Evaluation of developmental neurotoxicity of organotins via drinking water in rats: monomethyltin.
Organotins such as monomethyltin (MMT) are widely used as heat stabilizers in PVC and CPVC piping, which results in their presence in drinking water supplies. Concern for neurotoxicity produced by organotin exposure during development has been raised by published findings of a deficit on a runway learning task in rat pups perinatally exposed to MMT (Noland EA, Taylor DH, Bull RJ. Monomethyl and trimethyltin compounds induce learning deficiencies in young rats. Neurobehav Toxicol Teratol 1982;4:539-44). The objective of these studies was to replicate the earlier publication and further define the dose-response characteristics of MMT following perinatal exposure. In Experiment 1, female Sprague-Dawley rats were exposed via drinking water to MMT (0, 10, 50, 245 ppm) before mating and throughout gestation and lactation (until weaning at postnatal day [PND] 21). Behavioral assessments of the offspring included: a runway test (PND 11) in which the rat pups learned to negotiate a runway for dry suckling reward; motor activity habituation (PNDs 13, 17, and 21); learning in the Morris water maze (as adults). Other endpoints in the offspring included measures of apoptosis (DNA fragmentation) at PND 22 and as adults, as well as brain weights and neuropathological evaluation at PND 2, 12, 22, and as adults. There were no effects on any measure of growth, development, cognitive function, or apoptosis following MMT exposure. There was a trend towards decreased brain weight in the high dose group. In addition, there was vacuolation of the neuropil in a focal area of the cerebral cortex of the adult offspring in all MMT dose groups (1-3 rats per treatment group). In Experiment 2, pregnant rats were exposed from gestational day 6 until weaning to 500 ppm MMT in drinking water. The offspring behavioral assessments again included the runway task (PND 11), motor activity habituation (PND 17), and Morris water maze (as adults). In this second study, MMT-exposed females consumed significantly less water than the controls throughout both gestation and lactation, although neither dam nor pup weights were affected. As in Experiment 1, MMT-exposure did not alter pup runway performance, motor activity, or cognitive function. These results indicate that perinatal exposure to MMT, even at concentrations which decrease fluid intake, does not result in significant neurobehavioral or cognitive deficits. While mild neuropathological lesions were observed in the adult offspring, the biological significance of this restricted finding is unclear.
Moser
Virginia C
VC
Neurotoxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711, United States. Moser.ginger@epa.gov
Barone
Stanley
S
Phillips
Pamela M
PM
McDaniel
Katherine L
KL
Ehman
Kimberly D
KD
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000254:growth & development / Q000473:pathology; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology*; D009947:Organotin Compounds / Q000008:administration & dosage / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D014867:Water / Q000008:administration & dosage
D009947:Organotin Compounds; D014867:Water; C036564:methyltin