Reproductive, immunologie, and cytogenetic effects of dietary 3,3′,4,4′-tetrachloroazoxybenzene exposure to mice

Abstract

The effects of chronic dietary exposure to 3,3′,4,4′-tetrachloroazoxybenzene (TCAOB) on the reproductive efficiency of female Swiss-Webster mice were measured. The immunocompetence of their offspring was assayed at weaning. No indications of toxicosis were seen in the adult females with the exception of a reduction in the thymus weight of the animals consuming 10 ppm TCAOB. Pup mortality to weaning and the percentage of females whelping were not affected by 0.1 ppm, 1 ppm, or 10 ppm of TCAOB in the diet. There was, however, a significant reduction in the number of pups (at birth and at weaning) per female whelping at 10 ppm TCAOB in the diet. The thymus weight and plaque-forming-cell response of the pups were also significantly reduced below control levels. The lymphocyte blastogenic response to Concanavalin-A and lipopolysaccharide, and total peripheral blood leukocyte count, were not affected by the concentrations of TCAOB tested. Dietary treatment of female mice with relatively high concentrations of this chemical resulted in reduced reproductivity capacity, but only moderate immuno-suppression of their offspring exposed duringin utero and early postnatal development.

Spleen cells of mice exposedin vivo to TCAOB for 28 days via the diet were examined for chromosome damage and sister chromatid exchange. TCAOB was investigated because of its similarity to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD); TCAOB caused significantly increased chromatid breakage, suggesting that it may be affecting protein synthesis or may be a mutagen. However, TCAOB did not result in a significant increase in sister chromatid exchanges or isochromatid breaks even at a dietary concentration of 40 ppm.