ToxSci Advance Access published online on June 16, 2004
Toxicological Sciences, doi:10.1093/toxsci/kfh202
Toxicological Sciences © Society of Toxicology 2004; all rights reserved
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1 Linus Pauling Institute and the Marine/Freshwater Biomedical Sciences Center, 571 Weniger Hall, Oregon State University, Corvallis, OR, 97331
* To whom correspondence should be addressed. E-mail: Robert.tanguay{at}oregonstate.edu.
Sodium metam (NaM), a dithiocarbamate, is a general agricultural biocide applied prior to planting for the elimination of nematodes, soil pathogens and weeds. There is a remarkable paucity of information about the mechanism of action and the risk that dithiocarbamates may pose to developing vertebrates. We have characterized NaM toxicity during early life stage exposure in zebrafish. Zebrafish embryos are most sensitive to NaM exposure during gastrulation and early segmentation (4-14 hours post fertilization, hpf). For mortality, the dose response curve is steep with an LC50 estimate of 1.95 µM (248 ppb) at 48hpf. The most notable malformation among surviving embryos was a severely twisted notochord, which became evident by 24hpf. Surprisingly, this notochord defect was not immediately lethal and the animals continued to grow despite delays in hatching, apparent paralysis, and an inability to feed. We have characterized the notochord malformation using histological and in situ hybridization techniques. collagen 2a1 mRNA expression is normally localized to the notochord sheath cells at 24hpf, whereas in NaM-exposed embryos it is misexpressed in the notochord cells. Histological staining and myoD expression indicate that the myotomes of the NaM-exposed embryos are less defined, compacted and block-shaped compared to controls. The degradation product of NaM, methyl isothiocyanate (MITC), causes similar malformations at similar concentrations as NaM, suggesting that MITC or another common product may be the active toxicant. Our results indicate that developing zebrafish are sensitive to NaM and MITC and we believe that this model is ideal to elucidate the molecular mechanism(s) and etiology of NaM toxicity in vertebrates.
Accepted June 14, 2004
Reproductive and Developmental Toxicology
Developmental Toxicity of the Dithiocarbamate Pesticide Sodium Metam in Zebrafish
2 Environmental and Molecular Toxicology, the Environmental Health Sciences Center, 1007 Ag and Life Science Bldg, Oregon State University, Corvallis, OR, 97331
3 Linus Pauling Institute, Environmental and Molecular Toxicology, the Environmental Health Sciences Center and the Marine/Freshwater Biomedical Sciences Center, 435 Weniger Hall, Oregon State University, Corvallis, OR, 97331
4 Environmental and Molecular Toxicology, the Environmental Health Sciences Center and the Marine/Freshwater Biomedical Sciences Center, 1007 Ag and Life Science Bldg, Oregon State University, Corvallis, OR, 97331
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