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Administrative data

Description of key information

Oral NOAEL of 7.5 mg/kg bw/day with gender specific differences in the rat (OECD 422 and 408)
Oral NOAEL of 6 mg/kg bw/day in male and female mice (OECD 422)
Inhalation NOAEL of 19.3-52.6 ppm in male and female rats (published data)
Inhalation NOAEL of 3.2-8.8 ppm in male dogs (published data)

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
7.5 mg/kg bw/day
Study duration:
subchronic
Species:
rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEC
53.8 mg/m³
Study duration:
subchronic
Species:
rat

Additional information

ORAL TOXICITY

The key study (Ghanayem, 2000), conducted over 90 days, reports gender specific differences in the rat with a NOAEL of 7.5 mg/kg bw/day. Supporting studies confirm these data for the rat (Sunaga, 2001) and report a NOAEL of 6 mg/kg bw/day in the mouse (Ghanayem, 2000). Supporting studies also show an absence of abnormal change in electrophysical parameters in spite of obvious general toxicity (Gagnaire et al, 1998) and demonstrate impaired intracellular oxygen utilisation due to liberation of cyanide (Vasanthakumani et al, 1998).

INHALATION TOXICITY

The key study (Pozzani 1968) reports that the NOAEL for the rat is between 19.3 and 52.6 ppm.

Justification for classification or non-classification

As in the case of acute cyanide toxicity, the central nervous system is clearly among the most sensitive tissues because of high oxygen demand. However, in principle, there is no difference between short-term and long-term effects, which have the same toxicological basis. Repeated exposure only increases the the likelihood that the threshold for irreversible damage is exceeded on a particular treatment day as a result of normal variation in dose. From a mechanistic point of view, the central nervous system effects in repeated dose studies are due to single exposure events and are not cumulative. It is therefore considered sufficient to classify methacrylonitrile as toxic: danger of very serious irreversible effects through inhalation, in contact with skin and if swallowed under the terms of EU Directive 67/548/EEC and STOT Single Exp. 1 under GHS as implemented by Regulation (EC) 1272/2008.