2-methylglutaronitrile

Endpoint summary

Description of key information

Repeated dose toxicity by inhalation route: NOAEC is greater than 200 mg/m3.
Decrease of the Body weight gain was observed at 200 mg/m3 compared to control groups. The Food consumption was not examined. 
Moreover, the body weight gain was normal again and similar to the control group during the recovery period. Therefore, this decrease of body weight gain can not be considered as an adverse effect.
A increased of reticulocytes was also observed, however this reticulocyte increase was not relevant in the face of normal RBC mass and thus the changes in reticulocyte values were not considered to be adverse.

Key value for chemical safety assessment

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEC

200 mg/m³

Study duration:

subacute

Species:

rat

Additional information

Repeated dose toxicity by oral route:

No data available.

Repeated dose toxicity by dermal route:

No data available

Repeated dose toxicity by inhalation route:

One repeated dose toxicity study by inhalation route was available and was considered as a key study (Kelly, 2001).

In a subchronic inhalation toxicity study performed according to OECD 412 guideline, 2 -methylglutaronitrile (99.6%) was administered to 20 male Crl:CD (SD) IGS BR rats/concentration by nose only exposure at concentrations of 0, 5, 25, and 200 mg/m³(0, 0.005, 0.025 and 0.2 mg/L) for 6 hours per day, 5 days/week for a total of 20 days.

No effect was observed for all parameters examined except a slight/transient effect on body weight gain and a statistically significant

increased of reticulocytes. Indeed, at the highest concentration tested (200 mg/m³), the body weight gain was significantly lower in this group of rats (for a period between Day 15 and Day 26) than in the control group. The body weight gain was normal again and similar to the control group during the recovery period. As there is no information on the food consumption, no relevant link can be established between this depressed body weight gain and the Substance tested. Furthermore, this depressed body weight gain can not be considered as an adverse effect, because the rats exposed to the highest concentration did not present a true loss of weight. They continued to gain weight but in a lower extent in comparison to the control group. Moreover, reticulocyte increase was not relevant in the face of normal RBC mass and thus the changes in reticulocyte values were not considered to be adverse.

 

Therefore, based on these results, the NOAEC is greater than 200 mg/m³(0.2 mg/L) and the NOEC is 25 mg/m³(0.025 mg/L) for body weight gain reduction and increased of reticulocytes.

Justification for classification or non-classification

2 -methylglutaronitrile is not classified in the Annex VI of the CLP regulation (1272/2008).

Repeated dose toxicity by inhalation route/self classification:

Based on the key study, the NOAEC is greater than 200 mg/m³(0.2 mg/L) and the NOEC is 25 mg/m³(0.025 mg/L) for a decrease on the Body weight gain at 200 mg/m3 compared to control groups and for a increased of reticulocytes.

Based on these results, no classification is required according to the CLP regulation (1272/2008) and to the Directive 67/548/CEE.