Sodium dimethyldithiocarbamate

Endpoint summary

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

66

Absorption rate - dermal (%):

5

Additional information

The toxicokinetic behaviour of sodium dimethyldithiocarbamate (SDDC) is predicted on the basis of studies conducted with the zinc analogon, ziram. The target (SDDC) and the source substance (ziram) represent salts of dimethyl dithiocarbamic acid (DDC) and have similar physico-chemical properties. There is convincing evidence that these chemicals lie in the overall common profile with respect to the present analogue approach. For a detailed discussion please refer to the analogue justification attached in IUCLID section 13.

In rats, Ziram is well absorbed from the gastro-intestinal tract, within 48 h after oral administration for 58-61% after a single low dose, for 60-69% after a single high dose and for 71-75% after a repeated low dose. It was concluded that the oral absorbed dose reached approximately 60% after low dose and a correction factor of 66% can be applied for SDDC (worst case assumption). Partial inactivation, by a first-pass hepatic elimination, is suggested by the fact that, after inhalation, signs of systemic neurotoxicity were observed after 30 times lower doses than after oral ingestion. After repeated exposure, recovery of radioactivity in tissues and carcass was low 7 days after exposure, suggesting that the compound does not accumulate.

According to the JMPR (1996), Ziram is metabolized to dimethyldithiocarbamate and excreted as S-glucuronide conjugate. Other metabolic products include carbon disulfide, sulfate and dimethylamine. The most important elimination route of the radioactive marker was via expired air (36 to 53% of the dose administered), the majority of which was expired during the first 48 h post-dosing. Urinary excretion represented 17% (high dose within 24 h) to 35% (repeated low dose within 24 - 48 h). Faecal excretion represented 9 to 18.5% and decreased with increasing the dose.

Percutaneous absorption of ziram has been studied in vivo (Cheng, 1991) in the rat and in vitro (Kane, 2006) using human skin samples. Because of the volatile nature of the two metabolites, CS2 and dimethylamine (DMA), the recovery of radioactivity in the in vivo assay in rats was only 70-80%. The non-recovered radioactivity was assumed to be dermally absorbed giving rise to a dermal absorption between 5 (high dose) to almost 30% (low dose). Much better recoveries (91-94%) were obtained with an in vitro human skin model. Both with concentrated (approximately 64% w/v) and diluted aqueous solutions (approximately 0.16% w/v) of ziram, absorption through human skin was slow (0.004 and 0.05 μg/cm²/h for low and high dose, respectively) and inefficient (2.2% and 0.1% for low and high dose, respectively). A dermal absorption value of 5% was derived for SDDC based on feedback to the REACH registration dossier of ziram and the recommendation of the evaluating member state.