1,3Dichloropropene [factsheet]

1,3-DICHLOROPROPENE

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Please Note: The main sources of information for this fact sheet are EPA's Integrated Risk Information System (IRIS), which contains information on inhalation chronic toxicity of 1,3-dichloropropene and the RfC, oral chronic toxicity and the RfD, and the carcinogenic effects of 1,3-dichloropropene, and the Agency for Toxic Substances and Disease Registry's (ATSDR's) Toxicological Profile for 1,3-Dichloropropene. Other secondary sources include the Hazardous Substances Data Bank (HSDB), a database of summaries of peer-reviewed literature, and the Registry of Toxic Effects of Chemical Substances (RTECS), a database of toxic effects that are not peer reviewed.

Environmental/Occupational Exposure

* Workers may be occupationally exposed to 1,3-dichloropropene, dermally or by inhalation, during its manufacture, formulation, or application as a soil fumigant. (1, 2)

* The general public may be exposed via inhalation near source areas or from the consumption of contaminated drinking water. (1,2)

Assessing Personal Exposure

* 1,3-Dichloropropene or its breakdown products can be detected in blood and urine to determine whether or not exposure has occurred. However, metabolites measured in blood and urine are not specific to 1,3-dichloropropene. (1)

Health Hazard Information

Acute Effects:

* Acute (short-term) inhalation exposure of humans causes mucous membrane irritation, headache, dizziness, nausea, vomiting, malaise, chest pain, and breathing difficulties. (1)

* Effects on the lung, including emphysema and edema, have been observed in rats acutely exposed to 1,3-dichloropropene by inhalation. (1)

* Lung congestion and hemorrhage, ulcerations of the glandular stomach, hemorrhage of the small intestine, dark and patchy liver, and hemorrhage of the liver have been observed in rats acutely exposed to 1,3-dichloropropene in their diet or via gavage (experimentally placing the chemical in the stomach). Neurotoxic effects, including hunched posture, lethargy, ptosis, ataxia, and decreased respiratory rate, have also been observed in orally exposed rats. (1)

* Acute animal tests, such as the LC₅₀ and LD₅₀ tests in rats, mice, and rabbits, have demonstrated 1,3-dichloropropene to have moderate acute toxicity from inhalation, moderate to high acute toxicity from oral exposure, and high acute toxicity from dermal exposure. (3)

Chronic Effects (Noncancer):

* Chronic (long-term) dermal exposure may result in skin sensitization in humans. (1)

* Damage to the nasal mucosa and urinary bladder are the primary health effects of rodents chronically exposed to 1,3-dichloropropene by inhalation. Hyperplastic lesions of the upper respiratory tract and degeneration of the olfactory epithelium in the nasal turbinates have been observed in chronically exposed rats and mice. Chronic inhalation exposure of mice has resulted in changes in the urinary bladder. (1,4,5)

* In one study, reversible cloudy swelling of the renal tubular epithelium was reported in rats chronically exposed by inhalation. (1,4,5)

* In rats and mice chronically exposed by inhalation, hyperplasia and hyperkeratosis of the forestomach have been observed, while hyperplasia of the forestomach and of the urinary bladder have resulted from chronic oral exposure. (1,4)

* The RfC for 1,3-dichloropropene is 0.02 mg/m³ based on hypertrophy/hyperplasia of the nasal respiratory epithelium in mice. (5)

* EPA has high confidence in the study on which the RfC was based because it is a well-designed study using two species of animals (both sexes) and including detailed histopathological examinations of numerous tissues with extensive analysis of the respiratory system. Corroborative studies performed in both rats and mice have also shown this to be a sensitive endpoint. EPA has high confidence in the database because several studies reported similar effects on the respiratory system at comparable exposure levels, and acute effects observed in humans were similar to the animal effects; and, consequently, high confidence in the RfC. (5)

* The RfD for 1,3-dichloropropene is 0.0003 mg/kg/d based on increased organ weights in rats. (5)

* EPA has low confidence in the study on which the RfD was based because it is of low quality and of short duration (90 days); low confidence in the database because of the remaining studies, only two teratology studies were considered acceptable; and, consequently, low confidence in the RfD. (5)

Reproductive/Developmental Effects:

* A study of male workers engaged in the manufacture of 1,3-dichloropropene indicated no significant effect on fertility at exposure levels occurring in the work environment. (4)

* No evidence of developmental toxicity was observed in rats or rabbits exposed to 1,3-dichloropropene by inhalation, but significant maternal toxicity was seen in both species. (4)

* In one study of rats exposed by inhalation, fewer fetuses per litter were reported. (1)

* In other studies, no adverse reproductive effects were observed in rats and mice exposed by inhalation. (1,5)

Cancer Risk:

* Information on the carcinogenic effects of 1,3-dichloropropene in humans is limited. Two cases of histiocytic lymphomas and one case of leukemia have been reported in humans accidentally exposed to 1,3-dichloropropene vapors. (1,4,5)

* An increased incidence of bronchioalveolar adenomas has been reported in male mice exposed by inhalation but not in rats or female mice. (1,4)

* Forestomach, adrenal and thyroid tumors, and liver nodules in rats and forestomach, urinary bladder, and lung tumors in mice have been observed in rodents exposed to 1,3-dichloropropene via gavage. (1,4,5)

* EPA has classified 1,3-dichloropropene as a Group B2, probable human carcinogen. (5)

Physical Properties

* The chemical formula for 1,3-dichloropropene is C₃H₄Cl₂, and its molecular weight is 110.98 g/mol. (1)

* 1,3-Dichloropropene occurs as a colorless liquid that dissolves in water. (1)

* 1,3-Dichloropropene has a sweet chloroform-like odor, with an odor threshold of 1 ppm. (1)

* The vapor pressure for 1,3-dichloropropene is 34 to 43 mm Hg at 25 EC, and its log octanol/water partition coefficient (log K_ow) is 1.60. (1)

Uses

* 1,3-Dichloropropene is the predominant component of several formulations used in agriculture as soil fumigants for parasitic nematodes. (1,4)

Health Data from Inhalation Exposure

Concentration (mg/m³)	Health numbers^a	Regulatory, advisory numbers^b	Reference
10,000.0
_ _ _ _ 1,000.0	* LC₅₀ (mice) (4,650 mg/m³) * LC₅₀ (rats) (2,270 mg/m³)		3 3
_ _ _ _ 100.0
_ _ _ _ 10.0	* LOAEL^c (mice) (83.5 mg/m³) * NOAEL^c (mice) (20.9 mg/m³)		5 5
_ _ _ _ 1.0		* ACGIH TLV, NIOSH REL, and OSHA PEL (5 mg/m³)	3
_ _ _ _ 0.1	* RfC (0.02 mg/m³)		5

ACGIH TLVCAmerican Conference of Governmental and Industrial Hygienists' threshold limit value expressed as a time-weighted average; the concentration of a substance to which most workers can be exposed without adverse effects.

LC₅₀ (Lethal Concentration₅₀)CA calculated concentration of a chemical in air to which exposure for a specific length of time is expected to cause death in 50% of a defined experimental animal population.

LOAELCLowest-observed-adverse-effect level.

NIOSH RELCNational Institute of Occupational Safety and Health's recommended exposure limit; NIOSH-recommended exposure limit for an 8- or 10-h time-weighted-average exposure and/or ceiling.

NOAELCNo-observed-adverse-effect level.

OSHA PELCOccupational Safety and Health Administration's permissible exposure limit expressed as a time-weighted average; the concentration of a substance to which most workers can be exposed without adverse effect averaged over a normal 8-h workday or a 40-h workweek.

RfCCReference concentration.

^a Health numbers are toxicological numbers from animal testing or risk assessment values developed by EPA.

^b Regulatory numbers are values that have been incorporated in Government regulations, while advisory numbers are nonregulatory values provided by the Government or other groups as advice.

^c The LOAEL and NOAEL are from the critical study used as the basis for the EPA RfC.

References

1. Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological Profile for 1,3-Dichloropropene. U.S. Public Health Service, U.S. Department of Health and Human Services. 1992.

2. U.S. Department of Health and Human Services. Hazardous Substances Data Bank (HSDB, online database). National Toxicology Information Program, National Library of Medicine, Bethesda, MD. 1993.

3. U.S. Department of Health and Human Services. Registry of Toxic Effects of Chemical Substances (RTECS, online database). National Toxicology Information Program, National Library of Medicine, Bethesda, MD. 1993.

4. U.S. Environmental Protection Agency. Health and Environmental Effects Profile for 1,3-Dichloropropene. ECAO-CIN-G074. Environmental Criteria and Assessment Office, Office of Health and Environmental Assessment, Office of Research and Development, Cincinnati, OH. 1989.

5. U.S. Environmental Protection Agency. Integrated Risk Information System (IRIS) on 1,3-Dichloropropene. Environmental Criteria and Assessment Office, Office of Health and Environmental Assessment, Office of Research and Development, Cincinnati, OH. 1993.