Comment Period - Notice of Intent to List N,N-Dimethyl-p-Toluidine

The California Environmental Protection Agency’s Office of Environmental Health Hazard Assessment (OEHHA) intends to list N,N-dimethyl-p-toluidine as known to the State to cause cancer 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 the Proposition 65 regulations when two conditions are met:

1. An authoritative body formally identifies the chemical as causing cancer (Section 25306(d)³).
2. The evidence considered by the authoritative body meets the sufficiency criteria contained in the regulations (Section 25306(e)).

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(f)).

The National Toxicology Program (NTP) is one of several institutions designated as authoritative for the identification of chemicals as causing cancer (Section 25306(m)).

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: N,N-Dimethyl-p-toluidine meets the criteria for listing as known to the State to cause cancer under Proposition 65, based on findings of the NTP (2012).

Formal identification and sufficiency of evidence for N,N-dimethyl-p-toluidine:  In 2012, NTP published a report on N,N-dimethyl-p-toluidine, entitled Toxicology and Carcinogenesis Studies of N,N-Dimethyl-p-Toluidine (CAS No. 99-97-8) in F344/N Rats and B6C3F1/N Mice (Gavage Studies), that concludes that the chemical causes cancer (NTP, 2012).  This report satisfies the formal identification and sufficiency of evidence criteria in the Proposition 65 regulations.  OEHHA is relying on the NTP’s discussion of data and conclusions in the report that N,N-dimethyl-p-toluidine causes cancer. 

The NTP (2012) states in the Conclusion section of the report’s Summary (page 6):

“We conclude that N,N-dimethyl-p-toluidine caused cancers of the liver and nose in male and female rats, cancer of the liver in male and female mice, and cancers of the lung and forestomach in female mice.  Thyroid gland tumors in male rats may also have been related to exposure to N,N-dimethyl-p-toluidine.”

The NTP (2012) report states in the Conclusion section of the report’s Abstract and main body of the report (pages 10 and 89):

“Under the conditions of these 2-year oral gavage studies, there was clear evidence of carcinogenic activity of N,N-dimethyl-p-toluidine in male F344/N rats based on increased incidences of hepatocellular carcinoma, and hepatocellular adenoma or carcinoma (combined), and increased incidences of nasal cavity neoplasms (primarily nasal cavity transitional epithelium adenoma).  The increased incidences of thyroid gland follicular cell neoplasms may have been related to treatment.

“There was clear evidence of carcinogenic activity of N,N‑dimethyl-p-toluidine in female F344/N rats based on increased incidences of hepatocellular carcinoma and hepatocellular adenoma or carcinoma (combined).  The occurrence of nasal cavity transitional epithelium adenoma was considered to be related to treatment.

“There was clear evidence of carcinogenic activity of N,N-dimethyl-p-toluidine in male B6C3F1/N mice based on increased incidences of hepatocellular adenoma (multiple), hepatocellular carcinoma, and hepatoblastoma.

“There was clear evidence of carcinogenic activity of N,N‑dimethyl-p-toluidine in female B6C3F1/N mice based on increased incidences of hepatocellular adenoma, hepatocellular carcinoma, and hepatoblastoma and increased incidences of alveolar/bronchiolar neoplasms (primarily adenoma).  The increased incidences of forestomach squamous cell papilloma in female mice were considered to be related to treatment.” (Emphasis in the original.)

Thus, the NTP (2012) has found that N,N-dimethyl-p-toluidine causes increased incidences of malignant and combined malignant and benign tumors in male and female rats and male and female mice.

Request for comments:  OEHHA is requesting comments as to whether N,N-dimethyl-p-toluidinemeets 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, April 14, 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 - N,N-dimethyl-p-toluidine” 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.

References
NTP (2012).  National Toxicology Program.  Toxicology and Carcinogenesis Studies of N,N-Dimethyl-p-Toluidine (CAS No. 99-97-8) in F344/N Rats and B6C3F1/N Mice (Gavage Studies).  Technical Report Series No. 579. NIH Publication No. 12-5921.  U.S. Department of Health and Human Services, NTP, Research Triangle Park, NC.  Available at http://ntp.niehs.nih.gov/ntp/htdocs/LT_rpts/TR579_508.pdf.

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.

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