Developmental toxicity of carbendazim: comparison of no-observed-adverse-effect level and benchmark dose approach. 1998

A Mantovani, and F Maranghi, and C Ricciardi, and C Macrì, and A V Stazi, and L Attias, and G A Zapponi
Laboratorio di Tossicologia Comparata ed Ecotossicologia, Istituto Superiore di Sanità, Rome, Italy.

The benchmark dose (BD) approach has been applied to foetal data from four gavage segment II studies (rat studies 1 and 2, rabbit study, hamster study) on the teratogenic benzimidazole carbendazim. Nineteen parameters were assessed using the log-normal model as a practical tool to derive BDs; good model fitting was observed for all except two parameters. Data were evaluated on a 'per-implant/foetus' basis; BDs were derived from response rate increases of 1, 5, and 10%. The values were compared to the lowest-observed-adverse-effect levels (LOAELs) and no-observed-adverse effect levels (NOAELs) obtained by Fisher's exact test on a 'per-implant/foetus' basis. Frank effects observed only at the top dose and/or small sample size tended to increase the 95% confidence limits and this influenced the determination of BD. Generally, the BD approach provided slightly more conservative estimates than NOAEL; overall, BD01 and BD05 were similar to NOAEL, or even lower for several parameters. The LOAEL in most cases was similar to BD10. Reference doses obtained by dividing BD01 by a 10 or 100 uncertainty factor, corresponded to residual risks of 10(-5) or below. For two critical parameters (hydrocephalus in rat study 1 and resorption rate in the rabbit study) a NOAEL could not be found, whereas a BD was always determined.

UI MeSH Term Description Entries
D011817 Rabbits A burrowing plant-eating mammal with hind limbs that are longer than its fore limbs. It belongs to the family Leporidae of the order Lagomorpha, and in contrast to hares, possesses 22 instead of 24 pairs of chromosomes. Belgian Hare,New Zealand Rabbit,New Zealand Rabbits,New Zealand White Rabbit,Rabbit,Rabbit, Domestic,Chinchilla Rabbits,NZW Rabbits,New Zealand White Rabbits,Oryctolagus cuniculus,Chinchilla Rabbit,Domestic Rabbit,Domestic Rabbits,Hare, Belgian,NZW Rabbit,Rabbit, Chinchilla,Rabbit, NZW,Rabbit, New Zealand,Rabbits, Chinchilla,Rabbits, Domestic,Rabbits, NZW,Rabbits, New Zealand,Zealand Rabbit, New,Zealand Rabbits, New,cuniculus, Oryctolagus
D012016 Reference Values The range or frequency distribution of a measurement in a population (of organisms, organs or things) that has not been selected for the presence of disease or abnormality. Normal Range,Normal Values,Reference Ranges,Normal Ranges,Normal Value,Range, Normal,Range, Reference,Ranges, Normal,Ranges, Reference,Reference Range,Reference Value,Value, Normal,Value, Reference,Values, Normal,Values, Reference
D002219 Carbamates Derivatives of carbamic acid, H2NC( Carbamate,Aminoformic Acids,Carbamic Acids,Acids, Aminoformic,Acids, Carbamic
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D006224 Cricetinae A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS. Cricetus,Hamsters,Hamster
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001562 Benzimidazoles Compounds with a BENZENE fused to IMIDAZOLES.
D013723 Teratogens An agent that causes the production of physical defects in the developing embryo. Embryotoxins,Fetotoxins,Teratogen
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D018675 Toxicity Tests An array of tests used to determine the toxicity of a substance to living systems. These include tests on clinical drugs, foods, and environmental pollutants. Tests, Toxicity,Test, Toxicity,Toxicity Test

Related Publications

A Mantovani, and F Maranghi, and C Ricciardi, and C Macrì, and A V Stazi, and L Attias, and G A Zapponi
November 1994, Fundamental and applied toxicology : official journal of the Society of Toxicology,
A Mantovani, and F Maranghi, and C Ricciardi, and C Macrì, and A V Stazi, and L Attias, and G A Zapponi
January 2016, Methods in molecular biology (Clifton, N.J.),
A Mantovani, and F Maranghi, and C Ricciardi, and C Macrì, and A V Stazi, and L Attias, and G A Zapponi
January 2022, Methods in molecular biology (Clifton, N.J.),
A Mantovani, and F Maranghi, and C Ricciardi, and C Macrì, and A V Stazi, and L Attias, and G A Zapponi
February 2009, Human & experimental toxicology,
A Mantovani, and F Maranghi, and C Ricciardi, and C Macrì, and A V Stazi, and L Attias, and G A Zapponi
November 1994, Fundamental and applied toxicology : official journal of the Society of Toxicology,
A Mantovani, and F Maranghi, and C Ricciardi, and C Macrì, and A V Stazi, and L Attias, and G A Zapponi
April 1992, Regulatory toxicology and pharmacology : RTP,
A Mantovani, and F Maranghi, and C Ricciardi, and C Macrì, and A V Stazi, and L Attias, and G A Zapponi
February 2017, Toxins,
A Mantovani, and F Maranghi, and C Ricciardi, and C Macrì, and A V Stazi, and L Attias, and G A Zapponi
October 2015, Toxicology and applied pharmacology,
A Mantovani, and F Maranghi, and C Ricciardi, and C Macrì, and A V Stazi, and L Attias, and G A Zapponi
December 2020, SAR and QSAR in environmental research,
A Mantovani, and F Maranghi, and C Ricciardi, and C Macrì, and A V Stazi, and L Attias, and G A Zapponi
February 2006, Risk analysis : an official publication of the Society for Risk Analysis,
Copied contents to your clipboard!