Toxicity and irreversible binding of two DDT metabolites —3‐methylsulfonyl‐DDE and o,p'‐DDD‐in adrenal interrenal cells in birds

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Abstract
The toxicity and the metabolism dependent irreversible binding of the lipophilic DDT metabolites 3‐methylsulfonyl DDE (MeSO2 DDE) and o,p DDD in the adrenal gland of the chicken were examined As determined by histopathology, vacuolar degeneration and pycnosis of adrenal interrenal cells occurred 4 d after injection of a single dose of either compound (0 25 mmol/kg, 80–100 mg/kg body weight) to 6‐d old chicken In addition, o,p DDD, but not MeSO2 DDE, induced fatty degeneration of the liver According to autoradiography, irreversibly bound radioactivity was present in the interrenal cells after injection of the 14C‐labeled compounds into the air sacs of eggs Both DDT metabolites were also irreversibly bound to protein after incubation with adrenal 300 g supernatant in vitro, with apparent Km values of 2 0 and 8 3 μM for MeSO2 DDE and o,p DDD, respectively The irreversible binding in vitro was inhibited by metyrapone, SKF 525A, and carbon monoxide, suggest ing a cytochrome P450‐dependent metabolic activation to reactive intermediates Addition of glutathione to the incubations reduced the irreversible binding of MeSO2‐[14C]DDE significantly, whereas the irreversible binding of o,p [14C]DDD remained un changed The results indicate that MeSO2‐DDE and o,p DDD are adrenocorticolytic following an adrenal P450‐dependent met abolic activation in the chicken Experiments with embryonated eggs from common eider and domestic duck demonstrated that MeSO2 DDE and o,p DDD are also metabolically activated and irreversibly bound to adrenal tissue in embryos of these species