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Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Dose descriptor:
NOAEL
300 mg/kg bw/day
Additional information

In a combined repeated dose toxicity/reproduction and developmental toxicity study (Izumi, 1997) tetrahydromethylphthalic anhydride (MTHPA), of which 3 -MTHPA D4 is an isomer, was administered to groups of Crj:CD(SD) rats (12/sex), via gavage in corn oil at dose levels of 0 (Vehicle), 30, 100 and 300 mg/kg bw/day.

No effects were observed on the oestrous cycle, numbers of corpora lutea and implantations, copulation index or fertility indices to indicate an effect on reproductive performance. Examination at delivery and during the lactation period revealed no effects in terms of gestational days, litter size and live newborns, gestation index, stillborn index, birth index, sex ratio, body weights of offspring at birth and at day 4 after birth, or viability index on day 4. No external anomalies were apparent. The NOAEL is considered to be 300 mg/kg/day for reproductive performance of parents and for development of offspring.

A "higher tier" study such as a 2 -generation study was waived for the following reasons: The available data for structural homologues of MTHPA indicate neither the potential for teratogenic effects nor for reproduction toxicity in different species. These data, together with the available information on MTHPA, allow a scientific validated evaluation of the respective endpoints and further tests would not be in line with concerns regarding animal welfare and the use of animals for experimental purposes.


Short description of key information:
In a combined repeated dose toxicity/reproduction and developmental toxicity study with rats on tetrahydromethylphthalic anhydride (MTHPA), of which 3-MTHPA D4 is an isomer, the NOAEL is considered to be 300 mg/kg/day for reproductive performance of parents and for development of offspring.

Effects on developmental toxicity

Description of key information
In a combined repeated dose toxicity/reproduction and developmental toxicity study with rats, the NOAEL is considered to be 300 mg/kg/day for reproductive performance of parents and for development of offspring. The available data for structural homologues of tetrahydromethylphthalic anhydride (MTHPA) indicate neither potential for teratogenic effects nor for reproduction toxicity in different species. These data, together with the available information on MTHPA, allow a scientific validated evaluation of the respective endpoints and further tests would not be in line with concerns regarding animal welfare and the use of animals for experimental purposes.
Effect on developmental toxicity: via oral route
Dose descriptor:
NOAEL
300 mg/kg bw/day
Additional information

A developmental toxicity study was waived for the following reasons:

The available data for structural homologues of MTHPA indicate neither the potential for teratogenic effects nor for reproduction toxicity in different species. These data, together with the available information on MTHPA, allow a scientific validated evaluation of the respective endpoints and further tests would not be in line with concerns regarding animal welfare and the use of animals for experimental purposes.

The available data from an OECD 422 screening study are regarded as having supporting value only as only basic parameters for developmental toxicity were examined. In this, groups of Crj:CD(SD) rats (12/sex) received, by gavage dose levels of 0 (Vehicle), 30, 100 and 300 mg/kg bw/day MTHPA, of which 3 -MTHPA D4 is an isomer. No external anomalies were apparent. The NOAEL was considered to be 300 mg/kg/day for development of offspring.

Justification for classification or non-classification

Based on the available information methyltetrahydrophthalic anhydride and its isomers does not require classification or labelling according to Directive 677548/EEC (DSD) and to Regulation 1272/2008/EC (CLP).