Intent To List: Ethylene Glycol
The California Environmental Protection Agency’s Office of Environmental Health Hazard Assessment (OEHHA) intends to list the chemical ethylene glycol (EG) as known to the state to cause reproductive toxicity (developmental endpoint) under the Safe Drinking Water and Toxic Enforcement Act of 1986.1 This action is being proposed under the authoritative bodies listing mechanism.2
Chemical (CAS No.)
National Toxicology Program - Center for the Evaluation of Risks to Human Reproduction
Used as an intermediate in the synthesis of polyester compounds (e.g., polyethylene terephthalate and unsaturated polyester resins). It is also a constituent in antifreeze, deicing fluids, surface coatings, heat transfer fluids and industrial coolants, hydraulic fluids, surfactants, and emulsifiers.
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 National Toxicology Program (solely as to final reports of its Center for the Evaluation of Risks to Human Reproduction [NTP-CERHR]) 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: Ethylene glycol meets the criteria for listing as known to the state to cause reproductive toxicity (developmental endpoint) under Proposition 65, based on findings of the NTP-CERHR (2004), as outlined below.
Formal identification and sufficiency of evidence for ethylene glycol:
In 2004, the NTP-CERHR published a report on ethylene glycol titled, “NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects of Ethylene Glycol” (NTP-CERHR, 2004). This report satisfies the formal identification and sufficiency of evidence criteria in the Proposition 65 regulations.
OEHHA is relying on the NTP-CERHR’s discussion of data and conclusions in the report that EG causes reproductive toxicity. The conclusion in the NTP-CERHR Monograph identifies EG as causing developmental toxicity in laboratory animals, and satisfies the formal identification criteria in the Proposition 65 regulations.
With regard to developmental toxicity, NTP-CERHR concluded that there is clear evidence of adverse effects for reproductive toxicity (developmental endpoint) in laboratory animals at high oral doses:
“[T]he panel concluded that EG produces developmental toxicity in rodents after oral exposure to high doses. The critical developmental rodent studies showed that oral exposure of pregnant females to high doses of EG (≥500 mg/kg bw/day in mice and ≥1,000 mg/kg bw/day in rats) caused increased fetal deaths, skeletal malformations and external malformations, as well as reduced body weights in offspring.” (NTP-CERHR, 2004: NTP Brief, page 2)
“There were sufficient data to conclude that oral gavage exposure to high doses of ethylene glycol (CD-1 mice, ≥ 500 mg/kg bw/day on gd 6–15; Sprague-Dawley rats, ≥1,000 mg/kg bw/day on gd 6–15) causes developmental toxicity in mice and rats, including axial skeletal malformations, reduced body weights, external malformations, and increased post-implantation loss.” (NTP-CERHR, 2004: Summary and Conclusions of Reproductive and Developmental Hazards, page II-116)
The studies cited by NTP-CERHR in support of these conclusions were reviewed by OEHHA with regard to the sufficiency of evidence criteria in regulation (Section 25306(g)(2)). Information reviewed for each of the cited studies included parameters related to biological plausibility in humans, including adequacy of experimental design, pattern of dosing, route of administration, numbers of test animals, choice of species, choice of dosage levels, and maternal toxicity. On the basis of the studies, effects and species identified above, OEHHA concluded that the sufficiency-of-evidence criteria in the regulation were met.
Request for comments: OEHHA is requesting comments as to whether ethylene glycol 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, May 12, 2014 June 25, 2014. We encourage you to submit comments in electronic form, rather than in paper form. Comments transmitted by e-mail should be addressed to P65Public.Comments@oehha.ca.gov with “NOIL - Ethylene Glycol” in the subject line. Comments submitted in paper form may be mailed, faxed, or delivered in person to the addresses below:
Mailing Address: Sam Delson
Office of Environmental Health Hazard Assessment
P.O. Box 4010, MS-19B
Sacramento, California 95812-4010
Fax: (916) 323-2265
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 Sam Delson at firstname.lastname@example.org or at (916) 445‑6900.
- Extension of Comment Period - Notice of Intent to List Ethylene Glycol
- Intent to List: Ethylene Glycol - Additional Extension of Comment Period
- Comment Period - Notice of Intent to List: Ethylene Glycol
Link to Public Comments
Comment period closed on June 25, 2014.
- Ethylene glycol (ingested)
Footnotes and References
NTP-CERHR (2004). NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects of Ethylene Glycol. Research Triangle Park, NC, National Toxicology Program, Center for the Evaluation of Risks to Human Reproduction: NIH Publication No. 04 – 4481.
*Attachment available upon request to P65Public.email@example.com.
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, Cal. Code of Regs., section 25306.
3 All referenced sections are from Title 27 of the Cal. Code of Regulations.