No abstract

States. It is used clinically in the treatment of high-protein as a fragrance enhancer and stabilizer, was administered in the diet of Sprague-Dawley rats at dose levels of 0, 333, 1000, 2000, edema (Jamal et al., 1989), chronic brucellosis, and immune 3000, and 5000 ppm or in the diet of CD-1 mice at dose levels of suppression (Moran et al., 1987). In isolation (Thornes et 0, 300, 1000, or 3000 ppm. Rats receiving 333, 1000, and 2000 al., 1989) or in combination with cimetidine (Marshall et ppm coumarin were exposed to these dose levels in utero and al., 1987a, b, c;Dexeus et al., 1990), coumarin is currently during the lactational period, then chronically following weaning. undergoing several clinical trials for the treatment of several Rats in the 3000-and 5000-ppm dose groups and all mice received types of malignancies in humans, including the treatment of only postweaning chronic exposure. All male rats were terminated lung and kidney carcinoma. Due to its use as a drug, there after 104 weeks of postweaning exposure; female rats were termiis information in the literature concerning its toxicity, metab- have been conducted to examine the chronic toxicity and at 333 ppm, but significantly increased among rats in the 3000-carcinogenicity of coumarin, none were conducted in accorand 5000-ppm dose groups. Dramatic dose-related decreases in body weight gain were recorded for rats receiving 2000, 3000, and dance with current scientific guidelines. A GLP-compliant 5000 ppm, clearly indicating that the MTD (maximum tolerated study was therefore undertaken. (Since this study was comdose, as indicated by a body weight decrement of greater than 10-pleted, the U.S. National Toxicology Program has conducted 15%) was exceeded. Food consumption also was decreased at the a bioassay of coumarin in F344 rats and B6C3F1 mice.) chymal liver cell tumors were observed among male and female rats receiving 5000 ppm. One male rat receiving 3000 ppm devel-Animals and Treatments oped a cholangiocarcinoma; no tumor increase was observed in Rats. Rats were housed five per cage in suspended wire-mesh cages.males or females at 2000 ppm or below. Coumarin, at a dose Animal rooms were maintained at 22ЊC and 50% relative humidity, with a clearly exceeding the MTD can, therefore, induce liver tumors in 12-hr/12-hr light/dark cycle. Each cage was identified by cage card and rats, although survival, relative to controls, was increased at the each rat was individually identified by earmark and tattoo. Ad libitum access same dose levels. Among mice, a decrease in body weight gain to food and tap water was provided. was reported for males in the 1000-and 3000-ppm dose groups All animals for the chronic study were derived from Sprague-Dawley during the first 52 weeks of the study. No dose-related abnormali-rats received from Charles River (Charles River, Manston, Kent, UK) and ties in clinical signs, clinical pathology, hematology, or gross or bred at Huntingdon Research Centre, Huntingdon, Cambridgeshire, Enmicroscopic pathology were noted. ᭧ 1996 ...

Twelve workers were monitored for exposure to 18.75% lindane dust formulation during manual wheat seed treatment. The mean total actual exposure rate was 32.89 mg/hr. Potential respiratory exposure averaged 0.0057 mg/hr (less than 1% of the total), with seven workers receiving no measurable respiratory exposures. Mean hand exposure was 1.84 mg/hr (5.6%). Dermal exposure to the head and neck averaged 4.28 mg/hr (13%). Exposure measured beneath the workshirt and workpants averaged 26.8 mg/hr (81.4%). The workshirt and workpants provided 3.4-fold and 11.5-fold protection factors, respectively. Forearm exposure measured beneath the workshirt represented more than 40% of total actual exposure. The small contribution of hand exposure to total dermal exposure was consistent with the use of chemical-resistant gloves by all workers. Total dermal exposure could be reduced substantially by wearing coveralls over regular work clothing, and by the use of guantlet-type gloves. It is recommended that worker education concerning personal hygiene and the appropriate use of protection clothing be made essential components of exposure reduction programs.

No abstract

This study evaluated the potential for dietary para-nonylphenol (NP; CAS No. 84852-15-3) to affect parental fertility and growth and development of three offspring generations in CD (Sprague-Dawley [SD]) rats, including sperm counts across generations to determine the validity of equivocal reductions observed in the F2 generation by R. E. Chapin et al. (1999, Toxicol. Sci. 52, 80-91). Male rat kidney toxicity was also examined based on inconsistent observations in NP-exposed rats at 2000 ppm but not at 200 or 650 ppm in Purina 5002 (H. C. Cunny et al., 1997, Regul. Toxicol. Pharmacol. 26, 172-178) and at all of these NP concentrations in NIH-07 diet (R. E. Chapin et al., 1999, Toxicol. Sci. 52, 80-91). Concentrations were 0, 20, 200, 650, and 2000 ppm NP in Purina 5002 diet and 0 and 650 ppm NP in NIH-07 diet. 17beta-estradiol (E2) was used as a positive control at 2.5 ppm in Purina 5002 diet. There were no NP effects on any reproductive parameters in any generation, including sperm counts. Kidney toxicity (histopathology) occurred at 650 and 2000 ppm with no clear difference for the two diets. Ovarian weight was decreased at 2000 ppm NP in all generations, with no effect on reproduction. Dietary E2 at 2.5 ppm caused renal, reproductive, and developmental (lactational and peripubertal) toxicity in all generations. This study confirmed that dietary NP is not a selective reproductive toxicant with an no observable adverse effect level (NOAEL) of > 2000 ppm ( approximately > 150 mg/kg/day) and provided an NOAEL for male rat kidney toxicity of 200 ppm NP (approximately 15 mg/kg/day).