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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, 99.7%) 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.

As for reproductive performance, no effects related to the test article were observed on the estrous cycle, numbers of corpora lutea and implantations, copulation index or fertility indices. Examination at delivery and during the lactation period revealed, no effects related to the test article 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.

This study is acceptable and satisfies the guideline requirement for a combined repeated dose toxicity/reproduction and developmental toxicity study in rats (OECD 422).

A "higher tier" study like a 2 -generation study was waived for the following reasons:

The available data for structural homologues of MTHPA indicate neither potential for teratogenic effects nor for reproduction toxicity in different species. These data together with the available information of the OECD 422 study allow a scientific validated evaluation of the respective endpoints and further tests would not be in line with animal welfare ideas.


Short 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.

Effects on developmental toxicity

Description of key information
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 of the OECD 422 study allow a scientific validated evaluation of the respective endpoints and further tests would not be in line with animal welfare ideas.
Supporting 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.
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 potential for teratogenic effects nor for reproduction toxicity in different species. These data together with the available information of the OECD 422 study allow a scientific validated evaluation of the respective endpoints and further tests would not be in line with animal welfare ideas.

The available data from the OECD 422 study were given as supporting study as only basic parameters for developmental toxicity were observed:

In a combined repeated dose toxicity/reproduction and developmental toxicity study (Izumi, 1997), tetrahydromethylphthalic anhydride (MTHPA, 99.7%) 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 external anomalies were apparent. The NOAEL is considered to be 300 mg/kg/day for reproductive performance of parents and for development of offspring.

This study is acceptable and satisfies the guideline requirement for a combined repeated dose toxicity/reproduction and developmental toxicity study in rats (OECD 422).

Justification for classification or non-classification

Based on the results of the Reproduction/Developmental Toxicity Screening Test (OECD 422) the test item tetrahydromethyl-1,3-isobenzofurandione (MTHPA) is not classified and labelled according to Directive 677548/EEC (DSD) and to Regulation 1272/2008/EC (CLP).