Notice of Intent to List: Trichloroethylene
NOTE: In the CRNR there is a typographical error in the date at which the comment period closes. The public comment period will close on January 13, 2014.
The California Environmental Protection Agency’s Office of Environmental Health Hazard Assessment (OEHHA) intends to list the chemical trichloroethylene (TCE) as known to the State to cause reproductive toxicity under the Safe Drinking Water and Toxic Enforcement Act of 1986.1 This action is being proposed under the authoritative bodies listing mechanism.2
Occurrence and Uses
Male Reproductive Toxicity
U.S. Environmental Protection Agency
Used mainly in vapor degreasing of metal parts, also used as a solvent in the textile industry and is found in consumer products such as paint removers and adhesives.
Background on listing via the authoritative bodies mechanism: A chemical must be listed under the Proposition 65 regulations when two conditions are met:
- An authoritative body formally identifies the chemical as causing reproductive toxicity (Section 25306(d)3).
- The evidence considered by the authoritative body meets the sufficiency criteria contained in the regulations (Section 25306(g)).
However, the chemical is not listed if scientifically valid data which were not considered by the authoritative body clearly establish that the sufficiency of evidence criteria were not met (Section 25306(h)).
The U. S. Environmental Protection Agency (U.S. EPA) is one of several institutions designated as authoritative for the identification of chemicals as causing reproductive toxicity (Section 25306(l)).
OEHHA is the lead agency for Proposition 65 implementation. After an authoritative body has made a determination about a chemical, OEHHA evaluates whether listing under Proposition 65 is required using the criteria contained in the regulations.
OEHHA’s determination: Trichloroethylene meets the criteria for listing as known to the State to cause reproductive toxicity under Proposition 65, based on the findings of U.S. EPA (U. S. EPA, 2011a), as outlined below.
Formal identification and sufficiency of evidence for trichloroethylene: In 2011, U. S. EPA published a report on TCE, entitled Toxicological Review of Trichloroethylene (CAS No. 79-01-6) (U. S. EPA, 2011a). This report satisfies the formal identification and sufficiency of evidence criteria in the Proposition 65 regulations.
OEHHA is relying on U.S. EPA’s discussion of data and conclusions in the Toxicological Review that TCE causes reproductive toxicity. U.S. EPA also concluded that TCE causes reproductive toxicity in its entry in the Integrated Risk Information System (IRIS) for TCE (U.S. EPA, 2011b). That entry cites the Toxicological Review of TCE as providing the supporting documentation (U.S. EPA, 2011a).
The conclusions in the U.S. EPA (2011a) Toxicological Review document identify TCE as causing male reproductive and developmental toxicity in laboratory animals, and satisfy the formal identification criteria in the Proposition 65 regulations.
With regard to male reproductive toxicity, U. S. EPA stated that for TCE:
- “Together, the human and laboratory animal data support the conclusion that TCE exposure poses a potential hazard to the male reproductive system” (Major Conclusions in the Characterization of Hazard and Dose Response, page 6-9).
- “[T]here is strong and compelling evidence for adverse effects of TCE exposure on male reproductive system and function” (Discussion/Synthesis of Noncancer Reproductive Toxicity Findings, page 4-487).
In discussing the evidence on male reproductive toxicity for TCE, U.S. EPA states:
"The adverse effects that have been observed in both male humans and male animal models include altered sperm count, morphology, or motility (Kumar et al., 2001b; Veeramachaneni et al., 2001; Kumar et al., 2000a; Kumar et al., 2000b; Chia et al., 1996; Rasmussen et al., 1988; George et al., 1985; Land et al., 1981); decreased libido or copulatory behavior (Veeramachaneni et al., 2001; George et al., 1986; Zenick et al., 1984; Saihan et al., 1978; El Ghawabi et al., 1973; Bardodej and Vyskocil, 1956); alterations in serum hormone levels (Veeramachaneni et al., 2001; Kumar et al., 2000a; Goh et al., 1998; Chia et al., 1997); and reduced fertility (George et al., 1986). However, other studies in humans did not see evidence of altered sperm count or morphology (Rasmussen et al., 1988) or reduced fertility (Forkert et al., 2003; Sallmen et al., 1998), and some animal studies also did not identify altered sperm measures (Xu et al., 2004; Cosby and Dukelow, 1992; George et al., 1986; Zenick et al., 1984). Additional adverse effects observed in animals include histopathological lesions of the testes (Kumar et al., 2001b; Kumar et al., 2000b; George et al., 1986) or epididymides (Kan et al., 2007; Forkert et al., 2002) and altered in vitro sperm-oocyte binding and/or in vivo fertilization for TCE and/or its metabolites (DuTeaux et al., 2004a; Xu et al., 2004) (page 4-488, citations in U.S. EPA Toxicological Review (2011a)).
“In spite of the preponderance of studies demonstrating effects on sperm parameters, there is an absence of overwhelming evidence in the database of adverse effects of TCE on overall fertility in the rodent studies. That is not surprising, however, given the redundancy and efficiency of rodent reproductive capabilities. Nevertheless, the continuous breeding reproductive toxicity study in rats (George et al., 1986) did demonstrate a trend towards reproductive compromise (i.e., a progressive decrease in the number of breeding pairs producing third, fourth, and fifth litters).” (page 4-490, citations in U.S. EPA Toxicological Review (2011a)).”
Regarding developmental toxicity, the U.S. EPA Toxicological Review states that:
- “[B]ased on weakly suggestive epidemiologic data and fairly consistent laboratory animal data, 3.” (Major Conclusions in the Characterization of Hazard and Dose Response, page 6-10)
- “[B]ased on weakly suggestive, but overall consistent, epidemiologic data, in combination with evidence from experimental animal and mechanistic studies, it can be concluded that TCE exposure poses a potential hazard for congenital malformations, including cardiac defects, in offspring.” (Major Conclusions in the Characterization of Hazard and Dose Response, page 6-11)
Scientific evidence of developmental toxicity reviewed by the authoritative body in support of these conclusions includes a number of human and animal studies. With regard to prenatal loss and effects on growth, the U.S. EPA Toxicological Review (2011a) noted that some occupational and environmental epidemiological studies reported associations between parental exposure to TCE and spontaneous abortion or perinatal death, and decreased birth weight or SGA [small for gestational age], although other studies reported mixed or null findings, and that multiple well-conducted studies in rats and mice show analogous effects of TCE exposure; i.e., pre- or postimplantation losses, increased resorptions, perinatal death, and decreased birth weight. On that basis, U.S. EPA concluded that TCE exposure poses a potential hazard for prenatal losses and decreased growth or birth weight of offspring, based on weakly suggestive epidemiologic data and fairly consistent laboratory animal data.
With regard to malformations, the U.S. EPA Toxicological Review (2011a) noted that epidemiological studies, while individually limited, as a whole show relatively consistent elevations, some of which were statistically significant, in the incidence of cardiac defects in TCE-exposed populations compared to reference groups. In laboratory animal models, avian studies were the first to identify adverse effects of TCE exposure on cardiac development, and the initial findings have been confirmed multiple times. Additionally, administration of TCE and its metabolites, TCA and DCA, in maternal drinking water during gestation has been reported to induce cardiac malformations in rat fetuses.
The studies cited by U.S. EPA in support of these conclusions were reviewed by OEHHA with regard to the sufficiency of evidence criteria in regulation (Section 25306(g)). The criteria for listing TCE as known to cause reproductive toxicity by the authoritative bodies mechanism have been met.
Request for comments4: OEHHA is requesting comments as to whether trichloroethylene meets the criteria set forth in the Proposition 65 regulations for authoritative bodies listings. In order to be considered, OEHHA must receive comments by 5:00 p.m. on Monday, January 13, 2014. We encourage you to submit comments via e-mail, rather than in paper form. Comments transmitted by e-mail should be addressed to P65Public.Comments@oehha.ca.gov with “NOIL-TCE” in the subject line. Comments submitted in paper form may be mailed, faxed, or delivered in person to the addresses below:
Office of Environmental Health Hazard Assessment
P.O. Box 4010, MS-19B
Sacramento, California 95812-4010
Street Address: 1001 I Street
Sacramento, California 95814
Comments received during the public comment period will be posted on the OEHHA web site after the close of the comment period.
If you have any questions, please contact OEHHA at P65Public.Comments@oehha.ca.gov or at (916)445‑6900.
Link to Public Comments
Footnotes and References
U.S. EPA (U.S. Environmental Protection Agency) (2011a). Toxicological Review of Trichloroethylene (CAS No. 79-0106); In Support of Summary Information on the Integrated Risk Information System (IRIS). EPA/635/R-09/011F U.S. EPA, Washington D.C., September 2011. Available online at: http://www.epa.gov/iris/toxreviews/0199tr/0199tr.pdf
U.S. EPA (U.S. Environmental Protection Agency) (2011b). Trichloroethylene (CASRN 79-01-6). Integrated Risk Information System. Available online at: http://www.epa.gov/iris/subst/0199.htm
1Commonly 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, Cal. Code of Regs., section 25306.
3 All referenced sections are from Title 27 of the Cal. Code of Regulations.
4 Note: OEHHA requested information relevant to the possible listing of trichloroethylene in a notice published in the California Regulatory Notice Register on March 15, 2013 (Register 2013, Vol. No. 11-Z). OEHHA received and has responded to those comments in a separate document.