U.S. EPA

High Production Volume Chemical Challenge Program

Robust Summaries and Test Plan

for Trichlorinated Ketone

(CAS No. 145556-04-3)

Revised Submission

Submitted by:

Exponent, Inc. 

1800 Diagonal Road, Suite 500

Alexandria, VA 22314

On behalf of:

BASF Corporation

3150 Highway JJ

Palmyra, MO 63641

Date of submission:

December 21, 2011
- This page intentionally left blank -
HPV Robust Summaries and Test Plan – Trichlorinated ketone

ii

Table of Contents

1.0 Executive Summary 1

2.0 Introduction 4

2.1 Overview 4

2.2 Methods for Data Review 4

3.0 Substance Information for Trichlorinated Ketone 6

3.1 Substance Description 6

3.2 Use and Exposure Information 6

4.0 Analogs for Trichlorinated Ketone 7

4.1 EPA Guidance for Use of Analogs 7

4.2 Structural Similarity and Comparison of Data for TCK and DCP 8

5.0 Data Analysis 9

5.1 Physicochemical Properties 10

5.2 Environmental Fate and Pathways 10

5.2.1 Photodegradation, Volatilization, and Hydrolysis 10

5.2.2 Bioaccumulation, Fugacity, and Biodegradation 11

5.3 Ecotoxicity 12

5.4 Health Effects 14

5.4.1 Absorption, Distribution, Metabolism and Excretion 14

5.4.2 Acute Toxicity 14

5.4.3 Repeated Dose Toxicity 15

5.4.4 Genetic Toxicity 15

5.4.5 Reproductive Toxicity 16

5.4.6 Developmental Toxicity 16

5.4.7 Summary of Health Effects Data 17

6.0 Conclusions and Recommendations 19

7.0 SIDS Data Matrix 20

8.0 References 22
HPV Robust Summaries and Test Plan – Trichlorinated ketone

iii

List of Figures

Figure 1. Structure of trichlorinated ketone 6

Figure 2. Comparison of structures of TCK and DCP 8

List of Tables

Table 1. Testing plan and rationale 3

Table 2. Comparison of physicochemical properties of TCK and DCP 9

Table 3. Environmental fate and pathways information for TCK and DCP 12

Table 4. Ecotoxicity information for TCK and DCP 13

Table 5. Health effects information for TCK and DCP 18
HPV Robust Summaries and Test Plan – Trichlorinated ketone

1

1.0 Executive Summary

Trichlorinated ketone (CAS No. 145556-04-3), also known as TCK or 3-pentanone, 1,2,4-

trichloro-2-methyl, is a colorless to slightly yellow liquid with a pungent odor and a molecular 

weight of 203.5 g/mole. The available data for TCK (measured, estimated, and from references) 

were supplemented with data on a related chemical, dichloropinacolin (CAS No. 22591-21-5), 

also known as DCP, which was used as an analog. 

Trichlorinated ketone is a closed-system intermediate in the manufacturing process for the 

herbicide dimethenamid. Potential exposures are thought to be extremely limited, because of the 

moderately low volatility of TCK, which limits inhalation exposures, and because personal 

protective equipment is used during sampling events when any dermal contact might occur. 

Environmental exposures are expected to be extremely rare, because any spills would be handled 

in an appropriate manner to minimize release to the environment. 

EQC Level III fugacity modeling predicts that, if released to the environment, TCK is expected 

to partition primarily to soil (71.7%) and water (26.6%). Vapor-phase TCK, which is expected 

to be limited as a result of its moderate volatility, will be degraded in the atmosphere by reaction 

with hydroxyl radicals, with a half-life of 6.8 days. TCK is not expected to undergo hydrolysis 

in the environment because of the lack of functional groups that hydrolyze under environmental 

conditions. Because of its relatively low octanol-water partition coefficient, TCK is not expected 

to bioaccumulate to any great extent. TCK was not biodegradable in 28 days in a ready 

biodegradability test conducted according to OECD Guideline 310. 

The toxicity of TCK to aquatic plants was determined in a study conducted with the green alga, 

Pseudokirchneriella subcapitata, according to OECD Guideline 201. The resulting 72-hour

EC50 for TCK, based upon yield, was 6.32 mg/L. There are no studies available on the toxicity 

of TCK to fish or invertebrates. However, based upon structure-activity relationships, TCK is 

estimated to be highly toxic to fish (LC50 of 0.11 mg/L) and Daphnia (EC50 of 0.66 mg/L).
HPV Robust Summaries and Test Plan – Trichlorinated ketone

2

Reliable data from guideline studies conducted under Good Laboratory Practices (GLP) are 

available for TCK to fulfill the SIDS Level 1 endpoints for health effects. The acute oral LD50 

for TCK in rats was 500–2,500 mg/kg, while the acute dermal LD50 in rats was greater than 

2,000 mg/kg. Supporting data for DCP consist of an acute oral LD50 for rats of 1,820 mg/kg for 

males and 1,300 mg/kg for females, an acute dermal LD50 for rabbits of > 5,000 mg/kg for 

males and approximately 5,000 mg/kg for females, and acute inhalation LC50 values of > 1,179 

mg/m3for rats and mice and > 1,234 mg/m3for hamsters and rabbits. In a 13-week repeated 

dose oral study with rats, the NOAEL for TCK was 200 ppm (21.1−23.1 mg/kg bw/day). This 

study also found no evidence of gross or histopathological effects in the reproductive organs of 

male or female rats up to and including a dose of 2,000 ppm (211–231 mg/kg bw/day). 

In the bacterial reverse mutation assay, TCK was positive in only one of five strains, in which a 

4.7-fold increase in revertants per plate was observed. In an in vitro mammalian chromosomal 

aberration test conducted according to OECD 473, clastogenic effects were observed both in the 

presence and absence of metabolic activation. Effects on reproductive organs were not observed 

in a 90-day repeated dose study with rats at doses up to and including 211 mg/kg bw/day for 

males and 231 mg/kg bw/day for females. In developmental toxicity testing with rats and 

rabbits, effects on the offspring occurred only at maternally toxic doses. For rats, the maternal 

NOAEL was 125 mg/kg bw/day and the developmental NOAEL was 250 mg/kg bw/day. For 

rabbits, the maternal NOAEL was 50 mg/kg bw/day and the developmental NOAEL was 100 

mg/kg bw/day. 

The original test plan submitted by BASF to EPA for TCK in May 2008 identified several data 

gaps for HPV elements. This revised test plan incorporates the results of testing conducted on 

TCK by the sponsor since that date, to determine the boiling point, water solubility, 

biodegradability, acute toxicity to algae, and clastogenicity. Including these new data, the overall 

conclusions and recommendations are that adequate information exists for all HPV elements for 

trichlorinated ketone. This information is summarized in Table 1. 
HPV Robust Summaries and Test Plan – Trichlorinated ketone

3

Table 1. Testing plan and rationale

CAS #145556-04-3

Trichlorinated Ketone (TCK)

Information 

Available?

OECD Study?

GLP Study?

Supporting 

Information?

Estimation Method?

Acceptable?

Testing 

Recommended?

HPV Endpoint

Physicochemical Properties

Melting Point Y N N Y Y Y N

Boiling Point Y Y N Y N Y N

Vapor Pressure Y N N Y Y Y N

Partition Coefficient Y N N Y Y Y N

Water Solubility Y Y N Y N Y N

Environmental Fate

Photo-Degradation Y N N Y Y Y N

Water Stability Y N N Y Y Y N

Fugacity Y N N Y Y Y N

Biodegradation Y Y Y Y Y Y N

Ecotoxicity

96-Hour Fish Y N N Y Y Y N

48-Hour Invertebrate Y N N Y Y Y N

96-Hour Algae Y Y Y Y N Y N

Health Effects

Acute Y Y Y Y N Y N

Genetic Toxicology in vitro Y Y Y N N Y N

Genetic Toxicology in vivo Y Y Y N N Y N

Repeated Dose Y Y Y N N Y N

Reproductive Y Y Y N N Y N

Developmental Y Y Y N N Y N
HPV Robust Summaries and Test Plan – Trichlorinated ketone

4

2.0 Introduction

2.1 Overview

Exponent, on behalf of BASF Corporation, has prepared the revised robust summaries and 

revised test plan for trichlorinated ketone, also referred to as TCK or 3-pentanone, 1,2,4-

trichloro-2-methyl (CAS No. 145556-04-3), under the United States Environmental Protection 

Agency’s (U.S. EPA) Extended High Production Volume (eHPV) Chemical Challenge Program. 

The purpose of this plan is to develop physicochemical data, environmental fate and effects data, 

and mammalian health effects data for TCK consistent with the Screening Information Data Set 

(SIDS). Therefore, this plan summarizes the existing SIDS data for TCK and an analog, 

dichloropinacolin, and evaluates the need for testing to fill any data gaps in the SIDS endpoints.

2.2 Methods for Data Review

A review of the scientific literature and BASF Corporation’s company data was conducted on the 

physicochemical properties, environmental fate and effects, and mammalian toxicity endpoints 

for trichlorinated ketone and the analog, dichloropinacolin. Searches were conducted on CAS 

numbers and chemical names using the following databases and web sites: ATSDR, CICAD, 

ESIS, HPVIS, HERA, IARC, IPCS INTOX Databank, IRIS, Japanese Chemicals Evaluation and 

Research Institute, NTP, OECD, EFDB, ECOTOX, and TOXNET (including TOXLINE, 

MEDLINE, CCRIS, HSDB, DART, GENETOX, and CHEMIDPlus). In addition to these 

databases and web sites, a literature search was performed and standard handbooks (CRC 

Handbook on Chemicals, Hawley’s Condensed Chemical Dictionary, Merck Index, etc.) were 

consulted for physicochemical properties. 

This document addresses a single eHPV sponsored chemical; however, data for a closely related 

compound, dichloropinacolin (CAS No. 22591-21-5) have been used to support the data set for 

the sponsored chemical through a read-across approach. Data read-across means that 
HPV Robust Summaries and Test Plan – Trichlorinated ketone

5

physicochemical property and toxicological data from one chemical are used to estimate those 

same characteristics for another chemical, and is appropriate only when the two chemicals are 

deemed sufficiently similar in structure that they are likely to have similar chemical and 

toxicological properties. Typically, the more data-based information there is to support this 

assumption, the stronger the foundation for the read-across approach will be. The use of 

structural analogs is consistent with EPA guidance for use of structure-activity relationships 

(SAR) in the HPV Chemical Challenge Program (EPA, 1999a).

In accordance with U.S. EPA guidance, in those instances where measured physicochemical 

parameters and environmental fate data were not available, these properties were developed 

using EPIWIN (EPISuite version4.0) modeling. EPIWIN is an acronym for the Estimation 

Programs Interface for Microsoft Windows, and is a package of computer programs developed 

by the U.S. EPA Office of Pollution Prevention and Toxics (OPPTS), which uses computational 

methods and SARs in estimating chemical properties, environmental fate, and aquatic toxicity of 

organic chemicals. Because of the inherent limitations of SAR approaches, EPIWIN modeling 

may produce non-realistic estimates; therefore, EPIWIN data are evaluated for reasonableness 

prior to use as surrogate data. In accordance with EPA guidance, environmental transport and 

fate estimates were developed using the Level III Equilibrium Criteria Model (EQC) in EPIWIN 

v4.0 as described by Mackay et al. (1996). 

Robust summaries were prepared for trichlorinated ketone and dichloropinacolin in EPA’s High 

Production Volume Information System (HPVIS) for key studies to provide a detailed summary 

of the test methods and results. Though several studies may have been evaluated for a particular 

SIDS endpoint, robust summaries were generally prepared only for the critical study that 

represented the best available data. Selection of the critical study was based on a review of all 

studies using the ranking system developed by Klimisch et al. (1997), as well as the criteria 

outlined in the U.S. EPA’s (1999b) methods for determining the adequacy of existing data. 

Reliable studies that provided supporting data were also included. 
HPV Robust Summaries and Test Plan – Trichlorinated ketone

6

3.0 Substance Information for Trichlorinated Ketone

3.1 Substance Description

Trichlorinated ketone (CAS No. 145556-04-3), also known as 3-pentanone, 1,2,4-trichloro-2-

methyl, or TCK, is used in the manufacture of the herbicide dimethenamid. It is a colorless to 

slightly yellow liquid with a pungent odor and has a molecular weight of 203.5 g/mole. The 

structure of TCK is shown in Figure 1. 

Figure 1. Structure of trichlorinated ketone

3.2 Use and Exposure Information

Trichlorinated ketone is a closed-system intermediate used in the manufacture of the herbicide 

dimethenamid. Production volume is between 5 and 15 million pounds per year; hence TCK is 

an HPV chemical. Processing occurs in closed systems with no routine exposure possible except 

for QC sampling. Samples are handled in laboratory settings according to a chemical hygiene 

plan, and using engineering controls such as fume hoods. Trichlorinated ketone is a relatively 

non-volatile liquid, so the probability of inhalation exposure is quite low and air monitoring is 

not warranted. Dermal exposures that might be associated with sampling the materials (and 

waste streams) during the manufacturing process are prevented through worker training
HPV Robust Summaries and Test Plan – Trichlorinated ketone

7

regarding proper health and safety procedures, the use of proper personal protective equipment 

(PPE), and engineering controls.

The vast majority of TCK is converted to the desired product and the inventory onsite at any one 

time is small, i.e., less than 250,000 pounds of TCK in a single storage tank. No TCK is present

in the final product. The aqueous waste streams are sent to an onsite deep well. There is no 

organic waste stream for TCK. Potential environmental exposures are limited to spills onsite, 

which are handled in accordance with recognized emergency response and safety procedures to 

minimize potential exposures. The use of secondary containment at the manufacturing site 

further limits environmental release. In summary, TCK poses a minimal exposure threat to 

workers or the environment. 

4.0 Analogs for Trichlorinated Ketone

4.1 EPA Guidance for Use of Analogs

In its SAR guidance for the HPV Chemical Challenge Program, EPA states that the most likely 

analogs for an HPV chemical are those that resemble the candidate chemical in terms of the 

following:

1. Molecular structure/size; 

2. Some substructure that may play a critical functional role;

3. Some molecular property (e.g., lipophilicity, electronic and steric parameters); 

and/or 

4. Some precursor, metabolite, or breakdown product.
HPV Robust Summaries and Test Plan – Trichlorinated ketone

8

In general, valid analogs should have close structural similarity and the same functional groups 

as the HPV chemical. In addition, a high correlation is desired between the HPV chemical and 

the putative analog for the following parameters:

 Physicochemical properties (e.g., physical state, molecular weight, log Kow, 

water solubility);

 Absorption potential;

 Mechanism of action of biological activity; and

 Metabolic pathways/kinetics of metabolism.

4.2 Structural Similarity and Comparison of Data for TCK 

and DCP

The selected analog is dichloropinacolin or DCP. Also known as 1,1-dichloro-3,3-methyl-2-

butanone, or dichloromethyl tert-butyl ketone, this compound differs from the HPV chemical by 

having one less chlorine atom and an additional methyl group. It is believed to possess most of 

the desired properties for an analog as described in U.S. EPA guidance. The structures of the two 

chemicals are shown in Figure 2.

 

 Trichlorinated ketone Dichloropinacolin

Figure 2. Comparison of structures of TCK and DCP
HPV Robust Summaries and Test Plan – Trichlorinated ketone

9

Table 2 compares the properties of TCK and DCP. The source of the information is classified as 

“measured” or “estimated.” Measured data were obtained through experimental procedures, 

while estimated data were obtained through structure-activity correlations (EPIWIN). Complete 

details on the sources of information for each data element are provided in the Robust 

Summaries submitted with this Test Plan. 

Table 2. Comparison of physicochemical properties of TCK and DCP

Substance 

Information and 

Properties

Trichlorinated ketone

(145556-04-3)

Dichloropinacolin

(22591-21-5)

Synonym 3-pentanone, 1,2,4-trichloro-2-methyl; 

TCK

1,1-dichloro-3,3-dimethyl-2-butanone; 

dichloromethyl tert-butyl ketone; DCP 

Molecular Formula C6H9Cl3O C6H10Cl2O

Molecular weight 203.50 169.05

Melting point 13 °C (estimated) -14 °C (estimated)

Boiling point 190 - 195 °C (measured)1178 °C (estimated)

Vapor pressure 0.681 hPa (estimated) 1.44 hPa (estimated)

Water solubility 136.8 mg/L (measured)22882 mg/L (estimated)

Partition coefficient 

(log Kow) 1.82 (estimated) 1.56 (estimated)

Note: estimated values are from EPIWIN

1

Ji, 2009

2 Rachmalla, 2009

These compounds have reasonably similar physicochemical properties and would be expected to 

have similar environmental fate patterns. The absorption, distribution, metabolism, elimination 

and toxicity of these compounds are also expected to be similar. Therefore, data read-across from 

DCP is used in a supporting manner for the data for TCK. 

5.0 Data Analysis

A summary of the available data for TCK and DCP is shown, along with information on the 

reliability of the data, in the completed SIDS data matrix provided in Section 7. These data are 

discussed below, while details are provided in the Robust Summaries submitted concurrently 

with this Test Plan. 
HPV Robust Summaries and Test Plan – Trichlorinated ketone

10

5.1 Physicochemical Properties

BASF conducted testing to determine the boiling point and water solubility of TCK. Boiling 

point is a key property that is used in estimation of other properties, while water solubility is a 

key property because of its potential relevance for human and environmental risk assessment. 

These studies were conducted following OECD guidelines although they were not performed 

under GLP. The boiling point of TCK was determined to be 190–195 °C according to the 

distillation method in OECD Guideline 103 (Ji, 2009). The water solubility of TCK was 

determined following the flask method in OECD Guideline 105, with a result of 136.8 mg/L at

22 °C (Rachmalla, 2009). The remaining data values for physicochemical properties for TCK 

and DCP were estimated using EPIWIN. These data are presented in Table 2 (in the previous 

section) and in the Robust Summaries. 

Recommendation: No additional physicochemical properties studies are necessary. The 

available data fill the HPV required data elements with sufficient precision to define the potential 

hazards of TCK.

5.2 Environmental Fate and Pathways

The environmental fate data for trichlorinated ketone and dichloropinacolin are summarized in 

Table 3 along with identification of the sources of information (measured or estimated). 

Additional information is tabulated in Section 7 and more fully described in the Robust 

Summaries.

5.2.1 Photodegradation, Volatilization, and Hydrolysis

Indirect photodegradation in air was calculated for TCK using AOPWIN v1.92. The resulting 

half-life was 6.8 days. A similar estimation was made for DCP, resulting in an atmospheric halflife of 5.9 days. The predicted Henry’s Law Constant for TCK is 1.00 x 10−3

atm-m

3

/mole 
HPV Robust Summaries and Test Plan – Trichlorinated ketone

11

(HENRYWIN v3.20), which indicates moderate volatility. Neither TCK nor DCP is expected to 

undergo hydrolysis in the environment because of the lack of functional groups that hydrolyze 

under environmental conditions. 

5.2.2 Bioaccumulation, Fugacity, and Biodegradation

TCK is not expected to bioaccumulate to any extent, as its estimated log Kow value (1.82) and 

log BCF (0.865) are relatively low (U.S. EPA, 2011). If released to the environment, TCK is 

expected to partition primarily to soil (71.1%) and water (26.6%), as predicted by EQC Level III 

fugacity modeling. The behavior of DCP is predicted to be similar (63.5% soil, 33.3% water). 

A study to determine the biodegradability of TCK in the carbon dioxide headspace test (OECD 

Guideline 310) was performed, under GLP, by Schwarz (2009). The test substance, mixed with 

mineral salts and a non-adapted inoculum of municipal sludge, was incubated in sealed vessels 

with a headspace of air for 28 days. The extent of biodegradation was expressed as a percentage 

of the total inorganic carbon formed based on the amount of the total organic carbon initially 

added. The results (biodegradation of 1%) indicated that TCK was not readily biodegradable 

under the conditions of the test. Ready biodegradability studies have not been performed with 

DCP, but it is not predicted to be readily biodegradable according to BIOWIN v4.10.

Recommendation: No additional studies on environmental fate and pathways are necessary. 

The HPV required endpoints are fulfilled by a combination of test results and estimation using 

acceptable methods. 
HPV Robust Summaries and Test Plan – Trichlorinated ketone

12

Table 3. Environmental fate and pathways information for TCK and DCP

Environmental Fate 

Endpoint

Trichlorinated ketone (TCK)

(145556-04-3)

Dichloropinacolin (DCP)

(22591-21-5)

Photodegradation half-life 6.8 days (estimated)15.9 days (estimated)1

Hydrolysis Expected to be stable to hydrolysis Expected to be stable to hydrolysis

Fugacity (percent distribution 

over time assuming equal 

emissions to air, water and 

soil)

Air: 2.2%; Water: 26.6%; Soil: 71.1%; 

Sediment: <1% (estimated)2

Air: 3.1%; Water: 33.3%; Soil: 63.5%; 

Sediment: <1% (estimated)2

Biodegradation

Not readily biodegradable (1% in 28 days) 

per OECD 310 3

(Guideline study, valid without restriction)

Primary biodegradation in weeks, ultimate 

biodegradation in months4

1 estimated by AOPWIN v1.92

2

estimated by EQC Level III

3 Schwarz, 2009

4

estimated by BIOWIN v4.10

5.3 Ecotoxicity

The acute toxicity data are summarized in Table 4 along with identification of the sources of 

information (measured or estimated). Additional information is tabulated in Section 7 and more

fully described in the Robust Summaries. Because TCK is an intermediate in the production of 

an herbicide (dimethenamid), it might be expected that algae would be the most sensitive aquatic 

organisms relative to fish and invertebrates. Therefore, an algal toxicity test was conducted 

according to OECD Guideline 201 and under GLP (Salinas, 2011). In this study, the green alga 

Pseudokirchneriella subcapitata was exposed for 72 hours to five concentrations of TCK (1.0 to 

100 mg/L in algal medium). Test concentrations were analytically verified to be within 83% to 

98% of nominal at test initiation and 84% to 98% of nominal at test termination for the three 

highest test treatments; the two lowest test treatments were below the calibration curve and 

reported as below the limit of quantitation. The results of the study were calculated on the basis 

of the nominal concentrations. The EC50 for yield (final cell density minus initial cell density) 
HPV Robust Summaries and Test Plan – Trichlorinated ketone

13

was calculated to be 6.32 mg/L while the EC50 for growth rate (increase in cell density per day)

was calculated to be 19.2 mg/L, indicating that TCK is moderately to slightly toxic to algae.

1

There are no data on the acute toxicity of TCK to fish or invertebrates. These endpoints were 

fulfilled using estimates from ECOSAR v1.00 in EPI Suite. Estimates for DCP are also presented 

in Table 4. The ECOSAR class that forms the basis for the estimation of toxicity for TCK is the 

Halo Ketones (2 Free H) class, while the Halo Ketones (0-1 Free H) class is used for DCP, 

resulting in estimates that are dissimilar. The additional chlorine atom in TCK is likely affecting 

the aquatic toxicity estimate, as aqueous solutions of chlorine are quite toxic to aquatic animals. 

Based upon the ECOSAR prediction, TCK is conservatively estimated to be highly toxic to fish 

(96-hour LC50 of 0.11 mg/L) and invertebrates (48-hour LC50 of 0.66 mg/L). 

Recommendation: No additional ecotoxicity studies are necessary. The required HPV 

endpoints are fulfilled via a combination of test data and estimation.

Table 4. Ecotoxicity information for TCK and DCP

Ecotoxicity Endpoint Trichlorinated ketone (TCK)

(145556-04-3)

Dichloropinacolin (DCP)

(22591-21-5)

Acute fish LC50, 96-hour

(mg/L) 0.11 mg/L (estimated)1

317 mg/L (estimated)1

Acute invertebrate EC50, 48-

hour (mg/L) 0.66 mg/L (estimated)1

167 mg/L (estimated)1

Algal growth inhibition EC50, 

72-h (mg/L)

6.32 mg/L based upon yield for 

Pseudokirchneriella subcapitata (measured)2

(Guideline study, valid without restriction)

66 mg/L (96-h EC50, estimated)1

1

estimated by ECOSAR v1.00

2

Salinas, 2011

 

1 Ecotoxicity categories are according to http://www.epa.gov/oppefed1/ecorisk_ders/toera_analysis_eco.htm
HPV Robust Summaries and Test Plan – Trichlorinated ketone

14

5.4 Health Effects

5.4.1 Absorption, Distribution, Metabolism and Excretion

No information is available on the absorption, distribution, metabolism, and excretion of 

trichlorinated ketone or dichloropinacolin.

5.4.2 Acute Toxicity

The oral LD50 of trichlorinated ketone was determined in a GLP-compliant study using 12 rats 

(6 per sex) exposed to 500 and 2,500 mg/kg bw. All animals in the high dose group died while 

all animals in the low dose group survived, resulting in an LD50 between 500 and 2,500 mg/kg 

bw (Reagen, 1989a). The dermal LD50 of TCK was determined in a GLP-compliant study in 

which TCK was administered topically to 6 rats (3 per sex) at 500 and 2,000 mg/kg bw. One 

female rat in the high dose group died during the study, while all other animals survived until 

study termination. The acute dermal LD50 of TCK was thus greater than 2,000 mg/kg bw 

(Reagen, 1989b). 

The oral LD50 of dichloropinacolin was determined to be 1820 mg/kg bw for male rats and 

1,300 mg/kg bw for female rats, in a study using eight doses with 15 rats per sex per dose 

(Flucke and Kimmerle, 1978). Flucke and Kimmerle (1978) also reported the results of an acute 

inhalation study on dichloropinacolin conducted with male rats, male mice, male hamsters and 

female rabbits. Animals were exposed for 1 or 4 hours to three measured concentrations and 

observed for 14 days after exposure. Based upon 4-hour exposures, the LC50 values were 

> 1,179 mg/m3for rats and mice and > 1,234 mg/m3for hamsters and rabbits. In a dermal 

exposure of rats to 2500 and 5000 mg/kg bw dichloropinacolin, the LC50 for males was > 5,000 

mg/kg bw and the LD50 for females was approximately 5,000 mg/kg bw (Flucke and Kimmerle, 

1978). 
HPV Robust Summaries and Test Plan – Trichlorinated ketone

15

5.4.3 Repeated Dose Toxicity

In a GLP-compliant study conducted according to EPA guidelines (Pannock, 1994), rats (15 per 

sex per dose) were exposed via the diet for 13 weeks to 0, 200, 630, and 2,000 ppm trichlorinated 

ketone. (These values were converted to mg/kg bw/day using the default values given in U.S. 

EPA, 1988 as described in the robust summary). The NOAEL was 200 ppm (21.1 mg/kg bw/day 

for males and 23.1 mg/kg bw/day for females) based upon reductions in body weight gain in the 

630 ppm group. Reductions in body weight gain and in motor activity, increases in kidney 

weights, and microscopic changes in kidneys and nasal turbinates were noted in the 2,000 ppm 

group. 

5.4.4 Genetic Toxicity

For trichlorinated ketone, bacterial reverse mutation tests were conducted under GLP using five

strains of S. typhimurium (TA98, TA100, TA1535, TA1537, TA1538), both with and without 

metabolic activation. TCK caused a positive increase (4.7 fold) in the number of TA100 

revertants per plate in the presence of S9 mix. Positive results were not seen with this strain in 

the absence of S9, nor with any of the other four strains tested either with or without metabolic 

activation (Lawlor, 1989). An in vitro mammalian chromosome aberration test was performed 

according to OECD Guideline 473 and under GLP for trichlorinated ketone (Schulz and 

Landsiedel, 2009). Chinese hamster lung fibroblast cells (V79) were exposed to TCK with and 

without metabolic activation (S9 mix), including appropriate positive controls and vehicle 

controls. Seven doses from 0.31 to 20 μg/mL were used without metabolic activation and seven 

doses from 0.63 to 40 μg/mL were used with metabolic activation. A statistically significant and 

biologically relevant increase in the number of chromosomal aberrations was seen both with and 

without activation, indicating that TCK was clastogenic in this assay. Changes in the number of 

chromosomes (aneugenic activity) were not observed, either with or without activation. No 

genetic toxicity data were available for dichloropinacolin. 
HPV Robust Summaries and Test Plan – Trichlorinated ketone

16

5.4.5 Reproductive Toxicity

The 90-day repeated dose study of TCK with rats (Pannock, 1994) described in Section 5.4.3 

included gross and histopathological examinations of reproductive organs for both the males and 

females. No effects upon absolute or relative organ weights, or macroscopic or microscopic 

pathology, were found for the reproductive organs and tissues up to and including a dose level of 

2,000 ppm (211 mg/kg bw/day for males and 231 mg/kg bw/day for females). Additional 

information on the toxicity of TCK for reproductive parameters in rats and rabbits is discussed 

below. 

5.4.6 Developmental Toxicity

The developmental toxicity of TCK was determined in both rats and rabbits in studies conducted 

according to EPA guideline 798.4900 and under GLP. Groups of 25 pregnant rats received doses 

of 0, 125, 250 and 500 mg/kg bw/day of TCK via gavage daily on days 6 though 15 of gestation

(Martin, 1993a). Observations were made through day 20 of gestation, at which time the animals 

were sacrificed. The maternal NOAEL was 125 mg/kg bw/day, based upon reductions in body 

weight gain or weight losses and reduced absolute and relative feed consumption values in the 

higher dose groups. Significantly reduced live litter sizes were observed at 500 mg/kg bw/day, 

but reproductive parameters were not affected at 125 and 250 mg/kg bw/day. The developmental 

NOAEL was 250 mg/kg bw/day, based on an increase in early resorptions, reduced fetal body 

weights, and delayed fetal ossification in the 500 mg/kg bw/day group. Effects on development 

occurred only at the higher of two maternally toxic doses, so TCK was not considered a 

developmental toxicant to the offspring of rats. 

Pregnant rabbits (20 per group) were dosed via gavage on days 6 through 18 of gestation at 0, 25, 

50 and 100 mg/kg bw/day of TCK (Martin, 1993b). Animals were observed through sacrifice at 

day 29 of gestation. The maternal NOAEL was 50 mg/kg bw/day based on the following effects 

observed at 100 mg/kg bw/day: weight loss and reduced feed consumption, and in one doe, 

absent or dried feces, gastric erosions, abortion and death. No reproductive parameters were 

affected at doses up to and including 100 mg/kg bw/day. The developmental NOAEL was 
HPV Robust Summaries and Test Plan – Trichlorinated ketone

17

100 mg/kg bw/day, as the observed abortion was a maternal effect, and no other adverse effects 

of this dose were seen on embryo-fetal viability, body weights, or morphology. Thus, TCK was 

not considered a developmental toxicant to the offspring of rabbits. 

5.4.7 Summary of Health Effects Data

The SIDS endpoints relative to health effects for TCK are summarized in Table 5 and Section 7 

(SIDS Data Matrix), with more detailed information provided in the Robust Summaries 

submitted with this Test Plan.

Recommendation: No additional testing is necessary on health effects endpoints. Reliable data 

are available from recent, GLP-compliant studies for TCK for the following health effects 

endpoints: acute oral toxicity, acute dermal toxicity, repeated dose toxicity, mutagenicity, 

clastogenicity, reproductive toxicity and developmental toxicity. Data for DCP are available for 

acute oral toxicity that indicate the similarity in toxicity between TCK and DCP. Therefore, the 

additional data on acute toxicity for DCP (inhalation toxicity) are sufficient for use in read-across 

for TCK. 
HPV Robust Summaries and Test Plan – Trichlorinated ketone

18

Table 5. Health effects information for TCK and DCP

Toxicity Endpoint Trichlorinated ketone (TCK)

(145556-04-3)

Dichloropinacolin (DCP)

(22591-21-5)

Acute oral LD50 (mg/kg) 

Between 500 - 2500 (rat)1

(Similar to guideline study, valid without restriction)

1820 (male rat); 1300 (female 

rat)7

(Valid with restriction)

Acute dermal LD50 (mg/kg)

> 2000 (rat)2

(Similar to guideline study, valid without restriction) 

> 5000 for males; approx. 5000 

for females7

(Valid with restriction)

Acute inhalation LC50 (mg/m3) No data

Rat and Mouse: >11797

Hamster and Rabbit: >12347

(Valid with restriction)

Repeated dose, NOAEL

(mg/kg bw/day)

21.1 – 23.1 (rat)3

(Guideline study, valid without restriction) 

No data

Genetic Toxicity – in vitro

In bacterial reverse mutation test, positive in TA100 

strain with metabolic activation, negative without 

activation in TA100 and with and without activation in 4 

additional strains4

(Guideline study, valid without restriction) 

In chromosomal aberration test, clastogenic both with and 

without activation. Not aneugenic.8

(Guideline study, valid without restriction)

No data

Genetic Toxicity – in vivo No data No data

Reproductive toxicity, NOAEL

(mg/kg bw/day)

Rat: no effects on reproductive organs at doses up to and 

including 211 – 213 3

(Guideline study, valid without restriction)

Developmental toxicity, NOAEL

(mg/kg bw/day)

Rat: NOAEL for maternal toxicity = 125; NOAEL for 

developmental toxicity = 250 5

(Guideline study, valid without restriction)

Rabbit: NOAEL for maternal toxicity = 50; NOAEL for 

developmental toxicity = 100 6

(Guideline study, valid without restriction)

No data

1 Reagen, 1989a 5 Martin, 1993a

2 Reagen, 1989b 6 Martin, 1993b

3

Pannock, 1994 7Flucke and Kimmerle, 1978

4 Lawlor, 1989 8

Schulz and Landsiedel, 2009
HPV Robust Summaries and Test Plan – Trichlorinated ketone

19

6.0 Conclusions and Recommendations

The SIDS Level I endpoints for trichlorinated ketone (TCK) are filled by a combination of 

measured and estimated data for the chemical. The adequacy of this information is further 

supported by comparable data for a closely related chemical, dichloropinacolin (DCP). Where 

certain data are not available for TCK, but reliable data exist for DCP (e.g., acute inhalation 

toxicity), information on DCP is used in a read-across manner to fill these data gaps. No 

additional testing is proposed for TCK. 
HPV Robust Summaries and Test Plan – Trichlorinated ketone

20

7.0 SIDS Data Matrix 

SIDS Endpoint

trichlorinated ketone

(145556-04-3)

Supporting chemical: dichloropinacolin

(22591-21-5)

Value

Reference and 

Reliability1 Value

Reference and 

Reliability

Physicochemical

Melting point 13°C EPIWIN (K2) - 14°C EPIWIN (K2)

Boiling point 190 – 195 °C Ji, 2009 (K1) 178°C EPIWIN (K2)

Vapor pressure 0.681 hPa EPIWIN (K2) 1.44 hPa EPIWIN (K2)

Partition coefficient (Log Kow) 1.82 EPIWIN (K2) 1.56 EPIWIN (K2)

Water Solubility 136.8 mg/L Rachmalla, 2009 (K1) 2882 mg/L EPIWIN (K2)

Environmental fate

Photodegradation (t1/2) 6.8 days (12-hr day) EPIWIN (K2) 5.9 days (12-hr day) EPIWIN (K2)

Hydrolysis Stable Stable

Fugacity 2.2% air, 26.6% water, 71.1% soil, < 1% sediment EQC Level III (K2) 3.1% air, 33.3% water, 63.5% soil, 

< 1% sediment

EQC Level III (K2)

Biodegradability Not readily biodegradable (1% in 28 days) per 

OECD 310 

Schwarz, 2009 (K1) Primary biodegradation in weeks, 

ultimate biodegradation in months

EPIWIN (K2)

Ecotoxicity

Acute Fish 96-h LC50 0.11 mg/L (estimated) ECOSAR (K2) 317 mg/L (estimated) ECOSAR (K2)

Acute Invertebrate 48-h EC50 0.66 mg/L (estimated) ECOSAR (K2) 167 mg/L (estimated) ECOSAR (K2)

Algal Inhibition 72-h EC50 6.32 mg/L based upon yield (P. subcapitata) Salinas, 2011 (K1) 66 mg/L (estimated) ECOSAR (K2)

Toxicity

Acute Oral LD50 Between 500 – 2500 mg/kg (rat) Reagen, 1989a (K1) 1820 mg/kg (male rat); 1300 mg/kg 

(female rat)

Flucke and Kimmerle, 1978

(K2)

Acute Dermal LD50 > 2000 mg/kg (rat) Reagan, 1989b (K1) > 5000 mg/kg (male rabbit); approx. 

5000 mg/kg (female rabbit)

Flucke and Kimmerle, 1978

(K2)

Acute Inhalation LC50 > 1179 mg/m3(rat and mouse); > 1234 

mg/m3(hamster and rabbit)

Flucke and Kimmerle, 1978

(K2)

Repeated Dose NOAEL 211 – 231 mg/kg/day (rat) Pannock, 1994 (K1)
HPV Robust Summaries and Test Plan – Trichlorinated ketone

21

SIDS Endpoint

trichlorinated ketone

(145556-04-3)

Supporting chemical: dichloropinacolin

(22591-21-5)

Genetic Tox – In vitro In bacterial reverse mutation test, positive with S9 in 

TA100; negative without S9 in TA100 and negative 

with and without activation in four other strains.

In chromosomal aberration test, clastogenic both 

with and without activation. Not aneugenic.

Lawlor, 1989 (K1)

Schulz and 

Landsiedel, 2009 (K1)

Genetic Tox – In vivo

Reproductive NOAEL Rat: no effects on reproductive organs at 211 – 231 

mg/kg bw/day

Pannock, 1994 (K1)

Developmental NOAEL Rat: Maternal NOAEL = 125 mg/kg bw/day;

Developmental NOAEL = 250 mg/kg bw/day

Rabbit: Maternal NOAEL = 50 mg/kg bw/day; 

Developmental NOAEL = 100 mg/kg bw/day

Martin, 1993a (K1)

Martin, 1993b (K1)

1 Reliability refers to the Klimisch score: 

K1 = reliable without restriction

K2 = reliable with restriction

K3 = not reliable

K4 = not assignable
HPV Robust Summaries and Test Plan – Trichlorinated ketone

22

8.0 References

This list of references is for studies as cited in Sections 1 through 7, while a complete list of all 

data sources reviewed in the development of the Test Plan and Robust Summaries for

trichlorinated ketone can be found in the Robust Summaries.

EPISuite v4.00, U.S. Environmental Protection Agency, 2000-2008.

Flucke, W., and Kimmerle, G., 1978. Dichloropinacolin - Study of Acute Toxicity. Bayer AG 

Institüt für Toxikologie, Report No. 7305. March 8, 1978.

Ji, J., 2009. Determination of boiling point/boiling range of 1,2,4-trichloro-2-methyl-3-pentanone 

(TCK), CAS # 145556-04-3) by OECD guideline for the testing of chemicals #103. BASF 

DocID 2008/7019374, BASF Beaumont Plant, 14385 West Port Arthur Road, Beaumont, Texas 

77705.

Klimisch, H.J., Andreae, M., and Tillmann, U., 1997. A systematic approach for evaluating the 

quality of experimental toxicological and ecotoxicological data. Regulatory Toxicol. and 

Pharmacol. 25:1-5.

Lawlor, T.E., 1989. Mutagenicity Test On Trichlorinated Ketone 96.8% In the Ames 

Salmonella/Microsome Reverse Mutation Assay. Revised Final Report. May 31, 1989. Hazelton 

Laboratories America, Inc. 5516 Nicholson Lane, Kensington, MD 20895. HLA Study No.: 

10716-0-401. Submitted To: Sandoz Crop Protection Corp. 1300 East Touhy Ave., Des Plaines, 

IL 60018.

Mackay, D., DiGuardo, A., Paterson, S., and Cowan, C. et al., 1996. Evaluating the 

Environmental Fate of a Variety of Types of Chemicals Using the EQC Model. Envir. Toxicol. 

Chem. 15:1627-37.

Martin, T., 1993a. Developmental Toxicity (Embryo-Fetal Toxicity and Teratogenic Potential) 

Study of Trichlorinated Ketone (TCK) Administered Orally Via Gavage to Crl:CDBR VAF/Plus 

Presumed Pregnant Rats. December 14, 1993. Argus Research Laboratories, Inc., 905 Sheehy 

Drive, Bldg A, Horsham, PA 19044-1297. Laboratory Project ID: Protocol Number: 1819-007.

Martin, T., 1993b. Developmental Toxicity (Embryo-Fetal Toxicity and Teratogenic Potential) 

Study of Trichlorinated Ketone (TCK) Administered Orally Via Stomach Tube to New Zealand 

White Rabbits. December 14, 1993. Argus Research Laboratories, Inc., 905 Sheehy Drive, Bldg. 

A, Horsham, PA 19044-1297. Laboratory Project ID: Protocol Number: 1819-006.

Pannock, K.S., 1994. A subchronic (3-Month) Oral Toxicity/Neurotoxicity Study of Trichloro 

Ketone (TCK) in the Rat Via Dietary Administration. Final Report. Pharmaco LSR, Inc., 

Toxicology Services North America. Study No.93-4057. May 11, 1994.
HPV Robust Summaries and Test Plan – Trichlorinated ketone

23

Rachmalla, L.R., 2009. Determination of water solubility of 1,2,4-trichloro-2-methyl-3-

pentanone (TCK) by OECD guideline for the testing of chemicals #105 flask method. BASF 

DocID 2008/7019370. BASF Beaumont Plant, 1485 West Port Arthur Road, Beaumont, TX 

77705.

Reagen, E.L., 1989a. Acute Oral Toxicity Study of Trichlorinated Ketone (TCK) In SpragueDawley Rats. Food & Drug Research Laboratories, Division of Enviro/Analysis Corporation. 

FDRL Study No. 89.2385.019. April 28, 1989.

Reagen, E.L., 1989b. Acute Dermal Toxicity Study of Trichlorinated Ketone (TCK) In SpragueDawley Rats. Food & Drug Research Laboratories, Division of Enviro/Analysis Corporation. 

FDRL Study No. 89.2385.020. April 28, 1989.

Salinas, E., 2011. Report: Reg No. 395233 (Process-intermediate of BAS 656-PH, DMTA-P), 

Growth inhibition study in unicellular green algae Pseudokirchneriella subcapitata Korshikov. 

BASF DocID 2010/1154437. Experimental Toxicology and Ecology, BASF SE 67056 

Ludwigshafen, Germany, Project No. 60E0716/083698.

Schulz, M. and Landsiedel, R., 2009. Report: Reg. No. 395233 (Process-intermediate of BAS 

656-PH, DMTA-P), In vitro chromosome aberration assay in V79 cells. BASF DocID 

2009/1103581. Experimental Toxicology and Ecology, BASF SE 67056 Ludwigshafen, 

Germany, Project No. 32M0716/084315.

Schwarz, H., 2009. Report: Reg. No. 395233 (Process-intermediate of BAS 656-PH, DMTA-P), 

Determination of the biodegradability in the CO2-headspace test. BASF DocID 2009/1046772.

Experimental Toxicology and Ecology, BASF SE 67056 Ludwigshafen, Germany, Project No. 

27G0716/083671.

U.S. EPA, 1988. Recommendations for and Documentation of Biological Values for Use in Risk 

Assessment. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/6-87/008 

(NTIS PB88179874). 

U.S. EPA. 1999a. The use of structure-activity relationships (SAR) in the High Production 

Volume Chemicals Challenge Program. Available at http://www.epa.gov/chemrtk/sarfinl1.htm.

U.S. EPA. 1999b. Determining the adequacy of existing data. Available at: 

http://www.epa.gov/chemrtk/pubs/general/datadfin.htm.

U.S. EPA. 2011. Interpretive assistance document for assessment of discrete organic chemicals: 

sustainable futures summary assessment. Updated August 2011. Available at 

http://www.epa.gov/opptintr/sf/pubs/iad_discretes_092011.pdf.