Change to Basis for Identification of Male Reproductive Toxicity as an Endpoint of Reproductive Toxicity for Methyl Chloride

Effective March 7, 2014, the California Environmental Protection Agency’s Office of Environmental Health Hazard Assessment (OEHHA) has changed the basis for identifying male reproductive toxicity as an endpoint of reproductive toxicity for methyl chloride under the Safe Drinking Water and Toxic Enforcement Act of 1986¹.  

Background:  Methyl chloride was originally added to the Proposition 65 list as causing reproductive toxicity (developmental endpoint) on March 10, 2000, pursuant to the “authoritative bodies” listing mechanism².  This action was based on a formal identification of the chemical’s reproductive toxicity by the National Institute for Occupational Safety and Health (NIOSH)³.

On August 7, 2009, the endpoint of male reproductive toxicity was also identified for methyl chloride pursuant to the “Labor Code” mechanism based on Labor Code Section 6382(d), which is incorporated by reference in Health and Safety Code Section 25249.8(a).  Methyl chloride was identified as causing male reproductive toxicity in the American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit Values (TLVs).  The TLVs were previously incorporated by reference into the federal Occupational Health and Safety Administration (OSHA) Hazard Communication Standard (Title 29, Code of Federal Regulations [C.F.R.] section 1900.1200).  The Hazard Communication Standard is, in turn incorporated by reference into Labor Code Section 6382(d).  In March 2012, OSHA extensively amended the regulations contained in the Hazard Communication Standard.  Specifically, Title 29, C.F.R. 1910.1200 (d)(3)(ii), which referred to the ACGIH TLV list, was deleted from the 2012 version of the regulation.  OEHHA has determined that these changes have eliminated the ACGIH TLVs as a definitive source for identifying chemicals that are known to cause reproductive toxicity. 

However, the U.S. Environmental Protection Agency (U.S. EPA) has concluded that methyl chloride causes male reproductive toxicity⁴.  U.S. EPA is an authoritative body for the purpose of identifying chemicals as causing reproductive toxicity under Proposition 65⁵. 

OEHHA’s determination regarding identification of male reproductive toxicity as an endpoint of reproductive toxicity for methyl chloride: Methyl chloride meets the criteria for identification as causing reproductive toxicity (male reproductive endpoint) under Proposition 65, based on findings of U.S. EPA (U.S. EPA, 2001), as outlined below.

Formal identification and sufficiency of evidence: OEHHA is relying on U.S. EPA’s conclusion that methyl chloride causes male reproductive effects.  This conclusion meets the formal identification requirement of Section 26306(d)(1)⁶ and is made in the following document:

Toxicological Review of Methyl Chloride (CASRN 74-87-3); In Support of Summary Information on the Integrated Risk Information System (IRIS) (U.S. EPA, 2001)

The U.S. EPA (2001) document states on page 33 that:

“Conclusions: The testicular results in rats are consistent with a LOAEL of 1,000 ppm, based on early signs of seminiferous tubule degeneration and atrophy in the absence of age-related degeneration.”

The U.S. EPA (2001) synthesizes evidence on noncancer effects and concludes on pages 58-59 that:

“At high exposure concentrations (1,000 to 5,000 ppm), studies in rats have demonstrated that methyl chloride results in reduced fertility, testicular toxicity (seminiferous epithelium degeneration, delayed spermiation, reduced testicular weight and numbers of sperm and spermatids, sperm abnormalities and reduced motility, abnormal histopathology, reduced levels of NPSH [nonprotein sulfhydryls] and circulating testosterone), epididymal toxicity (inflammation, sperm granulomas, reduced NPSH levels) and dominant lethal effects.  The collective data, including studies with the anti-inflammatory agent BW755C, which inhibits methyl chloride-induced epididymal inflammation and postimplantation loss, but not testicular toxicity or preimplantation loss, strongly suggest that the preimplantation loss results from methyl chloride’s cytotoxic effects on sperm located in the testes, with consequent failure of fertilization due to low sperm number and poor sperm quality.

In male rats exposed to 475 ppm and mated with exposed and unexposed females, there was a small reduction in F0 male rat fertility that resolved during postexposure.  A statistically significant decreased percentage of males and temporary pup weight reductions in F1 litters were also observed at 475 ppm.  At 1,500 ppm, males were infertile. No effects on fertility were seen at the only other concentration tested, 150 ppm.”

Thus, this report meets the formal identification criterion in Section 26306(d)(2)(C)⁷.

OEHHA has reviewed the study descriptions provided by U.S. EPA (2001) as supporting U.S. EPA’s conclusions regarding the male reproductive toxicity of methyl chloride, relative to the criteria in Section 25306(g). 

Conclusion: OEHHA has determined that identification of the male reproductive endpoint for methyl chloride is consistent with the criteria for formal identification and sufficiency of evidence for the “authoritative bodies” listing mechanism⁸.  

OEHHA is providing this notice of change to the basis for identifying male reproductive toxicity as an endpoint of reproductive toxicity for methyl chloride.  The 2000 identification of methyl chloride as a chemical known to the state to cause reproductive toxicity (developmental endpoint) remains unchanged.

Chemical Reference

• Methyl Chloride

Related Notices

• Chemicals Listed Effective August 7, 2009 as Known to the State of California to Cause Cancer or Reproductive Toxicity

  Aug 7, 2009
• Chemical Listed Effective March 10, 2000 as Known to the State to Cause Reproductive Toxicity: Methyl Chloride

  Mar 10, 2000

Footnotes and References

¹ Commonly known as Proposition 65, the Safe Drinking Water and Toxic Enforcement Act of 1986 is codified in Health and Safety Code section 25249.5 et seq.

² See Health and Safety Code section 25249.8(b) and Title 27, California Code of Regulations, section 25306. All further references are to sections of Title 27 of the California Code of Regulations, unless indicated otherwise.

³ National Institute for Occupational Safety and Health (NIOSH, 1984).  Current Intelligence Bulletin 43:  Monohalomethanes (Methyl Chloride CH3Cl, Methyl Bromide CH3Br, Methyl Iodide CH3I). U.S.Department of Health and Human Services, Public Health Services, NIOSH.  Available at http://www.cdc.gov/niosh/docs/84-117/

⁴ U.S. Environmental Protection Agency (U.S. EPA, 2001).  Toxicological Review of Methyl Chloride (CASRN 74-87-3); In Support of Summary Information on the Integrated Risk Information System (IRIS).  EPA/635/R01/003. U.S. EPA, Washington DC, September. 

⁵ Section 25306(l).

⁶ “the chemical…is the subject of a report which is published by the authoritative body and which concludes that the chemical causes...reproductive toxicity”

⁷ “[the document is] Published by the authoritative body in a publication such as, but not limited to, the federal register…”

⁸ Section 25306.