2-hydroxy-4-(methylthio)butyronitrile

Endpoint summary

Description of key information

Oral: LD50 =  48 mg/kg bw  for rats (according to OECD Guideline 401)
Inhalation: LC50 = 0.651 mg/l/4h for rats (similar to OECD Guideline 403)

Additional information

Acute oral toxicity:

Two studies are reported for this endpoint. The first (Hazleton, 1991) consists in an acute oral toxicity study performed according to OECD 401 TG. Groups of fasted Sprague-Dawley rats (5 males and 5 females) were given a single oral dose by gastric gavage of cyanhydrine de l'AMTP at dose levels of 0, 35.5, 44.4, 56.6 and 71 mg/kg bw and observed for 14 days. The dose levels were chosen as a function of the results of a preliminary study and calculated according to a logarithmic progression of 1.26. Mortality occured at each dose level and was treatment related. Lethargy, sleeping or coma were the clinical signs observed in some animals after test substance administration. Congestive lung and intestine were observed in treated related dead animals. No macroscopic abnormalities were observed in surviving animals. From the results obtained under the experimental conditions employed, the LD50 by the oral route, of the test article is equal to 49 mg/kg according to Bliss'method and 48 mg/kg according to Litchfield & Wilcoxon's method. In the second study (Rhône-Poulenc, 1989), groups of fasted CD1 mice (5 males and 5 females) were given a single oral dose by gastric gavage of cyanhydrine de l'AMTP at dose levels of 0, 10, 20, 40 and 80 mg/kg bw and observed for 14 days. Mortality occured at 40 and 80 mg/kg and was treatment related. Decrease locomotor activity, tremor, bradypnea, dyspnea, akinesia, decubitus or ataxia were the clinical signs observed in some animals after test substance administration. No macroscopic abnormalities were observed in surviving animals. From the results obtained under the experimental conditions employed, the LD50 by the oral route, of the test article is equal to 56.6 mg/kg according to Thompson' method. All together these results showed that the test substance is toxic in rat and mouse after ingestion.

Conclusion:

Under the conditions of these tests, cyanhydrine de l'AMTP is therefore classified as toxic via oral route according to Directive 67/548/EEC and category 2 according to CLP (GHS classification).

Acute inhalation toxicity:

During an acute inhalation toxicity study (similar to OECD TG 403) with MMP-cyanhydrin in Wistar rats, groups of male and female rats were to be exposed one single time for a period of four hours to an atmosphere containing a concentration of MMP-cyanhydrin, in order to determine the LC50. MMP-cyanydrin was administered to rats via whole-body vapor exposure at actual concentrations of 480, 598, 560, 576, 720, 665 and 785 mg/m3. during the exposure and the observation period the rats were controlled for reactions to treatment daily. Body weights were recorded just prior to exposure and at days 1, 2, 4, 7 and 14. At the end of the observation period all survivors were killed. Gross pathological examination was performed on all exposed rats. The animal that died, invariably died within a period of 30 hours after the start of the exposure, but far the most of the animals died during the exposure period. Mortality was 0/10, 0/10, 1/10, 3/10, 6/10, 8/10 and 10/10 animals for the 480, 598, 560, 576, 720, 665, 785 mg/m3 groups, respectively. During the exposure period the animals, exposed to levels lower than 665 mg/m3 air, were lying with their eyes closed, but the animals of the 665, 720 and 785 mg/m3 groups had their eyes open and showed laboured respiration. After about 3 hours of exposure convulsions occurred in all groups, but degree and frequency were much higher in animals of the 665, 720 and 785 mg/m3 groups. Twelve hours after termination of the exposure all surviving animals were completely recovered. Most males lost body weight during the first 1é hours after termination of the exposure, except for males of the 480 mg/m3 group. Female lost body weight or gained hardly weight. After the second day both males and females gained weight in a normal way. Gross examination at necropsy of the animals that died during the exposure revealed red areas on the lungs with a diameter of about 3 mm. this finding, however, is frequenly encountered in animals found dead. Other abnormalities were not observed in any these animals. Survivors, which were killed after the two week observation period did not show gross abnormalities. The results of the present acute inhalation toxicity study in rats showed that the 4 hour LC50 of MMP-cyanhydrin is 651 mg/m3 air.

Conclusion:

Under the conditions of this test, MMP-cyanhydrin is therfore classified as toxic by inhalation according to Directive 67/548/EEC and category 2 according to CLP (GHS classification).

Justification for classification or non-classification

Acute oral: toxic (LD50 = 48 mg/l)

Based on this data, cyanhydrine de l'AMTP was classified toxic (R25) and category 2 according to EU Directive 67/584/EEC and EU regulation (EC) No 1272/2008 (CLP), respectively.

Acute Inhalation: toxic (LC50 = 0.651 mg/l/4h)

Based on this data, MMP-cyanhydrin was classified toxic (R23) and category 2 according to EU Directive 67/584/EEC and EU regulation (EC) No 1272/2008 (CLP), respectively.