Evaluation of 60 chemicals in a preliminary developmental toxicity test.
Hardin-BD; Schuler-RL; Burg-JR; Booth-GM; Hazelden-KP; MacKenzie-KM; Piccirillo-VJ; Smith-KN
Teratog, Carcinog, Mutagen 1987 Jan; 7(1):29-48
Consolidated results on evaluations of 60 chemicals for developmental toxicity performed in NIOSH and contract laboratories were presented. The Chernoff/Kavlock experimental protocol, in which pregnant mice were dosed midterm and then allowed to deliver, was used. Initially, nonpregnant CD-1-mice were given 10 milliliter/kilogram of chemicals orally in corn oil or water for 8 days to determine the 10 percent lethal dose. Then pregnant mice were orally dosed on gestation days six to 13. Litter size, birth weight, neonatal growth, and survival to postnatal day three were the indices of potential developmental toxicity. The results were tabulated according to maternal and neonatal response variables. The following 25 chemicals caused reduced number of viable litter, litter size or viability: p-nitroaniline (100016), ethylenethiourea (96457), 2-ethyl-1-hexanol (104767), ethylene-glycol (107211), seven ether derivatives of ethylene-glycol, two ether derivatives of diethylene-glycol (111466), triethylene-glycol-dimethyl-ether (112492), propylene-glycol-3-ethyl-ether (111353), naphthalene (91203), and nitrofurazone (59870). Neonatal toxicity was seen with di(n-butyl), di(isobutyl), di(n-hexyl), di(n-octyl), di(2- ethylhexyl), and mono(2-ethylhexyl) esters of phthalic-acid (88993). Also toxic to progeny were sodium-selenite (10102188) and 2,4- diaminotoluene (95807). Reduced birth weight and weight gain were observed with administration of aniline (62533), benzyl-alcohol (100516), dimethyl-methyl-phosphonate (756796), and Tween-60 (9005667). No effect on the neonatal response was seen with 29 other compounds. Not classified was N-isopropyl-N'-phenyl-p- phenylenediamine (101724). A 10 percent false negative rate was found among ten known teratogens. The authors conclude that this developmental assay is of value for preliminary testing in prioritizing chemicals for further conventional tests.
NIOSH-Author; Toxic-materials; Embryotoxicity; Screening-methods; In-vivo-studies; Laboratory-animals; Teratogenesis; Reproductive-hazards; Developmental-disorders;
Author Keywords: in vivo screen; teratogen; hazard detection; rodent; pregnancy outcome; neonatal viability
Bryan D. Hardin, Division of Standards Development and Technology Transfer, National Institute for Occupational Safety and Health, 4676 Columbia Parkway, Cincinnati, OH 45226
100-01-6; 96-45-7; 104-76-7; 107-21-1; 111-46-6; 112-49-2; 111-35-3; 91-20-3; 59-87-0; 88-99-3; 10102-18-8; 95-80-7; 62-53-3; 100-51-6; 756-79-6; 9005-66-7; 101-72-4
Teratogenesis, Carcinogenesis, and Mutagenesis