Developmental toxicity of the dithiocarbamate pesticide sodium metam in zebrafish.

TitleDevelopmental toxicity of the dithiocarbamate pesticide sodium metam in zebrafish.
Publication TypeJournal Article
Year of Publication2004
AuthorsHaendel, MA, Tilton, F, Bailey, GS, Tanguay, RL
JournalToxicol Sci
Date Published2004 Oct
KeywordsAnimals, Cell Differentiation, Embryo, Nonmammalian, Female, In Situ Hybridization, Isothiocyanates, Male, Notochord, Pesticides, Thiocarbamates, Tissue Fixation, Zebrafish

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 LC(50) estimate of 1.95 microM (248 ppb) at 48 hpf. The most notable malformation among surviving embryos was a severely twisted notochord, which became evident by 24 hpf. 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 24 hpf, 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.

Alternate JournalToxicol. Sci.
PubMed ID15201444
Grant ListP30 ES000210 / ES / NIEHS NIH HHS / United States
ES00210 / ES / NIEHS NIH HHS / United States
ES03850 / ES / NIEHS NIH HHS / United States
NS11170 / NS / NINDS NIH HHS / United States