Registration Dossier

Administrative data

Endpoint:
developmental toxicity
Data waiving:
other justification
Justification for data waiving:
other:

Data source

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Principles of method if other than guideline:
There are no developmental toxicity data available for MB2. The study should be conducted in rats since this is the standard species for this kind of studies. Rats should be dosed via the oral route because a) oral route is the standard route for developmental toxicity studies; b) the available Prenatal Development Toxicity Study according to OECD TG 422 conducted with ZMB2 used oral dosing and c) granulometric data of MB2 indicate that only 0.37% of all particles have a mass fraction with a mean diameter less than 50 μm.

Test item; rationale for read across from and conduct of the study with ZMB2.
For the endpoint reproductive toxicity a read across is scientifically justified between 1,3-dihydro-4(or 5)-methyl-2H-benzimidazole-2-thione; CAS n° 53988-10-6 (MB2) and 1,3-dihydro-4(or 5)-methyl-2H-benzimidazole-2-thione, zinc salt; CAS n° 61617-00-3 (ZMB2). ZMB2 is the zinc salt of MB2 and both substances are assumed to dissociate in aqueous media into the corresponding anion (1,3-dihydro-4(or5)-methyl-2H-benzimidazole-2-thione anion) and the corresponding cations. The read across is justified based on physicochemical and toxicological data (for further details see justification attached as background material to the EOGRTS test proposal)

The main constituent of MB2 and ZMB2 is the 1,3-dihydro-4(or5)-methyl-2H-benzimidazole-2-thione anion; 100% (w/w) for MB2 and 83% (w/w) for ZMB2. Water solubility of ZMB2 is reported to be 32 mg/l and thus in the same range as the water solubility of MB2 determined to be 120 mg/l. No data are available for the dissociation of MB2 or ZMB2, but it is assumed that both substances dissociate in aqueous solution to the MB2 anion and the corresponding cation.

Both substances have similar acute toxicity. Liver, thyroid and cholesterol effects are reported in the sub-acute toxicity study with MB2 and the Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test with ZMB2. Based on the similar toxicity profile of both substances and the available reproductive data with ZMB2 which led to a self-classification of both substances as GHS cat 2 reproductive toxicant, it is proposed to conduct the developmental toxicity study with ZMB2 to evaluate reproductive toxicity for both substances.

Results and discussion

Results (fetuses)

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Applicant's summary and conclusion