Human developmental toxicity and mutagenesis.
A previously described SAR model of human developmental toxicity was analyzed further. The model shows a number of mechanistic similarities with SAR models of other toxicological phenomena (systemic toxicity, chromosomal and genomic effects). This implies that there are many targets associated with developmental effects. Surprisingly the analyses revealed no significant mechanistic overlap between developmental toxicity in humans and mutagenicity in Salmonella, a surrogate for the occurrence of point mutations. Our study indicates that this lack of similarity is likely the result of the pre-screening strategies which largely eliminate Salmonella mutagens from among the therapeutics introduced into human medicine.
Rosenkranz
H S
HS
Department of Environmental and Occupational Health University of Pittsburgh, Pittsburgh, PA 15238, USA.rsnkranz@vms.cis.pitt.edu
Zhang
Y P
YP
Macina
O T
OT
Mattison
D R
DR
Klopman
G
G
D000818:Animals; D002657:Child Development / Q000187:drug effects*; D002675:Child, Preschool; D016208:Databases, Factual; D004353:Drug Evaluation, Preclinical; D005314:Embryonic and Fetal Development / Q000187:drug effects; D006801:Humans; D008962:Models, Theoretical; D009152:Mutagenicity Tests; D012475:Salmonella / Q000187:drug effects / Q000235:genetics; D013329:Structure-Activity Relationship