatives and the Toxic Substances Control Act

EPA’s Design for the Environment (DfE) program is administered by the Office of Pollution Prevention and 

Toxics (OPPT), which is charged with the implementation of the Toxic Substances Control Act (TSCA) and the 

Pollution Prevention Act (PPA).

Central to the administration of TSCA is the management of the TSCA Inventory. Section 8 (b) of TSCA 

requires EPA to compile, keep current, and publish a list of each chemical substance that is manufactured or 

processed in the United States. Companies are required to verify the TSCA status of any substance they wish to 

manufacture or import for a TSCA-related purpose. For more information, please refer to the TSCA Chemical 

Substance Inventory website: http://www.epa.gov/opptintr/existingchemicals/pubs/tscainventory/basic.html.

TSCA and DfE Alternatives Assessments

Substances selected for evaluation in a DfE Alternatives Assessment generally fall under the TSCA regulations 

and therefore must be listed on the TSCA inventory, or be exempt or excluded from reporting before being 

manufactured in or imported to, or otherwise introduced in commerce in, the United States. For more 

information see http://www.epa.gov/oppt/newchems/pubs/whofiles.htm 

To be as inclusive as possible, DfE Alternatives Assessments may consider substances that may not have 

been reviewed under TSCA, and therefore may not be listed on the TSCA inventory. DfE has worked with 

stakeholders to identify and include chemicals that are of interest and likely to be functional alternatives, 

regardless of their TSCA status. Chemical identities are gathered from the scientific literature and from 

stakeholders and, for non-confidential substances, appropriate TSCA identities are provided.

Persons are advised that substances, including DfE-identified functional alternatives, may not be introduced into 

U.S. commerce unless they are in compliance with TSCA. Introducing such substances without adhering to the 

TSCA provisions may be a violation of applicable law. Those who are considering using a substance discussed 

in this report should check with the manufacturer or importer about the substance’s TSCA status. If you have 

questions about reportability of substances under TSCA, please contact the OPPT Industrial Chemistry Branch 

at 202-564-8740.

3-7 
FINAL REPORT – January 2014 

Table 3-3: The Alternatives Selected for Analysis in the Hazard Assessment 

The chemicals included in this assessment are identified based on information provided to us by stakeholders, supplemented with publicly available information 

obtained through internet information searches.

CASRN Chemical Name(s) Common

Name(s)

Molecular 

Formula Structure

80-05-7 

Phenol, 4,4’-

(methylethylidene)bis- ; 

2,2-bis(phydroxyphenyl)propane

Bisphenol A, 

BPA C15H16O2

620-92-8 

Phenol, 4,4’-methylenebis-; 

Bis(4-

hydroxyphenyl)methane

Bisphenol F, 

BPF C13H12O2

79-97-0 

Phenol, 4,4’-(1-

methylethylidene)bis[2-

methyl; ,2’-Bis(4-hydroxy3-methylphenyl)propane

Bisphenol C, 

BPC C17H20O2

5129-00-0 

Benzeneacetic acid, 4-

hydroxy-.alpha.-(4-

hydroxyphenyl)-, methyl 

ester; Methyl bis(4-

hydroxyphenyl)acetate

MBHA C15H14O4

24038-68-4 

[1,1'-Biphenyl]-2-ol, 5,5''-

(1-methylethylidene)bis-; 

4,4’-Isopropyllidenebis(2-

phenylpheno)

BisOPP-A C27H24O2

1571-75-1 4,4’-(1-

Phenylethylidene)bisphenol

Bisphenol AP, 

BPAP C20H18O2

PROPRIETARY

Substituted 

phenolic 

compound #1

N/A N/A

OH OH

OH OH

OH OH

OH OH

O O

OH

OH

OH OH

3-8 
FINAL REPORT – January 2014 

CASRN Chemical Name(s) Common

Name(s)

Molecular 

Formula Structure

PROPRIETARY

Substituted 

phenolic 

compound #2

N/A N/A

94-18-8 

Benzoic acid, 4-hydroxy-, 

phenylmethyl ester; Benzyl 

4-hydroxybenzoate

PHBB C14H12O3

80-09-1 Phenol, 4,4'-sulfonylbis-; 

4-Hydroxyphenyl sulfone Bisphenol S C12H10O4S 

5397-34-2 

Phenol, 2-[(4-

hydroxyphenyl)sulfonyl]-; 

2,4’-

Bis(hydroxyphenyl)sulfone

2,4-BPS C12H10O4S 

41481-66-7 

Phenol, 4,4'-sulfonylbis[2-

(2-propen-1-yl)-; bis-(3-

allyl-4-hydroxyphenyl) 

sulfone

TGSA C18H18O4S 

97042-18-7 Phenol,4-[[4-(2-propen-1-

yloxy)phenyl]sulfonyl]- BPS-MAE C15H14O4S 

63134-33-8 

Phenol, 4-[[4-

(phenylmethoxy)phenyl]sulf

onyl]-; 4-Hydroxy-4’-

benzyloxydiphenylsulfone

BPS-MPE C19H16O4S 

95235-30-6 

Phenol, 4-[[4-(1-

methylethoxy)phenyl]sulfon

yl]-; 4-hydroxyphenyl 4-

isoprooxyphenylsulfone

D-8 C15H16O4S 

191680-83-8 4-[4'-[(1'-methylethyloxy) 

phenyl]sulfonyl]phenol D-90 C28H26O9S2 (n = 1); 

C44H42O14S3 (n = 2)

OH

O

O

S

O

O

OH OH

OH

S

O O OH

S

O

O

OH OH

S

O

O

OH O

S

O

O

O OH

S

O

O

O OH

S

OH O

O

O O

O

S

OH

O O

n

3-9 
FINAL REPORT – January 2014 

CASRN Chemical Name(s) Common

Name(s)

Molecular 

Formula Structure

93589-69-6 

Phenol, 4,4'-

[methylenebis(oxy-2,1-

ethanediylthio)]bis-; 1,7-

bis(4-Hydroxyphenylthio)-

3,5-dioxaheptane

DD-70 C17H20O4S2

232938-43-1 

N-(p-Toluenesulfonyl)-N'-

(3-ptoluenesulfonyloxyphenyl)u

rea

Pergafast 201 C21H20N2O6S2

151882-81-4 

Benzenesulfonamide, N,N'-

[methylenebis(4,1- 

phenyleneiminocarbonyl)]bi

s[4-methyl-; 4,4'-bis(Ncarbamoyl-4-

methylbenzenesulfonamide)

diphenylmethane

BTUM C29H28N4O6S2

321860-75-7 

UU, Urea 

Urethane 

Compound

C42H36N6O8S 

OH

S

O O

S

OH

N

H O

N

H

S

O

O

3CH

O S

O

O

CH3

N N

O

S

O O

N N

O

S

O O

3-10 
FINAL REPORT – January 2014 

3.5 Alternatives Not Included in this Assessment

The chemicals listed in this section were identified as possible alternatives to BPA, but were not 

included in this alternatives assessment. Chemicals were excluded based on feedback from the 

stakeholders, because their physical and/or chemical properties would likely render them 

incompatible as a functional replacement developer to BPA. Required physical properties of 

developers include acidity, water solubility, and melting point. A summary of the chemicals that 

were discussed but not included in this assessment are listed in Table 3 4. 

Table 3-4: Alternatives Considered but Not Included in this DfE Alternatives Assessment

CASRN Chemical and 

Common Name(s)

Molecular 

Formula Structure

98-54-4 

p-tert-butylphenol: 

Phenol, 4-(1,1-

dimethylethyl)-

C10H14O 

92-69-3 p-Phenylphenol; [1,1'-

Biphenyl]-4-ol C12H10O 

2664-63-3 4,4’-Thiodiphenol; 

Phenol, 4,4'-thiobis- C12H10O2S 

19715-19-6 

Benzoic acid, 3,5-

bis(1,1- 

dimethylethyl)-2-

hydroxy-; 3,5-di-tertbutylsalicylic acid

C15H22O3

120-47-8 

Benzoic acid, 4-

hydroxy-, ethyl

ester; ethyl-phydroxybenzoate, 

ethyl paraben

C9H10O3

22479-95-4 

Dimethyl-4-

hydroxyphthalate; 

DMP-OH

C10H10O5

1694-06-0 

N-(ptoluenesulphonyl)-N’-

(3-ptoluenesulphonyloxyp

henyl)urea

C8H10N2O3S 

4724-47-4 

poctadecylphosphonic 

acid; Phosphonic acid, 

P-octadecylC18H39O3P 

65-85-0 Benzoic acid C7H6O2

57-11-4 Octadecanoic acid; 

stearic acid C18H36O2

OH

OH

S

OH OH

O

O O

OH

O

O

OH

O

O

O

O

S

N

H

NH2

O O O

P O

OH OH

OH

O

OH

O

3-11 
FINAL REPORT – January 2014 

CASRN Chemical and 

Common Name(s)

Molecular 

Formula Structure

144-62-7 Ethanedioic acid; 

oxalic acid C2H2O4

11113-50-1 Boric acid H3BO3

149-91-7 Benzoic acid, 3,4,5-

trihydroxy-; gallic acid C7H6O5

OH

OH

O

O

B

OH OH

OH

OH

O

OH

OH

OH

3-12 
FINAL REPORT – January 2014 

References

Biedermann, S., P. Tschudin, et al. (2010). "Transfer of bisphenol A from thermal printer paper 

to the skin." Anal Bioanal Chem 398: 571-576. 

Charters Paper Pty Ltd (2006). Leaders in the field of Thermal Paper Technology. 

Koehler Thermal Papers (2011). Koehler Thermal Papers: Product Range. 

Koehler Thermal Papers (n.d.). Thermal Papers: Product Information. 

Mendum, T., E. Stoler, et al. (2011). "Concentration of bisphenol A in thermal paper." Green 

Chemistry Letters and Reviews 4(1): 81-86. 

U.S. International Trade Commission (2007). Certain Lightweight Thermal Paper From China, 

Germany, and Korea.

3-13 
FINAL REPORT – January 2014 

4. Hazard Evaluation of Bisphenol A (BPA) and Alternatives

This chapter summarizes the toxicological and environmental hazards of bisphenol A (BPA) and 

each of the 19 alternative chemicals that were identified as potential functional substitutes for 

BPA. Evaluations of chemical formulations may also require the consideration of associated 

substances (e.g., starting materials, byproducts, and impurities) if their presence is specifically 

required to allow that alternative to fully function in the assigned role. In general, associated 

substances were assumed to remain unchanged in this assessment, but may need to be considered 

in the selection of an alternative. Otherwise, pure substances were analyzed in this assessment. 

Users of the hazard information in this alternatives assessment should be aware of the purity of 

the trade product they purchase, as the presence of impurities may alter the assessment of the 

alternative. In general, associated substances were assumed to remain unchanged in this 

assessment, but may need to be considered in the selection of an alternative. This report is a 

hazard assessment, not a full risk assessment. Hazard assessment as a risk management tool is 

discussed in more detail in Section 1.3. 

Toxicological and environmental endpoints included in the hazard profiles are discussed in 

Section 4.1, along with the criteria used to evaluate each hazard endpoint. Data sources and the 

review methodology are described in Section 4.2. The report then offers a detailed description of 

the utility of physical/chemical properties in understanding hazard in Section 4.3, and the process 

of evaluating human health and environmental endpoints in Sections 4.4 and 4.5, respectively. A 

discussion of the evaluation of endocrine activity is included in Section 4.6. The characteristics 

of each chemical included in the alternatives assessment are summarized in the comparative 

hazard summary table in Section 4.1. Lastly, the collected data and hazard profile of each 

chemical are presented in Section 4.2.

4.1 Toxicological and Environmental Endpoints 

The assessment of endpoints with the intent to create hazard profiles for a Design for the 

Environment (DfE) Alternatives Assessment follows the guidance of the DfE Alternatives 

Assessment Criteria for Hazard Evaluation (U.S. EPA 2011b). The definitions for each endpoint 

evaluated following these criteria are outlined in Section 4.1.1 and the criteria by which these 

endpoints are evaluated are outlined in Section 4.1.2. Lastly, there are endpoints that DfE 

characterizes but does not assign criteria, which are summarized in Section 4.1.3. 

4.1.1 Definitions of Each Endpoint Evaluated Against Criteria

Hazard designations for each chemical discussed in this report were made by direct comparison 

of the experimental or estimated data to the DfE Alternatives Assessment Criteria for Hazard 

Evaluation (U.S EPA 2011b). Table 4 1 provides brief definitions of human health toxicity, 

environmental toxicity, and environmental fate endpoints 

4-1 
FINAL REPORT – January 2014 

Table 4-1: Definitions of Toxicological and Environmental Endpoints for Hazard Assessment

Endpoint 

Category Endpoint Definition

Human Health 

Effects

Acute Mammalian Toxicity Adverse effects occurring following oral or dermal 

administration of a single dose of a substance, or multiple 

doses given within 24 hours, or an inhalation exposure of 

4 hours.

Carcinogenicity Capability of a substance to increase the incidence of 

malignant neoplasms, reduce their latency, or increase 

their severity or multiplicity.

Mutagenicity/Genotoxicity Mutagenicity – The ability of an agent to induce 

permanent, transmissible changes in the amount, chemical 

properties, or structure of the genetic material. These 

changes may involve a single gene or gene segment, a 

block of genes, parts of chromosomes, or whole 

chromosomes. Mutagenicity differs from genotoxicity in 

that the change in the former case is transmissible to 

subsequent cell generations.

Genotoxicity – The ability of an agent or process to alter 

the structure, information content, or segregation of DNA, 

including those which cause DNA damage by interfering 

with normal replication process, or which in a nonphysiological manner (temporarily) alter its replication. 

Reproductive Toxicity The occurrence of biologically adverse effects on the 

reproductive systems of females or males that may result 

from exposure to environmental agents. The toxicity may 

be expressed as alterations to the female or male 

reproductive organs, the related endocrine system, or 

pregnancy outcomes. The manifestation of such toxicity 

may include, but is not limited to adverse effects on onset 

of puberty, gamete production and transport, reproductive 

cycle normality, sexual behavior, fertility, gestation, 

parturition, lactation, developmental toxicity, premature 

reproductive senescence, or modifications in other 

functions that were dependent on the integrity of the 

reproductive systems.

Developmental Toxicity Adverse effects in the developing organism that may 

result from exposure prior to conception (either parent), 

during prenatal development, or postnatally to the time of 

sexual maturation. Adverse developmental effects may be 

detected at any point in the lifespan of the organism. The 

major manifestations of developmental toxicity include: 

(1) death of the developing organism, (2) structural 

abnormality, (3) altered growth, and (4) functional 

deficiency. 

Neurotoxicity An adverse change in the structure or function of the 

central and/or peripheral nervous system following 

exposure to a chemical, physical, or biological agent.

4-2 
FINAL REPORT – January 2014 

Endpoint 

Category Endpoint Definition

Repeated Dose Toxicity Adverse effects (immediate or delayed) that impair normal 

physiological function (reversible and irreversible) of

specific target organs or biological systems following 

repeated exposure to a chemical substance by any route 

relevant to humans. Adverse effects include biologically 

significant changes in body and organ weights, changes 

that affect the function or morphology of tissues and 

organs (gross and microscopic), mortality, and changes in 

biochemistry, urinalysis, and hematology parameters that 

are relevant for human health; may also include 

immunological and neurological effects.

Respiratory Sensitization Hypersensitivity of the airways following inhalation of a

substance.

Skin Sensitization A cell-mediated or antibody-mediated allergic response 

characterized by the presence of inflammation that may 

result in cell death, following an initial induction exposure 

to the same chemical substance, i.e., skin allergy.

Eye Irritation/Corrosivity Irritation or corrosion to the eye following the application 

of a test substance.

Skin Irritation/Corrosion Skin irritation – Reversible damage to the skin following 

the application of a test substance for up to 4 hours. 

Skin corrosion – Irreversible damage to the skin namely, 

visible necrosis through the epidermis and into the dermis 

following the application of a test substance for up to 4 

hours.

Environmental 

Toxicity 

Environmental toxicity refers to adverse effects observed in living organisms that typically inhabit 

the wild; this assessment is focused on effects in three groups of surrogate aquatic organisms 

(freshwater fish, invertebrates, algae).

Aquatic Toxicity (Acute) The property of a substance to be injurious to an organism 

in a short-term, aquatic exposure to that substance.

Aquatic Toxicity (Chronic) The property of a substance to cause adverse effects to 

aquatic organisms during aquatic exposures which were 

determined in relation to the life-cycle of the organism. 

Environmental 

Fate

Environmental Persistence The length of time the chemical exists in the environment, 

expressed as a half-life, before it is destroyed (i.e., 

transformed) by natural or chemical processes. For 

alternatives assessments, the amount of time for complete 

assimilation (ultimate removal) is preferred over the initial 

step in the transformation (primary removal).

Bioaccumulation The process in which a chemical substance is absorbed in 

an organism by all routes of exposure as occurs in the 

natural environment (e.g., dietary and ambient 

environment sources). Bioaccumulation is the net result of 

competing processes of chemical uptake into the organism 

at the respiratory surface and from the diet and chemical 

elimination from the organism including respiratory 

exchange, fecal egestion, metabolic biotransformation of 

the parent compound, and growth dilution.

4-3 
FINAL REPORT – January 2014 

The hazard profile for each chemical contains endpoint-specific summary statements (see 

Section 4.2). For each of the endpoints listed in Table 4 1, these summary statements provide the 

hazard designation, the type of data (experimental or estimated), and the rationale. The endpoint 

summaries may also include explanatory comments, a discussion of confounding factors, or an 

indication of the confidence in the data to help put the results in perspective. 

4.1.2 Criteria

Table 4 2 summarizes the criteria that were used by the U.S. Environmental Protection Agency 

(EPA) DfE Program to interpret the data presented in the hazard evaluations. The DfE 

Alternatives Assessment Criteria for Hazard Evaluation underwent internal and public review 

and comment, and were finalized in 2011 (U.S. EPA 2011b). A hazard designation for each 

human health endpoint was not given for each route of exposure but rather was based on the 

exposure route with the highest hazard designation. Data may have been available for some or all 

relevant routes of exposure. 

The details as to how each endpoint was evaluated are described below and in the DfE full 

criteria document, DfE Alternatives Assessment Criteria for Hazard Evaluation, available at: 

http://www.epa.gov/dfe/alternatives_assessment_criteria_for_hazard_eval.pdf. 

Table 4-2: Criteria Used to Assign Hazard Designations

Endpoint Very High High Moderate Low Very Low

Human Health Effects

Acute mammalian toxicity

Oral median lethal dose 

(LD50) (mg/kg)

≤50 >50–300 >300–2000 >2000 –

Dermal LD50 (mg/kg) ≤200 >200–1000 >1000–2000 >2000 –

Inhalation median lethal 

concentration (LC50) - 

vapor/gas

(mg/L)

≤2 >2–10 >10–20 >20 –

Inhalation LC50 - dust/mist/

fume (mg/L)

≤0.5 >0.5–1.0 >1–5 >5 –

Carcinogenicity

Known or 

presumed 

human 

carcinogen 

(equivalent to 

Globally 

Harmonized 

System of 

Classification 

and Labeling of 

Chemicals

(GHS) 

Suspected 

human 

carcinogen 

(equivalent to 

GHS Category 

2)

Limited or 

marginal 

evidence of 

carcinogenicity 

in animals (and 

inadequate 

evidence in 

humans)

Negative studies 

or robust 

mechanismbased structure 

activity 

relationships 

(SAR) (as 

described above) 

–

4-4 
FINAL REPORT – January 2014 

Endpoint Very High High Moderate Low Very Low

Categories 1A 

and 1B)1

Mutagenicity/Genotoxicity

Germ cell mutagenicity

GHS Category 

1A or 1B: 

Substances 

known to 

induce heritable 

mutations or to 

be regarded as 

if they induce 

heritable 

mutations in the 

germ cells of 

humans

GHS Category 

2: Substances 

which cause 

concern for 

humans owing 

to the 

possibility that 

they may 

induce heritable 

mutations in the 

germ cells of 

humans

OR

Evidence of 

mutagenicity 

supported by 

positive results 

in in vitro OR in 

vivo somatic 

cells of humans 

or animals 

Negative for 

chromosomal 

aberrations and 

gene mutations, 

or no structural 

alerts 

– 

Mutagenicity and 

genotoxicity in somatic 

cells

Evidence of 

mutagenicity 

supported by 

positive results 

in in vitro AND 

in vivo somatic 

cells and/or 

germ cells of 

humans or 

animals

Reproductive toxicity

Oral (mg/kg/day) – <50 50–250 >250-1000 >1000

Dermal (mg/kg/day) – <100 100–500 >500-2000 >2000

Inhalation - vapor, gas 

(mg/L/day)

– <1 1–2.5 >2.5-20 >20

Inhalation - dust/mist/fume 

(mg/L/day)

– <0.1 0.1–0.5 >0.5-5 >5

Developmental toxicity

Oral (mg/kg/day) – <50 50–250 >250-1000 >1000

Dermal (mg/kg/day) – <100 100–500 >500-2000 >2000

Inhalation - vapor, gas 

(mg/L/day)

– <1 1–2.5 >2.5-20 >20

Inhalation - dust/mist/fume 

(mg/L/day)

– <0.1 0.1–0.5 >0.5-5 >5

Neurotoxicity

Oral (mg/kg/day) – <10 10–100 >100 –

Dermal (mg/kg/day) – <20 20–200 >200 –

Inhalation - vapor, gas 

(mg/L/day)

– <0.2 0.2–1.0 >1.0 –

1 The United Nations’ GHS document can be found at 

http://www.unece.org/fileadmin/DAM/trans/danger/publi/ghs/ghs_rev04/English/ST-SG-AC10-30-Rev4e.pdf. 

4-5 

 
FINAL REPORT – January 2014 

Endpoint Very High High Moderate Low Very Low

Inhalation - dust/mist/fume 

(mg/L/day)

– <0.02 0.02–0.2 >0.2 –

Repeated-dose toxicity1

Oral (mg/kg/day) – <10 10–100 >100 –

Dermal (mg/kg/day) – <20 20–200 >200 –

Inhalation - vapor, gas 

(mg/L/day)

– <0.2 0.2–1.0 >1.0 –

Inhalation - dust/mist/fume 

(mg/L/day)

– <0.02 0.02–0.2 >0.2 –

Sensitization

Skin sensitization – High frequency 

of sensitization 

in humans 

and/or high 

potency in 

animals (GHS 

Category 1A)

Low to moderate 

frequency of 

sensitization in 

human and/or 

low to moderate 

potency in 

animals (GHS 

Category 1B)

Adequate data 

available and not 

GHS Category 

1A or 1B

–

Respiratory sensitization – Occurrence in 

humans or 

evidence of 

sensitization in 

humans based 

on animal or 

other tests 

(equivalent to 

GHS Category 

1A and 1B)

Limited 

evidence 

including the 

presence of 

structural alerts

Adequate data 

available 

indicating lack 

of respiratory 

sensitization

–

Irritation/corrosivity

Eye irritation/corrosivity Irritation 

persists for 

>21 days or 

corrosive

Clearing in 8–

21 days, 

severely 

irritating

Clearing in 

≤7 days, 

moderately 

irritating

Clearing in 

<24 hours, 

mildly irritating

Not irritating

Skin irritation/corrosivity Corrosive Severe 

irritation at 

72 hours

Moderate 

irritation at 

72 hours

Mild or slight 

irritation at 

72 hours

Not irritating

Endocrine activity

Endocrine activity For this endpoint, High/Moderate/Low etc. characterizations will not apply. A 

qualitative assessment of available data will be prepared.

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Endpoint Very High High Moderate Low Very Low

Environmental Toxicity and Fate

Aquatic toxicity

Acute aquatic toxicity -

LC50 or Half Maximal 

Effective Concentration 

(EC50) (mg/L)

<1.0 1–10 >10–100 >100 or No 

Effects at 

Saturation

(NES)

–

Chronic aquatic toxicity –

Lowest Observed Effect 

Concentration (LOEC) or 

Chronic Value (ChV) 

(mg/L)

<0.1 0.1–1 >1–10 >10 or NES –

Environmental Persistence

Persistence in water, soil, 

or sediment

Half-life 

>180 days or 

recalcitrant

Half-life of 60–

180 days

Half-life <60 

but ≥16 days

Half-life 

<16 days OR 

passes Ready 

Biodegradability 

test not 

including the 

10-day window. 

No degradation 

products of 

concern

Passes Ready 

Biodegradability 

test with 10-day 

window. No 

degradation 

products of 

concern.

Persistence in air (half-life 

days)

For this endpoint, High/Moderate/Low etc. characterizations will not apply. A 

qualitative assessment of available data will be prepared.

Bioaccumulation 

Bioconcentration Factor 

(BCF)/Bioaccumulation 

Factor (BAF)

>5000 5000–1000 <1000–100 <100 –

Log BCF/BAF >3.7 3.7–3 <3-2 <2 – 1 Criteria values are to be applied to 90-day repeated dose studies. These values are tripled for chemicals evaluated 

in 28-day studies or similarly modified for studies of other durations.

Very High or Very Low designations (if an option for a given endpoint in Table 4 2) were assigned only when there 

were experimental data available for the chemical under evaluation. In addition, the experimental data must have 

been collected from a well conducted study specifically designed to evaluate the endpoint under review. If the 

endpoint was estimated using experimental data from a close structural analog, professional judgment, or a 

computerized model, then the next-level designation was assigned (i.e., High or Low).

4.1.3 Endpoints Characterized but Not Evaluated 

Several additional endpoints were characterized, but not evaluated against hazard criteria. This is 

because the endpoints lacked a clear consensus concerning the evaluation criteria (endocrine 

activity), data and expert judgment were limited for industrial chemicals (persistence in air, 

terrestrial ecotoxicology), or the information was valuable for interpretation of other toxicity and 

fate endpoints (including toxicokinetics and transport in the environment). 

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Table 4-3: Definitions of Endpoints and Information Characterized but Not Evaluated Against Hazard 

Criteria

Toxicological Endpoint Definition

Toxicokinetics The determination and quantification of the time course of absorption, distribution, 

metabolism, and excretion (ADME) of chemicals (sometimes referred to as 

pharmacokinetics). 

Biomonitoring Information The measured concentration of a chemical in biological tissues where the analysis 

samples were obtained from a natural or non-experimental setting.

Environmental Transport The potential movement of a chemical, after it is released to the environment, 

within and between each of the environmental compartments (air, water, soil, and 

sediment). Presented as a qualitative summary in the alternatives assessment based 

on physical/chemical properties, environmental fate parameters, and simple 

volatilization models. Also includes distribution in the environment as estimated 

from a fugacity model.

2

Persistence in Air The half-life for destructive removal of a chemical substance in the atmosphere. 

The primary chemical reactions considered for atmospheric persistence include 

hydrolysis, direct photolysis, and the gas phase reaction with hydroxyl radicals, 

ozone, or nitrate radicals. Results are used as input into the environmental transport 

models.

Immunotoxicology Adverse effects on the normal structure or function of the immune system caused 

by chemical substances (e.g., gross and microscopic changes to immune system 

organs, suppression of immunological response, autoimmunity, hypersensitivity, 

inflammation, and disruption of immunological mechanistic pathways).

Terrestrial Ecotoxicology Reported experimental values from guideline and nonguideline studies on adverse 

effects on the terrestrial environment. Studies on soil, plants, birds, mammals, 

invertebrates were also included.

Endocrine Activity A change in endocrine homeostasis caused by a chemical and/or other stressor.

4.2 Data Sources and Assessment Methodology 

This section explains how data were collected (Section 4.2.1), prioritized, and reviewed (Section 

0) for use in the development of hazard profiles. High-quality experimental studies lead to a 

thorough understanding of behavior and effects of the chemical in the environment and in living 

organisms. Analog approaches and SAR-based estimation methods are also useful tools and are 

discussed throughout Section 0. Information on how the evaluation of polymers differs from the 

evaluation of discrete chemicals is presented in Section 0.

4.2.1 Identifying and Reviewing Measured Data

For each chemical assessed, data were collected in a manner consistent with the High Production 

Volume (HPV) Chemical Challenge Program Guidance on searching for existing chemical 

information (U.S. EPA 1999b). This process resulted in a comprehensive search of the literature 

for available experimental data. For chemicals well characterized by experimental studies, this 

usually resulted in the collection of recent high-quality reviews or peer-reviewed risk 

assessments. In some cases, these reviews and risk assessments were supplemented by primary 

2 A fugacity model predicts partitioning of chemicals among air, soil, sediment, and water under steady state 

conditions for a default model “environment” (U.S. EPA, 2011e).

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FINAL REPORT – January 2014 

searches of scientific literature published after these secondary sources were released, which is 

explained in greater detail below. For chemicals that are not as well characterized, that is, where 

these secondary sources were not available or lacked relevant or adequate data, a comprehensive 

search of the primary scientific literature was done. Subsequently, these searches led to the 

collection and review of articles from the scientific literature, industrial submissions,

encyclopedic sources, and government reports. In addition, data presented in EPA public and 

confidential databases (e.g., Integrated Risk Information System (IRIS)) were obtained for this 

project. Generally, foreign language (non-English) reports were not used unless they provided 

information that was not available from other sources. 

Chemical assessments were performed by first searching for experimental data for all endpoints 

in Table 4 1. For most alternatives assessed, high-quality secondary sources were not available; 

therefore, a comprehensive search of the primary literature was performed to identify 

experimental data. In some cases, confidential studies submitted to EPA by chemical 

manufacturers were also available to support hazard designations. For those chemicals that were 

expected to form stable metabolites, searches were performed to identify relevant fate and 

toxicity information for the metabolite or degradation product. 

Well-Studied Chemicals – Literature Search Strategy

As mentioned above, for chemicals that have been well characterized (limited to BPA in this DfE 

Alternatives Assessment), the literature review began with recent, high-quality, authoritative 

secondary sources, such as in the case of BPA, the 2008 National Toxicology Program (NTP) 

expert panel review (National Toxicology Program-Center for the Evaluation of Risks to Human 

Reproduction (NTP-CERHR) 2008) and the 2011 Food and Agricultural Organization of the 

United Nations/World Health Organization expert panel review (FAO/WHO 2011). Using highquality secondary sources maximized available resources and eliminated potential duplication of 

effort. However, more than one secondary source was typically used to verify reported values, 

which also reduced the potential for presenting a value that was transcribed incorrectly from the 

scientific literature. Although other sources might also contain the same experimental value for 

an endpoint, effort was not focused on building a comprehensive list of these references, as it 

would not have enhanced the ability to reach a conclusion in the assessment. In some cases, 

primary studies were also evaluated to supplement the secondary sources. When data for a 

selected endpoint could not be located in a secondary source for an otherwise well-studied 

chemical, the primary literature was searched by endpoint and experimental studies were 

assessed for relevant information.

Making Predictions in the Absence of Measured Data

In the absence of primary or secondary data, hazard designations were based on (1) Quantitative 

Structure Activity Relationships (QSAR)-based estimations from the EPA New Chemical 

Program’s predictive methods; (2) analog data; (3) category-based assignments from the EPA 

Chemical Categories document; and (4) expert judgment by EPA subject matter experts.

For chemicals that lacked experimental information, QSAR assessments were made using either 

EPA’s Estimation Programs Interface (EPISuiteTM) for physical/chemical property and 

environmental fate endpoints or EPA’s Ecological Structure Activity Relationships 

(ECOSARTM) QSARs for ecotoxicity. For the cancer endpoint, estimates were also obtained 

from EPA’s OncoLogic expert system. These estimation methods have been automated, and are 

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FINAL REPORT – January 2014 

available for free (http://www.epa.gov/oppt/sf/tools/methods.htm). Often analog data were used 

to support predictions from models. These approaches were described in the EPA Pollution 

Prevention (P2) Framework (U.S. EPA 2005b) and Sustainable Futures (SF) program (U.S. EPA 

2011e). 

For some physical/chemical properties that could not be estimated using EPISuiteTM, such as 

acid/base dissociation constants, other available methods (e.g., the Sparc Performs Automated 

Reasoning in Chemistry (SPARC) website for dissociation constants) were used. All estimation 

methods employed were limited to those freely available in the public domain. 

The methodology and procedures used to assess polymers are described in Section 0. In addition, 

the endpoints for impurities or oligomers with a molecular weight (MW) >1,000 daltons were 

estimated using professional judgment and the results assessed for inclusion in the overall hazard 

designation. This process is described, as appropriate, under the corresponding endpoints 

appearing in Section 4.3. 

When QSAR models were not available, professional judgment was used to identify hazards for 

similar chemicals using the guidance from EPA’s New Chemicals Categories (U.S. EPA 2010). 

This document groups substances that have similar chemical structure and toxicological 

properties into categories based on EPA’s experience evaluating thousands of chemicals under 

the Toxic Substances Control Act (TSCA) New Chemicals Program. The categories identify 

substances that share chemical and toxicological properties and possess potential health or 

environmental concerns. In the absence of an identified category, analogs for which experimental 

data are available were identified using EPA’s Analog Identification Methodology (AIM) or by 

substructure searches of confidential EPA databases (U.S. EPA 2012a). If a hazard designation 

was still not available, the expert judgment of scientists from EPA’s New Chemical Program 

would provide an assessment of the physical/chemical properties, environmental fate, aquatic 

toxicity, and human health endpoints to fill remaining data gaps. 

Hierarchy of Data Adequacy 

Once the studies were obtained, they were evaluated to establish whether the hazard data were of 

sufficient quality to meet the needs of the assessment process. The adequacy and quality of the 

studies identified in the literature review are described in the Data Quality field of the chemical 

assessments presented in Section 4.2. The tiered approach described below represents a general 

preferred data hierarchy, but the evaluation of toxicological data also requires flexibility based 

on expert judgment. 

1. One or more studies conducted in a manner consistent with established testing guidelines 

2. Experimentally valid but nonguideline studies (i.e., do not follow established testing 

guidelines) 

3. Reported data do not have supporting experimental details 

4. Estimated data using SAR methods or professional judgment based on an analog 

approach

5. Expert judgment based on mechanistic and structural considerations 

In general, data were considered adequate to characterize an endpoint if they were obtained using 

the techniques identified in the HPV data adequacy guidelines (U.S. EPA 1999b). Studies 

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FINAL REPORT – January 2014 

performed according to Harmonized EPA or Organisation for Economic Cooperation and 

Development (OECD) guidelines were reviewed to confirm that the studies followed all required 

steps. 

Experimental studies published in the open literature were reviewed for their scientific rigor and 

were also compared and contrasted to guideline studies to identify potential problems arising 

from differences in the experimental design. Data from adequate, well-performed, experimental 

studies were used to assign hazard designations in preference to those lacking in sufficient 

experimental detail. When multiple adequate studies were available for a given endpoint, any 

discrepancies that were identified within the set of data were examined further and addressed 

using a weight-of-evidence approach that was described in the data entry to characterize the 

endpoint whenever possible. 

When available, experimental data from guideline or well-performed experimental studies were 

generally preferred (Items 1 and 2 in the hierarchy list). Information from secondary sources 

such as Material Safety Data Sheets (MSDS) or online databases (such as the National Library of 

Medicine’s Hazardous Substances Data Bank (HSDB)) (Item 3 in the hierarchy list) was 

considered appropriate for some endpoints when it included numerical values for effect levels 

that could be compared to the evaluation criteria. 

Assessment of Oligomeric Mixtures 

In this alternatives assessment, there are two chemicals that were mixtures of low molecular 

weight (MW) oligomers comprised of two or three repeating units. For these materials, all of the 

oligomers anticipated to be present in the mixture have MW of less than 1,000 daltons. The 

hazard assessment evaluated all oligomers present. From all the oligomers, the higher concern 

material was used to assign the hazard designation. This process is essentially identical to the 

evaluation of the hazards associated with impurities or byproducts present in discrete chemical 

products. As a result, the alternatives assessment process determined the amount of oligomers 

and unchanged monomers (starting materials) present and considered their potential hazards in 

the alternatives designation.

4.3 Importance of Physical and Chemical Properties, Environmental Transport, and 

Biodegradation 

Physical/chemical properties provide basic information on the characteristics of a chemical 

substance and were used throughout the alternatives assessment process to inform expert 

judgment and as inputs into predictive models. These endpoints provide information required to 

assess potential environmental release, exposure, and partitioning as well as insight into the 

potential for adverse toxicological effects. The physical/chemical properties are provided in the 

individual chemical hazard profiles presented in Section 4.2. For information on how key 

physical/chemical properties of alternatives can be used to address the potential for human and 

environmental exposure, please refer to Section 5.1.6. Descriptions of relevant physical/chemical 

properties and how they contribute to the hazard assessments are presented below. 

Molecular Weight (MW)

MW informs how a chemical behaves in a physical or biological system, including 

bioavailability and environmental fate. In general, but not strictly, larger compounds tend to be 

4-11 
FINAL REPORT – January 2014 

less mobile in biological and environmental systems. Their large size restricts their transport 

through biological membranes and lowers their vapor pressure. Oligomers evaluated in this 

alternatives assessment are mixtures that contain a distribution of components and they may not 

have a unique MW (see Section 0). To account for variation in these mixtures, the MW of a 

representative structure for each oligomer or mixture component was evaluated for this 

alternatives assessment. Selection of this representative structure is based on expert judgment on 

how the oligomer is produced. 

Melting Point and Boiling Point 

These two properties provide an indication of the physical state of the material at ambient 

temperature. Chemicals with a melting point more than 25°C were assessed as a solid. Those 

with a melting point less than 25°C and a boiling point more than 25°C were assessed as a liquid 

and those with a boiling point less than 25°C were assessed as a gas. The physical state was used 

throughout the assessment, such as in the determination of potential routes of human and 

environmental exposure, as described in Section 5.1. The melting and boiling points were also 

useful in determining the potential environmental fate, ecotoxicity, and human health hazards of 

a chemical. For example, organic compounds with high melting points generally have low water 

solubility and low rates of dissolution. These properties influence a material’s bioavailability and 

were therefore taken into account in both the assessment process and the evaluation of 

experimental studies. Similarly, chemicals with a low melting point also have a higher potential 

to be absorbed through the skin, gastrointestinal tract, and lungs. 

In the absence of experimental data, the melting point value was not reported and no estimations 

were performed. If a chemical decomposes before it melts, this information was included in the 

assessment. For boiling point, the maximum value reported in the assessment was 300°C for 

high boiling materials (U.S. EPA 1999b). Melting points for polymers and/or oligomers were not 

reported as these materials typically reach a softening point and do not undergo the phase change 

associated with melting (i.e., solid to liquid). 

Vapor Pressure

Vapor pressure is useful in determining the potential for a chemical substance to volatilize to the 

atmosphere from dry surfaces, from storage containers, or during mixing, transfer, or 

loading/unloading operations (see Section 5.2). In the assessment process, chemicals with a 

vapor pressure less than 1x10-6 mm Hg have a low potential for inhalation exposure resulting 

from gases or vapors. Vapor pressure is also useful for determining the potential environmental 

fate of a substance. Substances with a vapor pressure more than 1x10-4 mm Hg generally exist in 

the gas phase in the atmosphere. Substances with a vapor pressure between 1x10-4 and 1x10-8

mm Hg exist as a gas/particulate mixture. Substances with a vapor pressure less than 1x10-8 mm 

Hg exist as a particulate. The potential atmospheric degradation processes described below in the 

Reactivity section generally occur when a chemical exists in the gas phase. Gases in the 

atmosphere also have the potential to travel long distances from their original point of release. 

Materials in the liquid or solid (particulate) phases in the atmosphere generally undergo 

deposition onto the Earth’s surface. 

A maximum vapor pressure of 1x10-8 mm Hg was assigned for chemicals without experimental 

data or for those substances that were anticipated by professional judgment to be nonvolatile 

(U.S. EPA 1999b). 

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Water Solubility

The water solubility of a chemical provides an indication of its distribution between 

environmental media, potential for environmental exposure through release to aquatic 

compartments, and potential for human exposure through ingestion of drinking water. Water 

solubility was also used extensively to determine potential human health and ecotoxicity hazards. 

In general, chemicals with water solubility less than 1x10-5 g/L indicate a lower concern for both 

the expression of adverse effects, and potential aquatic and general population exposure due to 

their low bioavailability. However, chemicals with a low bioavailability also tend to be more 

environmentally persistent. Low bioavailability is different than no bioavailability, and the two 

should not be used interchangeably. 

Within the context of this alternatives assessment, the following descriptors were used according 

to ranges of water solubility values: >10,000 mg/L represents very soluble; 1,000–10,000 mg/L 

represents soluble; 100–1,000 mg/L represents moderately soluble, 1–100 mg/L represents 

slightly soluble, and <1 mg/L represents insoluble, noting that these guidelines were not 

followed consistently within the scientific literature (U.S. EPA 2011e). Chemicals with higher 

water solubility were more likely to be transported into groundwater with runoff during storm 

events, be absorbed through the gastrointestinal tract or lungs, partition to aquatic compartments, 

undergo atmospheric removal by rain washout, and possess a greater potential for human 

exposure through the ingestion of contaminated drinking water. Chemicals with lower water 

solubility are generally more persistent and have a greater potential to bioconcentrate. 

The water solubility of a substance was also used to evaluate the quality of experimental aquatic 

toxicity and oral exposure human health studies, as well as the reliability of aquatic toxicity 

estimates. If the water solubility of a substance was lower than the reported exposure level in 

these experiments, then the study was likely to be regarded as inadequate due to potentially 

confounding factors arising from the presence of undissolved material. For aquatic toxicity 

estimates obtained using SARs, when the estimated toxicity was higher than a chemical’s water 

solubility (i.e., the estimated concentration in water at which adverse effects appear cannot be 

reached because it was above the material’s water solubility), the chemical was described as 

having no effects at saturation (NES). An NES designation is equivalent to a low ecotoxicity 

hazard designation for that endpoint. 

While assessing the water solubility of a chemical substance, its potential to form a dispersion in 

an aqueous solution was also considered. Ideally, a chemical’s potential to disperse would be 

obtained from the scientific literature. In the absence of experimental data, dispersability can be 

determined from chemical structure and/or comparison to closely related analogs. There are two 

general structural characteristics that lead to the formation of dispersions in water: (1) chemicals 

that have both a hydrophilic (polar) head and a hydrophobic (nonpolar) tail (e.g., surfactants), 

and (2) molecules that have a large number of repeating polar functional groups (e.g., 

polyethylene oxide). 

The potential for a chemical to form a dispersion influences potential exposure, environmental 

fate, and toxicity. Dispersible chemicals have greater potential for human and environmental 

exposure, leachability, and aquatic toxicity than what might be anticipated based on the 

material’s water solubility alone.

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FINAL REPORT – January 2014 

Chemicals without experimental data or chemicals that were anticipated by professional 

judgment to be sufficiently insoluble and thus were not bioavailable were assigned a water 

solubility maximum value of 1x10-6 g/L (U.S. EPA 2011e). A water solubility of 1x10-3 mg/L is 

the default value used for discrete organics as well as nonionic polymers with a MW >1,000 

daltons. According to information contained in the literature concerning polymer assessment and 

the SF Polymer Assessment guidance assignment this is consistent with an analysis of the 

chemicals used in the development of the water solubility estimation program in EPA’s 

EPISuiteTM software (Boethling and Nabholz 1997; U.S. EPA 2010). The training set for this 

model included 1,450 chemicals with a MW range 27-628 daltons, and experimental water 

solubility values ranging from miscible to 4x10-7 mg/L (Meylan, Howard et al. 1996; U.S. EPA 

2011g). Given that water solubility decreases with MW, a default value of 1x10-3 mg/L is 

consistent with the limited bioavailability expected for materials with a MW >1,000 daltons. 

Although no BPA alternatives had a MW >1,000, there are two compounds that may contain 

small amounts of higher MW oligomeric materials or impurities that were evaluated using a 

water solubility suggestive of limited bioavailability.

Octanol/Water Partition Coefficient (Kow) 

The octanol/water partition coefficient, commonly expressed as its log value (i.e., log Kow) is one 

of the most useful properties for performing a hazard assessment. The log Kow indicates the 

partitioning of a chemical between octanol and water, where octanol is used to mimic fat and 

other hydrophobic components of biological systems. Chemicals with a log Kow less than 1 are 

highly soluble in water (hydrophilic), while those with a log Kow more than 4 are not very 

soluble in water (hydrophobic). A log Kow more than 8 indicates that the chemical is not readily 

bioavailable and is essentially insoluble in water. In addition, a log Kow value greater than 

approximately 8 may be difficult to obtain experimentally.

The log Kow can be used as a surrogate for the water solubility in a hazard assessment and is 

frequently used to estimate the water solubility if an experimental value is not available. The log 

Kow can also be used to estimate other properties important to the assessment, including 

bioconcentration and soil adsorption, and is a required input for SAR models used to estimate 

ecotoxicity values. 

For chemicals that are not within the domain of EPISuiteTM or that were expected to be insoluble 

in water (WS <1x10-6 g/L), a minimum value of 10 was assigned for the log Kow (U.S. EPA 

1999b). Insoluble chemicals that could be run through EPISuiteTM software were assigned a log 

Kow >10, if the result appeared to be valid based on expert review. This assignment is consistent 

with an analysis of the chemicals used in the development of the octanol/water partition 

coefficient estimation program in the EPISuiteTM software. The training set (chemicals used for 

calibration) for this model included 10,946 chemicals with a MW range of 18-720 daltons and 

experimental log Kow ranging from -3.89 to 8.70 (Meylan and Howard 1995; U.S. EPA 2011h). 

Given that log Kow increases with MW, a default value of 10 is consistent with the limited 

bioavailability expected for materials with a MW >1,000 daltons. Although no BPA alternatives 

had a MW >1,000, there are two compounds that may contain small amounts of higher MW 

oligomeric materials or other impurities that were evaluated using a log Kow suggestive of limited 

bioavailability. A maximum log Kow of -2 was used for water soluble materials. For most 

polymers and other materials that are anticipated to be insoluble in both water and octanol, the 

log Kow cannot be measured and was therefore not listed. 

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FINAL REPORT – January 2014 

Flammability (Flash Point)

The flash point of a substance is defined as the minimum temperature at which the substance 

emits sufficient vapor to form an ignitable mixture with air. Flash point can be used to identify 

hazards associated with the handling of volatile chemicals. Substances with a flash point above 

37.8°C (100°F) were commonly referred to as nonflammable, as this is the flammability 

definition used in the shipping industry. There are exceptions to this definition such as chemicals 

that may form explosive mixtures in the presence of air. 

Explosivity 

Explosivity refers to the potential for a chemical to form explosive mixtures in air and can be 

defined using the limits of flammability. The lower limit of flammability (LFL) is defined as the 

minimum concentration of a combustible substance that is capable of propagating a flame 

through a homogenous mixture in the presence of an ignition source. The upper limit of 

flammability (UFL) is similarly defined as the highest concentration that can propagate a flame. 

LFLs and UFLs are commonly reported as the volume percent or volume fraction of the 

flammable component in air at 25°C. If the ambient air concentration of the gas (or vapor) is 

between the upper and lower explosion limit, then the material has the potential to explode if it 

comes in contact with an ignition source. Knowledge regarding the explosivity of a given 

material in air is also useful in identifying potential hazards associated with the manufacture and 

use of that material.

pH

The pH scale measures how acidic or basic a substance is on a range from 0 to 14. A pH of 7 is 

neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. This scale is used primarily 

to identify potential hazards associated with skin or eye contact with a chemical or its aqueous 

solutions. The corrosive nature of chemicals that form either strongly basic (high pH) or strongly 

acidic (low pH) solutions are generally likely to result in harm to skin and other biological 

membranes. For corrosive chemicals, some experimental studies, such as biodegradation tests, 

require additional analysis to determine if the tests were performed at concentrations that cause 

harm to microbes in the test (and therefore may result in incorrectly identifying a chemical as 

persistent in the environment). For chemicals that form moderately basic or acidic solutions in 

water, the pH of the resulting solution can be used in lieu of a measured dissociation constant. 

Dissociation Constant in Water (pKa) 

The dissociation constant determines if a chemical will ionize under environmental conditions. 

The dissociation constant in water provides the amount of the dissociated and undissociated 

forms of an acid, base, or organic salt in water. Knowledge of the dissociation constant is 

required to assess the importance of the other physical/chemical properties used in the hazard 

assessment. As the percentage of ionization increases, the water solubility increases while the 

vapor pressure, Henry’s Law constant, and octanol/water partition coefficient decrease. For acids 

and bases, the dissociation constant is expressed as the pKA and pKB, respectively.

Henry’s Law Constant 

Henry’s Law constant is the ratio of a chemical’s concentration in the gas phase to that in the 

liquid phase (at equilibrium). In environmental assessments, the Henry’s Law constant is 

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FINAL REPORT – January 2014 

typically measured in water at 25°C. The Henry’s Law constant provides an indication of a 

chemical’s volatility from water, which can be used to derive information about the chemical’s 

tendency to partition within environmental compartments and the amount of material removed 

by stripping in a sewage treatment plant. Henry’s Law constant values less than 1x10-7 atmm3

/mole indicate slow volatilization from water to air (the Henry’s Law constant for the 

volatilization of water from water is 1x10-7 atm-m3/mole) and values more than 1x10-3 atmm3

/mole indicate rapid volatilization from water to air. To aid in determining the importance of 

volatilization, the assessment uses two models based on the Henry’s Law constant. These models 

determine the half-life for volatilization from a model river and a model lake. A maximum value 

of 1x10-8 atm-m3/mole for the Henry’s Law constant was assigned for chemicals without 

experimental data or for those that were anticipated by professional judgment to be nonvolatile. 

Sediment/Soil Adsorption/Desorption Coefficient (Koc)

The soil adsorption coefficient provides a measure of a chemical’s ability to adsorb to the 

organic portion of soil and sediment. This provides an indication of the potential for the chemical 

to leach through soil and be introduced into groundwater, which may lead to environmental 

exposures to wildlife or humans through the ingestion of drinking water drawn from 

underground sources. Chemicals with high soil adsorption coefficients are expected to be 

strongly adsorbed to soil and are less likely to leach into groundwater. The soil adsorption 

coefficient also describes the potential for a chemical to partition from environmental waters to 

suspended solids and sediment. The higher the Koc, the more strongly a chemical is adsorbed to 

soil. Strong adsorption may impact other fate processes, such as the rate of biodegradation, by 

making the chemical less bioavailable. 

The soil adsorption coefficient, Koc, is normalized with respect to the organic carbon content of 

the soil to account for geographic differences. The assignments for the degree that a chemical is 

adsorbed to soil within the context of the assessment were described qualitatively as very strong 

(above 30,000), strong (above 3,000), moderate (above 300), low (above 30), and negligible 

(above 3). When determining the potential for a chemical to adsorb to soil and suspended organic 

matter, the potential for a chemical to form chemical bonds with humic acids and attach to soil 

also needs to be considered, although this process is generally limited to a small number of 

chemical classes. A maximum value of 30,000 for the Koc was assigned for chemicals without 

experimental data or for those that were anticipated by professional judgment to be strongly 

absorbed to soil (U.S. EPA 2004). 

Reactivity

The potential for a substance to undergo irreversible chemical reactions in the environment can 

be used in the assessment of persistence. The primary chemical reactions considered in an 

environmental fate assessment are hydrolysis, photolysis, and the gas phase reaction with 

hydroxyl radicals, ozone, or nitrate radicals. The most important reaction considered in the 

hazard assessment of organic compounds is hydrolysis, or the reaction of a chemical substance 

with water. Because the rate of hydrolysis reactions can change substantially as a function of pH, 

studies performed in the pH range typically found in the environment (pH 5-9) were considered. 

The second reaction considered in the assessment is photolysis, the reaction of a chemical with 

sunlight. Both hydrolysis and photolysis occur in air, water, and soil, while only hydrolysis was 

considered in sediment. The half-lives for reactive processes, if faster than removal via 

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FINAL REPORT – January 2014 

biodegradation, were used to assign the hazard designation by direct comparison to the DfE 

persistence criteria.

For the atmospheric compartment, persistence also includes the evaluation of oxidative gasphase processes. These processes include the reaction with ozone, hydroxyl radicals, and nitrate 

radicals. Since the average concentration of these oxidative species in the atmosphere has been 

measured, the experimental or estimated rate constants were converted to, and reported as, a 

half-life in the assessment using standard pseudo first-order kinetics (U.S. EPA 2011f; U.S. EPA 

2011d). 

For inorganic compounds, an additional chemical process was considered, the potential to be 

reduced or oxidized (undergo a redox reaction) under environmental conditions. Redox reactions 

change the oxidation state of the species through the transfer of electrons to form another 

compound (such as the reduction of Cr(VI) to Cr(III)). A change in the oxidation state of a metal 

or inorganic species can result in significant changes in the material’s hazard designation. In this 

example, going from Cr(VI) to Cr(III) makes the compound less toxic. 

Environmental Transport 

The persistence of a chemical substance is based on determining the importance of removal 

processes that may occur once a chemical enters the environment. As noted in Section 4.1.2, 

chemicals with a half-life of less than 60 days are expected to be at most a Moderate hazard 

designation for persistence. Persistence does not directly address the pathways in which a 

chemical substance might enter the environment (e.g., volatilization or disposal in a landfill) and 

focuses instead on the removal processes that are expected to occur once it is released into air, 

water, soil, or sediment. Similarly, the persistence assessment does not address what might 

happen to a chemical substance throughout its life-cycle, such as disposal during incineration of 

consumer or commercial products. Understanding the environmental transport of a chemical 

substance can help identify processes relevant to environmental assessment. For example, if a 

chemical is toxic to benthic organisms and partitions primarily to sediment, its potential release 

to water should be carefully considered in the selection of alternatives. 

Biodegradation 

In the absence of rapid hydrolysis or other chemical reactions, biodegradation is typically the 

primary environmental degradation process for organic compounds. Determining biodegradation 

processes is, therefore, an important component of the assessment. Biodegradation processes are 

divided into two types. The first is primary biodegradation, in which a chemical substance is 

converted to another substance. The second is ultimate biodegradation, in which a chemical is 

completely mineralized to small building-block components (e.g., CO2 and water). DfE 

persistence criteria use data that are reported as a percent of theoretical ultimate degradation in 

the guideline Ready Biodegradability test or as a half-life in other experimental studies; both of 

these measurements can be compared directly to the DfE criteria in Section 4.1.2. When 

considering primary degradation, the assessment process includes an evaluation of the potential 

for the formation of metabolites that were more persistent than the parent materials. Chemical 

substances that undergo rapid primary degradation but only slow ultimate biodegradation were 

considered to have stable metabolites. In the absence of measured data on the substance of 

interest, DfE evaluated the potential for biodegradation for chemicals with a MW <1,000 daltons 

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using the EPA EPISuiteTM models. EPISuiteTM estimates the probability for ready biodegradation 

as well as the potential for primary and ultimate removal, as described in Section 4.5. 

4.4 Evaluating Human Health Endpoints

After data collection and analysis of the physical/chemical properties for the chemicals being 

assessed, the comparison of the data against the hazard criteria can begin. Section 4.4.1 discusses 

how measured data are used to make hazard designations for human health endpoints, and 

Section 4.4.2 presents the approach for filling in data gaps to make these hazard designations. 

4.4.1 Endpoints Characterized and Evaluated Against Criteria Based on Measured Data 

This section provides a short description of how measured data were used to designate the level 

of hazard for each endpoint. As a reminder, the criteria for the hazard designations are in Section 

4.1.2. 

For acute mammalian toxicity, the LD50s or LC50s were used to assign the hazard designation. 

Four levels of hazard designation have been defined ranging from Low to Very High. 

For cancer, the hazard designation was contingent on the level of evidence for increased 

incidence of cancer rather than potency. The definitions applied in DfE criteria are based on 

International Agency for Research Cancer (IARC) levels of evidence (International Agency for 

Research on Cancer 2006). For example, a designation of Very High concern requires that the 

substance be characterized as a “known or presumed human carcinogen,” whereas a designation 

of Low concern requires either negative studies or robust SAR conclusions. A designation of 

Moderate was applied as a default value when there was an absence of data suggesting High 

carcinogenicity, and an absence of data supporting Low carcinogenicity (i.e., a lack of negative 

studies or weak SAR conclusion). Information suggestive of pre-cancerous lesions also merits 

the designation of Moderate concern. 

Similarly, the hazard designation for mutagenicity/genotoxicity was also based on the level of 

evidence rather than potency. Complete data requirements for this endpoint include both gene 

mutation and chromosomal aberration assays. For instances of incomplete or inadequate 

mutagenicity/genotoxicity data, a Low hazard designation cannot be given. 

For chronic endpoints, such as reproductive, developmental, neurological and repeated dose 

toxicity, the hazard designation was based on potency. The evaluation considers both lowest 

observed adverse effect levels (LOAELs) and identification of no observed adverse effect levels 

(NOAELs), when available. The LOAEL and the NOAEL are experimental dose levels, and their 

reliability is dictated by the study design. In studies for which the lowest dose tested resulted in 

an adverse effect (and therefore a NOAEL was not established), and in studies for which the 

highest dose tested was a NOAEL, a conservative approach using professional judgment was 

used to address uncertainty regarding the lowest dose or exposure level that might be expected to 

cause a particular adverse effect. For example, in the absence of an established a NOAEL, an

identified LOAEL might fall within the range of a Moderate hazard; however, it is uncertain if a

lower dose, such as one that falls within the range of High hazard exists because no lower doses 

were tested. In such cases, professional judgment was applied to assign a hazard designation 

when possible. Some degree of uncertainty was evident in results from studies in which a 

NOAEL may fall within one hazard range (e.g., Moderate hazard) and the identified LOAEL 

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falls within a different hazard range (e.g., Low hazard) because the true LOAEL may fall in 

either category, but there were not enough experimental data points to determine the true 

LOAEL. Professional judgment was also applied to these cases to assign a hazard descriptor 

when possible, and the rationale used was described in the assessment.

Developmental neurotoxicity, for which data were only available for BPA, was considered and 

was evaluated using the developmental toxicity criteria, which are more stringent than the 

criteria for neurotoxicity, and thus more protective (U.S. EPA 2011b). 

The criteria for skin and respiratory sensitization, which are immune-based responses, consider 

the frequency and potency of the reactions. For skin sensitization, categories were based on the 

weight of evidence3 from traditional animal bioassays, but in vitro alternative studies were also 

considered. At this time, there are no standard test methods for respiratory sensitization; as a 

result there was often no designation for this endpoint. 

The evaluation of skin and eye irritation and corrosivity were based on the time to recovery. 

4.4.2 SAR – Application of SAR and Expert Judgment to Endpoint Criteria

If measured data pertaining to human health criteria were not available, potential adverse effects 

were estimated with SAR analysis. To make these estimates, DfE relied on the expertise of 

scientists in EPA’s New Chemicals Program who have reviewed thousands of chemicals and 

associated data using these methods. SAR uses the molecular structure of a chemical to infer a 

physicochemical property that can be related to specific effects on human health. These 

correlations may be qualitative (“simple SAR”) or quantitative (QSAR). Information on EPA’s 

use of SAR analysis has been published by EPA (1994). Public access to free validated QSAR 

models for human health endpoints is far more limited than physical/chemical properties, 

environmental fate parameters, or ecotoxicology. 

Carcinogenicity was assessed using the OncoLogic expert system that provides a qualitative 

result directly applicable to the DfE criteria. For other endpoints that required SAR approaches, 

an analog approach using expert judgment was used, as discussed in Section 4.2. All estimates 

obtained in this project were reviewed by EPA scientists having appropriate expertise. Estimates 

for the other human health endpoints were based on expert judgment using an analog approach 

and not through the use of computerized SAR methodologies. 

Carcinogenicity

The potential for a chemical to cause cancer in humans was estimated using OncoLogic expert 

system. This program uses a decision tree based on the known carcinogenicity of chemicals with 

similar chemical structures, information on mechanisms of action, short-term predictive tests, 

epidemiological studies, and expert judgment. 

Oligomeric Mixtures

Oligomers with MW <1,000 were assessed using a representative structure for all the MW 

species anticipated to be present in the mixture. The procedures were essentially identical to 

3 Generally, weight of evidence is defined as the process for characterizing the extent to which the available data 

support a hypothesis that an agent causes a particular effect (U.S. EPA, 1999a). 

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those employed for the evaluation of impurities or byproducts in discrete chemicals, although in 

this case, the oligomer with the highest concern was used to drive the hazard designation. 

Unreacted monomers, if present, were also assessed and considered in the hazard evaluation. In 

this alternatives assessment, two chemicals are mixtures of low MW oligomers comprised of two

or three repeating units. 

4.5 Evaluating Environmental Endpoints 

As with endpoints previously mentioned, the preferred method for the evaluation of 

environmental endpoints is the use of experimental data. In their absence, the alternatives

assessment uses computerized QSAR models developed by EPA for the evaluation of 

environmental endpoints that can be directly compared to the DfE criteria. When measured data 

were not available, the aquatic toxicity was estimated using EPA’s ECOSARTM software, and the 

persistence designation was estimated using models in EPA’s EPISuiteTM software. The hazard 

designation was determined by applying the criteria to these estimates. 

As a direct result of the design of these models and their direct application to DfE criteria, the 

evaluation of environmental endpoints using experimental or estimated data was discussed 

together in the following subsections. 

4.5.1 Ecotoxicity

For ecological toxicity, the alternatives assessment focused on the hazard designations for acute 

and chronic studies on freshwater species of algae, invertebrates, and fish (often referred to as 

the “three surrogate species”). Aquatic toxicity values were reported in the assessment as 

follows: 

•

•

•

Acute (estimated or experimental) - LC50 in mg/L or EC50 in mg/L

Chronic (experimental) - No observed effect concentration (NOEC) in mg/L 

Chronic (estimated) - ChV, or the geometric mean between the NOEC and the LOEC, in 

mg/L

Experimental data and estimates reported in the alternatives assessment includes information on 

the species tested and typically focus on freshwater aquatic organisms. Test data on other 

organisms (e.g., worms) were included in the assessment if data or models were readily 

available. These data would be evaluated using professional judgment in support of the hazard 

designations assigned using the three surrogate freshwater species; however, they were not used 

exclusively to assign a hazard designation as DfE criteria are not available. For the estimated 

results from ECOSAR, the equations are derived from surrogate species of fish, zooplankton, 

and phytoplankton. While these surrogate species can comprise several genera as well as 

families, the equations are not intended to be species specific, but rather estimate toxicity to the 

general trophic levels they represent (Mayo-Bean, Nabholz et al. 2011). 

If an experimental or estimated effect level exceeded the known water solubility of a chemical 

substance, or if the log Kow exceeded the ECOSARTM cut-off values for acute and chronic 

endpoints (which are class specific), No Effects at Saturation (NES) were determined for the 

aquatic toxicity endpoints. NES indicates that at the highest concentration achievable, which is 

the limit of a chemical’s water solubility, no adverse effects were observed (or would be 

expected). In these cases, a Low hazard designation was assigned. In the cases where both an 

estimated water solubility and ECOSARTM estimate were used, then an additional factor of ten 

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was applied to the water solubility before a NES designation was assigned to account for the 

combined uncertainty in the model estimates. 

In the case where an experimental aquatic toxicity value was significantly higher than the 

chemical’s water solubility, it was likely the result of a poorly conducted study. In this 

circumstance, which is generally more frequent for formulated products or mixtures, additional 

details were provided in the data quality section to describe why the reported values could not be 

used to assign a hazard designation. No effects at saturation are also expected in most cases for 

insoluble organics, oligomers, or non-ionic polymers with a MW >1,000 daltons resulting in an 

overall low hazard concern for aquatic toxicity (Nabholz, Clements et al. 1993). 

EPA’s ECOSARTM estimation program uses chemical structure to estimate toxicity of a 

substance using class-specific QSARs. ECOSARTM automatically determines all classes that a 

chemical may be related to based on the molecular features of the substance and, therefore, may 

provide multiple class-specific estimates for some or all of the species and durations estimated 

(Mayo-Bean, Nabholz et al. 2011). Modeled results are dependent on the functional groups 

present on the molecule as well as the diversity of chemicals with experimental data used to 

build the models (the training set). The hazard profiles report estimates for every class identified 

by ECOSARTM. However, the hazard designation was based on the most conservative 

ECOSARTM estimate (highest hazard value). If professional judgement indicate that certain 

class-specific estimates were not appropriate for a particular substance, the narcosis (baseline 

toxicity) associated with the neutral organic class will be used. Experimental log Kow values were 

used preferentially as input into ECOSARTM. In their absence, estimated log Kow values from 

EPISuiteTM were used. ECOSARTM is maintained and developed as a stand-alone program 

(http://www.epa.gov/oppt/newchems/tools/21ecosar.htm), but is also accessible through the EPA 

EPISuiteTM program after it is installed; therefore the Estimations Program Interface (EPI) 

program was may also be used as a citation for the ECOSARTM values in this report. 

There were instances where sufficient experimental data were not available to build a chronic 

QSAR for some of the three surrogate species. When ECOSARTM did not provide chronic 

estimates, the acute value (experimental or estimated) was divided by an acute to chronic ratio 

(ACR) to arrive at the ChV. ACRs of 10 were used for fish and daphnid, and an ACR of 4 was 

used for algae (Rand, Wells et al. 1995). 

Although no BPA alternatives had a MW >1,000, there are two oligomeric materials that may 

contain small amounts of higher MW components. The aquatic toxicity hazard potential for these 

materials was would be assigned a Low designation, as discussed above, and as a direct result, 

their presence did not influence the hazard designation for this endpoint.

4.5.2 Bioaccumulation 

Bioaccumulation is a process in which a chemical substance is absorbed in an organism by all 

routes of exposure as occurs in the natural environment (e.g., from dietary and ambient 

environment sources). Bioaccumulation is the net result of the competing processes; this includes 

uptake, metabolism and elimination of a chemical in an organism. Bioaccumulation can be 

evaluated using the bioaccumulation factor (BAF), the steady state ratio of a chemical in an 

organism relative to its concentration in the ambient environment, where the organism is exposed 

through ingestion and direct contact. Experimental BAFs have not been widely available in the 

scientific literature and, as a result, experimental bioconcentration factors (BCFs) are more 

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commonly used to evaluate the bioaccumulation hazard. BCFs are defined as the ratio of the 

concentration of a dissolved chemical in an aquatic organism to the concentration of the 

chemical in the exposure medium (surrounding water); BCFs are typically measured for fish (in 

water) using guideline studies. 

Experimental BAF or BCF values can be compared directly to the DfE criteria for this endpoint

to assign a hazard designation. The BCF and BAF designations range from <100 for a Low 

designation to >5,000 for a Very High designation (see Table 4 2). If experimental values were 

available for both of these endpoints, and the BCF and BAF were >100 (i.e., above the Low 

designation), the largest factor was used to assign hazard designation. If experimental BCFs 

<100 were available, the estimated upper trophic BAF from EPISuiteTM was used preferentially, 

if its use resulted in a more conservative hazard designation and the potential for metabolism was 

accurately accounted for within the model estimates.

In the absence of experimental data, evaluation of bioaccumulation potential can be done using 

the log Kow and the log octanol/air partition coefficient Koa as estimated by EPISuiteTM. 

However, analysis using Koa requires the use of metabolism data for higher trophic, air breathing 

organisms, which can be difficult to obtain from the scientific literature and cannot be readily 

estimated. BAFs and BCFs from EPISuiteTM were, therefore, typically used for the 

bioaccumulation hazard designation when experimental data were lacking. These values can be 

compared directly to DfE criteria, and the most conservative result was used for the hazard 

designation. For chemicals that had estimated bioaccumulation data, available experimental 

monitoring data were used to provide insight into the reliability of the model results. For 

example, an estimated Low bioaccumulation potential may be increased to a Moderate 

designation if a chemical was routinely identified in samples from higher trophic levels, or a 

High designation if the chemical was routinely measured in animals at the top of the food chain. 

An estimate of Low is the default value used for organics with a MW >1,000 daltons in the 

assignment of bioaccumulation hazard. This assignment is consistent with an analysis of the 

chemicals used in the development of the bioconcentration and bioaccumulation estimation 

programs in the EPISuiteTM software (U.S. EPA 2011g). The training sets for these models 

included 527 and 421 chemicals, respectively, with a MW range 68-992 daltons (959 daltons for 

BAF). Given that BCF and BAF reach a maximum and then decrease with increasing log Kow, a 

default value of Low is, in general, consistent with the limited bioavailability expected for 

materials with a MW >1,000 daltons. DfE used all available well‐conducted studies when 

evaluating bioaccumulation potential for materials with a MW >1,000, including environmental 

biomonitoring data on higher trophic levels. Although no BPA alternatives had a MW <1,000, 

there are two compounds that may contain small amounts of higher MW oligomeric impurities; 

the bioaccumulation hazard potential for these materials was assigned a Low designation as 

discussed above and, as a result, their presence did not influence the hazard designation for this 

endpoint. 

4.5.3 Environmental Persistence

A chemical’s persistence in the environment is evaluated by determining the type and rate of 

potential removal processes. These removal processes were generally divided into two 

categories: chemical and biological. Of the chemical degradation processes, an evaluation of 

environmental persistence includes the reaction of a chemical with water, also known as 

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hydrolysis, because water is ubiquitous in the environment. Hydrolysis rate constants can be 

obtained from the literature or can be estimated, and the resulting half-lives can be compared 

directly to DfE criteria. For chemicals without hydrolyzable groups, biodegradation tends to be 

the faster degradation process in water, soil, and sediments; however, numerous commercial 

chemicals possess labile groups, and these may hydrolyze in the environment at significant or 

even rapid rates. Direct and indirect photolysis also represents other potential chemical 

degradation processes that are considered in the alternatives assessment, and they are discussed 

later in this section. Oxidation by hydroxyl radicals and ozone is the dominant degradation 

process for organic chemicals in air.

Biodegradation, the most prevalent biological removal process, was divided into two types. The 

first is primary biodegradation, in which a chemical substance is converted to another substance 

through a single transformation. The second is ultimate biodegradation, in which a chemical is 

completely degraded to CO2, water, mineral oxides of certain other elements in the molecule, 

and low-MW compounds that can directly enter microbial metabolism. DfE criteria utilize 

ultimate biodegradation preferentially for the persistence hazard designation, although primary 

removal rates were informative in assigning hazard designations, particularly for materials that 

were transformed slowly, and to a lesser extent for those that are transformed rapidly. 

If ultimate biodegradation data were not available, primary removal data were used in some 

cases. For primary removal processes, the potential for the formation of degradation products 

that are more persistent than the parent compounds must be considered in the hazard designation. 

When present, the persistent degradation products should be evaluated for fate and toxicity. Halflife data on the persistent degradation products, if available, were used to determine the 

assignment for the persistence designation. In the absence of persistent degradation products, 

primary biodegradation half-life data were compared directly to the DfE criteria to assign a 

hazard designation. 

Biodegradation processes can be classified as either aerobic or anaerobic. Aerobic 

biodegradation is an oxidative process that occurs in the presence of oxygen. Anaerobic 

biodegradation is a reductive process that occurs only in the absence of oxygen. Aerobic 

biodegradation is typically assessed for soil and water, while anaerobic biodegradation is most 

relevant for sediments, landfills and sludge digesters in sewage treatment plants; although anoxic 

conditions can also occur in soil and the water column. For determining the persistence hazard 

designation, the importance of both aerobic and anaerobic biodegradation, as well as partitioning 

and transport in the environment, were considered to determine what removal processes were 

most likely to occur. Anaerobic degradation may use any of several electron acceptors, 

depending on their availability in a given environment and the prevailing redox potential (Eh). 

The biodegradative populations that are dominant in a given environment vary with the 

conditions, and so do their biodegradative capabilities. 

One aspect of the assessment is to determine the potential for removal of a chemical substance, 

and especially removal attributable to biodegradation, within a sewage treatment plant and other 

environments. In this assessment, the term “ready biodegradability” refers to a chemical’s 

potential to undergo ultimate degradation in guideline laboratory studies. A positive result in a 

test for ready biodegradability can be considered indicative of rapid and ultimate degradation in 

most environments, including biological sewage treatment plants. Ready tests typically include a 

10-day window, beginning when the biodegradation parameter (e.g., disappearance of dissolved 

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organic carbon from test substance, or theoretical oxygen demand) reaches 10%. If the pass level 

of the test (60% for oxygen demand and CO2 production; 70% for dissolved organic carbon 

disappearance) was met in the 10-day window, the chemical received a Very Low hazard 

designation. Those that did not pass the 10-day window criterion but met the pass level in 28 

days received a Low hazard designation. If ready biodegradability test data were available but 

the chemical did not meet the pass level, the chemical was evaluated based on measured data 

using the DfE half-life criteria (Table 4 1). These half-life criteria were also used to assign a 

hazard designation for nonguideline ultimate biodegradation studies reported in the scientific 

literature. 

In the absence of a reported half-life, experimental data were also used to approximate half-life, 

as appropriate. For example, a chemical that undergoes <5% removal in 30 days would be 

expected to have a half-life >60 days and would be assigned a High persistence hazard 

designation. 

When experimental data on the biodegradation of a chemical substance were not available, the 

potential of that substance to undergo this removal process was assessed from the results of the 

EPISuiteTM models. These models fall into one of four classes: rapid biodegradation models 

based on linear and non-linear regressions that estimate the probability that a chemical substance 

will degrade fast; expert survey models that estimate the rate of ultimate and primary 

biodegradation using semi-quantitative methods; probability of ready biodegradability in the 

OECD 301C test; and probability of rapid biodegradation under methanogenic anaerobic 

conditions (specifically under conditions of the OECD 311 test). Each of these is discussed in the 

following paragraphs. 

The first models (Biowin 5 and 6) used in the screening assessment estimated ready 

biodegradability in the OECD 301C test and are also known as the Japanese Ministry of 

International Trade and Industry (MITI) models. These models provided the probability that a 

material passes this standardized test. Those chemicals that were estimated to pass the ready 

biodegradability test received a Low persistence designation. If a chemical was not estimated to 

pass the MITI test, the results of the other EPISuiteTM biodegradation models were used. 

The rapid biodegradation potential models within EPISuiteTM (Biowin 1 and 2) were useful for 

determining if a chemical substance was expected to biodegrade quickly in the environment. If a 

chemical was likely to biodegrade quickly, it was generally assigned a Low hazard designation 

for persistence. The results of the estimates from these models may be used in concert with the 

semi-quantitative output from a second set of models, which include ultimate and primary 

biodegradation survey models (Biowin 3 and 4) for evaluating persistence. These models 

provided a numeric result, ranging from 1 to 5, that relates to the amount of time required for 

complete ultimate degradation (Biowin 3) and removal of the parent substance by primary 

degradation (Biowin 4) of the test compound. The numeric result from Biowin 3 was converted 

to an estimated half-life for removal that can be compared directly to DfE criteria. If results from 

different models (other than the MITI models) led to a different hazard designation, then the 

ultimate biodegradation model results were used preferentially. If the transport properties 

indicated the potential for the material to partition to sediment, an anoxic compartment, then the 

results of the anaerobic probability model (Biowin 7) were also evaluated. 

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Half-lives for hydrolysis from experimental studies or EPISuiteTM estimates were used in 

preference to biodegradation data when they suggested that hydrolysis is a more rapid removal 

process. Hydrolysis half-lives were compared directly to DfE criteria to assign the persistence 

designation. Similar to primary biodegradation, breakdown products resulting from hydrolysis 

were evaluated for fate and toxicity when they were expected to be more persistent than the 

parent compound. 

Photolysis may also be an important environmental removal process. In general, environmental 

removal rates from photolysis do not compete with biodegradation or hydrolysis, although there 

are exceptions such as iodides. Photolysis may be the predominant removal process for 

chemicals that were not bioavailable because of their limited water solubility. Estimation 

methods for photolysis rates were not available using computerized SAR tools. If experimental 

or suitable analog data were available, the rate of photolysis was evaluated relative to other 

removal processes.

When evaluating the environmental persistence designation, it should be noted that chemicals 

with a High or Very High designation can degrade over time, although this process may occur at 

a very slow rate. As a result, a Very High designation may have been assigned if persistent 

degradates were expected to be produced, even at a very slow rate, in the absence of 

experimental biodegradation data for the parent substance. 

4.6 Endocrine Activity

Chemicals included in this DfE Alternatives Assessment were screened for potential endocrine 

activity, consistent with the DfE Alternatives Assessment Criteria (U.S. EPA 2011b). Endocrine 

activity refers to a change in endocrine homeostasis caused by a chemical or other stressor. An 

endocrine disruptor is an external agent that interferes in some way with the role of natural 

hormones in the body, in a manner causing adverse effects. Relevant data are summarized in the 

hazard assessments for each chemical, located in Section 4.2. Data on endocrine activity were 

available for BPA and 10 of the 19 alternatives included in this report. For chemicals without 

available data on endocrine activity, this was acknowledged with a “no data available” statement. 

When endocrine activity data were available, the data were summarized as a narrative. A unique 

hazard designation of Low, Moderate or High is not provided for this endpoint in Table 4 3, for 

reasons discussed below. 

The document Special Report on Environmental Endocrine Disruption: An Effects Assessment 

and Analysis describes EPA’s activities regarding the evaluation of endocrine disruption (U.S. 

EPA 1997). This report was requested by the Science Policy Council and prepared by EPA’s 

Risk Assessment Forum. This report states that “Based on the current state of the science, the 

Agency does not consider endocrine disruption to be an adverse endpoint per se, but rather to be 

a mode or mechanism of action potentially leading to other outcomes, for example, carcinogenic, 

reproductive or developmental effects, routinely considered in reaching regulatory decisions” 

(U.S. EPA 1997). The report also states that “Evidence of endocrine disruption alone can 

influence priority setting for further testing, and the assessment of results of this testing could 

lead to regulatory action if adverse effects are shown to occur” (U.S. EPA 1997). 

The 1996 Food Quality Protection Act (FQPA) directed EPA to develop a scientificallyvalidated screening program to determine whether certain substances may cause hormonal 

effects in humans. In response, EPA established the Endocrine Disruptor Screening Program 

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(EDSP) (U.S. EPA 2012b). The EDSP is developing requirements for the screening and testing 

of thousands of chemicals for their potential to affect the endocrine system. When complete, 

EPA will use these screening and testing approaches to set priorities and conduct further testing, 

when warranted. The science related to measuring and demonstrating endocrine disruption is 

relatively new, and validated testing methods at EPA are still being developed. 

The EDSP proposes a two-tiered approach that includes initial screening, followed by more indepth testing when warranted (U.S. EPA 2011a). The Tier 1 screening battery is intended to 

identify chemicals with the potential to interact with the estrogen, androgen, or thyroid hormone 

systems through any of several recognized modes of action. Positive findings for Tier 1 tests 

identify the potential for an interaction with endocrine systems, but do not fully characterize the 

nature of possible effects in whole animals. Tier 2 testing is intended to confirm, characterize, 

and quantify the effects for chemicals that interact with estrogen, androgen, and thyroid hormone 

systems. These test methods must undergo a four-stage validation process (protocol 

development, optimization/prevalidation, validation, and peer-review) prior to regulatory 

acceptance and implementation. Validation is ongoing for Tier 1 and Tier 2 methods.4 Once 

validated test methods have been established for screening and testing of potential endocrine 

disruptors, guidance must be developed for interpretation of these test results using an overall 

weight-of-evidence characterization. 

To assess the data on endocrine activity, DfE applies the weight-of-evidence approach developed 

by the EDSP (U.S. EPA 2011c). Generally, weight of evidence is defined as the process for 

characterizing the extent to which the available data support a hypothesis that an agent causes a 

particular effect (U.S. EPA 1999a; U.S. EPA 2002; U.S. EPA 2005a). This process integrates 

and evaluates data, and always relies on professional judgment (U.S. EPA 2011c). To evaluate 

endocrine activity with this weight-of-evidence approach, DfE examined multiple lines of 

evidence (when available) and considered the nature of the effects within and across studies, 

including number, type, and severity/magnitude of effects, conditions under which effects 

occurred (e.g., dose, route, duration), consistency, pattern, range, and interrelationships of effects 

observed within and among studies, species, strains, and sexes, strengths and limitations of the in 

vitro and in vivo information, and biological plausibility of the potential for an interaction with 

the estrogen, androgen, or thyroid hormonal pathways. 

Most test data for chemicals in this report consist of in vitro assays, but results of in vitro assays 

alone were not generally expected to provide a sufficient basis to support a hazard designation 

for endocrine disruption. EPA expects that in vivo evidence would typically be given greater 

overall influence in the weight-of-evidence evaluation than in vitro findings because of the 

inherent limitations of such assays. Although in vitro assays can provide insight into the mode of 

action, they have limited ability to account for normal metabolic activation and clearance of the 

compound, as well as normal intact physiological conditions (e.g., the ability of an animal to 

compensate for endocrine alterations). 

As described in the DfE Alternatives Assessment Criteria, endocrine activity was summarized in 

a narrative, rather than by High, Moderate or Low hazard designation. The endocrine activity 

summaries can be found in the hazard profiles. This is an appropriate approach because there is 

4 Information on the status of assay development and validation efforts for each assay in EPA’s EDSP can be found 

at: http://www.epa.gov/oscpmont/oscpendo/pubs/assayvalidation/status.htm. 

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no consensus on what constitutes high, moderate or low concern for this endpoint. The summary 

of endocrine activity largely relies on representative studies and expert review summaries.

Chemical Alternatives and the Toxic Substances Control Act

EPA’s Design for the Environment (DfE) program is administered by the Office of Pollution Prevention and Toxics 

(OPPT), which is charged with the implementation of the Toxic Substances Control Act (TSCA) and the Pollution 

Prevention Act (PPA).

Central to the administration of TSCA is the management of the TSCA Inventory. Section 8 (b) of TSCA requires 

EPA to compile, keep current, and publish a list of each chemical substance that is manufactured or processed in the 

United States. Companies are required to verify the TSCA status of any substance they wish to manufacture or 

import for a TSCA-related purpose. For more information, please refer to the TSCA Chemical Substance Inventory 

website: http://www.epa.gov/opptintr/existingchemicals/pubs/tscainventory/basic.html. 

TSCA and DfE Alternatives Assessments

Substances selected for evaluation in a DfE Alternatives Assessment generally fall under the TSCA regulations and 

therefore must be listed on the TSCA inventory, or be exempt or excluded from reporting before being 

manufactured in or imported to, or otherwise introduced in commerce in, the United States. For more information 

see http://www.epa.gov/oppt/newchems/pubs/whofiles.htm. 

To be as inclusive as possible, DfE Alternatives Assessments may consider substances that may not have been 

reviewed under TSCA, and therefore may not be listed on the TSCA inventory. DfE has worked with 

stakeholders to identify and include chemicals that are of interest and likely to be functional alternatives, regardless 

of their TSCA status. Chemical identities are gathered from the scientific literature and from stakeholders and, for 

non-confidential substances, appropriate TSCA identities are provided.

Persons are advised that substances, including DfE-identified functional alternatives, may not be introduced into US 

commerce unless they are in compliance with TSCA. Introducing such substances without adhering to the TSCA 

provisions may be a violation of applicable law. Those who are considering using a substance discussed in this 

report should check with the manufacturer or importer about the substance’s TSCA status. If you have questions 

about reportability of substances under TSCA, please contact the OPPT Industrial Chemistry Branch at 202-564-

8740.

4-27 
FINAL REPORT – January 2014 

4.7 Hazard Summary Table 

Table 4-4: Screening Level Hazard Summary

This table only contains information regarding the inherent hazards of the chemicals evaluated. Evaluation of risk considers both the hazard and exposure. 

The caveats listed in the legend and footnote sections must be taken into account when interpreting the hazard information in the table below.

VL = Very Low hazard L = Low hazard M = Moderate hazard H = High hazard VH = Very High hazard  Endpoints in colored text (VL, L, M, H, and VH) 

were assigned based on empirical data. Endpoints in black italics (VL, L, M, H, and VH) were assigned using values from estimation software and professional judgment.

§ Based on analogy to experimental data for a structurally similar compound.

Structure

Chemical

(for TSCA inventory name and 

relevant trade names see the 

individual profiles in Section 4.8) CASRN

Human Health Effects

Aquatic 

Toxicity

Environmental 

Fate

Acute ToxicityCarcinogenicity Genotoxicity ReproductiveDevelopmentalNeurological Repeated DoseSkin SensitizationRespiratory SensitizationEye IrritationDermal IrritationAcuteChronicPersistenceBioaccumulation

Bisphenol A and Phenolic Alternatives

Bisphenol A

2,2-bis(p-hydroxyphenyl)propane 80-05-7 L M L M H M M M M M H H VL L

Bisphenol F

Bis(4-hydroxyphenyl)methane 620-92-8 L M L M § H§ M H L VH M§ M H L L

Bisphenol C

2,2’-Bis(4-hydroxy-3-

methylphenyl)propane

79-97-0 L§ M M M § H§ M M§ M§ H§ M§ H H M M 

MBHA

Methyl bis(4-

hydroxyphenyl)acetate

5129-00-0 L§ M L§ M § H§ M M§ L M§ M§ H H M L 

BisOPP-A

4,4’-Isopropyllidenebis(2-

phenylphenol)

24038-68-4 L§ M L§ M § H§ M M§ M§ M§ M§ L H H M 

Bisphenol AP

4,4’-(1-Phenylethylidene)bisphenol 1571-75-1 L§ M L§ M § H§ M M§ M§ M§ M§ H H H M 

Substituted phenolic compound, 

PROPRIETARY #1 L§ M L M § H§ M M§ M§ M§ M§ H M M L 

Substituted phenolic compound, 

PROPRIETARY #2 L§ M L§ M § H§ M M§ M§ M§ M§ H H H H 

PHBB

Benzyl 4-hydroxybenzoate 94-18-8 L M M L M M L M§ VL VL H H L§ L 

OH OH

OH OH

OH OH

O O

OH

OH

OH OH

OH

O

O

OH OH

4-28 
FINAL REPORT – January 2014 

Table 4-5: Screening Level Hazard Summary (Continued)

This table only contains information regarding the inherent hazards of the chemicals evaluated. Evaluation of risk considers both the hazard and exposure.

The caveats listed in the legend and footnote sections must be taken into account when interpreting the hazard information in the table below.

VL = Very Low hazard L = Low hazard M = Moderate hazard H = High hazard VH = Very High hazard  Endpoints in colored text (VL, L, M, H, and VH) 

were assigned based on empirical data. Endpoints in black italics (VL, L, M, H, and VH) were assigned using values from estimation software and professional judgment.

§ Based on analogy to experimental data for a structurally similar compound.

Structure

Chemical

(for TSCA inventory name and 

relevant trade names see the 

individual profiles in Section 4.8) CASRN

Human Health Effects

Aquatic 

Toxicity

Environmental 

Fate

Acute ToxicityCarcinogenicity Genotoxicity ReproductiveDevelopmentalNeurological Repeated DoseSkin SensitizationRespiratory SensitizationEye IrritationDermal IrritationAcuteChronicPersistenceBioaccumulation

Hydroxyphenyl Sulfone Alternatives

Bisphenol S

4-Hydroxyphenyl sulfone 80-09-1 L M M M M M H L L L M M M L

2,4-BPS

2,4’-Bis(hydroxyphenyl)sulfone 5397-34-2 L§ M M M§ M§ M H§ L§ L§ L§ M H M L

TGSA

Bis-(3-allyl-4-hydroxyphenyl) 

sulfone

41481-66-7 L M L M§ M§ M H M M L VL H M H L 

BPS-MAE 

Phenol,4-[[4-(2-propen-1-

yloxy)phenyl]sulfonyl]-

97042-18-7 L M§ M M§ M§ M L L M L VL H H H L 

BPS-MPE

4-Hydroxy-4’-

benzyloxydiphenylsulfone

63134-33-8 L M M§ M§ M§ M H§ L L L VH H H M 

D-8

4-Hydroxyphenyl 

4-isoprooxyphenylsulfone

95235-30-6 L M L M§ M§ M M L§ L§ L§ H H M M

OH

S

O O OH

S

O

O

OH OH

S

O

O

OH O

S

O

O

O OH

S

O

O

O OH

S

O

O

HO OH

4-29 
FINAL REPORT – January 2014 

Table 4-6: Screening Level Hazard Summary (Continued)

This table only contains information regarding the inherent hazards of the chemicals evaluated. Evaluation of risk considers both the hazard and exposure. 

The caveats listed in the legend and footnote sections must be taken into account when interpreting the hazard information in the table below.

VL = Very Low hazard L = Low hazard M = Moderate hazard H = High hazard VH = Very High hazard  Endpoints in colored text (VL, L, M, H, and VH) were 

assigned based on empirical data. Endpoints in black italics (VL, L, M, H, and VH) were assigned using values from estimation software and professional judgment.

◊ The highest hazard designation of a representative component of the oligomeric mixture with MWs <1,000. 

‡ The highest hazard designation of any of the oligomers with MW <1,000

§ Based on analogy to experimental data for a structurally similar compound.

Structure

Chemical

(for TSCA inventory name and 

relevant trade names see the 

individual profiles in Section 4.8) CASRN

Human Health Effects

Aquatic 

Toxicity

Environmental 

Fate

Acute ToxicityCarcinogenicity GenotoxicityReproductiveDevelopmentalNeurological Repeated DoseSkin SensitizationRespiratory SensitizationEye IrritationDermal IrritationAcuteChronicPersistenceBioaccumulation

Oligomeric and Polymeric Alternatives

D-90 

Phenol, 4,4’-sulfonylbis-, polymer 

with 1,1’-oxybis[2-chloroethane] 

191680-83-8 L M L L L M L L M VL L‡ L‡ VH‡ H‡

DD-70

1,7-bis(4-Hydroxyphenylthio)-3,5-

dioxaheptane

93589-69-6 L M L M M§ M M§ M§ H§ M§ H H H L 

Pergafast 201

N-(p-Toluenesulfonyl)-N'-(3-ptoluenesulfonyloxyphenyl)urea232938-43-1 L M L M H L M L L VL H H VH L

BTUM

4,4'-bis(N-carbamoyl-4-

methylbenzenesulfomide)diphenylme

thane

151882-81-4 L M L L L L M L L L H H H L 

UU 

Urea Urethane Compound 321860-75-7 L M L L L L L L L L L L◊ VH L

OH

S O O S

OH

N

H O

N

H S

O

O

3CH

O S

O

O

CH3

N N

O

S

O O

N N

O

S

O O

S

O

O

HO O O O S

O

O

O

n

H

4-30 
FINAL REPORT – January 2014 

4.8 Hazard Profiles

Bisphenol A

OH OH

CASRN: 80-05-7

MW: 228.29

MF: C15H16O2

Physical Forms:

Neat: Solid

Use: Developer for thermal papers

SMILES: Oc1ccc(cc1)C(c1ccc(O)cc1)(C)C

Synonyms: Phenol,4,4'-(1-methylethylidene)bis-; BPA; 2,2-(4,4’-dihydroxydiphenyl)propane; 2,2-bis(4’-hydroxyphenyl)propane; 2,2-bis(4-

hydroxyphenyl)propane; 2,2-bis-(4-hydroxy-phenyl)-propane; 2,2-bis(p-hydroxyphenyl)propane; 2,2-bis-4’-hydroxyfenylpropan; 2,2-di(4-hydroxyphenyl)propane; 

2,2-di(4-phenylol)propane; 4,4’-(1-Methylethylidene)bisphenol; 4,4’-Dihydroxy-2,2’-diphenylpropane; 4,4’-Dihydroxydiphenyl-2,2’-propane; 4,4’-bisphenol A; 

4,4’-dihydroxydiphenyl-2,2-propane; 4,4’-dihydroxydiphenyldimethylmethane; 4,4’-dihydroxydiphenylpropane; 4,4’-dihydroxyphenyl-2,2-propane; 4,4’-

isopropylidenebisphenol; 4,4’-isopropylidenediphenol; 4,4-isopropylidenediphenyl; beta, beta’-bis(p-hydroxylphenyl)propane; beta-di-p-hydroxyphenylpropane; 

bis(4-hydroxyphenyl)dimethylmethane; bis(4-hydroxyphenyl)propane; bis[phenol],4,4’-(1-methylethylidene)-; Bisferol A; bisphenol; Bisphenol,4,4’-(1-

methylethylidene)-; Bisphenol-a; Dian; Diano; dimethylbis(p-hydroxyphenyl)methane; dimethylmethylene-p,p’-di-phenol; dimethylmethylene-p,p’-diphenol; 

Diphenolmethylethylidene; diphenylolpropane; Ipognox88; Isopropylidenebis(4-hydroxybenzene); p,p’-Isopropylidene-bisphenol; p,p’-Isopropylidene-di-phenol; 

p,p’-bisphenolA; p,p’-dihydroxydiphenyldimethylmethane; p,p’-dihydroxydiphenylpropane; p,p’-isopropylidenebisphenol; p,p’-isopropylidenediphenol; Parabis; 

ParabisA; Phenol,(1-methylethylidene)bis-; Phenol,4,4’-Isopropylidene-di; Phenol,4,4’-dimethylmethylenedi-; Phenol,4,4’-isopropylidenedi-; Pluracol 245; 

propane,2,2-bis(p-hydroxyphenyl)-; Rikabanol; ß-Di-p-Hydroxyphenylpropane; Ucarbisphenol A; Ucarbisphenol HP

4-31 
FINAL REPORT – January 2014 

Polymeric: No

 Oligomers: Not applicable

Metabolites, Degradates and Transformation Products: BPA glucuronide, BPA sulfate conjugate, BPA diglucuronide, 5-hydroxy BPA and the corresponding 

sulfate conjugate, isopropyl-hydroxyphenol, BPA glutathione conjugate, glutathionyl-phenol, glutathionyl 4-isopropylphenol, BPA dimmers, monohydroxybisphenol 

A, beta-glucoside, BPA mono-O-ß-D-gentiobioside and the trisaccharide BPA, ß-D -glucopyranoside, mono- and di- O-ß-D-glucopyranosides, phenol, 

4-isopropenylphenol, 4-isopropylphenol, hexestrol, 5,5’-bis-[1-(4-hydroxy-phenyl)-1-methylethyl]-bisphenyl-2,2’-diol, 4-hydroxyacetephenone, 4-hydroxybenzoic 

acid, 2,2-bis(4-hydrozyphenyl)-1-propanol, 2, 3- bis(4-hydroxyphenyl)-1, 2-propanediol (Kang, Katayama et al., 2006)

Analog: None

 Endpoint(s) using analog values: Not applicable

Analog Structure: Not applicable

Structural Alerts: Phenols, neurotoxicity (U.S. EPA, 2010)

Risk Phrases: 37 - Irritating to respiratory system; 41 - Risk of serious damage to eyes; 43 - May cause sensitization by skin contact; 52 - Harmful to aquatic 

organisms; 62 - Possible risk of impaired fertility (ESIS, 2011). 

Risk Assessments: Risk assessment completed for Bisphenol A by Canada in 2008, the European Union in 2010, and Japan in 2007 (Canada, 2008; EINECS, 2010; 

Nakanishi and Miyamoto, 2007).

4-32 
FINAL REPORT – January 2014 

Bisphenol A CASRN 80-05-7

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

PHYSICAL/CHEMICAL PROPERTIES

Melting Point (°C) 155 (Measured) EINECS, 2010 Adequate; consistent values reported in 

secondary sources. 150-157 (Measured) EINECS, 2010; Canada, 2008

150-155 (Measured) O’Neil, 2010

Boiling Point (°C) 360.5 at 760 mm Hg (Measured) EINECS, 2010; IUCLID, 2000 Adequate. 

250-252 at 13 mm Hg (decomposes) 

(Measured)

EINECS, 2010 Reduced boiling point consistent with 

values reported in secondary sources.

220-398 (Measured) Canada, 2008 Range of values not entirely consistent 

with other located sources.

220 at 4 mm Hg (Measured); decomposes 

when heated above 220°C 

O’Neil, 2010 Data indicate that BPA will decompose 

at elevated temperatures.

Vapor Pressure (mm Hg) 3.99x10-8 (Measured) EINECS, 2010; Canada, 2008 Adequate; consistent with values 

reported in other secondary sources.

3.08x10-9 - 3.99x10-8 (Measured) EINECS, 2010

Water Solubility (mg/L) 300 (Measured) EINECS, 2010 Adequate; selected value for 

assessment.

120-301 (Measured) Canada, 2008 Adequate; consistent values which span 

a narrow range have been reported in 

secondary sources.

120 (Measured) Dorn, Chou et al., 1987 Adequate; well conducted nonguideline 

study.

Log Kow 3.32 (Measured) Hansch, Leo et al., 1995; 

Canada, 2008 

Adequate; consistent values that span a 

relatively narrow range have been 

reported in secondary sources; selected 

value for assessment.

2.2 (Measured) EINECS, 2010 Adequate; reported in a secondary 

source.

Flammability (Flash Point) 79.4-227°C (Measured) EINECS, 2010 Lower temperatures in this range are 

inconsistent with values reported in 

other secondary sources.

4-33 
FINAL REPORT – January 2014 

Bisphenol A CASRN 80-05-7

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

213°C (Measured)

Reported as 415°F

CHRIS, 1999 Adequate; reported in a secondary 

source.

Auto flammability = approximately 532°C 

(Measured)

EINECS, 2010 Substantial degradation is anticipated 

to occur before this temperature is 

reached.

Explosivity Minimum explosive concentration (in air) 

0.012 g/L with oxygen >5% (Measured)

EINECS, 2010 Adequate; reported in a secondary 

source.

Dust is flammable if ignited (Measured) IUCLID, 2000 Adequate; reported in a secondary 

source.

pH No data located.

pKa 9.59–11.30 (Measured) Canada, 2008 Adequate; initial value in range is for 

first ionization. Higher values likely for 

second ionization step.

HUMAN HEALTH EFFECTS

Toxicokinetics In rats, BPA was rapidly absorbed following oral administration and extensively metabolized, predominantly 

via first-pass metabolism. BPA and its metabolites did not appear to accumulate. In rats, excretion following 

oral exposure occurred mainly in the feces (50-83% of the administered dose) and urine (13-42% of the 

administered dose, mainly as the glucuronide conjugate). Maternal transfer to the rat fetus was demonstrated 

and excretion may also occur via the mother’s milk. In humans, essentially 100% of a relatively small oral dose 

of BPA was rapidly absorbed, readily metabolized, and excreted in the urine as BPA-glucuronide (essentially 

100% of the administered dose). Information was not located regarding the toxicokinetics of BPA following in 

vivo inhalation or dermal exposure.

Dermal Absorption in vitro Human skin, 10% of applied millimolar 

dose was absorbed.

EINECS, 2010 Adequate.

Pig skin, 10 μg/mL radiolabeled BPA. 

2, 5, and 10 hours of exposure; the total 

BPA skin content was 3%, 6.9%, and 

11.4% of the applied dose, respectively. 

BPA remained in the skin surface and 

accumulated primarily in the dermis.

NIOSH, 2010 Adequate.

4-34 
FINAL REPORT – January 2014 

Bisphenol A CASRN 80-05-7

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Absorption, 

Distribution, 

Metabolism & 

Excretion

Oral, Dermal or Inhaled Data located for rats, mice, monkeys, and 

humans indicate that ingested BPA is 

rapidly and extensively absorbed from the 

gastrointestinal tract (up to 85-86% in rats 

and monkeys and essentially 100% of a 

relatively small dose in humans). Orallyabsorbed BPA undergoes extensive firstpass metabolism. In all species studied, the 

major metabolic pathway involved the 

conjugation of BPA to BPA-glucuronide. 

There does not appear to be a selective 

affinity of yolk sac/placenta or embryo/

fetus for BPA or BPA metabolites. 

Enterohepatic recirculation of BPAglucuronide readily occurs in rats, resulting 

in availability of some free BPA to tissues. 

Enterohepatic recirculation does not appear 

to occur in humans. Approximately 13-42% 

of an administered BPA dose was recovered 

in the urine of rats as the glucuronide 

metabolite; 50-83% was eliminated in the 

feces, mostly as free BPA. Limited 

excretion in the milk was observed. In 

monkeys, 82-85% of an orally-administered 

BPA dose was recovered in the urine; only 

2-3% was detected in the feces. In 

volunteers given relatively low doses of 

BPA, the dose was completely recovered as 

BPA-glucuronide in the urine. No animal 

data were located regarding the 

toxicokinetics of BPA following in vivo

exposure via inhalation or dermal routes.

EINECS, 2010 Summary of multiple studies reported 

in secondary source. 

4-35 
FINAL REPORT – January 2014 

Bisphenol A CASRN 80-05-7

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Acute Mammalian Toxicity LOW: The acute oral and dermal toxicity hazard of BPA is low based on experimental data in animals. Data 

for exposure via inhalation were inconclusive, as only a single concentration was tested and a LC50 was not 

provided. 

Acute Lethality Oral Rat LD50 = 3,200 to >5,000 mg/kg bw EINECS, 2010; European 

Commission, 2000; NTP, 1982 

Adequate; multiple studies, some 

guideline studies. 

Mouse LD50 = 4,000–5,200 mg/kg bw EINECS, 2010; European 

Commission, 2000; NTP, 1982

Adequate; multiple studies, some 

guideline studies.

Mouse LD50 = 1,600 mg/kg bw EINECS, 2010; European 

Commission, 2000 

Inadequate; insufficient study details, 

relatively old study, results not 

supported by other studies.

Rabbit LD50 = 2,230 mg/kg bw EINECS, 2010; European 

Commission, 2000

Inadequate; insufficient study details, 

old study.

Dermal Rabbit LD50 = 3,000–6,400 mg/kg bw EINECS, 2010; European 

Commission, 2000 

Adequate; limited study details for 

multiple studies reported in secondary 

sources.

Inhalation No deaths among male and female F344 

rats (10/sex) exposed to BPA dust at 

0.17 mg/L (highest attainable 

concentration) for 6 hours; transient slight 

nasal tract epithelial damage was evident.

EINECS, 2010; European 

Commission, 2000 

Adequate, although test guidelines 

were not reported in secondary sources.

4-36 
FINAL REPORT – January 2014 

Bisphenol A CASRN 80-05-7

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Carcinogenicity MODERATE: Two standard 2-year guideline carcinogenicity studies found no increased incidence of cancer 

associated with adult exposures. There is concern for carcinogenicity associated with endocrine related 

mechanisms due to its estrogenic properties. Several nonguideline studies indicate proliferation of mammary 

ductal epithelium and squamous metaplasia of prostatic epithelium in offspring, conditions thought by many to 

predispose to neoplasia (FAO/WHO 2011). In response to the uncertainty, NTP and FDA are conducting a new

GLP study that is designed to include a wide oral dosing range, to include pre- and perinatal exposures 

(FAO/WHO 2011). Since data from guideline studies suggest low concern for cancer but there are nonguideline 

studies that demonstrate evidence of proliferative lesions, carcinogenicity cannot be ruled out at this time. DfE 

criteria calls for the assignment of a Moderate hazard designation.

OncoLogic Results Moderate (Estimated)

OncoLogic class: phenols and phenolic 

compounds 

However, several types of phenolic 

compounds are of concern based on 

structural similarities to estrogenic and 

androgenic compounds known to be 

potential carcinogens or tumor promoters

via endocrine-related mechanisms.

OncoLogic OncoLogic SAR analysis using the 

phenols and phenolic compounds class.

Carcinogenicity Based on existing carcinogenicity study 

data,

There is confidence that exposure to BPA: 

• Exhibits endocrine activity and has 

estrogenic properties 

• Estradiol-17β is classified as 

carcinogenic (IARC); 

It is likely that exposure to BPA: 

• May be associated with increased 

cancers of the hematopoietic system 

and increased interstitial-cell tumors 

in the testes

• Alters function of microbules 

• Induces aneuploidy in cells and tissues

Keri, Ho et al., 2007 2007 consensus statement for NIEHSfunded cancer researchers evaluating 

evidence of carcinogenicity in human 

and animal models following exposure 

to BPA.

4-37 
FINAL REPORT – January 2014 

Bisphenol A CASRN 80-05-7

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

• Exposure early in life may cause a 

predisposition for pre-neoplastic 

lesions in adult mammary gland and 

prostate gland tissues

• Prenatal exposure alters mammary 

gland development in mice and 

increases effects relevant to markers 

of breast cancer risk in humans; 

It is possible that exposure to BPA:

• Induces in vitro cellular 

transformation 

• Promotes tumor progression and 

reduces time to recurrence in 

advanced prostate cancers with 

androgen receptor mutations.

Combined Chronic 

Toxicity/Carcinogenicity

2-year dietary study in male and female 

F344 rats (50/sex/group)

Dietary concentrations: 0, 1,000, and 

2,000 ppm (estimated doses 0, 84, and 

167 mg/kg-day for males and females 

combined). 

Chronic toxicity: Lower mean body weight 

of low- and high-dose females and highdose males likely the result of decreased 

food consumption. 

Carcinogenicity: Marginally significant 

increase in leukemia in male rats, nonsignificant increase in female rats, 

significant increase in interstitial-cell 

tumors of testes (known to occur at high 

incidence in aging F344 rats) not considered 

by NTP to be convincing evidence of a 

carcinogenic effect for BPA.

NTP, 1982 Adequate.

4-38 
FINAL REPORT – January 2014 

Bisphenol A CASRN 80-05-7

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

2-year dietary study in male and female 

B6C3F1 mice (50/sex/group) 

Dietary concentrations: 0, 1,000, and 

5,000 ppm (males); 0, 5,000, and 10,000 

ppm (females) (estimated doses 0, 172, and 

858 mg/kg-day for males and 0, 864, and 

1,728 mg/kg-day for females).

Chronic toxicity: Increased incidence of 

multinucleated giant hepatocytes in males 

(incidences of 41/49 and 41/50 versus 

1/49 in controls) 

Carcinogenicity: Non-significant increased 

incidences of leukemia or lymphomas in 

low- and high-dose male mice (9/50, 5/50 

versus 2/50 in controls) not considered by 

NTP to be convincing evidence of 

carcinogenic effect for BPA.

NTP, 1982 Adequate.

Studies that included perinatal (gestational 

and/or lactational) exposures to BPA (oral 

doses to the dam from ~10 to 250 μg/kg bw 

per day) have reported, among other 

lesions, proliferation of mammary ductal 

epithelium and squamous metaplasia of 

prostatic epithelium in offspring, conditions 

thought by many to predispose to neoplasia 

(Timms et al., 2005; Moral et al., 2008). 

Additional treatments with initiating or 

promoting agents have led to earlier onset 

of mammary tumors (Jenkins et al., 2009) 

or prostatic intraepithelial neoplasia (Prins 

et al., 2011). However, the studies that 

included exposures to BPA during the 

appropriate periods all suffered from one or 

FAO/WHO, 2011 Summary of data, data quality, and 

conclusions from the expert panel.

4-39 
FINAL REPORT – January 2014 

Bisphenol A CASRN 80-05-7

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

more deficiencies in design or execution 

that prevent a definitive evaluation of its 

potential as a carcinogen. These include 1) 

lack of consideration of litter effects, 2) 

small numbers of animals, 3) insufficient 

study duration to determine whether 

developmental conditions thought to 

enhance cancer susceptibility actually did 

so, and 4) additional treatment with a strong 

initiating or additional promoting agent(s). 

In the absence of additional studies 

addressing these deficiencies, there is 

currently insufficient evidence on which to 

judge the carcinogenic potential of BPA.

Genotoxicity LOW: Based on determination by FAO/WHO (2011) that: (1) BPA is not a mutagen in in vitro test systems, 

(2) BPA does not induce cell transformation, and (3) in vivo evidence for BPA-induced clastogenic effects is 

inconsistent and inconclusive, although some in vitro studies have shown BPA to affect chromosomal structure 

in dividing cells. The conclusion of FAO/WHO (2011) is that BPA is not likely to pose a genotoxic hazard to 

humans.

Largely negative results in a variety of in 

vitro test systems, including studies with 

Salmonella typhimurium, Chinese hamster 

V79 cells, Syrian hamster embryo cells, and 

mouse lymphoma cells. However, DNA 

damage was induced in MCF-7 and MDAMB-231 cells, DNA adduct formation in 

Syrian hamster ovary cells, and a number of 

positive findings have been reported for the 

potential for BPA to inhibit purified 

microtubule polymerization, affect the 

spindle apparatus, and produce aneuploidy 

in in vitro studies with Chinese hamster 

V79 cells or oocytes from Balb/c or MF1 

FAO/WHO, 2011 Summary of data, data quality, and 

conclusions from the expert panel.

4-40 
FINAL REPORT – January 2014 

Bisphenol A CASRN 80-05-7

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

mice.

FAO/WHO Expert Panel concludes: 

BPA is not a mutagen in in vitro test 

systems, nor does it induce cell 

transformation. BPA has been shown to 

affect chromosomal structure in dividing 

cells in in vitro studies, but evidence for this 

effect in in vivo studies is inconsistent and 

inconclusive. BPA is not likely to pose a 

genotoxic hazard to humans. 

Reproductive Effects MODERATE: Key studies identified by NTP indicate there are multiple distinct endpoints with NOAELs in 

the range of Moderate hazard concern with LOAELs in the range of Low hazard concern. At the target dose of 

50 mg/kg-day, the NOAELs are on the margin of High and Moderate hazard, according to DfE criteria. 

Benchmark Dose (BMD) Modeling conducted by NTP, which interpolates between NOAEL and LOAEL 

values, yields values that further support a Moderate hazard designation.

Reproduction/ 

Developmental Toxicity 

Screen

No data located.

Combined Repeated 

Dose with Reproduction/ 

Developmental Toxicity 

Screen

No data located.

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Reproduction and 

Fertility Effects

Multigenerational dietary study on fertility 

and reproductive performance in SpragueDawley rats (30/sex/group)

BPA concentrations: 0, 0.015, 0.3, 4.5, 75, 

750, and 7,500 ppm (Tyl, et al., 2002 

estimated target doses of 0, 0.0095, 0.019, 

0.285, 5, 50, and 500 mg/kg bw-day)

Exposure period: 10 weeks premating, 

2 weeks mating, gestation (parental males 

and females), lactation (parental females); 

similar exposure regimen for F1 and F2

parental males and females; F3 weanlings 

exposed for 10 weeks 

Parental systemic toxicity:

NOAEL = 5 mg/kg bw-day 

LOAEL = 50 mg/kg bw-day for 12% 

decreased terminal body weight in F1

parental males

Reproductive toxicity:

Females: NOAEL = 50 mg/kg bw-day 

LOAEL = 500 mg/kg bw-day for decreases 

in number of implantation sites, delayed 

vaginal opening in F1, F2, F3 offspring 

BMDLs (change of 1 standard deviation 

from control) reported for delayed vaginal 

opening (females)- 

F1 = 176 mg/kg-day 

F2 = 228 mg/kg-day 

F3 = 203 mg/kg-day 

Males: NOAEL = 50 mg/kg bw-day, 

LOAEL = 500 mg/kg-day for delayed 

preputial separation in F1 males

BMDLs (change of 1 standard deviation 

from control) reported for delayed preputial 

separation (males)- 

F1 = 163 mg/kg-day 

F2 = 203 mg/kg-day 

F3 = 189 mg/kg-day

Chapin et al. 2008; NTPCERHR, 2008 Adequate, guideline study as reported 

in the secondary source. 

Classified by NTP-CERHR as having 

as High Utility.

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Two-generation dietary study of fertility 

and reproductive performance in CD-1 mice 

(28/sex/group) 

Dietary concentrations: 0, 0.018, 0.18, 1.8, 

30, 300, and 3,500 ppm (Tyl, et al., 2002 

estimated target doses of 0.003, 0.03, 0.3, 5, 

50, and 600 mg/kg bw-day) 

Exposure period: 8 weeks premating, 

2 weeks mating, gestation, and lactation for 

F0 and F1 parental mice

Parental systemic toxicity: 

NOAEL = 5 mg/kg bw-day 

LOAEL = 50 mg/kg bw-day for increased 

incidences of centrilobular hepatocellular 

hypertrophy in males and females 

Reproductive toxicity: 

NOAEL = 50 mg/kg bw-day 

LOAEL = 600 mg/kg bw-day for increased 

gestation length, decreased epididymal 

sperm concentration in F1 males, increased 

incidence of gross ovarian cysts in F1 and F2

females

BMD1 (change of 1 standard deviation from 

control) reported for increased gestation 

length

F0 = 1144 mg/kg-day (BMDL = 599 mg/kgday) 

F1 = 772 mg/kg-day (BMDL = 531 mg/kgday) 

BMD10s (10% extra risk) reported for 

increased incidence of gross ovarian cysts

F0 = 225 mg/kg-day (BMDL = 141 mg/kgday) 

F1 = 202 mg/kg-day (BMDL = 120 mg/kgday)

Chapin et al. 2008; NTPCERHR, 2008 Adequate; guideline study as reported 

in the secondary source. 

Classified by NTP-CERHR as having 

as High Utility.

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Summary of 

Reproductive Effects

A large experimental animal literature was 

reviewed by the NTP-CERHR Expert 

Panel, assessed for its utility, and weighted 

based on the criteria established by this 

expert panel, including an evaluation of 

experimental design and statistical 

procedures. These animal data are assumed 

relevant for the assessment of human 

hazard. The NTP-CERHR Expert Panel 

concluded the following:

Female effects: There is sufficient evidence 

in rats and mice that BPA causes female 

reproductive toxicity with subchronic or 

chronic oral exposures with a NOAEL of 50 

mg/kg bw-day and a LOAEL of 500 mg/kg 

bw-day.

Male effects: There is sufficient evidence 

in rats and mice that BPA causes male 

reproductive toxicity with subchronic or 

chronic oral exposures with a NOAEL of 50 

mg/kg bw-day and a LOAEL of 500 mg/kg 

bw/day.

Chapin et al. 2008; NTPCERHR, 2008 Classified by NTP-CERHR as having 

High Utility.

The joint FAO/WHO Expert Panel 

reviewed located reproductive and 

developmental toxicity data for BPA as of 

November 2010 and noted that most 

regulatory bodies reviewing the numerous 

studies on BPA have indicated an oral 

reproductive and developmental NOAEL of 

50 mg/kg bw-day.

Regarding the potential for low oral doses 

(<1 mg/kg bw-day) of BPA to alter 

FAO/WHO, 2011 Summary of data, data quality, and 

conclusions from the expert panel.

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reproduction and development in rodents, 

the FAO/WHO noted that: 

(1) There is sufficient evidence that BPA 

does not: 

* induce gross morphological reproductive 

abnormalities in F1 offspring; 

* reduce F1 pup survival or body weight; 

* alter F1 growth or survival during 

lactation; 

* alter F1 anogenital distance in males or 

females; or 

* cause under masculinization of male 

morphology or masculinization of female 

morphology. 

(2) There is evidence (with some 

uncertainty) that BPA does not: 

* reduce P0 implantation, infertility, or 

fecundity. 

(3) There is conflicting evidence (with 

higher uncertainty) that BPA: 

* alters F1 pubertal landmarks; 

* alters P0 male or female reproductive 

tract organ weights or histopathology; and 

* alters F1 male reproductive tract organ 

weights or histopathology and semen 

parameters. 

Furthermore, changes in brain biochemical 

signaling, morphometric, and cellular 

endpoints within sexually dimorphic 

anatomical structures and neuroendocrine 

endpoints were reported at dietary 

exposures below 5 mg/kg bw-day.

Methodological limitations introduce 

uncertainty in interpretation of the findings.

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Developmental Effects HIGH: The NTP-CERHR (2008) Expert Panel concluded that there is suggestive evidence that BPA causes 

neural and behavioral alterations related to disruptions in normal sex differences in rats and mice (0.01-

0.2 mg/kg bw-day) following developmental exposures. The FAO/WHO (2011) Expert Panel also concluded 

that while there was broad agreement in a NOAEL of 50 mg/kg bw-day for developmental toxicity based on 

standard bioassays, specific targeted studies identified neurodevelopmental effects at low doses (<1 mg/kg bwday), but the human relevance is less certain. There is great variation in results with different types of studies 

measuring different endpoints; developmental effects at lower doses cannot be ruled out. Taken together these 

findings support a hazard designation of High concern.

Reproduction/ 

Developmental Toxicity 

Screen

No data located.

Combined Repeated 

Dose with Reproduction/ 

Developmental Toxicity 

Screen

No data located.

Summary of 

Developmental Effects

The NTP-CERHR Expert Panel concluded 

that BPA: 

* does not cause malformations or birth 

defects in rats or mice at levels up to the 

highest doses evaluated: 640 mg/kg/day 

(rats) and 1,250 mg/kg bw-day (mice). 

* does not alter male or female fertility after 

gestational exposure up to doses of 

450 mg/kg bw/day in the rat and 600 mg/kg 

bw-day in the mouse (highest dose levels 

evaluated). 

* does not permanently affect prostate 

weight at doses up to 500 mg/kg bw-day in 

adult rats or 600 mg/kg bw-day in mice. 

* does not cause prostate cancer in rats or 

mice after adult exposure at up to 148 or 

600 mg/kg bw-day, respectively. 

* does change the age of puberty in male or 

Chapin et al., 2008; NTP–

CERHR, 2008 

Summary of data, data quality, and 

conclusions from the expert panel.

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female rats at high doses (ca. 500 mg/kg 

bw-day).

And that rodent studies suggest that BPA:

* causes neural and behavioral alterations 

related to disruptions in normal sex 

differences in rats and mice (0.01-0.2 mg/kg 

bw-day).

The joint FAO/WHO Expert Panel 

reviewed reproductive and developmental 

toxicity data for BPA located as of 

November 2010 and noted that most 

regulatory bodies reviewing the numerous 

studies on BPA have indicated an oral 

reproductive and developmental NOAEL of 

50 mg/kg bw-day.

Regarding the potential for low oral doses 

(<1 mg/kg bw-day) of BPA to alter 

reproduction and development in rodents, 

the FAO/WHO noted that:

(1) There is sufficient evidence that BPA 

does not:

*induce gross morphological reproductive 

abnormalities in F1 offspring; 

*reduce F1 pup survival or body weight; 

*alter F1 growth or survival during 

lactation;

*alter F1 anogenital distance in males or 

females; or

*cause under masculinization of male 

morphology or masculinization of female 

morphology.

(2) There is evidence (with some 

FAO/WHO, 2011 Summary of data, data quality, and 

conclusions from the expert panel.

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uncertainty) that BPA does not:

*reduce P0 implantation, infertility or 

fecundity. 

(3) There is conflicting evidence (with 

higher uncertainty) that BPA: 

*alters F1 pubertal landmarks; 

*alters P0 male or female reproductive tract 

organ weights or histopathology; and 

*alters F1 male reproductive tract organ 

weights or histopathology and semen 

parameters. 

Furthermore, changes in brain biochemical 

signaling, morphometric and cellular endpoints within sexually dimorphic 

anatomical structures and neuroendocrine 

end-points were reported at dietary 

exposures below 5 mg/kg bw-day.

Methodological limitations introduce 

uncertainty in interpretation of the findings.

Neurotoxicity MODERATE: Estimated to have potential for neurotoxicity based on the presence of the phenol structural 

alert.

Neurotoxicity Screening 

Battery (Adult)

There is potential for neurotoxicity effects 

based on the presence of the phenol 

structural alert 

(Estimated)

U.S. EPA, 2010; Professional 

judgment 

Estimated based on structural alert.

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Repeated Dose Effects MODERATE: BPA produced histopathologic changes in the liver (centrilobular hepatocyte hypertrophy) 

from oral dosing at 50 mg/kg bw-day (NOAEL = 5 mg/kg bw-day) and there is uncertainty regarding the 

potential for BPA doses between the NOAEL of 5 mg/kg bw-day and the LOAEL of 50 mg/kg-day to cause 

adverse systemic effects. Furthermore, lesions in the nasal cavity of rats were reported following repeated 

inhalation exposure to BPA dust at 0.05 mg/L. These findings indicate a Moderate hazard concern for the oral 

and inhalation exposure routes.

The FAO/WHO Expert Panel reviewed the 

located information regarding repeated-dose 

oral toxicity of BPA and concluded that 

results demonstrated effects on the liver, 

kidney, and body weight at doses of 50 

mg/kg bw-day and higher and that the 

lowest NOAEL was 5 mg/kg-day, as 

identified in several studies.

FAO/WHO, 2011 Summary of data, data quality, and 

conclusions from the expert panel.

Multigenerational dietary study on fertility 

and reproductive performance in SpragueDawley rats (30/sex/group) 

BPA concentrations: 0, 0.015, 0.3, 4.5, 75, 

750, and 7,500 ppm (Tyl, et al., 2002 

estimated target doses of 0, 0.0095, 0.019, 

0.285, 5, 50, and 500 mg/kg bw-day) 

Exposure period: 10 weeks premating, 

2 weeks mating, gestation (parental males 

and females), lactation (parental females); 

similar exposure regimen for F1 and F2

parental males and females; F3 weanlings 

exposed for 10 weeks 

Parental systemic toxicity: 

NOAEL = 4.75 mg/kg bw-day 

LOAEL = 47.5 mg/kg bw-day for 12% 

decreased terminal body weight in F1

parental males

Chapin et al. 2008; NTPCERHR, 2008 Adequate; guideline study as reported 

in the secondary source. 

Classified by NTP-CERHR as having 

High Utility.

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Two-generation dietary study of fertility 

and reproductive performance in CD-1 mice 

(28/sex/group)

Dietary concentrations: 0, 0.018, 0.18, 1.8, 

30, 300, and 3,500 ppm (Tyl, et al., 2002 

estimated target doses of 0.003, 0.03, 0.3, 5, 

50, and 600 mg/kg bw-day)

Exposure period: 8 weeks premating, 

2 weeks mating, gestation, lactation for F0

and F1 parental mice

Parental systemic toxicity:

NOAEL = 5 mg/kg bw-day

LOAEL = 50 mg/kg bw-day for increased 

incidences of centrilobular hepatocellular 

hypertrophy in males and females

Chapin et al. 2008; NTPCERHR, 2008Adequate; guideline study as reported 

in the secondary source.

Classified by NTP-CERHR as having 

High Utility.

Inhalation study (whole body, dust) in 

Fischer 344 rats

Exposure concentrations: 0, 10, 50, 150 

mg/m3 (0, 0.01, 0.05, 0.15 mg/L)

Exposure period: 6 hours/day, 5 days/week 

for 13 weeks

NOAEL = 0.01 mg/L

LOAEL = 0.05 mg/L based on microscopic 

changes in the anterior portion of the nasal 

cavity

Nasal epithelium changes were

reversible (not apparent after 4-week 

recovery period)

EINECS, 2010; European 

Commission, 2000

Adequate.

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Inhalation study in rats (species not defined)

Exposure concentrations: 0, 15-86 mg/m3; 

Mean = 47 mg/m3

 (0.047 mg/L) 

Exposure period: 4 hours/day for 4 months.

NOAEL = None established

LOAEL = 0.047 mg/L for decreased body 

weight gain, increased liver and kidney 

weight, unspecified “morphological 

changes” in liver, kidney, and lungs

European Commission, 2000; 

EINECS, 2010 

Inadequate; single exposure level, 

insufficient study details in secondary 

sources. 

Inhalation study in male Alderley Park rats

Exposure concentrations: Saturated 

atmosphere 

Exposure period: 6 hours/day for five

exposures 

Results: No signs of toxicity, no gross 

macroscopic changes

EINECS, 2010 Inadequate; single exposure level, 

insufficient study duration, lack of 

study details in secondary sources. 

Skin Sensitization MODERATE: Recent data from three BPA manufacturing facilities indicate that BPA does not elicit skin 

sensitization. However, results of some human studies suggest the possibility of a dermal sensitization response, 

although cross-sensitization was not ruled out. Most animal studies were negative for dermal sensitization, 

although assays may not have been maximized. There is evidence of ear swelling in a photoallergy test in mice 

and moderate redness and swelling following repeated dermal exposure in rabbits. Based on suggestive 

evidence of skin sensitization in humans and mice, a Moderate hazard designation is warranted.

Skin Sensitization Negative in a modified local lymph node 

assay of mice administered BPA 

epicutaneously on the ears at concentrations 

up to 30% on 3 consecutive days.

EINECS, 2010 Adequate, although the assay did not 

include concentrations >30%. 

Negative in a local lymph node assay 

modified to test for photoreactivity in mice 

administered BPA epicutaneously on the 

ears at concentrations up to 30% on 

3 consecutive days and irradiated with UV 

light immediately following application.

EINECS, 2010 Adequate, although the assay did not 

include concentrations >30%. 

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Negative in several sensitization tests using 

guinea pigs.

European Commission, 2000;

EINECS, 2010

Inadequate; study details lacking and 

induction and challenge concentrations 

may not have been maximized.

Negative, mouse; BPA applied as 1% 

solution in acetone and corn oil for 2 days; 

induced UV-photosensitization on flank and 

ears.

European Commission, 2000 Inadequate; insufficient experimental 

details.

Positive in 2/16 guinea pigs receiving BPA 

(50% in dimethyl phthalate) for 4 hours 

(occluded) once per week for 3 weeks and 

single challenge (4 hours occluded) 2 weeks 

later.

European Commission, 2000;

EINECS, 2010

Inadequate; insufficient experimental 

details.

Positive, mouse ear swelling photoallergy 

test.

European Commission, 2000 Inadequate; no data on concentrations, 

methods, or GLP.

Negative in comprehensive medical 

surveillance data obtained from three BPA 

manufacturing plants for 875 employees 

examined for several years where workers 

were potentially exposed to other chemicals 

(phenol, acetone) that are not considered to 

be skin sensitizers.

EINECS, 2010 Adequate.

Positive, rabbits; repeated dermal 

application (30 times over 37 days) of BPA 

(pure powder) produced moderate swelling 

and redness; skin turned yellow followed by 

dark pigmentation after day 15. 

NIOSH, 2010 Adequate.

Limited human data provide suggestive 

evidence that BPA may potentially act as a 

dermal sensitizer, although concomitant 

exposure to other potential dermal 

sensitizers may reflect a cross-sensitization 

response.

EINECS, 2010 Inadequate; possible cross-sensitization 

responses.

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The Joint FAO/WHO Expert Meeting 

review of the toxicological aspects of BPA

concludes that BPA is capable of producing 

a skin sensitization response in humans.

FAO/WHO, 2011 Summary of data, data quality, and 

conclusions from the expert panel.

Respiratory Sensitization No data located.

Respiratory Sensitization No data located.

Eye Irritation MODERATE: BPA was slightly to highly irritating to rabbit eyes.

Eye Irritation Rabbit, slightly to highly irritating EINECS, 2010; European 

Commission, 2000 

Adequate; study details provided for 

multiple studies indicate potential for 

BPA to cause eye irritation.

Dermal Irritation MODERATE: BPA was slightly irritating to moderately irritating to rabbit skin. NIOSH has assigned BPA as 

a skin irritant.

Dermal Irritation Rabbit, nonirritating to slightly irritating 

when applied as undiluted or 10% aqueous 

suspension to intact or abraded skin.

European Commission, 2000;

EINECS, 2010; NIOSH, 2010 

Adequate; study details provided for 

multiple studies indicate potential for 

BPA to cause dermal irritation.

Rabbit, moderately irritating when applied 

as 40% solution in dimethyl sulfoxide under 

non-occlusive conditions.

European Commission, 2000 Adequate.

Guinea pig, not irritating when applied as 

5% solution in acetone for 24 hours under 

occlusive conditions.

European Commission, 2000 Adequate.

Although a limited number of studies were 

identified that contained data on the direct 

hazard of skin exposures to BPA, located

evidence indicates that mild skin irritation 

following prolonged dermal exposure may 

occur. Therefore, on the basis of the data for 

this assessment, BPA is assigned the SK: 

DIR (IRR) notation; (potential to be a skin 

irritant following exposure to the skin).

NIOSH, 2010 Adequate; summary of conclusions 

provided by NIOSH. 

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Endocrine Activity BPA displays endocrine activity in in vitro assays, but yields mixed results in in vivo studies. In vitro assays 

demonstrate that BPA can bind to estrogen receptors, elicit estrogen-induced gene transcription, induce 

progesterone receptors, and induce cell proliferation in MCF7 cancer cells. The data located indicate that the 

in vitro endocrine activity of BPA is approximately 3-5 orders of magnitude less than that of 17β-estradiol, 

although the results are influenced by cell-type. In vitro assays suggest that BPA did not elicit an androgenic

response but there is some evidence of anti-androgenic activity. Limited comparative in vitro data suggest that 

the estrogenicity of BPA is similar in magnitude to that of bisphenol AP, bisphenol C, and bisphenol F and 

somewhat more potent than bisphenol S. Based on in vitro data, there is also evidence of biological interactions 

involving rapid signaling networks. Data from in vivo studies exhibit a more complex picture; oral BPA does 

not consistently produce robust estrogenic responses. EINECS provides summary data to suggest that BPA has 

been shown to act as an estrogen or xenoestrogen in ecological systems.

Reviews

The estrogenicity of BPA has since been 

evaluated using several different kinds of in 

vitro assays, including binding assays, 

recombinant reporter systems, MCF-7 cells, 

rat pituitary cells, rat uterine 

adenocarcinoma cells, human 

adenocarcinoma cells, fish hepatocytes 

(vitellogenin production), and frog 

hepatocytes (vitellogenin production). 

According to the NTP-CERHR Expert 

Panel, there is considerable variability in 

the results of these studies with the 

estrogenic potency of BPA ranging over 

about 8 orders of magnitude.

NTP-CERHR, 2008 Summary of data, data quality, and 

conclusions from NTP-CERHR.

A number of in vivo tests have been 

conducted with most of the focus on effects 

on uterine weight in immature or 

ovariectomized animals. These studies 

indicate that the potency of BPA in 

increasing uterine weight varies over ~4 

orders of magnitude. According to the NTPNTP-CERHR, 2008 Summary of data, data quality, and 

conclusions from NTP-CERHR.

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CERHR Expert Panel, oral BPA does not 

consistently produce robust estrogenic 

responses and, when seen, estrogenic 

effects after oral treatment occur at highdose levels.

A limited number of studies have evaluated 

androgen activity of BPA. These studies 

provide little evidence of androgenic 

effects, but there is limited evidence of 

antiandrogenicity.

NTP-CERHR, 2008 Summary of data, data quality, and 

conclusions from NTP-CERHR.

Positive estrous response; subcutaneous 

injections of BPA to ovariectomized rats 

(strain not specified) (positive response 

measured by cornification in vaginal 

smears).

European Commission, 2000 Adequate.

Numerous studies were located regarding 

the behavior of BPA as an estrogen or 

xenoestrogen in ecological organisms. 

Important results include findings that BPA 

increases plasma vitellogenin concentration 

in freshwater and saltwater fish at a potency 

in the range of 10-4 that of 17β-estradiol and 

that BPA can bind to the estrogen receptor 

of fish, albeit at a lower affinity than that of 

17β-estradiol.

EINECS, 2010 Adequate.

BPA can interact with non-classic estrogen 

receptor systems at similar or lower 

concentrations than interactions with ERα 

and ERβ. BPA has a high binding affinity to 

estrogen-related receptor-γ (ERRγ), an 

orphan receptor that shares a sequence 

homology with ERα and ERβ but is not 

activated by estradiol.

NTP, 2010 Adequate.

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BPA also impacts cellular physiology 

through rapid signaling mechanisms, 

independent of nuclear hormone receptor 

activity, to modify the activities of various 

intracellular signaling networks. Maximal 

rapid signaling effects for BPA and 17βestradiol are often observed at similar 

concentrations.

NTP, 2010 Adequate.

Representative in vitro studies

Receptor Binding Assays

In a human ER binding assay, the relative 

binding affinity (RBA) of BPA was 0.195% 

compared to 126% for 17β-estradiol. RBAs 

for other bisphenol compounds included 

0.129% for bisphenol C, 0.0803% for 

bisphenol AP, 0.0719% for bisphenol F, 

and 0.0055% for bisphenol S. An RBA of 

0.00473% was reported for PHBB.

METI, 2002 Adequate.

In a competitive ER binding assay using 

human ERα, the RBA for BPA was 0.32% 

that of 17β-estradiol. RBAs for other 

bisphenol compounds included 1.68% for 

bisphenol C, 1.66% for bisphenol AP, and 

0.09% for bisphenol F.

Coleman, Toscano et al., 2003 Adequate.

In a rat uterine cytosol assay that evaluated 

ER binding affinity, ER binding affinities 

for BPA and bisphenol F were 

approximately 3 orders of magnitude less 

than that for 17β-estradiol.

Perez, Pulgar et al., 1998 Adequate.

In a rat uterine cytosolic ER-competitive 

binding assay, results for BPA, bisphenol S, 

and PHBB indicated a weak affinity for ER.

Laws, Yavanhxay et al., 2006 Adequate.

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BPA exhibited weak ER binding activity in 

preparations from uteri of ovariectomized 

Sprague-Dawley rats as evidenced by a 

relative binding affinity (RBA) that was 

0.008% of the binding affinity of 17βestradiol. RBAs for other tested chemicals 

included 0.003% for PHBB, 0.0009% for 

bisphenol F, and 0.0007% for the 

proprietary substituted phenolic compound.

Blair, Branham et al., 2000 Adequate.

Representative in vitro studies

Gene Transcription Assays

BPA exhibited evidence of estrogenic 

activity in a yeast (Saccharomyces 

cerevisiae) two-hybrid assay using ERα and 

the coactivator TIF2. Based on estrogenic 

activity that was 5 orders of magnitude 

lower than that of 17β-estradiol, BPA was 

considered weakly estrogenic. Assessment 

of other bisphenols resulted in a ranking of 

relative potency as follows: bisphenol C ≥ 

BPA > bisphenol F > bisphenol S.

Chen, Michihiko et al., 2002 Adequate.

BPA exhibited estrogenic activity 

approximately 10,000-fold less than that of 

17β-estradiol) in an in vitro recombinant 

yeast estrogen assay; the estrogenic 

activities of bisphenol F and PHBB were 

9,000-fold and 4,000-fold less than that of 

17β-estradiol.

Miller, Wheals et al., 2001 Adequate.

BPA exhibited evidence of estrogenic 

activity in a yeast (Saccharomyces 

cerevisiae) two-hybrid assay using ERα and 

the coactivator TIF2.

Nishihara, Nishikawa et al., 

2000 

Adequate.

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In a yeast two-hybrid system (reporter gene 

assay) using β-galactosidase activity as a 

measure of estrogenic activity, an 

estrogenic response was elicited by BPA 

and bisphenol F but not by bisphenol S.

Hashimoto and Nakamura, 2000 Adequate.

In a yeast two-hybrid assay (reporter gene 

assay) using β-galactosidase activity as a 

measure of estrogenic activity, an 

estrogenic response was elicited by BPA 

and bisphenol F.

Ogawa, Kawamura et al. 2006 Adequate.

In a reporter gene assay of estrogen-induced 

transcriptional activity, relative activity 

(RA) for BPA was 0.00278% compared to 

81.7% for 17β-estradiol. RAs for other 

bisphenol compounds included 0.00189% 

for bisphenol C, 0.000639% for bisphenol 

F, 0.000254% for bisphenol S, and 

0.000184% for bisphenol AP. An RA of 

0.000592% was reported for PHBB.

METI, 2002 Adequate.

In an ER-mediated reporter gene expression 

assay, BPA induced reporter gene 

expression at a relative activity (RA) of 

2.75x10-3 that of 17β-estradiol. RAs for 

other bisphenol compounds included 

5.3x10-4 for bisphenol F, 4.9x10-4 for

bisphenol C, and 9.0x10-5 for bisphenol AP.

Coleman, Toscano et al., 2003 Adequate.

In an ERE-luciferase reporter assay using 

MCF-7 cells, an EC50 was 0.63 μM for BPA 

compared to an EC50 of 8.6x10-6 for 17βestradiol (i.e., BPA was approximately 5 

orders of magnitude less potent than 17βestradiol at inducing estrogenic activity). 

EC50 values for other bisphenol compounds 

Kitamura, Suzuki et al., 2005 Adequate.

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included 0.42 μM for bisphenol C, 1.0 μM 

for bisphenol F, and 1.1 μM for bisphenol 

S.

In an ERE-luciferase reporter assay using 

MCF-7 cells in the presence of 17βestradiol, neither BPA, bisphenol C, 

bisphenol F, bisphenol S, nor bisphenol M 

appeared to exert an anti-estrogenic effect.

Kitamura, Suzuki et al., 2005 Adequate.

Representative in vitro studies

Progesterone Receptor Induction

BPA induced progesterone receptors in 

cultured human mammary cancer cells 

(MCF-7) cells, but the magnitude of the 

induction was not specified.

EINECS, 2010; European 

Commission, 2000 

Adequate.

In an assay designed to evaluate estrogenic 

effects on the number of progesterone 

receptors (PgR) in MCF7 cells, 17βestradiol, BPA, and bisphenol F each 

increased the concentration of PgR by 

approximately 10- to 15-fold.

Perez, Pulgar et al., 1998 Adequate.

Representative in vitro studies

Cell Proliferation Assays

In an E-SCREEN test of MCF7 cell 

proliferation (an indicator of estrogenic 

activity), the proliferative potency of BPA 

was approximately 10-5 that of 17βestradiol, suggestive of a weakly estrogenic 

effect for BPA. The potency of bisphenol F 

was somewhat less than that of BPA.

Perez, Pulgar et al., 1998 Adequate.

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In a proliferation assay of MCF-7 human 

breast cancer cells that contain ERα and 

ERβ and are known to proliferate in 

response to estrogens, BPA induced a 

proliferative response that was 2.0x10-3 that 

of 17β-estradiol. Proliferative values for 

other bisphenol compounds included 

1.6x10-3 for bisphenol C, 1.0x10-3 for 

bisphenol F, and 6.0x10-4 for bisphenol AP.

Coleman, Toscano et al., 2003 Adequate.

In an E-screen test for estrogenicity, BPA 

and bisphenol F increased proliferation of 

MCF-7 cells with EC50 values of 410 nM 

and 84.8 nM, respectively, compared to an 

EC50 of 0.0045 nM for 17β-estradiol. The 

results indicate a weak estrogenic effect 

with bisphenol F exerting a more potent 

effect than BPA.

Stroheker, Picard et al., 2004 Adequate.

In an E-screen test for estrogenicity, BPA,

bisphenol F, and bisphenol S increased 

proliferation of MCF-7 cells at 

concentrations in the range of 10-4 to 10-7

M. BPA appeared to be more effective than 

bisphenol S or bisphenol F.

Hashimoto, Moriguchi et al., 

2001 

Adequate.

BPA increased the rate of proliferation of 

MCF-7 cells at 3-5 orders of magnitude less 

than that of 17β-estradiol.

EINECS, 2010; European 

Commission, 2000 

Adequate.

In an assay that measured induction and 

secretion of pS2 in cultured MCF7 cells 

(ELSA-pS2 immunoradiometric assay), 

induction of pS2 by BPA and bisphenol F 

was approximately 1,000-fold less than that 

of 17β-estradiol.

Perez, Pulgar et al., 1998 Adequate.

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Representative in vivo studies

Exposure of immature female rats to BPA 

(gavage dosing once daily for 4 days) 

resulted in no apparent effects on uterine 

weight. Bisphenol F-treated rats exhibited 

significantly increased uterine weight. 

There were no effects on uterine weight of 

bisphenol F- or BPA-treated 

ovariectromized rats.

Stroheker, Picard et al., 2004 Adequate.

In uterotrophic assays using ovariectomized 

mice, BPA treatment at doses in the range 

of 20 to 500 mg/kg/day for 3 days resulted 

in dose-related increased relative uterus 

weights of 147-185% that of controls 

compared to nearly 500% increased uterus 

weight in mice administered 17β-estradiol 

at 50 μg/kg/day. This result is indicative of 

an estrogenic effect in vivo.

Kitamura, Suzuki et al., 2005 Adequate.

In an uterotrophic assay in which immature 

female rats were injected with bisphenol F, 

bisphenol S, or bisphenol M subcutaneously 

for three consecutive days, observed 

changes in uterine weight indicated that 

bisphenol F, bisphenol S, and bisphenol M 

exerted both estrogenic and anti-estrogenic 

responses.

Akahori, Makai et al., 2008 Adequate.

Representative Androgen Assays

In an ARE-luciferase reporter assay using a 

mouse fibroblast cell line (NIH3T3 cells), 

neither BPA, bisphenol C, bisphenol F, nor 

bisphenol S exerted an androgenic effect

Kitamura, Suzuki et al., 2005 Adequate.

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In an ARE-luciferase reporter assay using a 

mouse fibroblast cell line (NIH3T3 cells), 

BPA inhibited the androgenic activity of 

dihydrotestosterone. Anti-androgenic 

responses were elicited by bisphenol C, 

bisphenol F, and bisphenol S as well.

Kitamura, Suzuki et al., 2005 Adequate.

BPA and bisphenol F induced androgenic 

effects in MDA-MB453 cells transfected 

with an AR responsive luciferase reporter 

gene; anti-androgenic effects were elicited 

in the presence of dihydrotestosterone. 

Relative potency of the androgenic and antiandrogenic effects elicited by BPA was 

similar to that of bisphenol F.

Stroheker, Picard et al., 2004 Adequate.

Representative Thyroid Assays

In an assay of thyroid hormonal activity 

whereby induction of growth hormone 

production is assessed in GH3 cells, neither 

BPA nor bisphenol C inhibited growth 

hormone production.

Kitamura, Suzuki et al., 2005 Adequate.

BPA did not exhibit thyroid hormone 

receptor binding in a yeast two-hybrid assay 

system with TRα and coactivator TIF-2.

Kitagawa, Takatori et al., 2003 Adequate.

Immunotoxicity Sufficient data was not located to determine a hazard designation for the immunotoxicity endpoint.

Immune System Effects

(Included under 

Repeated Dose)

Rodent studies (direct or in utero exposure) 

suggest that BPA may modulate immune 

homeostasis, but due to study variations and 

deficiencies, there is no clear evidence that 

BPA interferes with immune function.

Willhite, Ball et al., 2008; 

FAO/WHO, 2011

Inadequate; few of the studies followed 

regulatory protocols (U.S. EPA, 1999) 

or GLP requirements. 

ECOTOXICITY

ECOSAR Class Phenols

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Acute Toxicity HIGH: Based on experimental data indicating a High hazard concern for fish, Daphnid, and green algae.

Fish LC50

Freshwater

Oryzias latipes (Medaka fish) 96-hour LC50

= 13 mg/L 

(Experimental)

EINECS, 2010; Wright-Walters

et al., 2011 

Adequate; guideline study (OECD 

204).

Oryzias latipes (Medaka fish, early life 

stage) 96-hour LC50 = 13.9 mg/L

(Experimental)

Wright-Walters et al., 2011 Adequate; secondary source considered 

the study valid. Test concentrations 

were not analytically measured.

Oryzias latipes (Medaka fish) 

72-hour LC50 = 5.1 mg/L (embryo) 

72-hour LC50 = 6.8 mg/L ( adult male) 

72-hour LC50 = 8.3 mg/L (adult female) 

(Nominal, daily renewal)

EINECS, 2010; Wright-Walters, 

et al., 2011 

Adequate; secondary sources 

considered the study valid. Measured 

test concentrations.

Pimephales promelas (fathead minnow)

96-hour LC50 = 4.7 mg/L (static) 

96-hour LC50 = 4.6 mg/L (flow-through) 

(Experimental) 

No toxicity at levels ≤2.29 mg/L

Alexander, Dill et al., 1988; 

EINECS, 2010; European 

Commission, 2000 

Adequate; ASTM guideline study. 

Similar LC50 values for static and flowthrough measurements indicated 

stability of BPA in water during the 96-

hour test period.

Multiple additional studies of freshwater 

fish species reported 48-96-hour LC50

values in the range of 3-15 mg/L 

European Commission, 2000; 

Wright-Walters et al., 2011 

Although individual studies were 

inadequate based on lack of provided 

study details or insufficient exposure 

duration, the LC50 range supports the 

results of studies considered adequate.

Fish 96-hour LC50 = 12 mg/L

(Estimated) 

ECOSAR: Neutral organics

ECOSAR version 1.11 Narcosis classes (neutral organics) are 

provided for comparative purposes; 

DfE assessment methodology will use 

the lowest estimated toxicity value 

provided by ECOSAR classes that have 

a more specific mode of action relative 

to narcosis.

Fish 96-hour LC50 = 2 mg/L

(Estimated) 

ECOSAR: polyphenols

ECOSAR version 1.11

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Fish LC50

Saltwater

Menidia menidia (silverside fish)

96-hour LC50 = 9.4 mg/L (flow-through) 

(Experimental) 

No discernible effect concentration >4.8 

mg/L

EINECS, 2010; Wright-Walters

et al., 2011; European 

Commission, 2000 

Adequate; U.S. EPA guideline study.

Cyprinodon variegates (sheepshead 

minnow) 

96-hour LC50 = 7.5 mg/L 

(Experimental)

EINECS, 2010 Adequate; EINECS considered the 

study “apparently valid”, but noted 

missing data such as pH, temperature, 

dissolved oxygen.

Daphnid LC50 Daphnia magna (water flea)

48-hour EC50 = 10.2 mg/L 

(Experimental)

EINECS, 2010; European 

Commission, 2000; Alexander, 

Dill et al., 1988

Adequate; ASTM guideline study.

Daphnia magna (water flea)

48-hour EC50 = 3.9 mg/L 

(Nominal)

EINECS, 2010; European 

Commission, 2000 

Adequate; European Commission, 

2000 indicates that analytical 

monitoring was used. 

Daphnid 48-hour LC50 = 7.9 mg/L

(Estimated) 

ECOSAR: Neutral organics

ECOSAR version 1.11 Narcosis classes (neutral organics) are 

provided for comparative purposes; 

DfE assessment methodology will use 

the lowest estimated toxicity value 

provided by ECOSAR classes that have 

a more specific mode of action relative 

to narcosis.

Daphnid 48-hour LC50 = 9.3 mg/L

(Estimated) 

ECOSAR: polyphenols 

ECOSAR version 1.11

Saltwater Invertebrate LC50 Mysidopsis bahia (mysid shrimp)

96-hour LC50 (flow-through) = 1.1 mg/L

(Experimental)

EINECS, 2010; European 

Commission, 2000; Alexander, 

Dill et al., 1988

Adequate; OPPT 830.1035 guideline 

study. 

Acartia tonsa (copepod)

48-hour LC50 (static) = 3.4-5.0 mg/L 

(Nominal)

EINECS, 2010 Inadequate; nominal concentrations 

only, organisms 10-12 days old at start 

of test.

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Green Algae EC50

Freshwater

Pseudokirchneriella subcapitata

96-hour EC50 = 2.7 mg/L (biomass) 

96-hour EC50 = 3.1 mg/L (cell volume) 

(Experimental)

EINECS, 2010; European 

Commission, 2000; Alexander, 

Dill et al., 1988

Adequate; ASTM guideline study.

Pseudokirchneriella subcapitata

96-hour EC50 (biomass) = 2.5 mg/L

(Experimental)

European Commission, 2000 Inadequate; test conditions not 

specified in secondary source. 

Green algae 96-hour EC50 = 9.7 mg/L

(Estimated) 

ECOSAR: Neutral organics

ECOSAR version 1.11 Narcosis classes (neutral organics) are 

provided for comparative purposes; 

DfE assessment methodology will use 

the lowest estimated toxicity value 

provided by ECOSAR classes that have 

a more specific mode of action relative 

to narcosis.

Green algae 96-hour EC50 = 1.7 mg/L

(Estimated)

ECOSAR: polyphenols

ECOSAR version 1.11

Green Algae EC50

Saltwater

Skeletonema costatum

96-hour EC50 = 1.0 mg/L (biomass) 

96-hour EC50 = 1.8 mg/L (chlorophyll a 

content) 

(Experimental)

European Commission, 2000; 

Wright-Walters, Volz et al., 

2011; Alexander, Dill et al., 

1988 

Adequate; ASTM guideline study. Cell 

count and chlorophyll a content are 

both measures of biomass.

Chronic Aquatic Toxicity HIGH: Based on experimental data from multiple studies indicating a High hazard concern for fish.

Fish ChV Branchydanio rerio (Zebrafish) 14-day 

survival

NOEC = 3.2 mg/L 

LOEC = 10.15 mg/L 

(Experimental) 

EINECS, 2010; Wright-Walters, 

Volz et al., 2011 

Adequate; guideline study (OECD 

204).

Branchydanio rerio (Zebrafish) growth and 

reproduction 

NOEC = 0.75 mg/L 

LOEC = 1.5 mg/L

EINECS, 2010; Wright-Walters, 

Volz et al., 2011 

Inadequate; lack of experimental 

design details. 

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(Experimental)

Oryzias latipes (Medaka fish)

60-day survival: 

NOEC = 1.82 mg/L 

Growth: 

NOEC = 0.355 mg/L 

LOEC = 1.82 mg/L 

(Experimental)

EINECS, 2010; Wright-Walters, 

Volz et al., 2011 

Adequate; modified OECD 210 early 

life stage study. 

Oryzias latipes (Medaka fish) 14-day

hatchability

NOEC = 6.25 mg/L 

LOEC = 12.5 mg/L 

(Nominal)

EINECS, 2010; Wright-Walters, 

Volz et al., 2011 

Adequate; early life stage toxicity 

study, although test concentrations 

apparently not measured analytically. 

Oryzias latipes (Medaka fish) 21-day 

reproductive capacity test 

NOEC = 3.1 mg/L 

(Experimental)

EINECS, 2010 Adequate; reproductive toxicity study 

of adult fish. Test methods 

subsequently recommended by OECD 

for elucidation of effects on survival, 

growth, and reproduction of potential 

endocrine disrupting compounds.

Oryzias latipes (Medaka fish) 14-day

hatchability

NOEC = 0.68 mg/L 

LOEC = 2.3 mg/L 

(Experimental)

EINECS, 2010; Wright-Walters, 

Volz et al., 2011 

Inadequate; early life stage toxicity 

study, insufficient study details in 

secondary sources. Test concentrations 

not measured analytically.

Pimephales promelas (Fathead minnow) 

multigenerational toxicity study

Survival, growth: 

NOEC = 0.16 mg/L 

LOEC: = 0.64 mg/L 

Hatchability: 

NOEC = 0.016 mg 

LOEC = 0.16 mg/L

EINECS, 2010; Wright-Walters, 

Volz et al., 2011 

Adequate, although secondary sources 

did not mention guidelines followed. 

Test concentrations were analytically 

measured.

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(Experimental)

Pimephales promelas (Fathead minnow) 

32-day post-hatch survival and growth 

NOEC = 0.64 mg/L 

(Experimental)

Wright-Walters, Volz et al., 

2011 

Adequate; considered valid GLP study 

by secondary source. Chemical 

exposures measured analytically.

Pimephales promelas (Fathead minnow) 

29-30 day survival, growth, and 

development study 

Survival, growth: 

NOEC = 1.0 mg/L 

Development: 

NOEC = 0.1 mg/L 

(Experimental)

Wright-Walters, Volz et al., 

2011 

Adequate; considered valid GLP study 

by secondary source. Chemical 

exposures measured analytically.

Oncorhynchus mykiss (Rainbow trout)

28-day growth

NOEC = 3.64 mg/L 

LOEC = 11 mg/L

(Experimental)

EINECS, 2010; Wright-Walters, 

Volz et al., 2011 

Adequate; guideline study (OECD 215) 

of juvenile growth rate. 

Cyrinus carpio (carp) 28- and 49-day 

growth

28-day NOEC = 0.6 mg/L 

49-day NOEC = 0.1 mg/L 

(Experimental)

EINECS, 2010 Adequate; guideline study (not 

specified).

Cyrinus carpio (carp) 28-day survival/

growth

NOEC = 0.74 mg/L 

(Experimental)

Wright-Walters, Volz et al., 

2011 

Inadequate; non-GLP and abstract 

only. 

Poecilia reticulata (guppy)

21-day sperm count 

LOEC = 0.274 mg/L 

(Experimental)

Wright-Walters, Volz et al., 

2011 

Inadequate; insufficient study details in 

secondary source.

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Poecilia reticulata (guppy) 30-day survival

NOEC = 0.5 mg/L 

LOEC = 5.0 mg/L 

(Experimental)

EINECS, 2010; Wright-Walters, 

Volz et al., 2011 

Inadequate; insufficient study details in 

secondary source.

Fish ChV = 1.4 mg/L

(Estimated) 

ECOSAR: Neutral organics

ECOSAR version 1.11 Narcosis classes (neutral organics) are 

provided for comparative purposes; 

DfE assessment methodology will use 

the lowest estimated toxicity value 

provided by ECOSAR classes that have 

a more specific mode of action relative 

to narcosis.

Fish ChV = 0.9 mg/L

(Estimated) 

ECOSAR: polyphenols

ECOSAR version 1.11

Daphnid ChV Daphnia magna 21-day survival, molting 

success, growth, reproduction 

NOEC = 3.16 mg/L 

(Experimental) 

Caspers, 1998; EINECS, 2010; 

European Commission, 2000

Adequate; guideline study (OECD 

202). 

Daphnid ChV = 1.1 mg/L

(Estimated) 

ECOSAR: Neutral organics

ECOSAR version 1.11 Narcosis classes (neutral organics) are 

provided for comparative purposes; 

DfE assessment methodology will use 

the lowest estimated toxicity value 

provided by ECOSAR classes that have 

a more specific mode of action relative 

to narcosis.

Daphnid ChV = 3.2 mg/L

(Estimated) 

ECOSAR: polyphenols 

ECOSAR version 1.11

Green Algae ChV Green algae ChV = 3.3 mg/L

(ECOSAR: Neutral organics) 

ECOSAR version 1.11 Narcosis classes (neutral organics) are 

provided for comparative purposes; 

DfE assessment methodology will use 

the lowest estimated toxicity value 

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provided by ECOSAR classes that have 

a more specific mode of action relative 

to narcosis.

Green algae ChV = 0.278 mg/L

(ECOSAR: polyphenols)

ECOSAR version 1.11

Teratogenicity in Frog Embryos Rana temporaria (common frog) 20-day 

embryo survival

NOEC = 0.1 mg/L 

LOEC = 1 mg/L

(Experimental)

EINECS, 2010; Wright-Walters, 

Volz et al., 2011 

Inadequate; embryos used, no chemical 

analysis of exposure concentrations.

Xenopus laevis (African clawed frog) 

90-day survival, growth, development 

NOEC = 0.5 mg/L 

(Experimental)

EINECS, 2010; Wright-Walters, 

Volz et al., 2011 

Adequate GLP study, although study 

guidelines were not mentioned in the 

secondary source. Test concentrations 

were analytically measured.

Xenopus laevis (African clawed frog) 

12-week survival, growth

NOEC = 0.23 mg/L 

(Experimental) 

EINECS, 2010; Wright-Walters, 

Volz et al., 2011 

Inadequate; study report lacks 

information regarding test conditions 

(e.g., temperature, water quality). Test 

concentrations were not analytically 

measured. Non-GLP study.

ENVIRONMENTAL FATE

Transport Based on the Level III fugacity models incorporating the located experimental property data, BPA is expected 

to partition primarily to soil. BPA is expected to be moderately mobile in soil based on experimental Koc

studies. Leaching of BPA through soil to groundwater is not expected to be an important transport mechanism. 

Estimated volatilization half-lives indicate that it will be nonvolatile from surface water. Volatilization from 

dry surfaces is also not expected based on its measured vapor pressure. In the atmosphere, BPA is expected to 

exist in the particulate phase based on its measured vapor pressure. Particulates will be removed from air by 

wet or dry deposition. 

Henry’s Law 

Constant(atm-m3/mole)

<1x10-8 (Estimated) EPI Cutoff value for nonvolatile 

compounds based on professional 

judgment.

Sediment/Soil 890 ± 30 L/kg Höllrigl-Rosta, Vinken et al., Adequate, data from guideline study as 

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Adsorption/Desorption

Coefficient – Koc

OECD Test Guideline 106 (Measured) 2003; EINECS, 2010 reported in secondary source.

795.9 

OECD Test Guideline 106 (Measured)

Fent, Hein et al., 2003; EINECS, 

2010

Adequate, data from guideline study as 

reported in secondary source.

251-1507, mean value of 962 (Measured) Ying and Kookana, 2005; 

EINECS, 2010 

Adequate, data from guideline study as 

reported in secondary source.

335-703, mean value of 375 (Measured) Loffredo and Senesi, 2006; 

EINECS, 2010

Adequate, data from guideline study as 

reported in secondary source.

778 (Measured) Ying and Kookana, 2003; 

EINECS, 2010

Adequate, valid nonguideline study as 

reported in secondary source.

115 (Measured) Zeng, Zhang et al., 2006; 

EINECS, 2010

Adequate, valid nonguideline study as 

reported in secondary source.

335-703; reported as Log Koc = 2.53-2.85 at 

pH 4.5-5.9 (Measured)

Canada, 2008 Adequate, data from guideline study as 

reported in secondary source.

The levels of BPA measured in water and 

bed sediments were used to calculate Koc

values. The range of results was 11,220-

17,000 (log Koc 4.04-4.23). (Measured)

Patrolecco, Capri et al., 2006; 

EINECS, 2010 

Adequate, data are from a valid

nonguideline study; Koc values are 

likely for the unionized species. 

Level III Fugacity Model Air = <1% (Estimated)

Water = 8.4%

Soil = 74%

Sediment = 18%

EPI Experimental water solubility 

(0.12 g/L) and vapor pressure

(3.99x10-8 mm Hg) used in model 

calculations.

Persistence VERY LOW: BPA has passed Ready Biodegradability tests, OECD 301 F and OECD 301C, within the 10-day 

window. Experimental data using a wide variety of innocula have demonstrated that rapid primary and 

ultimate biodegradation of BPA occurs under aerobic condition in water and soil. The biodegradation of BPA 

does not result in the formation of stable metabolites. Aerobic biodegradation processes are anticipated to be 

the predominant environmental removal process. Experimental data indicate that BPA does not biodegrade 

under anaerobic conditions. Although models suggest that BPA may display limited partitioning to sediment, it 

has been detected in sediment samples. BPA may also undergo removal by both direct and indirect photolysis 

in environmental waters, although this process is anticipated to be far slower than aerobic biodegradation 

processes.

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Water Aerobic Biodegradation OECD 301B: No biodegradation of BPA 

was observed with modified Sturm test 

(Measured)

EINECS, 2010 Adequate, data from a guideline study

as reported in secondary source. 

OECD 301C: Reported biodegradation 

half-lives of <3.5 days in river surface 

water samples (Measured)

MITI, 1992; Canada, 2008 Adequate, data from a guideline study

as reported in secondary source. 

OECD 301D: No biodegradation of BPA 

was observed with OECD 301D closed 

bottle test (Measured)

EINECS, 2010 Adequate, data from a guideline study

as reported in secondary source. 

OECD 301F: Average percent removal by 

biochemical oxygen demand (BOD) was 

89%; 10-day window met and no BPA 

detected by HPLC after 28 days (Measured)

CERI, 2004; EINECS, 2010 Adequate, data from a guideline study.

OECD 301F: Rapid biodegradation by 

standard aerobic 28-day ready 

biodegradability test (Measured)

West and Goodwin, 1997; 

Canada, 2008; EINECS, 2010

Adequate, data from a guideline study.

BPA met the criteria for inherently 

biodegradable substances; using a modified 

semi-continuous activated sludge (SCAS) 

procedure (Measured)

Turner and Watkinson, 1986; 

EINECS, 2010 

Adequate, data from a valid

nonguideline study. 

Degradation was noted in 40 of 44 river 

water systems; 6 river water systems were 

able to mineralize the substance completely 

and 34 showed total organic carbon (TOC) 

removal of 40-90% (Measured)

Ike, Chen et al., 2006; EINECS, 

2010 

Adequate, data from a valid 

nonguideline study. 

BPA biodegradation half-life of <4 days 

was measured in natural waters following a 

1- to 4-day adaptation period – acclimation

(Measured)

Dorn, Chou et al., 1987; Canada, 

2008 

Adequate, data from a valid 

nonguideline study. 

Biodegradation half-lives of 0.5-3.5 days in 

river surface water samples after a lag phase 

of 2-8 days (Measured)

Klečka, Gonsior et al., 2001; 

Canada, 2008 

Adequate, data from a valid 

nonguideline study. 

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River water samples had BPA 

biodegradation half-lives of 2, 3 and 6 days; 

BPA was completely degraded after 10-15 

days (Measured)

Kang and Kondo, 2002; Canada, 

2008; EINECS, 2010 

Adequate, data from a valid 

nonguideline study. 

River water degradation of BPA half-life of 

3-4 days; some seawater degradation of 

BPA after lag period of 30-40 days 

(Measured)

Kang and Kondo, 2005; 

EINECS, 2010 

Adequate, data from a valid 

nonguideline study. 

>90% degradation after 56 days in 

seawater; or BPA degradation half-life of 

14.4 after lag period of 35 days (Measured)

Ying and Kookana, 2003; 

EINECS, 2010 

Adequate, data from a valid 

nonguideline study. 

Volatilization Half-life 

for Model River

>1 year (Estimated) EPI

Volatilization Half-life 

for Model Lake

>1 year (Estimated) EPI

Soil Aerobic Biodegradation Biodegradation half-life of 7 days 

(Measured)

EINECS, 2010; Canada, 2008; 

Ying and Kookana, 2005

Adequate, data from a valid 

nonguideline study.

Biodegradation half-life of 3 days 14C-BPA 

was transiently converted to up to five 

metabolites. The parent 14C-BPA and 

14C-BPA metabolites were not detected 

after 3 days (Measured)

Fent, Hein et al., 2003; Canada, 

2008 

Adequate, data from a valid 

nonguideline study. 

Anaerobic 

Biodegradation

No biodegradation after 70 days (Measured) Ying and Kookana, 2005; 

EINECS, 2010 

Adequate, data from a valid 

nonguideline study.

Soil Biodegradation w/ 

Product Identification

No data located.

Sediment/Water 

Biodegradation 

No biodegradation after 70 days; anaerobic 

conditions with aquifer water and sediment 

(Measured)

Ying and Kookana, 2003; 

Canada, 2008; EINECS, 2010 

Adequate, data from a valid 

nonguideline study. 

50% dissipation times in days

Aerobic conditions:

Canada, 2008 Invalid; losses of up to 40% of the 

initial amount applied occurred in the 

4-72 
FINAL REPORT – January 2014 

Bisphenol A CASRN 80-05-7

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

river water-sediment test system: 0.57

groundwater-aquifer test system: 1.212 

Anaerobic conditions: 

river water-sediment test system: 1.38

groundwater-aquifer test system: 2.75

(Measured)

sterile (control) treatments.

BPA was not biodegraded under anaerobic 

conditions using estuarine sediments 

(Measured)

Voordeckers, Fennell et al., 

2002 

Adequate, data from a valid 

nonguideline study. 

Air Atmospheric Half-life 1.6 hours (Estimated) EPI

Reactivity Photolysis Direct and indirect photochemical 

transformation of BPA in aquatic media has 

been described (Measured)

Chin, Miller et al., 2004; 

Canada, 2008; EINECS, 2010 

Adequate; the located secondary 

sources do not quantify the importance 

of this process, although it is not 

anticipated to compete with 

biodegradation in natural waters. 

Hydrolysis Not a significant fate process (Estimated) Wolfe and Jeffers, 2000; 

Professional judgment 

Substance does not contain functional 

groups that would be expected to 

hydrolyze readily under environmental 

conditions.

Pyrolysis No data located.

Environmental Half-life 75 days (Estimated) EPI; PBT Profiler Half-life estimated for the predominant 

compartment as determined by EPI and 

the PBT Profiler methodology.

Bioconcentration LOW: The measured fish BCF values reported for a number of experimental studies are <100.

Fish BCF 3.5–68 (Measured) Canada, 2008 As reported in secondary source.

67 (Measured) EINECS, 2010 As reported in secondary source.

38 ± 21 L/kg in halibut (Varaspar

variegates) (Measured)

EINECS, 2010; Lee, Soyano et 

al., 2004

As reported in secondary source.

73.4 Killifish (Oryzias latipes) (Measured) Takino, Tsuda et al., 1999; 

EINECS, 2010

Adequate.

4-73 
FINAL REPORT – January 2014 

Bisphenol A CASRN 80-05-7

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

5.1-13.8 (Measured)

<20-67.7 (Measured)

Canada, 2008; MITI, 1992 Adequate.

3.5-5.5 (Measured) Lindholst, Pedersen et al., 2001; 

Canada, 2008;

Adequate.

Green Algae BCF From the Tama River, Japan

Periphytons: 18-650 

Benthos: 8-170 (Measured)

Adequate.

Earthworms BCF 7.9 kg/kg (Estimated) EINECS, 2010 Adequate.

Metabolism in fish Metabolites identified 7 days after exposure 

in fish (Danio rerio) (Measured)

Kang, Katayama et al., 2006; 

Canada, 2008, 

Adequate.

Fish plasma half-life of BPA was calculated 

to be 3.75 hours following injection of the 

compound (Measured)

Lindholst, Pedersen et al., 2001; 

Canada, 2008 

Adequate.

ENVIRONMENTAL MONITORING AND BIOMONITORING

Environmental Monitoring BPA was detected in environmental samples, including those from groundwater, wastewater treatment plume water, 

landfill lagoon water, drinking water, streams and rivers, and sediments.

Ecological Biomonitoring BPA was found in ecological samples; detectable levels were found in snails, mussels, fish, clams, and zooplankton.

Human Biomonitoring BPA was detected in a variety of human biological samples including serum, breast milk, urine, fetal blood, and 

umbilical cord blood. This chemical was included in the NHANES biomonitoring report (CDC, 2011).

4-74 
FINAL REPORT – January 2014 

Akahori, Y.; Makai, M.; Yamasaki, K.; et al. Relationship between the results of in vitro receptor binding assay to human estrogen 

receptor α and in vivo uterotrophic assay: Comparative study with 65 selected chemicals. Toxicol. In vitro 2008, 22:225-231. 

Alexander, H., Dill, D., Smith, L., et al. Bisphenol-A: Acute aquatic toxicity. Environ. Toxicol. Chem., 1988. 7:19-26. 

Blair, R., Branham, W., Hass, B., et al. The estrogen receptor relative binding affinities of 188 natural and xenochemicals: Structural 

diversity of ligands. Toxicol. Sci., 2000. 54:138-153. 

Canada. Environment Canada, Health Canada. Screening Assessment for the Challenge Phenol, 4,4' (1-methylethylidene)bis- 

(Bisphenol A) CAS 80-05-7. October 2008. 

CDC (Centers for Disease Control and Prevention). Fourth national report on human exposure to environmental chemicals, updated 

tables. Department of Health and Human Services. 2011. http://www.cdc.gov/exposurereport/ (accessed on May 10, 2011). 

Chapin, R.E., Adams, J., Boekelheide, K., et al. NTP-CERHR Expert Panet report on the reproductive and developmental toxicity of 

bisphenol A. Birth Defects Research. Part B. Developmental and Reproductive Toxicology. 2008. 83:157-395. 

Chemicals Evaluation and Research Institute (CERI, Japan), 2004. Biodegradation study of BPA by microorganisms. Study number 

14293, Final Report. 

Chen, M.-Y., Michihiko, I., Fujita, M. Acute toxicity, mutagenicity, and estrogenicity of bisphenol-A and other bisphenols. Environ. 

Toxicol., 2002. 17:80-86. 

Chin, Y-P.; Miller, P.; Zeng, L.; Cawley, k.; Weavers, L. Photosensitized Degradation of Bisphenol A by Dissolved Organic Matter. 

Environ. Sci. Technol. 2004, 38, 5888-5894. 

CHRIS, Chemical Hazards Response Information System. Cautionary Response Information. Bisphenol A. 

http://cameochemicals.noaa.gov/chris/BPA.pdf. 1999. 

Coleman, K.P., Toscano, W.A., Wiese, T.E. QSAR Models of the in vitro estrogen activity of bisphenol A analogs. QSAR & 

Combinatorial Science. 2003. 22:78-88. 

Dorn, P.; Chou, C.; Gentempo, J. Degradation of bisphenol-A in natural waters. Chemosphere, 1987, 16(7), 1501-1507. 

ECOSAR (2012) Ecological Structure Activity Relationship (ECOSAR) Version 1.11. Washington, DC: U.S. Environmental 

Protection Agency. http://www.epa.gov/oppt/newchems/tools/21ecosar.htm. 

EINECS. 4,4’-Isopropylidenediphenol (bisphenol A). European Union Risk Assessment Report. 2010.

4-75 
FINAL REPORT – January 2014 

EPI (EPIWIN/EPISUITE) Estimations Programs Interface for Windows, Version 4.00. U.S. Environmental Protection Agency: 

Washington D.C. http://www.epa.gov/opptintr/exposure/. 

ESIS (European chemical Substances Information System) Classification, labeling and Packaging of dangerous substances annex VI 

to regulation (EC) No 1272/2008 [Online] http://esis.jrc.ec.europa.eu/ (accessed on June 10, 2011). 

European Commission. IUCLID Dataset for 4,4-isopropylidenediphenol (CAS No. 80-05-7). European Chemicals Bureau, February 

19, 2000. 2000. 

FAO/WHO. Toxicological and health aspects of bisphenol A. Report of Joint FAO/WHO expert meeting 2-5 November 2010 and 

report of stakeholder meeting on bisphenol A 1 November 2010. Food and Agriculture Organization of the United Nations; 

World Health Organization. Ottawa, Canada. 2011. 

Fent, G.; Hein, W.; Moendel, M.; Kubiak, R. Fate of 14C-bisphenol A in soils. Chemosphere, 2003, 51; 735-746. 

Hansch, C., Leo, A., D. Hoekman. Exploring QSAR - Hydrophobic, Electronic, and Steric Constants. Washington, DC: American 

Chemical Society., 1995., p. 131 

Hashimoto, Y.; Nakamura, M. Estrogenic activity of dental materials and bisphenol-A related chemicals in vitro. Dent. Mater. J.

2000, 19(3):245-262. 

Hashimoto, Y.; Moriguchi, Y.; Oshima, H.; et al. Measurement of estrogenic activity of chemicals for the development of new dental 

polymers. Toxicol. In vitro 2001, 15:421-425. 

Höllrigl-Rosta, A.; Vinken, R.; Lenz, M.; Schäffer, A. Sorption and dialysis experiments to assess the binding of phenolic xenobiotics 

to dissolved organic matter in soil. Environ. Toxicol. Chem., 2003, 22(4), 746-752. 

Ike, M.; Chen, M.Y.; Danzl, E.; et al. Biodegradation of a variety of bisphenols under aerobic and anaerobic conditions. Water Sci. 

Technol. 2006, 53:153-159. 

Kang, J-H.; Kondo, F. Bisphenol A degradation by bacteria isolated from river water. Arch. Environ. Contam. Toxicol., 2002, 43, 

265-269. 

Kang, J-H.; Kondo, F. Bisphenol A degradation in seawater is different from that in river water. Chemosphere, 2005, 60, 1288-1292. 

Kang, J-H.; Katayama, Y.; Kondo, F. Biodegradation or metabolism of bisphenol A: from microorganisms to mammals. Toxicology, 

2006, 217, 81-90. 

4-76 
FINAL REPORT – January 2014 

Kitagawa, Y., Takatori, S., Oda, H., et al. Detection of thyroid hormone receptor-binding activities of chemicals using a yeast twohybrid assay. J. Health Sci. 2003, 49(2):99-104. 

Keri R.A., Ho S-M, Hunt, P., et al. An evaluation of evidence for the carcinogenic activity of bisphenol A. Reprod Toxicol. 2007. 

24(2):240-252. 

Kitamura, S, Suzuki, T., Sanoh, S., et al. Comparative study of the endocrine-disrupting activity of bisphenol A and 19 related 

compounds. Toxicol. Sci., 2005. 84:249-259. 

Klečka, G.; Gonsior, S.; West, R.; Goodwin, P.; Markham, D.; Biodegradation of bisphenol A in aquatic environments: river dieaway. Environ. Toxicol., Chem. 2001, 20(12): 2725-2735. 

Laws, S., Yavanhxay, S, Cooper, R., et al. Nature of the binding interaction for 50 structurally diverse chemicals with rat estrogen 

receptors. Toxicol. Sci. 2006, 94(1):46-56. 

Lee, H.; Soyano, K.; Ishimatsu, A.; Nagae, M.; Kohra, S.; Ishibashi, Y.; Arizono, K.; Takao, Y. Bisphenol A and nonylphenol 

bioconcentration in spotted halibut Varaspar variegates. Fisheries Science, 2004, 70, 192-194. 

Lindholst, C.; Pedersen, S.; Bjerregaard, P. Uptake, metabolism and excretion of bisphenol A in the rainbow trout (Oncorhynchus 

mykiss). Aquat. Toxicol., 2001, 55:75-84. 

Loffredo, E.; Senesi, N. Fate of anthropogenic organic pollutants in soils with emphasis on adsorption/desorption processes of 

endocrine disruptor compounds. Pure Appl. Chem., 2006, 78(5), 947-961. 

METI. Current status of testing methods development for endocrine disruptors. Ministry of Economy, Trade and Industry, Japan. 6th

meeting of the task force on Endocrine Disruptors Testing and Assessments (EDTA). 24-25 June, 2002. Tokyo. 2002.

Miller, D.; Wheals, B.B.; Beresford, N.; et al. Estrogenic activity of phenolic additives determined by an in vitro yeast bioassay. 

Environ. Health Perspect. 2001, 109(2):133-138. 

MITI. Biodegradation and bioaccumulation data of existing chemicals based on the CSCL Japan. 1998, Compiled under the 

supervision of Chemical Products Safety Division, Basic Industries Bureau, Ministry of International Trade & Industry, Japan; 

Chemicals Inspection & Testing Institute, Japan. Ed.; Japan Chemical Industry Ecology- Toxicology & Information Center: 

1998. 

Nakanishi, J.; Miyamoto, K.; AIST Risk Assessment Document Series No. 4 – Bisphenol A. 2007 Available at: 

http://unit.aist.go.jp/crm/index_e.html as of February 09, 2010. 

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NIOSH. Skin Notation (SK) Profile, Bisphenol A (BPA) [CAS No. 80-05-7]. Department of Health and Human Services; Centers for 

Disease Control and Prevention; National Institute for Occupational Safety and Health. 2010.

Nishihara, T.; Nishikawa, J.; Kanayama, T.; et al. Estrogenic activities of 517 chemicals by yeast two-hybrid assay. J. Health Sci.

2000, 46(4) 282-298. 

NTP-CERHR. Monograph on the potential human reproductive and developmental effects of bisphenol A. National Toxicology 

Program; U.S. Department of Health and Human Service. Center for the Evaluation of Risks to Human Reproduction. NIH 

Publication No. 08-5994. September 2008. 

NTP. Carcinogenesis bioassay of bisphenol-A (CAS No. 80-05-7) in F344 rats and B6C3F1 mice (feed study). National Toxicology 

Program. Technical Report No. 215, Order No. PB82-184060. 1982.

NTP. Bisphenol A. National Toxicology Program, Department of Health and Human Services. http://ntpapps.niehs.nih.gov/ntp_tox/index.cfm?searchterm=80-05-7&fuseaction=ntpsearch.searchresults. 2010.

Ogawa, Y.; Kawamura, Y.; Wakui, C.; et al. Estrogenic activities of chemicals related to food contact plastics and rubbers tested by 

the yeast two-hybrid assay. Food Addit. Contam. 2006, 23(4):422-430. 

O’Neil, M., et al. eds. e-Merck Index. 14th ed. Basic Search. Whitehouse Station, NJ: Merck & Co., Inc. 2010. 

https://themerckindex.cambridgesoft.com/TheMerckIndex/index.asp as of December 10, 2010. 

Patrolecco, L.; Capri, S.; De Angelis, S.; Pagnotta, R.; Polesello, S.; Valsecchi, S. Partition of nonylphenol and related compounds 

among different aquatic compartments in Tiber River (central Italy). Water, Air and Soil Pollution, 2006, 172, 151-166. 

PBT Profiler Persistent (P),Bioaccumulative (B), and Toxic (T) Chemical (PBT)Profiler, U.S. Environmental Protection Agency: 

Washington D.C. www.pbtprofiler.net. 

Perez, P., Pulgar, R., Olea-Serrano, F., et al. 1998. The estrogenicity of bisphenol A-related diphenylalkanes with various substituents 

at the central carbon and the hydroxyl groups. Environ. Health Perspect., 1998. 106(3):167-174. 

Stroheker, T., Picard, K., Lhuguenot, J., et al. Steroid activities comparison of natural and food wrap compounds in human breast 

cancer cell lines. Food Chem. Toxicol. 2004, 42:887-897. 

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latipes) Rep Shiga Prefecture. Public Health & Environ Sci, 1999, 34, 65-67. 

Turner, S.; Watkinson, R. Diphenylol Propane: An Assessment of Inherent Biodegradability. Shell Company Report. 1986.

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Tyl, R.W.; Myers, C.B.; Marr, M.C.; Thomas, B.F.; Keimowitz, A.R.; Brine, D.R.; Veselica, M.M.; Fail, P.A.; Chang, T.Y.; Seely, 

J.C.; Joiner, R.L.; Butala, J.H.; Dimond, S.S.; Cagen, S.Z.; Shiotsuka, R.N.; Stropp, G.D.; Waechter, J.M. Three-generation 

reproductive toxicity study of dietary bisphenol A in CD Sprague-Dawley rats. Toxicol Sci. 2002. 68:121–146. As cited in 

NTP-CERHR, 2008 and Chapin et al., 2008. 

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Initiative Environmental Protection Agency: Washington D.C. 2010. http://www.epa.gov/opptintr/sf/pubs/noncanscreen.htm#systemic (accessed on February 09, 2011). 

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and bisphenol A in estuarine sediments. Environ. Sci. Technol. 2002. 36, 696-701. 

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Environmental Health Sciences (311-334). Boca Raton: Lewis Publishers. 

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Zeng, G.; Zhang, C.; Huang, G.; Yu, J.; Wang, Q.; Li, J.; Xi, B.; Liu, H. Adsorption behaviour of bisphenol A on sediments in 

Xiangjiang River, south-central China. Chemosphere, 2006, 65, 1490-1499. 

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Bisphenol F

OH OH CASRN: 620-92-8

MW: 200.24

MF: C13H12O2

Physical Forms: 

 Neat: Solid

Use: Developer for thermal paper

SMILES: OC(CCC(C1)CC(CCC(O)C2)C2)C1

Synonyms: Phenol, 4,4'-methylenebis-; Bis(4-hydroxyphenyl)methane; 4,4'-Methylenebis(phenol); 4,4'-Dihydroxydiphenylmethane; 4,4'-Methylene diphenol; Bis(4-

hydroxyphenyl)methane; Bis(p-hydroxyphenyl)methane; Phenol, 4,4'-methylenedi-; p,p'-Bis(hydroxyphenyl)methane; p-(p-Hydroxybenzyl)phenol

Polymeric: No

 Oligomers: Not applicable

Metabolites, Degradates and Transformation Products: 4,4’-dihydroxybenzophenone, bis(4-hydroxyphenyl)methanol, 4-hydroxyphenyl-4-hydroxybenzoate, 

4-hydroxybenzoate and 1,4-hydroquinine, sulfate conjugate of bisphenol F

Analog: Bisphenol A (80-05-7)

 Endpoint(s) using analog values: Reproductive and developmental 

toxicity, dermal irritation

Analog Structure: 

OH OH

4-80 

Structural Alerts: Phenols, neurotoxicity (U.S. EPA, 2010)

Risk Phrases: Not classified by Annex VI Regulation (EC) No 1272/2008 (ESIS, 2011).

Risk Assessments: None identified
FINAL REPORT – January 2014 

Bisphenol F CASRN 620-92-8

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

PHYSICAL/CHEMICAL PROPERTIES

Melting Point (°C) 162.5 (Measured) Lide, 2008 Adequate.

Boiling Point (°C) Sublimes Lide, 2008 Adequate.

Vapor Pressure (mm Hg) 3.7x10-7 (Estimated) EPI

Water Solubility (mg/L) 190 (Estimated) EPI

Log Kow 2.91 (Measured) Hansch, Leo et al., 1995 Adequate.

Flammability (Flash Point) No data located.

Explosivity No data located.

pH No data located.

pKa 7.55 (Measured) Serjeant and Dempsey, 1979 Adequate.

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FINAL REPORT – January 2014 

Bisphenol F CASRN 620-92-8

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

HUMAN HEALTH EFFECTS

Toxicokinetics Bisphenol F is readily absorbed following oral exposure and is widely distributed, metabolized to multiple 

metabolites, and excreted primarily in the urine and to a lesser extent in the feces.

Dermal Absorption in vitro No data located.

Absorption, 

Distribution, 

Metabolism & 

Excretion

Oral, Dermal or Inhaled Single gavage doses of 7 or 100 mg/kg 

[

3

H]bisphenol F were administered to 

pregnant or nonpregnant Sprague-Dawley 

rats. Approximately 15-20% of the 

administered radioactivity was recovered 

in the urine during the first 24 hours 

postdosing, indicating that bisphenol F 

was readily absorbed. By 96 hours 

postdosing, nearly 50% of the dose had 

been recovered in the urine; fecal 

excretion accounted for <20% of the 

dose. Parent compound accounted for 

<25% of the radioactivity in the urine and 

at least six urinary metabolites were 

detected; the major urinary metabolite 

(>50%) appeared to be a sulfate 

conjugate of bisphenol F. At 96 hours 

postdosing, <1% of the administered 

radioactivity was detected in selected 

organs and tissues; the highest levels 

were found in the liver (0.5% of dose). 

Radioactivity was detected in placenta, 

amniotic fluid, and fetuses of pregnant 

rats. In bile-cannulated rats, nearly 50% 

of an administered dose of [3

H]bisphenol 

F was collected in the bile between 2 and 

8 hours postdosing, indicating the 

involvement of enterohepatic cycling of 

bisphenol F and/or its metabolites.

Cabaton, Chagnon et al., 2006 Adequate.

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FINAL REPORT – January 2014 

Bisphenol F CASRN 620-92-8

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Acute Mammalian Toxicity LOW: Based on an experimental rat LD50 of 4,950 mg/kg. No data were located to assess acute inhalation or 

dermal toxicity. 

Acute Lethality Oral Rat oral LD50 = 4,950 mg/kg Smyth, Carpenter et al., 1962 Adequate.

Dermal No data located.

Inhalation No data located.

Carcinogenicity MODERATE: Estimated using OncoLogic expert system which describes a concern for this compound as a 

potential carcinogen or tumorigenesis promoter arising from its structural similarity to 

estrogenic/androgenic compounds, using the “phenols and phenolic compounds” structural alert.

OncoLogic Results Moderate (Estimated)

OncoLogic class: phenols and phenolic 

compounds 

OncoLogic OncoLogic SAR analysis using the 

phenols and phenolic compounds 

class. 

Carcinogenicity (Rat and 

Mouse)

No data located.

Combined Chronic 

Toxicity/Carcinogenicity

No data located.

Genotoxicity LOW: Bisphenol F did not cause gene mutations or chromosomal aberrations in located in vitro assays in 

multiple test strains and cell types. Bisphenol F did cause DNA damage in a Comet assay. However, 

assessment guidance indicates a low concern given the negative results for gene mutations and chromosomal 

aberrations assays.

Gene Mutation in vitro Negative; Ames assay in Salmonella 

Typhimurium strains TA98, TA100, 

TA1535, TA1537, and Escherichia coli

W2 uvrA pKM101 with and without 

metabolic activation

Cabaton, Dumont et al., 2009 Adequate.

Negative; umu test in S. typhimurium 

strain TA1335 with and without 

metabolic activation

Chen, Michihiko et al., 2002 Adequate.

Negative; gene mutation tests at the 

Na+/K+ ATPase locus and hprt locus of 

Syrian hamster embryo cells

Tsutsui, Tamura et al., 2000 Adequate.

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FINAL REPORT – January 2014 

Bisphenol F CASRN 620-92-8

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Gene Mutation in vivo No data located.

Chromosomal Aberrations 

in vitro

Negative; chromosomal aberrations in 

Syrian hamster embryo cells

Tsutsui, Tamura et al., 2000 Adequate.

Negative; micronucleus test in HepG2 

cells

Cabaton, Dumont et al., 2009 Adequate.

Chromosomal Aberrations 

in vivo

No data located.

DNA Damage and Repair Positive; DNA damage (single and 

double strand breaks); Comet assay 

HepG2 cells

Cabaton, Dumont et al., 2009 Adequate.

Other No data located.

Reproductive Effects MODERATE: Estimated based on analogy to BPA. Key studies identified by NTP for the analog BPA 

indicate there are multiple distinct endpoints with NOAELs in the range of Moderate hazard concern with 

LOAELs in the range of Low hazard concern. At the target dose of 50 mg/kg-day (BPA), the NOAELs are 

on the margin of High and Moderate hazard, according to DfE criteria. Benchmark Dose (BMD) Modeling 

conducted by NTP, which interpolates between NOAEL and LOAEL values, yields values that further 

support a Moderate hazard designation. The limited test data on bisphenol F were inadequate for the 

evaluation of hazard using DfE criteria. Changes in uterine weight were reported following in vivo exposure 

in rats. However, a 28-day gavage study reported no effects on reproductive organ weights, estrous cycles, or 

spermatocytes at doses up to 500 mg/kg-day. 

Reproduction/ 

Developmental Toxicity 

Screen

Bisphenol F increased absolute and 

relative uterine weight in a rat 

uterotrophic assay.

Yamasaki, Noda et al., 2004 Adequate.

28-Day study with Crj:CD SpragueDawley rats (10/sex/dose), gavaged with 

0, 20, 100, or 500 mg/kg-day: 

NOAEL = 500 mg/kg-day

(endocrine/reproductive parameters). 

No changes in spermatological findings, 

estrous cycles, reproductive organ 

weight, or thyroid weight.

Higashihara, Shiraishi et al., 2007 Adequate.

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FINAL REPORT – January 2014 

Bisphenol F CASRN 620-92-8

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Exposure to bisphenol F in immature rats 

resulted in a dose-dependent increase in 

relative wet and dry uterine weight and 

increased vaginal cornification in 

immature female Wistar rats. 

LOAEL = 100 mg/kg-day (based on 

increased relative wet uterine weight

NOAEL = 50 mg/kg-day

Stroheker, Chagnon et al., 2003 Adequate.

Combined Repeated Dose 

with Reproduction/ 

Developmental Toxicity 

Screen

No data located.

4-85 
FINAL REPORT – January 2014 

Bisphenol F CASRN 620-92-8

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Reproduction and Fertility 

Effects

Parental systemic toxicity:

NOAEL = 5 mg/kg bw-day 

LOAEL = 50 mg/kg bw-day for 12% 

decreased terminal body weight in F1

parental males

Reproductive toxicity: 

Females: NOAEL = 50 mg/kg bw-day 

LOAEL = 500 mg/kg bw-day for 

decreases in number of implantation sites, 

delayed vaginal opening in F1, F2, F3

offspring 

BMDLs (change of 1 standard deviation 

from control) reported for delayed 

vaginal opening (females)- 

F1 = 176 mg/kg-day 

F2 = 228 mg/kg-day 

F3 = 203 mg/kg-day 

Males: NOAEL = 50 mg/kg bw-day, 

LOAEL = 500 mg/kg-day for delayed 

preputial separation in F1 males

BMDLs (change of 1 standard deviation 

from control) reported for delayed 

preputial separation (males)- 

F1 = 163 mg/kg-day 

F2 = 203 mg/kg-day 

Estimated by analogy)

NTP-CERHR, 2008; Professional 

judgment 

Based on the analog BPA; 

adequate, guideline study as 

reported in the secondary source. 

Classified by NTP-CERHR as

having High Utility. 

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Parental systemic toxicity:

NOAEL = 5 mg/kg bw-day 

LOAEL = 50 mg/kg bw-day for increased 

incidences of centrilobular hepatocellular 

hypertrophy in males and females 

Reproductive toxicity: 

NOAEL = 50 mg/kg bw-day 

LOAEL = 600 mg/kg bw-day for 

increased gestation length, decreased 

epididymal sperm concentration in F1

males, increased incidence of gross 

ovarian cysts in F1 and F2 females

BMD1 (change of 1 standard deviation 

from control) reported for increased 

gestation length

F0 = 1144 mg/kg-day (BMDL = 599 

mg/kg-day) 

F1 = 772 mg/kg-day (BMDL = 531 

mg/kg-day) 

BMD10s (10% extra risk) reported for 

increased incidence of gross ovarian cysts

F0 = 225 mg/kg-day (BMDL = 141 

mg/kg-day) 

F1 = 202 mg/kg-day (BMDL = 120 

mg/kg-day) 

(Estimated by analogy)

NTP-CERHR, 2008; Professional 

judgment 

Based on the analog BPA; 

adequate, guideline study as 

reported in the secondary source. 

Classified by NTP-CERHR as

having High Utility. 

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Female effects: There is sufficient 

evidence in rats and mice that BPA 

caused female reproductive toxicity with 

subchronic or chronic oral exposures with 

a NOAEL of 50 mg/kg bw-day and a 

LOAEL of 500 mg/kg bw-day. 

Male effects: There is sufficient evidence 

in rats and mice that BPA causes male 

reproductive toxicity with subchronic or 

chronic oral exposures with a NOAEL of 

50 mg/kg bw-day and a LOAEL of 500 

mg/kg bw/day. 

(Estimated by analogy)

NTP-CERHR, 2008; Professional 

judgment 

Based on the analog BPA; 

Classified by NTP-CERHR as 

having High Utility.

The joint FAO/WHO Expert Panel 

reviewed reproductive and developmental 

toxicity data for BPA located as of 

November 2010 and noted that most 

regulatory bodies reviewing the 

numerous studies on BPA have indicated 

an oral reproductive and developmental 

NOAEL of 50 mg/kg bw-day. 

(Estimated by analogy)

FAO/WHO, 2011; Professional 

judgment 

Based on the analog BPA.

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Developmental Effects HIGH: Estimated based on analogy to BPA. The NTP-CERHR (2008) Expert Panel concluded that there is 

suggestive evidence that BPA causes neural and behavioral alterations related to disruptions in normal sex 

differences in rats and mice (0.01-0.2 mg/kg bw-day) following developmental exposures. The FAO/WHO 

(2011) Expert Panel also concluded that while there was broad agreement in a NOAEL of 50 mg/kg bw-day 

for developmental toxicity based on standard bioassays, specific targeted studies identified 

neurodevelopmental effects at low doses (<1 mg/kg bw-day), but the human relevance is less certain. There 

is great variation in results with different types of studies measuring different endpoints; developmental 

effects at lower doses cannot be ruled out. Taken together these findings support a hazard designation of 

High concern.

Reproduction/ 

Developmental Toxicity 

Screen

No data located.

Combined Repeated Dose 

with Reproduction/ 

Developmental Toxicity 

Screen

No data located.

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Summary of 

Developmental effects

The NTP-CERHR Expert Panel 

concluded that BPA: 

*does not cause malformations or birth 

defects in rats or mice at levels up to the 

highest doses evaluated: 640 mg/kg/day 

(rats) and 1,250 mg/kg bw-day (mice). 

*does not alter male or female fertility 

after gestational exposure up to doses of 

450 mg/kg bw-day in the rat and 

600 mg/kg bw-day in the mouse (highest 

dose levels evaluated). 

*does not permanently affect prostate 

weight at doses up to 475 mg/kg bw-day 

in adult rats or 600 mg/kg bw-day in 

mice. 

*does not cause prostate cancer in rats or 

mice after adult exposure at up to 148 or 

600 mg/kg bw-day, respectively. 

*does change the age of puberty in male 

or female rats at high doses (ca. 

475 mg/kg/day). 

And that rodent studies suggest that BPA:

*causes neural and behavioral alterations 

related to disruptions in normal sex 

differences in rats and mice (0.01–

0.2 mg/kg/day). 

(Estimated by analogy)

NTP–CERHR, 2008; Professional 

judgment 

Based on the analog BPA.

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Bisphenol F CASRN 620-92-8

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The joint FAO/WHO Expert Panel 

reviewed reproductive and developmental 

toxicity data for BPA located as of 

November 2010 and noted that most 

regulatory bodies reviewing the 

numerous studies on BPA have indicated 

an oral reproductive and developmental 

NOAEL of 50 mg/kg bw-day.

FAO/WHO, 2011; Professional 

judgment 

Based on the analog BPA.

Neurotoxicity MODERATE: Estimated to have potential for neurotoxicity based on the presence of the phenol structural 

alert.

Neurotoxicity Screening 

Battery (Adult)

There is potential for neurotoxicity 

effects based on the presence of the 

phenol structural alert. 

(Estimated)

U.S. EPA, 2010; Professional 

judgment 

Estimated based on structural alert.

Repeated Dose Effects HIGH: Based on adverse effects (12% lower body weight than controls; decreased total cholesterol, glucose, 

and albumin in the serum) in female rats administered bisphenol F by gavage for 28 days at 20 mg/kg-day 

(the lowest dose tested). Because the standard criteria thresholds are for 90-day studies, this study was 

evaluated using modified criteria at 3 times the threshold values. 

28-day oral study of Crj:CD SpragueDawley rats (10/sex/dose), gavaged with 

0, 20, 100, or 500 mg/kg-day. 

LOAEL = 20 mg/kg-day (based on 

significant decreases in final mean body 

weight [12% less than controls], serum 

total cholesterol, glucose, and albumin in 

female rats).

Higashihara, Shiraishi et al., 2007 Adequate 28-day repeated dose 

toxicity study; this study will be 

evaluated using modified criteria at 

3 times the thresholds because the 

standard thresholds are based on 

90-day studies. 

Skin Sensitization LOW: One study in guinea pigs suggested bisphenol F is not a skin sensitizer.

Skin Sensitization Negative for skin sensitizing capacity in 

guinea pig maximization test

Bruze, 1986 Adequate.

Respiratory Sensitization No data located.

Respiratory Sensitization No data located.

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Eye Irritation VERY HIGH: One study of rabbits indicated that bisphenol F caused severe eye injury.

Eye Irritation Severe corneal injury in rabbits Smyth, Carpenter et al., 1962 Adequate.

Dermal Irritation MODERATE: Bisphenol F is estimated to be slightly irritating to moderately irritating to rabbit skin based 

on test data for the analog BPA. NIOSH has assigned the analog BPA as a skin irritant.

Dermal Irritation Rabbit, nonirritating to slightly irritating 

when applied as undiluted or 10% 

aqueous suspension to intact or abraded 

skin. 

(Estimated by analogy)

EINECS, 2010; European 

Commission, 2000; NIOSH, 2010; 

Professional judgment

Based on the analog BPA; the 

details provided for multiple studies

indicate potential for BPA to cause 

dermal irritation. 

Rabbit, moderately irritating when 

applied as 40% solution in dimethyl 

sulfoxide under non-occlusive conditions.

(Estimated by analogy)

European Commission, 2000; 

Professional judgment

Based on the analog BPA; 

adequate. 

Guinea pig, not irritating when applied as 

5% solution in acetone for 24 hours under 

occlusive conditions. 

(Estimated by analogy)

European Commission, 2000; 

Professional judgment

Based on the analog BPA; 

adequate. 

Endocrine Activity Based on in vitro and in vivo data. Bisphenol F exhibited estrogenic and anti-estrogenic activity in some in 

vivo studies of female rats. In vitro assays indicate that BPA can bind to estrogen receptors (ERs), elicit 

estrogen-induced gene transcription, induce progesterone receptors (PgR), and induce cell proliferation in 

MCF7 cancer cells. Bisphenol F has been shown to exhibit androgenic and anti-androgenic properties in 

vitro. Bisphenol F appears to exhibit estrogenic potency similar to or somewhat less than the potency of BPA.

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Receptor Binding Assays

Bisphenol F exhibited weak ER binding 

activity in preparations from uteri of 

ovariectomized Sprague-Dawley rats as 

evidenced by a relative binding affinity 

(RBA) that was 0.0009% of the binding 

affinity of 17β-estradiol. RBAs for other 

tested chemicals included 0.008% for 

BPA, 0.003% for PHBB, and 0.0007% 

for the proprietary substituted phenolic 

compound.

Blair, Branham et al., 2000 Adequate.

In a human ER binding assay, the RBA of 

bisphenol F was 0.0719% compared to 

126% for 17β-estradiol. RBAs for other 

bisphenol compounds included 0.195% 

for BPA, 0.129% for bisphenol C, 

0.0803% for bisphenol AP, and 0.0055% 

for bisphenol S. An RBA of 0.00473% 

was reported for PHBB.

METI, 2002 Adequate.

In a competitive ER binding assay using 

human ERα, the RBA for BPA was 

0.32% that of 17β-estradiol. RBAs for 

other bisphenol compounds included 

1.68% for bisphenol C, 1.66% for 

bisphenol AP, and 0.09% for bisphenol F.

Coleman, Toscano et al., 2003 Adequate.

In a human ER binding assay, the RBA of 

bisphenol F was 0.0719% relative to 17βestradiol (set at 100%). RBAs for other 

bisphenol compounds included 0.175% 

for bisphenol M and 0.0055% for BPA.

Yamasaki, Noda et al., 2004 Adequate.

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In a rat uterine cytosol assay that 

evaluated ER binding affinity, ER 

binding affinities for BPA and bisphenol 

F were approximately 3 orders of 

magnitude less than that for 17βestradiol.

Perez, Pulgar et al., 1998 Adequate.

Gene Transcription and Reporter 

Gene Assays

Bisphenol F exhibited evidence of 

estrogenic activity in a yeast 

(Saccharomyces cerevisiae) two-hybrid 

assay using ERα and the coactivator 

TIF2. Based on estrogenic activity that 

was 5 orders of magnitude lower than that 

of 17β-estradiol, BPA was considered 

weakly estrogenic. Assessment of other 

bisphenols resulted in a ranking of 

relative potency as follows: bisphenol C 

≥ BPA > bisphenol F > bisphenol S.

Chen, Michihiko et al., 2002 Adequate.

Bisphenol F exhibited estrogenic activity 

approximately 9,000-fold less than that of 

17β-estradiol) in an in vitro recombinant 

yeast estrogen assay. The estrogenic 

activities of BPA and PHBB were 

10,000-fold and 4,000-fold less than that 

of 17β-estradiol.

Miller, Wheals et al., 2001 Adequate.

In a yeast two-hybrid system (reporter 

gene assay) using β-galactosidase activity 

as a measure of estrogenic activity, an 

estrogenic response was elicited by 

bisphenol F and BPA but not by 

bisphenol S.

Hashimoto and Nakamura, 2000 Adequate.

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In yeast two-hybrid systems (reporter 

gene assay) using β-galactosidase activity 

as a measure of estrogenic activity, an 

estrogenic response was elicited by 

bisphenol F and BPA both in the absence 

and presence of exogenous metabolic 

activation. Bisphenol S elicited a similar 

response only in the presence of 

exogenous metabolic activation. 

Hashimoto and Nakamura, 2000; 

Hashimoto, Moriguchi et al. 2001 

Adequate.

In a yeast two-hybrid assay (reporter gene 

assay) using β-galactosidase activity as a 

measure of estrogenic activity, an 

estrogenic response was elicited by 

bisphenol F and BPA. 

Ogawa, Kawamura et al. 2006 Adequate. 

In a reporter gene assay of estrogeninduced transcriptional activity, relative 

activity (RA) for bisphenol F was 

0.000639% compared to 81.7% for 17βestradiol. RAs for other bisphenol 

compounds included 0.00278% for BPA, 

0.00189% for bisphenol C, 0.000254% 

for bisphenol S, and 0.000184% for 

bisphenol AP. An RA of 0.000592% was 

reported for PHBB.

METI, 2002 Adequate. 

In an ER-mediated reporter gene 

expression assay, bisphenol F induced 

reporter gene expression at a RA of 

5.3x10-4 that of 17β-estradiol. RAs for 

other bisphenol compounds included 

2.75x10-3 for BPA, 4.9x10-4 for

bisphenol C, and 9.0x10-5 for bisphenol 

AP.

Coleman, Toscano et al., 2003 Adequate.

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In an ERE-luciferase reporter assay using 

MCF-7 cells, an EC50 was 1.0 μM for 

bisphenol F compared to an EC50 of 

8.6x10-6 for 17β-estradiol (i.e., BPA was 

approximately 5 orders of magnitude less 

potent than 17β-estradiol at inducing 

estrogenic activity). EC50 values for other 

bisphenol compounds included 0.63% for 

BPA, 0.42 μM for bisphenol C, and 1.1 

μM for bisphenol S.

Kitamura, Suzuki et al., 2005 Adequate.

In an ERE-luciferase reporter assay using 

MCF-7 cells in the presence of 17βestradiol, neither bisphenol F, BPA, 

bisphenol C, nor bisphenol S appeared to 

exert an anti-estrogenic effect

Kitamura, Suzuki et al., 2005 Adequate.

Weakly estrogenic in a transcriptional 

activation assay using human ER and 

HepG2 cells.

Cabaton, Dumont et al., 2009 Adequate.

Progesterone Receptor Induction

In an ERE-luciferase reporter assay using 

MCF-7 cells, an EC50 was 1.0 μM for 

bisphenol F compared to an EC50 of 

8.6x10-6 for 17β-estradiol (i.e., BPA was 

approximately 5 orders of magnitude less 

potent than 17β-estradiol at inducing 

estrogenic activity). EC50 values for other 

bisphenol compounds included 0.63% for 

BPA, 0.42 μM for bisphenol C, and 1.1 

μM for bisphenol S.

Kitamura, Suzuki et al., 2005 Adequate.

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In an assay designed to evaluate 

estrogenic effects on the number of 

progesterone receptors (PgR) in MCF7 

cells, 17β-estradiol, bisphenol F, and 

BPA each increased the concentration of 

PgR by approximately 10- to 15-fold.

Perez, Pulgar et al., 1998 Adequate.

Cell Proliferation Assays

Weakly estrogenic in a transcriptional 

activation assay using human ER and 

HepG2 cells.

Cabaton, Dumont et al., 2009 Adequate.

In an E-screen test for estrogenicity, 

bisphenol F, BPA, and bisphenol S 

increased proliferation of MCF-7 cells at 

concentrations in the range of 10-4 to 10-7

M. BPA appeared to be more effective 

than bisphenol S or bisphenol F.

Hashimoto, Moriguchi et al., 2001 Adequate.

In an E-SCREEN test of MCF7 cell 

proliferation (an indicator of estrogenic 

activity), the proliferative potency of 

BPA was approximately 10-5 that of 17βestradiol, suggestive of a weakly 

estrogenic effect for BPA. The potency of 

bisphenol F was somewhat less than that 

of BPA.

Perez, Pulgar et al., 1998 Adequate.

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In an E-screen test for estrogenicity, 

bisphenol F and BPA increased 

proliferation of MCF-7 cells with EC50

values of 84.8 nM and 410 nM, 

respectively, compared to an EC50 of 

0.0045 nM for 17β-estradiol. The results 

indicate a weak estrogenic effect with 

bisphenol F exerting a more potent effect 

than BPA.

Stroheker, Picard et al., 2004 Adequate.

In a proliferation assay of MCF-7 human 

breast cancer cells that contain ERα and 

ERβ and are known to proliferate in 

response to estrogens, BPA induced a 

proliferative response that was 1.0x10-3

that of 17β-estradiol. Proliferative values 

for other bisphenol compounds included 

2.0x10-3 for BPA, 1.6x10-3 for bisphenol 

C, and 6.0x10-4 for bisphenol AP.

Coleman, Toscano et al., 2003 Adequate.

In an assay that measured induction and 

secretion of pS2 in cultured MCF7 cells 

(ELSA-pS2 immunoradiometric assay), 

induction of pS2 by bisphenol F and BPA 

was approximately 1,000-fold less than 

that of 17β-estradiol.

Perez, Pulgar et al., 1998 Adequate.

Androgen Assays

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Bisphenol F and BPA induced androgenic 

effects in MDA-MB453 cells transfected 

with an AR responsive luciferase reporter 

gene; anti-androgenic effects were 

elicited in the presence of 

dihydrotestosterone. Relative potency of 

the androgenic and anti-androgenic 

effects elicited by bisphenol F was 

similar to that of BPA.

Stroheker, Picard et al., 2004 Adequate.

In an ARE-luciferase reporter assay using 

a mouse fibroblast cell line (NIH3T3 

cells), neither bisphenol F, BPA, 

bisphenol C, nor bisphenol S exerted an 

androgenic effect.

Kitamura, Suzuki et al., 2005 Adequate.

In an ARE-luciferase reporter assay using 

a mouse fibroblast cell line (NIH3T3 

cells), bisphenol F inhibited the 

androgenic activity of 

dihydrotestosterone. Anti-androgenic 

responses were elicited by BPA, 

bisphenol C, and bisphenol S as well.

Kitamura, Suzuki et al., 2005 Adequate. 

Bisphenol F induced an anti-androgenic 

response in a transcriptional activation 

assay at a concentration of 10-5M.

Cabaton, Dumont et al., 2009 Adequate.

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In Vivo Studies

28-Day study with Crj:CD SpragueDawley rats (10/sex/dose), gavaged with 

0, 20, 100, or 500 mg/kg-day: 

NOAEL = 500 mg/kg-day 

(endocrine/reproductive parameters). 

No changes in spermatological findings, 

estrous cycles, reproductive organ 

weight, or thyroid weight.

Higashihara, Shiraishi et al., 2007 Adequate. 

Exposure of immature female rats to 

bisphenol F (gavage dosing once daily for 

4 days) resulted in a dose-dependent 

increase in uterine weight in immature 

female rats. 

LOAEL = 100 mg/kg-day (based on 

increased relative wet uterine weight

NOAEL = 50 mg/kg-day 

There were no significant effects on 

uterine weight in BPA-treated immature 

female rats and no effects on uterine 

weight in bisphenol F- or BPA-treated 

ovariectromized rats.

Stroheker, Chagnon et al., 2003 Adequate.

In an uterotrophic assay of rats 

subcutaneously injected with bisphenol F 

once daily for 3 days, an apparent 

estrogenic effect was evidenced by 

increased absolute and relative uterine 

weight. Similar effects were elicited by 

bisphenol S and bisphenol M.

Yamasaki, Noda et al., 2004 Adequate.

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In an uterotrophic assay in which 

immature female rats were injected with 

bisphenol F, bisphenol S, or bisphenol M 

subcutaneously for three consecutive 

days, observed changes in uterine weight 

indicated that bisphenol F, bisphenol S, 

and bisphenol M exerted both estrogenic 

and anti-estrogenic responses.

Akahori, Makai et al., 2008 Adequate.

Immunotoxicity No data located.

Immune System Effects No data located.

ECOTOXICITY

ECOSAR Class Polyphenols

Acute Toxicity MODERATE: Based on an experimental 48-hour EC50 of 56 mg/L in Daphnia magna.

Fish LC50 Fish 96-hour LC50 = 4.55 mg/L 

(Estimated) 

ECOSAR: polyphenols

ECOSAR version 1.00

Fish 96-hour LC50 = 19.74 mg/L 

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.00 Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided 

by ECOSAR classes that have a 

more specific mode of action 

relative to narcosis.

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Daphnid LC50 Daphnia magna 48-hour EC50 = 56 mg/L

24-hour EC50 = 80 mg/L 

(Experimental)

Chen, Michihiko et al., 2002 Adequate. 

Daphnid 48-hour LC50 = 12.94 mg/L

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.00 Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided 

by ECOSAR classes that have a 

more specific mode of action 

relative to narcosis.

Daphnid 48-hour LC50 = 13.0 mg/L

(Estimated) 

ECOSAR: polyphenols

ECOSAR version 1.00

Green Algae EC50 Green algae 96-hour EC50 = 1.37 mg/L

(Estimated) 

ECOSAR: polyphenols

ECOSAR version 1.00

Green algae 96-hour EC50 = 8.6 mg/L

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.00 Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided 

by ECOSAR classes that have a 

more specific mode of action 

relative to narcosis.

Chronic Aquatic Toxicity HIGH: Based on an estimated ChV of 0.29 mg/L for green algae that is within the range of 0.1-1.0 mg/L.

Fish ChV Fish 30-day ChV = 1.18 mg/L 

(Estimated) 

ECOSAR: polyphenols

ECOSAR version 1.00

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Fish 30-day ChV = 1.83 mg/L

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.00 Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided 

by ECOSAR classes that have a 

more specific mode of action 

relative to narcosis.

Daphnid ChV Daphnid ChV = 1.44 mg/L

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.00 Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided 

by ECOSAR classes that have a 

more specific mode of action 

relative to narcosis.

Daphnid ChV = 4.56 mg/L

(Estimated) 

ECOSAR: polyphenols

ECOSAR version 1.00

Green Algae ChV Green algae ChV = 0.29 mg/L

(Estimated) 

ECOSAR: polyphenols

ECOSAR version 1.00

Green algae ChV = 3.78 mg/L

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.00 Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided 

by ECOSAR classes that have a 

more specific mode of action 

relative to narcosis.

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ENVIRONMENTAL FATE

Transport Based on the Level III fugacity models incorporating the located experimental property data, bisphenol F is 

expected to partition primarily to soil. Bisphenol F is expected to exist in both neutral and anionic forms at 

environmentally-relevant pH, based on its measured pKa. The neutral form of bisphenol F is expected to 

have low mobility in soil based on its estimated Koc. The anionic form may be more mobile, as anions do not 

bind as strongly to organic carbon and clay due to their enhanced water solubility. However, leaching of 

bisphenol F through soil to groundwater is not expected to be an important transport mechanism. Estimated 

volatilization half-lives indicate that it will be nonvolatile from surface water. Volatilization from dry 

surfaces is also not expected based on its estimated vapor pressure. In the atmosphere, bisphenol F is 

expected to exist in both vapor and particulate phases, based on its estimated vapor pressure. Particulates 

will be removed from air by wet or dry deposition. Vapor-phase bisphenol F will be susceptible to 

atmospheric degradation processes. 

Henry’s Law Constant 

(atm-m3/mole)

<1x10-8 (Estimated) EPI Cutoff value for nonvolatile 

compounds according to 

professional judgment. 

Sediment/Soil 

Adsorption/Desorption

Coefficient – Koc

1.5x104 (Estimated) EPI

Level III Fugacity 

Model

Air = <1% (Estimated)

Water = 15%

Soil = 79%

Sediment = 6.5%

EPI

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Persistence LOW: Bisphenol F degraded 100% after 2 weeks in a modified river die-away test (TOC-Handai Method). 

Complete mineralization was reported. Based on these data, the aerobic biodegradation half-life is expected 

to be <16 days. An anaerobic biodegradation test assessing primary degradation in concentrated pond 

sediment reported >80% after ca. 80 days with no lag period. A pure culture study evaluating the ability of a 

Sphingobium yanoikuyae strain to degrade bisphenol F suggested that the mechanism for biodegradation 

started at the bridging carbon between the two phenols via hydroxylation and subsequent oxidation to 

4,4’-dihydroxybenzophenone. This degradation mechanism can occur for this BPA alternative because of 

the presence of labile benzylic hydrogens. Bisphenol F did not pass a ready biodegradability test (Japanese 

MITI), which reported only 1% degradation after 4 weeks, indicating that it may be resistant to 

biodegradation under more stringent conditions. Bisphenol F is not expected to undergo hydrolysis since it 

does not contain hydrolyzable functional groups. Absorption of light at environmentally relevant 

wavelengths indicates that it may be susceptible to direct photolysis by sunlight. The atmospheric half-life 

for the hydroxyl radical reaction of vapor phase bisphenol F is estimated to be 1.6 hours, although it is 

expected to exist in both the vapor and particulate phases in air. Based on these findings, biodegradation of 

bisphenol F is expected to be the main fate process in aquatic and terrestrial environments. 

Water Aerobic Biodegradation 100% after 2 weeks (Measured; TOCHandai Method). Method similar to 

aerobic river die-away test. Used 

concentrated (10 times) river water 

microcosms diluted in “artificial water”. 

Reported complete mineralization at TOC

concentration of 10 mg/L.

Ike, Chen et al., 2006 Valid, nonguideline study 

demonstrating river water 

microcosms have the potential to 

biodegrade bisphenol F. 

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Biodegradation efficiencies varied from 

8% to 58% after 30 days, depending on 

the sampling site. A modified TOCHandai Method was used, which is 

similar to aerobic river die-away test. 

Used concentrated seawater microcosms 

diluted in “artificial water”. Resistance to 

seasonal variation was noted. Efficiencies 

varied from 75% to 100% after 30 days, 

depending on the sampling site using a 

sea-die away method. Purified seawater 

inoculums were used. 

Danzl, Sei et al., 2009 Valid, nonguideline study 

demonstrating seawater 

microcosms have the potential to 

biodegrade bisphenol F. 

Sphingobium yanoikuyae strain FM-2 

(isolated from river water) biodegraded 

bisphenol F. Reported mechanism 

suggested hydroxylation and subsequent 

oxidation at the bridging carbon to form 

the following metabolites: 

bis(4-hydroxyphenyl)methanol to 

4,4’-dihydroxybenzophenone to 

4-hydroxyphenyl-4-hydroxybenzoate to 

4-hydroxybenzoate and 1,4-hydroquinone, all of which are mineralized. 

Inoue, Hara et al., 2008 Valid, pure culture study 

demonstrating biodegradation 

potential and mechanism. 

Volatilization Half-life 

for Model River

>1 year (Estimated) EPI

Volatilization Half-life 

for Model Lake

>1 year (Estimated) EPI

Soil Aerobic Biodegradation 1% after 4 weeks (Measured in activated 

sludge). Japanese MITI test (OECD 

301C) measuring BOD with test 

concentration of 100 mg/L and 

concentration of activated sludge 

inoculum = 30 mg/L

MITI, 1998 Adequate, guideline study.

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Bisphenol F CASRN 620-92-8

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Anaerobic 

Biodegradation 

>80% after ca. 80 days (Measured; no lag 

period). Anaerobic pond sediment 

condensed to twice its original 

concentration. TOC = 10 mg/L. 

Measured primary degradation only. No 

discussion of metabolites. 

Ike, Chen et al., 2006 Valid nonguideline study, 

demonstrating anaerobic seawater 

sediments have potential to 

biodegrade bisphenol F. 

Soil Biodegradation w/ 

Product Identification

No data located.

Sediment/Water 

Biodegradation

No data located.

Air Atmospheric Half-life 1.6 hours (Estimated for hydroxyl radical 

reaction assuming a 12-hour day and a 

hydroxyl radical concentration of 

1.5x106 OH/cm3)

EPI

Reactivity Photolysis Susceptible to direct photolysis, with a 

reported UV absorption at 279 nm. Partial 

absorption at environmental wavelengths 

expected. 

Lide and Milne, 1994; Professional 

judgment 

Qualitative assessment based on 

functional groups. 

Hydrolysis Not a significant fate process (Estimated) Wolfe and Jeffers, 2000; 

Professional judgment

Substance does not contain 

functional groups that would be 

expected to hydrolyze readily under 

environmental conditions.

Pyrolysis No data located.

Environmental Half-life 30 days EPI, PBT Profiler Half-life estimated for the 

predominant compartment, as 

determined by EPI and the PBT 

Profiler methodology.

Bioaccumulation LOW: The measured fish BCFs are <100.

Fish BCF 6.6 (25 μg/L) (Measured);

11 (2.5 μg/L) (Measured)

MITI, 1998 Adequate, guideline study.

BAF 28 (Estimated) EPI

4-107 
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Bisphenol F CASRN 620-92-8

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Metabolism in Fish No data located.

ENVIRONMENTAL MONITORING AND BIOMONITORING 

Environmental Monitoring Detected in landfill leachates (Öman and Hynning, 1993).

Ecological Biomonitoring No data located.

Human Biomonitoring This chemical was not included in the NHANES biomonitoring report (CDC, 2011).

4-108 
FINAL REPORT – January 2014 

Akahori, Y.; Makai, M.; Yamasaki, K.; et al. Relationship between the results of in vitro receptor binding assay to human estrogen 

receptor α and in vivo uterotrophic assay: Comparative study with 65 selected chemicals. Toxicol. In vitro 2008, 22:225-231. 

Blair, R.; Branham, W.; Hass, B.; et al. The estrogen receptor relative binding affinities of 188 natural and xenochemicals: Structural 

diversity of ligands. Toxicol. Sci. 2000, 54:138-153. 

Bruze, M. Sensitizing capacity of dihydroxydiphenyl methane (bisphenol F) in the guinea pig. Contact Dermatitis 1986, 14:228-232. 

Cabaton, N.; Chagnon, M-C.; Lhuguenot, J-C.; et al. Disposition and metabolic profiling of bisphenol F in pregnant and nonpregnant 

rats. J. Agric. Food Chem. 2006, 54:10307-10314. 

Cabaton, N.; Dumont, C.; Severin, I.; et al. Genotoxic and endocrine activities of bis(hydroxyphenyl)methane (bisphenol F) and its 

derivatives in the HepG2 cell line. Toxicology 2009, 255:15-24. 

CDC (Centers for Disease Control and Prevention). Fourth national report on human exposure to environmental chemicals, updated 

tables. Department of Health and Human Services. 2011. http://www.cdc.gov/exposurereport/ (accessed on May 10, 2011). 

Chen, M-Y.; Michihiko, I.; Fujita, M. Acute toxicity, mutagenicity, and estrogenicity of bisphenol-A and other bisphenols. Environ. 

Toxicol. 2002, 17:80-86. 

Coleman, K.P., Toscano, W.A., Wiese, T.E. QSAR Models of the in vitro estrogen activity of bisphenol A analogs. QSAR & 

Combinatorial Science 2003. 22:78-88. 

Danzl, E.; Sei, K.; Soda, S., et al. Biodegradation of Bisphenol A, Bisphenol F and Bisphenol S in Seawater. Int. J. Environ. Res. 

Public Health 2009, 6:1472-1484. 

ECOSAR (2010) Ecological Structure Activity Relationship (ECOSAR) Version 1.00. Washington, DC: U.S. Environmental 

Protection Agency. http://www.epa.gov/oppt/newchems/tools/21ecosar.htm. 

EINECS. 4,4’-Isopropylidenediphenol (bisphenol A). European Union Risk Assessment Report. 2010.

EPI (EPIWIN/EPISUITE) Estimations Programs Interface for Windows, Version 4.00. U.S. Environmental Protection Agency: 

Washington D.C. http://www.epa.gov/opptintr/exposure/. 

ESIS (European chemical Substances Information System) Classification, labeling and Packaging of dangerous substances annex VI 

to regulation (EC) No 1272/2008 [Online] http://esis.jrc.ec.europa.eu/ (accessed on June 10, 2011). 

4-109 
FINAL REPORT – January 2014 

European Commission. IUCLID Dataset for 4,4-isopropylidenediphenol (CAS No. 80-05-7). European Chemicals Bureau, February 

19, 2000. 2000. 

FAO/WHO. Toxicological and health aspects of bisphenol A. Report of Joint FAO/WHO expert meeting 2-5 November 2010 and 

report of stakeholder meeting on bisphenol A 1 November 2010. Food and Agriculture Organization of the United Nations; 

World Health Organization. Ottawa, Canada. 2011.

Hansch, C.; Leo, A.; Hoekman, D. Exploring QSAR: Hydrophobic, electronic, and steric constants. Washington, D.C.: American 

Chemical Society. 1995. 

Hashimoto, Y.; Nakamura, M. Estrogenic activity of dental materials and bisphenol-A related chemicals in vitro. Dent. Mater. J.

2000, 19(3):245-262. 

Hashimoto, Y.; Moriguchi, Y.; Oshima, H.; et al. Measurement of estrogenic activity of chemicals for the development of new dental 

polymers. Toxicol. In vitro 2001, 15:421-425. 

Higashihara, N.; Shiraishi, K.; Miyata, K.; et al. Subacute oral toxicity study of bisphenol F based on the draft protocol for the 

“Enhanced OECD Test Guideline No. 407”. Arch. Toxicol. 2007, 81:825-832. 

Ike, M.; Chen, M.Y.; Danzl, E.; et al. Biodegradation of a variety of bisphenols under aerobic and anaerobic conditions. Water Sci. 

Technol. 2006, 53:153-159. 

Inoue, D.; Hara, S.; Kashihara, M.; et al. Degradation of Bis(4-Hydroxyphenyl)Methane (Bisphenol F) by Sphingobium yanoikuyae

Strain FM-2 isolated from river water. Appl. Environ. Microbiol. 2008, 74(2):352-358. 

Kitamura, S.; Suzuki, T.; Sanoh, S.; et al. Comparative study of the endocrine-disrupting activity of bisphenol A and 19 related 

compounds. Toxicol. Sci. 2005, 84:249-259. 

Lide, D. R., ed. CRC Handbook of Chemistry and Physics, 88th edition, CRC Press: Boca Raton. 2008.

METI. Current status of testing methods development for endocrine disruptors. Ministry of Economy, Trade and Industry, Japan. 6th

meeting of the task force on Endocrine Disruptors Testing and Assessments (EDTA). 24-25 June, 2002. Tokyo. 2002.

Miller, D.; Wheals, B. B.; Beresford, N.; et al. Estrogenic activity of phenolic additives determined by an in vitro yeast bioassay. 

Environ. Health Perspect. 2001, 109(2):133-138. 

4-110 
FINAL REPORT – January 2014 

MITI. Biodegradation and bioaccumulation data of existing chemicals based on the CSCL Japan. Compiled under the supervision of 

Chemical Products Safety Division, Basic Industries Bureau, Ministry of International Trade & Industry, Japan; Chemicals 

Inspection & Testing Institute, Japan. Ed.; Japan Chemical Industry Ecology- Toxicology & Information Center: 1998. 1998.

NIOSH (National Institute for Occupational Safety and Health). Skin Notation (SK) Profile, bisphenol A (BPA) [CAS No. 80-05-7]. 

Department of Health and Human Services; Centers for Disease Control and Prevention, 2010. 

NTP-CERHR. Monograph on the potential human reproductive and developmental effects of biphenol A. National Toxicology 

Program; U.S. Department of Health and Human Service. Center for the Evaluation of Risks to Human Reproduction. NIH 

Publication No. 08-5994. 2008. 

Ogawa, Y.; Kawamura, Y.; Wakui, C.; et al. Estrogenic activities of chemicals related to food contact plastics and rubbers tested by 

the yeast two-hybrid assay. Food Addit. Contam. 2006, 23(4):422-430. 

Öman, C. and Hynning, P-Å.; Identification of organic compounds in municipal landfill leachates. Environ Pollut. 1993, 80: 265-271. 

OncoLogic. U.S. EPA and LogiChem, Inc. 2005, Version 7.0. 2008. 

PBT Profiler Persistent (P),Bioaccumulative (B), and Toxic (T) Chemical (PBT)Profiler. U.S. Environmental Protection Agency: 

Washington D.C. www.pbtprofiler.net. 

Perez, P.; Pulgar, R.; Olea-Serrano, F.; et al. The estrogenicity of bisphenol A-related diphenylalkanes with various substituents at the 

central carbon and the hydroxyl groups. Environ. Health Perspect. 1998, 106(3):167-174. 

Serjeant, E.; Dempsey, B. Ionisation constants of organic acids in aqueous solution. 1979, New York: Pergamon Press.

Smyth, H.F. Jr.; Carpenter, C.P.; Weil, C.S. Range-finding toxicity data: List VI. Am. Ind. Hyg. Assoc. J. 1962, 23:95-107. 

Stroheker, T., Chagnon, M-C., Pinnert, M-F., et al. Estrogenic effects of food wrap packaging xenoestrogens and flavonoids in female 

Wistar rats: a comparative study. Reprod. Toxicol. 2003, 17:421-432. 

Stroheker, T., Picard, K., Lhuguenot, J., et al. Steroid activities comparison of natural and food wrap compounds in human breast 

cancer cell lines. Food Chem. Toxicol. 2004, 42:887-897. 

Tsutsui, T.; Tamura, Y.; Suzuki, A.; et al. Mammalian cell transformation and aneuploidy induced by five bisphenols. Int. J. Cancer

2000, 86:151-154. 

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U.S. EPA (Environmental Protection Agency). Sustainable Futures Using NonCancer Screening within the Sustainable Futures 

Initiative Environmental Protection Agency: Washington D.C. 2010. http://www.epa.gov/opptintr/sf/pubs/noncanscreen.htm#systemic (accessed on February 09, 2011). 

Wolfe, N.; Jeffers, P. 2000. Hydrolysis. In Boethling, R.; Mackay, D., Handbook of Property Estimation Methods for Chemicals, 

Environmental Health Sciences (311-334). Boca Raton: Lewis Publishers. 

Yamasaki, K.; Noda, S.; Imatanaka, N.; et al. Comparative study of the uterotrophic potency of 14 chemicals in a uterotrophic assay 

and their receptor-binding affinity. Toxicol. Lett. 2004, 146:111-120. 

4-112 
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Bisphenol C

OH OH

CASRN: 79-97-0

MW: 256.35

MF: C17H20O2

Physical Forms: 

Neat: Solid

Use: Developer for thermal paper

SMILES: Cc1cc(ccc1O)C(C)(C)c2ccc(c(c2)C)O 

Synonyms: Phenol, 4,4'-(1-methylethylidene) bis[2-methyl-; Bisphenol C; 2,2-Bis(3-methyl-4-hydroxyphenyl)propane; 2,2-Bis(3-methyl-4-hydroxyphenyl)propane; 

2,2-Bis(4-hydroxy-3-methylphenyl)propane; 2,2-Bis-(4-hydroxy-3-methylphenyl)propane; 3,3'-Dimethylbisphenol A; 3,3'-Dimethyldian; 4,4'-(1-

Methylethylidene)bis(2-methylphenol); 4,4'-Isopropylidenebis(2-methylphenol); 4,4'-Isopropylidenebis[2-methylphenol]; 4,4'-isopropylidenedi-o-cresol

Polymeric: No

 Oligomers: Not applicable

Metabolites, Degradates and Transformation Products: 4-hydroxy-3-methyl acetophenone, 4-hydroxy-3-methyl benzoic acid, and 2,2-bis[4-hydroxy3-methylphenyl]-1-propanol

Analog: Bisphenol A (80-05-7)

 Endpoint(s) using analog values: Acute toxicity, reproductive, 

developmental, repeated dose, skin sensitization, dermal irritation

Analog: Confidential analog (structure not available)

Endpoint(s) using analog values: eye irritation

Analog Structure: 

Structural Alerts: Phenols, neurotoxicity (U.S. EPA, 2010)

Risk Phrases: Not classified by Annex VI Regulation (EC) No 1272/2008 (ESIS, 2011).

Risk Assessments: None identified

OH OH

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Bisphenol C CASRN 79-97-0

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

PHYSICAL/CHEMICAL PROPERTIES

Melting Point (°C) 138-140 (Measured) Aldrich, 2009 Adequate; reported values that span a 

relatively narrow range and are 

consistent with those provided in 

other sources.

140 (Measured) Lide, 2008 Adequate.

Boiling Point (°C) 368 (Extrapolated from the reduced 

boiling point reported by Aldrich, 2009) 

Professional judgment The boiling point at 760 mm Hg was 

extrapolated from the measured 

boiling point at reduced pressure 

using a computerized nomograph.

238-240 at 12 mm Hg (Measured) Aldrich, 2009 Inadequate; value obtained at a 

reduced pressure.

Vapor Pressure (mm Hg) 2.3x10-6 (Estimated from the reduced 

boiling point reported by Aldrich, 2009) 

Professional judgment The vapor pressure was extrapolated 

from the measured boiling point at 

reduced pressure using a 

computerized nomograph.

Water Solubility (mg/L) 4.7 (Estimated) EPI

Log Kow 4.7 (Estimated) EPI

Flammability (Flash Point) No data located.

Explosivity No data located.

pH No data located.

pKa 10.5 (Estimated) SPARC

HUMAN HEALTH EFFECTS

Toxicokinetics Bisphenol C as a neat material is estimated to not be absorbed through the skin and have poor skin 

absorption when in solution. Bisphenol C is expected to be absorbed via the lungs and gastrointestinal tract.

Dermal Absorption in vitro No data located.

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Bisphenol C CASRN 79-97-0

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Absorption, 

Distribution, 

Metabolism & 

Excretion

Oral, Dermal or Inhaled Not absorbed through the skin as neat 

material and has poor absorption in 

solution; can be absorbed through the 

lung and gastrointestinal tract

(Estimated by analogy)

Professional judgment Based on closely related confidential 

analog with similar structure, 

functional groups, and 

physical/chemical properties. 

Acute Mammalian Toxicity LOW: Based on analogy to BPA, the acute oral and dermal toxicity hazard of bisphenol C is estimated to 

be low based on experimental data in animals for the analog. Data for exposure to the analog BPA via 

inhalation were inconclusive, as only a single concentration was tested and a LC50 was not provided. 

Acute Lethality Oral Rat LD50 = 3,200->5,000 mg/kg bw

(Estimated by analogy)

NTP, 1982; European 

Commission, 2000; EINECS, 

2010; Professional judgment

Based on the analog BPA; multiple 

studies, some guideline studies. 

Mouse LD50 = 4,000-5,200 mg/kg bw

(Estimated by analogy)

NTP, 1982; European 

Commission, 2000; EINECS, 

2010; Professional judgment

Based on the analog BPA; multiple 

studies, some guideline studies. 

Dermal Rabbit LD50 = 3,000-6,400 mg/kg bw

(Estimated by analogy)

European Commission, 2000; 

EINECS, 2010; Professional 

judgment 

Based on the analog BPA; limited 

study details provided for multiple 

studies reported in secondary sources.

Inhalation No deaths among male and female F344 

rats (10/sex) exposed to BPA dust at 

0.17 mg/L (highest attainable 

concentration) for 6 hours; transient 

slight nasal tract epithelial damage was 

evident. 

(Estimated by analogy)

European Commission, 2000; 

EINECS, 2010; Professional 

judgment 

Based on the analog BPA; test 

guidelines were not reported in 

secondary sources. 

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Bisphenol C CASRN 79-97-0

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Carcinogenicity MODERATE: Estimated using OncoLogic expert system which describes a concern for this compound as a 

potential carcinogen or tumorigenesis promoter arising from its structural similarity to 

estrogenic/androgenic compounds, using the “phenols and phenolic compounds” structural alert.

OncoLogic Results Moderate (Estimated)

OncoLogic class: phenols and phenolic 

compounds 

OncoLogic OncoLogic SAR analysis using the 

phenols and phenolic compounds 

class. 

Carcinogenicity (Rat and 

Mouse)

No data located.

Combined Chronic 

Toxicity/Carcinogenicity

No data located.

Genotoxicity MODERATE: Bisphenol C induced micronuclei in Chinese hamster V79 cells and human AG1522C 

fibroblasts, but was not mutagenic in one assay of Salmonella typhimurium strain TA1335 either with or 

without exogenous metabolic activity and did not induce chromosomal aberrations in Syrian hamster ovary 

cells.

Gene Mutation in vitro Negative; umu test in S. typhimurium

TA1335 with and without metabolic 

activation

Chen, Michihiko et al., 2002 Adequate.

Negative; gene mutation tests at the 

Na+/K+ ATPase locus and hprt locus of 

Syrian hamster embryo cells

Tsutsui, Tamura et al., 2000 Adequate.

Gene Mutation in vivo No data located.

Chromosomal Aberrations 

in vitro

Negative; chromosomal aberrations in 

Syrian hamster embryo cells

Tsutsui, Tamura et al., 2000 Adequate.

Positive; induction of micronuclei in 

Chinese hamster V79 cells

Pfeiffer, Rosenberg et al., 1997 Adequate.

Positive; induction of micronuclei in 

human AG1522C fibroblasts

Lehmann and Metzler, 2004 Adequate.

Chromosomal Aberrations 

in vivo

No data located.

DNA Damage and Repair No data located.

Other No data located.

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Bisphenol C CASRN 79-97-0

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Reproductive Effects MODERATE: Estimated based on analogy to BPA. Key studies identified by NTP for the analog BPA 

indicate that there are multiple distinct endpoints with NOAELs in the range of Moderate hazard concern 

and LOAELs in the range of Low hazard concern. At the target dose of 50 mg/kg-day (BPA), the NOAELs 

are on the margin of High and Moderate hazard, according to DfE criteria. Benchmark Dose (BMD) 

Modeling conducted by NTP, which interpolates between NOAEL and LOAEL values, yields values that 

further support a Moderate hazard designation.

Reproduction/ 

Developmental Toxicity 

Screen

No data located.

Combined Repeated Dose 

with Reproduction/ 

Developmental Toxicity 

Screen

No data located.

Reproduction and Fertility 

Effects

Potential for toxic effects to testes and 

ovaries

(Estimated by analogy)

Professional judgment Estimated based on located test data 

for a confidential analog.

Potential for reproductive toxicity

(Estimated by analogy)

Professional judgment Estimated based on reported 

experimental data for the analog BPA.

Parental systemic toxicity:

NOAEL = 5 mg/kg bw-day 

LOAEL = 50 mg/kg bw-day for 12% 

decreased terminal body weight in F1

parental males

Reproductive toxicity: 

Females: NOAEL = 50 mg/kg bw-day 

LOAEL = 500 mg/kg bw-day for 

decreases in number of implantation 

sites, delayed vaginal opening in F1, F2, 

F3 offspring 

BMDLs (change of 1 standard deviation 

from control) reported for delayed 

vaginal opening (females)- 

F1 = 176 mg/kg-day

NTP-CERHR, 2008; Professional 

judgment 

Based on the analog BPA; adequate, 

guideline study as reported in the 

secondary source. 

Classified by NTP-CERHR as having 

High Utility.

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PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

F2 = 228 mg/kg-day

F3 = 203 mg/kg-day 

Males: NOAEL = 50 mg/kg bw-day, 

LOAEL = 500 mg/kg-day for delayed 

preputial separation in F1 males

BMDLs (change of 1 standard deviation 

from control) reported for delayed 

preputial separation (males)- 

F1 = 163 mg/kg-day 

F2 = 203 mg/kg-day 

F3 = 189 mg/kg-day 

(Estimated by analogy)

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Bisphenol C CASRN 79-97-0

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Parental systemic toxicity:

NOAEL = 5 mg/kg bw-day 

LOAEL = 50 mg/kg bw-day for 

increased incidences of centrilobular 

hepatocellular hypertrophy in males and 

females

Reproductive toxicity: 

NOAEL = 50 mg/kg bw-day 

LOAEL = 600 mg/kg bw-day for 

increased gestation length, decreased 

epididymal sperm concentration in F1

males, increased incidence of gross 

ovarian cysts in F1 and F2 females

BMD1 (change of 1 standard deviation 

from control) reported for increased 

gestation length

F0 = 1144 mg/kg-day (BMDL = 599 

mg/kg-day) 

F1 = 772 mg/kg-day (BMDL = 531 

mg/kg-day) 

BMD10s (10% extra risk) reported for 

increased incidence of gross ovarian 

cysts

F0 = 225 mg/kg-day (BMDL = 141 

mg/kg-day) 

F1 = 202 mg/kg-day (BMDL = 120 

mg/kg-day) 

(Estimated by analogy)

NTP-CERHR, 2008; Professional 

judgment 

Based on the analog BPA; adequate, 

guideline study as reported in the 

secondary source. 

Classified by NTP-CERHR as having 

High Utility.

Summary of Reproductive 

effects

Female effects: There is sufficient 

evidence in rats and mice that BPA 

caused female reproductive toxicity with 

subchronic or chronic oral exposures 

with a NOAEL of 50 mg/kg bw-day and 

NTP-CERHR, 2008; Professional 

judgment 

Based on the analog BPA; Classified 

by NTP-CERHR as having High 

Utility.

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PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

a LOAEL of 500 mg/kg bw-day.

Male effects: There is sufficient 

evidence in rats and mice that BPA 

causes male reproductive toxicity with 

subchronic or chronic oral exposures 

with a NOAEL of 50 mg/kg bw-day and 

a LOAEL of 500 mg/kg bw/day. 

(Estimated by analogy)

The joint FAO/WHO Expert Panel 

reviewed reproductive and 

developmental toxicity data for BPA 

located as of November 2010 and noted 

that most regulatory bodies reviewing the 

numerous studies on BPA have indicated 

an oral reproductive and developmental 

NOAEL of 50 mg/kg bw-day. 

(Estimated by analogy)

FAO/WHO, 2011 Based on the analog BPA.

Developmental Effects HIGH: Estimated based on analogy to BPA. The NTP-CERHR (2008) Expert Panel concluded that there is 

suggestive evidence that BPA causes neural and behavioral alterations related to disruptions in normal sex 

differences in rats and mice (0.01-0.2 mg/kg bw-day) following developmental exposures. The FAO/WHO 

(2011) Expert Panel also concluded that while there was broad agreement in a NOAEL of 50 mg/kg bw-day 

for developmental toxicity based on standard bioassays, specific targeted studies identified 

neurodevelopmental effects at low doses (<1 mg/kg bw-day), but the human relevance is less certain. There 

is great variation in results with different types of studies measuring different endpoints; developmental 

effects at lower doses cannot be ruled out. Taken together these findings support a hazard designation of 

High concern.

Reproduction/ 

Developmental Toxicity 

Screen

No data located.

Combined Repeated Dose No data located.

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Bisphenol C CASRN 79-97-0

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

with Reproduction/ 

Developmental Toxicity 

Screen

Summary of Developmental 

Effects

Potential for developmental 

neurotoxicity due to effects of thyroid 

toxicity

(Estimated by analogy)

Professional judgment Estimated based on located test data 

for a confidential analog. 

Potential for developmental toxicity

(Estimated by analogy)

Professional judgment Estimated based on reported 

experimental data for the analog BPA.

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Bisphenol C CASRN 79-97-0

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

The NTP-CERHR (2008) Expert Panel 

concluded that BPA: 

*Does not cause malformations or birth 

defects in rats or mice at levels up to the 

highest doses evaluated: 640 mg/kg-day 

(rats) and 1,250 mg/kg bw-day (mice). 

*Does not alter male or female fertility 

after gestational exposure up to doses of 

450 mg/kg bw-day in the rat and 

600mg/kg bw-day in the mouse (highest 

dose levels evaluated). 

*Does not permanently affect prostate 

weight at doses up to 475 mg/kg-day in 

adult rats or 600 mg/kg-day in mice. 

*Does not cause prostate cancer in rats or 

mice after adult exposure at up to 148 or 

600 mg/kg-day, respectively. 

*Does change the age of puberty in male 

or female rats at high doses (ca. 

475 mg/kg-day). 

And that rodent studies suggest that 

BPA: 

*Causes neural and behavioral alterations 

related to disruptions in normal sex 

differences in rats and mice

(0.01-0.2 mg/kg/day). 

(Estimated by analogy)

NTP–CERHR, 2008; Professional 

judgment 

Based on the analog BPA.

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Bisphenol C CASRN 79-97-0

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

The joint FAO/WHO Expert Panel 

reviewed reproductive and 

developmental toxicity data for BPA 

located as of November 2010 and noted 

that most regulatory bodies reviewing the 

numerous studies on BPA have indicated 

an oral reproductive and developmental 

NOAEL of 50 mg/kg bw-day.

FAO/WHO, 2011; Professional 

judgment 

Based on the analog BPA.

Neurotoxicity MODERATE: Estimated to have potential for neurotoxicity based on the presence of the phenol structural 

alert.

Neurotoxicity Screening 

Battery (Adult)

There is potential for neurotoxicity 

effects based on the presence of the 

phenol structural alert. 

(Estimated)

U.S. EPA, 2010; Professional 

judgment 

Estimated based on structural alert.

Repeated Dose Effects MODERATE: Estimated based on analogy to BPA, which produced histopathologic changes in the liver 

(centrilobular hepatocyte hypertrophy) from oral dosing at 50 mg/kg bw-day (NOAEL = 5 mg/kg bw-day) 

and there is uncertainty regarding the potential for BPA doses between the NOAEL of 5 mg/kg bw-day and 

the LOAEL of 50 mg/kg bw-day to cause adverse systemic effects. Furthermore, lesions in the nasal cavity 

of rats were reported following repeated inhalation exposure to BPA dust at 0.05 mg/L. These findings 

indicate a Moderate hazard potential for the oral and inhalation exposure routes.

Potential for liver toxicity

(Estimated by analogy)

Professional judgment Estimated based on reported 

experimental data for the analog BPA.

The FAO/WHO Expert Panel reviewed 

the located information regarding 

repeated-dose oral toxicity of BPA and 

concluded that results demonstrated 

effects on the liver, kidney, and body 

weight at doses of 50 mg/kg bw-day and 

higher and that the lowest NOAEL was 5 

mg/kg-day, as identified in several 

studies. 

(Estimated by analogy)

FAO/WHO, 2011; Professional 

judgment

Based on the analog BPA.

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Parental systemic toxicity:

NOAEL = 4.75 mg/kg bw-day 

LOAEL = 47.5 mg/kg bw-day for 12% 

decreased terminal body weight in F1

parental males

(Estimated by analogy)

NTP-CERHR, 2008; Professional 

judgment

Based on the analog BPA; guideline 

study as reported in the secondary 

source. 

Classified by NTP-CERHR as having 

High Utility.

Parental systemic toxicity:

NOAEL = 5 mg/kg bw-day 

LOAEL = 50 mg/kg bw-day for 

increased incidences of centrilobular 

hepatocellular hypertrophy in males and 

females

(Estimated by analogy)

NTP-CERHR, 2008; Professional 

judgment

Based on the analog BPA; guideline 

study as reported in the secondary 

source. 

Classified by NTP-CERHR as having 

High Utility.

NOAEL = 0.01 mg/L

LOAEL = 0.05 mg/L based on 

microscopic changes in the anterior 

portion of the nasal cavity

(Estimated by analogy)

European Commission, 2000; 

EINECS, 2010; Professional 

judgment

Based on the analog BPA.

NOAEL = None established

LOAEL = 0.047 mg/L for decreased 

body weight gain, increased liver and 

kidney weight, unspecified 

“morphological changes” in liver, 

kidney, and lungs

(Estimated by analogy)

European Commission, 2000; 

EINECS, 2010; Professional 

judgment

Based on the analog BPA; single 

exposure level, insufficient study 

details in secondary sources. 

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Skin Sensitization MODERATE: Based on analogy to BPA, bisphenol C is estimated to be a skin sensitizer. Recent data from 

three BPA manufacturing facilities indicate that it does not elicit skin sensitization. However, results of 

some human studies suggest the possibility of a dermal sensitization response, although cross-sensitization 

was not ruled out. Most animal studies conducted on the analog were negative for dermal sensitization, 

although assays may not have been maximized. There is evidence of ear swelling in a photoallergy test in 

mice and moderate redness and swelling following repeated dermal exposure in rabbits. Based on 

suggestive evidence of skin sensitization in humans and mice for the analog, a Moderate hazard designation

is warranted.

Skin Sensitization Potential for dermal sensitization

(Estimated by analogy)

Professional judgment Estimated based on reported 

experimental data for the analog BPA.

Negative in a modified local lymph node 

assay of mice administered BPA 

epicutaneously on the ears at 

concentrations up to 30% on three 

consecutive days. 

(Estimated by analogy)

EINECS, 2010; Professional 

judgment 

Based on the analog BPA; adequate, 

although the assay did not include 

concentrations >30%.

Negative in a local lymph node assay 

modified to test for photoreactivity in 

mice administered BPA epicutaneously 

on the ears at concentrations up to 30% 

on three consecutive days and irradiated 

with UV light immediately following 

application. 

(Estimated by analogy)

EINECS, 2010; Professional 

judgment 

Based on the analog BPA; adequate, 

although the assay did not include 

concentrations >30%.

Negative in comprehensive medical 

surveillance data obtained from three 

BPA manufacturing plants for 875 

employees examined for several years 

where workers were potentially exposed 

to other chemicals (phenol, acetone) that 

are not considered to be skin sensitizers. 

(Estimated by analogy)

EINECS, 2010; Professional 

judgment 

Based on the analog BPA; adequate.

Positive, rabbits; repeated dermal NIOSH, 2010; Professional Based on the analog BPA; adequate.

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application (30 times over 37 days) of 

BPA (pure powder) produced moderate 

swelling and redness. Skin turned yellow 

followed by dark pigmentation after day 

15. 

(Estimated by analogy) 

judgment

The Joint FAO/WHO Expert Meeting 

review of the toxicological aspects of 

BPA concludes that BPA is capable of 

producing a skin sensitization response 

in humans. 

(Estimated by analogy)

FAO/WHO, 2011; Professional 

judgment 

Based on the analog BPA; adequate.

Respiratory Sensitization No data located.

Respiratory Sensitization No data located.

Eye Irritation HIGH: Based on analogy to a confidential analog, bisphenol C is estimated to potentially cause severe 

irritation and corrosion to eyes.

Eye Irritation Potential for severe irritation and 

corrosion to eyes

(Estimated by analogy)

Professional judgment Estimated based on located test data 

for a confidential analog. 

Dermal Irritation MODERATE: Bisphenol C is estimated to be slightly irritating to moderately irritating to rabbit skin 

based on test data for the analog BPA. NIOSH has assigned the analog, BPA, as a skin irritant.

Dermal Irritation Rabbit, nonirritating to slightly irritating 

when applied as undiluted or 10% 

aqueous suspension to intact or abraded 

skin. 

(Estimated by analogy)

European Commission, 2000; 

EINECS, 2010; NIOSH, 2010; 

Professional judgment

Based on the analog BPA; Adequate, 

study details provided for multiple 

studies indicate potential for BPA to 

cause dermal irritation. 

Rabbit, moderately irritating when 

applied as 40% solution in dimethyl 

sulfoxide under non-occlusive 

conditions. 

(Estimated by analogy) 

European Commission, 2000; 

Professional judgment

Based on the analog BPA; adequate.

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Guinea pig, not irritating when applied as 

5% solution in acetone for 24 hours 

under occlusive conditions. 

(Estimated by analogy)

European Commission, 2000; 

Professional judgment

Based on the analog BPA; adequate.

Endocrine Activity Based on limited in vitro data it appears that Bisphenol C exhibits endocrine activity. In vitro assays 

demonstrate that bisphenol C can bind to estrogen receptors, elicit estrogen-induced gene transcription, 

and induce cell proliferation in MCF7 cancer cells. In an ARE-luciferase reporter assay using a mouse 

fibroblast cell line, bisphenol C did not elicit an androgenic response, but did inhibit the androgenic activity 

of dihydrotestosterone. Data located indicate that the in vitro endocrine activity of bisphenol C is 

approximately 3-5 orders of magnitude less than that of 17β-estradiol, suggesting that bisphenol C acts as a 

weak estrogen. Limited comparative in vitro data suggest that the endocrine activity of bisphenol C is 

similar in magnitude to that of BPA, bisphenol AP, and bisphenol F and somewhat more potent than 

bisphenol S. Bisphenol C elicited estrogenic and anti-estrogenic responses in a CARP-HEP/vitellogenin 

assay.

Binding Assays

In a human ER binding assay, the 

relative binding affinity (RBA) of 

bisphenol C, was 0.129% compared to 

126% for 17β-estradiol. RBAs for other 

bisphenol compounds included 0.195% 

for BPA, 0.0803% for bisphenol AP, 

0.0719% for bisphenol F, and 0.0055% 

for bisphenol S. An RBA of 0.00473% 

was reported for PHBB.

METI, 2002 Adequate.

In a competitive ER binding assay using 

human ERα, the RBA for bisphenol C 

was 1.68% that of 17β-estradiol. RBAs 

for other bisphenol compounds included 

0.32% for BPA, 1.66% for bisphenol 

AP, and 0.09% for bisphenol F.

Coleman, Toscano et al., 2003 Adequate.

Gene Transcription and Reporter 

Gene Assays

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Bisphenol C exhibited evidence of 

estrogenic activity in a yeast 

(Saccharomyces cerevisiae) two-hybrid 

assay using ERα and the coactivator 

TIF2. Based on estrogenic activity that 

was 5 orders of magnitude lower than 

that of 17β-estradiol, bisphenol C was 

considered weakly estrogenic. 

Assessment of other bisphenols resulted 

in a ranking of relative potency as 

follows: bisphenol C ≥ BPA > bisphenol 

F > bisphenol S.

Chen, Michihiko et al., 2002 Adequate.

Bisphenol C did not exhibit evidence of 

estrogenic activity in a yeast 

(Saccharomyces cerevisiae) two-hybrid 

assay using ERα and the coactivator 

TIF2.

Nishihara, Nishikawa et al., 2000 Adequate.

In a reporter gene assay of estrogeninduced transcriptional activity, relative 

activity (RA) for bisphenol C was 

0.00189% compared to 81.7% for 17βestradiol. RAs for other bisphenol 

compounds included 0.00278% for BPA, 

0.000639% for bisphenol F, 0.000254% 

for bisphenol S, and 0.000184% for 

bisphenol AP. An RA of 0.000592% was 

reported for PHBB.

METI, 2002 Adequate.

In an ERE-luciferase reporter assay 

using MCF-7 cells, an EC50 was 0.42 μM 

for bisphenol C compared to an EC50 of 

8.6x10-6 for 17β-estradiol (i.e., BPA was 

approximately 5 orders of magnitude less 

potent than 17β-estradiol at inducing 

Kitamura, Suzuki et al., 2005 Adequate.

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estrogenic activity). EC50 values for 

other bisphenol compounds included 

0.63 μM for BPA, 1.0 μM for bisphenol 

F, and 1.1 μM for bisphenol S

In an ER-mediated reporter gene 

expression assay, bisphenol C induced 

reporter gene expression at a relative 

activity (RA) of 4.9x10-4 that of 17βestradiol. RAs for other bisphenol 

compounds included 5.3x10-4 for 

bisphenol F, 9.0x10-5 for bisphenol AP, 

and 2.75x10-3 for BPA.

Coleman, Toscano et al., 2003 Adequate.

In an ERE-luciferase reporter assay 

using MCF-7 cells in the presence of 

17β-estradiol, neither bisphenol C, BPA, 

bisphenol F, nor bisphenol S appeared to 

exert an anti-estrogenic effect

Kitamura, Suzuki et al., 2005 Adequate.

In a proliferation assay of MCF-7 human 

breast cancer cells that contain ERα and 

ERβ and are known to proliferate in 

response to estrogens, bisphenol C 

induced a proliferative response that was 

1.6x10-3 that of 17β-estradiol. Respective 

proliferative responses for other 

bisphenol compounds were 2.0x10-3 for

BPA, 1.0x10-3 for bisphenol F, and 

6.0x10-4 for bisphenol AP.

Coleman, Toscano et al., 2003 Adequate.

In an ERE-luciferase reporter assay 

using MCF-7 cells in the presence of 

17β-estradiol, neither bisphenol C, BPA, 

bisphenol F, nor bisphenol S appeared to 

exert an anti-estrogenic effect

Kitamura, Suzuki et al., 2005 Adequate.

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Cell Proliferation Assays

In a proliferation assay of MCF-7 human 

breast cancer cells that contain ERα and 

ERβ and are known to proliferate in 

response to estrogens, bisphenol C 

induced a proliferative response that was 

1.6x10-3 that of 17β-estradiol. Respective 

proliferative responses for other 

bisphenol compounds were 2.0x10-3 for

BPA, 1.0x10-3 for bisphenol F, and 

6.0x10-4 for bisphenol AP.

Coleman, Toscano et al., 2003 Adequate.

Androgen Assays

In an ARE-luciferase reporter assay 

using a mouse fibroblast cell line 

(NIH3T3 cells), neither bisphenol C, 

BPA, bisphenol F, nor bisphenol S 

exerted an androgenic effect

Kitamura, Suzuki et al., 2005 Adequate.

In an ARE-luciferase reporter assay 

using a mouse fibroblast cell line 

(NIH3T3 cells), bisphenol C inhibited 

the androgenic activity of 

dihydrotestosterone. Anti-androgenic 

responses were elicited by BPA, 

bisphenol F, and bisphenol S as well.

Kitamura, Suzuki et al., 2005 Adequate.

Thyroid Assays

In an assay of thyroid hormonal activity 

whereby induction of growth hormone 

production is assessed in GH3 cells, 

neither bisphenol C nor BPA inhibited 

growth hormone production.

Kitamura, Suzuki et al., 2005 Adequate.

Vitellogenin Assays

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In a CARP-HEP/vitellogenin assay, 

bisphenol C and BPA induced 

vitellogenin production by up to 5 and 

3%, respectively, of the vitellogenin 

production elicited by 17β-estradiol, 

indicating an estrogenic effect. In 17βestradiol-induced preparations, bisphenol 

C inhibited vitellogenin production with 

a potency approximately one-hundredth 

that of the known estrogen antagonist 

tamoxifen, indicating an anti-estrogenic 

effect for bisphenol C.

Letcher, Sanderson et al., 2005 Adequate.

Immunotoxicity No data located.

Immune System Effects No data located.

ECOTOXICITY

ECOSAR Class Polyphenols

Acute Toxicity HIGH: Based on an experimental LC50 value for Daphnid (1.6 mg/L) and estimated acute toxicity values.

Fish LC50 Fish 96-hour LC50 = 0.60 mg/L

(Estimated) 

ECOSAR: polyphenols

ECOSAR version 1.00

Fish 96-hour LC50 = 0.95 mg/L

(Estimated) 

ECOSAR: neutral organics

ECOSAR version 1.00 Narcosis classes (neutral organics) are 

provided for comparative purposes; 

DfE assessment methodology will use 

the lowest estimated toxicity value 

provided by ECOSAR classes that 

have a more specific mode of action 

relative to narcosis.

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Daphnid LC50 Daphnia magna 48-hour EC50 = 

1.6 mg/L; 24-hour EC50 = 4 mg/L 

(Experimental)

Chen, Michihiko et al., 2002 Adequate.

Daphnid 48-hour LC50 = 0.77 mg/L

(Estimated) 

ECOSAR: neutral organics

ECOSAR version 1.00 Narcosis classes (neutral organics) are 

provided for comparative purposes; 

DfE assessment methodology will use 

the lowest estimated toxicity value 

provided by ECOSAR classes that 

have a more specific mode of action 

relative to narcosis.

Daphnid 48-hour LC50 = 0.85 mg/L

(Estimated) 

ECOSAR: polyphenols

ECOSAR version 1.00

Green Algae EC50 Green algae 96-hour EC50 = 1.02 mg/L

(Estimated) 

ECOSAR: neutral organics

ECOSAR version 1.00 Narcosis classes (neutral organics) are 

provided for comparative purposes; 

DfE assessment methodology will use 

the lowest estimated toxicity value 

provided by ECOSAR classes that 

have a more specific mode of action 

relative to narcosis.

Green algae 96-hour EC50 = 1.25 mg/L

(Estimated) 

ECOSAR: polyphenols

ECOSAR version 1.00

Chronic Aquatic Toxicity HIGH: Estimated LC50 values for fish (neutral organics) <0.1 mg/L. All other estimated LC50 and EC50

values for neutral organics and polyphenol classes fall within 0.1 and 1.0.

Fish ChV Fish ChV = 0.09 mg/L

(Estimated) 

ECOSAR: neu

tral organics

ECOSAR version 1.00 Narcosis classes (neutral organics) are 

provided for comparative purposes; 

DfE assessment methodology will use 

the lowest estimated toxicity value 

provided by ECOSAR classes that 

have a more specific mode of action 

relative to narcosis. 

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Fish ChV = 0.12 mg/L

(Estimated) 

ECOSAR: polyphenols

ECOSAR version 1.00

Daphnid ChV Daphnid ChV = 0.12 mg/L

(Estimated) 

ECOSAR: neutral organics

ECOSAR version 1.00 Narcosis classes (neutral organics) are 

provided for comparative purposes; 

DfE assessment methodology will use 

the lowest estimated toxicity value 

provided by ECOSAR classes that 

have a more specific mode of action 

relative to narcosis.

Daphnid ChV = 0.27 mg/L

(Estimated) 

ECOSAR: polyphenols

ECOSAR version 1.00

Green Algae ChV Green algae ChV = 0.13 mg/L

(Estimated) 

ECOSAR: polyphenols

ECOSAR version 1.00

Green algae ChV = 0.61 mg/L

(Estimated) 

ECOSAR: neutral organics

ECOSAR version. 1.00 Narcosis classes (neutral organics) are 

provided for comparative purposes; 

DfE assessment methodology will use 

the lowest estimated toxicity value 

provided by ECOSAR classes that 

have a more specific mode of action 

relative to narcosis.

ENVIRONMENTAL FATE

Transport If released to air, a vapor pressure of 2.3x10-6 mm Hg at 25°C indicates that bisphenol C will exist in both 

the vapor and particulate phases in the atmosphere. Particulate-phase bisphenol C will be removed from 

the atmosphere by wet or dry deposition. If released to soil, bisphenol C is expected to have low mobility 

based upon an estimated Koc of >30,000. Volatilization from water surfaces is not expected to be an 

important fate process based upon this compound's estimated Henry's Law constant. Level III fugacity 

model results, which utilized estimated values as the input parameters, indicate that bisphenol C will 

partition primarily to soil and sediment.

Henry’s Law Constant <1x10-8 (Estimated) EPI Cutoff value for nonvolatile 

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(atm-m3/mole) compounds based on professional 

judgment. 

Sediment/Soil 

Adsorption/Desorption

Coefficient – Koc

>30,000 (Estimated) EPI; U.S. EPA 2004; 

Professional judgment 

Cutoff value for nonmobile 

compounds. 

Level III Fugacity Model Air = <1% (Estimated)

Water = 6%

Soil = 63%

Sediment = 31%

EPI

Persistence MODERATE: Experimental studies indicate that bisphenol C may be removed from the environment by 

aerobic biodegradation. Bisphenol C has a measured primary biodegradation half-life in water of less than 

2 weeks in a TOC Handai river die away method. Ultimate biodegradation will take longer based on 

experimental studies demonstrating 17% mineralization after 2 weeks (Ike, Chen et al, 2006). Although 

three bisphenol C degradation intermediates have been identified (Sakai, Yamanaka et al., 2007), the 

ultimate biodegradation data indicate that they do not persist in the environment. Bisphenol C lacks 

functional groups susceptible to hydrolysis and so hydrolysis is not an expected removal process. In 

addition, photolysis and anaerobic biodegradation have not been reported for bisphenol C.

Water Aerobic Biodegradation 17% in 2 weeks (complete degradation)

(Measured)

Ike, Chen et al., 2006 Adequate; valid nonguideline study 

demonstrating river water 

microcosms have the potential to 

biodegrade bisphenol C.

58% in 2 weeks; % removal in a 

microcosm study (partial degradation) 

(Measured)

Ike, Chen et al., 2006 Supporting information presented; 

nonguideline study.

94% in four days by Sphingomonas sp. 

Strain BP-7 (degradation intermediates 

detected) 

(Measured)

Sakai, Yamanaka et al., 2007 Adequate; valid nonguideline study 

using a pure culture inoculum 

supporting the potential for aerobic 

biodegradation.

Degradation products 4-hydroxy3-methyl acetophenone, 4-hydroxy3-methyl benzoic acid, and 

2,2-bis[4-hydroxy-3-methylphenyl]-

Lobos, Leib et al., 1992 Adequate, nonguideline study that 

provides supporting information on 

environmental persistence.

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1-propanol identified; no biodegradation 

rate information included 

(Measured)

Volatilization Half-life for 

Model River

>1 year (Estimated) EPI

Volatilization Half-life for 

Model Lake

>1 year (Estimated) EPI

Soil Aerobic Biodegradation No data located.

Anaerobic 

Biodegradation

Not probable (anaerobic-methanogenic 

biodegradation probability model)

EPI

Soil Biodegradation w/ 

Product Identification

No data located.

Sediment/Water 

Biodegradation

No data located.

Air Atmospheric Half-life 1.3 hours (Estimated) EPI

Reactivity Photolysis Not a significant fate process 

(Estimated)

Mill, 2000; Professional 

judgment 

The substance does not contain 

functional groups that would be 

expected to absorb light at 

environmentally significant 

wavelengths.

Hydrolysis Not a significant fate process 

(Estimated)

Wolfe and Jeffers, 2000; 

Professional judgment

The substance does not contain 

functional groups that would be 

expected to hydrolyze readily under 

environmental conditions.

Pyrolysis No data located.

Environmental Half-life 75 days (Estimated) EPI; PBT Profiler Half-life estimated for the 

predominant compartment, as 

determined by EPI and the PBT 

Profiler methodology.

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Bioaccumulation MODERATE: The estimated fish BCF is <1,000.

Fish BCF 620 (Estimated) EPI

BAF 110 (Estimated) EPI

Metabolism in Fish No data located.

ENVIRONMENTAL MONITORING AND BIOMONITORING 

Environmental Monitoring No data located.

Ecological Biomonitoring No data located.

Human Biomonitoring This chemical was not included in the NHANES biomonitoring report (CDC, 2011).

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FINAL REPORT – January 2014 

Aldrich. Handbook of Fine Chemicals and Laboratory Equipment. 2009-2010. Milwaukee, WI: Aldrich Chem Co. 2009, p.344. 

Chen, M-Y.; Michihiko, I.; Fujita, M. Acute toxicity, mutagenicity, and estrogenicity of bisphenol-A and other bisphenols. Environ. 

Toxicol. 2002, 17:80-86. 

Coleman, K.P., Toscano, W.A., Wiese, T.E. QSAR Models of the in vitro estrogen activity of bisphenol A analogs. QSAR & 

Combinatorial Science 2003. 22:78-88. 

CDC (Centers for Disease Control and Prevention). Fourth national report on human exposure to environmental chemicals, updated 

tables. Department of Health and Human Services. 2011. http://www.cdc.gov/exposurereport/ (accessed on May 10, 2011). 

ECOSAR (2010) Ecological Structure Activity Relationship (ECOSAR) Version 1.00. Washington, DC: U.S. Environmental 

Protection Agency. http://www.epa.gov/oppt/newchems/tools/21ecosar.htm. 

EINECS. 4,4’-Isopropylidenediphenol (bisphenol A). European Union Risk Assessment Report. 2010.

EPI (EPIWIN/EPISUITE) Estimations Programs Interface for Windows, Version 4.00. U.S. Environmental Protection Agency: 

Washington D.C. http://www.epa.gov/opptintr/exposure/. 

ESIS (European chemical Substances Information System) Classification, labeling and Packaging of dangerous substances annex VI 

to regulation (EC) No 1272/2008 [Online] http://esis.jrc.ec.europa.eu/ (accessed on June 10, 2011). 

European Commission. IUCLID Dataset for 4,4-isopropylidenediphenol (CAS No. 80-05-7). European Chemicals Bureau, February 

19, 2000. 2000. 

FAO/WHO. Toxicological and health aspects of bisphenol A. Report of Joint FAO/WHO expert meeting 2-5 November 2010 and 

report of stakeholder meeting on bisphenol A 1 November 2010. Food and Agriculture Organization of the United Nations; 

World Health Organization. Ottawa, Canada. 2011. 

Ike, M.; Chen, M.Y.; Danzl, E.; et al. Biodegradation of a variety of bisphenols under aerobic and anaerobic conditions. Water Sci. 

Technol. 2006, 53:153-159. 

Kitamura, S.; Suzuki, T.; Sanoh, S.; et al. Comparative study of the endocrine-disrupting activity of bisphenol A and 19 related 

compounds. Toxicol. Sci. 2005, 84:249-259. 

Lehmann L., Metzler M. Bisphenol A and its methylated congeners inhibit growth and interfere with microtubules in human 

fibroblasts in vitro. Chem. Biol. Interact. 2004, 147:273-285. 

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Letcher, R. J., Sanderson, J.T., Bokkers, A., et al. Effects of bisphenol A-related diphenylalkanes on vitellogenin production in male 

carp (Cyprinus carpio) hepatocytes and aromatase (CYP19) activity in human H295R adrenocortical carcinoma cells. Toxicol. 

Appl. Pharmacol. 2005, 209:95-104. 

Lide, D. R, ed. CRC Handbook of Chemistry and Physics, 88th edition; CRC Press Taylor Francis: Boca Raton, FL. 2008. 

Lobos, J., Leib, T., Su, T. Biodegradation of Bisphenol A and Other Bisphenols by a Gram-Negative Aerobic Bacterium. Appl. 

Environ. Microbiol. 1992, 58(6):1823-1831. 

Mill, T. 2000. Photoreactions in Surface Waters. In Boethling, R.; Mackay, D., Handbook of Property Estimation Methods for 

Chemicals, Environmental Health Sciences (355-382). Boca Raton: Lewis Publishers. 

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Japan. 6th meeting of the task force on Endocrine Disruptors Testing and Assessments (EDTA). 24-25 June, 2002. Tokyo. 

NIOSH (National Institute for Occupational Safety and Health). Skin notation (SK) profile, bisphenol A (BPA) [CAS No. 80-05-7]. 

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2000, 46(4) 282-298. 

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(feed study). Technical Report No. 215, PB82-184060. 1982. 

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Program; U.S. Department of Health and Human Service. Center for the Evaluation of Risks to Human Reproduction. NIH 

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Oncologic. U.S. EPA and LogiChem, Inc. 2005, Version 7.0. 2008. 

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Washington D.C. www.pbtprofiler.net. 

Perez, P., Pulgar, R., Olea-Serrano, F., et al. The estrogenicity of bisphenol A-related diphenylalkanes with various substituents at the 

central carbon and the hydroxyl groups. Environ. Health Perspect. 1998, 106(3):167-174. 

Pfeiffer, E., Rosenberg, B., Deuschel, S., et al. Interference with microtubules and induction of micronuclei in vitro by various 

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Sakai, K., Yamanaka, H., Moriyoshi, K, et al. Biodegradation of bisphenol A and related compounds by Sphingomonas sp. strain BP-7 

isolated from seawater. Biosci. Biotechnol. Biochem. 2007, 71(1):51-57. 

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Pollution Prevention and Toxics 7403M, U.S. Environmental Protection Agency, Washington, DC. 20460. October 2003 

version updated in January 2004. Latest version available at http://www.epa.gov/opptintr/newchems/pubs/sustainable/p2framejune05a2.pdf

U.S. EPA (Environmental Protection Agency). Sustainable Futures Using NonCancer Screening within the Sustainable Futures 

Initiative Environmental Protection Agency: Washington D.C. 2010. http://www.epa.gov/opptintr/sf/pubs/noncanscreen.htm#systemic (accessed on February 09, 2011). 

Wolfe, N.; Jeffers, P. (2000) Hydrolysis. In Boethling, R.; Mackay, D., Handbook of Property Estimation Methods for Chemicals, 

Environmental Health Sciences (311-334). Boca Raton: Lewis Publishers. 

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MBHA

OH OH

O O CASRN: 5129-00-0

MW: 258.28

MF: C15H14O4

Physical Forms: 

Neat: Solid

Use: Developer for thermal paper 

SMILES: O=C(OC)C(c(ccc(O)c1)c1)c(ccc(O)c2)c2

Synonyms: Benzeneacetic acid, 4-hydroxy-.alpha.-(4-hydroxyphenyl)-, methyl ester; Methyl bis(4-hydroxyphenyl)acetate

Polymeric: No

 Oligomers: Not applicable

Metabolites, Degradates and Transformation Products: None identified

Analog: Bisphenol A (80-05-7)

 Endpoint(s) using analog values: Acute toxicity, reproductive, 

developmental, repeated dose, skin and eye irritation, genotoxicity

Analog Structure:

OH OH

4-140 

Structural Alerts: Phenols, neurotoxicity (U.S. EPA, 2010)

Risk Phrases: Not classified by Annex VI Regulation (EC) No 1272/2008 (ESIS, 2011).

Risk Assessments: None identified
FINAL REPORT – January 2014 

MBHA CASRN 5129-00-0

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

PHYSICAL/CHEMICAL PROPERTIES

Melting Point (°C) No data located.

Boiling Point (°C) >300 (Estimated) EPI; U.S. EPA, 1999 Cutoff value for high boiling point 

compounds according to HPV 

assessment guidance.

Vapor Pressure (mm Hg) 3.3x10-8 (Estimated) EPI

Water Solubility (mg/L) 360 (Estimated) EPI

Log Kow 2.8 (Estimated) EPI

Flammability (Flash Point) No data located.

Explosivity No data located.

pH No data located.

pKa 9.7-9.9 (Estimated) SPARC

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HUMAN HEALTH EFFECTS

Toxicokinetics MBHA as a neat material is estimated to not be absorbed through the skin and will have poor skin 

absorption when in solution. MBHA is expected to be absorbed via the lungs and gastrointestinal tract. It is 

expected that MBHA will undergo ester hydrolysis by esterases in the body.

Dermal Absorption in vitro No data located.

Absorption, 

Distribution, 

Metabolism & 

Excretion

Oral, Dermal or Inhaled Not absorbed through the skin as neat 

material and has poor absorption in 

solution; can be absorbed through the lung 

and gastrointestinal tract

(Estimated by analogy)

Professional judgment Based on closely related confidential 

analog with similar structure, 

functional groups, and 

physical/chemical properties. 

Acute Mammalian Toxicity LOW: The acute oral and dermal toxicity hazard of MBHA is estimated to be low based on experimental 

data in animals for the analog BPA. Data for exposure to the analog BPA via inhalation were inconclusive, 

as only a single concentration was tested and a LC50 was not provided. 

Acute Lethality Oral Rat LD50 = 3,200->5,000 mg/kg bw

(Estimated by analogy) 

NTP, 1982; European 

Commission, 2000; EINECS, 

2010; Professional judgment

Based on the analog BPA; multiple 

studies, some guideline studies. 

Mouse LD50 = 4,000-5,200 mg/kg bw

(Estimated by analogy) 

NTP, 1982; European 

Commission, 2000; EINECS, 

2010; Professional judgment

Based on the analog BPA; multiple 

studies, some guideline studies. 

Dermal Rabbit LD50 = 3,000-6,400 mg/kg bw

(Estimated by analogy) 

European Commission, 2000;

EINECS, 2010; Professional 

judgment 

Based on the analog BPA; adequate 

by weight of evidence, multiple 

studies, although study details were 

not reported in secondary sources.

Inhalation No deaths among male and female F344 

rats (10/sex) exposed to BPA dust at 

0.17 mg/L (highest attainable 

concentration) for 6 hours; transient slight 

nasal tract epithelial damage was evident. 

(Estimated by analogy)

European Commission, 2000;

EINECS, 2010; Professional 

judgment 

Based on the analog BPA; test 

guidelines were not reported in 

secondary sources. 

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Carcinogenicity MODERATE: Estimated using OncoLogic expert system which describes a concern for this compound as a 

potential carcinogen or tumorigenesis promoter arising from its structural similarity to 

estrogenic/androgenic compounds, using the “phenols and phenolic compounds” structural alert.

OncoLogic Results Moderate (Estimated)

OncoLogic class: phenols and phenolic 

compounds

OncoLogic OncoLogic SAR analysis using the 

phenols and phenolic compounds 

class.

Carcinogenicity (Rat and 

Mouse)

No data located.

Combined Chronic 

Toxicity/Carcinogenicity

No data located.

Genotoxicity LOW: Based on analogy to BPA. FAO/WHO (2011) determined that: (1) the analog BPA is not a mutagen 

in in vitro test systems, (2) the analog BPA does not induce cell transformation, and (3) in vivo evidence for 

clastogenic effects induced by the analog BPA is inconsistent and inconclusive, although some in vitro studies 

have shown BPA to affect chromosomal structure in dividing cells. The conclusion of FAO/WHO (2011) is 

that the analog BPA is not likely to pose a genotoxic hazard to humans.

Potential for mutagenicity

(Estimated by analogy) 

Professional judgment Estimated based on reported 

experimental data for the analog 

BPA.

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Largely negative results in a variety of in 

vitro test systems, including studies with 

Salmonella typhimurium, Chinese hamster 

V79 cells, Syrian hamster embryo cells 

and mouse lymphoma cells. However, 

DNA damage was induced in MCF-7 and 

MDA-MB-231 cells, DNA adduct 

formation in Syrian hamster ovary cells 

and a number of positive findings have 

been reported for the potential for BPA to 

inhibit purified microtubule 

polymerization, affect the spindle 

apparatus, and produce aneuploidy in in 

vitro studies with Chinese hamster V79 

cells or oocytes from Balb/c or MF1 mice.

FAO/WHO Expert Panel concludes: 

BPA is not a mutagen in in vitro test 

systems, nor does it induce cell 

transformation. BPA has been shown to 

affect chromosomal structure in dividing 

cells in in vitro studies, but evidence for 

this effect in in vivo studies is inconsistent 

and inconclusive. BPA is not likely to pose 

a genotoxic hazard to humans. 

(Estimated by analogy)

FAO/WHO, 2011 Based on the analog BPA.

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MBHA CASRN 5129-00-0

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Reproductive Effects MODERATE: Based on analogy to BPA. Key studies identified by NTP for the analog BPA indicate there 

are multiple distinct endpoints with NOAELs in the range of Moderate hazard concern with LOAELs in the 

range of Low hazard concern. At the target dose of 50 mg/kg-day (BPA), the NOAELs are on the margin of 

High and Moderate hazard, according to DfE criteria. Benchmark Dose (BMD) Modeling conducted by 

NTP, which interpolates between NOAEL and LOAEL values, yields values that further support a Moderate 

hazard designation.

Reproduction/ 

Developmental Toxicity 

Screen

No data located.

Combined Repeated Dose 

with Reproduction/ 

Developmental Toxicity 

Screen

No data located.

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Reproduction and Fertility 

Effects

Potential for reproductive toxicity

(Estimated by analogy) 

Professional judgment Estimated based on reported 

experimental data for the analog 

BPA.

Parental systemic toxicity:

NOAEL = 5 mg/kg bw-day 

LOAEL = 50 mg/kg bw-day for 12% 

decreased terminal body weight in F1

parental males

Reproductive toxicity: 

Females: NOAEL = 50 mg/kg bw-day 

LOAEL = 500 mg/kg bw-day for 

decreases in number of implantation sites, 

delayed vaginal opening in F1, F2, F3

offspring 

BMDLs (change of 1 standard deviation 

from control) reported for delayed vaginal 

opening (females)- 

F1 = 176 mg/kg-day 

F2 = 228 mg/kg-day 

F3 = 203 mg/kg-day 

Males: NOAEL = 50 mg/kg bw-day, 

LOAEL = 500 mg/kg-day for delayed 

preputial separation in F1 males

BMDLs (change of 1 standard deviation 

from control) reported for delayed 

preputial separation (males)- 

F1 = 163 mg/kg-day 

F2 = 203 mg/kg-day 

F3 = 189 mg/kg-day 

(Estimated by analogy)

NTP-CERHR, 2008; Professional 

judgment 

Based on the analog BPA; adequate, 

guideline study as reported in the 

secondary source. 

Classified by NTP-CERHR as 

having High Utility.

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Parental systemic toxicity:

NOAEL = 5 mg/kg bw-day 

LOAEL = 50 mg/kg bw-day for increased 

incidences of centrilobular hepatocellular 

hypertrophy in males and females 

Reproductive toxicity: 

NOAEL = 50 mg/kg bw-day 

LOAEL = 600 mg/kg bw-day for 

increased gestation length, decreased 

epididymal sperm concentration in F1

males, increased incidence of gross 

ovarian cysts in F1 and F2 females

BMD1 (change of 1 standard deviation 

from control) reported for increased 

gestation length

F0 = 1144 mg/kg-day (BMDL = 599 

mg/kg-day) 

F1 = 772 mg/kg-day (BMDL = 531 mg/kgday) 

BMD10s (10% extra risk) reported for 

increased incidence of gross ovarian cysts

F0 = 225 mg/kg-day (BMDL = 141 mg/kgday) 

F1 = 202 mg/kg-day (BMDL = 120 mg/kgday) 

(Estimated by analogy)

NTP-CERHR, 2008; Professional 

judgment 

Based on the analog BPA; adequate, 

guideline study as reported in the 

secondary source. 

Classified by NTP-CERHR as 

having High Utility.

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Summary of Reproductive 

Effects

Female effects: There is sufficient 

evidence in rats and mice that BPA caused

female reproductive toxicity with 

subchronic or chronic oral exposures with 

a NOAEL of 50 mg/kg bw-day and a 

LOAEL of 500 mg/kg bw-day. 

Male effects: There is sufficient evidence 

in rats and mice that BPA causes male 

reproductive toxicity with subchronic or 

chronic oral exposures with a NOAEL of 

50 mg/kg bw-day and a LOAEL of 500 

mg/kg bw/day. 

(Estimated by analogy)

NTP-CERHR, 2008; Professional 

judgment 

Based on the analog BPA.

Classified by NTP-CERHR as 

having High Utility.

The joint FAO/WHO Expert Panel (2011)

reviewed are productive and 

developmental toxicity data for BPA 

located as of November 2010 and noted 

that most regulatory bodies reviewing the 

numerous studies on BPA have indicated 

an oral reproductive and developmental 

NOAEL of 50 mg/kg bw-day. 

(Estimated by analogy)

FAO/WHO, 2011; Professional 

judgment 

Based on the analog BPA.

Developmental Effects HIGH: Based on analogy to BPA. The NTP-CERHR (2008) Expert Panel concluded that there is suggestive 

evidence that BPA causes neural and behavioral alterations related to disruptions in normal sex differences 

in rats and mice (0.01-0.2 mg/kg bw-day) following developmental exposures. The FAO/WHO (2011) Expert 

Panel also concluded that while there was broad agreement in a NOAEL of 50 mg/kg bw-day for 

developmental toxicity based on standard bioassays, specific targeted studies identified neurodevelopmental 

effects at low doses (<1 mg/kg bw-day), but the human relevance is less certain. There is great variation in 

results with different types of studies measuring different endpoints; developmental effects at lower doses 

cannot be ruled out. Taken together these findings support a hazard designation of High concern.

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Reproduction/ 

Developmental Toxicity 

Screen

No data located.

Combined Repeated Dose 

with Reproduction/ 

Developmental Toxicity 

Screen

No data located.

Summary of 

Developmental Effects

Potential for developmental toxicity

(Estimated by analogy) 

Professional judgment Estimated based on reported 

experimental data for the analog 

BPA.

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The NTP-CERHR (2008) Expert Panel 

concluded that BPA: 

*does not cause malformations or birth 

defects in rats or mice at levels up to the 

highest doses evaluated: 640 mg/kg bwday (rats) and 1,250 mg/kg bw-day (mice).

*does not alter male or female fertility 

after gestational exposure up to doses of 

450 mg/kg bw-day in the rat and 

600mg/kg bw-day in the mouse (highest 

dose levels evaluated). 

*does not permanently affect prostate 

weight at doses up to 475 mg/kg bw-day in 

adult rats or 600 mg/kg bw-day in mice. 

*does not cause prostate cancer in rats or 

mice after adult exposure at up to 148 or 

600 mg/kg bw-day, respectively. 

*does change the age of puberty in male or 

female rats at high doses (ca. 475 mg/kg 

bw-day). 

And that rodent studies suggest that BPA:

*causes neural and behavioral alterations 

related to disruptions in normal sex 

differences in rats and mice (0.01–

0.2 mg/kg bw-day). 

(Estimated by analogy)

NTP–CERHR, 2008; Professional 

judgment 

Based on the analog BPA.

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MBHA CASRN 5129-00-0

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

The joint FAO/WHO (2011) Expert Panel 

reviewed reproductive and developmental 

toxicity data for BPA located as of 

November 2010 and noted that most 

regulatory bodies reviewing the numerous 

studies on BPA have indicated an oral 

reproductive and developmental NOAEL 

of 50 mg/kg bw-day. 

(Estimated by analogy)

FAO/WHO, 2011; Professional 

judgment 

Based on the analog BPA.

Neurotoxicity MODERATE: Estimated to have potential for neurotoxicity based on the presence of the phenol structural 

alert.

Neurotoxicity Screening 

Battery (Adult)

There is potential for neurotoxicity effects 

based on the presence of the phenol 

structural alert. 

(Estimated)

U.S. EPA, 2010; Professional 

judgment 

Estimated based on structural alert.

Repeated Dose Effects MODERATE: Estimated based on analogy to BPA, which produced histopathologic changes in the liver 

(centrilobular hepatocyte hypertrophy) from oral dosing at 50 mg/kg bw-day (NOAEL = 5 mg/kg bw-day) 

and there is uncertainty regarding the potential for BPA doses between the NOAEL of 5 mg/kg bw-day and 

the LOAEL of 50 mg/kg bw-day to cause adverse systemic effects. Furthermore, lesions in the nasal cavity of 

rats were reported following repeated inhalation exposure to BPA dust at 0.05 mg/L. These findings indicate 

a Moderate hazard concern for the oral and inhalation exposure routes.

Potential for liver toxicity

(Estimated by analogy)

Professional judgment Estimated based on reported 

experimental data for the analog 

BPA.

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PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

The FAO/WHO (2011) Expert Panel 

reviewed the available information 

regarding repeated-dose oral toxicity of 

BPA and concluded that results 

demonstrated effects on the liver, kidney, 

and body weight at doses of 50 mg/kg bwday and higher and that the lowest 

NOAEL was 5 mg/kg-day, as identified in 

several studies. 

(Estimated by analogy)

FAO/WHO, 2011; Professional 

judgment 

Based on the analog BPA.

Parental systemic toxicity:

NOAEL = 4.75 mg/kg bw-day 

LOAEL = 47.5 mg/kg bw-day for 12% 

decreased terminal body weight in F1

parental males

(Estimated by analogy)

NTP-CERHR, 2008; Professional 

judgment 

Based on the analog BPA; guideline 

study as reported in the secondary 

source. 

Classified by NTP-CERHR as 

having High Utility.

Parental systemic toxicity:

NOAEL = 5 mg/kg bw-day 

LOAEL = 50 mg/kg bw-day for increased 

incidences of centrilobular hepatocellular 

hypertrophy in males and females 

(Estimated by analogy)

NTP-CERHR, 2008; Professional 

judgment 

Based on the analog BPA; guideline 

study as reported in the secondary 

source. 

Classified by NTP-CERHR as 

having High Utility.

NOAEL = 0.01 mg/L

LOAEL = 0.05 mg/L based on 

microscopic changes in the anterior 

portion of the nasal cavity 

(Estimated by analogy)

European Commission, 2000; 

EINECS, 2010; Professional 

judgment 

Based on the analog BPA. 

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NOAEL = None established

LOAEL = 0.047 mg/L for decreased body 

weight gain, increased liver and kidney 

weight, unspecified “morphological 

changes” in liver, kidney, and lungs 

(Estimated by analogy)

European Commission, 2000; 

EINECS, 2010; Professional 

judgment 

Based on the analog BPA; single 

exposure level, insufficient study 

details in secondary sources. 

Skin Sensitization LOW: Based on experimental data, MBHA is not a skin sensitizer in guinea pigs. 

Skin Sensitization Not a skin sensitizer in maximization 

assay in guinea pigs

Kawaguchi Chemical Co., 2011 Conducted according to OECD 

guideline 406.

Respiratory Sensitization No data located.

Respiratory Sensitization No data located.

Eye Irritation MODERATE: Based on analogy to BPA. The analog BPA was slightly to highly irritating to rabbit eyes.

Eye Irritation Rabbit, slightly to highly irritating

(Estimated by analogy) 

European Commission, 2000; 

EINECS, 2010; Professional 

judgment 

Based on the analog BPA. Adequate;

multiple studies, weight of evidence 

indicates potential for BPA to cause 

eye irritation.

Dermal Irritation MODERATE: Based on analogy to BPA. The analog BPA was slightly irritating to moderately irritating to 

rabbit skin. NIOSH has assigned the analog, BPA as a skin irritant.

Dermal Irritation Rabbit, nonirritating to slightly irritating 

when applied as undiluted or 10% aqueous 

suspension to intact or abraded skin. 

(Estimated by analogy)

European Commission, 2000; 

EINECS, 2010; NIOSH 2010; 

Professional judgment

Based on the analog BPA. Adequate;

multiple studies, weight of evidence 

indicates potential for BPA to cause 

dermal irritation.

Rabbit, moderately irritating when applied 

as 40% solution in dimethyl sulfoxide 

under non-occlusive conditions. 

(Estimated by analogy)

European Commission, 2000; 

Professional judgment

Based on the analog BPA; adequate.

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Guinea pig, not irritating when applied as 

5% solution in acetone for 24 hours under 

occlusive conditions. 

(Estimated by analogy)

European Commission, 2000; 

Professional judgment

Based on the analog BPA; adequate.

Endocrine Activity No data located.

No data located.

Immunotoxicity No data located.

Immune System Effects No data located.

ECOTOXICITY

ECOSAR Class Polyphenols, esters

Acute Toxicity HIGH: Estimated 96-hour LC50 for fish and 96-hour EC50 for algae are in the range of 1-10 mg/L.

Fish LC50 Fish 96-hour LC50 = 8.80 mg/L 

(Estimated) 

ECOSAR: polyphenols

ECOSAR version 1.00

Fish 96-hour LC50 = 13.0 mg/L 

(Estimated) 

ECOSAR: esters

ECOSAR version 1.00

Fish 96-hour LC50 = 45.72 mg/L 

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.00 Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided by 

ECOSAR classes that have a more 

specific mode of action relative to 

narcosis.

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Daphnid LC50 Daphnid 48-hour LC50 = 24.24 mg/L

(Estimated) 

ECOSAR: esters

ECOSAR version 1.00

Daphnid 48-hour LC50 = 28.52 mg/L

(Estimated) 

ECOSAR: polyphenols 

ECOSAR version 1.00

Daphnid 48-hour LC50 = 28.9 mg/L

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.00 Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided by 

ECOSAR classes that have a more 

specific mode of action relative to 

narcosis.

Saltwater Invertebrate LC50 Mysid shrimp 96-hour LC50 = 12.60 mg/L

(Estimated) 

ECOSAR: esters

ECOSAR version 1.00

Green Algae EC50 Green algae 96-hour EC50 = 1.88 mg/L

(Estimated) 

ECOSAR: polyphenols

ECOSAR version 1.00

Green algae 96-hour EC50 = 9.53 mg/L

(Estimated) 

ECOSAR: esters

ECOSAR version 1.00

Green algae 96-hour EC50 = 16.98 mg/L

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.00 Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided by 

ECOSAR classes that have a more 

specific mode of action relative to 

narcosis.

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PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Chronic Aquatic Toxicity HIGH: Estimated ChV for fish and ChV for algae are in the range of 0.1-1.0 mg/L.

Fish ChV Fish 32/33-day ChV = 0.97 mg/L

(Estimated) 

ECOSAR: esters

ECOSAR version 1.00

Fish 30-day ChV = 2.41 mg/L

(Estimated) 

ECOSAR: polyphenols

ECOSAR version 1.00

Fish ChV = 4.27 mg/L

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.00 Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided by 

ECOSAR classes that have a more 

specific mode of action relative to 

narcosis.

Daphnid ChV Daphnid ChV = 3.050 mg/L

(Estimated) 

ECOSAR: neutral organics

ECOSAR version 1.00

Daphnid 21-day ChV = 12.60 mg/L

(Estimated) 

ECOSAR: esters

ECOSAR version 1.00

Daphnid 21-day ChV = 10.19 mg/L

(Estimated) 

ECOSAR: polyphenols

ECOSAR version 1.00

Saltwater Invertebrate ChV Mysid shrimp ChV = 194.76 mg/L

(Estimated) 

ECOSAR: esters

ECOSAR version 1.00

Green Algae ChV Green algae ChV = 0.450 mg/L

(Estimated) 

ECOSAR: polyphenols

ECOSAR version 1.00

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Green algae ChV = 3.07 mg/L

(Estimated) 

ECOSAR: esters

ECOSAR version 1.00

Green algae ChV = 7.05 mg/L

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.00 Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided by 

ECOSAR classes that have a more 

specific mode of action relative to 

narcosis.

Earthworm Subchronic Toxicity Earthworm 14-day LC50 = 1,922.81 mg/L

(Estimated) 

ECOSAR: esters

(MBHA may not be soluble enough to 

measure this predicted effect)

ECOSAR version 1.00

ENVIRONMENTAL FATE

Transport MBHA is expected to partition primarily to soil based on results from a level III fugacity model

incorporating estimated property data. Based on its estimated pKa, it is expected to exist primarily in the 

neutral form at environmentally-relevant pH, but anionic forms may be present at the upper-range of 

environmental pH. The neutral form of MBHA is expected to be moderately mobile in soil based on its 

estimated Koc. The anionic form may have higher mobility, as anions do not bind as strongly to organic 

carbon and clay. However, leaching of MBHA through soil to groundwater is not expected to be an 

important transport mechanism. In the atmosphere, MBHA is expected to exist in the particulate phase, 

based on its estimated vapor pressure. Particulates will be removed from air by wet or dry deposition. If 

released to soil, MBHA is expected to bind strongly to soils with minimal migration to subsurface depths. It 

is not expected to migrate from water or soil surfaces to air. Release of particulates to the atmosphere will 

result in deposition to soil and water surfaces. 

Henry’s Law Constant 

(atm-m3/mole)

<1x10-8 (Estimated) EPI Cutoff value for nonvolatile 

compounds based on professional 

judgment. 

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Sediment/Soil 

Adsorption/Desorption

Coefficient – Koc

7,300 (Estimated) EPI

Level III Fugacity 

Model

Air = <1%

Water = 15 %

Soil = 81%

Sediment = 3% (Estimated)

EPI

Persistence MODERATE: The persistence of MHBA is based on an estimated half-life of 30 days in soil. MBHA is 

expected to partition primarily to soil. Experimental biodegradation data for MBHA were not available. 

Results from biodegradation models estimate ultimate biodegradation in weeks and primary degradation in 

days-weeks. Biodegradation under anaerobic methanogenic conditions is not probable based on results from 

estimation models. MBHA does not contain chromophores that absorb light at environmentally-relevant 

wavelengths. Therefore, it is not expected to be susceptible to direct photolysis. Hydrolysis is expected to be 

negligible based on hydrolysis rate estimations. The atmospheric half-life of MBHA is estimated at 1.8 hours, 

although it is expected to exist primarily as a particulate in air. Biodegradation is expected to be the 

predominant fate pathway for MBHA in the environment. 

Water Aerobic 

Biodegradation

Days-weeks (primary survey model)

Weeks (ultimate survey model)

EPI

Volatilization Half-life 

for Model River

>1 year (Estimated) EPI

Volatilization Half-life 

for Model Lake

>1 year (Estimated) EPI

Soil Aerobic 

Biodegradation

No data located.

Anaerobic 

Biodegradation

Not probable (anaerobic-methanogenic 

biodegradation probability model)

EPI

Soil Biodegradation w/ 

Product Identification

No data located.

Sediment/Water 

Biodegradation

No data located.

Air Atmospheric Half-life 1.6 hours (Estimated) EPI

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Reactivity Photolysis Not a significant fate process (Estimated) Mill, 2000; Professional 

judgment 

The substance does not contain 

functional groups that would be 

expected to absorb light at 

wavelengths >290 nm.

Hydrolysis Half-life at pH 8 = 200 days (Estimated)

Half-life at pH 7 >1 year (Estimated)

EPI

Pyrolysis No data located.

Environmental Half-life 30 days EPI, PBT Profiler Half-life estimated for the 

predominant compartment, as 

determined by EPI and the PBT 

Profiler methodology.

Bioaccumulation LOW: The estimated BCF is <100.

Fish BCF 31 (Estimated) EPI

BAF 6 (Estimated) EPI

Metabolism in Fish No data located.

ENVIRONMENTAL MONITORING AND BIOMONITORING 

Environmental Monitoring No data located.

Ecological Biomonitoring No data located.

Human Biomonitoring This chemical was not included in the NHANES biomonitoring report (CDC, 2011).

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FINAL REPORT – January 2014 

CDC (Centers for Disease Control and Prevention). Fourth national report on human exposure to environmental chemicals, updated 

tables. Department of Health and Human Services. 2011. http://www.cdc.gov/exposurereport/ (accessed on May 10, 2011). 

ECOSAR (2010) Ecological Structure Activity Relationship (ECOSAR) Version 1.00. Washington, DC: U.S. Environmental 

Protection Agency. http://www.epa.gov/oppt/newchems/tools/21ecosar.htm. 

EINECS (European Inventory of Existing Commercial Chemical Substances). 4,4’-Isopropylidenediphenol (bisphenol A). European 

Union Risk Assessment Report. 2010.

EPI (EPIWIN/EPISUITE) Estimations Programs Interface for Windows, Version 4.00. U.S. Environmental Protection Agency: 

Washington D.C. http://www.epa.gov/opptintr/exposure/. 

European Commission. IUCLID Dataset for 4,4-isopropylidenediphenol (CAS No. 80-05-7). European Chemicals Bureau, February 

19, 2000. 2000.

ESIS (European chemical Substances Information System) Classification, labeling and Packaging of dangerous substances annex VI 

to regulation (EC) No 1272/2008 [Online] http://esis.jrc.ec.europa.eu/ (accessed on June 10, 2011). 

FAO/WHO. Toxicological and health aspects of bisphenol A. Report of Joint FAO/WHO expert meeting 2-5 November 2010 and 

report of stakeholder meeting on bisphenol A 1 November 2010. Food and Agriculture Organization of the United Nations; 

World Health Organization. Ottawa, Canada. 2011. 

Kawaguchi Chemical Co. Skin sensitization test of MBHA in guinea pigs (maximization test). Study No. STG045. Sumika 

Technoservice corporation, Osaka, Japan. 2011. 

Mill, T. 2000. Photoreactions in Surface Waters. In Boethling, R.; Mackay, D., Handbook of Property Estimation Methods for 

Chemicals, Environmental Health Sciences (355-382). Boca Raton: Lewis Publishers. 

NIOSH (National Institute for Occupational Safety and Health). Skin Notation (SK) Profile, Bisphenol A (BPA) [CAS No. 80-05-7]. 

Department of Health and Human Services; Centers for Disease Control and Prevention. 2010.

NTP-CERHR. Monograph on the potential human reproductive and developmental effects of biphenol A. National Toxicology 

Program; U.S. Department of Health and Human Service. Center for the Evaluation of Risks to Human Reproduction. NIH 

Publication No. 08-5994. September 2008. 

NTP (National Toxicology Program). Carcinogenesis bioassay of bisphenol-A (CAS No. 80-05-7) in F344 rats and B6C3F1 mice 

(feed study). Technical Report No. 215, PB82-184060. 1982. 

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Oncologic. U.S. EPA and LogiChem, Inc. 2005, Version 7.0. 2008. 

PBT Profiler Persistent (P),Bioaccumulative (B), and Toxic (T) Chemical (PBT)Profiler. U.S. Environmental Protection Agency: 

Washington D.C. www.pbtprofiler.net. 

SPARC On Line Calculator pKa/property server. Ver 4.5 September, 2009. Available from, http://ibmlc2.chem.uga.edu/sparc/

(accessed on August 12, 2010). 

U.S. EPA (Environmental Protection Agency). High Production Volume (HPV) Challenge. Determining the Adequacy of Existing 

Data. U.S. Environmental Protection Agency: Washington D.C. 1999. http://www.epa.gov/hpv/pubs/general/datadfin.htm 

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BisOPP-A 

OH

OH

CASRN: 24038-68-4

MW: 380.49

MF: C27H24O2

Physical Forms:

Neat: Solid

Use: Developer for thermal paper

SMILES: CC(C1=CC(C2=CC=CC=C2)=C(O)C=C1)(C)C3=CC(C4=CC=CC=C4)=C(O)C=C3

Synonyms: [1,1’-bisohenyl-2-ol]-2-ol, 5,5’(1-methylethylidene)bis-; 5,5'-Propane-2,2-diyldibiphenyl-2-ol; 4,4’-Isopropyllidenebis(2-phenylphenol); 2,2-Bis(2-

hydroxy-5-biphenyl)propane

Polymeric: No

 Oligomers: Not applicable

Metabolites, Degradates and Transformation Products: None

Analog: Bisphenol A (80-05-7)

 Endpoint(s) using analog values: Acute toxicity, eye and dermal 

irritation, skin sensitization, reproductive and developmental toxicity, 

genotoxicity, repeated dose effects

Analog Structure: 

OH OH

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Structural Alerts: Phenols, neurotoxicity (U.S. EPA, 2010)

Risk Phrases: Not classified by Annex VI Regulation (EC) No 1272/2008 (ESIS, 2011).

Risk Assessments: None identified
FINAL REPORT – January 2014 

BisOPP-A CASRN 24038-68-4

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

PHYSICAL/CHEMICAL PROPERTIES

Melting Point (°C) 118 (Measured) ChemSpider, 2010 Secondary source; study details and 

test conditions were not provided.

Boiling Point (°C) >300 (Estimated) EPI; U.S. EPA, 1999 Cutoff value for high boiling point 

compounds according to HPV 

assessment guidance.

Vapor Pressure (mm Hg) <1x10-8 (Estimated) EPI; U.S. EPA, 1999 Cutoff value for nonvolatile 

compounds according to HPV

assessment guidance.

Water Solubility (mg/L) 0.011 (Estimated) EPI

Log Kow 7.2 (Estimated) EPI

Flammability (Flash Point) No data located.

Explosivity No data located.

pH No data located.

pKa 10.8-10.9 (Estimated) SPARC

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HUMAN HEALTH EFFECTS

Toxicokinetics BisOPP-A is estimated not to be absorbed through the skin and poorly absorbed via the lungs and 

gastrointestinal tract based on data for structurally similar compounds.

Dermal Absorption in vitro No data located.

Absorption, 

Distribution, 

Metabolism & 

Excretion

Oral, Dermal or Inhaled Not absorbed through the skin and has 

poor absorption through the lung and 

gastrointestinal tract

(Estimated by analogy)

Professional judgment Based on closely related confidential 

analog with similar structure, 

functional groups, and 

physical/chemical properties.

Acute Toxicity LOW: Based on analogy to BPA. Potential for acute oral and dermal toxicity of bisOPP-A is estimated to be

low based on experimental data in animals for the analog BPA. Data for exposure to the analog BPA via 

inhalation were inconclusive, as only a single concentration was tested and a LC50 was not provided. 

Acute Lethality Oral Rat LD50 = 3,200>5,000 mg/kg bw

(Estimated by analogy)

NTP, 1982; European 

Commission, 2000; EINECS, 

2010; Professional judgment

Based on the analog BPA; multiple 

studies, some guideline studies. 

Mouse LD50 = 4,000-5,200 mg/kg bw

(Estimated by analogy)

NTP, 1982; European 

Commission, 2000; EINECS, 

2010; Professional judgment

Based on the analog BPA; multiple 

studies, some guideline studies. 

Dermal Rabbit LD50 = 3,000-6,400 mg/kg bw

(Estimated by analogy)

European Commission, 2000; 

EINECS, 2010; Professional 

judgment

Based on the analog BPA. Adequate;

limited study details for multiple 

studies reported in secondary sources.

Inhalation No deaths among male and female F344 

rats (10/sex) exposed to BPA dust at 

0.17 mg/L (highest attainable 

concentration) for 6 hours; transient slight 

nasal tract epithelial damage was evident. 

(Estimated by analogy)

European Commission, 2000; 

EINECS, 2010; Professional 

judgment

Based on the analog BPA; test 

guidelines were not reported in 

secondary sources. 

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Carcinogenicity MODERATE: Estimated using OncoLogic expert system, which describes a potential for this compound as a 

potential carcinogen or tumorigenesis promoter arising from its structural similarity to estrogenic/androgenic 

compounds. The “phenols and phenolic compounds” structural alert was used.

OncoLogic Results Moderate (Estimated)

OncoLogic class: phenols and phenolic 

compounds 

OncoLogic OncoLogic SAR analysis using the 

phenols and phenolic compounds 

class. 

Carcinogenicity (Rat and 

Mouse)

No data located.

Combined Chronic 

Toxicity/Carcinogenicity

No data located.

Genotoxicity LOW: Based on analogy to BPA. FAO/WHO (2011) determined that: (1) the analog BPA is not a mutagen in 

in vitro test systems, (2) does not induce cell transformation, and (3) in vivo evidence for clastogenic effects 

induced by the analog BPA is inconsistent and inconclusive, although some in vitro studies have shown BPA to 

affect chromosomal structure in dividing cells. FAO/WHO (2011) concluded that the analog BPA is not likely 

to pose a genotoxic hazard to humans.

Potential for mutagenicity

(Estimated by analogy)

Professional judgment Estimated based on reported 

experimental data for the analog BPA.

Largely negative results in a variety of in 

vitro test systems, including studies with 

Salmonella typhimurium, Chinese hamster 

V79 cells, Syrian hamster embryo cells and 

mouse lymphoma cells. However, DNA 

damage was induced in MCF-7 and MDAMB-231 cells, DNA adduct formation in 

Syrian hamster ovary cells and a number of 

positive findings have been reported for 

the potential for BPA to inhibit purified 

microtubule polymerization, affect the 

spindle apparatus and produce aneuploidy 

in in vitro studies with Chinese hamster 

V79 cells or oocytes from Balb/c or MF1 

mice. 

FAO/WHO, 2011 Based on the analog BPA. 

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PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

FAO/WHO Expert Panel concludes:

BPA is not a mutagen in in vitro test 

systems, nor does it induce cell 

transformation. BPA has been shown to 

affect chromosomal structure in dividing 

cells in in vitro studies, but evidence for 

this effect in in vivo studies is inconsistent 

and inconclusive. BPA is not likely to pose 

a genotoxic hazard to humans. 

(Estimated by analogy)

Reproductive Effects MODERATE: Estimated based on analogy to BPA. Key studies identified by NTP for the analog BPA

indicate there are multiple distinct endpoints with NOAELs in the range of Moderate hazard concern with 

LOAELs in the range of Low hazard concern. At the target dose of 50 mg/kg-day (BPA), the NOAELs are on 

the margin of High and Moderate hazard, according to DfE criteria. Benchmark Dose (BMD) Modeling 

conducted by NTP, which interpolates between NOAEL and LOAEL values, yields values that further 

support a Moderate hazard designation.

Reproduction/ 

Developmental Toxicity 

Screen

No data located.

Combined Repeated Dose 

with Reproduction/ 

Developmental Toxicity 

Screen

No data located.

Reproduction and Fertility 

Effects

Potential for reproductive toxicity

(Estimated by analogy)

Professional judgment Estimated based on test data located 

for a confidential analog.

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Parental systemic toxicity:

NOAEL = 5 mg/kg bw-day 

LOAEL = 50 mg/kg bw-day for 12% 

decreased terminal body weight in F1

parental males

Reproductive toxicity: 

Females: NOAEL = 50 mg/kg bw-day 

LOAEL = 500 mg/kg bw-day for decreases

in number of implantation sites, delayed 

vaginal opening in F1, F2, F3 offspring 

BMDLs (change of 1 standard deviation 

from control) reported for delayed vaginal 

opening (females)- 

F1 = 176 mg/kg-day 

F2 = 228 mg/kg-day 

F3 = 203 mg/kg-day 

Males: NOAEL = 50 mg/kg bw-day, 

LOAEL = 500 mg/kg-day for delayed 

preputial separation in F1 males

BMDLs (change of 1 standard deviation 

from control) reported for delayed 

preputial separation (males)- 

F1 = 163 mg/kg-day 

F2 = 203 mg/kg-day 

F3 = 189 mg/kg-day 

(Estimated by analogy)

NTP-CERHR, 2008; Professional 

judgment

Based on the analog BPA; adequate, 

guideline study as reported in the 

secondary source. 

Classified by NTP-CERHR as having 

High Utility.

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Parental systemic toxicity:

NOAEL = 5 mg/kg bw-day 

LOAEL = 50 mg/kg bw-day for increased 

incidences of centrilobular hepatocellular 

hypertrophy in males and females

Reproductive toxicity: 

NOAEL = 50 mg/kg bw-day 

LOAEL = 600 mg/kg bw-day for increased 

gestation length, decreased epididymal 

sperm concentration in F1 males, increased 

incidence of gross ovarian cysts in F1 and 

F2 females

BMD1 (change of 1 standard deviation 

from control) reported for increased 

gestation length

F0 = 1144 mg/kg-day (BMDL = 599 

mg/kg-day) 

F1 = 772 mg/kg-day (BMDL = 531 mg/kgday) 

BMD10s (10% extra risk) reported for 

increased incidence of gross ovarian cysts

F0 = 225 mg/kg-day (BMDL = 141 mg/kgday) 

F1 = 202 mg/kg-day (BMDL = 120 mg/kgday) 

(Estimated by analogy)

NTP-CERHR, 2008; Professional 

judgment

Based on the analog BPA; adequate,

guideline study as reported in the 

secondary source. 

Classified by NTP-CERHR as having 

High Utility.

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Summary of Reproductive 

Effects

Female effects: There is sufficient 

evidence in rats and mice that BPA caused 

female reproductive toxicity with 

subchronic or chronic oral exposures with 

a NOAEL of 50 mg/kg bw-day and a 

LOAEL of 500 mg/kg bw-day. 

Male effects: There is sufficient evidence 

in rats and mice that BPA causes male 

reproductive toxicity with subchronic or 

chronic oral exposures with a NOAEL of 

50 mg/kg bw-day and a LOAEL of 500 

mg/kg bw/day. 

(Estimated by analogy)

NTP-CERHR, 2008; Professional 

judgment

Based on the analog BPA; Classified 

by NTP-CERHR as having High 

Utility.

The FAO/WHO Expert Panel reviewed 

reproductive and developmental toxicity 

data for BPA located as of November 2010 

and noted that most regulatory bodies 

reviewing the numerous studies on BPA

have indicated an oral reproductive and 

developmental NOAEL of 50 mg/kg bwday. 

(Estimated by analogy)

FAO/WHO, 2011; Professional 

judgment

Based on the analog BPA.

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Developmental Effects HIGH: Estimated based on analogy to BPA. The NTP-CERHR (2008) Expert Panel concluded that there is 

suggestive evidence that BPA causes neural and behavioral alterations related to disruptions in normal sex 

differences in rats and mice (0.01-0.2 mg/kg bw-day) following developmental exposures. The FAO/WHO 

(2011) Expert Panel also concluded that while there was broad agreement in a NOAEL of 50 mg/kg bw-day 

for developmental toxicity based on standard bioassays, specific targeted studies identified 

neurodevelopmental effects at low doses (<1 mg/kg bw-day), but the human relevance of these studies is less 

certain. There is great variation in results with different types of studies measuring different endpoints; 

developmental effects at lower doses cannot be ruled out. Taken together these findings support a hazard 

designation of High concern.

Reproduction/ 

Developmental Toxicity 

Screen

No data located.

Combined Repeated Dose 

with Reproduction/ 

Developmental Toxicity 

Screen

No data located.

Summary of 

Developmental Effects

Potential for developmental toxicity

(Estimated by analogy)

Professional judgment Estimated based on test data located 

for a confidential analog.

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The NTP-CERHR Expert Panel concluded

that BPA: 

*does not cause malformations or birth 

defects in rats or mice at levels up to the 

highest doses evaluated: 640 mg/kg bwday (rats) and 1,250 mg/kg bw-day (mice).

*does not alter male or female fertility 

after gestational exposure up to doses of 

450 mg/kg bw-day in the rat and 600mg/kg 

bw-day in the mouse (highest dose levels 

evaluated). 

*does not permanently affect prostate 

weight at doses up to 475 mg/kg bw-day in 

adult rats or 600 mg/kg bw-day in mice. 

*does not cause prostate cancer in rats or 

mice after adult exposure at up to 148 or 

600 mg/kg bw-day, respectively. 

*does change the age of puberty in male or 

female rats at high doses (ca. 475 mg/kg

bw-day).

And that rodent studies suggest that BPA: 

*causes neural and behavioral alterations 

related to disruptions in normal sex 

differences in rats and mice (0.01–

0.2 mg/kg bw-day). 

(Estimated by analogy)

NTP–CERHR, 2008; Professional 

judgment

Based on the analog BPA.

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PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

The FAO/WHO Expert Panel reviewed 

reproductive and developmental toxicity 

data for BPA located as of November 2010 

and noted that most regulatory bodies 

reviewing the numerous studies on BPA 

have indicated an oral reproductive and 

developmental NOAEL of 50 mg/kg bwday.

FAO/WHO, 2011; Professional 

judgment

Based on the analog BPA.

Neurotoxicity MODERATE: Estimated to have potential for neurotoxicity based on the presence of the phenol structural 

alert.

Neurotoxicity Screening 

Battery (Adult)

There is potential for neurotoxicity effects 

based on the presence of the phenol 

structural alert. 

(Estimated)

U.S. EPA, 2010; Professional 

judgment

Estimated based on structural alert.

Repeated Dose Effects MODERATE: Estimated based on analogy to BPA which produced histopathologic changes in the liver 

(centrilobular hepatocyte hypertrophy) from oral dosing at 50 mg/kg bw-day (NOAEL = 5 mg/kg bw-day) and 

there is uncertainty regarding the potential for BPA doses between the NOAEL of 5 mg/kg bw-day and the 

LOAEL of 50 mg/kg bw-day to cause adverse systemic effects. Furthermore, lesions in the nasal cavity of rats 

were reported following repeated inhalation exposure to BPA dust at 0.05 mg/L. These findings indicate a 

moderate hazard potential for the oral and inhalation exposure routes.

The FAO/WHO Expert Panel reviewed 

located information regarding repeateddose oral toxicity of BPA and concluded 

that results demonstrated effects on the 

liver, kidney, and body weight at doses of 

50 mg/kg bw-day and higher and that the 

lowest NOAEL was 5 mg/kg bw-day, as 

identified in several studies. 

(Estimated by analogy)

FAO/WHO, 2011; Professional 

judgment

Based on the analog BPA.

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Parental systemic toxicity:

NOAEL = 4.75 mg/kg bw-day 

LOAEL = 47.5 mg/kg bw-day for 12% 

decreased terminal body weight in F1

parental males

(Estimated by analogy)

NTP-CERHR, 2008; Professional 

judgment

Based on the analog BPA; guideline 

study as reported in the secondary 

source. 

Classified by NTP-CERHR as having 

High Utility.

Parental systemic toxicity:

NOAEL = 5 mg/kg bw-day 

LOAEL = 50 mg/kg bw-day for increased 

incidences of centrilobular hepatocellular 

hypertrophy in males and females

(Estimated by analogy)

NTP-CERHR, 2008; Professional 

judgment

Based on the analog BPA; guideline 

study as reported in the secondary 

source. 

Classified by NTP-CERHR as having 

High Utility.

NOAEL = 0.01 mg/L

LOAEL = 0.05 mg/L based on microscopic 

changes in the anterior portion of the nasal 

cavity

(Estimated by analogy)

European Commission, 2000; 

EINECS, 2010; Professional 

judgment

Based on the analog BPA.

NOAEL = None established

LOAEL = 0.047 mg/L for decreased body 

weight gain, increased liver and kidney 

weight, unspecified “morphological 

changes” in liver, kidney, and lungs

(Estimated by analogy)

European Commission, 2000; 

EINECS, 2010; Professional 

judgment

Based on the analog BPA; single 

exposure level, insufficient study 

details in secondary sources. 

Skin Sensitization MODERATE: Based on analogy to BPA, bisOPP-A is estimated to be a skin sensitizer. Recent data from 

three BPA manufacturing facilities indicated that the chemical does not elicit skin sensitization. However, 

results of some human studies suggested the possibility of a dermal sensitization response, although crosssensitization was not ruled out. Most animal studies conducted on the analog were negative for dermal 

sensitization, although assays may not have been maximized. There is evidence of ear swelling in a 

photoallergy test in mice and moderate redness and swelling following repeated dermal exposure in rabbits. 

The Moderate hazard designation is based on suggestive evidence of skin sensitization in humans and mice for 

the analog.

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Skin Sensitization Negative in a modified local lymph node 

assay of mice administered BPA

epicutaneously on the ears at 

concentrations up to 30% on 3 consecutive 

days. 

(Estimated by analogy)

EINECS, 2010; Professional 

judgment

Based on the analog BPA; adequate, 

although the assay did not include 

concentrations >30%.

Negative in a local lymph node assay 

modified to test for photoreactivity in mice 

administered BPA epicutaneously on the 

ears at concentrations up to 30% on 

3 consecutive days and irradiated with UV 

light immediately following application. 

(Estimated by analogy)

EINECS, 2010; Professional 

judgment

Based on the analog BPA; adequate, 

although the assay did not include 

concentrations >30%. 

Negative in comprehensive medical 

surveillance data obtained from three BPA

manufacturing plants for 875 employees 

examined for several years where workers 

were potentially exposed to other 

chemicals (phenol, acetone) that are not 

considered to be skin sensitizers. 

(Estimated by analogy)

EINECS, 2010; Professional 

judgment

Based on the analog BPA; adequate.

Positive, rabbits; repeated dermal 

application (30 times over 37 days) of BPA

(pure powder) produced moderate swelling 

and redness. Skin turned yellow followed 

by dark pigmentation after day 15. 

(Estimated by analogy) 

NIOSH, 2010; Professional 

judgment

Based on the analog BPA; adequate.

The Joint FAO/WHO Expert Meeting 

review of the toxicological aspects of BPA

concludes that BPA is capable of 

producing a skin sensitization response in 

humans. 

(Estimated by analogy)

FAO/WHO, 2011; Professional 

judgment

Based on the analog BPA.

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Respiratory Sensitization No data located.

Respiratory Sensitization No data located.

Eye Irritation MODERATE: Based on analogy to BPA. BisOPP-A is estimated to be slightly to highly irritating to rabbit 

eyes based on test data for the analog BPA.

Eye Irritation Rabbit, slightly to highly irritating European Commission, 2000; 

EINECS, 2010; Professional 

judgment

Based on the analog BPA. Adequate; 

study details provided for multiple 

studies indicate potential for BPA to 

cause eye irritation.

Dermal Irritation MODERATE: Based on analogy to BPA. BisOPP-A is estimated to be slightly to moderately irritating to 

rabbit and guinea pig skin based on test data for the analog and NIOSH identifying BPA as a skin irritant.

Dermal Irritation Rabbit, nonirritating to slightly irritating 

when applied as undiluted or 10% aqueous 

suspension to intact or abraded skin. 

(Estimated by analogy)

European Commission, 2000; 

EINECS, 2010; NIOSH, 2010; 

Professional judgment

Based on the analog BPA. Adequate, 

study details provided for multiple 

studies indicate potential for BPA to 

cause dermal irritation.

Rabbit, moderately irritating when applied 

as 40% solution in dimethyl sulfoxide 

under non-occlusive conditions. 

(Estimated by analogy)

European Commission, 2000; 

Professional judgment

Based on the analog BPA; adequate.

Guinea pig, not irritating when applied as 

5% solution in acetone for 24 hours under 

occlusive conditions. 

(Estimated by analogy)

European Commission, 2000; 

Professional judgment

Based on the analog BPA; adequate.

Endocrine Activity No data located.

No data located.

Immunotoxicity No data located.

Immune System Effects No data located.

ECOTOXICITY

ECOSAR Class Polyphenols

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Acute Toxicity LOW: The log Kow of 7.17 for this compound exceeds the SAR limitations to predict acute aquatic toxicity. No 

effects at saturation (NES) are predicted for these endpoints.

Fish LC50 Fish 96-hour LC50 = 0.012 mg/L

(Estimated) 

ECOSAR: neutral organics

ECOSAR version 1.00 NES: The chemical may not be 

soluble enough to measure this 

predicted effect; the log Kow of 7.17 

for this chemical exceeds the SAR 

limitation for log Kow of 7.0; NES are 

predicted for these endpoints. 

Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided by 

ECOSAR classes that have a more 

specific mode of action relative to 

narcosis.

Fish 96-hour LC50 = 0.034 mg/L

(Estimated) 

ECOSAR: phenols, poly

ECOSAR version 1.00 NES: The chemical may not be 

soluble enough to measure this 

predicted effect; the log Kow of 7.17 

for this chemical exceeds the SAR 

limitation for log Kow of 7.0; NES are 

predicted for these endpoints.

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Daphnid LC50 Daphnid 48-hour LC50 = 0.013 mg/L

(Estimated) 

ECOSAR: neutral organics

ECOSAR version 1.00 NES: The chemical may not be 

soluble enough to measure this 

predicted effect; the log Kow of 7.17 

for this chemical exceeds the SAR 

limitation for log Kow of 5.5; NES are 

predicted for these endpoints. 

Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided by 

ECOSAR classes that have a more 

specific mode of action relative to 

narcosis.

Daphnid 48-hour LC50 = 0.017 mg/L

(Estimated) 

ECOSAR: phenols, poly

ECOSAR version 1.00 NES: The chemical may not be 

soluble enough to measure this 

predicted effect; the log Kow of 7.17 

for this chemical exceeds the SAR 

limitation for log Kow of 5.5; NES are 

predicted for these endpoints.

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Green Algae EC50 Green algae 96-hour LC50 = 0.048 mg/L

(Estimated) 

ECOSAR: neutral organics

ECOSAR version 1.00 NES: The chemical may not be 

soluble enough to measure this 

predicted effect; the log Kow of 7.17 

for this chemical exceeds the SAR 

limitation for log Kow of 6.4; NES are 

predicted for these endpoints. 

Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided by 

ECOSAR classes that have a more 

specific mode of action relative to 

narcosis.

Green algae 96-hour LC50 = 1.13 mg/L

(Estimated) 

ECOSAR: phenols, poly

ECOSAR version 1.00 NES: The chemical may not be 

soluble enough to measure this 

predicted effect; the log Kow of 7.17 

for this chemical exceeds the SAR 

limitation for log Kow of 6.4; NES are 

predicted for these endpoints.

Chronic Aquatic Toxicity HIGH: Based on estimated ChV values <0.1 mg/L for fish, Daphnid, and green algae.

Fish ChV Fish ChV = 0.0010 mg/L (Estimated)

ECOSAR: neutral organics

ECOSAR version 1.00 Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided by 

ECOSAR classes that have a more 

specific mode of action relative to 

narcosis.

Fish 30-day ChV = 0.004 mg/L

(Estimated) 

ECOSAR: phenols, poly

ECOSAR version 1.00

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Daphnid ChV Daphnid ChV = 0.003 mg/L (Estimated)

ECOSAR: neutral organics

ECOSAR version 1.00 Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided by 

ECOSAR classes that have a more 

specific mode of action relative to 

narcosis.

Daphnid 21-day ChV = 0.005 mg/L 

(Estimated) 

ECOSAR: phenols, poly

ECOSAR version 1.00

Green Algae ChV Green algae ChV = 0.041 mg/L

(Estimated) 

ECOSAR: phenols, poly

ECOSAR version 1.00

Green algae ChV = 0.045 mg/L

(Estimated)

ECOSAR: neutral organics 

ECOSAR version 1.00 Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided by 

ECOSAR classes that have a more 

specific mode of action relative to 

narcosis.

ENVIRONMENTAL FATE

Transport Evaluation of bisOPP-A transport is based entirely on QSAR estimations for fugacity (level III), 

disassociation constant (pKa), Koc, volatilization, and vapor pressure. It is expected to exist in neutral form at 

environmentally-relevant pH. BisOPP-A is expected to partition primarily to soil; therefore, leaching through 

soil to groundwater is not expected to be an important transport mechanism. In the atmosphere, bisOPP-A is 

expected to exist in the particulate phase, which will be deposited back to the soil and water surfaces through 

wet or dry deposition. 

Henry’s Law Constant 

(atm-m3/mole)

<1x10-8 (Estimated) EPI Cutoff value for nonvolatile 

compounds, based on professional 

judgment.

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Sediment/Soil 

Adsorption/

Desorption

Coefficient – Koc

>30,000 (Estimated) EPI; U.S. EPA, 2004; Professional 

judgment 

Cutoff value for nonmobile 

compounds. 

Level III Fugacity 

Model

Air = <1%

Water = 2% 

Soil = 36%

Sediment = 62% (Estimated)

EPI

Persistence HIGH: The persistence of bisOPP-A is based on an estimated half-life of 340 days in soil. BisOPP-A is 

expected to partition primarily to soil. Experimental biodegradation data for bisOPP-A were not located. The 

biodegradation assessment for bisOPP-A is based entirely on QSARs of aerobic and anaerobic 

biodegradation. Results from these models estimate primary biodegradation in weeks and ultimate 

degradation in weeks-months. Biodegradation under anaerobic methanogenic conditions is estimated to be

not probable. BisOPP-A does not contain functional groups that absorb light at environmentally-relevant 

wavelengths. Therefore, it is not expected to be susceptible to direct photolysis. It is not expected to undergo 

hydrolysis as it does not contain hydrolyzable functional groups. The atmospheric half-life of bisOPP-A is 

estimated to be 1.8 hours, although it is expected to exist primarily as a particulate in air. Based on the 

estimated data and qualitative assessments based on functional groups, biodegradation of bisOPP-A is 

expected to be the major removal process in the environment. 

Water Aerobic 

Biodegradation

Weeks (primary survey model)

Weeks-months (ultimate survey model)

EPI

Volatilization Half-life 

for Model River

>1 year (Estimated) EPI

Volatilization Half-life 

for Model Lake

>1 year (Estimated) EPI

Soil Aerobic 

Biodegradation

No data located.

Anaerobic 

Biodegradation

Not probable (anaerobic-methanogenic 

biodegradation probability model)

EPI

Soil Biodegradation w/ 

Product Identification

No data located.

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Sediment/Water 

Biodegradation

No data located.

Air Atmospheric Half-life 2 hours (Estimated assuming 12-hour day 

and hydroxyl radical concentration of 

1.5x106 molecules/cm3)

EPI

Reactivity Photolysis Not a significant fate process (Estimated) Mill, 2000; Professional judgment The substance does not contain 

functional groups that would be 

expected to absorb light at 

wavelengths >290 nm.

Hydrolysis Not a significant fate process (Estimated) Wolfe and Jeffers, 2000; 

Professional judgment 

The substance does not contain 

functional groups that would be 

expected to hydrolyze readily under 

environmental conditions. 

Pyrolysis No data located.

Environmental Half-life 340 days (Estimated) EPI; PBT Profiler Half-life estimated for the 

predominant compartment, as 

determined by EPI and the PBT 

Profiler methodology.

Bioaccumulation MODERATE: The estimated fish BAF is <1,000. Although the BCF suggests a High potential hazard, the 

BAF model is anticipated to better account for metabolism of this substance.

Fish BCF 11,000 (Estimated) EPI

BAF 590 (Estimated) EPI

Metabolism in Fish No data located.

ENVIRONMENTAL MONITORING AND BIOMONITORING 

Environmental Monitoring No data located.

Ecological Biomonitoring No data located.

Human Biomonitoring This chemical was not included in the NHANES biomonitoring report (CDC, 2011).

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CDC (Centers for Disease Control and Prevention). Fourth national report on human exposure to environmental chemicals, updated 

tables. Department of Health and Human Services. 2011. http://www.cdc.gov/exposurereport/ (accessed on May 10, 

2011). 

Chemspider. ChemSpider; Structure-based Chemistry Information. Royal Society of Chemistry:London. 2010. 

http://www.chemspider.com (accessed on December 11, 2010). 

ECOSAR (2010) Ecological Structure Activity Relationship (ECOSAR) Version 1.00. Washington, DC: U.S. Environmental 

Protection Agency. http://www.epa.gov/oppt/newchems/tools/21ecosar.htm. 

EINECS. 4,4’-Isopropylidenediphenol (bisphenol A). European Union Risk Assessment Report. 2010.

EPI (EPIWIN/EPISUITE) Estimations Programs Interface for Windows, Version 4.00. U.S. Environmental Protection Agency: 

Washington D.C. http://www.epa.gov/opptintr/exposure/. 

ESIS (European chemical Substances Information System) Classification, labeling and Packaging of dangerous substances annex VI 

to regulation (EC) No 1272/2008 [Online] http://esis.jrc.ec.europa.eu/ (accessed on June 10, 2011). 

European Commission. IUCLID Dataset for 4,4-isopropylidenediphenol (CAS No. 80-05-7). European Chemicals Bureau, February 

19, 2000. 2000. 

FAO/WHO. Toxicological and health aspects of bisphenol A. Report of Joint FAO/WHO expert meeting 2-5 November 2010 and 

report of stakeholder meeting on bisphenol A 1 November 2010. Food and Agriculture Organization of the United 

Nations; World Health Organization. Ottawa, Canada. 2011. 

Mill, T. 2000. Photoreactions in Surface Waters. In Boethling, R.; Mackay, D., Handbook of Property Estimation Methods for 

Chemicals, Environmental Health Sciences (355-382). Boca Raton: Lewis Publishers. 

NIOSH (National Institute for Occupational Safety and Health). Skin Notation (SK) profile, bisphenol A (BPA) [CAS No. 80-05-7]. 

Department of Health and Human Services; Centers for Disease Control and Prevention. 2010. 

NTP (National Toxicology Program). Carcinogenesis bioassay of bisphenol-A (CAS No. 80-05-7) in F344 rats and B6C3F1 mice 

(feed study). Technical Report No. 215, PB82-184060. 1982. 

NTP-CERHR. Monograph on the potential human reproductive and developmental effects of biphenol A. National Toxicology 

Program; U.S. Department of Health and Human Service. Center for the Evaluation of Risks to Human Reproduction. 

NIH Publication No. 08-5994. September 2008. 

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FINAL REPORT – January 2014 

OncoLogic. U.S. EPA and LogiChem, Inc. 2005, Version 7.0. 2008. 

PBT Profiler Persistent (P),Bioaccumulative (B), and Toxic (T) Chemical (PBT)Profiler. U.S. Environmental Protection Agency: 

Washington D.C. www.pbtprofiler.net. 

SPARC On Line Calculator pKa/property server. Ver 4.5 September, 2009. Available from, http://ibmlc2.chem.uga.edu/sparc/

(accessed on August 12, 2010). 

U.S. EPA (Environmental Protection Agency). High Production Volume (HPV) Challenge. Determining the Adequacy of Existing 

Data. U.S. Environmental Protection Agency: Washington D.C. 1999. 

http://www.epa.gov/hpv/pubs/general/datadfin.htm

U.S. EPA (Environmental Protection Agency). 2004. The Pollution Prevention (P2) Framework, EPA-748-B-03-001. Office of 

Pollution Prevention and Toxics 7403M, U.S. Environmental Protection Agency, Washington, DC. 20460. October 

2003 version updated in January 2004. Latest version available at 

http://www.epa.gov/opptintr/newchems/pubs/sustainable/p2frame-june05a2.pdf

U.S. EPA (Environmental Protection Agency). Sustainable Futures Using NonCancer Screening within the Sustainable Futures 

Initiative Environmental Protection Agency: Washington D.C. 2010. http://www.epa.gov/opptintr/sf/pubs/noncanscreen.htm#systemic (accessed on February 09, 2011). 

Wolfe, N.; Jeffers, P. (2000) Hydrolysis. In Boethling, R.; Mackay, D., Handbook of Property Estimation Methods for Chemicals, 

Environmental Health Sciences (311-334). Boca Raton: Lewis Publishers. 

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Bisphenol AP

OH OH

CASRN: 1571-75-1

MW: 290.36

MF: C20H18O2

Physical Forms:

Neat: Solid

Use: Developer for thermal paper

SMILES: OC1=CC=C(C(C)(C2=CC=CC=C2)C3=CC=C(O)C=C3)C=C1

Synonyms: 4,4'-(α-methylbenzylidene)diphenol; 4,4′-(1-Phenylethylidene)bisphenol; phenol, 4,4'-(1-phenylethylidene)bisPolymeric: No

 Oligomers: Not applicable

Metabolites, Degradates and Transformation Products: None

Analog: Bisphenol A (80-05-7)

 Endpoint(s) using analog values: Acute toxicity, dermal irritation, 

skin sensitization, reproductive and developmental toxicity, genotoxicity, 

repeated dose effects

Analog: Confidential analog (structure not available) 

 Endpoint(s) using analog values: Eye irritation, immunotoxicity

Analog Structure:

Structural Alerts: Phenols, neurotoxicity (U.S. EPA, 2010)

Risk Phrases: 50/53 - Very toxic to aquatic organisms may cause long-term adverse effects in the aquatic environment (ESIS, 2011).

Risk Assessments: None identified

OH OH

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PHYSICAL/CHEMICAL PROPERTIES

Melting Point (°C) 189 ChemSpider, 2010 Secondary source, consistent with 

other reported values.

188-191 (Measured) Aldrich, 2009 Adequate; measured by chemical 

supplier. Consistent with other 

reported values.

Boiling Point (°C) >300 (Estimated) EPI; U.S. EPA, 1999 Cutoff value for high boiling 

compounds according to HPV 

assessment guidance.

Vapor Pressure (mm Hg) <1x10-8 (Estimated) EPI; U.S. EPA, 1999 Cutoff value for nonvolatile 

compounds according to HPV

assessment guidance.

Water Solubility (mg/L) 1.1 (Estimated) EPI

Log Kow 4.9 (Estimated) EPI

Flammability (Flash Point) No data located.

Explosivity No data located.

pH No data located.

pKa 9.9-10.1 (Estimated) SPARC

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HUMAN HEALTH EFFECTS

Toxicokinetics Bisphenol AP, as a neat material, is estimated to not be absorbed through the skin and have poor skin 

absorption when in solution. Bisphenol AP is expected to have poor absorption via the lungs and 

gastrointestinal tract.

Dermal Absorption in vitro No data located.

Absorption, 

Distribution, 

Metabolism & 

Excretion

Oral, Dermal or Inhaled Not absorbed through the skin and has 

poor absorption to skin when in a solution; 

poor absorption through the lung and 

gastrointestinal tract. 

(Estimated by analogy)

Professional judgment Based on closely related confidential 

analog with similar structure, 

functional groups, and 

physical/chemical properties. 

Acute Mammalian Toxicity LOW: The acute oral and dermal toxicity hazard of bisphenol AP is estimated to be low based on analogy 

to BPA. Data for exposure to the analog BPA via inhalation were inconclusive, as only a single 

concentration was tested and a LC50 was not provided. 

Acute Lethality Oral Rat LD50 = 3,200->5,000 mg/kg bw

(Estimated by analogy) 

NTP, 1982; European 

Commission, 2000; EINECS, 

2010; Professional judgment

Based on the analog BPA; multiple 

studies, some guideline studies. 

Mouse LD50 = 4,000-5,200 mg/kg bw

(Estimated by analogy) 

NTP, 1982; European 

Commission, 2000; EINECS, 

2010; Professional judgment

Based on the analog BPA; multiple 

studies, some guideline studies. 

Dermal Rabbit LD50 = 3,000-6,400 mg/kg bw

(Estimated by analogy) 

European Commission, 2000; 

EINECS, 2010; Professional 

judgment

Based on the analog BPA; limited 

study details for multiple studies 

reported in secondary sources.

Inhalation No deaths among male and female F344 

rats (10/sex) exposed to BPA dust at 

0.17 mg/L (highest attainable 

concentration) for 6 hours; transient slight 

nasal tract epithelial damage was evident. 

(Estimated by analogy)

EINECS, 2010; European

Commission, 2000; Professional 

judgment

Based on the analog BPA; test 

guidelines were not reported in 

secondary sources. 

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Carcinogenicity MODERATE: Estimated using OncoLogic expert system, which describes potential for this compound as a 

potential carcinogen or tumorigenesis promoter arising from its structural similarity to 

estrogenic/androgenic compounds, using the “phenols and phenolic compounds” structural alert.

OncoLogic Results Moderate (Estimated)

OncoLogic class: phenols and phenolic 

compounds 

OncoLogic OncoLogic SAR analysis using the 

phenols and phenolic compounds 

class.

Carcinogenicity (Rat and 

Mouse)

No data located.

Combined Chronic Toxicity/ 

Carcinogenicity

No data located.

Genotoxicity LOW: Based on analogy to BPA. FAO/WHO (2011) determined that: (1) the analog BPA is not a mutagen 

in in vitro test systems, (2) does not induce cell transformation, and (3) in vivo evidence for clastogenic effects 

induced by the analog BPA is inconsistent and inconclusive although some in vitro studies have shown BPA

to affect chromosomal structure in dividing cells. The conclusion of FAO/WHO (2011) is that the analog 

BPA is not likely to pose a genotoxic hazard to humans.

Gene Mutation in vitro Potential for mutagenicity

(Estimated by analogy) 

Professional judgment Estimated based on located test data 

for a confidential analog with 

additional substituents.

Gene Mutation in vivo No data located.

Chromosomal Aberrations 

in vitro

Potential for mutagenicity;

positive for chromosomal aberrations in 

Chinese hamster ovary (CHO) cells with 

metabolic activation 

(Estimated by analogy)

Professional judgment Estimated based on located test data 

for a confidential analog with 

additional substituents. 

Chromosomal Aberrations 

in vivo

No data located.

DNA Damage and Repair No data located.

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Other Largely negative results in a variety of in 

vitro test systems, including studies with 

Salmonella typhimurium, Chinese hamster 

V79 cells, Syrian hamster embryo cells, 

and mouse lymphoma cells. However, 

DNA damage was induced in MCF-7 and 

MDA-MB-231 cells, DNA adduct 

formation in Syrian hamster ovary cells 

and a number of positive findings have 

been reported for the potential for BPA to 

inhibit purified microtubule 

polymerization, affect the spindle 

apparatus and produce aneuploidy in in 

vitro studies with Chinese hamster V79 

cells or oocytes from Balb/c or MF1 mice.

FAO/WHO Expert Panel concludes: 

BPA is not a mutagen in in vitro test 

systems, nor does it induce cell 

transformation. BPA has been shown to 

affect chromosomal structure in dividing 

cells in in vitro studies, but evidence for 

this effect in in vivo studies is inconsistent 

and inconclusive. BPA is not likely to 

pose a genotoxic hazard to humans.

(Estimated by analogy)

FAO/WHO, 2011 Based on the analog BPA.

Reproductive Effects MODERATE: Estimated based on analogy to BPA. Key studies identified by NTP for the analog BPA

indicate there are multiple distinct endpoints with NOAELs in the range of Moderate hazard concern with 

LOAELs in the range of Low hazard concern. At the target dose of 50 mg/kg-day (BPA), the NOAELs are 

on the margin of High and Moderate hazard, according to DfE criteria. Benchmark Dose (BMD) Modeling 

conducted by NTP, which interpolates between NOAEL and LOAEL values, yields values that further 

support a Moderate hazard designation.

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Reproduction/ 

Developmental Toxicity 

Screen

No data located.

Combined Repeated Dose 

with Reproduction/ 

Developmental Toxicity 

Screen

No data located.

Reproduction and Fertility 

Effects

Potential for toxic effects to prostate, 

testes and ovaries. 

Rat, 28-day oral study 

NOAEL = 5 mg/kg-day 

(Estimated by analogy)

Professional judgment Estimated based on located test data 

for a confidential analog with 

additional substituents; a LOAEL for 

these effects was not identified.

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Parental systemic toxicity:

NOAEL = 5 mg/kg bw-day 

LOAEL = 50 mg/kg bw-day for 12% 

decreased terminal body weight in F1

parental males

Reproductive toxicity: 

Females: NOAEL = 50 mg/kg bw-day 

LOAEL = 500 mg/kg bw-day for 

decreases in number of implantation sites, 

delayed vaginal opening in F1, F2, F3

offspring 

BMDLs (change of 1 standard deviation 

from control) reported for delayed vaginal 

opening (females)- 

F1 = 176 mg/kg-day 

F2 = 228 mg/kg-day 

F3 = 203 mg/kg-day 

Males: NOAEL = 50 mg/kg bw-day, 

LOAEL = 500 mg/kg-day for delayed 

preputial separation in F1 males

BMDLs (change of 1 standard deviation 

from control) reported for delayed 

preputial separation (males)- 

F1 = 163 mg/kg-day 

F2 = 203 mg/kg-day 

F3 = 189 mg/kg-day 

(Estimated by analogy)

NTP-CERHR, 2008; Professional 

judgment

Based on the analog BPA; adequate, 

guideline study as reported in the 

secondary source. 

Classified by NTP-CERHR as 

having High Utility.

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Parental systemic toxicity:

NOAEL = 5 mg/kg bw-day 

LOAEL = 50 mg/kg bw-day for increased 

incidences of centrilobular hepatocellular 

hypertrophy in males and females 

Reproductive toxicity: 

NOAEL = 50 mg/kg bw-day 

LOAEL = 600 mg/kg bw-day for 

increased gestation length, decreased 

epididymal sperm concentration in F1

males, increased incidence of gross 

ovarian cysts in F1 and F2 females

BMD1 (change of 1 standard deviation 

from control) reported for increased 

gestation length

F0 = 1144 mg/kg-day (BMDL = 599 

mg/kg-day) 

F1 = 772 mg/kg-day (BMDL = 531 

mg/kg-day) 

BMD10s (10% extra risk) reported for 

increased incidence of gross ovarian cysts

F0 = 225 mg/kg-day (BMDL = 141 

mg/kg-day) 

F1 = 202 mg/kg-day (BMDL = 120 

mg/kg-day) 

(Estimated by analogy)

NTP-CERHR, 2008; Professional 

judgment

Based on the analog BPA; adequate, 

guideline study as reported in the 

secondary source. 

Classified by NTP-CERHR as 

having High Utility.

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Summary of Reproductive 

Effects

Female effects: There is sufficient 

evidence in rats and mice that BPA caused

female reproductive toxicity with 

subchronic or chronic oral exposures with 

a NOAEL of 50 mg/kg bw-day and a 

LOAEL of 500 mg/kg bw-day. 

Male effects: There is sufficient evidence 

in rats and mice that BPA causes male 

reproductive toxicity with subchronic or 

chronic oral exposures with a NOAEL of 

50 mg/kg bw-day and a LOAEL of 500 

mg/kg bw/day. 

(Estimated by analogy)

NTP-CERHR, 2008; Professional 

judgment

Based on the analog BPA; Classified 

by NTP-CERHR as having High 

Utility.

The joint FAO/WHO Expert Panel 

reviewed reproductive and developmental 

toxicity data for BPA located as of 

November 2010 and noted that most 

regulatory bodies reviewing the numerous 

studies on BPA have indicated an oral 

reproductive and developmental NOAEL 

of 50 mg/kg bw-day.

(Estimated by analogy)

FAO/WHO, 2011; Professional 

judgment

Based on the analog BPA.

Developmental Effects HIGH: Estimated based on analogy to BPA. The NTP-CERHR (2008) Expert Panel concluded that there is 

suggestive evidence that BPA causes neural and behavioral alterations related to disruptions in normal sex 

differences in rats and mice (0.01-0.2 mg/kg bw-day) following developmental exposures. The FAO/WHO 

(2011) Expert Panel also concluded that while there was broad agreement in a NOAEL of 50 mg/kg bw-day 

for developmental toxicity based on standard bioassays, specific targeted studies identified 

neurodevelopmental effects at low doses (<1 mg/kg bw-day), but the human relevance is less certain. There 

is great variation in results with different types of studies measuring different endpoints; developmental 

effects at lower doses cannot be ruled out. Taken together these findings support a hazard designation of 

High concern.

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Reproduction/ 

Developmental Toxicity 

Screen

No data located.

Combined Repeated Dose 

with Reproduction/ 

Developmental Toxicity 

Screen

No data located.

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Summary of Developmental 

Effects

The NTP-CERHR Expert Panel concluded 

that BPA: 

*does not cause malformations or birth 

defects in rats or mice at levels up to the 

highest doses evaluated: 640 mg/kg bwday (rats) and 1,250 mg/kg bw-day (mice).

*does not alter male or female fertility 

after gestational exposure up to doses of 

450 mg/kg bw-day in the rat and 

600mg/kg bw-day in the mouse (highest 

dose levels evaluated). 

*does not permanently affect prostate 

weight at doses up to 475 mg/kg bw-day 

in adult rats or 600 mg/kg bw-day in mice.

*does not cause prostate cancer in rats or 

mice after adult exposure at up to 148 or 

600 mg/kg bw-day, respectively. 

*does change the age of puberty in male 

or female rats at high doses (ca. 

475 mg/kg bw-day). 

And that rodent studies suggest that BPA: 

*causes neural and behavioral alterations 

related to disruptions in normal sex 

differences in rats and mice 

(0.01-0.2 mg/kg bw-day). 

(Estimated by analogy)

NTP–CERHR, 2008; Professional 

judgment

Based on the analog BPA.

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The joint FAO/WHO Expert Panel 

reviewed reproductive and developmental 

toxicity data for BPA located as of 

November 2010 and noted that most 

regulatory bodies reviewing the numerous 

studies on BPA have indicated an oral 

reproductive and developmental NOAEL 

of 50 mg/kg bw-day.

FAO/WHO, 2011; Professional 

judgment

Based on the analog BPA.

Neurotoxicity MODERATE: Estimated to have potential for neurotoxicity based on the presence of the phenol structural 

alert.

Neurotoxicity Screening 

Battery (Adult)

There is potential for neurotoxicity effects 

based on the presence of the phenol 

structural alert. 

(Estimated)

U.S. EPA, 2010; Professional 

judgment

Estimated based on structural alert.

Repeated Dose Effects MODERATE: Estimated based on analogy to BPA, which produced histopathologic changes in the liver 

(centrilobular hepatocyte hypertrophy) from oral dosing at 50 mg/kg bw-day (NOAEL = 5 mg/kg bw-day) 

and there is uncertainty regarding the potential for BPA doses between the NOAEL of 5 mg/kg bw-day and

the LOAEL of 50 mg/kg-day to cause adverse systemic effects. Furthermore, lesions in the nasal cavity of 

rats were reported following repeated inhalation exposure to BPA dust at 0.05 mg/L. These findings indicate 

a Moderate hazard potential for the oral and inhalation exposure routes. In addition, while no LOAEL was 

identified, data located for a confidential analog indicates the potential that bisphenol AP may cause toxic 

effects to the blood, liver, and kidney. 

Potential for toxic effects to blood, liver,

and kidney 

Rat, 28-day oral study 

NOAEL = 5 mg/kg-day 

(Estimated by analogy)

Professional judgment Estimated based on located test data 

for a confidential analog with 

additional substituents; a LOAEL for 

these effects was not identified. 

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The FAO/WHO Expert Panel reviewed 

the located information regarding 

repeated-dose oral toxicity of BPA and 

concluded that results demonstrated 

effects on the liver, kidney, and body 

weight at doses of 50 mg/kg bw-day and 

higher and that the lowest NOAEL was 5 

mg/kg bw-day, as identified in several 

studies. 

(Estimated by analogy)

FAO/WHO, 2011; Professional 

judgment

Based on the analog BPA.

Parental systemic toxicity:

NOAEL = 4.75 mg/kg bw-day 

LOAEL = 47.5 mg/kg bw-day for 12% 

decreased terminal body weight in F1

parental males

(Estimated by analogy)

NTP-CERHR, 2008; Professional 

judgment

Based on the analog BPA; guideline 

study as reported in the secondary 

source. 

Classified by NTP-CERHR as 

having High Utility.

Parental systemic toxicity:

NOAEL = 5 mg/kg bw-day 

LOAEL = 50 mg/kg bw-day for increased 

incidences of centrilobular hepatocellular 

hypertrophy in males and females 

(Estimated by analogy)

NTP-CERHR, 2008; Professional 

judgment

Based on the analog BPA; guideline 

study as reported in the secondary 

source. 

Classified by NTP-CERHR as 

having High Utility.

NOAEL = 0.01 mg/L

LOAEL = 0.05 mg/L based on 

microscopic changes in the anterior 

portion of the nasal cavity 

(Estimated by analogy)

European Commission, 2000; 

EINECS, 2010; Professional 

judgment

Based on the analog BPA.

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Bisphenol AP CASRN 1571-75-1

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

NOAEL = None established

LOAEL = 0.047 mg/L for decreased body 

weight gain, increased liver and kidney 

weight, unspecified “morphological 

changes” in liver, kidney, and lungs 

(Estimated by analogy)

European Commission, 2000; 

EINECS, 2010; Professional 

judgment

Based on the analog BPA; single 

exposure level, insufficient study 

details in secondary sources. 

Skin Sensitization MODERATE: Based on analogy to BPA, bisphenol AP is estimated to be a skin sensitizer. Recent data 

from three BPA manufacturing facilities indicate that it does not elicit skin sensitization. However, results 

of some human studies suggest the possibility of a dermal sensitization response, although crosssensitization was not ruled out. Most animal studies conducted on the analog, BPA, were negative for 

dermal sensitization, although assays may not have been maximized. There is evidence of ear swelling in a 

photoallergy test in mice and moderate redness and swelling following repeated dermal exposure in rabbits. 

Based on suggestive evidence of skin sensitization in humans and mice for the analog, a Moderate hazard 

designation is warranted.

Skin Sensitization Negative in a modified local lymph node 

assay of mice administered BPA

epicutaneously on the ears at 

concentrations up to 30% on 3 consecutive 

days. 

(Estimated by analogy)

EINECS, 2010; Professional 

judgment

Based on the analog BPA; adequate, 

although the assay did not include 

concentrations >30%.

Negative in a local lymph node assay 

modified to test for photoreactivity in 

mice administered BPA epicutaneously on 

the ears at concentrations up to 30% on 

3 consecutive days and irradiated with UV 

light immediately following application. 

(Estimated by analogy)

EINECS, 2010; Professional 

judgment

Based on the analog BPA; adequate, 

although the assay did not include 

concentrations >30%. 

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Bisphenol AP CASRN 1571-75-1

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Negative in comprehensive medical 

surveillance data obtained from three BPA

manufacturing plants for 875 employees 

examined for several years where workers 

were potentially exposed to other 

chemicals (phenol, acetone) that are not 

considered to be skin sensitizers. 

(Estimated by analogy)

EINECS, 2010; Professional 

judgment

Based on the analog BPA; adequate.

Positive, rabbits; repeated dermal 

application (30 times over 37 days) of 

BPA (pure powder) produced moderate 

swelling and redness. Skin turned yellow 

followed by dark pigmentation after day 

15. 

(Estimated by analogy) 

NIOSH, 2010; Professional 

judgment

Based on the analog BPA; adequate.

The Joint FAO/WHO Expert Meeting 

review of the toxicological aspects of BPA

concludes that BPA is capable of 

producing a skin sensitization response in 

humans. 

(Estimated by analogy)

FAO/WHO, 2011; Professional 

judgment

Based on the analog BPA.

Respiratory Sensitization No data located.

Respiratory Sensitization No data located.

Eye Irritation MODERATE: Based on confidential analog, bisphenol AP was moderately irritating to rabbit eyes. 

Bisphenol AP may potentially be irritating to eyes.

Eye Irritation Potential for irritation to eyes; caused 

moderate eye irritation in rabbits 

(Estimated by analogy)

Professional judgment Estimated based on located test data 

for a confidential analog. 

Dermal Irritation MODERATE: Based on analogy to BPA. Bisphenol AP is estimated to be slightly to moderately irritating 

to rabbit skin based on test data for the analog and NIOSH identifying BPA as a skin irritant.

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Bisphenol AP CASRN 1571-75-1

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Dermal Irritation Rabbit, nonirritating to slightly irritating 

when applied as undiluted or 10% aqueous 

suspension to intact or abraded skin. 

(Estimated by analogy)

European Commission, 2000; 

EINECS, 2010; NIOSH, 2010; 

Professional judgment

Based on the analog BPA; the 

details provided for multiple studies 

indicate potential for BPA to cause 

dermal irritation.

Rabbit, moderately irritating when applied 

as 40% solution in dimethyl sulfoxide 

under non-occlusive conditions. 

(Estimated by analogy)

European Commission, 2000; 

Professional judgment

Based on the analog BPA; adequate.

Guinea pig, not irritating when applied as 

5% solution in acetone for 24 hours under 

occlusive conditions. 

(Estimated by analogy)

European Commission, 2000; 

Professional judgment

Based on the analog BPA; adequate.

Endocrine Activity Based on in vitro data, Bisphenol AP exhibits endocrine activity. In vitro assays indicate that bisphenol AP 

can bind to estrogen receptors, elicit estrogen-induced gene transcription, and induce cell proliferation in 

MCF7 cancer cells. Bisphenol AP appears to be similar to or somewhat less potent than BPA in its 

estrogenic responses in vitro.

In a human ER binding assay, the relative 

binding affinity (RBA) of bisphenol AP 

was 0.0803% compared to 126% for 17βestradiol. RBAs for other bisphenol 

compounds included 0.195% for BPA, 

0.129% for bisphenol C, 0.0719% for 

bisphenol F, and 0.0055% for bisphenol S. 

An RBA of 0.00473% was reported for 

PHBB.

METI, 2002 Adequate.

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Bisphenol AP CASRN 1571-75-1

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

In a reporter gene assay of estrogeninduced transcriptional activity, relative 

activity (RA) for bisphenol AP was 

0.000184% compared to 81.7% for 17βestradiol. RAs for other bisphenol 

compounds included 0.00278% for BPA, 

0.00189% for bisphenol C, 0.000639% for 

bisphenol F, and 0.000254% for bisphenol 

S. An RA of 0.000592% was reported for 

PHBB.

METI, 2002 Adequate.

In a competitive ER binding assay using 

human ERα, the RBA for bisphenol AP 

was 1.66% that of 17β-estradiol. RBAs for 

other bisphenol compounds included 

1.68% for bisphenol C, 0.32% for BPA, 

and 0.09% for bisphenol F.

Coleman, Toscano et al., 2003 Adequate.

In an ER-mediated reporter gene 

expression assay, bisphenol AP induced 

reporter gene expression at a relative 

activity (RA) of 9.0x10-5 that of 17βestradiol. RAs for other bisphenol 

compounds included 2.75x10-3 for BPA, 

5.3x10-4 for bisphenol F, and 4.9x10-4 for

bisphenol C.

Coleman, Toscano et al., 2003 Adequate.

In a proliferation assay of MCF-7 human 

breast cancer cells that contain ERα and 

ERβ and are known to proliferate in 

response to estrogens, bisphenol AP 

induced a proliferative response that was 

6.0x10-4 that of 17β-estradiol. Proliferative 

values for other bisphenol compounds 

included 2.0x10-3 for BPA, 1.6x10-3 for 

bisphenol C, and 1.0x10-3 for bisphenol F.

Coleman, Toscano et al., 2003 Adequate.

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Bisphenol AP CASRN 1571-75-1

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Immunotoxicity Estimated based on analogy to confidential analog. There is uncertain potential for immunotoxicity based 

on effects to the spleen.

Immune System Effects Uncertain potential for toxic effects to 

adrenal glands and spleen. 

Rat, 28-day oral study 

NOAEL = 5 mg/kg-day 

(Estimated by analogy)

Professional judgment Estimated based on located test data 

for a confidential analog with 

additional substituents; a LOAEL for 

these effects was not identified.

ECOTOXICITY

ECOSAR Class Phenols, poly

Acute Toxicity HIGH: Based on estimated LC50 values for fish and Daphnid and EC50 value for algae, which are all <1.0 

mg/L.

Fish LC50 Fish 96-hour LC50 = 0.580 mg/L

(Estimated) 

ECOSAR: phenols, poly

ECOSAR version 1.00

Fish 96-hour LC50 = 0.851mg/L

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.00 Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided by 

ECOSAR classes that have a more 

specific mode of action relative to 

narcosis.

Daphnid LC50 Daphnid 48-hour LC50 = 0.694 mg/L

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.00 Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided by 

ECOSAR classes that have a more 

specific mode of action relative to 

narcosis.

Daphnid 48-hour LC50 = 0.774 mg/L

(Estimated) 

ECOSAR: phenols, poly

ECOSAR version 1.00

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Bisphenol AP CASRN 1571-75-1

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Green Algae EC50 Green algae 96-hour EC50 = 0.967 mg/L 

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.00 Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided by 

ECOSAR classes that have a more 

specific mode of action relative to 

narcosis.

Green algae 96-hour EC50 = 1.38 mg/L 

(Estimated) 

ECOSAR: phenols, poly

ECOSAR version 1.00

Chronic Aquatic Toxicity HIGH: Based on an estimated fish ChV of 0.076 mg/L.

Fish ChV Fish ChV = 0.076 mg/L

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.00 Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided by 

ECOSAR classes that have a more 

specific mode of action relative to 

narcosis.

Fish 30-day ChV = 0.110 mg/L

(Estimated) 

ECOSAR: phenols, poly

ECOSAR version 1.00

Daphnid ChV Daphnid ChV = 0.106 mg/L

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.00 Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided by 

ECOSAR classes that have a more 

specific mode of action relative to 

narcosis.

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Bisphenol AP CASRN 1571-75-1

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Daphnid 21-day ChV = 0.243 mg/L

(Estimated) 

ECOSAR: phenols, poly

ECOSAR version 1.00

Green Algae ChV Green algae ChV = 0.134 mg/L 

(Estimated) 

ECOSAR: phenols, poly

ECOSAR version 1.00

Green algae ChV = 0.590 mg/L

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.00 Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided by 

ECOSAR classes that have a more 

specific mode of action relative to 

narcosis.

ENVIRONMENTAL FATE

Transport Evaluation of bisphenol AP transport is based entirely on QSAR estimations for fugacity (level III), 

disassociation constant (pKa), Koc, volatilization, and vapor pressure. Bisphenol AP is expected to exist in 

neutral form at environmentally-relevant pH. Bisphenol AP is expected to partition primarily to soil; 

therefore, leaching through soil to groundwater is not expected to be an important transport mechanism. In 

the atmosphere, bisphenol AP is expected to exist in the particulate phase which will be deposited back to 

the soil and water surfaces through wet or dry deposition.

Henry’s Law Constant 

(atm-m3/mole)

<1x10-8 (Estimated) EPI Cutoff value for nonvolatile 

compounds, based on professional 

judgment.

Sediment/Soil 

Adsorption/Desorption

Coefficient – Koc

>30,000 (Estimated) EPI; U.S. EPA, 2004 Cutoff value for nonmobile 

compounds. 

Level III Fugacity Model Air = <1%

Water = 2.4%

Soil = 44%

Sediment = 53% (Estimated)

EPI

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Bisphenol AP CASRN 1571-75-1

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Persistence HIGH: The persistence of bisphenol AP is based on an estimated half-life of 75 days in soil. Bisphenol AP is 

expected to partition primarily to soil based on results from a Level III fugacity model. Evaluation of the 

persistence of bisphenol AP is based entirely on QSARs of aerobic and anaerobic biodegradation. Results 

from these models estimate primary biodegradation in days-weeks and ultimate degradation in weeksmonths. Biodegradation under anaerobic methanogenic conditions is not probable. Bisphenol AP does not 

contain chromophores that absorb light at environmentally-relevant wavelengths. Therefore, it is not 

expected to be susceptible to direct photolysis. It is not expected to undergo hydrolysis as it does not contain 

hydrolyzable functional groups. The atmospheric half-life of bisphenol AP is estimated at 1.5 hours, 

although it is expected to exist primarily as a particulate in air. Based on the estimated data and qualitative 

assessments based on functional groups, biodegradation of bisphenol AP is expected to be the major 

removal process in the environment.

Water Aerobic Biodegradation Days-weeks (primary survey model)

Weeks-months (ultimate survey model)

EPI

Volatilization Half-life 

for Model River

>1 year (Estimated) EPI

Volatilization Half-life 

for Model Lake

>1 year (Estimated) EPI

Soil Aerobic Biodegradation No data located.

Anaerobic 

Biodegradation

Not probable (anaerobic-methanogenic 

biodegradation probability model)

EPI

Soil Biodegradation w/ 

Product Identification

No data located.

Sediment/Water 

Biodegradation

No data located.

Air Atmospheric Half-life 1.5 hours EPI

Reactivity Photolysis Not a significant fate process (Estimated) Mill, 2000; Professional judgment Substance does not contain 

functional groups that would be 

expected to absorb light at 

wavelengths >290 nm.

Hydrolysis Not a significant fate process (Estimated) Wolfe and Jeffers, 2000; 

Professional judgment

Substance does not contain 

functional groups that would be 

expected to hydrolyze readily under 

environmental conditions.

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Bisphenol AP CASRN 1571-75-1

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Pyrolysis No data located.

Environmental Half-life 75 days EPI Half-life estimated for the 

predominant compartment, as 

determined by EPI and the PBT 

Profiler methodology.

Bioaccumulation MODERATE: The estimated BCF is <1,000.

Fish BCF 750 (Estimated) EPI

BAF 250 (Estimated) EPI

Metabolism in Fish No data located.

ENVIRONMENTAL MONITORING AND BIOMONITORING 

Environmental Monitoring No data located.

Ecological Biomonitoring No data located.

Human Biomonitoring This chemical was not included in the NHANES biomonitoring report (CDC, 2011).

4-205 
FINAL REPORT – January 2014 

Aldrich. Handbook of Fine Chemicals and Laboratory Equipment. 2009-2010. Milwaukee, WI: Aldrich Chem Co. 2009, p.344. 

CDC (Centers for Disease Control and Prevention). Fourth national report on human exposure to environmental chemicals, updated 

tables. Department of Health and Human Services. 2011. http://www.cdc.gov/exposurereport/ (accessed on May 10, 

2011). 

ChemSpider. ChemSpider; Structure-based Chemistry Information. Royal Society of Chemistry: London. 2010. 

http://www.chemspider.com, accessed on December 11, 2010. 

Coleman, K.P., Toscano, W.A., Wiese, T.E. QSAR Models of the in vitro estrogen activity of bisphenol A analogs. QSAR & 

Combinatorial Science. 2003, 22:78-88. 

ECOSAR (2010) Ecological Structure Activity Relationship (ECOSAR) Version 1.00. Washington, DC: U.S. Environmental 

Protection Agency. http://www.epa.gov/oppt/newchems/tools/21ecosar.htm. 

EINECS. 4,4’-Isopropylidenediphenol (bisphenol A). European Union Risk Assessment Report. 2010. 

EPI (EPIWIN/EPISUITE) Estimations Programs Interface for Windows, Version 4.00. U.S. Environmental Protection Agency: 

Washington D.C. http://www.epa.gov/opptintr/exposure/. 

ESIS (European chemical Substances Information System) Classification, labeling and Packaging of dangerous substances annex VI 

to regulation (EC) No 1272/2008 [Online] http://esis.jrc.ec.europa.eu/ (accessed on June 10, 2011). 

European Commission. IUCLID Dataset for 4,4-isopropylidenediphenol (CAS No. 80-05-7). European Chemicals Bureau, February 

19, 2000. 2000. 

FAO/WHO. Toxicological and health aspects of bisphenol A. Report of Joint FAO/WHO expert meeting 2-5 November 2010 and 

report of stakeholder meeting on bisphenol A 1 November 2010. Food and Agriculture Organization of the United 

Nations; World Health Organization. Ottawa, Canada. 2011. 

METI. Current status of testing methods development for endocrine disruptors. Ministry of Economy, Trade and Industry, Japan. 6th

meeting of the task force on Endocrine Disruptors Testing and Assessments (EDTA). Tokyo. 2002. 

Mill, T. 2000. Photoreactions in Surface Waters. In Boethling, R.; Mackay, D., Handbook of Property Estimation Methods for 

Chemicals, Environmental Health Sciences (355-382). Boca Raton: Lewis Publishers. 

NIOSH (National Institute for Occupational Safety and Health). Skin Notation (SK) Profile, bisphenol A (BPA) [CAS No. 80-05-7]. 

Department of Health and Human Services; Centers for Disease Control and Prevention, 2010. 

4-206 
FINAL REPORT – January 2014 

NTP. Carcinogenesis bioassay of bisphenol-A (CAS No. 80-05-7) in F344 rats and B6C3F1 mice (feed study). National Toxicology 

Program. Technical Report No. 215, Order No. PB82-184060. 1982.

NTP-CERHR. Monograph on the potential human reproductive and developmental effects of biphenol A. National Toxicology 

Program; U.S. Department of Health and Human Service. Center for the Evaluation of Risks to Human Reproduction. 

NIH Publication No. 08-5994. September 2008. 

Oncologic. U.S. EPA and LogiChem, Inc. 2005, Version 7.0. 2008. 

PBT Profiler Persistent (P),Bioaccumulative (B), and Toxic (T) Chemical (PBT)Profiler. U.S. Environmental Protection Agency: 

Washington D.C. www.pbtprofiler.net. 

SPARC On Line Calculator pKa/property server. Ver 4.5 September, 2009. Available from, http://ibmlc2.chem.uga.edu/sparc/

(accessed on August 12, 2010). 

U.S. EPA (Environmental Protection Agency). High Production Volume (HPV) Challenge. Determining the Adequacy of Existing 

Data. U.S. Environmental Protection Agency: Washington D.C. 1999. 

http://www.epa.gov/hpv/pubs/general/datadfin.htm 

U.S. EPA (Environmental Protection Agency). 2004. The Pollution Prevention (P2) Framework, EPA-748-B-03-001. Office of 

Pollution Prevention and Toxics 7403M, U.S. Environmental Protection Agency, Washington, DC. 20460. October 

2003 version updated in January 2004. Latest version available at 

http://www.epa.gov/opptintr/newchems/pubs/sustainable/p2frame-june05a2.pdf

U.S. EPA (Environmental Protection Agency). Sustainable Futures Using NonCancer Screening within the Sustainable Futures 

Initiative Environmental Protection Agency: Washington D.C. 2010. http://www.epa.gov/opptintr/sf/pubs/noncanscreen.htm#systemic (accessed on February 09, 2011). 

Wolfe, N.; Jeffers, P. (2000) Hydrolysis. In Boethling, R.; Mackay, D., Handbook of Property Estimation Methods for Chemicals, 

Environmental Health Sciences (311-334). Boca Raton: Lewis Publishers. 

4-207 
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Substituted Phenolic Compound #1 

CASRN: Confidential CASRN

MW: Confidential MW

MF: Confidential MF

Physical Forms: 

Neat: Solid

Use: Developer for thermal paper 

SMILES: This mixture containing confidential material is not amenable to the generation of a single SMILES notation.

Synonyms: 

Polymeric: No

 Oligomers: Not applicable

Metabolites, Degradates and Transformation Products: None identified

Analog: Bisphenol A (80-05-7)

 Endpoint(s) using analog values: Acute toxicity, eye and skin irritation, skin 

sensitization, reproductive and developmental toxicity, repeated dose effects

Analog Structure: 

OH OH

4-208 

Structural Alerts: Phenols, neurotoxicity (U.S. EPA, 2010)

Risk Phrases: Not classified by Annex VI Regulation (EC) No 1272/2008 (ESIS, 2011).

Risk Assessments: None identified
FINAL REPORT – January 2014 

PROPRIETARY SUBSTITUTED PHENOLIC COMPOUND #1

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

PHYSICAL/CHEMICAL PROPERTIES

Melting Point (°C) 171.5 (Measured) Lide, 2008 Adequate; selected value for 

assessment.

171-172 (Measured) O’Neil et al., 2010 Adequate; reported values, which 

span a relatively narrow range, are 

consistent with those provided in 

other sources.

Boiling Point (°C) >300 (Estimated) EPI; U.S. EPA, 1999 Cutoff value for high boiling point 

compounds according to HPV 

assessment guidance.

Vapor Pressure (mm Hg) <1x10-8 (Estimated) EPI; U.S. EPA, 1999 Cutoff value for nonvolatile 

compounds according to HPV

assessment guidance.

Water Solubility (mg/L) 180 (Estimated) EPI

Appreciably soluble in water O’Neil et al., 2010 Inadequate; qualitative, nonspecific 

value.

Very soluble in water Lide, 2008

Log Kow 3.4 (Estimated) EPI

Flammability (Flash Point) 208°C (Measured) Alfa Aesar, 2010 Adequate.

Explosivity No data located.

pH No data located.

pKa 4.7; 10 (Estimated) SPARC

HUMAN HEALTH EFFECTS

Toxicokinetics As a neat material, this substituted phenolic compound is estimated to not be absorbed through the skin and 

have poor skin absorption when in solution. This compound is expected to be moderately absorbed via the 

lungs and gastrointestinal tract.

Dermal Absorption in vitro No data located.

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PROPRIETARY SUBSTITUTED PHENOLIC COMPOUND #1

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Absorption, 

Distribution, 

Metabolism & 

Excretion

Oral, Dermal or Inhaled Not absorbed through the skin as neat 

material and has poor absorption in

solution; can be moderately absorbed 

through the lung and gastrointestinal tract

(Estimated by analogy)

Professional judgment Based on closely related confidential 

analog with similar structure, 

functional groups, and 

physical/chemical properties. 

Acute Mammalian Toxicity LOW: Based on analogy to BPA. The acute oral and dermal toxicity hazard of this substituted phenolic 

compound is estimated to be low based on experimental data in animals for a closely related substance. Data 

for exposure to the analog BPA via inhalation were inconclusive, as only a single concentration was tested and 

a LC50 was not provided. 

Acute Lethality Oral Rat LD50 = 3,200->5,000 mg/kg bw

(Estimated by analogy)

NTP, 1982; European 

Commission, 2000; EINECS, 

2010; Professional judgment

Based on the analog BPA; multiple 

studies, some guideline studies. 

Mouse LD50 = 4,000-5,200 mg/kg bw

(Estimated by analogy)

NTP, 1982; European 

Commission, 2000; EINECS, 

2010; Professional judgment

Based on the analog BPA; multiple 

studies, some guideline studies. 

Dermal Rabbit LD50 = 3,000-6,400 mg/kg bw

(Estimated by analogy)

European Commission, 2000; 

EINECS, 2010; Professional 

judgment 

Based on the analog BPA; adequate 

by weight of evidence, multiple 

studies, although study details were

not reported in secondary sources.

Inhalation No deaths among male and female F344 

rats (10/sex) exposed to BPA dust at 

0.17 mg/L (highest attainable 

concentration) for 6 hours; transient slight 

nasal tract epithelial damage was evident. 

(Estimated by analogy)

European Commission, 2000; 

EINECS, 2010; Professional 

judgment 

Based on the analog BPA; test 

guidelines were not reported in 

secondary sources. 

Carcinogenicity MODERATE: Estimated using OncoLogic expert system, which describes a concern for this compound as a 

potential carcinogen or tumorigenesis promoter arising from its structural similarity to estrogenic/androgenic 

compounds, using the “phenols and phenolic compounds” structural alert.

OncoLogic Results Moderate (Estimated)

OncoLogic class: phenols and phenolic 

compounds 

OncoLogic OncoLogic SAR analysis using the 

phenols and phenolic compounds 

class.

Carcinogenicity (Rat and 

Mouse)

No data located.

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PROPRIETARY SUBSTITUTED PHENOLIC COMPOUND #1

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Combined Chronic 

Toxicity/ Carcinogenicity

No data located.

Genotoxicity LOW: This compound was not mutagenic in one assay that included several strains of Salmonella 

typhimurium and did not induce micronuclei in peripheral bone marrow of male B6C3F1 mice in vivo.

Gene Mutation in vitro Negative, Ames assay (standard plate) in 

S. typhimurium strains TA97, TA98, 

TA100, and TA1535 with and without 

metabolic activation

NTP, 2010 Adequate.

Gene Mutation in vivo No data located.

Chromosomal Aberrations 

in vitro

No data located.

Chromosomal Aberrations 

in vivo

Negative, micronucleus assay of peripheral 

bone marrow and blood in B6C3F1 mice 

(males only)

Mutat. Res., 2008 (Sanitized) Adequate.

DNA Damage and Repair No data located.

Other No data located.

Reproductive Effects MODERATE: Based on analogy to BPA. Key studies identified by NTP for the analog BPA indicate there 

are multiple distinct endpoints with NOAELs in the range of Moderate hazard concern with LOAELs in the 

range of Low hazard concern. At the target dose of 50 mg/kg-day (BPA), the NOAELs are on the margin of 

High and Moderate hazard, according to DfE criteria. Benchmark Dose (BMD) Modeling conducted by NTP, 

which interpolates between NOAEL and LOAEL values, yields values that further support a Moderate 

hazard designation.

Reproduction/ 

Developmental Toxicity 

Screen

No data located.

Combined Repeated Dose 

with Reproduction/ 

Developmental Toxicity 

Screen

No data located.

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PROPRIETARY SUBSTITUTED PHENOLIC COMPOUND #1

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Reproduction and Fertility 

Effects

Parental systemic toxicity:

NOAEL = 5 mg/kg bw-day 

LOAEL = 50 mg/kg bw-day for 12% 

decreased terminal body weight in F1

parental males

Reproductive toxicity: 

Females: NOAEL = 50 mg/kg bw-day 

LOAEL = 500 mg/kg bw-day for decreases

in number of implantation sites, delayed 

vaginal opening in F1, F2, F3 offspring 

BMDLs (change of 1 standard deviation 

from control) reported for delayed vaginal 

opening (females)- 

F1 = 176 mg/kg-day 

F2 = 228 mg/kg-day 

F3 = 203 mg/kg-day 

Males: NOAEL = 50 mg/kg bw-day, 

LOAEL = 500 mg/kg-day for delayed 

preputial separation in F1 males

BMDLs (change of 1 standard deviation 

from control) reported for delayed preputial 

separation (males)- 

F1 = 163 mg/kg-day 

F2 = 203 mg/kg-day 

F3 = 189 mg/kg-day 

(Estimated by analogy)

NTP-CERHR, 2008; Professional 

judgment 

Based on the analog BPA; adequate, 

guideline study as reported in the 

secondary source. 

Classified by NTP-CERHR as having 

High Utility.

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PROPRIETARY SUBSTITUTED PHENOLIC COMPOUND #1

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Parental systemic toxicity:

NOAEL = 5 mg/kg bw-day 

LOAEL = 50 mg/kg bw-day for increased 

incidences of centrilobular hepatocellular 

hypertrophy in males and females

Reproductive toxicity: 

NOAEL = 50 mg/kg bw-day 

LOAEL = 600 mg/kg bw-day for increased 

gestation length, decreased epididymal 

sperm concentration in F1 males, increased 

incidence of gross ovarian cysts in F1 and 

F2 females

BMD1 (change of 1 standard deviation 

from control) reported for increased 

gestation length

F0 = 1144 mg/kg-day (BMDL = 599 

mg/kg-day) 

F1 = 772 mg/kg-day (BMDL = 531 mg/kgday) 

BMD10s (10% extra risk) reported for 

increased incidence of gross ovarian cysts 

F0 = 225 mg/kg-day (BMDL = 141 mg/kgday) 

F1 = 202 mg/kg-day (BMDL = 120 mg/kgday) 

(Estimated by analogy)

NTP-CERHR, 2008; Professional 

judgment 

Based on the analog BPA; adequate, 

guideline study as reported in the 

secondary source. 

Classified by NTP-CERHR as having 

High Utility.

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Summary of Reproductive 

Effects

Female effects: There is sufficient 

evidence in rats and mice that BPA caused 

female reproductive toxicity with 

subchronic or chronic oral exposures with a 

NOAEL of 50 mg/kg bw-day and a 

LOAEL of 500 mg/kg bw-day. 

Male effects: There is sufficient evidence 

in rats and mice that BPA causes male 

reproductive toxicity with subchronic or 

chronic oral exposures with a NOAEL of 

50 mg/kg bw-day and a LOAEL of 500 

mg/kg bw/day. 

(Estimated by analogy)

NTP-CERHR, 2008; Professional 

judgment 

Based on the analog BPA.

Classified by NTP-CERHR as having 

High Utility.

The joint FAO/WHO Expert Panel 

reviewed reproductive and developmental 

toxicity data for BPA located as of 

November 2010 and noted that most 

regulatory bodies reviewing the numerous 

studies on BPA have indicated an oral 

reproductive and developmental NOAEL of 

50 mg/kg bw-day. 

(Estimated by analogy)

FAO/WHO, 2011 Based on the analog BPA.

Developmental Effects HIGH: Estimated based on analogy to BPA. The NTP-CERHR (2008) Expert Panel concluded that there is 

suggestive evidence that BPA causes neural and behavioral alterations related to disruptions in normal sex 

differences in rats and mice (0.01-0.2 mg/kg bw-day) following developmental exposures. The FAO/WHO 

(2011) Expert Panel also concluded that while there was broad agreement in a NOAEL of 50 mg/kg bw-day 

for developmental toxicity based on standard bioassays, specific targeted studies identified 

neurodevelopmental effects at low doses (<1 mg/kg bw-day), but the human relevance is less certain. There is 

great variation in results with different types of studies measuring different endpoints; developmental effects 

at lower doses cannot be ruled out. Taken together these findings support a hazard designation of High 

concern.

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Reproduction/ 

Developmental Toxicity 

Screen

No data located.

Combined Repeated Dose 

with Reproduction/ 

Developmental Toxicity 

Screen

No data located.

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Summary of 

Developmental Effects

The NTP-CERHR (2008) Expert Panel 

concluded that BPA: 

*does not cause malformations or birth 

defects in rats or mice at levels up to the 

highest doses evaluated: 640 mg/kg bw-day 

(rats) and 1,250 mg/kg bw-day (mice). 

*does not alter male or female fertility after 

gestational exposure up to doses of 450 

mg/kg bw-day in the rat and 600 mg/kg 

bw-day in the mouse (highest dose levels 

evaluated). 

*does not permanently affect prostate 

weight at doses up to 475 mg/kg bw-day in 

adult rats or 600 mg/kg bw-day in mice. 

*does not cause prostate cancer in rats or 

mice after adult exposure at up to 148 or 

600 mg/kg bw-day, respectively. 

*does change the age of puberty in male or 

female rats at high doses (ca. 475 mg/kg 

bw-day). 

And that rodent studies suggest that BPA: 

*causes neural and behavioral alterations 

related to disruptions in normal sex 

differences in rats and mice (0.01–

0.2 mg/kg bw-day). 

(Estimated by analogy)

NTP–CERHR, 2008; Professional 

judgment 

Based on the analog BPA.

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The joint FAO/WHO (2011) Expert Panel 

reviewed reproductive and developmental 

toxicity data for BPA located as of 

November 2010 and noted that most 

regulatory bodies reviewing the numerous 

studies on BPA have indicated an oral 

reproductive and developmental NOAEL of 

50 mg/kg bw-day. 

(Estimated by analogy)

FAO/WHO, 2011; Professional 

judgment 

Based on the analog BPA.

Neurotoxicity MODERATE: Estimated to have potential for neurotoxicity based on the presence of the phenol structural 

alert.

Neurotoxicity Screening 

Battery (Adult)

There is potential for neurotoxicity effects 

based on the presence of the phenol 

structural alert. 

Estimated)

U.S. EPA, 2010; Professional 

judgment 

Estimated based on structural alert.

Repeated Dose Effects MODERATE: Estimated based on analogy to BPA, which produced histopathologic changes in the liver 

(centrilobular hepatocyte hypertrophy) from oral dosing at 50 mg/kg bw-day (NOAEL = 5 mg/kg bw-day) 

and there is uncertainty regarding the potential for BPA doses between the NOAEL of 5 mg/kg bw-day and 

the LOAEL of 50 mg/kg bw-day to cause adverse systemic effects. Furthermore lesions in the nasal cavity of 

rats were reported following repeated inhalation exposure to BPA dust at 0.05 mg/L. These findings indicate a 

Moderate hazard concern for the oral and inhalation exposure routes.

The FAO/WHO (2011) Expert Panel 

reviewed the available information 

regarding repeated-dose oral toxicity of 

BPA and concluded that results 

demonstrated effects on the liver, kidney, 

and body weight at doses of 50 mg/kg bwday and higher and that the lowest NOAEL 

was 5 mg/kg-day, as identified in several 

studies. 

(Estimated by analogy)

FAO/WHO, 2011; Professional 

judgment 

Based on the analog BPA.

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Parental systemic toxicity:

NOAEL = 4.75 mg/kg bw-day 

LOAEL = 47.5 mg/kg bw-day for 12% 

decreased terminal body weight in F1

parental males

(Estimated by analogy)

NTP-CERHR, 2008; Professional 

judgment 

Based on the analog BPA; guideline 

study as reported in the secondary 

source. 

Classified by NTP-CERHR as having 

High Utility.

Parental systemic toxicity:

NOAEL = 5 mg/kg bw-day 

LOAEL = 50 mg/kg bw-day for increased 

incidences of centrilobular hepatocellular 

hypertrophy in males and females

(Estimated by analogy)

NTP-CERHR, 2008; Professional 

judgment 

Based on the analog BPA; guideline 

study as reported in the secondary 

source. 

Classified by NTP-CERHR as having 

High Utility.

NOAEL = 0.01 mg/L

LOAEL = 0.05 mg/L based on microscopic 

changes in the anterior portion of the nasal 

cavity

(Estimated by analogy)

EINECS, 2010; European 

Commission, 2000; Professional 

judgment 

Based on the analog BPA.

NOAEL = None established

LOAEL = 0.047 mg/L for decreased body 

weight gain, increased liver and kidney 

weight, unspecified “morphological 

changes” in liver, kidney, and lungs

(Estimated by analogy)

EINECS, 2010; European 

Commission, 2000; Professional 

judgment 

Based on the analog BPA; single 

exposure level, insufficient study 

details in secondary sources. 

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Skin Sensitization MODERATE: Based on analogy to BPA, this substituted phenolic compound is estimated to be a skin 

sensitizer. Recent data from three BPA manufacturing facilities indicate that it does not elicit skin 

sensitization. However, results of some human studies suggest the possibility of a dermal sensitization 

response, although cross-sensitization was not ruled out. Most animal studies conducted on the analog were 

negative for dermal sensitization, although assays may not have been maximized. There is evidence of ear 

swelling in a photoallergy test in mice and moderate redness and swelling following repeated dermal exposure 

in rabbits. Based on suggestive evidence of skin sensitization in humans and mice for the analog, a Moderate

hazard designation is warranted.

Skin Sensitization Negative in a modified local lymph node 

assay of mice administered BPA

epicutaneously on the ears at 

concentrations up to 30% on 3 consecutive 

days. 

(Estimated by analogy)

EINECS, 2010; Professional 

judgment

Based on the analog BPA; adequate, 

although the assay did not include 

concentrations >30%.

Negative in a local lymph node assay 

modified to test for photoreactivity in mice 

administered BPA epicutaneously on the 

ears at concentrations up to 30% on three 

consecutive days and irradiated with UV 

light immediately following application. 

(Estimated by analogy)

EINECS, 2010; Professional 

judgment

Based on the analog BPA; adequate, 

although the assay did not include 

concentrations >30%. 

Negative in comprehensive medical 

surveillance data obtained from three BPA

manufacturing plants for 875 employees 

examined for several years where workers 

were potentially exposed to other chemicals 

(phenol, acetone) that are not considered to 

be skin sensitizers. 

(Estimated by analogy)

EINECS, 2010; Professional 

judgment

Based on the analog BPA; adequate.

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Positive, rabbits; repeated dermal 

application (30 times over 37 days) of BPA

(pure powder) produced moderate swelling 

and redness; skin turned yellow followed 

by dark pigmentation after day 15. 

(Estimated by analogy) 

NIOSH, 2010; Professional 

judgment

Based on the analog BPA; adequate.

The Joint FAO/WHO Expert Meeting 

review of the toxicological aspects of BPA

concludes that BPA is capable of producing 

a skin sensitization response in humans. 

(Estimated by analogy)

FAO/WHO, 2011; Professional 

judgment

Based on the analog BPA.

Respiratory Sensitization No data located.

Respiratory Sensitization No data located.

Eye Irritation MODERATE: Based on analogy to BPA. The analog BPA was slightly to highly irritating to rabbit eyes.

Eye Irritation Rabbit, slightly to highly irritating European Commission, 2000; 

EINECS, 2010; Professional 

judgment 

Based on the analog BPA. Adequate;

multiple studies, weight of evidence 

indicates potential for BPA to cause 

eye irritation.

Dermal Irritation MODERATE: This substituted phenolic compound is estimated to be slightly irritating to moderately 

irritating based on test data for the analog BPA.

Dermal Irritation Rabbit, nonirritating to slightly irritating 

when applied as undiluted or 10% aqueous 

suspension to intact or abraded skin. 

(Estimated by analogy)

European Commission, 2000; 

EINECS, 2010; NIOSH, 2010; 

Professional judgment

Based on the analog BPA. Adequate;

multiple studies, weight of evidence 

indicates potential for BPA to cause 

dermal irritation.

Rabbit, moderately irritating when applied 

as 40% solution in dimethyl sulfoxide 

under non-occlusive conditions. 

(Estimated by analogy)

European Commission, 2000; 

Professional judgment

Based on the analog BPA; adequate.

Guinea pig, not irritating when applied as 

5% solution in acetone for 24-hours under 

occlusive conditions. 

(Estimated by analogy)

European Commission, 2000;

Professional judgment

Based on the analog BPA; adequate.

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Endocrine Activity This compound exhibited a weakly positive ER binding affinity in one in vitro assay.

The proprietary phenolic compound 

exhibited weak ER binding activity in 

preparations from uteri of ovariectomized 

Sprague-Dawley rats as evidenced by a 

relative binding affinity (RBA) that was 

0.0007% of the binding affinity of 17βestradiol. RBAs for other tested chemicals 

included 0.008% for BPA, 0.003% for 

PHBB and 0.0009% for bisphenol F.

Blair, Fang et al., 2000 Adequate.

Immunotoxicity No data located.

Immune System Effects No data located.

ECOTOXICITY

ECOSAR Class Phenols, poly – acid

Acute Toxicity HIGH: Based on an estimated 96-hour EC50 of 7.67 (ECOSAR class: neutral organics) for green algae.

Fish LC50 Fish 96-hour LC50 = 14.75 mg/L

(Estimated) 

ECOSAR: neutral organics

ECOSAR version 1.00 Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided by 

ECOSAR classes that have a more 

specific mode of action relative to 

narcosis.

Fish 96-hour LC50 = 41.53 mg/L

(Estimated) 

ECOSAR: phenols, poly - acid 

ECOSAR version 1.00

Daphnid LC50 Daphnid 48-hour LC50 = 10.07 mg/L

(Estimated) 

ECOSAR: neutral organics

ECOSAR version 1.00 Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided by

ECOSAR classes that have a more 

specific mode of action relative to 

narcosis.

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Daphnid 48-hour LC50 = 103.05 mg/L

(Estimated) 

ECOSAR: phenols, poly - acid 

ECOSAR version 1.00

Green Algae EC50 Green algae 96-hour EC50 = 7.67 mg/L

(Estimated) 

ECOSAR: neutral organics

ECOSAR version 1.00 Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided by 

ECOSAR classes that have a more 

specific mode of action relative to 

narcosis.

Green algae 96-hour EC50 = 18.35 mg/L

(Estimated) 

ECOSAR: phenols, poly - acid 

ECOSAR version 1.00

Chronic Aquatic Toxicity MODERATE: Based on ECOSAR-estimated data for fish, Daphnid, and green algae.

Fish ChV Fish ChV = 1.36 mg/L

(Estimated) 

ECOSAR: neutral organics

ECOSAR version 1.00 Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided by 

ECOSAR classes that have a more 

specific mode of action relative to 

narcosis.

Fish 30-day ChV = 10.16 mg/L

(Estimated) 

ECOSAR: phenols, poly - acid 

ECOSAR version 1.00

Daphnid ChV Daphnid ChV = 1.19 mg/L

(Estimated) 

ECOSAR: neutral organics

ECOSAR version 1.00 Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided by 

ECOSAR classes that have a more 

specific mode of action relative to 

narcosis.

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Daphnid 21-day ChV = 35.44 mg/L

(Estimated) 

ECOSAR: phenols, poly - acid 

ECOSAR version 1.00

Green Algae ChV Green algae ChV = 3.34 mg/L

(Estimated) 

ECOSAR: phenols, poly - acid

ECOSAR version 1.00

Green algae ChV = 3.58 mg/L

(Estimated) 

ECOSAR: neutral organics

ECOSAR version 1.00 Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided by 

ECOSAR classes that have a more 

specific mode of action relative to 

narcosis.

ENVIRONMENTAL FATE

Transport Based on the Level III fugacity models incorporating the available experimental property data, this 

substituted phenolic compound is expected to partition primarily to soil where it is expected to be immobile in 

based on its estimated Koc. Estimated volatilization half-lives indicate it will be nonvolatile from surface 

water. Volatilization from dry surface is also not expected based on its estimated vapor pressure. In the 

atmosphere, this substituted phenolic compound is expected to exist solely in the particulate phase, based on 

its estimated vapor pressure. Particulates may be removed from air by wet or dry deposition. 

Henry’s Law Constant 

(atm-m3/mole)

<1x10-8 (Estimated) EPI Cutoff value for nonvolatile 

compounds based on professional 

judgment. 

Sediment/Soil 

Adsorption/Desorption

Coefficient – Koc

8,900 (Estimated) EPI

Level III Fugacity 

Model

Air = <1% (Estimated)

Water = 15%

Soil = 81% 

Sediment = 4%

EPI

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Persistence MODERATE: Evaluation of the persistence of this compound is based entirely on QSARs in the 

compartment that this compound is most likely to be found, soil. Results from these models estimate a 

persistence half-life in soil of 30 days. The biodegradation models estimate primary biodegradation in daysweeks and ultimate degradation in weeks. Based on these data, the biodegradation half-life is expected to be 

<60 days. Biodegradation under anaerobic methanogenic conditions is not probable. This compound is not 

expected to undergo hydrolysis since it does not contain hydrolyzable functional groups. The atmospheric 

half-life of this compound is estimated at 1.5 hours, although it is expected to exist primarily in the particulate 

phase in air. Based on the estimated data and qualitative assessments based on functional groups, 

biodegradation of this compound is expected to be the primary removal process in the environment.

Water Aerobic 

Biodegradation

Days-weeks (primary survey model)

Weeks (ultimate survey model)

EPI

Volatilization Half-life 

for Model River

>1 year (Estimated) EPI

Volatilization Half-life 

for Model Lake

>1 year (Estimated) EPI

Soil Aerobic 

Biodegradation

No data located.

Anaerobic 

Biodegradation

Not probable (anaerobic-methanogenic 

biodegradation probability model)

EPI

Soil Biodegradation w/ 

Product Identification

No data located.

Sediment/Water 

Biodegradation

No data located.

Air Atmospheric Half-life 1.5 hours (Estimated) EPI

Reactivity Photolysis Not a significant fate process (Estimated) Mill, 2000; Professional judgment Substance does not contain 

functional groups that would be 

expected to absorb light at 

environmentally significant 

wavelengths.

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PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Hydrolysis Not a significant fate process (Estimated) Wolfe and Jeffers, 2000; 

Professional judgment

Substance does not contain 

functional groups that would be 

expected to absorb light at 

environmentally significant 

wavelengths.

Pyrolysis No data located.

Environmental Half-life 30 days (Estimated) EPI; PBT Profiler Half-life estimated for the 

predominant compartment, as 

determined by EPI and the PBT 

Profiler methodology.

Bioaccumulation LOW: The fish BCF and BAF estimates are <100.

Fish BCF 3.2 (Estimated) EPI

BAF 84 (Estimated) EPI

Metabolism in Fish No data located.

ENVIRONMENTAL MONITORING AND BIOMONITORING 

Environmental Monitoring No data located.

Ecological Biomonitoring No data located.

Human Biomonitoring This chemical was not included in the NHANES biomonitoring report (CDC, 2011).

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Alfa Aesar - A Johnson Matthey Company. Material Safety Data Sheet (MSDS). Available at http://www.alfa.com. Accessed on 

November, 19, 2010. 

Blair R.M., Fang H., Branham, W.S., et al. The estrogen receptor relative binding affinities of 188 natural and xenochemicals: 

structural diversity of ligands. Toxicol. Sci. 2000, 54:138-153. 

CDC (Centers for Disease Control and Prevention). Fourth national report on human exposure to environmental chemicals, updated 

tables. Department of Health and Human Services. 2011. http://www.cdc.gov/exposurereport/ (accessed on May 10, 2011). 

ECOSAR (2010) Ecological Structure Activity Relationship (ECOSAR) Version 1.00. Washington, DC: U.S. Environmental 

Protection Agency. http://www.epa.gov/oppt/newchems/tools/21ecosar.htm. 

EINECS (European Inventory of Existing Commercial chemical Substances). 4,4’-Isopropylidenediphenol (bisphenol A). European 

Union Risk Assessment Report. 2010.

EPI (EPIWIN/EPISUITE) Estimations Programs Interface for Windows, Version 4.00. U.S. Environmental Protection Agency: 

Washington D.C. http://www.epa.gov/opptintr/exposure/. 

ESIS (European chemical Substances Information System) Classification, labeling and Packaging of dangerous substances annex VI 

to regulation (EC) No 1272/2008 [Online] http://esis.jrc.ec.europa.eu/ (accessed on June 10, 2011). 

European Commission. IUCLID Dataset for 4,4-isopropylidenediphenol (CAS No. 80-05-7). European Chemicals Bureau, February 

19, 2000. 

FAO/WHO (Food and Agriculture Organization/World Health Organization). 2010. Joint FAO/WHO expert meeting to review 

toxicological and health aspects of bisphenol A. Summary report including report of stakeholder meeting on bisphenol A. Food 

and Agriculture Organization of the United Nations; World Health Organization. Ottawa, Canada. November 1-5, 2010. 

Lide, D. R, ed. CRC Handbook of Chemistry and Physics, 88th edition; CRC Press Taylor & Francis: Boca Raton, FL. 2008. 

Mill, T. 2000. Photoreactions in Surface Waters. In Boethling, R.; Mackay, D., Handbook of Property Estimation Methods for 

Chemicals, Environmental Health Sciences (355-382). Boca Raton: Lewis Publishers. 

Mutat Res. 2008 (Sanitized - article title and author)

NIOSH (National Institute for Occupational Safety and Health). Skin Notation (SK) Profile, bisphenol A (BPA) [CAS No. 80-05-7]. 

Department of Health and Human Services; Centers for Disease Control and Prevention, 2010. 

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NTP (National Toxicology Program). Carcinogenesis bioassay of bisphenol-A (CAS No. 80-05-7) in F344 rats and B6C3F1 mice 

(feed study). Technical Report No. 215, PB82-184060. 1982. 

NTP (National Toxicology Program). Department of Health and Human Services. 2010. http://ntp-apps.niehs.nih.gov/ntp_tox/ 

NTP-CERHR. Monograph on the potential human reproductive and developmental effects of biphenol A. National Toxicology 

Program; U.S. Department of Health and Human Service. Center for the Evaluation of Risks to Human Reproduction. NIH 

Publication No. 08-5994. September 2008. 

Oncologic. U.S. EPA and LogiChem, Inc. 2005, Version 7.0. 2008. 

O’Neil, M., et al. eds. e-Merck Index. 14th ed. Basic Search. Whitehouse Station, NJ: Merck & Co., Inc. 2010. 

https://themerckindex.cambridgesoft.com/TheMerckIndex/index.asp (accessed on December 10, 2010). 

PBT Profiler Persistent (P), Bioaccumulative (B), and Toxic (T) Chemical (PBT) Profiler, U.S. Environmental Protection Agency: 

Washington D.C. www.pbtprofiler.net. 

SPARC On Line Calculator pKa/property server. Ver 4.5 September, 2009. Available from, http://ibmlc2.chem.uga.edu/sparc/

(accessed on August 12, 2010). 

U.S. EPA (Environmental Protection Agency). High Production Volume (HPV) Challenge. Determining the Adequacy of Existing 

Data. U.S. Environmental Protection Agency: Washington D.C. 1999. http://www.epa.gov/hpv/pubs/general/datadfin.htm

U.S. EPA (Environmental Protection Agency). Sustainable Futures Using NonCancer Screening within the Sustainable Futures 

Initiative Environmental Protection Agency: Washington D.C. 2010. http://www.epa.gov/opptintr/sf/pubs/noncanscreen.htm#systemic (accessed on February 09, 2011). 

Wolfe, N.; Jeffers, P. (2000) Hydrolysis. In Boethling, R.; Mackay, D., Handbook of Property Estimation Methods for Chemicals, 

Environmental Health Sciences (311-334). Boca Raton: Lewis Publishers. 

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Substituted Phenolic Compound #2

CASRN: Confidential CASRN

MW: Confidential MW

MF: Confidential MF

Physical Forms:

Neat: Solid

Use: Developer for thermal paper

SMILES: This confidential material is not amenable to the generation of a single SMILES notation.

Synonyms: None

Polymeric: No

 Oligomers: Not applicable

Metabolites, Degradates and Transformation Products: None identified

Analog: Bisphenol A (80-05-7)

Endpoint(s) using analog values: Acute toxicity, eye and skin irritation, skin 

sensitization, reproductive and developmental toxicity, genotoxicity, repeated dose 

effects

Analog Structure: 

OH OH

4-228 

Structural Alerts: Phenols, neurotoxicity (U.S. EPA, 2010)

Risk Phrases: R43 - May cause sensitization by skin contact; 62 Possible risk of impaired fertility; 51/53 - Toxic to aquatic organisms, may cause long-term adverse 

effects in the aquatic environment (ESIS, 2011).

Risk Assessments: None identified
FINAL REPORT – January 2014 

PROPRIETARY SUBSTITUTED PHENOLIC COMPOUND #2

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

PHYSICAL/CHEMICAL PROPERTIES

Melting Point (°C) 138 (Measured) Chemspider, 2010 Adequate; secondary source, study 

details and test conditions were not 

provided; selected value for 

assessment.

135-139 (Measured) Aldrich, 2009 Adequate; measured by chemical 

supplier, consistent with other 

reported values.

Boiling Point (°C) >300 (Estimated) EPI; U.S. EPA, 1999 Cutoff value for high boiling point 

compounds according to HPV 

assessment guidance.

Vapor Pressure (mm Hg) <1x10-8 (Estimated) EPI; U.S. EPA, 1999 Cutoff value for nonvolatile 

compounds according to HPV 

assessment guidance.

Water Solubility (mg/L) 0.12 (Estimated) EPI

Log Kow 6.3 (Estimated) EPI

Flammability (Flash Point) No data located.

Explosivity No data located.

pH No data located.

pKa 10 (Estimated) SPARC

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PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

HUMAN HEALTH EFFECTS

Toxicokinetics Substituted phenolic compound #2 is estimated to not be absorbed through the skin and have poor 

absorption when in solution via the lungs and gastrointestinal tract.

Dermal Absorption in vitro No data located.

Absorption, 

Distribution, 

Metabolism & 

Excretion

Oral, Dermal or Inhaled Not absorbed through the skin and has 

poor absorption through the lung and 

gastrointestinal tract

(Estimated by analogy)

Professional judgment Based on closely related confidential 

analog with similar structure, 

functional groups, and 

physical/chemical properties. 

Acute Mammalian Toxicity LOW: Based on analogy to BPA. The acute oral and dermal toxicity hazard of substituted phenolic 

compound #2 is estimated to be low based on experimental data in animals for a closely related substance. 

Data for exposure to the analog BPA via inhalation were inconclusive, as only a single concentration was 

tested and a LC50 was not provided. 

Acute Lethality Oral Rat LD50 = 3,200-5,000 mg/kg bw

(Estimated by analogy) 

NTP, 1982; European 

Commission, 2000; EINECS, 

2010; Professional judgment

Based on the analog BPA; multiple 

studies, some guideline studies. 

Mouse LD50 = 4,000-5,200 mg/kg bw

(Estimated by analogy) 

NTP, 1982; European 

Commission, 2000; EINECS, 

2010; Professional judgment

Based on the analog BPA; multiple 

studies, some guideline studies. 

Dermal Rabbit LD50 = 3,000-6,400 mg/kg bw

(Estimated by analogy) 

European Commission, 2000; 

EINECS, 2010; Professional 

judgment 

Based on the analog BPA; adequate 

by weight of evidence, multiple 

studies, although study details were 

not reported in secondary sources.

Inhalation No deaths among male and female F344 

rats (10/sex) exposed to BPA dust at 

0.17 mg/L (highest attainable 

concentration) for 6 hours; transient 

slight nasal tract epithelial damage was 

evident. 

(Estimated by analogy)

European Commission, 2000; 

EINECS, 2010; Professional 

judgment 

Based on the analog BPA; test 

guidelines were not reported in 

secondary sources. 

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PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Carcinogenicity MODERATE: Estimated using OncoLogic expert system, which describes a concern for this compound as a 

potential carcinogen or tumorigenesis promoter arising from its structural similarity to 

estrogenic/androgenic compounds, using the “phenols and phenolic compounds” structural alert.

OncoLogic Results Moderate (Estimated)

OncoLogic class: phenols and phenolic 

compounds 

OncoLogic OncoLogic SAR analysis using the 

phenols and phenolic compounds 

class.

Carcinogenicity (Rat and 

Mouse)

No data located.

Combined Chronic 

Toxicity/ Carcinogenicity

No data located.

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Genotoxicity LOW: Based on analogy to BPA. FAO/WHO (2011) determined that: (1) the analog BPA is not a mutagen 

in in vitro test systems, (2) the analog BPA does not induce cell transformation, and (3) in vivo evidence for 

clastogenic effects induced by the analog BPA is inconsistent and inconclusive although some in vitro studies 

have shown BPA to affect chromosomal structure in dividing cells. The conclusion of FAO/WHO (2011) is 

that the analog BPA is not likely to pose a genotoxic hazard to humans.

Largely negative results in a variety of in 

vitro test systems, including studies with 

Salmonella typhimurium, Chinese 

hamster V79 cells, Syrian hamster 

embryo cells, and mouse lymphoma 

cells. However, DNA damage was 

induced in MCF-7 and MDA-MB-231 

cells, DNA adduct formation in Syrian 

hamster ovary cells and a number of 

positive findings have been reported for 

the potential for BPA to inhibit purified 

microtubule polymerization, affect the 

spindle apparatus and produce 

aneuploidy in in vitro studies with 

Chinese hamster V79 cells or oocytes 

from Balb/c or MF1 mice. 

FAO/WHO Expert Panel concludes: 

BPA is not a mutagen in in vitro test 

systems, nor does it induce cell 

transformation. BPA has been shown to 

affect chromosomal structure in dividing 

cells in in vitro studies, but evidence for 

this effect in in vivo studies is 

inconsistent and inconclusive. BPA is 

not likely to pose a genotoxic hazard to 

humans. 

(Estimated by analogy)

FAO/WHO, 2011; Professional 

judgment 

Based on the analog BPA.

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Reproductive Effects MODERATE: Based on analogy to BPA. Key studies identified by NTP for the analog BPA indicate there 

are multiple distinct endpoints with NOAELs in the range of Moderate hazard concern with LOAELs in the 

range of Low hazard concern. At the target dose of 50 mg/kg-day (BPA), the NOAELs are on the margin of 

High and Moderate hazard, according to DfE criteria. Benchmark Dose (BMD) Modeling conducted by 

NTP, which interpolates between NOAEL and LOAEL values, yields values that further support a 

Moderate hazard designation.

Reproduction/ 

Developmental Toxicity 

Screen

No data located.

Combined Repeated Dose 

with Reproduction/ 

Developmental Toxicity 

Screen

No data located.

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Reproduction and Fertility 

Effects

Parental systemic toxicity:

NOAEL = 5 mg/kg bw-day 

LOAEL = 50 mg/kg bw-day for 12% 

decreased terminal body weight in F1

parental males

Reproductive toxicity: 

Females: NOAEL = 50 mg/kg bw-day 

LOAEL = 500 mg/kg bw-day for 

decreases in number of implantation 

sites, delayed vaginal opening in F1, F2, 

F3 offspring 

BMDLs (change of 1 standard deviation 

from control) reported for delayed 

vaginal opening (females)- 

F1 = 176 mg/kg-day 

F2 = 228 mg/kg-day 

F3 = 203 mg/kg-day 

Males: NOAEL = 50 mg/kg bw-day, 

LOAEL = 500 mg/kg-day for delayed 

preputial separation in F1 males

BMDLs (change of 1 standard deviation 

from control) reported for delayed 

preputial separation (males)- 

F1 = 163 mg/kg-day 

F2 = 203 mg/kg-day 

F3 = 189 mg/kg-day 

(Estimated by analogy)

NTP-CERHR, 2008; Professional 

judgment 

Based on the analog BPA; adequate, 

guideline study as reported in the 

secondary source. 

Classified by NTP-CERHR as having 

High Utility.

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Parental systemic toxicity:

NOAEL = 5 mg/kg bw-day 

LOAEL = 50 mg/kg bw-day for 

increased incidences of centrilobular 

hepatocellular hypertrophy in males and 

females

Reproductive toxicity: 

NOAEL = 50 mg/kg bw-day 

LOAEL = 600 mg/kg bw-day for 

increased gestation length, decreased 

epididymal sperm concentration in F1

males, increased incidence of gross 

ovarian cysts in F1 and F2 females

BMD1 (change of 1 standard deviation 

from control) reported for increased 

gestation length

F0 = 1144 mg/kg-day (BMDL = 599 

mg/kg-day) 

F1 = 772 mg/kg-day (BMDL = 531 

mg/kg-day) 

BMD10s (10% extra risk) reported for 

increased incidence of gross ovarian 

cysts

F0 = 225 mg/kg-day (BMDL = 141 

mg/kg-day) 

F1 = 202 mg/kg-day (BMDL = 120 

mg/kg-day) 

(Estimated by analogy)

NTP-CERHR, 2008; Professional 

judgment 

Based on the analog BPA; adequate, 

guideline study as reported in the 

secondary source. 

Classified by NTP-CERHR as having 

High Utility.

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Summary of Reproductive 

Effects

Female effects: There is sufficient 

evidence in rats and mice that BPA

caused female reproductive toxicity with 

subchronic or chronic oral exposures 

with a NOAEL of 50 mg/kg bw-day and 

a LOAEL of 500 mg/kg bw-day. 

Male effects: There is sufficient 

evidence in rats and mice that BPA

causes male reproductive toxicity with 

subchronic or chronic oral exposures 

with a NOAEL of 50 mg/kg bw-day and 

a LOAEL of 500 mg/kg bw/day. 

(Estimated by analogy)

NTP-CERHR, 2008; Professional 

judgment 

Based on the analog BPA.

Classified by NTP-CERHR as having 

High Utility.

The joint FAO/WHO Expert Panel 

reviewed reproductive and 

developmental toxicity data for BPA 

located as of November 2010 and noted 

that most regulatory bodies reviewing 

the numerous studies on BPA have 

indicated an oral reproductive and 

developmental NOAEL of 50 mg/kg bwday. 

(Estimated by analogy)

FAO/WHO, 2011 Based on the analog BPA.

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Developmental Effects HIGH: Based on analogy to BPA. The NTP-CERHR (2008) Expert Panel concluded that there is suggestive 

evidence that BPA causes neural and behavioral alterations related to disruptions in normal sex differences 

in rats and mice (0.01-0.2 mg/kg bw-day) following developmental exposures. The FAO/WHO (2011) Expert 

Panel also concluded that while there was broad agreement in a NOAEL of 50 mg/kg bw-day for 

developmental toxicity based on standard bioassays, specific targeted studies identified neurodevelopmental 

effects at low doses (<1 mg/kg bw-day), but the human relevance is less certain. There is great variation in 

results with different types of studies measuring different endpoints; developmental effects at lower doses 

cannot be ruled out. Taken together these findings support a hazard designation of High concern.

Reproduction/ 

Developmental Toxicity 

Screen

No data located.

Combined Repeated Dose 

with Reproduction/ 

Developmental Toxicity 

Screen

No data located.

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Summary of 

Developmental Effects

The NTP-CERHR (2008) Expert Panel 

concluded that BPA: 

*does not cause malformations or birth 

defects in rats or mice at levels up to the 

highest doses evaluated: 640 mg/kg bwday (rats) and 1,250 mg/kg bw-day 

(mice). 

*does not alter male or female fertility 

after gestational exposure up to doses of 

450 mg/kg bw-day in the rat and 

600mg/kg bw-day in the mouse (highest 

dose levels evaluated). 

*does not permanently affect prostate 

weight at doses up to 475 mg/kg bw-day 

in adult rats or 600 mg/kg bw-day in 

mice. 

*does not cause prostate cancer in rats or 

mice after adult exposure at up to 148 or 

600 mg/kg bw-day, respectively. 

*does change the age of puberty in male 

or female rats at high doses (ca. 

475 mg/kg bw-day). 

And that rodent studies suggest that 

BPA: 

*causes neural and behavioral alterations 

related to disruptions in normal sex 

differences in rats and mice 

(0.01-0.2 mg/kg bw-day). 

(Estimated by analogy)

NTP–CERHR, 2008; Professional 

judgment 

Based on the analog BPA.

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The joint FAO/WHO (2011) Expert 

Panel reviewed reproductive and 

developmental toxicity data for BPA 

located as of November 2010 and noted 

that most regulatory bodies reviewing 

the numerous studies on BPA have 

indicated an oral reproductive and 

developmental NOAEL of 50 mg/kg bwday. 

(Estimated by analogy)

FAO/WHO, 2011; Professional 

judgment 

Based on the analog BPA.

Neurotoxicity MODERATE: Estimated to have potential for neurotoxicity based on the presence of the phenol structural 

alert.

Neurotoxicity Screening

Battery (Adult)

There is potential for neurotoxicity 

effects based on the presence of the 

phenol structural alert. 

(Estimated)

U.S. EPA, 2010; Professional 

judgment 

Estimated based on structural alert.

Repeated Dose Effects MODERATE: Estimated based on analogy to BPA, which produced histopathologic changes in the liver 

(centrilobular hepatocyte hypertrophy) from oral dosing at 50 mg/kg bw-day (NOAEL = 5 mg/kg bw-day) 

and there is uncertainty regarding the potential for BPA doses between the NOAEL of 5 mg/kg bw-day and 

the LOAEL of 50 mg/kg bw-day to cause adverse systemic effects. Furthermore, lesions in the nasal cavity of 

rats were reported following repeated inhalation exposure to BPA dust at 0.05 mg/L. These findings indicate 

a Moderate hazard concern for the oral and inhalation exposure routes.

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The FAO/WHO (2011) Expert Panel 

reviewed the available information 

regarding repeated-dose oral toxicity of 

BPA and concluded that results 

demonstrated effects on the liver, 

kidney, and body weight at doses of 

50 mg/kg bw-day and higher and that the 

lowest NOAEL was 5 mg/kg bw-day, as 

identified in several studies. 

(Estimated by analogy)

FAO/WHO, 2011; Professional 

judgment 

Based on the analog BPA.

Parental systemic toxicity:

NOAEL = 4.75 mg/kg bw-day 

LOAEL = 47.5 mg/kg bw-day for 12% 

decreased terminal body weight in F1

parental males

(Estimated by analogy)

NTP-CERHR, 2008; Professional 

judgment 

Based on the analog BPA; guideline 

study as reported in the secondary 

source. 

Classified by NTP-CERHR as having 

High Utility.

Parental systemic toxicity:

NOAEL = 5 mg/kg bw-day 

LOAEL = 50 mg/kg bw-day for 

increased incidences of centrilobular 

hepatocellular hypertrophy in males and 

females

(Estimated by analogy)

NTP-CERHR, 2008; Professional 

judgment 

Based on the analog BPA; guideline 

study as reported in the secondary 

source. 

Classified by NTP-CERHR as having 

High Utility.

NOAEL = 0.01 mg/L

LOAEL = 0.05 mg/L based on 

microscopic changes in the anterior 

portion of the nasal cavity 

(Estimated by analogy)

EINECS, 2010; European 

Commission, 2000; Professional 

judgment 

Based on the analog BPA.

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NOAEL = None established

LOAEL = 0.047 mg/L for decreased 

body weight gain, increased liver and 

kidney weight, unspecified 

“morphological changes” in liver, 

kidney, and lungs 

(Estimated by analogy)

EINECS, 2010; European 

Commission, 2000; Professional 

judgment 

Based on the analog BPA; single 

exposure level, insufficient study 

details in secondary sources. 

Skin Sensitization MODERATE: Based on analogy to BPA, substituted phenolic compound #2 is estimated to be a skin 

sensitizer. Recent data from three BPA manufacturing facilities indicate that it does not elicit skin 

sensitization. However, results of some human studies suggest the possibility of a dermal sensitization 

response, although cross-sensitization was not ruled out. Most animal studies conducted on the analog were 

negative for dermal sensitization, although assays may not have been maximized. There is evidence of ear 

swelling in a photoallergy test in mice and moderate redness and swelling following repeated dermal 

exposure in rabbits. Based on suggestive evidence of skin sensitization in humans and mice for the analog, a 

Moderate hazard designation is warranted.

Skin Sensitization Negative in a modified local lymph node 

assay of mice administered BPA

epicutaneously on the ears at 

concentrations up to 30% on 

3 consecutive days. 

(Estimated by analogy)

EINECS, 2010; Professional 

judgment

Based on the analog BPA; adequate, 

although the assay did not include 

concentrations >30%.

Negative in a local lymph node assay 

modified to test for photoreactivity in 

mice administered BPA epicutaneously 

on the ears at concentrations up to 30% 

on 3 consecutive days and irradiated 

with UV light immediately following 

application. 

(Estimated by analogy)

EINECS, 2010; Professional 

judgment

Based on the analog BPA; adequate, 

although the assay did not include 

concentrations >30%. 

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Negative in comprehensive medical 

surveillance data obtained from three 

BPA manufacturing plants for 875 

employees examined for several years 

where workers were potentially exposed 

to other chemicals (phenol, acetone) that 

are not considered to be skin sensitizers. 

(Estimated by analogy)

EINECS, 2010; Professional 

judgment

Based on the analog BPA; adequate.

Positive, rabbits; repeated dermal 

application (30 times over 37 days) of 

BPA (pure powder) produced moderate 

swelling and redness. Skin turned yellow 

followed by dark pigmentation after day 

15. 

(Estimated by analogy) 

NIOSH, 2010; Professional 

judgment

Based on the analog BPA; adequate.

The Joint FAO/WHO Expert Meeting 

review of the toxicological aspects of 

BPA concludes that BPA is capable of 

producing a skin sensitization response 

in humans. 

(Estimated by analogy)

FAO/WHO, 2011; Professional 

judgment

Based on the analog BPA.

Respiratory Sensitization No data located.

Respiratory Sensitization No data located.

Eye Irritation MODERATE: Based on analogy to BPA. Substituted phenolic compound #2 is estimated to be slightly to 

highly irritating to rabbit eyes based on test data for the analog BPA.

Eye Irritation Rabbit, slightly to highly irritating European Commission, 2000; 

EINECS, 2010; Professional 

judgment 

Based on the analog BPA. Adequate;

multiple studies, weight of evidence 

indicates potential for BPA to cause 

eye irritation.

Dermal Irritation MODERATE: Substituted phenolic compound #2 is estimated to be slightly irritating to moderately 

irritating to rabbit skin based on test data for the analog BPA. NIOSH has assigned the analog BPA as a 

skin irritant.

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Dermal Irritation Rabbit, nonirritating to slightly irritating 

when applied as undiluted or 10% 

aqueous suspension to intact or abraded 

skin. 

(Estimated by analogy)

European Commission, 2000; 

EINECS, 2010; NIOSH, 2010; 

Professional judgment

Based on the analog BPA. Adequate;

multiple studies, weight of evidence 

indicates potential for BPA to cause 

dermal irritation. 

Rabbit, moderately irritating when 

applied as 40% solution in dimethyl 

sulfoxide under non-occlusive 

conditions. 

(Estimated by analogy)

European Commission, 2000; 

Professional judgment

Based on the analog BPA; adequate.

Guinea pig, not irritating when applied 

as 5% solution in acetone for 24 hours 

under occlusive conditions. 

(Estimated by analogy)

European Commission, 2000; 

Professional judgment

Based on the analog BPA; adequate.

Endocrine Activity Substituted phenolic compound #2 is capable of eliciting an estrogenic response in rats injected with 

substituted phenolic compound #2 subcutaneously, as evidenced by increased uterine weight. Substituted 

phenolic compound #2 did not bind to estrogen receptors in one in vitro assay and did not elicit androgenic 

or anti-androgenic responses in another in vitro assay.

In a uterotrophic assay in which 

immature female rats were injected with 

bisphenol F, bisphenol S, or substituted 

phenolic compound #2 subcutaneously 

for 3 consecutive days, observed 

changes in uterine weight indicated that 

bisphenol F, bisphenol S, and substituted 

phenolic compound #2 exerted both 

estrogenic and anti-estrogenic responses.

Akahori et al., 2008 Adequate.

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In a uterotrophic assay of rats 

subcutaneously injected with bisphenol 

F once daily for 3 days, an apparent 

estrogenic effect was evidenced by 

increased absolute and relative uterine 

weight. Similar effects were elicited by 

bisphenol S and substituted phenolic 

compound #2.

Toxicol. Lett. 2004 (Sanitized) Adequate.

In a human ER binding assay, the 

relative binding affinity (RBA) of 

substituted phenolic compound #2 was 

0.175% relative to 17β-estradiol (set at 

100%). RBAs for other bisphenol 

compounds included 0.0719% for 

bisphenol F and 0.0055% for BPA.

Toxicol. Lett. 2004 (Sanitized) Adequate.

In an ERE-luciferase reporter assay 

using MCF-7 cells, substituted phenolic 

compound #2 did not appear to elicit an 

estrogenic response (EC50 >1,000 μM). 

EC50 values for other bisphenol 

compounds included 0.63% for BPA, 

0.42 μM for bisphenol C, 1.0 μM for 

bisphenol F, and 1.1 μM for bisphenol S.

Toxicol. Sci., 2005 (Sanitized) Adequate.

In an ERE-luciferase reporter assay 

using MCF-7 cells in the presence of 

17β-estradiol, neither substituted 

phenolic compound #2, BPA, bisphenol 

C, bisphenol F, nor bisphenol S, 

appeared to exert an anti-estrogenic 

effect.

Toxicol. Sci., 2005 (Sanitized) Adequate.

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In an ARE-luciferase reporter assay 

using NIH3T3 cells without expressing 

AR, substituted phenolic compound #2 

did not elicit an androgenic response or 

an anti-androgenic response in the 

presence of dihydrotestosterone.

Toxicol. Sci., 2005 (Sanitized) Adequate although actual data were 

not shown in study report. 

Immunotoxicity No data located.

Immune System Effects No data located.

ECOTOXICITY

ECOSAR Class Phenols, Poly

Acute Toxicity HIGH: Based on estimated 96-hour LC50 for fish, 48-hour LC50 for Daphnid, and 96-hour EC50 for green 

algae (neutral organics).

Fish LC50 Fish 96-hour LC50 = 0.067 mg/L 

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.00 Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided by 

ECOSAR classes that have a more 

specific mode of action relative to 

narcosis.

Fish 96-hour LC50 = 0.106 mg/L 

(Estimated) 

ECOSAR: phenols, poly 

ECOSAR version 1.00

Daphnid LC50 Daphnid 48-hour LC50 = 0.065 mg/L 

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.00 Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided by 

ECOSAR classes that have a more 

specific mode of action relative to 

narcosis.

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Daphnid 48-hour LC50 = 0.078 mg/L 

(Estimated) 

ECOSAR: phenols, poly

ECOSAR version 1.00

Green Algae EC50 Green algae 96-hour EC50 = 0.16 mg/L 

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.00 Chemical may not be sufficiently 

soluble to measure this predicted 

effect. Narcosis classes (neutral 

organics) are provided for 

comparative purposes; DfE 

assessment methodology will use the 

lowest estimated toxicity value 

provided by ECOSAR classes that 

have a more specific mode of action 

relative to narcosis.

Green algae 96-hour EC50 = 1.24 mg/L

(Estimated) 

ECOSAR: phenols, poly

ECOSAR version 1.00 Chemical may not be sufficiently 

soluble to measure this predicted 

effect.

Chronic Aquatic Toxicity HIGH: Based on estimated ChVs for fish, Daphnid, and green algae.

Fish ChV Fish ChV = 0.006 mg/L

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.00 Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided by 

ECOSAR classes that have a more 

specific mode of action relative to 

narcosis.

Fish 30-day ChV = 0.016 mg/L

(Estimated) 

ECOSAR: phenols, poly

ECOSAR version 1.00

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Daphnid ChV Daphnid ChV = 0.013 mg/L (Estimated)

ECOSAR: neutral organics 

ECOSAR version 1.00 Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided by 

ECOSAR classes that have a more 

specific mode of action relative to 

narcosis.

Daphnid ChV = 0.023 mg/L

(Estimated) 

ECOSAR: phenols, poly

ECOSAR version 1.00

Green Algae ChV Green algae ChV = 0.066 mg/L 

(Estimated) 

ECOSAR: phenols, poly

ECOSAR version 1.00

Green algae ChV = 0.126 mg/L 

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.00 Chemical may not be sufficiently 

soluble to measure this predicted 

effect. Narcosis classes (neutral 

organics) are provided for 

comparative purposes; DfE 

assessment methodology will use the 

lowest estimated toxicity value 

provided by ECOSAR classes that 

have a more specific mode of action 

relative to narcosis.

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ENVIRONMENTAL FATE

Transport The transport evaluation for substituted phenolic compound #2 is based on available experimental and 

estimated physical and chemical properties. Based on the Level III fugacity models incorporating the 

available experimental property data, substituted phenolic compound #2 is expected to partition to sediment 

and soil. Additionally, substituted phenolic compound #2 is expected to have low mobility in soil based on its 

estimated Koc therefore, leaching of substituted phenolic compound #2 through soil to groundwater is not 

expected to be an important transport mechanism. Estimated volatilization half-lives indicate that it will be 

nonvolatile from surface water. In the atmosphere, substituted phenolic compound #2 is expected to exist in 

the particulate phase, based on its estimated vapor pressure. Particulates will be removed from air by wet or 

dry deposition.

Henry’s Law Constant 

(atm-m3/mole)

<1x10-8 (Estimated) EPI Cutoff value for nonvolatile 

compounds based on professional 

judgment. 

Sediment/Soil 

Adsorption/Desorption

Coefficient – Koc

>30,000 (Estimated) EPI; U.S. EPA, 2004 Cutoff value for nonmobile 

compounds. 

Level III Fugacity 

Model

Air = <1% (Estimated)

Water = 1%

Soil = 42%

Sediment = 57%

EPI

Persistence HIGH: Evaluation of the persistence of substituted phenolic compound #2 is based entirely on QSARs of 

aerobic and anaerobic biodegradation. Results from these models estimate ultimate biodegradation in 

months and primary degradation in weeks. Biodegradation under anaerobic methanogenic conditions is not 

probable based on results from estimation models. Substituted phenolic compound #2 does not contain 

chromophores that absorb light at wavelengths >290 nm. Therefore, it is not expected to be susceptible to 

direct photolysis. It is not expected to undergo hydrolysis as it does not contain hydrolyzable functional 

groups. The atmospheric half-life of substituted phenolic compound #2 is estimated at 1.4 hours, although it 

is expected to exist primarily as a particulate in air. Therefore, biodegradation is expected to be the main 

degradation pathway for substituted phenolic compound #2.

Water Aerobic Biodegradation Weeks (primary survey model)

Months (ultimate survey model)

EPI

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Volatilization Half-life 

for Model River

>1 year (Estimated) EPI

Volatilization Half-life 

for Model Lake

>1 year (Estimated) EPI

Soil Aerobic Biodegradation No data located.

Anaerobic 

Biodegradation

Not probable (Anaerobic-methanogenic 

biodegradation probability model)

EPI

Soil Biodegradation w/ 

Product Identification

No data located.

Sediment/Water 

Biodegradation

No data located.

Air Atmospheric Half-life 1.4 hours (Estimated) EPI

Reactivity Photolysis Not a significant fate process 

(Estimated)

Mill, 2000; Professional judgment Substance does not contain functional 

groups that would be expected to 

absorb light at environmentally 

significant wavelengths.

Hydrolysis Not a significant fate process 

(Estimated)

Wolfe and Jeffers, 2000; 

Professional judgment 

Substance does not contain functional 

groups that would be expected to 

hydrolyze readily under 

environmental conditions.

Pyrolysis No data located.

Environmental Half-life >180 days (Estimated) EPI; PBT Profiler Half-life estimated for the 

predominant compartment, as 

determined by EPI and the PBT 

Profiler methodology.

Bioaccumulation HIGH: The estimated BAF and fish BCF values are >5,000.

Fish BCF 6,200 (Estimated) EPI

BAF 9,100 (Estimated) EPI

Metabolism in fish No data located.

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ENVIRONMENTAL MONITORING AND BIOMONITORING

Environmental Monitoring No data located.

Ecological Biomonitoring No data located.

Human Biomonitoring This chemical was not included in the NHANES biomonitoring report (CDC, 2011).

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Aldrich. Material Safety Data Sheet (MSDS). Available at: http://www.sigmaaldrich.com/ Accessed on December 21, 2010.

Akahori, Y., Makai, M., Yamasaki, K., et al. Relationship between the results of in vitro receptor binding assay to human estrogen 

receptor α and in vivo uterotrophic assay: Comparative study with 65 selected chemicals. Toxicology In Vitro 2008, 22:225-

231. 

CDC (Centers for Disease Control and Prevention). Fourth national report on human exposure to environmental chemicals, updated 

tables. Department of Health and Human Services. 2011. http://www.cdc.gov/exposurereport/ (accessed on May 10, 2011). 

ChemSpider. ChemSpider; Structure-based Chemistry Information. Royal Society of Chemistry:London. 2010. 

http://www.chemspider.com (accessed on December 11, 2010). 

ECOSAR (2010) Ecological Structure Activity Relationship (ECOSAR) Version 1.00. Washington, DC: U.S. Environmental 

Protection Agency. http://www.epa.gov/oppt/newchems/tools/21ecosar.htm. 

ECOSAR/EPI (EPIWIN/EPISUITE) Estimations Programs Interface for Windows, Version 3.20. U.S. Environmental Protection 

Agency: Washington D.C. http://www.epa.gov/opptintr/exposure/. 

EINECS (European Inventory of Existing Commercial chemical Substances). 4,4’-Isopropylidenediphenol (bisphenol A). European 

Union Risk Assessment Report. 2010.

EPI (EPIWIN/EPISUITE) Estimations Programs Interface for Windows, Version 4.00. U.S. Environmental Protection Agency: 

Washington D.C. http://www.epa.gov/opptintr/exposure/. 

ESIS (European chemical Substances Information System) Classification, labeling and Packaging of dangerous substances annex VI 

to regulation (EC) No 1272/2008 [Online] http://esis.jrc.ec.europa.eu/ (accessed on June 10, 2011). 

European Commission. IUCLID Dataset for 4,4-isopropylidenediphenol (CAS No. 80-05-7). European Chemicals Bureau, February 

19, 2000. 2000. 

FAO/WHO (Food and Agriculture Organization/World Health Organization). Joint FAO/WHO expert meeting to review toxicological 

and health aspects of bisphenol A. Summary report including report of stakeholder meeting on bisphenol A. Food and 

Agriculture Organization of the United Nations; World Health Organization. Ottawa, Canada. November 1-5, 2010. 

Mill, T. 2000. Photoreactions in Surface Waters. In Boethling, R.; Mackay, D., Handbook of Property Estimation Methods for 

Chemicals, Environmental Health Sciences (355-382). Boca Raton: Lewis Publishers. 

4-251 
FINAL REPORT – January 2014 

NIOSH (National Institute for Occupational Safety and Health). Skin Notation (SK) Profile, Bisphenol A (BPA) [CAS No. 80-05-7]. 

Department of Health and Human Services; Centers for Disease Control and Prevention. 2010.

NTP (National Toxicology Program). Carcinogenesis bioassay of bisphenol-A (CAS No. 80-05-7) in F344 rats and B6C3F1 mice 

(feed study). Technical Report No. 215, PB82-184060. 1982. 

NTP-CERHR. Monograph on the potential human reproductive and developmental effects of biphenol A. National Toxicology 

Program; U.S. Department of Health and Human Service. Center for the Evaluation of Risks to Human Reproduction. NIH 

Publication No. 08-5994. September 2008. 

Oncologic. U.S. EPA and LogiChem, Inc. 2005, Version 7.0. 2008. 

PBT Profiler Persistent (P),Bioaccumulative (B), and Toxic (T) Chemical (PBT)Profiler, U.S. Environmental Protection Agency: 

Washington D.C. www.pbtprofiler.net. 

SPARC On Line Calculator pKa/property server. Ver 4.5 September, 2009. Available from, http://ibmlc2.chem.uga.edu/sparc/

(accessed on August 12, 2010). 

Toxicol. Lett. 2004 (Sanitized - article title and author). 

Toxicol. Sci., 2005 (Sanitized - article title and author). 

U.S. EPA (Environmental Protection Agency). High Production Volume (HPV) Challenge. Determining the Adequacy of 

Existing Data. U.S. Environmental Protection Agency: Washington D.C. 1999. 

http://www.epa.gov/hpv/pubs/general/datadfin.htm

U.S. EPA (Environmental Protection Agency). 2004. The Pollution Prevention (P2) Framework, EPA-748-B-03-001. Office of 

Pollution Prevention and Toxics 7403M, U.S. Environmental Protection Agency, Washington, DC. 20460. October 2003 

version updated in January 2004. Latest version available at http://www.epa.gov/opptintr/newchems/pubs/sustainable/p2framejune05a2.pdf

U.S. EPA Sustainable Futures. Using Non Cancer Screening within the SF Initiative. Environmental Protection Agency: Washington 

D.C. 2010. http://www.epa.gov/opptintr/sf/pubs/noncan-screen.htm#systemic as of February 09, 2011. 

Wolfe, N.; Jeffers, P. (2000) Hydrolysis. In Boethling, R.; Mackay, D., Handbook of Property Estimation Methods for Chemicals, 

Environmental Health Sciences (311-334). Boca Raton: Lewis Publishers. 

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FINAL REPORT – January 2014 

PHBB

 

OH

O

O CASRN: 94-18-8

MW: 228.25

MF: C14H12O3

Physical Forms: 

Neat: Solid

Use: Developer for thermal paper

SMILES: c1(C(OCc2ccccc2)=O)ccc(O)cc1

Synonyms: Benzoic acid, 4-hydroxy-, phenylmethyl ester; Benzyl 4-hydroxybenzoate; Benzyl p-hydroxybenzoate; Benzyl parahydroxybenzoate; Benzylparaben; 

Phenylmethyl 4-hydroxybenzoate; AI3-02955; Benzyl Parasept; Benzyl Tegosept; Nipabenzyl; Parosept; Solbrol Z; p-Hydroxybenzoic acid benzyl ester

Polymeric: No 

 Oligomers: Not applicable

Metabolites, Degradates and Transformation Products: Hydrolysis products - 4-hydroxybenzoic acid (99-96-7) and benzyl alcohol (100-51-6)

Analog: Benzyl-2-hydroxybenzoate (118-58-1) 

Endpoint(s) using analog values: Aerobic biodegradation, persistence, 

and genotoxicity

Analog Structure:

O

O

OH

4-253 

Structural Alerts: Phenols, neurotoxicity (U.S. EPA, 2010)

Risk Phrases: Not classified by Annex VI Regulation (EC) No 1272/2008 (ESIS, 2011).

Risk Assessments: None identified
FINAL REPORT – January 2014 

PHBB CASRN 94-18-8

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

PHYSICAL/CHEMICAL PROPERTIES

Melting Point (°C) 111 (Measured) PhysProp Adequate; consistent values 

reported in secondary source.

110–112 (Measured) CIR, 1986 Adequate; valid, nonguideline 

study.

Boiling Point (°C) >300 (Estimated) EPI; U.S. EPA, 1999 Cutoff value for high boiling point 

compounds according to HPV 

assessment guidance.

Vapor Pressure (mm Hg) 3.8x10-6 (Estimated) EPI

Water Solubility (mg/L) 60 at 25 oC (Measured) Thomas, 2006 Nonguideline study reported in 

secondary source. Although the 

value is consistent with other 

reported properties, the pH of the 

measurement was not reported, and 

was interpreted as pH 7.

Log Kow 3.56 (Measured) PhysProp Adequate; nonguideline study 

reported in secondary source. 

Value is consistent with other 

reported properties.

Flammability (Flash Point) No data located.

Explosivity No data located.

pH No data located.

pKa 7.8 (Estimated) SPARC

4-254 
FINAL REPORT – January 2014 

PHBB CASRN 94-18-8

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

HUMAN HEALTH EFFECTS

Toxicokinetics PHBB is estimated to not be absorbed through the skin as neat material and has moderate absorption 

through skin when in solution. PHBB can be absorbed through the lung and gastrointestinal tract. 

Although not readily hydrolyzed, PHBB is expected to undergo ester hydrolysis by esterases in the body 

and produce the metabolites benzyl alcohol and p-hydroxybenzoic acid.

Dermal Absorption in vitro At 24 hours following application of 

PHBB to human skin (in vitro), recoveries 

in the receptor medium as parent 

compound and its hydrolysis product 

(4-hydroxybenzoic acid) were 17 and 

2.4%, respectively. Hydrolysis of PHBB to 

4-hydroxybenzoic acid in the human skin 

was catalyzed by carboxylesterases, 

particularly human carboxylesterase 2.

Jewell, Prusakiewicz et al., 2007 Adequate.

20% dermal absorption in vitro (Estimated 

by analogy)

Professional judgment Based on a confidential study on a 

closely related analog.

Absorption, 

Distribution, 

Metabolism & 

Excretion

Oral, Dermal, Inhaled Trace amounts of PHBB (in conjugated 

form) were detected in the urine of 

39/100 demographically-diverse adult 

volunteers with no known occupational 

exposure to PHBB.

Ye, Bishop et al., 2006 Adequate.

Following ingestion of PHBB (2 g/day for 

5 days) by two volunteers, analysis of the 

urine revealed that 6% of the administered 

dose was eliminated unchanged; 87% was 

eliminated as the sulfate conjugate of the 

ester. Only small quantities of PHBB 

metabolites (4-hydroxybenzoic acid, 

benzyl alcohol, benzoic acid, 

4-hydroxyhippuric acid, and hippuric acid) 

were detected.

Sabalitschka and NeufeldCrzellitzer, 1954 (as cited in 

CIR 1986, 2008)

Adequate.

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FINAL REPORT – January 2014 

PHBB CASRN 94-18-8

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Not absorbed through the skin as neat 

material and has moderate absorption 

through skin when in solution. Can be 

absorbed through the lung and 

gastrointestinal tract. PHBB is expected to 

undergo ester hydrolysis by esterases in 

the body and produce benzyl alcohol and 

p-hydroxybenzoic acid. 

(Estimated by analogy)

Professional judgment Based on closely related 

confidential analog with similar 

structure, functional groups, and 

physical/chemical properties. 

93% absorbed in gastrointestinal tract 

(Estimated by analogy)

Professional judgment Based on a confidential study on a 

closely related analog.

Acute Mammalian Toxicity LOW: Based on experimental data in which no overt clinical signs of toxicity or death occurred as result 

of acute oral exposure of laboratory animals to doses 2,000-10,000 mg/kg, although the information located 

was limited to summary statements in secondary sources that did not include important study details. No 

data were located regarding the hazard of acute inhalation or dermal exposure. 

Acute Lethality Oral No deaths or clinical signs of toxicity were 

observed in slc-ddy mice administered 

10,000 mg/kg PHBB via gavage.

Sabalitschka, 1933 (as cited in 

CIR, 1986)

Inadequate; details are missing as 

this is a review on various animal 

toxicity studies.

No deaths occurred when Charles River 

CD rats were given 5,000 mg/kg PHBB.

CTFA, 1985 (as cited in CIR, 

1986, 2008)

Adequate.

No signs of toxicity were evident in guinea 

pigs fed 2,000 mg PHBB/day for an 

unspecified period.

Sabalitschka and NeufeldCrzellitzer, 1954 (as cited in CIR, 

1986, 2008)

Adequate.

Dermal No data located.

Inhalation No data located.

Carcinogenicity MODERATE: Estimated to have potential for carcinogenicity based on the benzyl alcohol hydrolysis 

product. Potential for carcinogenicity is dependent on the rate of hydrolysis and oxidation of the alcohol to 

an aldehyde. Also, there is uncertainty due to the lack of data located for this substance. Carcinogenic 

effects cannot be ruled out.

OncoLogic Results No data located.

4-256 
FINAL REPORT – January 2014 

PHBB CASRN 94-18-8

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Carcinogenicity (Rat and 

Mouse)

Potential for carcinogenicity

(Estimated)

Professional judgment Estimated based on professional 

judgment and concern for the 

benzyl alcohol hydrolysis product; 

concern is dependent on the rate of 

hydrolysis and oxidation of the 

alcohol to an aldehyde. 

Combined Chronic 

Toxicity/Carcinogenicity

No data located.

Genotoxicity MODERATE: Estimated to have potential for genotoxicity based on the benzyl alcohol hydrolysis 

product; potential is dependent on the rate of hydrolysis and oxidation of the alcohol to an aldehyde. This 

endpoint was also evaluated by analogy to measured data for the closely related compound benzyl2 hydroxybenzoate. These chemicals differ only by the position of the hydroxyl grouped (ortho vs. para), 

which is not anticipated to result in significant differences in the mechanistic interpretation of this end 

point. In addition, there is uncertainty due to the lack of data for this substance. Carcinogenic effects 

cannot be ruled out.

Gene Mutation in vitro No data for PHBB. An analog (benzyl 

2-hydroxybenzoate) did not induce 

mutations in Salmonella typhimurium

strains TA 98, TA100, TA1535, or 

TA1537 with and without metabolic 

activation.

Zeiger, Anderson et al., 1987 Adequate.

Uncertain concern for mutagenicity based 

on the benzyl alcohol hydrolysis product

(Estimated by analogy)

Professional judgment Estimated based on test data 

located for a hydrolysis product 

benzyl alcohol and is dependent on 

the rate of hydrolysis and oxidation 

of the alcohol to an aldehyde.

Gene Mutation in vivo No data located.

Chromosomal Aberrations 

in vitro

No data located.

Chromosomal Aberrations 

in vivo

No data located.

DNA Damage and Repair No data located.

4-257 
FINAL REPORT – January 2014 

PHBB CASRN 94-18-8

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Other (Mitotic Gene 

Conversion)

No data located.

Reproductive Effects LOW: Estimated to have low potential for reproductive effects based on no identified structural alerts 

and expert judgment. 

Reproduction/ 

Developmental Toxicity 

Screen

No data located.

Combined Repeated Dose 

with Reproduction/ 

Developmental Toxicity 

Screen

No potential for reproductive effects

(Estimated)

Expert judgment Estimated based on expert 

judgment and because no structural 

alerts were identified.

Reproduction and Fertility 

Effects

No data located.

Developmental Effects MODERATE: Estimated to have potential for developmental effects based on the 4-hydroxybenzoic acid 

hydrolysis product and professional judgment.

Reproduction/ 

Developmental Toxicity 

Screen

Potential for developmental effects

(Estimated)

Professional judgment Estimated based on the 4-

hydroxybenzoic acid hydrolysis 

product.

Combined Repeated Dose 

with Reproduction/ 

Developmental Toxicity 

Screen

No data located.

Prenatal Development No data located.

Postnatal Development No data located.

Neurotoxicity MODERATE: Estimated to have potential for neurotoxicity based on the presence of the phenol 

structural alert.

Neurotoxicity Screening 

Battery (Adult)

There is potential for neurotoxicity effects 

based on the presence of the phenol 

structural alert. 

(Estimated)

U.S. EPA, 2010; Professional 

judgment

Estimated based on the phenol

structural alert.

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FINAL REPORT – January 2014 

PHBB CASRN 94-18-8

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Repeated Dose Effects LOW: Estimated to have low potential for repeated dose effects based on no identified structural alerts 

and expert judgment.

No signs of toxicity were evident in guinea 

pigs fed 1,000 mg PHBB/day for 19 days.

Ishizeki, Ayoama et al., 1955 (as 

cited in CIR, 1986)

Inadequate; details are missing as 

this is a review on various animal 

toxicity studies. Test methodology 

appears not to be standard with 

only a 19-day exposure duration 

period.

Low potential for repeated dose effects

(Estimated)

Expert judgment Estimated to have low potential for 

repeated dose effects based on 

expert judgment and because no 

structural alerts were identified.

Skin Sensitization MODERATE: Potential for skin sensitization based on close structural analog and based on concerns for 

the 4-hydroxybenzoic acid hydrolysis product.

Skin Sensitization Contact dermatitis has been observed in 

several studies of large numbers of 

eczematous patients or single case reports 

of patients with dermal disorders topically 

administered products containing mixed 

4-hydroxybenzoates that typically 

included PHBB. The overall rate of 

allergic reactions is in the range of 1%. 

Among patients sensitized to mixed 4-

hydroxybenzoate substances, patch testing 

for sensitivity to individual 4-hydroxy

benzoate substances reveal significant 

cross-sensitization potential and the lowest 

frequency of sensitization to PHBB 

compared to the other 

4-hydroxybenzoates.

Bandmann, Calnan et al., 1972

(as cited in CIR, 1986, 2008); 

Meynadier, Meynadier et al., 

1982 (as cited in CIR, 1986, 

2008); Romaguera and Grimalt, 

1980 (as cited in CIR, 1986, 

2008); Rudner, 1978 (as cited in 

CIR, 1986, 2008); 

Menné and Hjorth, 1988; 

Würbach, Schubert et al., 1993; 

Tosi, Fanti et al., 1989 

Inadequate; patients were 

sensitized to mixed 

4-hydroxybenzoates prior to patch 

testing of individual 

4-hydroxybenzoates and crosssensitization was apparent. 

4-259 
FINAL REPORT – January 2014 

PHBB CASRN 94-18-8

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Potential for dermal sensitization

(Estimated by analogy)

Professional judgment Estimated based on reported 

experimental data for a confidential 

analog and for the 4-

hydroxybenzoic acid hydrolysis 

product.

Respiratory Sensitization No data located.

Respiratory Sensitization No data located.

Eye Irritation VERY LOW: PHBB is not an eye irritant.

Eye Irritation Negative for ocular irritation in New 

Zealand rabbits (n = 3) 1, 24, 48 and 

72 hours after instillation of 100 mg into 

the conjunctival sac.

CTFA, 1985 (as cited in CIR, 

1986)

Adequate.

Dermal Irritation VERY LOW: PHBB is not a skin irritant.

Dermal Irritation Negative for skin irritation in New 

Zealand rabbits when applied under 

occlusive conditions to intact and abraded 

skin at 500 mg.

European Economic 

Commission, 1984 (as cited in 

CIR, 1986)

Inadequate; details are missing as 

this is a review on various animal 

toxicity studies. 

Negative for skin irritation/corrosion in 

rabbits when 500 mg PHBB was applied 

under semi-occlusive conditions.

CTFA, 1985 (as cited in CIR 

1986, 2008)

Adequate.

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PHBB CASRN 94-18-8

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Endocrine Activity Based on primarily in vitro test data, PHBB exhibits endocrine activity. PHBB exhibited estrogenic and 

anti-estrogenic activity in various test systems.

PHBB demonstrated estrogen agonistic 

properties both in vitro and in vivo by 

displacing 17β-estradiol from cytosolic ER 

of MCF-7 human breast cancer cells, 

increasing expression of a stably 

transfected estrogen-responsive reporter 

gene in MCF-7 cells, increasing the 

growth of estrogen-dependent MCF-7 cells 

(which could be inhibited by pure antiestrogen ICI182 780 indicating that the 

growth effects were ER mediated), 

increasing the growth of a second 

estrogen-dependent human breast cancer 

cell line ZR-75-1 but not the estrogen 

insensitive MDA-MB-231 line, and by 

inducing increased uterine weight in 

immature mice receiving three daily 

dermal applications of PHBB to unshaven 

dorsal skin (NOAEL = 10mg, LOAEL = 

33 mg).

Darbre, Byford et al., 2003 Adequate.

Receptor Binding Assays

PHBB exhibited weak ER binding activity 

in preparations from uteri of 

ovariectomized Sprague-Dawley rats. 

Relative binding affinity (RBA) = 0.003% 

of the binding affinity of 17β-estradiol. An 

RBA of 0.008% was observed for BPA.

Blair, Fang et al., 2000 Adequate.

In a rat uterine cytosolic ER-competitive 

binding assay, results for PHBB, bisphenol 

S, and BPA indicated a weak affinity for 

ER.

Laws, Yavanhxay et al., 2006 Adequate.

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FINAL REPORT – January 2014 

PHBB CASRN 94-18-8

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

In a human ER binding assay, the relative 

binding affinity (RBA) of PHBB was 

0.00473% compared to 126% for 17βestradiol. RBAs for bisphenol compounds 

included 0.195% for BPA, 0.129% for 

bisphenol C, 0.0803% for bisphenol AP, 

0.0719% for bisphenol F, and 0.0055% for 

bisphenol S.

METI, 2002 Adequate.

PHBB did not elicit an estrogenic response 

in a receptor binding assay with human 

ERα or ERβ.

Schultis and Metzger, 2004 Adequate.

Gene Transcription and Reporter Gene 

Assays

PHBB exhibited estrogenic activity 

approximately 4,000-fold less than that of 

17β-estradiol in an in vitro recombinant 

yeast estrogen assay. The estrogenic 

activities of BPA and bisphenol F were 

10,000-fold and 9,000-fold less than that 

of 17β-estradiol.

Miller, Wheals et al., 2001 Adequate.

PHBB exhibited estrogenic activity in 

multiple in vitro assays. Compared to the 

activity of 17β-estradiol, the relative 

activity (RA) values were E-Screen RA 

(relative to = 1.0x10-4 for the E-screen 

assay, 6.0x10-5 for the LYES-assay, and 

3.7x10-4 for the YES-assay.

Schultis and Metzger, 2004 Adequate.

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FINAL REPORT – January 2014 

PHBB CASRN 94-18-8

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

In a reporter gene assay of estrogeninduced transcriptional activity, relative 

activity (RA) for PHBB was 0.000592% 

compared to 81.7% for 17β-estradiol. RAs 

for bisphenol compounds included 

0.00278% for BPA, 0.00189% for 

bisphenol C, 0.000639% for bisphenol F, 

0.000254% for bisphenol S, and 

0.000184% for bisphenol AP.

METI, 2002 Adequate.

PHBB exhibited estrogenic activity in in 

vitro yeast two-hybrid assays 

incorporating human or medaka ERα. 

hER α assay: RA (relative to 17βestradiol)= 1.1x10-4

MedER α assay: RA = 3.3x10-3

Terasaki, Kamata et al., 2009b Adequate.

PHBB exhibited estrogenic activity in a 

hERα competitive enzyme-linked 

immunosorbent assay (ER-ELISA). 

RBA (relative to DES) = 8.1x10-4

Terasaki, Kamata et al., 2009b Adequate.

PHBB showed relatively high estrogenic 

activity in an ER yeast reporter assay.

Ozaki, Shinohara et al., 2007 Adequate.

Cell Proliferation Assays

PHBB was estrogenic in an E-screen 

(MCF-7 proliferation assay) and inhibited 

aromatase activity in microsomes derived 

from a human placenta. Inhibition of 

aromatase activity results in decreased 

conversion of testosterone into estrogens 

suggestive of an anti-estrogenic effect.

van Meeuwen, van Son et al., 

2008

Adequate.

Thyroid Assays

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FINAL REPORT – January 2014 

PHBB CASRN 94-18-8

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

PHBB did not exhibit thyroid hormone 

receptor binding in a yeast two-hybrid 

assay system with TRα and coactivator 

TIF-2.

Kitagawa, Takatori et al., 2003 Adequate.

Immunotoxicity No data located.

Immune System Effects No data located.

ECOTOXICITY

ECOSAR Class Phenols, esters

Acute Toxicity HIGH: Based on experimental data for fish and Daphnid with LC50 values between 1.0 and 10 mg/L. 

Fish LC50 Fathead minnow, static conditions

48-hour LC50 = 3.3 mg/L (Experimental) 

Dobbins, Usenko et al., 2009 Adequate; follows standardized 

acute and subchronic tests for 

freshwater fish.

Fish 96-hour LC50 = 2.452 mg/L

(Estimated) 

ECOSAR: phenols

ECOSAR version 1.00

Fish 96-hour LC50 = 3.98 mg/L

(Estimated) 

ECOSAR: esters

ECOSAR version 1.00

Fish 96-hour LC50 = 8.42 mg/L

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.00 Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided 

by ECOSAR classes that have a 

more specific mode of action 

relative to narcosis.

Daphnid LC50 Daphnia magna, static conditions

48-hour LC50 = 4.0 mg/L (Experimental) 

Dobbins, Usenko et al., 2009 Adequate; follows standardized 

acute and subchronic tests for 

daphnia.

Daphnia magna, acute immobilization 

test. 

48-hour EC50 = 6.6 mg/L (Experimental)

Terasaki, Makino et al., 2009a Adequate.

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FINAL REPORT – January 2014 

PHBB CASRN 94-18-8

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Daphnid 48-hour LC50 = 1.559 mg/L

(Estimated) 

ECOSAR: phenols

ECOSAR version 1.00

Daphnid 48-hour LC50 = 6.69 mg/L

(Estimated) 

ECOSAR: esters

ECOSAR version 1.00

Daphnid 48-hour LC50 = 5.86 mg/L

(Estimated) 

ECOSAR: neutral organics

ECOSAR version 1.00 Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided 

by ECOSAR classes that have a 

more specific mode of action 

relative to narcosis.

Saltwater Invertebrate LC50 Mysid shrimp 96-hour LC50 = 2.526 mg/L

(Estimated) 

ECOSAR: esters

ECOSAR version 1.00

Green Algae EC50 Green algae 96-hour EC50 = 2.411 mg/L

(Estimated) 

ECOSAR: esters

ECOSAR version 1.00

Green algae 96-hour EC50 = 6.16 mg/L

(Estimated) 

ECOSAR: phenols

ECOSAR version 1.00

Green algae 96-hour EC50 = 4.79 mg/L

(Estimated) 

ECOSAR: neutral organics

ECOSAR version 1.00 Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided 

by ECOSAR classes that have a 

more specific mode of action 

relative to narcosis.

4-265 
FINAL REPORT – January 2014 

PHBB CASRN 94-18-8

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Chronic Aquatic Toxicity HIGH: Based on an estimated fish 30-day ChV of 0.029 mg/L (ECOSAR class: phenol). The ECOSAR 

phenol class resulted in the lowest estimated chronic toxicity value. Experimental studies located for fish 

and Daphnid were of insufficient exposure duration to be utilized to assign the hazard concern.

Fish ChV Fathead minnow, static-renewal 

conditions, 7-day LOEC-growth = 

1.7 mg/L

(Experimental)

Dobbins, Usenko et al., 2009 Inadequate; exposure duration only 

7 days. 

Fish 30-day ChV = 0.293 mg/L

(Estimated) 

ECOSAR: phenol

ECOSAR version 1.00

Fish 60-day ChV = 0.007 mg/L

(Estimated) 

ECOSAR: phenol

ECOSAR version 1.00

Fish 32/33-d-day ChV = 0.246 mg/L

(Estimated) 

ECOSAR: esters

ECOSAR version 1.00

Fish ChV = 0.772 mg/L

(Estimated) 

ECOSAR: neutral organics

ECOSAR version 1.00 Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided 

by ECOSAR classes that have a 

more specific mode of action 

relative to narcosis.

Daphnid ChV Daphnia magna, static-renewal conditions, 

10-day LOEC (growth) = 0.1 mg/L 

10-day LOEC (reproduction) = 2.0 mg/L 

(Experimental)

Dobbins, Usenko et al., 2009 Inadequate; exposure duration only 

10 days. 

Daphnid 21-day ChV = 0.296 mg/L

(Estimated) 

ECOSAR: phenols

ECOSAR version 1.00

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FINAL REPORT – January 2014 

PHBB CASRN 94-18-8

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Daphnid 21-day ChV = 2.825 mg/L

(Estimated) 

ECOSAR: esters

ECOSAR version 1.00

Daphnid ChV = 0.714 mg/L

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.00 Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided 

by ECOSAR classes that have a 

more specific mode of action 

relative to narcosis.

Saltwater Invertebrate ChV Mysid shrimp ChV = 7.231 mg/L

(Estimated) 

ECOSAR: esters

ECOSAR version 1.00

Green Algae ChV Green algae ChV = 1.010 mg/L

(Estimated) 

ECOSAR: esters

ECOSAR version 1.00

Green algae ChV = 2.84 mg/L

(Estimated) 

ECOSAR: phenols

ECOSAR version 1.00

Green algae ChV = 2.31 mg/L

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.00 Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided 

by ECOSAR classes that have a 

more specific mode of action 

relative to narcosis.

Earthworm Subchronic Toxicity Earthworm 14-day LC50 = 48.812 mg/L

(Estimated) 

ECOSAR: phenols

ECOSAR version 1.00

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FINAL REPORT – January 2014 

PHBB CASRN 94-18-8

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Earthworm 14-day LC50 = 934.7 mg/L

(Estimated) 

ECOSAR: esters

ECOSAR version 1.00

ENVIRONMENTAL FATE

Transport The transport evaluation for PHBB is based on located experimental data and estimated physical/chemical 

properties. Based on the Level III fugacity models incorporating the located experimental property data, 

PHBB is expected to partition primarily to soil. It is expected to exist in both neutral and anionic forms at 

environmentally-relevant pH, based on its estimated pKa. The neutral form of PHBB is expected to have 

moderate mobility in soil based on its estimated Koc. The anionic form may have more mobility, as anions 

do not bind as strongly to organic carbon and clay due to their enhanced water solubility. However, 

leaching of PHBB through soil to groundwater is not expected to be an important transport mechanism. 

Estimated volatilization half-lives indicate that it will be nonvolatile from surface water. In the 

atmosphere, PHBB is expected to exist in both vapor and particulate phases, based on its estimated vapor 

pressure. Particulates will be removed from air by wet or dry deposition. Vapor-phase PHBB will be 

susceptible to atmospheric degradation processes. 

Henry’s Law Constant 

(atm-m3/mole)

2.9x10-10 (Estimated) EPI

Sediment/Soil 

Adsorption/Desorption

Coefficient – Koc

3,200 (Estimated) EPI

Level III Fugacity Model Air = <1%

Water = 16%

Soil = 83%

Sediment = 1.6% (Estimated)

EPI

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PHBB CASRN 94-18-8

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Persistence LOW: No experimental data were located regarding the persistence of PHBB and it was evaluated using 

measured biodegradation data for the analog benzyl-2-hydroxybenzoate. These chemicals differ only by 

the position of the hydroxyl group (ortho vs. para) and this is not anticipated to result in a different 

mechanistic interpretation of this endpoint. Estimates based on this analog are expected to be superior to 

those based solely on modeling. The analog benzyl-2-hydroxybenzoate passed two ready biodegradability 

tests, one that met the 10-day window in an activated sludge inoculum and one that did not meet the 10-

day window in a secondary effluent inoculum. Based on these data, the environmental persistence of 

PHBB is estimated to be Low. PHBB is not expected to undergo hydrolysis based on estimated half-lives of 

>1 year at pH 7 and 8. PHBB does not absorb light at environmentally significant wavelengths, and is not 

expected to be susceptible to direct photolysis. The atmospheric half-life for the vapor-phase hydroxyl 

radical reaction of PHBB is estimated at 7.5 hours. This is an important removal process for vapor-phase 

PHBB in the atmosphere. However, it is also expected to exist in the particulate form in the atmosphere. 

Biodegradation of PHBB is expected to be the primary removal process in aquatic and terrestrial 

environments. 

Water Aerobic Biodegradation Days (primary survey model); 

Weeks (ultimate survey model)

EPI

Volatilization Half-life for

Model River

>1 year (Estimated) EPI

Volatilization Half-life for 

Model Lake

>1 year (Estimated) EPI

Soil Aerobic Biodegradation 87% after 28 days; readily biodegradable, 

10-day window met (Estimated by analogy 

to benzyl-2-hydroxybenzoate in activated 

sludge inoculum)

HPV Robust Summary, 2003 Adequate; PHBB and benzyl2-hydroxybenzoate are closely 

related structures that differ only 

by position of the hydroxyl group. 

Benzyl-2-hydroxybenzoate data are 

for a guideline study.

62% after 28 days; 10-day window not 

met. (Estimated by analogy to benzyl-2-

hydroxybenzoate in secondary effluent 

inoculum during an ISO 14593 Carbon 

Dioxide Evolution Test)

HPV Robust Summary, 2003 Adequate; PHBB and benzyl2-hydroxybenzoate are closely 

related structures that differ only 

by position of the hydroxyl group. 

Benzyl-2-hydroxybenzoate data are 

for a guideline study.

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PHBB CASRN 94-18-8

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Anaerobic 

Biodegradation

No data located.

Soil Biodegradation w/ 

Product Identification

No data located.

Sediment/Water 

Biodegradation

No data located.

Air Atmospheric Half-life 7.5 hours (Estimated) EPI

Reactivity Photolysis Not a significant fate process (Estimated) Mill, 2000; Professional 

judgment

The substance does not contain 

functional groups that would be 

expected to absorb light at 

wavelengths >290 nm.

Hydrolysis Half-life >1 year (Estimated at pH = 8 and 

pH =7)

EPI Hydrolysis products expected: 

4-hydroxybenzoic acid (99-96-7) 

and benzyl alcohol (100-51-6).

Pyrolysis No data located.

Environmental Half-life 30 days EPI; PBT Profiler Half-life estimated for the 

predominant compartment, as 

determined by EPI and the PBT 

Profiler methodology.

Bioaccumulation LOW: The estimated fish BAF is <100. Although the BCF is estimated to be 100, the BAF model is 

anticipated to better account for metabolism for this substance. 

Fish BCF 100 (Estimated) EPI

BAF (upper trophic) 9.8 (Estimated) EPI

Metabolism in Fish No data located.

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FINAL REPORT – January 2014 

PHBB CASRN 94-18-8

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

ENVIRONMENTAL MONITORING AND BIOMONITORING 

Environmental Monitoring No data located.

Ecological Biomonitoring No data located.

Human Biomonitoring PHBB and its metabolites have been detected in human urine biological samples (CIR, 1986; Ye, 2006). This

chemical was not included in the NHANES biomonitoring report (CDC, 2011).

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FINAL REPORT – January 2014 

Bandmann, H.J., Calnan C.D., Cronin, E., et al. Dermatitis from applied medicaments. Arch. Dermatol. 1972, 106:335–337 (as cited 

in CIR 1986, 2008). 

Blair, R. M., Fang, H., Branham, W. S., et al. The estrogen receptor relative binding affinities of 188 natural and xenochemicals: 

structural diversity of ligands. Toxicol. Sci. 2000, 54:138-153. 

CDC (Centers for Disease Control and Prevention). Fourth national report on human exposure to environmental chemicals, updated 

tables. Department of Health and Human Services. 2011. http://www.cdc.gov/exposurereport/ (accessed on May 10, 

2011). 

CIR. Final report on the safety assessment of benzylparaben. J. Am. Coll. Toxicol. 1986, 5(5):301-307. 

CIR. Final amended report on the safety assessment of methylparaben, ethylparaben, propylparaben, isopropylparaben, butylparaben, 

isobutylparaben, and benzylparaben as used in cosmetics products. Int. J. Toxicol. 2008, 27(Suppl. 4):1-82. 

CTFA. Acute oral toxicity, acute dermal irritation/corrosion, acute eye irritation/corrosion, and COLIPA summary. Submission of 

unpublished data by CFTA.1985. (as cited in CIR 1986; Golden et al., 2005). 

Darbre, P.D., Byford, J.R., Shaw, L.E., et al. Oestrogenic activity of benzylparaben. J. Appl. Toxicol. 2003, 23:43-51. 

Dobbins, L., Usenko, S., Brain, R., et al. Probabilistic ecological hazard assessment of parabens using Daphnia magna and 

Pimephales promelas. Environ. Toxicol. Chem. 2009, 28(12):2744-2753. 

ECOSAR (2010) Ecological Structure Activity Relationship (ECOSAR) Version 1.00. Washington, DC: U.S. Environmental 

Protection Agency. http://www.epa.gov/oppt/newchems/tools/21ecosar.htm. 

ECOSAR/EPI (EPIWIN/EPISUITE) Estimations Programs Interface for Windows, Version 3.20. U.S. Environmental Protection 

Agency: Washington D.C. http://www.epa.gov/opptintr/exposure/. 

EPI (EPIWIN/EPISUITE) Estimations Programs Interface for Windows, Version 4.00. U.S. Environmental Protection Agency: 

Washington D.C. http://www.epa.gov/opptintr/exposure/. 

ESIS (European chemical Substances Information System) Classification, labeling and Packaging of dangerous substances annex VI 

to regulation (EC) No 1272/2008 [Online] http://esis.jrc.ec.europa.eu/ (accessed on June 10, 2011). 

European Economic Commission. Colipa number 7. 1984. (as cited in CIR, 1986). 

4-272 
FINAL REPORT – January 2014 

FAO/WHO. Toxicological and health aspects of bisphenol A. Report of Joint FAO/WHO expert meeting 2-5 November 2010 and 

report of stakeholder meeting on bisphenol A 1 November 2010. Food and Agriculture Organization of the United 

Nations; World Health Organization. Ottawa, Canada. 2011. 

HPV Robust Summary from The Flavor and Fragrance High Production Volume Consortia. HPV Robust Summary for Benzyl 

Derivatives. 2003. Available at: http://www.epa.gov/chemrtk/pubs/summaries/benzylde/c13450rs.pdf. 

Ishizeki, Ch., Aoyama, S., Hatta, Y., et al. 1955. Studies on food antiseptic. I. Bull. Natl. Hyg. Lab. Tokyo No. 73, 237-243 (as cited in 

CIR, 1986) 

Jewell, C., Prusakiewicz, J.J., Ackerman, C., et al. Hydrolysis of a series of parabens by skin microsomes and cytosol from human and 

minipigs and in whole skin short-term culture. Toxicol. Appl. Pharmacol. 2007, 225:221-228. 

Kitagawa, Y., Takatori, S., Oda, H., et al. Detection of thyroid hormone receptor-binding activities of chemicals using a yeast twohybrid assay. J. Health Sci. 2003, 49(2):99-104. 

Laws, S.C., Yavanhxay, S., Cooper, R.L., et al. Nature of the binding interaction from 50 structurally diverse chemicals with rat 

estrogen receptors. Toxicol. Sci. 2006, 94(1):45-56. 

Menné, T., Hjorth, N. Routine patch testing with paraben esters. Contact Derm. 1988, 19:189-191. 

METI. Current status of testing methods development for endocrine disruptors. Ministry of Economy, Trade and Industry, Japan. 6th

meeting of the task force on Endocrine Disruptors Testing and Assessments (EDTA). 24-25 June, 2002. Tokyo. 2002.

Meynadier, J. M., Meynadier, J., Colmas, A., et al. Allergie aux conservateurs (translated from the original French). Ann. Dermatol. 

Venereol. 1982, 109:1017–1023 (as cited in CIR, 1986). 

Mill, T. 2000. Photoreactions in Surface Waters. In Boethling, R.; Mackay, D., Handbook of Property Estimation Methods for 

Chemicals, Environmental Health Sciences (355-382). Boca Raton: Lewis Publishers. 

Miller, D., Wheals, B.B., Beresford, N. et al. Estrogenic activity of phenolic additives determined by an in vitro yeast bioassay. 

Environ. Health Perspect. 2001, 109(2):133-138. 

Ozaki, H., Shinohara, S., Tange, S., et al. Parabens and phthalates: Their metabolism, AHR ligand activity, estrogenic activity, and 

P450-inhibitory activity. Organohalogen Compounds 2007, 69: 2991-2994. 

PhysProp. Physical Properties Database SRC, Inc.

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FINAL REPORT – January 2014 

PBT Profiler Persistent (P),Bioaccumulative (B), and Toxic (T) Chemical (PBT)Profiler. U.S. Environmental Protection Agency: 

Washington D.C. www.pbtprofiler.net. 

Romaguera, C., Grimalt. F. Statistical and comparative study of 4,600 patients tested in Barcelona. Contact Derm. 1980, 6:309-315 

(as cited in CIR, 1986; Golden et al., 2005). 

Rudner, E. J. Patch test results of the North American Contact Dermatitis Group. Cosmet. Toilet. 1978, 93:53-54 (as cited in CIR, 

1986, 2008). 

Sabalitschka, T. Arztl. Apotheker. Krankenhaus. Nr. 10. 1933. (as cited in CIR, 1986). 

Sabalitschka, T., Neufeld-Crzellitzer, R. Zum Verhalten der poxybenzoesäureester im menschlichen Körper (translated from the 

original German). Arzneimittelforschung 1954, 4:575–579 (as cited in CIR, 1986, 2008). 

Schultis, T., Metzger, J.W. Determination of estrogenic activity by LYES-assay (yeast estrogen screen-assay assisted by enzymatic 

digestion with lyticase). Chemosphere 2004, 57:1649-1655. 

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(accessed on August 12, 2010). 

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fischeri bioassays. J. Appl. Toxicol. 2009, 29:242-247. 

Terasaki M., Kamata, R., Shiraishi, F., et al. Evaluation of estrogenic activity of parabens and their chlorinated derivatives by using 

the yeast two-hybrid assay and the enzyme-linked immunosorbent assay. Environ. Toxicol. Chem. 2009, 28(1):204-

208. 

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Posted online: January 27, 2006. 

Tosi A., Fanti, F.A., Pileri, S. Short communications. Dermal contact dermatitis from benzylparaben. Contact Derm. 1989, 21:49-63. 

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Data. U.S. Environmental Protection Agency: Washington D.C. 1999. 

http://www.epa.gov/hpv/pubs/general/datadfin.htm 

van Meeuwen, J.A., van Son, O., Piersma, A.H., et al. Aromatase inhibiting and combined estrogenic effects of parabens and 

estrogenic effects of other additives in cosmetics. Toxicol. Appl. Pharmacol. 2008, 230:372-382. 

4-274 
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Würbach, G., Schubert H., Phillipp, I. Contact allergy to benzyl alcohol and benzyl paraben. Contact Derm. 1993, 28:187-188. 

Ye, X., Bishop, A.M., Reidy, J.A., et al. Parabens as urinary biomarkers of exposure in humans. Environ. Health Perspect. 2006, 

114(12):1843-1846. 

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Mutagen. 1987, 9(Suppl. 9), 1-110. 

4-275 
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Bisphenol S

S

O

O

HO OH

4-276 

CASRN: 80-09-1

MW: 250.27

MF: C12H10O4S

Physical Forms:

Neat: Solid

Use: Developer for thermal paper

SMILES: O=S(=O)(c1ccc(O)cc1)c2ccc(O)cc2

Synonyms: Phenol, 4,4'-sulfonylbis-; bis(4-hydroxyphenyl)sulfone; 1,1'-Sulfonylbis(4-hydroxybenzene); 2,4'-Sulfonyldiphenol; 4,4'-Bisphenol S; 4,4'-

Dihydroxydiphenyl sulfone; 4,4'-Sulfonylbisphenol; 4,4'-Sulfonyldiphenol; 4-Hydroxyphenyl sulfone; Bis(4-hydroxyphenyl) sulfone; Bis(p-hydroxyphenyl) sulfone; 

Diphone C; p,p'-Dihydroxydiphenyl sulfone

Polymeric: No

 Oligomers: Not applicable

Metabolites, Degradates and Transformation Products: None

Analog: None

 Endpoint(s) using analog values: Not applicable 

Analog Structure: Not applicable

Structural Alerts: Phenols, neurotoxicity (U.S. EPA, 2010)

Risk Phrases: Not classified by Annex VI Regulation (EC) No 1272/2008 (ESIS, 2011).

Risk Assessments: None identified
FINAL REPORT – January 2014 

Bisphenol S CASRN 80-09-1

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

PHYSICAL/CHEMICAL PROPERTIES

Melting Point (°C) 240.5 (Measured) Lide, 2008 Adequate.

245-248 (Measured) ECHA, 2011 Adequate; reported values, which 

span a relatively narrow range, are 

consistent with other sources.

242-247 (Measured) ECHA, 2011 Adequate; reported values, which 

span a relatively narrow range, are 

consistent with other sources.

Boiling Point (°C) >300 (Estimated) EPI; U.S. EPA, 1999 Cutoff value for high boiling point 

compounds according to HPV 

assessment guidance; decomposition 

is anticipated to occur before the 

melting point is reached.

315 decomposition temperature

Boiling point of the test item could not be 

determined, OECD 103 (Measured)

ECHA, 2011 Inadequate; nonspecific value.

Vapor Pressure (mm Hg) <1x10-8 (Estimated) EPI; U.S. EPA, 1999 Cutoff value for nonvolatile 

compounds according to HPV 

assessment guidance.

Water Solubility (mg/L) 1.1x103 (Measured)

Reported as 1.1 g/L at 20°C

ECHA, 2011 Adequate, nonguideline study 

reported in secondary source; value 

is consistent with other reported 

properties.

<2x103 (Measured) HSNO, 2010 Inadequate; sufficient details were 

not provided to assess the quality of 

this study.

Log Kow 1.2

OECD Method 117 (Measured)

ECHA, 2011 Adequate guideline study.

Flammability (Flash Point) ≥400°C

auto-flammability/self-ignition 

temperature DIN 51 794 (Measured)

ECHA, 2011 Adequate guideline study.

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Bisphenol S CASRN 80-09-1

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Not highly flammable

EU Method A.10 (Measured)

ECHA, 2011

Explosivity No data located.

pH No data located.

pKa 8 

OECD Method 112 (Measured)

ECHA, 2011 Adequate, guideline study.

HUMAN HEALTH EFFECTS

Toxicokinetics No toxicokinetic data located.

Dermal Absorption in vitro No data located.

Absorption, 

Distribution, 

Metabolism & 

Excretion

Oral, Dermal or Inhaled No data located.

Acute Mammalian Toxicity LOW: The weight of evidence indicates that the acute oral toxicity of bisphenol S is low. A reported acute 

oral LD50 of 1,600 mg/kg for the mouse could not be verified because no study details were available. 

Located data suggest a low hazard concern for acute dermal exposure. No data were located regarding the 

acute inhalation hazard. 

Acute Lethality Oral Rat oral LD50 >5,000 mg/kg ECHA, 2011 Adequate guideline study (OECD 

401); no deaths at limit dose of 

5,000 mg/kg.

Wistar rat (male)

LD50 = 2,830 mg/kg 

ECHA, 2011 Adequate guideline comparable to 

OECD guideline 401; the LD50

value supports other reported 

results.

Rat oral LD50 = 4,556 mg/kg BIOFAX Industrial Bio-Test 

Laboratories, Inc., 1974, cited in 

CHEMID

Although no study details were 

provided in the secondary source, 

the LD50 value supports other 

reported results.

Rat (male, female; strain unspecified)

LD50 = 2,540 mg/kg (females) 

LD50 = >3,200 mg/kg (males) 

Eastman Kodak, 1991 Although study details were lacking 

in the study summary, the LD50

value supports other reported 

results.

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Bisphenol S CASRN 80-09-1

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Sprague-Dawley rat (male, female)

LD50 >2,000 mg/kg 

ECHA, 2011 Although the secondary source 

indicated that the study followed 

OECD guideline 401, it was noted 

that only an abstract of the study 

was located.

Wistar rat (gender unspecified)

A single dosed rat died following a single 

oral dose of 10,000 mg/kg; a single rat 

given 7,000 mg/kg survived

Monsanto Company, 1945 

(OTS0555048)

Although insufficient numbers of 

animals were assessed, the results 

support study results for rats.

Mouse (gender, strain unspecified)

LD50 = 1,600 mg/kg 

Eastman Kodak, 1991 This value could not be verified 

because the study summary provides 

only the LD50 value for the mouse.

Albino rabbit (gender unspecified)

One of two rabbits died following a single 

oral dose of 7,000 mg/kg; a single rabbit 

given 4,700 mg/kg survived

Monsanto Company, 1945 

(OTS0555048)

Although insufficient numbers of 

animals were assessed, the results 

support study results for rats.

Dermal Rabbit dermal LD50 >10,250 mg/kg BIOFAX Industrial Bio-Test 

Laboratories, Inc., 1974, cited in 

CHEMID

Although limited study information 

was located, the high dose suggests 

a low hazard concern for the dermal 

exposure route.

Guinea pig (strain and gender 

unspecified) dermal LD50 >1,000 mg/kg 

Eastman Kodak, 1991 Inadequate, limited study 

information located.

Inhalation No data located.

Carcinogenicity MODERATE: Estimated using OncoLogic expert system which describes a concern for this compound as a 

potential carcinogen or tumorigenesis promoter arising from its structural similarity to 

estrogenic/androgenic compounds, using the “phenols and phenolic compounds” structural alert.

OncoLogic Results Moderate (Estimated)

OncoLogic class: phenols and phenolic 

compounds 

OncoLogic OncoLogic SAR analysis using the 

phenols and phenolic compounds 

class. 

Carcinogenicity (Rat and 

Mouse)

No data located.

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Bisphenol S CASRN 80-09-1

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Combined Chronic 

Toxicity/ Carcinogenicity

No data located.

Genotoxicity MODERATE: Bisphenol S did not induce gene mutations in several in vitro assays and did not induce 

chromosomal aberrations in vivo in a mammalian erythrocyte micronucleus assay in NMRI mice or in 

Chinese hamster ovary (CHO) cells in vitro in the presence of exogenous metabolic activation. However, 

bisphenol S did induce chromosomal aberrations in CHO cells in vitro in the absence of exogenous 

metabolic activation (at a noncytotoxic concentration). The positive result in the in vitro assay and negative 

result in the in vivo test suggest an equivocal response and therefore a Moderate hazard concern.

Gene Mutation in vitro Negative, mouse lymphoma L5178Y 

(TK+/TK-) cells, with and without 

metabolic activation 

CCRIS, 2010 Adequate.

Negative, Ames assay (standard plate) in 

Salmonella typhimurium strains TA98, 

TA100, TA1537, TA1535, and TA1538 

with and without metabolic activation

CCRIS, 2010 Adequate.

Negative, Salmonella/microsome test, S.

typhimurium strains TA1535, TA100, 

TA1537, and TA98 with and without 

metabolic activation

Miles Inc., 1992; ECHA, 2011 Adequate guideline study (OECD 

471). 

Negative, Ames assay (preincubation) in 

S. typhimurium strains TA98, TA100, 

TA1537, and TA1535, and Escherichia 

coli WP2UVRA with and without 

metabolic activation 

CCRIS, 2010; ECHA, 2011 Adequate guideline study (OECD 

471). 

Negative, umu test in S. typhimurium

strain TA1335 

Chen, Michihiko et al., 2002 Adequate.

Negative, CHO HGPRT mutation assay, 

with and without metabolic activation 

Amoco Corp., 1991a; ECHA, 

2011

Adequate.

Gene Mutation in vivo No data located.

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FINAL REPORT – January 2014 

Bisphenol S CASRN 80-09-1

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Chromosomal Aberrations 

in vitro

Positive, chromosomal aberrations in 

CHO cytogenetics assay, without 

metabolic activation, negative with 

metabolic activation. Results were 

obtained in the absence of cytotoxicity.

Amoco Corp., 1991b; ECHA, 

2011

Adequate guideline study (similar to 

OECD 473). 

Chromosomal Aberrations 

in vivo

Negative, did not produce chromosomal 

aberrations in vivo in a mammalian 

erythrocyte micronucleus assay in male 

NMRI mice (5/group) administered 

bisphenol S via single gavage dose at dose 

levels up to 2,000 mg/kg.

ECHA, 2011 Adequate guideline study (OECD 

474). 

DNA Damage and Repair No data located.

Other (Mitotic Gene 

Conversion)

No data located.

Reproductive Effects MODERATE: In a reproduction/developmental toxicity screening test, oral exposure of parental rats to 

bisphenol S resulted in marked systemic effects and the NOAEL for reproductive effects is 60 mg/kg-day

(prolonged estrous cycle, decreased fertility index and decreased number of live offspring). Based on the 

NOAEL for reproductive effects, a Moderate hazard designation is selected.

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Bisphenol S CASRN 80-09-1

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Reproduction/ 

Developmental Toxicity 

Screen

In a reproduction/developmental toxicity 

screening test, groups of Sprague-Dawley 

rats (12/sex/group) were administered 

bisphenol S by gavage at 0, 10, 60, or 

300 mg/kg bw-day (males for 45 days and 

females from 14 days before mating to 

LD 3). The mid dose caused parental 

gross- and histo-pathological changes in 

cecum of both sexes. The high dose 

caused decreased body weight gain and 

food consumption in females, increased 

relative liver weight in males, hypertrophy 

of hepatocytes in both sexes, prolonged 

estrous cycle, decreased fertility index, 

and decreased number of live offspring on 

LD 4. 

Parental toxicity: 

NOAEL = 10 mg/kg bw-day 

LOAEL = 60 mg/kg bw-day for effects on 

cecum (distension, diffuse hyperplasia of 

mucosal epithelium) 

Reproductive toxicity: 

NOAEL = 60 mg/kg bw-day 

LOAEL = 300 mg/kg bw-day for 

prolonged estrous cycle, decreased 

fertility index, and decreased number of 

live offspring on LD 4.

ECHA, 2011 Adequate guideline study (OECD 

421) reported in a secondary source.

Combined Repeated Dose 

with Reproduction/ 

Developmental Toxicity 

Screen

No data located.

Reproduction and Fertility 

Effects

No data located.

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FINAL REPORT – January 2014 

Bisphenol S CASRN 80-09-1

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Developmental Effects MODERATE: In a reproduction/developmental toxicity screening test, oral exposure of parental rats to 

bisphenol S resulted in marked systemic effects and decreased number of live offspring (PND 4) at the 

highest dose level (300 mg/kg-day), with a NOAEL of 60 mg/kg-day. Based on the NOAEL, a Moderate 

hazard designation is selected.

Reproduction/ 

Developmental Toxicity 

Screen

In a reproduction/developmental toxicity 

screening test, groups of Sprague-Dawley 

rats (12/sex/group) were administered 

bisphenol S by gavage at 0, 10, 60, or 

300 mg/kg bw-day (males for 45 days and 

females from 14 days before mating to 

LD 3). The mid dose caused parental 

gross- and histo-pathological changes in 

cecum of both sexes. The high dose 

caused decreased body weight gain and 

food consumption in females, increased 

relative liver weight in males, hypertrophy 

of hepatocytes in both sexes, prolonged 

estrous cycle, decreased fertility index, 

and decreased number of live offspring on 

LD 4. No changes attributable to the 

compound were observed in parameters 

including the sex ratio, the live birth 

index, body weight, viability index on day 

4, anogenital distance, external or 

necropsy findings. 

Parental toxicity: 

NOAEL = 10 mg/kg bw-day 

LOAEL = 60 mg/kg bw-day for effects on 

cecum (distension, diffuse hyperplasia of 

mucosal epithelium) 

Reproductive toxicity: 

NOAEL = 60 mg/kg bw-day 

LOAEL = 300 mg/kg bw-day for 

prolonged estrous cycle, decreased 

ECHA, 2011 Adequate guideline study (OECD 

421) reported in a secondary source.

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FINAL REPORT – January 2014 

Bisphenol S CASRN 80-09-1

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

fertility index, and decreased number of 

live offspring on LD 4.

Combined Repeated Dose 

with Reproduction/ 

Developmental Toxicity 

Screen

No data located.

Prenatal Development No data located.

Postnatal Development No data located.

Neurotoxicity MODERATE: Estimated to have potential for neurotoxicity based on the presence of the phenol structural 

alert.

Neurotoxicity Screening 

Battery (Adult)

There is potential for neurotoxicity effects 

based on the presence of the phenol 

structural alert. 

(Estimated)

U.S. EPA, 2010; Professional 

judgment

Estimated based on structural alert.

Repeated Dose Effects HIGH: Among two adequately-designed, repeated-dose oral studies in rats, one study identified a NOAEL 

of 10 mg/kg-day and a LOAEL of 60 mg/kg-day for systemic effects and the other study identified a 

NOAEL of 40 mg/kg-day and a LOAEL of 200 mg/kg-day for systemic effects. Based on uncertainty as to 

the potential systemic toxicity in the range of 40 to 60 mg/kg-day, a High hazard designation is selected. It 

should be noted that because the standard criteria thresholds are for 90-day studies, the 28-day study was 

evaluated using modified criteria at 3 times the threshold values.

In a repeated-dose oral study, SpragueDawley rats (6/sex/dose group) were 

administered bisphenol S by gavage at 0, 

40, 200, or 1,000 mg/kg bw-day. No 

treatment-related effects were seen at low 

dose. Effects at the 200 mg/kg bw-day 

dose level included decreased body 

weight gain in females, increased 

incidences of proteinuria in males and 

females and urobilinogen in males, 

increased kidney weight in males, and 

increased incidences of hyperplasia and 

necrosis in cecal mucosal epithelium of 

ECHA, 2011 Adequate 28-day repeat dose 

toxicity guideline study; this study 

will be evaluated using modified 

criteria at 3 times the thresholds 

because the standard thresholds are 

based on 90-day studies. 

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males and females.

NOAEL = 40 mg/kg bw-day 

LOAEL = 200 mg/kg-bw-day

In a reproduction/developmental toxicity 

screening test, groups of Sprague-Dawley 

rats (12/sex/group) were administered 

bisphenol S by gavage at 0, 10, 60, or 

300 mg/kg bw-day (males for 45 days and 

females from 14 days before mating to 

LD 3). The mid dose caused parental 

gross- and histo-pathological changes in 

cecum of both sexes. The high dose 

caused decreased body weight gain and 

food consumption in females, increased 

relative liver weight in males, and 

hypertrophy of hepatocytes in both sexes.

NOAEL = 10 mg/kg bw-day 

LOAEL = 60 mg/kg bw-day for effects on 

cecum (distension, diffuse hyperplasia of 

mucosal epithelium)

ECHA, 2011 Adequate guideline study (OECD 

421). 

In a 13-day oral (dietary) study in rats, 

increases in red blood cell count, 

hemoglobin concentrations, and 

hematocrit were observed; histopathologic 

examinations revealed cytoplasmic 

basophilia of the renal distal convoluted 

tubule epithelium. Decreased weight gain, 

decreased absolute liver and kidney 

weight, and atrophy in adipose tissue may 

have been secondary effects of decreased 

food consumption. 

NOAEL = 97 mg/kg-day 

LOAEL = 810 mg/kg-day

Eastman Kodak, 1991 Inadequate; exposure duration only 

13 days. 

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Skin Sensitization LOW: Studies on guinea pigs and mice indicate that bisphenol S not a likely skin sensitizer.

Skin Sensitization Negative for skin sensitization, guinea 

pig

Eastman Kodak, 1991 Limited study details.

Negative for skin sensitization, mouse 

local lymph node assay

ECHA, 2011 Adequate guideline study (OECD 

429).

Respiratory Sensitization No data located.

Respiratory Sensitization No data located.

Eye Irritation LOW: Bisphenol S was non-irritating to mildly irritating to rabbit eyes.

Eye Irritation Slightly irritating, rabbit Eastman Kodak, 1991 Limited study details.

Mildly irritating, rabbit Monsanto, 1991 Limited study details.

Nonirritating, rabbit ECHA, 2011 Adequate guideline study (OECD 

405).

Dermal Irritation LOW: Bisphenol S was slightly irritating to guinea pig skin and not irritating to rabbit skin.

Dermal Irritation Slight skin irritant, guinea pig Eastman Kodak, 1991 Limited study details.

Non-irritant, rabbit Monsanto, 1991 Adequate.

Non-irritant, rabbit ECHA, 2011 Adequate guideline study (OECD 

404).

Endocrine Activity Based on limited data, it appears that bisphenol S exhibits endocrine activity. In vitro assays demonstrate 

that bisphenol S can bind to estrogen receptors (ER), elicit estrogen-induced gene transcription, and induce 

cell proliferation in MCF7 cancer cells, and inhibit the androgenic activity of dihydrotestosterone. In an 

ARE-luciferase reporter assay using a mouse fibroblast cell line, bisphenol S did not elicit an androgenic 

response, but did inhibit the androgenic activity of dihydrotestosterone. Located data indicate that the in 

vitro endocrine activity of bisphenol S is approximately 5-7 orders of magnitude less than that of 17βestradiol, suggesting that bisphenol S acts as a weak estrogen. Comparative in vitro data suggest that the 

endocrine activity of bisphenol S is somewhat less than that of BPA, bisphenol AP, bisphenol C, and 

bisphenol F. Limited in vivo data suggest the potential for estrogenic activity.

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In a human ER binding assay, the relative 

binding affinity (RBA) of bisphenol S was 

0.0055% relative to 17β-estradiol (set at 

100%). RBAs for other bisphenol 

compounds included 0.175% for 

bisphenol M and 0.0719% for bisphenol 

F.

Yamasaki, Noda et al., 2004 Adequate.

In a human ER binding assay, the RBA of 

bisphenol S was 0.0055% compared to 

126% for 17β-estradiol. RBAs for other 

bisphenol compounds included 0.195% 

for BPA, 0.129% for bisphenol C, 

0.0803% for bisphenol AP, and 0.0719% 

for bisphenol F. A RBA of 0.00473% was 

reported for PHBB.

METI, 2002 Adequate.

In a rat uterine cytosolic ER-competitive 

binding assay, results for bisphenol S, 

BPA, and PHBB indicated a weak affinity 

for ER.

Laws, Yavanhxay et al., 2006 Adequate.

Gene Transcription and Reporter Gene 

Assays

Bisphenol S exhibited evidence of 

estrogenic activity in a yeast 

(Saccharomyces cerevisiae) two-hybrid 

assay using ERα and the coactivator TIF2. 

Based on estrogenic activity that was 

approximately 7 orders of magnitude 

lower than that of 17β-estradiol, bisphenol 

S was considered less estrogenic than 

BPA which was considered weakly 

estrogenic (5 orders of magnitude less 

active than 17β-estradiol). Assessment of 

other bisphenols resulted in a ranking of 

Chen, Michihiko et al., 2002 Adequate.

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relative potency as follows: bisphenol C ≥ 

BPA > bisphenol F > bisphenol S.

In a yeast two-hybrid assay using 

β-galactosidase activity as a measure of 

estrogenic activity, bisphenol S did not 

appear to elicit an estrogenic response but 

a weakly estrogenic response was elicited 

by BPA.

Nishihara, Nishikawa et al., 2000 Adequate.

In yeast two-hybrid systems (reporter 

gene assay) using β-galactosidase activity 

as a measure of estrogenic activity, an 

estrogenic response was elicited by 

bisphenol S only in the presence of 

exogenous metabolic activation; 

estrogenic responses were elicited by 

BPA and bisphenol F both in the absence 

and presence of exogenous metabolic 

activation.

Hashimoto and Nakamura, 2000; 

Hashimoto, Moriguchi et al., 2001

Adequate.

In a reporter gene assay of estrogeninduced transcriptional activity, relative 

activity (RA) for bisphenol S was 

0.000254% compared to 81.7% for 17βestradiol. RAs for other bisphenol 

compounds included 0.00278% for BPA, 

0.00189% for bisphenol C, 0.000639% for 

bisphenol F, and 0.000184% for bisphenol 

AP. An RA of 0.000592% was reported 

for PHBB.

METI, 2002 Adequate.

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In an ERE-luciferase reporter assay using 

MCF-7 cells, an EC50 was 1.1 μM for 

bisphenol S compared to an EC50 of 

8.6x10-6 for 17β-estradiol (i.e., BPA was 

approximately 5 orders of magnitude less 

potent than 17β-estradiol at inducing 

estrogenic activity). EC50 values for other 

bisphenol compounds included 0.63 μM 

for BPA, 0.42 μM for bisphenol C, and 

1.0 μM for bisphenol F.

Kitamura, Suzuki et al., 2005 Adequate.

In an E-screen test for estrogenicity, 

bisphenol S, BPA, and bisphenol F 

increased proliferation of MCF-7 cells at 

concentrations in the range of 10-4 to 10-7

M. BPA appeared to be more effective 

than bisphenol S or bisphenol F.

Hashimoto, Moriguchi et al., 2001 Adequate.

In an ERE-luciferase reporter assay using 

MCF-7 cells in the presence of 17βestradiol, neither bisphenol S, BPA, 

bisphenol C, nor bisphenol F appeared to 

exert an anti-estrogenic effect

Kitamura, Suzuki et al., 2005 Adequate.

Cell Proliferation Assays

In a cell proliferation assay using human 

breast cancer MCF-7 cells, bisphenol S 

elicited a proliferative response 

comparable to that of BPA. 

Kuruto-Niwa, Nowaza et al., 2005 Adequate.

Androgen Activity

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In an ARE-luciferase reporter assay using 

a mouse fibroblast cell line (NIH3T3 

cells), bisphenol S inhibited the 

androgenic activity of 

dihydrotestosterone. Anti-androgenic 

responses were elicited by BPA, 

bisphenol C, and bisphenol F as well.

Kitamura, Suzuki et al., 2005 Adequate.

In an ARE-luciferase reporter assay using 

a mouse fibroblast cell line (NIH3T3 

cells), neither bisphenol S, BPA, 

bisphenol C, nor bisphenol F exerted an 

androgenic effect

Kitamura, Suzuki et al., 2005 Adequate.

In Vivo Studies

In an uterotrophic assay of rats 

subcutaneously injected with bisphenol S 

once daily for 3 days, an apparent 

estrogenic effect was evidenced by 

increased absolute and relative uterine 

weight. Similar effects were elicited by 

bisphenol F and bisphenol M.

Yamasaki, Noda et al., 2004 Adequate.

Immunotoxicity No data located.

Immune System Effects No data located.

ECOTOXICITY

ECOSAR Class Phenols, poly

Acute Toxicity MODERATE: Based on an experimental 48-hour LC50 value of 55 mg/L for Daphnid.

Fish LC50 Fish (species unspecified)

96-hour LC50 >100 mg/L 

(Experimental, nominal) 

ECHA, 2011 Adequate guideline study (OECD 

203), although information 

regarding measured test substance 

concentrations was not located.

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Oryzias latipes (orange-red killifish)

96-hour LC50 >500 mg/L (semi-static) 

(Experimental, nominal) 

ECHA, 2011 Adequate guideline study (Japanese 

Industrial Standard JIS K 0102-

1986-71), although information 

regarding measured test substance 

concentrations was not located.

Fish 96-hour LC50 = 38 mg/L

(Estimated) 

ECOSAR: neutral organics

ECOSAR version 1.11 Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided by 

ECOSAR classes that have a more 

specific mode of action relative to 

narcosis.

Fish 96-hour LC50 = 38 mg/L

(Estimated) 

ECOSAR: phenols, poly

ECOSAR version 1.11

Daphnid LC50 Daphnia magna (water flea)

48-hour EC50 = 55 mg/L

24-hour EC50 = 76 mg/L 

(Experimental)

Chen, Michihiko et al., 2002; 

ECHA, 2011

Adequate guideline study (OECD 

202), although information 

regarding measured test substance 

concentrations was not located.

Daphnid (water flea)

96-hour LC50 = 45 mg/L 

NOEC = 10 mg/L

(Experimental)

Eastman Kodak, 1991 Adequate, non guideline study, 

although information regarding 

measured test substance 

concentrations was not located.

Daphnia sp. (water flea)

48-hour EC50 = 100 mg/L 

(Experimental) 

ECHA, 2011 Adequate guideline study (OECD 

202), although information 

regarding measured test substance 

concentrations was not located.

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Daphnid

48-hour LC50 = 195 mg/L

(Estimated) 

ECOSAR: neutral organics

ECOSAR version 1.11 Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided by 

ECOSAR classes that have a more 

specific mode of action relative to 

narcosis.

Daphnid

48-hour LC50 = 195 mg/L

(Estimated) 

ECOSAR: phenols, poly

ECOSAR version 1.11

Green Algae EC50 Desmodesmus subspicatus (green algae)

72-hour EC50 = 106 mg/L (growth) 

72-hour NOEC = 10 mg/L 

(Measured; static conditions)

ECHA, 2011 Adequate guideline study (OECD 

201). 

Green algae

72-hour EC50 = 65 mg/L (growth) 

72-hour NOEC = 4.6 mg/L 

(Experimental) 

ECHA, 2011 Adequate guideline study (OECD 

201); secondary source noted that 

test substance concentrations were 

measured, but did not indicate 

whether nominal or measured 

concentrations were used for effect 

levels.

Green algae

96-hour EC50 = 2.29 mg/L 

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.11 Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided by 

ECOSAR classes that have a more 

specific mode of action relative to 

narcosis.

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Green algae

96-hour EC50 = 2.3 mg/L

(Estimated) 

ECOSAR: phenols, poly

ECOSAR version 1.11

Chronic Aquatic Toxicity MODERATE: The measured EC50 value for Daphnid is 14 mg/L while the measured NOEC is 2.7mg/L. 

Using a conservative approach, the unidentified LOEC for chronic toxicity in Daphnid is assumed to fall 

between 2.7 and 14 mg/L, which partly spans across the range of values that indicate a Moderate hazard 

concern (1-10 mg/L).

Fish ChV Fish

30-day ChV = 12.58 mg/L

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.11 Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided by 

ECOSAR classes that have a more 

specific mode of action relative to 

narcosis.

Fish

30-day ChV = 13 mg/L

(Estimated) 

ECOSAR: phenols, poly

ECOSAR version 1.11

Daphnid ChV Daphnia sp. (water flea)

21-day EC50 = 14 mg/L (reproduction) 

21-day NOEC = 2.7 mg/L (Experimental) 

ECHA, 2011 Adequate guideline study (OECD 

211), although information 

regarding measured test substance 

concentrations was not located.

Daphnid ChV = 18.31 mg/L

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.11 Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided by 

ECOSAR classes that have a more 

specific mode of action relative to

narcosis.

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Green Algae ChV Green algae

ChV = 0.88 mg/L

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.11 Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided by 

ECOSAR classes that have a more 

specific mode of action relative to 

narcosis.

Green algae

ChV = 0.88 mg/L 

(Estimated) 

ECOSAR: phenols, poly

ECOSAR version 1.11

ENVIRONMENTAL FATE

Transport The transport evaluation for bisphenol S is based on located experimental and estimated physical and 

chemical properties. Based on the Level III fugacity models incorporating the located experimental property 

data, bisphenol S is expected to partition primarily to soil. It is expected to exist in both neutral and anionic 

forms at environmentally-relevant pH, based on its measured pKa. The neutral form of bisphenol S is 

expected to have slight mobility in soil based on its estimated Koc. The anionic form may be more mobile, as 

anions do not bind as strongly to organic carbon and clay due to their enhanced water solubility. However, 

leaching of bisphenol S through soil to groundwater is not expected to be an important transport 

mechanism. Estimated volatilization half-lives indicate that it will be nonvolatile from surface water. In the 

atmosphere, bisphenol S is expected to exist in the particulate phase, based on its estimated vapor pressure. 

Particulates will be removed from air by wet or dry deposition.

Henry’s Law Constant 

(atm-m3/mole)

<1x10-8 (Estimated) EPI Cutoff value for nonvolatile 

compounds based on professional 

judgment. 

Sediment/Soil 

Adsorption/Desorption

Coefficient – Koc

1800 (Estimated) EPI

Level III Fugacity 

Estimations

Air = 0% (Estimated)

Water = 16%

Soil = 83%

Sediment = 1%

EPI

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Persistence MODERATE: Degradation of bisphenol S did not occur in a river die-away test and bisphenol S did not 

pass a Japanese MITI ready biodegradability test (OECD TG 301C), which reported 0% degradation after 

4 weeks. However in a nonguideline, less-stringent test, results indicate potential for biodegradation under 

aerobic conditions. The persistence of bisphenol S is supported by an estimated half-life of 30 days in soil. 

Bisphenol S is expected to partition primarily to soil. Bisphenol S may degrade under anaerobic conditions 

with approximately 60% removal measured after 70 days in anoxic bottles with pond sediment. However, it 

is not expected to significantly partition to sediment and removal under anaerobic conditions is not 

anticipated to be a significant fate process. Bisphenol S is not expected to undergo hydrolysis since it does 

not contain hydrolyzable functional groups. Bisphenol S does not absorb UV light at environmentally 

significant wavelengths. The vapor phase reaction of bisphenol S with atmospheric hydroxyl radicals is 

estimated at 8.8 hours, although it is expected to exist primarily in the particulate phase in air. 

Considerations of all these factors indicate that the persistence concern is Moderate for bisphenol S.

Water Aerobic Biodegradation Bisphenol S aerobic degradation was not 

detected after 2 weeks; degradation based 

on TOC decrease in river water and 

measured with HPLC (Measured)

Ike, Chen et al., 2006 Adequate nonguideline study.

This study measured the degradation of 

BPA, bisphenol F, and bisphenol S in 

seawater. Degradation of bisphenol S was 

not detected in seawater. This study used 

TOC Handai and river die-away methods. 

(Measured) 

Danzl, Sei et al., 2009 Adequate nonguideline study.

Volatilization Half-life 

for Model River

>1 year (Estimated) EPI

Volatilization Half-life 

for Model Lake

>1 year (Estimated) EPI

Soil Aerobic Biodegradation Ready Test: MITI-I (OECD 301C) No 

biodegradation detected; Bisphenol S for 

4 weeks with 100 mg/L in 30 mg/L 

activated sludge BOD 0%; TOC 0% 

(Measured)

MITI, 1998 Adequate guideline study.

Anaerobic 

Biodegradation

Not probable (anaerobic-methanogenic 

biodegradation probability model)

EPI

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Soil Biodegradation w/ 

Product Identification

No data located.

Sediment/Water 

Biodegradation

Anaerobic degradation of bisphenol S was 

detected by HPLC analysis. 

Approximately 60% of bisphenol S was 

removed after 70 days in anoxic bottles 

with pond sediment (Measured)

Ike, Chen et al., 2006 Adequate, nonguideline study.

Air Atmospheric Half-life 8.8 hours (Estimated) EPI

Reactivity Photolysis Not a significant fate process (Estimated) Mill, 2000; Professional judgment Substance does not contain 

functional groups that would be 

expected to absorb light at 

wavelengths >290 nm

Hydrolysis Not a significant fate process (Estimated) Wolfe and Jeffers, 2000; 

Professional judgment

Substance does not contain 

functional groups that would be 

expected to hydrolyze readily under 

environmental conditions.

Pyrolysis No data located.

Environmental Half-life 30 days (Estimated) EPI; PBT Profiler Half-life estimated for the 

predominant compartment, as 

determined by EPI and the PBT 

Profiler methodology.

Bioaccumulation LOW: The low concern for bioaccumulation was based on two experimental BCF values. Both values are 

well below the low criteria cutoff of 100.

Fish BCF A BCF of <2.2 at a concentration of 

50 μg/L after 6 weeks in carp (Cyprinus 

carpio); OECD 305C 

(Measured)

MITI, 1998 Adequate guideline study.

A BCF of <0.2 at a concentration of 

500 μg/L after 6 weeks in carp (Cyprinus 

carpio); OECD 305C 

(Measured)

MITI, 1998 Adequate guideline study.

BAF 1.8 (Estimated) EPI

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Metabolism in Fish No data located.

ENVIRONMENTAL MONITORING AND BIOMONITORING 

Environmental Monitoring No data located.

Ecological Biomonitoring No data located.

Human Biomonitoring BPS was detected in human urine samples from general populations of the United States, China, India, Japan, 

Korea, Kuwait, Malaysia and Vietnam (Liao, Liu, et al., 2012). This chemical was not included in the NHANES 

biomonitoring report (CDC, 2011).

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FINAL REPORT – January 2014 

Amoco Corp. CHO/HGPRT mutation assay (final report) with attachment and cover letter dated 111491. TSCATS submission 

OTS0534324. 1991a. 

Amoco Corp. Chromosome aberrations in Chinese hamster ovary (CHO) cells (final report) with attachment and cover letter dated 

111491. TSCATS submission OTS0534325. 1991b. 

BIOFAX Industrial Bio-Test Laboratories, Inc. Data sheets. Vol. 601-05501, 1974, as cited in ChemID. 

http://chem.sis.nlm.nih.gov/chemidplus/. 

CCRIS. Chemical Carcinogenesis Research Information System. Bisphenol S. 2010. http://toxnet.nlm.nih.gov/cgibin/sis/htmlgen?CCRIS, (accessed on August, 2010). 

CDC (Centers for Disease Control and Prevention). Fourth national report on human exposure to environmental chemicals, updated 

tables. Department of Health and Human Services. 2011. http://www.cdc.gov/exposurereport/ (accessed on May 10, 2011). 

Chen, M-Y.; Michihiko, I.; Fujita, M. Acute toxicity, mutagenicity, and estrogenicity of bisphenol-A and other bisphenols. Environ. 

Toxicol. 2002, 17:80-86. 

Danzl, E.; Sei, K.; Soda, S., et al. Biodegradation of Bisphenol A, Bisphenol F and Bisphenol S in Seawater. Int. J. Environ. Res. 

Public Health. 2009, 6:1472-1484. 

Eastman Kodak. Letter concerning enclosed information on bisphenol S with attachments. Eastman Kodak Company, Rochester NY. 

TSCATS submission OTS0534330. 1991. 

ECHA. European Chemicals Agency. Information on registered substances. http://apps.echa.europa.eu/registered/registered-sub.aspx

(accessed February 18, 2011).

ECOSAR (2012) Ecological Structure Activity Relationship (ECOSAR) Version 1.11. Washington, DC: U.S. Environmental 

Protection Agency. http://www.epa.gov/oppt/newchems/tools/21ecosar.htm. 

ECOSAR/EPI (EPIWIN/EPISUITE) Estimations Programs Interface for Windows, Version 3.20. U.S. Environmental Protection 

Agency: Washington D.C. http://www.epa.gov/opptintr/exposure/. 

EPI (EPIWIN/EPISUITE) Estimations Programs Interface for Windows, Version 4.00. U.S. Environmental Protection Agency: 

Washington D.C. http://www.epa.gov/opptintr/exposure/. 

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Hashimoto, Y.; Nakamura, M. Estrogenic activity of dental materials and bisphenol-A related chemicals in vitro. Dent. Mater. J. 2000,

19(3):245-262. 

Hashimoto, Y.; Moriguchi, Y.; Oshima, H.; et al. Measurement of estrogenic activity of chemicals for the development of new dental 

polymers. Toxicol. In Vitro 2001, 15:421-425. 

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Risk Management Authority (ERMA) – New Zealand. August 5, 2010. 

Ike, M.; Chen, M.Y.; Danzl, E.; et al. Biodegradation of a variety of bisphenols under aerobic and anaerobic conditions. Water Sci. 

Technol. 2006, 53:153-159. 

Kitamura, S.; Suzuki, T.; Sanoh, S.; et al. Comparative study of the endocrine-disrupting activity of bisphenol A and 19 related 

compounds. Toxicol. Sci. 2005, 84:249-259. 

Kuruto-Niwa, R.; Nozawa, R.; Miyakoshi, T.; et al. Estrogenic activity of alkylphenols, bisphenol S, and their chlorinated derivatives 

using a GFP expression system. Environ. Toxicol. Pharmacol. 2005, 19:121-130. 

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SPARC On Line Calculator pKa/property server. Ver 4.5 September, 2009. Available from, http://ibmlc2.chem.uga.edu/sparc/

(accessed on August 12, 2010). 

U.S. EPA (Environmental Protection Agency). High Production Volume (HPV) Challenge. Determining the Adequacy of Existing 

Data. U.S. Environmental Protection Agency: Washington D.C. 1999. http://www.epa.gov/hpv/pubs/general/datadfin.htm

U.S. EPA (Environmental Protection Agency). Sustainable Futures Using NonCancer Screening within the Sustainable Futures 

Initiative Environmental Protection Agency: Washington D.C. 2010. http://www.epa.gov/opptintr/sf/pubs/noncanscreen.htm#systemic (accessed on February 09, 2011). 

Wolfe, N.; Jeffers, P. (2000) Hydrolysis. In Boethling, R.; Mackay, D., Handbook of Property Estimation Methods for Chemicals, 

Environmental Health Sciences (311-334). Boca Raton: Lewis Publishers. 

Yamasaki, K.; Noda, S.; Imatanaka, N.; et al. Comparative study of the uterotrophic potency of 14 chemicals in a uterotrophic assay 

and their receptor-binding affinity. Toxicol. Lett. 2004, 146:111-120. 

4-300 
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2,4-BPS

OH

S

O O OH CASRN: 5397-34-2

MW: 250.3

MF: C12H10O4S

Physical Forms: 

Neat: Solid

Use: Developer for thermal paper

SMILES: O=S(=O)(c1ccc(O)cc1)c1c(O)cccc1

Synonyms: Phenol, 2-[(4-hydroxyphenyl)sulfonyl]-; 2,4'-Dihydroxydiphenyl sulfone; 2,4'-Sulfonyldiphenol; 2-((4-Hydroxyphenyl)sulfonyl)phenol; 4,2'-

Dihydroxydiphenyl sulfone; O,P-Dihydroxydiphenyl sulfone; Phenol, 2,4'-sulfonyldi-; o-((4-Hydroxyphenyl)sulphonyl)phenol

Polymeric: No

 Oligomers: Not applicable

Metabolites, Degradates and Transformation Products: None

Analog: Bisphenol S (80-09-1)

 Endpoint(s) using analog values: Boiling point, Acute lethality (oral 

and dermal); Irritation (eye, dermal); dermal sensitization, repeated dose 

effects, reproductive and developmental toxicity 

Analog Structure:

Structural Alerts: Phenols, neurotoxicity (U.S. EPA, 2010)

Risk Phrases: Not classified by Annex VI Regulation (EC) No 1272/2008 (ESIS, 2011).

Risk Assessments: None identified

S

O

O

OH OH

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2,4-BPS CASRN 5397-34-2

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

PHYSICAL/CHEMICAL PROPERTIES

Melting Point (°C) 184 ChemSpider, 2010 Secondary source; study details and test 

conditions were not provided.

Boiling Point (°C) >300 (Estimated) EPI; U.S. EPA, 1999 Decomposition may occur before the 

boiling point is reached based on the 

experimental decomposition 

temperature of 315°C for the analog 

bisphenol S. Cutoff value for high 

boiling point compounds according to 

HPV assessment guidance.

Vapor Pressure (mm Hg) <1x10-8 (Estimated) EPI; U.S. EPA, 1999 Cutoff value for nonvolatile compounds 

according to HPV assessment guidance.

Water Solubility (mg/L) 1.7x103 (Estimated) EPI

Log Kow 1.7 (Estimated) EPI

Flammability (Flash Point) No data located.

Explosivity No data located.

pH No data located.

pKa 7.6; 8.2 (Estimated) SPARC Estimates are for pK1 and pK2.

HUMAN HEALTH EFFECTS

Toxicokinetics 2,4-BPS as a neat material is estimated to not be absorbed through the skin and will have poor skin absorption 

when in solution. 2,4-BPS is expected to be absorbed via the lungs and gastrointestinal tract. 

Dermal Absorption in vitro No data located.

Absorption, 

Distribution, 

Metabolism & 

Excretion

Oral, Dermal or Inhaled Not absorbed through the skin as neat 

material and has poor absorption in solution; 

can be absorbed through the lung and 

gastrointestinal tract

(Estimated by analogy)

Professional judgment Based on closely related confidential 

analog with similar structure, functional 

groups, and physical/chemical 

properties. 

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PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Acute Mammalian Toxicity LOW: Estimated based on analogy to bisphenol S. The weight of evidence indicates that the acute oral 

toxicity of the analog bisphenol S is low. Located data suggest a low hazard concern for acute dermal exposure 

to this analog. No data were located regarding the acute inhalation hazard. 

Acute Lethality Oral Rat oral LD50 >5,000 mg/kg 

(Estimated by analogy) 

ECHA, 2011; Professional 

judgment 

Adequate; using the analog bisphenol S.

Data are for an adequate guideline study 

(OECD 401). No deaths at limit dose of 

5,000 mg/kg.

Wistar rat (male)

LD50 = 2,830 mg/kg 

(Estimated by analogy) 

ECHA, 2011; Professional 

judgment 

Adequate; using the analog bisphenol S.

Data are for an adequate guideline 

comparable to OECD guideline 401. 

The LD50 value supports other reported 

results.

Rat oral LD50 = 4,556 mg/kg 

(Estimated by analogy) 

BIOFAX Industrial Bio-Test 

Laboratories, Inc., Data Sheets. 

Vol. 601-05501, 1974, cited in 

CHEMID, 2010; Professional 

judgment

Adequate; using the analog bisphenol S.

Although no study details were 

provided in the secondary source, the 

LD50 value supports other reported 

results.

Rat oral LD50 = 2,540 mg/kg (females) and 

>3,200 mg/kg (males) 

(Estimated by analogy) 

Eastman Kodak, 1991; 

Professional judgment

Adequate; using the analog bisphenol S. 

Although study details were lacking in 

the study summary, the LD50 value 

supports other reported results.

Sprague-Dawley rat (male, female)

LD50 >2,000 mg/kg 

(Estimated by analogy) 

ECHA, 2011; Professional 

judgment 

Adequate; using the analog bisphenol S.

Although the secondary source 

indicated that the study followed OECD 

guideline 401, it was noted that only an 

abstract of the study was located.

Dermal Guinea pig dermal LD50 >1,000 mg/kg 

(Estimated by analogy) 

Eastman Kodak, 1991; 

Professional judgment

Adequate; using the analog bisphenol S.

Data are for an adequate, nonguideline 

study.

Inhalation No data located.

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2,4-BPS CASRN 5397-34-2

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Carcinogenicity MODERATE: Estimated using OncoLogic expert system, which describes a potential for this compound as a 

potential carcinogen or tumorigenesis promoter arising from its structural similarity to estrogenic/androgenic 

compounds. The “phenols and phenolic compounds” structural alert was used.

OncoLogic Results Moderate (Estimated)

OncoLogic class: phenols and phenolic 

compounds 

OncoLogic OncoLogic SAR analysis using the 

phenols and phenolic compounds class. 

Carcinogenicity (Rat and 

Mouse)

No data located.

Combined Chronic 

Toxicity/Carcinogenicity

No data located.

Genotoxicity MODERATE: 2,4-BPS did not cause genetic mutations in Salmonella typhimurium, but did cause 

chromosomal aberrations in Chinese hamster ovary (CHO) cells in vitro. Based on evidence of mutagenicity in 

animal cells, Moderate hazard is designated.

Gene Mutation in vitro Negative for gene mutations in S. 

typhimurium strains TA98, TA100, TA1535, 

and TA1538 with and without metabolic 

activation, and TA1537 with exogenous 

metabolic activation; positive in TA1537 

without exogenous metabolic activation, but 

only at cytotoxic concentration.

NICCA USA Inc., 1996 Adequate; guideline (OECD 473).

Gene Mutation in vivo No data located.

Chromosomal 

Aberrations in vitro

Positive for chromosomal aberrations in 

CHO cells with and without metabolic 

activation.

NICCA USA Inc., 1996 Adequate; guideline (OECD 473).

Chromosomal 

Aberrations in vivo

DNA Damage and Repair No data located.

Other (Mitotic Gene 

Conversion)

No data located.

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2,4-BPS CASRN 5397-34-2

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Reproductive Effects MODERATE: Estimated based on analogy to bisphenol S. In a reproductive/developmental toxicity screening 

test, oral exposure of parental rats to the analog bisphenol S resulted in marked systemic and the NOAEL for 

reproductive effects is 60 mg/kg-day (prolonged estrous cycle, decreased fertility index and decreased number 

of live offspring). Based on the NOAEL for reproductive effects, a Moderate hazard designation is selected.

Reproduction/ 

Developmental Toxicity 

Screen

Parental toxicity:

NOAEL = 10 mg/kg bw-day 

LOAEL = 60 mg/kg bw-day 

Reproductive toxicity: 

NOAEL = 60 mg/kg bw-day 

LOAEL = 300 mg/kg bw-day 

(Estimated by analogy)

ECHA, 2011; Professional 

judgment 

Adequate; using the analog bisphenol S. 

Data are for an adequate guideline study 

(OECD 421) reported in a secondary 

source.

Combined Repeated Dose 

with Reproduction/ 

Developmental Toxicity 

Screen

No data located.

Reproduction and 

Fertility Effects

Potential for reproductive toxicity

(Estimated by analogy) 

Professional judgment Estimated based on reported 

experimental data for the analog 

bisphenol S.

Developmental Effects MODERATE: Estimated based on analogy to bisphenol S. In a reproductive/developmental toxicity screening 

test, oral exposure of parental rats to the analog bisphenol S resulted in marked systemic effects and decreased 

number of live offspring (PND 4) at the highest dose level (300 mg/kg-day) with a NOAEL of 60 mg/kg-day. 

Based on the NOAEL, a Moderate hazard designation is selected.

Reproduction/ 

Developmental Toxicity 

Screen

Parental toxicity:

NOAEL = 10 mg/kg bw-day 

LOAEL = 60 mg/kg bw-day 

Reproductive toxicity: 

NOAEL = 60 mg/kg bw-day 

LOAEL = 300 mg/kg bw-day

(Estimated by analogy)

ECHA, 2011; Professional 

judgment 

Adequate; using the analog bisphenol S.

Data are for an adequate guideline study 

(OECD 421) reported in a secondary 

source.

Potential for developmental toxicity

(Estimated by analogy) 

Professional judgment Estimated based on reported 

experimental data for the analog 

bisphenol S.

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2,4-BPS CASRN 5397-34-2

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Combined Repeated Dose 

with Reproduction/ 

Developmental Toxicity 

Screen

No data located.

Prenatal Development No data located.

Postnatal Development No data located.

Neurotoxicity MODERATE: Estimated to have potential for neurotoxicity based on the presence of the phenol structural 

alert.

Neurotoxicity Screening 

Battery (Adult)

There is potential for neurotoxicity effects 

based on the presence of the phenol 

structural alert. 

(Estimated)

U.S. EPA, 2010; Professional 

judgment 

Estimated based on structural alert.

Repeated Dose Effects HIGH: Based on analogy to bisphenol S. Among two adequately-designed repeated-dose oral studies in rats, 

one study identified a NOAEL of 10 mg/kg-day and a LOAEL of 60 mg/kg-day for systemic effects and the 

other study identified a NOAEL of 40 mg/kg-day and a LOAEL of 200 mg/kg-day for systemic effects 

following exposure to the analog bisphenol S. Based on uncertainty as to the potential systemic toxicity in the 

range of 40-60 mg/kg-day, a High hazard designation is selected.

In a repeated-dose oral study, SpragueDawley rats, NOAEL = 40 mg/kg bw-day 

LOAEL = 200 mg/kg-bw-day 

(Estimated by analogy)

ECHA, 2011; Professional 

judgment 

Adequate; using the analog bisphenol S.

Data are for an adequate 28-day repeat 

dose toxicity guideline study. 

In a reproduction/developmental toxicity 

screening test, Sprague-Dawley rats, 

NOAEL = 10 mg/kg bw-day 

LOAEL = 60 mg/kg bw-day 

(Estimated by analogy)

ECHA, 2011; Professional 

judgment 

Adequate; using the analog bisphenol S.

Data are for an adequate guideline study 

(OECD 421). 

Skin Sensitization LOW: Not considered a skin sensitizer for guineas pig based on analog data for bisphenol S.

Skin Sensitization Negative for skin sensitization, guinea pig 

(Estimated by analogy)

Eastman Kodak, 1991; 

Professional judgment

Adequate; using the analog bisphenol

S. Data are for an adequate study with 

limited details.

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2,4-BPS CASRN 5397-34-2

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Negative for skin sensitization, mouse local 

lymph node assay 

(Estimated by analogy)

ECHA, 2011; Professional 

judgment 

Adequate; using the analog bisphenol 

S. Data are for an adequate guideline 

study (OECD 429).

Respiratory Sensitization No data located.

Respiratory Sensitization No data located.

Eye Irritation LOW: Estimated based on analogy to bisphenol S. The analog bisphenol S was nonirritating to mildly 

irritating to rabbit eyes.

Eye Irritation Slight eye irritant, rabbit 

(Estimated by analogy) 

Eastman Kodak, 1991; 

Professional judgment

Adequate; using the analog bisphenol 

S. Data are for an adequate, 

nonguideline study.

Mild eye irritant, rabbit 

(Estimated by analogy) 

Monsanto, 1991; Professional 

judgment 

Adequate; using the analog bisphenol 

S. Data are for an adequate, 

nonguideline study.

Nonirritating, rabbit 

(Estimated by analogy) 

ECHA, 2011; Professional 

judgment 

Adequate; using the analog bisphenol 

S. Data are for an adequate guideline 

study (OECD 405).

Dermal Irritation LOW: Estimated based on analogy to bisphenol S. The analog bisphenol S was slightly irritating to guinea pig 

skin, and not irritating to rabbit skin.

Dermal Irritation Slight skin irritant, guinea pig 

(Estimated by analogy) 

Eastman Kodak, 1991; 

Professional judgment

Adequate; using the analog bisphenol 

S. Data are for an adequate, 

nonguideline study.

Non-irritant, rabbit 

(Estimated by analogy) 

Monsanto, 1991; Professional 

judgment 

Adequate; using the analog bisphenol 

S, data are for an adequate, 

nonguideline study.

Non-irritant, rabbit

(Estimated by analogy)

ECHA, 2011; Professional 

judgment 

Adequate; using the analog bisphenol 

S. Data are for an adequate guideline 

study (OECD 404).

Endocrine Activity No data located.

No data located.

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2,4-BPS CASRN 5397-34-2

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Immunotoxicity No data located.

Immune System Effects No data located.

ECOTOXICITY

ECOSAR Class Phenols, Poly

Acute Toxicity MODERATE: Based on estimated 96-hour EC50 of 2.3 mg/L for green algae.

Fish LC50 Fish 96-hour LC50 = 37.91 mg/L

(Estimated) 

ECOSAR: phenols, poly

ECOSAR version 1.00

Fish 96-hour LC50 = 383.85 mg/L

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.00 Narcosis classes (neutral organics) are 

provided for comparative purposes; DfE 

assessment methodology will use the 

lowest estimated toxicity value 

provided by ECOSAR classes that have 

a more specific mode of action relative 

to narcosis.

Daphnid LC50 Daphnid 48-hour LC50 = 196.26 mg/L

(Estimated) 

ECOSAR: phenols, poly

ECOSAR version 1.00

Daphnid 48-hour LC50 = 212.23 mg/L

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.00 Narcosis classes (neutral organics) are 

provided for comparative purposes; DfE 

assessment methodology will use the 

lowest estimated toxicity value 

provided by ECOSAR classes that have 

a more specific mode of action relative 

to narcosis.

Green Algae EC50 Green algae 96-hour EC50 = 2.29 mg/L

(Estimated) 

ECOSAR: phenols, poly

ECOSAR version 1.00

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2,4-BPS CASRN 5397-34-2

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Green algae 96-hour EC50 = 79.15 mg/L

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.00 Narcosis classes (neutral organics) are 

provided for comparative purposes; DfE 

assessment methodology will use the 

lowest estimated toxicity value 

provided by ECOSAR classes that have 

a more specific mode of action relative 

to narcosis.

Chronic Aquatic Toxicity HIGH: Based on estimated a ChV value of 0.88 mg/L for green algae.

Fish ChV Fish 30-day ChV = 12.64 mg/L

(Estimated) 

ECOSAR: phenols, poly

ECOSAR version 1.00

Fish ChV = 36.72 mg/L

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.00 Narcosis classes (neutral organics) are 

provided for comparative purposes; DfE 

assessment methodology will use the 

lowest estimated toxicity value 

provided by ECOSAR classes that have 

a more specific mode of action relative 

to narcosis.

Daphnid ChV Daphnia sp. (water flea)

21-day EC50 = 14 mg/L (reproduction) 

21-day NOEC = 2.7 mg/L (Estimated by 

analogy) 

(Estimated by analogy)

ECHA, 2011; Professional 

judgment

Adequate; using the analog bisphenol S. 

Data are for an adequate guideline study 

(OECD 211). 

Daphnid ChV = 18.42 mg/L

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.00 Narcosis classes (neutral organics) are 

provided for comparative purposes; DfE 

assessment methodology will use the 

lowest estimated toxicity value 

provided by ECOSAR classes that have 

a more specific mode of action relative 

to narcosis.

Daphnid 21-day ChV = 74.99 mg/L

(Estimated) 

ECOSAR: phenols, poly

ECOSAR version 1.00

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2,4-BPS CASRN 5397-34-2

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Green Algae ChV Green algae ChV = 0.88 mg/L

(Estimated) 

ECOSAR: phenols, poly

ECOSAR version 1.00

Green algae ChV = 26.85 mg/L

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.00 Narcosis classes (neutral organics) are 

provided for comparative purposes; DfE 

assessment methodology will use the 

lowest estimated toxicity value 

provided by ECOSAR classes that have 

a more specific mode of action relative 

to narcosis.

ENVIRONMENTAL FATE

Transport 2,4-BPS is expected to exist in both neutral and anionic forms at environmentally-relevant pH, based on its 

estimated pKa. The neutral form of 2,4-BPS is expected to have moderate mobility in soil based on its 

estimated Koc. The anionic form may be more mobile although leaching of 2,4-BPS through soil to 

groundwater is not expected to be an important transport mechanism. Estimated volatilization half-lives 

indicate that it will be nonvolatile from surface water. Volatilization from dry surface is also not expected 

based on its estimated vapor pressure. In the atmosphere, 2,4-BPS is expected to exist solely in the particulate 

phase, based on its estimated vapor pressure. Particulates may be removed from air by wet or dry deposition. 

Level III fugacity models incorporating the located experimental property data, indicate that the unionized 

form of 2,4-BPS is expected to partition primarily to soil.

Henry’s Law Constant

(atm-m3/mole)

<1x10-8 (Estimated) EPI Cutoff value for nonvolatile compounds 

based on professional judgment. 

Sediment/Soil 

Adsorption/Desorption

Coefficient – Koc

1.9x103 (Estimated) EPI

Level III Fugacity 

Model

Air = <1% (Estimated)

Water = 16%

Soil = 83%

Sediment = <1%

EPI

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2,4-BPS CASRN 5397-34-2

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Persistence MODERATE: Evaluation of the persistence of 2,4-BPS is based entirely on QSARs for aerobic and anaerobic 

biodegradation. Results from these models estimate primary biodegradation in days-weeks and ultimate 

degradation in weeks. The persistence of 2,4-BPS is supported by an estimated half-life of 30 days in soil. 2,4-

BPS is expected to partition primarily to soil. 2,4-BPS is not expected to partition to sediment and removal 

under anaerobic conditions is not anticipated to be a significant fate process. 2,4-BPS is not expected to 

undergo hydrolysis since it does not contain hydrolyzable functional groups. 2,4-BPS does not absorb UV light 

at environmentally significant wavelengths. The vapor phase reaction of 2,4-BPS with atmospheric hydroxyl 

radicals is estimated at 8.8 hours, although it is expected to exist primarily in the particulate phase in air. 

Consideration of all of these factors indicates that the persistence concern is Moderate for 2,4-BPS.

Water Aerobic Biodegradation Days-weeks (primary survey model)

Weeks (ultimate survey model)

EPI

Volatilization Half-life 

for Model River

>1 year (Estimated) EPI

Volatilization Half-life 

for Model Lake

>1 year (Estimated) EPI

Soil Aerobic Biodegradation No data located.

Anaerobic 

Biodegradation

Not probable (anaerobic-methanogenic 

biodegradation probability model)

EPI

Soil Biodegradation w/ 

Product Identification

No data located.

Sediment/Water 

Biodegradation

No data located.

Air Atmospheric Half-life 8.8 hours (Estimated) EPI

Reactivity Photolysis Not a significant fate process (Estimated) Mill, 2000; Professional 

judgment 

Substance does not contain functional 

groups that would be expected to absorb 

light at wavelengths >290 nm.

Hydrolysis Not a significant fate process (Estimated) Wolfe and Jeffers, 2000; 

Professional judgment 

Substance does not contain functional 

groups that would be expected to 

hydrolyze readily under environmental 

conditions.

Pyrolysis No data located.

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2,4-BPS CASRN 5397-34-2

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Environmental Half-Life 30 days (Estimated) EPI; PBT Profiler Half-life estimated for the predominant 

compartment, as determined by EPI and 

the PBT Profiler methodology.

Bioaccumulation LOW: The low potential for bioaccumulation is based on an estimated BCF for fish that is less than the low 

criteria cutoff of 100. In addition, the estimated BAF of 3.5, which accounts for metabolism, suggests that 

2,4-BPS will not bioaccumulate in higher trophic levels.

Fish BCF 5.7 (Estimated) EPI

BAF 3.5 (Estimated) EPI

Metabolism in Fish No data located.

ENVIRONMENTAL MONITORING AND BIOMONITORING 

Environmental Monitoring No data located.

Ecological Biomonitoring No data located.

Human Biomonitoring This chemical was not included in the NHANES biomonitoring report (CDC, 2011).

4-312 
FINAL REPORT – January 2014 

BIOFAX Industrial Bio-Test Laboratories, Inc. Data sheets. Vol. 601-05501, 1974, as cited in ChemID. 

http://chem.sis.nlm.nih.gov/chemidplus/. 

CDC (Centers for Disease Control and Prevention). Fourth national report on human exposure to environmental chemicals, updated 

tables. Department of Health and Human Services. 2011. http://www.cdc.gov/exposurereport/ (accessed on May 10, 2011). 

ChemID. ChemIDplus. National Library of Medicine. 2010: http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?CHEM (accessed on 

December 10, 2010). 

ChemSpider. ChemSpider; Structure-based Chemistry Information. Royal Society of Chemistry:London. 2010. 

http://www.chemspider.com (accessed on December 11, 2010). 

Eastman Kodak. Letter concerning enclosed information on bisphenol S with attachments. Eastman Kodak Company, Rochester NY. 

TSCATS submission OTS0534330. 1991.

ECHA. European Chemicals Agency. Information on registered substances. 2011. http://apps.echa.europa.eu/registered/registeredsub.aspx (accessed February 18, 2011). 

ECOSAR (2010) Ecological Structure Activity Relationship (ECOSAR) Version 1.00. Washington, DC: U.S. Environmental 

Protection Agency. http://www.epa.gov/oppt/newchems/tools/21ecosar.htm. 

ECOSAR/EPI (EPIWIN/EPISUITE) Estimations Programs Interface for Windows, Version 3.20. U.S. Environmental Protection 

Agency: Washington D.C. http://www.epa.gov/opptintr/exposure/. 

EPI (EPIWIN/EPISUITE) Estimations Programs Interface for Windows, Version 4.00. U.S. Environmental Protection Agency: 

Washington D.C. http://www.epa.gov/opptintr/exposure/. 

ESIS (European chemical Substances Information System) Classification, labeling and Packaging of dangerous substances annex VI 

to regulation (EC) No 1272/2008 [Online] http://esis.jrc.ec.europa.eu/ (accessed on June 10, 2011). 

Mill, T. 2000. Photoreactions in Surface Waters. In Boethling, R.; Mackay, D., Handbook of Property Estimation Methods for 

Chemicals, Environmental Health Sciences (355-382). Boca Raton: Lewis Publishers. 

Monsanto. Toxicological investigation of dihydroxydiphenyl sulfone (final report) with cover letter dated112190. TSCATS 

submission OTS0534356. 1991. 

NICCA USA Inc. Letter from NICCA U.S.A. Inc to USEPA regarding genotoxicity testing of phenol, 2-[(4-hydroxyphenyl)-sulfonyl], 

with attachments and dated 3/5/96. Nicca Chemical Company Limited. OTS0558479. 1996. 

4-313 
FINAL REPORT – January 2014 

Oncologic. U.S. EPA and LogiChem, Inc. 2005, Version 7.0. 2008. 

PBT Profiler Persistent (P),Bioaccumulative (B), and Toxic (T) Chemical (PBT)Profiler. U.S. Environmental Protection Agency: 

Washington D.C. www.pbtprofiler.net. 

SPARC On Line Calculator pKa/property server. Ver 4.5 September, 2009. Available from, http://ibmlc2.chem.uga.edu/sparc/

(accessed on August 12, 2010). 

U.S. EPA (Environmental Protection Agency). High Production Volume (HPV) Challenge. Determining the Adequacy of Existing 

Data. U.S. Environmental Protection Agency: Washington D.C. 1999. http://www.epa.gov/hpv/pubs/general/datadfin.htm. 

U.S. EPA Sustainable Futures. Using Non-Cancer Screening within the SF Initiative. Environmental Protection Agency: Washington 

D.C. 2010. http://www.epa.gov/opptintr/sf/pubs/noncan-screen.htm#systemic (accessed on February 09, 2011). 

Wolfe, N.; Jeffers, P. 2000. Hydrolysis. In Boethling, R.; Mackay, D., Handbook of Property Estimation Methods for Chemicals, 

Environmental Health Sciences (311-334). Boca Raton: Lewis Publishers. 

4-314 
FINAL REPORT – January 2014 

TGSA

S

O

O

OH OH

CASRN: 41481-66-7

MW: 330.40

MF: C18H18O4S

Physical Forms: 

Neat: Solid

Use: Developer for thermal paper

SMILES: S(c1cc(CC=C)c(cc1)O)(c1cc(CC=C)c(cc1)O)(=O)=O

Synonyms: Phenol, 4,4'-sulfonylbis[2-(2- propen-1-yl)-; bis-(3-Allyl-4-hydroxyphenyl) sulfone; Phenol, 4,4'-sulfonylbis(2-(2-propenyl)-; 2,2'-diallyl-4,4'-

sulfonyldiphenol; 2-allyl-4-(3-allyl-4-hydroxyphenyl)sulfonylphenol; 4-(4-hydroxy-3-prop-2-enyl-phenyl)sulfonyl-2-prop-2-enyl-phenol

Polymeric: No

 Oligomers: Not applicable

Metabolites, Degradates and Transformation Products: Potential for epoxide formation on terminal double bonds.

Analog: Bisphenol S (80-09-1)

 Endpoint(s) using analog values: Reproductive and developmental 

toxicity.

Analog Structure: 

S

O

O

OH OH

4-315 

Structural Alerts: Phenols, neurotoxicity (U.S. EPA, 2010)

Risk Phrases: 43 - May cause sensitization by skin contact; 51/53 - Toxic to aquatic organisms, may cause long-term adverse effects in the aquatic environment 

(ESIS, 2011).

Risk Assessments: None identified 
FINAL REPORT – January 2014 

TGSA CASRN 41481-66-7

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

PHYSICAL/CHEMICAL PROPERTIES

Melting Point (°C) 151-155 ±1 (Measured) Nippon Kayaku Co., 1992b Adequate; guideline study.

144 (Measured) Submitted confidential study Adequate.

Boiling Point (°C) Decomposed prior to boiling (Measured) Nippon Kayaku Co., 1992b Adequate; decomposition occurs

before the boiling point is reached.

Vapor Pressure (mm Hg) 9.5x10-10 (Measured) Nippon Kayaku Co., 1992b Adequate; guideline study.

Water Solubility (mg/L) 4.79 at 20.3°C ±0.5 (Measured) Nippon Kayaku Co., 1992b Adequate; guideline study.

Log Kow 3.22 (Measured) Nippon Kayaku Co., 1992b Adequate; guideline study.

Flammability (Flash Point) Not highly flammable (Measured) Nippon Kayaku Co., 1992b Adequate; guideline study.

Explosivity Not explosive (Measured) Nippon Kayaku Co., 1992b Adequate; guideline study.

pH No data located.

pKa 8.3-8.5 (Estimated) SPARC

HUMAN HEALTH EFFECTS

Toxicokinetics TGSA as a neat material is not estimated to be absorbed through the skin and is expected to have poor skin 

absorption when in solution. It is estimated to be absorbed via the lungs and gastrointestinal tract based on 

data for BPA. TSGA is a potential cross-linking agent because it has two terminal double bonds that are 

expected to be oxidized in the body via an epoxide intermediate. 

Dermal Absorption in vitro No data located.

Absorption, 

Distribution, 

Metabolism & 

Excretion

Oral, Dermal or Inhaled Not absorbed through the skin as neat 

material and has poor absorption in 

solution. Can be absorbed through the lung 

and gastrointestinal tract. 

(Estimated by analogy) 

Oxidation of the terminal double bonds in 

the body via an epoxide intermediate is 

expected. TGSA is a potential cross-linking 

agent because it has two terminal double 

bonds. 

(Estimated by analogy)

Professional judgment Estimate based on reported 

experimental data for the analog 

BPA; the potential for crosslinking 

is based on a mechanistic analysis.

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TGSA CASRN 41481-66-7

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Acute Mammalian Toxicity LOW: Based on experimental values for oral and dermal exposure. Experimental data indicated that the

acute oral and dermal toxicity of TGSA is low. No data were located regarding the acute inhalation hazard. 

Acute Lethality Oral Sprague-Dawley rat LD50 >2,000 mg/kg Nippon Kayaku Co., 1991f Adequate guideline study (OECD 

401). 

Dermal Rat dermal LD50 >2,000 mg/kg Nippon Kayaku Co., 1991d Adequate guideline study (OECD 

402).

Inhalation No data located.

Carcinogenicity MODERATE: Estimated to be a concern for carcinogenicity based on data reported for the epoxide 

oxidation product. In addition, there is uncertainty due to the lack of data located for this substance. 

Carcinogenic effects cannot be ruled out.

OncoLogic Results No data located; not amenable to 

available estimation method.

Carcinogenicity (Rat and 

Mouse)

Concern for carcinogenicity

(Estimated)

Professional judgment Estimated based on potential for 

the epoxide oxidation product. 

Combined Chronic 

Toxicity/Carcinogenicity

No data located.

Genotoxicity LOW: Based on experimental data showing that TGSA did not induce gene mutations or chromosomal 

aberrations in vitro, and was negative in a mammalian erythrocyte micronucleus assay in mice.

Gene Mutation in vitro Negative, Ames assay (standard plate) in S. 

typhimurium strains TA98, TA100, 

TA1537, TA1535, and E. coli WP2uvrAwith and without metabolic activation

Nippon Kayaku Co., 1991g Test conducted in accordance with 

OECD 471; test substance purity: 

96.2%. 

Gene Mutation in vivo No data located.

Chromosomal 

Aberrations in vitro

Negative for chromosome aberrations in 

human lymphocytes

Nippon Kayaku Co., 2000c Test conducted in accordance with 

OECD 473.

Negative for sister chromatid exchanges Submitted confidential study Adequate.

Chromosomal 

Aberrations in vivo

No data located.

DNA Damage and Repair No data located.

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TGSA CASRN 41481-66-7

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Other (Mitotic Gene 

Conversion) 

Negative, mammalian erythrocyte 

micronucleus test in mice (gavage)

Nippon Kayaku Co., 1991i Test conducted in accordance with 

OECD 474; test substance purity: 

96.2%. 

Reproductive Effects MODERATE: Estimated based on analogy to bisphenol S. In a reproductive/developmental toxicity 

screening test, oral exposure of parental rats to the analog bisphenol S resulted in marked systemic effects 

and the NOAEL for reproductive effects is 60 mg/kg-day (prolonged estrous cycle, decreased fertility index 

and decreased number of live offspring). Based on the NOAEL for reproductive effects, a Moderate hazard 

designation is selected.

Reproduction/ 

Developmental Toxicity 

Screen

Parental toxicity:

NOAEL = 10 mg/kg bw-day 

LOAEL = 60 mg/kg bw-day 

Reproductive toxicity: 

NOAEL = 60 mg/kg bw-day 

LOAEL = 300 mg/kg bw-day 

(Estimated by analogy)

ECHA, 2011; Professional 

judgment 

Using the analog bisphenol S, data 

are for an adequate guideline study 

(OECD 421) reported in a 

secondary source.

Combined Repeated Dose 

with Reproduction/ 

Developmental Toxicity 

Screen

No data located.

Reproduction and 

Fertility Effects

Concern for male reproductive toxicity

(Estimated)

Professional judgment Estimated based on reported data 

for the epoxide oxidation product 

and on reported experimental data 

for the analog bisphenol S.

Developmental Effects MODERATE: Estimated based on analogy to bisphenol S. In a reproductive/developmental toxicity 

screening test, oral exposure of parental rats to the analog bisphenol S resulted in marked systemic effects 

and decreased number of live offspring (PND 4) at the highest dose level (300 mg/kg-day) with a NOAEL of 

60 mg/kg-day. Based on the NOAEL, a Moderate hazard designation is selected.

Reproduction/ 

Developmental Toxicity 

Screen

Concern for developmental toxicity

(Estimated)

Professional judgment Estimated based on reported data 

for the epoxide oxidation product 

and on reported experimental data 

for the analog bisphenol S.

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TGSA CASRN 41481-66-7

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Parental toxicity:

NOAEL = 10 mg/kg bw-day 

LOAEL = 60 mg/kg bw-day 

Reproductive toxicity: 

NOAEL = 60 mg/kg bw-day 

LOAEL = 300 mg/kg bw-day

(Estimated by analogy)

ECHA, 2011; Professional 

judgment 

Using the analog bisphenol S, data 

are for an adequate guideline study 

(OECD 421) reported in a 

secondary source.

Combined Repeated Dose 

with Reproduction/ 

Developmental Toxicity 

Screen

No data located.

Prenatal Development No data located.

Postnatal Development No data located.

Neurotoxicity MODERATE: Estimated to have potential for neurotoxicity based on the presence of the phenol structural 

alert.

Neurotoxicity Screening 

Battery (Adult)

There is potential for neurotoxicity effects 

based on the presence of the phenol 

structural alert 

(Estimated)

U.S. EPA, 2010; Professional 

judgment 

Estimated based on structural alert.

Repeated Dose Effects HIGH: Based on experimental data for a 28-day oral exposure to TGSA in rats. A NOAEL of 15 mg/kg-day 

and a LOAEL of 150 mg/kg-day was identified for repeated dose effects that would indicate a MODERATE 

hazard designation based on a 90-day study. Based on the DfE criteria, when the study duration is less than

90-days, this study is to be evaluated using modified criteria at 3 times the threshold values. The NOAEL 

value of 15 mg/kg-day is within the High hazard designation range (< 30 mg/kg-day). In addition, there is 

concern for liver and kidney toxicity based on data for the epoxide oxidation product. 

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TGSA CASRN 41481-66-7

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

28-day repeated-dose oral exposure study, 

Sprague-Dawley rats; 

There was no mortality and no clinical 

signs of toxicity; increased salivation with 

wet fur and red/brown staining of body 

surface at doses of 150 mg/kg-day and 

higher; Decreased body weight gain in 

females administered 1,000 mg/kg-day; no 

treatment related effects on hematology, 

serum chemistry, necropsy, or organ 

weights; increased incidence of basophilic 

tubules and interstitial mononuclear cell 

infiltrates in kidneys of males in the 1,000 

mg/kg-day group; similar but less 

pronounced effect occurred at 150 mg/kgday in males. 

NOAEL = 15 mg/kg-day 

LOAEL = 150 mg/kg-day (microscopic 

renal changes)

Nippon Kayaku Co., 1991j Test conducted in accordance with 

OECD 474; test substance purity: 

96.2%.; 28-day study was

evaluated and applied to the DfE 

criteria using modified criteria at 3

times the thresholds because the 

standard thresholds are based on 

90-day studies. 

Skin Sensitization MODERATE: There is moderate concern that TGSA is a weak skin sensitizer based on test concentrations 

and positive incidence rates in the guinea pig maximization test and on negative results for the Buehler test 

and local lymph node assay. 

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PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Skin Sensitization Weak skin sensitizer in guinea pigs; 

produced a positive result of 70% (14/20) 

sensitization rate in guinea pigs.

Nippon Kayaku Co., 1991h Test conducted in accordance with 

OECD 406 skin sensitization 

Magnusson and Kligman 

maximization test; test substance 

purity: 96.2%; intradermal 

induction: 25% in arachis oil B.P, 

topical induction: 50% in arachis 

oil B.P., topical challenge: 50% in 

arachis oil B.P.; categorized as a 

weak skin sensitizer based on 

criteria for skin sensitization for 

guinea pig maximization test 

(Kimber et al., 2003; as cited in 

CERI, 2012). 

Did not produce skin sensitization in guinea 

pigs in Buehler test. 

Nippon Kayaku Co., 1992b Test conducted in accordance with 

EEC methodology 84/449/EEC 

(OJ No. L251, 19.9.84), Part B, 

test substance purity: 97.9 %; 

Method B.6; Induction: 60% 

Alembicol D; challenge: 60% in 

Alembicol D.

Classified as non-sensitizer in local lymph 

node assay in female CBA/JN mice; 

applied to dorsum of ears for 3 days; all 

stimulation indexes were below 3.

Nippon Kayaku Co., 2010 Test conducted in accordance with 

OECD TG429; test substance 

purity: 97.8%. 

Respiratory Sensitization MODERATE: There is concern that TGSA is a respiratory sensitizer based on the epoxide oxidation 

product.

Respiratory Sensitization Concern for respiratory sensitization Professional judgment Estimated based on reported data 

for the epoxide oxidation product.

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PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Eye Irritation LOW: Based on experimental data suggesting that TGSA is a minimal irritant to rabbit eyes. 

Eye Irritation Minimal irritant, rabbit Nippon Kayaku Co., 1991e Test conducted in accordance with 

OECD 405; test substance purity: 

96.2%. 

Dermal Irritation VERY LOW: Based on experimental data indicating that TGSA is not an irritant to rabbit skin. 

Dermal Irritation Non-irritant, rabbit Nippon Kayaku Co., 1991c Test conducted in accordance with 

OECD 404; test substance purity: 

96.2%.

Endocrine Activity There was no evidence that TGSA elicits estrogenic activity. TGSA did not bind to estrogen receptors in 

yeast, and did not have estrogenic effects on uterus of immature rats in vivo.

Did not cause significant estrogenic activity 

in a recombinant yeast screen assay in 

Saccharomyces cerevisiae; did not bind to 

estrogen receptor in recombinant yeast; 

there was an estrogenic response that was 4 

orders of magnitude less than 17B-estradiol 

and 1 order of magnitude less than BPA.

Nippon Kayaku Co., 1999a Adequate study details provided.

Uterotrophic assay in immature rat; No 

evidence of estrogenic effects on uterus of 

immature rats at oral doses up to 100 mg/kg 

bd. Wt. 

Nippon Kayaku Co., 1999b Adequate study details provided; 

TGSA also did not provide a 

synergistic effect when 

administered in combination with 

diethylstilbestrol (positive control). 

Immunotoxicity No data located.

Immune System Effects No data located.

ECOTOXICITY

ECOSAR Class Phenols, poly

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PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Acute Toxicity HIGH: Based on experimental acute aquatic toxicity values for fish and Daphnid which are in the range of 1-

10 mg/L.

Fish LC50 Oncorhynchus mykiss (rainbow trout) 96 

hour LC50 = 4.0 mg/L; 

NOEC – 96 hour = 1.8 mg/L

(Experimental)

Nippon Kayaku Co., 1991b Test conducted in accordance with 

OECD 203. 

Oryzias latipes (medaka) 96 hour LC50 >9.8 

mg/L

(Experimental) 

Nippon Kayaku Co., 2011b Test conducted in accordance with 

OECD 203; test substance purity: 

98%. 

Fish 96-hour LC50 = 1.17 mg/L

(Estimated) 

ECOSAR: phenols, poly

ECOSAR version 1.00

Fish 96-hour LC50 = 2.22 mg/L

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.00 Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided 

by ECOSAR classes that have a 

more specific mode of action 

relative to narcosis.

Daphnid LC50 Daphnia (Daphnia magna) 48-hour EC50 = 

5.5 mg/L (immobilization); 

24-hour EC50 = 7.8 mg/L (immobilization); 

NOEC – 48-hour = 3.2 mg/L 

(Experimental)

Nippon Kayaku Co., 1991a Test conducted in accordance with 

OECD 202. 

Daphnia (Daphnia magna) 48-hour EC50

>12 mg/L (immobilization); 

24-hour EC50 >12 mg/L (immobilization); 

(Experimental)

Nippon Kayaku Co., 2011a Test conducted in accordance with 

OECD 202; test substance purity: 

98%. 

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PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Daphnid 48-hour LC50 = 1.72 mg/L

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.00 Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided 

by ECOSAR classes that have a 

more specific mode of action 

relative to narcosis.

Daphnid 48-hour LC50 = 1.87 mg/L

(Estimated) 

ECOSAR: phenols, poly

ECOSAR version 1.00

Green Algae EC50 Green algae (Scenedesmus subspicatus) 

72-hour EC50 = >100 mg/L 

(Experimental)

Nippon Kayaku Co., 2000b Test conducted in accordance with 

OECD 201; test substance purity: 

50% TGSA, 4%PVA, 46% water.

Green algae 96-hour EC50 = 1.71 mg/L

(Estimated) 

ECOSAR: phenols, poly

ECOSAR version 1.00

Green algae 96-hour EC50 = 2.01 mg/L

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.00 Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided 

by ECOSAR classes that have a 

more specific mode of action 

relative to narcosis.

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TGSA CASRN 41481-66-7

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Chronic Aquatic Toxicity MODERATE: Based on experimental LOEC/NOEC and chronic EC50 values for fish and Daphnid that are 

in the range of 1.0-10 mg/L. There were no experimental chronic toxicity data for algae available, though 

estimated values fall within the High and Moderate hazard designation categories. 

Fish ChV Fish ChV = 0.20 mg/L (Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.00 Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided 

by ECOSAR classes that have a 

more specific mode of action 

relative to narcosis.

Fish ChV = 0.24 mg/L (Estimated) 

ECOSAR: phenols, poly 

ECOSAR version 1.00

Oryzias latipes (Madeka) 28-day NOEC 

(growth) = >8.0 mg/L (highest dose tested) 

LOEC ≥8.0 mg/L 

CERI, 2011 Test conducted in accordance with 

OECD 215; test substance purity: 

98%; impurities: 2% unknown 

organic constituents.

Daphnid ChV Daphnia (Daphnia magna) 14-day EC50 = 

4.1 mg/L (immobilization) 

(Experimental) 

Nippon Kayaku Co., 2000a Test conducted in accordance with 

OECD 211; 14-day value 

determined during 21-day 

reproduction test in parental 

daphnia generation; based on timeweighted mean measured test 

concentrations of the filtered test 

substance.

Daphnia (Daphnia magna) 21-day EC50 = 

2.8 mg/L (immobilization) 

(Experimental) 

Nippon Kayaku Co., 2000a Test conducted in accordance with 

OECD 211; 21-day reproduction 

test in parental daphnia generation;

Based on time-weighted mean 

measured test concentrations of the 

filtered test substance.

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PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Daphnia (Daphnia magna) 21-day EC50 = 

2.0 mg/L (reproduction) 

(Experimental) 

Nippon Kayaku Co., 2000a Test conducted in accordance with 

OECD 211; 21-day reproduction 

test; Based on time-weighted mean 

measured test concentrations of the 

filtered test substance.

Daphnia (Daphnia magna) 

LOEC = 1.6 mg/L (reproduction) 

NOEC = 0.50 mg/L 

(Experimental) 

Nippon Kayaku Co., 2000a Test conducted in accordance with 

OECD 211; 21-day reproduction 

test; based on time-weighted mean 

measured test concentrations of the 

filtered test substance.

Daphnid ChV = 0.25 mg/L (Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.00 Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided 

by ECOSAR classes that have a 

more specific mode of action 

relative to narcosis.

Daphnid ChV = 0.61 mg/L (Estimated) 

ECOSAR: phenols, poly

ECOSAR version 1.00

Green Algae ChV Green algae ChV = 0.20 mg/L (Estimated) 

ECOSAR: phenols, poly

ECOSAR version 1.00

Green algae ChV = 1.14 mg/L (Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.00 Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided 

by ECOSAR classes that have a 

more specific mode of action 

relative to narcosis.

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PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

ENVIRONMENTAL FATE

Transport TGSA is expected to exist in both the neutral and anionic forms at environmentally-relevant pH. TGSA is 

expected to have moderate mobility in soil. Anionic TGSA may have higher mobility due to enhanced water 

solubility. However, leaching through soil to groundwater is not expected to be an important transport 

mechanism. In the atmosphere, TGSA is expected to exist in the particulate phase, which will be deposited 

back to the soil and water surfaces through wet or dry deposition. The Level III fugacity model indicates that 

TGSA will partition primarily to soil.

Henry’s Law Constant 

(atm-m3/mole)

8.6x10-8 (Estimated) EPI

Sediment/Soil 

Adsorption/Desorption

Coefficient – Koc

996 (Measured)

HPLC screening method using cyanopropyl 

packed column; GLP compliance

TSCATS Adequate, nonguideline study yet 

established method considered to 

have higher reliability than QSARbased estimations.

>30,000 (Estimated) EPI; U.S. EPA, 2004 Cutoff value for nonmobile 

compounds.

Level III Fugacity 

Estimations 

Air = <1% (Estimated)

Water = 9.8% 

Soil = 58.2% 

Sediment = 31.9%

EPI

Persistence HIGH: The persistence of TGSA is based on an estimated half-life of 75 days in soil. TGSA is expected to 

partition primarily to soil. Experimental biodegradation data for TGSA were not located. Evaluation of the 

biodegradation potential for TGSA is based entirely on QSARs of aerobic and anaerobic biodegradation. 

Results from these models estimate ultimate biodegradation in weeks-months and primary degradation in 

days-week. Biodegradation under anaerobic methanogenic conditions is not probable based on results from 

estimation models. TGSA does not contain functional groups that absorb light at environmentally-relevant

wavelengths. Therefore, it is not expected to be susceptible to direct photolysis. It is not expected to undergo 

hydrolysis as it does not contain hydrolyzable functional groups. The atmospheric half-life of TGSA is 

estimated at 1.8 hours, although it is expected to exist primarily as a particulate in air. Therefore, 

biodegradation is expected to be the main degradation pathway for TGSA. 

Water Aerobic Biodegradation Days-weeks (primary survey model)

Weeks-months (ultimate survey model)

EPI

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PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Volatilization Half-life 

for Model River

>1 year (Estimated) EPI

Volatilization Half-life 

for Model Lake

>1 year (Estimated) EPI

Soil Aerobic Biodegradation No data located.

Anaerobic 

Biodegradation

Not probable (anaerobic-methanogenic 

biodegradation probability model)

EPI

Soil Biodegradation w/ 

Product Identification

No data located.

Sediment/Water 

Biodegradation

No data located.

Air Atmospheric Half-life 1.8 hours (Estimated) EPI

Reactivity Photolysis Not a significant fate process (Estimated) Mill, 2000; Professional judgment Substance does not contain 

functional groups that would be 

expected to absorb light at 

wavelengths >290 nm.

Hydrolysis <10% in 5 days at 50°C, pH 4 Nippon Kayaku Co., 1992b Adequate; guideline study.

Pyrolysis No data located.

Environmental Half-life 75 days EPI; PBT Profiler Half-life estimated for the 

predominant compartment, as 

determined by EPI and the PBT 

Profiler methodology. 

Bioaccumulation LOW: The estimated fish BAF and BCF is <100. 

Fish BCF 62 (Estimated) EPI Estimate performed using 

experimental log Kow.

BAF 18 (Estimated) EPI Estimate performed using 

experimental log Kow.

Metabolism in Fish No data located.

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PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

ENVIRONMENTAL MONITORING AND BIOMONITORING 

Environmental Monitoring No data located.

Ecological Biomonitoring No data located.

Human Biomonitoring This chemical was not included in the NHANES biomonitoring report (CDC, 2011).

4-329 
FINAL REPORT – January 2014 

CDC (Centers for Disease Control and Prevention). Fourth national report on human exposure to environmental chemicals, updated 

tables. Department of Health and Human Services. 2011. http://www.cdc.gov/exposurereport/ (accessed on May 10, 2011). 

CERI (Chemicals Assessment and Research Center). Final report. A growth study of TG-SH(H) in Medaka. Chemicals Evaluation and 

Research Institute, Japan. 2011. 662-10-E-5541. 

CERI (Chemicals Assessment and Research Center). Report. Evaluation for outcomes from different skin sensitization tests. 

Chemicals Evaluation and Research Institute, Japan. 2012. 924-12-D-0048-E.

ECHA (European Chemicals Agency). Information on registered substances. http://apps.echa.europa.eu/registered/registered-sub.aspx

(accessed February 18, 2011) 

ECOSAR (2010) Ecological Structure Activity Relationship (ECOSAR) Version 1.00. Washington, DC: U.S. Environmental 

Protection Agency. http://www.epa.gov/oppt/newchems/tools/21ecosar.htm. 

ECOSAR/EPI (EPIWIN/EPISUITE) Estimations Programs Interface for Windows, Version 3.20. U.S. Environmental Protection 

Agency: Washington D.C. http://www.epa.gov/opptintr/exposure/. 

EPI (EPIWIN/EPISUITE) Estimations Programs Interface for Windows, Version 4.00. U.S. Environmental Protection Agency: 

Washington D.C. http://www.epa.gov/opptintr/exposure/. 

ESIS (European chemical Substances Information System) Classification, labeling and Packaging of dangerous substances annex VI 

to regulation (EC) No 1272/2008 [Online] http://esis.jrc.ec.europa.eu/ (accessed on June 10, 2011). 

Mill, T. 2000. Photoreactions in Surface Waters. In Boethling, R.; Mackay, D., Handbook of Property Estimation Methods for 

Chemicals, Environmental Health Sciences (355-382). Boca Raton: Lewis Publishers. 

Nippon Kayaku Co. The acute toxicity of TG-SA to daphnia magna. Nippon Kayaku Co. Limited, Tokyo Japan. Project Number: 189-

320. 1991a. 

Nippon Kayaku Co. The acute toxicity of TG-SA to rainbow trout (Oncorhynchus mykiss). Nippon Kayaku Co. Limited, Tokyo Japan. 

Project Number: 189/321. 1991b. 

Nippon Kayaku Co. TG-SA: Acute dermal irritation test in the rabbit. Nippon Kayaku Co. Limited, Tokyo Japan. Project number: 

189/316. 1991c. 

Nippon Kayaku Co. TG-SA: Acute dermal toxicity (limit test) in the rat. Nippon Kayaku Co. Limited, Tokyo Japan. Project number: 

189/315. 1991d. 

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FINAL REPORT – January 2014 

Nippon Kayaku Co. TG-SA: Acute eye irritation test in the rabbit. Nippon Kayaku Co. Limited, Tokyo Japan. Project number 

189/317. 1991e. 

Nippon Kayaku Co. TG-SA: Acute oral toxicity (limit test) in the rat. Nippon Kayaku Co. Limited, Tokyo Japan. Project number: 

189/314. 1991f. 

Nippon Kayaku Co. TG-SA: Determination of Physico-Chemical Properties. Nippon Kayaku Co. Limited, Tokyo Japan. Project 

number: 189/324. 1992a. 

Nippon Kayaku Co. TG-SA: Reverse mutation assay "Ames test" using Salmonella typhimurium and Escherichia coli. Nippon Kayaku 

Co. Limited, Tokyo Japan. Project number 189/322. 1991g. 

Nippon Kayaku Co. TG-SA: Magnusson & Kligman maximization. Study in the guinea pig. Nippon Kayaku Co. Limited, Tokyo 

Japan. Project number: 189/318. 1991h. 

Nippon Kayaku Co. TG-SA: Micronucleus test. Nippon Kayaku Co. Limited, Tokyo Japan. Project number: 189/323. 1991i. 

Nippon Kayaku Co. TG-SA: Twenty-eight day sub-acute oral toxicity study in the rat. Nippon Kayaku Co. Limited, Tokyo Japan. 

Project number 189/325. 1991j. 

Nippon Kayaku Co. TG-SA: Skin sensitisation in the guinea-pig. Nippon Kayaku Co. Limited, Tokyo Japan. 920596D/NKU 268/SS. 

1992b. 

Nippon Kayaku Co. TG-SA (Lot No. 710427): Assessment of oestrogenic activity using a recombinant yeast screen assay. Nippon 

Kayaku Co. Limited, Tokyo Japan.SPL project number: 189/1663. 1999a. 

Nippon Kayaku Co. TG-SA: Uterotrophic assay in the immature rat. Nippon Kayaku Co. Limited, Tokyo Japan. SPL project number: 

189/1659. 1999b. 

Nippon Kayaku Co. TG-SA: Daphnia magna reproduction test. Nippon Kayaku Co. Limited, Tokyo Japan. SPL project number: 

189/1717. 2000a. 

Nippon Kayaku Co. TG-SA 50% liquid: Algal inhibition test. Nippon Kayaku Co. Limited, Tokyo Japan. SPL project number: 

189/1743. 2000b. 

Nippon Kayaku Co. TG-SA: Chromosome aberration test in human lymphocytes in vitro. Nippon Kayaku Co. Limited, Tokyo Japan. 

SPL project number: 189/1716. 2000c. 

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FINAL REPORT – January 2014 

Nippon Kayaku Co. Evaluation of skin sensitization potency of TG-SH based on EC3 value derived from local lymph node assay 

(LLNA). Nippon Kayaku Co. Limited, Tokyo Japan. Study code 937-10-V-0069. 2010. 

Nippon Kayaku Co. A 48-hour acute immobilization study of TG-SH(H) in daphnia magna. Nippon Kayaku Co. Limited, Tokyo 

Japan. Receipt number 662-10-E-5538. Study number 95538. 2011a. 

Nippon Kayaku Co. A 96-hour acute toxicity study of TG-SH(H) in Medaka. Nippon Kayaku Co. Limited, Tokyo Japan. Receipt 

number 662-10-E-5540. Study number 95540. 2011b. 

Nippon Kayaku Co. A 96-hour acute toxicity study of TG-SH(H) in Medaka. Nippon Kayaku Co. Limited, Tokyo Japan. Receipt 

number 662-10-E-5540. Study number 95540. 2011c. 

SPARC On Line Calculator pKa/property server. Ver 4.5 September, 2009. Available from, http://ibmlc2.chem.uga.edu/sparc/

(accessed on August 12, 2010). 

TSCATS. Marubeni. PMN # P-85-67 2, 2’-diallyl-4,4’-sulfonyl diphenol (or commonly known as TGSA). Marubeni Specialty 

Chemicals Inc., White Plains NY. Submitted March 22, 2005 to TSCATS submission FYI. 

U.S. EPA (Environmental Protection Agency). 2004. The Pollution Prevention (P2) Framework, EPA-748-B-03-001. Office of 

Pollution Prevention and Toxics 7403M, U.S. Environmental Protection Agency, Washington, DC. 20460. October 2003 

version updated in January 2004. Latest version available at http://www.epa.gov/opptintr/newchems/pubs/sustainable/p2framejune05a2.pdf 

U.S. EPA (Environmental Protection Agency). Sustainable Futures Using NonCancer Screening within the Sustainable Futures 

Initiative Environmental Protection Agency: Washington D.C. 2010. http://www.epa.gov/opptintr/sf/pubs/noncanscreen.htm#systemic (accessed on February 09, 2011). 

4-332 
FINAL REPORT – January 2014 

BPS-MAE

S

O

O

OH O

CASRN: 97042-18-7

MW: 290.34

MF: C15H14O4S

Physical Forms:

Neat: Solid

Use: Developer for thermal paper

SMILES: C=CCOc2ccc(cc2)S(=O)(=O)c1ccc(O)cc1

Synonyms: BPS-MAE; bis(4-Hydroxyphenyl) sulfone monoallyl ether; 4-[[4-(2-Propenyloxy)phenyl]sulfonyl]phenol; 4-{[4-(allyloxy)phenyl]sulfonyl}phenol

Polymeric: No

 Oligomers: Not applicable 

Metabolites, Degradates and Transformation Products: Potential for epoxide formation on terminal double bond.

Analog: Bisphenol S (80-09-1)

 Endpoint(s) using analog values: Boiling point, carcinogenicity, 

reproductive and developmental toxicity. 

Analog Structure:

4-333 

Structural Alerts: Phenols, neurotoxicity (U.S. EPA, 2010)

Risk Phrases: Not classified by Annex VI Regulation (EC) No 1272/2008 (ESIS, 2011).

Risk Assessments: None identified
FINAL REPORT – January 2014 

BPS-MAE CASRN 97042-18-7

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

PHYSICAL/CHEMICAL PROPERTIES

Melting Point (°C) 172 (Measured) Submitted confidential study Adequate.

Boiling Point (°C) >300 (Estimated) EPI; U.S. EPA, 1999 Decomposition may occur before the 

boiling point is reached based on the 

experimental decomposition 

temperature of 315°C for an analogous 

structure, bisphenol S. Cutoff value 

for high boiling point compounds 

according to HPV assessment 

guidance.

Vapor Pressure (mm Hg) <1x10-8 (Estimated) EPI; U.S. EPA, 1999 Cutoff value for nonvolatile 

compounds according to HPV 

assessment guidance.

Water Solubility (mg/L) 83 (Estimated) EPI

Log Kow 3.1 (Estimated) EPI

Flammability (Flash Point) No data located.

Explosivity No data located.

pH No data located.

pKa 8.2 (Estimated) SPARC

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FINAL REPORT – January 2014 

BPS-MAE CASRN 97042-18-7

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

HUMAN HEALTH EFFECTS

Toxicokinetics BPS-MAE is estimated not to be absorbed through the skin as the neat material and have poor skin 

absorption when in solution. BPS-MAE is estimated to have good absorption via the lungs and 

gastrointestinal tract based on data for the analog BPA. BPS-MAE is a potential cross-linking agent because 

it has two terminal double bonds that are expected to be oxidized in the body via an epoxide intermediate. 

Dermal Absorption in vitro No data located.

Absorption, 

Distribution, 

Metabolism & 

Excretion

Oral, Dermal or Inhaled Estimated to be poorly absorbed as neat 

material and in solution through the 

skin. Absorption through lungs and 

gastrointestinal tract is expected to be 

good. The terminal double bonds have

the potential be oxidized metabolically 

to the epoxide. 

(Estimated by analogy)

Professional judgment Estimated based on reported 

experimental data for the analog BPA; 

the potential for epoxide formation is 

based on a mechanistic analysis. 

Acute Mammalian Toxicity LOW: BPS-MAE was not toxic following acute oral exposure based on the acute oral LC50 value of >2,000 

mg/kg-bw in rats.

Acute Lethality Oral Rat (Sprague-Dawley CD) oral LD50

>2,000 mg/kg-bw, no mortalities or 

signs of systemic toxicity at the highest 

dose tested (2,000 mg/kg-bw).

Submitted Confidential Study Adequate; guideline study (OECD 

423). 

Dermal No data located.

Inhalation No data located.

Carcinogenicity MODERATE: Estimated to have potential for carcinogenicity based on data reported for the epoxide 

oxidation product and structural analogy to bisphenol S. In addition, there is uncertainty due to the lack of 

data for this substance. Carcinogenic effects cannot be ruled out.

OncoLogic Results Not amenable to available estimation 

method.

Carcinogenicity (Rat and 

Mouse)

Potential for carcinogenicity

(Estimated)

Professional judgment Estimated based on potential for the 

epoxide oxidation product and based 

on analogy to bisphenol S.

Combined Chronic 

Toxicity/Carcinogenicity

No data located.

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FINAL REPORT – January 2014 

BPS-MAE CASRN 97042-18-7

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Genotoxicity MODERATE: BPS-MAE was clastogenic in CHL/IU cells with metabolic activation, but did not cause 

mutations in bacterial cells nor cause an increase in the induction of micronucleated immature erythrocytes 

or bone marrow cells in CD-1 mice.

Gene Mutation in vitro Negative, Reverse Mutation assay in 

Salmonella typhimurium strains TA98, 

TA100, TA1535, and TA1537 and 

Escherichia coli WP2 uvrA/pKM101 

with and without metabolic activation.

Cytotoxicity was observed in 

Salmonella typhimurium strains TA98, 

TA1535, and TA1537 in the presence of 

activation at 5000 μg/plate.

Submitted Confidential Study Adequate; guideline study (OECD 

471). 

Gene Mutation in vivo No data located.

Chromosomal Aberrations 

in vitro

Positive for chromosome aberrations 

with activation in the CHL/IU cell line; 

the incidences of cells with structural 

chromosome aberrations was 6.0% 

(1250 μg/mL), 7.5% (2500 μg/mL) and

11% (5000 μg/ml) with metabolic 

activation.

Submitted Confidential Study Adequate; guideline study (Japanese 

Guidelines on Industrial Chemicals 

(1997) and OECD Guideline (1997)). 

Chromosomal Aberrations 

in vivo

BPS-MAE did not cause an increase in 

the induction of micronucleated 

immature erythrocytes or bone marrow 

cells following oral gavage exposure to 

CD-1 mice.

Submitted Confidential Study Adequate; guideline study (OECD 

474). 

DNA Damage and Repair No data located.

Other (Mitotic Gene 

Conversion)

No data located.

Reproductive Effects MODERATE: Estimated based on analogy to bisphenol S. In a reproduction/developmental toxicity 

screening test, oral exposure of parental rats to the analog bisphenol S resulted in marked systemic effects 

and the NOAEL for reproductive effects is 60 mg/kg-day (prolonged estrous cycle, decreased fertility index

and decreased number of live offspring). Based on the NOAEL for reproductive effects, a Moderate hazard 

designation is selected.

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FINAL REPORT – January 2014 

BPS-MAE CASRN 97042-18-7

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Reproduction/ 

Developmental Toxicity 

Screen

Parental toxicity:

NOAEL = 10 mg/kg bw-day 

LOAEL = 60 mg/kg bw-day 

Reproductive toxicity: 

NOAEL = 60 mg/kg bw-day 

LOAEL = 300 mg/kg bw-day

(Estimated by analogy)

ECHA, 2011; Professional 

judgment 

Using the analog bisphenol S, data are 

for an adequate guideline study 

(OECD 421) reported in a secondary 

source. 

Combined Repeated Dose 

with Reproduction/ 

Developmental Toxicity 

Screen

No data located.

Reproduction and Fertility 

Effects

Potential for male reproductive toxicity

(Estimated)

Professional judgment Estimated based on reported data for 

the epoxide oxidation product and on 

reported experimental data for the 

analog bisphenol S.

Developmental Effects MODERATE: Estimated based on analogy to bisphenol S. In a reproduction/developmental toxicity 

screening test, oral exposure of parental rats to the analog bisphenol S resulted in marked systemic effects 

and decreased number of live offspring (PND 4) at the highest dose level (300 mg/kg-day with a NOAEL of 60 

mg/kg-day. Based on the NOAEL, a Moderate hazard designation is selected.

Reproduction/ 

Developmental Toxicity 

Screen

Parental toxicity:

NOAEL = 10 mg/kg bw-day 

LOAEL = 60 mg/kg bw-day 

Reproductive toxicity: 

NOAEL = 60 mg/kg bw-day 

LOAEL = 300 mg/kg bw-day

(Estimated by analogy)

ECHA, 2011; Professional 

judgment 

Using the analog bisphenol S, data are 

for an adequate guideline study 

(OECD 421) reported in a secondary 

source. 

4-337 
FINAL REPORT – January 2014 

BPS-MAE CASRN 97042-18-7

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Potential for developmental toxicity

(Estimated)

Professional judgment Estimated based on reported data for 

the epoxide oxidation product and on 

reported experimental data for the 

analog bisphenol S.

Combined Repeated Dose 

with Reproduction/ 

Developmental Toxicity 

Screen

No data located.

Prenatal Development No data located.

Postnatal Development No data located.

Neurotoxicity MODERATE: Estimated to have potential for neurotoxicity based on the presence of the phenol structural 

alert.

Neurotoxicity Screening 

Battery (Adult)

There is potential for neurotoxicity 

effects based on the presence of the 

phenol structural alert. 

(Estimated)

U.S. EPA, 2010; Professional 

judgment 

Estimated based on structural alert.

Repeated Dose Effects LOW: Effects from BPS-MAE were limited to increased kidney weights at 1,000 mg/kg/day in a 28-day 

repeated-dose toxicity study in rats.

Adverse effects were limited to higher 

absolute and relative kidney weights in 

female Crj:CD (SD) IGS rats at 1,000 

mg/kg-bw; NOEL = 1,000 mg/kgbw/day (males) and 200 mg/kg-bw/day 

(females).

Submitted Confidential Study Adequate; guideline study (OECD 

407). 

Skin Sensitization LOW: BPS-MAE was not a skin sensitizer in one study of guinea pigs.

Skin Sensitization Negative for skin sensitization in 

Dunkin Hartley guinea pigs.

Submitted Confidential Study Adequate; guideline study (OECD 

406).

Respiratory Sensitization MODERATE: BPS-MAE is estimated to have potential to be a respiratory sensitizer based on the epoxide 

oxidation product.

Respiratory Sensitization Potential for respiratory sensitization Professional judgment Estimated based on reported data for 

the epoxide oxidation product.

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FINAL REPORT – January 2014 

BPS-MAE CASRN 97042-18-7

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Eye Irritation LOW: Minimal conjunctival irritation was observed that cleared by the 24-hour observation.

Eye Irritation Slight irritant (maximum group mean 

score: 2.7) in New Zealand White 

rabbits, minimal conjunctival irritation, 

treated eyes appeared normal at the 24-

hour observation.

Submitted Confidential Study Adequate; guideline study (OECD 

405). 

Dermal Irritation VERY LOW: BPS-MAE was not a dermal irritant in one study of rabbits.

Dermal Irritation Non-irritant (primary irritation index: 0) 

in New Zealand White rabbits.

Submitted Confidential Study Adequate; guideline study (OECD 

404).

Endocrine Activity No data located.

No data located.

Immunotoxicity No data located.

Immune System Effects No data located.

ECOTOXICITY

ECOSAR Class Phenols; Vinyl/allyl ethers

Acute Toxicity HIGH: Based on measured EC50 values for fish, daphnia, and algae of 4.5, 13.5, and 4.5 mg/L, respectively.

Fish LC50 Rainbow trout (Oncorhynchus mykiss) 

96-hour LC50 = 4.5 mg/L; mean 

measured concentrations; static-renewal 

test system; solvent: 

dimethylformamide (DMF); sub-lethal 

effects included loss of equilibrium, 

hyperventilation, lying on base of tank, 

increased pigmentation, and erratic 

swimming.

Submitted Confidential Study Adequate; guideline study (OECD 

203). 

Fish 96-hour LC50 = 27 mg/L 

(Estimated) 

ECOSAR: neutral organics

ECOSAR version 1.11 Narcosis classes (neutral organics) are 

provided for comparative purposes; 

DfE assessment methodology will use 

the lowest estimated toxicity value 

provided by ECOSAR classes that 

have a more specific mode of action 

relative to narcosis.

4-339 
FINAL REPORT – January 2014 

BPS-MAE CASRN 97042-18-7

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Fish 96-hour LC50 = 8 mg/L (Estimated)

ECOSAR: phenols

ECOSAR version 1.11

Fish 96-hour LC50 = 1.7 mg/L 

(Estimated) 

ECOSAR: Vinyl/allyl ethers

ECOSAR version 1.11

Daphnid LC50 Daphnia magna 48-hour EC50 = 

13.5 mg/L; mean measured 

concentrations; static test system; 

solvent: DMF.

Submitted Confidential Study Adequate; guideline study (OECD 

202). 

Daphnid 48-hour LC50 = 17 mg/L 

(Estimated) 

ECOSAR: neutral organics

ECOSAR version 1.11 Narcosis classes (neutral organics) are 

provided for comparative purposes; 

DfE assessment methodology will use 

the lowest estimated toxicity value 

provided by ECOSAR classes that 

have a more specific mode of action 

relative to narcosis.

Daphnid 48-hour LC50 = 3.8 mg/L 

(Estimated) 

ECOSAR: phenols

ECOSAR version 1.11

Daphnid 48-hour LC50 = 7.9 mg/L 

(Estimated) 

ECOSAR: Vinyl/allyl ethers

ECOSAR version 1.11

Green Algae EC50 Pseudokirchneriella subcapitata 72-

hour EC50 = 4.5 mg/L (biomass), 7.8 

mg/L (growth rate); mean measured 

concentrations; solvent: DMF.

Submitted Confidential Study Adequate; guideline study (OECD 

201). 

Green algae 96-hour EC50 = 19 mg/L 

(Estimated) 

ECOSAR: neutral organics

ECOSAR version 1.11 Narcosis classes (neutral organics) are 

provided for comparative purposes; 

DfE assessment methodology will use 

the lowest estimated toxicity value 

provided by ECOSAR classes that 

have a more specific mode of action 

relative to narcosis.

4-340 
FINAL REPORT – January 2014 

BPS-MAE CASRN 97042-18-7

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Green algae 96-hour EC50 = 16 mg/L 

(Estimated) 

ECOSAR: phenols

ECOSAR version 1.11

Green algae 96-hour EC50 = 18 mg/L 

(Estimated) 

ECOSAR: Vinyl/allyl ethers

ECOSAR version 1.11

Chronic Aquatic Toxicity HIGH: Based on measured fish and Daphnid ChV values of 0.162 mg/L and 0.102 mg/L, respectively.

Fish ChV Fathead minnow (Pimephales promelas) 

32-day NOEC = 0.0939 mg/L, LOEC = 

0.28 mg/L, ChV (MATC) = 0.162 

mg/L; mean measured concentrations; 

flow-through test system; solvent: 

tetrahydrofuran (THF); basis of effect 

level: survival.

Submitted Confidential Study Adequate; guideline study (OECD 

210). 

Fish ChV = 3 mg/L

(Estimated) 

ECOSAR: neutral organics

ECOSAR version 1.11 Narcosis classes (neutral organics) are 

provided for comparative purposes; 

DfE assessment methodology will use 

the lowest estimated toxicity value 

provided by ECOSAR classes that 

have a more specific mode of action 

relative to narcosis.

Fish ChV = 0.940 mg/L

(Estimated) 

ECOSAR: phenols

ECOSAR version 1.11

Fish ChV = 0.047 mg/L

(Estimated) 

ECOSAR: Vinyl/allyl ethers

ECOSAR version 1.11

4-341 
FINAL REPORT – January 2014 

BPS-MAE CASRN 97042-18-7

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Daphnid ChV Daphnia magna 21-day NOEC= 0.0664 

mg/L, LOEC= 0.157 mg/L, ChV = 

0.102 mg/L; mean measured 

concentrations; static-renewal test 

system; solvent: DMF; basis of effect 

level: parental survival and 

reproduction.

Submitted Confidential Study Adequate; guideline study (OECD 

211). 

Daphnid ChV = 2.2 mg/L

(Estimated) 

ECOSAR: neutral organics

ECOSAR version 1.11 Narcosis classes (neutral organics) are 

provided for comparative purposes; 

DfE assessment methodology will use 

the lowest estimated toxicity value 

provided by ECOSAR classes that 

have a more specific mode of action 

relative to narcosis.

Daphnid ChV = 0.73 mg/L

(Estimated) 

ECOSAR: phenols

ECOSAR version 1.11

Daphnid ChV = 1.9 mg/L

(Estimated) 

ECOSAR: Vinyl/allyl ethers

ECOSAR version 1.11

Green Algae ChV Pseudokirchneriella subcapitata 72-

hour NOEC = 1.8 mg/L, LOEC = 3.7 

mg/L, ChV = 2.6 mg/L; mean measured

concentrations; solvent: DMF.

Submitted Confidential Study Adequate; guideline study (OECD 

201). 

Green algae ChV = 6.1 mg/L

(Estimated) 

ECOSAR: neutral organics

ECOSAR version 1.11 Narcosis classes (neutral organics) are 

provided for comparative purposes; 

DfE assessment methodology will use 

the lowest estimated toxicity value 

provided by ECOSAR classes that 

have a more specific mode of action 

relative to narcosis.

4-342 
FINAL REPORT – January 2014 

BPS-MAE CASRN 97042-18-7

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Green algae ChV = 7.4 mg/L

(Estimated) 

ECOSAR: phenols

ECOSAR version 1.11

Green algae ChV = 3.5 mg/L

(Estimated) 

ECOSAR: Vinyl/allyl ethers

ECOSAR version 1.11

Earthworm Subchronic Toxicity Earthworm 14-day LC50 = 

100.029 mg/L 

(Estimated) 

ECOSAR: phenols

ECOSAR version 1.11

ENVIRONMENTAL FATE

Transport BPS-MAE is expected to exist in both neutral and anionic forms at environmentally-relevant pH, based on its 

estimated pKa. The neutral form of BPS-MAE is expected to be immobile in soil based on its estimated Koc. 

The anionic form may be more mobile although leaching of BPS-MAE through soil to groundwater is not 

expected to be an important transport mechanism. Estimated volatilization half-lives indicate that it will be 

nonvolatile from surface water. Volatilization from dry surface is also not expected based on its estimated 

vapor pressure. In the atmosphere, BPS-MAE is expected to exist solely in the particulate phase based on its 

estimated vapor pressure. Particulates may be removed from air by wet or dry deposition. Level III fugacity 

models incorporating the available experimental property data indicate that the unionized form of BPS-MAE 

is expected to partition primarily to soil.

Henry’s Law Constant 

(atm-m3/mole)

<1x10-8 (Estimated) EPI; Professional judgment Cutoff value for nonvolatile 

compounds. 

Sediment/Soil 

Adsorption/Desorption

Coefficient – Koc

3.0x103 (Estimated) EPI

Level III Fugacity Model Air = <1% (Estimated)

Water = 11%

Soil = 87%

Sediment = 2%

EPI

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FINAL REPORT – January 2014 

BPS-MAE CASRN 97042-18-7

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Persistence HIGH: High persistence concern for BPS-MAE results from an estimated half-life of 75 days in soil, the 

compartment where according to fugacity models; it is expected to primarily partition. Evaluation of QSARs 

models estimate ultimate biodegradation in weeks to months, which suggest a biodegradation half-life of 

<60 days with no persistent metabolites in aquatic environments. Biodegradation under anaerobic 

methanogenic conditions is not probable based on results from estimation models. BPS-MAE is not expected 

to undergo hydrolysis since it does not contain hydrolyzable functional groups. The atmospheric half-life of 

BPS-MAE is estimated at 3 hours although it is expected to exist primarily in the particulate phase in air.

Water Aerobic Biodegradation Days-weeks (primary survey model)

Weeks-months (ultimate survey model)

EPI

Volatilization Half-life 

for Model River

>1 year (Estimated) EPI

Volatilization Half-life 

for Model Lake

>1 year (Estimated) EPI

Soil Aerobic Biodegradation No data located.

Anaerobic 

Biodegradation

Not probable (anaerobic-methanogenic 

biodegradation probability model)

EPI

Soil Biodegradation w/ 

Product Identification

No data located.

Sediment/Water 

Biodegradation

No data located.

Air Atmospheric Half-life 3.0 hours (Estimated) EPI

Reactivity Photolysis Not a significant fate process 

(Estimated)

Mill, 2000; Professional judgment Substance does not contain functional 

groups that would be expected to 

absorb light at wavelengths >290 nm.

Hydrolysis Not a significant fate process 

(Estimated)

Wolfe and Jeffers, 2000; 

Professional judgment 

Substance does not contain functional 

groups that would be expected to 

hydrolyze readily under environmental 

conditions.

Pyrolysis No data located.

4-344 
FINAL REPORT – January 2014 

BPS-MAE CASRN 97042-18-7

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Environmental Half-life 75 days (Estimated) EPI; PBT Profiler Half-life estimated for the 

predominant compartment, as 

determined by EPI and the PBT 

Profiler methodology.

Bioaccumulation LOW: The estimated BCF and BAF are both <100.

Fish BCF 48 (Estimated) EPI

BAF 76 (Estimated) EPI

Metabolism in Fish No data located.

ENVIRONMENTAL MONITORING AND BIOMONITORING 

Environmental Monitoring No data located.

Ecological Biomonitoring No data located.

Human Biomonitoring This chemical was not included in the NHANES biomonitoring report (CDC, 2011).

4-345 
FINAL REPORT – January 2014 

CDC (Centers for Disease Control and Prevention). Fourth national report on human exposure to environmental chemicals, updated 

tables. Department of Health and Human Services. 2011. http://www.cdc.gov/exposurereport/ (accessed on May 10, 2011). 

ECHA (European Chemicals Agency). Information on registered substances. http://apps.echa.europa.eu/registered/registered-sub.aspx

(accessed February 18, 2011). 

ECOSAR (2012) Ecological Structure Activity Relationship (ECOSAR) Version 1.11. Washington, DC: U.S. Environmental 

Protection Agency. http://www.epa.gov/oppt/newchems/tools/21ecosar.htm. 

EPI (EPIWIN/EPISUITE) Estimations Programs Interface for Windows, Version 4.00. U.S. Environmental Protection Agency: 

Washington D.C. http://www.epa.gov/opptintr/exposure/. 

ESIS (European chemical Substances Information System) Classification, labeling and Packaging of dangerous substances annex VI 

to regulation (EC) No 1272/2008 [Online] http://esis.jrc.ec.europa.eu/ (accessed on June 10, 2011). 

Mill, T. 2000. Photoreactions in Surface Waters. In Boethling, R.; Mackay, D., Handbook of Property Estimation Methods for 

Chemicals, Environmental Health Sciences (355-382). Boca Raton: Lewis Publishers. 

PBT Profiler Persistent (P), Bioaccumulative (B), and Toxic (T) Chemical (PBT) Profiler, U.S. Environmental Protection Agency: 

Washington D.C. www.pbtprofiler.net. 

SPARC, 2010. SPARC On Line Calculator pKa/property server. Ver 4.5 September, 2009. Available from, 

http://ibmlc2.chem.uga.edu/sparc/ (accessed on August 12, 2010). 

U.S. EPA (Environmental Protection Agency). High Production Volume (HPV) Challenge. Determining the Adequacy of Existing 

Data. U.S. Environmental Protection Agency: Washington D.C. 1999. http://www.epa.gov/hpv/pubs/general/datadfin.htm

U.S. EPA (Environmental Protection Agency). Sustainable Futures Using NonCancer Screening within the Sustainable Futures 

Initiative Environmental Protection Agency: Washington D.C. 2010. http://www.epa.gov/opptintr/sf/pubs/noncanscreen.htm#systemic (accessed on February 09, 2011). 

Wolfe, N.; Jeffers, P. (2000) Hydrolysis. In Boethling, R.; Mackay, D., Handbook of Property Estimation Methods for Chemicals, 

Environmental Health Sciences (311-334). Boca Raton: Lewis Publishers. 

4-346 
FINAL REPORT – January 2014 

BPS-MPE

S

O

O

O OH

CASRN: 63134-33-8

MW: 340.4

MF: C19H16O4S

Physical Forms: 

Neat: Solid

Use: Developer for thermal paper

SMILES: O=S(=O)(c(ccc(OCc(cccc1)c1)c2)c2)c(ccc(O)c3)c3

Synonyms: Phenol, 4-[[4-(phenylmethoxy)phenyl]sulfonyl]-; 4-Benzyloxy-4'-hydroxydiphenyl sulfone; 4-Hydroxy-4’-benzyloxydiphenylsulfone

Polymeric: No

 Oligomers: Not applicable

Metabolites, Degradates and Transformation Products: None

Analog: Bisphenol S (80-09-1)

 Endpoint(s) using analog values: Boiling point, reproductive and 

developmental toxicity, repeated dose toxicity, genotoxicity

Analog Structure: 

Structural Alerts: Phenols, neurotoxicity (U.S. EPA, 2010)

Risk Phrases: Not classified by Annex VI Regulation (EC) No 1272/2008 (ESIS, 2011).

Risk Assessments: None identified

S

O

O

OH OH

4-347 
FINAL REPORT – January 2014 

BPS-MPE CASRN 63134-33-8

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

PHYSICAL/CHEMICAL PROPERTIES

Melting Point (°C) 170 ChemSpider, 2010 Secondary source; study details and 

test conditions were not provided.

Boiling Point (°C) >300 (Estimated) EPI; U.S. EPA, 1999 Cutoff value for high boiling point 

compounds according to the HPV 

assessment guidance; decomposition 

may occur before the boiling point is 

reached based on the experimental 

decomposition temperature of 315°C 

for the analog bisphenol S (80-09-1). 

Vapor Pressure (mm Hg) <1x10-8 (Estimated) EPI; U.S. EPA, 1999 Cutoff value for nonvolatile 

compounds according to the HPV 

assessment guidance.

Water Solubility (mg/L) 10 (Estimated) EPI

Log Kow 3.9 (Estimated) EPI

Flammability (Flash Point) No data located.

Explosivity No data located.

pH No data located.

pKa 8.2 (Estimated) SPARC

4-348 
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BPS-MPE CASRN 63134-33-8

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

HUMAN HEALTH EFFECTS

Toxicokinetics One experimental study indicated that BPS-MPE was not absorbed through the skin in guinea pigs. BPSMPE is estimated not to be absorbed through the skin as a neat material and to have poor skin absorption 

when in solution. BPS-MPE is estimated to have good absorption via the lungs and gastrointestinal tract 

based on data for the analog BPA. 

Dermal Absorption in vitro No data located.

Absorption, 

Distribution, 

Metabolism & 

Excretion

Oral Not absorbed through the skin as a neat 

material and has poor absorption in 

solution; can be absorbed through the lung 

and gastrointestinal tract 

(Estimated by analogy)

Professional judgment Estimated based on experimental data 

for the analog BPA. 

Dermal No evidence of skin absorption at 

1,000 mg/kg; three guinea pigs, solidmoist with water

Eastman Kodak, 1991 Adequate.

Acute Mammalian Toxicity LOW: Based on acute oral LD50 values >2,000 mg/kg in rats and mice. The acute dermal lethality study in 

guinea pigs failed to identify an LD50, although the results indicated that the LD50 was >1,000 mg/kg, the 

highest dose tested.

Acute Lethality Oral Rat LD50 >3,200 mg/kg; 10 male rats, 

moderate weakness and diarrhea

Eastman Kodak, 1991 Adequate.

Mouse LD50 = 3,200 mg/kg; 10 male mice, 

moderate weakness, rough hair coats

Eastman Kodak, 1991 Adequate.

Dermal Guinea pig LD50 >1,000 mg/kg; slight 

edema, desquamation, slight to moderate 

alopecia

Eastman Kodak, 1991 Adequate.

Inhalation No data located.

Carcinogenicity MODERATE: There is uncertain potential for carcinogenicity due to the lack of data located for this 

substance. Carcinogenic effects cannot be ruled out.

OncoLogic Results No data located.

Carcinogenicity (Rat and 

Mouse)

No data located.

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Combined Chronic 

Toxicity/Carcinogenicity

No data located.

Genotoxicity MODERATE: Estimated based on analogy to bisphenol S. Bisphenol S did not induce gene mutations in 

several in vitro assays and did not induce chromosomal aberrations in vivo in a mammalian erythrocyte 

micronucleus assay in NMRI mice or in Chinese hamster ovary (CHO) cells in vitro in the presence of 

exogenous metabolic activation. However, the analog bisphenol S did induce chromosomal aberrations in 

CHO cells in vitro in the absence of exogenous metabolic activation (at a noncytotoxic concentration). The 

positive result in the in vitro assay and negative result in the in vivo test suggest an equivocal response and 

therefore a Moderate hazard potential.

Gene Mutation in vitro Negative, mouse lymphoma L5178Y 

(TK+/TK-) cells, with and without 

metabolic activation 

(Estimated by analogy)

CCRIS database; Professional 

judgment

Adequate; based on experimental data 

measured for the analog bisphenol S. 

Negative, Ames assay (standard plate) in 

Salmonella typhimurium strains TA98, 

TA100, TA1537, TA1535, and TA1538 

with and without metabolic activation

(Estimated by analogy)

CCRIS database; Professional 

judgment

Adequate; based on experimental data 

measured for the analog bisphenol S. 

Negative, Salmonella/microsome test, S.

typhimurium strains TA1535, TA100, 

TA1537, and TA98 with and without 

metabolic activation 

(Estimated by analogy)

Miles Inc., 1992; ECHA, 2011; 

Professional judgment

Adequate; based on experimental data 

measured for the analog bisphenol S 

in an adequate guideline study 

(OECD 471). 

Negative, Ames assay (preincubation) in S. 

typhimurium strains TA98, TA100, 

TA1537, TA1535 and Escherichia coli 

WP2UVRA with and without metabolic 

activation 

(Estimated by analogy)

CCRIS database, 2010; ECHA, 

2011; Professional judgment

Adequate; based on experimental data 

measured for the analog bisphenol S 

in an adequate guideline study 

(OECD 471). 

Negative, umu test in S.typhimurium strain 

TA1335 

(Estimated by analogy)

Chen, Michihiko et al., 2002; 

Professional judgment

Adequate; based on experimental data 

measured for the analog bisphenol S. 

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Negative, CHO HGPRT mutation assay, 

with and without metabolic activation

(Estimated by analogy)

Amoco Corp., 1991a; Professional 

judgment

Adequate; based on experimental data 

measured for the analog bisphenol S. 

Potential for mutagenicity

(Estimated by analogy)

Professional judgment Estimated based on experimental data 

for the analog bisphenol S.

Gene Mutation in vivo No data located.

Chromosomal 

Aberrations in vitro

Positive, without metabolic activation;

negative, with metabolic activation

(Estimated by analogy) 

Amoco Corp., 1991b; ECHA, 

2011; Professional judgment

Adequate; based on experimental data 

measured for the analog bisphenol S 

in an adequate guideline study 

(similar to OECD 473).

Chromosomal 

Aberrations in vivo

Negative, mammalian erythrocyte 

micronucleus assay in male NMRI mice 

(gavage) 

(Estimated by analogy)

ECHA, 2011; Professional 

judgment

Adequate; based on experimental data 

measured for the analog bisphenol S 

in an adequate guideline study 

(OECD 474).

DNA Damage and Repair No data located.

Other (Mitotic Gene 

Conversion)

No data located.

Reproductive Effects MODERATE: Estimated based on analogy to bisphenol S. In a reproductive/developmental toxicity 

screening test, oral exposure of parental rats to the analog bisphenol S resulted in marked systemic effects 

and the NOAEL for reproductive effects is 60 mg/kg-day (prolonged estrous cycle, decreased fertility index 

and decreased number of live offspring). Based on the NOAEL for reproductive effects, a Moderate hazard 

designation is selected.

Reproduction/ 

Developmental Toxicity 

Screen

Parental toxicity:

NOAEL = 10 mg/kg bw-day 

LOAEL = 60 mg/kg bw-day 

Reproductive toxicity: 

NOAEL = 60 mg/kg bw-day 

LOAEL = 300 mg/kg bw-day 

(Estimated by analogy)

ECHA, 2011; Professional 

judgment

Adequate; based on experimental data 

measured for the analog bisphenol S 

in an adequate guideline study 

(OECD 421) reported in a secondary 

source. 

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PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Combined Repeated Dose 

with Reproduction/ 

Developmental Toxicity 

Screen

No data located.

Reproduction and 

Fertility Effects

Potential for reproductive toxicity

(Estimated by analogy)

Professional judgment Estimated based on experimental data 

for the analog bisphenol S.

Developmental Effects MODERATE: Estimated based on analogy to bisphenol S. In a reproductive/developmental toxicity 

screening test, oral exposure of parental rats to the analog bisphenol S resulted in marked systemic effects 

and a decreased number of live offspring (PND 4) at the highest dose level (300 mg/kg-day) with a NOAEL of 

60 mg/kg-day. Based on the NOAEL, a Moderate hazard designation is selected.

Reproduction/ 

Developmental Toxicity 

Screen

Parental toxicity:

NOAEL = 10 mg/kg bw-day 

LOAEL = 60 mg/kg bw-day 

Reproductive toxicity: 

NOAEL = 60 mg/kg bw-day 

LOAEL = 300 mg/kg bw-day

(Estimated by analogy)

ECHA, 2011; Professional 

judgment

Adequate; based on experimental data 

measured for the analog bisphenol S 

in an adequate guideline study 

(OECD 421) reported in a secondary 

source. 

Potential for developmental toxicity

(Estimated by analogy)

Professional judgment Estimated based on experimental data 

for the analog bisphenol S.

Combined Repeated Dose 

with Reproduction/ 

Developmental Toxicity 

Screen

No data located.

Prenatal Development No data located.

Postnatal Development No data located.

Neurotoxicity MODERATE: Estimated to have potential for neurotoxicity based on the presence of the phenol structural 

alert.

Neurotoxicity Screening 

Battery (Adult)

There is potential for neurotoxicity effects 

based on the presence of the phenol 

structural alert. 

(Estimated)

U.S. EPA, 2010; Professional 

judgment

Estimated based on structural alert.

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Repeated Dose Effects HIGH: Based on analogy to bisphenol S. In two adequately-designed repeated dose oral studies in rats, one 

study identified a NOAEL of 10 mg/kg-day and a LOAEL of 60 mg/kg-day for systemic effects and the other 

study identified a NOAEL of 40 mg/kg-day and a LOAEL of 200 mg/kg-day for systemic effects following 

exposure to the analog bisphenol S. The High hazard designation is based on uncertainty as to the potential 

systemic toxicity in the range of 40-60 mg/kg-day. Data located for BPS-MPE are inadequate to assess the

hazard for repeated dose effects.

Oral 12-Day repeated dose oral (dietary) study, 

5 male rats/group, test compound 

concentrations of 0, 0.1, and 1.0% in corn 

oil (~0, 100, and 980 mg/kg-day, 

respectively), slightly increased absolute 

(high dose) and relative (high and low 

dose) liver weights, no abnormalities or 

changes in body weight, clinical 

chemistry, gross pathology, or 

histopathology 

NOAEL = 100 mg/kg-day 

LOAEL = 980 mg/kg-day 

Eastman Kodak, 1991 Inadequate; exposure duration only 

12 days, and only one species tested. 

In a repeated-dose oral study, SpragueDawley rats, NOAEL = 40 mg/kg bw-day 

LOAEL = 200 mg/kg-bw-day 

(Estimated by analogy)

ECHA, 2011; Professional 

judgment

Adequate; based on experimental data 

measured for the analog bisphenol S 

in an adequate 28-day repeat dose 

toxicity guideline study.

In a reproduction/developmental toxicity 

screening test, Sprague-Dawley rats, 

NOAEL = 10 mg/kg bw-day 

LOAEL = 60 mg/kg bw-day 

(Estimated by analogy)

ECHA, 2011; Professional 

judgment

Adequate; based on experimental data 

measured for the analog bisphenol S 

in an adequate guideline study 

(OECD 421). 

Potential for liver and kidney toxicity

(Estimated by analogy)

Professional judgment Estimated based on experimental data 

for the analog bisphenol S.

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PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Dermal 10-Day repeated-dose dermal study, 

5 guinea pigs; repeated dosing slightly 

exacerbated skin reaction; by day 10, 

severe erythema and minute eschar 

formation in 2/5 guinea pigs

Eastman Kodak, 1991 Inadequate; treatment period only 

10 days, no dose level. 

Skin Sensitization LOW: Not an apparent skin sensitizer in guinea pigs.

Skin Sensitization Negative for skin sensitization; 10 guinea 

pigs

Eastman Kodak, 1991 Adequate.

Respiratory Sensitization No data located.

Respiratory Sensitization No data located.

Eye Irritation LOW: Slightly irritating to rabbit eyes with clearing within 24 hours.

Eye Irritation Slight irritant, rabbits, clearing within 

24 hours

Eastman Kodak, 1991 Adequate.

Dermal Irritation LOW: Slightly irritating to the skin of guinea pigs.

Dermal Irritation Slight irritant at 24 hours recovering within 

2 weeks, guinea pigs

Eastman Kodak, 1991 Adequate.

Endocrine Activity No data located.

No data located.

Immunotoxicity No data located.

Immune System Effects No data located.

ECOTOXICITY

ECOSAR Class Phenols

Acute Toxicity VERY HIGH: Based on measured 96-hour LC50 values for fish and Daphnid in the range of 0.34-3.4 mg/L, 

although detailed study results were not provided.

Fish LC50 Fathead minnow 96-hour LC50 = 0.34-

3.4 mg/L (Experimental) 

Eastman Kodak, 1991 Although experimental details were 

not provided, the study demonstrates 

the potential for adverse effects at 

concentrations corresponding to a 

Very High hazard concern.

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PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Fish 96-hour LC50 = 2.01 mg/L 

(Estimated) 

ECOSAR: phenols

ECOSAR version 1.11

Fish 96-hour LC50 = 6.28 mg/L 

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.11 Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided by 

ECOSAR classes that have a more 

specific mode of action relative to 

narcosis.

Daphnid LC50 Daphnid 96-hour LC50 = 0.34-3.4 mg/L

(Experimental) 

Eastman Kodak, 1991 Although experimental details were 

not provided, the study demonstrates 

the potential for adverse effects at 

concentrations corresponding to a 

Very High hazard concern.

Daphnid 48-hour LC50 = 1.46 mg/L

(Estimated) 

ECOSAR: phenols

ECOSAR version 1.11

Daphnid 48-hour LC50 = 4.57 mg/L

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.11 Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided by 

ECOSAR classes that have a more 

specific mode of action relative to 

narcosis.

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BPS-MPE CASRN 63134-33-8

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Green Algae EC50 Green algae 96-hour EC50 = 4.32 mg/L

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.11 Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided by 

ECOSAR classes that have a more 

specific mode of action relative to 

narcosis.

Green algae 96-hour EC50 = 5.58 mg/L

(Estimated) 

ECOSAR: phenols

ECOSAR version 1.11

Chronic Aquatic Toxicity HIGH: Based on an estimated fish 30-day ChV of 0.27 mg/L.

Fish ChV Fish 30-day ChV = 0.27 mg/L 

(Estimated) 

ECOSAR: phenols

ECOSAR version 1.11

Fish ChV = 0.57 mg/L

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.11 Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided by 

ECOSAR classes that have a more 

specific mode of action relative to 

narcosis.

Daphnid ChV Daphnid 21-day ChV = 0.28 mg/L

(Estimated) 

ECOSAR: phenols

ECOSAR version 1.11

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PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Daphnid ChV = 0.59 mg/L

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.11 Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided by 

ECOSAR classes that have a more 

specific mode of action relative to 

narcosis.

Green Algae ChV Green algae ChV = 2.22 mg/L

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.11 Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided by 

ECOSAR classes that have a more 

specific mode of action relative to 

narcosis.

Green algae ChV = 2.56 mg/L

(Estimated) 

ECOSAR: phenols 

ECOSAR version 1.11

Earthworm Subchronic Toxicity Earthworm 14-day LC50 = 52.09 mg/L

(Estimated) 

ECOSAR: phenols

ECOSAR version 1.11 chemical may not be soluble enough 

to measure this predicted effect

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PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

ENVIRONMENTAL FATE

Transport Based on the Level III fugacity models incorporating the located experimental property data, BPS-MPE is 

expected to partition primarily to soil. BPS-MPE is expected to exist in both neutral and anionic forms at 

environmentally-relevant pH, based on its estimated pKa. The neutral form of BPS-MPE is expected to be 

immobile in soil based on its estimated Koc. The anionic form may be more mobile, as anions do not bind as 

strongly to organic carbon and clay as their neutral counterparts. However, leaching of BPS-MPE through 

soil to groundwater is not expected to be an important transport mechanism. Estimated volatilization halflives indicate that it will be nonvolatile from surface water. Volatilization from dry surface is also not 

expected based on its estimated vapor pressure. In the atmosphere, BPE-MPE is expected to exist solely in 

the particulate phase, based on its estimated vapor pressure. Particulates may be removed from air by wet or 

dry deposition. 

Henry’s Law Constant

(atm-m3/mole)

<1x10-8 (Estimated) EPI, Professional judgment Cutoff value for nonvolatile

compounds, based on professional 

judgment.

Sediment/Soil 

Adsorption/Desorption

Coefficient – Koc

>30,000 (Estimated) EPI; U.S. EPA, 2004 Cutoff value for nonmobile 

compounds. 

Level III Fugacity 

Model

Air = <1% (Estimated)

Water = 8.5%

Soil = 75%

Sediment = 16%

EPI

Persistence HIGH: Evaluation of the persistence of BPS-MPE is based entirely on QSARs for aerobic and anaerobic 

biodegradation. Results from these models estimate primary biodegradation in days-weeks and ultimate 

degradation in weeks-months. BPS-MPE is expected to partition primarily to soil. Based on these data, the 

biodegradation half-life is expected to be 75 days in soil. Biodegradation under anaerobic methanogenic 

conditions is not probable. BPS-MPE is not expected to undergo hydrolysis since it does not contain 

hydrolyzable functional groups. BPS-MPS does not absorb UV light at environmentally significant 

wavelengths. The vapor phase reaction of BPS-MPE with atmospheric hydroxyl radicals is estimated at 5.7 

hours, although it is expected to exist primarily in the particulate phase in air. Considerations of all these 

factors indicate that the persistence concern is High for BPS-MPE.

Water Aerobic 

Biodegradation

Days-weeks (Primary survey model)

Weeks-months (Ultimate survey model)

EPI

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PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Volatilization Half-life 

for Model River

>1 year (Estimated) EPI

Volatilization Half-life 

for Model Lake

>1 year (Estimated) EPI

Soil Aerobic 

Biodegradation

No data located.

Anaerobic 

Biodegradation

Not probable (anaerobic-methanogenic 

biodegradation probability model)

EPI

Soil Biodegradation w/ 

Product Identification

No data located.

Sediment/Water 

Biodegradation

No data located.

Air Atmospheric Half-life 5.7 hours (Estimated) EPI

Reactivity Photolysis Not a significant fate process (Estimated) Mill, 2000; Professional judgment The substance does not contain 

functional groups that would be 

expected to absorb light at 

wavelengths >290 nm.

Hydrolysis Not a significant fate process (Estimated) Wolfe and Jeffers, 2000; 

Professional judgment 

The substance does not contain 

functional groups that would be 

expected to hydrolyze readily under 

environmental conditions.

Pyrolysis No data located.

Environmental Half-life 75 days (Estimated) EPI, PBT Profiler Half-life estimated for the 

predominant compartment, as 

determined by EPI and the PBT 

Profiler methodology.

Bioaccumulation MODERATE: Both the estimated BCF for fish and the BAF are in the range from 100 to 1,000.

Fish BCF 180 (Estimated) EPI

BAF 110 (Estimated) EPI

Metabolism in Fish No data located.

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PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

ENVIRONMENTAL MONITORING AND BIOMONITORING 

Environmental Monitoring No data located.

Ecological Biomonitoring No data located.

Human Biomonitoring This chemical was not included in the NHANES biomonitoring report (CDC, 2011).

4-360 
FINAL REPORT – January 2014 

Amoco Corp. CHO/HGPRT mutation assay (final report) with attachment and cover letter dated 111491. TSCATS submission 

OTS0534324. 1991a.

Amoco Corp. Chromosome aberrations in Chinese hamster ovary (CHO) cells (final report) with attachment and cover letter dated 

111491. TSCATS submission OTS0534325. 1991b. 

CCRIS. Chemical Carcinogenesis Research Information System. Bisphenol S. 2010. http://toxnet.nlm.nih.gov/cgibin/sis/htmlgen?CCRIS (accessed on August, 2010). 

Chemspider. ChemSpider; Structure-based Chemistry Information. Royal Society of Chemistry: London. 2010. 

http://www.chemspider.com (accessed on December 11, 2010). 

Chen, M-Y.; Michihiko, I.; Fujita, M. Acute toxicity, mutagenicity, and estrogenicity of bisphenol-A and other bisphenols. Environ. 

Toxicol. 2002, 17:80-86. 

CDC (Centers for Disease Control and Prevention). Fourth national report on human exposure to environmental chemicals, updated 

tables. Department of Health and Human Services. 2011. http://www.cdc.gov/exposurereport/ (accessed on May 10, 2011). 

Eastman Kodak. Letter concerning enclosed information on bisphenol S with attachments. Eastman Kodak Company, Rochester NY. 

TSCATS submission OTS0534330. 1991.

ECHA. European Chemicals Agency. Information on registered substances. http://apps.echa.europa.eu/registered/registered-sub.aspx

(accessed February 18, 2011).

ECOSAR (2012) Ecological Structure Activity Relationship (ECOSAR) Version 1.11. Washington, DC: U.S. Environmental 

Protection Agency. http://www.epa.gov/oppt/newchems/tools/21ecosar.htm. 

EPI (EPIWIN/EPISUITE) Estimations Programs Interface for Windows, Version 4.00. U.S. Environmental Protection Agency: 

Washington D.C. http://www.epa.gov/opptintr/exposure/. 

ESIS (European chemical Substances Information System) Classification, labeling and Packaging of dangerous substances annex VI 

to regulation (EC) No 1272/2008 [Online] http://esis.jrc.ec.europa.eu/ (accessed on June 10, 2011). 

Miles Inc. Salmonella/microsome test (final report) with cover letter dated 04392. TSCATS submission OTS0435648. 1992. 

Mill, T. 2000. Photoreactions in Surface Waters. In Boethling, R.; Mackay, D., Handbook of Property Estimation Methods for 

Chemicals, Environmental Health Sciences (355-382). Boca Raton: Lewis Publishers. 

4-361 
FINAL REPORT – January 2014 

PBT Profiler Persistent (P), Bioaccumulative (B), and Toxic (T) Chemical (PBT) Profiler. U.S. Environmental Protection Agency: 

Washington D.C. www.pbtprofiler.net. 

SPARC On Line Calculator pKa/property server. Ver 4.5 September, 2009. Available from, http://ibmlc2.chem.uga.edu/sparc/

(accessed on August 12, 2010). 

U.S. EPA (Environmental Protection Agency). High Production Volume (HPV) Challenge. Determining the Adequacy of Existing 

Data. U.S. Environmental Protection Agency: Washington D.C. 1999. http://www.epa.gov/hpv/pubs/general/datadfin.htm 

U.S. EPA (Environmental Protection Agency). 2004. The Pollution Prevention (P2) Framework, EPA-748-B-03-001. Office of 

Pollution Prevention and Toxics 7403M, U.S. Environmental Protection Agency, Washington, DC. 20460. October 2003 

version updated in January 2004. Latest version available at http://www.epa.gov/opptintr/newchems/pubs/sustainable/p2framejune05a2.pdf

U.S. EPA (Environmental Protection Agency). Sustainable Futures Using NonCancer Screening within the Sustainable Futures 

Initiative Environmental Protection Agency: Washington D.C. 2010. http://www.epa.gov/opptintr/sf/pubs/noncanscreen.htm#systemic (accessed on February 09, 2011). 

Wolfe, N.; Jeffers, P. (2000) Hydrolysis. In Boethling, R.; Mackay, D., Handbook of Property Estimation Methods for Chemicals, 

Environmental Health Sciences (311-334). Boca Raton: Lewis Publishers. 

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D-8 

S

O

O

O OH

CASRN: 95235-30-6

MW: 292.35

MF: C15H16O4S

Physical Forms:

Neat: Solid

Use: Developer for thermal paper

SMILES: O=S(=O)(c1ccc(O)cc1)c2ccc(OC(C)C)cc2

Name: 4-hydroxyphenyl 4-isoprooxyphenylsulfone

Synonyms: Phenol, 4-[[4-(1-methylethoxy)phenyl]sulfonyl]-; 4-(4-isopropoxyphenylsulfonyl)phenol; Phenol, 4-[[4-(1-methylethoxy)phenyl]sulfonyl]-; 4-Hydroxy4-isopropoxydiphenylsulfone; D-8; DD-8; ALD-2000

Polymeric: No

 Oligomers: Not applicable

Metabolites, Degradates and Transformation Products: None identified

Analog: Bisphenol S (80-09-1)

 Endpoint(s) using analog values: Reproductive effects, developmental effects, and repeated 

dose effects 

Analog: BPS-MPE (63134-33-8) 

Endpoint(s) using analog values: Acute mammalian toxicity; eye irritation; dermal irritation; 

skin sensitization

Analog Structures:

Structure:

Name: Bisphenol S (80-09-1) BPS-MPE (63134-33-8)

Structural Alerts: Phenols, neurotoxicity (U.S. EPA, 2010)

Risk Phrases: 51/53 - Toxic to aquatic organisms, may cause long-term adverse effects in the aquatic environment (ESIS, 2011).

Risk Assessments: None identified

S

O

O

O OH

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D-8 CASRN 95235-30-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

PHYSICAL/CHEMICAL PROPERTIES

Melting Point (°C) 129 (Measured) Submitted confidential study Adequate.

129.3 (Measured)

at 101.3 kPa; using capillary method 

ECHA, 2013 Reported in a secondary source.

Boiling Point (°C) >300 (Estimated) EPI; U.S. EPA, 1999 Decomposition may occur before the 

boiling point is reached based on the 

experimental decomposition 

temperature. Cutoff value for high 

boiling point compounds according to 

HPV assessment guidance.

260 (Measured)

at 101.3 kPa

ECHA, 2013 Reported in a secondary source with 

limited study details.

Decomposes (Measured)

reported as 363 K at 2.128 kPa using 

Siwoloboff method 

ECHA, 2013 Reported in a secondary source. This 

compound was found to decompose at 

a reduced pressure of 2.128 kPa. 

Vapor Pressure (mm Hg) <1x10-8 (Estimated) EPI; U.S. EPA, 1999 Cutoff value for nonvolatile 

compounds according to HPV 

assessment guidance.

<7.5x10-7 (Measured) 

reported as < 0.0001 Pa 

at 27°C using gas saturation method

ECHA, 2013 Cutoff value reported in a secondary 

source. 

<7.5x10-8 (Measured) 

reported as < 0.00001 Pa at 27°C

ECHA, 2013

Water Solubility (mg/L) 21 (Measured) Submitted confidential study Adequate.

19.7 (Measured)

at pH of 6.85; 25°C

ECHA, 2013 Reported in a secondary source.

Log Kow 3.36 (Measured)

using shake-flask method

ECHA, 2013 Reported in a secondary source.

Flammability (Flash Point) Auto flammability temperature: ≥129°C ECHA, 2013 Cutoff value reported in a secondary 

source.

Explosivity No data located.

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D-8 CASRN 95235-30-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

pH No data located.

pKa 8.2 (Estimated) SPARC

HUMAN HEALTH EFFECTS

Toxicokinetics D-8 is estimated not to be absorbed through the skin as the neat material and have poor skin absorption 

when in solution. D-8 is estimated to have good absorption via the lungs and gastrointestinal tract based on 

data for the analog BPA.

Dermal Absorption in vitro No data located.

Absorption, 

Distribution, 

Metabolism & 

Excretion

Oral, Dermal or Inhaled Estimated to not be absorbed through the 

skin as neat material and has poor 

absorption in solution. Can be absorbed 

through the lung and gastrointestinal 

tract 

(Estimated by analogy)

Professional judgment Estimated based on reported 

experimental data for the analog BPA.

Acute Mammalian Toxicity LOW: Based on experimental oral, dermal and inhalation data.

Acute Lethality Oral Rat LD50 >3,200 mg/kg; 10 male rats, 

moderate weakness and diarrhea

Eastman Kodak, 1991 Adequate.

Mouse LD50 = 3,200 mg/kg; 10 male 

mice, moderate weakness, rough hair 

coats

Eastman Kodak, 1991 Adequate.

Rat, LD50 > 5,000 mg/kg ECHA, 2013 Limited study details reported in a 

secondary source.

Dermal Guinea pig LD50 >1,000 mg/kg; slight 

edema, desquamation, slight to moderate 

alopecia

Eastman Kodak, 1991 Adequate.

Rat LD50 > 2,000 mg/kg ECHA, 2013 Limited study details reported in a 

secondary source.

Inhalation Rat LC50 > 5.04 mg/L ECHA, 2013 Limited study details reported in a 

secondary source.

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D-8 CASRN 95235-30-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Carcinogenicity MODERATE: There is uncertain potential for carcinogenicity due to the lack of data for this substance. 

Carcinogenic effects cannot be ruled out.

OncoLogic Results No data located.

Carcinogenicity (Rat and 

Mouse)

No data located.

Combined Chronic 

Toxicity/Carcinogenicity

No data located.

Genotoxicity LOW: This substance is not mutagenic in bacteria and does not cause chromosome aberrations in Chinese 

hamster lung cells in vitro, or in mice in vivo.

Gene Mutation in vitro Potential for mutagenicity

(Estimated)

Professional judgment Estimated by analogy to confidential 

analog and professional judgment.

Negative, reverse mutation assay in S.

typhimurium TA98, TA100, TA1535, 

TA1538

Submitted confidential study; 

ECHA, 2013 

Adequate.

Gene Mutation in vivo No data located.

Chromosomal Aberrations 

in vitro

Negative, chromosomal aberrations in 

Chinese hamster lung cells 

(Measured)

Submitted confidential study; 

ECHA, 2013

Adequate.

Chromosomal Aberrations 

in vivo

Negative, chromosomal aberrations in 

male/female NMRI mice

ECHA, 2013 Limited study details reported in a 

secondary source.

DNA Damage and Repair No data located.

Other (Mitotic Gene 

Conversion)

No data located.

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D-8 CASRN 95235-30-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Reproductive Effects MODERATE: Estimated based on analogy to bisphenol S. In a reproduction/developmental toxicity 

screening test, oral exposure of parental rats to the analog bisphenol S resulted in marked systemic effects 

and the NOAEL for reproductive effects is 60 mg/kg-day (prolonged estrous cycle, decreased fertility index 

and decreased number of live offspring). Based on the NOAEL for reproductive effects, a Moderate hazard 

designation is selected.

Reproduction/ 

Developmental Toxicity 

Screen

Parental toxicity:

NOAEL = 10 mg/kg bw-day 

LOAEL = 60 mg/kg bw-day 

Reproductive toxicity: 

NOAEL = 60 mg/kg bw-day 

LOAEL = 300 mg/kg bw-day

(Estimated by analogy)

ECHA, 2011; Professional 

judgment

Adequate; using the analog bisphenol 

S, data are for an adequate guideline 

study (OECD 421) reported in a 

secondary source.

One-generation oral (gavage) study in 

rats

Parental NOEL = 125 mg/kg-day 

F1 NOEL = 125 mg/kg-day

ECHA, 2013 No study details reported in a 

secondary source; administered doses 

not specified; unclear if a LOAEL 

was identified.

Combined Repeated Dose 

with Reproduction/ 

Developmental Toxicity 

Screen

No data located.

Reproduction and Fertility 

Effects

Potential for reproductive toxicity

(Estimated by analogy) 

Professional judgment Estimated based on reported 

experimental data for the analog 

bisphenol S.

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PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Developmental Effects MODERATE: Estimated based on analogy to bisphenol S. In a reproduction/developmental toxicity 

screening test, oral exposure of parental rats to the analog bisphenol S resulted in marked systemic effects 

and decreased number of live offspring (PND 4) at the highest dose level (300 mg/kg-day with a NOAEL of 

60 mg/kg-day. Based on the NOAEL, a Moderate hazard designation is selected.

Reproduction/ 

Developmental Toxicity 

Screen

Parental toxicity:

NOAEL = 10 mg/kg bw-day 

LOAEL = 60 mg/kg bw-day 

Reproductive toxicity: 

NOAEL = 60 mg/kg bw-day 

LOAEL = 300 mg/kg bw-day

(Estimated by analogy)

ECHA, 2011; Professional 

judgment

Adequate; using the analog bisphenol 

S, data are for an adequate guideline 

study (OECD 421) reported in a 

secondary source.

Potential for developmental toxicity

(Estimated by analogy) 

Professional judgment Estimated based on reported 

experimental data for the analog 

bisphenol S.

Combined Repeated Dose 

with Reproduction/ 

Developmental Toxicity 

Screen

No data located.

Prenatal Development No data located.

Postnatal Development No data located.

Neurotoxicity MODERATE: Estimated to have potential for neurotoxicity based on the presence of the phenol structural 

alert.

Neurotoxicity Screening 

Battery (Adult)

There is potential for neurotoxicity 

effects based on the presence of the 

phenol structural alert. 

(Estimated)

U.S. EPA, 2010; Professional 

judgment

Estimated based on structural alert.

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D-8 CASRN 95235-30-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Repeated Dose Effects MODERATE: There were no significant effects observed in a 90-day oral toxicity test in rats at doses ≤50 

mg/kg-day (highest dose tested). This value falls within the Moderate hazard criteria (10-100 mg/kg-day). 

There is uncertainty if there would be adverse effects occurring at doses between 50 and 100 mg/kg-day so 

the hazard designation is assigned a Moderate for this endpoint.

90-day repeated dose oral study in CLR: 

(WI) BR Wistar rats

NOAEL = 50 mg/kg-day (highest dose 

tested) 

LOAEL = not established

Submitted confidential study; 

ECHA, 2013

Adequate; conducted to OECD 

guideline 408. A LOAEL could not be 

established because there were no 

effects. 

Subchronic oral (dietary) repeated dose 

study in F344 rats 

NOAEL = 10.9 mg/kg-day (males), 11.9 

mg/kg-day (females); actual doses 

received

ECHA, 2013 Limited study details reported in a 

secondary source; administered doses 

not specified; unclear if a LOAEL 

was identified.

Skin Sensitization LOW: Estimated based on analogy to BPS-MPE. Not considered a skin sensitizer for guinea pigs based on 

analog data for BPS-MPE.

Skin Sensitization Negative for skin sensitization; 

10 guinea pigs

Eastman Kodak, 1991 Adequate.

Respiratory Sensitization No data located.

Respiratory Sensitization No data located.

Eye Irritation LOW: Estimated based on analogy to BPS-MPE. The analog bisphenol BPS-MPE was non-irritating to 

slightly irritating to rabbit eyes.

Eye Irritation Slight irritant, rabbits, clearing within 

24 hours

Eastman Kodak, 1991 Adequate.

No eye irritation in rabbits ECHA, 2013 Limited study details reported in a 

secondary source.

Dermal Irritation LOW: Estimated based on analogy to BPS-MPE. The analog bisphenol BPS-MPE was slightly irritating to 

guinea pig skin.

Dermal Irritation Slight irritant at 24 hours recovering 

within 2 weeks, guinea pigs

Eastman Kodak, 1991 Adequate.

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PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

No skin irritation reported in rabbits ECHA, 2013 Limited study details reported in a 

secondary source.

Endocrine Activity Based on several in vitro studies, there is limited evidence of endocrine activity. D-8 was negative for 

estrogenicity in two ER binding assays and one competitive ER binding assay, and positive for antiestrogenicity in a competitive binding assay in the presence of 17β-estradiol.

Negative for ER binding in yeast twohybrid assay using human and medaka 

fish estrogen receptor (hERα and 

medERα, respectively) and coactivator 

TIF2 in Saccharomyces cerevisiae with 

or without exogenous metabolic 

activation.

Terasaki et al., 2007 Adequate.

Negative for competitive ER-binding 

affinity in ER-ELISA assay with or 

without exogenous metabolic activation.

Terasaki et al., 2007 Adequate.

Positive for anti-estrogenic activity in 

cell proliferation assay of ERE-GFPMCF7 cells treated with 17β-estradiol.

Kuruto-Niwa et al., 2005 Adequate.

Negative for estrogenic activity in cell 

proliferation assay of ERE-GFP-MCF7 

cells in the absence of 17β-estradiol.

Kuruto-Niwa et al., 2005 Adequate.

Immunotoxicity No data located.

Immune System Effects No data located.

ECOTOXICITY

ECOSAR Class Phenols

Acute Toxicity HIGH: Based on an experimental EC50 for algae, which is in the range of 1-10 mg/L. Estimated LC50s for 

fish and Daphnid also fall within the High hazard category criteria, while experimental data for fish and 

Daphnid are within the Moderate hazard criteria range.

Fish LC50 Oryzias latipes 96-hour LC50 = 18.8 

mg/L (nominal) 

(semi-static test conditions)

ECHA, 2013 Limited study details reported in a 

secondary source.

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D-8 CASRN 95235-30-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Fish 96-hour LC50 = 6.64 mg/L

(Estimated) 

ECOSAR: phenols

ECOSAR version 1.00

Fish 96-hour LC50 = 25.58 mg/L

(Estimated) 

ECOSAR: neutral organics

ECOSAR version 1.00 Narcosis classes (neutral organics) are 

provided for comparative purposes; 

DfE assessment methodology will use 

the lowest estimated toxicity value 

provided by ECOSAR classes that 

have a more specific mode of action 

relative to narcosis.

Daphnid LC50 Daphnia magna 48-hour EC50 = 12 

mg/L

(static test conditions)

ECHA, 2013 Limited study details reported in a 

secondary source.

Daphnia magna 48-hour EC50 = 21 mg/L

(static test conditions)

ECHA, 2013 Limited study details reported in a 

secondary source.

Daphnid 48-hour LC50 = 3.56 mg/L

(Estimated) 

ECOSAR: phenols

ECOSAR version 1.00

Daphnid 48-hour LC50 = 16.89 mg/L

(Estimated) 

ECOSAR: neutral organics

ECOSAR version 1.00 Narcosis classes (neutral organics) are 

provided for comparative purposes; 

DfE assessment methodology will use 

the lowest estimated toxicity value 

provided by ECOSAR classes that 

have a more specific mode of action 

relative to narcosis.

Green Algae EC50 Pseudokirchnerella subcapitata 72-hour 

EC50 = 2.22 mg/L 

ECHA, 2013 Limited study details reported in a 

secondary source.

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D-8 CASRN 95235-30-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Green algae 96-hour EC50 = 11.52 mg/L

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.00 Narcosis classes (neutral organics) are 

provided for comparative purposes; 

DfE assessment methodology will use 

the lowest estimated toxicity value 

provided by ECOSAR classes that 

have a more specific mode of action 

relative to narcosis.

Green algae 96-hour EC50 = 14.70 mg/L

(Estimated) 

ECOSAR: phenols

ECOSAR version 1.00

Chronic Aquatic Toxicity HIGH: Based on estimated ChVs for fish and Daphnid, which are in the range of 0.1-1 mg/L. One 

experimental study in Daphnia reported a 21-day LC50 value of 2.7 mg/L; however, a NOEC was not 

reported. No chronic aquatic toxicity studies were located for fish or algae.

Fish ChV Fish 30-day ChV = 0.69 mg/L

(Estimated) 

ECOSAR: phenols

ECOSAR version 1.00

Fish 60-day ChV = 2.37 mg/L

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.00 Narcosis classes (neutral organics) are 

provided for comparative purposes; 

DfE assessment methodology will use 

the lowest estimated toxicity value 

provided by ECOSAR classes that 

have a more specific mode of action 

relative to narcosis.

Daphnid ChV Daphnia magna 21-day LC50 = 2.7 mg/L 

(static test conditions) 

No NOEC reported

ECHA, 2013 Limited study details reported in a 

secondary source.

Daphnid 21-day ChV = 0.68 mg/L

(Estimated)

ECOSAR: phe

nols

ECOSAR version 1.00

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D-8 CASRN 95235-30-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Daphnid 21-day ChV = 1.90 mg/L

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.00 Narcosis classes (neutral organics) are 

provided for comparative purposes; 

DfE assessment methodology will use 

the lowest estimated toxicity value 

provided by ECOSAR classes that 

have a more specific mode of action 

relative to narcosis.

Green Algae ChV Green algae ChV = 5.11 mg/L 

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.00 Narcosis classes (neutral organics) are 

provided for comparative purposes; 

DfE assessment methodology will use 

the lowest estimated toxicity value 

provided by ECOSAR classes that 

have a more specific mode of action 

relative to narcosis.

Green algae ChV = 5.11 mg/L 

(Estimated) 

ECOSAR: phenols

ECOSAR version 1.00

Earthworm Subchronic Toxicity Earthworm 14-day LC50 = 6.81 mg/L

(Estimated) 

ECOSAR: phenols

ECOSAR version 1.00

ENVIRONMENTAL FATE

Transport Evaluation of D-8 transport is based entirely on estimations on QSARs for fugacity (level III), disassociation 

constant (pKa), soil adsorption coefficient (Koc), volatilization, and vapor pressure. If released to air, an 

estimated vapor pressure of <1x10-8 mm Hg at 25°C indicates that D-8 will exist in the particulate phase in 

the atmosphere. Particulate-phase D-8 will be removed from the atmosphere by wet or dry deposition. If 

released to soil, D-8 is expected to have moderate mobility based upon an estimated Koc of 2,500. 

Volatilization from water surfaces is not expected to be an important fate process based upon this 

compound's estimated Henry's Law constant.

Henry’s Law Constant 

(atm-m3/mole)

<1x10-8 (Estimated) EPI Cutoff value for nonvolatile 

compounds based on professional 

judgment. 

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D-8 CASRN 95235-30-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Sediment/Soil Adsorption/

Desorption

Coefficient – Koc

2.5x103 (Estimated) EPI

Level III Fugacity Model Air = 0% (Estimated)

Water = 11%

Soil = 87%

Sediment = 2%

EPI

Persistence MODERATE: Based on experimental biodegradation study results that indicate D-8 will undergo aerobic 

biodegradation in domestic activated sludge. A Dissovled Organic Carbon (DOC) removal test 

demonstrated 85% degradation of D-8 after 81 days. D-8 was also found to have 31-60% degradation after 

39 days in a CO2 evolution test.

Water Aerobic Biodegradation Days-weeks (primary survey model)

Weeks-months (ultimate survey model)

EPI

Study results: 31-60%/39 days

Test method: CO2 evolution

10-20 mg/L test material in domestic, 

activated sludge screening test

(Measured)

ECHA, 2013 Nonguideline study reported in a 

secondary source.

No data located.

Volatilization Half-life for 

Model River

>1 year (Estimated) EPI

Volatilization Half-life for 

Model Lake

>1 year (Estimated) EPI

Soil Aerobic Biodegradation No data located.

Anaerobic 

Biodegradation

Not probable (anaerobic-methanogenic 

biodegradation probability model)

EPI

Soil Biodegradation w/ 

Product Identification

No data located.

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D-8 CASRN 95235-30-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Sediment/Water 

Biodegradation

Study results: 85%/81 days

Test method: DOC removal

15, 25, 50 mg/L test material in 

domestic, activated non-adapted sludge 

simulation test

(Measured)

ECHA, 2013 Nonguideline study reported in a 

secondary source.

Air Atmospheric Half-life 5.3 hours (Estimated) EPI

Reactivity Photolysis Not a significant fate process 

(Estimated)

Mills, 2000; Professional 

judgment

The substance does not contain 

functional groups that would be 

expected to absorb light at 

environmentally significant 

wavelengths.

Hydrolysis Not a significant fate process 

(Estimated)

Wolfe and Jeffers, 2000; 

Professional judgment

The substance does not contain 

functional groups that would be 

expected to hydrolyze readily under 

environmental conditions.

Reported as the recovery of test 

substance with no method indicated: 

>96% to <102% recovery at pH 4.07, 7.1 

and 8.92; at 50°C after ≥24 to ≤120 

hours (Measured)

ECHA, 2013 Nonguideline study reported in a 

secondary source with limited details.

Pyrolysis No data located.

Environmental Half-life 75 days EPI; PBT Profiler Half-life estimated for the 

predominant compartment, as 

determined by EPI and the PBT 

Profiler methodology.

Bioaccumulation MODERATE: The measured fish BCF values are less than 1000.

Fish BCF >27-<78 after 28 days

>40-<132 after 42 days 

in Carp (Measured)

ECHA, 2013 Nonguideline study reported in a 

secondary source.

BAF 83 (Estimated) EPI

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D-8 CASRN 95235-30-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Metabolism in Fish No data located.

ENVIRONMENTAL MONITORING AND BIOMONITORING 

Environmental Monitoring No data located.

Ecological Biomonitoring No data located.

Human Biomonitoring This chemical was not included in the NHANES biomonitoring report (CDC, 2011).

4-376 
FINAL REPORT – January 2014 

CDC (Centers for Disease Control and Prevention). Fourth national report on human exposure to environmental chemicals, updated 

tables. Department of Health and Human Services. 2011. http://www.cdc.gov/exposurereport/ (accessed on May 10, 2011). 

Eastman Kodak. Letter concerning enclosed information on bisphenol S with attachments. Eastman Kodak Company, Rochester NY. 

TSCATS submission OTS0534330. 1991.

ECHA (European Chemicals Agency). Information on registered substances. http://apps.echa.europa.eu/registered/registered-sub.aspx

(accessed February 18, 2011) 

ECHA (European Chemicals Agency). Information on registered substances. http://apps.echa.europa.eu/registered/registered-sub.aspx

(accessed September 30, 2013) 

ECOSAR (2010) Ecological Structure Activity Relationship (ECOSAR) Version 1.00. Washington, DC: U.S. Environmental 

Protection Agency. http://www.epa.gov/oppt/newchems/tools/21ecosar.htm. 

EPI (EPIWIN/EPISUITE) Estimations Programs Interface for Windows, Version 4.00. U.S. Environmental Protection Agency: 

Washington D.C. http://www.epa.gov/opptintr/exposure/. 

ESIS (European chemical Substances Information System) Classification, labeling and Packaging of dangerous substances annex VI 

to regulation (EC) No 1272/2008 [Online] http://esis.jrc.ec.europa.eu/ (accessed on June 10, 2011). 

Kuruto-Niwa, R., Nozawa, R., Miyakoshi, T., et al. Estrogenic activity of alkylphenols, bisphenol S, and their chlorinated derivatives 

using a GFP expression system. Environ. Toxicol. Pharmacol. 2005, 19:121-130. 

Mill, T. 2000. Photoreactions in Surface Waters. In Boethling, R.; Mackay, D., Handbook of Property Estimation Methods for 

Chemicals, Environmental Health Sciences (355-382). Boca Raton: Lewis Publishers. 

PBT Profiler Persistent (P),Bioaccumulative (B), and Toxic (T) Chemical (PBT)Profiler, U.S. Environmental Protection Agency: 

Washington D.C. www.pbtprofiler.net. 

SPARC On Line Calculator pKa/property server. Ver 4.5 September, 2009. Available from, http://ibmlc2.chem.uga.edu/sparc/ 

(accessed on August 12, 2010). 

Terasaki, M., Shiraishi, F., Fukazawa, H., et al. Occurrence and estrogenicity of phenolics in paper-recycling process water: 

Pollutants originating from thermal paper in waste paper. Environ. Toxicol. Chem. 2007, 26(11):2356-2366. 

U.S. EPA (Environmental Protection Agency). High Production Volume (HPV) Challenge. Determining the Adequacy of Existing 

Data. U.S. Environmental Protection Agency: Washington D.C. 1999. http://www.epa.gov/hpv/pubs/general/datadfin.htm 

4-377 
FINAL REPORT – January 2014 

U.S. EPA (Environmental Protection Agency). Sustainable Futures Using NonCancer Screening within the Sustainable Futures 

Initiative Environmental Protection Agency: Washington D.C. 2010. http://www.epa.gov/opptintr/sf/pubs/noncanscreen.htm#systemic (accessed on February 09, 2011). 

Wolfe, N.; Jeffers, P. (2000) Hydrolysis. In Boethling, R.; Mackay, D., Handbook of Property Estimation Methods for Chemicals, 

Environmental Health Sciences (311-334). Boca Raton: Lewis Publishers. 

4-378 
FINAL REPORT – January 2014 

D-90 

S

O

O

HO O O O S

O

O

O

n

H

4-379 

CASRN: 191680-83-8

MW: 570.63 (n = 1)

 891.00 (n = 2) 

MF: C28H26O9S2 (n = 1)

 C44H42O14S3 (n = 2)

Physical Forms:

Neat: Solid

Use: Developer for thermal paper

SMILES: (n = 1): O=S(C1=CC=C(OCCOCCOC2=CC=C(S(=O)(C3=CC=C(O)C=C3)=O)C=C2)C=C1)(C4=CC=C(O)C=C4)=O

(n = 2): O=S(C1=CC=C(OCCOCCOC2=CC=C(S(=O)(C3=CC=C(OCCOCCOC4=CC=C(S(=O)(C5=CC=C(O)C=C5)=O)C=C4)C=C3)=O)C=C2)C=C1)(C6=CC=C 

(O)C=C6)=O

Synonyms: Bis(2-chloroethyl)ether-4,4'-dihydroxydiphenyl sulfone copolymer; Ethane, 1,1'-oxybis(2-chloro-, polymer with 4,4'-sulfonylbis(phenol); Phenol, 4,4'-

sulfonylbis-, polymer with 1,1'-oxybis(2-chloroethane); 4,4'-Dihydroxydiphenyl sulfone- 2,2'-dichlorodiethyl ether copolymer; 4,4'-Dihydroxydiphenyl sulfonebis(2-chloroethyl) ether copolymer

Polymeric: Yes

 Oligomers: Two representative structures for the low MW oligomers evaluated in this assessment are indicated above (n = 1 or 2). These representative structures 

are anticipated to be the predominant components of the polymeric mixture. 

Metabolites, Degradates and Transformation Products: None identified

Analog: No analogs

 Endpoint(s) using analog values: Not applicable

Analog Structure: Not applicable

Structural Alerts: Phenols, neurotoxicity (U.S. EPA, 2010)

Risk Phrases: Not classified by Annex VI Regulation (EC) No 1272/2008 (ESIS, 2011).

Risk Assessments: None identified
FINAL REPORT – January 2014 

D-90 CASRN 191680-83-8

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

PHYSICAL/CHEMICAL PROPERTIES

Melting Point (°C) No data located.

Boiling Point (°C) >300 (Estimated for n = 1 and n = 2) EPI; U.S. EPA, 1999 Estimates were performed on 

representative components of the 

polymer that have a MW <1,000; 

those with n = 1 or 2. Higher 

oligomers are expected to have a 

similar value. Cutoff value for high 

boiling point compounds according 

to HPV assessment guidance.

Vapor Pressure (mm Hg) <1x10-8 (Estimated for n = 1 and n = 2) EPI; U.S. EPA, 1999 Estimates were performed on 

representative components of the 

polymer that have a MW <1,000; 

those with n = 1 or 2. Higher 

oligomers are expected to have a 

similar value. Cutoff value for 

nonvolatile compounds according to 

HPV assessment guidance.

Water Solubility (mg/L) 0.54 (n = 1) (Estimated) EPI Estimates performed on 

representative components of the 

polymer indicated.

<1x10-3 (n = 2) (Estimated) EPI; U.S. EPA, 1999 Estimates performed on 

representative components of the 

polymer indicated. Cutoff value for 

non-soluble compounds according to 

HPV assessment guidance.

Log Kow 3.8 (n = 1) (Estimated) EPI Estimates performed on 

representative components of the 

polymer indicated.

5.9 (n = 2) (Estimated) EPI Estimates performed on 

representative components of the 

polymer indicated.

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PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Flammability (Flash Point) No data located.

Explosivity No data located.

pH No data located.

pKa 6.9-7.5 (Estimated, identical values 

obtained for both n = 1 and n = 2) 

ACD/Labs, 2010 SMILES notation was too long for 

SPARC estimations, which were 

used for the other chemicals 

assessed, and an alternative 

estimation method was used.

HUMAN HEALTH EFFECTS

Toxicokinetics No data located.

Dermal Absorption in vitro No data located.

Absorption, 

Distribution, 

Metabolism & 

Excretion

Oral, Dermal or Inhaled No data located.

Acute Mammalian Toxicity LOW: D-90 was not toxic following acute exposure, based on the acute oral and dermal LC50 values of 

>2,000 mg/kg-bw in rats.

Acute Lethality Oral Rat (Sprague-Dawley CD) oral LD50

>2,000 mg/kg bw; no mortalities or signs 

of systemic toxicity at the highest dose 

tested (2,000 mg/kg bw).

Submitted confidential study Adequate; guideline study (OECD 

401). 

Dermal Rat (Sprague-Dawley CD) dermal LD50

>2,000 mg/kg bw; no mortalities or signs 

of systemic toxicity at the highest dose 

tested (2,000 mg/kg bw).

Submitted confidential study Adequate; guideline study (OECD 

402). 

Inhalation No data located.

Carcinogenicity MODERATE: There is uncertainty due to the lack of data for this substance. Carcinogenic effects cannot 

be ruled out.

OncoLogic Results No data located.

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PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Carcinogenicity (Rat and 

Mouse)

No data located.

Combined Chronic 

Toxicity/Carcinogenicity

No data located.

Genotoxicity LOW: D-90 does not cause mutations in bacterial cells in vitro and is not clastogenic in human lymphocytes 

in vitro.

Gene Mutation in vitro Negative, reverse mutation assay in 

Salmonella typhimurium strains TA98, 

TA100, TA1535, and TA1537 and 

Escherichia coli WP2 uvrA with and 

without metabolic activation.

Submitted confidential study Adequate; non-standard guideline 

study (Japanese guideline for 

mutagenicity tests using 

microorganisms). 

Gene Mutation in vivo No data located.

Chromosomal Aberrations 

in vitro

Non-clastogenic, chromosome 

aberrations test in human lymphocytes 

with and without activation.

Submitted confidential study Adequate; guideline study (OECD 

473). 

Chromosomal Aberrations 

in vivo

No data located.

DNA Damage and Repair No data located.

Other (Mitotic Gene 

Conversion)

No data located.

Reproductive Toxicity LOW: A combination of limited predicted absorption, low predicted metabolism, and lack of significant 

toxicological concerns from repeated dose testing suggests low potential for reproductive effects based on 

professional judgment.

Reproduction/ 

Developmental Toxicity 

Screen

Low potential for reproductive toxicity

(Estimated)

Professional judgment Estimated based on predicted limited 

absorption, low metabolism, lack of 

evidence from repeated dose studies.

Combined Repeated Dose 

with Reproduction/ 

Developmental Toxicity 

Screen

No data located.

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D-90 CASRN 191680-83-8

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Reproduction and Fertility 

Effects

No data located.

Developmental Toxicity LOW: A combination of limited predicted absorption, low predicted metabolism, and lack of significant 

toxicological concerns from repeated dose testing suggests low potential for developmental effects based on 

professional judgment.

Reproduction/ 

Developmental Toxicity 

Screen

Low potential for developmental toxicity

(Estimated)

Professional judgment Estimated based on predicted limited 

absorption, low metabolism, lack of 

evidence from repeated dose studies.

Combined Repeated Dose 

with Reproduction/ 

Developmental Toxicity 

Screen

No data located.

Prenatal Development No data located.

Postnatal Development No data located.

Neurotoxicity MODERATE: Estimated to have potential for neurotoxicity based on the presence of the phenol structural 

alert.

Neurotoxicity Screening 

Battery (Adult)

There is potential for neurotoxicity 

effects based on the presence of the 

phenol structural alert. 

(Estimated)

U.S. EPA, 2010, Professional 

judgment 

Estimated based on structural alert.

4-383 
FINAL REPORT – January 2014 

D-90 CASRN 191680-83-8

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Repeated Dose Effects LOW: D-90 did not cause mortality or systemic effects at oral doses as high as 1,000 mg/kg-day in a 28-day 

repeated-dose toxicity study in rats.

No adverse effects (e.g., mortality;

clinical signs; and changes in body

weights, food consumption, urinalysis 

data, hematology data, gross pathology, 

organ weights, organ-to-body weight 

ratios or histopathology) were observed 

in a 28-day oral (gavage) study in male 

and female Fischer 344 rats; increases in 

y-glutamyl transpeptidase was observed 

in females exposed to 300 and 

1,000 mg/kg-bw-day, which did not 

correspond to histopathological effects. 

NOEL = 1,000 mg/kg-bw-day (highest 

dose tested)

Submitted confidential study Adequate; not specified as a 

guideline study, but follows general 

OECD guidelines. 

Skin Sensitization LOW: D-90 was not a skin sensitizer in one study of guinea pigs.

Skin Sensitization Negative for skin sensitization, Dunkin 

Hartley guinea pigs

Submitted confidential study Adequate; guideline study (OECD 

406).

Respiratory Sensitization No data located.

Respiratory Sensitization No data located.

Eye Irritation MODERATE: Iridial inflammation and moderate conjunctival irritation were observed up to the 48- or 

72-hour observation in one study of rabbits.

Eye Irritation Irritant (maximum group mean score: 

13), iridial inflammation and moderate 

conjunctival irritation, treated eyes 

appeared normal at the 48- or 72-hour 

observation, New Zealand White rabbits

Submitted confidential study Adequate; guideline study (OECD 

405). 

Dermal Irritation VERY LOW: D-90 was not a dermal irritant in one study of rabbits.

Dermal Irritation Non-irritant (primary irritation index: 0), 

New Zealand White rabbits

Submitted confidential study Adequate; guideline study (OECD 

404).

4-384 
FINAL REPORT – January 2014 

D-90 CASRN 191680-83-8

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Endocrine Activity No data located.

No data located. 

Immunotoxicity No data located.

Immune System Effects No data located.

ECOTOXICITY

ECOSAR Class Phenols, poly

Acute Toxicity LOW: Based on estimated 96-hour LC50 for fish, 48-hour LC50 for Daphnid, and 96-hour EC50 for green 

algae that result in no effects at saturation (NES), as obtained for representative components of the 

polymer that have a MW <1,000. Higher MW components of the polymer are expected to have similar 

behavior.

Fish LC50 Fish 96-hour LC50 = 4.76 mg/L (n = 1)

(Estimated) 

ECOSAR: phenols, poly

ECOSAR version 1.11 NES for representative component 

of the polymer with a MW <1,000. 

Fish 96-hour LC50 = 0.31 mg/L (n = 2)

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.11 NES for representative component 

of the polymer with a MW <1,000. 

Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided by 

ECOSAR classes that have a more 

specific mode of action relative to 

narcosis.

4-385 
FINAL REPORT – January 2014 

D-90 CASRN 191680-83-8

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Daphnid LC50 Daphnid 48-hour LC50 = 9.46 mg/L 

(n = 1) (Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.11 NES for representative component 

of the polymer with a MW <1,000. 

Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided by 

ECOSAR classes that have a more 

specific mode of action relative to 

narcosis.

Daphnid 48-hour LC50 = 0.29 mg/L 

(n = 2) (Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.11 NES for representative component 

of the polymer with a MW <1,000. 

Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided by 

ECOSAR classes that have a more 

specific mode of action relative to 

narcosis.

Green Algae EC50 Green algae 96-hour EC50 = 3.36 mg/L 

(n = 1) (Estimated) 

ECOSAR: phenols, poly

ECOSAR version 1.11 NES for representative component 

of the polymer with a MW <1,000. 

Green algae 96-hour EC50 = 0.63 mg/L 

(n = 2) (Estimated) 

ECOSAR: phenols, poly

ECOSAR version 1.11 NES for representative component 

of the polymer with a MW <1,000. 

Chronic Aquatic Toxicity LOW: Based on ChV values for fish, Daphnid, and green algae that result in no effects at saturation

(NES), as obtained for representative components of the polymer that have a MW <1,000. Higher MW 

components of the polymer are expected to have similar behavior.

Fish ChV Fish 30-day ChV = 1.08 mg/L (n = 1)

(Estimated) 

ECOSAR: phenols, poly

ECOSAR version 1.11 NES for representative component 

of the polymer with a MW <1,000. 

4-386 
FINAL REPORT – January 2014 

D-90 CASRN 191680-83-8

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Fish 30-day ChV = 0.027 mg/L (n = 2)

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.11 NES for representative component 

of the polymer with a MW <1,000 

Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided by 

ECOSAR classes that have a more 

specific mode of action relative to 

narcosis..

Daphnid ChV Daphnid ChV = 1.20 mg/L (n = 1)

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.11 NES for representative component 

of the polymer with a MW <1,000. 

Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided by 

ECOSAR classes that have a more 

specific mode of action relative to 

narcosis.

Daphnid ChV = 0.054 mg/L (n = 2)

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.11 NES for representative component 

of the polymer with a MW <1,000. 

Narcosis classes (neutral organics) 

are provided for comparative 

purposes; DfE assessment 

methodology will use the lowest 

estimated toxicity value provided by 

ECOSAR classes that have a more 

specific mode of action relative to 

narcosis.

Green Algae ChV Green algae ChV = 0.51 mg/L (n = 1)

(Estimated) 

ECOSAR: phenols, poly

ECOSAR version 1.11 NES for representative component 

of the polymer with a MW <1,000. 

4-387 
FINAL REPORT – January 2014 

D-90 CASRN 191680-83-8

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Green algae ChV = 0.206 mg/L (n = 2)

(Estimated) 

ECOSAR: phenols, poly

ECOSAR version 1.11 NES for representative component 

of the polymer with a MW <1,000. 

ENVIRONMENTAL FATE

Transport Evaluation of D-90 transport is based entirely on estimations on QSARs that were performed on two 

representative components of the polymer (n = 1 and n = 2) that are a MW <1,000, although the higher 

MW oligomers are anticipated to behave similarly. These representative structures are anticipated to be 

the predominate components of the polymeric mixture. D-90 is expected to have low mobility in soil based 

on its expected strong absorption to soil. If released to the atmosphere, D-90 is likely to exist solely as 

particulate. As a particulate, atmospheric oxidation is not expected to be a significant route of 

environmental removal. Level III fugacity models indicate that D-90 will partition predominantly to the soil 

and sediment.

Henry’s Law Constant 

(atm-m3/mole)

<1x10-8 (Estimated for n = 1 and n = 2) Professional judgment; EPI Estimates were performed on 

representative components of the 

polymer that have a MW <1,000; 

those with n = 1 or 2. Higher 

oligomers are expected to have a 

similar value. Cutoff value for 

nonvolatile compounds based on 

professional judgment.

Sediment/Soil 

Adsorption/Desorption

Coefficient – Koc

>30,000 (Estimated for n = 1 and n = 2) EPI; U.S. EPA, 2004 Estimates were performed on 

representative components of the 

polymer that have a MW <1,000; 

those with n = 1 or 2. Higher 

oligomers are expected to have a 

similar value. Cutoff value for 

nonmobile compounds. 

4-388 
FINAL REPORT – January 2014 

D-90 CASRN 191680-83-8

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Level III Fugacity 

Estimations 

Estimated for n = 1: 

Air = 0% 

Water = 3%

Soil = 57%

Sediment = 40%

EPI Estimates performed on 

representative components of the 

polymer indicated. 

Estimated for n = 2: 

Air = 0% 

Water = 1% 

Soil = 52%

Sediment = 48%

EPI Estimates performed on 

representative components of the 

polymer indicated. 

Persistence VERY HIGH: Evaluation of D-90 persistence is based entirely on estimations that were performed on two 

representative components of the polymer (n = 1 and n = 2) that have a MW <1,000 and are anticipated to 

be the predominant component of the polymeric mixture. Primary aerobic degradation was estimated to be 

in the order of weeks for both representative structures. Ultimate biodegradation was estimated to be in the 

order of months for the n = 1 polymer, and the n = 2 polymer was estimated to be recalcitrant. Estimated 

volatilization half-lives of >1 year for both representative structures indicate that volatilization is not 

expected to occur. D-90 does not contain functional groups that absorb light at environmentally-relevant 

wavelengths, and is not expected to be susceptible to direct photolysis. Atmospheric hydroxyl-radical 

photooxidation half-lives were estimated to be 2.5 and 1.4 hours, respectively. However, this is not expected 

to be an important removal process since D-90 is expected to exist in the particulate phase in the 

atmosphere. Higher MW components of the polymer are expected to have similar persistence behavior.

Water Aerobic Biodegradation Weeks (primary survey model; n = 1 )

Months (ultimate survey model; n = 1) 

Weeks (primary survey model; n = 2) 

Recalcitrant (ultimate survey model; 

n = 2)

EPI Estimates performed on 

representative components of the 

polymer indicated. 

Volatilization Half-life 

for Model River

>1 year (Estimated for n = 1 and n = 2) EPI Estimates performed on 

representative components of the 

polymer indicated.

4-389 
FINAL REPORT – January 2014 

D-90 CASRN 191680-83-8

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Volatilization Half-life 

for Model Lake

>1 year (Estimated for n = 1 and n = 2) EPI Estimates performed on 

representative components of the 

polymer indicated.

Soil Aerobic Biodegradation No data located.

Anaerobic 

Biodegradation 

Not probable (anaerobic-methanogenic 

biodegradation probability model; for 

n = 1 and n = 2)

EPI Estimates performed on 

representative components of the 

polymer that have a MW <1,000; 

those with n = 1 or 2; higher 

oligomers are expected to have a 

similar value.

Soil Biodegradation w/ 

Product Identification

No data located.

Sediment/Water 

Biodegradation

No data located.

Air Atmospheric Half-life 2.5 hours (Estimated for n = 1 for 

hydroxyl radical reaction assuming a 12-

hour day and a hydroxyl radical 

concentration of 1.5x106 OH/cm3

);

1.4 hours (Estimated for n = 2 for 

hydroxyl radical reaction assuming a 

12-hour day and a hydroxyl radical 

concentration of 1.5x106 OH/cm3)

EPI Estimates performed on 

representative components of the 

polymer that have a MW <1,000; 

those with n = 1 or 2; higher 

oligomers are expected to have a 

similar value.

Reactivity Photolysis Not a significant fate process (Estimated) Mill, 2000; Professional 

judgment 

Substance does not contain 

functional groups that would be 

expected to absorb light at 

wavelengths >290 nm.

Hydrolysis Not a significant fate process (Estimated) Wolfe and Jeffers, 2000; 

Professional judgment 

Substance does not contain 

functional groups that would be 

expected to hydrolyze readily under 

environmental conditions.

Pyrolysis No data located.

4-390 
FINAL REPORT – January 2014 

D-90 CASRN 191680-83-8

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Environmental Half-life 120 days in soil 540 days in sediment 

(Estimated for n =1) 

360 days in soil; 

1,600 days in sediment (Estimated for n = 

2) 

EPI; PBT Profiler Half-life estimated for the 

predominant compartment, as 

determined by EPI and the PBT 

Profiler methodology; estimates 

were performed on representative 

components of the polymer 

indicated.

Bioaccumulation HIGH: The estimated BAF value for the low MW oligomers with n = 2 is >1,000, indicating that this 

component has the potential to bioaccumulate.

Fish BCF 149 (n = 1) (Estimated) EPI Estimates performed on 

representative components of the 

polymer indicated.

166 (n = 2) (Estimated) EPI Estimates performed on 

representative components of the 

polymer indicated.

BAF 163 (n = 1) (Estimated) EPI Estimates performed on 

representative components of the 

polymer indicated.

4,270 (n = 2) (Estimated) EPI Estimates performed on 

representative components of the 

polymer indicated.

Metabolism in Fish No data located.

ENVIRONMENTAL MONITORING AND BIOMONITORING 

Environmental Monitoring No data located.

Ecological Biomonitoring No data located.

Human Biomonitoring This chemical was not included in the NHANES biomonitoring report (CDC, 2011).

4-391 
FINAL REPORT – January 2014 

ACD/Labs, 2010. ACD/LogP, version 5.0, Advanced Chemistry Development, Inc., Toronto, ON, Canada, www.acdlabs.com, 2010. 

CDC (Centers for Disease Control and Prevention). Fourth national report on human exposure to environmental chemicals, updated 

tables. Department of Health and Human Services. 2011. http://www.cdc.gov/exposurereport/ (accessed on May 10, 2011). 

ECOSAR (2012) Ecological Structure Activity Relationship (ECOSAR) Version 1.11. Washington, DC: U.S. Environmental 

Protection Agency. http://www.epa.gov/oppt/newchems/tools/21ecosar.htm. 

EPI (EPIWIN/EPISUITE) Estimations Programs Interface for Windows, Version 4.00. U.S. Environmental Protection Agency: 

Washington D.C. http://www.epa.gov/opptintr/exposure/. 

ESIS (European chemical Substances Information System) Classification, labeling and Packaging of dangerous substances annex VI 

to regulation (EC) No 1272/2008 [Online] http://esis.jrc.ec.europa.eu/ (accessed on June 10, 2011). 

Mill, T. 2000. Photoreactions in Surface Waters. In Boethling, R.; Mackay, D., Handbook of Property Estimation Methods for 

Chemicals, Environmental Health Sciences (355-382). Boca Raton: Lewis Publishers. 

PBT Profiler Persistent (P),Bioaccumulative (B), and Toxic (T) Chemical (PBT)Profiler. U.S. Environmental Protection Agency: 

Washington D.C. www.pbtprofiler.net. 

U.S. EPA (Environmental Protection Agency). High Production Volume (HPV) Challenge. Determining the Adequacy of Existing 

Data. U.S. Environmental Protection Agency: Washington D.C. 1999. http://www.epa.gov/hpv/pubs/general/datadfin.htm

U.S. EPA (Environmental Protection Agency). 2004. The Pollution Prevention (P2) Framework, EPA-748-B-03-001. Office of 

Pollution Prevention and Toxics 7403M, U.S. Environmental Protection Agency, Washington, DC. 20460. October 2003 

version updated in January 2004. Latest version available at http://www.epa.gov/opptintr/newchems/pubs/sustainable/p2framejune05a2.pdf 

U.S. EPA (Environmental Protection Agency). Sustainable Futures Using NonCancer Screening within the Sustainable Futures 

Initiative Environmental Protection Agency: Washington D.C. 2010. http://www.epa.gov/opptintr/sf/pubs/noncanscreen.htm#systemic (accessed on February 09, 2011). 

Wolfe, N.; Jeffers, P. (2000) Hydrolysis. In Boethling, R.; Mackay, D., Handbook of Property Estimation Methods for Chemicals, 

Environmental Health Sciences (311-334). Boca Raton: Lewis Publishers. 

4-392 
FINAL REPORT – January 2014 

DD-70 

OH

S

O O

S

OH

4-393 

CASRN: 93589-69-6

MW: 352.5

MF: C17H20O4S2

Physical Forms: 

Neat: Solid

Use: Developer for thermal paper

SMILES: Oc1ccc(cc1)SCCOCOCCSc2ccc(cc2)O

Synonyms: Phenol, 4,4'-(methylenebis(oxy-2,1-ethanediylthio))bisPolymeric: No

 Oligomers: Not applicable

Metabolites, Degradates and Transformation Products: None identified

Analog: Confidential analog (structure not available)

 Endpoint(s) using analog values: Developmental toxicity, repeated 

dose toxicity, skin sensitization, and skin and eye irritation.

Analog Structure: Not applicable

Structural Alerts: Phenols, neurotoxicity (U.S. EPA, 2010)

Risk Phrases: 51/53 - Toxic to aquatic organisms, may cause long-term adverse effects in the aquatic environment (ESIS, 2011).

Risk Assessments: None identified
FINAL REPORT – January 2014 

DD-70 CASRN 93589-69-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

PHYSICAL/CHEMICAL PROPERTIES

Melting Point (°C) 108 (Measured) Submitted 

confidential study

Adequate.

Boiling Point (°C) >350 (Estimated) EPI; U.S. EPA, 1999 Cutoff value for high boiling 

compounds according to HPV 

assessment guidance.

Vapor Pressure (mm Hg) <1x10-8 (Estimated) EPI; U.S. EPA, 1999 Cutoff value for nonvolatile 

compounds according to HPV 

assessment guidance.

Water Solubility (g/L) 0.13 (Estimated) EPI

Log Kow 3.4 (Estimated) EPI

Flammability (Flash Point) No data located.

Explosivity No data located.

pH No data located.

pKa 9.6 (Estimated) SPARC

4-394 
FINAL REPORT – January 2014 

DD-70 CASRN 93589-69-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

HUMAN HEALTH EFFECTS

Toxicokinetics DD-70, as a neat material, is estimated to not be absorbed through the skin and have poor skin absorption 

when in solution. DD-70 is expected to be poorly absorbed via the lungs and gastrointestinal tract.

Dermal Absorption in vitro No data located.

Absorption, 

Distribution, 

Metabolism & 

Excretion

Oral, Dermal or Inhaled Not absorbed through the skin as neat 

material and has poor absorption in 

solution. Poorly absorbed through the 

lung and gastrointestinal tract

(Estimated by analogy)

Professional judgment Based on closely related confidential 

analog with similar structure, 

functional groups, and 

physical/chemical properties. 

Acute Mammalian Toxicity LOW: Acute mammalian toxicity is estimated for DD-70 based on high MW, lack of absorption, and the 

absence of structural alerts.

Acute Lethality Oral Low potential for acute mammalian 

toxicity

(Estimated)

Professional judgment Estimated based on professional 

judgment. 

Dermal No data located.

Inhalation No data located.

Carcinogenicity MODERATE: Estimated using OncoLogic expert system, which describes a concern for this compound as a 

potential carcinogen or tumorigenesis promoter arising from its structural similarity to 

estrogenic/androgenic compounds, using the “phenols and phenolic compounds” structural alert.

OncoLogic Results Moderate (Estimated)

OncoLogic class: phenols and phenolic 

compounds 

OncoLogic OncoLogic SAR analysis using the 

phenols and phenolic compounds class. 

Carcinogenicity (Rat and 

Mouse)

No data located.

Combined Chronic 

Toxicity/Carcinogenicity

No data

Genotoxicity LOW: Based on professional judgment, the absence of structural alerts suggests lower concern. 

Gene Mutation in vitro Low potential for genotoxicity toxicity

(Estimated)

Professional judgment Estimated based on professional 

judgment.

Gene Mutation in vivo No data located.

4-395 
FINAL REPORT – January 2014 

DD-70 CASRN 93589-69-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Chromosomal Aberrations 

in vitro

No data located.

Chromosomal Aberrations 

in vivo

No data located.

DNA Damage and Repair No data located.

Other (Mitotic Gene 

Conversion)

No data located.

Reproductive Effects MODERATE: There are no data and no appropriate analog for this endpoint, however an analog for DD-70 

is toxicologically active in repeated dose and developmental toxicity studies. Based on professional judgment, 

potential reproductive toxicity cannot be ruled out. 

Reproduction/ 

Developmental Toxicity 

Screen

No data located.

Combined Repeated Dose 

with Reproduction/ 

Developmental Toxicity 

Screen

No data located.

Reproduction and Fertility 

Effects

No data located.

Developmental Effects MODERATE: Based on confidential analog. Unspecified effects occurred at a dose of 100 mg/kg-day in a 

developmental study in rats.

Developmental Toxicity 

Screen

Rabbit, oral, developmental study

NOAEL = 300 mg/kg-day 

(Estimated by analogy)

Professional judgment Estimated based on available test data 

for a confidential analog.

Rat, oral, developmental study

LOAEL = 100 mg/kg-day (NOAEL not 

established) 

(Estimated by analogy)

Professional judgment Estimated based on available test data 

for a confidential analog.

4-396 
FINAL REPORT – January 2014 

DD-70 CASRN 93589-69-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Neurotoxicity MODERATE: Estimated to have potential for neurotoxicity based on the presence of the phenol structural 

alert.

Neurotoxicity Screening 

Battery (Adult)

There is potential for neurotoxicity effects 

based on the presence of the phenol 

structural alert. 

(Estimated)

U.S. EPA, 2010; Professional 

judgment

Estimated based on structural alert.

Repeated Dose Effects MODERATE: Based on a confidential analog. Repeated dose effects including blood toxicity, severe 

gastrointestinal irritation and histopathological changes to the glandular stomach occurred at doses 

>50 mg/kg-day. Because the LOAEL is not specified, there is uncertainty as to the dose at which these effects 

occur. Using a conservative approach in the absence of a specified LOAEL, a Moderate hazard concern is 

selected because it is possible that effects can occur at doses between 50 and 100 mg/kg-day.

Rat, 13-week oral exposure

Blood toxicity, severe gastrointestinal 

irritation, histopathogical changes in the 

glandular stomach

NOAEL = 50 mg/kg-day 

LOAEL = not identified

(Estimated by analogy)

Professional judgment Estimated based on available test data 

for a confidential analog.

Skin Sensitization MODERATE: Based on confidential analog. DD-70 may potentially cause dermal sensitization.

Skin Sensitization Positive for dermal sensitization in guinea 

pigs

(Estimated by analogy)

Professional judgment Estimated based on available test data 

for a confidential analog.

Respiratory Sensitization No data located.

Respiratory Sensitization No data located.

Eye Irritation HIGH: Based on confidential analog. DD-70 may potentially cause corrosion to eyes.

Eye Irritation Concern for potential corrosion to mucous 

membranes and eyes

(Estimated by analogy)

Professional judgment Estimated based on available test data 

for a confidential analog.

Dermal Irritation MODERATE: Based on confidential analog. DD-70 may have the potential to cause dermal irritation.

Dermal Irritation Concern for dermal irritation

(Estimated by analogy)

Professional judgment Estimated based on available test data 

for a confidential analog.

4-397 
FINAL REPORT – January 2014 

DD-70 CASRN 93589-69-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Endocrine Activity No data located.

No data located.

Immunotoxicity No data located.

Immune System Effects No data located.

ECOTOXICITY

ECOSAR Class Phenols, poly

Acute Toxicity HIGH: Based on estimated 96-hour LC50 value for fish and 96-hour EC50 value for green algae that are in 

the range of 1-10 mg/L.

Fish LC50 Fish 96-hour LC50 = 5.39 mg/L

(Estimated) 

ECOSAR: phenols, poly

ECOSAR version 1.00

Fish 96-hour LC50 = 19.6 mg/L

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.00 Narcosis classes (neutral organics) are 

provided for comparative purposes; 

DfE assessment methodology will use 

the lowest estimated toxicity value 

provided by ECOSAR classes that 

have a more specific mode of action 

relative to narcosis.

Daphnid LC50 Daphnia 48-hour LC50 = 13.30 mg/L

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.00 Narcosis classes (neutral organics) are 

provided for comparative purposes; 

DfE assessment methodology will use 

the lowest estimated toxicity value 

provided by ECOSAR classes that 

have a more specific mode of action 

relative to narcosis.

Daphnia 48-hour LC50 = 13.6 mg/L

(Estimated) 

ECOSAR: phenols, poly

ECOSAR version 1.00

Green Algae EC50 Green algae 96-hour EC50 = 2.28 mg/L

(Estimated) 

ECOSAR: phenols, poly

ECOSAR version 1.00

4-398 
FINAL REPORT – January 2014 

DD-70 CASRN 93589-69-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Green algae 96-hour EC50 = 9.98 mg/L

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.00 Narcosis classes (neutral organics) are 

provided for comparative purposes; 

DfE assessment methodology will use 

the lowest estimated toxicity value 

provided by ECOSAR classes that 

have a more specific mode of action 

relative to narcosis.

Chronic Aquatic Toxicity HIGH: Based on an estimated ChV of 0.42 mg/L for green algae.

Fish ChV Fish 30-day ChV = 1.33 mg/L

(Estimated) 

ECOSAR: phenols, poly

ECOSAR version 1.00

Fish ChV = 1.80 mg/L

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.00 Narcosis classes (neutral organics) are 

provided for comparative purposes; 

DfE assessment methodology will use 

the lowest estimated toxicity value 

provided by ECOSAR classes that 

have a more specific mode of action 

relative to narcosis.

Daphnid ChV Daphnid ChV = 1.56 mg/L 

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.00 Narcosis classes (neutral organics) are 

provided for comparative purposes; 

DfE assessment methodology will use 

the lowest estimated toxicity value 

provided by ECOSAR classes that 

have a more specific mode of action 

relative to narcosis.

Daphnid ChV = 4.68 mg/L 

(Estimated) 

ECOSAR: phenols, poly

ECOSAR version 1.00

Green Algae ChV Green algae ChV = 0.422 mg/L

(Estimated) 

ECOSAR: phenols, poly

ECOSAR version 1.00

4-399 
FINAL REPORT – January 2014 

DD-70 CASRN 93589-69-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Green algae ChV = 4.62 mg/L

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.00 Narcosis classes (neutral organics) are 

provided for comparative purposes; 

DfE assessment methodology will use 

the lowest estimated toxicity value 

provided by ECOSAR classes that 

have a more specific mode of action 

relative to narcosis.

ENVIRONMENTAL FATE

Transport Based on the Level III fugacity models incorporating the available experimental property data, DD-70 is 

expected to partition primarily to soil. DD-70 is expected to exist in both neutral and anionic forms at 

environmentally-relevant pH, based on its estimated pKa. The neutral form of DD-70 is expected to be 

immobile in soil based on its estimated Koc. The anionic form may be more mobile, as anions do not bind as 

strongly to organic carbon and clay as their neutral counterparts. However, leaching of DD-70 through soil 

to groundwater is not expected to be an important transport mechanism. Estimated volatilization half-lives 

indicate that it will be nonvolatile from surface water. Volatilization from dry surface is also not expected 

based on its estimated vapor pressure. In the atmosphere, DD-70 is expected to exist solely in the particulate 

phase, based on its estimated vapor pressure. Particulates may be removed from air by wet or dry 

deposition. 

Henry’s Law Constant 

(atm-m3/mole)

<1x10-10 (Estimated) EPI; U.S. EPA, 1999 Cutoff value for nonvolatile 

compounds according to HPV 

assessment guidance.

Sediment/Soil 

Adsorption/Desorption

Coefficient – Koc

3.3x104 (Estimated) EPI

Level III Fugacity Model Air = <1% (Estimated)

Water = 8.6%

Soil = 75%

Sediment = 16%

EPI

4-400 
FINAL REPORT – January 2014 

DD-70 CASRN 93589-69-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Persistence HIGH: Evaluation of the persistence of DD-70 is based entirely on QSARs for aerobic and anaerobic 

biodegradation. Results from these models estimate primary biodegradation in days-weeks and ultimate 

degradation in weeks-months. DD-70 is expected to partition primarily to soil; the half-life is estimated as 75 

days. Biodegradation under anaerobic methanogenic conditions is not probable. DD-70 is not expected to 

undergo hydrolysis since it does not contain hydrolyzable functional groups. DD-70 does not contain 

chromophores that absorb at wavelengths >290 nm, and therefore, it is not expected to be susceptible to 

direct photolysis by sunlight. The vapor phase reaction of DD-70 with atmospheric hydroxyl radicals is 

estimated at 1.2 hours, although it is expected to exist primarily in the particulate phase in air. 

Considerations of all these factors indicate that the persistence concern is High for DD-70.

Water Aerobic Biodegradation Days-weeks (primary survey model)

Weeks-months (ultimate survey model)

EPI

Volatilization Half-life 

for Model River

>1 year (Estimated) EPI

Volatilization Half-life 

for Model Lake

>1 year (Estimated) EPI

Soil Aerobic Biodegradation No data located.

Anaerobic 

Biodegradation

Not probable (anaerobic-methanogenic 

biodegradation probability model)

EPI

Soil Biodegradation w/ 

Product Identification

No data located.

Sediment/Water 

Biodegradation

No data located.

Air Atmospheric Half-life 1.2 hours (Estimated) EPI

Reactivity Photolysis Not a significant fate process (Estimated) Mill, 2000; Professional 

judgment 

Substance does not contain functional 

groups that would be expected to 

absorb light at environmentally 

significant wavelengths.

Hydrolysis Not a significant fate process (Estimated) Wolfe and Jeffers, 2000; 

Professional judgment 

Substance does not contain functional 

groups that would be expected to 

hydrolyze readily under environmental 

conditions.

4-401 
FINAL REPORT – January 2014 

DD-70 CASRN 93589-69-6

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Pyrolysis No data located.

Environmental Half-life 75 days (Estimated) EPI, PBT Profiler Half-life estimated for the predominant 

compartment, as determined by EPI 

and the PBT Profiler methodology.

Bioaccumulation LOW: The estimated BCF for fish is less than the low criteria cutoff of 100. In addition, the estimated BAF 

of 35, which accounts for metabolism, suggests that DD-70 will not bioaccumulate in higher trophic levels.

Fish BCF 75 (Estimated) EPI

BAF 35 (Estimated) EPI

Metabolism in Fish No data located.

ENVIRONMENTAL MONITORING AND BIOMONITORING 

Environmental Monitoring No data located.

Ecological Biomonitoring No data located.

Human Biomonitoring This chemical was not included in the NHANES biomonitoring report (CDC, 2011).

4-402 
FINAL REPORT – January 2014 

CDC (Centers for Disease Control and Prevention). Fourth national report on human exposure to environmental chemicals, updated 

tables. Department of Health and Human Services. 2011. http://www.cdc.gov/exposurereport/ (accessed on May 10, 2011). 

ECOSAR (2010) Ecological Structure Activity Relationship (ECOSAR) Version 1.00. Washington, DC: U.S. Environmental 

Protection Agency. http://www.epa.gov/oppt/newchems/tools/21ecosar.htm

EPI (EPIWIN/EPISUITE) Estimations Programs Interface for Windows, Version 4.00. U.S. Environmental Protection Agency: 

Washington D.C. http://www.epa.gov/opptintr/exposure/. 

ESIS (European chemical Substances Information System) Classification, labeling and Packaging of dangerous substances annex VI 

to regulation (EC) No 1272/2008 [Online] http://esis.jrc.ec.europa.eu/ (accessed on June 10, 2011). 

Mill, T. 2000. Photoreactions in Surface Waters. In Boethling, R.; Mackay, D., Handbook of Property Estimation Methods for 

Chemicals, Environmental Health Sciences (355-382). Boca Raton: Lewis Publishers. 

Oncologic. U.S. EPA and LogiChem, Inc. 2005, Version 7.0. 2008. 

PBT Profiler Persistent (P),Bioaccumulative (B), and Toxic (T) Chemical (PBT)Profiler. U.S. Environmental Protection Agency: 

Washington D.C. www.pbtprofiler.net. 

SPARC On Line Calculator pKa/property server. Ver 4.5 September, 2009. Available from, http://ibmlc2.chem.uga.edu/sparc/

(accessed on August 12, 2010). 

U.S. EPA (Environmental Protection Agency). High Production Volume (HPV) Challenge. Determining the Adequacy of Existing 

Data. U.S. Environmental Protection Agency: Washington D.C. 1999. http://www.epa.gov/hpv/pubs/general/datadfin.htm 

Wolfe, N.; Jeffers, P. (2000) Hydrolysis. In Boethling, R.; Mackay, D., Handbook of Property Estimation Methods for Chemicals, 

Environmental Health Sciences (311-334). Boca Raton: Lewis Publishers. 

4-403 
FINAL REPORT – January 2014 

Pergafast 201 

N

H O

N

H

S

O

O

3CH

O S

O

O

CH3

4-404 

CASRN: 232938-43-1

MW: 460.5

MF: C21H20N2O6S2

Physical Forms: 

Neat: Solid

Use: Developer for thermal paper

SMILES: O=S(=O)(Oc1cccc(c1)NC(=O)NS(=O)(=O)c2ccc(C)cc2)c3ccc(C)cc3

Synonyms: Benzenesulfonamide, 4-Methyl-N-(((3-(((4-Methylphenyl)Sulfonyl)Oxy)Phenyl)Amino)Carbonyl)-; 

N-(P-Toluenesulfonyl)-N'-(3-P-Toluenesulfonyloxyphenyl)Urea; 

N-(4-Methylphenylsulfonyl)-N'-(3-(4-Methylphenylsulfonyloxy)Phenyl)Urea; N-P-Tolylsulfonyl-N'-3-(P-Tolylsulfonyloxy)Phenylurea; 

Pergafast 201; PF 201

Polymeric: No

 Oligomers: Not applicable

Metabolites, Degradates and Transformation Products: None identified

Analog: No 

 Endpoint(s) using analog values: Not applicable

Analog Structure: Not applicable 

Structural Alerts: Sulfonamides, photoreactions; Alkyl esters of sulfonic acids, toxicity caused by electrophiles (U.S. EPA, 2010)

Risk Phrases: 51/53 - Toxic to aquatic organisms, may cause long-term adverse effects in the aquatic environment (ESIS, 2011).

Risk Assessments: Risk assessment completed for Pergafast 201 by the Australian Department of Health and Ageing in 2004 (NICNAS, 2004).
FINAL REPORT – January 2014 

Pergafast 201 CASRN 232938-43-1

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

PHYSICAL/CHEMICAL PROPERTIES

Melting Point (°C) 157.7 (Measured) NICNAS, 2004 Adequate; selected value.

>155 (Measured) BASF, 2010 Adequate; measured by chemical 

supplier.

Boiling Point (°C) Decomposes at 250 (Measured) NICNAS, 2004 Adequate.

Vapor Pressure (mm Hg) <1x10-8 (Estimated) EPI; U.S. EPA, 1999 Cutoff value for nonvolatile compounds 

according to HPV assessment guidance.

Water Solubility (mg/L) 35 (Measured) NICNAS, 2004 Adequate; selected value.

35 at 20 °C(Measured) BASF, 2010 Adequate; measured by chemical 

supplier.

Log Kow 2.6 (Measured) NICNAS, 2004 Adequate.

Flammability (Flash Point) Not highly flammable; not autoflammable (Measured)

NICNAS, 2004 Adequate.

Explosivity Non-explosive either by thermal or 

mechanical (shock and friction) stress. 

(Measured)

NICNAS, 2004 Adequate. 

pH No data located.

pKa pKa1 = 12.5

pKa2 = 5.3 

pKa3 = -3.8 

pKa4 = -13.6 (Estimated)

SPARC

HUMAN HEALTH EFFECTS

Toxicokinetics Pergafast 201 is not estimated to be absorbed through the skin as the neat material and has poor absorption 

through the skin if in solution. Furthermore, Pergafast 201 has poor absorption from the lungs and 

gastrointestinal tract. 

Dermal Absorption in vitro No data located.

Absorption, 

Distribution, 

Metabolism & 

Excretion

Oral, Dermal or Inhaled Not absorbed through the skin as the neat 

material poor absorption through the skin 

if in solution; poor absorption from the 

lungs and gastrointestinal tract. 

Professional judgment Based on closely related confidential 

analog with similar structure, functional 

groups, and physical/chemical 

properties.

Acute Mammalian Toxicity LOW: Based on acute oral and dermal LD50 values >2,000 mg/kg. No data were located regarding the acute 

inhalation hazard. 

4-405 
FINAL REPORT – January 2014 

Pergafast 201 CASRN 232938-43-1

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Acute Lethality Oral Rat oral LD50 >2,000 mg/kg NICNAS, 2004 Adequate.

Dermal Rat dermal LD50 >2,000 mg/kg NICNAS, 2004 Adequate.

Inhalation No data located.

Carcinogenicity MODERATE: There is uncertainty due to the lack of data for this substance. Carcinogenic effects cannot be 

ruled out.

OncoLogic Results No data located.

Carcinogenicity (Rat and 

Mouse)

No data located.

Combined Chronic 

Toxicity/Carcinogenicity

No data located.

Genotoxicity LOW: Pergafast 201 did not cause gene mutations in vitro or chromosomal aberrations in vivo. Pergafast 201 

did induce chromosomal aberrations in Chinese hamster V79 cells in vitro, but only at cytotoxic 

concentrations.

Gene Mutation in vitro Negative, Ames assay of Salmonella 

typhimurium strains TA98, TA100, 

TA1535, TA1537 and Escherichia coli

WP2 uvrA both with and without 

metabolic activation

NICNAS, 2004 Adequate.

Gene Mutation in vivo No data located.

Chromosomal Aberrations 

in vitro

Positive, chromosomal aberrations in 

Chinese hamster V79 cells at cytotoxic 

concentrations

NICNAS, 2004 Adequate.

Chromosomal Aberrations 

in vivo

Negative, in vivo micronucleus test in 

mouse, gavage exposure

NICNAS, 2004 Adequate.

DNA Damage and Repair No data located.

Other No data located.

Reproductive Effects MODERATE: There was a decrease in implantation sites in dams receiving 200 mg/kg, the highest dose 

tested, but the decrease was not statistically significant. Since significant reproductive toxicity cannot be 

ruled out at doses between 200 and 250 mg/kg, the hazard designation is Moderate.

4-406 
FINAL REPORT – January 2014 

Pergafast 201 CASRN 232938-43-1

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Reproduction/ 

Developmental Toxicity 

Screen

Rat, oral gavage; 

Males exposed for 29 days pre-mating, 

during mating, and up to sacrifice; 

Females exposed 42-46 days (2 weeks 

pre-mating, during mating, during postcoitum, up to LD 4. 

No statistically significant reproductive 

effects were observed, although there 

was a decrease in implantation sites in 

dams at 200 mg/kg, the highest dose

tested. 

NOAEL (maternal toxicity): 50 mg/kg 

bw-day 

LOAEL (maternal toxicity): 100 mg/kg 

bw-day (hematology and accentuated 

lobular pattern of the liver) 

NOAEL (reproductive toxicity): >200 

mg/kg (highest dose tested)

Submitted confidential study Adequate; according to OECD 

guideline 421. 

Combined Repeated Dose 

with Reproduction/ 

Developmental Toxicity 

Screen

No data located.

Reproduction and Fertility 

Effects

No data located.

4-407 
FINAL REPORT – January 2014 

Pergafast 201 CASRN 232938-43-1

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Developmental Effects HIGH: There was a decrease in pup viability at all treatment levels. Treatments at 50 and 100 mg/kg bw-day 

were significantly dose-dependent. There was a decrease in pup body weight at 200 mg/kg bw-day. A NOAEL 

could not be established for decreased pup viability; therefore Pergafast has been designated High for 

developmental toxicity.

Reproduction/ 

Developmental Toxicity 

Screen

Rat, oral gavage; 

Males exposed for 29 days pre-mating, 

during mating, and up to sacrifice; 

Females exposed 42-46 days (2 weeks 

pre-mating, during mating, during postcoitum, up to LD 4. 

There was a significant decrease in pup 

viability at all treatment levels. There 

was a significant decrease in female pup 

body weight at all treatments during day1 of lactation. A significant decrease in 

pup body weight was observed in all 

animals at 200 mg/kg bw-day. 

NOAEL (maternal toxicity): 50 mg/kg 

bw-day 

LOAEL (maternal toxicity): 100 mg/kg 

bw-day (accentuated lobular pattern of 

the liver, increased liver to body weight 

ratio) 

NOAEL (F1 pups): Not established

LOAEL (F1 pups): 50 mg/kg bw-day 

(decreased pup viability)

Submitted confidential study Adequate; according to OECD 

guideline 421. 

Combined Repeated Dose 

with Reproduction/ 

Developmental Toxicity 

Screen

No data located.

Prenatal Development No data located.

4-408 
FINAL REPORT – January 2014 

Pergafast 201 CASRN 232938-43-1

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Postnatal Development No data located.

Neurotoxicity LOW: No structural alerts or mechanistic pathways associated with neurotoxic effect identified.

Neurotoxicity Screening

Battery (Adult)

Low potential for neurotoxicity effects.

(Estimated)

Professional judgment Estimated based on no identified 

structural alerts or mechanistic 

pathways associated with neurotoxicity. 

Repeated Dose Effects MODERATE: A 90-day study identified a LOAEL of 50 mg/kg bw-day and a NOAEL of 25 mg/kg bw-day; 

due to effects on the liver of female rats therefore a Moderate hazard designation is selected.

28-Day repeated-dose study, rat, oral 

gavage, salivation, indications of 

hemolytic anemia, increased liver and 

kidney weights, microscopic changes 

including minimal hypertrophy of 

ventrilobular hepatocytes in liver of 

males and females and extramedullary 

haemopoiesis in spleen of females. 

NOAEL = 30 mg/kg bw-day, 

LOAEL = 150 mg/kg bw-day

NICNAS, 2004 Adequate.

4-409 
FINAL REPORT – January 2014 

Pergafast 201 CASRN 232938-43-1

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

90-Day repeated-dose study, rat, oral 

gavage; Changes in hematology 

parameters and increased extramedullary 

hematopoiesis, increased absolute and 

relative organ weights with 

histopathological correlation in the liver; 

histopathological changes in spleen and 

adrenal glands. 

NOAEL = 25 mg/kg bw-day (increased 

liver weights and liver histopathological 

changes in females) 

LOAEL = 50 mg/kg bw-day 

NOAEL = 50 mg/kg bw-day (increased 

globulin B and liver hypertrophy in 

males) 

LOAEL = 150 mg/kg bw-day

Submitted confidential study Adequate; according to OECD 

guideline 408.

5-Day range finding study, rat, oral 

gavage; decreased mean daily food 

consumption (male and female), 

decreased body weight gain (females), 

decreased absolute and relative thymus 

weights (males), increased absolute and 

relative liver weight (male and female). 

LOAEL = 200 mg/kg bw-day (lowest 

dose tested)

Submitted confidential study Adequate.

4-410 
FINAL REPORT – January 2014 

Pergafast 201 CASRN 232938-43-1

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Skin Sensitization LOW: Pergafast 201 did not appear to be a skin sensitizer in guinea pigs.

Skin Sensitization Skin irritation was observed in 1/10 

guinea pigs at 24 hours (but not at 

48 hours) following induction and 

subsequent challenge. The severity of 

the response was not described in the 

available source.

NICNAS, 2004 Inadequate; limited study details.

Non-sensitizing, Guinea pig BASF, 2010 Valid.

Respiratory Sensitization No data located.

Respiratory Sensitization No located.

Eye Irritation LOW: Pergafast 201 was slightly irritating to rabbit eyes.

Eye Irritation Slightly irritating, rabbits NICNAS, 2004 Adequate.

Non-irritating, rabbits BASF, 2010 Valid.

Dermal Irritation VERY LOW: Pergafast 201 was not irritating to rabbit skin.

Dermal Irritation Non-irritating, rabbits NICNAS, 2004 Adequate.

Endocrine Activity A single study showed Pergafast 201 to be non-estrogenic with a relative potency substantially low compared 

to 17-beta-estradiol.

Negative for estrogenic activity; 

Increased luciferase activity in a human 

estrogen receptor-α transcriptional 

activation assay. Relative potency was 

estimated to be about 107 times less than 

estrogen.

Submitted confidential study Adequate; similar to OECD guideline 

455.

Immunotoxicity There is uncertain concern for immunotoxicity based on effects to the spleen and adrenal glands. 

Immune System Effects 90-day repeated-dose study, rat, oral 

gavage; changes in spleen and adrenal 

glands. 

NOAEL = 25 mg/kg bw-day 

LOAEL = 150 mg/kg bw-day

Submitted confidential study Adequate; according to OECD 

guideline 408. 

ECOTOXICITY

ECOSAR Class Esters, Amides, Sulfonyl ureas

4-411 
FINAL REPORT – January 2014 

Pergafast 201 CASRN 232938-43-1

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Acute Aquatic Toxicity HIGH: Based on the 72-hour EC50 of 3 mg/L (nominal) for decreased growth rate in green algae. The level of 

concern for green algae varies from Moderate to Very High based on metric. The 96-hour assay using 

zebrafish and the 48-hour assay using Daphnids both yielded threshold results in the Low to Moderate range.

Fish LC50 Zebra fish 96-hour LC50 >63 mg/L,

NOEC = 63 mg/L

(Experimental)

NICNAS, 2004 Chemical may not be soluble enough to 

measure this effect; LC50 value exceeds 

water solubility.

Brachydanio rerio 96-hour LC50 ≥100 

mg/L (Experimental) 

BASF, 2010 Chemical may not be soluble enough to 

measure this effect; LC50 value exceeds 

water solubility.

Fish 96-hour LC50 = 19.88 mg/L

(Estimated) 

ECOSAR: amides

ECOSAR version 1.00

Fish 96-hour LC50 = 28.42 mg/L

(Estimated) 

ECOSAR: esters

ECOSAR version 1.00

Fish 96-hour LC50 = 110.21 mg/L

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.00 Chemical may not be soluble enough to 

measure this predicted effect; LC50 

value exceeds water solubility. Narcosis 

classes (neutral organics) are provided 

for comparative purposes; DfE 

assessment methodology will use the 

lowest estimated toxicity value 

provided by ECOSAR classes that have 

a more specific mode of action relative 

to narcosis.

4-412 
FINAL REPORT – January 2014 

Pergafast 201 CASRN 232938-43-1

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Daphnid LC50 Daphnia magna 48-hour EC50 = 57 mg/L

(Experimental) 

NICNAS, 2004 Inadequate (OECD 202). Chemical may 

not be soluble enough to measure this 

effect; EC50 value exceeds water 

solubility.

Daphnid 48-hour LC50 = 13.78 mg/L

(Estimated) 

ECOSAR: amides

ECOSAR version 1.00

Daphnid 48-hour LC50 = 54.07 mg/L

(Estimated) 

ECOSAR: esters

ECOSAR version 1.00 Chemical may not be soluble enough to 

measure this predicted effect; LC50 

value exceeds water solubility.

Daphnid 48-hour LC50 = 40.69 mg/L

(Estimated) 

ECOSAR: Sulfonyl ureas

ECOSAR version 1.00 Chemical may not be soluble enough to 

measure this predicted effect; LC50 

value exceeds water solubility.

Daphnid 48-hour LC50 = 68.38 mg/L

(Estimated) 

ECOSAR: neutral organics

ECOSAR version 1.00

Saltwater Invertebrate LC50 Mysid shrimp 96-hour LC50 = 

29.89 mg/L 

(Estimated) 

ECOSAR: esters

ECOSAR version 1.00

Green Algae EC50 Scenedesmus subspicatus

72-hour EC50 = 0.77 mg/L (nominal) 

(biomass); 

72-hour EC50 = 3 mg/L (nominal) 

(growth rate) 

(Experimental)

NICNAS, 2004; 

Submitted confidential study

Adequate; OECD 201.

Scenedesmus subspicatus

72-hour EC50 = 1.3 mg/L (nominal) 

(biomass); 

72-hour EC50 = 3.2 mg/L (nominal) 

(growth rate) 

Static conditions

(Experimental)

Submitted confidential study Adequate; OECD 201.

4-413 
FINAL REPORT – January 2014 

Pergafast 201 CASRN 232938-43-1

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Scenedesmus subspicatus

96-hour EC50 = 6.3 mg/L (nominal) 

(biomass); 

96-hour EC50 >10 mg/L (nominal) 

(growth rate) 

Static conditions

(Experimental)

Submitted confidential study Addition of sediment is not appropriate 

for this chemical class.

Scenedesmus subspicatus; static 

conditions in the presence of sediment

96-hour EC50 = 5 mg/L (biomass) 

96-hour EC50 = 7.4 mg/L (growth rate) 

96-hour NOEC = 1.6 mg/L 

96-hour LOEC = 3.6 mg/L 

96-hour ChV = 2.4 mg/L 

(Experimental)

Submitted confidential study Addition of sediment is not appropriate 

for this chemical class.

Green algae 96-hour EC50 = 21.60 mg/L

(Estimated) 

ECOSAR: esters

ECOSAR version 1.00

Green algae 96-hour EC50 = 0.69 mg/L

(Estimated) 

ECOSAR: amides

ECOSAR version 1.00

Green algae 96-hour EC50 = 0.05 mg/L

(Estimated) 

ECOSAR: sulfonyl ureas

ECOSAR version 1.00

4-414 
FINAL REPORT – January 2014 

Pergafast 201 CASRN 232938-43-1

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Green algae 96-hour EC50 = 37.71 mg/L

(Estimated) 

ECOSAR: neutral organics

ECOSAR version 1.00 Chemical may not be soluble enough to 

measure this predicted effect; EC50 

value exceeds water solubility. Narcosis 

classes (neutral organics) are provided 

for comparative purposes; DfE 

assessment methodology will use the 

lowest estimated toxicity value 

provided by ECOSAR classes that have 

a more specific mode of action relative 

to narcosis.

Chronic Aquatic Toxicity HIGH: Based on the 72-hour toxicity test using green algae (Scenedesmus subspicatus), which yielded a 

chronic toxicity value of 0.270 mg/L. Results for fish and Daphnid range from Low to High. 

Fish ChV Pimephales promelas, flow through 

conditions. 

32-day NOEC ≥ 0.89 mg/L (highest dose 

tested) 

(Experimental)

Submitted confidential study Adequate; EPA OPPTS 850.1400 

guidelines; LOEC not identified. 

Fish ChV = 0.12 mg/L 

(Estimated) 

ECOSAR: amides

ECOSAR version 1.00

Fish 32/33-day ChV = 2.21 mg/L 

(Estimated) 

ECOSAR: esters

ECOSAR version 1.00

Fish ChV = 10.32 mg/L 

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.00 Narcosis classes (neutral organics) are 

provided for comparative purposes; 

DfE assessment methodology will use 

the lowest estimated toxicity value 

provided by ECOSAR classes that have 

a more specific mode of action relative 

to narcosis.

Daphnid ChV Daphnia magna 21-day EC50 = 21 mg/L

(Experimental)

NICNAS, 2004 Adequate; LOEC not identified.

4-415 
FINAL REPORT – January 2014 

Pergafast 201 CASRN 232938-43-1

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Daphnid ChV = 0.18 mg/L 

(Estimated) 

ECOSAR: amides

ECOSAR version 1.00

Daphnid 21-day ChV = 29.23 mg/L 

(Estimated) 

ECOSAR: esters

ECOSAR version 1.00

Daphnid ChV = 4.11 mg/L 

(Estimated) 

ECOSAR: sulfonyl ureas

ECOSAR version 1.00

Daphnid ChV = 7.02 mg/L 

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.00 Narcosis classes (neutral organics) are 

provided for comparative purposes; 

DfE assessment methodology will use 

the lowest estimated toxicity value 

provided by ECOSAR classes that have 

a more specific mode of action relative 

to narcosis.

Daphnia magna 21-day NOEC = 

10.2 mg/L 

(Experimental)

BASF, 2010 Valid; LOEC not identified.

Daphnia Magna; semi-static conditions;

21-day NOEC = 10.2 mg/L 

21-day LOEC = 34.5 mg/L (for 

immobilization) 

(Experimental)

Submitted confidential study Adequate; OECD 211; Chemical may 

not be soluble enough to measure this 

predicted effect; LOEC value is at the 

level of water solubility. 

Saltwater Invertebrate ChV Mysid shrimp ChV = 640 mg/L

(Estimated) 

ECOSAR: esters

ECOSAR version 1.00 Chemical may not be soluble enough to 

measure this predicted effect. 

Green Algae ChV Green algae ChV = 0.013 mg/L

(Estimated) 

ECOSAR: sulfonyl ureas

ECOSAR version 1.00

Green algae ChV = 6.62 mg/L

(Estimated) 

ECOSAR: esters

ECOSAR version 1.00

4-416 
FINAL REPORT – January 2014 

Pergafast 201 CASRN 232938-43-1

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Green algae ChV = 0.77 mg/L

(Estimated) 

ECOSAR: amides

ECOSAR version 1.00

Green algae ChV = 15.23 mg/L

(Estimated) 

ECOSAR: neutral organics

ECOSAR version 1.00 Narcosis classes (neutral organics) are 

provided for comparative purposes; 

DfE assessment methodology will use 

the lowest estimated toxicity value 

provided by ECOSAR classes that have 

a more specific mode of action relative 

to narcosis.

Terrestrial Ecotoxicity Earthworm 

Subchronic Toxicity

Earthworm 14-day LC50 = 3,500 mg/L 

(Estimated) 

ECOSAR: esters

ECOSAR version 1.00 NES for measured water solubility of 

35 mg/L.

Toxicity to Terrestrial 

Plants

Avena sativa, Pisum sativum and 

Brassica napus: NOEC (21 d) = >1000 

mg/kg (nominal) soil dw test material 

(based on: seedling emergence) 

Avena sativa, Pisum sativum and 

Brassica napus: NOEC (21 d) = >1000 

mg/kg (nominal) soil dw test material. 

(based on: growth) 

Submitted confidential study Study conducted according to OECD 

guideline 208. 

ENVIRONMENTAL FATE

Transport The transport evaluation for Pergafast 201 is based on available experimental and estimated physical and 

chemical properties. Based on the Level III fugacity models incorporating the available experimental 

property data, Pergafast 201 is expected to partition primarily to soil. Pergafast 201 is expected to have slight 

mobility in soil based on its estimated Koc. However, leaching of Pergafast 201 through soil to groundwater is 

not expected to be an important transport mechanism. Estimated volatilization half-lives indicate that it will 

be nonvolatile from surface water. In the atmosphere, Pergafast 201 is expected to exist in the particulate 

phase, based on its estimated vapor pressure. Particulates will be removed from air by wet or dry deposition.

Henry’s Law Constant 

(atm-m3/mole)

<1x10-8 (Estimated) EPI; Professional judgment Cutoff value for nonvolatile 

compounds, based on professional 

judgment.

4-417 
FINAL REPORT – January 2014 

Pergafast 201 CASRN 232938-43-1

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Sediment/Soil 

Adsorption/Desorption

Coefficient – Koc

12,000 (Estimated) EPI

Level III Fugacity 

Estimations

Air = <1% (Estimated)

Water = 8%

Soil = 85%

Sediment = 7%

EPI

Persistence VERY HIGH: Experimental guideline studies indicate that little or no biodegradation was observed under 

aerobic conditions.

Water Aerobic Biodegradation OECD TG 301 F Ready 

Biodegradability: Manometric 

Respirometry Test. Pergafast 201 is not 

readily biodegradable; 1.5% degradation 

of the test substance occurred after 28 

days (Measured)

NICNAS, 2004 Adequate; guideline study described in 

secondary source. 

OECD 302B: Not readily 

biodegradable; >99% after 28 days 

(Measured)

BASF, 2010 Adequate, guideline study.

No biodegradation occurred after 28 

days. Ready biodegradability test with 

non-adapted, activated sludge. 

(Measured)

Submitted confidential study Adequate; nonguideline study reported 

in secondary source. 

Volatilization Half-life 

for Model River

>1 year (Estimated) EPI

Volatilization Half-life 

for Model Lake

>1 year (Estimated) EPI

Soil Aerobic Biodegradation Half-life of 4.9 days according to OECD 

307; decreased to 14% of applied amount 

in 30 days (Measured)

Submitted confidential study Inadequate as reported in a secondary 

source. The cited source indicated that 

the material did not mineralize over the 

course of the study, although no mass 

balance information was provided. 

These are results are not consistent with 

other biodegradation results.

4-418 
FINAL REPORT – January 2014 

Pergafast 201 CASRN 232938-43-1

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Anaerobic 

Biodegradation

Not probable (anaerobic-methanogenic 

biodegradation probability model)

EPI

Soil Biodegradation w/ 

Product Identification

No data located.

Sediment/Water 

Biodegradation

No data located.

Air Atmospheric Half-life 0.64 hours (Estimated) EPI

Reactivity Photolysis Not a significant fate process Professional judgment Qualitative assessment based on 

functional groups.

Hydrolysis Half-life >1 year at pH 4, 7, and 9

OECD 111; <10% hydrolysis after 5 

days (Measured)

NICNAS, 2004 Adequate; guideline study described in 

secondary source. 

Pyrolysis No data located.

Environmental Half-life 120 days (Estimated) EPI; PBT Profiler Half-life estimated for the predominant 

compartment, as determined by EPI and 

the PBT Profiler methodology.

Bioaccumulation LOW: The measured BCF in fish is <100.

Fish BCF <1 (0.2 mg/L) (Measured);

<8 (0.02 mg/L) (Measured) 

according to guideline study OECD 305

Submitted confidential study Adequate; guideline study described in 

a secondary source. 

30 (Measured) NICNAS, 2004 Reported in a secondary source, 

although the resulting hazard is 

consistent with other studies.

BAF 18 (Estimated) EPI

Metabolism in Fish No data located.

ENVIRONMENTAL MONITORING AND BIOMONITORING 

Environmental Monitoring No data located.

Ecological Biomonitoring No data located.

Human Biomonitoring This chemical was not included in the NHANES biomonitoring report (CDC, 2011).

4-419 
FINAL REPORT – January 2014 

BASF. BASF The Chemical Company. Material Safety Data Sheet. 2010. 

CDC (Centers for Disease Control and Prevention). Fourth national report on human exposure to environmental chemicals, updated 

tables. Department of Health and Human Services. 2011. http://www.cdc.gov/exposurereport/ (accessed on May 10, 2011). 

ECOSAR (2010) Ecological Structure Activity Relationship (ECOSAR) Version 1.00. Washington, DC: U.S. Environmental 

Protection Agency. http://www.epa.gov/oppt/newchems/tools/21ecosar.htm

EPI (EPIWIN/EPISUITE) Estimations Programs Interface for Windows, Version 4.00. U.S. Environmental Protection Agency: 

Washington D.C. http://www.epa.gov/opptintr/exposure/. 

ESIS (European chemical Substances Information System) Classification, labeling and Packaging of dangerous substances annex VI 

to regulation (EC) No 1272/2008 [Online] http://esis.jrc.ec.europa.eu/ (accessed on June 10, 2011). 

NICNAS (National Industrial Chemicals Notification and Assessment Scheme). Full public report. Pergafast 201. National Industrial 

Chemicals Notification and Assessment Scheme. National Occupational Health and Safety Commission, Australia. 2004. 

PBT Profiler Persistent (P), Bioaccumulative (B), and Toxic (T) Chemical (PBT) Profiler, U.S. Environmental Protection Agency: 

Washington D.C. www.pbtprofiler.net. 

SPARC On Line Calculator pKa/property server. Ver 4.5 September, 2009. Available from, http://ibmlc2.chem.uga.edu/sparc/

(accessed on August 12, 2010). 

[HPV Assessment Guidance] EPA (U.S. Environmental Protection Agency). Determining the Adequacy of Existing Data. U.S. 

Environmental Protection Agency: Washington D.C. 1999. http://www.epa.gov/hpv/pubs/general/datadeqfn.pdf 

U.S. EPA (Environmental Protection Agency). Sustainable Futures Using NonCancer Screening within the Sustainable Futures 

Initiative Environmental Protection Agency: Washington D.C. 2010. http://www.epa.gov/opptintr/sf/pubs/noncanscreen.htm#systemic (accessed on February 09, 2011). 

4-420 
FINAL REPORT – January 2014 

BTUM

N N

O

S

O O

N N

O

S

O O

4-421 

CASRN: 151882-81-4

MW: 592.70

MF: C29H28N4O6S2

Physical Forms:

Neat: Solid

Use: Developer for thermal paper

SMILES: O=C(NS(C1=CC=C(C)C=C1)(=O)=O)NC(C=C2)=CC=C2CC3=CC=C(NC(NS(C4=CC=C(C)C=C4)(=O)=O)=O)C=C3

Synonyms: Benzenesulfonamide, N,N’-[methylenebis(4,1-phenyleneiminocarbonyl)]bis[4-methyl-; 4,4'-bis(N-carbamoyl-4-

methylbenzenesulfonamide)diphenylmethane

Polymeric: No

 Oligomers: Not applicable

Metabolites, Degradates and Transformation Products: None identified

Analog: None

 Endpoint(s) using analog values: Not applicable

Analog Structure: Not applicable 

Structural Alerts: None identified

Risk Phrases: Not classified by Annex VI Regulation (EC) No 1272/2008 (ESIS, 2011).

Risk Assessments: None identified
FINAL REPORT – January 2014 

BTUM CASRN 151882-81-4

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

PHYSICAL/CHEMICAL PROPERTIES

Melting Point (°C) 154-156 (Measured) Non-confidential PMN 

submission

Adequate.

Boiling Point (°C) >300 (Estimated) EPI; U.S. EPA, 1999 Cutoff value for high boiling 

compounds according to HPV 

assessment guidance.

Vapor Pressure (mm Hg) <1x10-8 (Estimated) EPI; U.S. EPA, 1999 Cutoff value for nonvolatile 

compounds according to HPV

assessment guidance.

Water Solubility (mg/L) 0.77 (Measured) Non-confidential PMN 

submission

Adequate.

Log Kow 2.61 (Measured) Non-confidential PMN 

submission

Adequate.

Flammability (Flash Point) No data located.

Explosivity No data located.

pH No data located.

pKa 4.8-5.4 (Estimated) SPARC

HUMAN HEALTH EFFECTS

Toxicokinetics BTUM is not absorbed through the skin and will have poor absorption from the lungs and gastrointestinal 

tract.

Dermal Absorption in vitro No data located.

Absorption, 

Distribution, 

Metabolism & 

Excretion

Oral, Dermal or Inhaled Not absorbed through the skin; poor 

absorption through the lung and 

gastrointestinal tract

Professional judgment Based on closely related confidential 

analog with similar structure, 

functional groups, and 

physical/chemical properties.

4-422 
FINAL REPORT – January 2014 

BTUM CASRN 151882-81-4

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Acute Mammalian Toxicity LOW: The acute oral and dermal toxicity concern of BTUM is low based on experimental data in animals. 

Data indicate no mortality or signs of toxicity at doses up to 2,000 mg/kg.

Acute Lethality Oral Rat, LD0 = 2,000 mg/kg

No signs of toxicity

Non-confidential PMN 

submission

Adequate.

Dermal Rat, LD0 = 2,000 mg/kg

No signs of toxicity

Non-confidential PMN 

submission

Adequate.

Inhalation No data located.

Carcinogenicity MODERATE: There is uncertainty due to the lack of data for this substance. Carcinogenic effects cannot be 

ruled out.

OncoLogic Results No data located.

Carcinogenicity (Rat and 

Mouse)

No data located.

Combined Chronic 

Toxicity/Carcinogenicity

No data located.

Genotoxicity LOW: BTUM did not cause mutations in bacteria or chromosomal aberrations in human lymphocytes.

Gene Mutation in vitro Negative for mutations in Salmonella

typhimurium and Escherichia coli with 

and without activation

Non-confidential PMN 

submission 

Adequate.

Gene Mutation in vivo No data located.

Chromosomal Aberrations 

in vitro

Negative for chromosomal aberrations in 

human lymphocytes

Non-confidential PMN 

submission

Adequate.

Chromosomal Aberrations 

in vivo

No data located.

DNA Damage and Repair No data located.

Other (Mitotic Gene 

Conversion)

No data located.

4-423 
FINAL REPORT – January 2014 

BTUM CASRN 151882-81-4

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Reproductive Effects LOW: A combination of poor predicted absorption through all routes, low predicted metabolism, and lack of 

significant toxicological concerns from repeated dose testing suggests low potential hazard based on 

professional judgment.

Reproduction/ 

Developmental Toxicity 

Screen

Low potential for reproductive effects

(Estimated)

Professional judgment Estimated based on professional 

judgment. 

Combined Repeated Dose 

with Reproduction/ 

Developmental Toxicity 

Screen

No data located.

Reproduction and Fertility 

Effects

No data located.

Developmental Effects LOW: A combination of poor predicted absorption through all routes, low predicted metabolism, and lack of 

significant toxicological concerns from repeated dose testing suggests low potential hazard based on 

professional judgment.

Reproduction/ 

Developmental Toxicity 

Screen

Low potential for reproductive effects

(Estimated)

Professional judgment Estimated based on professional 

judgment. 

Combined Repeated Dose 

with Reproduction/ 

Developmental Toxicity 

Screen

No data located.

Prenatal Development No data located.

Postnatal Development No data located.

Neurotoxicity LOW: No structural alerts or mechanistic pathways associated with neurotoxic effect identified.

Neurotoxicity Screening 

Battery (Adult)

Low potential for neurotoxicity effects

(Estimated)

U.S. EPA, 2010; Professional 

judgment 

Estimated based on no identified 

structural alerts or mechanistic 

pathways associated with 

neurotoxicity. 

4-424 
FINAL REPORT – January 2014 

BTUM CASRN 151882-81-4

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Repeated Dose Effects MODERATE: Blood toxicity and liver changes resulted in rats at a dose of 1,000 mg/kg-day following a 28-

day exposure to BTUM. While the LOAEL identified in the study indicates a Low hazard concern (>300 

mg/kg-day), the NOAEL is within the Moderate hazard concern range for a 28-day study duration (30-300 

mg/kg-day). The uncertainty of where effects might occur warrants a Moderate hazard concern.

Rat, 28-day oral (gavage)

blood toxicity and liver changes. 

NOAEL = 200 mg/kg-day 

LOAEL = 1,000 mg/kg-day

Non-confidential PMN 

submission 

Adequate.

Skin Sensitization LOW: BTUM did not cause dermal sensitization in one study of guinea pigs.

Skin Sensitization No skin sensitization in guinea pigs using 

the Magnusson Kligman assay

Non-confidential PMN 

submission

Adequate.

Respiratory Sensitization No data located.

Respiratory Sensitization No data located.

Eye Irritation LOW: BTUM was slightly irritating to eyes in one study of rabbits.

Eye Irritation Mild eye irritation in rabbits Non-confidential PMN 

submission

Adequate.

Dermal Irritation LOW: BTUM did not cause dermal irritation in one study of rabbits.

Dermal Irritation No skin irritation in rabbits Non-confidential PMN 

submission

Adequate.

Endocrine Activity No data located.

No data located.

Immunotoxicity No data located.

Immune System Effects No data located.

ECOTOXICITY

ECOSAR Class Sulfonyl ureas

Acute Toxicity HIGH: Based on an estimated acute toxicity value of <1.0 mg/L for algae, although there is a high degree of 

uncertainty and limited confidence in the estimation.

4-425 
FINAL REPORT – January 2014 

BTUM CASRN 151882-81-4

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Fish LC50 Fish 96-hour LC50 = 37 mg/L

ECOSAR: sulfonyl ureas 

(Estimated)

ECOSAR version 1.00 NES; estimated LC50 is greater than 

the measured water solubility (0.77 

mg/L).

Fish 96-hour LC50 = 137 mg/L

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.00 NES; estimated LC50 is greater than 

the measured water solubility (0.77 

mg/L). Narcosis classes (neutral 

organics) are provided for 

comparative purposes; DfE 

assessment methodology will use the 

lowest estimated toxicity value 

provided by ECOSAR classes that 

have a more specific mode of action 

relative to narcosis.

Daphnid LC50 Daphnid 48-hour LC50 = 34 mg/L

(Estimated) 

ECOSAR: sulfonyl ureas

ECOSAR version 1.00 NES; estimated LC50 is greater than 

the measured water solubility (0.77 

mg/L).

Daphnid 48-hour LC50 = 82 mg/L

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.00 NES; estimated LC50 is greater than 

the measured water solubility (0.77 

mg/L). Narcosis classes (neutral 

organics) are provided for 

comparative purposes; DfE 

assessment methodology will use the 

lowest estimated toxicity value 

provided by ECOSAR classes that 

have a more specific mode of action 

relative to narcosis.

Green Algae EC50 Green algae 96-hour EC50 = 0.188 mg/L

(Estimated) 

ECOSAR: sulfonyl ureas 

ECOSAR version 1.00 There is some uncertainty to the 

estimated value for this compound 

since all chemicals in the training set 

for the sulfonyl urea class equation 

consists solely of triazine herbicides. 

4-426 
FINAL REPORT – January 2014 

BTUM CASRN 151882-81-4

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Green algae 96-hour EC50 = 76 mg/L

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.00 NES; estimated EC50 is greater than 

the measured water solubility (0.77 

mg/L). Narcosis classes (neutral 

organics) are provided for 

comparative purposes; DfE 

assessment methodology will use the 

lowest estimated toxicity value 

provided by ECOSAR classes that 

have a more specific mode of action 

relative to narcosis.

Chronic Aquatic Toxicity HIGH: Based on an estimated ChV of 0.73 mg/L for daphnid and 0.035 for algae, although there is a high 

degree of uncertainty and limited confidence in the estimations.

Fish ChV Fish ChV = 2.5 mg/L

(Estimated) 

ECOSAR: sulfonyl ureas

ECOSAR version 1.00 NES; estimated ChV is greater than 

the measured water solubility (0.77 

mg/L).

Fish ChV = 14 mg/L

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.00 NES; estimated ChV is greater than 

the measured water solubility (0.77 

mg/L). Narcosis classes (neutral 

organics) are provided for 

comparative purposes; DfE 

assessment methodology will use the 

lowest estimated toxicity value 

provided by ECOSAR classes that 

have a more specific mode of action 

relative to narcosis.

Daphnid ChV Daphnid ChV = 0.73 mg/L

(Estimated) 

ECOSAR: sulfonyl ureas 

ECOSAR version 1.00 There is a high degree of uncertainty 

for this estimate since the chemical 

may not be soluble enough to measure 

this predicted effect; ChV value is 

near the water solubility.

4-427 
FINAL REPORT – January 2014 

BTUM CASRN 151882-81-4

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Daphnid ChV = 9.4 mg/L

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.00 NES; estimated ChV is greater than 

the measured water solubility (0.77 

mg/L). Narcosis classes (neutral 

organics) are provided for 

comparative purposes; DfE 

assessment methodology will use the 

lowest estimated toxicity value 

provided by ECOSAR classes that 

have a more specific mode of action 

relative to narcosis.

Green Algae ChV Green algae ChV = 0.035 mg/L

(Estimated) 

ECOSAR: sulfonyl ureas 

ECOSAR version 1.00 There is some uncertainty to the 

estimated value for this compound 

since all chemicals in the training set 

for the sulfonyl urea class equation 

consists solely of triazine herbicides. 

Green algae ChV = 76 mg/L

(Estimated) 

ECOSAR: neutral organics 

ECOSAR version 1.00 NES; estimated ChV is greater than 

the measured water solubility (0.77 

mg/L). Narcosis classes (neutral 

organics) are provided for 

comparative purposes; DfE 

assessment methodology will use the 

lowest estimated toxicity value 

provided by ECOSAR classes that 

have a more specific mode of action 

relative to narcosis.

ENVIRONMENTAL FATE

Transport Evaluation of BTUM transport is based entirely on estimations based on QSARs for fugacity (level III), 

disassociation constant (pKa), soil adsorption coefficient (Koc), volatilization, and vapor pressure. It is 

expected to exist in both the neutral and anionic form at environmentally-relevant pH. BTUM is expected to 

have low mobility in soil. Anionic BTUM may have higher mobility due to enhanced water solubility. 

However, leaching through soil to groundwater is not expected to be an important transport mechanism. In 

the atmosphere, BTUM is expected to exist in the particulate phase, which will be deposited back to the soil 

and water surfaces through wet or dry deposition.

4-428 
FINAL REPORT – January 2014 

BTUM CASRN 151882-81-4

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Henry’s Law Constant 

(atm-m3/mole)

<1x10-8 (Estimated) EPI; Professional judgment Cutoff value for nonvolatile 

compounds, based on professional 

judgment.

Sediment/Soil 

Adsorption/Desorption

Coefficient – Koc

>30,000 (Estimated) EPI; U.S. EPA, 2004 Cutoff value for nonmobile 

compounds. 

Level III Fugacity 

Model

Air = <1%

Water = 2 % 

Soil = 72% 

Sediment = 26% (Estimated)

EPI

Persistence HIGH: Evaluation of the persistence of BTUM is based entirely on QSARs of aerobic and anaerobic 

biodegradation. Results from these models estimate ultimate biodegradation in months and primary 

degradation in weeks. Biodegradation under anaerobic methanogenic conditions is not probable based on 

results from estimation models. BTUM does not contain chromophores that absorb light at wavelengths >290 

nm. Therefore, it is not expected to be susceptible to direct photolysis. BTUM is not expected to undergo 

hydrolysis as it does not contain hydrolyzable functional groups. The atmospheric half-life of BTUM is 

estimated at 1.2 hours, although it is expected to exist primarily as a particulate in air. Therefore, 

biodegradation is expected to be the main degradation pathway for BTUM.

Water Aerobic 

Biodegradation

Weeks (primary survey model); 

Recalcitrant (ultimate survey model)

EPI

Volatilization Half-life 

for Model River

>1 year (Estimated) EPI

Volatilization Half-life 

for Model Lake

>1 year (Estimated) EPI

Soil Aerobic 

Biodegradation

No data located.

Anaerobic 

Biodegradation

Not probable (anaerobic-methanogenic 

biodegradation probability model)

EPI

Soil Biodegradation w/ 

Product Identification

No data located.

4-429 
FINAL REPORT – January 2014 

BTUM CASRN 151882-81-4

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Sediment/Water 

Biodegradation

No data located.

Air Atmospheric Half-life 1.2 hours (Estimated) EPI

Reactivity Photolysis Not a significant fate process (Estimated) Mill, 2000; Professional 

judgment 

Substance does not contain functional 

groups that would be expected to 

absorb light at environmentally 

significant wavelengths.

Hydrolysis Not a significant fate process (Estimated) Wolfe and Jeffers, 2000; 

Professional judgment 

Substance does not contain functional 

groups that would be expected to 

hydrolyze readily under 

environmental conditions.

Pyrolysis No data located.

Environmental Half-life 120 days (Estimated) EPI; PBT Profiler Half-life estimated for the 

predominant compartment, as 

determined by EPI and the PBT 

Profiler methodology.

Bioaccumulation LOW: Based on both the estimated BCF and BAF that are <100.

Fish BCF 25 (Estimated) EPI

BAF 4 (Estimated) EPI

Metabolism in Fish No data located.

ENVIRONMENTAL MONITORING AND BIOMONITORING 

Environmental Monitoring No data located.

Ecological Biomonitoring No data located.

Human Biomonitoring This chemical was not included in the NHANES biomonitoring report (CDC, 2011).

4-430 
FINAL REPORT – January 2014 

CDC (Centers for Disease Control and Prevention). Fourth national report on human exposure to environmental chemicals, updated 

tables. Department of Health and Human Services. 2011. http://www.cdc.gov/exposurereport/ (accessed on May 10, 2011). 

ECOSAR (2010) Ecological Structure Activity Relationship (ECOSAR) Version 1.00. Washington, DC: U.S. Environmental 

Protection Agency. http://www.epa.gov/oppt/newchems/tools/21ecosar.htm. 

EPI (EPIWIN/EPISUITE) Estimations Programs Interface for Windows, Version 4.00. U.S. Environmental Protection Agency: 

Washington D.C. http://www.epa.gov/opptintr/exposure/. 

ESIS (European chemical Substances Information System) Classification, labeling and Packaging of dangerous substances annex VI 

to regulation (EC) No 1272/2008 [Online] http://esis.jrc.ec.europa.eu/ (accessed on June 10, 2011). 

Mill, T. 2000. Photoreactions in Surface Waters. In Boethling, R.; Mackay, D., Handbook of Property Estimation Methods for 

Chemicals, Environmental Health Sciences (355-382). Boca Raton: Lewis Publishers.

PBT Profiler Persistent (P),Bioaccumulative (B), and Toxic (T) Chemical (PBT)Profiler, U.S. Environmental Protection Agency: 

Washington D.C. www.pbtprofiler.net. 

SPARC On Line Calculator pKa/property server. Ver 4.5 September, 2009. Available from, http://ibmlc2.chem.uga.edu/sparc/

(accessed on August 12, 2010. 

U.S. EPA (Environmental Protection Agency). High Production Volume (HPV) Challenge. Determining the Adequacy of Existing 

Data. U.S. Environmental Protection Agency: Washington D.C. 1999. http://www.epa.gov/hpv/pubs/general/datadfin.htm

U.S. EPA (Environmental Protection Agency). 2004. The Pollution Prevention (P2) Framework, EPA-748-B-03-001. Office of 

Pollution Prevention and Toxics 7403M, U.S. Environmental Protection Agency, Washington, DC. 20460. October 2003 

version updated in January 2004. Latest version available at http://www.epa.gov/opptintr/newchems/pubs/sustainable/p2framejune05a2.pdf 

Wolfe, N.; Jeffers, P. (2000) Hydrolysis. In Boethling, R.; Mackay, D., Handbook of Property Estimation Methods for Chemicals, 

Environmental Health Sciences (311-334). Boca Raton: Lewis Publishers. 

4-431 
FINAL REPORT – January 2014 

UU

4-432 

CASRN: 321860-75-7

MW: 784.9

(for representative structure)

MF: C42H36N6O8S

(for representative structure)

Physical Forms:

Neat: Solid

Use: Developer for thermal paper 

SMILES: c1(NC(=O)Oc6ccccc6)c(C)cc(NC(=O)Nc2ccc(S(=O)(=O)c3ccc(NC(=O)Nc4c(C)cc(NC(=O)Oc5ccccc5)cc4)cc3)cc2)cc1 (for representative structure)

Synonyms: Urea Urethane Compound

Polymeric: Yes

 Oligomers: A representative structure for the low molecular weight oligomer evaluated in this assessment is drawn above.

Metabolites, Degradates and Transformation Products: None

Analog: Confidential analog

 Endpoint(s) using analog values: Eye and skin irritation, respiratory 

and skin sensitization, immunotoxicity, neurotoxicity, genotoxicity, 

repeated dose

Analog Structure: Not applicable 

Structural Alerts: None identified

Risk Phrases: Not classified by Annex VI Regulation (EC) No 1272/2008 (ESIS, 2011).

Risk Assessments: None identified
FINAL REPORT – January 2014 

UU CASRN 321860-75-7

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

PHYSICAL/CHEMICAL PROPERTIES

Melting Point (°C) No data located.

Boiling Point (°C) >300 (Estimated) EPI; U.S. EPA, 1999 Estimates were performed on a 

representative component of the 

polymer shown above. This 

representative structure is anticipated 

to be the predominant component of 

the polymeric mixture. Cutoff value 

for high boiling point compounds 

according to HPV assessment 

guidance.

Vapor Pressure (mm Hg) <1x10-8 (Estimated) EPI; U.S. EPA, 1999 Estimates were performed on a 

representative component of the 

polymer shown above. This 

representative structure is anticipated 

to be the predominant component of 

the polymeric mixture. Cutoff value 

for nonvolatile compounds according 

to HPV assessment guidance.

Water Solubility (mg/L) <1x10-3 (Estimated) EPI; U.S. EPA, 1999 Estimates were performed on a 

representative component of the 

polymer shown above. This 

representative structure is anticipated 

to be the predominant component of 

the polymeric mixture. Cutoff value 

for nonsoluble compounds according 

to HPV assessment guidance.

4-433 
FINAL REPORT – January 2014 

UU CASRN 321860-75-7

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Log Kow 6.5 (Estimated) EPI Estimates were performed on a 

representative component of the 

polymer shown above. This 

representative structure is anticipated 

to be the predominant component of 

the polymeric mixture.

Flammability (Flash Point) No data located.

Explosivity No data located.

pH No data located.

pKa 10.3 (Estimated) SPARC Estimates were performed on a 

representative component of the 

polymer shown above. This 

representative structure is anticipated 

to be the predominant component of 

the polymeric mixture.

HUMAN HEALTH EFFECTS

Toxicokinetics UU is not absorbed by skin, poorly absorbed by the lung, and can be absorbed in the gastrointestinal tract.

Dermal Absorption in vitro No data located.

Absorption, 

Distribution, 

Metabolism & 

Excretion

Oral, Dermal, or Inhaled No absorption through skin, poor 

absorption by lung, and can be absorbed 

by the gastrointestinal tract.

Professional judgment Based on closely related confidential 

analog with similar structure, 

functional groups, and 

physical/chemical properties.

Acute Mammalian Toxicity LOW: No acute mammalian toxicity observed at oral and dermal exposure doses of less than or equal to 

2,000 mg/kg.

Acute Lethality Oral Rat oral LD0=2,000 mg/kg

(Measured)

Submitted Confidential Study Adequate.

Dermal Rat dermal LC0=3161 mg/kg (Measured) Submitted Confidential Study Adequate.

Inhalation No data located.

4-434 
FINAL REPORT – January 2014 

UU CASRN 321860-75-7

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Carcinogenicity MODERATE: There is uncertainty due to the lack of data located for this substance. Carcinogenic effects 

cannot be ruled out.

OncoLogic Results No data located.

Carcinogenicity (Rat and 

Mouse)

No data located.

Combined Chronic 

Toxicity/Carcinogenicity

No data located.

Genotoxicity LOW: UU was negative in bacterial mutagenicity assays and negative for chromosomal aberration in 

mammalian cells.

Gene Mutation in vitro Negative, Ames Assay, with and without 

activation (Measured)

Submitted Confidential Study Adequate.

Negative, E. coli reverse mutation assay, 

with and without activation (Measured)

Submitted Confidential Study Adequate.

Gene Mutation in vivo No data located.

Chromosomal Aberrations 

in vitro

No data located.

Chromosomal Aberrations 

in vivo

Negative, chromosomal aberration in 

CHL cells, with and without activation

(Measured)

Submitted Confidential Study Adequate.

DNA Damage and Repair No data located.

Other (Mitotic Gene 

Conversion)

No data located.

Reproductive Effects LOW: Based on professional judgment. A combination of limited predicted absorption, low predicted 

metabolism, and lack of significant toxicological concerns from repeated dose testing on a close analog 

suggests low potential hazard, with lower confidence.

Reproduction/ 

Developmental Toxicity 

Screen

Low potential for reproductive effects

(Estimated)

Professional judgment Estimated based on professional 

judgment.

4-435 
FINAL REPORT – January 2014 

UU CASRN 321860-75-7

PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Combined Repeated Dose 

with Reproduction/ 

Developmental Toxicity 

Screen

No data located.

Reproduction and Fertility 

Effects

No data located.

Developmental Effects LOW: Based on professional judgment. A combination of limited predicted absorption, low predicted 

metabolism, and lack of significant toxicological concerns from repeated dose testing on a close analog 

suggests low potential hazard, with lower confidence.

Reproduction/ 

Developmental Toxicity 

Screen

Low potential for developmental effects

(Estimated)

Professional judgment Estimated based on professional 

judgment.

Combined Repeated Dose 

with Reproduction/ 

Developmental Toxicity 

Screen

No data located.

Prenatal Development No data located.

Postnatal Development No data located.

Neurotoxicity LOW: No structural alerts or mechanistic pathways associated with neurotoxic effect identified.

Neurotoxicity Screening 

Battery (Adult)

Low potential for neurotoxicity effects

(Estimated)

U.S. EPA, 2010; Professional 

judgment

Estimated based on no identified 

structural alerts or mechanistic 

pathways associated with 

neurotoxicity. 

Repeated Dose Effects LOW: There were no repeated dose effects at oral doses ≤1,000 mg/kg-day.

28-Day repeated-dose study, rat, oral, 

gavage, no clinical signs, no macroscopic 

or histopathological abnormalities, 

NOAEL = 1000 mg/kg-day. (Measured)

Submitted Confidential Study Adequate.

Skin Sensitization LOW: Based on closely related confidential analog with similar structure, functional groups, and 

physical/chemical properties.

Skin Sensitization Non-sensitizing, Guinea pigs (Measured)Submitted Confidential Study Adequate.

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PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Respiratory Sensitization No data located.

Respiratory Sensitization No data located.

Eye Irritation LOW: UU is not an eye irritant.

Eye Irritation Slight irritation, rabbits (Measured) Submitted Confidential Study Adequate.

Dermal Irritation LOW: UU is not a dermal irritant.

Dermal Irritation Non-irritating, rabbits (Measured) Submitted Confidential Study Adequate.

Endocrine Activity No data located.

No data located.

Immunotoxicity No data located.

Immune System Effects No data located.

ECOTOXICITY

ECOSAR Class Substituted ureas; Amides; Carbamate esters

Acute Toxicity LOW: Based on measured 96-hour LC50 for fish and on estimated 96-hour LC50 for fish, 48-hour LC50 for 

Daphnid, and 96-hour EC50 for green algae that result in no effects at saturation (NES), as obtained for a 

representative component of the polymer that has a MW <1,000.

Fish LC50 Fish 96-hour LC50>250 mg/L (Measured) Submitted Confidential Study Adequate

Fish 96-hour LC50 = 0.028 mg/L

(Estimated)

ECOSAR: amides

ECOSAR version 1.00 NES; estimates were performed for 

the representative component of the 

polymer shown above.

Fish 96-hour LC50 = 0.118 mg/L

(Estimated)

ECOSAR: substituted ureas

ECOSAR version 1.00 NES; estimates were performed for 

the representative component of the 

polymer shown above.

Fish 96-hour LC50 = 0.061 mg/L

(Estimated)

ECOSAR: carbamate esters

ECOSAR version 1.00 NES; estimates were performed for 

the representative component of the 

polymer shown above.

Daphnid LC50 Daphnid 48-hour LC50 = 0.074 mg/L

(Estimated)

ECOSAR: amides

ECOSAR version 1.00 NES; estimates were performed for 

the representative component of the 

polymer shown above.

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PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Daphnid 48-hour LC50 = 0.088 mg/L

(Estimated)

ECOSAR: substituted ureas 

ECOSAR version 1.00 NES; estimates were performed for 

the representative component of the 

polymer shown above.

Daphnid 48-hour LC50 = 0.958 mg/L

(Estimated)

ECOSAR: carbamate esters

ECOSAR version 1.00 NES; estimates were performed for 

the representative component of the 

polymer shown above.

Green Algae EC50 Green algae 96-hour EC50 = 0.096 mg/L

(Estimated)

ECOSAR: amides

ECOSAR version 1.00 NES; estimates were performed for 

the representative component of the 

polymer shown above.

Green algae 96-hour EC50 = 0.288 mg/L

(Estimated)

ECOSAR: substituted ureas

ECOSAR version 1.00 NES; estimates were performed for 

the representative component of the 

polymer shown above.

Green algae 96-hour EC50 = 0.223

(Estimated)

ECOSAR: carbamate esters

ECOSAR version 1.00 NES; estimates were performed for 

the representative component of the 

polymer shown above.

Chronic Aquatic Toxicity LOW: Based on ChV values for fish, Daphnid, and green algae that result in no effects at saturation (NES), 

as obtained for a representative component of the polymer that has a MW <1,000.

Fish ChV Fish ChV = 0.00016 mg/L

(Estimated)

ECOSAR: amides

ECOSAR version 1.00 NES; estimates were performed for 

the representative component of the 

polymer shown above.

Fish ChV = 0.003 mg/L

(Estimated)

ECOSAR: substituted ureas 

ECOSAR version 1.00 NES; estimates were performed for 

the representative component of the 

polymer shown above.

Fish ChV = 0.005 mg/L

(Estimated)ECOSAR: carbamate esters 

ECOSAR version 1.00 NES; estimates were performed for 

the representative component of the 

polymer shown above.

Daphnid ChV Daphnid ChV = 0.00098 mg/L

(Estimated)ECOSAR: amides

ECOSAR version 1.00 NES; estimates were performed for 

the representative component of the 

polymer shown above.

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PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Daphnid ChV = 0.019 mg/L

(Estimated) 

ECOSAR: substituted ureas 

ECOSAR version 1.00 NES; estimates were performed for 

the representative component of the 

polymer shown above.

Daphnid ChV = 0.006 mg/L

(Estimated) 

ECOSAR: carbamate esters 

ECOSAR version 1.00 NES; estimates were performed for 

the representative component of the 

polymer shown above.

Green Algae ChV Green algae ChV = 0.046 mg/L

(Estimated) 

ECOSAR: substituted ureas

ECOSAR version 1.00 NES; estimates were performed for 

the representative component of the 

polymer shown above.

Green algae ChV = 1.311mg/L

(Estimated) 

ECOSAR: amides

ECOSAR version 1.00 NES; estimates were performed for 

the representative component of the 

polymer shown above.

Green algae ChV = 0.488 mg/L

(Estimated) 

ECOSAR: carbamate esters 

ECOSAR version 1.00 NES; estimates were performed for 

the representative component of the 

polymer shown above.

ENVIRONMENTAL FATE

Transport Evaluation of UU transport is based entirely on QSAR estimations that were performed on a representative 

component of the polymer that has a MW <1,000. This representative structure is anticipated to be the 

predominant component of the polymeric mixture. UU is expected to have low mobility in soil based on its 

expected strong absorption to soil. If released to the atmosphere, UU is likely to exist solely as particulate. As 

a particulate, atmospheric oxidation is not expected to be a significant route of environmental removal. 

Based on the Henry’s Law constant, volatilization from water or moist soil is not expected to occur at an 

appreciable rate. Level III fugacity models indicate that UU will partition predominantly to the soil and 

sediment. 

Henry’s Law Constant 

(atm-m3/mole)

<1x10-8 (Estimated) EPI Estimates were performed on a 

representative component of the 

polymer shown above. This 

representative structure is anticipated 

to be the predominant component of 

the polymeric mixture. Cutoff value 

for nonvolatile compounds based on 

professional judgment.

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PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Sediment/Soil 

Adsorption/Desorption

Coefficient – Koc

>30,000 (Estimated) EPI Estimates were performed on a 

representative component of the 

polymer shown above. This 

representative structure is anticipated 

to be the predominant component of 

the polymeric mixture. Cutoff value 

for nonmobile compounds.

Level III Fugacity 

Model

Air = <1% (Estimated)

Water = 1%

Soil = 52%

Sediment = 47%

EPI Estimates were performed on a 

representative component of the 

polymer shown above. This 

representative structure is anticipated 

to be the predominant component of 

the polymeric mixture.

Persistence VERY HIGH: UU is not ready biodegradable based on a Japanese MITI test. Further evaluation of the 

persistence of UU is based on predictive QSAR models for the representative component estimates UU to be 

recalcitrant to ultimate biodegradation, and suggest a biodegradation half-life of >180 days. In addition, the 

larger oligomers in the polymeric mixture with a MW>1,000 are expected to have Very High persistence 

potential based on DfE assessment guidance as they are likely too large and too water insoluble to be 

bioavailable. 

Water Ready Biodegradability Not ready biodegradable in Japanese 

MITI test (OECD 301C). 1% (by BOD) 

and 2% (by HPLC) biodegradation in 28 

days. (Measured)

Submitted Confidential Study Adequate.

Aerobic Biodegradation Weeks (primary survey model)

Recalcitrant (ultimate survey model))

EPI Estimates were performed on a 

representative component of the 

polymer shown above. This 

representative structure is anticipated 

to be the predominant component of 

the polymeric mixture.

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PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Volatilization Half-life 

for Model River

>1 year (Estimated) EPI Estimates were performed on a 

representative component of the 

polymer shown above. This 

representative structure is anticipated 

to be the predominant component of 

the polymeric mixture.

Volatilization Half-life 

for Model Lake

>1 year (Estimated) EPI Estimates were performed on a 

representative component of the 

polymer shown above. This 

representative structure is anticipated 

to be the predominant component of 

the polymeric mixture.

Soil Aerobic Biodegradation No data located.

Anaerobic 

Biodegradation

No data located.

Soil Biodegradation w/ 

Product Identification

No data located.

Sediment/Water 

Biodegradation

No data located.

Air Atmospheric Half-life 0.64 hours (Estimated) EPI The estimated half-life is for a gasphase reaction; UU is expected to 

exist as a particulate in the 

atmosphere and the rate of this 

process will be highly attenuated.

Reactivity Photolysis Not a significant fate process 

(Estimated)

Mill, 2000; Professional judgment Substance does not contain functional 

groups that would be expected to 

absorb light at environmentally 

significant wavelengths.

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PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Hydrolysis 42 minutes at pH 8;

7 hours at pH 7 (Estimated)

EPI Limited confidence in the estimated 

half-lives given the limited solubility 

anticipated for this material. 

Hydrolysis is not expected to occur to 

an appreciable extent and UU is 

anticipated to lie outside the domain 

of this model. 

Pyrolysis No data located.

Environmental Half-life 360 days (Estimated) EPI; PBT Profiler Half-life estimated for the 

predominant compartment, as 

determined by EPI and the PBT 

Profiler methodology for the 

representative component of the 

polymer shown above.

Bioaccumulation LOW: The measured BCF for UU is <100 (4.6). The estimated BAF for the representative component of the 

polymer is <100 (7.9). Although the BCF model results in a higher hazard concern, the BAF model is 

anticipated to better account for metabolism for this class of compounds. In addition, the polymeric 

components of the mixture that have a MW >1,000 are not expected to be bioaccumulative because, in 

general, substances with a MW >1,000 are not bioaccumulative due to their large size.

Fish BCF 0.46-4.6 (Measured) Submitted Confidential Study Adequate.

Fish BCF 9,100 (Estimated) EPI Estimates were performed on a 

representative component of the 

polymer shown above. This 

representative structure is anticipated 

to be the predominant component of 

the polymeric mixture.

BAF 7.9 (Estimated) EPI Estimates were performed on a 

representative component of the 

polymer shown above. This 

representative structure is anticipated 

to be the predominant component of 

the polymeric mixture.

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PROPERTY/ENDPOINT DATA REFERENCE DATA QUALITY

Metabolism in Fish No data located.

ENVIRONMENTAL MONITORING AND BIOMONITORING 

Environmental Monitoring No data located.

Ecological Biomonitoring No data located.

Human Biomonitoring This chemical was not included in the NHANES biomonitoring report (CDC, 2011).

4-443 
FINAL REPORT – January 2014 

CDC (Centers for Disease Control and Prevention). Fourth national report on human exposure to environmental chemicals, updated 

tables. Department of Health and Human Services. 2011. http://www.cdc.gov/exposurereport/ (accessed on May 10, 2011). 

ECOSAR (2010) Ecological Structure Activity Relationship (ECOSAR) Version 1.00. Washington, DC: U.S. Environmental 

Protection Agency. http://www.epa.gov/oppt/newchems/tools/21ecosar.htm. 

EPI (EPIWIN/EPISUITE) Estimations Programs Interface for Windows, Version 4.00. U.S. Environmental Protection Agency: 

Washington D.C. http://www.epa.gov/opptintr/exposure/. 

ESIS (European chemical Substances Information System) Classification, labeling and Packaging of dangerous substances annex VI 

to regulation (EC) No 1272/2008 [Online] http://esis.jrc.ec.europa.eu/ (accessed on June 10, 2011). 

Mill, T. 2000. Photoreactions in Surface Waters. In Boethling, R.; Mackay, D., Handbook of Property Estimation Methods for 

Chemicals, Environmental Health Sciences (355-382). Boca Raton: Lewis Publishers. 

PBT Profiler Persistent (P), Bioaccumulative (B), and Toxic (T) Chemical (PBT) Profiler, U.S. Environmental Protection Agency: 

Washington D.C. www.pbtprofiler.net. 

SPARC On Line Calculator pKa/property server. Ver 4.5 September, 2009. Available from, http://ibmlc2.chem.uga.edu/sparc/

(accessed on August 12, 2010). 

U.S. EPA (Environmental Protection Agency). High Production Volume (HPV) Challenge. Determining the Adequacy of Existing 

Data. U.S. Environmental Protection Agency: Washington D.C. 1999. http://www.epa.gov/hpv/pubs/general/datadfin.htm 

U.S. EPA (Environmental Protection Agency). Sustainable Futures Using NonCancer Screening within the Sustainable Futures 

Initiative Environmental Protection Agency: Washington D.C. 2010. http://www.epa.gov/opptintr/sf/pubs/noncanscreen.htm#systemic (accessed on February 09, 2011). 

4-444 
FINAL REPORT – January 2014

References

Boethling, R. S. and J. V. Nabholz (1997). Environmental Assessment of Polymers under the 

U.S. Toxic Substances Control Act. Ecological Assessment of Polymers Strategies for 

Product Stewardship and Regulatory Programs. J. D. Hamilton and R. Sutcliffe. New 

York, Van Nostrand Reinhold: 187-234.

FAO/WHO (2011). Toxicological and Health Aspects of Bisphenol A: Report of Joint 

FAO/WHO Expert Meeting 2-5 November 2010 and Report of Stakeholder Meeting on 

Bisphenol A 1 November 2010. Ottawa.

International Agency for Research on Cancer. (2006). "Preamble to the IARC Monographs." 

Retrieved April 17, 2012, from 

http://monographs.iarc.fr/ENG/Preamble/currentb6evalrationale0706.php.

Mayo-Bean, K., K. V. Nabholz, et al. (2011). Methodology Document for the Ecological 

Structure-Activity Relationship Model (ECOSAR) Class Program. Office of Pollution 

Prevention and Toxics. Washington, DC.

Meylan, W. M. and P. H. Howard (1995). "Atom/fragment contribution method for estimating 

octanol-water partition coefficients." J Pharm Sci 84(1): 83-92. 

Meylan, W. M., P. H. Howard, et al. (1996). "Improved method for estimating water solubility 

from octanol/water partition coefficient." Environ Toxicol Chem 15(2): 100-106. 

Nabholz, J. V., R. G. Clements, et al. (1993). Validation of Structure Activity Relationships 

Used by the USEPA’s Office of Pollution Prevention and Toxics for the Environmental 

Hazard Assessment of Industrial Chemcials. Environmental Toxicology and Risk 

Assessment. J. W. Gorsuch, F. J. Dwyer, C. G. Ingersoll and T. W. La Point. 

Philadelphia, American Society for Testing and Materials. 2: 571-590.

National Toxicology Program-Center for the Evaluation of Risks to Human Reproduction (NTPCERHR) (2008). NTP-CERHR Monograph on the Potential Human Reproductive and 

Developmental Effects of Bisphenol A. U.S. Department of Health and Human Services.

Rand, G. M., P. G. Wells, et al. (1995). Introduction to Aquatic Toxicity. Fundamentals of 

Aquatic Toxicity. G. M. Rand. Washington, DC, Taylor & Francis: 3-67.

U.S. Environmental Protection Agency. (2004). "The Pollution Prevention (P2) Framework, 

EPA-748-B-03-001. Office of Pollution Prevention and Toxics 7403M, U.S. 

Environmental Protection Agency, Washington, DC. 20460. October 2003 version 

updated in January 2004 ", from 

http://www.epa.gov/opptintr/newchems/pubs/sustainable/p2frame-june05a2.pdf.

U.S. Environmental Protection Agency (U.S. EPA) (1994). Joint Project on the Evaluation of 

(Quantitative Structure Activity Relationships. Office of Prevention Pesticides and Toxic 

Substances. Washington DC, EPA 743R-94-001. .

U.S. Environmental Protection Agency (U.S. EPA) (1997). Special Report on Environmental 

Endocrine Disruption: An Effects Assessment and Analysis. R. A. Forum. Washington, 

DC.

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U.S. Environmental Protection Agency (U.S. EPA) (1999a). Guidelines for Carcinogen Risk 

Assessment, Review Draft. Office of Research and Development. CEA-F-0644.

U.S. Environmental Protection Agency (U.S. EPA) (1999b). High Production Volume (HPV) 

Challenge: Determining the Adequacy of Existing Data. Office of Pollution Prevention & 

Toxics. Washington, DC.

U.S. Environmental Protection Agency (U.S. EPA) (2002). A Review of the Reference Dose and 

Reference Concentration Processes. Risk Assessment Forum. December 2002 Final 

Report. Washington, DC, EPA. EPA/630/P-02/002F.

U.S. Environmental Protection Agency (U.S. EPA) (2005a). Guidelines for Carcinogen Risk 

Asessment. Risk Assessment Forum. Washington, DC, EPA. EPA/630/P-03/001F.

U.S. Environmental Protection Agency (U.S. EPA) (2005b). Pollution Prevention (P2) 

Framework. Office of Pollution Prevention and Toxics. Washington D.C.

U.S. Environmental Protection Agency (U.S. EPA) (2010). TSCA New Chemicals Program 

(NCP) Chemical Categories. Office of Pollution Prevention and Toxics. Washington, DC.

U.S. Environmental Protection Agency (U.S. EPA). (2011a). "Assay Development." Retrieved 

April 17, 2012, from 

http://www.epa.gov/oscpmont/oscpendo/pubs/assayvalidation/index.htm.

U.S. Environmental Protection Agency (U.S. EPA) (2011b). Design for the Environment 

Program Alternatives Assessment Criteria for Hazard Evaluation, Version 2.0. Office of 

Pollution Prevention & Toxics. Washington D.C.

U.S. Environmental Protection Agency (U.S. EPA) (2011c). Endocrine Disruptor Screening 

Program, Weight-of-Evdence: Evaluating Results of EDSP Tier 1 Screening to Identify 

the Need for Tier 2 Testing. Office of Chemical Safety and Pollution Prevention. 

Washington, DC.

U.S. Environmental Protection Agency (U.S. EPA). (2011d). "Estimation Program Interface 

(EPI) Suite." Retrieved April 18, 2012, from 

http://www.epa.gov/oppt/exposure/pubs/episuite.htm.

U.S. Environmental Protection Agency (U.S. EPA) (2011e). Interpretive Assistance Document 

for Assessment of Discrete Organic Chemicals. Sustainable Futures Summary 

Assessment. Office of pollution Prevention and Toxics. Washington, DC.

U.S. Environmental Protection Agency (U.S. EPA) (2011f). On-line AOPWINTM User's Guide.

U.S. Environmental Protection Agency (U.S. EPA) (2011g). On-line BCFBAFTM User's Guide.

U.S. Environmental Protection Agency (U.S. EPA) (2011h). On-line KOWWINTM User's Guide.

U.S. Environmental Protection Agency (U.S. EPA). (2012a). "Analog Identification 

Methodology (AIM)." Retrieved April 17, 2012, from 

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U.S. Environmental Protection Agency (U.S. EPA). (2012b). "Endocrine Disruptor Screening 

Program (EDSP)." Retrieved April 17, 2012, from 

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Futures Summary Assessment. Office of Pollution Prevention and Toxics. 

Washington D.C.

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5. General Exposure and Life-cycle Information

The purpose of this chapter is to provide general information on exposure and life-cycle

considerations of thermal paper developers. This discussion is framed in the context of six lifecycle stages: manufacture of developers (Section 5.2.1), manufacture of thermal paper (Section 

5.2.2), conversion of thermal paper (Section 5.2.3), use of thermal paper (Section 5.2.4), end-oflife (Section 5.2.5), and manufacture of recycled paper products (Section 5.2.6), as shown in 

Figure 5 1. A quantitative exposure assessment is outside the scope of this project and not 

necessary for comparative hazard assessment. Rather, this chapter represents a qualitative review 

of potential environmental releases and exposures based on limited information from the 

published literature and publicly available sources (Section 5.3). Understanding the factors that 

affect exposure to bisphenol A (BPA) and alternative developers across the life-cycle provides 

additional context to the alternative selection process. This chapter includes information on the 

presence of BPA in people and the environment, with the understanding that thermal paper is 

only one of the sources of BPA. This type of information is generally not available for other 

chemicals in the assessment, however, the information on BPA in thermal paper can be 

considered as a surrogate for the other developers that have similar physical/chemical properties 

and behaviors and use patterns. 

Figure 5-1: Summary of Life-cycle of Developers in Thermal Paper

Manufacture of 

Thermal Paper

(coat)

Section 5.2.2

Manufacture of 

Developers

Section 5.2.1

1 2

Conversion of 

Thermal Paper

(add adhesives, 

resize, and package)

Section 5.2.3

3

Manufacture of 

Recycled Paper 

Products

Section 5.2.6

6

Recycling

End of Use

Section 5.2.5

Incineration

Landfill

5

Use of 

Thermal Paper

(receipts, labels, 

tickets, etc.)

Section 5.2.4

4

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FINAL REPORT – January 2014 

5.1 Potential Exposure Pathways and Routes (General) 

Exposure to developers can occur at many points in the life-cycle of thermal paper. There is a 

potential for occupational exposures during chemical and product manufacturing and product 

end-of-life (i.e., recycling, landfilling, or incineration). Additionally, there may be exposures to 

workers and consumers while thermal paper is being used and to the general population and the 

environment from releases during product manufacturing, use, and end-of-life.

The risk associated with a given chemical or substance is influenced by how exposure occurs. 

For example, the level of exposure associated with inhaling the chemical can be different from 

exposure via ingestion, in turn influencing the toxic outcome. As a result, exposure is typically 

characterized by different pathways and routes. An exposure pathway is the physical course a 

chemical takes from the source of release to the organism that is exposed, whereas the exposure 

route is how the chemical gets inside the organism. The three primary routes of exposure are 

inhalation, dermal absorption, and ingestion. The physical/chemical properties of the chemical 

influence the pathways and routes of exposure. 

The physical state of the chemical during chemical manufacturing, downstream processing, 

incorporation into consumer use products, and after release to the environment significantly 

influences the potential for inhalation exposure. In particular, there are three types of inhalation 

exposures to consider: dust, vapor, and mist. 

5.1.1 Inhalation Exposures

Dust: Chemicals that are manufactured, processed, and used as solids have the potential to result 

in occupational and consumer exposures to fugitive dusts. The potential for fugitive dust 

formation depends on whether the solid chemical is handled in the crystalline form, as an 

amorphous solid, or as a fine powder, as well as the particle size distribution and solids handling 

techniques. It is important to note the physical state of the chemical at the potential point of 

release and contact. The pure chemical may be manufactured as a solid powder, indicating a 

potential occupational exposure to dust. However, it may be formulated into solution before 

anyone comes in contact with it, thereby eliminating inhalation exposure to dust as a potential 

route. If there is exposure to dust, particle size influences the degree to which the chemical enters 

the body. Particles less than 10 microns in diameter are “respirable” with potential to reach and 

attach to tissues in the respiratory tract and deep lung where they may irritate lung tissue or be 

absorbed into the body. Once released into air or other media, the chemical can associate with 

particulate material through sorption onto particles or as particulates. For example, vapor phase 

chemicals can partition onto house dust and contribute to ingestion and dermal exposure 

pathways as well as inhalation.

Vapor: Exposure to vapors can occur when chemicals volatilize during manufacturing, 

processing, and use, or are associated with particulates in air. Most chemical manufacturing 

operations occur in closed systems. However, fugitive emissions are expected during 

manufacturing processes if there are open mixing operations, transfer operations, and 

loading/unloading of raw materials. The more volatile the chemical, the greater the fugitive 

releases and higher the potential occupational and consumer exposures. Therefore, vapor 

pressure (a measure of volatility) is a key indicator of potential exposures to vapors. Particulate 

exposures can result from physical breakdown of products, erosion of materials from surfaces, 

etc.

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Mist: Both volatile and nonvolatile liquids can result in inhalation exposure if manufacturing 

operations or use results in the formation of mist. Droplet size is an important consideration in 

determining exposure to chemicals released as a mist; as with dust, mist particles less than 10 

microns in diameter are “respirable” with potential to be absorbed in the respiratory tract. 

5.1.2 Dermal Exposures

Dermal exposure is also affected by the physical state of the chemical at the point of release and 

contact. For example, the likelihood of liquids being splashed or spilled during sampling and 

drumming operations is different than for similar operations involving polymerized solids, 

powders, or pellets. Dermal exposure is also generally assumed to be proportional to the 

concentration of chemical in the formulation. For example, the dermal exposure from contacting 

a pure chemical is generally greater than the exposure from contacting a solution that contains 

only 10 percent of the chemical (unless the formulation contains penetration enhancers). 

Screening-level evaluations of dermal exposure can be based on worker activities involving the 

chemical, consumer uses, and contact. For instance, there may be significant exposure when 

workers handle bags of solid materials during loading and transfer operations. Maintenance and 

cleanup activities during shutdown procedures, connecting transfer lines, and sampling activities 

also result in potential for dermal exposures. In the case of thermal paper, workers may be 

exposed to high concentrations of developer while changing cash register receipt rolls or 

cleaning machines. Consumer exposure from dermal contact will be dependent upon the amount 

and availability of the chemical in the product.

5.1.3 Ingestion Exposures 

Exposures via ingestion typically occur when individuals eat food or drink water that has become 

contaminated with chemicals. Dust particles may spread throughout the facility and settle (or 

deposit) on tables, on lunchroom surfaces, or even on food itself. Vapors may similarly spread 

throughout the facility and may be adsorbed onto food or particles in drinking water or dissolved 

in the drinking water. Another potential pathway for ingestion occurs from dust particles that are 

too large to be absorbed through the lungs. These “non-respirable particles” are often swallowed, 

resulting in exposures from this route. Children and others can be exposed by transfer from dust 

or other media to hands to mouth. Compared to inhalation and dermal exposures, ingestion is 

typically considered a less significant exposure pathway from an occupational and consumer 

health standpoint. However, ingestion is often an equally or more significant exposure route for 

the general population, and especially for children that ingest house dust, than inhalation and 

dermal exposure, as described in the next section. 

5.1.4 Environmental and General Population Exposures 

Releases to the environment can result in contamination of environmental media, leading to 

exposures in the general population and environmental organisms. In general, exposure 

concentrations to humans and other organisms by this route may be relatively low, but they may 

be most widespread, and may occur over a lifetime. Also, wildlife may be impacted by direct 

contact with contaminated media. If a chemical is bioaccumulative, it may concentrate in the 

animal and reach higher trophic levels and people through the food chain. Food contamination 

can also come from contaminants in biosolids derived from wastewater treatment plants

(WWTP) that are applied to agricultural fields or the ingestion of contaminated feed by 

livestock. 

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Direct human contact with contaminated environmental media, such as soil, sediment, house 

dust, and surface water, can lead to dermal exposure and incidental ingestion. Contact with 

contaminated drinking water can result in dermal and inhalation exposures, via washing and 

showering, as well as ingestion through consumption. 

Products used in the home can lead to exposures in the general population. Chemicals can 

volatilize from products and become incorporated into indoor air, or dust in the home, office, car, 

or other locations where products are used. Inhalation of contaminants in air, dermal contact with 

contaminated surfaces and dust, and incidental ingestion of dust or hand-to-mouth contact are all 

viable exposure pathways in the home. The physical properties of the chemical, along with how 

the chemical is incorporated into the product, influence how much of a chemical will enter the 

dust in a consumer’s environment. A person who does not have direct contact with products 

containing a particular chemical still has the potential to be exposed to them once the chemical is 

released. 

5.1.5 Exposures to Susceptible Populations

Susceptibility and exposure can vary for individuals within a population. Variability can be 

characterized but not reduced, and therefore it can be helpful to consider potentially exposed 

susceptible populations when considering chemical alternatives. Genetics, gender, life stage, 

pregnancy status, lifestyle, predisposition to diseases and other medical conditions, and other 

chemical exposures are examples of factors that lead to differential susceptibility (National 

Academy of Sciences 2008). 

For example, children may be more susceptible to environmental exposures than adults because: 

•

•

•

•

Their bodily systems are still developing; 

They eat more, drink more, and breathe more in proportion to their body size; 

Their behavior can expose them more to chemicals and organisms, for example, hand-tomouth and object-to-mouth behaviors (Xue, Zartarian et al. 2007); and 

They may be exposed to chemicals, including BPA, in human milk (Landrigan, 

Sonawane et al. 2002) and infant formula (Cao, Dufresne et al. 2008). 

Prenatal development represents a potential window of susceptibility whereby exposures to 

chemicals in the environment can contribute to adverse pregnancy and developmental outcomes 

(Stillerman 2008). During prenatal development, biological systems are forming, and disruption 

of these processes can have consequences later in life. While the placenta is designed to protect 

the fetus from stressors, including chemical exposures, chemicals (including BPA) have been 

shown to pass through this organ resulting in prenatal exposures (Perera, Rauh et al. 2003; 

Myren, Mose et al. 2006). 

Potential perinatal and childhood exposures to thermal paper chemicals can occur via exposure 

pathways that are unique to, or more common during early life, including: 

•

•

•

•

Maternal consumer and occupational exposures resulting in exposures to the fetus; 

Maternal consumer and occupational exposures resulting in ingestion via human milk; 

Transfer of thermal paper chemicals on hands to mouth; and 

Mouthing of thermal paper (chew and/or swallow). 

5-4 
FINAL REPORT – January 2014 5.1.6

Physical/Chemical Properties that May Impact Exposure to BPA and Alternatives 

CASRN Chemical Name

Common 

Name

Molecular 

Formula Structure

MW

pKa 

MP (oC)

BP (oC)

VP (mmHg @ 25 oC)

H

O2 sol (g/L)

Henry’s Law 

(atm•m3/mole)

Log Kow

80-05-7 2,2-bis(phydroxyphenyl)propane Bisphenol A C15H16O2 228.29 9.59-11.30 55 60.5 3.99×10-8 120-300 <1×10-8 a 3.32 

620-92-8 Bis(4-

hydroxyphenyl)methane Bisphenol F C13H12O2 200.24 7.55 162.5 sub 3.73×10-7 a 190a <1×10-8 a 2.91 

79-97-0 2,2’-Bis(4-hydroxy-3-

methylphenyl)propane Bisphenol C C17H20O2 256.35 10.5a 138-140 368b 2.3×10-6 b 4.7 a <1×10-8 a 4.7 

5129-00-0 Methyl bis(4-

hydroxyphenyl)acetate MBHA C15H14O4 258.28 9.7-9.9 ND >300a 3.3×10-8a 360a <1×10-8 a 2.8a

24038-68-4 4,4’-Isopropyllidenebis(2-

phenylpheno) BisOPP-A C27H24O2 380.49 10.8-10.9a 118 >300a <1×10-8 a 0.011a <1×10-8 a 7.2a

1571-75-1 4,4’-(1-

Phenylethylidene)bisphenol Bisphenol AP C20H18O2 290.36 9.91-10.1 189 >300a <1×10-8 a 1.1a <1×10-8 a 4.9a

PROPRIETARY PROPRIETARY Substituted 

phenolic 

compound #1

4.7, 10a 171-172 >300a <1×10-8 a 180a <1×10-8 a 3.4a

PROPRIETARY PROPRIETARY Substituted 

phenolic 

compound #2

10a 135-139 >300a <1×10-8 a 0.12a <1×10-8 a 6.3a

94-18-8 Benzyl 4-hydroxybenzoate PHBB C14H12O3 228.25 7.8a 111-112 >300a 3.8×10-6 60 2.9×10-10 a 3.56 

80-09-1 4-Hydroxyphenyl sulfone Bisphenol S C12H10O4S 250.27 8 240.5 >300a <1×10-8 a 1.1×10-3 <1×10-8 a 1.2 

5397-34-2 2,4’-

Bis(hydroxyphenyl)sulfone 2,4-BPS C12H10O4S 250.3 7.6, 8.2a 184 >300a <1×10-8 a 1.7×103a <1×10-8 a 1.7a

OH OH

OH OH

OH OH

OH OH

O O

OH

OH

OH OH

OH

O

O

S

O

O

OH OH

OH

S

O O OH

5-5 
FINAL REPORT – January 2014 

CASRN Chemical Name

Common 

Name

Molecular 

Formula Structure

MW

pKa 

MP (oC)

BP (oC)

VP (mmHg @ 25 oC)

H

O2 sol (g/L)

Henry’s Law 

(atm•m3/mole)

Log Kow

41481-66-7 bis-(3-allyl-4-hydroxyphenyl) 

sulfone TGSA C18H18O4S 330.40 8.3-8.5a 151-155 dec 9.2×10-10 4.79 8×10-8a 3.22 

97042-18-7 Phenol,4-[[4-(2-propen-1-

yloxy)phenyl]sulfonyl]- BPS-MAE C15H14O4S 290.34 8.20a 172 >300a <1×10-8 a 83a <1×10-8 a 3.1 

63134-33-8 4-Hydroxy-4’-

benzyloxydiphenylsulfone BPS-MPE C19H16O4S 340.40 8.2 170c >300a <1×10-8 a 10a <1×10-8 a 3.9 

95235-30-6 4-hydroxyphenyl 4-

isoprooxyphenylsulfone D-8 C15H16O4S 292.35 8.2a 129 >300a <1×10-8 a 21 <1×10-8 a 3.36 

191680-83-8 4-[4'-[(1'-methylethyloxy) 

phenyl]sulfonyl]phenol D-90 

C28H26O9S2

(n = 1); 

C44H42O14S3

(n = 2)

570.6; 

891.00 6.9-7.5a ND >300a <1×10-8 a 0.54 a; <1×10-3 a <1×10-8 a 3.8a

; 

5.9a

93589-69-6 

1,7-bis(4-

Hydroxyphenylthio)-3,5-

dioxaheptane

DD-70 C17H20O4S2 352.5 9.6a 108 >300a <1×10-8 a 130a <1×10-8 a 3.4a

232938-43-1 

N-(p-Toluenesulfonyl)-N'-(3-

ptoluenesulfonyloxyphenyl)ure

a 

Pergafast 201 C21H20N2O6S

2

460.5 

12.5; 5.3; 

-3.8; 

-13.6a

157.7 250 

(dec) <1×10-8 a 35 <1×10-8 a 2.6 

151882-81-4 

4,4'-bis(N-carbamoyl-4-

methylbenzenesulfonamide)d

iphenylmethane

BTUM C29H28N4O6S

2

592.70 4.8-5.4a 154-156 >300a <1×10-8 a 0.77 <1×10-8 a 2.61 

321860-75-7 Urea Urethane Compound UU C42H36N6O8S 784.9d 10.3 ND >300a <1×10-8 a <1×10-3 <1×10-8 a 6.5a

S

O

O

OH OH

S

O

O

OH O

S

O

O

O OH

S

O

O

O OH

S

OH O O

O O

O

S

OH

O O

n

OH

S O O S

OH

N

H O

N

H S

O

O

3CH

O S

O

O

CH3

N N

O

S

O O

N N

O

S

O O

5-6 
FINAL REPORT – January 2014 

5.2 Potential Sources of Exposure in the Life-cycle of Thermal Paper

This section addresses potential releases and exposures throughout the life-cycle of thermal 

paper. Exposure pathways can be extremely complex. For example, the release of a chemical to 

the environment during manufacture and use could potentially lead to environmental 

contamination. The entry of chemicals into the environment may then lead to exposure of the 

general population to substances through the consumption of contaminated drinking water, 

contact with contaminated environmental media (e.g., soil, house dust, sediment, water), and/or 

the consumption of contaminated food. This section is not intended to be a comprehensive 

exposure assessment but instead is designed to offer readers a general overview of potential 

sources of exposure throughout the life-cycle of thermal paper. It is important to note that the 

sources of BPA and other developers are numerous, and it is often not known to what degree 

thermal paper is contributing to releases.

5.2.1 Manufacture of Developers

This section addresses potential exposure scenarios associated with the manufacture of BPA and 

alternative developers. Unit operations, operating conditions, transfer procedures, and packaging 

operations vary with the manufacture of different developers. Potential releases and occupational 

exposures will depend on each of these parameters. While it is outside the scope of this report to 

identify and quantify the releases and exposures associated with individual chemicals, this 

section presents a general description of typical chemical manufacturing processes and identifies 

potential releases.

Throughout the chemical manufacturing process, there are several release points that may pose 

an exposure risk to workers including packaging operations, leaks from pumps and tanks, 

fugitive emissions from equipment, cleaning of process equipment, and product sampling 

activities. Additionally, crude or finished products are often stored on site in drums, day-tanks, or 

more permanent storage vessels until the chemical is packaged and shipped to next user. Transfer 

and packaging operations, any routine and unplanned maintenance activities, and spills or 

accidents may result in releases of chemicals to environmental media, leading to general 

population exposures. 

Potential release points from manufacturing and formulating can include: 

•

•

•

•

•

•

•

Transfer and packaging operations involving handling a chemical product; 

Routine and unplanned maintenance activities; 

Leaks from pumps and pipelines; 

Fugitive emissions from equipment; 

Product sampling; 

Transport and cleaning or equipment and storage vessels; and

Accidental releases. 

BPA is present in the environment as a result of direct releases from a variety of manufacturing 

or processing facilities (U.S. EPA 2010). BPA may also be present in the environment as a result 

of fugitive emissions during processing and handling, or a release of unreacted monomer from 

products (NTP-CERHR 2008). Workers may be exposed to BPA by inhalation or skin contact 

during the manufacture of BPA and BPA-containing products. A worst-case potential inhalation 

exposure to BPA during manufacturing is estimated at 100 μg/kg body weight/day (NTP5-7 
FINAL REPORT – January 2014 

CERHR 2008). The general population may be exposed to BPA through the contamination of 

drinking water or contact with contaminated environmental media. Alternative chemicals with 

similar physical/chemical properties are likely to result in similar exposure and release pathways.

5.2.2 Manufacture of Thermal Paper

A general manufacturing process for paper, in six major steps, is depicted in Figure 5–2 below 

(Evergreen Packaging 2011). 

Figure 5-2: The Overall Paper Production Process

•

•

•

•

•

•

5-8 

The first step of the paper manufacturing process involves the generation of pulp. To 

accomplish this, wood chips and cooking liquor are mixed in a digester and heated. The 

wood chips are then expelled through the high-pressure digester, which breaks them up into 

individual fibers, or pulp. 

The oxygen delignification step next removes 40 to 50 percent of the lignin that remains in 

the pulp. The pulp is washed and bleached, which aids in the removal of the pulp’s raw 

brown color. 

A large volume of water is then added in order to manufacture the paper. A slurry is created, 

with a pulp to water ratio of about 1 to 99. The slurry is moved on a moving wire mesh to 

form a uniform sheet. As the wet sheet travels along the wire, water drains through the wire 

mesh. 

This wet sheet is then moved onto a moving belt of felt where the sheet is pressed and 

squeezed in sections to compact the fibers. 

Once the fibers have been pressed, the sheet is moved onto dryer felts that pass over a series 

of heating rollers. Nine-five percent of the water is removed, leaving a small percentage of 

moisture to prevent cracking. 

Lastly, in the paper winding process, the paper is wound onto large reels, which are then cut 

into smaller rolls for convenient shipping and packaging. 

The manufacture of thermal paper follows the same general manufacturing process as for nonspecialty paper, with a few extra steps to incorporate additives in the formulation. The 

manufacturing process for thermal paper is shown below in Figure 5 3. 

A release liner is added to the pulp prior to the coalescing of the thermal paper’s multiple layers. 

This liner contains a release agent that provides a release effect against any type of sticky 

material. The various formulated layers (see Section 3.1), which contain the key additives in 

thermal paper (see Section 3.1.2), are pressed or calendered together between metal cylinders 

called calendars; this renders the paper’s surface smooth. This step also defines the paper’s 

texture: matte or glossy. The paper is then wound, bound, and shipped to product stores (see 

Section 5.2.3for further details on the conversion process) (Torraspapel 2008). 
FINAL REPORT – January 2014 

Figure 5-3: The Production Process for Thermal Paper

•

•

•

5-9 

Reference: (Torraspapel 2008) 

Potential release points from paper manufacturing can include: 

Addition and handling of chemicals, 

Fugitive emissions from equipment, and 

Wastewater discharges.

The amount of thermal paper manufactured in Europe in 2005–2006 was approximately 370 

million pounds of paper or an area of approximately 2.9 billion square yards (JRC-IHCP 2010). 

This value accounts for 4.2 million pounds of BPA. Similar statistics are not available for 

manufacture of thermal paper in the United States, or for the amounts of alternatives used in 

thermal paper. 

Very little information exists regarding releases of BPA, or alternative developers, by paper 

manufacturers in the United States. BPA is listed under section 313 of the Emergency Planning 
FINAL REPORT – January 2014 

and Community Right-to-Know Act (EPCRA) of 1986. Under EPCRA, facilities with more than 

10 employees, subject to Toxics Release Inventory (TRI) reporting requirements, that are 

manufacturing or processing more than 25,000 pounds of a listed chemical within a calendar 

year, or are using more than 10,000 pounds of a listed chemical within a calendar year, must 

report releases and transfers to the U.S. Environmental Protection Agency (EPA). None of the 

alternatives are TRI-listed chemicals. A review of TRI reporting for 2009 for BPA by paper 

companies (North American Industry Classification System (NAICS) Code 322) indicates two 

companies reporting: one that reported releases of 60 pounds for fugitive emissions, and another 

that reported total off-site transfers of 14,796 pounds (4,829 pounds transferred to treatment; 

9,967 pounds transferred to a wastewater treatment facility) (U.S. EPA 2011b). Note that the TRI 

reporting for BPA in the paper industry is not specific to thermal paper, although it is likely that 

this is the dominant use in paper manufacturing. 

5.2.3 Conversion of Thermal Paper 

Once thermal paper is manufactured, it is then sent to a facility where it is converted into a 

specific paper application. During this conversion process, thermal paper is wound onto large 

rolls. If the paper is to be used for label applications, such as shipping labels or labels for deli 

food packaging, adhesives may be applied to the paper. (See Section 2.2 for additional 

applications of thermal paper.) The thermal paper is then cut into smaller rolls, packaged, and 

sent to product stores (Torraspapel 2008). 

Potential release points from converting thermal paper can include: 

•

•

•

Addition or handling of chemicals, such as adhesives applied to labels, 

Cutting and packaging operations, and

Fugitive emissions from equipment.

Up to 10 percent of thermal paper from European manufacturers, which manufacture an 

estimated three millions pounds of thermal paper annually (JRC-IHCP 2010), is removed during 

manufacturing as trimmings. This waste material, known as “broke,” is immediately sent to a 

recycling facility. Similar statistics are not available for U.S. thermal paper conversion industry. 

5.2.4 Use of Thermal Paper 

Thermal paper is used in a variety of applications. Most commonly this includes point-of-sale 

(POS) receipts, but it may also include tickets, labels, and medical applications. In its finished 

form, thermal paper may release chemicals, including developers such as BPA, via dermal 

contact. While thermal paper does not account for a large percentage of the production volume of 

BPA, unlike most applications, BPA in thermal paper is a free monomer and is not chemically 

bound; thus, it is expected that the free BPA in this use would be more readily available to 

humans and the environment (Zalko, Jacques et al. 2011). Studies show that BPA is transferred 

from thermal receipt paper to currency when they come in contact, suggesting thermal receipt 

paper is an important source of BPA in paper currency (Schreder 2010; Liao and Kannan 2011a). 

Braun, Kalkbrenner et al. (2011) found that, by occupation, cashiers had the highest relative BPA 

concentrations in their blood. 

5-10 
FINAL REPORT – January 2014 

5.2.5 End-of-Life

After use, thermal paper has several end-of-life possibilities, including recycling, landfilling, and 

incineration, as well as abandonment. Limited information is available on the fate of BPA in 

thermal paper during end-of-life processes. No information is available on the other thermal 

paper developers. The European Union (EU) Risk Assessment Report for BPA included an 

analysis of thermal paper recycling and disposal practices that estimated that approximately 4 

million pounds of BPA was used to produce thermal paper in 2005–2006, with 1.5 million 

pounds of BPA reaching paper recycling sites each year (JRC-IHCP 2010). In the EU, about 10 

percent of thermal paper is sent for recycling when trimmed, with an additional 30 percent from 

commercial uses and consumer uses eventually ending up in the paper recycling stream (JRCIHCP 2010). According to the EU report, BPA releases from paper recycling plants can vary 

greatly based on capacity and process differences, such as the de-inking and pulping processes, 

and the level of wastewater treatment. There is also some evidence from Europe that BPA is 

entering recycled paper streams, including consumer paper products such as towels and tissue 

paper (Vinggaard, Körner et al. 2000). It is expected that disposal practices in the EU differ from 

the United States because recycling and incineration are much more common in the EU. 

Information on U.S. practices is not available, but it is likely that recycled paper in the U.S. also 

contains BPA. 

The concentration of BPA in paper processing wastewater effluent depends on the recycled

paper treated. The concentration of BPA in the final effluent of 20 recycling facilities in Japan 

ranged from 0.2 to 370 μg/L (average of 59 μg/L) (Fukazawa, Watanabe et al. 2002). Effluents 

from facilities where only pulp was processed contained lower BPA concentrations. 

Chlorinated BPA byproducts may be formed in secondary paper mills that use recycled paper 

feedstock containing thermal paper with BPA. BPA contaminants from recycled thermal paper 

can react with low concentrations of chlorine and sodium hypochlorite, which is added as a 

bleaching agent, yielding polychlorinated derivatives of BPA (Fukazawa, Watanabe et al. 2002). 

Chlorinated derivatives of BPA were detected at concentrations ranging from trace to 2.0 μg/L. 

Estrogenic activities of chlorinated derivatives of BPA were found to be relatively more potent 

than BPA, based on the yeast two-hybrid system assay (Fukazawa, Watanabe et al. 2002). 

Post-use thermal paper that is sent to a landfill can contribute to leachate (i.e., the mixture of 

rainwater and contaminants within the waste). This leachate has the potential to seep into the 

ground or drain into nearby surface water, transporting chemicals to places where humans and 

wildlife might be exposed to them. For example, there is concern that free monomeric BPA can 

leach out of thermal paper and contaminate landfill leachate. Gehring et al. (2004) concluded that 

continuous emissions of BPA from leachate from landfills receiving significant amounts of 

wastepaper can occur under anaerobic conditions. Although no data are available, the same 

concern would exist for alternatives to BPA, depending on their suitability to anaerobic 

degradation and transport processes. 

5.2.6 Manufacture of Recycled Paper Products

Several researchers have analyzed the BPA content in recycled paper products. Gehring et al. 

examined various sources of recycled paper collected in the city of Dresden, Germany (2004). 

Samples included toilet paper, imported cellulose, and various types of post-use paper stock

including brown/grey corrugated board, advertising supplements, magazines, catalogues, 

5-11 
FINAL REPORT – January 2014 

newspapers, free advertising papers, and chromo board. Of the types of recycled products 

analyzed, Gehring et al. found the most significant levels of BPA in toilet paper. The amount of 

BPA in toilet paper derived from recycled paper varied greatly, ranging from 3.2 to 41.1 mg/kg 

dry matter (2004). Gehring et al. also demonstrated that BPA in toilet paper also results in 

significant emission of the chemical into domestic wastewater, contributing about 36,000 pounds 

of BPA to wastewater annually (2004). 

Other sources of BPA in recycled paper products include paper and paperboard commonly used 

for food packaging. These products are often adapted to directly contact foodstuff. According to 

a study conducted by Ozaki et al. (2004), 67 percent of the recycled paper analyzed contained 

BPA (0.19-26 μg/g) (2004). BPA was also detected in virgin paper products; however, its 

concentrations were ten-fold higher in recycled paper products (Ozaki, Yamaguchi et al. 2004). 

Similarly, Vinggaard et al. (2000) analyzed BPA levels in 20 different brands of paper towels 

sold in retail shops in Denmark. Results indicated that paper towels manufactured from recycled 

paper contained 0.6 to 24 mg/kg of BPA whereas extracts from virgin paper contained negligible 

levels. Although no data are available, it is likely that alternatives to BPA would also be present 

in recycled paper products. 

5.3 Available Data on Occupational, Consumer, and Environmental Exposures to BPA, 

Thermal Paper Life-cycle

A quantitative exposure assessment is outside the scope of this project and not necessary for 

comparative hazard assessment. However, this section presents information on the levels of 

human and environmental exposures to developers in thermal paper that have already been 

published in the literature. Most published studies pertain to BPA, but chemicals with similar 

physical/chemical and environmental properties can be expected to behave similarly. 

5.3.1 BPA in Receipts

As discussed in Chapter 2, BPA is widely used as a developer in thermal paper, including 

receipts. Several studies evaluated the presence of BPA in thermal paper, noting that alternatives 

to BPA are currently on the market. In one study, BPA was detected at levels up to 2.2 percent of 

the total weight in 11 of the 22 POS receipts sampled, but half of the receipts were BPA-free 

(Biedermann, Tschudin et al. 2010). Mendum et al. (2011) likewise found BPA in 8 of 10 

receipts tested with levels ranging from 0.3-1.54 percent of the total weight. 

The Environmental Working Group (EWG) conducted a similar study to determine BPA levels 

in cash register receipts. Of the 36 receipts tested, 16 contained BPA in levels from 0.8 percent to 

2.8 percent (Lunder, Andrews et al. 2010). The Washington Toxics Coalition found BPA in 11 

of the 22 receipts it tested (Schreder 2010). The study also found BPA in 21 of the 22 dollar bills 

it tested, concluding that BPA travels from receipts to other objects. 

Liao and Kannan studied levels of BPA in paper currency from 21 countries (2011a). BPA was 

found in all paper currencies analyzed at concentrations ranging from 0.001 to 82.7 μg/g (equal 

to 0.000001 to 0.0827 mg/g). They also found that concentrations of BPA increased after 24 

hours of contact with thermal paper, which suggests that thermal paper is a major source of BPA 

in paper currency bills. Liao and Kannan conducted a similar study that found BPA in 94 percent 

of receipts tested at a geometric mean level of 0.211 mg/g (Liao and Kannan 2011b). Other paper 

products tested, such as napkins and toilet paper made from recycled paper, contained BPA at 

5-12 
FINAL REPORT – January 2014 

microgram-per-gram concentrations, and the authors concluded that contamination during the 

paper recycling process is a source of BPA in paper products.

5.3.2 Bisphenol S (BPS) in Receipts

Liao, Liu et al. (2012b) also evaluated levels of BPS in 16 types of paper and paper products and 

paper currency from 21 countries. BPS was found in all thermal receipt paper samples at 

concentrations ranging from 0.0000138 to 22.0 mg/g. BPS was detected in 14 other types of 

paper products, such as napkins and toilet paper, at concentrations ranging from the level of 

quantitation to 0.00838 mg/g. BPS was found in 87 percent of paper currencies analyzed at 

concentrations ranging from the limit of quantitation to 0.00626 mg/g. 

5.3.3 BPA Transfer to Skin and Potential for Dermal Absorption 

Releases of free BPA monomers in thermal paper can occur upon contact with the paper and can 

be subsequently absorbed into the skin, leading to exposure during handling and use. Several 

studies have analyzed such releases of BPA, particularly in POS receipts. Biedermann et al. 

(2010) demonstrated that BPA can be extracted from the receipts and has the potential to be 

absorbed in the skin upon contact. The researchers founds that two hours after contact, about 

0.17 μg (equal to 0.00017 mg) BPA migrated into the skin, such that it could not be recovered by 

washing with water. 

Zalko, Jacques et al. (2011) demonstrated that BPA can penetrate the skin under experimental 

conditions. Applying BPA to pig and human explants demonstrated that only two percent of the 

BPA remained on the skin surface; nearly half of the chemical passed completely through the 

skin and the rest persisted in the skin after 72 hours. There is also evidence that enzymes located 

in the skin glucuronidate BPA (Zalko, Jacques et al. 2011), a mechanism that facilitates 

elimination. 

5.3.4 Occupational Exposure 

Occupational exposures may occur during the manufacture of developers, the manufacture of 

thermal paper, or the handling of thermal paper. There is limited information on worker 

exposures to BPA during chemical manufacture. A series of studies conducted by Li and 

colleagues suggests a relationship between exposure to BPA and reproductive and 

developmental effects in Chinese workers in the BPA and epoxy manufacturing industry (Li, 

Zhou et al. 2010; Li, Zhou et al. 2011; Miao, Yuan et al. 2011); however, similar studies are not 

available for U.S. manufacturers of BPA. To our knowledge, there are no studies examining 

BPA exposures in thermal paper manufacturing. 

Occupational exposure to BPA may come from handling receipts. Biedermann et al. (2010) 

estimated that repeated handling of thermal paper containing BPA could result in transfer of up 

to 71 μg/day (equal to 0.071 mg/day), which is well below 3,000 μg/day (equal to 3 mg/day), a 

value derived by Biederman et al. from the present total daily intake (TDI)1 of 0.050 mg/kg 

bw/day, assuming 60 kg body weight. Liao and Kannan estimated that mean daily intake (MDI) 

1 TDI is a protective estimate of the amount of a chemical substance humans can be exposed to daily basis over the 

course of a lifetime without experiencing significant health risk. The TDI value set by the European Food Safety 

Authority (EFSA) for BPA is 0.05 mg/kg bw. More information about EFSA and BPA can be found at: 

http://www.efsa.europa.eu/en/topics/topic/bisphenol.htm. 

5-13 

 
FINAL REPORT – January 2014 

of BPA through dermal absorption in adults handling thermal paper was 921 ng/day (equal to 

0.000921 mg/day) for occupationally exposed individuals (2011b), significantly lower than the 

estimates of Biederman et al. The cumulative occupational exposure from handling a variety of 

thermal paper products was estimated to be 1,303 ng/day (equal to 0.001303 mg/day) (Liao and 

Kannan 2011b). Liao and Kannan (2011a) also estimated that the MDI of BPA from handling 

U.S. paper currency to be 1.02 ng/day (equal to 0.00000102 mg/day) for occupationally exposed 

individuals in the United States. 

In one U.S. study, pregnant women who worked as cashiers, who presumably had frequent 

contact with thermal paper used in cash register receipts, had the highest urinary BPA 

concentrations at 2.8 μg/g (equal to 0.0028 mg/g) compared with pregnant women in other 

occupations, including 1.8 μg/g (equal to 0.0018 mg/g) in teachers and 1.2 μg/g (equal to 0.0012 

mg/g) in industrial workers (Braun, Kalkbrenner et al. 2011). 

To date, one study has estimated the MDI of BPS from handling paper products and currency. 

Liao, Liu et al. (2012b) estimated that MDI of BPS through dermal absorption in adults handling 

paper products and paper currency was 789 ng/day (equal to 0.000789 mg/day) for 

occupationally exposed individuals. 

5.3.5 Consumer and General Population Exposure 

Several studies have estimated consumer and/or general population exposures. This section 

provides an overview of this research. Based on BPA concentrations in thermal paper, the 

Washington Toxics Coalition estimated that an average shopper would transfer approximately 30 

μg (equal to 0.030 mg) of BPA to the skin by rubbing a receipt (five times between two fingers 

and a thumb) (Schreder 2010). Liao and Kannan (2011b) estimated that the MDI of BPA, via 

handling of thermal paper to be 12.3 ng/day (equal to 0.0000123 mg/day) for the general 

population (2011b). Liao and Kannan (2011a) also estimated that the MDI of BPA from 

handling paper currency to be 0.102 ng/day (equal to 0.000000102 mg/day) for the general 

population in the United States. 

Although BPA exposure from dietary sources is estimated to be much greater, thermal paper 

accounted for more than 98 percent of the exposure from paper products, mainly because thermal 

receipt papers contain relatively high concentrations of BPA (Liao and Kannan 2011b). BPA is 

also used in numerous other applications with which consumers and the general public come into 

contact on a regular basis, contributing to exposure. Measured levels of urinary BPA reflect these 

complex exposure patterns. 

The Centers for Disease Control (CDC) reported that 95 percent of a sample size of 294 

Americans had detectable levels of BPA in their urine (Calafat, Ye et al. 2008). The median 

concentration of BPA in urine across all ages was found to be 2.7 ng/mL (equal to 0.0000027 

mg/mL) (uncorrected for creatinine) (Calafat, Ye et al. 2008). Based on currently available 

exposure data, BPA exposures appear to be higher in infants and children (NTP-CERHR 2008). 

Two studies evaluating exposure in children based on the National Health and Nutrition 

Examination Survey indicate that children ages 6-11 have higher exposures relative to adults 

(LaKind and Naiman 2008; LaKind and Naiman 2011). 

Subsequent studies have sought to clarify sources of BPA exposures in children. In one recent 

study, Morgan, Jones et al. (2011) quantified urinary total BPA in 81 Ohio preschool children 

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FINAL REPORT – January 2014 

ages 23-64 months over 48-hours. This study found the BPA intake through diet correlated with 

urinary excretion, suggesting that diet is the predominant source. The study authors estimated 

mean intake of 156.5 ng/kg/day (equal to 0.0001565 mg/kg/day) through dietary ingestion, and 

0.11 ng/kg/day (equal to 0.00000011 mg/kg/day) through non-dietary ingestion. The data were in 

agreement with an earlier study in which dietary ingestion through the consumption of both solid 

and liquid foods was shown to be the major route of exposure for 257 preschool children to BPA 

at their homes and daycare centers in North Carolina and Ohio (Wilson, Chuang et al. 2007).

BPA is also found in breast milk; in a study of 23 healthy women, all breast milk samples 

registered positive for BPA (Sun, Irie et al. 2004). Additionally, the presence of BPA has been 

documented in human amniotic fluid (Ikezuki, Tsutsumi et al. 2002), although there is 

controversy regarding the ability of the fetus to metabolize BPA (Nishikawa, Iwano et al. 2010; 

Doerge, Twaddle et al. 2011), which would influence the concentration of free and 

glucuronidated BPA in this compartment. 

To date, one study has estimated the MDI of BPS from handling paper products and currency. 

Liao, Liu et al. (2012b) estimated that MDI of BPS through dermal absorption in adults handling 

paper products and paper currency was 12.0 ng/day (equal to 0.000012 mg/day) for the general 

population. The results of this study suggest that other alternatives with similar 

physical/chemical properties and behavior would also transfer from the surface of thermal paper 

at least to the surface of skin, and potentially be absorbed through the skin or ingested. 

Another study reported exposure to bisphenol S based on urinary measurements (Liao, Liu et al. 

2012a). BPS was detected in 81% of the urine samples collected from 315 individuals in eight 

countries. The mean value in the U.S. was reported as 0.299 ng/ml (equal to 0.000000299 

mg/ml). Using a pharmokinetic model, the authors estimated that the median estimated daily 

intake of BPS associated with these urinary values is 0.316 μg/person (equal to 0.000316 

mg/person). 

5.3.6 Environmental Exposure 

As noted above, there are releases and transfers of BPA from the paper sector that are reportable 

to TRI. The relationship between these releases and transfers and environmental concentrations 

is not known. There are several studies on concentrations of BPA in the environment (Klecka, 

Staples et al. 2009). BPA is present in the environment as a result of direct releases and fugitive 

emissions from a variety of manufacturing or processing facilities (U.S. EPA 2011a). In addition, 

based on information from European and Japanese studies, the use of monomeric BPA in 

thermal paper also may contribute to environmental releases of BPA from paper manufacturing 

and recycling plants and to the presence of BPA in the stream of recycled paper used in toilet 

paper, paper tableware, and other products, and may contribute to the presence of BPA in 

landfills because paper products are a major contributor to the U.S. solid waste stream (JRCIHCP 2010; Vinggaard, Körner et al. 2000; Fukazawa, Hoshino et al. 2001; Gehring, Vogel et al. 

2004; Ozaki, Yamaguchi et al. 2004; Terasaki, Shiraishi et al. 2007). Liao and Kannan estimated 

that between 33.5 tons (based on the median concentration of BPA in thermal paper) and 1,040 

tons (based on the 95th percentile) are released into the environment per year in the United States 

and Canada through the disposal of thermal receipt papers (2011b). The following paragraphs 

provide a brief overview of some of the available studies of BPA in environmental media. 

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Surface Water: Most environmental monitoring results show that the concentrations of BPA in 

surface water bodies are lower than 1 μg/L (ppb), mainly due to its partitioning and 

biodegradability (Tsai 2006). Current predicted no effect concentrations (PNEC) for ecological 

organisms are 1.5 μg/L (EU), 1.6 μg/L (Japan), and 0.175 μg/L (Canada) (U.S. EPA 2010). BPA 

was detected at a median concentration of 0.14 μg/L (ppb) and a maximum concentration of 12 

μg/L (ppb) in 41.2 percent of 85 samples collected from U.S. streams in 1999 and 2000, 

although the authors suggest that the maximum concentration of 12 μg/L (ppb) may be an outlier 

as it was much higher than any of the other samples (Kolpin, Furlong et al. 2002). A recent 

review of BPA monitoring studies found that out of 26 studies in North America (2 in Canada 

and 24 in the United States), 80 percent (852 of 1,068) of surface water samples reported BPA 

concentrations below the detection limit. The median concentration reported was 0.081 μg/L 

(ppb) and the 95th percentile concentration was 0.47 μg/L (ppb) (Klecka, Staples et al. 2009). 

Wastewater: Two studies have addressed individual WWTPs; BPA was not detected above the 

detection limit of 0.0001 μg/L (ppb) in Louisiana in effluent from a WWTP, in samples collected 

from surface waters in Louisiana, or in drinking water at various stages of treatment at plants in 

Louisiana (Boyd, Reemtsma et al. 2003). A California study detected BPA in two of three treated 

wastewater samples at 0.38 and 0.31 μg/L (ppb) (limit of detection = 0.25 μg/L (ppb)) (Jackson 

and Sutton 2008). It also reported detecting BPA in wastewater generated by a pharmaceutical 

manufacturer (0.295 μg/L (ppb)), an industrial laundry (21.5 μg/L (ppb)), and a paper products 

manufacturer (0.753 μg/L (ppb)). 

A Canadian study reported BPA concentrations ranging from 0.031 to 49.9 μg/L (ppb) in sewage

influent and effluent (generally <1 μg/L (ppb) in the influent and <0.3 μg/ L (ppb) in the 

effluent) and from 0.104 to 36.7 μg/g (ppm) in raw and digested sewage sludge from multiple 

WWTPs in Canada (Lee and Peart 2000b). The same authors reported that BPA was detected in 

100 percent of sewage samples from 31 WWTPs across Canada with concentrations ranging 

from 0.080 to 4.98 μg/L (ppb) (median 0.329 μg/L (ppb)) for the influent and from 0.010 to 1.08 

μg/L (ppb)(median 0.136 μg/L (ppb)) for the effluent (Lee and Peart 2000a). Based on 

comparison of influent and effluent levels, they estimated that BPA in the influent was removed 

by the sewage treatment process with a median reduction rate of 68 percent. BPA was detected 

in sludge samples at concentrations ranging from 0.033 to 36.7 μg/g (ppm) on a dry weight basis.

A wide range of BPA was detected in wastewater discharges from industrial facilities with 

concentrations ranging from 0.23 to 149.2 μg/L (ppb). Higher BPA levels in wastewater were 

associated with facilities producing chemicals and chemical products and packaging and paper 

products, and with commercial dry cleaning establishments. BPA concentrations in pulp and 

paper mill sludge ranged from <0.02 (below detection limit) to 3.33 μg/g (ppm), with a median 

value of 0.076 μg/g (ppm), on a dry weight basis (Lee and Peart 2000a; Melcer and Klecka 

2011).

WWTP Biosolids: One recent study measured BPA in biosolids (treated municipal waste 

sewage sludge) products from WWTPs in seven states and found concentrations between 1,090 

and 14,400 μg/kg (ppb) BPA (median 4,690 μg/kg (ppb)) (Kinney, Furlong et al. 2006). Another

study reported BPA in treated biosolids from a single municipal U.S. WWTP at 4,600 μg/kg 

(ppb) and reported 81μg/ kg (ppb) in soil that received the land applied biosolids, and

concentrations of 147μg/ kg (ppb) in a nearby “control” soil that did not receive treatment with 

biosolids (Kinney, Furlong et al. 2008). That study also detected BPA at 81 μg/kg (ppb) in 

earthworms living in treated soil. A separate study conducted by Staples, Friederich et al. (2010)

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investigated the risk of BPA in sludge-amended soil to invertebrates and plants at the bottom of 

the terrestrial food chain. The risks for adverse effects to potworms, springtails, and six plant 

species were found to be low based on hazard quotient values that were ≤0.04 (Staples, 

Friederich et al. 2010) 

Groundwater: The U.S. Geological Survey (USGS) collected samples from 47 ambient 

groundwater sites (not drinking water wells) in 18 States and analyzed them for 65 organic 

wastewater contaminants. BPA was detected in 29.8 percent of the sampled groundwater sites, 

with a mean detected concentration of 1.78 μg/L (ppb) and a range of 1.06 to 2.55 μg/L (ppb). 

BPA was among the top five most frequently detected organic compounds in this study (Barnes, 

Kolpin et al. 2008a; Barnes, Kolpin et al. 2008b). The analysis of BPA concentrations in areas 

that were known or suspected to have at least some human and/or animal wastewater sources in 

upstream or upgradient areas detected BPA in 9.5 percent of the samples at a reporting level of 1 

μg/L (ppb). The maximum concentration of BPA measured in these samples was 1.9 μg/ L (ppb) 

(Barnes, Kolpin et al. 2008a; Focazio, Kolpin et al. 2008). 

Landfill Leachate: BPA has been detected in landfill leachate with maximum concentrations of 

1.7 μg/L (ppb) and 1.4 μg/L (ppb) in the receiving groundwater plume at a landfill that was 

known to be leaking (Rudel, Melly et al. 1998). Data for other landfill sites in the United States 

were not available, and this single point is not likely to be representative of the country. Landfill 

leachate measured in other countries contained more than 500 μg/L (ppb) of BPA (Tsai 2006). 

Studies conducted at Japanese landfills resulted in maximum untreated leachate concentrations 

of 17,200 μg/L (ppb) and treated leachate concentrations of 5.1 μg/L (ppb) (Crain, Eriksen et al. 

2007). 

Soil: Wilson et al. reported that BPA concentrations in soil samples taken from outdoor play 

areas of homes and daycare centers ranged from 4-14 ppb dry weight, with means of 6-7 ppb dry 

weight (2003). Klecka et al. reported a median concentration of 0.6 ppb BPA in North American 

freshwater sediments, including samples with measurements below the detection limit; BPA 

concentrations in samples from the United States ranged from 1.4 to 140 ppb dry weight (2009). 

Levels in U.S. marine sediments were reported to have a median of 3.5 ppb of BPA and to range 

from 1.5 to 5 ppb dry weight (Stuart, Capulong et al. 2005). 

No data have been reported on releases to the environment for any of the alternative developers. 

However, it is possible that alternatives will be released to the environment during the thermal 

paper life-cycle. This is particularly true of alternatives with physicochemical properties that are 

similar to BPA.

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FINAL REPORT – January 2014 

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Gehring, M., D. Vogel, et al. (2004). Bisphenol A contamination of wastepaper, cellulose and 

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Li, D.-K., Z. Zhou, et al. (2011). "Urine bisphenol-A (BPA) level in relation to semen quality." 

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Lunder, S., D. Andrews, et al. (2010). "Synthetic estrogen BPA coats cash register receipts." 

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6. Considerations for Selecting Thermal Paper Developers 

Selecting an appropriate developer for use in the manufacture of thermal paper involves 

consideration of a range of factors. Design for the Environment (DfE) Alternatives Assessments

provide information on chemical hazards and discuss other factors relevant to substitution 

decisions, such as use information, exposure considerations, cost and performance. Decisionmakers will likely supplement the human health and environmental information in this report 

with these other factors. 

This chapter begins by describing five general attributes evaluated in this assessment that can 

inform decision-making about chemical hazards: human health hazard, ecotoxicity, persistence, 

bioaccumulation, and exposure potential. It provides a discussion of data gaps in the full 

characterization of chemicals included in this assessment. Performance, economic, and social 

considerations are also briefly addressed. This chapter concludes by discussing interim risk 

management measures that may be relevant for instances in which alternatives are associated 

with trade-offs, and by providing additional resources related to state, federal, and international 

regulations, and available life-cycle assessment information. 

6.1 Human Health and Environmental Considerations

This section identifies a set of attributes for consideration when formulating or selecting 

alternative thermal paper developers. In general, a safer chemical has low human health hazard, 

low exposure potential, low ecotoxicity, rapid degradability, and low potential for 

bioaccumulation. 

6.1.1 Human Health Hazard 

The DfE Alternatives Assessment criteria address a consistent and comprehensive list of hazard 

endpoints (U.S. EPA 2011). Chemical hazards to human health include acute lethality, 

carcinogenicity, genotoxicity, reproductive and developmental toxicity, neurotoxicity, repeated 

dose toxicity, skin and respiratory sensitization, irritation/corrosivity, and endocrine activity. DfE 

criteria for most of these endpoints involve thresholds establishing levels of concern. Where data 

for certain endpoints were not available, hazard values were assigned using structure-activity 

modeling and professional judgment. 

Several of the chemicals evaluated in this assessment are structurally similar to either bisphenol 

A (BPA) or bisphenol S, resulting in similar human health hazard profiles. Some general trends 

based on the information provided in Chapter 4 include: all chemicals exhibit low concern for 

acute toxicity; and most chemicals exhibit low to moderate concern for carcinogenicity, 

genotoxicity, repeated dose toxicity, irritation, and sensitization; however an important caveat is 

that most hazard designations are based on modeled data and expert judgment. There are some 

opportunities for distinction based on reproductive and developmental toxicity. With lower 

absorption, systemic effects are not as likely. 

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6.1.2 Ecotoxicity 

Ecotoxicity includes adverse effects observed in wildlife, discussed in detail in Section 

4.5.1.Aquatic organisms have historically been the focus of this endpoint.1 Industry and 

government chemical reviews have traditionally focused on fish, aquatic invertebrates, and algae. 

Both acute and chronic aquatic toxicity should be considered in choosing a developer for use in 

thermal paper. Where data or expert knowledge is available, ecotoxic effects on other classes of 

animals and plants should be included in the hazard evaluation. Data from standard laboratory 

animals presented in respect to human health attributes can also be relevant to wildlife. To 

prevent concerns for higher trophic level organisms, bioaccumulation potential (Section 6.1.4) is

an important consideration for substitution decisions. 

For the thermal paper developers evaluated in this report, acute and chronic aquatic toxicity are 

variable, and thus may present an opportunity for distinction among the alternatives. 

6.1.3 Persistence

Persistence describes the tendency of a chemical to resist degradation and removal from 

environmental media, such as air, water, soil, and sediment. This is an important characteristic 

for chemicals used in thermal paper, as the paper may be recycled with potential releases to the 

environment. Chemical degradation in the environment either occurs through chemical reactivity 

with its surroundings or through biodegradation by microorganisms. Chemical reactivity is most 

commonly a result of hydrolysis (reactions with water) and photolysis (reactions with sunlight). 

Oxidative gas-phase processes may also play a role. In the absence of rapid chemical reactivity, 

biodegradation is the primary process that causes degradation. The destruction of a chemical by 

biodegradation is accomplished by the action of a living organism. Depending on the organism 

and chemical substrate combination, chemicals may degrade into other chemical substances 

(primary degradation) or may be completely mineralized into carbon dioxide and water (ultimate 

degradation). 

The rate of degradation is important, but equally important are the byproducts formed through 

the degradation process. In some cases, the products of biodegradation might be more toxic and 

persistent than the parent compound. 

For the thermal paper developers evaluated in this report, persistence is variable and may be an 

opportunity for distinction among the alternatives (see Chapter 4).

6.1.4 Bioaccumulation Potential 

The ability of a chemical to accumulate in living organisms is described by the bioconcentration, 

bioaccumulation, biomagnification, and/or trophic magnification factors. Most of the alternatives 

assessed in this report have been assessed as having Low to Moderate potential for 

bioaccumulation, but nearly all of the assessments are based on computer models. Based on 

structure activity relationships (SARs), the potential for a molecule to be absorbed by an 

organism tends to be lower when the molecule is larger than 1,000 daltons. None of the 

chemicals in this assessment meet this threshold. Note that care should be taken not to consider 

1 Aquatic organisms became the focus of ecotoxicology assessments for several reasons: releases to water were a 

prominent concern, data were more abundant, and hence computer models were developed based on aquatic 

organisms.

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FINAL REPORT – January 2014 

the 1,000 daltons size to be an absolute threshold for absorption – biological systems are 

dynamic and even relatively large chemicals may be absorbed under certain conditions. 

The test guidelines available to predict potential for bioaccumulation have some limitations. 

Bioconcentration tests tend to be limited for chemicals that have low water solubility

(hydrophobic). Even if performed properly, a bioconcentration test may not adequately measure 

bioaccumulation potential because bioaccumulation is a measure of all uptake, while most 

bioconcentration tests do not currently measure dietary uptake (i.e., uptake by fish via food 

versus via their gills, respectively). Under review in the Organisation for Economic Cooperation 

and Development (OECD) program and close to finalization is a major upgrade to the fish 

bioconcentration test, in which dietary uptake is included for the first time. Dietary uptake is of 

critical importance and is probably the dominant route of exposure for hydrophobic chemicals. 

For the thermal paper developers evaluated in this report, bioaccumulation concerns generally 

fall within the Low to Moderate range (see Chapter 4). 

6.1.5 Exposure Considerations 

For humans, chemical exposures may occur at different points throughout the chemical and 

product life-cycle through skin contact, by inhalation, and by ingestion, and exposures are

affected by multiple physicochemical factors, as discussed in Chapter 5. The DfE Alternatives 

Assessment begins with the assumption that exposure scenarios for chemicals and their 

alternatives within a functional use class are roughly equivalent. The assessment also recognizes 

that in some instances, chemical properties or use patterns may affect exposure scenarios. For

example, some BPA alternatives may require different amounts to achieve the same technical 

specifications. Stakeholders should evaluate whether manufacturing changes, life-cycle

considerations, and physicochemical properties will result in different patterns of exposure as a 

result of informed chemical substitution. In general, the chemicals included in this assessment 

have similar physicochemical parameters, and their use as developers is roughly equivalent. 

Therefore, exposure patterns are expected to be similar.

6.2 Considerations for Poorly or Incompletely Characterized Chemicals and Variable 

Amounts of Data 

For most industrial chemicals, experimental data for hazard characterization are limited. For 

chemicals in this report without full data sets, analogs, SAR modeling, and expert judgment were 

used. More information on predicted hazard levels can be found in Chapter 4. Estimated values 

in the report can be used to prioritize testing needs. 

Several chemicals included in this analysis appear to have more preferable profiles, with Low 

human health and ecotoxicity endpoints (see Chapter 4). However, because no chemical-specific 

empirical data were available, their hazard evaluations were entirely predicted based on SARs, 

analogs, and expert judgment. Empirical data will allow for a more robust assessment that will 

support expert judgments and we therefore strongly encourage additional studies to fill these data 

gaps. 

In the absence of measured data, users of this alternatives assessment should be cautious in the 

interpretation of hazard profiles. For chemicals without data, developing data would prevent 

unexpected consequences if a prediction did not hold true. If chemicals are used at higher 

volumes, or are likely to be used at higher volumes in the future, this fact should also be given 

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FINAL REPORT – January 2014 

weight when considering data needs. Decision-makers should proceed with caution and are 

advised to read the full hazard assessments for each chemical (see Chapter 4) which may inform 

whether additional testing is needed. 

Where hazard characterizations are based on measured data, there are often cases where the 

amount of test data supporting the hazard rating varies considerably between alternative 

chemicals. In Table 4 4, the hazard characterizations based on SAR or expert judgment are listed 

in black italics, while those with hazard characterizations based on measured test data are listed 

in bold color. The amount of measured test data available to inform the evaluation of endpoints 

can vary from only one study to many studies in many species with different routes of exposure 

and exposure duration. In some instances, testing may go beyond basic guideline studies, and it 

can be difficult to compare data for such chemicals against those with only a single guideline 

study, even though hazard designations for both chemicals are “based on empirical data” and 

thus come with a higher level of confidence. 

Comparisons between a chemical with only one study and a second chemical with many studies 

are complex and merit careful consideration. For hazard screening assessments, such as the DfE 

approach, a single adequate study can be sufficient to provide a hazard rating. Therefore, some 

ratings reflect assessment based on one study, while others reflect assessment based on multiple 

studies of different design. The hazard rating does not convey these differences – the full hazard 

profile should be consulted to understand the limitations of the available data. 

6.3 Performance Considerations

This section identifies general performance attributes that companies can consider when 

formulating or selecting alternative chemicals. These attributes are critical to the overall function 

and marketability of the chemicals and can be considered jointly with economic considerations 

and the human health and environmental attributes described above. 

Known thermal paper developers are typically organic or organometallic compounds that have 

the following physical properties: low water solubility, substantially colorless, odorless, and 

chemically inert towards water and oxygen over a pH range from 6 to 10 (D. Keller, personal 

communication, December 1, 2011). 

As discussed in Chapter 3, performance characteristics of effective developers in thermal paper 

include: 

•

•

•

•

•

•

•

Appropriate acidity, such that it produces no background imaging; 

Ability to fully react with the colorformer when heated;

Reaction at the temperature of the specific printer;

Stable at end use temperatures;

Appropriate level of permanence for the application; 

Appropriate performance vs. cost balance; and

Feasibility for large-scale production. 

In considering alternative formulations or chemical substitutions, decision-makers will need to 

consider the pH, temperature, and water solubility of the developer, as well as the stability and 

durability of the resulting image. The following conditions may limit the durability of thermal 

images: exposure to temperatures greater than 40 ̊C, wet environments, direct sunlight, and 

certain chemicals such as alcohol, fuels, and oils (Koehler Thermal Papers 2011). However, 

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FINAL REPORT – January 2014 

depending on the grade, thermal papers can retain their image integrity even in conditions of 

bright lights, moisture, scuffing, and high temperatures up to 180 ̊F (Appleton 2003). 

In addition to considering the hazard information provided in Chapter 4 and the performance 

characteristics described above, other considerations include: 

•

•

•

Printer Compatibility: Modifications to thermal paper manufacture, either to 

developers or more broadly to other chemistry or process, should require consideration of 

how these changes may affect compatibility with existing thermal printers or what 

changes to printer technology or re-design may be required as a result.

Compatibility with End Use: Specific developers and types of thermal paper are used 

for specific applications, depending on performance, design, and economic 

considerations. Direct thermal paper can be used in a wide range of applications, 

including amusement park tickets, produce labels, retail hang tags, ski lift tickets,

baggage tags, mass transit tickets, parking receipts, and lottery tickets (Appleton 2011). 

Modifications to thermal paper design would require consideration of appropriateness for 

specific end uses.

Appropriate Image Quality: Alternatives should ensure appropriate image quality at 

the time of printing and stability for the required time period. Thermal images have 

sufficient resolutions for printing of text, graphics, and barcodes. Depending on grade, 

image integrity can last up to 10 years (Appleton 2003; Koehler Thermal Papers 2011). 

6.4 Economic Considerations

This section identifies economic attributes that companies can consider when formulating or 

selecting alternative chemicals. A comprehensive consideration of economic factors is often 

more fully addressed by decision-makers within the context of their companies or organizations. 

Accurate cost estimations are company-specific, and the impact of substituting chemicals on 

complex product formulations can only be analyzed using in-house data that is likely to be 

business confidential. A company should determine for itself how changes will impact market 

share or other business factors. Cost considerations may be relevant across the chemical and/or 

product life-cycle. These attributes are critical to the overall function and marketability of 

alternatives and can be considered jointly with performance attributes and human health and 

environmental attributes. 

To ensure economic viability, alternatives should be easy to process and cost-effective to 

integrate into products. The most desirable alternatives are compatible with existing process 

equipment and can be integrated in existing products. If this compatibility is not available, 

manufacturers will need to modify their processes and potentially purchase new equipment. 

From an economic standpoint, the ideal alternative would be a drop-in replacement that has 

similar physical and chemical properties such that existing storage and transfer equipment as 

well as manufacturing technologies could be used without significant modification. However, 

chemicals with similar physical and chemical properties may have similar hazard and exposure 

profiles.

Substituting chemicals can involve significant costs, as industries may need to adapt their 

production processes and have products re-tested for all required performance and product 

standards. Decision-makers are advised to see informed chemical substitution decisions as longterm investments and to replace the use of BPA with a chemical they anticipate using for many 

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FINAL REPORT – January 2014 

years to come. This includes attention to potential future regulatory actions as well as market 

trends. 

Alternatives that are either more expensive per pound or require more chemical per unit area to 

be functional will increase costs. In this situation, the cost of a chemical that must be used at a 

higher application rate may be passed on to customers, who will subsequently pass the cost on to 

consumers. In some cases, the price premium may diminish over the different stages of the value 

chain. 

Some of the alternative chemicals assessed in this report are currently manufactured in high 

volume. Others are not currently available in quantities that would allow for immediate 

widespread use. Prices and availability are likely to change with an increase in demand.

Handling, disposal, and treatment costs may be important considerations when evaluating 

alternatives. Inherently high hazard chemicals may require special engineering controls and 

worker protections that are not required of less hazardous alternatives. Disposal costs for high 

hazard chemicals may also be greater than for low hazard alternatives. High hazard chemicals 

may be more likely to result in unanticipated cleanup requirements should risk management 

protections fail or unanticipated exposures or spills occur. Additionally, some chemicals may 

require specific treatment technologies prior to discharge through wastewater treatment systems. 

These costs can be balanced against the up-front costs for the purchase of the alternative 

chemical, new equipment, etc. Finally, initial chemical substitution expenses may reduce future 

costs of mitigating consumer concerns and perceptions related to hazardous chemicals.

6.5 Social Considerations 

Decision-makers should be mindful of a number of social considerations when choosing 

alternative chemicals. This section highlights occupational, consumer, and environmental justice 

considerations. Stakeholders may identify additional social considerationsfor application to their 

own decision-making processes.

Awareness of social considerations related to informed substitutions includes attention to 

participation in decision-making processes, the impacts of human behaviors on the 

implementation or on outcomes of interventions, and the distributions of impacts across 

populations. Social considerations are one of the three pillars of sustainability (National 

Academy of Sciences 2011) and a focus on sustainability recognizes that human and 

environmental systems are coupled and interdependent (Clark 2007). Decisions should be made 

to maximize social, environmental, and economic benefits and to minimize the adverse effects of 

conflicts between these areas. According to the National Academy of Sciences report on 

“Sustainability and the U.S. EPA” (2011), the U.S. Environmental Protection Agency (EPA) 

would benefit from working with stakeholders to develop robust indicators for these attributes. 

Occupational considerations: Some stakeholders have raised concerns for differential 

exposure to BPA based on occupation. In particular, some partners noted that cashier jobs are 

often held by young women of childbearing age, who may experience greater exposures to BPA 

due to frequent handling of thermal paper receipts. Existing research reinforces these concerns

(see Section 5.3.4). Braun et al. (2011) found that prenatal urinary BPA exposures were highest 

among cashiers, although this finding was attenuated after adjustment for socioeconomic factors. 

Prenatal exposures are of particular concern due to the increased susceptibility of early life 

stages, discussed in Section 5.3.4. Liao and Kannan (2011) compared occupational exposure, 

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FINAL REPORT – January 2014 

based on handling 150 pieces of thermal paper/day to exposure in the general population, based 

on handling two pieces of thermal paper/day. They estimated occupational exposure to thermal 

paper at 1,303 ng/day of BPA, compared to BPA exposure in the general population of only 17.5 

ng/day. 

Consumer considerations: Consumers are potentially exposed to any chemicals found on 

thermal paper. As detailed in Section 5.3.5, exposure research has found that Americans carry 

body burdens of BPA (Calafat, Ye et al. 2008), although thermal paper is not considered to be 

the primary source of exposure (Rudel, Gray et al. 2011). Nonetheless, consumer reactions to 

exposure concerns can impact markets by creating pressure for substitution. DfE Alternatives 

Assessments can assist companies navigating these substitution pressures. There is greater 

emphasis on “green” products, and some consumers and non-governmental organizations 

(NGOs) advocate for informed substitution of chemicals, moving away from certain classes of 

chemicals entirely, with product re-design. 

In addition to substituting in alternative chemicals, some organizations advocate for moving 

away from certain classes of chemicals entirely, with product re-design, to avoid future 

substitutions altogether. Product manufacturers should be mindful of the role of these 

organizations in creating market pressure for alternative chemicals and strategies, and should 

choose replacement chemicals – or re-designs – that meet the demands of their customers. 

Environmental justice considerations: At EPA, environmental justice concerns refer to the 

disproportionate impacts on minority, low-income, or indigenous populations that exist prior to 

or that may be created by the proposed action. These disproportionate impacts arise because 

these population groups experience higher exposures, are more susceptible in response to 

exposure, or experience both conditions. Factors that are likely to influence resilience/ability to 

withstand harm from a toxic insult can vary with sociodemographics (e.g., co-morbidities, diet, 

metabolic enzyme polymorphisms) and are therefore important considerations. Adverse 

outcomes associated with exposure to chemicals may be disproportionately borne by minority 

and low income populations. Insights into EPA’s environmental justice policy can be accessed 

at: www.epa.gov/compliance/ej/resources/policy/considering-ej-in-rulemaking-guide-07-

2010.pdf. 

Some populations have higher exposures to certain chemicals in comparison to the general 

population. Minority and low-income populations are over-represented in the manufacturing 

sector, increasing their occupational exposure to chemicals (Bureau of Labor Statistics 2012). 

Higher exposures to environmental chemicals may also be attributable to atypical product use 

patterns and exposure pathways. This may be due to a myriad of factors such as cultural 

practices, language and communication barriers, and economic conditions. The higher exposures 

may also be a result of the proximity of these populations to sources that emit the environmental 

chemical (e.g., manufacturing industries, industries that use the chemical as production input, 

hazardous waste sites), access to and use of consumer products that may result in additional 

exposures to the chemical, or higher employment of these groups in occupations associated with 

exposure to the chemical. 

Considering environmental justice in the assessment of an alternative chemical may include 

exploring product use patterns, pathways and other sources of exposure to the substitute, 

recognizing how upstream factors such as socio-economic position, linguistic and 

communication barriers may alter typical exposure considerations. One tool available to these 

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FINAL REPORT – January 2014 

populations is the Toxics Release Inventory (TRI), which was established under the Emergency 

Planning and Community Right-to-Know Act (EPCRA) to provide information about the 

presence, releases, and waste management of toxic chemicals. Communities can use information 

reported to TRI to learn about facilities in their area that release toxic chemicals and to enter into 

constructive dialogue with those facilities. This information can empower impacted populations 

by providing an understanding about chemical releases and the associated environmental impacts 

in their community. Biomonitoring data for an alternative chemical, if available, can also signal 

the potential for disproportionate exposure among populations with environmental justice issues. 

6.6 Trade-offs and Interim Risk Mitigation 

In the absence of clearly-preferable low hazard functional alternatives, risk mitigation may be 

necessary in the interim. The hazard evaluations in Chapter 4 of this alternatives assessment 

include an analysis of the intrinsic properties that influence exposure, fate, and transport. Further 

information on exposure pathways and life-cycle considerations is presented in Chapter 5. A 

chemical alternative that poses a significantly greater opportunity for exposure should be further 

evaluated, and decision-makers should supplement the comparative chemical hazard assessment 

described in this report with other assessments, such as risk assessments, for potentially 

preferable alternatives.

In many instances, it is apparent that alternative chemicals come with trade-offs. For any 

chemical identified as a potential alternative, some endpoints may appear preferable, while 

others indicate increased concern relative to the original chemical. For example, a chemical may 

have a lower concern for human health but a higher concern for aquatic toxicity or persistence. 

These types of trade-offs can be difficult to evaluate, and such decisions should take into account 

relevant information about the chemical’s hazard profile, expected product use, the potential for 

worker and consumer exposure, and the opportunity for the chemical to enter various waste 

streams, among other life-cycle and mitigation considerations. For example, chemicals expected 

to have high levels of developmental or reproductive toxicity should not be used in products 

intended for use by children or women of child-bearing age. Chemicals with high aquatic 

toxicity concerns should not be used if releases to water cannot be mitigated in the 

manufacturing, use, and disposal process. 

Risk mitigation actions provide the opportunity to limit human health and environmental 

exposure. These actions provide immediate opportunities to address exposure concerns and may 

be considered alone or in conjunction with selection of an alternative, if appropriate. Examples 

of actions that may be appropriate are presented below. 

The traditional hierarchy of exposure control practices begins with elimination and substitution 

(NIOSH 2011). When chemicals cannot be eliminated or substituted with safer alternatives, there 

are a variety of modifications and engineering controls that should be considered. For example, 

in the manufacture and use of chemicals in industrial processes, exposure can be limited through 

innovative engineering controls such as containment, improvements to local ventilation, and the 

use of negative-pressure systems for feeding materials (He, Miao et al. 2009). Personal 

protective equipment can also be used and is considered to be the last line of protection in the 

exposure control hierarchy. 

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FINAL REPORT – January 2014 

Figure 6-1: Traditional Hierarchy of Exposure Control Practices

6-9 

Source: (NIOSH 2011) 

In consumer and occupational settings, risk mitigation measures may help reduce or avoid 

exposure to BPA in thermal paper. For example, after handling receipts, consumers and retail 

workers can limit their exposure to BPA by washing their hands prior to preparing or eating

food, storing receipts separately in a wallet or purse, and avoiding the use of alcohol-based hand 

cleaners, which have the potential to increase dermal BPA absorption (Lunder, Andrews et al. 

2010). 

Risk mitigation measures may also limit human and environmental exposures to BPA and other 

chemicals during recycling or disposal. For example, recycling of thermal paper can lead to 

release of BPA into the environment through sludge and wastewater (JRC-IHCP 2010) and BPA 

contamination of recycled paper products, which are often used to store food (Ozaki, Yamaguchi 

et al. 2004). As an alternative to recycling, thermal paper can be disposed of in a landfill. While 

the anaerobic conditions associated with many landfills do not favor the degradation of BPA 

(Ying and Kookana 2005), the collection and treatment of landfill leachate can decrease the 

likelihood of BPA entering the environment. 

A recent study suggests that the burning of plastics in waste disposal is a significant source of 

atmospheric BPA, but further research is needed to confirm the results and determine if 

prolonged exposure to low level atmospheric BPA could be associated with negative health 

effects (Fu and Kawamura 2010). Incineration produces negligible waste to soil and aquatic 

environments (JRC-IHCP 2010). 

6.7 Innovation and Design Challenges 

A DfE Alternatives Assessment can suggest directions for innovation and product development, 

especially when clearly preferable alternatives are not available. This can spur innovation by 

identifying design challenges and by highlighting the hazard endpoints and measures of exposure 

potential that delineate safer chemicals. 

Green chemistry tools and expertise are growing. The DfE approach can enable identification of 

safer substitutes that emphasize greener chemistry, and it points the way to innovation in safer 

chemical design, where hazard becomes a part of a performance evaluation. EPA encourages 

collaboration to identify safer solutions to complex chemical hazards. For more information on 

green chemistry, please refer to the EPA Green Chemistry Program 
FINAL REPORT – January 2014 

(http://www.epa.gov/greenchemistry/) or the American Chemical Society Green Chemistry 

Institute (www.acs.org/greenchmistry). 

Innovation options that could be considered include the development of new chemicals that have 

a preferable hazard profile, while still meeting the performance considerations required by 

particular applications. Another option would be to re-design thermal paper, and could include 

using recycled materials and low concern chemicals as developers, colorformers, and sensitizers. 

Other approaches could include conducting additional research to determine if the application of 

a top coat (currently an optional design characteristic depending on a particular application) 

helps to limit exposure to consumers or workers. It is important to note that these approaches are 

not mutually exclusive; a combination of techniques may be appropriate. 

In addition to reconfiguring thermal printing systems, decision-makers may wish to consider 

alternative printing systems. These systems should be evaluated and compared to thermal 

printing to better understand relative performance, cost, and hazard. To make an informed 

substitution, chemicals used in alternative printing systems must not be assumed to be low 

hazard. Thermal transfer printing, impact printing, and laser printing are all alternatives to direct 

thermal printing (Seiko Instruments U.S.A. Inc. n.d.). However, thermal paper printers are 

unique because they require no ribbons, inks, or toner cartridges. Thermal paper printers 

typically have fewer moving parts and low maintenance costs compared to similar technology 

(Appleton 2003). 

A significant use of thermal paper is for point-of-sale (POS) receipts. Every year, an estimated 

9.6 million trees are cut down in the United States for receipts (Clifford 2011), although many 

companies strive for sustainability through stewardship and management programs and studies 

show paper product industries are not a significant cause of deforestation (Behreandt 2012). 

Electronic receipts (e-receipts) are becoming increasingly common in the retail industry, being 

offered by Apple, Nordstrom, Whole Foods, and other major retailers. They are either emailed 

directly to consumers or uploaded to a password-protected website. While e-receipts may 

generate certain benefits, such as reducing manufacture, transport, storage, and disposal of 

thermal paper and its associated chemicals, they also require the establishment of additional data 

storage devices and electronic products and peripherals. A full examination of the relative merits 

and trade-offs of thermal paper versus e-receipts requires the consideration of life-cycle

attributes, which is beyond the scope of this project. 

6.8 Relevant Resources

In addition to the information provided in this report, there are a variety of resources that provide 

information on chemical regulations at the state, national, and global levels, some of which are 

cited in this section. Tools, including GreenScreenTM (see Section 6.6.4) are also available to 

assist in using the information in this report to make a substitution decision. 

6.8.1 Resources for State and Local Authorities

The University of Massachusetts at Lowell created an online database that contains a collection 

of state and local legislative and executive branch policies from all 50 states from 1990 to the 

present that regulate or ban specific chemicals, provide comprehensive state policy reform, 

establish biomonitoring programs, or foster “green” chemistry (National Caucus of 

Environmental Legislators 2008): 

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FINAL REPORT – January 2014 

http://www.chemicalspolicy.org/chemicalspolicy.us.state.database.php. 

The Washington Department of Ecology concluded that averting toxic exposures and avoiding 

future health and cleanup costs is the smartest, cheapest and healthiest approach to preventing 

the harm associated with toxic chemicals, and created the Reducing Toxic Threats initiative to 

coordinate activities to achieve this goal (see: http://www.ecy.wa.gov/toxics/index.htm). 

Although the Department has conducted alternatives assessments as part of this effort, they are 

now focused on developing tools and guidance documents to allow businesses to conduct their 

own alternatives assessments to facilitate the movement to safer substitutes for chemicals of 

concern. The Department of Ecology has developed the Quick Chemical Assessment Tool, based 

on GreenScreenTM (see Section 6.8.4), to rapidly assess chemical options and remove from 

consideration those that are likely to be most toxic, so that in-depth assessments can focus on 

those chemicals that are likely to be safer. This is particularly important for businesses with 

limited resources. At the time of the writing of this report, the Department is in the process of 

developing an alternatives assessment guidance document. 

6.8.2 Federal Agency Resources

EPA’s website contains information on how the Agency develops regulations, the regulations 

that are in place, and information to assist companies in maintaining compliance with 

regulations. The website also provides information on EPA’s partnership programs, such as DfE. 

Some EPA resources are listed below.

EPA Laws and Regulations http://www.epa.gov/lawsregs/

EPA Office of Pollution Prevention and Toxics (OPPT) http://www.epa.gov/oppt/

EPA DfE Program http://www.epa.gov/oppt/dfe/

Websites from other federal agencies that may be relevant to this alternatives assessment are 

provided below. 

Consumer Product Safety Commission (CPSC) http://www.cpsc.gov/

U.S. Food and Drug Administration (FDA) http://www.fda.gov/

National Institute for Occupational Safety and Health (NIOSH) (part of the Centers for Disease 

Control and Prevention (CDC)) http://www.cdc.gov/niosh/

6.8.3 Resources for Global Regulations 

The European Union (EU)’s REACH (Registration, Evaluation, Authorisation and Restriction of 

Chemical substances) legislation was enacted in 2007 and aims “to improve the protection of 

human health and the environment through the better and earlier identification of the intrinsic 

properties of chemical substances” (European Commission 2011a). Their website contains 

information on legislation, publications and enforcement. 

http://ec.europa.eu/environment/chemicals/reach/enforcement_en.htm

The EU’s Restriction of Hazardous Substances (RoHS) legislation ensures that new electrical 

and electronic equipment put on the market does not contain any of the six banned substances: 

lead, mercury, cadmium, hexavalent chromium, poly-brominated biphenyls (PBB) or 

polybrominated diphenyl ethers (PBDE) above specified levels (European Commission 2011b). 

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FINAL REPORT – January 2014 

http://www.rohs.eu/english/index.html

6.8.4 GreenScreenTM for Safer Chemicals

The GreenScreenTM for Safer Chemicals was developed by the non-profit group Clean 

Production Action. It is a method for chemical hazard assessment to help move society toward 

the use of greener and safer chemicals. At the foundation of the GreenScreenTM method are the 

Principles of Green Chemistry and the work of the EPA DfE program. The GreenScreenTM 

addresses many of the principles of green chemistry and design for the environment through its 

focus on hazard reduction and informed substitution.

http://www.cleanproduction.org/Greenscreen.php 

6.9 Related Assessments

In 2008, the European Commission published an environmental and human health addenda to its 

risk assessment of BPA. 

European Union Risk Assessment Report, Human Health Addendum of April 2008, 4,4'-

ISOPROPYLIDENEDIPHENOL (Bisphenol-A), Part 1 Environment 

http://publications.jrc.ec.europa.eu/repository/bitstream/111111111/15063/1/lbna24588enn.pdf

European Union Risk Assessment Report, Human Health Addendum of April 2008, 4,4'-

ISOPROPYLIDENEDIPHENOL (Bisphenol-A), Part 2 Human Health

http://publications.jrc.ec.europa.eu/repository/bitstream/111111111/15069/1/lbna24589enn.pdf

French Agency for Food, Environmental and Occupational Health & Safety, Health effects of 

Bisphenol A, Collective Expert Report, September 2011. 

http://www.anses.fr/Documents/CHIM-Ra-BisphenolAEN.pdf

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FINAL REPORT – January 2014 

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