Vitamin A acetate: a behavioral teratology study in rats.

We evaluated the effects of maternal administration of vitamin A acetate on pup development and behavior. Vitamin A acetate was administered by oral gavage to pregnant rats (N = 10/treatment) on gestation days 6-19 at doses of 25,000, 50,000 or 100,000 I.U./kg/day. Male and female pups from dams that received 100,000 I.U./kg/day showed a significantly reduced live birth index but few external abnormalities. Twenty-four and 48 hour survival indices were also significantly reduced. The mean pup body weight gain at 100,000 I.U./kg/day was significantly reduced at days 1-3, 3-7 and 21-42. Pinna detachment and eye opening were significantly delayed in all male pups and in female pups from the 50,000 and 100,000 I.U./kg/day groups. Incisor eruption was significantly delayed in male and female pups from the 25,000 and 50,000 I.U./kg/day groups. The following showed no treatment effects: dam mean weight change, length of gestation, total litter size, surface righting, cliff avoidance, negative geotaxis, swimming development, open field activity and discriminatory learning.

Comparative carcinogenicity of the PAHs as a basis for acceptable exposure levels (AELs) in drinking water.

The carcinogenicity of various polynuclear aromatic hydrocarbons (PAHs) has generally been demonstrated by their ability to act as complete carcinogens in the development of cancers in rodent skin tests. In order to develop proposed acceptable concentration levels for various PAHs in drinking water, we reviewed the studies that formed the basis for determining that these specific PAHs were carcinogenic in animals. We found that the relative potency of these PAHs varied over a range of many orders of magnitude. For example, the carcinogenic strength of benz[a]anthracene (BaA) is found to be about 1/2000th that of benzo[a]pyrene (BaP). We have used the calculated carcinogenic potency of the various PAHs relative to that of BaP as a means for proposing specific acceptable concentration levels in drinking water for each of the specific PAHs. BaP is the only carcinogenic PAH for which EPA has published an acceptable concentration level based on carcinogenicity. Based on the level EPA set for BaP (0.028 micrograms/liter), this methodology has provided for the specific PAHs a determination of proposed acceptable concentration levels quantitatively based on the same data that were used to qualitatively determine them to be animal carcinogens. We have proposed acceptable concentration levels for the carcinogenic PAHs in drinking water that range from 0.03 micrograms/liter for BaP to 6.5 micrograms/liter for BaA. We recommend that acceptable concentration levels for the various PAHs be based on their relative carcinogenic potencies rather than the EPA method of using the potency of only one specific PAH, BaP, to serve as the exposure level determinant for all PAHs. We further suggest that this methodology may be applicable to other classes of carcinogenic compounds. We have also found useful for the determination of acceptable concentration levels for the noncarcinogenic PAHs an analogous methodology based on the relative toxicities of the noncarcinogenic PAHs.

A computerized data management system for behavioral teratology studies.

A computerized system was designed for behavioral teratology studies to (1) generate preprinted data recording/submission forms, (2) calculate testing dates, (3) generate a daily activity schedule for testing, and (4) update established data sets for access by data entry personnel. The computer-generated forms are used to record data from the following behavioral/developmental tests for rats: pup weights, pinna detachment, surface righting, cliff avoidance, incisor eruption, eye opening, negative geotaxis, olfactory discrimination, swimming development, open field, swimming maze and operant visual discrimination learning. Three behavioral teratology studies have been conducted in our laboratory using this computerized system. The human error rates in these studies were 0.26, 0.34 and 0.46 percent, respectively. The advantages of this system include: (1) computer-calculated test dates; (2) elimination of manual data transcription; (3) more consistent data recording and scoring conditions; (4) better scheduling control; and (5) faster data entry and statistical analysis.