Comparative reprotoxicity of three oximes.

Drug Chem Toxicol

Honeywell International, Morristown, New Jersey 07962-1139, USA.

Published: January 2010

AI Article Synopsis

  • Three oximes (AAO, ADO, MIBKO) were studied for reproductive toxicity, following OECD 415 guidelines, with rats exposed before and during mating, as well as through gestation and lactation.
  • No major reproductive or litter issues were found, except for increased stillbirths in the ADO high-dose group, while signs of hemolytic anemia were observed in all F0 animals exposed to the oximes.
  • NOAELs varied: AAO (<5 mg/kg/day for F0, 50 mg/kg/day for F1), ADO (<5 mg/kg/day for F0, 25 mg/kg/day for F1), and MIBKO (30 mg/kg/day for F0

Article Abstract

One-generation reproductive toxicity studies have been conducted on the following three oximes: acetaldehyde oxime (AAO), aldecarb oxime (ADO), and methyl isobutyl ketoxime (MIBKO). The studies followed the OECD 415 guideline (One-Generation Reproduction Toxicity Study), with a few modifications. Rats were exposed to the test material for 10 weeks prior to mating and 2 weeks of mating. Males were killed following mating, and females were continuously exposed through gestation and lactation. For MIBKO, the F1 generation was exposed from weaning until approximately 7 weeks of age to include when the vaginal opening occurred in females or when balanopreputial separation occurred in males. With the exception of an increased number of stillbirths in the ADO high-dose-group animals, no adverse effects were observed in any of the reproductive or litter parameters or in the F1 pups. Toxicity to the F0 animals included signs of hemolytic anemia, along with compensatory extramedullary hematopoiesis and hemosiderosis of the spleen. This occurred for all three test materials. For AAO, the no-observed-adverse-effect level (NOAEL) for the F0 generation was considered to be less than 5 mg/kg/day, based on decreased mean corpuscular hemoglobin concentration values and histological changes in the spleen. The NOAEL for the F1 generation and reproductive toxicity was considered to be 50 mg/kg/day, the highest dose tested. For ADO, the NOAEL for parental toxicity was considered to be less than 5 mg/kg/day, based on the histological changes observed in the livers of females in all groups. The NOAEL for reproductive toxicity and the F1 generation was considered to be 25 mg/kg/day, based on the higher number of stillborn pups in the high-dose group. For MIBKO, the NOAEL for parental toxicity was considered to be 30 mg/kg/day, based on the histological effects on the spleen. The NOAEL for the F1 generation and reproductive toxicity was 100 mg/kg/day, the highest dose tested.

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http://dx.doi.org/10.1080/01480540903154187DOI Listing

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