Potential teratogenic effects of benomyl in rat embryos cultured in vitro. 2005

Matthew J Hewitt, and Philip Mutch, and Margaret K Pratten
University of Leeds, Gledhow Wing, St James's University Hospital, Department of Obstetrics and Gynaecology, Level 9, Leeds LS97TF, UK. matt.hewitt@doctors.org.uk

A possible association between environmental exposure to benomyl and anophthalmia has been suggested. The aim of the present study was to investigate potential teratogenic effects of benomyl using the 9.5 day rat embryo culture method using rat and human serum. Explanted rat embryos were cultured in rat serum (n=121) or human serum (n=90) with differing concentrations of benomyl [170 nM to 13.6 microM], dissolved in ethanol (0.136%), at least five embryos per concentration being cultured. In addition, 18 embryos were cultured in both human and rat serum with the equivalent concentration of ethanol to act as a vehicle control. The cultured embryos were then measured and scored for growth and differentiation by two blinded observers. Embryotoxic effects were considered to be demonstrated by a decrease in parameters of growth such as crown rump length, yolk sac diameter and protein content, whereas embryopathic effects were considered to be those causing a decease in parameters of differentiation such as morphological score, somite number and optic development. Benomyl [> or =5 microM] produced a significant concentration dependent deterioration in morphological score, somite number and optic development. Gross toxic effects were noticed at concentrations of >12 microM in rat serum and >10microM in human serum as indicated by a significant effect on parameters measuring size (crown rump length; yolk sac diameter and protein content). This study provides evidence that benomyl is a potential developmental toxicant, affecting many parameters of differentiation, including optic development at levels below those that could be considered embryotoxic.

UI MeSH Term Description Entries
D011247 Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. Gestation,Pregnancies
D004622 Embryo, Mammalian The entity of a developing mammal (MAMMALS), generally from the cleavage of a ZYGOTE to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the FETUS. Embryonic Structures, Mammalian,Mammalian Embryo,Mammalian Embryo Structures,Mammalian Embryonic Structures,Embryo Structure, Mammalian,Embryo Structures, Mammalian,Embryonic Structure, Mammalian,Embryos, Mammalian,Mammalian Embryo Structure,Mammalian Embryonic Structure,Mammalian Embryos,Structure, Mammalian Embryo,Structure, Mammalian Embryonic,Structures, Mammalian Embryo,Structures, Mammalian Embryonic
D005260 Female Females
D005659 Fungicides, Industrial Chemicals that kill or inhibit the growth of fungi in agricultural applications, on wood, plastics, or other materials, in swimming pools, etc. Industrial Fungicides
D000014 Abnormalities, Drug-Induced Congenital abnormalities caused by medicinal substances or drugs of abuse given to or taken by the mother, or to which she is inadvertently exposed during the manufacture of such substances. The concept excludes abnormalities resulting from exposure to non-medicinal chemicals in the environment. Drug-Induced Abnormalities,Abnormalities, Drug Induced,Abnormality, Drug-Induced,Drug Induced Abnormalities,Drug-Induced Abnormality
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
D001542 Benomyl A systemic agricultural fungicide used for control of certain fungal diseases of stone fruit. Benlate,Fundasol,Fundazol
D013723 Teratogens An agent that causes the production of physical defects in the developing embryo. Embryotoxins,Fetotoxins,Teratogen
D017208 Rats, Wistar A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain. Wistar Rat,Rat, Wistar,Wistar Rats
D046508 Culture Techniques Methods of maintaining or growing biological materials in controlled laboratory conditions. These include the cultures of CELLS; TISSUES; organs; or embryo in vitro. Both animal and plant tissues may be cultured by a variety of methods. Cultures may derive from normal or abnormal tissues, and consist of a single cell type or mixed cell types. Culture Technique,Technique, Culture,Techniques, Culture

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