Toxaphene congeners differ from toxaphene mixtures in their dysmorphogenic effects on cultured rat embryos

Abstract

The presence of persistent organic pollutants, including the pesticide toxaphene has been reported even in remote regions such as the Arctic and is becoming a health concern. The technical mixture of toxaphene contains over 800 different congeners. The numbers of prevalent congeners, however, decrease along the food chain. About 20 major congeners are found in fish, eight in marine mammals and only two major ones in human, 2- exo,3- endo,5- exo,6- endo,8,8,10,10-octachlorobornane (T 2) and 2- exo,3- endo,5- exo,6- endo,8,8,9,10,10-nonachlorobornane (T 12). Embryotoxicity of these individual congeners is not known, as previous studies focused on the toxaphene technical mixture. We studied the relative dysmorphogenic activity of toxaphene technical mixture and individual congeners (T 2 and T 12) using rat embryo culture. Explanted embryos (0–2 somites) were treated for 48 h with concentrations of 0 (DMSO 0.01%), 100, 1000 and 5000 ng/ml of either (a) toxaphene technical mixture; (b) T 2; (c) T 12; or (d) a 50:50 mixture of T 2 and T 12. The treatment period corresponds to gestational days (GD) 10–12, a period within the critical time of morphogenesis and organogenesis. Both the technical mixture and the two individual congeners had a significant adverse effects on the total morphological score, somite number, head and crown rump length and the central nervous system scores of embryos. All treatments caused a high incidence of central nervous system defects. The T 2 and T 12 congeners differed in their spectrum of abnormalities as exposure to T 2 caused limb and flexion defects which were not observed with the T 12 congener. Differences were also observed in the type of toxicity and the target sites between the technical mixture and the congeners. T 2 showed a more potent adverse effect on the morphological score as compared to the technical mixture. Both T 2 and T 12 were less inhibitory on growth than the technical mixture as indicated by crown-rump length but they showed a stronger inhibitory effect on otic system development. The mixture of T 2+T 12 showed a synergistic effect on decreasing crown-rump and head length. Conversely, the combination of T 2 and T 12 inhibited the strong adverse effect of the individual congeners on otic development. The results suggest environmentally predominant toxaphene congeners can have organ specific embryotoxic effects not predicted by the toxaphene technical mixture.