500R89002 "!IJL
United States ECAO-CIN-G074
Environmental Protection September, 1989
K
'PA Research and
Development
HEALTH AND ENVIRONMENTAL EFFECTS DOCUMENT
FOR 1.3-DICHLOROPROPENE
Prepared for
OFFICE OF SOLID WASTE AND
EMERGENCY RESPONSE
Prepared by
Environmental Criteria and Assessment Office
Office of Health and Environmental Assessment
U.S. Environmental Protection Agency
Cincinnati, OH 45266
DRAFT: DO NOT CITE OR QUOTE
NOTICE
This document 1s a preliminary draft. It has not been formally released
by the U.S. Environmental Protection Agency and should not at this stage be
construed to represent Agency policy. It 1s being circulated for comments
on Us technical accuracy and policy Implications.
-------
DISCLAIMER
This report 1s an external draft for review purposes only and does not
constitute Agency policy. Mention of trade names or commercial products
does not constitute endorsement or recommendation for use.
11
-------
PREFACE
Health and Environmental Effects Documents (HEEOs) are prepared for the
Office of Solid Waste and Emergency Response (OSUER). This document series
Is Intended to support listings under the Resource Conservation and Recovery
Act (RCRA) as well as to provide health-related limits and goals for emer-
gency and remedial actions under the Comprehensive Environmental Response,
Compensation and Liability Act (CERCLA). Both published literature and
Information obtained for Agency Program Office files are evaluated as they
pertain to potential human health, aquatic life and environmental effects of
hazardous waste constituents. The literature searched for In this document
and the dates searched are Included In "Appendix: Literature Searched."
Literature search material 1s current up to 8 months previous to the final
draft date listed on the front cover. Final dr.aft document dates (front
cover} reflect the date the document Is sent to the Program Officer (OSWER).
Several quantitative estimates are presented provided sufficient data
are available. For systemic toxicants, these Include: Reference doses
(RfDs) for chronic and subchronlc exposures for both the Inhalation and oral
exposures. The subchronlc or partial lifetime RfD, Is an estimate of an
exposure level which would not be expected to cause adverse effects when
exposure occurs during a limited time Interval I.e., for an Interval which
does not constitute a significant portion of the llfespan. This type of
exposure estimate has not been extensively used, or rigorously defined as
previous risk assessment efforts have focused primarily on lifetime exposure
scenarios. Animal data used for subchronlc estimates generally reflect
exposure durations of 30-90 days. The general methodology for estimating
subchronlc RfDs 1s the same as traditionally employed for chronic estimates,
except that subchronlc data are utilized when available.
In the case of suspected carcinogens, RfDs are not estimated. Instead,
a carcinogenic potency factor, or q-j* (U.S. EPA, 1980a) Is provided.
These potency estimates are derived for both oral and Inhalation exposures
where possible. In addition, unit risk estimates for air and drinking water
are presented based on Inhalation and oral data, respectively.
Reportable quantities (RQs) based on both chronic toxlclty and cardno-
genlclty are derived. The RQ Is used to determine the quantity of a
hazardous substance for which notification 1s required In the event of a
release as specified under the Comprehensive Environmental Response,
Compensation and Liability Act {CERCLA). These two RQs (chronic toxldty
and carc1nogen1c1ty) represent two of six scores developed (the remaining
four reflect 1gn1tab1l1ty, reactivity, aquatic toxlclty, and acute mammalian
toxlclty). Chemical-specific RQs reflect the lowest of these six primary
criteria. The methodology for chronic toxlclty and cancer based RQs are
defined 1n U.S. EPA, 1984 and 1986a, respectively.
111
-------
EXECUTIVE SUMMARY
1,3-D1chloropropene Is a colorless liquid with the odor of chloroform
(Wlndholz, 1983). It occurs In els- and trans-TsomeMc forms. The
cls-lsomer has a slightly higher vapor pressure than the trans-lsomer (43
versus 34 mm Hg), but the water solubilities are similar (2700-2800 ppm at
20°C) (DHUng, 1977). Current production figures for 1,3-dlchloropropene
are not available. According to the public portion of the U.S. EPA TSCA
Production File for 1977, two U.S. manufacturers (Dow and Shell Chemical)
produced a combined total of 10-60 million pounds In 1977 (U.S. EPA, 1977).
1,3-Olchloropropene has been produced as a by-product of allyl chloride
production In conjunction with other by-products, such as 3,3-dlchloro-
propene and l,2-d1chloropropene (KMJgsheld and van der Gen, 1986;
DeBened1ct1s, 1979). By-product mixtures of l,3-d1chloropropene and
1,2-dlchloropropane have been marketed as a fumlgant under the trade name
D-D by Shell Chemical Co. (Worthing and Walker, 1987; Yang, 1986).
l,3-D1chloropropene Is used as a soil fumlgant and nematldde (Worthing and
Walker, 1987). Several different commercial formulations containing
1,3-d1chloropropene have been marketed as a fumlgant. Telone II*
(currently marketed by Dow Chemical) Is widely used In agriculture as a soil
fumlgant for parasitic plant nematodes (Yang, 1986; SRI, 1986). Current
Telone !!• formulations contain 98% 1,3-d1chloropropene (Albrecht, 1987a),
although original formulations contained only 92% (Yang, 1986).
Degradation of l,3-d1chloropropene 1n the ambient atmosphere results
primarily by reaction with photochemically generated HO* (Tuazon et al.,
1984). Based upon experimentally determined rate constants (Tuazon et al.,
1984), the half-lives for the reaction of els- and trans-1,3-d1chloropropene
1v
-------
with HO- In air are ~2.1 and 1.2 days, respectively. l,3-D1chloropropene
has been detected 1n rainwater (Mazurek and Slmonettl, 1986), Indicating
that physical removal by wet deposition can occur. Hydrolysis and volatili-
zation are Important environmental fate processes 1n water. The rate of
hydrolysis has been found to be Independent of pH at pHs 5, 7 and 9 and to
be essentially Identical for the c1s- and trans-lsomers. The measured
hydrolysis half-lives at 10, 20 and 30°C were 51, 11.3 and 3.1 days,
respectively, with 3-chloroallyl alcohol Identified as a hydrolysis product
(McCall, 1987). Volatilization half-lives of 3.8-4.2 and 46-50 hours have
been estimated for a model river (1 m deep} and a model environmental pond,
respectively (Thomas, 1982; U.S. EPA, 1986b). The fate of 1,3-d1chloro-
propene In soil has been studied extensively. It hydrolyzes In wet soil to
yield els- and trans-3-chloroallyl alcohol (Castro.and Belser, 1966; Roberts
and Stoydln, 1976). Since the rate of hydrolysis Is strongly dependent upon
temperature, the Importance of hydrolysis In soil will depend upon moisture
content and temperature. In warm, moist soil, hydrolysis may be one of the
dominant degradation processes. 1,3-Dlchloropropene Is susceptible to
degradation by soil microorganisms (Krljgsheld and van der Gen, 1986).
Adapted microbes appear capable of degrading l,3-d1chloropropene at signifi-
cant rates (Tabak et al., 1981; van der Pas and Lelstra, 1987). Volatiliza-
tion Is an Important physical removal process for 1,3-d1chloropropene In
soil. The volatilization rate of l,3-d1chloropropene that Is applied to
soil as a fumlgant can vary greatly with application methods, temperature,
moisture content, soil porosity and soil organic content (Albrecht and
Chenchln, 1985). Volatilization losses from soil may exceed 50% of the
amount applied (Roberts and Stoydln, 1976) or range from only 5-10X
-------
(Munnecke and Van Gundy, 1979). Dissolved 1,3-dlchloropropene 1s suscept-
ible to significant leaching In soil (Kenaga, 1980). Although leaching In
wet soil can occur, concurrent hydrolysis and blodegradatlon should
attenuate the amounts of 1,3-dlchloropropene that may reach groundwaters.
Vapor phase 1,3-dlchloropropene 1s more strongly adsorbed to soil than the
dissolved chemical (Munnecke and Van Gundy, 1979). The overall half-lives of
l,3-d1chloroprolene In soil have been observed to vary from 3-69 days (van
der Pas and Lelstra, 1987; Lelstra, 1970;. Albrecht; 1987a).
l,3-D1chloropropene has been Identified In a very limited number of
drinking waters. It has been qualitatively detected In New Orleans, LA
drinking water collected 1n August 1974 (Dowty et al., 1975; Shackelford and
Keith, 1976). Monitoring studies conducted In Denver, CO and In nine
municipalities along the Great Lakes failed to detect any trace of 1,3-dl-
chloropropene (Rogers et al., 1987; Otson, 1987). Extensive groundwater
monitoring for agricultural chemicals In California (Including areas where
Telone and D-D had been applied for years) has detected 1,3-dlchloropropene
In only three of thousands of samples analyzed (Cohen, 1986; Maddy et al.,
1982). 1,3-Dlchloropropene has been detected In leachate from municipal
waste landfills and sewage treatment plants (Sabel and Clark, 1984; Lao et
al., 1982). It has been suggested that chlorlnatlon of water can lead to
the formation of 1,3-dlchloropropene and that the Identification of
1,3-dlchloropropene In various water samples may be due to chlorlnatlon
treatment (Krljgsheld and van der Gen, 1986). Examination of 231 different
ready-to-eat foods (collected during the U.S. Food and Drug Administration's
Market Basket Survey) for 22 fumlgants and Industrial residues failed to
detect any 1,3-dlchloropropene at a detection limit of -1 ppb (Daft, 1988).
v1
-------
The major source of 1,3-d1chloropropene release to the atmosphere Is
probably volatile losses from soil following soil application as a fumlgant
(KMjgsheld and van der Gen, 1986). Albrecht (1987b) studied the Inhalation
exposure of 1,3-d1chloropropene 1n workers Involved 1n applying Telone !!•
to pineapple fields In Hawaii and found exposures to be predominantly <1 ppm.
Data are available on the acute toxlclty of l,3-d1chloropropene to
several species of Invertebrates and vertebrates. As shown In Table 4-1,
96-hour IC50 values reveal a similar, range of sensitivity, among six
freshwater fish species native to U.S. waters (Applegate et a!., 1957;
Buccafusco et al., 1981; Hermens et al., 1985; Johnson and Flnley, 1980;
LeBlanc, 1984; Schneider, 1979; U.S. EPA, 1978). A seventh species, the
walleye, S. vltreum vltreum. showed markedly greater sensitivity, with a
96-hour LC5Q of 1.08 ppm. The water flea, j). magna. (Leblanc, 1980, 1984;
U.S. EPA, 1978) showed a sensitivity comparable with that of the blueglll
sunflsh, L. macrochlrus. the least sensitive of the freshwater fish species
tested (Buccafusco et al., 1981; LeBlanc, 1984; U.S. EPA, 1978). 1,3-dl-
chloropropene 1s more acutely toxic to the saltwater Invertebrate, M. bahla
(LeBlanc, 1984; U.S. EPA, 1978), than to the freshwater species, D. magna.
The sheepshead minnow, C. vaMeqatus. a saltwater fish. Is highly sensitive
to 1,3-dlchloropropene (mean 96-hour LC,Q = 1.76 ppm) (LeBlanc, 1984).
Chronic toxlclty tests of 1,3-dlchloropropene to the fathead minnow, P.
promelas, and mysld shrimp, H_._ bahla. revealed NOECs of 0.18 ppm and 4.2
ppm, respectively (U.S. EPA, 1978).
Data regarding the toxlclty of 1,3-dlchloropropene to aquatic flora
follow a similar pattern to that for aquatic fauna. The saltwater alga, S.
costatum. has a mean 96-hour EC™ of 1.01 ppm (LeBlanc, 1984; U.S. EPA,
1978); the freshwater alga, S. caprlcornutum. has a mean 96-hour EC™ of
-------
4.95 ppra (LeBlanc, 1984; U.S. EPA, 1978). Data on effects of 1,3-dlchloro-
propene on bacteria Indicate that Aerobacter sp.. and Pseudomonas sj>. are
more resistant to the compound than are higher aquatic species reported
above.
Studies on the bloconcentratlon/bloaccuroulatlon potential of l,3-d1-
chloropropene 1n aquatic fauna and flora were not located In the available
literature, but BCFs of 7 (based on water solubility) and 1 (based on KQW)
were predicted for this compound by Kenaga (1980).-
Data support 1,3-dlchloropropene's effectiveness as a nematodde
(Ablvardl, 1970; Blackmon and Husen, 1974; Costante et al., 1987; Kotcon and
Lorla, 1987) and Us toxlclty to the earthworm, Lumbrlcus terrestrls. and to
Dlpter and Coleopter larvae (Edwards and Re1ch1e, 1969).
Data regarding the effectiveness of 1,3-dlchloropropene for control of
soil microorganisms are equivocal. Nathur et al. (1980) noted Increased
numbers of fungi, bacteria and actlnomycetes after treating field plots with
the chemical, but Cook et al. (1987) noted 95-10074 elimination of a popu-
lation of Pythlum spp. with 1,3-dlchloropropene.
The lack of pertinent data regarding effects of exposure of aquatic
fauna and flora to 1,3-dlchloropropene prevented the development of fresh-
water or saltwater criteria.
Approximately 80% of the administered dose of 1,3-dlchloropropene was
absorbed Into the body following Inhalation or oral exposure (Stott and
Kastl, 1986; Hutson et al., 1971). As the Inhaled concentration of 1,3-dl-
chloropropene Increased, the absorption did not Increase linearly because of
an exposure level-related decrease In respiratory ventllatory frequency and
to saturation of the metabolism of 1,3-dlchloropropene (see Section 5.1.).
-------
1,3-D1chloropropene was rapidly eliminated from the body, primarily 1n the
urine as N-acetyl-S-(3-chloroprop-2-enyl) cystelne, following Inhalation or
oral exposure (Hutson et al., 1971; CUmle et al., 1979; D1etz et al., 1965;
Stott and Kastl, 1986; Fisher and Kllgore, 1988b). 1,3-D1chloropropene
elimination 1s due to an efficient glutathlone-dependent blotransformatlon:
l,3-d1chloropropene conjugates with glutathlone, enters the mercapturlc acid
pathway and Is excreted In the urine as N-acetyl-S-(3-chloroprop-2-enyl)
cystelne (Cllmle et al., 1979; Fisher and Kllgore,O988a).
Differences In disposition exist between the els- and the trans-lsomers.
Greater concentrations of the trans-lsomer were found In the blood of rats
after Inhalation exposure to approximately equal concentrations of the two
Isomers (Stott and Kastl, 1986), and greater amounts of the ds- than the
trans-lsomer were found 1n the urine, while much greater amounts of the
trans-lsomer were excreted as CCL In the expired breath (Hutson et al.,
1971).
Distinct differences exist In the elimination of l,3-d1chloropropene
between rats and mice. Following oral dosing with 14C-l,3-d1chloropro-
pene, more of the administered dose of radioactivity was excreted In the
urine and expired air of mice than of rats (D1etz et al., 1985). The rate
of urinary excretion of the mercapturlc acid of l,3-d1chloropropene was
comparable between rats (Fisher and Kllgore, 1988b) and humans (Osterloh et
al., 1984).
The LC5Q for l,3-d1chloropropene In rats and mice was 4530 mg/m3
(H1ne et al., 1953). Information regarding subchronlc and chronic Inhala-
tion of 1,3-dlchloropropene suggests that damage to the nasal mucosa of rats
and mice and damage to the urinary bladders of mice may result from exposure
(Stott et al., 1988; Torkelson and Rowe, 1981; Lomax et al., 1989).
1x
-------
Evidence of damage to the liver and kidneys was also found (Parker et at.,
1982; Torkelson and Rowe, 1981).
Oral LD5_ values In rats ranged from 140-740 mg/kg and. In mice, from
300-640 mg/kg {Torkelson and Rowe, 1981; Mine et al.f 1953; Toyoshlma et
al., 1978a,b). Subchronlc studies suggested Increases 1n the relative
weight of the kidneys 1n rats treated orally with l,3-d1chloropropene
(Torkelson and Rowe, 1981). Chronic oral studies suggest that hyperplasla
of the fore stomach and of the urinary-bladders of rats and mice resulted
from exposure (NTP, 1985).
The only data available regarding the carclnogenldty of 1,3-dlchloro-
propene 1n humans are three reported cases of hematologlc malignancies that
may have been the result of acute exposure to 1,3-d1chloropropene (Markovltz
and Crosby, 1984). There 1s sufficient evidence that 1,3-dlchloropropene Is
a carcinogen 1n orally exposed animals. NTP (1985) found Increased
Incidences of squamous-cell paplllomas and carcinomas of the forestomach and
neoplastlc nodules or carcinomas of the liver In male rats treated chronic-
ally with 1,3-dlchloropropene by gavage. Mice similarly treated showed
Increased Incidences of forestomach tumors, lung adenomas or carcinomas and
transitional cell carcinomas of the urinary bladder. There 1s weak evidence
that 1,3-dlchloropropene 1s carcinogenic In animals exposed by Inhalation.
Lomax et al. (1989) found an Increase 1n the Incidence of benign lung tumors
(bronchloloalveolar adenomas) In male mice treated chronically with
1,3-dlchloropropene, but no evidence of any Increase 1n neoplasms In either
male or female rats or In female mice following Inhalation. 1,3-Dlchloro-
propene has been found to be mutagenlc In various strains of S. typhlmurlum
(NTP, 1985; Stolzenberg and H1ne, 1980; Haworth et al., 1983). 1,3-01-
chloropropene has also been found to be positive for sex-linked lethal
-------
mutations, but negative for reciprocal translocatlons 1n D. melanoqaster
i
{NTP, 1985). l,3-D1chloropropene does not appear to be a reproductive or a
developmental toxicant.
The only available data regarding the carclnogenlclty of l,3-d1chloro-
propene In humans are three reported cases of hematologlc malignancies that
may have resulted from acute exposure to 1,3-dlchloropropene (MarkowHz and
Crosby, 1984). The available animal data Indicate evidence that 1,3-dl-
chloropropene Is carcinogenic by the oral route of exposure (NTP, 1985) and
may be carcinogenic following Inhalation exposure (Lomax et a!., 1989).
Mutagenlclty studies Indicate that 1,3-dlchloropropene 1s mutagenlc to
various strains of S. typhlmuMum (NTP, 1985; Haworth et al., 1983;
Stolzenberg and Hlne, 1980). According to U.S. EPA (1986c) guidance,
1,3-dlchloropropene can be placed In Group 82 - probable human carcinogen.
An Inhalation q * of l.SxlO"1 (mg/kg/day)"1 1s derived based on an
Increased Incidence of bronchloloalveolar adenomas 1n male mice exposed to
60 ppm for 2 years (Lomax et al., 1989).
An oral q * of l.SxltT1 (mg/kg/day)"1 Is derived based on the
combined Incidences of tumors In the forestomach and liver and pheochromo-
cytoma In the adrenals of male rats (NTP, 1985).
A subchronlc Inhalation RfD of 0.01 mg/m" 1s calculated by adjusting a
NOEL of 10 ppm from the Stott et al. (1988) study for Intermittent exposure,
multiplying by the RGDR and dividing by an uncertainty factor of 100 (10 for
Interspedes extrapolation and 10 to protect the most sensitive Individual).
The subchronlc Inhalation RfD of 0.01 mg/ma Is adopted as the chronic
Inhalation RfO because the chronic LOAEL In mice (20 ppm) Is higher than the
NOEL of 10 ppm In rats 1n the subchronlc study used as the basis for the
subchronlc RfD.
xl
-------
A subchronlc oral RfD of 3xlO~9 mg/kg/day Is calculated taking the
NOEL of 3 mg/kg/day from the T11 et al. (1973) study, adjusting for Inter-
mittent exposure to 2.6 mg/kg/day and dividing by an uncertainty factor of
1000 (10 for Interspedes extrapolation, 10 to protect the most sensitive
Individuals and an additional modifying factor of 10 for the deficient data
base). A chronic oral RfD of 3xlO~4 mg/kg/day Is calculated by adjusting
the NOEL of 3 mg/kg/day from the T11 et al. (1973) study for Intermittent
exposure and dividing by an uncertainly factor-of 10,000 (10 for Inter-
species extrapolation, 10 to protect the most sensitive Individuals, 10 for
the use of a subchronlc study and an additional modifying factor of 10 for
the deficient data base). This oral RfD of 3x10"4 mg/kg/day has been
verified (U.S. EPA, 1987b). An RQ of 100 Is calculated on the basis of
chronic toxldty and an RQ of 100 1s calculated based on cardnogenlclty.
xll
-------
TABLE OF CONTENTS
Page
1. INTRODUCTION 1-1
1.1. STRUCTURE AND CAS NUMBER 1-1
1.2. PHYSICAL AND CHEMICAL PROPERTIES 1-1
1.3. PRODUCTION DATA 1-3
1.4. USE DATA 1-3
1.5. SUMMARY 1-4
2. ENVIRONMENTAL FATE AND TRANSPORT 2-1
2.1. AIR 2-1
•
2.2. WATER 7 2-1
2.2.1. Hydrolysis 2-1
2.2.2. Photolysis 2-2
2.2.3.' Mlcroblal Degradation 2-2
2.2.4. Volatilization 2-2
2.2.5. Adsorption 2-2
2.3. SOIL 2-3
2.3.1. Chemical Degradation 2-3
2.3.2. Mlcroblal Degradation 2-3
2.3.3. Volatilization 2-4
2.3.4. Adsorption/Leaching 2-4
2.3.5. Persistence 2-5
2.4. SUMMARY 2-5
3. EXPOSURE 3-1
3.1. HATER 3-1
3.2. FOOD 3-2
3.3. INHALATION 3-2
3.4. DERMAL 3-3
3.5. SUMMARY 3-3
4. ENVIRONMENTAL TOXICOLOGY 4-1
4.1. AQUATIC TOXICOLOGY 4-1
4.1.1. Acute Toxic Effects on Fauna 4-1
4.1.2. Chronic Effects on Fauna 4-1
4.1.3. Effects on Flora 4-4
4.1.4. Effects on Bacteria 4-5
4.2. TERRESTRIAL TOXICITY 4-5
4.2.1. Effects on Fauna 4-5
4.2.2. Effects on Flora 4-5
-------
TABLE OF CONTENTS (cent.)
Page
4.3. FIELD STUDIES 4-6
4.4. AQUATIC RISK ASSESSMENT 4-7
4.5. SUMMARY 4-10
5. PHARMACOKINETICS 5-1
5.1. ABSORPTION 5-1
5.2. DISTRIBUTION 5-2
5.3. METABOLISM 5-3
5.4. EXCRETION 5-5
5.5. SUMMARY 5-9
6. EFFECTS 7 6-1
6.1. SYSTEMIC TOXICITY 6-1
6.1.1 Inhalation Exposure 6-1
6.1.2. Oral Exposure 6-5
6.1.3. Other Relevant Information 6-8
6.2. CARCINOGENICITY 6-11
6.2.1 Inhalation 6-11
6.2.2. Oral 6-12
6.2.3. Other Relevant Information 6-16
6.3. MUTAGENICITY 6-17
6.4. DEVELOPMENTAL TOXICITY 6-20
6.5. OTHER REPRODUCTIVE EFFECTS 6-21
6.6. SUMMARY 6-22
7. EXISTING GUIDELINES AND STANDARDS 7-1
7.1. HUMAN 7-1
7.2. AQUATIC 7-1
8. RISK ASSESSMENT 8-1
8.1. CARCINOGENICITY 8-1
8.1.1. Inhalation 8-1
8.1.2. Oral 8-2
8.1.3. Other Routes 8-3
8.1.4. Weight of Evidence 8-3
8.1.5. Quantitative Risk Estimates 8-4
8.2. SYSTEMIC TOXICITY 8-5
8.2.1. Inhalation Exposure 8-5
8.2.2. Oral Exposure 8-9
xlv
-------
TABLE Of CONTENTS (cont.)
Page
9. REPORTABLE QUANTITIES 9-1
9.1. BASED ON SYSTEHIC TOXICITY , 9-1
9.2. BASED ON CARCINOGENICITY 9-4
10. REFERENCES 10-1
APPENDIX A A-l
APPENDIX B B-l
APPENDIX C : C-l
APPENDIX D D-l
xv
-------
LIST OF TABLES
No, Title Page
1-1 Synonyms, CAS Numbers. Molecular Weight, Empirical Formula
and Structure of 1,3-Dlchloropropene 1-2
4-1 Acute Toxlclty of 1,3-Dlchloropropene to Aquatic Fauna 4-2
5-1 Rates of Excretion of Radioactivity After Oral
Administration of 1,3-Dlchloropropene '.. 5-7
5-2 Recoveries of Radioactivity from Rats 1n the 4 Days Following
Oral Administration of 1,3-Dlchloropropene 5-8
*
6-1 LDso/LCso Values for Dlchloropropene 6-10
6-2 Incidence of BroncMoloalveolar Adenomas 1n Nice Exposed to
1,3-Dlchloropropene for 24 Months 6-13
6-3 Chronic Oral Exposure to Telone !!• for 2 Years 6-14
6-4 Mutagenlclty of 1,3-Dlchloropropene 6-18
6-5 Testlcular Weights, Sperm Counts and Percent Abnormal Sperm
After IntraperHoneal Injection of 1,3-Qlchloropropene 6-23
9-1 Toxlclty Summary for 1,3-Dlchloropropene 9-2
9-2 Oral Composite Scores for 1,3-Dlchloropropene 9-5
9-3 1,3-Dlchloropropene: Minimum Effective Dose (MED) and
Reportable Quantity (RQ) 9-6
9-4 Derivation of Potency Factor (F) for Inhalation Exposure to
1,3-D1chloropropene 9-8
9-5 Derivation of Potency Factor (F) for Oral Exposure to
1,3-D1chloropropene 9-9
xv1
-------
LIST OF ABBREVIATIONS
AEL Adverse effects level
ALB Albumla
BCF B1oconcentrat1on factor
BOO Biological oxygen demand
BUN Blood urea nitrogen
CBI Confidential Business Information
cc Cubic centimeter
CNS Central nervous system
CS Composite score
EC5Q Concentration effective to 50% of recipients
EDgo Effective dose to 50X of recipients
F Potency factor
F344 Fischer 344
GEMS Graphical Exposure Modeling System
GLU Glutamyl
GMAV Genus mean acute value
GMCV Genus mean chronic value
GPT Glutamlc pyruvlc transamlnase
HCT HematocrH
NEC Human equivalent concentration
HGB Hemoblobln
Koc Soil sorptlon coefficient standardized
with respect to organic carbon
Kow Octanol/water partition coefficient
LC5Q Concentration lethal to SOX of recipients
1059 Dose lethal to SOX of recipients
xv11
-------
LIST OF ABBREVIATIONS (cont.)
LOAEL Lowest-observed-adverse-effect level
LOEC Lowest-observed-effect concentration
NOEC No-observed-effect concentration
NOEL No-observed-effect level
NPS Non-protein sulfhydryl
ppb Parts per billion
ppm Parts per million
RBC Red blood cell
RfD Reference dose
RGDR Regional gas dose ratio
RQ Reportable quantity
RV(j Dose rating value
RVe Effect rating value
TLV Threshold HmH value
THA Time-weighted average
WBC White blood cell
XV111
-------
1. INTRODUCTION
1.1. STRUCTURE AND CAS NUMBER
The structures, CAS Registry numbers, synonyms, molecular weights and
empirical formulas of c1s- and trans-l,3-d1chloropropene are presented In
Table 1-1 with the c1s- and trans-lsomer mixture. Mixtures of the ds- and
trans-1somers are known by Dow Chemical Company trade names Telone, Telone
C, Telone II and Dorlone II (Yang, 1986; Worthing and Walker, 1987).
The Shell Chemical Co. trade name for ^hls mixture Is 0-D92 (Worthing and
Walker, 1987). The trade-named products are not pure 1,3-dlchloropropene but
contain other chlorinated compounds (Section 1.4).
1.2. PHYSICAL AND CHEMICAL PROPERTIES
1,3-Dlchloropropene 1s a colorless liquid with the odor of chloroform
(Wlndholz, 1983). The technical product (92% pure) Is a colorless to amber-
colored liquid with a pungent odor (Worthing and Walker, 1987). 1,3-
Dlchloropropene Is soluble In chloroform, ether, benzene, acetone, carbon
tetrachlorlde, heptane and methanol (Dean, 1985; Worthing and Walker, 1987).
Selected physical properties of els- and trans-l,3-d1chloropropene are as
follows:
Melting point: no data
Boiling point: 104.3°C (c1s-) Yang, 1986
112°C (trans-) Yang, 1986
Specific gravity: 1.224 (c1s-) Yang, 1986
(20/4'C) 1.217 (trans-) Yang, 1986
Water solubility:
at 20°C 2700 ppm (ds-) Dllllng, 1977
2800 ppm (trans-) Dllllng, 1977
Vapor pressure:
at 25'C 43 mm Hg (els-) Ollllng, 1977
34 mm Hg (trans-) DUlIng, 1977
5968H 1-1 07/25/89
-------
TABLE 1-1
Synonyms, CAS Numbers, Molecular Weight, Empirical Formula and
Structure of 1,3-Dichloropropene
Chemical
(Synonyms)"
CAS
Number
Molecular
Weight
Empirical
Formula
Structure
ci s-1,1-Oichloropropene
l-propene, 1,3-dichloro-, (Z)-
cis-l,3-dichloropropyle»e
10061-01-5
110.98
H, Cl,
CL CHt-CL
trans-1.3-Dichloropropene
l-propene, 1,3-dichloro-, (£)-
trans-1,3-dichloropropylene
10061-02-6
110.98
, H, Cl,
CL
CH*CH
CH,-CL
1,3-Dichtoropropene (mixture)
l-propene, 1,3-dichloro-
1,3-dichloropropylene
1,3-dichloropropene, E.Z
alpha-chloroallyl chloride
gaimia-chloroallyl chloride
alpha, gamma-chloroallyl chloride
i
ro
542-75-6
110.98
C3 H,
CL-CH=CH-CHf-CL
"SANSS, 1989
5969H
05/09/69
-------
Log Kow: 1.603 (estimated by U.S. EPA, 1987a
GEMS)
Conversion factor: 1 mg/m3 = 0.217 ppm
(air at 20°C) 1 ppm = 4.614 mg/m3
1,3-Dlchloropropene hydrolyzes In water to form 3-chloroallyl alcohol. The
hydrolysis half-life Is Independent of pH and Is =11.3 days at 20°C
(McCall. 1987).
1.3. PRODUCTION DATA
Current production figures for 1,3-dlchloropropene are not available.
According to the public portion of the U.S. EPA TSCA Production File for
1977 (U.S. EPA, 1977), Dow Chemical Co. (Freeport, TX) manufactured 10-50
million pounds, Shell Chemical Co. manufactured 1-10 million pounds and
Columbia Organic Chemicals manufactured <1000 pounds 1n 1977. Dow Chemical
(Freeport, TX) 1s listed as the sole current producer of 1,3-dlchloropropene
(SRI, 1988).
l,3-D1chloropropene has been produced as a by.-product of ally! chloride
production (Krljgsheld and van der Gen, 1986), which Is accomplished by the
direct chlorlnatlon of propylene (DeBenedlctls, 1979). Other by-products
formed Include 3,3-dlchloropropene and 1,2-dlchloropropane (DeBenedlctls,
1979). By-product mixtures of l,3-d1chloropropene and 1,2-dlchloropropane
have been marketed as a fumlgant under the trade name D-D by Shell Chemical
Co. (Worthing and Walker, 1987; Yang, 1986).
1.4. USE DATA
l,3-D1chloropropene Is used as a soil fumlgant and nematIcicle (Worthing
and Walker, 1987). Several different commercial formulations containing
1,3-d1chloropropene have been marketed as a fumlgant. Telone II
(marketed by Dow Chemical) Is widely used In agriculture as a soil fumlgant
5968H 1-3 07/25/89
-------
for parasitic plant nematodes (Yang, 1986). Originally, Telone II
contained *92X 1,3-dlchloropropene, 2% 1,2-dUhloropropane and 5% other
chlorinated propenes and hexenes with a IX addition of eplchlorohydrln as
stabilizer (Yang, 1986). Currently, Telone II* 1s marketed as 98%
1,3-d1chloropropene with no eplchlorohydrln addition (Albrecht, 1987a). The
fumlgant D-D (marketed by Shell Chemical) contained roughly 50-80% 1,3-dl-
chloropropene and 20-40% 1,2-d1chloropropane with several percent of other
chlorinated compounds (Krljgsheld and^van der-Gen, 1986; Yang, 1986).
Fumlgants marketed under trade names Telone C, Terr-0-C1de and Terr-0-Gas
contained either Telone II or D-D with additions of the pesticide
chloroplcrln (Yang, 1986).
1.5. SUMMARY
1,3-D1chloropropene Is a colorless liquid with the odor of chloroform
(Hlndholz, 1983). It occurs 1n ds- and trans-lsomerlc forms. The
cls-lsomer has a slightly higher vapor pressure than the trans-lsomer (43
versus 34 mm Hg), but the water solubilities are similar (2700-2800 ppm at
20°C) (Dining, 1977). Current production figures for 1,3-d1chloropropene
are not available. According to the public portion of the U.S. EPA TSCA
Production File for 1977, two U.S. manufacturers (Dow and Shell Chemical)
produced a combined total of 10-60 million pounds In 1977 (U.S. EPA, 1977).
1,3-D1chloropropene has been produced as a by-product of allyl chloride
production 1n conjunction with other by-products, such as 3,3-d1chloro-
propene and 1,2-dlchloropropane (Krljgsheld and van der Gen, 1986;
DeBened1ct1s, 1979). By-product mixtures of 1,3-dlchloropropene and
1,2-dlchloropropane have been marketed as a fumlgant under the trade name
D-D by Shell Chemical Co. (Worthing and Walker, 1987; Yang, 1986).
5968H 1-4 07/25/89
-------
1,3-Dichloropropene is used as a soil fumigant and nematlclde (Northing and
Nalker, 1987). Several different commercial formulations containing
1,3-dichloropropene have been marketed as a fumigant. Telone II®
(currently marketed by Dow Chemical) 1s widely used 1n agriculture as a soil
fumigant for parasitic plant nematodes (Yang, 1986; SRI, 1986). Current
Telone II® formulations contain 981 1,3-dichloropropene (Albrecht,
1987a), although original formulations contained only 92% (Yang. 1986).
5968H 1-5 06/21/89
-------
2. ENVIRONMENTAL FATE AND TRANSPORT
2.1. AIR
1,3-Dlchloropropene 1s degraded In the atmosphere primarily by reaction
with photocheroically generated HO*. Reaction with ozone will contribute
to Its destruction at a much slower rate than reaction with HO*. Rate
constants for the reaction of ds- and trans-l,3-d1chloropropene with HO*
have been experimentally determined to be 7.7xlO~1JZ and 13.0xlO~12
cm3/molecule-sec, respectively, at 22'C. Assuming an average atmospheric
HO- concentration of 5xl05 molecules/cm3, the respective els- and
trans- half-lives can be calculated to be 2.1 days and 1.2 days. Rate
constants for the reaction of els- and trans-l,3-d1chloropropene with ozone
have been experimentally determined to be l.SxIO"19 and 6.7xlO~19
cm3/molecule-sec, respectively, at 22°C. Assuming an average atmospheric
ozone concentration of 7X1011 molecules/cm3, the respective c1s- and
trans- half-lives can be calculated to be 67.4 days and 17.1 days. Formyl
chloride and chloroacetaldehyde have been Identified as reaction products of
1,3-dlchloropropene with both HO* and ozone (Tuazon et a!., 1984).
Reaction with ozone also yields chloroacetlc acid formic add, hydrogen
chloride, carbon dioxide and carbon monoxide.
Concentrations of 10 and 2 ng/9. of ds- and trans-1,3-dlchloropropene,
respectively, were detected In rainwater collected 1n Portland, OR In 1982
(Hazurek and S1monett1, 1986). This Indicates that physical removal of
1,3-dlchloropropene from the atmosphere by wet deposition can occur.
2.2. WATER
2.2.1. Hydrolysis. McCall (1987) studied the hydrolysis of "C-radlo-
labeled 1,3-dlchloropropene In sterile buffered water at 10, 20 and 30°C.
The rate of hydrolysis was Independent of pH at pHs 5, 7 and 9 and was
6225H 2-1 07/25/89
-------
essentially Identical for the els- and trans-lsomers. The measured
hydrolysis half-lives at 10, 20 and 30°C were 51. 11.3 and 3.1 days.
respectively. 3-Chloroallyl alcohol was Identified as a hydrolysis product.
2.2.2. Photolysis. Direct photolysis Is not an Important environmental
fate process with respect to 1,3-dlchloropropene (Mabey et al., 1981).
2.2.3. Mlcroblal Degradation. Tabak et al. (1981) used a static-culture
flask-screening procedure utilizing BOD dilution water and settled domestic
wastewater as mlcroblal Inoculum to deiermlne that 1,3-dlchloropropene 1s
significantly biodegradable with gradual mlcroblal adaptation. After a 28-
day Incubat.lon period, 81-89% of Input 1,3-dlchloropropene {5-10 mg/l) was
blodegraded.
2.2.4. Volatilization. The Henry's Law constant for els- and trans-
1,3-dlchloropropene have been measured experimentally to be 0.0012 and
0.0008 atm-ma/mol at 20°C, respectively (Lelstra, 1970). Henry's Law
constants of this magnitude Indicate that volatilization from environmental
waters 1s probably significant (Thomas, 1982). Using a model river estima-
tion method (Thomas, 1982), the volatilization half-lives of els- and
trans-l,3-d1chloropropene from a river 1 meter deep flowing 1 m/sec with a
wind velocity of 3 m/sec can be estimated to be =3.8 and 4.2 hours,
respectively. The volatilization half-lives from a model environmental pond
can be estimated to be =46 and 50 hours (U.S. EPA, 1986b). Based upon
these estimates, volatilization from water Is expected to be a major process
for the removal of 1,3-dlchloropropene from the aquatic environment.
2.2.5. Adsorption. Experimental data pertaining to the adsorption of
1,3-dlchloropropene to aquatic sediments were not located; however, the
water solubilities of 2700-2800 ppm (Dllllng, 1977) suggest that
partitioning from the water column to sediment may not be Important.
6225H 2-2 07/25/89
-------
2.3. SOIL
The fate of 1,3-dichloropropene In soil has been extensively studied.
The Important fate processes In soil are briefly discussed below.
2.3.1. Chemical Degradation. The els- and trans-1somers of 1,3-dichloro-
propene have been observed to hydrolyze In wet soil to form corresponding
els- and trans-3-chloroal1yl alcohol under laboratory conditions (Castro and
Belser, 1966). The rate of hydrolysis was observed to Increase as the soil
content of aqueous solutions was Increased. -Other studies conducted under
laboratory and outdoor conditions have found the 3-chloroallyl alcohol to be
the major degradation product of 1,3-dichloropropene (Roberts and Stoydln,
1976). Degradation of 3-chloroallyl alcohol in soil occurs primarily by
microbial transformation (McCall, 1987). As noted in Section 2.2.1, the
hydrolysis rate of 1,3-dichloropropene .Is strongly dependent upon
temperature. Therefore, the importance of hydrolysis in soil will depend
upon moisture content and temperature. In warm moist soils, hydrolysis
should be relatively rapid and a dominant removal process; however, in dry
or cold soils, the importance of hydrolysis will be diminished.
2.3.2. Microbial Degradation. Although 1,3-dichloropropene 1s susceptible
to degradation by soil microorganisms (Krijgsheld and van der Gen, 1986),
the relative importance of biodegradation in soil has not been determined
with certainty. Experiments specific to 1,3-dichloropropene involving
degradation in nonsterile soil versus control experiments In sterilized soil
are not available. Results of 1,3-dichloropropene transformation experiments
In flower-bulb fields have suggested that microbes In fields previously
exposed to the compound become adapted to 1,3-dichloropropene and are able
to rapidly degrade it at low input concentrations (12 ppm). Half of the
compound degraded in <5 days (van der Pas and Leistra, 1987).
6225H 2-3 06/21/89
-------
2.3.3. Volatilization. Volatilization Is an Important physical removal
process for 1,3-dlchloropropene In soil. The amount of 1,3-dlchloropropene
applied to soil as a fumlgant that volatilizes can vary greatly with
application methods, temperature, moisture content, soil porosity and soil
organic content (Albrecht and Chenchln, 1985). In experiments performed In
Jars to trap escaping vapor, a major portion of the 1,3-dlchloropropene
applied to a soil was observed to evaporate unchanged from the soil and some
degradation of 1,3-dlchloropropene In, soil was detected (Roberts and
Stoydln, 1976). It has also been reported that commercial applications at a
depth of 0.3 m In a warm, moist, sandy loam soil result 1n evaporative
losses of only 5-10 percent (Munnecke and Van Gundy, 1979; Thomas and
McKenry, 1974).
2.3.4. Adsorption/Leaching. 1,3-D1chloropropene can occur 1n soil as a
gas and as an aqueous solution. The adsorption characteristics of each of
these phases Is different. Experimental K values for the els- and
trans-1somers of 1,3-dlchloropropene In aqueous solution are reported to be
23-26 (Kenaga, 1980). These KQC values Indicate high mobility In soil
{Swann et al., 1983} and a significant potential for leaching. Although
leaching In wet soil can occur, concurrent hydrolysis and blodegradatlon
should attenuate the amounts of 1,3-dlchloropropene that may reach ground-
waters. Extensive groundwater monitoring conducted 1n California have
demonstrated that field-applied 1,3-dlchloropropene Is not significantly
contaminating well waters (Maddy et al., 1982; Cohen, 1986).
Vapor-phase 1,3-dlchloropropene Is more strongly adsorbed to soil than
the dissolved chemical (Munnecke and Van Gundy, 1979). Vapor-phase
adsorption has been found to depend partially upon organic content of the
soil and temperature. Adsorption Isotherms Indicate Increasing adsorption
with Increasing organic content. Adsorption at 2°C 1s =3 times higher
6225H 2-4 07/25/89
-------
than adsorption at 20"C. Adsorption Isotherms measured for humous sand,
peaty sand and peat Indicate vapor-phase Koc values of ^450-750
(Lelstra, 1970).
2.3.5. Persistence. The persistence of 1,3-dlchloropropene In soil has
been measured by a number of Investigators, van der Pas and Lelstra (1987)
observed half-lives of 3-4 days 1n fields used for planting flower-bulbs
with only very small amounts remaining after periods £49 days. Lelstra
(1970) reported slower degradation-rates of-0.035/day (half-life of 19.8
days) In a loam soil and 0.01/day (half-life of 69 days) In- sandy and peat
soils. Albrecht (1987a) reported half-lives of 3-25 days at 20°C for ds-
and trans-l,3-d1chloropropene. Twelve weeks after radlolabeled els- and
trans-1,3-d1chloropropene was applied to soils and stored 1n sealed jars,
19% of the cls-isomer and 18% of the trans-i.somer remained in a sandy loam
soil while 10% of the cis-1somer and 22% of the trans-1 somer remained In a
•edlum loam soil (Roberts and Stoydin, 1976).
As noted previously, the removal of 1,3-dlchloropropene from soil can
occur from hydrolysis, microbial degradation and volatilization. Since the
rate of these processes can vary significantly with soil conditions, the
wide range of reported persistence half-lives demonstrates that the
persistence of 1,3-d1chloropropene 1n soil depends upon local conditions.
2.4. SUMMARY
Degradation of 1,3-dlchloropropene in the ambient atmosphere results
primarily by reaction with photochemically generated HO (Tuazon et al.,
1984). Based upon experimentally determined rate constants (Tuazon et al.,
1984), the half-lives for the reaction of ds- and trans-1,3-dlchloropropene
with H0« In air are «2.1 and 1.2 days, respectively. 1,3-Dlchloropro-
pene has been detected In rainwater (Mazurek and Slmonetti, 1986),
6225H 2-5 06/21/89
-------
Indicating that physical removal by wet deposition can occur. Hydrolysis
•
and volatilization are Important environmental fate processes In water. The
rate of hydrolysis has been found to be Independent of pH at pHs 5, 7 and 9
and to be essentially Identical for the els- and trans-1somers. The
measured hydrolysis half-lives at 10, 20 and 30°C were 51, 11.3 and 3.1
days, respectively, with 3-chloroallyl alcohol Identified as a hydrolysis
product (McCall. 1987). Volatilization half-lives of 3.8-4.2 and 46-50
hours have been estimated for a model river (1 m
-------
should attenuate the amounts of 1.3-
-------
3. EXPOSURE
3.1. WATER
1,3-Olchloropropene has been Identified In a very limited number of
drinking waters. It has been qualitatively detected In New Orleans, LA
drinking water collected 1n August 1974 (Dowty et al., 1975; Shackelford and
Keith, 1976). Analysis of 15 drinking water samples from Denver collected
between October 1, 1985 and March 31, 1986 did not detect any els- or
trans-1,3-d1chloropropene at or above detection Tirolts of 0.13 ppb (Rogers
et al., 1987). 1,3-Dlchloropropene was not detected (detection limit 0.1
ppb) In.42 raw and 42 finished drinking water samples collected between July
1982 and May 1983 from nine municipalities along the Great lakes (Otson,
1987).
Trans-1,3-d1chloropropene has been qualitatively Identified In river
water from the Genesee River and Mine Creek, which flow Into Lake Ontario
(Great Lakes Water Quality Board, 1983). Extensive groundwater monitoring
for agricultural chemicals In California has detected cls-1,3-dlchloropro-
pene 1n only two groundwater samples and trans-1,3-dlchloropropene In only
one groundwater sample (Cohen, 1986). By comparison, dlbromochloropropane
(another soil fumlgant) was detected 1n 2522 groundwater samples. In
municipal wells In areas of California where Telone or D-D was applied for
>15 years (54 wells, 65-1200 ft deep), 1,3-dlchloropropene was not
detectable In any sample at the quantification limit of 0.1 ppb (Maddy et
al., 1982). c1s-l,3-01ch1oropropene has been detected In municipal solid
waste leachate from Wisconsin (18 ppb) and In a contaminated ground water
adjacent to a munlclple landfill In Minnesota (Sabel and Clark. 1984). The
preliminary findings of the U.S. EPA Nationwide Urban Runoff Program re-
ported the detection of 1,3-dlchloropropene (1-2 ppb) 1n stormwater runoff
6226H 3-1 07/25/89
-------
from Eugene, OR (Cole et al., 1984). Concentrations of 1-8 ppb
trans-dlchloropropene have been Identified In raw sewage and effluents from
sewage treatment plants (Lao et al., 1982).
It has been suggested that chlorlnatlon of water can lead to the
formation of l,3-d1chloropropene and that the observed presence of 1,3-
dlchloropropene 1n some drinking water samples after treatment may be due to
chlorlnatlon. As an example, the effluent from municipal wastewater
treatment plants was found to contain hJgher amounts of l,3-d1chloropropene
than the Influent wastewater (KMJgsheld and Van der Gen. 1986).
3.2. FOOD
Daft (1988) examined 231 different ready-to-eat foods (collected during
the U.S. Food and Drug Administration's Market Basket Survey) for 22
fumlgants and Industrial residues. 1,3-Dlchloropropene was not detected In
concentrations >1 ppb 1n any of the food samples.
3.3. INHALATION
Atmospheric monitoring data for 1,3-dlchloropropene are limited. 1,3-
Dlchloropropene was detected In 2 of 11 air samples collected In the Baton
3
Rouge, LA area at levels of a trace to 10 ng/m (0.0022 ppb) (PelUzzarl
et al., 1979). A mean dlchloropropene level (Isomers not specified) of
0.071 ppb was detected In 14 air samples collected at source dominated areas
In Texas and Louisiana; source dominated areas are areas where the compound
Is produced or used. Dlchloropropene was not detected (detection limit not
reported) In seven remote air samples from the Grand Canyon (Brodzlnsky and
S1nght 1982).
Albrecht (1987b) studied the Inhalation exposure of l,3-d1chloropropene
In workers Involved In applying Telone II to pineapple fields In
Hawaii. Exposures were predominantly found to be <1 ppm.
6226H 3-2 07/25/89
-------
1,3-Dichloropropene is a volatile compound and after soil application as
a fumlgant, a fraction of the compound will volatilize and escape into the
atmosphere (Krljgsheld and van der Gen, 1986). This 1s probably the major
source of release to the atmosphere.
3.4. DERMAL
Pertinent monitoring data regarding the dermal exposure of 1,3-
dichloropropene were not located in the available literature cited in
Appendix A. Dermal exposure 1s possible to' workers involved in fumlgant
applications of 1,3-dichloropropene.
3.5. SUMMARY
1,3-Dichloropropene has been identified In a very limited number of
drinking waters. It has been qualitatively detected In New Orleans, LA
drinking water collected In August 1974 (Dowty et al., 1975; Shackelford and
Keith, 1976). Monitoring studies conducted in Denver, CO, and in nine
municipalities along the Great Lakes, failed to detect any trace of 1,3-
dlchloropropene (Rogers et al., 1987; Otson, 1987). Extensive groundwater
monitoring for agricultural chemicals in California (including areas where
Telone and D-D had been applied for years) has detected 1,3-d1chloropropene
in only 3 of thousands of samples analyzed (Cohen, 1986; Maddy et al.,
1982). 1,3-Dichloropropene has been detected in leachate from municipal
waste landfills and sewage treatment plants (Sabel and Clark, 1984; Lao et
al., 1982). It has been suggested that chlorination of water can lead to
the formation of 1,3-dichloropropene and that the Identification of
1,3-dichlofopropene In various water samples may be due to chlorination
treatment (Krljgsheld and van der Gen, 1986). Examination of 231 different
ready-to-eat foods (collected during the United States Food and Drug
Administration's Market Basket Survey) for 22 fumigants and industrial
6226H 3-3 06/21/89
-------
residues failed to detect any l,3-d1chloroprppene at a detection limit of
«1 ppb (Daft, 1988). The major source of 1,3-dlchloropropene release to
the atmosphere Is probably volatile losses from soil following soil
application as a fumlgant (Krljgsheld and van der Gen, 1986). Albrecht
(1987b) studied the Inhalation exposure of 1,3-d1chloropropene In workers
Involved 1n applying Telone II to pineapple fields 1n Hawaii and found
exposures to be predominantly <1 ppm.
6226H 3-4 07/25/89
-------
4. ENVIRONMENTAL TOXICOLOGY
4.1. AQUATIC TOXICOLOGY
4.1.1. Acute Toxic Effects on Fauna. Toxic effects from acute exposure to
l,3-d1chloropropene are summarized 1n Table 4-1 for several freshwater and
saltwater species of Invertebrates and vertebrates. Host of the acute
toxldty data show similar sensitivity between the blueglll, Lepj>mU
macrochlrus. and the water flea, Daphnla magna. with LC5_s of 6.15 mg/a
(U.S. EPA, 1978) and 6.20 mg/i (LeBlanc, 1980,- 1984; Buccafusco et al.,
1981). The one exception 1s a very low value (LC5Q = 0.09 mg/8. In j).
magna) reported by Johnson and Flnley (1980). The most sensitive resident
species of fish was the walleye, StVzostedlon vltreum (LC5Q = 1.08 mg/l
(Johnson and Flnley, 1980). Comparable data on the guppy, Poecllla
retlculata. were not located, but the 14-day LC-- value of 4.57 mg/l
(Hermens et al., 1985) was, as would be expected, lower than the shorter-term
acute values for species stated above. It appears that l,3-d1chloropropene
Is more toxic to saltwater than to freshwater Invertebrates, and that mysld
shrimp, Hys1dops1s bahla. with an LC,n of 0.79 mg/l, (U.S.EPA, 1978;
ijU
LeBlanc, 1984), are affected by lower concentrations of 1,3-d1chloropropene
than are sheepshead minnows, CyprlngdQn varlegatus (1.77-1.80 mg/l, U.S.
EPA, 1978; He Urdu Her et al., 1981).
4.1.2. Chronic Effects on Fauna.
4.1.2.1. TOXICITY -- Chronic toxldty data have been reported for the
fathead minnow, Plmephales promelas. and mysld shrimp, Hysldopsls bahlj (U.S.
EPA, 1978). An embryolarval test of the toxldty of 1,3-dlchloropropene to
fathead minnows revealed a NOEC of 180 yg/l and a LOEC of 330 yg/l.
Chronic toxldty data on saltwater fauna are limited to a life-cycle study
6227H 4-1 07/25/89
-------
Acute Toxicity of 1,3-Dichloropropene to Aquatic Fauna
Species
F reshwater fauna
Daphp j a magna
Q. magna
b. magna
Pimeohales
promelas
lepomi s
macrochirus
L- macrochirus
"^ t'etroinvzon
«"»> mar i mis
Sal mo gairdneri
Microotertis
sal mo ides
vitreum v i treum
Poecilla
Ld_us idu&
melanotus*
Common Name
water flea
water flea
water flea
fathead
minnow
bluegill
bluegill
1 anprey
(larvae)
rainbow trout
larqemonth
bass
walleye
guppy
golden orfe
Test Type
NR
static acute
static acute
static acute
NR
static acute
NR
static acute
static acute
static acute
static, renewal
static acute
Du ra t i on/Endpo i n t
48-hour EC ;,„
48-hour ECr.0
48-hour EC so
96-hour LCio
96-hour LC^o
96-hour LC50
24 hours
96-hour LCi0
96-hour LCso
96-hour LCSO
14-day LC50
96-hour LCSO
Concentration,
(95% Confidence Limits)
(tng/e)
6.15 (4.33-8.99)
6.20 (4.3-9.0)
0.09 (0.063-0.13)
4.10 (3.29-4.47)
6.06 (5.14-6.82)
6.10 (5.1-6.8)
NR
5.90
3.65 (3.52-3.78)
1.08 (0.99-1.18)
4.57 (NR)
0.9 (0.8-1.1)
Temperature
NR
22±1
NR
NR
NR
22±1
NR
NR
NR
NR
NR
20
No Effect Level
(mg/e)
0.41
0.41
NR
NR
<3.6
Nft
5.0
NR
NR
NR
NR
0.63
Reference
U.S. EPA. 1978;
LeBlanc. 1984
LeBlanc, 1980
Johnson and
Finley, 1980
Johnson and
Finley, 1980
U.S. EPA, 1978;
LeBlanc, 1984
Buccafusco et
al., 1981
Applegate et
al., 1957
Schneider, 1979
Johnson and
Finley. 1980
Johnson and
Finley. 1980
Hermens et al . ,
1985
Reiff, 1978
6149H
06/26/89
-------
4-T (cont.)
Species
Mixed group of
Ni tropis,
atherinoide.s.
and
P. oromelas
Saltwater fauna
Mysidopsis
bahia
Cyprinodon
varieoatus
£. Varieqatus
Common Name
emerald shiner
fathead minnow
mysid shrimp
sheepshead
mi nnow
sheepshead
minnow
Test Type
NR
NR
static acute
static acute
static acute
Duration/Endpoint
3-day 100% lethality
3-day 0% lethality
96-hour LC5(>
96-hour LC.,0
96-hour LCio
Concentration
(95% Confidence Limits)
(mg/tf)
NR
0.79 (0.62-0.98)
1.77 (0.71-4.49)
1.80 (0.7-4.5)
Temperature
CO
NR
NR
NR
25-31
No Effect Level Reference
(mq/e)
NR Scott and
Wolf. 1962
0.37 U.S. EPA, 1978;
LeBlanc, 1984
<1.22 U.S. EPA, 1978;
LeBlanc. 1984
1.2 Heitmuller et
al.. 1981
"Not a resident of U.S. waters
NR - Not reported
6149H
06/26/89
-------
mysld shrimp, Hysldopsls bahla. 1n which a NOEC of 2200 yg/l and a LOEC
of 4200 ug/l were reported (U.S. EPA, 1978).
The effects of the pesticide. Shell -DD, on rhythmic adductor muscle
activity of the freshwater mussel, Anodonta cygnea. were Investigated by
Varanka (1979). Shell-DD, which contains two active Ingredients (1,3-
dlchloropropene and 1,2-dlchloropropane), caused 50% Inhibition of the
tryptamlne-lnduced activity at a concentration of 2xlO~2 mi test com-
pound/a. water. The concentration of 1,3^1 chloropropene was not reported.
4.1.2.2. B1oaccumulat1on/B1oconcentrat1on -- Pertinent data regarding
the bloaccumulatlon/bloconcentratlon potential of 1,3-dlchloropropene In
aquatic fauna were not located In the available literature cited In Appendix
A. Predicted bloconcentratlon factors of 7 (based on water solubility) and
1 (based on octanol/water partition coefficients) calculated for
1,3-dlchloropropene by Kenaga (1980) suggest that this compound will not be
accumulated by aquatic organisms.
4.1.3. Effects on Flora.
4.1.3.1. TOXICITY -- Toxlclty of 1 ,3-dlchloropropene to aquatic plants
has been reported for one freshwater alga and one saltwater alga. A 96-hour
EC5Q of 4950 jig/8. was determined for Selenastrum caprlcornutum (U.S.
EPA, 1978; LeBlanc, 1984). In this same species, a 96-hour EC5Q (reduced
cell division) of 4960 pg/i was reported In the same study.
The saltwater alga, Skeletonema CQitaJum. has a 96-hour EC5Q of 1000
when treated with 1,3-dlchloropropene (U.S. EPA, 1978; LeBlanc,
1984). The 96-hour EC5Q for cell division 1n this same species was
reported as 1040 vq/l by the U.S. EPA (1978).
6227H 4-4 07/25/89
-------
4.1,3.2. BIOCONCENTRATION -- Pertinent data on the bloconcentratlon
potential of 1,3-dichloropropene In aquatic flora were not located 1n the
available literature cited in Appendix A.
4.1.4. Effects on Bacteria. Scott and Wolf (1962) examined the anti-
bacterial activity of 1,3-dichloropropene 1n dilute aqueous solutions and
found that 40% aqueous solutions lost much of their antimicrobial activity
when stored at room temperature for 90 days. The same products In the solid
state were stable at storage temperatures of <40°C for >90 days.
Concentrations of 0.50% 1,3-dlchloropropene killed samples of Aerobacter sj>.
1n 21 hours, and 1.07. concentrations killed Pseudomonas s_£. In 21 hours.
These lethal concentrations are considerably higher than those that are
lethal to higher aquatic species.
4.2. TERRESTRIAL TOXICOLOGY
4.2.1. Effects on Fauna. Abivardi (1970) tested the nematocidal effects of
solutions of two commercial nematicides, 1,3-D and Telone (content of
1,3-dichloropropene not reported) under controlled laboratory conditions.
Half-cc samples of 400, 800 and 1200 ppm active material in water and
containing 50 active larvae of Pratylenchus hamatus and Tylenchulus
semipenetrans were added to spot plates covered for 24 hours and then
examined. Mortality was- 100%.
4.2.2. Effects on Flora. Toxlclty of the commercial product, 1,3-D (98%
1,3-dichloropropene) to mlcrosclerotia of the fungus, Verticil 11 urn dahliae.
was tested by Ben-Yephet et al. (1981) in sealed containers of air and soil.
A concentration of 20 \>.q/m£ 1.3-0 1n air killed 100% of the mlcro-
sclerotia after 30 hours Incubation, and 100 yg/g 1,3-D Induced total
lethality of the organism 1n soil Incubated for 3 days.
6227H 4-5 06/21/89
-------
4.3. FIELD STUDIES
Edwards and Relchle (1969) applied the soil fumlgant, dlchloropropene,
D-D (concentration of dlchloropropene not reported) In an Ui sVtu field
experiment on soil systems. Approximately 170 cc/m2 of D-D was applied to
a plot of soil with an Injection gun; the soil was then covered with plastic
sheeting for 2 weeks. D-D fumigation eliminated the earthworm, Lumbrlcus
terrestMs. and reduced the mlcroarthropod population (Dlpter and Coleopter
larvae) by 98.3%. Costante et al. _(1987) Injected Telope C-17 (74%
1,3-dlchloropropene and 16.5% chloroplcMn) Into soil at 374 8,/hectare and
noted significantly reduced populations of Pratylenchus penetrans after 50
and 156 days posttreatment. Another report describing the nematlcldal
activity of DO, a commercial pesticide containing 1,3-dlchloropropene, was
located, but the percentage of active Ingredient was not quantified (Blackmon
and Musen, 1974).
Kotcon and Lor la (1987) applied a fumlgant containing 94% 1,3-dlchloro-
propene at 0, 94, 117 or 140 l of formulated compound/hectare to plots in
two commercial potato fields and noted significant reduction of nematodes,
Pratylenchus crenatus. within 2 weeks at all levels of treatment. Mortality
was <96% with application of 140 l/ha.
Hathur et al. (1980) tested two commercial products that contain
1,3-dlchloropropene, Telone II and Telone C17, on organic field plots of
carrots and noted Increased numbers of fungi, bacteria and acUnomycetes
between 0 and 28 days. The concentration of 1,3-dlchloropropene applied to
these plots was not reported, however.
Cook et al. (1987) tested the funglcldal properties of 1,3-dlchloropro-
pene combined with 17% chloroplcrln In wheat field plots and noted 95-100%
6227H 4-6 07/25/89
-------
elimination of Inoculum (population of Pythlum spp. at start of test was >300
propagules/gram of soil).
4.4. AQUATIC RISK ASSESSMENT
The lack of pertinent data regarding the effects of exposure of aquatic
fauna and flora to 1,3-dlchloropropene precluded the development of a
freshwater criterion (U.S. EPA/OWRS, 1986) (Figure 4-1). Available data
Indicate that acute toxic effects can occur at concentrations >1.08 mg/l In
freshwater, and that chronic effects ..can occur at concentrations >0.33
mg/l. Additional data required for the development of a freshwater
criterion Includes the results of acute assays with benthlc crustaceans, an
Insect, a nonarthropod and nonchordate species and an Insect or species from
a phylum not previously represented. The development of a freshwater
criterion also requires data from chronic toxldty tests with two species of
fauna and at least one bloconcentratlon study.
The lack of pertinent data regarding the effects of exposure of aquatic
fauna and flora to l,3-d1chloropropene precluded the development of a
saltwater criterion (U.S. EPA/OWRS, 1986) (Figure 4-2). Available data
Indicate that acute toxic effects can occur at concentrations >0.79 mg/i,
and chronic toxic effects at concentrations >4.20 mg/s.. Additional data
required for the development of a saltwater criterion Include the results of
acute assays with one chordate species a nonarthropod and nonchordate
species, two additional nonchordate species, and one other species of marine
fauna. The development of a saltwater criterion also requires data from
chronic toxlclty tests with two species of fauna and at least one
bloconcentratlon study.
6227H 4-7 07/25/89
-------
Farni ly
#1
Chordate (Salrnonid-f ish)
Chord ate (warrnwater fish)
#3
Chordate
-------
Fami ly
#1
Chordate
#£
Chordate
#3
riori— flrthropod/— Chordate
Crustacean (Mysid/Panaeid)
#5
non— Chordate
#6
non-Chordate
#7
non-Chordat e
#8
other
#9
algae
#10
Vascular plant
TEST TYPE
GMflV GMCV*
1 . 76» Nfl
Nfl Nfl
Nfl Nfl
0.79- £. SO*
Nfl Nfl
Nfl Nfl
Nfl Nfl
Nfl Nfl
XXXXXXXXXXXX
XXXXXXXXXXXX l.O«
XXXXXXXXXXXX
XXXXXXXXXXXX Nfl
BCF«
Nfl
Nfl
Nfl
Nfl
Nfl
Nfl
Nfl
Nft
Nfl
Nfl
•NA-Not available; "mean 96-hour LC,0 for sheepshead minnow, Cyprln-
odon varleqatus: e96-nour LC50 for mysld shrimp, Mysldopsls bahla;
TTfe-cycle NOEC for mysld shrimp, M. bahla: e96-houf~EC50 for the
alga, Skeletonema costatum. based on chlorophyl a content.
FIGURE 4-2.
Organization Chart For Listing GMAVs, GMCVs And BCFs Required To Derive
Numerical Hater Quality Criteria By The Method Of U.S. EPA/OWRS (1986) To
Protect Saltwater Aquatic Life From Exposure To 1,3-D1chloropropene
6227H
4-9
06/26/89
-------
4.5. SUMMARY
Data are available on the acute toxlcUy of 1,3-dlchloropropene to
several species of Invertebrates and vertebrates. As shown 1n Table 4-1,
96-hour LC5Q values reveal a similar range of sensitivity among six
freshwater fish species native to U.S. waters (Applegate et al., 1957;
Buccafusco et al., 1981; Hermens et al., 1985; Johnson and Flnley, 1980;
LeBlanc, 1984; Schneider, 1979; U.S. EPA, 1978). A seventh species, the
walleye, j>. yltreum vltreum. showed markedly greater sensitivity, with a
96-hour LC50 of 1.08 ppm. The water flea, EL magna. (Leblanc, 1980, 1984;
U.S. EPA, 1978) showed a sensitivity comparable with that of the blueglll
sunflsh, L. macrochlrus. the least sensitive of the freshwater fish species
tested {Buccafusco, 1981; LeBlanc, 1984; U.S. EPA, 1978). 1,3-dlchloropro-
pene Is more acutely toxic to the saltwater Invertebrate, M. bah la (LeBlanc,
1984; U.S. EPA, 1978), than to the freshwater species, D. magna. The
sheepshead minnow, £. varlegatus. a saltwater fish, 1s highly sensitive to
1,3-dlchloropropene (mean 96-hour LC™ = 1.76 ppm) (LeBlanc, 1984).
Chronic toxlclty tests of 1,3-dlchloropropene to the fathead minnow, £.
promelas. and mysld shrimp, H_.. bahla. revealed NOECs of 0.18 ppm and 4.2
ppm, respectively (U.S. EPA, 1978).
Data regarding the toxlclty of 1,3-dlchloropropene to aquatic flora
follow a similar pattern to that for aquatic fauna. The saltwater alga, S.
costatum. has a mean 96-hour EC50 of 1.01 ppm (LeBlanc, 1984; U.S. EPA.
1978); the freshwater alga, S. caprlcornutum. has a mean 96-hour EC5Q of
4.95 ppm (LeBlanc, 1984; U.S. EPA, 1978). Data on effects of 1,3-dlchloro-
propene on bacteria Indicate that Aerobacter s_£. and Pseudomonas sj>. are
more resistant to the compound than are higher aquatic species reported
above.
6227H 4-10 07/25/89
-------
Studies on the bloconcentratlon/bloaccumulatlon potential of 1,3-dlchlo-
ropropene 1n aquatic fauna and flora were not located In the available
literature, but BCFs of 7 (based on water solubility) and 1 (based on KQW)
were predicted for this compound by Kenaga (1980).
Data support 1,3-dlchloropropene1s effectiveness as a nematodde
(Ablvardl, 1970; Blackmon and Musen, 1974; Costante et a!., 1987, Kotcon and
Lorla, 1987) and Us toxldty to the earthworm, Lumbrlcus terrestrls. and to
Dlpter and Coleopter larvae (Edwards andJtelchle, 1969).
Data regarding the effectiveness of 1,3-dlchloropropene for control of
soil microorganisms are equivocal. Nathur et al. (1980) noted Increased
numbers of fungi, bacteria and actlnomycetes after treating field plots with
the chemical, but Cook et al. (1987) noted 95-100% elimination of a
population of Pythlum spp. with 1,3-dlchloropropene.
The lack of pertinent data regarding effects of exposure of aquatic
fauna and flora to 1,3-dlchloropropene prevented the development of
freshwater or saltwater criteria.
6227H 4-11 07/25/89
-------
5. PHARHACOKINETICS
5.1. ABSORPTION
The absorption of 1,3-dlchloropropene during head-only Inhalation
exposure to 30, 90, 300 or 900 ppm (49.3% ds- and 42.8% trans-l,3-d1chloro-
propene and =8 minor contaminants) for 3 hours was determined In male F344
rats (Stott and Kastl, 1986). The average amounts of 1,3-d1chloropropene
absorbed by the rats exposed to 30, 90, 300 and 900 ppm were =14 mg/kg (82%
of the available vapors absorbed), 29 -mg/kg (65% absorbed), 85 mg/kg (66%
absorbed) and 171 mg/kg (62% absorbed), respectively. -The rate of absorption
1s calculated to be 144, 307, 880 and 1810 nmol/mln for the 30, 90, 300 and
900 ppm exposure levels, respectively. The nonllnearlty In absorption rate
and absorbed dose with Increasing concentration may have been due to a
concentration-related decrease 1n the respiratory ventHatory frequency In
rats exposed to >90 ppm and to the saturation of metabolism of the compound
1n rats exposed to >300 ppm. As determined 1n Isolated upper and lower
respiratory tracts from rats exposed to 90 or 150 ppm, absorption occurred
mainly through the lower respiratory tract (calculated to be =73 and 79% of
the total amount absorbed at 90 and 150 ppm, respectively). A small amount
was also absorbed by the nasal mucosa. Blood levels of 1,3-dlchloropropene
suggested that 1,3-dlchloropropene 1n the blood reached a steady state with
both the els- and trans-1somers within 60 minutes of exposure at 30 and 90
ppm and within 2 hours at 300 ppm and within =3 hours at 900 ppm.
Hutson et al. (1971) treated Carworth Farm E rats by gavage with c1s- or
trans-l,3-d1chloro(2l4C)propene In arachls oil at doses of =11.2 or 12
mg/kg, respectively. After 24 hours, =80-84% of the administered radio-
activity from either Isomer was excreted In the urine or as 14CO?,
Indicating that >80% of the dose was absorbed by the gastrointestinal tract.
6228H 5-1 7/25/89
-------
Similar results were obtained by Cllmle et al. (1979) In rats and by D1etz et
al. (1985) (Sections 5.3 and 5.4). Absorption through the skin of rabbits
occurred when 1,3-dlchloropropene was applied In propylene glycol solution or
when evaporation was retarded with a cuff (Torkelson and Oyen, 1977;
Torkelson and Rowe, 1981).
5.2. DISTRIBUTION
The relationship between Inhaled 1,3-dlchloropropene and the tissue
levels of reduced glutathlone, which Indicates i,3-dlchloropropene metabo-
lism, was assessed (Fisher and Kllgore, 1988a; Fisher, 1988). The gluta-
thlone content was measured 1n the heart, kidney, liver, lung, nasal mucosa
and testes of male Sprague-Dawley rats exposed to 0, 1.8, 4.5, 33, 306.1,
771.8, 954.6 or 1716 ppm Telone II (94% 1,3-dlchloropropene with
approximately equal concentrations of the els- and trans-lsomers and
epoxldlzed soybean oil as the stabilizing agent) for 1 hour. The decrease 1n
glutathlone was exposure-related. At the 4.5 ppm level, a decrease was
observed In the nasal mucosa. Liver glutathlone was depleted In an exposure-
related manner at levels >306 ppm. At exposures <955 ppm, the content of
lung glutathlone remained relatively constant at =75% of control levels.
Only at 1716 ppm did the glutathlone content significantly decrease In the
heart, liver and testes. No 1,3-dlchloropropene was detected In the blood of
animals 2 hours after exposure to <955 ppm. These data Indicate that a
substantial portion of the Inhaled 1,3-dlchloropropene Is metabolized to a
glutathlone conjugate In the nasal mucosa and 1s subsequently transported to
the blood.
D1etz et al. (1985) measured the NFS (the majority of which 1s gluta-
thlone} content of tissues and covalent binding to macromolecules of the
forestomach, glandular stomach, liver, kidney and urinary bladder of rodents
6228H 5-2 7/25/89
-------
treated wHh l,3-d1chloropropene. Hale F344 rats and male B6C3F1 mice were
fed a single oral dose of 14C-l,3-d1chloropropene. For the NFS studies,
the doses were 0, 1, 5, 25, 50 or 100 mg/kg; for binding studies, doses were
0, 1, 50 or 100 mg/kg. Significant depletion of NPS levels occurred In the
forestomach of rats and mice at >25 mg/kg, with a depletion range of 17-51%
of control values. NPS levels In the glandular stomach and liver were also
depleted In a dose-dependent manner but at a less severe level. Limited
macromolecular binding was noted In the. liver, kidneys and urinary bladder,
and was greatest at doses that caused the most depletion of tissue NPS In the
forestomach and glandular stomach. These results also Indicate that a
substantial conjugation occurs In the stomach after oral dosing and before
distribution to other tissues.
Dletz et al. (1985) fed a single oral dose of 1 or 50 mg/kg
14C-ds,trans-l,3-d1chloropropene to male F344 rats and 1 or 100 mg/kg to
male B6C3F1 mice. Urine, feces and expired air were collected for 48 hours
after dosing, and the rats were then sacrificed. The tissues and the carcass
were analyzed for remaining radioactivity. Only 2-6% of the administered
dose remained In the carcasses of both species 48 hours after dosing. Host
of the radioactivity was excreted 1n the urine, feces and expired air
(Section 5.4). Similarly, Hutson et al. (1971) found <5X of the administered
oral dose of 11.2 or 12 mg/kg 1,3-d1chloro(214C)propene 1n the gut, feces
and skin and carcass 4 days after dosing.
5.3. METABOLISM
Hutson et al. (1971) administered =11.2 or 12 mg/kg of els- or
trans-l,3-d1chloro(214C)propene, respectively, to rats by gavage and found
differences In metabolism between the Isomers (see Section 5.1). In the
first 24 hours, 80-90% of the radioactivity dose was eliminated. Most of the
6228H 5-3 7/25/89
-------
radioactivity was excreted In the urine; 80.7% of the radioactivity from
ds-l,3-d1chloropropene and 56. 5X from trans-l,3-d1chloropropene was
recovered from urine within the first 24 hours. The amount of 14C02
excreted was different for the two Isomers; 3.9 and 23.6% of the dose from
the 14C-c1s- and trans-lsomers, respectively, were excreted as ^CO^
within 4 days. A small amount of l,3-d1chloropropene was exhaled unchanged
When rates of degradation of the trans-lsomer and the cH-1somer were
compared J[n vitro, the ds-1somer degraded 4-5 times faster than the
trans-lsomer, with absolute rates of 4.9 and 1.0 nmol/mlnute/mg cytosol for
els- and trans-lsomers, respectively (Cllmle et a!., 1979).
Two female Wlstar rats were given a single oral dose of cls-1 ,3-dlchlo-
ro(214C}propene of 20 mg/kg body weight In corn oil (Cllmle et a!., 1979).
Eighty-two to 84% of the radioactivity appeared In the urine within 24 hours
after treatment. Host of the urinary radioactivity (92%) was present as
N-acetyl-S-[c1s-3-chloroprop-2-enyl] cystelne (ds- dlchloropropene mercap-
turlc add or 3C-NAC), as determined by comparative chromatography procedures.
When cls-dlchloropropene (O.lmH) was Incubated at 37°C in vitro with rat
liver supernatant (3.55 mg protein/ml) containing glutathlone S-alkyl
transferase and added glutathlone (5 mM), no substrate remained after 10
minutes (Cllmle et al., 1979). When glutathlone was omitted, 72% of the
substrate was recovered. Therefore, It appears that the rapid urinary
elimination of radioactivity from rats given cls-1 ,3-d1chloro(14C)propene
Is due to an efficient glutathlone-dependent b1otransformat1on. The compound
conjugates with glutathlone, enters the mercapturlc acid pathway and Is
excreted In the urine as N-acetyl-S-(3-chloroprop-2-enyl ) cystelne, 3C-NAC.
6228H 5-4 7/25/89
-------
Studies done by Fisher (Fisher, 1988; Fisher and Kllgore, 1988a) (see Section
5.2) Indicated that, following Inhalation exposure, a substantial amount of
l,3-d1chloropropene was metabolized to the less toxic glutathlone conjugate
1n the nasal mucosa, was transported to the bloodstream and was subsequently
degraded to the mercapturlc acid form and excreted 1n the urine.
5.4. EXCRETION
In a previously described study (see Section 5.1), Stott and Kastl (1986)
determined that, following Inhalation in rats of 30, 90, 300 or 900 ppm
1,3-dlchloropropene, both the els- and trans-1somers were rapidly eliminated
from the blood 1n a blphaslc manner 1n rats exposed to <300 ppm. The rapid
elimination phase had a half-life of 3-6 minutes, and the slower elimination
phase had a half-life of 33-43 minutes. In rats exposed to 900 ppm,
1,3-dlchloropropene was also eliminated blphaslcally, but the Initial phase
was longer, with a half-life of 14-27 minutes.
Fisher and Kllgore (1988b) determined the relationship between the
concentration of Inhaled 1,3-dlchloropropene (Telone II -94% 1,3-dl-
chloropropene In approximately equal concentrations of the els- and trans-
Isomers, stabilized by epoxldlzed soybean oil) and the urinary excretion of
the mercapturlc acid of ds-l,3-d1chloropropene In male Sprague-Dawley rats.
The rats were exposed for <1 hour to 0, 284, 398 or 789 ppm and urine was
collected for <24 hours after exposure. The quantity of the mercapturlc acid
found In the urine was concentration-dependent from 0-284 ppm, but the amount
did not Increase at the 398 or 789 ppm exposure levels. It was postulated
that the nonllnearlty at the higher concentrations may be a result of changes
1n the absorption of 1,3-dlchloropropene, which are due to altered
respiration rates at the higher levels. Stott and Kastl (1986) found that
absorption of 1,3-dlchloropropene was not linear with Increasing exposure
6228H 5-5 7/25/89
-------
concentrations because of decrease In the respiratory ventilation frequency
that are exposure-related, and to the saturation of metabolism of
1,3-dlchloropropene (see Section 5.1). Osterloh et al. (1984) monitored the
quantity of the mercaptuHc add found 1n the 24-hour urine collections of
agricultural workers exposed to 1,3-dlchloropropene (=0.4 ppm for 3 hours).
A linear relationship was found between exposure to 1,3-dlchloropropene (the
product of airborne concentrations and duration of exposure) and excretion of
the metabolite, 3C-NAC (see Section 5.J3.). The. amount of the metabolite
excreted 1n the urine by the rats (exposed to a high concentration for a
short period of time) In the Fisher and Kllgore (1988b) study (2-59 jimol
3C-NAC/24 hours) was similar to the amount excreted by agricultural workers
(exposed to a low concentration for a longer period of time) In the Osterloh
et al. (1984) study (4-36 ymol 3C-NAC/24 hours).
In the previously described study by Hutson et al. (1971) {see Section
5.1), the excretion by rats of radioactivity as a percentage of the adminis-
tered oral dose of 11.2 mg/kg or 12 mg/kg of ds- or trans-1,3~d1chlo-
ro(214C)propene, respectively, was determined for urine, feces and expired
air. Measurements were taken at 24-hour Intervals over a 4-day period. The
animals were sacrificed after the fourth day following the administration of
the labeled compounds, and radioactivity remaining In the carcasses was
measured. Excretion data are summarized In Tables 5-1 and 5-2. As seen from
Table 5-1, most of the radioactivity was excreted In the urine; =80% and
55X of administered dose of els- and trans-1,3-dlchloropropene, respectively,
was eliminated during the first 24 hours.
When oral doses of 14C-c1s or trans-1,3-dlchloropropene were given to
male F344 rats (1 or 50 mg/kg) and to male B6C3F1 mice (1 or 100 mg/kg),
urinary excretion was the major route of elimination after 48 hours (Dletz et
6228H 5-6 7/25/89
-------
T&RI F *_1
Rates of Excretion of Radioactivity After Oral
Administration of 1,3-D1chloropropene
U1
-J
Excretion of Radioactivity (1 of administered dose) In 24-Hour
Periods (hour after administration)"
Compound
cls-1 ,3-D1ch1oropropene
trans-1 ,
3-Dtchloropropene
cls-1 ,3-D1chloropropene
trans-1 ,
3-D1ch1oropropene
Sex
M
F
M
f
M
F
M
F
0-24
81.3+2.76
80.3+5.34
54.6+1.92
58.7+1.08
2.0+0.38
1.4+0.43
1.3+0.37
1.9+0.24
24-48
Urine
1.9+0.21
1.2+0.29
0.6+0.06
1.1+0.16
Feces
0.8+0.28
0.2+0.04
0.2+0.11
0.2+0.10
48-72
0.6+0.14
0.4+0.23
0.3+0.04
0.5+0.13
0.3+0.14
0.1+0.03
0.4+0.15
0.2+0.10
72-96
0.3+0.06
0.4+0.23
O.M+0.02
0.2+0.09
• 0.2+0.08
0.1+0.05
0.1+0.05
0.1+0.02
Total
(0- to 96-hour)
84.1+2.94
82.3+5.18
55.6+1.90
60.5+1.00
•
3.3+0.53
1.8+0.42
2.0+0.28
2.4+0.26
"Source: Hutson et al., 1971
"The values given are the means + SEM for groups of six rats
6138H
06/26/89
-------
TABLE 5-2
Recoveries of Radioactivity from Rats in the 4 Days Following
Oral Administration of 1,3-Dichloropropene
Compound Sex
i is-l ,3-Dichloropropene H
F
( rdiis-1 ,3-Oichloropropene H
L/l F
»
Recovery of
Urine
84.0*2.94
82.3*5.18
55-6*1.90
60.4*1.00
Radioactivity 1% of Administered Dose in 4 Davsb
Feces
3.3*0.53
1.8*0.42
2.1*0.28
2.3*0.26
Gut
0.1*0.01
0.1*0.02
0.2*0.10
0.1*0.01
Skin
0.5*0.09
0.5*0.07
0.6*0.07
0.5*0.13
Carcass
0.8*0.06
0.5*0.02
1.1*0.11
0.9*0.11
Exhaled Air
Carbon
Dioxide0
5.3 (3)
2.4 <3)
22.7 (3)
24.4 (3)
Other
Volatile
Radio-
activity6
NR
1.4 (2)
NR
•3.5 (2)
Total Radioactivity Recovered
(% of Administered Dose)
Less
Volatile
Radio-
activity
88.7*4.27
85.2*4.27
59.6*2.57
64.2*1.01
Including
Volatile
Rad i o-
activity
NR
89.0
NR
92.1
'Source: Hutson et al.. 1971
txtept where indicated otherwise, values given are the means * SEN for groups of six rats.
'Values given are means for the numbers of animals indicated in parentheses.
HK =: Not reported
6139H
06/20/89
-------
al., 1985}. In rats, 51-61% of the dose was excreted In the urine; In mice,
63-79%. Approximately 18 and 6X, respectively, of the administered radio-
activity was excreted In feces and as expired 14C02 In rats, and 15 and
14%, respectively, In mice. After 48 hours, only 2-6% of the original dose
remained In the carcasses. Major metabolites were the mercapturlc acid
conjugate and the sulfoxlde or sulfone derivative of N-acetyl-S-{3-ch1oro-
prop-2-enyl) cystelne.
5.5. SUMMARY
Approximately 80% of the administered dose of 1,3-dlchloropropene was
absorbed Into the body following Inhalation or oral exposure (Stott and
Kastl, 1986; Hutson et al., 1971). As the Inhaled concentration of 1,3-dl-
chloropropene Increased, the absorption did not Increase linearly because of
exposure level-related decreases In respiratory ventllatory frequency and to
saturation of the metabolism of 1,3-dlchloropropene (see Section 5.1).
1,3-Olchloropropene was rapidly eliminated from the body, primarily In the
urine as N-acetyl-S-(3-chloroprop-2-enyl) cystelne, following Inhalation or
oral exposure {Hutson et al., 1971; CUmle et al., 1979; D1etz et al., 1985;
1988b . 1,3-Olchloropropene
t blotransformatlon:
the mercapturlc add
3-chloroprop-2-enyl)
d the trans-lsomers.
n the blood of rats
itratlons of the two
>f the els- than the
ater amounts of the
7/25/89
-------
trans-isomer were excreted as C02 tn the expired breath (Hutson et al.,
1971).
Distinct differences exist In the elimination of 1,3-d1chloropropene
between rats and mice. Following oral dosing with '4C-l,3-d1chloropropene,
more of the administered dose of radioactivity was excreted In the urine and
expired air of mice than of rats (Dietz et al., 1985). The rate of urinary
excretion of the mercapturlc acid of 1,3-dlchloropropene was comparable
between rats (Fisher and Kllgore, 1988b) and humans (Osterloh et al., 1984).
6228H 5-10 6/20/89
-------
6. EFFECTS
6.1. SYSTEMIC TOXICITY
4
6.1.1. Inhalation Exposure.
6.1.1.1. SUBCHRONIC — Stott et al. (1988) exposed male and female F344
rats and B6C3F1 mice (10/sex/exposure level) to 0, 10, 30, 90 or 150 ppm of
technical grade 1,3-dlchloropropene (48.6% cls-1,3-dlchloropropene, 42.3%
1,3-dlchloropropene, 2.4% 1,2-d1chloropropane and 1.2% eplchlorohydrln and
mixed Isomers of chlorohexane, chloroliexene and trlchloropropene) for 6
hours/day, 5 days/week for 13 weeks. The animals were observed for clinical
signs of toxlclty and body weight changes. Hematologlcal, clinical chemistry
and urlnalysls determinations were conducted at the end of the study. All
surviving animals underwent gross necropsy. Comprehensive hlstologlcal
examination was limited to high-dose and control animals and those animals
that died before scheduled sacrifice. Selected tissues were examined
ilstologlcally In the other groups. Significantly decreased body weight
'3aIn was observed 1n both sexes of rats and mice treated at >90 ppm.
Degenerative changes or hyperplasla In the nasal mucosa were observed In
almost all animals of both sexes of rats and mice exposed to >90 ppm and In
;i/10 male rats exposed to 30 ppm. Respiratory metaplasia of the damaged
portions of the olfactory region of the mucosa was found 1n both sexes of
mice In the high exposure group. This effect Involved the replacement of the
damaged sensory olfactory epithelium with normal-appearing, ciliated,
respiratory-type epithelium. Hyperplasla of the urinary bladder transitional
epithelium was found 1n most female mice exposed to 90 or ISO ppm of the
vapor, but not In male mice or In rats. No treatment-related effects were
observed 1n male rats exposed to 10 ppm 1,3-dlchloropropene and In female
rats or male and female mice exposed to 30 ppm of the vapor.
6229H 6-1 07/25/89
-------
Coate et al. (1979) exposed groups of 10 male and 10 female F344 rats and
10 male and 10 female CD-I mice to 0, 12, 32 or 93 ppm of Telone II (47%
ds- and 45% trans-1,3-dlchloropropene, 8% related compounds) for 7 hours/
day, 5 days/week for 13 weeks. Both sexes of rats and female mice exposed to
the highest concentration (93 ppm) had reduced body weight gain. No
treatment-related hlstopathologlcal effects were noted In the lungs, kidneys,
liver, heart, brain, gonads or nasal turblnates of rats or mice. Other
tissues were not examined microscopically..
Parker et al. (1982) exposed groups of 28 male and 28 female CD-I mice
and F344 rats to 0, 5, 15 or 50 ppm of the D-D mixture (2S% c1s-l,3-dlchloro-
propene, 27X trans-dlchloropropene, 29X 1,2-dlchloropropane) for 6 hours/day,
5 days/week for 6 or 12 weeks. No clinical signs of toxldty or effects on
body weight changes, hematology (HGB, HCT, R8C, WBC and differential
leukocyte count), serum chemistry (BUN, GLU, ALB, and GPT), urlnalysls, gross
pathology, hlstopathology, organ weights and organ-to-body weight ratios of
brain, heart, testes or ovaries and adrenals were observed following 12 weeks
of exposure. Increased mean I1ver-to-body weight ratios of male rats and
Increased mean kidney-to-body weight ratios of female rats were seen at the
50 ppm exposure level at 12 weeks. In male and female mice exposed to the
highest concentration for 12 weeks, a slight to moderate diffuse hepatocytlc
enlargement was seen 1n 12/21 treated males. 4/18 control males, 6/18 treated
females and 1/18 control females. No compound-related-effects were seen at
lower concentration levels.
Torkelson and Oyen (1977) described a preliminary Dow Chemical Company
study that exposed rats (5/sex/group) and guinea pigs (3-5/sex/group) to 50
ppm l,3-d1chloropropene (composition not specified) for 19 seven-hour
exposures over a period of 28 days or to 11 ppm for 27 seven-hour exposures
6229H 6-2 07/25/89
-------
over a period of 39 days. In both experiments, marked liver and kidney
changes, Including necrosis, were observed.
Torkelson and Oyen {1977} repeatedly exposed rats (9-11 animals/sex/
exposure level), guinea pigs (7-12 animals/sex/group), rabbits (1-4 animals/
sex/group) and dogs (1-2 animals/sex/group) by Inhalation to 1 or 3 ppm
1,3-dlchloropropene (46% c1s- and 53% trans-1,3-dlchloropropene, 1%
eplchlorohydrln) for 7 hours/day, 5 days/week for 6 months. In addition to
the rats exposed for 7 hours/day, groups of five male rats were exposed at 3
ppm for 4, 2, 1 or 0.5 hours/day, 5 days/week for 6 months. Controls
consisted of animals exposed to normal laboratory environments and animals
exposed In sealed chambers to air only. Following the last exposure, the
animals were sacrificed and the following tissues and organs were
hlstologlcally examined: lung, heart, liver, kidney, spleen, testes, ovaries,
adrenals, pancreas, lymph nodes, Intestines, stomachs, brains, thyroids,
thymus, peripheral nerves, skeletal muscles, bladders and gall bladders.
Hematologlcal tests were also performed (hemocrlt, hemoglobin and
differential WBC counts). Additional groups of rats were allowed a 3-month
recovery period before sacrifice. No effects on any organs were found 1n any
species at either concentration except for a slight, cloudy swelling 1n the
renal epithelium of male rats exposed to 3 ppm 1,3-dlchloropropene for 4 or 7
hours/day. Following the 3-month recovery period, the cloudy swelling was no
longer apparent.
Reduced body weights and degeneration and hyperplasla of respiratory
epithelium were reported In male and female F344 rats exposed to Telone
II (94% 1,3-dlchloropropene, nearly equally divided between the two
Isomers) at 90 ppm, 6 hours/day, 5 or 6 days/week 1n a multlgeneratlon
6229H 6-3 07/25/89
-------
reproduction study (Breslln et al., 1987), discussed more fully 1n
Section 6.5.
6.1.1.2. CHRONIC -- The chronic toxldty of Inhaled technical grade
l,3-d1chloropropene was determined 1n F344 rats and B6C3F1 mice (Lomax et
al., 1989). Groups of 50 male and 50 female rats were exposed to 0, 5, 20 or
60 ppm (0, 22.7, 90.8 or 272 mg/m3) 1,3-dlchloropropene (49.5% ds- and
42.654 trans-l,3-d1chloropropene, 0.754 1,2-d1chloropropane and 254 epoxldlzed
soybean oil) 6 hours/day, 5 days/week tor <2 years. Ancillary groups of 10
rats and mice/sex/exposure level were similarly exposed for 6 and 12 months.
Clinical laboratory determinations (hematologlcal and clinical chemistry
parameters), along with extensive gross and hlstologlcal examinations, were
determined at the scheduled sacrifice Intervals of 6, 12 or 24 months. No
clinical signs of toxldty and no significant differences In survival were
observed. Mean body weights of both male and female rats exposed to 60 ppm
l,3-d1chloropropene were significantly decreased (5%) as compared with
controls on test days 6-425 In males and 6-327 1n females (a = 0.05 by
Dunnett's test). The terminal weights of the treated rats, however, were
similar to those of control animals. The mean body weights of both male and
female mice exposed to 60 ppm l,3-d1chloropropene were lower In some
Instances than those of controls during the study (3-954 1n males and 2-1154 In
females). The terminal weights of the male mice exposed to 60 ppm were
significantly lower than those of the control mice (a - 0.05 by Dunnett's
test). No statistical differences were found between the terminal body
weights of treated female mice and those of controls. No treatment-related
effects were observed 1n hematologlcal, biochemical or urlnalysls parameters.
Gross pathological examination of all rats In the study showed no
apparent exposure-related effects following exposure to 1,3- dlchloropropene.
6229H 6-4 07/25/89
-------
Hlstopathologlcal examination, however, revealed exposure-related effects In
the nasal tissues of male and female rats exposed to 60 ppm 1,3-dlchloropro-
pene for 24 months. These changes were characterized by unilateral or
bilateral decreased thickness of the olfactory epithelium that 1s due to
degenerative changes, erosions of the olfactory epithelium and flbrosls
beneath the olfactory epithelium. No lesions were observed at the 6- or
12-month sacrifices.
Hlstopathologlcal examination of J.he mice • revealed exposure-related
morphological changes 1n the urinary bladder and nasal tissue. Urinary
bladder hyperplasla, characterized by diffuse, uniform thickening of the
transitional epithelium, was observed In both sexes of mice with duratlon-
and concentration-related Increased frequency and severity. The Incidence
of this lesion was significantly Increased In males at 60 ppm and In females
at 20 and 60 ppm at 24, but not at 6 or 12 months of exposure. The effect
was much more pronounced In the female mice than In male mice. Both the male
and female mice also had compound-related microscopic changes In the nasal
tissues characterized by hypertrophy and hyperplasla of the respiratory
epithelium or degeneration of the olfactory epithelium. Significant
Increases 1n the Incidence of hyperplasla of the respiratory epithelium were
found 1n female mice exposed to 20 and 60 ppm for 24 months and In male mice
exposed to 60 ppm for 24 months. The Incidence of degeneration of the
olfactory epithelium was measured significantly 1n mice of both sexes at 60
ppm after 24 months. An additional exposure-related change was the hyper-
plasla and hyperkeratlnlzatlon In the forestomach of 8/50 male mice following
exposure to 60 ppm for 24 months.
6229H 6-5 07/25/89
-------
6.1.2. Oral Exposure.
6.1.2.1. SUBCHRONIC -- Solutions of Telone II* (78.5X 1,3-d1chloro-
propene) In propylene glycol were administered by gavage at doses of 0, 1, 3,
10 or 30 mg/kg/day to 10 rats (strain unspec1f1ed)/sex/dose level for 6
days/week for 13 weeks (T11 et al., 1973). No significant effects on body
weight, food consumption, hematology, clinical chemistry, urlnalysls or
hlstopathology were noted at any dose level. A statistically significant
higher relative kidney weight, however, was found -1n males treated with 10 or
30 mg/kg/day and In females at 30 mg/kg/day.
As reported In abstracts of Russian studies, the effects of 1,3-dlchloro-
propene on trypsln, trypsln Inhibitor, amylase and llpase activities In the
serum of albino rats was Investigated by Strusevlch and Ekshtat (1974) and
Strusevlch and Sadovnlk (1975). The rats were fed dally doses of 0.1, 0.5 or
2.5 mg/kg/day !,3-d1chloropropene for 6 months. Trypsln activity Increased
and trypsln Inhibitor activity of the blood decreased during the 6 months of
treatment. Blood Upase activity Increased and amylase activity was
unaffected. No additional details of the studies were reported In the
abstracts.
•
6.1.2.2. CHRONIC — Groups of 52 male and 52 female F344 rats were
given doses of 0, 25 or 50 mg/kg/day Telone II (89% els- and trans-1,3-
dlchloropropene, 2.5% 1,2-dlchloropropane, 1.5% trlchloropropene and 1.0%
epIchlorohydMn) 1n corn oil by gavage 3 days/week for 104 weeks (NTP,
1985). In the same bloassay, groups of 50 male and 50 female B6C3F1 mice
were given doses of 0, 50 or 100 mg/kg/day by gavage 3 days/week for 104
weeks. In ancillary studies, groups of 28 male and 28 female rats and mice
were given Telone II at the above doses, and Interim kills of five
animals/sex/group were performed at 9, 16, 21, 24 or 27 months.
6229H 6-6 07/25/89
-------
No differences tn survival were found among the groups of rats 1n the
2-year study; 35-42 rats/sex/group survived until the end of the study. In
mice, survival of the control males was significantly lower than either the
low or high dose groups. Only 8/50 control male mice survived until the end
of the experiment, compared with 28/50 animals 1n the low-dose group and
31/50 animals In the high-dose group. Twenty-five of the deaths among the
male control mice occurred at weeks 48-51 and were attributed to myocarditis,
which was not treatment-related. Survival of the high-dose female mice was
significantly less than that of the controls; 36/40 high-dose females and
46/50 female controls survived. Survival In the low-dose group of female
mice was 45/50.
The mean body weights of male rats In the high-dose group (50 mg/kg/day)
were =5% lower than those of the control group after 28 weeks, while body
weights In the low-dose male group (25 mg/kg/day) and In both groups of
treated females were comparable with controls. There were no significant
differences In hematologlc and clinical chemistry Indices among all groups of
rats. Basal cell hyperplasla of the forestomach was observed In Increased
Incidences In treated male and female rats, but these lesions were considered
preneoplastlc, since rats also had Increased Incidences of paplllomas and
carcinomas of the forestomach. The Incidences of edema of the submucosa of
the urinary bladder was 9/52 and 3/52 for high-dose males and females,
respectively, compared with 0/52 for the control and low-dose groups.
Increased Incidences of nephropathy were observed \t\ treated female rats
(15/52, control; 24/52, low dose and 22/52, high dose), but not In male rats,
as compared with controls.
6229H 6-7 07/25/89
-------
The mean body weights of treated mice were Initially lower than those of
the vehicle controls and remained lower throughout the study (5-9%). This
difference was due to lack of randomization at the beginning of the experi-
ment. No significant differences In hematologlc or clinical chemistry
parameters were observed. Dose-related Increased Incidences of epithelial
hyperplasla of the urinary bladder were observed 1n male and female treated
mice. The Incidences were as follows: 0/50 for male controls, 9/50 for
low-dose males and 18/50 for high-dose males; 2/50- for female controls, 15/50
for low-dose females and 19/48 for female high-dose groups. Increased
Incidences of transitional cell carcinomas of the urinary bladder were also
observed In the treated groups (Section 6.2.2). High-dose female mice also
had Increased Incidences of epithelial hyperplasla of the forestomach. A
dose-related Increased Incidence of hydronephrosls occurred In female, but
not male, mice. The Incidences were 0/50 for controls, 2/50 for low-dose and
14/50 for the high-dose groups.
6.1.3. Other Relevant Information. Torkelson and Oyen (1977) tested human
volunteers for their ability to detect the odor of 1,3-dlchloropropene. At
each concentration of 4.5 or 13.6 mg/m3 for 1-3 minutes, 7/10 Individuals
detected the odor, which was stronger at the higher concentration.
Dermatosls was reported In three men derma11y exposed to D-D (53%
1,3-dlchloropropene, 27.1% 1,2-dlchloropropane, 1% eplchlorohydrln and the
remainder, dlchloropropene Isomers) while spraying the fumlgant on their
crops (Nater and Gooskens, 1976). An Itchy erythematous rash was found at
the site of exposure. Patch tests revealed that, In one case, an allergic
contact sensitivity to D-D existed.
Irritation to eyes and upper respiratory mucosa of humans occurs after
exposure to vapors of dlchloropropene. Inhalation of vapor 1n concentrations
6229H 6-8 . 07/25/89
-------
>1500 ppm produces headache. Irritation to the mucous membranes, dizziness,
nausea, vomiting, gasping, coughing, substernal pain and respiratory
distress, with slight elevation of serum enzyme levels. At concentrations
<1500 ppm, CNS depression and moderate Irritation of the respiratory system
occur (Gosselln et al., 1976). Ingestlon of l,3-d1chloropropene produces
acute gastrointestinal distress, pulmonary congestion and edema, and CNS
depression 1n humans. Dermal exposure causes severe skin Irritation with a
marked Inflammatory response.
LD_0 and LC5Q values for rats, mice -and rabbits are listed in Table
6-1. Torkelson and Oyen (1977) found that 2700 ppm (=12,000 mg/m3)
1,3-dlchloropropene was extremely Irritating to the respiratory tract and
caused lung, nasal, liver and kidney Injury In rats. Rats survived a 1-hour
exposure to 1000 ppm (=4500 mg/m3), but death occurred when exposure was
Increased to 2 hours. Guinea pigs died following a single 7-hour exposure to
400 ppm (=0800 mg/m3); rats survived the same exposure, but severe Injury
and weight loss was evident. Weight loss was recovered after 8 days but lung
Injury was still present.
Torkelson and Rowe (1981) reported that direct application of two drops
of 1,3-dlchloropropene to the eyes of rabbits caused moderate to severe
Injury; vapors of 1,3-dlchloropropene caused Irritation and lacrlmatlon.
Application of 1,3-dlchloropropene to the skin of rabbits, accompanied by the
prevention of evaporation, caused necrosis and edema. Carreon and Mall (1983)
reported that 4/10 guinea pigs exhibited signs of sensltlzatlon to Telone
II , and Jeffrey et al. (1987) reported edema, erythema and dermal
necrosis at the site of administration of 200 mg/kg Telone II .
Torkelson and Oyen (1977) reported that Telone II , 1n a 12.5X
solution In propylene glycol, was applied under a cuff to rabbits that were
ii229H 6-9 07/25/89
-------
TA« -1
L05Q/LC50 Values for Dlchloropropene
Route Species
Oral rat (M)
rat (F)
rat (N)
rat (F)
rat
rat
LD50/LC5Q Value
(95% Confidence L1m1
(rag/kg)
710
470
560 (452-695)
510 (480-726)
140+25
150 (130-170)
t) Comments
Liver and kidneys grossly affected,
lung Injury 1n survivors
Animals died 1-3 days after dosing.
NC
LD5Q for all rats was 150 mg/kg;
Reference
Torkelson and
Rowe, 1981
Toyoshlma et al.,
1987a
Nine et al.. 1953
Jones and Collier,
r\j
ifi
2 *mg/m3
mouse
300+37
mouse (N) 640 (582-704)
mouse (F) 640 (547-749)
LD5Q for males was 130 mg/kg;
1050 for females was between
110 and 250 mg/kg.
NC
Animals died 1-2 days after dosing.
1986
H1ne et al, 1953
Toyoshlma et al.,
1978b
Inhalation rat 4530*
mouse
Dermal rat >1211
mouse
rabbit 2100+260
rabbit 333 (102-610)
Cumulative high
NC
acute toxlclty
Single dose skin penetration
Dose was admlnl
was covered for
stered and the area
24 hours.
H1ne et al
Toyoshlma
1978a,b
H1ne et al
Jeffrey et
1987
., 1953
et al.,
., 1953
al.
NC = No comment
-------
then left undisturbed for 24 hours. Absorption occurred by this route,
resulting 1n deaths with doses of 0.125 and 0.25 g/kg. When undiluted Telone
II was applied In the same manner to a group of both species of rabbits,
a dermal LD-D value of 504 mg/kg was obtained. When applied to the eyes of
six rabbits, four of the rabbits had severe conjunctiva! Irritation and two
exhibited slight to moderate cornea! Injury after 24 hours of observation.
The effects disappeared after 8 days.
6.2. CARCINOGENICITY
6.2.1. Inhalation. Harkovltz and Crosby (1984) described three reported
cases of hematologlc malignancies In humans that may have been the result of
acute exposure to 1,3-dlchloropropene. Two of the cases Involved two firemen
exposed to 1,3-dlchloropropene after a spill from a tank truck. In nine
firemen exposed to the vapors, symptoms Included headache, neck pain, nausea
and breathing difficulty. Eight years following the spill, two of the
firemen developed malignant hlstlocytlc lymphomas and died. In the third
case, a farmer was exposed to 1,3-dlchloropropene In the field for 30 days
and developed redness and pain In the right ear, the nasal mucosa and the
pharynx. The farmer returned to the field 1 year later and was exposed again
to 1,3-dlchloropropene; the symptoms worsened. The farmer was diagnosed with
acute myelomonocytlc leukemia and died of pneumonia 5 weeks after admission
to the hospital.
The chronic toxldty and oncogenlclty of technical grade 1,3-dlchloropro-
pene was determined In rats and mice (see Section 6.1.1.2) (Lomax et al.,
1989). Groups of 50 male and 50 female F344 rats and B6C3F1 mice were
exposed to 0, 5, 20 or 60 ppm (0, 22.7, 90.8 or 272 mg/m3) 1,3-dlchloropro-
pene (49.5% els- and 42.6% trans-1,3-d1chloropropene, 0.7% 1,2-dlchloropro-
pane and 2% epoxldlzed soybean oil) 6 hours/day, 5 days/week for <2 years.
6229H 6-11 09/28/89
-------
Ancillary groups of 10 rats and mlce/sex/exposure level were similarly
exposed for 6 and 12 months.
No statistically significant Increases In primary, benign or malignant
tumor Incidence was found In male or female rats when compared with the
controls. The Incidence of bronchloloalveolar adenomas (a benign lung tumor)
was significantly Increased In male mice exposed to 60 ppm 1,3-dlchloropro-
pene for 24 months (Table 6-2). No Increase 1n Incidence was found 1n the
male mice exposed to 5 or 20 ppm. -No increase 1n primary, benign or
malignant tumors was found In the treated female mice. A hyperplastlc
response was found In the urinary bladders of both male and female treated
mice (see Section 6.1.1.2.), but no dose-related tumorlgenlc response was
found. A dose-related, statistically significant decrease was found In the
Incidence of liver and lymphoretlcular tissue tumors In the mice.
6.2.2. Oral. In the previously reported chronic oral bloassay (NTP, 1985),
rats and mice were treated by gavage with Telone II , a commercial
product containing 89% els- and trans-1,3-d1chloropropene, 2.5% 1,2-dlchloro-
propane, 1.554 trlchloropropene and 1.0% eplchlorohydrln. Details regarding
the dosing schedule, numbers of animals and survival were presented In
Section 6.1.2.2.
Significantly Increased Incidences of neoplastlc lesions were observed In
the forestomach and liver of rats and 1n the forestomach, urinary bladder and
lungs of mice. Tumor Incidences and the results of Fischer Exact Tests and
Cochran-Armltage Tests for dose-related trends are presented In Table 6-3.
;:n addition, the Incidence of adrenal gland pheochromocytoma were signifi-
cantly (p=0.029 by life table and Incidental tumor tests) Increased In male
rats treated at 25 mg/kg. The Incidence of thyroid folllcular cell adenomas
6229H 6-12 07/25/89
-------
TABLE 6-2
Incidence of Bronchloloalveolar Adenomas In B6C3F1 Mice
Exposed to l,3-D1chloropropene for 24 Months3
Sex Dose _ . Tumor Incidence
(ppm)
Male 0 9/50
5 6/50
20 13/50
60 22/50b
Female 0 4/50
5 3/50
20 5/50
60 3/50
QUALITY OF EVIDENCE
Strengths of study: Compound was administered by a relevant route of
exposure at three concentrations. Adequate numbers of
animals/group survived to be at risk for late-developing
tumors. Adequate duration of exposure. Two species
(rats and mice) and both sexes were used.
Overall adequacy: Adequate
aSource: Lomax et al., 1989
Statistical difference from control mean by Yate's x2 palrwlse test,
a=0.05 and linear trend by Cochran-Armltage linear trend test, <*=O.Q2,
two-sided.
5229H 6-13 07/25/89
-------
TAB
-3
Chronic Oral Exposure to Telone n*a,b,c for 2 Years
CD
10
Species/Strain Sex
(No.)
Rat/F344 H (52)
Rat/F344 H (52)
Rat/F344 F (52)
Rat/F334 H (52)
Rat/F334 H (52)
Rat/F344 F (52)
M1ce/B6C3Fl F (50)
H1ce/B6C3Fl F (50)
Dose Target Organ
(rog/kg/day)
0 forestomach
25
50
0 forestomach
25
50
0 liver
25
50
0 forestomach
25
50
0 liver
25
50
0 forestomach
25
50
0 forestomach
25
50
0 urinary bladder
50
100
Tumor Type
squamous-cell
papllloma
squamous-cell
carcinoma
neoplastlc
nodule or
carcinoma
squamous-cell
papllloma or
carcinoma
neoplastlc
nodules
squamous-cell
papllloma
squamous-cell
papllloma or
carcinoma
transitional
cell carcinoma
Tumor Incidence
(p value)
1/52
1/52
9/52
0/52
0/52f
4/52
1/52
6/52
8/52
, 1/52
1/52
13/52
1/52
. 6/52
7/52
0/52
2/52
3/52
0/50
1/50
4/50
0/50
8/50
21/48
0.002d
0.7526
0.008e
0.015d
0.0596
0.015d
D.0566
0.016e
<0.001d
0.7526
<0.001e
0.030d
0.0566
0.030e
0.082d
0.2486
0.1216
0.026d
0.5006
0.0596
<0.001d
0.0036
<0.001e
-------
TABLE 6-3 (cont.l
V
IV*
ro
Species/Strain Sex
(No.)
M1ce/B6C3Fl F (50)
M1ce/B6C3Fl M (50)
Dose Target Organ
(mg/kg/day)
0 lung
50
100
0 lung
50
100
Tumor Type
alveolar/
bronchlolar
ademona
alveolar/
bronchlolar
adenoma or
carcinoma
Tumor Incidence
(p value)
0/50
2/50
8/50
2/50
4/50
8/50
0.002d
0.12ie
0.0036
0.029d
0.339*
0.046^
QUALITY OF EVIDENCE
?] Strenghts of study: Two-year study; sufficient number of animals, both sexes, two dose levels, two species
3^ were used; ancillary studies were Included (see text). . ,
Weakness of study: Hale mouse vehicle control had many early deaths from myocarditis.
Overall adequacy: Adequate
aSource: NTP, 1985
bCorn oil vehicle 1n all studies
°Pur1ty of compound: 89% ds- and trans-1somers of 1,3 dlchloropropene with 1.0% eplchlorohydrln
^Cochran-Armltage Trent Test
eF1scher Exact Test
fNo p value 1s presented because no tumors were observed 1n the 25 mg/kg and vehicle control groups.
ro
en
00
us
-------
or carcinomas \n female rats showed a marginally significant (p<0.05)
positive dose-related trend. NTP (1985) reported that, under the conditions
of the study, there was clear evidence of cardnogenldty for male F344/N
rats and for female B6C3F1 mice, and there was some evidence 1n female F344/N
rats. The study was deemed an Inadequate study of carclnogenlclty In male
B6C3F1 mice because of high mortality In the control group. Although the
early deaths of the control male mice confounded the results, a carcinogenic
effect of Telone II was suggested by the tumor Incidences of transi-
tional cell carcinomas of the urinary bladder, alveolar/bronchlolar neoplasms
and squamous cell paplllomas of the forestomach 1n male mice.
Results of the ancillary studies Indicated that the development of
forestomach lesions was time-dependent. Pooling of the tumor Incidences from
the ancillary studies and the 2-year study (not shown In Table 6-3} enhanced
the statistical significance.
The Telone II used In the bloassay contained 1.0% eplchlorohydrln, a
known carcinogen, which may have Influenced the development of forestomach
lesions.
6.2.3. Other Relevant Information. A group of 30 female Ha:ICR mice was
given weekly subcutaneous Injections of cls-1,3-d1chloropropene In trlocta-
noln at a dose of 3 mg/mouse/week (Van Duuren et al., 1979). After 538 days,
six mice had local sarcomas (flbrosarcomas) (6/30; p<0.0005) and no distant
tumors were observed. No tumors developed In untreated and vehicle-treated
animals.
Van Duuren et al. (1979) also studied ds-l,3-d1chloropropene as a
tumor-Initiator and as a whole carcinogen when applied to the skin of mice. A
group of 30 female Ha:ICR mice received a single dermal application of 122 mg
6229H 6-16 09/21/89
-------
1,3-dlchloropropene In 0.2 mi acetone followed by phorbol myrlstate acetate
In acetone at 5 ng, 3 times/week for 428-576 days. Controls consisted of
100 untreated mice, 90 mice treated with 0.0025 mg/appllcatlon and 120 mice
treated with 0.005 rag/application of the tumor promoter. No significant
differences were observed between the d1chloropropene-1n1t1ated mice and
those treated with the promoter alone, with respect to local or distant
tumors. When 1,3-dlchloropropene was tested as a whole carcinogen, three
paplllomas developed In 3/30 female mice treated, with 122 mg/appllcatlon 3
days/week for <589 days. Two of the mice had carcinomas. Although no local
tumors were observed In mice treated at 41 mg/appllcatlon, or In acetone-
treated or untreated controls, the Incidence In high-dose mice was not
significantly different. The number of mice with distant tumors was also not
different from that In controls.
6.3. MUTAGENICITY
Studies on the mutagenlclty of 1,3-dlchloropropene are summarized In
Table 6-4. 1,3-Dlchloropropene was positive for reverse mutation In
Salmonella tvphlmuMum strains TA100 and TA1535 both with and without
metabolic activation (NTP, 1985; Stolzenberg and Mine, 1980; Haworth et al.,
1983). In S. typhlmuMum strain TA98, a positive reaction was obtained
without metabolic activation {NTP, 1985; Haworth et al. 1983; VHhayathll et
al. 1983). Although Talcott and King (1984) and Watson et al. (1987)
demonstrated that the mutagenlclty to strain TA100 of mixtures of els- and
trans-l,3-d1chloropropene was abolished following removal of polar Impuri-
ties, other Investigators (Greedy et al., 1984; Neudecker et al., 1977;
DeLorenzo et al., 1977) found that both the ds-1somer and the trans-lsomer
(both relatively pure) were mutagenlc In strains TA100, TA1538, TA1537,
<»229H 6-17 07/25/89
-------
TABLF 6-4
CTv
ro
i
GO
o
-J
to
in
CO
IP
Assay
Reverse
mutation
Reverse
mutation
Reverse
mutation
Reverse
mutation
Reverse
mutation
Reverse
mutation
Reverse
mutation
Indicator
Organism
Salmonella
tyj>h1imir1um
TA 100
TA 1535
TA 1537
TA 98
i-
typhlmurlum
TA 98
S.
typhlmurlum
TA 100
S.
typhlmurlum
TA 1978
TA 1535
TA 100
FyphlmuMum
TA 100
S.
typhlmurlum
TA 1538
TA 1537
TA 1535
lyphlmurlum
TA 100
Compound/
Purity
95. 6X
NR
NR
els- and trans-
Isomers/Nft
ds- and trans-
isomers/98%
cls-lsomer/
99.97X; trans-
1somer/97.46X
mix of ds-
and trans-/
77-95X pure
Application
plate
Incorporation
liquid Incubation
plate
Incorporation
plate
Incorporation
plate
Incorporation
plate
Incorporation
plate
Incorporation
Concentration Activating
or Dose System
0.3333 v8/ » S-9
plate
100 pg/plate none
10. 1, 10-1 i S-9
timol/plate
20. 50, 100 * S-9
MQ/plate
10-200Mg/plate » S-9
0. 0.1. 0.5. 1.0 * S-9
jig/flll
<1 mg/plate none
Response Comment
S-9 mixtures from both rats and
hamsters were used. No
»/* difference was found between
*/+ species. Where a positive re-
-/- sponse was found, the chemical
-/* was cytotoxlc at >333 i»g/plate.
«- NC
NC
»/*
*/+ NC
t/t addition of glutathlone pro-
tected against mutagenlclty.
*/* NC
+ Impurities In the DCP prepa-
ration were removed and the
mutagenlc response was no longer
found. The Impurities them-
selves were mutagenlc.
Reference
NTP, 1985; Haworth
et al., 1983
VHhayatMe et al.,
1983
Stolzenberg and
H1ne, 1980
Oelorenzo et al.,
1977
Creedy et al.,
1984
Neudecker et al.,
1977
Talcott and King,
1984
-------
TABLE 6-4 (cont.)
ro
to
X
Assay
Reverse
mutation
Reverse
mutation
Sister
chromatld
exchange
Sex-linked
recessive
Indicator '
Organism
Salmonella
typhlmuMum
TA 100
S.
Yvphlmurlum
TA 100
Chinese
hamster
V79 cell
Drosophlla
melanoqaster
Compound/
Purity
els- Isomer/
99. 7X
els- and
translsomers/
>99.5X
98X
95. 5X
Application
plate
Incorporation
plate
Incorporation
cell culture
feeding
Concentration
or Dose
?5-2000 wg/
plate
NR
3.3, 6.6, 10.0 r
0.5750 ppm
Activating
System Response
* S-9 *
i S-9 */»
m * S-9 -/»
NA *
Comment
the study showed that previously
shown Intrinsic mutagenlclty was
probably due to Impurities and
not 1.3 DCP.
activation was Increased by
greater amounts of and longer
Incubation with S-9.
1.3 OCP was Inactivated by the
S-9 mixture In the V79/SCE assay.
NC
Reference
Watson et al.,
1987
Neudecker and
Henschler, 1986
von der Hude et
al.. 1987
NTP, 19B5; Valencia
et al.. 1985
lethal
Redprocol 0.
trans- melanoqaster
locations
95.5X
feeding/Injection 0.5750 ppm
NA
NC
NTP. 1985; Valencia
et al., 1985
o
~J
X.
rv>
NA = Not applicable; NC * no comment; NR * not reported
us
-------
TA1535 and TA1978. Neudecker and Henschler 11986} found that the mutagenl-
clty of 1,3-dlchloropropene 1n S. typhlmurlum Increased with Increasing
levels of the S-9 mixture and with longer Incubation periods. Greedy et al.
(1984) also demonstrated that, If glutathlone was added to the assay system,
the mutagenlcHy of either Isomer was reduced.
1,3-Olchloropropene was positive for sex-linked recessive lethal
mutations, but negative for reciprocal translocatlons 1n Drosophlla melano-
gaster (NTP, 1985; Valencia et al., 1985).
6.4. DEVELOPMENTAL TOXICITY
Hanley et al. (1987) studied the effects of Inhalation exposure to 0, 20,
60 or 120 ppm 1,3-dlchloropropene (47.754 c1s- and 42.454 trans-l,3-d1chloro-
propene) for 6 hours/day during gestation days 6-15 In 30 F344 rats and on
days 6-18 In 25-31 New Zealand White rabbits. Maternal toxlclty (body weight
gain, liver weight, kidney weight, mortality, food and water consumption and
reproductive parameters) and developmental toxlclty (fetal body weight,
number of resorptlons, external and skeletal examination and visceral exami-
nation) were assessed. No evidence of developmental toxlclty was observed In
rats or rabbits, but significant maternal toxlclty was seen In both species
of animals. Signs of maternal toxlclty Increased with Increasing exposure
concentrations In both species. Maternal toxlclty was evidenced 1n the
rabbits by a decrease 1n weight gain at the highest two exposure levels.
Decreases In maternal weight gain were observed at all exposure levels 1n
rats. In rats, maternal toxlclty was also evidenced at all exposure levels
by decreases 1n food and water consumption and statistically significant
decreases In absolute liver weights, and, at the highest level, by statis-
tically significant Increases 1n relative kidney weights. A statistically
significant Increase In the Incidence of one minor skeletal variant (delayed
*229H 6-20 09/21/89
-------
ossification of the vertebral centra) was observed among fetuses of dams
exposed to 120 ppm 1,3-dlchloropropene, but this was considered secondary to
the maternal toxldty. No adverse effects on other ossification sites were
found In the fetal rats.
6.5. OTHER REPRODUCTIVE EFFECTS
Venable et al. (1980) reported a fertility study of 79 male workers
engaged 1n the manufacture of 1,3-dlchloropropene. Results from this study
Indicated no significant effect on fertility frofti exposure to 1,3-dlchloro-
propene at levels occurring 1n the work environment.
Unnett et al. (1988} exposed 30 male and 24 female Wlstar rats to 0. 10,
30 or 90 ppm D-D (28.1% cls-1,3-dlchloropropene, 25.6% trans-1,3-dlchloropro-
pene, 25.6% 1,2-dlchloropropane and the remainder, primarily dlchloropropene
Isomers} for 6 hours/day, 5 days/week for 10 weeks. Treated males were mated
with untreated females, and treated females were mated with untreated males.
Libido, fertility and morphology of the reproductive tract of either sex were
not affected and no treatment-related dominant lethal effect was observed In
male rats. Body weight gain decreased slightly and liver and kidney weights
Increased slightly In both sexes at the highest exposure concentration.
In a U.S. EPA (1988) review of an unpublished experiment (Breslln et al.,
1987), groups of 30 male and 40 female F344 rats were exposed by Inhalation
to Telone II (94X 1,3-d1chloropropane, nearly equally divided between
els and trans Isomers) at concentrations of 0, 10, 30 or 90 ppm, 6 hours/day,
5 days/week 1n a mu HI generation reproduction study. Exposure began 10 weeks
before mating and was Increased to 7 days/week during a 2-week breeding
period. Exposure of the F, generation began after weaning on the 6
hours/day, 5 days/week schedule and continued for 12 weeks. The highest
concentration tested was considered by U.S. EPA (1988) to be a NOAEL for
6229H 6-21 09/21/89
-------
reproductive effects associated with a slight decrease In the conception
Indices 1n F, and F~ females. NonreproductWe effects reported 1n the 90
ppm groups Included hyperplasla of the respiratory epithelium, degeneration
of olfactory tissue and decreased body weight gain 1n rats of both sexes.
In a mouse sperm morphology assay (Osterloh et al., 1983), male mice
(C57BL/6XC3H, four mice/dose level) were Injected 1ntraper1toneally for 5
consecutive days with 1,3-dlchloropropene (Telone II ) In 0.25 ml corn
oil at doses of 10, 19, 38, 75, 150,-300 and "600 mg/kg/day. A negative
control group received only corn oil, and 90 mg/kg/day methyl methanesulfo-
nate was Injected as a positive control. The morphology of 200 sperm/mouse
was assessed 35 days following the first Injection. Testlcular weights,
total epldldymal sperm counts and percentage of abnormally-shaped sperm were
averaged and compared with controls after 35 days. Methyl methanesulfonate
produced a high percentage of abnormally-shaped sperm (16.4-22.9J4). At the
three highest dose levels (150, 300 and 600 mg/kg/day), all mice died before
day 35. Host of the animals Injected with the lower doses survived and
exhibited no significant changes 1n testes weight, total sperm count or
percent of abnormal sperm compared to vehicle controls. Data are presented
1n Table 6-5. Ten pesticides, Including four known testlcular toxins and
three known mutagens, were tested 1n this study. None of the pesticides
tested positive. The authors concluded that the mouse sperm morphology assay
only tested for damage at the spermatic! stage of sperm development and was
not a suitable test for testlcular toxins.
(>.&. SUMMARY
The LC5_ for l,3-d1chloropropene 1n rats and mice was 4530 mg/m3
(Hlne et al., 1953). Information regarding subchronlc and chronic Inhalation
of l,3-d1chloropropene suggests that damage to the nasal mucosa of rats and
6229H 6-22 09/21/89
-------
TABLE 6-5
Testlcular Weights, Sperm Counts and Percent Abnormal Sperm After
IntraperHoneal Injection "of 1,3-D1chloropropenea
Testes weight (mg)
Total sperm count
(million/ma)
Percent abnormal
sperm
Methyl methanesul-
fonate (positive
control) percent
abnormal sperm
Control 75 mg/kg 38 mg/kgb 19 mg/kg 10 mg/kgc
203±40 229+14 21U7 218+9 218^9
25.9+8.9 32.0*3.0 32.3+4.5 29.1+6.1 25.8.+Q.6
1.0+0.4 0.9^0.9 0.8*1.0 1.U0.3. 1.8+1.1
16.4f22.9 NA
NA
NA
NA
aSource: Osterloh et al., 1983
bThree of four survived 35 days.
cTwo of four survived 35 days.
NA = Not applicable
6229H
6-23
07/25/89
-------
mice and damage to the urinary bladders of mice may result from exposure
(Stott et al., 1988; Torkelson and Rowe, 1981; Lomax et a!., 1989). Evidence
of damage to the liver and kidneys was also found (Parker et al., 1982;
Torkelson and Rowe, 1981).
Oral LD5Q values 1n rats ranged from 140-740 mg/kg and. In mice, from
300-640 mg/kg {Torkelson and Rowe, 1981; H1ne et al., 1953; Toyoshlma et al.,
1978a,b). Subchronlc studies suggested Increases 1n the relative weight of
the kidneys 1n rats treated orally with 1,3-d1chloropropene (Torkelson and
Rowe, 1981). Chronic oral studies suggest that hyperplasla of the fore-
stomach and of the urinary bladders of rats and mice resulted from exposure
(NTP, 1985).
The only data available regarding the carclnogenlcHy of l,3-d1chloro-
propene 1n humans are three reported cases of hematologlc malignancies that
may have been the result of acute Inhalation exposure to 1,3-d1chloropropene
(MarkovHz and Crosby, 1984). There 1s sufficient evidence that 1,3-dl-
chloropropene Is a carcinogen In orally exposed animals. NTP (1985) found
Increased Incidences of squamous-cell paplllomas and carcinomas of the
forestomach and neoplastlc nodules or carcinomas of the liver In rats treated
chronically with 1,3-dlchloropropene by gavage. Mice similarly treated
showed Increased Incidences of forestomach tumors, lung adenomas or
carcinomas and transitional cell carcinomas of the urinary bladder. There Is
rfeak evidence that 1,3-dlchloropropene Is carcinogenic 1n animals exposed by
Inhalation. Lomax et al. (1989) found an Increase 1n the Incidence of benign
lung tumors (bronchloloalveolar adenomas) In male mice treated chronically
with 1,3-dlchloropropene. l,3-Q1chloropropene has been found to be mutagenlc
'in various strains of S. typhlmurlum (NTP, 1985; Stolzenberg and Hlne, 1980;
Maworth et al., 1983). l,3-D1chloropropene has also been found to be
6229H 6-24 09/27/89
-------
positive for sex-linked lethal mutations,, but negative for reciprocal
translocatlons 1n D. melanoqaster (NTP, 1985). l,3-D1chloropropene does not
appear to be a reproductive or a developmental toxicant.
6229H 6-25 09/21/89
-------
7. EXISTING GUIDELINES AND STANDARDS
7.1. HUMAN
The ACGIH (1986, 1988} has recommended and adopted a TWA-TLV of 1 ppm (5
mg/m3) for l,3-d1chloropropene. This value 1s based on the findings of
Torkelson and Oyen (1977) that exposure to 1 ppm, 7 hours/day for 6 months
resulted In no Injury to four species and that 3 ppm resulted In slight,
reversible Injury In one species (see Section 6.1.1.2). A skin notation Is
also listed by the ACGIH (1988), wh1ch_ means that appreciable exposure may
occur through skin contact with the vapors. OSHA (1989) has also recommended
and adopted a TWA of 1 ppm (5 mg/m3} with a skin designation for l,3-d1-
chloropropene. The U.S. EPA (1987b) verified a chronic oral RfD of 3x10"*
mg/kg/day, based on Increased organ weights In rats fed 1,3-dlchloropropene
for 90 days (Til et al., 1973). The U.S. EPA (1987b) reported an oral slope
factor for cardnogenlclty of 1.8xlO~Vmg/kg/day and a carclnogenlclty
classification of B2 (probable human carcinogen); based on tumors In rats and
mice In the NTP (1985) study (see Section 6.2.2), positive mutagenlc
activity, and structural similarity to known oncogens that produce similar
types of tumors 1n rodents. IARC (1987) classified 1,3-d1chloropropene as a
class 28 carcinogen (probable human carcinogen).
7.2. AQUATIC
Pertinent data regarding guidelines for exposure of aquatic organisms to
1,3-dlchloropropene were not located 1n the available literature cited In
Appendix A.
6;?30H 7-1 07/25/89
-------
8. RISK ASSESSMENT
Statements concerning available literature 1n this document refer to
published, quotable sources and are In no way meant to Imply that confi-
dential business Information (CBI), which this document could not address,
does not exist. However, It was determined that existing CBI data would not
alter the approach to risk assessment or the risk assessment values presented
herein.
8.1. CARCINOGENICITY
8.1.1. Inhalation. The chronic toxlclty and oncogenlclty of technical
grade l,3-d1chloropropene were determined 1n rats and mice (see Sections
6.1.1.2. and 6.2.1.) (Lomax et al., 1989). Groups of rats and mice were
exposed to 0, 5, 20 or 60 ppm {0, 22.7, 90.8 or 272 mg/m3) 1,3-dlchloropro-
pene (49.5X ds- and 42.6X trans-l,3-d1chloropropene, 0.7X 1,2-dlchloropro-
pane and 254 epoxldlzed soybean oil) 6 hours/day, 5 days/week for <2 years.
Clinical signs of toxldty were not observed, and no significant differences
In survival were found In any group of exposed animals.
No statistically significant Increases In primary, benign or malignant
tumor Incidence were found In male or female rats when compared with the
controls. The Incidence of bronchloloalveolar adenomas (benign lung tumors)
was significantly Increased 1n male mice exposed to 60 ppm 1,3-dlchloropro-
pene fop 24 months (22/50 treated, 9/50 controls). No Increase In Incidence
was found In male mice exposed to 5 or 20 ppm (see Table 6-2). No Increase
In primary, benign or malignant tumors was found 1n the treated female mice.
In contrast to these results, NTP (1985) found significantly Increased
Incidences of neoplastlc lesions 1n the forestomach and liver of rats and In
the forestomach, urinary bladder and lungs of mice 1n a chronic gavage
6231H 8-1 07/25/89
-------
study. In both studies, a tumorIgenlc response was found In the tissues
through which the 1,3-dlchloropropene was absorbed, I.e., the forestomach 1n
the gavage study and the lungs In the Inhalation study. In the gavage study,
however, tumors were also Induced at sites distant from the point of entry.
Hyperplasla of the urinary bladder, however, was found 1n animals exposed by
both Inhalation and 1ngest1on. Lomax et al. (1989) determined that, when the
concentration of 1,3-dlchloropropene administered by Inhalation was converted
to mg/kg, the dose given In the 1nhalai1on study was 2-3 times higher than
the dose given In the oral study. A major difference between the studies was
the compound used to stabilize the 1,3-dkhloropropene mixture. In the oral
study, IX eplchlorohydrln, a compound that reportedly causes nasal and
forestomach tumors 1n rats following chronic Inhalation and oral exposure,
respectively, was used as a stabilizer; In the Inhalation study, a relatively
nontoxlc epoxldlzed soybean oil stabilizer was used. The levels of eplchlo-
rohydrln used In the gavage study, however, were about 30-fold lower than the
doses shown to be tumorlgenlc by 1ngest1on. The differing results, there-
fore, are most likely due to the differences In administration: repeated
bolus doses administered by gavage vs. repeated 7-hour Inhalation exposures.
Another reason for differing results can be differences In metabolic pathways
following oral vs. Inhalation exposures. Results from pharmacoklnetlc
studies (Fisher. 1988; Fisher and Kllgore, 1988a) (see Section 5.3.) have
Indicated that, following Inhalation exposure, a substantial amount of
1,3-dlchloropropene 1s metabolized to the less toxic glutathlone conjugate,
transported to the bloodstream and Is subsequently degraded to the mercap-
turlc add form and excreted In the urine.
8.1.2. Oral. In the NTP (1985) chronic gavage study, Increased Incidences
of squamous-cell paplllomas and carcinomas of the forestomach and neoplastlc
6231H 8-2 09/25/89
-------
nodules or carcinomas of the liver were observed In rats treated with Telone
II* (8954 1,3-dlchloropropene, 2.5% 1,2-dlchloropropane, 1.5X tMchloro-
propene and IX eplchlorohydrln) at doses of 25 and 50 mg/kg/day, 3 days/week
for 2 years. In addition, the Incidence of adrenal gland pheochromocytoma
Increased significantly In male rats treated at 25 mg/kg, and the Incidence
of thyroid folUcular cell adenoma or carcinoma In female rats showed a
significant (p<0.05) positive dose-related trend. Mice similarly treated at
50 and 100 mg/kg/day had Increased Incidences of forestomach tumors, lung
adenomas or carcinomas and transitional cell carcinomas of the urinary
bladder (see Table 6-3). NTP (1985) noted that eplchlorohydrln may have
Influenced the development of forestomach lesions, but 1t was concluded that
there was clear evidence for the cardnogenldty of Telone II In male
rats and female mice, some evidence In female rats and Inadequate evidence In
male mice, due to high mortality 1n the male control group.
8.1.3. Other Routes. Weekly subcutaneous Injection of c1s-l,3-d1chloropro-
pene In mice at 3 mg/mouse/week resulted In significantly Increased Inci-
dences of Injection-site fIbrosarcomas. No significant differences between
treated mice and control mice were observed when cls-1,3-d1chloropropene was
tested as a tumor Initiator or as a whole carcinogen on the skin (Van Duuren
et al., 1979).
8.1.4. Weight of Evidence. The only available data regarding the cardno-
genldty of 1,3-dlchloropropene In humans are three reported cases of
hematologlc malignancies that may have resulted from acute exposure to
1,3-dlchloropropene (MarkovUz and Crosby, 1984). The available animal data
Indicate evidence that 1,3-dlchloropropene is carcinogenic by the oral route
of exposure and may be carcinogenic following Inhalation exposure (NTP, 1985;
Lomax et al., 1989). Hutagenldty studies Indicate that 1,3-dlchloropropene
6231H 8-3 09/25/89
-------
1s mutagenlc to various strains of S. typhlmurlum (NTP, 1985; Haworth et
al., 1983; Stolzenberg and Nine, 1980). According to U.S. EPA (1986c)
guidelines, 1,3-d1chloropropene can be placed In Group B2: probable human
carcinogen.
8.1.5. Quantitative Risk Estimates.
8.1.5.1. INHALATION — The only long-term Inhalation study available
that assesses the carclnogenlclty of 1,3-dlchloropropene Indicates that
exposure 1s associated with an Increased Incidence of bronchloloalveolar
adenomas (benign tumors) In male mice exposed to 60 ppm (272 mg/m3) for 2
*
years (Lomax et al., 1989). (Data used to calculate the q-j value are
presented In Appendix B.) Only benign tumors were observed 1n this study and
quantitative risk estimate based solely on benign tumor alone Is not
routinely performed; however, Incidences of lung adenomas as well as other
types of tumors were also Increased following oral exposure. Therefore, the
results from the Inhalation study by Lomax et al. (1980) are considered
'*
relevant and a quantitative risk estimate Is derived. The value for q-j
was calculated using the linearized multistage model developed by Kenneth
Crump and adopted by U.S. EPA. The conversion factor used to adjust for
spec1es-to-spec1es extrapolation was the cube root of the ratio of the
average body weight of a man (assumed to be 70 kg) to the body weight of the
*
experimental animal (Appendix B). The value for the q-j In humans 1s
calculated to be 1.3xlO-1 (mg/kg/day)"1. Assuming a reference human body
weight of 70 kg and a respiratory rate of 20 mVday, ambient air concentra-
tions of 2.7xlO~*, 2.7xlO~s and 2.7xlO~* mg/m3 are associated with
Increased cancer risks of IxlO"5, IxlO"8 and IxlO"7, respectively.
8.1.5.2. ORAL — The only long-term study available that assesses the
carclnogenlclty of 1,3-dlchloropropene following chronic oral exposure 1s
6231H 8-4 09/27/89
-------
that by NTP (1985). This study Indicates that chronic exposure Is associated
with Increased Incidences of squamous-cell paplllomas and carcinomas of the
forestomach, neoplastlc nodules or carcinomas of the liver, possibly adrenal
and thyroid tumors 1n rats, and Increased Incidences of forestomach tumors,
lung adenomas or carcinomas and transitional cell carcinomas of the urinary
bladder In mice. Because of the demonstrated carclnogenlclty of Telone
!!•, H Is appropriate to derive a q,* for 1,3-dlchloropropene. The
value for q,* was calculated using the linearized multistage model
developed by Kenneth Crump and adopted by U.S. EPA. The conversion factor
used to adjust for spec1es-to-spec1es extrapolation was the cube root of the
ratio of the average body weight of a man (assumed to be 70 kg) to the body
weight of the experimental animal (Appendix B). A q,* of l.SxlO"1/
mg/kg/day Is calculated based on the combined Incidences of tumors In the
forestomach and liver and pheochromocytoma In the adrenals of male rats. The
concentrations of 1,3-dlchloropropene In drinking water associated with risk
levels of 10~5, 10~6 and 10~7 are 2xl(T3, 2xlO"« and 2xlO~s
mg/a, respectively.
8.2. SYSTEMIC TOXICITY
8.2.1. Inhalation Exposure.
8.2.1.1. LESS THAN LIFETIME EXPOSURE (SUBCHRONIC) -- Stott et al.
(1988) exposed F344 rats and B6C3F1 mice to 0, 10, 30, 90 or 150 ppm of
technical-grade 1,3-dlchloropropene (90X 1,3-dlchloropropene) 6 hours/day, 5
days/week for 13 weeks. Degenerative or hyperplastlc changes In the nasal
mucosa were observed In both sexes of rats and mice exposed to >90 ppm and 1n
2/10 male rats exposed to 30 ppm. Hyperplasla of the urinary bladder
transitional epithelium was found In female mice exposed to 90 or 150 ppm of
the vapor. No treatment-related effects were observed In rats or mice
6231H 8-5 09/27/89
-------
exposed to 10 ppm 1,3-d1ch1oropropene. A NOEL of 10 ppm (45.4 mg/m3) (rec
#2) and a LOAEL of 30 ppm (136.2 mg/m3} (rec #13} for respiratory effects
In rats were Identified. This study will be used as the basis for the
subchronlc RfD, since a higher percentage of the vapor administered 1n this
study consisted of 1,3-dlchloropropene compared with the Parker et al. (1982)
study below.
Parker et al. (1982) exposed mice and rats to 0, 5, 15 or 50 ppm of a
mixture of D-D (52X cls-and trans-1,3-dlchloropr.opene and 29% !,2-d1chloro
propane) 6 hours/day, 5 days/week for 6 or 12 weeks. Slight to moderate
diffuse hepatocytlc enlargement was found In male and female mice exposed to
50 ppm for 12 weeks. Increased mean I1ver-to-body weight ratios of male rats
and Increased mean kidney-to-body weight ratios of female rats were seen at
the 50 ppm level. No compound-related effects were found at lower levels, so
15 ppm (68 mg/m3) can be defined as the NOAEL (rec #25) and 50 ppm (227
mg/m3} can be defined as the LOAEL (rec #26} for liver effects 1n rats and
mice. Although a higher LOEL value Is Identified In the Parker et al. (1982)
study than 1n the Stott et al. (1988) study (15 ppm vs. 10 ppm}, the Stott et
al. (1988) study will be used as the basis for the Inhalation RfD, since the
vapor used In this study was 90X 1,3-dlchloropropene, while the vapor used In
the Parker et al. (1982) study was only 52X.
Coate et al. (1979) reported that rats and mice exposed to 93 ppm Telone
II for 13 weeks had reduced body weight gain (rec #20-24). Tor kelson
and Oyen (1977) reported a Dow Chemical study 1n which liver and kidney
necrosis was found In rats and guinea pigs exposed to >11 ppm (rec #33,
34). Neither of these studies will be used as the basis for the subchronlc
Inhalation RfD, since the former study reports a NOAEL higher than the LOAEL
In the Stott et al. (1988) study and the latter study was a pilot consisting
6231H 8-6 09/27/89
-------
of very few animals. Torkelson and Oyen (1977) reported a slight, apparently
reversible cloudy swelling of the renal epithelium In male rats exposed to 3
ppm, but not to 1 ppm, of l,3-d1chloropropene (99% 1,3-d1chloropropene) for 4
or 7 hours/day, 5 days/week for 6 months. The renal effect was not substan-
tiated In a study In which 50 rats/sex/group were exposed to <60 ppm for 2
years, or 10 rats/sex/group were exposed to <60 ppm for 6 or 12 months. No
compound-related effects were found following exposure of rabbits, guinea
pigs or dogs to 1 or 3 ppm 1,3-d1chloropropene for 6 months. It Is reasona-
ble, therefore, to consider the 3 ppm level In the study by Torkelson and
Oyen (1977) as a NOAEL (rec #5).
The subchronlc Inhalation RfD Is calculated by adjusting 10 ppm (45.4
mg/m3) from the Stott et al. (1988) study for Intermittent exposure,
multiplying by the RGDR and dividing by an uncertainty factor of 100 (10 for
Interspecles extrapolation and 10 to protect the most sensitive Individual).
The RGDR 1s the ratio of (rat ventilation rate/the extrathoraclc surface area
of the rat) to (human ventilation rate/extrathoraclc surface area of the
human) [(0.223 mVday/11.6 m*)/(20 mVday/177 m*)J (Jarabek, 1988).
Therefore, the calculated subchronlc Inhalation RfD Is 0.01 mg/m3.
Confidence In the key study used to derive the RfD Is high; the study was
well conducted and extensive hlstopathologlcal examinations of the animals
were done. Confidence In the data base 1s medium, since several studies were
conducted, two of which were of high quality, but effects seen In a lower
quality study were not substantiated. Therefore, confidence In the
subchronlc Inhalation RfD Is medium.
8.2.1.2. CHRONIC EXPOSURE — Lomax et al. (1989) determined the chronic
toxldty of Inhaled l,3-d1chloropropene (93X l,3-d1chloropropene) In rats and
mice exposed to 5, 20 or 60 ppm for 6 hours/day, 5 days/week for <2 years.
6231H 8-7 09/27/89
-------
Examinations of hematologlcal, biochemical and urlnalysls data 1n treated
animals did not Indicate toxlclty from l,3-d1chloropropene exposure.
Hlstopathologlcal examination of rats revealed exposure-related effects In
the nasal tissue of male and female rats exposed to 60 ppm for 24 months, but
not after exposure for 6 or 12 months. Hlstopathologlcal examination of mice
revealed exposure-related morphological changes In the urinary bladder and
lung of both sexes. Significant Increases 1n the Incidence of hyperplasla
and Inflammation of the transitional epithelium .of the urinary bladder was
found In male mice exposed to 60 ppm for 24 months and In female mice exposed
to 20 and 60 ppm for 24 months. Significant Increases In the Incidence of
hyperplasla of the respiratory and olfactory epithelium were found 1n male
mice exposed to 60 ppm for 24 months and In female mice exposed to 20 and 60
ppm for 24 months. Therefore, a NOEL of 5 ppm (22.7 mg/m3) {rec #5) and a
LOAEL of 20 ppm (90.8 mg/ma) (rec #6) 1s defined for the respiratory and
bladder effects of 1,3-dlchloropropene In mice. A NOEL of 20 ppm (90.8
mg/m3} (rec #3) and a LOAEL of 60 ppm (272 mg/m3) (rec #4) are defined
for the respiratory effects In rats. Although the exposure level of 5 ppm 1n
mice Is a NOEL for respiratory and bladder effects, the respiratory effects
cannot be considered In the derivation of the RfO because values for
respiratory tract surface areas are not yet available for B6C3F1 mice. The
bladder effects, however, are systemic effects for which methodology exists.
A chronic Inhalation RfD of 0.04 mg/m3 could be calculated by adjusting
22.7 mg/m3 (5 ppm) for Intermittent exposure to 4.1 mg/m3, multiplying by
the ratio of the blood/gas partition coefficient for animals/humans (no
Information available, so the default value of 1 Is used), and dividing by an
uncertainty factor of 100 (10 for Interspedes extrapolation and 10 to
protect the most sensitive Individual). The pharmacoklnetlc study by Stott
6231H 8-8 09/27/89
-------
and Kastl (1986) suggests that a steady state of 1,3-dlchloropropene was
reached In the blood within the duration period of the dally exposures. This
RfD, however, 1s greater than the subchronlc Inhalation RfD of 0.01 mg/m3,
based on a NOEL of 10 ppm for respiratory effects In rats. The I GAEL 1n the
subchronlc study was 30 ppm, at which 2/10 rats had degenerative changes In
the nasal mucosa. Only 2/50 rats exposed to 20 ppm 1n the chronic study had
nasal tissue lesions; the Increased Incidence Is not statistically signifi-
cant when compared with the Incidence (0/50) 1n .the controls. Furthermore,
20 ppm Is a chronic LOAEL In mice and Is higher than the NOEL of 10 ppm 1n
rats In the subchronlc study used as the basis for the subchronlc RfD.
Therefore, the Inhalation RfD of 0.01 mg/m3 1s adopted as the chronic
Inhalation RfD. As discussed In Section 8.2.1.1., confidence In the key
study 1s high and In the data base, medium. Overall confidence In the
chronic Inhalation RfD 1s medium because H protects for the critical effect
of respiratory effects In rats, but 1t may not be protective for the
respiratory effects 1n mice.
8.2.2. Oral Exposure.
8.2.2.1. LESS THAN LIFETIME EXPOSURE (SUBCHRONIC) — T11 et al. (1973)
administered 1,3-d1chloropropene (Telone II ) 1n propylene glycol to 10
Albino rats/sex/dose to 0, 1, 3, 10 or 30 mg/kg/day, 6 days/week for 90
days. No significant differences between the groups were found In the means
of body weight and food consumption. No biologically significant differences
1n hematology or clinical chemistry parameters were found, and no compound-
related abnormalities were seen upon gross autopsy. Increased relative
kidney weights, however, were found In male rats at 10 and 30 mg/kg/day and
1n female rats at 30 mg/kg/day. Therefore, a NOEL for kidney effects of 3
mg/kg/day (rec #1) and a LOAEL of 10 mg/kg/day (rec #7} were Identified.
6231H 8-9 09/27/89
-------
This study will be used as the basis for the subchronlc oral RfD. since the
only other subchronlc oral studies are abstracts of Russian studies which
lack experimental details (Strusevlch and Ekshtat, 1974; Strusevlch and
Sadovnlk, 1975).
The subchronlc oral RfD Is calculated by taking the NOEL of 3 mg/kg/day
from the Til et al. (1973) study, adjusting for Intermittent exposure to 2.6
mg/kg/day and dividing by an uncertainty factor of 1000 (10 for Interspedes
extrapolation, 10 to protect the most sensitive Individuals and an additional
modifying factor of 10 for the deficient data base). An RfO of 3xlO~3
mg/kg/day 1s calculated. Confidence In the key study that 1s the basis for
the subchronlc RfD 1s low because the study Is of poor quality. Confidence
1n the data base Is low since few subchronlc oral studies exist. Overall
confidence 1n the subchronlc oral RfD 1s low.
8.2.2.2. CHRONIC EXPOSURES -- NTP (1985) determined the chronic
toxlclty of 1,3-d.1chloropropene 1n rats given 0, 25 or 50 mg/kg/day and mice
given 0, 50 or 100 mg/kg/day Telone II (89J4 1,3-dlchloropropene) by
gavage ^n corn oil 3 days/week for 104 weeks. No effects on survival were
found 1n male and female rats. Basal cell hyperplasla of the forestomach was
observed In Increased Incidences In both sexes of treated rats In the high
dose group; edema of the submucosa of the urinary bladder Increased 1n high
dose male and female rats. Increased Incidences of nephropathy were found In
both the high and low dose female rats. In mice, the survival of the control
male mice was significantly reduced due to myocarditis (not treatment-re-
lated). Survival of the high dose female mice was significantly less than
controls. Increased Incidences of epithelial hyperplasla of the urinary
bladder were found In both dose groups of both sexes of mice. High-dose
female mice also had Increased Incidences of epithelial hyperplasla of the
6231H 8-10 09/27/89
-------
forestomach and of hydronephrosls. An AEL of 25 mg/kg was defined for kidney
neuropathy In female rats (rec #2) and hyperplasla of the forestomach In male
rats (rec #4); an AEL of 50 mg/kg was defined for hyperplasla of the urinary
bladder In both male and female mice (rec #5, 6). Consequently, the T11 et
al. (1973) study described In Section 8.2.2.1., which was the basis for the
subchronlc oral RfD, Is used as the basis for the chronic oral RfD. In the
90-day gavage study by T11 et al. (1973), kidney weights Increased In male
rats given 10 mg/kg/day and In female rats given 30 mg/kg/day. The RfD Is
calculated by adjusting the NOEL of 3 mg/kg/day for Intermittent exposure and
dividing by an uncertainty factor of 10,000 (10 for Interspedes extrapola-
tion, 10 to protect the most sensitive Individuals, 10 for the use of a
subchronlc study and an additional modifying factor of 10 for the deficient
data base). A chronic oral RfD of 3xlO~* mg/kg/day Is calculated and this
value has been verified (U.S. EPA, 1987b). As discussed In Section 8.2.2.1.,
confidence In the key study used as the basis for the chronic oral RfD 1s low
because of Us poor quality and Us short duration. Confidence In the data
base Is low, as the chronic NTP (1985) study was not designed to study
chronic toxlclty and does not define a NOAEL. Overall confidence In the
chronic oral RfD Is low.
6231H 8-11 09/27/89
-------
9. REPORTABLE QUANTITIES
9.1. BASED ON SYSTEMIC TOXICITY
The available data on the effects of long-term administration of 1,3-
dichloropropene in animals were discussed in detail in Chapter 6. Studies
that provide dose-response data are summarized in Table 9-1. Subchronic
studies are included In Table 9-1 because effects of subchronic exposure are
similar to those of chronic exposure and occur at doses and exposure
concentrations not appreciably different than- those given in the chronic
studies. Por this reason, no uncertainty factors were applied to doses in
subchronic studies.
Several studies discussed in Chapter 6 are not included in Table 9-1.
Torkelson and Oyen (1977) reported that, at exposures of 50 ppm (227 mg/m3)
1,3-dichloropropene (19 exposures in 28 days) or 11 ppm (50 mg/m3) 1,3-
dichloropropene (27 exposures in 39 days), liver and kidney necrosis was
found in rats. The only effect observed among rats, guinea pigs, dogs or
rabbits exposed by inhalation to 1,3-dichloropropene <7 hours/day, 5
days/week for 6 months was cloudy swelling of the renal tubule epithelium of
male rats (13.6 mg/m3, 4 or 7 hours/day). These studies were not included
in Table 9-1 because the composition of the 1,3-dichloropropene was not
specified and the reported effects have not been substantiated in other
studies using higher exposure levels of 1,3-dichloropropene of >891. for
longer durations.
Parker et al. (1982) found increased relative liver and kidney weights 1n
rats and hepatocellular hypertrophy in mice exposed by inhalation to 50 ppm
of the D-D mixture (521 1,3-dichloropropene, 29X 1,2-dichloropropane). This
study is not included in Table 9-1 since the concentration of 1,2-dichloro-
propane in the D-D mixture was very high. Similarly, Linnett et al. (1988)
6232H 9-1 06/19/89
-------
TABLE 9-1
Toxicity Summary for 1,3-Oichloropropene
Species/
Route Strain Sex
Inhalation rat/F344 M
Inhalation rat/F344 M
F
..hd-ldtion rat/F344 M
F
•o
IVJ
inhalation mouse/ M
B6C3F1 F
inhalation mouse/ F
CD-I
inhalation mouse/ F
B6C3F1
Average Vehicle/
Number Body Physical Transformed
at Start Weight State Purity Exposure Animal Oose
(kg) (mg/kg/day)
10 0.26" air 90.9% 30 ppm (136 mg/ 17. lc
m3) 6 hours/
day, 5 days/week
for 13 weeks
10 0.235" air 92% 93 ppm (422 mg/ 64. Oc
10 0.160 m3) 7 hours/ 72. 5C
day, 5 days/
week for 13
weeks
50 0.380" air 92.1% 60 ppm (272 mg/ 30. 2C
50 0.230 m3) 6 hours/ 35.7
day. 5 days/
week for 2
years
10 0.027" air 90.9% 90 ppm (409 mg/ 97. 4C
10 0.022 m3) 6 hours/ 106.2
day, 5 days/
week for 13
weeks
10 0.031" air 92% 93 ppm (422 mg/ 1133
m3) 7 hours/
day, 5 days/
week for 13
weeks
50 0.03d air 92.1% 20 ppm (90.8 mg/ 21.1"
m3 ) 6 hours/
day, 5 days/
week for 2 years
Equivalent
Human Dose* Response
(rog/kg/day)
2.6 degenerative changes in
nasal nucosa
9.6 reduced body weight gain
5.3 decreased body weight gain;
degeneration of nasal
mucosa
i
7.1 degenerative changes in
nasal mucosa (both sexes);
hyperplasia of urinary bladder
epithelium (females)
•
8.6 reduced body weight gain
1.6 hyperplasia of respiratory
mucosa and urinary bladder
epithel ium
Reference
Stott et al . ,
1988
Coate et «1 . ,
1979
Lomax et al . ,
1989
Stott et al.,
1988-
Coate et al . ,
1979
Lomax et al . ,
1989
(>139H
06/29/89
-------
TABLE 9-1 (cent.)
Route
Oral
»r«l
Oral
Oral
to
i
Species/
Strain
rat/
albino
rat/F344
rat/F334
mouse/
B6C3F1
Average
Number Body
Sex at Start Weight
(kg)
M 10 0.221"
F 50 0.25"
M 50 0.425"
F 50 0.25
F 50 0.028
Vehicle/
Physical
State Purity
propylene 78.5%
glycol
corn oil 89%
corn oil 89%
corn oil 89%
Exposure
10 mg/ kg/day, 6
days/week for
13 weeks
25 mg/kg/day
3 days/week
for 104 weeks
50 mg/kg/day
3 days/week
for 104 weeks
100 mg/kg/day,
3 days/week
for 104 weeks
Transformed
Animal Dose
(mg/kg/day)
8.6e
10. 7"
21.4"
42. 9e
Equivalent
Human Dose"
(mg/kg/day)
1.3
1.6
3.9
3.3
3.2
Response Reference
increased relative kidney Til et al . .
weight 1973
increased incidence of NTP. 1985
nephropathy
edema of submucosa of NTP, 1985
urinary bladder
reduced survival NTP, 1985
"Calculated by multiplying the transformed animal dose by the cube root of the ratio of the animal body weight to the human body weight (70 kg)
"Estimated from data in the study
'Calculated by expanding exposure concentration in ntg/m3 from intermittent to continuous, multiplying by the animal inhalation rate (U.S. EPA, I980a)
and dividing by the animal body weight
"Reference body weight (U.S. EPA. 1980a)
''Calculated by expanding dose over a 7-day week
6139H
06/26/89
-------
found a decrease In body weight and an Increase 1n liver and kidney weights
In male and female rats exposed to 90 ppm D-D In a reproduction study. This
also will not be used as a basis for an RQ value because of the composition
of the D-D mixture (53.7% 1,3-dlchloropropene).
The effects of exposure to 1,3-dlchloropropene Include degenerative
changes In the nasal mucosa, hyperplastlc changes In the urinary bladder,
reduced body weight gain. Increased kidney weights, nephropathy and reduced
survival. The lowest doses resulting Vn each of'these effects were used to
calculate CSs (Table 9-2). The highest CS (20) was obtained In the chronic
oral study by NTP (1985) In which mice treated with 10 mg/kg/day had reduced
survival. The corresponding RQ Is 100 pounds and Is recommended as the basis
for the RQ for chronic toxldty to 1,3-dlchloropropene (Table 9-3).
9.2. BASED ON CARCINOGENICITY
The NTP (1985) reports clear evidence of carclnogenldty In rats and mice
following oral exposure to Telone II (1,3-dlchloropropene} (Table 6-3).
Squamous cell paplllomas and carcinomas of the forestomach and Increased
Incidence of neoplastlc nodules of the liver were observed 1n male F344
rats. Squamous-cell paplllomas were found In female F344 rats. In addition,
the Incidence of adrenal gland pheochromocytoma were significantly Increased
1n male rats treated at 25 mg/kg, and the Incidence of thyroid folllcular
cell adenoma or carcinoma In female rats showed a marginally significant
(p<0.05) positive dose-related trend. In female B6C3F1 mice. Increased
Incidences of transitional-cell carcinomas of the urinary bladder were found
as well as alveolar/bronchlolar adenomas of the lung and squamous-cell
paplllomas or carcinomas of the forestomach. Results 1n male B6C3F1 mice
were not clear because of high mortality 1n the control group. Dose-related
Increased Incidences of transitional-cell carcinomas of the urinary bladder,
6232H 9-4 09/21/89
-------
TABLE 9-2
Oral Composite Scores for 1,3-Dichloropropene
Animal
Koutf Species Dose
(mg/kg/day)
I nlMlat ion rat 17. 1
initiation rat 30.2
; .iiid"lal ion mouse 21.1
l
U1
liul rat 8.6
<>,,,! rat 10.7
Oral rat 21.4
Ordl mouse 42.9
Chronic
Human MED
(mg/day)
182
371
112
91
112
231
224
RVd
2,1
1.6
2.4
2.6
2.4
2.0
2.0
Effect
degenerative changes in
nasal mucosa
reduced body weight
gain
hyperplasia of respiratory
mucosa and urinary bladder
epi thleum
increased kidney weight
increased incidence of
nephropathy
edema of urinary bladder
reduced survival
RVe
6
4
4
4
7
5
10
cs
12.6
6.4
9.6
10.4
16.8
40.0
20.0
RQ
1000
1000
1000
1000
1000
1000
100
Reference
Stott et al
Lomax et al
Lomax et al
Til et al. ,
NTP, 1985
NTP, 1985
NTP, 1985
., 1988
., 1989
., 1989
1973
m
6I39H
06/29/89
-------
TABLE 9-3
1,3-Dichloropropene
Minimum Effective Dose (MED) and Reportable Quantity
-------
squamous-cell paplllomas of the forestomach and alveolar/bronchlolar adenomas
and carcinomas of the lung, however, were found 1n the male mice. Lomax et
al. (1989) found no statistically significant Increase In tumor Incidence 1n
F344 rats treated with 1,3-dUhloropropene by Inhalation. In B6C3F1 mice, an
Increased Incidence of a benign lung tumors (bronchloloalveolar adenomas) was
found In male mice exposed to 60 ppm 1,3-d1chloropropene. Van Duuren et al.
(1979) also observed sarcomas In Swiss mice Injected with 1,3-d1chloro-
propene. MarkovUz and Crosby (1984), found some evidence for a causal
relationship between acute exposure of humans to l,3-d1chloropropene and the
development of hematologlc malignancies.
l,3-D1chloropropene 1s given a cancer classification of B2, a probable
human carcinogen, by U.S. EPA (1987b) and 28, as a chemical or group of
chemicals that Is probably carcinogenic for humans, by IARC (1987).
Data used to calculate the potency factors (F or 1/ED,Q) for Inhalation
and oral exposure are summarized In Table 9-4 and Table 9-5. Fs were derived
using the linearized multistage model developed by Kenneth Crump and adopted
by the U.S. EPA. For the Inhalation data, the unadjusted I/ED-,- obtained
from the animal data (4.8xl(TVmg/kg/day) was corrected for Interspecles
extrapolation by multiplying the cube root of the weight of a human (70 kg)
by the weight of the animal, and the resultant F Is 6.4xlO~1/mg/kg/day
(Table 9-4) (Lomax et al., 1989). For the oral data, equivalent human doses
and combined Incidences of forestomach and liver tumors and adrenal pheo-
chromocytoma In male rats (U.S. EPA, 1987b) were used (Table 9-5). The
resultant F for oral data Is g^xlO'Ving/kg/day. Since the F for oral
exposure 1s <1, l,3-d1chloropropene Is placed 1n Potency Group 3; since the
chemical Is In group B2, l,3-d1chloropropene has a Low Hazard Ranking,
according to the Hazard Ranking Scheme for Reportable Quantities under
CERCLA. The RQ associated with Medium Hazard ranking 1s 100.
6232H 9-7 09/28/89
-------
TABLE 9-4
Derivation of Potency Factor (FJ for Inhalation Exposure to
1,3 Dlchloropropene (Telone II*)
Exposure route:
Species:
Strain:
Sex:
Vehicle or physical state:
Body weight:
Duration of treatment:
Duration of study:
Llfespan of animal:
Target organ:
Tumor type:
Experimental doses/
exposure:
(mg/m3. 6 hours/
day, 5 days/week)
Transformed doses
(mg/kg/day):
Tumor Incidence:
Unadjusted 1/ED10
(F)
Adjusted I/ED™
(F)
Reference:
aReported
Estimated
Inhalation
mouse
B6C3Fi
male
vapor
0.0303
2 years
2 years
2 yearsb
lung
benign adenoma
0 22.7
0
9/50
5.3
6/50
90.8
272.0
21.2
13/50
63.1
22/50
4.8 x 10~2/mg/kg/day
6.4 x 10~Vmg/kg/day
Lomax et al., 1989
6232H
9-8
09/21/89
-------
TABLE 9-5
Derivation of Potency Factor (F) for Oral Exposure to
1,3 Dlchloropropene (Telone II*)
Exposure route:
Species:
Strain:
Sex:
Vehicle or physical state:
Body weight:
Duration of treatment:
Duration of study:
Llfespan of animal:
Target organ:
Tumor type:
Experimental doses/
exposure:
(mg/kg/day, 3 days/week)
Transformed doses(human)
(mg/kg/day):
Tumor Incidence:
VEDIO (f factor)
Reference:
oral, gavage
rat
F344
male
corn oil
0.42 kgb
104 weeks
104 weeks
104 weeks3
forestomach, liver
paplllomas, carcinomas, neoplastlc nodules,
pheochromocytomas, folUcular cell adenoma/
carcinoma
0 50 100
024
4/52 13/52 23/52
9.6xlO~Vmg/kg/day
NTP, 1985
Estimated
Reported
6232H
9-9
09/28/89
-------
10. REFERENCES
Ab1vard1, C. 1970. Occurrence of paratylenchus hamatus on citrus In Iran
and Us sensitivity to two nematlddes under laboratory conditions. Plant.
D1s. Rep. 54(12): 1085-1088.
ACGIH (American Conference of Governmental Industrial Hyglenlsts). 1986.
Documentation of the Threshold Limit Values and Biological Exposure Indices.
5th ed. ACGIH, Cincinnati, OH. p. 189.-
ACGIH (American Conference of Governmental Industrial Hyglenlsts). 1988.
Threshold limit Values and Biological Exposure Indices for 1988-1989. ACGIH,
Cincinnati, OH. p. 18.
Albrecht, N.N. 1987a. Toxicology and hazard assessment of 1,3-dlchloropro-
pene. Arch. Env. Health 42: 292-296.
Albrecht, W.N. 1987b. Occupational exposure to 1,3-dlchloropropene (lelone
II ) In Hawaiian pineapple culture. Arch. Env. Health. 42: 286-291.
Albrecht, W.N. and K. Chenchln. 1985. Dissipation of 1,2-d1bromo-3-chloro-
propane (DBCP), ds-l,3-d1chloropropene (1,3-DCP), and dUhloropropenes from
soil to atmosphere. Bull. Env. Contain. Toxlcol. 34: 824-831.
Applegate, V.C., J.H. Howell, A.E. Hall, Jr. and M.A. Smith. 1957. Toxlc-
Ity of 4346 chemicals to larval lampreys and fishes. Spec. Scl. Rep. Fish.
No. 207, U.S. Dept. Interior, Fish Wildlife Service, Washington, DC. p. 1-3,
8-9. 108-109.
6233H 10-1 07/25/89
-------
Ben-Yephet, Y., D. Letham and G. Evans. 1981. Toxlclty of 1,2-dibromoethane
and 1,3-dichloropropene to microsclerotia of verticilllum dahliae. Pestic.
Sci. 12(2): 170-174.
Blackmon, C.W. and H.L. Musen. 1974. Controls of the Columbia dance)
nematode Hoplolaimus columbus or soybeans. Plant. Dis. Rep. 58(7): 641-645.
Breslin, W.J., H.D. Kirk, C.M. Streeter, J.F. Quast and O.R. Szabo. 1987.
Telone II® soil fumigant: Two-generation inhalation reproduction study in
Fischer 344 rats. Prepared by Health and Environmental Sciences USA.
Submitted by Oow Chemical Co., Midland MI. MRID 403124. (Cited in U.S. EPA,
1988).
Brodzinsky. R. and H.B. Singh. 1982. Volatile organic chemicals in the
atmosphere: An assessment of available data. EPA-600/S3-83-021. p. 155.
Buccafusco, R.J., S.J. Ells and G.A. LeBlanc. 1981. Acute toxicity of
priority pollutants to bluegill (Lepomis machrochlrus). Bull. Environ.
Contam. Toxicol. 26(4): 446-452.
Carreon, R.E. and O.M. Wall. 1983. Telone IIs: Skin sensitization
potential in the guinea pig. Office of Pesticide Programs, U.S. EPA,
Washington, DC. TSCAT fiche # OTS0515850.
Castro, C.E. and N.O. Belser. 1966. Hydrolysis of cis- and trans-1,3-di-
chloropropene 1n wet soil. J. Agric. Food Chem. 14: 69-70.
6233H 10-2 06/19/89
-------
C11m1e, I.J.G., D.H. Hutson. B.J. Morrison and G. Sioydln. 1979.
Glutathlone conjugation 1n the detoxlcatlon of (Z)-l,3-d1chloropropene {a
component of the nematoclde D-D) 1n the rat, Xenoblotlca. 9: 149-156.
Coate, W.B., D.L. Keenan, R. Voelker and R.J. Hardy. 1978. Subacute
Inhalation toxlclty study In rats and mice of Telone II
(1,3-dlchloropropene). TSCAT flche # OTS0515834.
Coate, W.B., D.L. Keenan, R.W. Voelker and R.J. Hardy. 1979. 90-Day
Inhalation study 1n rats and mice - Telone II {Final Report). Office of
Pesticide Programs, U.S. EPA, Washington, DC. TSCAT flche # OTS0515855.
Cohen, D.B. 1986. Groundwater contamination by toxic substances. A
California assessment. in: ACS. Symp. Ser. 315 (Eval. Pestle. Ground
Water): Amer. Chem. Soc. 29: 499-529.
Cole, R.H., R.E. Frederick, R. P. Healy and R.G. Rolan. 1984. Preliminary
findings of the priority pollutant monitoring project of the Nationwide Urban
Runoff Program. J. Water Pollut. Control Fed. 56: 898-908.
Cook, R.J., J.W. Sltton and W.A. Haglund. 1987. Influence of soil treat-
ments on growth and yield of wheat and Implications for control of pythlum
root rot. Phytopathology. 77(8): 1192-1198.
Costante, J.F., W.F. Ma1, J. Aleong and R.M. Klein. 1987. Effects of apple
rootstocks and nematlcldes on Pratylenchus penetrans populations and apple
tree growth. J. Am. Soc. Hortlc. Sc1. 112(3): 441-444.
6233H 10-3 07/25/89
-------
Greedy, C.L., T.M. Brooks, B.J. Dean, D.H. Hutson and A.S. Nright. 1984.
The protective action of glutathione on the microbial mutagenicity of the Z-
and E-lsomers of 1,3-dichloropropene. Chem. 81ol. Interact. 50: 39-48.
Crockett, P.M., B. Killan, K.S. Crump and R.B. Howe. 1985. Descriptive
Methods for Using Data from Dissimilar Experiments to Locate a
No-Adverse-Toxic-Effects Region in the dose-duration plane. Prepared by K.S.
Crump and Co., Inc.. under Contract No. 6807-007 for Environmental Criteria
and Assessment Office, U.S. EPA, Cincinnati, OH.
Daft, J.L. 1988. Rapid determination of fumigant and industrial chemical
residues in food. J. Assoc. Off. Anal. Chem. 71(4): 748-760.
Dean, J.A., Ed. 1985. Lange's Handbook of Chemistry. 13th ed. McGrawHill
Book Co., New York, NY. p. 7-294.
DeBenedictis, A. 1979. Chlorocarbons, hydrocarbons (allyl chloride).- ITK
Klrk-Othmer Encyclopedia of Chemical Technology. Vol. 5, 3rd ed., Grayson,
M. and D. Eckroth, Eds. John Wiley and Sons, Inc., New York. p. 766-767.
DeLorenzo, F., S. Degl'Innocenti, A. Ruocco, L. Silengo and R. Cortese.
1977. Mutagenicity of pesticides containing 1,3-dichloropropene. Cancer
Res. 37: 1915-1917.
6233H 10-4 06/19/89
-------
D1etz, F.K., E.A. Hermann, P.E. Kastl, D.A. OHtenber and J.C. Ramsey.
1985. 1,3-Olchloropropene: Pharmacok1net1c effects on tissue non-protein
sulfhydryls and macromolecular binding In Fischer 344 rats and B6C3F1 mice
following oral administration. TSCAT flche # OTS0515836.
Dllllng, W.I. 1977. Interphase transfer processes. II. Evaporation rates
of chloromethanes, ethanes, ethylenes, propanes and propylenes from dilute
aqueous solutions. Comparisons with -theoretical predictions. Env. Sd.
Tech. 11: 405-409.
Oowty, B., D. Carlisle, J.L. Laseter and 3. Storer. 1975. Halogenated
hydrocarbons In New Orleans drinking water and blood plasma. Science. 187:
75-77.
Durkln, P. and W. Meylan. 1988. Users guide for D2PLOT: A program for
dose/duration graphs. Prepared by Chemical Hazard Assessment Division,
Syracuse Research Corp. under Contract No. 68-C8-0004 for Environmental
Criteria and Assessment Office, U.S. EPA, Cincinnati, OH.
Edwards, C.A. and D. Relchle. 1969. Experimental manipulation of soil
Invertebrate populations for trophic studies. Ecology. 50(3): 495-498.
Fisher, G.D. 1988. The disposition of 1,3-dlchloropropene In the rat
following acute Inhalation exposure. Dlss. Abstr. Int. 48: 3537-B.
Fisher, G.D. and W.W. Kllgore. 1988a. Tissue levels of glutathlone
following acute Inhalation of 1,3-dlchloropropene. J. Tox. Env. Health. 23:
171-182.
6233H 10-5 07/25/89
-------
Fisher, G.D. and H.W. Kllgore. 1988b. Mercapturlc add excretion by rats
following Inhalation exposure to 1,3-d1chloropropene. Fundam. Appl. Tox.
11: 300-307.
Gosselln R., H. Hodge, R. Smith and M. Gleason III. 1976.
Dlchloropropenes. In.: Clinical Toxicology of Commercial Products, 4th ed.
Williams and Wllklns, Baltimore. MD. p. 119-121.
•
Great Lakes Water Quality Board. 1983. An Inventory of chemical substances
Identified In the Great Lakes ecosystem. Report to the Great Lakes Water
Quality Board. Windsor, Ontario, Canada. Vol. 1, Summary, p. 64.
Hanley, T.R. Jr., J.A. John-Greene, J. T. Young, L.L. Calhoun and K.S. Rao.
1987. Evaluation of the effects of Inhalation exposure to
1,3-dlchloropropene on fetal development In rats and rabbits. Fundam. App.
Tox. 8: 562-570.
Haworth, S., T. Lawlor, K. Mortelmans, W. Speck and E. Zelger. 1983.
Salmonella mutagenldty test results for 250 chemicals. Env. Mutagen.
Suppl. 1: 3-142.
Heltntuller, P.T., T.A. HolHster and P.R. Parrlsh. 1981. Acute toxlclty of
54 Industrial chemicals to sheepshead minnow cyprlnodon varlegatus. Bull.
Environ. Contam. Toxlcol. 27(5): 596-604.
6233H 10-6 07/25/89
-------
Hermens, J., F. Busser, P. Leeuwanch and A. Musch. 1985. Quantitative
correlation studies between the acute lethal toxicity of 15 organic halldes
to the guppy (PoeciHa reticulata) and chemical reactivity towards
4-nitrobenzylpyridine. Toxicol. Environ. Chem. 9(3): 219-236.
H1ne, C.H., et al. 1953. Toxicology and sage handling of CBP-55 (technical
l-chloro-3-bromopropene-1>. Am. Med. Assoc. Arch. Ind. Hyg. Occup. Med. 7:
118. (Cited In U.S. EPA, 1980)
Hutson, D.H., J.A. Moss and B.A. Pickering. 1971. Excretion and retention
of components of the soil fumigant D-D and their metabolites in the rat.
Food Cosmet. Tox. 9: 677-680.
IARC. 1987. IARC monographs on the evaluation of carcinogenic risks to
humans. Supp. 7. p.62.
Oarabek, A. 1988. U.S. EPA, Research Triangle Park. Telephone conversation
with Gary Diamond, Syracuse Research Corporation, Syracuse, NY. December 20,
1988.
Jeffrey, M.M., D.J. Schuetz and L.G. Lomax. 1987. Telone II® Soil
Fumigant: Acute Dermal Toxlcity Study in New Zealand White Rabbits. Office
Of Pesticide Programs, U.S. EPA, Washington, DC. TSCAT fiche # OTS0515820.
Johnson, W.W. and M.T. Fin ley. 1980. Handbook of acute toxicity of
chemicals to fish and aquatic Invertebrates. U.S. Department of the
Interior, Fish Wildlife Service, Washington, DC. Resource Publ. 137.
6233H 10-7 06/26/89
-------
Jones J.R. and T.A. Collier. 1986. .Telone II®: OECD 40! acute oral
toxidty test In the rat. TSCAT fiche » OTS0515823.
Kenaga, E.E. 1980. Predicted bioconcentratlon factors and soil sorption
coefficients of pesticides and other chemicals. Ecotoxicol. Env. Safety. 4:
26-38.
Kotcon, J.B. and R. Loria. 1987. "Fall fumigation of potato with 1,3-di-
chloropropene: Efficacy against Pratylenchus crenatus. yield response and
groundwater contamination potential. Plant Dis. 71(12): 1122-1124.
Krijgsheld, K.R. and A. van der Gen. 1986. Assessment of the impact of the
emission of certain organochlorine compounds on the aquatic environment.
Part II: Allylchloride, 1,3- and 2,3-dichloropropene. Chemoshpere. 15:
861-880.
Lao, R.C., R.S. Thomas, P. Bastien, R.A. Halman and J.A. Lockwood. 1982.
Analysis of organic priority and non-priority pollutants In environmental
samples by GC/MS/computer systems. In: Analytical Techniques in
Environmental Chemistry II. Albaiges, J., Ed. Pergamon Press LTD., New
York, NY. p. 107-118.
LeBlanc, G.A. 1980. Acute toxicity of priority pollutants to water flea.
(daphnia maqna). Bull. Environ. Contam. Toxlcol. 24: 684-691.
LeBlanc, G.A. 1984. Interspecies relationships in acute toxicity of
chemicals to aquatic organisms. Environ. Toxicol. Chem. 3(1): 47-60.
6233H 10-8 06/19/89
-------
Leistra, M. 1970. Distribution of 1,3-dichloropropene over the phases in
soil. J. Agrk. Food Chem. 18: 1124-1126.
Llnnett, S.L., D.G. Clark, D. Blair and S.L. Cassidy. 1988. Effects of
subchronic inhalation of D-D (1,3-dichloropropene/l,2-dichloropropane) on
reproduction in male and female rats. Fund. Appl. Tox. 10: 214-223.
•
Lomax, L.G., W.T. Stott, K.A. Johnson, L.L. Calhoun, B.L. Yano and J.F.
Quast. 1989. The chronic toxicity and oncogenicity of inhaled technical
grade 1,3 dichloropropene in rats and mice. Fund. Appl. Tox. 12: 418-431.
Mabey, N.R., J.H. Smith, R.T., H.L. Johnson, et al. 1981. Aquatic fate
process data for organic priority pollutants. EPA-440/4-81-014. U.S. EPA,
Washington, DC. p. 434.
Maddy, K.T., H.R. Fong, J.A. Lowe, D.W. Conrad and A.S. Fredrickson, 1982.
A study of well water in selected California communities for residues of
1,3-dich1oropropene, chloroallyl alcohol and 49 organophosphate or
chlorinated hydrocarbon pesticides. Bull. Env. Contam. Toxicol. 29: 354-359.
Mantel, N. and M.A. Schneiderman. 1975. Estimating "safe" levels, a
hazardous undertaking. Cancer Res. 35: 1379-1386.
Markovitz, A. and N.H. Crosby. 1984. Chemical carcinogenesis. A -soil
fumlgant, 1,3-dichloropropene, as possible cause of hematologic
malignancies. Arch. Intern. Med. 144: 1409-1411.
6233H 10-9 06/19/89
-------
Mathur, S.P., H.A. Hamilton and T.C. Vraln. 1980. Influence of some field-
applied nematlcldes on mlcroflora and mineral nutrients In an organic soil.
J. Environ. Sc1. Health. 815(1): 61-76.
Mazurek, H.A. and B.R.T. Slmonettl. 1986. Organic components In bulk and
wet-only precipitation. Critical Review Env. Control. 16: 27.
HcCall, P.J. 1987. Hydrolysis of lJ3-d1chloropropene In dilute aqueous
solution. Pestle. Scl. 19: 235-242.
Munnecke, O.E. and S.O. Van Gundy. 1979. Movement of fumlgants In soil,
dosage responses and differential effects. Annu. Rev. Phytopathol. 17:
405-429.
Nater, 3.P. and V.H.J. Gooskens. 1976. Occupational dermatosls due to a
soil fumlgant. Contact Dermatitis. 2: 227-229.
Neudecker, T. and D. Henschler. 1986. HutagenlcHy of chloroolefIns In the
Salmonella/mammalian mlcrosome test. III. Metabolic activation of- the
allyllc chloropropenes allyl chloride, 1,3-dlchloropropene, 2,3-dlchloro-l-
propene, 1,2,3-tMchlorpropene, 1,l,2,3-tetrachloro-2-propene and hexachloro-
propene by S9 mix via two different metabolic pathways. Mutal. Res. 170:
1-9.
Neudecker, T., A. Stefanl and D. Henschler. 1977. lin vitro mutagenlclty of
the soil nematlclde l,3-d1chloropropene. Enperlantla. 33: 1084-1085.
6233H 10-10 07/25/89
-------
NTP (National Toxicology Program). 1985. Toxicology and carcinogenesis
studies of Telone IT in F344/N rats and B6C3F1 mice. U.S. Department of
Health and Human Services. NTP TR 269. NIH Publication No. 85-2525.
OSHA (Occupational Safety and Health Administration). 1989. Air
contaminants: Final rule. 29 CFR Part 1910. 54: 2933.
Osterloh, 0., G. Letz, S. Pond and C. Becker. 1983. An assessment of the
potential testicular toxicity of 10 pesticides using the mouse-sperm
morphology assay. Mutat. Res. 116: 407-415.
Osterloh, O.D., B.S. Cohen, W. Popendorf and S.M. Pond. 1984. Urinary
excretion of the N-acetyl cysteine conjugate of cis-1,3-dichloroporpene by
exposed individuals. Arch. Env. Health. 39: 271-275. '
Otson, R. 1987. Purgeable organics in Great Lakes raw and treated water.
Intern. J. Environ. Anal. Chem. 31: 41-53.
Parker, C.M., W.B. Coate and R.W. Voelker. 1982. Subchronic inhalation
toxicity of 1,3-dichloropropene/l,2-dichloropropane (D-D) in mice and rats.
J. Tox. Env. Health. 9: 899-910.
Pellizzari, E.D, M.D. Erlckson and R.A. Zweidinger. 1979. Formulation of
preliminary assessment of halogenated organic compounds in man and
environmental media. EPA/560/13-79-006. U.S. EPA, Research Triangle Park,
NC. p. 469.
6233H 10-11 06/19/89
-------
Refff, B. 1978. The acute toxicity of 1,3-dichloropropene to the golen orfe
(Idus Idus melanotus). Shell Oil Company. NTIS OT 50515717.
Roberts, T.R. and G. Stoydin. 1976. The degradation of (Z)- and (E)-l,3
dlchloropropenes and 1,2-dichloropropane in soil. Pestic. Scl. 7: 325-335.
•*
Rogers, S.E., D.L. Peterson and w7c. Lauer. 1987. Organic contaminants
removal for potable reuse. J. Wat. Pollut. Con. Fed. 59: 722-732.
Sabel, G.V. and T.P. Clark. 1984. Volatile organic compounds as indicators
of municipal solid waste leachate contamination. Waste Manag. Res. 2:
119-130.
SANSS (Structure and Nomenclature Search System). 1989. Chemical
Information System (CIS computer database).
Schneider, B.A. 1979. Toxicology Handbook. Mammalian and Aquatic Data Book
1. Toxicology Data. OPP, U.S. EPA, Washington, DC. EPA 540/9-79-003A.
NTIS PB 80-196876.
Scott, C.R. and P.A. Wolf. 1962. The antibacterial activity of a series of
quaternaries prepared from hexatnethylenetetramine and halohydrocarbons.
Appl. Microbiol. 10: 211-216.
Shackelford, W.M. and L.H. Keith. 1976. Frequency of organic compounds
Identified in water. EPA-600/4-76-062. U.S. EPA., Athens, GA. p. 208.
6233H 10-12 06/19/89
-------
SRI
-------
Tabak, H.H., S.A. Quave, c.I. Mashni and E.F. Barth. 1981. BiodegradabiHty
studies with organic priority pollutant compounds. J. Water Pollut. Contr.
Fed. 53: 1503-1518.
Talcott, R.E. and J. King. 1984. Mutagenk impurities in 1,3-dichloro-
propene preparations. J. Natl. Cancer Inst. 72: 1113-1116.
Thomas, I.J. and M.V. McKenry. 1974. Part 1. Movement and fate as affected
by various conditions in several soils. Hilgardia. 42: 393-421.
Thomas, R.G. 1982. Volatilization from water. In: Handbook of Chemical
Property Estimation Methods, Lyman, W.J., N.F, Reehl and D.H. Rosenblatt,
Eds. McGraw Hill Book Co., Inc. New York, NY. p. 15-1-15-34.
Til, H.P., M.T. Spanjers, V.J. Fernon and P.J.G. Reuzel. 1973. Subchronic
(90-day) toxicity study with Telone II® in albino rats. Office of
Pesticide Programs, U.S. EPA, Washington, DC. TSCAT fiche # OTS0515825.
Torkelson, T.R. and F. Oyen. 1977. The toxicity of 1,3-dichloropropene as
determined by repeated exposure of laboratory animals. Am. Ind. Hyg. Assoc.
J. 38: 217-223.
Torkelson, T.R. and V.K. Rowe. 1981. Halogenated alephatlc hydrocarbons.
In: Patty's Industrial Hygiene and Toxicology. 3rd ed. G.D. Clayton and
F.E. Clayton, Eds. John Wiley and Sons, Inc., New York, NY. IIB: 3573-3577.
6233H 10-14 06/19/89
-------
Toyoshlma, S.t R. Sato and S. Sato. 1978a. The acute toxlclty test of
Telone II* 1n rats. TSCAT flche # OTS0515832.
Toyoshlma, S., R. Sato and S. Sato. 1978b. The acute toxlclty test of
Telone II In mice. Office of PesUdde Programs, U.S. EPA, Washington,
DC. TSCAT flche* OTS0515833.
Tuazon, E.C. R. Atkinson, A.M. Winer and J.N. Pitts. 1984. A study of the
atmospheric reactions of l,3-d1chloropropene and other selected
organochlorlne compounds. Arch. Env. Contam. Toxlcol. 13: 691-700.
U.S. EPA. 1977. Computer printout of nonconfIdentlal production data from
TSCA production file for 1977. Washington, DC.
U.S. EPA. 1978. In-depth Studies on Health Environmental Impacts of
Selected Water Pollutants. U.S. EPA Contract No. 68-01-4646. (CHed 1n U.S.
EPA, 1980b)
U.S. EPA. 1980a. Guidelines and Methodology Used In the Preparation of
Health Effect Assessment Chapters of the Consent Decree Water Criteria.
Federal Register. 45(231): 79347-79357.
U.S. EPA. 1980b. Ambient Water Quality Criteria for Dlchloropropane and
Dlchloropropene. Prepared by the Office of Health and Environmental
Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH for
the Office of Water Regulations and Standards Criteria, Washington, DC. EPA
440/5-80-043. NTIS PB81-117541.
6233H 10-15 09/28/89
-------
U.S. EPA. 1984. Methodology and Guidelines,for Ranking Chemicals Based on
Chronic Toxlclty Data. Prepared by the Office of Health and Environmental
Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH for
the Office of Emergency and Remedial Response, Washington, DC.
U.S. EPA. 1985. Health and Environmental Effects Profile for 1,3-D1chloro-
propene. Prepared by the Office of Health and Environmental Assessment,
Environmental Criteria and Assessment Office, Cincinnati, OH for the Office
of Solid Waste and Emergency Response. Washington, DC. EPA/600/X-85/399.
NTIS PB88-174594.
U.S. EPA. 1986a. Methodology for Evaluating Reportable Quantity Adjustments
Pursuant to CERCLA Section 102. Prepared by the Carcinogen Assessment Group,
Office of Health and Environmental Assessment, Washington, DC for the Office
of Emergency and Remedial Response, Washington, DC.
U.S. EPA. 1986b. Exams II computer model. Athens, GA. Version 2.91.
U.S. EPA. 1986c. Guidelines for Carcinogen Risk Assessment. " Federal
Register. 51: 33992-34003.
U.S. EPA. 1987a. Graphical exposure modeling system (GEMS). PC Version,
April, 1987. CLOGP. Computer program.
U.S. EPA. 1987b. Integrated Risk Information System (IRIS). Reference Dose
(RfD) for Oral Exposure for 1,3-dlchloropropene. Online. (Verification date
04/15/87.) Office of Health and Environmental Assessment, Environmental
Criteria and Assessment Office. Cincinnati, OH.
6233H 10-16 09/28/89
-------
U.S. EPA. 1988. Health Advisory for 1,3-D1chloropropene. Prepared by the
Office of Drinking Water, Washington, DC.
U.S. EPA/OWRS. 1986. Guidelines for Deriving Numerical National Water
Quality Criteria for the Protection of Aquatic Organisms and Their Uses.
U.S. EPA, Washington, DC. p. 22-58, 98. NTIS PB85-227049/XAB.
Valencia R., J.H. Mason, R.C. Woodruff- and S. Zlmmerlng. 1985. Chemical
mutagenesls testing In drosophlla. III. Results of 48 coded compounds
tested for the National Toxicology Program. Env. Mutagen. 7: 325-348.
van der Pas, L.J.T. and M. Lelstra. 1987. Movement and transformation of
1,3-dlchloropropene In the soil of flower bulb fields. Arch. Env. Contam.
Toxlcol. 16: 417-422.
Van Duuren, B.L., B.M. Goldschmldt, G. Lowengart, et al. 1979.
Carclnogenlclty of halogenated oleflnlc and aliphatic hydrocarbons In mice.
J. Natl. Cancer Inst. 63: 1433-1440.
Varanka, I. 1979. Effect of some pesticides on the rhythmic adductor muscle
activity of freshwater mussel larvae. Symp. B1ol. Hung. 19: 177-196.
Venable, J.R., C.D. McCllmans, R.E. Flake and D.B. Dlmlck. 1980. A
fertility study of male employees engaged In the manufacture of glycerine.
J. Occup. Med. 22(2): 87-91.
6233H 10-17 09/28/89
-------
Vlthayathll, A.J., C. McClure and J.W. Meyers. 1983. Salmonella/mlcrosome
multiple Indicator mutagen1c1ty test. Muta. Res. 121: 33-37.
von der Hude, H., M. Scheutwlnkel, U. Gramllch and B. Flssler. 1987.
Geontoxldty of three carbon compounds evaluated 1n the SCE test in vitro.
Env. Mutagenesls. 9: 401-410.
Watson, M.P., T.M. Brooks, K.R. Huckle, D.H. Hutson, K.L. Lang and R.J.
Smith. 1987. Nlcroblal mutagenlclty studies with (2)-l,3-d1chloropropene.
Chem. Blol. Interact. 61: 17-30.
Wlndholz, M., Ed. 1983. The Merck Index. 10th ed. Merck and Co., Inc.,
Rahway, NJ. p 446.
Worthing, C.R. and S.B. Walker. 1987. The Pesticide Manual. 8th ed. The
British Crop Protection Council, Croydon, England, p. 4410, 4420.
Yang, R.S.H. 1986. 1,3-d1chloropropene. Res. Rev. 97: 19-35.
6233H 10-18 09/28/89
-------
APPENDIX A .
This HEED Is based on data Identified by computerized literature
searches of:
CHEMLINE
TSCATS
CASR online (U.S. EPA Chemical Activities Status Report)
TOXLINE
TOXLIT
TOXLIT 65
RTECS
OHM TADS
STORET
SRC Environmental Fate Data Bases
SANSS
AQUIRE
TSCAPP
NTIS
Federal Register
CAS ONLINE (Chemistry and Aquatic}
HSDB
SCISEARCH
Federal Research In Progress
These searches were conducted In March, 1989, and the following secondary
sources were reviewed:
ACGIH (American Conference of Governmental Industrial Hyglenlsts).
1986. Documentation of the Threshold Limit Values and Biological
Exposure Indices. 5th ed. Cincinnati, OH.
ACGIH (American Conference of Governmental Industrial Hyglenlsts).
1987. TLVs: Threshold Limit Values for Chemical Substances 1n the
Work Environment adopted by ACGIH with Intended Changes for
1987-1988. Cincinnati, OH. 114 p.
Clayton, G.D. and F.E. Clayton, Ed. 1981. Patty's Industrial
Hygiene and Toxicology. 3rd rev. ed. Vol. 2A. John Wiley and Sons,
NY. 2878 p.
Clayton, G.O. and F.E. Clayton, Ed. 1981. Patty's Industrial
Hygiene and Toxicology. 3rd rev. ed. Vol. 28. John Wiley and Sons,
NY. 2879-3816 p.
Clayton, G.D. and F.E. Clayton, Ed. 1982. Patty's Industrial
Hygiene and Toxicology. 3rd rev. ed. Vol. 2C. John Wiley and Sons,
NY. 3817-5112 p.
6140H A-l 07/25/89
-------
Grayson, M. and 0. Eckroth, Ed. 1978-84. Klrk-Othmer Encyclopedia
of Chemical Technology, 3rd ed. John Wiley and Sons, NY. 23 Volumes.
Hamilton, A. and H.L. Hardy. 1974. Industrial Toxicology. 3rd
edition. Publishing Sciences Group, Inc., HA. 575 p.
IARC (International Agency for Research on Cancer). IARC Monographs
on the Evaluation of Carcinogenic Risk of Chemicals to Humans. IARC,
Lyons, France: WHO.
Jaber, H.M., W.R. Mabey, A.T. L1eu, T.W. Chou and H.L. Johnson.
1984. Data acquisition for environmental transport and fate
screening for compounds of Interest to the Office of Solid Waste.
EPA-600/6-84-010. (NTIS PB84-243906) Henlo Park, CA: SRI Inter-
national.
NTP (National Toxicology Program). 1988. Toxicology Research and
Testing Program. Chemicals on Standard Protocol. Management Status.
Ouellette, R.P. and J.A. King. 1977. Chemical Week Pesticide
Register. McGraw-Hill Book Co., NY.
Sax, I.N. 1984. Dangerous Properties of Industrial Materials. 6th
ed. Van Nostrand Relnhold Co., NY.
SRI (Stanford Research Institute). 1987. Directory of Chemical
Producers. Stanford, CA.
U.S. EPA. 1986. Report on Status Report 1n the Special Review
Program, Registration Standards Program and the Data Call In
Programs. Registration Standards and the Data Call In Programs.
Office of Pesticide Programs, Washington, DC.
USITC (United States International Irade Commission). 1986.
Synthetic Organic Chemicals. U.S. Production and Sales, 1985, USITC
Publication 1892. Washington, DC.
Verschueren, K. 1983. Handbook of Environmental Data on Organic
Chemicals. 2nd ed. Van Nostrand Relnhold Co., NY.
Worthing, C.R. and S.6. Walker, Ed. 1983. The Pesticide Manual.
British Crop Protection Council. 695 p.
Wlndholz, M. Ed. 1983. The Merck Index. 10th ed. Merck and Co.,
Inc., Rahway, NJ.
6140H A-2 07/25/89
-------
In addition, approximately 30 compendia of aquatic toxicity data were
reviewed, including the following:
Battelle's Columbus Laboratories. 1971. Water Quality Criteria Data
Book. Volume 3. Effects of Chemicals on Aquatic Life. Selected
Data from the Literature through 1968. Prepared for the U.S. EPA
under Contract No. 68-01-0007. Washington, DC.
Johnson, W.W. and M.T. Finley. 1980. Handbook of Acute Toxicity of
Chemicals to Fish and Aquatic Invertebrates. Summaries of Toxicity
Tests Conducted at Columbia National Fisheries Research Laboratory.
1965-1978. United States Dept. Interior, Fish and Wildlife Serv.
Res. Publ. 137, Washington, DC.
McKee, J.E. and H.W. Wolf. 1963. Water Quality Criteria. 2nd ed.
Prepared for the Resources Agency of California, State Water Quality
Control Board. Publ. No. 3-A.
Pimental, D. 1971. Ecological Effects of Pesticides on Non-Target
Species. Prepared for the U.S. EPA, Washington, DC. PB-269605.
Schneider, 8.A. 1979. Toxicology Handbook. Mammalian and Aquatic
Data. Book 1: Toxicology Data. Offi'ce of Pesticide Programs, U.S.
EPA, Washington, DC. EPA 540/9-79-003. NTIS PB 80-196876.
6140H A-3 06/16/89
-------
APPENDIX 6
Cancer Data Sheet for Derivation of q! for
Inhalation Exposure
Compound: 1,3-dlchloropropene
Reference: lomax et al., 1989
Specles/straln/sex: mouse, B6C3F1, male
Body weight = 0.030 kg (measured)
Length of exposure = 24 months
Length of experiment (Le) - 24 months
Llfespan of animal (L) * 24 months
Tumor site and type: lung, benign adenoma
Experimental Doses or
Exposures
-------
APPENDIX C
Summary Table for 1,3-Olchloropropene
Species
Exposure
Effect
RfO or qj*
Reference
Inhalation exposure
Subchronlc
Chronic
Carclnogenlclty
Oral exposure
Subchronlc
Chronic
Cardnogenlclty
rat
rat
mouse
rat
rat
rat
10 ppm (45.4 mg/m») 6
hours/day. 5 days/week for
13 weeks (HEC. 1.4 mg/m')
10 ppm (45.4 mg/m») 6
hours/day, 5 days/week for
13 weeks (HEC. 1.4 mg/m»)
5, 20. 60 ppm (22.7, 90.6.
272 mg/m*} 6 hours/day, S
days/week for 2 years
3 mg/kg/day, 6 days/week
for 90 days
3 mg/kg/day, 6 days/week
for 90 days
0. 25, 50 mg/kg/day,
3 days/week for 104 weeks
degenerative changes 1n nasal
mucosa at higher doses
degenerative changes In nasal
mucosa at higher doses
benign lung tumors
Increased kidney weight at
higher doses
Increased kidney weight at
higher doses
forestomach, liver
0.01 mg/m*
0.01 mg/m»
1.3 x 10~l
( mg/kg/day T1
3 x 10~»
(mg/kg/day }
3 x 10~«
(mg/kg/day)
1.8 x 10'»
(mg/kg/day)"1
Stott et al.. 1982
Stott et al., 1988
Umax et al.. 1989
T11 et al., 1973
Til et al., 1973
NTP. 1985
»EPO)>T*BLE QUANTITIES
Based on chronic
toxlclty:
Based on care Inogenl city:
100
100
CD
CD
10
-------
APPENDIX D
DOSE-DURATION RESPONSE GRAPHS FOR EXPOSURE TO
1,3-DICHLOROPROPENE
D.I. DISCUSSION
Dose-duration response graphs for inhalation and oral exposure to 1,3-
dlchloropropene generated by the method of Crockett et al. (1985) using the
computer software by Durkin and Meylan (1988) developed under contract to
ECAO-Clndnnatl are presented In Figures D-l to D-6. Data used to generate
these graphs are presented in Section D.2. In generation of these figures,
all responses are classified as adverse (PEL, AEL or LOAEL) or' non-adverse
(NOEL or NOAEL) for plotting. For Inhalation exposure, the ordinate
expresses concentration in either of two ways. In Figures D-l and D-2, the
experimental concentration expressed as mg/m3 was multiplied by the time
parameters of the exposure protocol (e.g., hours/day and days/week) and is
presented as expanded experimental concentration (mg/m3). In Figures D-3
and D-4, the expanded experimental concentration was multiplied by the cube
root of the ratio of the animal ihuman body weight to adjust for species
differences In basal metabolic rate (Mantel and Schnelderman, 1975) to
estimate an equivalent human or scaled concentration (mg/m3). For oral
exposure, the ordinate expresses dosage as human equivalent dose (Figures
D-5 and D-6). The animal dosage in mg/kg/day Is multiplied by the cube root
of the ratio of the animal .'human body weight to adjust for species
differences in basal metabolic rate (Mantel and Schnelderman, 1976). The
result is then multiplied by 70 kg, the reference human body weight, to
express the human equivalent dose as mg/day for a 70 kg human.
The Boundary for Adverse Effects (solid line) 1s drawn to identify the
lowest adverse effect dose or concentration at the shortest duration of
6234H D-l 06/16/89
-------
0
N
9
V
X
U
B
U
B
i
0.
X
U
iieeei
10001 • r
IBM
B.0001
Exposure)
0.001 0.01 0.1
HUNAN EQUIU DURATION (fraction tifespan)
ENVELOP METHOD
Figure D-l
Dose/Duration - Response Graph for Inhalation Exposure to
1,3-01chloropropene: Expanded Experimental Concentration, Envelop Method
Key: N - NOEL
n - NOAEL
L « LOAEL
A » AEL
F « FEL
Solid Line - Adverse Effects Boundary
Dotted Line » No Adverse Effects Boundary
6234H
0-2
06/16/89
-------
P]
x;
ui
i
A,
bj
100000
loeoo •-
1000 - -
100 •-
10--
i--
e.i
A41
F40
n24
L4 1
n3
NJL2
B •8881
< Inhat at i on Exposure )
t | j f j i III.
0.001 0.01 0.1
HUNAN EQUIU DURATION (fraction lifespan)
CENSORED DATA METHOD
1 2
Figure D-2
Dose/Duration - Response Graph for Inhalation Exposure to
1,3 Dichloropropene: Expanded Experimental
Concentration, Censored Data Method
Key:
N
n
L
A
F
NOEL
NOAEL
LOAEL
AEL
FEL
Solid Line » Adverse Effects Boundary
Dotted Line - No Adverse Effects Boundary
6234H
0-3
06/16/89
-------
e
hi
3
e.ei
010001.
(Inhalat ion Exposure >
0.001 0.01 e.i
HUMAN EQUIV DURATION (Fraction lifespan)
ENMELOP METHOD
Figure D-3
Dose/Duration - Response Graph for Inhalation Exposure to
1,3 Dkhloropropene: Scaled Concentration, Envelop Method
Key: N - NOEL
n - NOAEL
L » LOAEL
A . AEL
F . FEL
Solid Line - Adverse Effects Boundary
Dotted Line » No Adverse Effects Boundary
6234H
0-4
06/16/89
-------
n
A
U
•J
W
0.1--
0.01
0.0001
-------
I
\
i
e.eei
B.81 6.1
HUMAN EQUIV DURATION (fraction Ufespan)
ENUELOP METHOD
Figure D-5
Dose/Duration - Response Graph for Oral Exposure to
1,3 DUhloropropene: Human Equivalent Dose, Envelop Method
Key:
N
L
A
F
NOEL
LOAEL
AEL
FEL
Solid Line - Adverse Effects Boundary
Dotted Line « No Adverse Effects Boundary
6234H
D-6
06/16/89
-------
ft
*.*
t\
If
bl
fl
w
S1
2:
1M0
18 T
0.1
: ]'13
8,881
-------
exposure at which an adverse effect occurred. From this point, an infinite
line is extended upward, parallel to the dose axis. The starting point is
then connected to the lowest adverse effect dose or concentration at the
next longer duration of exposure that has an adverse effect dose or
concentration equal to or lower than the previous one. This process is
continued to the lowest adverse effect dose or concentration. From this
point, a line Is extended to the right, parallel to the duration axis. This
Region of Adverse Effects lies above the Adverse Effects Boundary.
Using the envelope method, the Boundary for No Adverse Effects (dashed
line) is drawn by identifying the highest no adverse effects dose or
concentration. From this point, a line parallel to the duration axis is
extended to the dose or concentration axis. The starting point is then
connected to the next lower or equal no adverse effect dose or concentration
at a longer duration of exposure. When this process can no longer be
continued, a line is dropped parallel to the dose or concentration axis to
the duration axis. The Region of No Adverse Effects lies below the No
Adverse Effects Boundary. At either ends of the graph between the Adverse
Effects and No Adverse Effects Boundaries are Regions of Ambiguity. The
area (if any) resulting from Intersection of the Adverse Effects and No
Adverse Effects Boundaries is defined as the Region of Contradiction.
In the censored data method, all no adverse effect points located in the
Region of Contradiction are dropped from consideration and the No Adverse
Effect Boundary is redrawn so that it does not intersect the Adverse Effects
Boundary and no Region of Contradiction 1s generated. This method results
1n the most conservative definition of the No Adverse Effects Region.
6234K D-8 06/16/89
-------
In the graphs depicting the Inhalation data (Figures D-l to D-4), no
one species, effect or study figures predominantly In defining the Adverse
Effects Boundary. The LOAELs for the primary Inflection of the Adverse
Effects Boundary (rec #35 and 36), «0.004-0.007 llfespan of the human
equivalent durations, reflect toxic maternal effects (decreased body weight
gain) In rats and rabbits 1n a teratogenlclty study (Hanley et al. 1987).
The AELs (rec #33 and 34) found at =0.02-0.05 Hfespan of the human
equivalent durations reflect kidney- and liver necrosis in rats and guinea
pigs (Torkelson and Oyen, 1977). The Region of Contradiction Is quite large
and is contained within the 0.003-1.0 llfespan region of the human
equivalent duration. This region is not characterized by any one species,
effect or study, and probably reflects differences in study protocol and
quality. The chronic and subchronic inhalation RfO of 0.01 mg/m3 is based
on a NOEL for degenerative changes in the nasal mucosa of rats (rec #1)
(Stott et al. 1988). The Inhalation RfDs are well below the Boundary for No
Adverse Effects.
In the graphs depicting the oral data (Figure D-5 and 0-6), the data
points concentrated at sO.0015 lifespan of the human equivalent duration
reflect oral LDsos for rats and mice (rec #10, 13, 16, 17). The LOAEL for
the primary Inflection point (rec #7, *0.15 lifespan of the human
equivalent duration, in the Adverse Effect Boundary reflects an Increase In
kidney weights in male rats (Til et al., 1973). The Adverse Effect Boundary
is nearly without slope at human equivalent durations =0.1 lifespan,
suggesting little difference between the subchronic and chronic toxldty of
l,3-d1chloropropene. This conclusion, however, cannot be drawn due to the
small number of oral studies available. The Region of Contradiction is
quite small, reflecting the small number of oral studies available. The
6234H D-9 06/26/89
-------
chronic and subchronic oral RfOs of 3 x 10"" and 3 x 10~3, respectively,
are based on a NOEL for kidney effects In the T11 et al. study (rec #1) and
are well below the boundary for No Adverse Effects.
D.2. DATA USED TO GENERATE DOSE/DURATION-RESPONSE GRAPHS
D.2.1. INHALATION EXPOSURE
Chemical Name:
CAS Number:
Document Title:
Document Number:
Document Date:
Document Type:
1,3-dlchloropropene
542-75-6
Health and Environmental Effects Document on
1,3-Dichloropropene
FOltO-106
5/16/89
HEED
RECORD #1 :
Species: Rats
Sex: Male
Effect: NOEL
Route: Inhalation
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
Dose: 8.
Duration
Duration
10
0
DEGEN
NASAL
6
100
Exposure: 13
Observation:
.0 Weeks
13.0 Weeks
Comment: Concentrations given: 0, 10, 30, 90, 150 ppm,
6 hours/day, 5 days/week. Basis of subchronic
and chronic RfD. Degeneration of the nasal
mucosa seen In all rats at 90 and 150 ppm
and in male rats at 30 ppm.
Citation: Stott et al., 1988
6234H
D-10
06/26/89
-------
RECORD #2:
RECORD #3:
Species:
Sex:
Effect:
Route:
Rats
Male
NOEL
Inhalation
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
Dose: 0.500
Duration Exposure: 6.0 Months
Duration Observation: 6.0 Months
11
0
HYPRT
KIDNY
3
Comment: Concentrations given: 1, 3 ppm 4 or 7 hours/
day, 5 days/week. Slight reversible cloudy
swelling of the renal epithelium at 3 ppm.
Composition of test material not specified.
Citation: Torkelson and Oyen, 1977
Species:
Sex:
Effect:
Route:
Rats
Both
NOAEL
Inhalation
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
Dose: 16.200
Duration Exposure: 24.0 Months
Duration Observation: 24.0 Months
100
1.
DEGEN
NASAL
6
Comment: Concentrations given: 0, 5, 20, 60 ppm. Degen-
eration of the nasal tissues seen at high Inci-
dence in one male and females at 60 ppm and in
one male at 20 ppm at 24, but not at 6 or 12
months.
Citation: Lomax et al., 1989
RECORD #4:
Species:
Sex:
Effect:
Route:
Rats
Both
LOAEL
Inhalation
Dose: 48.600
Duration Exposure: 24.0 Months
Duration Observation: 24.0 Months
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
100
35
DEGEN
NASAL
6
Comment: Concentrations given: 0. 5, 20, 60 ppm 6 hours/
day, 5 days/week. Degeneration of the nasal
tissues seen at high Incidence in male and fe-
male at 60 ppm at 24, but not at 6 or 12 months
Citation: Lomax et al,, 1989
6234H
0-11
06/26/89
-------
RECORD #5:
Species:
Sex:
Effect:
Route:
Mice
Female
LOAEL
Inhalation
Dose: 16.200
Duration Exposure: 24.0 Months
Duration Observation: 24.0 Months
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
0
21
HYPRP
OTHER
3
50
28
HYPRP
NASAL
3
Comment: Concentrations given: 0, 5, 20, 60 ppm 6
hours/day, 5 days/week. Hyperplasia of the
urinary bladder and the nasal epithelium were
found at 20 arid 60 ppm.
Citation: Lomax et al. 1989
RECORD #6:
Species:
Sex:
Effect:
Route:
Mice
Female
NOAEL
Inhalation
Dose: 4.000
Duration Exposure: 24.0 Months
Duration Observation: 24.0 Months
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
46
4
HYPRP
OTHER
3
50
4
HYPRP
NASAL
3
Comment: Concentrations given: 0, 5, 20, 60 ppm,
Hyperplasia of the urinary bladder and nasal
epithelium were found at 20 ppm and greater.
Citation: Lomax et al., 1989
RECORD #7:
Species:
Sex:
Effect:
Route :
Mice
Male
NOAEL
Inhalation
Dose: 16.200
Duration Exposure: 24.0 Months
Duration Observation: 24.0 Months
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
48
11
HYPRP
OTHER
3
50
4
HYPRP
NASAL
3
Comment: Concentrations given: 0, 5, 20, 60 ppm.
Hyperplasia of the urinary bladder and nasal
epithelium were found at 60 ppm.
Citation: Lomax et al., 1989
6234H
D-12
06/26/89
-------
RECORD #8:
Species:
Sex:.
Effect:
Route:
Mice
Male
AEL
Inhalation
Dose: 48.600
Duration Exposure: 24.0 Months
Duration Observation: 24.0 Months
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
47
37
HYPRP
OTHER
3
50
48
HYPRP
NASAL
3
Comment: Concentrations given: 0, 5, 20, 60 ppm.
Hyperplasla of the urinary bladder and nasal
epithelium were found at 60 ppm.
Citation: Lomax et al., 1989
RECORD #9:
Species:
Sex:
Effect:
Route:
Rats
Male
LOAEL
Inhalation
Dose: 2.800
Duration Exposure: 6.0
Duration Observation: 6
Months
.0 Months
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
9
NR
HYPRT
KIDNY
3
Comment: Concentrations given: 1, 3 ppm. Slight,
reversible cloudy swelling of the renal
epithelium at 3 ppm. Composition of test
material not specified.
Citation: Torkelson and Oyen, 1977
RECORD #10:
Species:
Sex:
Effect:
Route:
Dogs
Both
NOEL
Inhalation
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
Dose: 2.800
Duration Exposure: 6.0 Months
Duration Observation: 6.0 Months
2
0
TOXSL
BODY
2
Comment: Concentrations given: 1, 3 ppm.
histological effects found.
Citation: Torkelson and Oyen, 1977
No
6234H
D-13
06/26/89
-------
RECORD #11
Species:
Sex:
Effect:
Route:
Rabbits
Both
NOEL
Inhalation
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
Dose: 2.800
Duration Exposure: 6.0 Months
Duration Observation: 6.0 Months
5
0
TOXSL
BODY
2
Comment: Concentrations given: 1, 3 ppm.
histologlcal effects seen.
Citation: Torlcelson and Oyen, 1977
No
RECORD #12:
Species:
Sex:
Effect:
Route:
Guinea Pigs
Both
NOEL
Inhalation
Dose: 2.800
Duration Exposure: 6
Duration Observation
.0 Months
: 6.0 Months
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
18
0
TOXSL
BODY
2
Comment: Concentrations given: 1, 3 ppm.
histologlcal effects seen.
Citation: Torkelson and Oyen, 1977
No
RECORD #13:
Species:
Sex:
Effect:
Route:
Rats
Male
LOAEL
Inhalation
Dose: 24
Duration
Duration
.300
Exposure: 13
Observation:
.0
13
Neeks
.0 Weeks
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
10
2
DEGEN
NASAL
6
Comment: Concentrations given: 0, 10, 30, 90, 150 ppm
6 hours/day, 5 days/week. Degeneration of
nasal epithelium seen at 30 ppm.
Citation: Stott et al., 1988
6234H
D-14
06/16/89
-------
RECORD #14:
Species:
Sex:
Effect:
Route:
Rats
Female
NOEL
Inhalation
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
Dose: 24.300
Duration Exposure: 13.0 Neeks
Duration Observation: 13.0 Heeks
10
0
DEGEN
NASAL
6
Comment: Concentrations given: 0, 10, 30, 90, 150 ppm
Degeneration of nasal epithelium seen at >
Citation: Stott. et al., 1-988
RECORD #15:
Species: Rats
Sex: Female
Effect: LOAEL
Route: Inhalation
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
Dose: 73.000
Duration Exposure: 13.0
Duration Observation: 13
10
10
DEGEN
NASAL
6
Weeks
.0 Neeks
Comment: Concentrations given: 0, 10, 30, 90, 150 ppm.
Degeneration of the nasal epithelium seen at
_>90 ppm.
Citation: Stott et al., 1988
RECORD #16:
Species:
Sex:
Effect:
Route:
Mice
Female
NOAEL
Inhalation
Dose: 24.300
Duration Exposure: 13
Duration Observation:
.0 Neeks
13.0 Neeks
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
9
0
HYPRP
OTHER
3
9
0
DEGEN
NASAL
6
Comment: Concentrations given: 0, 10, 30, 90, 150 ppm.
Hyperplasia of the urinary bladder and nasal
degeneration seen at >9Q ppm.
Citation: Stott et al., 1988
6234H
D-15
06/16/89
-------
RECORD #17:
Species:
Sex: '
Effect:
Route:
Mice
Fema1e
LOAEL
Inhalation
Dose: 73.000
Duration Exposure: 13.0 Weeks
Duration Observation: 13.0 Weeks
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
9
7
HYPRP
OTHER
3
9
9
DEGEN
NASAL
6
Comment: Concentrations given: 0, 10, 30, 90, 150 ppm.
Degeneration of the urinary bladder and nasal
degeneration seen at ^90 ppm.
Citation: Stott et al.. 1988
RECORD #18:
Species:
Sex:
Effect:
Route:
Mice
Male
NOEL
Inhalation
Dose: 24
Duration
Duration
.300
Exposure: 13
Observation:
.0
13
Weeks
.0 Weeks
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
10
0
DEGEN
NASAL
6
Comment: Concentrations given: 0, 10, 30, 90, 150 ppm.
Nasal degeneration found at ,>90 ppm.
Citation: Stott et al., 1988
RECORD #19:
Species:
Sex:
Effect:
Route :
Mice
Male
LOAEL
Inhalation
Dose: 73
Duration
Duration
.000
Exposure: 13
Observation:
.0
13
Weeks
.0 Weeks
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
10
10
DEGEN
NASAL
6
Comment: Concentrations given: 0, 10, 30, 90, 150 ppm.
Nasal degeneration seen at >9Q ppm.
Citation: Stott et al., 1988
6234H
D-16
06/26/89
-------
RECORD #20:
Species:
Sex:
Effect:
Route:
Rats
Both
NOAEL
Inhalation
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
Dose: 30.300
Duration Exposure: 13.0 Neeks
Duration Observation: 13.0 Weeks
NR
NR
WGTDC
BODY
4
Comment: Concentrations given: 0, 12, 32, 93 ppm.
Decreased body weight gain at 93 ppm.
Citation: Coate et al.,-1979
RECORD #21:
Species:
Sex:
Effect:
Route :
Rats
Both
LOAEL
Inhalation
Dose: 88
Duration
Duration
.000
Exposure:
1
3
Observation:
.0
13
Weeks
.0 Weeks
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
NR
NR
WGTDC
BODY
4
Comment: Concentrations given: 0, 12, 32, 93 ppm.
Decreased body weight gain at 93 ppm.
Citation: Coate et al., 1979
RECORD #22:
Species:
Sex:
Effect:
Route:
Mice
Female
NOAEL
Inhalation
Dose: 30
Duration
Duration
.300
Exposure: 13
Observation:
.0
13
Weeks
.0 Weeks
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
NR
NR
WGTDC
BODY
4
Comment: Concentrations given: 0, 12, 32, 93 ppm.
Decreased body weight gain at 93 ppm.
Citation: Coate et al., 1979
6234H
0-17
06/16/89
-------
RECORD #23;
Species:
Sex:
Effect:
Route:
Mice
Female
LOAEL
Inhalation
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
Dose: 88.000
Duration Exposure: 13.0 Weeks
Duration Observation: 13.0 Weeks
NR
NR
WGTDC
BODY
4
Comment: Concentrations given: 0, 12, 32, 93 ppm.
Decreased body weight gain at 93 ppm.
Citation: Coate,etal., V979
RECORD #24:
Species:
Sex:
Effect:
Route:
Mice
Male
NOAEL
Inhalation
Dose: 88
Duration
Duration
.000
Exposure: 13
Observation:
.0
13
Weeks
.0 Weeks
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
NR
NR
WGTDC
BODY
4
Comment: Concentrations given: 0, 12, 32, 93 ppm.
Decreased body weight gain at 93 ppm.
Citation: Coate et al., 1979
RECORD #25:
Species:
Sex:
Effect:
Route:
Rats
Both
NOAEL
Inhalation
Dose: 12
Duration
Duration
.200
Exposure: 12
Observation:
.0
12
Weeks
.0 Weeks
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
18
NR
WGTIN
BODY
4
Comment: Concentrations given: 0, 5, 15, 50 ppm.
Increased liver-to-body weight seen in males
and increased kidney-to-body weight seen In
females at 50 ppm.
Citation: Parker et al., 1982
6234H
D-18
06/16/89
-------
RECORD #26:
Species:
Sex:
Effect:
Route:
Rats
Both
LOAEL
Inhalation
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
Dose: 40.500
Duration Exposure: 12.0 Weeks
Duration Observation: 12.0 Weeks
18
NR
WGTIN
BODY
4
Comment: Concentrations given: 0, 5, 15, 50 ppm.
Increased liver-to-body weight In males and
Increased kidney-to-body weight In females at
50 ppm.
Citation: Parker et al., 1982
RECORD #27:
Species:
Sex:
Effect:
Route:
Mice
Male
LOAEL
Inhalation
Dose: 40.500
Duration Exposure: 12.0 Weeks
Duration Observation: 12.0 Weeks
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
Zl
12
HYPRT
LIVER
3
Comment: Concentrations given: 0, 5, 15, 50 ppm.
Hepatocytlc enlargement seen at 50 ppm.
Citation: Parker et al., 1982
RECORD #28:
Species:
Sex:
Effect:
Route:
Mice
Male
NOAEL
Inhalation
Dose: 12.200
Duration Exposure: 12.0 Weeks
Duration Observation: 12.0 Weeks
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
NR
NR
HYPRT
LIVER
3
Comment: Concentrations given: 0, 5, 15, 50 ppm.
Hepatocytic enlargement seen at 50 ppm.
Citation: Parker et al., 1982
6234H
D-19
06/16/89
-------
RECORD #29:
Species:
Sex:
Effect:
Route:
Mice
Female
NOAEL
Inhalation
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
Dose: 12.200
Duration Exposure: 12.0 Weeks
Duration Observation: 12.0 Weeks
18
NR
HYPRT
LIVER
3
Comment: Concentrations given: 0, 5, 15, 50 ppm.
Nepatocytic enlargement seen at 50 ppm.
Citation: Parker et al./1982
RECORD #30:
Species:
Sex:
Effect:
Route:
Mice
Female
LOAEL
Inhalation
Dose: 40.500
Duration Exposure: 12
Duration Observation:
.0 Neeks
12.0 Weeks
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
18
6
HYPRT
LIVER
3
Comment:
Concentrations given: 0, 5, 15, 50 ppm.
Hepatocytic enlargement seen at 50 ppny;
Citation: Parker et al., 1982
RECORD #31 :
Species:
Sex:
Effect:
Route:
Rats
Both
NOEL
Inhalation
Dose: 24.300
Duration Exposure: 10.0 Weeks
Duration Observation: 10.0 Weeks
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
30
NR
WGTDC
BODY
3
30
NR
WGTIN
KIDNY
4
30
NR
WGTIN
LIVER
4
Comment: Concentrations given: 0, 10, 30, 90 ppm.
Small decrease In body weight gain and slight
increases in liver and kidney weights were
found at 90 ppm in this reproduction study.
Citation: Llnnett et al., 1988
6234H
D-20
06/16/89
-------
RECORD #32;
Species:
Sex:
Effect:
Route:
Rats
Both
LOAEL
Inhalation
Dose: 73.000
Duration Exposure: 10.0 Weeks
Duration Observation: 10.0 Weeks
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
30
NR
WGTDC
BODY
3
30
NR
WGTIN
KIDNY
4
30
NR
WGTIN
LIVER
4
Comment: Concentrations given: 0, TO, 30, 90 ppm.
Small decrease 1n body weight gain and slight
Increase In liver and kidney weights at 90 ppm
In this reproduction study.
Citation: Llnnett et al., 1988
RECORD #33:
Species: Rats
Sex: N.S.
Effect: AEL
Route: Inhalation
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect: ,
Dose: 10.100
Duration Exposure: 39
Duration Observation:
NR
NR
NECRO
KIDNY
6
.0 Days
39.0 Days
NR
NR
NECRO
LIVER
6
Comment: Concentrations given: 11, 50 ppm.
Citation: Torkelson and Oyen, 1977
RECORD #34:
Species: Guinea P1gs Dose: 10.100
Sex: N.S. Duration Exposure: 39.0 Days
Effect: AEL Duration Observation: 39.0 Days
Route: Inhalation
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
NR
NR
NECRO
KIDNY
6
NR
NR
NECRO
LIVER
6
Comment: Concentrations given: 11, 50 ppm.
Citation: Torkelson and Oyen, 1977
6234H
0-21
06/16/89
-------
RECORD #35:
Species:
Sex: •
Effect:
Route:
Rats
Female
LOAEL
Inhalation
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
Dose: 22.700
Duration Exposure: 6.0 Days
Duration Observation: 15.0 Days
30
NR
WGTDC
BODY
4
Comment: Concentrations given: 0, 20, 60, 120 ppm.
No teratogeniclty found but maternal toxlcity
seen at >20 ppm.
Citation: Hanley et al., 1987
RECORD #36:
Species:
Sex:
Effect:
Route:
Rabbits
Female
LOAEL
Inhalation
Dose: 22,700
Duration Exposure: 12.0 Days
Duration Observation: 23.0 Days
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
25
NR
WGTDC
BODY
4
Comment: Concentrations given: 0, 20, 60, 120 ppm.
No teratogenicity seen but maternal toxlcity
found at _>20 ppm.
Citation: Hanley et al., 1987
RECORD #37:
Species:
Sex:
Effect:
Route :
Rats
N.S.
FEL
Inhalation
Dose: 4530.000
Duration Exposure: 1 .0
Duration Observation: 1
Days
.0 Days
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
NR
NR
DEATH
BODY
10
Comment: 4530 mg/m3 was an
Citation: Hlne et al., 1953
6234H
D-22
06/16/89
-------
RECORD #38:
Species:
Sex:
Effect:
Route:
Mice
N.S.
FEL
Inhalation
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
Dose: 4530.000
Duration-Exposure: 1.0 Days
Duration Observation: 1.0 Days
NR
NR
DEATH
BODY
10
Comment: 4530 mg/m3 was the LC50.
Citation: Mine et al., 1953
RECORD #39:
RECORD #40:
Species: Guinea P1gs Dose: 1800.000
Sex: N.S. Duration Exposure: 1.0
Effect: FEL Duration Observation: 1
Route: Inhalation
Number Exposed: NR
Number Responses: NR
Type of Effect: DEATH
Site of Effect: BODY
Severity Effect: 10
Comment: Concentration given: 400 ppm. Death
after 7-hour exposure.
Citation: Torkelson and Oyen, 1977
Species: Rats Dose: 4500.000
Sex: N.S. Duration Exposure: 1.0
Effect: FEL Duration Observation: 1
Route: Inhalation
Days
.0 Days
seen
Days
.0 Days
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
NR
NR
DEATH
BODY
10
Comment: 1000 ppm was the LC50.
Citation: Torkelson and Oyen, 1977
6234H
D-23
06/16/89
-------
RECORD #41
Species:
Sex:
Effect:
Route:
Rats
N.S.
AEL
Inhalation
Dose: 12000.000
Duration Exposure: 1.0 Days
Duration Observation: 1.0 Days
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
NR
NR
IRRIT
MMBRN
3
NR
NR
TOXDF
KIDNY
6
NR
NR
TOXDF
LIVER
6
Comment: Concentration given: 2700 ppm 1,3-DCP was a
mucous membrane Irritant and caused injury to
lung, kidney, liver and nasal area.
Citation: Torkelson and Oyen, 1977
RECORD #42:
Species:
Sex:
Effect:
Route:
Rats
Both
LOAEL
Inhalation
Dose: 72.900
Duration Exposure: 15.0 Weeks
Duration Observation: 15.0 Weeks
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
70
NR
DEGEN
LUNG
6
70
NR
WGTDC
BODY
4
Comment: 90 ppm (range 0, 10, 30, 90 ppm) 6 hours/day,
5 days/week 1n multigeneration repro study.
NOAEL for repro (slight reduction in female
conception indices); respiratory epithelial
lesions, body weight loss.
Citation: Breslin et al., 1987
RECORD #43:
Species:
Sex:
Effect:
Route:
Rats
Both
NOAEL
Inhalation
Dose: 24
Duration
Duration
.300
Exposure: 15
Observation:
.0
15
Weeks
.0 Weeks
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
70
NR
DEGEN
LUNG
6
70
NR
WGTDC
BODY
4
Comment: 30 ppm
-------
D.2.2. ORAL EXPOSURE
Chemical Name:
CAS Number:
Document Title:
Document Number:
Document Date:
Document Type:
1,3-d1chloropropene
542-75-6
Health and Environmental
1,3-01chloropropene
F0110-106
5/16/89
HEED
Effects Document on
RECORD #1 :
Species:
Sex:
Effect:
Route:
Rats
Male
NOEL
Gavage-
Dose: 2.600
Duration Exposure: 13.0 Keeks
Duration Observation: 13.0 Weeks
*
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
NR
NR
WGTIN
KIDNY
4
Comment: Doses given: 0, 1, 3, 10, 30 mg/kg. Used as
the basis for the chronic and subchronlc
oral RfD. A higher relative kidney weight was
seen 1n male rats at 210 mg/kg.
Citation: T11 et al.. 1973
RECORD #2:
Species:
Sex:
Effect:
Route:
Rats
Female
AEL
Gavage
Dose: 10.700
Duration Exposure: 2.0
Duration Observation: 2
Years
.0 Years
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
52
24
NEURP
KIDNY
6
Comment: Doses given: 0. 25. 50 mg/kg 15/52 control,
24/52 low dose and 22/52 high dose.
Citation: NTP, 1985
6234H
D-25
06/27/89
-------
RECORD #3:
Species:
Sex:
Effect:
Route:
Rats
Male
NOAEL
Gavage
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
Dose: 10.700
Duration Exposure: 2.0 Years
Duration Observation: 2.0 Years
52
5
HYPRP
OTHER
3
Comment: Doses given: 0, 25, 50 mg/kg. Hyperplasia of
the forestomach seen at 50 mg/kg.
Citation: NTP,~1985
RECORD #4: Species: Rats
Sex: Male
Effect: AEL
Route: Gavage
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
Dose: 21
Duration
Duration
52
13
HYPRP
OTHER
3
.400
Exposure: 2.0 Years
Observation: 2.0 Years
Comment: Doses given: 0, 25, 50 mg/kg. Hyperplasia of
the forestomach seen at 50 mg/kg.
Citation: NTP, 1985
RECORD #5:
Species:
Sex:
Effect:
Route:
Mice
Female
AEL
Gavage
Dose: 21.400
Duration Exposure: 2.0
Duration Observation: 2
Years
.0 Years
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
50
15
HYPRP
OTHER
3
Comment: Doses given: 0, 25, 50 mg/kg. Hyperplasia of
the urinary bladder was found at 50 mg/kg.
Citation: NTP, 1985
6234H
D-26
06/27/89
-------
RECORD #6:
Species:
Sex:
Effect:
Route:
Mice
Male
AEL
Gavage
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
Dose: 21.400
Duration Exposure: 2.0 Years
Duration Observation: 2.0 Years
50
9
HYPRP
OTHER
3
Comment: Doses given: 0, 50, 100 mg/kg. Hyperplasla of
the urinary bladder found at 50 mg/kg.
Citation: NTP,-1985
RECORD #7 :
Spedes:
Sex:
Effect:
Route:
Rats
Male
LOAEL
Gavage
Dose: 8.600
Duration Exposure: 13
Duration Observation:
.0
13
Weeks
.0 Weeks
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
NR
NR
WGTIN
KIDNY
4
Comment: Doses given: 0, 1, 3, 10, 30 mg/kg. Increase
1n kidney weight was found in male rats
treated with ^10 mg/kg. The NOAEL 2.6 mg/kg
is basis for chronic and subchronic RfD.
Citation: Til et al., 1973
RECORD #8:
Species:
Sex:
Effect:
Route:
Rats
Female
NOEL
Gavage
Dose: 8.600
Duration Exposure: 13.0 Weeks
Duration Observation: 13.0 Weeks
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
NR
NR
WGTIN
KIONY
4
Comment: Doses given: 0, 1, 3, 10, 30 mg/kg.
Citation: Til et al., 1973
6234H
D-27
06/27/89
-------
RECORD #9:
Species:
Sex: '
Effect:
Route:
Rats
Female
LOAEL
Gavage
Number Exposed:
Number Responses:
Type of Effect:
SUe of Effect:
Severity Effect:
Dose: 25,700
Duration Exposure: 13.0 Weeks
Duration Observation: 13.0 Weeks
NR
NR
WGTIN
KIDNY
4
Comment: Doses given: 0, 1, 3, 10, 30 mg/kg
Citation: Til et al.t 1973
RECORD #10:
RECORD #1 1 :
Species: Rats
Sex: Male
Effect: FEL
Route: Oral, NOS
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
Comment: LD50 was
Citation: Torkelson
Species: Rats
Sex: Female
Effect: FEL
Route: Oral, NOS
Dose: 710.000
Duration Exposure: 1.0
Duration Observation: 1
NR
NR
DEATH
BODY
10
710 mg/kg.
and Rowe, 1981
Dose: 470.000
Duration Exposure: 1 .0
Duration Observation: 1
Days
.0 Days
Days
.0 Days
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
NR
NR
DEATH
BODY
10
Comment: LD50 was 470 mg/kg.
Citation: Torkelson and Rowe, 1981
6234H
D-28
06/27/89
-------
RECORD #12:
Species:
Sex:
Effect:
Route:
Rats
Male
PEL
Oral, NOS
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
Dose: 560.000
Duration Exposure: 1.0 Days
Duration Observation: 1.0 Days
NR
NR
DEATH
BODY
10
Comment: LD5o was 560 mg/kg (95% confidence limits
were 452-695).
Citation: ToyosMma et al.", 1978a
RECORD #13:
Species:
Sex:
Effect:
Route:
Rats
Female
PEL
Oral, NOS
Dose: 510.000
Duration Exposure: 1.0
Duration Observation: 1
Days
.0 Days
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
NR
NR
DEATH
BODY
10
Comment: LD50 was 510 mg/kg (951 confidence limits
were 480-726)
Citation: Toyoshlma et al., 1978a
RECORD #14:
Species:
Sex:
Effect:
Route :
Rats
N.S.
PEL
Oral, NOS
Dose: 140.000
Duration Exposure: 1.0
Duration Observation: 1
Days
.0 Days
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
NR
NR
DEATH
BODY
10
Comment: LDSQ was 140 +/- 25 mg/kg.
Citation: Mine et al., 1953
6234H
D-29
06/16/89
-------
RECORD #15;
RECORD #16:
Species:
Sex:
Effect:
Route:
Rats
N.S.
PEL
Oral,
NOS
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
Dose: 150.000
Duration Exposure: 1.0 Days
Duration Observation: 1.0 Days
NR
NR
DEATH
BODY
10
Comment: LDSO was 150 mg/kg (95X confidence limits
were 130-170) LDSO for males was 130 mg/kg
and the LD,0 for females was between 110
and 250 mg/kg. *
Citation: Jones and Collier, 1986
Species:
Sex:
Effect:
Route:
Mice
N.S.
PEL
Oral,
NOS
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
Dose: 300.000
Duration Exposure: 1.0 Days
Duration Observation: 1.0 Days
NR
NR
DEATH
BODY
10
Comment: LD5a was 300 W- 37 mg/kg.
Citation: Hine et al., 1953
RECORD #17:
Species:
Sex:
Effect:
Route :
Mice
Both
PEL
Oral, NOS
Dose: 640.000
Duration Exposure: 1 .0
Duration Observation: 1
Days
.0 Days
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
NR
NR
DEATH
BODY
10
Comment: LD,0 for both males and females was 640
mg/kg.
Citation: Toyoshima et al., 1978b
6234H
D-30
06/16/89
------- |