NTP announces bioassay results. (NIEHS News).

On 3 May 2001, the National Toxicology Program (NTP) presented for public review five technical reports by the NTP's Board of Scientific Counselors Technical Reports Subcommittee at the NIEHS. NTP technical reports describe an ongoing series of toxicity and carcinogenicity studies conducted on chemical or physical agents to which humans are exposed. The findings from these studies are unique information and knowledge used by health and regulatory agencies in making decisions that affect public health.

Each report reviewed at the meeting involved a series of short- and long-term studies in which male and female rats and/or mice were given a range of doses of test chemical followed by extensive histopathologic examination plus characterizations of clinical chemistry, metabolism and disposition, and genotoxicity. The NTP applies established criteria to classify the strength of the experimental evidence for carcinogenicity in these studies, and the board's subcommittee review included a rigorous evaluation of the studies' findings.

Acrylonitrile and methacrylonitrile--Over 1 million tons of acrylonitrile are used each year in the production of acrylic fibers, elastomers, plastics, and resins. Acrylonitrile is known to be a multisite carcinogen in rats and has been classified as a likely human carcinogen. The NTP studied the effects of acrylonitrile given to mice by gavage and found clear evidence of carcinogenic activity in the forestomach and harderian gland of the eye for both males and females.

Methacrylonitrile is used as an alternative or replacement for acrylonitrile in some of the same applications. No evidence of carcinogenicity was seen for methacrylonitrile in male or female rats or mice. Methacrylonitrile also tested negative in a battery of genetic toxicity assays.

o- and p-Nitrotoluene--The ortho- and para- isomers of nitrotoluene are widely used in production of agricultural and rubber chemicals and a variety of dyes for cotton, wool, silk, leather, and paper, o-Nitrotoluene yielded clear evidence of carcinogenic activity in all four sex/species groups, producing skin and mammary gland neoplasms in male and female rats and hemangiosarcomas and large intestine carcinomas in male and female mice. In supplementary mechanistic studies, NIEHS scientists identified p53 and [beta]-catenin gene mutations in hemangiosarcomas taken from mice exposed to o-nitrotoluene; similar mutations were rarely seen in spontaneously occurring hemangiosarcomas from control animals.

By contrast, p-nitrotoluene yielded some evidence of carcinogenic activity in female rats (clitoral gland neoplasms) and equivocal evidence of carcinogenic activity in male rats and male mice.

Citral--Citral is a lemon flavoring and fragrance used widely in foods, cosmetics, and other consumer products. Because of the volatility and reactivity of the chemical, it was administered inside starch microcapsules mixed with the animals' feed. This was the NTP's first report using this route of administration in long-term studies. A marginal increase in malignant lymphomas in female mice was judged to be equivocal evidence of carcinogenic activity; there was no evidence of carcinogenicity of citral in rats or in male mice.

A listing of all NTP technical reports including an abstract of each study is available from the NTP home page, located at http://ntp-server.niehs.nih.gov/ (see NTP Study Information). The Environmental Health Information Service (EHIS) also maintains a library of NTP technical reports, adding new reports as available. Access to the EHIS is available online at http://ehis.niehs.nih.gov/ or by calling 1-800-315-3010.