IRIS

Chloroform

CASRN 67-66-3 | DTXSID1020306

Noncancer Assessment

Reference Dose for Oral Exposure (RfD) (PDF) (41 pp, 234 K) Last Updated: 10/19/2001

System RfD (mg/kg-day) Basis PoD Composite UF Confidence
Hepatic 1 x 10 -2 Moderate/marked fatty cyst formation in the liver and elevated SGPT BMDL 10 : 1.0
mg/kg-day
100 Medium

 


Reference Concentration for Inhalation Exposure (RfC) (PDF) (41 pp, 234 K)
Not assessed under the IRIS Program.

 

Cancer Assessment

Weight of Evidence for Cancer (PDF) (41 pp, 234 K) Last Updated: 10/19/2001

WOE Characterization Framework for WOE Characterization
B2 (Probable human carcinogen - based on sufficient evidence of carcinogenicity in animals) Guidelines for Carcinogen Risk Assessment (U.S. EPA, 1986)
Likely to be carcinogenic to humans Revised Draft Guidelines for Carcinogen Risk Assessment (U.S. EPA, 1999)
Not likely to be carcinogenic to humans Revised Draft Guidelines for Carcinogen Risk Assessment (U.S. EPA, 1999)
Basis:
  • 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.

WOE Note:  1. Likely to be carcinogenic to humans by all routes of exposure under high-exposure conditions that lead to cytotoxicity and regenerative hyperplasia. 2. Not likely to be carcinogenic to humans by any route of exposure under exposure conditions that do not cause cytotoxicity and cell regeneration.


Quantitative Estimate of Carcinogenic Risk from Oral Exposure (PDF) (41 pp, 234 K)

A dose of 1 x 10-2 mg/kg-day (equal to the RfD) can be considered protective against cancer risk.


Quantitative Estimate of Carcinogenic Risk from Inhalation Exposure (PDF) (41 pp, 234 K)

Inhalation Unit Risk: 2.3 x 10-5 per µg/m3
Extrapolation Method: Linearized multistage procedure, extra risk
Tumor site(s): Hepatic
Tumor type(s): Hepatocellular carcinoma (NCI, 1976)

Program Outlook Details

Public Assessment Materials Date
Problem Formulation Materials/IRIS Assessment Plan Sep-2017
Preliminary Assessment Materials/Systematic Review Protocol Jan-2018
Public Comment Oct-2023
External Peer Review FY24/Q2
Post Final Assessment TBD

Note: Any future dates displayed in the table above should be considered estimates and are subject to change. Once the external peer review is complete, estimated dates for release of the final assessment will be published. For the latest information on the status of this assessment, please refer to the IRIS Program Outlook. To access assessment documents, meeting materials or other supporting documents related to this assessment, visit the Chemical Documents tab. For more information about the development process, visit the IRIS Process page.

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