Request for Relevant Information on Chemical Being Considered for Listing by the Authoritative Bodies Mechanism: Methyl Isobutyl Ketone

The California Environmental Protection Agency’s Office of Environmental Health Hazard Assessment (OEHHA) is requesting information as to whether methyl isobutyl ketone meets the criteria for listing as a reproductive toxicant under the Safe Drinking Water and Toxic Enforcement Act of 1986.¹  This action is being proposed under the authoritative bodies listing mechanism.²

Background on listing via the authoritative bodies mechanism: A chemical must be listed under Proposition 65³ and its implementing regulations when two conditions are met:

1. An authoritative body formally identifies the chemical as causing reproductive toxicity (Section 25306(d)⁴).
2. 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 implementation of Proposition 65⁵.  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: Methyl isobutyl ketone appears to meet the criteria for listing as known to the State to cause reproductive toxicity under Proposition 65, based on findings of U.S. EPA in their documents, as indicated in the table below.

Formal identification and sufficiency of evidence:  In 2003, U.S. EPA updated its online Integrated Risk Information System (IRIS) entry for methyl isobutyl ketone (U.S. EPA, 2003a). The inhalation reference concentration (RfC) was based on developmental toxicity manifested as reduced fetal body weight, skeletal variations, and increased fetal death in mice, and skeletal variations in rats. This appears to meet the criterion in Section 25306(d)(1) that the chemical “has otherwise been identified as causing …reproductive toxicity by the authoritative body in a document that indicates that such identification is a final action”.

In support of the IRIS entry, a comprehensive review and summary of the available toxicological data was published as a Toxicological Review (U.S. EPA, 2003b). Under the Section of that document titled “Major Conclusions in the Characterization of Hazard and Dose Response”, the authoritative body concludes that:

“The developmental effects in rats and mice after gestational inhalation exposure are considered to be the most clearly adverse effects in the animal database.” (page 42)

The document also states that:

“… delayed ossification in rats and mice and reduced fetal body weight and increased fetal death in mice were identified as the critical effects in a substantial database of repeat-dose inhalation studies.” (page 36)

“An RfC of 3 mg/m3 was derived on the basis of effects observed in fetuses after repeated exposure on gestation days 6 to 15 (Tyl et al., 1987). The RfC was based on developmental effects in fetuses reported in a toxicity assay in which maternal exposure occurred only during gestation.” (page 41)

This appears to meet the criterion in Section 25306(d)(1) that the chemical “is the subject of a report which is published by the authoritative body and which concludes that the chemical causes.... reproductive toxicity”.

OEHHA has also evaluated the studies cited by U.S. EPA in support of its formal identification of methyl isobutyl ketone as causing developmental toxicity relative to the criteria in Section 25306(g).  Based on both the U.S. EPA (2003a) IRIS entry and the Toxicological Review document (U.S. EPA 2003b), and the studies cited in those documents, the criteria for listing methyl isobutyl ketone as known to cause reproductive toxicity by the authoritative bodies mechanism appear to be met.

Request for relevant information:  OEHHA is requesting comments as to whether methyl isobutyl ketone meets the criteria set forth in the Proposition 65 regulations for authoritative bodies listings.

After reviewing all comments received, OEHHA will determine whether the identified chemical meets the regulatory criteria for administrative listing.  If the chemical is determined to meet the listing criteria, OEHHA will proceed with the formal listing process by publishing a Notice of Intent to List.

In order to be considered, OEHHA must receive comments by 5:00 p.m. on Tuesday May 14, 2013.  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 “DCI – methyl isobutyl ketone” in the subject line.  Comments submitted in paper form may be mailed, faxed, or delivered in person to the addresses below:

Mailing Address:Proposition 65
Office of Environmental Health Hazard Assessment
P.O. Box 4010, MS-19B
Sacramento, California 95812-4010
Fax:(916) 324-6511
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.

Optional public forum:  Upon request, OEHHA will schedule an informal public forum to provide individuals an opportunity to present oral comments on the possible listing of this chemical.  At the forum, the public may discuss the scientific data and other relevant information related to whether the chemical meets the criteria for listing in the regulations.

The request for a public forum must be submitted in writing to the Proposition 65 Office of OEHHA via email at P65Public.Comments@oehha.ca.gov or to the attention of the Proposition 65 Office at the address listed above no later than Friday, April 12, 2013.  If a public forum is requested, a notice will be posted on the OEHHA web site at least ten days before the forum date.  The notice will provide the date, time and location of the forum.  Notices will also be sent to those individuals requesting such notification. 

If you have any questions, please contact OEHHA at P65Public.Comments@oehha.ca.gov or at (916) 445-6900.

Comment Period

• Comment Period - Request for Relevant Information on Chemical Being Considered for Listing by the Authoritative Bodies Mechanism: Methyl Isobutyl Ketone

Link to Public Comments

Footnotes and References

References

Tyl, R. W., K.A. France, L.C. Fisher, I.M. Pritts, T.R. Tyler, R.D. Phillips and E.J. Moran (1987). "Developmental toxicity evaluation of inhaled methyl isobutyl ketone in Fischer 344 rats and CD-1 mice". Fundam Appl Toxicol 8(3): 310-27.

U.S. EPA (U.S. Environmental Protection Agency) (2003a).  Methyl Isobutyl Ketone (MIBK) (CASRN 108-10-1).  Integrated Risk Information System.  Available online at: http://www.epa.gov/iris/subst/0173.htm.

U.S. EPA (U.S. Environmental Protection Agency) (2003b).  Toxicological Review of Methyl Isobutyl Ketone; In Support of Summary Information on the Integrated Risk Information System (IRIS). EPA/635/R-03/002. U.S. EPA, Washington DC, March. 

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.

²See Health and Safety Code section 25249.8(b) and Title 27, Cal. Code of Regs. section 25306.

³Health and Safety Code section 25249.8(b)

⁴ All referenced sections are from Title 27 of the Cal. Code of Regulations.

⁵ Health and Safety Code section 25249.12 and Title 27, Cal. Code of Regs., section 25102(o).