Chloroform Quickview (CASRN 67-66-3)

Status of Data for Chloroform

File First On-Line: 01/31/1987; Last Significant Revision: 10/19/2001

Category (section)	Status	Last Revised
Oral RfD Assessment	On-line	10/19/2001
Inhalation RfC Assessment	No data
Carcinogenicity Assessment	On-line	10/19/2001
Under Re-Assessment

Synonyms

67-66-3 Chloroform Formyl trichloride Freon 20 Methane trichloride

Methane, trichloro- Methenyl chloride Methenyl trichloride Methyl trichloride more...

Chronic Health Hazard Assessments for Noncarcinogenic Effects

Reference Dose for Chronic Oral Exposure (RfD)

Critical Effect	Point of Departure*	UF	MF	RfD
Moderate/marked fatty cyst formation in the liver and elevated SGPT	BMDL10 : 1.0 mg/kg-day	100	1	1 x10-2 mg/kg-day

* The Point of Departure listed serves as a basis from which the Oral RfD was derived. See Discussion of Conversion Factors and Assumptions for more details.

• Principal and Supporting Studies (Oral RfD)
  • Dog, chronic oral bioassay, Heywood et al., 1979
• Confidence in the Oral RfD
  • Study -- Medium
  • Database -- Medium
  • RfD -- Medium

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Reference Concentration for Chronic Inhalation Exposure (RfC)

Not Assessed under the IRIS Program.

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Carcinogenicity Assessment for Lifetime Exposure

• Weight-of-Evidence Characterization
  • B2 (Probable human carcinogen - based on sufficient evidence of carcinogenicity in animals)
  • Likely to be carcinogenic to humans
  • Not likely to be carcinogenic to humans
• Weight-of-Evidence Narrative:
  • Under the Proposed Guidelines for Carcinogen Risk Assessment (U.S. EPA, 1996; U.S. EPA, 1999), chloroform is likely to be carcinogenic to humans by all routes of exposure under high-exposure conditions that lead to cytotoxicity and regenerative hyperplasia in susceptible tissues (U.S. EPA, 1998a,b). Chloroform is not likely to be carcinogenic to humans by any route of exposure under exposure conditions that do not cause cytotoxicity and cell regeneration. This weight-of-evidence conclusion is based on: 1) observations in animals exposed by both oral and inhalation pathways which indicate that sustained or repeated cytotoxicity with secondary regenerative hyperplasia precedes, and is probably required for, hepatic and renal neoplasia; 2) there are no epidemiological data specific to chloroform and, at most, equivocal epidemiological data related to drinking water exposures that cannot necessarily be negative, although there are some scattered positive results that generally have limitations such as excessively high dose or with confounding factors. Thus, the weigh-of-evidence of the genotoxicity data on chloroform supports a conclusion that chloroform is not strongly mutagenic, and the genotoxicity is not likely to be the predominant mode of action underlying the carcinogenic potential of chloroform. Although no cancer data exist for exposures via the dermal pathway, the weight-of-evidence conclusion is considered to be applicable to this pathway as well, because chloroform absorbed through the skin and into the blood is expected to be metabolized and to cause toxicity in much the same way as chloroform absorbed by other exposure routes.
  • This may be a synopsis of the full weight-of-evidence narrative. See IRIS Summary.

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Quantitative Estimate of Carcinogenic Risk from Oral Exposure

• A dose of 1x10^-2 mg/kg-day (equal to the RfD) can be considered protective against cancer risk.

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Quantitative Estimate of Carcinogenic Risk from Inhalation Exposure

Inhalation Unit Risk(s)	Extrapolation Method
2.3 x10-5 per ug/m3	Linearized multistage procedure, extra risk

Inhalation Concentrations at Specified Risk Levels

Risk Level	Concentration
E-4 (1 in 10,000)	4 ug/m3
E-5 (1 in 100,000)	4x10-1 ug/m3
E-6 (1 in 1,000,000)	4x10-2 ug/m3

• Dose-Response Data (Carcinogenicity, Inhalation Exposure)
  • Tumor Type: Hepatocellular carcinoma
  • Test Species: Mouse, B6C3F1, female
  • Route: Oral, Gavage
  • Reference: NCI, 1976