Testing of selected workplace chemicals for teratogenic potential.
Hardin BD; Bond GP; Sikov MR; Andrew FD; Beliles RP; Niemeier RW
Scand J Work Environ Health 1981 Dec; 7(Suppl 4):66-75
Teratogenicity was tested in 19 chemicals. Pregnant female Sprague- Dawley-rats were injected intraperitoneally with the test chemical dissolved or suspended in corn oil at the previously determined maximum tolerated dose on days 1 through 15 of gestation. On day 21, they were killed and uterine contents examined. In inhalation studies, pregnant Wistar-rats or Sprague-Dawley-rats and New-Zealand- white-rabbits were exposed for 6 to 7 hours per day on gestation days 1 to 19 (rats) or 1 to 24 (rabbits) to the test chemicals. Pregnant animals were killed on the day before term and the litters examined. In injected animals, a significant incidence of delayed fetal development was seen with 2-nitropropane (79469) at 170 milligrams per kilogram (mg/kg) and hexachlorobutadiene (87683) at 10mg/kg. With methyl-styrene (1319739) at 250mg/kg, resorption was significantly increased. With allyl-chloride (107051) at 80mg/kg, there was a significant increase in resorption and a significant incidence of fetuses from treated litters with edema and protruding tongue. Bisphenol-A (80057) at 1215mg/kg impaired the establishment of pregnancy. The small number of fetuses available for study showed incomplete skeletal ossification, enlarged cerebral ventricles or hydrocephaly. With inhalation exposure, trichloroethylene (79016) at 500 parts per million (ppm) produced four fetuses with external hydrocephaly. In both rats and rabbits, 2-ethoxyethanol (110805) (rats, 150 and 650ppm; rabbits, 160 and 615ppm) produced teratogenic effects. Fetal morphological examinations of rabbits revealed a significantly increased incidence of renal, cardiovascular, and ventral body wall defects in fetuses from the 160ppm exposure group. All litters at the higher dose were partially resorbed in both animals. At the lower dose, rats showed increased incidence of cardiovascular and skeletal defects. The authors conclude that 2-ethoxyethanol is embryotoxic and teratogenic. Further study is recommended for allyl-chloride, bisphenol-A, trichloroethylene, and ethyl-benzene.
NIOSH-Author; Animal-studies; Physiological-response; Dose-response; Biological-effects; Teratogens; Exposure-levels; Pathogenesis; Biological-factors; Embryopathology;
Author Keywords: allyl chloride; bisphenol A; butylene oxide; carbon disulfide; copper naphthenate; 2-ethoxyethanol; ethyl benzene; ethylene dibromide; hexachlorobutadiene; 2-mercaptobenzothiazole; methyl styrene; naphthalene; 2-nitropropane; nitrous oxide; reproductive toxicity; styrene oxide; teratogenesis; tetrachloroethylene; trichloroethylene; 1,2,3-trichloropropane
Mr BD Hardin, Division of Biomedical and Behavioral Science, National Institute for Occupational Safety and Health, 4676 Columbia Parkway, Cincinnati, OH 45226, USA
79-46-9; 87-68-3; 1319-73-9; 107-05-1; 80-05-7; 79-01-6; 110-80-5
Scandinavian Journal of Work, Environment & Health