Role of iodine in diiodomethyl-p-tolylsulfone induced reproductive toxicity in rats: proposed mode of action |
| |
Authors: | Saghir Shakil A Yano Barry L Zablotny Carol L Carney Edward W |
| |
Affiliation: | Toxicology & Environmental Research and Consulting, The Dow Chemical Company, 1803 Building, Midland, MI 48674, USA. ssaghir@dow.com |
| |
Abstract: | The biocide diiodomethyl-p-tolylsulfone (DIMPTS) caused dystocia, decreased neonatal survival and hypothyroidism in rat reproduction studies resembling the effects caused by iodine. One molecule of DIMPTS contains two iodine moieties that are hydrolyzed upon ingestion and systemically absorbed, suggesting iodine toxicity as a probable mode of action for the effects observed in rats. This study compared the effects induced by DIMPTS and an equimolar concentration of its de-iodinated analogue, methyl-p-tolylsulfone (MPTS). Groups of 20 female Sprague Dawley rats were fed diets supplying 80 mg DIMPTS/kg/day, 32 mg MPTS/kg/day or control feed from prior to breeding through lactation and gonadal function, mating performance, conception, gestation, parturition, lactation, survival, growth and development of pups evaluated through postnatal day 7. Serum thyroid hormones and iodine levels in milk and sera were also determined. Females given DIMPTS had increased incidence of vulvar discharge and dystocia, decreased litter size, decreased body weights and feed consumption, increased thyroid weights, thyroid follicular cell hypertrophy with decreased colloid, decreased triidothyronine, and increased thyroid stimulating hormone levels. DIMPTS pups had decreased neonatal survival and body weights. These effects were associated with elevated levels of iodine in milk and sera. In contrast, MPTS did not produce similar effects in adult females or their offspring. These data support the hypothesis that the dystocia, altered neonatal survival and hypothyroidism following repeated dietary administration of DIMPTS were due to excessive iodine released from DIMPTS during absorption and metabolism. |
| |
Keywords: | ANOVA, analysis of variance DIMPTS, diiodomethyl-p-tolylsulfone GD, gestational day LC/APPI/MS, liquid chromatography atmospheric pressure photo ionization mode mass spectrometry detection LC/MS, liquid chromatography mass spectrometry LD, lactational day MPTS, methyl-p-tolylsulfone PND, postnatal day SD, Sprague Dawley T3, triidothyronine T4, thyroxine TSH, thyroid stimulating hormone |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|