1,2,3,6-tetrahydro-4-methylphthalic anhydride

Endpoint summary

Description of key information

Acute toxicity - Oral: LD50 - >2000 mg/kg

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

Oral:

Different studies were available investigating acute oral toxicity of an analogue of the substance, tetrahydromethylphthalic anhydride (MTHPA). The study by Furukawa (1997) was chosen as key study, as this is the only study which was conducted according to a recognised test guideline (OECD 401) and GLP. LD50 values of the supporting studies are in the same concentration range as the key study (some slightly below) but are regarded as less reliable than the key study.

In the key study MTHPA was studied for oral toxicity in rats in a single dose toxicity test at doses of 0, 500, 1000 and 2000 mg/kg for both sexes. No deaths occurred of either males or females. Clinical signs of hypoactivity, bradypnea and prone position were observed in males and females of the 2000 mg/kg group on the day of administration. Decrease of body weights was observed in males of the 2000mg/kg group and suppression of body weight gain was observed in females of the 2000mg/kg group on the day of administration. At necropsy, thickening of the forestomach mucosal was observed in males and females of the 1000 and 2000 mg/kg groups. Adhesion of forestomach and liver was noted in one female of the 2000 mg/kg group. Histopathologically, squamous hyperplasia and granulomatous inflammation in submucosal of the forestomach were observed in the 1000 and 2000 mg/kg groups. A foreign body granuloma in the adhesion area was also noted in the female of the 2000 mg/kg group. As the result, LD50 value was decided as >2000 mg/kg.

In a supporting acute oral toxicity study (Irie, 1969a), groups of T23-48:Donryu rats (6/sex) were given a single oral dose of MTHPA in olive oil at doses of 1160, 1390, 1660, 2000 and 2400 mg/kg bw and observed for 7 days. Oral LD50 = 2102 mg/kg bw

In a supporting acute oral toxicity study (Irie, 1969b), groups of dd mice (10/sex) were given a single oral dose of MTHPA in olive oil at doses of 920, 1100, 1330, 1590, 1900, 2280, 2720 mg/kg bw and observed for 7 days. Oral LD50 = 1707 mg/kg bw

In a supporting acute oral toxicity study (Sheena, 1980), groups of Crj: CD(SD) rats (105/sex) were given a single oral dose of MTHPA in olive oil at doses of 1000, 1600, 2000, 3200, 5000 and 6400 mg/kg bw and observed for 14 days. Oral LD50 = 1900 mg/kg bw (1600-2900 mg/kg bw)

In a supporting acute oral toxicity study, groups of rats were given a single oral dose of MTHPA. Oral LD50 = 25894 mg/kg bw

Justification for classification or non-classification

Based on the results obtained in the acute toxicity studies (oral: LD50 (rat) > 20000 mg/kg bw; dermal LD50 (rat) > 2000 mg/kg bw) and taking into account the provisions laid down in Council Directive 67/548/EEC and CLP (1272/2008/EC), MTHPA has not to be classified regarding acute toxicity.