Page 3 of 33

Table of Contents

1 Introduction............................................................................................................................. 5

1.1 Statutory and Regulatory Authority ................................................................................. 5

1.2 Updates to Work Plan ...................................................................................................... 6

1.3 Case Overview ................................................................................................................. 7

1.4 Chemical Identification and Properties............................................................................ 7

1.5 Use/Usage Description..................................................................................................... 9

1.5.1 Registrations ............................................................................................................. 9

1.5.2 Summary of Registered Uses.................................................................................... 9

1.5.3 Usage Information .................................................................................................. 10

1.6 Regulatory History ......................................................................................................... 10

1.6.1 Recent/Pending Regulatory Actions....................................................................... 11

1.6.2 Tolerance Information ............................................................................................ 11

1.7 Incidents......................................................................................................................... 11

1.7.1 Human Health ......................................................................................................... 11

1.7.2 Ecological ............................................................................................................... 11

2 Anticipated Data Needs ........................................................................................................ 11

3 Human Health Risk Assessment........................................................................................... 14

3.1 Existing Toxicological Endpoints.................................................................................. 14

3.2 Dietary Exposure............................................................................................................ 15

3.2.1 Food ........................................................................................................................ 15

3.2.2 Drinking Water ....................................................................................................... 16

3.3 Occupational and Residential Exposures....................................................................... 16

3.3.1 Occupational Handler Exposure ............................................................................. 16

3.3.2 Residential Handler Exposures............................................................................... 17

3.3.3 Residential Post-Application Exposures................................................................. 17

3.4 Aggregate and Cumulative Exposure............................................................................. 17

3.4.1 Aggregate Exposures.............................................................................................. 18

3.4.2 Cumulative Exposures............................................................................................ 18

4 Environmental Risk Assessment........................................................................................... 18

4.1 Environmental Conceptual Model Exposure Pathways................................................. 18

4.2 Ecological Effects Assessment....................................................................................... 19
Page 4 of 33

5 Endocrine Disruptor Screening Program (EDSP)................................................................. 20

6 Next Steps............................................................................................................................. 20

7 References............................................................................................................................. 21

Appendix A Toxicology Profile............................................................................................... 24

Appendix B Ecotoxicology Profile.......................................................................................... 29

List of Tables

Table 1 - Summary of Anticipated Risk Assessments and Data Needs: Phenol ............................ 6

Table 2 - Anticipated Registration Review Schedule..................................................................... 6

Table 3 - Chemical Facts of Phenol and Salt.................................................................................. 7

Table 4 - Physical-Chemical and Fate Properties for Phenol and Salt ........................................... 8

Table 5 - Summary of Phenol and Salt Registered Uses.............................................................. 10

Table 6 – Studies Anticipated as Needed for the Registration Review of Phenol and Salt.......... 12

Table 7 – Existing Toxicological Endpoints................................................................................. 14

Table 8 – Occupational Handler Exposure Scenarios for Phenol and Salt................................... 16

Table 9 – Residential Post-Application Exposure Scenarios for Phenol and Salt........................ 17

Table 10 - Acute Toxicity for Freshwater Fish............................................................................. 29

Table 11 – Acute Toxicity for Aquatic Invertebrates................................................................... 31

Table 12 - Acute Toxicity of Phenol to Marine/Estuarine Invertebrates...................................... 33

Table 13 - Chronic Toxicity of Phenol to Marine/Estuarine Invertebrates................................... 33

List of Figures

Figure 1 - Conceptual Model for Ecological Exposure and Effects of Phenol and Salt to Aquatic 

and Terrestrial Organisms............................................................................................................. 19
Page 5 of 33

1 Introduction 

This document is the Environmental Protection Agency’s (EPA or “the agency”) Final Work 

Plan (FWP) for the registration review of the Phenol and Salt Case. The FWP document explains 

what EPA's Office of Pesticide Programs knows about the chemicals, highlighting anticipated 

data and assessment needs, identifying the types of information that would be especially useful 

to the Agency in conducting the review, and providing an anticipated timeline for completing 

their review. There were no public comments received concerning the Preliminary Work Plan 

(PWP), which was posted in the Phenol and Salt registration review docket (EPA-HQ-OPP2012-0810). In the PWP, the Agency solicited comments on specific topics: environmental 

justice, water body impairment, trade irritants, and structure activity relationships. No comments 

or information were received during the public comment period concerning these issues. 

Therefore, the data needs, work plan, and timeline described in the PWP remain as they were 

presented initially. Further, this document makes final the work plan for the Phenol and Salt

registration review process.

1.1 Statutory and Regulatory Authority

The Food Quality Protection Act (FQPA) of 1996 mandated a registration review program. All 

pesticides distributed or sold in the United States generally must be registered by the U.S. 

Environmental Protection Agency (USEPA, EPA, or the Agency) based on scientific data 

showing that they will not cause unreasonable risks to human health or the environment when 

used as directed on product labeling. The registration review program is intended to make sure 

that, as the ability to assess risk evolves and as policies and practices change, all registered 

pesticides continue to meet the statutory standard of no unreasonable adverse effects to human 

health or the environment. Changes in science, public policy, and pesticide use practices will 

occur over time. Through the registration review program, the Agency periodically reevaluates 

pesticides to make sure that as change occurs, products in the marketplace can be used safely. 

Information on this program is provided at http://www.epa.gov/oppsrrd1/registration_review/.

The Agency is implementing the registration review program pursuant to Section 3(g) of the 

Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and will review each registered 

pesticide every 15 years to determine whether it continues to meet the FIFRA standard for 

registration. The regulations governing registration review begin at 40 CFR 155.40. The Agency 

will consider benefits information and data as required by FIFRA. The public phase of 

registration review begins when the initial docket is opened for each case. The docket is the 

Agency’s opportunity to state what it knows about the pesticide and what additional risk analyses 

and data or information it believes are needed to make a registration review decision. The Phenol 

and Salt Preliminary Work Plan (PWP) was published on December 19, 2012 and the 60-day 

comment period ended on February 12, 2013. 

Documents associated with this registration review can be viewed at http://www.regulations.gov 

in docket EPA-HQ-OPP-2012-0810. Below is a summary of the issues relevant to this 

registration review case. 
Page 6 of 33

1.2 Updates to Work Plan

Since the publication of the PWP, the agency has made the following updates:

• The akgency will conduct a tolerance review for indirect-food contact uses 

• Corrected formatting and typographical errors

Table 1 - Summary of Anticipated Risk Assessments and Data Needs: Phenol

Risk Assessment 

Assessment 

Necessary to 

Support 

Registration 

Review 

Date of Most 

Recent 

Assessment 

Type of 

Assessment 

Required 

(New/Updated) 

Data Anticipated as Needed 

(See Table 6 for more detail about 

anticipated data needs)

Dietary (food) No 5/26/2005 None None

Dietary (drinking water) No 5/26/2005 None None 

Occupational Handler Yes 5/26/2005 Updated Indoor Exposure Data 

Inhalation Toxicity Study 

Residential Handler No 5/26/2005 None None

Residential Post 

Application - Incidental 

Oral and Dermal 

Yes 5/26/2005 Updated Surface Residue Data 

Residential Post 

Application - Inhalation Yes 5/26/2005 Updated Indoor Exposure Data 

Inhalation Toxicity Study 

Aggregate Yes 5/26/2005 Updated Dietary, Residential Handler and 

Residential Post Application

Cumulative No N/A None None

Tolerance Review Yes N/A New None

Ecological No N/A None None

N/A = Not applicable

Table 2 - Anticipated Registration Review Schedule

Anticipated Activity Target Date1 Completion Date

Phase 1: Opening the Docket 

Open Docket and 60-Day Comment Period for Preliminary Work Plan 2012-12 2012-12-18

Close Public Comment Period 2013-02 2013-02-12

Phase 2: Case Development 

Issue Final Work Plan 2013-06 2013-05

Issue Data Call-In (DCI) 2014-06

Receive Data to be Considered in Risk Assessment 2016-06

Open 30-Day Public Comment Period for Preliminary Risk Assessment(s) 2017-12

Close Public Comment Period 2018-01

 1 The anticipated schedule will be revised as necessary (e.g., on any need arising under the Endocrine Disruptor Screening 

Program with respect to the active ingredients in this case).
Page 7 of 33

Phase 3: Registration Review Decision and Implementation 

Open 60-Day Public Comment Period for Proposed Decision 2019-06

Close Public Comment Period 2019-08

Issue Final Decision 2019-12

Begin Post-Decision Follow-up 2019

Total (years) 7

1.3 Case Overview

The docket for the Phenol & Salt Case (Case 4074) has been established at 

http://www.regulations.gov in docket number EPA-HQ-OPP-2012-0810

1.4 Chemical Identification and Properties

Table 3 presents the two active ingredients to be assessed in Case 4074: phenol (PC Code 

064001) and sodium phenate (PC Code 064002). Phenol and sodium phenate are considered to 

be toxicologically and ecologically equivalent for the purposes of registration review; and except 

where otherwise noted, the two active ingredients in this case will be referred to collectively as 

“phenols”. 

Table 3 - Chemical Facts of Phenol and Salt

Chemical Name Phenol Sodium phenate

Classification Phenol Phenoxy

PC Code 064001 064002

CAS No. 108-95-2 139-02-6

Molecular Formula C6H5OH C6H5ONa

Molecular Weight 94.11 g/mol 116.10 g/mol

First registered in US as a pesticide 1969 1969

RED issued 2004 2004

RED updated 2009 2009

EPA Registered Products 4 3

Tolerances None2 None2

Molecular Structure

 2 See Section 1.5.2 Tolerance Information for further information 
Page 8 of 33

The phenol and sodium phenate product chemistry information (source: MRIDs 41443603 and 

42930901; EPI Suite v 4.10; TOXNET) relevant to risk assessment is summarized in Table 4. 

Table 4 - Physical-Chemical and Fate Properties for Phenol and Salt

OPPTS 

Guideline 

No.

Physical and Chemical 

Properties Phenol Sodium Phenate 

830.1550 Product identity and 

composition Refer to Table 3. Refer to Table 3.

830.1800 Enforcement analytical 

method Gas Chromatography, FID detector GC MS

830.6302 Color Colorless to slight pink crystalline solid White to reddish rods or 

granules

830.6303 Physical State Solid. Pure phenol absorbs easily water from air 

and liquefies. Crystalline needles or rods

830.6304 Odor Sharp medicinal, sweet odor Slight phenolic odor

830.6313

Stability to sunlight, normal 

and elevated temperature, 

metals/metal ions

Stable under ordinary conditions of use and 

storage. Heat will contribute to instability. May 

discolor in light.

Substances to be avoided include strong oxidizing 

agents, strong bases, strong acids, alkalis, calcium 

hypochlorite. Not highly flammable and not 

explosive. No oxidizing properties.

Conditions to Avoid: Heat, flames, ignition sources 

and incompatibles.

Stable under normal 

temperatures and pressures.

Deliquescent

830.7000 pH About 6.0 (aqueous solution) Alkaline in aqueous

830.7050 UV/Visible Absorption UV: 258 nm; photo-degrade, especially in air. N/A

830.7200 Melting point 40.5-41.5°C; 43°C 174.06 ◦

C

830.7220 Boiling point 182°C @ 760 mmHg 439.17 ◦

C

830.7300 Density 1.071 g/cm3 @ 20°C N/A

830.7370 Dissociation Constant Phenol is a weak acid.

pKa = 9.89 at 20°C; pKa 9.95 (in water); N/A

830.7550 Partition coefficient (noctanol/water) Log Kow is 1.46 at 25°C Log Kow is -1.170 at 25°C

830.7840 Solubility in water 84 g/l at 20°C;

1 gram/9 grams of water.

Highly soluble in water.

1,000 gm/L at 25°C.

830.7860 Solubility in organic 

solvents

Very soluble in alcohol, chloroform, ether, 

glycerol, carbon disulfide Soluble in alcohol

830.7950 Vapor pressure 0.4mm Hg at 20°C

0.341 mm Hg at 25°C

2.60E-08 mm Hg at

25 °C

N/A Henry's Law Constant 3.33X10-7 atm-cu m/mol @ 25 °C

1.529E-006 atm-m3

/mole 3.972E-015 atm-m3

/mole

N/A Log Koc (organic carbon 

ratio in soil)3 1.21-1.96 N/A

 3 Source: EPI-Suite v4.1
Page 9 of 33

N/A Photolysis3 Absorbs light in the region of 290-330 nm, likely 

photodegrade directly in surface water. N/A

N/A Half-life in freshwater3 <1 day N/A

N/A Biodegradability3 Completely biodegrades in soil within 5 days N/A

N/A Estimated half-life in air3 <1 day N/A

N/A Log bioconcentration factor 

(BCF)3 0.28 in goldfish and 1.3 for golden orf N/A

1.5 Use/Usage Description

Products containing phenol and sodium phenate are registered for use as a hard surface 

disinfectants, deodorizers and cleaners on the following hard non-porous surfaces: agricultural 

premises and equipment; HVAC systems; food handling/storage establishment premises and

equipment; residential and public access premises; and medical/dental/veterinary premises; and 

equipment.

1.5.1 Registrations

There are four EPA-registered products that contain phenol as an active ingredient (a.i.). Three

of the four products also contain the alkali metal salt of phenol, sodium phenate, as an active 

ingredient. The percent a.i. of phenol ranges from 0.6 percent to 7.8 percent and the formulations 

include ready to use liquid, as a wipe and as a liquid concentrate. The percent a.i. of sodium 

phenate ranges from 0.06 percent to 0.3 percent and the formulations include ready to use liquid, 

as a wipe and liquid concentrate. The amount of the active phenol moiety in formulations 

containing both phenol and sodium phenate is expressed as the total phenol acid equivalent4

(a.e.). Products containing phenol and sodium phenate range from 1.61 to 8.04 percent a.e.

There is no registered manufacturing use product or registered technical grade active ingredient.

There are eight products containing phenol as an inert ingredient (PC Code 800189).

1.5.2 Summary of Registered Uses 

Table 5 presents a summary of the registered uses of phenols that will be assessed in this 

registration review. Phenols can be applied by the following application methods: ready to use 

liquid, mop, soaking, fogging, spray, wipe and liquid concentrate.

 4 The phenol acid equivalent content for sodium phenate is 80 percent: 

; therefore 

1.56% phenol (acid) content + (0.06% sodium phenate x 80% a.e.) = 1.61% phenol a.e. and 7.8% phenol (acid) 

content + (0.3% sodium phenate x 80% a.e.) = 8.04% phenol a.e. content 
Page 10 of 33

Table 5 - Summary of Phenol and Salt Registered Uses

Use Application Method Application Rate

Agricultural Premises and Equipment – Indirect Food Contact

Farm Equipment, Animal and Poultry Housing Spray, Mop, Wipe, Soak

1.56 percent phenol

(1.61 percent phenol 

a.e.)

Commercial, Industrial, Institutional, Premises and Equipment

HVAC systems in commercial, industrial, institutional areas Fogging

1.56 percent phenol

(1.61 percent phenol 

a.e.)

Food Handling/Storage Establishments Premises and Equipment – Indirect Food Contact

Food Processing Plants Spray, Mop, Wipe, Soak

1.56 percent phenol

(1.61 percent phenol 

a.e.)

Residential and Public Access Premises

HVAC systems in residential areas (including cruise ships) Fogging

1.56 percent phenol

(1.61 percent phenol 

a.e.)

Day Care Centers, Schools, Health Clubs Trigger Spray

1.56 percent phenol

(1.61 percent phenol 

a.e.)

Medical/Dental/Veterinary Premises and Equipment

Hospital Disinfection Spray, Mop, Wipe, Soak

1.56 percent phenol

(1.61 percent phenol 

a.e.)

Clean Room Production Areas Fogging

1.56 percent phenol

(1.61 percent phenol 

a.e.)

1.5.3 Usage Information 

The Kline Biocides Report does not mention phenols.

1.6 Regulatory History 

Phenol and sodium phenate (PC Codes 064001 and 064002) were first registered as pesticide 

active ingredients by the United Sates Department of Agriculture (USDA) on June 11, 1969. In 

1970, the Environmental Protection Agency (EPA) was established and assumed all pesticide 

registration responsibilities from USDA. Phenol and sodium phenate are currently regulated by 

both the U.S. EPA and the U.S. Food and Drug Administration (FDA). EPA regulates the 

pesticidal uses of phenols summarized in Table 5 and FDA regulates uses of phenols such as 
Page 11 of 33

those found in over-the-counter drugs used for the treatment of various conditions including 

insect bites, poison ivy, diaper rash, antiseptics and acne (21 CFR §310.531 and §310.545). Prior 

to April 12, 2005, phenols were registered for use as a materials preservative in paints; however, 

this use was terminated in response to the risks identified in the “Phenol/Sodium Phenate 

Reregistration Decision” memorandum dated September 30, 2004. EPA completed a RED

addendum for Phenols and Salt on March 30, 2009 to include the use of fogging in clean rooms 

and HVAC ductwork uses that were inadvertently omitted from 2004 “Phenol/Sodium Phenate 

Reregistration Decision” memorandum. The post-RED data call-in (DCI) has not been issued.

1.6.1 Recent/Pending Regulatory Actions 

There are no recent regulatory actions for phenol and salt case. EPA anticipates issuing the postRED DCI in the near future.

1.6.2 Tolerance Information 

No tolerances have been established for phenol or sodium phenate. Two tolerance exemptions 

have been established for phenol as an inert ingredient (solvent/co solvent) in pesticide products 

used on growing crops (40 CFR 180.920) or on livestock (40 CFR180.930). The Agency will 

assess the need for a tolerance during registration review.

1.7 Incidents

1.7.1 Human Health 

EPA identified 10 incidents in the OPP Incident Data System associated with dermal and 

inhalation exposure from the period 1989 to 2012. Most of the dermal incidents resulted in skin 

irritation, rash, itching and skin discoloration. Inhalation exposure resulted in respiratory 

irritation, difficult breathing, throat and chest congestion and sore throat. In incidents where 

dermal and inhalation exposure occurred, the following symptoms were reported: headache, 

dizziness, night sweats, and heart palpitation. 

1.7.2 Ecological

No phenol ecological incidents resulting from its use as a registered antimicrobial have been

reported to the Agency’s Ecological Incident Information System (EIIS, v 2.11) from the period 

1970 to2012.

2 Anticipated Data Needs 

Table 6 presents a summary of the data anticipated as being needed to support this registration 

review.
Docket Number EPA-HQ-OPP-2012-0810

www.regulations.gov

Page 12 of 33

Table 6 – Studies Anticipated as Needed for the Registration Review of Phenol and Salt

GLN Study Name Test 

Substance

Time Frame 

(Measured in 

months from DCI 

Receipt)

Risk Assessment(s) 

Data Will Support

Use Site(s) Triggering

Anticipated Data 

Requirement

Applicable Exposure Scenario

Studies Anticipated to be Required through the Registration Review DCI

875.1400 Indoor Exposure, 

Inhalation 

TGAI 24 Occupational and 

Residential 

Hard Surface 

Disinfection 

1. Trigger pump sprayer, low pressure 

handwand, mop, and wipe5

2. Hand held fogging of clean rooms6 

3. HVAC treatment

875.1700 Product Use 

Information 

TGAI 12 All All All scenarios. 

875.23007 Indoor Surface 

Residue 

Dissipation 

TGAI 24 Residential Surface disinfection of 

household floors and 

carpets 

Dermal and incidental exposures to phenol are 

expected for toddlers who sit or play on 

household floors or carpets after they are 

disinfected with phenol products. 

875.2500 Post Application 

Exposure, 

Inhalation 

TGAI 24 Residential Air Deodorization, 

HVAC Treatments 

Inhalation exposure following the use of air 

deodorizers or HVAC treatments. 

Studies Expected to be Required through the Anticipated Post-RED DCI8

875.1200 Dermal exposure--

Indoor

TGAI 24 Occupational and 

Residential 

Hard Surface 

Disinfection 

Air Deodorization

HVAC Treatment

1. Trigger pump sprayer, low pressure 

handwand, mop, and wipe5

2. Hand held fogging of clean rooms6 

3. HVAC treatment

 5 It may be possible to use proprietary surrogate exposure data if data compensation issues can be addressed. 6 If the labels are modified to require automatic foggers in place of hand held foggers, then the study likely would not be needed. 7 If surface residue data are not available, then the standard assumption of 100 percent transferable surface residue will be used which might overestimate the risk. 8 The 850.1010 Aquatic invertebrate acute toxicity, test, freshwater daphnids, 850.1075 Fish acute toxicity test, freshwater and marine, and 850.2100 Avian acute 

oral toxicity test were anticipated as being required as a result of the RED. The Agency now believes that these data are not anticipated to be necessary to support 

Registration Review because of the low environmental exposure to non-target organisms. Therefore, these studies will not be required through the post-RED DCI.
Page 13 of 33

GLN Study Name Test 

Substance

Time Frame 

(Measured in 

months from DCI 

Receipt)

Risk Assessment(s) 

Data Will Support

Use Site(s) Triggering

Anticipated Data 

Requirement

Applicable Exposure Scenario

875.1400a9,10 Indoor Inhalation 

Exposure - whole 

building

TGAI 12 Occupational and 

Residential

Air Deodorization, 

HVAC Treatment

HVAC treatment

875.1400b10,11

Indoor Inhalation 

Exposure -

chamber study TGAI 12 Occupational and 

Residential

Air Deodorization, 

HVAC Treatments HVAC treatment

 9 A whole building study is anticipated as needed as confirmatory data for the HVAC ductwork treatment use. The anticipated DCI will provide that the whole 

building study is to be based on OPPTS Guideline 875.1400 Indoor Inhalation Exposure, and conducted at a representative application site during an actual 

application or at a simulated application site that is configured to match the characteristics of a representative application. The anticipated DCI will provide that the 

specific conditions such as ventilation rate, air temperature, application method and application rate must match the conditions of the labeled use and will 

recommend that a study protocol be submitted for review by the Agency prior to the initiation of the actual study. 10 Due to a typographical error, guideline 875.1400 was incorrectly presented as 875.1200 in the RED. 11 A chamber study is anticipated as needed as confirmatory data for the HVAC ductwork treatment use. The anticipated DCI will provide that the chamber study 

is to be based on OPPTS Guideline 875.1400 Indoor Inhalation Exposure and ASTM D5116-06 Standard Guide for Small-Scale Environmental Chamber 

Determinations of Organic Emissions from Indoor Materials/Products. The anticipated DCI will provide that the specific conditions of the chamber study such as 

ventilation rate, air temperature, application method and application rate must match the conditions of the labeled use and recommend that a study protocol be 

submitted for review by the Agency prior to the initiation of the actual study.
Docket Number EPA-HQ-OPP-2012-0810

www.regulations.gov

Page 14 of 33

3 Human Health Risk Assessment

The Agency anticipates the need to conduct a human health risk assessment for phenols. The 

Agency expects to require additional data for use in conducting the registration review.

3.1 Existing Toxicological Endpoints 

On March 9, 2004, the Antimicrobials Division Toxicology Endpoint Selection Committee 

(ADTC) reviewed the available toxicology data for phenols and selected the toxicological doses

and endpoints listed in Table 7. These endpoints as well as the associated data base uncertainty 

factors, the FQPA safety factor and targets for margin of exposure (MOE) are subject to 

reevaluation during registration review, particularly if any new toxicity data via future 

submissions and/or literature publications become available for phenols.

Table 7 – Existing Toxicological Endpoints 

Exposure 

Scenario

Dose Used in Risk 

Assessment 

(mg/kg/day) 

Target Margin of Exposure 

(MOE), UF, Special FQPA 

SF, for Risk Assessment

Study and Toxicological Effects

Acute Dietary

(gen population) An acute dietary endpoint has not been identified for phenol.

Acute Dietary

(females 13-49) An acute dietary endpoint has not been identified for phenol.

Chronic Dietary

(all populations)

NOAEL= 60

mg/kg/day

UF = 100

Chronic RfD = 

0.6 mg/kg/day

UF = 100 

FQPA SF = 1

Developmental toxicity study in rats (MRID 

No. 43735402)

Based on significant reductions from the 

control in mean fetal body weight/litter at 120 

mg/kg/day. 

Incidental Oral

Short-Term 

(1 - 30 Days)

Residential Only

NOAEL= 60 

mg/kg/day

MOE = 100

FQPA SF = 1

Developmental toxicity study in rats (MRID 

No. 43735402)

Based on significant reductions from the 

control in mean fetal body weight/litter at 120

mg/kg/day.

Incidental Oral 

IntermediateTerm

(1 - 6 Months)

Residential Only

NOAEL= 60 

mg/kg/day

MOE = 100

FQPA SF = 1

Developmental toxicity study in rats (MRID 

No. 43735402)

Based on significant reductions from the 

control in mean fetal body weight/litter at 120 

mg/kg/day.
Page 15 of 33

Exposure 

Scenario

Dose Used in Risk 

Assessment 

(mg/kg/day) 

Target Margin of Exposure 

(MOE), UF, Special FQPA 

SF, for Risk Assessment

Study and Toxicological Effects

Dermal12

Short and 

intermediateterm

NOAEL = 60 

mg/kg/day

MOE = 100 Developmental toxicity study in rats (MRID 

No. 43735402). 

Based on significant reductions from the 

control in mean fetal body weight/litter at 120 

mg/kg/day.

Inhalation

(All durations)

LOAEL = 0.1 mg/L MOE = 300 

(ST, IT)

MOE = 1000 (LT)

Dalin and Kristofferson: Physiological Effects 

of a Sub-lethal Concentration of Inhaled 

Phenol on the Rat. Ann. Zool. Fennici 11: 

193-199, 1974

LOAEL of 0.1 mg/L, based on alterations in 

sliding angle from tilting plane test, and 

significant increases in liver enzymes

Cancer Data are inadequate for classification of human carcinogenic potential (U.S. EPA, 2005). No 

additional carcinogenicity data will be needed.13

3.2 Dietary Exposure 

The Agency does not anticipate the need to revise the dietary assessments conducted in support 

of the 2004 RED.

3.2.1 Food

There are no chronic dietary risks of concern associated with the approved uses of phenol and 

sodium phenate and no additional residue chemistry data are expected to be needed. 

Human dietary exposure to phenol and sodium phenate residues may occur as a result of the use 

of products on food contact surfaces of food processing plants and any food-handling facilities 

including public eating places. After treatment, all food contact surfaces must be washed with 

soap or detergent and rinsed with potable water prior to reuse. In the RED, use of these products 

to disinfect food contact surfaces was assessed based on use on kitchen countertops. EPA 

believes the results to be conservative. An acute dietary assessment was not conducted because 

phenol and sodium phenate do not elicit adverse systemic effects resulting from a single dose. 

Chronic dietary risks were below the Agency’s level of concern (7.5% of the cPAD for adult 

males, 9.0% for adult females, and 36% for children). A transfer efficiency of 10% was assumed

in the RED due to the high vapor pressure of phenol (0.35 mmHg at 25 C). Use of the 10% 

transfer efficiency is considered appropriate due to volatilization of phenol and reduction of 

residues on the treated surface following the required washing and rinsing steps prior to reuse.

 12 From the available data, dermal absorption percentages of 20-50% have been observed from in vivo and in vitro

studies. The ADTC selected the 50% dermal absorption value for phenol for use as a conservative value in risk 

assessments. This value also takes into account the irritant properties of phenol which may increase its dermal 

absorption. Phenol is not expected to result in chronic dermal exposure due to its volatile nature and short half-life. 

Therefore, the ADTC did not select a long-term dermal endpoint for phenol, and the dermal exposure risk 

assessment is not required.

13 See Appendix A Carcinogenic Potential of Phenol for further explanation.
Page 16 of 33

3.2.2 Drinking Water 

The Agency does not anticipate the need to revise the drinking water assessment conducted in 

support of the 2004 RED. Phenol and sodium phenate are registered only for indoor uses. 

Although minimal, some surface water contamination could occur resulting from washing downthe-drain or running off from livestock premises. Phenol has a high water solubility (8.3 g/100 

ml at 20 ◦C) and low adsorption to soil (log KOC = 1.21-1.96) both of which favor leaching to 

groundwater. However, as the half-life in water is less than one day (0.6 days), biodegradation in 

soil is complete within five days, and photodegradation in water is likely, neither surface water 

nor groundwater contamination is likely. Therefore, at this time, phenol and sodium phenate are 

not expected to reach wastewater treatment plants or to contaminate drinking water and a 

drinking water assessment is not deemed to be necessary.

3.3 Occupational and Residential Exposures 

The Agency anticipates the need to revise the occupational and residential assessments 

conducted in support of the 2004 RED. Uses of phenols that may result in occupational handler 

and residential post-application exposure are presented in Table 8 and Table 9.

3.3.1 Occupational Handler Exposure

The Agency anticipates the need to revise the occupational handler assessment conducted in 

support of the 2004 RED. Occupational handler dermal and inhalation exposures were assessed 

in the RED for hard surface disinfection using aerosol spray and towelette, loading foggers for 

clean room fogging and application of disinfectant to HVAC ductwork – fogging. The dermal 

MOEs were assessed using an oral NOAEL of 60 mg/kg/day from a developmental toxicity 

study in rats along with a dermal absorption factor of 50 percent. Inhalation MOEs were assessed 

using a LOAEL of 0.1 mg/liter from an inhalation toxicity study in rats. With the exception of 

the dermal MOE of 70 for surface disinfection using towelettes (while wearing gloves), all of the 

dermal and inhalation MOEs exceeded the target MOEs and were not of concern. Occupational 

post application inhalation exposures were assessed in the RED for general cleaning solution 

vapor exposures and re-entering clean rooms after fogging treatment. The MOEs were above 

target MOE of 300 and were not of concern.

If new endpoints are identified from the toxicology studies that are anticipated to be required for 

registration review, then exposures to phenol will need to be re-assessed during registration 

review. The exposure routes could include dermal and inhalation for occupational exposures. 

Occupational handler scenarios to be assessed are presented in Table 8. 

Table 8 – Occupational Handler Exposure Scenarios for Phenol and Salt

Scenario Exposure Route(s) Duration

Occupational Exposures
Page 17 of 33

Spray, mop and wipe for hard surface disinfection Dermal and Inhalation Short and Intermediate Term

Fog clean rooms for adjunct treatments Dermal and Inhalation Short and Intermediate Term

ULV applications for HVAC treatments Dermal and Inhalation Short and Intermediate Term

3.3.2 Residential Handler Exposures

Residential handler exposure is not expected based on currently registered uses. Based on the 

information available, the Agency believes that an occupational user will apply phenol pesticide 

products in residential settings. 

3.3.3 Residential Post-Application Exposures

The Agency anticipates the need to revise the residential post-application assessment conducted 

in support of the 2004 RED once the data to be required through the post-RED DCI are received 

and reviewed. Residential post-application exposures could result when bystanders (adults and 

children) who come in contact with phenols products applied to HVAC systems or when children 

have contact with floors treated with phenol disinfectant products. The exposure routes could 

include dermal, inhalation and incidental oral. The residential post-application exposure 

scenarios applicable to phenol are listed in Table 9.

Table 9 – Residential Post-Application Exposure Scenarios for Phenol and Salt

Scenario Exposure Route(s) Duration

Residential Exposures

Toddlers playing on phenol disinfected floors Dermal and Incidental Oral Short and Intermediate Term

Post application exposure following HVAC treatmentsInhalation Short and Intermediate Term

Post application inhalation exposures following the application of Sporicidin, a pesticide product 

containing phenol, to HVAC ductwork were previously assessed in the Memorandum:

Occupational and Residential Exposure and Risk Assessment for the Duct Cleaning Use of 

Phenol (Sporicidin) of December 12, 2009 (D313122). The results of these assessments 

indicated the estimated risks would be below EPA’s level of concern if re-entry were delayed for 

16 or 24 hours after application, depending upon which model is used. The registrant has since 

voluntarily amended the registration and label to change the application rate for the HVAC use 

to 4 ounces per 2,000 square feet of building area to reduce the re-entry interval to 3 hours. The 

Agency will be assessing the new application rate as a part of registration review.

3.4 Aggregate and Cumulative Exposure 
Page 18 of 33

3.4.1 Aggregate Exposures 

The Agency anticipates the need to revise the aggregate assessment conducted in support of the 

2004 RED. Upon reevaluation and selection of toxicological endpoints, combined with the 

human health exposure assessments expected as a part of this registration review case, aggregate

exposures will need to be assessed. 

3.4.2 Cumulative Exposures 

With respect to cumulative exposure, unlike other pesticides for which the Agency has followed 

a cumulative risk approach based on a common mechanism of toxicity, EPA has not made a 

common mechanism of toxicity finding as to phenol and any other substances and phenol does 

not appear to produce a toxic metabolite produced by other substances. For the purposes of this 

registration review, therefore, EPA has not assumed that phenol has a common mechanism of 

toxicity with other substances. For information regarding EPA’s efforts to determine which 

chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such 

chemicals, see the policy statements released by EPA’s Office of Pesticide Programs at 

http://www.epa.gov/pesticides/cumulative/. 

4 Environmental Risk Assessment 

The Agency does not anticipate conducting an environmental risk assessment because of the low 

environmental exposure to non-target organisms. The wipe use pattern is not expected to result 

in any exposure of fish and wildlife because used wipes will be disposed of in the trash. 

Disposal of used solution down the drain is not expected to result in exposure of fish and wildlife 

to phenol or toxic degradates because of the short half lives in various environmental media like 

water, soils, and air. The half life of phenol in air is less than a day (0.6 days), its half life in 

water is less than a day and it degrades in aerobic and anaerobic soil systems in less than five 

days. Due to low KOW (1.46 at 25°C), it is not likely to bioaccummulate in aquatic organisms. 

For those uses which would result in down-the-drain disposal of used solutions, it is unlikely that 

environmental exposure of fish and wildlife would occur because phenols degrade rapidly in the 

environment and are not expected to bioaccumulate. If exposure were to occur, phenols have a 

low toxicity to fish, aquatic invertebrates and aquatic plants which would indicate a low potential 

for risk. No avian studies were available, so the toxicity of phenols to avian species could not be 

assessed. However, since the exposure to avian species is considered to be very low, risk to 

avian species is unlikely. Therefore, since the environmental exposure to non-target organisms 

is considered to be low from registered antimicrobial uses, no environmental risk assessment will 

conducted for this chemical (see Appendix B). The available ecological data are summarized in 

the Tables 12-15 in Appendix B.

4.1 Environmental Conceptual Model Exposure Pathways

Phenol has many degradation pathways as shown in Figure 1. The short half lives in various 

environmental media like water, soils, and air, make contamination of the surface water, soils, 

and sediments is unlikely. The half life of phenol in air is less than a day (0.6 days), and it 
Page 19 of 33

degrades in aerobic and anaerobic soil systems in less than five days. The dashed lines in the 

conceptual model below emphasize that the adverse eco-effects are unlikely for phenols.

Figure 1 - Conceptual Model for Ecological Exposure and Effects of Phenol and Salt to 

Aquatic and Terrestrial Organisms

4.2 Ecological Effects Assessment

EPA does not anticipate conducting an ecological risk assessment because of the low 

environmental exposure to non-target organisms. Based on the low likelihood of exposure due to 

the short half life of phenol in various environmental media like water, soils, and air, the Agency 

intends to conclude that the registered uses of phenol and sodium phenate will have 'no effect' 

on endangered or threatened terrestrial or aquatic species, or their designated critical habitats, as 

listed by the U.S. Fish and Wildlife Service (USFWS) and the National Oceanic and 

Atmospheric Administration's (NOAA) National Marine Fisheries Service (NMFS). EPA 

anticipates conducting no further analysis of potential risks to endangered or threatened species 

unless public comment or other submissions provide data or information that would otherwise 

inform the Agency's determination. 
Page 20 of 33

5 Endocrine Disruptor Screening Program (EDSP)

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse 

outcomes from exposure to chemicals. Collectively, these studies include acute, sub chronic and 

chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, 

reproductive, and general or systemic toxicity. These studies include endpoints which may be 

susceptible to endocrine influence, including effects on endocrine target organ histopathology, 

organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, 

and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and 

chronic studies that assess growth, developmental and reproductive effects in different 

taxonomic groups. As part of its reregistration decision, for phenols, EPA reviewed these data 

and selected the most sensitive endpoints for relevant risk assessment scenarios from the existing 

hazard database. However, as required by FFDCA section 408(p), phenol and sodium phenate is

subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP). 

EPA has developed the EDSP to determine whether certain substances (including pesticide 

active and other ingredients) may have an effect in humans or wildlife similar to an effect 

produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator 

may designate.” The EDSP employs a two-tiered approach to making the statutorily required 

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a 

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal 

systems. Chemicals that go through Tier 1 screening and are found to have the potential to 

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 

testing is designed to identify any adverse endocrine-related effects caused by the substance, and 

establish a dose-response relationship between the dose and the E, A, or T effect. 

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between October 

2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 chemicals, 

which contains 58 pesticide active ingredients and 9 inert ingredients. Phenol and sodium 

phenate are not among the group of 58 pesticide active ingredients on the initial list to be 

screened under the EDSP. Accordingly, as part of registration review, EPA will issue future 

EDSP orders/data call-ins, requiring the submission of EDSP screening assays for phenol and 

sodium phenate.

For further information on the status of the EDSP, the policies and procedures, the list of 67 

chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our 

website: http://www.epa.gov/endo/. 

6 Next Steps

A DCI will be developed regarding the data needs listed under the “Anticipated Data Needs” 

section of this document. The Agency expects to issue the DCI in June 2014. The Agency will 

conduct an human health hazard assessment for all uses. 
Page 21 of 33

7 References 

Arambasic, M.B., Bjelic, S., and G. Subakov. (1995). Acute Toxicity of Heavy Metals

(Copper, Lead, Zinc), Phenol and Sodium on Allium cepa L., Lepidium sativum L. and

Daphnia magna Strauss. Water Res. 29(2): 497-503.

Behl, C.R., et al. (1983). Permeation of Skin and Eschar by Antiseptics I: Baseline Studies With 

Phenol. J Pharm Sci 72.4:391-396.

Bishop, J.B., et al. (1977). Alterations in the Reproductive Patterns of Female Mice Exposed to 

Xenobiotics. Fundamental and Applied Toxicology 40:191-204.

Boutwell, R.K. and D.K. Bosch. (1959). The Tumor-Promoting Action of Phenol and Related 

Compounds for Mouse Skin. Cancer Res. 19:413-424.

Brown VKH, VL Box, BJ Simpson (1975) Decontamination Procedures for Skin Exposed to 

Phenolic Compounds." 1975. Arch. Environ. Health, Vol 30.1-6

Capel, I.D., et al. (1971) The Fate of [14C] Phenol in Various Species. Xenobiotica 2:25-34; 

1971.

Carpenter, C.P. (1948) "Skin Absorption and Irritation of Sodium Phenate." Mellon Institute of 

Industrial Research, University of Pittsburgh. May 5, 1948 (unpublished, U.S. EPA/OPTS 

Public Files Fiche OTS0515564/ 86-870001402).

Carpenter, C.P. (1949) "The Acute Toxicity of Phenol." Mellon Institute of Industrial Research, 

University of Pittsburgh. May 6, 1949 (Unpublished, U.S. EPA/OPTS Public Files Fiche 

OTS0515567/ 86-870001405).

ClinTrials BioResearch (1998) A 13-week neurotoxicity study of phenol administered in the 

drinking water to the rat. Volumes 1 and 2. Senneville, Quebec, Canada. Project I.D.: 

97439. P. Beyrouty, study director.

Conning DM, Hayes MJ (1970) The dermal toxicity of phenol: An investigation of the most 

effective first-aid measures. Br J Ind Med 27: 155-159

Dalin, N.M. and R. Kristoffersson (1974) Physiological effects of a sub-lethal concentration of 

inhaled phenol on the rat. Ann Zool Fennici 11: 193-199.

Dow Chemical Co., (1994) Hiser, M.F., B.E. Kropscott, R.J. McGuirk, and J.S. Bus (1994) 

Pharmacokinetics, metabolism, and distribution of C 14 phenol in Fischer 344 rats after 

gavage, drinking water, and inhalation exposure, with cover letter dated 07/13/1994. Dow 

Chemical Co., (U.S. EPA/OPTS Public Files Fiche OTS0557473/86940001296).

Hodson, P.V., Dixon D.G., and K.L. Kaiser. (1984). Measurement of Median Lethal Dose as a 

Rapid Indication of Contaminant Toxicity to Fish. Environ. Toxicol. Chem. 3(2):243-254.

Hoffman et al. (2001). Two-week (ten-day) inhalation toxicity and two-week recovery study of 

phenol vapor in the rat. Int. J. Toxicol. 20: 45-52.
Page 22 of 33

Hughes, M.F. and L.L. Hall (1995) Disposition of Phenol in Rat after Oral, Dermal, Intravenous, 

and Intratracheal Administration. Xenobiotica 25, 873-883, cited in ATSDR, 1998.

IARC, International Agency for Research on Cancer (1999) Phenol. In IARC Monographs on the 

Evaluation of Carcinogenic Risks to Humans. Vol. 71, Re-Evaluation of Some Organic 

Chemicals, Hydarzine and Hydrogen Peroxide (Part 1-3). WHO, World Health 

Organization, Geneva, Switzerland. Pp. 749-768.

Kavlock, R.J. (1990) Structure-Activity Relationships in the Developmental Toxicity of 

Substituted Phenols: In Vivo Effects. Teratology 41:43-59. 

Moser, V.C., B.M. Cheek and R.C. MacPhail (1995) A multidisciplinary approach to 

toxicological screening: III. Neurobehavioral toxicity. J Toxicol Environ Health. 45(2): 

173-210.

Narotsky M,G. and R.J. Kavlock (1995) A multidisciplinary approach to toxicological screening: 

II. Developmental Toxicity. J Toxicol Env Health 45: 145-171.

NCI (1980) Bioassay of Phenol for Possible Carcinogenicity. U.S. National Cancer Institute, 

Bethesda, M.D., U.S. Department of Health and Human Services. Technical Report Series 

No. NCI-CG-TR-203 (cited in BUA, 1998), Hazleton Laboratories Americal Inc., Vienna, 

VA, NIH publication No. 80-1759, August 1980, 123 pp.

NRC (2004) National Academy of Sciences Spacecraft Water Exposure Guidelines for Selected 

Contaminants, Volume 1, Phenol. Board of Environmental Studies and Toxicology Division 

on Earth and Life Sciences, National Research Council (NRC) Committee on Toxicology, 

The National Academies Press, Washington, D.C., 2004

Ryan et al. (2001) Two-generation reproduction study and immunotoxicity screen in rats dosed 

with phenol via the drinking water. International Journal of Toxicology 20: 121-142.

Salaman, M.H. and O.M. Glendenning (1957) Tumor promotion in mouse skin by sclerosing 

agents. Br. J. Cancer. 11: 434-444.

Stenius U., M. Warholm, A. Rannug, et al. (1989) The role of GSH depletion and toxicity in 

hydroquinone-induced development of enzyme-altered foci. Carcinogenesis. 10:593-599.

Tisler, T. and J. Zagorc-Koncan. (1995). Relative Sensitivity of some Selected Aquatic

Organisms to Phenol. Bulletin of Environmental Contamination and Toxicology, 54: 717-

723.

U.S. Environmental Protection Agency (EPA). (1980). Ambient Water Quality Criteria for 

Phenol. U.S. EPA 440/5-80-066. October, 1980.

U.S. Environmental Protection Agency (EPA). (1986) Guidelines for carcinogen risk 

assessment. Federal Register 51(185):33992-34003.

U.S. Environmental Protection Agency (EPA). (2002). ECOTOX User Guide: ECOTOXicology 

Database System. Version 3.0. Available: http://www.epa.gov/ecotox/
Page 23 of 33

U.S. Environmental Protection Agency (EPA). (2002) Toxicological Review of Phenol. 

Integrated Risk Information System (IRIS).

U.S. Environmental Protection Agency (EPA). (2004) Incident Reports Associated with Phenol, 

Antimicrobials Division, July 27, 2004.

U.S. Environmental Protection Agency (EPA). (2005) Guidelines for Carcinogen Risk 

Assessment, Risk Assessment Forum, U.S. Environmental Protection Agency, Washington, 

DC, EPA/630/P-03/001F, March, 2005.

Wynder, E.L. and D. Hoffmann (1961) A study of tobacco carcinogenesis. VIII. The role of the 

acidic fractions as promoters. Cancer. 14(6): 1306-1315.
Page 24 of 33

Appendix A Toxicology Profile

The following is a summary of the toxicology information for phenol and sodium phenate taken 

from the AD Memorandum: PHENOL AND SALT (Phenol; hydroxybenzene, carbolic acid, 

phenyl hydroxide and Sodium Phenate; phenol sodium salt, phenoxy): Hazard Characterization 

for the Human Health Assessment Scoping Document in Support of Registration Review of 

Phenol and Salt. DP403983, TXR Number 1003265

Acute Toxicity for Product Labeling 

The acute toxicity database for registration review of phenol and sodium phenate is considered 

incomplete. Acute toxicity studies (OTS0515567) submitted to satisfy toxicology guideline 

requirements in support of registration of phenol and sodium phenate-containing pesticide 

products were determined to be unacceptable for regulatory purposes. In addition, studies 

reporting LC50 inhalation values or test results addressing the skin sensitizing potential of the 

technical grade active ingredient, phenol or sodium phenate, have not been submitted to the 

Agency. 

Currently, no registrations exist for a phenol or sodium phenate technical grade active ingredient 

and therefore, no registered source has been identified for any of the registered phenol and 

sodium phenate end-use products. In the absence of a registered source as well as no 

manufacturing limitations in producing a phenol and sodium phenate technical grade active 

ingredient, each end-use product registrant is responsible for citing and/or submitting acute 

toxicity data. These data include acute oral, dermal, inhalation, eye irritation and dermal 

irritation toxicity studies and a skin sensitization study. 

Data which fully characterizes the acute toxicity of phenol and/or sodium phenate may be 

available in the published literature. The Agency will accept submission of published literature 

addressing acute toxicity of phenol and/or sodium phenate for review and determination of the 

regulatory acceptability of these data. 

Subchronic Toxicity 

The database for subchronic toxicity is considered complete. Although oral range-finding 

studies in both the rat and the mouse were reviewed and classified non-guideline (due to the lack 

of subchronic parameter measurements), systemic toxicities were noted at 10,000 ppm in both 

species, based on a decrease in mean body weight gain (NCI, 1980). In a two-week (wholebody, chamber) inhalation study (Dalin and Kristoffersson, 1974), rats had elevated plasma K1+ 

and Mg2+ levels, increased activities of plasma enzymes LDH, GOT, GPT, and GLDH and 

exhibited toxic effects in the central nervous system (muscle tremors, twitching, abnormal gait 

and posture) up to 5 days following continuous exposure at 26 ppm for a 15-day period (24 

hours/day). In contrast, a two-week (nose-only) inhalation study conducted in rats (Hoffman, et 
Page 25 of 33

al. 2001) did not result in any portal of entry adverse toxic effects, or any other toxicity, at any 

exposure level up to and including 25 ppm following intermittent exposure for 6 hours/day, 5 

days/week (for a total of 10 exposures) to the vapors of phenol. The results from this second 

inhalation study also indicated that there was no delayed occurrence of toxic effects following a 

14-day follow-up recovery period.

Developmental Toxicity 

The database for developmental toxicity is considered complete. Phenol was administered in 

two developmental guideline studies in rats (MRID 43735402) and mice (MRID 43735401) at 

concentrations of 30, 60, or 120 mg/kg/day and 70, 140, or 280 mg/kg/day, respectively. There 

was no evidence of toxicity in these animals at concentrations below the high-dose. Fetal body 

weight was significantly reduced at 120 and 280 mg/kg/day in rat and mouse studies, 

respectively. Additionally, female mice experienced increased mortality and clinical signs of 

CNS toxicity (tremors, ataxia, lethargy) at the high-dose (280 mg/kg/day). Significant weight 

loss in dams and clinical signs of toxicity in pups (paralysis and/or palsy of the hind limbs) were 

observed in animals administered phenol in a non-guideline developmental study (Kavlock,

1990), at the two highest doses of 667 and 1000 mg/kg/day. In a non-guideline special study 

(Nartosky and Kavlock, 1995) maternal and developmental toxic effects were observed at the 2 

doses (40 and 53.3 mg/kg/day).

Reproductive Toxicity

The database for reproductive toxicity is considered complete. In a two-generational 

reproductive study (Ryan et al., 2001), rats were exposed to 200, 1,000, or 5,000 ppm phenol 

(equivalent to 0, 14, 70, and 310 mg/kg/day in males and 0, 20, 93, and 350 mg/kg/day in 

females) for 10 weeks/generation. There were significant reductions in food and water 

consumption, body weight and body weight gain in dams and F1 generation dams at 5,000 ppm 

(potential flavor aversion). The decreased birth weight, and body weight gains observed in the 

F1 generation pups at 5,000 ppm occurred concomitantly with maternal toxicity (decreased 

maternal body weight) as a result of decreased maternal food and water consumption during 

lactation. Decreases in body weight as well as litter survival were observed at 5,000 ppm in the 

F1 and more so in the F2 generation offspring. The increased mortality in the pups occurred 

concurrently with maternal toxicity (decreased maternal body weight). Similarly to the F1 

generation offspring, decreased maternal body weight (F1 dams) and reduced palatability were 

likely significant factors that contributed to the decreased body weights in the high-dose F2 

generation. In a non-guideline reproductive study (Bishop, et al. 1997) phenol was administered 

to mice at a concentration of 350 mg/kg. There were no treatment-related clinical signs or 

mortality observed in maternal, developmental, or reproductive parameters and a LOAEL was 

not established (highest dose tested, 350 mg/kg). 

Chronic Toxicity and Carcinogenicity

Chronic toxicity/carcinogenicity studies in rats and mice were performed by the National Cancer 

Institute (NCI, 1980) to examine the carcinogenicity of phenol. Phenol was administered in 
Page 26 of 33

drinking water to male and female rats at doses of (M/F) 0, 322/360, and 645/721 mg/kg/day 

for 103 weeks. In mice, phenol was administered in drinking water at doses of (M/F) 0, 590/602, 

and 1180/1204 mg/kg/day for 103 weeks. There was no evidence of carcinogenicity in any dose 

group except low dose male rats, where a statistically significant increase in the occurrence of 

leukemia, lymphoma, or interstitial-cell tumors was observed. Although there was an increased 

incidence of these tumor types at the low dose, there was also a high spontaneous tumor rate in 

matched control rats, as well as a lack of carcinogenicity at the high dose. Therefore, it was 

concluded in this study that phenol was not carcinogenic in male or female rats and mice. 

A 20-week dermal study in the rat showed chronic irritation and hair growth inhibition with 

administration of 3 mg phenol (in 200 uL acetone). A single papilloma was found 7 weeks into 

the study, but there was no evidence that it was significantly increased or treatment-related. In a 

special, mechanistic study (Stenius, et al. 1989) there was no evidence of tumor initiation or 

hepatocyte GSH depletion following administration of 100 mg/kg/day phenol.

Carcinogenic Potential of Phenol

Several epidemiology studies have evaluated the carcinogenesis of phenol, but they have not 

found a consistent dose-related association. Because all of the subjects were also exposed to 

other chemicals and there was no correction for smoking, these studies are not adequate to reach 

conclusions on the carcinogenic potential of phenol in humans. 

Phenol was negative for carcinogenicity in drinking water studies conducted in rats and mice 

(NCI, 1980), although an increased incidence of leukemias was observed only in low-dose male 

rats. In short-term dermal assays, tumorigenicity (production of papillomas in the absence of 

treatment by an initiating agent) was observed only at a dose/concentration combination that 

produced ulceration and thus was well above the MTD (Salaman and Glendenning, 1957). 

Similarly, although phenol was a promoter when tested in initiation/promotion studies, the doses 

tested typically caused ulceration (Salaman and Glendenning, 1957; Boutwell and Bosch, 1959) 

and death (Boutwell and Bosch, 1959). There were two exceptions. First, the low concentration 

tested by Salaman and Glendenning) caused promotion as well as "transient light crusting." 

Because the site of the weekly treatment was rotated across four sites on the body, it is unclear 

whether more severe effects would have been observed if the same site had been treated for the 

entire study. The second exception was that the low concentration tested by Wynder and 

Hoffmann (1961) was reported as causing no toxicity, although the sensitivity of the evaluation 

is unclear. On the basis of the high observed toxicity, it is not clear whether the promoting

activity observed for phenol in several dermal studies was secondary to the repeated injury and 

healing of the skin. 

Evaluations conducted by the Agency (U.S. EPA, 2002) have concluded that there is inadequate 

evidence in humans and animals to classify phenol as a carcinogen. Similar conclusions have 

been reached by other groups in assessments of potential carcinogenic risk to humans for phenol. 

For example, IARC (1999) concluded that there is inadequate evidence in humans and animals to 

conduct an assessment of carcinogenicity for phenol and therefore, phenol is not classifiable as 

to its carcinogenicity to humans (Group 3). 
Page 27 of 33

Although the available data for carcinogenicity do not permit a definitive classification for the 

carcinogenic potential of phenol, additional data on carcinogenicity will not be needed. This is 

due to the selection of a chronic Reference Dose value of 0.6 mg/kg/day for phenol and phenol 

salts for non-carcinogenic effects that may occur over a lifetime. This value of 0.6 mg/kg/day,

when compared to the dose level that caused an increased incidence of tumors in male rats (322 

mg/kg/day) is orders of magnitude lower and is considered protective as a regulatory endpoint 

against any potential carcinogenic effects of phenol. 

Mutagenicity 

The results of the mutagenicity studies indicated that phenol was not mutagenic in Salmonella 

typhimurium or Drosophila melanogaster and did not induce micronuclei or bone marrow 

chromosomal aberrations in mice. However, mutagenic effects were observed in Chinese 

Hamster Ovary (CHO) cells and spermatocytes in mice and HL60 cells. The genotoxic potential 

of phenol appears to depend on the competing processes of activation to a genotoxic form and 

metabolic inactivation (e.g., via conjugation). Phenol tended to be negative in bacterial gene 

mutation assays but was positive or equivocal in mammalian cell gene mutation assays. Phenol 

tended to induce micronuclei in mice when administered intraperitoneally but was negative (or 

positive only at very high doses) when administered orally. This difference is likely due to the 

first-pass conjugation and inactivation of orally administered phenol. Phenol was also positive in 

in vitro micronucleus tests with human lymphocytes and CHO cells. Results from DNA damage 

assays are inconsistent, but they tend to show that phenol can cause sister chromatid exchanges 

or cell transformation if it is not metabolically inactivated. Overall, phenol did not exhibit strong 

mutagenic effects.

Other Toxicological Effects 

Neurotoxicity

Neurotoxic signs were observed in an acute dermal toxicity studies (at concentrations ranging 

from 0.625 to 0.68 mL/kg) and included convulsions (Brown, et al., 1975), tremors (Carpenter, 

1949), and stimulation of motor nerve endings or spinal motor centers (Conning, 1970). 

Impaired balance, involuntary muscle twitches, jerkiness, and increased sluggishness were 

observed in rats exposed continuously to 26 ppm (100 mg/m3

) phenol in air for 15 days (Dalin 

and Kristoffersson, 1974). The IRIS Toxicological Profile for Phenol (US EPA, 2002) reports 

numerous nervous system effects (tremors, decreased motor activity and increased rearing postexposure) following phenol dosing in animals. Studies performed by ClinTrials BioResearch 

presented one animal with tremors that later died (apparently of dehydration) following dosing in 

drinking water (1998). Additionally, several gavage studies have shown rats and mice with 

phenol-related tremors (43735402; Dow Chemical Co., 1994; Moser et al., 1995). However, in a 

specialized 13-week neurotoxicity study in male and female rats that included a Functional 

Observational Battery (FOB) and a detailed neurohistopathology evaluation (ClinTrials 

BioResearch, 1998), nervous system effects were observed as tremors in one animal and 

decreased motor activity in females. A short-term gavage screening study (Moser et al., 1995)
Page 28 of 33

found that the only effect in an FOB was a marginal decrease in motor activity and increased 

rearing post-exposure. Part of this could be attributed to the dehydration observed in the study, 

but it was also concluded that phenol contributed to the decreased motor activity.

Metabolism

The database for Phenol metabolism is considered to be complete. Phenol is readily absorbed by 

the inhalation, oral, and dermal routes and is completely metabolized within 24 hours following 

administration. The portal-of-entry metabolism for the inhalation and oral routes appears to be 

extensive and involves sulfate and glucuronide conjugation and, to a lesser extent, oxidation. 

Once absorbed, phenol is widely distributed in the body, although the levels in the lung, liver, 

and kidney are often reported as being higher than in other tissues (on a per-gram-tissue basis). 

Elimination from the body is rapid and phenol does not appear to accumulate significantly in the 

body. Phenol was predominantly conjugated with sulfate and lower amounts of glucuronic acid 

and the metabolites were rapidly excreted in the urine, regardless of the route of administration.

The major urinary metabolites identified include phenyl sulfate, quinol sulfate, phenyl 

glucuronide, and quinol glucuronide (Capel et al., 1971; Hughes and Hall, 1995).

Dermal Absorption

Dermal penetration studies were available from the open literature and IRIS Toxicological 

profile (Behl, 1983; Hughes and Hall, 1995; US EPA, 2002) for phenol. Phenol is readily 

absorbed via the dermal route and systemic effects can result from dermal exposure. Age and 

hydration seemed to have little effect on the permeability of phenol through human and mouse 

skin. Permeation and chemical denaturation of skin by phenol were found to be similar between 

mouse and human skin tissue; indicating that the hairless mouse is an adequate model for 

chemical permeability in humans. The effects on the skin were apparently a result of destroyed 

barrier integrity and the results suggest that the stratum corneum is proportionally impaired as 

the phenol concentration is increased. Dermal absorption is considered the primary route of entry for 

vapor, liquid, and solid phenol. The skin has relatively low potential to detoxify phenol. Therefore, 

absorption through the skin may represent the greatest hazard from phenol because it readily 

passes through the skin and there is no first-pass metabolic effect as is observed following oral 

exposure.
Page 29 of 33

Appendix B Ecotoxicology Profile

Toxicity to Terrestrial Receptors

No data have been submitted for acute or chronic effects of phenols on avian species. 

Toxicity to Aquatic Receptors

1. Acute Toxicity of Phenol to Freshwater Fish

As shown in the following Table 10, acute toxicity for freshwater fish ranged from 5 mg/L 

(rainbow trout) to 23.9 mg/L (bluegill), with average values of 9.1 mg/L for rainbow trout and

17.1 mg/L for bluegill. These data indicate that phenol is moderately toxic to coldwater species,

such as the rainbow trout, and slightly toxic to warm water species, such as the bluegill. 

Table 10 - Acute Toxicity for Freshwater Fish

Organism

Results -

LC50 (mg/L)

(95% 

Confidence 

Toxicity

Category Comments Reference

Rainbow trout 

(Oncorhynchus 

mykiss)

5.02 

(4.23 - 7.49)

moderately 

toxic

- 96h test duration;

- juvenile organisms;

- renewal system

EPA AWQC, 1980;

and U.S. EPA, 2002

Rainbow trout 

(Oncorhynchus 

mykiss)

11.6 slightly 

toxic

- 96h test duration;

- flow-through system

- used active ingredient 

concentration

EPA AWQC, 1980;

and U.S. EPA, 2002

Rainbow trout 

(Oncorhynchus 

mykiss)

13.1 

(11.9-14.1)

slightly 

toxic

- 48h test duration;

- system type not reported;

- used active ingredient 

concentration

Tisler and ZagorcKoncan, 1995

Rainbow trout 

(Oncorhynchus 

mykiss)

6.1 

(5.5-6.8)

moderately 

toxic

- 96h test duration;

- flow-through system;

- used active ingredient 

concentration

U.S. EPA, 2002

Rainbow trout 

(Oncorhynchus 

mykiss)

8.9 moderately 

toxic

- 96h test duration;

- flow-through system

U.S. EPA, 2002

Rainbow trout 

(Oncorhynchus 

mykiss)

9.7 moderately 

toxic

- 96h test duration;

- flow-through system;

- used active-ingredient

Hodson et al., 1984. 

U.S. EPA, 2002
Page 30 of 33

Organism

Results -

LC50 (mg/L)

(95% 

Confidence 

Toxicity

Category Comments Reference

concentration

Rainbow trout 

(Oncorhynchus 

mykiss)

10.5 

(9.1 - 12.2)

slightly 

toxic

- 96h test duration;

- flow-through system;

- used active-ingredient 

concentration

U.S. EPA, 2002

Rainbow trout 

(Oncorhynchus 

mykiss)

7.7 moderately 

toxic

- 96h duration;

- flow-through system

U.S. EPA, 2002

Rainbow trout 

(Oncorhynchus 

mykiss)

8.9 moderately 

toxic

- 96h duration;

- flow-through system

U.S. EPA, 2002

Bluegill (Lepomis 

macrochirus) 17.4 

(11.9 - 25.3)

slightly 

toxic

- 96h test duration;

- flow-through system

- used active ingredient 

concentration.

U.S. EPA, 2002

Bluegill (Lepomis 

macrochirus) 13.5 slightly 

toxic

- 96h test duration;

- static system

EPA AWQC, 1980;

and U.S. EPA, 2002

Bluegill (Lepomis 

macrochirus) 19.3 slightly 

toxic

- 96h test duration;

- juvenile organisms;

- renewal system

EPA AWQC, 1980;

and U.S. EPA, 2002

Bluegill (Lepomis 

macrochirus) 11.5 slightly 

toxic

- 96h test duration;

- renewal system;

- used active ingredient 

concentration.

EPA AWQC, 1980;

and U.S. EPA, 2002

Bluegill (Lepomis 

macrochirus) 23.9 

(20.2 - 31.5)

slightly 

toxic

- 96h test duration;

- static system

EPA AWQC, 1980;

and U.S. EPA, 2002

2. Acute Toxicity of Phenol to Freshwater Invertebrates

As shown in the following Table 11, acute toxicity for aquatic invertebrates (Daphnia magna)

ranged from 4.2 mg/L to 88 mg/L. The endpoint for these studies is the EC50 for

immobilization or the LC50. The average value for the endpoint concentrations shown in Table

2 is 18.8 mg/L. Notably, when considering only the studies where the endpoint is reported to be

based on the active ingredient concentration (Table 2), the average concentration is relatively

lower at 14.6 mg/L. These data results indicate that phenol is moderately to slightly toxic to

aquatic invertebrates. 

 
Page 31 of 33

 

Table 11 – Acute Toxicity for Aquatic Invertebrates

Organism

Results - EC50 

(mg/L) (95% 

Confidence

Toxicity

Category Comments Reference

Water flea

(Daphnia magna) 9.6 moderately 

toxic

- 48h test duration;

- static system

EPA AWQC, 1980;

and U.S. EPA, 2002

Water flea

(Daphnia magna) 7 moderately 

toxic

- 50h test duration;

- juvenile organisms;

- static system

EPA AWQC, 1980;

and U.S. EPA, 2002

Water flea

(Daphnia magna) 88 slightly toxic

- 48h test duration;

-static system

EPA AWQC, 1980;

and U.S. EPA, 2002

Water flea 

(Daphnia magna 

St.)

0.102 (mmol/L) 

(= 9.6 mg/L)

moderately 

toxic

- 48h test duration;

- renewal system

Arambasic at al.,

1995

Water flea 

(Daphnia magna 

Strauss)

33.9 

(30 - 39.2)

slightly toxic

- 24h test duration;

- system type not 

reported

- used active ingredient 

concentration

Tisler and ZagorcKoncan, 1995

Water flea

(Daphnia magna) 23.5

( 21 - 26.3)

slightly toxic

- 48h test duration;

- static system

U.S. EPA, 2002

Water flea

(Daphnia magna) 6.6 moderately 

toxic

- 48h test duration;

- static system;

- used active ingredient 

concentration

U.S. EPA, 2002

Water flea 

(Daphnia magna 

Strauss)

4.2 moderately 

toxic

- 48h test duration;

- static system;

- used active ingredient 

concentration

U.S. EPA, 2002

Water flea

(Daphnia magna) 30 slightly toxic

- 48h test duration;

- static system;

U.S. EPA, 2002

Water flea

(Daphnia magna) 12.6 slightly toxic

- 48h test duration;

- flow-through system;

U.S. EPA, 2002
Page 32 of 33

Organism

Results - EC50 

(mg/L) (95% 

Confidence

Toxicity

Category Comments Reference

(10.2 -15.5) - used active ingredient 

concentration

Water flea

(Daphnia magna) 10 

(8.8 -12)

moderately to 

slightly toxic

- 48h test duration;

- static system;

U.S. EPA, 2002

Water flea

(Daphnia magna) 15 slightly toxic

- 48h test duration;

- static system;

U.S. EPA, 2002

Water flea

(Daphnia magna) 5.5 

(4.9 - 6.3)

moderately 

toxic

- 48h test duration;

- system type not 

reported;

- used active ingredient 

concentration

U.S. EPA, 2002

Water flea

(Daphnia magna) 12* 

(7.3 - 20)

slightly toxic

- 48h test duration;

- static system

U.S. EPA, 2002

Water flea

(Daphnia magna) 30.1* slightly toxic

- 48h test duration;

- system type not 

reported

U.S. EPA, 2002

Water flea

(Daphnia magna) 32* 

(24 - 43)

slightly toxic

- 48h test duration;

- static system

U.S. EPA, 2002

Water flea

(Daphnia magna) 8.6* 

(7.2 - 10.2)

moderately 

toxic

- 48h test duration;

- static system

U.S. EPA, 2002

Water flea

(Daphnia magna) 19.8* 

(18 - 22)

slightly toxic

- 48h test duration;

- static system;

- used active ingredient 

concentration

U.S. EPA, 2002

Water flea

(Daphnia magna) 23* slightly toxic

- 48h test duration;

- static system;

- used active ingredient 

concentration

U.S. EPA, 2002

Water flea

(Daphnia magna) 13* 

(10- 17)

slightly toxic

- 48h test duration;

- static system

U.S. EPA, 2002

Water flea

(Daphnia magna) 11.2* 

(9.8 - 12.6)

slightly toxic

- 48h test duration;

- static system;

- used active ingredient 

concentration

U.S. EPA, 2002

Water flea

(Daphnia magna) 8.3* 

(5.8 - 12.5)

moderately 

toxic

- 48h test duration;

- system type not 

reported

U.S. EPA, 2002

* Endpoint in study is identified as LC50
Page 33 of 33

 3. Toxicity to Estuarine and Marine Organisms

Acute toxicity testing with estuarine and marine organisms using the TGAI is not required for

the indoor uses of phenol or sodium phenate. Several studies on marine/estuarine invertebrates 

were found in the ECOTOX database (EPA, 2002). The endpoints from these studies are 

summarized in the Table 12 below:

Table 12 - Acute Toxicity of Phenol to Marine/Estuarine Invertebrates

Organism

Results - LC50

or EC (flg/L)

(95% Confidence

Toxicity

Category Comments Reference

Mysid 

(Archaeomysis 

kokuboi)

96-hr LC50 = 260 -

4530 (formulation) highly to 

moderately 

toxic

- 96h test duration;

- static system

U.S. EPA, 2002

Opossum shrimp 

(Americamysis 

bahia)

96-h LC50 = 12500 

(10700 - 15600) 

(formulation)

slightly toxic

- 96h test duration;

- static system

U.S. EPA, 2002

Daggerblade grass 

shrimp 

(Palaemonetes 

pugio)

96-hr LC50 = 5800 

(4330 - 7770)

moderately 

toxic

- 96h test duration;

-static system

U.S. EPA, 2002

Table 13 - Chronic Toxicity of Phenol to Marine/Estuarine Invertebrates

Organism

Results -

LOEC, NOEC,

MATC (flg/L) Comments Reference

Opossum shrimp

(Americamysis 

bahia)

mortality

27-d NOEC=2410

LOEC = 6880

MATC = 4080

- 27 day test duration;

- flow-through system

U.S. EPA, 2002

4. Toxicity to Plants

Terrestrial and aquatic plant testing is not required for the registered indoor uses of phenol or 

sodium phenate. There were aquatic phytotoxicity endpoints reported in the ECOTOX database

(EPA, 2002). While these data were reported in summary form, they indicate that phenol

demonstrates low toxicity to various aquatic plant species, with 4-day EC50 values ranging from

12,000 ppb (duckweed, Lemna minor) to 370,000 ppb (green alga, Chlorella vulgaris).