Methacrylonitrile

Endpoint summary

Description of key information

Oral LD50 64 mg/kg bw in male rats and 73 mg/kg bw in female rats (OECD 401)
Dermal LD50 256 mg/kg bw in male rabbits (weight of evidence from published data)
Inhalation LD50 496 ppm in female rats and 398 ppm in male rats (published data)

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

64 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

1 092 mg/m³ air

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

256 mg/kg bw

Additional information

OVERALL CONSIDERATIONS

The primary mechanism of toxicity is considered to be generation of free cyanide during metabolism of methacrylonitrile. This, in turn, inhbits the cellular cytochrome oxidase, the primary reason for cyanide toxicity in vertebrates. The hypothesis is demonstrated by effectiveness of cyanide antidotes in the treatment of methacrylonitrile intoxication. Furthermore, cyanide toxicity is indicated by a threshold-like effect once the dose exceeds the short-term detoxification capacity of the organism.

ORAL TOXICITY

Non-GLP investigations of varying reliability report the LD50 as lying between 25 and 240 mg/kg bw in the rat. These data are confirmed by a modern GLP study in which the LD50 was found to be 64 mg/kg bw in male rats and 73 mg/kg bw in females. Supporting evidence of test substance toxicity is provided by non-GLP investigations involving mice, gerbils and rabbits.

INHALATION TOXICITY

The key study reports the LD50 as 496 ppm in female rats and 398 ppm in male rats. These toxicity data are supported by investigations in other species.

DERMAL TOXICITY

A modern GLP study reports the dermal LD50 as 1.32 mL/kg bw, which converts to 1.06 g/kg bw assuming relative density of 0.8. However, systemic toxicity was assessed for only seven days and classification has been based on previous data where the LD50 converts to 256-280 mg/kg bw.

Justification for classification or non-classification

ORAL TOXICITY

The test substance meets criteria for classification as toxic if swallowed under the terms of EU Directive 67/548/EEC and as acute oral toxicity category 3 under GHS as implemented by Regulation 1272/2008.

INHALATION TOXICITY

The test substance meets criteria for classification as toxic by inhalation under the terms of EU Directive 67/548/EEC and as acute inhalation toxicity category 2 under GHS as implemented by Regulation 1272/2008. The harmonised classification in Annex VI of Regulation 1272/2008, which is understood to be a minimum, has consequently been been amplified.

DERMAL TOXICITY

The test substance meets criteria for classification as toxic in contact with skin under the terms of EU Directive 67/548/EEC and as acute dermal toxicity category 3 under GHS as implemented by Regulation 1272/2008.