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CHLOROFORM [14]
CASRN: 67663

Update: May 2004

Current Massachusetts Regulatory Limit
This document addresses chloroform in non-chlorinated water supplies. Please consult the supporting documentation for Total Trihalomethanes (TTHMs) for guidance on chloroform in chlorinated water supplies. 
For non-chlorinated supplies, the ORSGL = 0.07 mg/L. Documentation is provided below.

Federal Regulatory Limit
The U.S. EPA has not published an MCL for chloroform in non-chlorinated water supplies.

Basis for Criteria
For a non-chlorinated water supply, a guideline of 0.07 mg/L has been established based on the potential for noncancer and cancer effects. The ORSGL is based on the RfD presented below and assumes that a 70 kg adult ingests 2 L/day of drinking water. A relative source contribution factor of 20% is incorporated into the final value.

RfD: 0.01 mg/kg/day
UF: 1000 (10 = intraspecies; 10 = interspecies; 10 = LOAEL to NOAEL)
MF: 1 Confidence in RfD: Medium

(U.S. EPA, 2001)

Critical Effects
The RfD is based upon the results of a chronic study (Heywood et al., 1979) in which beagle dogs were exposed to chloroform at either 15 or 30 mg/kg/day in gelatin capsules in a toothpaste base 6 days per week for 7.5 years, followed by a 20 to 24-week recovery period. Effects noted (in a dose-dependent manner) included moderate/marked fatty cyst formation in the liver and elevated serum glutamate pyruvate transaminase (SGPT), both indicators of liver effects (U.S. EPA, 2001). No NOAEL was identified in this study. A LOAEL of 15 mg/kg/day was identified based on elevated serum SGPT levels and increased incidence and severity of fatty cysts (U.S. EPA, 2001).
(A benchmark approach was also used to arrive at the same RfD. The benchmark dose (BMDL10) of 1.2 mg/kg/day (time adjusted to 1.0 mg/kg/day) was derived from the same chronic oral bioassay in dogs (U.S. EPA, 2001). A total uncertainty factor of 100 (10 for interspecies; 10 for intraspecies) was applied to the adjusted BMDL10 to derive the RfD.)

Cancer Assessment: 
B2/Likely to be carcinogenic to humans
Under the Proposed Guidelines for Carcinogen Risk Assessment, chloroform is likely to be carcinogenic to humans by all routes of exposure under high-dose conditions that lead to cytotoxicity and regenerative hyperplasia in susceptible tissues. Chloroform is not likely to be carcinogenic to humans by any route of exposure at a dose level that does not cause cytotoxicity and cell regeneration. This conclusion is based upon the results of a number of studies in animals exposed both via inhalation and oral routes, in which sustained or repeated cytotoxicity with secondary regenerative hyperplasia precedes and is probably a causal factor for hepatic and renal neoplasia (U.S. EPA, 2001). Because these data indicate that chloroform is carcinogenic via a nongenotoxic mechanism of toxicity, U.S. EPA considers a dose of 0.01 mg/kg/day (equal to the RfD) to be protective against cancer risk (U.S. EPA, 2001).

Class
VOC

Analytical Information
PQL
: 0.05 ug/L

Analytical Methods
U.S. EPA Methods 502.2; 524.2; 551.1

PQLs and analytical methods may have been updated since this guidance value was last revised. Updated analytical methods for drinking water and their associated PQLs may be found at http://www.epa.gov/safewater/methods/methods.html.

Other Regulatory Data
Any Health Advisories, Reference Doses (RfDs), cancer assessments or Cancer Potency Factors (CPFs) referenced in this document pertain to the derivation of the current guidance value. Updated information may be obtained from the following sources:

Health Advisories - The U.S. EPA provides guidance for shorter-term exposures for chemicals based on their non-cancer effects. Current health advisories may be more current than those used to derive MCLs and may be found at http://www.epa.gov/waterscience/drinking/standards/dwstandards.pdf.

RfDs, cancer assessments and CPFs - For specific information pertaining to derivation of drinking water criteria, consult the Federal Register notice that announces the availability of the most current guidance for that chemical. In addition, information on other current RfDs and CPFs as well as cancer assessments for specific chemicals may be found in the U.S. EPA Integrated Risk Information System (IRIS) at http://www.epa.gov/iris/. Please note that the information in IRIS may differ from that used in the derivation process as published in the Federal Register notice.

References
Heywood, R., Sortwell, R.J., Noel, PRB et al. 1979. Safety evaluation of toothpaste containing chloroform: III. Long-term study in beagle dogs. J Environ Pathol Toxicol. 2:835-851.

U.S. EPA (U.S. Environmental Protection Agency). October 19, 2001. IRIS (Integrated Risk Information System). Washington, D.C. http://cfpub.epa.gov/ncea/iris/index.cfm.

U.S. EPA (U.S. Environmental Protection Agency). October 19, 2001. Toxicological review of chloroform (CAS No. 6766-3) - in support of summary information on the Integrated Risk Information System. EPA/635/R-01/001.