Chlorobenzene [factsheet]

CHLOROBENZENE

Please Note: The main sources of information for this fact sheet are EPA's Integrated Risk Information System (IRIS), which contains information on oral chronic toxicity and the RfD, and the carcinogenic effects of chlorobenzene, and the Agency for Toxic Substances and Disease Registry's (ATSDR's) Toxicological Profile for Chlorobenzene. 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literature, and the Registry of Toxic Effects of Chemical Substances (RTECS), a database of toxic effects that are not peer reviewed.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

* Human exposure to chlorobenzene appears to be primarily occupational. (1)

* In urban areas, chlorobenzene may be released to the ambient air during its manufacture and use. (1)

Assessing Personal Exposure

* Chlorobenzene or its breakdown products can be detected in urine, exhaled breath, blood, and body fat to determine whether or not exposure has occurred. (1)

Health Hazard Information

Acute Effects:

* A child who ingested chlorobenzene became unconscious and cyanotic and had muscle spasms but recovered completely. (1)

* Acute (short-term) inhalation exposure of cats to chlorobenzene produced narcosis, restlessness, tremors, and muscle spasms. (1,2)

* Acute animal tests, such as the LC₅₀ and LD₅₀ tests in rats, mice, rabbits, and guinea pigs, have demonstrated chlorobenzene to have low acute toxicity by inhalation and moderate acute toxicity from oral exposure. (1,3)

Chronic Effects (Noncancer):

* Chronic (long-term) exposure of humans to chlorobenzene affects the CNS. Signs of neurotoxicity include numbness, cyanosis, hyperesthesia (increased sensation), and muscle spasms. (1,4)

* Headaches and irritation of the mucosa of the upper respiratory tract and eyes have also been reported in humans chronically exposed via inhalation. (4)

* The CNS, liver, and kidneys have been affected in animals chronically exposed to chlorobenzene by inhalation. (1)

* Chronic ingestion of chlorobenzene has resulted in damage to the kidneys and liver in animals. (1,4)

* The RfC for chlorobenzene is under review by EPA. (5)

* The RfD for chlorobenzene is 0.02 mg/kg/d based on histopathologic changes in the liver in dogs. (5)

* EPA has medium confidence in the study on which the RfD was based because it provided both a no-observed-adverse-effect level (NOAEL) and a lowest-observed-adverse-effect level (LOAEL) and incorporated several biochemical and biological endpoints; medium confidence in the database because several subchronic, chronic, developmental, and reproductive toxicity studies provide supportive data, but they did not give a complete assessment of toxicity; and, consequently, medium confidence in the RfD. (5)

* EPA's Office of Air Quality Planning and Standards, for a hazard ranking under Section 112(g) of the Clean Air Act Amendments, has evaluated chlorobenzene for chronic toxicity and has given it a composite score of 3 (scores range from 1 to 100, with 100 being the most toxic). These scores are nonlinear and are the product of two ratings: a rating based on the minimal-effect-dose and a rating based on the type of effect. (6)

Reproductive/Developmental Effects:

* No information is available on the reproductive or developmental effects of chlorobenzene in humans.

* Chronic inhalation exposure of rats to chlorobenzene did not adversely affect reproductive performance or fertility. However, a slight increase in the incidence of degenerative testicular changes was observed. (1,4)

* Chlorobenzene does not appear to be a developmental toxicant and did not produce structural malformations in rats and rabbits acutely exposed via inhalation. (1,4)

Cancer Risk:

* No information is available on the carcinogenic effects of chlorobenzene in humans.

* In a study of rats and mice exposed to chlorobenzene via gavage (experimentally placing the chemical in the stomach), an increased incidence of neoplastic nodules of the liver in male rats was observed but not in mice or female rats. (1,4,5)

* EPA has classified chlorobenzene as a Group D, not classifiable as to human carcinogenicity. (5)

Physical Properties

* The chemical formula for chlorobenzene is C₆H₅Cl, and its molecular weight is 112.56 g/mol. (1)

* Chlorobenzene occurs as a colorless flammable liquid, with low solubility in water. (1,4)

* Chlorobenzene has an aromatic, almond-like odor, with an odor threshold of 1 to 8 mg/m³. (1)

* The vapor pressure for chlorobenzene is 8.8 mm Hg at 20 EC, and its log octanol/water partition coefficient (log K_ow) is 2.84. (1)

Uses

* The primary uses of chlorobenzene are as a solvent for pesticide formulations, diisocyanate manufacture, and degreasing automobile parts and for the production of nitrochlorobenzene. (1)

* In the past, chlorobenzene was used as an intermediate in phenol and DDT production. (1)

Health Data from Inhalation Exposure

Concentration (mg/m³)	Health numbers^a	Regulatory, advisory numbers^b	Reference
1,000,000.0
_ _ _ _ 100,000.0
_ _ _ _ 10,000.0	* LC₅₀ (mice) (19,780 mg/m³)		1
_ _ _ _ 1,000.0
_ _ _ _ 100.0		* OSHA PEL and MSHA standard (350 mg/m³)	3
_ _ _ _ 10.0		* ACGIH TLV (45 mg/m³)	3

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.

MSHACMine Safety and Health Administration.

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.

^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.

References

1. Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological Profile for Chlorobenzene. U.S. Public Health Service, U.S. Department of Health and Human Services, Atlanta, GA. 1990.

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. Updated Health Effects Assessment for Chlorobenzene. EPA/600/8-89/099. 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 Chlorobenzene. Environmental Criteria and Assessment Office, Office of Health and Environmental Assessment, Office of Research and Development, Cincinnati, OH. 1993.

6. U.S. Environmental Protection Agency. Technical Background Document to Support Rulemaking Pursuant to the Clean Air ActCSection 112(g). Ranking of Pollutants with Respect to Hazard to Human Health. EPAB450/3-92-010. Emissions Standards Division, Office of Air Quality Planning and Standards, Research Triangle Park, NC. 1994.