U.S. Environmental Protection Agency 3/18/08
Supporting Documents for Risk-Based Prioritization
Supporting Documents for Initial Risk-Based Prioritization of HPV Chemicals
Chemical/Category:
CAS No. 79-36-7 Dichloroacetyl chloride (DCAC)
Supporting Chemicals:
CAS No. 79-43-6 Dichloroacetic acid (DCA)
CAS No. 79-11-8 Monochloroacetic acid (MCA)
Contents:
• Page 2: Screening-Level Risk Characterization, 3/13/08
• Page 6: Screening-Level Hazard Characterization, 2/22/08
• Page 20: Screening-Level Exposure Characterization, 3/14/08
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QUALITATIVE SCREENING-LEVEL RISK CHARACTERIZATION FOR
Dichloroacetyl chloride (CAS No. 79-36-7)
1. Background
The High Production Volume (HPV) Challenge Program1 is a voluntary initiative aimed at developing and making
publicly available screening-level health and environmental effects information on chemicals manufactured in or
imported into the United States (U.S.) in quantities greater than one million pounds per year. In the Challenge
Program, producers and importers of HPV chemicals voluntarily sponsor chemicals; sponsorship entails the
identification and initial assessment of the adequacy of existing toxicity data/information, conducting new testing if
adequate data do not exist, and making both new and existing data and information available to the public. Each
complete data submission contains data on 18 internationally agreed to "SIDS" (Screening Information Data Set1,2)
endpoints that are screening-level indicators of potential hazards (toxicity) for humans or the environment and
environmental fate.
The Environmental Protection Agency's Office of Pollution Prevention and Toxics (OPPT) is evaluating the data
submitted in the HPV Challenge Program on approximately 1,400 sponsored chemicals. Data submitted to the
Organisation for Economic Co-operation and Development (OECD) HPV Programme are also being evaluated.
OPPT developed a screening-level hazard characterization that consists of an objective evaluation, conducted
according to established EPA guidance2'3, of the quality and completeness of the data set provided and is based
primarily on hazard data provided by sponsors. The characterization does not draw conclusions regarding the
completeness of all data generated with respect to a specific chemical substance or mixture. The OECD SIDS
documents (SIDS Initial Assessment Profile; SIAP and SIDS Initial Assessment Report; SIAR) provide similar
information. Under both the HPV Challenge and OECD HPV Programs, chemicals that have similar chemical
structures, properties and biological activities may be grouped together and their data shared across the resulting
category. Evaluation of chemical category formation and data extrapolation(s) among category members is
performed in accord with established U.S. EPA1 and OECD4 guidance.
In 2006 and 2007, EPA received data on uses of and reasonably likely exposures to chemicals on the Toxic
Substances Control Act (TSCA) Inventory of existing chemicals, submitted in accordance with the requirements of
the Inventory Update Reporting (IUR) rule5. Information is collected every five years under IUR, promulgated
under the authority of section 8(a) of TSCA. The most recent reports pertain to chemicals manufactured in
(including imported into) the U.S. during calendar year 2005 in quantities of 25,000 pounds or more at a single site.
Information is reported on the identity of the chemical manufactured or imported and the quantity, physical form,
and number of persons reasonably likely to be exposed during manufacture of the chemical. For chemicals
manufactured or imported in quantities of 300,000 pounds or more at a single site during calendar year 2005,
additional information was reported on the industrial processing and uses of the chemical, the number of industrial
processing sites and of employees reasonably to be exposed to the chemical at these sites, the consumer and
commercial uses of the chemical and an indication whether the chemical is used in products intended for use by
children under 14 years of age.
For these qualitative screening-level risk characterization documents, EPA has reviewed the IUR data to evaluate
exposure potential. In addition, exposure information that may have become available through prior Agency actions
has been considered, as appropriate. The resulting exposure information has been combined with the screening-
level hazard characterizations to develop this qualitative screening-level risk characterization6,7. These screening-
level risk characterizations are technical documents intended to support subsequent decisions and actions by OPPT.
1 U.S. EPA. High Production Volume (HPV) Challenge Program; http://www.epa.gov/chemrtk/index.htm.
2 U.S. EPA. HPV Challenge Program - Information Sources; http://www.epa.gov/chemrtk/pubs/general/guidocs.htm.
3 U.S. EPA. Risk Assessment Guidelines; http://cfpub.epa.gov/ncea/raf/rafguid.cfm.
4 OECD. Guidance Document on the Development and Use of Chemical Categories;
http://www.oecd.Org/document/7/0.2340.en 2649 34379 1947463 111 1.00.html.
5 U.S. EPA - Basic IUR Information: http://www.epa.gov/opptintr/iur/pubs/guidance/basic-information.htm
6 U.S. EPA Guidelines for Exposure Assessment; http://cfpub.epa.gov/ncea/raf/recordisplav.cfm?deid=15263
7 U.S. EPA. Risk Characterization Program; http://www.epa.gov/osa/spc/2riskchr.htm.
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Accordingly, the document is not written with the goal of informing the general public. The purpose of the
qualitative screening-level risk characterization is two-fold: to support initial risk-based decisions to prioritize
chemicals and inform risk management options, and to identify data needs for individual chemicals or chemical
categories.
2. Justification for Supporting Chcmical(s)
2,2-Dichloroacetyl chloride (DCAC) hydrolyzes rapidly in the presence of water (half-life < 0.22 seconds) yielding
dichloroacetic acid (DCA) and hydrochloric acid (HC1). The sponsor provides this simple chemical reaction as the
rationale for using data on DCA as an analog for DCAC. EPA agrees and considers DCA a reasonable analog for
DCAC. Thus, DCA data are considered adequate for addressing human health SIDS endpoints for this screening-
level risk characterization. In addition, based on similar physical-chemical properties, EPA agrees with the proposal
that monochloroacetic acid (MCA) be used to support aquatic organism SIDS endpoints for DCA. Details can be
found in the Hazard Characterization.
3. Physical-Chemical Properties and Environmental Fate
This report was prepared using the best available data from a number of sources, but draws no conclusions regarding
whether additional relevant data may exist. DCAC is a liquid at room temperature. It is highly volatile and
hydrolyzes rapidly to form HC1 and DCA. DCA is highly mobile in soil and water systems. DCA is not persistent
and is notbioaccumulative. DCA is expected to photolyze slowly and biodegrade rapidly. The properties and
environmental behavior of MCA - which is used as an analog for DCAC to assess aquatic toxicity - is essentially the
same as DCA. An exception is that unlike DCA, MCA is a solid at room temperature.
In summary, DCAC, DCA, and MCA are all ranked low for the potential to persist in the environment or
bioaccumulate.
4. Hazard Characterization
Aquatic Organism Toxicity: The potential aquatic toxicity of DCA (as the hydrolysis product of DCAC) was
assessed primarily using data from the analog MCA. The evaluation of available aquatic toxicity data for DCA
(using MCA data) indicates the acute hazard to fish and aquatic invertebrates is low and hazard to aquatic plants is
high.
Human Health Toxicity: DCAC and its hydrolysis product, DCA, exhibit toxic properties in animal studies. Acute
toxicity of DCAC and/or DCA is low via the oral route, but is moderate via inhalation and dermal exposure. DCAC
and DCA produced severe skin and eye irritation in rabbits. Repeated oral exposure to DCA in both dogs and rats
resulted in mortality; neurological effects; hepatic, pancreatic and gall bladder effects and effects on the male
reproductive organs. Reduced fetal weight, reduced crown-rump length and cardiovascular abnormalities were seen
in developing animals when pregnant rats were given oral doses of DCA during gestation days 6-15. In vitro and in
vivo genetic toxicity assays using DCAC and DCA provide some positive evidence for mutagenicity. An in vitro
mouse lymphoma test indicated that DCA induced chromosomal aberrations. Existing data suggest that DCAC and
DCA are carcinogenic in animal studies. Repeated inhalation exposure to DCAC in rats resulted in nasal tumors.
Mice exposed to DCAC via subcutaneous injection developed skin tumors. DCA exposure via drinking water
induced hepatocellular carcinoma in male rats.
The potential health hazard of DCAC and DCA is high based on repeated-dose studies in animals via all routes of
exposure in a variety of organ systems; including the ability to cause developmental toxicity and possible
reproductive effects due to observed effects on the male reproductive organs in animal studies. Available data
indicates DCAC and DCA have the potential to be genotoxic. Finally, both DCAC and DCA induced tumors in
animals via oral, inhalation, and dermal exposure studies.
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5. Exposure Characterization
This exposure characterization was completed using available 2006 Inventory Update Rule submissions. Data and
information that are claimed Confidential Business Information (CBI) by the submitter were reviewed and
considered by EPA in preparing this assessment but are not disclosed in this summary.
In addition, the following sources were reviewed to identify exposure and use information: the HPV Challenge
Submissions, OECD SIDS Data, the Toxics Release Inventory (TRI), OSHA PEL documentation, various databases
and public sources.
DCAC was manufactured (including imported) in the United States in amounts ranging from 1,000,000 to
10,000,000 lbs. in 2005. Information provided in the HPV Challenge submission indicates DCAC is manufactured
in closed systems and shipped to customers for use as a chemical intermediate in the synthesis of other products8.
Exposures to Workers
A search of the National Occupational Exposure Survey (NOES) database, conducted between 1981 and 1983, did
not provide any additional information on possible worker exposures. Based on IUR reporting, the total number of
workers reasonably likely to be exposed to DCAC during manufacturing and industrial processing and use is
believed to be less than 100. There may be additional potentially exposed workers that are not included in this
estimate since not all workers engaged in industrial processing of this chemical have been accounted for.
Processes for manufacturing and processing DCAC are closed limiting releases during manufacturing and
processing. Although workers may be exposed to this chemical as a result of spillage or cleaning of process
equipment, exposure is likely to be minimized by personal protective equipment (PPE). Because DCAC is rapidly
hydrolyzed upon contact with water to form strong acids, it is presumed that potentially exposed workers wear
personal protective equipment. DCAC does not have an OSHA Permissible Exposure Limit.
Based on IUR data, specifically the number of potentially exposed workers and use codes, the potential for worker
exposure is considered low.
Exposure to the General Population and the Environment
DCAC is not on the Toxic Release Inventory. However, the HPV Challenge submission indicates that potential
DCAC manufacturing and processing releases would be limited by closed system operations, and any fugitive
release would not be expected to persist due to rapid hydrolysis and biodegradation of the DCA hydrolysis product.
Based on this information, the potential for general population and/or environmental exposure to this chemical is
considered low.
Exposure to Commercial Workers and Consumers
There were no commercial or consumer uses identified in the IUR data or in the additional non-CBI data sources
searched for the exposure assessment. Therefore, the IUR-based ranking for commercial workers/consumers
exposure is low.
Exposure to Children
As described above for commercial and consumer products, DCAC is not expected to be present in children's
products. Therefore, the IUR-based ranking for children exposure is low.
8 HPV Challenge submission: http://www.epa.gov/chemrtk/pubs/summaries/dichlrac/cl5628tc.htm
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Supporting Documents for Risk-Based Prioritization
6. Risk Characterization
The statements and rationale provided below are intended solely for the purpose of this screening-level and
qualitative risk characterization and will be used for prioritizing substances for future work in the U.S. HPV
Challenge Program.
6.1. Risk Statement and Rationale
Potential Risk to Aquatic Organisms from Environmental Releases (LOW CONCERN): The potential for DCAC
to be released to the environment is expected to be low and would likely be mitigated due the following: its
chemical properties (corrosive); environmental fate properties (hydrolyzes and biodegrades quickly, is not
persistent); and use pattern (chemical intermediate used to synthesize other products). The potential hazard to
aquatic plants is high but the potential exposure from environmental releases is low suggesting a low concern
for potential risk to aquatic organisms.
Potential Risk to the General Population from Environmental Releases (LOW CONCERN): The potential for
DCAC to be released to the environment is expected to be low based on the reasons stated above. Thus,
although the potential hazard to human health is high, potential exposure from environmental releases is low
suggesting a low concern for potential risk to the general population.
Potential Risk to Workers (LOW CONCERN): There is potential for skin and eye irritation to occur as a result
of worker exposure from DCAC use as a chemical intermediate or in the event of accidental release. However,
because DCAC is rapidly hydrolyzed upon contact with water to form strong acids, it is presumed that
potentially exposed workers wear personal protective equipment. Thus, although the potential hazard to human
health is high, the exposure issues (use as an intermediate, corrosive and thus self-limiting in terms of personal
protective equipment) suggest a low concern for potential risk to workers.
Potential Risk to Commercial Workers and Consumers from Known Uses (LOW CONCERN): DCAC is not
expected to be present in commercial and consumer products. Thus, although the potential hazard to human
health is high, little or no exposure suggests a low concern for potential risk to commercial workers and
consumers.
Potential Risk to Children (LOW CONCERN): DCAC is not expected to be present in children's products.
Thus, although the potential hazard to human health is high, little or no exposure suggests a low concern for
potential risk to children.
6.2. Uncertainties
DCAC may have minor uses that were not reported in IUR.
6.3. Data Needs
No data needs have been identified at this time.
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SCREENING-LEVEL HAZARD CHARACTERIZATION
OF HIGH PRODUCTION VOLUME CHEMICALS
SPONSORED CHEMICAL
Dichloroacetyl chloride (CAS No. 79-36-7)
[9th CI Name: 2,2-Dichloroacetyl chloride]
SUPPORTING CHEMICALS
Dichloroacetic acid (CAS No. 79-43-6)
Monochloroacetic acid (CAS No. 79-11-8)
August 2007
Revised: February 2008
Prepared by
High Production Volume Chemicals Branch
Risk Assessment Division
and
Exposure Assessment Branch
Economics, Exposure and Technology Division
Office of Pollution Prevention and Toxics
Environmental Protection Agency
1200 Pennsylvania Avenue, NW
Washington, DC 20460-0001
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SCREENING-LEVEL HAZARD CHARACTERIZATION
OF HIGH PRODUCTION VOLUME CHEMICALS
The High Production Volume (HPV) Challenge Program9 is a voluntary initiative aimed at developing and making
publicly available screening-level health and environmental effects information on chemicals manufactured in or
imported into the United States in quantities greater than one million pounds per year. In the Challenge Program,
producers and importers of HPV chemicals voluntarily sponsor chemicals; sponsorship entails the identification and
initial assessment of the adequacy of existing toxicity data/information, conducting new testing if adequate data do
not exist, and making both new and existing data and information available to the public. Each complete data
submission contains data on 18 internationally agreed to "SIDS" (Screening Information Data Set1'10) endpoints that
are screening-level indicators of potential hazards (toxicity) for humans or the environment.
The Environmental Protection Agency's Office of Pollution Prevention and Toxics (OPPT) is evaluating the data
submitted in the HPV Challenge Program on approximately 1,400 sponsored chemicals. OPPT is using a hazard-
based screening process to prioritize review of the submissions. The hazard-based screening process consists of two
tiers described below briefly and in more detail on the Hazard Characterization website11.
Tier 1 is a computerized sorting process whereby key elements of a submitted data set are compared to established
criteria to "bin" chemicals/categories for OPPT review. This is an automated process performed on the data as
submitted by the sponsor. It does not include evaluation of the quality or completeness of the data.
In Tier 2, a screening-level hazard characterization is developed by EPA that consists of an objective evaluation of
the quality and completeness of the data set provided in the Challenge Program submissions. The evaluation is
performed according to established EPA guidance2'12 and is based primarily on hazard data provided by sponsors.
EPA may also include additional or updated hazard information of which EPA, sponsors or other parties have
become aware. The hazard characterization may also identify data gaps that will become the basis for a subsequent
data needs assessment where deemed necessary. Under the HPV Challenge Program, chemicals that have similar
chemical structures, properties and biological activities may be grouped together and their data shared across the
resulting category. This approach often significantly reduces the need for conducting tests for all endpoints for all
category members. As part of Tier 2, evaluation of chemical category rationale and composition and data
extrapolation(s) among category members is performed in accord with established EPA2 and OECD13 guidance.
The screening-level hazard characterizations that emerge from Tier 2 are important contributors to OPPT's existing
chemicals review process. These hazard characterizations are technical documents intended to support subsequent
decisions and actions by OPPT. Accordingly, the documents are not written with the goal of informing the general
public. However, they do provide a vehicle for public access to a concise assessment of the raw technical data on
HPV chemicals and provide information previously not readily available to the public. The public, including
sponsors, may offer comments on the hazard characterization documents.
The screening-level hazard characterizations, as the name indicates, do not evaluate the potential risks of a chemical
or a chemical category, but will serve as a starting point for such reviews. In 2007, EPA received data on uses of
and exposures to high-volume TSCA existing chemicals, submitted in accordance with the requirements of the
Inventory Update Reporting (IUR) rule. For the chemicals in the HPV Challenge Program, EPA will review the
IUR data to evaluate exposure potential. The resulting exposure information will then be combined with the
screening-level hazard characterizations to develop screening-level risk characterizations4'14. The screening-level
risk characterizations will inform EPA on the need for further work on individual chemicals or categories. Efforts
are currently underway to consider how best to utilize these screening-level risk characterizations as part of a risk-
based decision-making process on HPV chemicals which applies the results of the successful U.S. High Production
Volume Challenge Program and the IUR to support judgments concerning the need, if any, for further action.
9 U.S. EPA. High Production Volume (HPV) Challenge Program; http://www.epa.gov/chemrtk/index.htm.
10 U.S. EPA. HPV Challenge Program - Information Sources; http://www.epa.gov/chemrtk/pubs/general/guidocs.htm.
11 U.S. EPA. HPV Chemicals Hazard Characterization website (http://www.epa.gov/hpvis/abouthc.html).
12 U.S. EPA. Risk Assessment Guidelines; http://cfpub.epa.gov/ncea/raf/rafguid.cfm.
13 OECD. Guidance on the Development and Use of Chemical Categories; http://www.oecd.org/dataoecd/60/47/1947509.pdf.
14 U.S. EPA. Risk Characterization Program; http://www.epa.gov/osa/spc/2riskchr.htm.
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SCREENING-LEVEL HAZARD CHARACTERIZATION
Dichloroacetyl chloride (CAS No. 79-36-7)
Introduction
The sponsor, E.I. du Pont de Nemours & Company, Inc., submitted a Test Plan and Robust Summaries to EPA for
dichloroacetyl chloride (CAS No. 79-36-7; 9th CI name: 2,2-dichloroacetyl chloride) on September 29, 2004. EPA
posted the submission on the ChemRTK HPV Challenge website on October 18, 2004
(http://www.epa.gov/chemrtk/pubs/summaries/dichlrac/cl5628tc.htm'). Public comments were also received and
posted to the website. EPA comments on the original submission were posted to the website on April 19, 2006. The
sponsor submitted revised documents on December 13, 2006, which were posted to the ChemRTK website on
January 31, 2007.
This screening-level hazard characterization is based primarily on the review of the test plan and robust summaries
of studies submitted by the sponsor(s) under the HPV Challenge Program. In preparing the hazard characterization,
EPA considered its own comments and public comments on the original submission as well as the sponsor's
responses to comments and revisions made to the submission. A summary table of SIDS endpoint data with the
structure(s) of the sponsored chemical(s) is included in the appendix. The screening-level hazard characterization
for environmental and human health toxicity is based largely on SIDS endpoints and is described according to
established EPA or OECD effect level definitions and hazard assessment practices.
Justification for Supporting Chemical
DCAC hydrolyzes rapidly in the presence of water (half-life < 0.22 seconds) yielding dichloroacetic acid (DCA,
CAS No. 79-43-6) and hydrochloric acid (HC1, CAS No. 7647-01-0). The sponsor provides this simple chemical
reaction as the rationale for using data on DCA as a logical analog for DCAC. In addition, the sponsor provided
data on the analog, monochloroacetic acid (MCA, CAS No. 79-11-8), for ecotoxicity endpoints.
EPA considers DCA, a hydrolysis product of DCAC, a reasonable analog for DCAC and DCA data adequate for
addressing all human health SIDS endpoints in this hazard characterization. In addition, based on similar physical-
chemical properties, EPA agrees that MCA, a hydrolysis product of monochloroacetyl chloride (MCAC), supports
the pattern of aquatic toxicity observed for DCA.
Sum man-Conclusion
2.2-1 )ichloioaccl> I chloride (DC \C i is a liquid al mom temperature ll is higliK \olalile and h\drol\/es rapidls lo
form h\drochloric acid and dichloroacelic acid (DC \i DC \ is higliK mobile in soil and waler s\stems DC \ is
e\pec led lo photoK/e slowk and hiodegrade rapidls DC \C and DC \ are noi persistent il'l i. uoiarc i lie\
hioacciiiinilali\e (I! 11. I lie properties and en\ iioiinicuial helia\ ior of niouochloioacelic acid (\1C \ i are esscuiialK
llie same as lor dicliloroacelic acid \n c\cepiiou is dial unlike DC V \1C \ is a solid al loom temperature
I lie poienlial aqualic lo\icil> ol' DC \ (as ilie liulroksis product of DC \('i was assessed piiniariK using dala from
llie analog \l( \ I lie e\alualioii of a\ailahle aqualic lo\icil> dala for DC \ (using \l( \ dalai mdicales llie acule
lia/ard lo fish and aqualic iu\ eriehrales is low and hazard lo aqualic plants is high
\cuie lo\icil\ of DC \C and or DC \ is low \ la oral rouie. hul is moderate \ ta hotli uihalalioii and dermal exposure
routes DC \C and DC \ produced se\ere skin and e\e irritation in nihhils Repealed oral exposure lo DC \ mi hoili
dogs and rals resulted m niorialiis. neurological effects, hepatic, pancreatic and gall bladder effects and effects on
male i'cproducli\ e organs Th\ niic atrophs w nil marked depletion of l\ niphoid tissue was also ohser\ed mi dogs
I!fleets on male i'cprodiicli\ e organs included se\ ere testicular lesions. s\ uc> lial giaut cell formation, degeneration
of germinal epithelium and prostatic glandular airophs in dogs lu rats, morphological abnormalities of sperm
(distorted sperm heads and decrease mi the percentage of motile spermi. decreased sperm counts, increase m the
iiiiniherof fused epidids mal sperm and a decrease mi epidids mal weight were reported follow nig DC \ exposure
Results from the de\elopmeiital toxicity studs indicate that DC \ affects de\eloping fetuses Reduced fetal weight.
reduced crow ii-riinip length and cardunascnlar abnormalities were seen w lien dams recei\ cd oral doses diiiing
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ucstaliou da\s (i-15 In viini and in r/w< ueuelic lo\icil\ ;iss;i\s usiim DC \C and DC \ pro\ iclc posiu\e e\ idence
for niulaueiiicils \11 in viim mouse l\ mplioma lest indicated thai DC \ induced chromosomal aberrations IaisIiiiu
d;il;i suuuesi lh;il DC \( ;md DC \ arc potential carcuioucus Repealed inhalation exposure In DC \( in nils resulted
mi ii;is;iI tumors Mice exposed lo DC \C \ i;i subcutaneous injection dc\ eloped skin tumors DC \C is also show n
carcinogenic initiator properties w here mice were exposed once \ i;i ihe derin;il mule ;md followed In ;i series of
I'M \ (proinolcri e\posiire DC \ e\posiire \ la driiikum w;iler induced hep;ilocellul;ir c;irciuoni;i mi m;ile r;ils
I lie potential he;i 11 h h;i/;ird of DC \C ;iud DC \ is liiuli hnsed oil repe;iled-dose siudies in ;iuim;ils \ i;i ;ill roules of
exposure mi ;i \ aricls of oruan s\ sienis. iucludiim I he ;ihihl\ lo c;iuse dc\ elopnieul;il lo\icil> ;uid possible
reproducliNe effects due lo ohser\ ed effects on ihe m;ile rcproducli\ e oruaus in ;iiiun;il studies (see note helow for
more del;nlsi \\ ;n l;ihle d;il;i uidic;iles DC \C ;ind DC \ h;i\e I he potential lo he ueuoloMc I'malls. hoili DC \C
;uid DC \ induced tumors iu ;niiin;ils \ i;i oral. iiih;il;iliou. ;iud derm;il exposure studies
\o d;il;i mips h;i\e heeu ideuiified under ilie I ll'Y ( h;iIlenue houram
\( ) TI!' \ reproducliN e lo\icil> siud> w;is not suhniilled lor DC \C or lis ;ui;ilou DC \ I !\ ;ilu;iliou of reprodiicli\ e
ormius suhniilled w illi repe;iled-dose studies ;ilouu w illi ;i de\elopnieul;il lo\icil> siud\ were used lo ;iddress ilie
reproducliN e eiidpoiuis lorilie purposes of I he I IPX" Ch;illeuue I'rouriini Repealed iiir;ih e\posure lo DC \ resulied
in effects tin m;ile reproducli\ e oruniis I Tl'ecls of these chennc;ils on feni;ile reproducli\ e p;ir;uiielers h;i\ e uoi heen
pro\ ided. hut ihe de\ elopnieiit;il io\icil> siutl\ identified ni;iieru;il ;md fel;il effects I leuce. w lnle ilie d;il;i suhniilled
;ire ;idct|ii;iie lor perlornnim ilns screeuiuu-le\ el h;i/;ird ch;ii,icleri/;iiKiu. ilie results of ihe reproducli\ e oru;ui
e\ ;ilii;iliou ;md I he de\ elopnieul;il to\icil> siud\ uidic;ile DC \C iDC \i h;is the polculuil lo c;iuse reproducti\e
lOMCItS
1. Physical-Chemical Properties and Environmental Fate
This report was prepared using the best available data from a number of sources, including information within High
Production Volume Test Plans for 2,2-dichloroacetyl chloride (du Pont, 2004), with some additional information
added from EPI Suite (USEPA, 2007) as well as the Hazardous Substance Database (HSDB, 2007). Basic physical-
chemical and environmental fate properties of these compounds are listed in Tables la and lb, respectively.
Physical-Chemical Properties Characterization
2,2-Dichloroacetyl chloride (DCAC) is a liquid at room temperature. It is highly volatile and hydrolyzes rapidly to
form hydrochloric acid (HC1) and dichloroacetic acid (DCA). DCA is highly mobile in soil and water systems.
DCA is highly soluble in water. The properties of monochloroacetic acid (MCA), which is used as an analog for
environmental effects, are essentially the same as for DCA except that MCA is a solid at room temperature.
Environmental Fate Characterization
DCAC reacts rapidly upon contact with water (half-life substantially less than one second). The expected primary
products from hydrolysis are DCA and HC1. Both DCAC and DCA, the major organic hydrolysis product of
DCAC, will tend to exist in the vapor phase in the atmosphere DCAC that becomes vaporized and is not contacted
by water or atmospheric moisture is subject to hydroxyl radical oxidation with an estimated half-life of 855 days. A
half-life of 22 days is estimated for hydroxyl radical oxidation of vapor phase DCA. DCA, based on its Henry's
Law constant, has little tendency to volatilize from water. The estimated BCF suggests it will not tend to
bioaccumulate. DCA is readily biodegradable. These characteristics indicate that DCAC and DCA are not
persistent (PI), nor are they bioaccumulative (Bl). Because of the fast degradation rate of DCAC, very little DCAC
would be expected to exist in the environment. The environmental fate, persistence and bioaccumulation properties
of MCA are essentially the same as for DCA.
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Tabic la. Physical-Chemical Properties1 of Dichloroacctyl Chloride (DCAC), Dichloroacetic Acid
(DCA) and Monochloroacetic Acid (MCA)
DCAC
DCA
MCA
Structure
CI
CI
CIH°
CI OH
O
civA
OH
Property
Value/Descriptor
Value/Descriptor
Value/Descriptor
CAS No.
79-36-7
79-43-6
79-11-8
IUPAC
Dichloroacetyl chloride
Dichloroacetic acid
Monochloroacetic acid
MW
147.39
128.9
94.5
Physical State
Colorless liquid
Colorless liquid
Solid
Melting Point
-32.51 °C
13.5°C
61.3°C
Boiling Point
108°C
193-194°C
189°C
Vapor Pressure
23 mm Hg (a)y 25°C
0.179 mm Hg (5) 25°C
0.065 mm Hg (8} 25°C
Water Solubility
Hydrolyzes to DCA and HC1
> 100 g/L
> 100 g/L
Density
1.53 @ 16/4°C
1.57 @ 13°C
1.58 @20°C
Log Kow
-0.04 (estimated)3
0.92 (measured)
0.22 (measured)2
1 Unless otherwise noted, values from Du Pont, (2004).
2 Hansch et al. (1995)
3 Note that DCAC decomposes upon contact with water; thus Kow is not experimentally measurable.
Tabic lb. Environmental Fate Properties1 of Dichloroacctyl Chloride (DCAC), Dichloroacetic Acid (DCA) and
Monochloroacetic Acid (MCA)
DCAC
DCA
MCA
Property
Value/Descriptor
Value/Descriptor
Value/Descriptor
Photodegradation
Half life = 855 days
(calculated)
Half life = 22 days
(calculated)
No information
Aerobic Degradation
Unstable in water
97% ThOD, 14 days
53-100%; readily biodegradable
Hydrolysis
<1 sec
No information
No information
Bioaccumulation2
(unstable in water)
BCF = 3
BCF = 3
Henry's Law
Constant2
(unstable in water)
3.52 xlO"7 (estimated)
No information
Photolysis2
Not significant
Not significant
No information
Koc2
0.374 ml/g (calculated)
1.9 (calculated)
No information
Fugacity 2'3
Not likely to exist due to
Air 17.7%, water 25.4%,
Air 36%, water 25%, soil 39%,
short hydrolysis half life
soil 56.9%, sediment
0.033%
sediment 0.031%
Persistence4
PI (low)
PI (low)
PI (low)
Bioaccumulation4
B1 (low)
B1 (low)
B1 (low)
1 Unless otherwise noted , values from Du Pont, (2004).
2 USEPA, 2007. EPI Suite™ (version 3.2y
3 Level III fugacity, assuming a water half life of 48 hours (per aerobic degradation data), a soil half life of 96 hours
(EPI default ratio water to soil), a sediment half life of 432 hours (EPI default ratio water to sediment), and air half
life of 22 days (AOPWIN).
4 Persistence and bioaccumulation are qualitatively characterized according to the criteria set forth in the PMN
program. FR (1999)
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2. Environmental Effects - Aquatic Toxicity
Because DCAC hydrolyzes quickly to DCA, it is not reasonable to test DCAC for aquatic toxicity. EPA considered
the aquatic toxicity data submitted for DCA inadequate because the study designs deviated from those recommended
by the OECD guidelines (see link to EPA comments for details:
http://www.epa.gov/chemrtk/pubs/summaries/dichlrac/cl5628ct.pdf). Although initially questioning the use of
MCA as an appropriate analog for DCA (see comments cited above), EPA now agrees it is a reasonable analog
because of additional physical-chemical property information provided by the sponsor. Coupled with the DCA data
(which are inadequate by itself) EPA considers the weight-of-the-evidence supports the decision that new aquatic
toxicity data are not necessary for the purposes of the US HPV Challenge Program. All data presented below are
from the submission by the sponsor (DuPont, 2004) unless otherwise noted.
Acute Toxicity to Fish
Monochloroacetic acid (CAS No. 79-11-8, supporting chemical)
Zebrafish (Brachydanio rerio) were exposed to MCA under semi-static conditions for 96-hours. Details regarding
the concentration range tested were not provided.
96-h LC50 = 370 mg/L (measured)
Acute Toxicity to Aquatic Invertebrates
Monochloroacetic acid (CAS No. 79-11-8, supporting chemical)
(1) Daphnia magna (20/concentration) were exposed to MCA under semi-static conditions for 24- and 48-hours.
The concentration range tested was not provided in the robust summary.
24-h EC50 = 99 mg/L (nominal)
48-h EC50 = 77 mg/L (nominal)
(2) Daphnia magna (20/concentration) were exposed to MCA at concentration of 0.032 - 100 mg/L under semi-
static conditions for 24-hours. The concentration range tested was not provided in the robust summary.
24-h EC50 = 96 mg/L (nominal)
Toxicity to Aquatic Plants
Monochloroacetic acid (CAS No. 79-11-8, supporting chemical)
(1) Scenedesmus subspicatus was exposed to MCA for 72 hours. The concentrations tested were not provided in the
robust summary.
72-h EC50 (biomass) = 0.025 mg/L (nominal)
72-h EC50 (growth) = 0.033 mg/L (nominal)
(2) Scenedesmus subspicatus was exposed to MCA at concentrations ranging from 0.0008 - 1.0 mg/L for 48-hours.
Biomass and growth inhibition were measured.
48-h EC50 (biomass) = 0.028 mg/L
48-h ECS0 (growth) = 0.07 mg/L
Chronic Toxicity to Fish
Monochloroacetic acid (CAS No. 79-11-8, supporting chemical)
Zebrafish (Brachydanio rerio) were exposed to MCA at concentrations ranging from 25 - 400 mg/L for 28-days.
28-d LOEC = 25 mg/L
28-d NOEC = Not established
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Chronic Toxicity to Aquatic Invertebrates
Monochloroacetic acid (CAS No. 79-11-8, supporting chemical)
Daphnia magna (20/concentration) were exposed to MCA at concentration of 0.032 - 100 mg/L under semi-static
conditions for 21-days.
21-d NOEC = 32 mg/L
Conclusion: The potential aquatic toxicity of DCA (as the hydrolysis product of DCAC) was assessed primarily
using data from the analog MCA. As shown in the Appendix, the DCA fish data (LC50 of 100 after 24-hour
exposures) suggest that DCA may be more toxic to fish than MCA (LC50 of 370 after 96 hours). However, even if
it is assumed that the 96-hour LC50for DCA is five times lower (from 100 to 20 mg/L), it would still be considered a
low hazard. The invertebrate data for MCA and DCA are in reasonable agreement and again are in the same hazard
concern rating. The algae data, however, suggest that MCA is much more toxic than DCA. Since the DCA data are
with plants and not algae, the MCA data will be used for this endpoint. Thus, the evaluation of available aquatic
toxicity data for DCA (using MCA data) indicates the acute hazard to fish and aquatic invertebrates is low and
hazard to aquatic plants is high.
2. Human Health Effects
Acute Oral Toxicity
Dichloroacetyl chloride (CAS No. 79-36-7)
Male Wistar or Sherman rats (5/dose group) were administered a geometric series four different doses of DCAC.
Actual doses administered were not provided in the robust summary. The results of this test were consistent with an
additional acute oral toxicity study in rats in which mortality was observed at doses of 1000 and 2250 mg/kg-bw and
an Approximate Lethal Dose (ALD) of 1000 mg/kg-bw was reported. Clinical signs included weakness in hind legs,
paleness and labored breathing.
LD50 = 2460 mg/kg-bw
Dichloroacetic acid (CAS No. 79-43-6, supporting chemical)
(1) Albino rats (10/dose group) were administered DCA at doses of 2200, 2500, 2800, 3200, 3600, 4000, 4400 and
4800 mg/kg-bw and observed for 6 days. The animals quickly passed into a state of narcosis or seminarcosis, and
within 36 hours either recovered or died without coming out of the narcosis.
LD50 = 4480 mg/kg-bw
(2) Albino mice (10/dose group) were administered DCA at doses of 3000, 3162, 4000, 5012, 5623, 6310, 7943 and
8913 mg/kg-bw and observed for 6 days. The quickly passed into a state of narcosis or seminarcosis, and within 36
hours either recovered or died without coming out of the narcosis.
LD50 = 5520 mg/kg-bw
Acute Inhalation Toxicity
Dichloroacetyl chloride (CAS No. 79-36-7)
Groups of male albino rats were exposed to a saturated vapor of DCAC for 4 hours. An LQ0 was established based
on mortality in 2 of 6 rats. No other clinical signs of toxicity were reported.
LCio = 2000 ppm (approximately 12 mg/L)
Acute Dermal Toxicity
Dichloroacetyl chloride (CAS No. 79-36-7)
Rabbits (5/dose) were exposed to undiluted DCAC by application to clipped skin at concentrations up to 20 mL/kg.
LDS0 = 0.65 mL/kg-bw (995 mg/kg-bw)
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Dichloroacetic acid (CAS No. 79-43-6, supporting chemical)
Rabbits (5/dose) were exposed to undiluted DCA by application to clipped skin at concentrations up to 20 mL/kg.
LD50 = 0.51 mL/kg-bw (801 mg/kg-bw)
Repeated-Dose Toxicity
Dichloroacetyl chloride (CAS No. 79-36-7)
Male rats (50/dose) were exposed to DCAC via inhalation at 0, 0.5, 1.0 or 2.0 ppm (approximately 0.012 mg/L at
the highest dose) for 6 hours/day, 5 days/week for 30 days. The post-exposure period was 128 weeks. Nasal tumors
were reported following exposure to 2.0 ppm DCAC; 2 of 50 rats developed squamous cell carcinoma or mixed cell
carcinoma of the nasal mucosa, which was attributed to DCAC exposure.
Oncogenic effects were observed at the highest dose tested.
Dichloroacetic acid (CAS No. 79-43-6, supporting chemical)
(1) Male and female Beagle dogs were orally administered DCA once daily in gelatin capsules at 0, 12.5, 39.5 and
72 mg/kg-bw/day for 90 days. Dyspnea, bilateral conjunctivitis, slight bilateral posterior paresis, and diarrhea were
major signs of toxicity. Significant decreases in body weight, food consumption and water consumption were noted
at doses of 39.5 mg/kg-bw/day and above. At necropsy, several changes were noted in animals from the high-dose
group—mottled, discolored lungs, pale and discolored kidneys, white frothy material in the trachea and mild yellow
discoloration of liver. Liver weights were significantly greater in all dosed animals when compared to controls.
Increased kidney weights of the animals dosed at 39.5 mg/kg-bw/day and above; increased lung weight and relative
brain weights in the 72 mg/kg-bw/day dose group animals were seen. Microscopic examination showed incidence
of mild vacuolization of white myelinated tracts in the brain in all treated animals. In some dogs, the vacuolization
was present in the cerebrum and cerebellum. Some males from the 72 mg/kg-bw/day group had vacuolar changes in
the medulla and spinal cord. Dose-dependent hepatic and pancreatic lesion incidents were reported. Testicular
lesions were reported in all male animals exposed to DCA with severity increasing in the mid- and high-dose
groups. These lesions included syncytial giant cell formation, degeneration of germinal epithelium and prostatic
glandular atrophy. Thymic atrophy seen in high-dose males was characterized by marked depletion of lymphoid
tissue.
NOAEL = Not established
LOAEL = 12.5 mg/kg-bw/day (based on liver weight increase)
(2) Male and female Beagle dogs (3-4/sex/dose) were orally administered DCA once daily in gelatin capsules at 0,
50, 75 or 100 mg/kg-bw/day for 13 weeks. Additional groups (control and high-dose) were included as recovery
animals and were monitored for an additional 5 weeks following the 13-week dosing period. Mortality occurred in
two high-dose groups (75 and 100 mg/kg/day). Dose-dependent body weight loss was seen in both sexes. All
treated animals had high incidence of ocular abnormalities, progressive depression in hematology parameters
(erythrocyte count, hematocrit, and hemoglobin) and decreases in the following clinical chemistry: pyruvate, lactate
and glucose. Except for lenticular opacities, these changes were reversible following cessation of treatment.
Histopathological examination revealed slight to moderate vacuolization of the myelinated tracts of the cerebrum in
all treated dogs (persistent in some recovery animals), as well as increased incidence of hemosiderin-laden Kupffer
cells in the liver, cystic mucosal hyperplasia in the gall bladder and lung consolidation. Prostate glandular atrophy
and testicular changes were reported in all male dogs receiving DCA. Prostate appeared normal and germinal
epithelium regeneration with spermatogenesis was evident in recovery animals. However, liver and gall bladder
changes were still evident in recovery animals.
NOAEL = Not established
LOAEL = 50 mg/kg-bw/day (based on effect on body weight, ocular anomalies, histopathological changes in brain,
liver and gall bladder in both sexes and prostate and testicular changes in males)
(3) Male and female rats were orally administered DCA once daily by gavage at 0, 125, 500 or 2000 mg/kg-bw/day
for 13 weeks. Additional groups (control and high-dose) were included as recovery animals and were monitored for
an additional 4 weeks following the 13-week dosing period. Mortality occurred in high-dose groups with hindlimb
paralysis and pollakiuria (abnormally frequent urination) as major signs of toxicity. Reductions in body weights and
food consumption were seen all DCA-treated rats—reversal was seen during the recovery period. Moderate but
significant suppression of erythroid parameters were induced at all dose levels—bone marrow and spleen appeared
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normal histologically and no effects were seen during the recovery period. Changes in blood chemistry seen during
the treatment period returned to normal during the recovery period. Small testes observed following treatment with
the high dose persisted in recovery animals. However, changes in liver weights (increases in all animals of both
sexes), kidney weights (females at all doses) and adrenal weights (500 mg/kg-bw/day males and 2000 mg/kg-
bw/day males and females) were dose-dependent and were comparable to the control animals following the recovery
period. Histopathological examination revealed brain and testes were the target organs for toxicity. Brain lesions
included edema, mainly in the cerebrum, which persisted in some animals after cessation of treatment. Testicular
lesions included germinal epithelium degeneration at 500 and 2000 mg/kg-bw/day. In all males treated at 2000
mg/kg-bw/day, the testes were aspermatogenic and contained syncytial giant cells in the germinal epithelium while
the epididymis ducts were devoid of spermatozoa. After the recovery period, some germinal epithelium
regeneration was noted; however, the majority of the testes were aspermatogenic and showed loss of germinal
epithelium.
NOAEL = Not established
LOAEL = 125 mg/kg-bw/day (based on effects on body weight, food consumption and suppression of erythroid
parameters)
Reproductive Toxicity
No data were submitted to address the reproductive toxicity endpoint. Evaluations of reproductive organs reported
in the repeated-dose toxicity studies along with the submitted developmental toxicity study (next section) were used
to address the reproductive endpoints for the purposes of the HPV Challenge Program. Therefore,
NOAEL/LOAELs for fertility and/or reproductive toxicity cannot be determined for these studies.
Dichloroacetic acid (CAS No. 79-43-6, supporting chemical)
(1) Male rats were orally administered the DCA daily at 0, 18, 54, 160, 480 or 1440 mg/kg-bw/day for 14-days. The
reproductive tracts were used to determine effects on testes and epididymes. Sperm count and sperm morphology
were investigated. Delayed spermiation and formation of atypical residual bodies were seen at doses of 54 mg/kg-
bw/day and above. Distorted spermheads and acrosomes were seen at doses of 480 and 1440 mg/kg-bw/day.
Morphological abnormalities occurred at doses of 160 mg/kg-bw/day and above. In the highest dose groups,
distorted sperm heads, decreased percentage of motile sperm and sperm counts, increased number of fused
epididymal sperm and decreased epididymal weight were effects attributed to DCA exposure.
(2) In the repeated-dose toxicity study described previously, severe testicular lesions were reported in all male dogs
exposed to DCA via oral gavage at 0, 12.5, 39.5 or 72 mg/kg-bw/day for 90-days. Lesions included syncytial giant
cell formation, degeneration of germinal epithelium, and prostatic glandular atrophy.
(3) In the repeated-dose toxicity study described previously, male and female dogs were orally administered DCA
once daily in gelatin capsules at 0, 50, 75 or 100 mg/kg-bw/day for 13 weeks. Additional groups (control and high-
dose) were included as recovery animals and were monitored for an additional 5 weeks following the 13-week
dosing period. Prostate glandular atrophy and testicular changes were reported in all male dogs receiving DCA.
Prostate appeared normal and germinal epithelium regeneration with spermatogenesis was evident in recovery
animals.
(4) In the repeated-dose toxicity study described previously, male and female rats were orally administered DCA
once daily by gavage at 0, 125, 500, or 2000 mg/kg-bw/day for 13 weeks. Additional groups (control and high-
dose) were included as recovery animals and were monitored for an additional 4 weeks following the 13-week
dosing period. Testicular lesions included germinal epithelium degeneration at 500 and 2000 mg/kg-bw/day. In all
males at 2000 mg/kg-bw/day, the testes were aspermatogenic and contained syncytial giant cells in the germinal
epithelium while the epididymis ducts were devoid of spermatozoa. At recovery, some germinal epithelium
regeneration was noted; however, majority of them were aspermatogenic and showed loss of germinal epithelium.
Developmental Toxicity
Dichloroacetic acid (CAS No. 79-43-6, supporting chemical)
Pregnant female rats were administered DCA via oral gavage at 0, 14, 140 and 400 mg/kg-bw/day during gestation
days 6-15. Maternal toxicity occurred in dams at doses of 140 mg/kg-bw/day and above. Effects include reduced
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growth rate and increased liver, spleen and kidney weights. Fetal body weight and crown-rump length were reduced
in fetuses of rats receiving 400 mg/kg-bw/day. An increased incidence of soft tissue malformations (cardiovascular
system; ascending aorta and right ventricles) was seen in fetuses of rats receiving 140 mg/kg-bw/day or greater.
LOAEL (maternal/developmental toxicity) = 140 mg/kg-bw/day (based on increased incidence of soft tissue
malformations)
NOAEL (maternal/developmental toxicity) = 14 mg/kg-bw/day
Genetic Toxicity - Gene Mutation
In vitro
Dichloroacetyl chloride (CAS No. 79-36-7)
(1) DCAC tested positive in an in vitro bacterial reverse mutation assay using Salmonella typhimurium TA 100
strain, with and without exogenous metabolic activation and using bag vaporization method. The results were
positive in TA 100 without metabolic activation at 600 ppm and negative in TA 100 with metabolic activation when
tested up to 700 ppm.
DCAC was mutagenic in this assay.
(2) In an in vitro bacterial reverse mutation assay, S. typhimurium strains TA 98 and TA 100 were exposed to up to
6666 ng/plate with and without metabolic activation systems. DCAC was positive in TA 100 without metabolic
activation and negative in TA 98 with and without metabolic activation.
DCAC was mutagenic in this assay.
Dichloroacetic acid (CAS No. 79-43-6, supporting chemical)
(1) DCA tested positive in an in vitro bacterial reverse mutation assay in S. typhimurium TA 100 strain, with and
without metabolic activation system using the bag vaporization method.
DCA was mutagenic in this assay.
(2) In an in vitro bacterial reverse mutation assay using S. typhimurium strains TA 102 and TA 2638 and two
Escherichia coli strains, DCA was negative when tested with and without metabolic activation systems.
DCA was not mutagenic in this assay.
(3) Using S. typhimurium TA 98, TA 100, TA 1535 and TA 1537, and E. coli WP2 uvrA strains, the results were
negative with and without metabolic activation when tested in triplicate assay.
DCA was not mutagenic in this assay.
Genetic Toxicity - Chromosomal Aberrations
In vitro
Dichloroacetic acid (CAS No. 79-43-6, supporting chemical)
(1) In an in vitro clastogenicity study using mouse lymphoma cell line, the results were weakly positive. Dose-
related cytotoxic and mutagenic effects were reported. There was no significant increase in micronuclei or
aneuploidy frequencies.
DCA was clastogenic in this assay.
(2) A chromosomal aberration assay in Chinese hamster ovary cell was negative.
DCA did not induce chromosomal aberrations in this assay.
In vivo
Dichloroacetic acid (CAS No. 79-43-6, supporting chemical)
When tested in two in vivo assays, DCA was positive, but was negative in one mouse micronucleus test. Several
other non-standard tests (mutagenicity in mouse liver, 8-OH DNA adduct test, DNA strand-break test) for DNA
effects show mostly positive results.
DCA was mutagenic in several of these assays.
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Additional Information
Skin Irritation
Dichloroacetyl chloride (CAS No. 79-36-7)
Undiluted DCAC was applied to the skin of rabbits and the animals observed for 24-hours. Severe irritation and
edema were noted.
DCAC caused severe skin irritation in this assay.
Dichloroacetic acid (CAS No. 79-43-6, supporting chemical)
Undiluted DCA was applied to the skin of rabbits and the animals observed for 24-hours. Severe irritation and
edema were noted.
DCA caused severe skin irritation in this assay.
Eye Irritation
Dichloroacetyl chloride (CAS No. 79-36-7)
Undiluted DCAC (0.001, 0.005, 0.02, 0.1 and 0.5 mL) was applied to the eyes of rabbits and the animals observed
for 24-hours. Severe eye injury was observed.
DCAC caused severe eye irritation in this assay.
Dichloroacetic acid (CAS No. 79-43-6, supporting chemical)
Undiluted DCA (0.001, 0.005, 0.02, 0.1 and 0.5 mL) was applied to the eyes of rabbits and the animals observed for
24-hours. Severe eye injury was observed.
DCA caused severe eye irritation in this assay.
Carcinogenicity
Dichloroacetyl chloride (CAS No. 79-36-7)
An 18- to 22-month carcinogenicity study of DCAC was carried out using female mice. Three different exposure
scenarios were followed in this study: dermal exposure to DCAC (3 times/week), one-time dermal exposure to
DCAC followed by promoter exposure (PMA) 3 times/week, and subcutaneous injections in the right flank once/
week. The one-time exposure to DCAC followed by repeated exposure to PMA resulted in incidence of
carcinogenicity (papilloma and squamous carcinoma), where DCAC acted an initiator. In addition, the
subcutaneous injections of DCAC resulted in squamous carcinoma, papilloma, sarcoma and hemangioma.
Furthermore, in the critical inhalation study, male rats exposed to 2.0 ppm DCAC via inhalation for 6 hours/day, 5
days/week for 30 days developed nasal tumors.
Dichloroacetic acid (CAS No. 79-43-6, supporting chemical)
In a carcinogenicity study conducted using male rats exposed to DCA via drinking water for approximately 100
weeks, an increase in the incidence of hepatocellular carcinomas was observed.
Conclusion: Acute toxicity of DCAC and/or DCA is low via oral route, but is moderate via both inhalation and
dermal exposure routes. DCAC and DCA produced severe skin and eye irritation in rabbits. Repeated oral
exposure to DCA in both dogs and rats resulted in mortality; neurological effects; hepatic, pancreatic and gall
bladder effects and effects on male reproductive organs. Thymic atrophy with marked depletion of lymphoid tissue
was also observed in dogs. Effects on male reproductive organs included severe testicular lesions, syncytial giant
cell formation, degeneration of germinal epithelium and prostatic glandular atrophy in dogs. In rats, morphological
abnormalities of sperm (distorted sperm heads and decrease in the percentage of motile sperm), decreased sperm
counts, increase in the number of fused epididymal sperm and a decrease in epididymal weight were reported
following DCA exposure. Results from the developmental toxicity study indicate that DCA affects developing
fetuses. Reduced fetal weight, reduced crown-rump length and cardiovascular abnormalities were seen when dams
received oral doses during gestation days 6-15. In vitro and in vivo genetic toxicity assays using DCAC and DCA
provide positive evidence for mutagenicity. An in vitro mouse lymphoma test indicated that DCA induced
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chromosomal aberrations. Existing data suggest that DCAC and DCA are animal carcinogens. Repeated inhalation
exposure to DCAC in rats resulted in nasal tumors. Mice exposed to DCAC via subcutaneous injection developed
skin tumors. DCAC is also shown carcinogenic initiator properties where mice were exposed once via the dermal
route and followed by a series of PMA (promoter) exposure. DCA exposure via drinking water induced
hepatocellular carcinoma in male rats.
The potential health hazard of DCAC and DCA is high based on repeated-exposure toxicity via all routes of
exposure. Available data also indicates DCAC and DCA have the potential to be genotoxic. Both DCAC and DCA
induced tumors in animals via oral, inhalation, and dermal exposure studies.
3. Hazard Characterization
2,2-Dichloroacetyl chloride (DCAC) is a liquid at room temperature. It is highly volatile and hydrolyzes rapidly to
form hydrochloric acid and dichloroacetic acid (DCA). DCA is highly mobile in soil and water systems. DCA is
expected to photolyze slowly and biodegrade rapidly. DCAC and DCA are not persistent (PI), nor are they
bioaccumulative (Bl). The properties and environmental behavior of monochloroacetic acid (MCA) are essentially
the same as for dichloroacetic acid. An exception is that unlike DCA, MCA is a solid at room temperature.
The potential aquatic toxicity of DCA (as the hydrolysis product of DCAC) was assessed primarily using data from
the analog MCA. The evaluation of available aquatic toxicity data for DCA (using MCA data) indicates the acute
hazard to fish and aquatic invertebrates is low and hazard to aquatic plants is high.
Acute toxicity of DCAC and/or DCA is low via oral route, but is moderate via both inhalation and dermal exposure
routes. DCAC and DCA produced severe skin and eye irritation in rabbits. Repeated oral exposure to DCA in both
dogs and rats resulted in mortality; neurological effects; hepatic, pancreatic and gall bladder effects and effects on
male reproductive organs. Thymic atrophy with marked depletion of lymphoid tissue was also observed in dogs.
Effects on male reproductive organs included severe testicular lesions, syncytial giant cell formation, degeneration
of germinal epithelium and prostatic glandular atrophy in dogs. In rats, morphological abnormalities of sperm
(distorted sperm heads and decrease in the percentage of motile sperm), decreased sperm counts, increase in the
number of fused epididymal sperm and a decrease in epididymal weight were reported following DCA exposure.
Results from the developmental toxicity study indicate that DCA affects developing fetuses. Reduced fetal weight,
reduced crown-rump length and cardiovascular abnormalities were seen when dams received oral doses during
gestation days 6-15. In vitro and in vivo genetic toxicity assays using DCAC and DCA provide positive evidence
for mutagenicity. An in vitro mouse lymphoma test indicated that DCA induced chromosomal aberrations. Existing
data suggest that DCAC and DCA are potential carcinogens. Repeated inhalation exposure to DCAC in rats resulted
in nasal tumors. Mice exposed to DCAC via subcutaneous injection developed skin tumors. DCAC is also shown
carcinogenic initiator properties where mice were exposed once via the dermal route and followed by a series of
PMA (promoter) exposure. DCA exposure via drinking water induced hepatocellular carcinoma in male rats.
The potential health hazard of DCAC and DCA is high based on repeated-exposure toxicity via all routes of
exposure in a variety of organ systems. Available data indicates DCAC and DCA have the potential to be
genotoxic. Available data indicates that DCAC(DCA) has the potential to cause reproductive effects (see data gaps
below for details). Both DCAC and DCA induced tumors in animals via oral, inhalation, and dermal exposure
studies.
4. Data Gaps
No data gaps have been identified under the HPV Challenge Program.
A reproductive toxicity study was not submitted for DCAC or its analog DCA. Evaluation of reproductive organs
submitted with repeated-dose studies along with a developmental toxicity study were used to address the
reproductive endpoints for the purposes of the HPV Challenge Program. Repeated (oral) exposure to DCA resulted
in effects on male reproductive organs. Effects of these chemicals on female reproductive parameters have not been
provided, but the developmental toxicity study identified maternal and fetal effects. Thus, these data are adequate
for performing this screening-level hazard characterization and suggest that DCAC (DCA) has the potential to cause
reproductive toxicity.
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APPENDIX
Summary Tabic of the Screening Information Data Set
as submitted under the U.S. HPV Challenge Program
Endpoints
SPONSORED CHEMICAL
Dichloroacctvl chloride
(DCAC)
(79-36-7)
SUPPORTING
CHEMICAL
Dichloroacctic acid
(DCA)
(79-43-6)
SUPPORTING
CHEMICAL
Monochloroacctic acid
(MCA)
(79-11-8)
CI
CI
O O
O
civA
OH
Summary of Environmental Effects - Aquatic Toxicity Data
Fish
96-h LC50 (mg/L)
DCAC expected to
hydrolyze quickly to DCA.
100 (24-hours)1
370
Aquatic Invertebrates
48-h EC50 (mg/L)
23 (96 hours)1
77
Aquatic Plants
72-h EC50 (mg/L)
(growth)
(biomass)
No Data2
(RA)
0.025
0.033
0.025
0.033
Chronic Toxicity to Fish
28-day NOEC, (mg/L)
-
Not established
(LOEC = 25)
Chronic Toxicity to Invertebrates
21-day NOEC, (mg/L)
-
32
Summary of Human Health Data
Acute Oral Toxicity
LDS0 (mg/kg-bw)
2460
2820 - 5520
-
Acute Dermal Toxicity
LDS0 (mg/kg-bw)
995
801
-
Acute Inhalation Toxicity
LC50 (mg/L/6h/day)
LQo ~ 12.1
-
-
Repeated-Dose Toxicity
NOAEL/LOAEL (mg/kg-bw/day)
No Data
(RA)
NOAEL = Not established
LOAEL = 12.5 - 50
NOAEL = Not established
LOAEL = 12.5 - 50
Reproductive Toxicity
NOAEL/LOAEL
(mg/kg-bw/day)
No Data
(RA)
Effects were seen on
reproductive organs in the
repeated-dose toxicity study
with DCA
Effects observed in
reproductive organs in
repeated dose study
(testicular effects in dogs and
sperm abnormalities in rats)
Developmental Toxicity
NOAEL/LOAEL
(mg/kg-bw/day)
No Data
(RA)
NOAEL (mat/dev.)3 = 14
LOAEL (mat/dev.) = 140
NOAEL (mat/dev.)3 = 14
LOAEL (mat/dev.) = 140
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Summary Table of the Screening Information Data Set
as submitted under the U.S. HPV Challenge Program
Endpoints
SPONSORED CHEMICAL
Dichloroacetyl chloride
(DCAC)
(79-36-7)
SUPPORTING
CHEMICAL
Dichloroacetic acid
(DCA)
(79-43-6)
SUPPORTING
CHEMICAL
Monochloroacctic acid
(MCA)
(79-11-8)
Genetic Toxicity - Gene Mutation
In vitro
Positive
-
-
Genetic Toxicity - Gene Mutation
In vivo
Positive
-
-
Genetic Toxicity - Chromosomal
Aberrations
In vitro
Positive
"
Genetic Toxicity - Chromosomal
Aberrations
In vivo
Positive
"
—
Additional Information -
Skin Irritation
Severe
Severe
-
Additional Information -
Eye Irritation
Severe
Severe
-
Additional Information
Positive in rats
Positive in mice
-
- indicates that the endpoint was not addressed for this chemical; mat/dev = maternal/developmental; RA = Read
across.
1 Submitted data considered inadequate because of study duration and summaries not provided in the text. However,
MCA is considered a reasonable analog and so values reported for MCA may be used to represent DCA in this
hazard characterization.
2 The lowest EC50 value among three different aquatic plant species tested to the following concentrations of DCA:
0, 3, 10, 30, and 100 mg/L was 29.8 (based on 14-day exposures). These data were deemed inadequate because they
were higher plants and not algae. Thus, MCA data were used for this endpoint
3 In this case, both the maternal and developmental NOAELs and LOAELs were the same.
1. References
Du Pont, 2004. Robust Summaries & Test Plans: Dichloroacetyl chloride HPV Test Plan, submitted by E.I. du Pont
de Nemours and Company, Inc. http://www.epa.gov/chemrtk/pubs/summaries/dichlrac/cl5628tc.htm
FR 1999, Category for Persistent, Bioaccumulative, and Toxic New Chemical Substances. Federal Register 64,
Number 213 (November 4, 1999) Page 60194-60204
HSDB, 2007. Hazard Substances Data Base. As cited in HSDB record for 2,2-dichloroacetyl chloride, accessed
August 2, 2007. http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen7HSDB.
OECD, 2001. OECD Series on Testing and Assessment, Number 33. Harmonized Integrated Classification System
For Human Health and Environmental Hazards of Chemical Substances and Mixtures. Joint Meeting of the
Chemicals Committee and the Working Party on Chemicals, Pesticides and Biotechnology, August 14, 2001.
USEPA, 2007. EPI Suite™ (version 3.2), PC-Computer software developed by EPA's Office of Pollution
Prevention Toxics and Syracuse Research Corporation, http://www.epa.gov/opptintr/exposure/pubs/episuite.htm
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U.S. Environmental Protection Agency
Supporting Documents for Risk-Based Prioritization
3/18/08
Exposure Characterization for HPV Challenge Chemical
Acetyl Chloride, Dichloro
CAS #79-36-7
March 14, 2008
Prepared by
Exposure Assessment Branch
Chemical Engineering Branch
Economics Exposure and Technology Division
Office of Pollution Prevention and Toxics
Environmental Protection Agency
1200 Pennsylvania Avenue, NW
Washington, DC 20460-0001
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U.S. Environmental Protection Agency
Supporting Documents for Risk-Based Prioritization
3/18/08
Exposure Characterization for HPV Challenge Chemical
Acetyl Chloride, Dichloro- (79-36-7)
Non-CBI Executive Summary
Acetyl Chloride, Dichloro- (DCAC) was manufactured (including imported) in the United States
in a quantity between one million and 10 million lbs in 2005 (USEPA, 2006). Persons
submitting Inventory Update Reporting (IUR) information in 2006 asserted that some or all of
the information was confidential and therefore cannot be disclosed. The HPV challenge test plan
and robust summary were submitted by DuPont (U.S. EPA, 2007c). The HPV Challenge test
plan describes the manufacturing process as a closed system, dedicated to DC AC manufacture.
DC AC is shipped to a small number of customers by tank truck or ISO which are dedicated to
DCAC service. Companies receiving DCAC utilize it as a chemical intermediate in synthesis of
other products in closed systems. Another source also indicated that the primary use of
dichloroacetyl chloride is as an intermediate (HSDB, 2007).
A SIDS dossier has not been prepared for this chemical (SIDS, 2008).
Exposure was characterized using both public, non-confidential sources and one or more IUR
submissions available at the time this exposure characterization was written. If additional
information warrants an update of the exposure characterization, the update will be posted on the
EPA website.
Exposures to Workers
Based on IUR reporting, the total number of workers reasonably likely to be exposed to
dichloroacetyl chloride during manufacturing and industrial processing and use is believed to be
less than 100. There may be additional potentially exposed workers that are not included in this
estimate since not all workers engaged in industrial processing of this chemical have been
accounted for. The NOES database which summarizes a survey of industrial workplaces
conducted by NIOSH between 1981 and 1983 does not contains any information regarding the
number of potentially exposed workers for this chemical (NIOSH, 2007b).
Differences between numbers of workers estimated by IUR submitters and by the NOES are
attributable to many factors, including time, scope, and method of the estimates. For example,
NOES estimates are for all workplaces while IUR are for industrial workplaces only, and NOES
used a survey and extrapolation method while IUR submitters simply provide their best estimates
based on available information for the specific reporting year.
Although workers may be exposed to this chemical as a result of spillage or cleaning of process
equipment, exposure is likely to be minimized by personal protective equipment (PPE).
Processes for manufacturing and processing DCAC are closed limiting releases during
manufacturing and processing (U.S. EPA, 2007c). Any DCAC released would not be expected
to persist due to rapid hydrolysis and biodegradation of the DCA hydrolysis product (U.S. EPA,
2007a).
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3/18/08
DCAC does not have an OSHA Permissible Exposure Limit (NIOSH, 2007a).
Based on IUR data, specifically the number of potentially exposed workers and use codes, the
potential for worker exposure is considered low.
Exposures to General Population and the Environment
DCAC is not listed on the Toxics Release Inventory (US EPA, 2007b). One non-CBI source
indicated that DCAC may be released to the environment by fugitive atmospheric emissions
from industrial production and use operations (HSDB, 2007).
DCAC is ranked low for fate, since it is not persistent (PI), nor is it bioaccumulative (Bl). Any
DCAC released would not be expected to persist due to rapid hydrolysis and biodegradation of
the DCA hydrolysis product (USEPA, 2007a).
Based on the totality of the information considered and expert judgment, releases may be
possible; however, other sources indicate that potential releases of DCAC for manufacturing and
processing would be limited by closed system operations (U.S. EPA, 2007c), and any fugitive
release would not be expected to persist due to rapid hydrolysis and biodegradation of the DCA
hydrolysis product (U.S. EPA, 2007a). EPA assumes, for the purposes of this risk based
prioritization, that the potential for general population and/or environmental exposure to this
chemical is low.
Exposure to Commercial Workers and Consumers
There were no commercial or consumer uses identified in the IUR data or in the additional non-
CBI data sources searched for the exposure assessment.
The likelihood that this chemical is used in consumer/commercial products is low based on IUR
data.
Exposure to Children
This chemical is not in the Voluntary Children's Chemical Evaluation Program (USEPA, 2007c).
It is not expected to be present in children's products.
The likelihood that this chemical is used in products intended to be used by children is low based
on IUR data.
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Supporting Documents for Risk-Based Prioritization
References:
Du Pont, 2004. Robust Summaries & Test Plans: Dichloroacetyl chloride HPV Test Plan
HSDB,2007. Hazard Substances Data Base. As cited in HSDB record for 2,2-
dichloroacetyl chloride, accessed August 2, 2007. http://toxnet.nlm.nih.gov/cgi-
bin/sis/htmlqen?HSDB.
NIOSH, 2007a. OSHAPEL Project Documentation. Accessed August, 2007.
http://www.cdc.gov/niosh/pel88/npelcas.html
NIOSH, 2007b. National Occupational Exposure Survey (NOES). Accessed December
2007.
http://www.osha.gov/pls/oshaweb/owadisp.show document?p table=STANDARDS&p
id=9992
SIDS, 2008. United Nations Environment Programme (UNEP) Chemicals Screening Information
Dataset (SIDS) for High Volume Chemicals. Accessed February 2008.
http://www.chem.unep.ch/irptc/sids/oecdsids/sidspub.html
U.S. EPA, 2006. 2006 Partial Updating of TSCA Chemical Inventory (confidential business
information)
U.S. EPA, 2007a. Physical/Chemical and Environmental Fate Characterization for High
Production Volume Chemicals, Chemical Name: Acetyl Chloride, Dichloro-
U.S. EPA, 2007b. Toxic Release Inventory. Accessed August, 2007.
http://www.epa.gov/tri/
U.S. EPA, 2007c. HPV challenge program. Robust Summaries & Test Plans: Dichloroacetyl
Chloride
http://www.epa.gov/chemrtk/pubs/summaries/dichlrac/cl5628tc.htm
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