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DEVELOPMENTAL NEUROTOXICITY OF ORGANOTINS IN PVC LEACHATES
Impact/Purpose:
The objective of this research is to identify and characterize potential developmental immunotoxic and neurotoxic effects associated with exposure to organotins that may leach from PVC pipe used in residences and distribution systems. Results of this research will aid the Office of Water in its regulatory determination process for these Candidate Contaminant List (CCL) chemicals.
Description:
Developmental exposure to monomethyltin or trimethyltin in the drinking water can produce a dose-dependent learning impairment consistent with altered development of the limbic system. The relative potency of organotins to disrupt developmental events is related to their physical properties and these properties can be used to predict the toxicity of mixtures of organotins corresponding to those found in PVC leachates.
The primary source of organotins in drinking water is believed to be PVC leachates. Limited occurrence data from residential surveys indicate as much as 300 ng/l of monomethyltin can be detected. Noland et al., (1982) reported that exposure of rats to monomethyltin (12, 40, 120 mg/L) or trimethyltin (0.15, 0.5, 1.0 mg/L) in drinking water during pregnancy and postnatal development results in a learning impairment in the offspring consistent with altered development of the limbic system. The proposed research will: 1) characterize the dose-dependence of the learning impairment and identify structural and developmental correlates, and 2) assess the relative potency of various organotin species and their mixtures to disrupt developmental events.
Characterization of Learning Impairment and Limbic System Injury Following Developmental Drinking Water Exposure to Organotins Rats will be developmentally exposed to monomethyltin and trimethyltin in drinking water at exposure levels used in the Noland study and at least one additional lower exposure level. Learning will be characterized in the offspring and morphological assessment of the limbic system will focus on identifying structural and developmental correlates of observed impairments. The morphological assessment will include animals sacrificed at PND-11 and PND-22, as part of larger effort by NTD to evaluate the relative value of these different time points in the assessment of developmental neurotoxicity.
Effects of Organotins on Biomarkers of Developmental Neurotoxicity. The effects of drinking water exposure to organotins during development will be assessed with ex vivo assays for developmental neurotoxicity that include biomarkers of proliferation (BrdU), differentiation (neurite outgrowth, neurotrophins, integrin, PKC, MAPK, calcium channel expression and function), and apoptosis (apototic specific DNA fragmentation). In vivo test systems that utilize corresponding assays for these biomarkers will characterize structure-activity relationships of different tin species and characterize effects of organotin mixtures.