2-methylglutaronitrile

Endpoint summary

Description of key information

Oral: LD50 male (rats) is 170 mg/kg bw. Therefore, the product is considered as Toxic by oral route according to EU criteria.
Dermal: LD50 male (rats) is 982 mg/kg bw. Therefore, the product is considered as Toxic by dermal route according to EU criteria.
Inhalation: LC50/4h male (rats) is 0.66 mg/L. Therefore the product is considered as Toxic by inhalation route according to EU criteria.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Dose descriptor:

LD50

Value:

170 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Dose descriptor:

LC50

Value:

660 mg/m³ air

Acute toxicity: via dermal route

Endpoint conclusion

Dose descriptor:

LD50

Value:

982 mg/kg bw

Additional information

1- Acute toxicity: oral:

Three studies were available. Two of them were considered as not reliable (Kr: 3) and the study of Rondot, 1981 was identified as the key study (Kr: 2). This acute oral toxicity study was performed similarly to the OECD test guideline No. 401 and a groups of Sprague-Dawley rat (5/sex/group) were given a single oral dose of 2- Methylglutaronitrile (2-MGN) in aqueous suspension of 10% arabic gum at doses of 0, 150, 200, 250, 300 or 400 mg/kg bw and observed for 14 days. At all tested doses (males and females), the clinical signs observed were reduced activity, apathy, prostration, piloerection, trembling and convulsion. All these signs were reversible 24 hours after the treatment. Haemorrhagic digestive tract, thymus and lungs was observed in the animals died during the study. The body weight and weight gain were not affected.

Oral LD₅₀male/female = 205 mg/kg bw

Oral LD₅₀male = 170 mg/kg bw

Oral LD₅₀female = 225 mg/kg bw

Based on these results, the oral LD50 males = 170 mg/kg bw was chosen considering as the worst case (males were more sensitive than females). Thus, 2-Methylglutaronitrile is considered as toxic if swallowed.

2- Acute toxicity: inhalation

Three studies were available for this point. Two of them were considered as not reliable (Kr: 3). Another study (Reinhardt, 1974) was chosen as a key study (Kr: 2). A groups of male ChR-CD rats (6 animals/dose) were exposed to vapors for 4 hours in a whole body method at the concentrations of vapors 0.33; 0.34; 0.49 and 1.1 mg/L. Severe convulsions, exophthalmos and cyanosis were followed by death immediately to one day post-exposure, when the animals were exposed to lethal dose. Inhalation LC₅₀males = 0.66 mg/L. Thus, 2 -Methylglutaronitrile is considered as toxic by inhalation route.

3- Acute toxicity: dermal

Four studies were available. Two of them were considered as not reliable (Kr: 3). A study of Rondot, 1981 was identified as the key study. In this study, 2-Methylglutaronitrile was tested for acute dermal toxicity similarly to the OECD test guideline No. 402. Groups of Sprague-Dawley rats (5 or 10 animals/sex/group) were exposed to2-Methylglutaronitrileundiluted for 24 hours at doses of 0,1000, 1100, 1500 and 2000 mg/kg bw and observed for 14 days. At equivalent dose level, mortality was more pronounced in males than in females. Therefore the LD50 males was considered as the worst case and was the reference to propose the classification. Clinical signs include reduced activity, apathy, prostration, slight ptosis, slight trembling. The autopsy of animals died during the test revealed haemorrhagic lungs, pale and mottled liver, thickened peritoneum, hemorrhagic patch on the skin.

Dermal LD₅₀males (rats) = 982 mg/kg bw. 

A study of Dashiell, 1983 was considered as a supporting study (Kr: 2), the LD50/male rabbits = 776 mg/kg bw.

Based on the Dermal LD₅₀males (rats) = 982 mg/kg bw and the LD50/rabbits = 776 mg/kg bw, 2-Methylglutaronitrile is considered as toxic in contact with skin.

Justification for classification or non-classification

2 -Methylglutaronitrile is not classified in the Annex VI of the CLP regulation (1272/2008). A self-classification is proposed as followed:

1- Acute oral toxicity:

Based on LD50 male rats = 170 mg/kg bw (the worst case, males were more sensitive than females), 2 -methylglutaronitrile is classified as:

- Category III, H301 (Toxic if swallowed) according to the CLP regulation (1272/2008)

- Toxic if swallowed (T, R25) according to the Directive 67/548/EEC.

2- Acute inhalation toxicity:

Based on LC50/ male rats/4h = 0.66 mg/L (95% confidence limits of 0.39 and 1.34 mg/L). 2 -methylglutaronitrile is classified as:

- Category II, H330 (Fatal if inhaled) according to the CLP regulation (1272/2008)

- Toxic by inhalation (T, R23) according to the Directive 67/548/EEC.

3- Acute dermal toxicity:

Based on LD50 male rats = 982 mg/kg bw (Key study, the worst case, males were more sensitive than females) and on LD50 male rabbits = 776 mg/kg bw (supporting study), 2 -methylglutaronitrile is classified as:

- Category III, H311 (Toxic in contact with skin) according to the CLP regulation

- Harmful in contact with skin (Xn, R21) according to the Directive 67/548/EEC.