A two-generation chronic mixture toxicity study of Clophen A60 and diethyl phthalate on histology of adrenal cortex and thyroid of rats.

This study was undertaken to observe the type of interaction that exists between polychlorinated biphenyls (Clophen A60) and diethyl phthalate (DEP) on the adrenal and thyroid glands of male and female Wistar rats. Animals were divided into four groups of six animals each, group I male and female rats were fed on a normal diet and water ad libitum. Groups II, III and IV male and female rats were given Clophen A60, DEP, or mixture of Clophen A60 and DEP, respectively, each dissolved in corn oil mixed with the diet at 50mg/kg of the diet/day. One hundred days after treatment, females were mated with males for 10 days. Exposure to the pollutants was continued throughout mating, gestation (21 days) until termination at weaning (21 days), which was 150 days of total treatment period of the parental generation. When the F1-generation pups (six males and six females of each group) were 75-100g in weight, they were treated in a similar manner to the parental generation, again for a period of 150 days, with the dose reduced to 25mg/kg of the diet/day in all treated groups. After 150 days of treatment, animals were sacrificed and histology of the adrenal and thyroid glands was asessed. An antagonistic interactive effect of treatment was seen in male parental and F1-generation rats, while an inhibitory type of interactive effect was observed in female rats. In the zona fasciculata region of the adrenal cortex of treated rats of both generations, vacuolations and degeneration were seen in samples from male animals and intracellular vacuolations in samples from females. A synergistic interactive toxic effect to the thyroid gland was observed in treated parental generation male rats, and mild changes in F1-generation-treated male rats, showing follicular shrinkage, loss of thyroglobulin and fibrosis of the interfollicular epithelium. In females, an antagonistic effect to the thyroid gland was observed in both parental and F1-generation-treated rats, showing similar effects as observed in males. From this study, we can conclude that combined administration of Clophen A60 and DEP shows an enhanced toxic effect on adrenal glands of F1-generation male and female rats, but the effect is much more marked in the thyroid gland of F1-generation male rats, and seen to a lesser extent in F1-generation female rats.