Registration Dossier

Administrative data

Description of key information

Oral: LD50 rat = 500 mg/kg bw

Dermal (similar to OECD 402 limit test): LD50 rat: > 2000 mg/kg bw (both sexes)

Inhalation (similar to EPA-OPP 81-3): LC50 = 5.45 mg/L (both sexes, based on read-across)

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
LD50
500 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Dose descriptor:
LC50
5 450 mg/m³

Additional information

Oral:

In an acute oral toxicity study performed similar to OECD Guideline 401, the LD50 was found to be greater than 5200 mg/kg for male rats and 4573 mg/kg for female rats (Branch, 1983b). The rats exhibited tremors, ataxia and lethargy.

In rabbits the oral LD50 for disulfiram was found to be 650 mg/kg bw when combined with administration of 1.5 g alcohol/kg bw 20 -24 hours after disulfiram administration (Barnes and Fox, 1955).

In a NIOSH publication from 1993, the acute oral LD50 in rats was reported to be 500 mg/kg bw (NIOSH, 1993).

 

Inhalation:

There were no data located with disulfiram on acute toxicity after inhalative exposure. However, there are reliable data on a surrogate substance. An acute inhalation study conducted with the read-across substance, thiram (CAS 137 -26 -8), gave an 4-h LC50 of 4.42 mg/L for both sexes (Holbert, 1987). After correction for the molecular weight difference between disulfiram and thiram (factor: 1.234), an LC50 of 5.45 mg/L for both sexes is to be assumed for disulfiram.

 

Dermal:

In GLP-compliant guideline study (limit test), 5 male and 5 female rabbits were dosed with 2000 mg/kg bw disulfiram under occlusive conditions (Branch, 1983a). The acute dermal LD50 value was > 2000 mg/kg bw, as no mortality was observed. The clinical signs were limited to erythema in 3 animals.

Justification for classification or non-classification

Based on the acute oral LD50 of 500 mg/kg bw in rats, the substance should be classified as harmful if swallowed Xn, R22 and Category 4, according to the EU Directive 67/548/EEC and the CLP Regulation, respectively.

The data on acute toxicity dermal and inhalative exposure are conclusive but not sufficient for classification according to the criteria of Directives 67/548/EEC (DSD) and 1272/2008/EC (CLP).