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A recommended protocol for the Chernoff/Kavlock preliminary developmental toxicity test and a proposed method for assigning priority scores based on results of that test.

Authors
Hardin-BD
Source
Teratog, Carcinog, Mutagen 1987 Jan; 7(1):85-94
NIOSHTIC No.
00169370
Abstract
An ordered standardized protocol for the ranking of agents in a preliminary developmental toxicity test was proposed. The recommendations were based on experience in testing 60 chemicals. The appropriate dose was found by dosing three groups of three nonpregnant female mice with 10, 100, and 1000mg/kg per day for 5 days and observing them for another 7 days. After the completion of this phase, animals were treated with five dose levels on gestation days six to 15. Survivors were killed on gestation day 17. This phase differentiated between pregnant and nonpregnant females with different sensitivities and was capable of identifying chemicals that were very toxic to the fetus. Two protocol changes in this method were that treatment duration was extended from days eight to 12 to gestation days six to 15, and that treatment doses were based on the daily pretreatment body weight, thereby accounting for possible weight changes. Each female that died or was killed was necropsied to exclude dosing error. Maternal weight gain in the first four to five days of treatment were evaluated to obtain an index of maternal toxicity. Five indices of pregnancy outcome were: viable litters, litter size, percent neonatal survival to day three, average pup birth weight, and neonatal weight gain to day three. The proposed ranking system placed different emphasis on these indices. The score was calculated by assigning the maximum score of 22 and then subtracting points for each response variable that did not differ significantly from control. No points were subtracted if there was a statistically significant treatment effect or if statistics could not be applied. The remaining points, after all five indices were considered, constituted the priority score that might range from zero (low) to 22 (high priority). Of 60 agents tested, 18 were low priority, 21 were high priority, and 21 were in the intermediate or "no decision" range.
Keywords
NIOSH-Author; Laboratory-animals; Toxic-materials; Comparative-toxicology; Toxic-effects; In-vivo-studies; Teratogenesis; Screening-methods; Reproductive-hazards; Transplacental-exposure; Author Keywords: in vivo screen; teratogen; hazard detection; rodent; pregnancy outcome; neonatal viability
Contact
Bryan D. Hardin, Division of Standards Development and Technology Transfer, National Institute for Occupational Safety and Health, 4676 Columbia Parkway, Cincinnati, Ohio 45226
CODEN
TCMUD8
Publication Date
19870101
Document Type
Journal Article
Fiscal Year
1987
NTIS Accession No.
NTIS Price
Issue of Publication
1
ISSN
0270-3211
NIOSH Division
DSDTT
Source Name
Teratogenesis, Carcinogenesis, and Mutagenesis
State
OH
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