Registration Dossier

Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
extended one-generation reproductive toxicity - basic test design (Cohorts 1A, and 1B without extension)
Type of information:
experimental study planned
Study period:
January 2020 - January 2021
Justification for type of information:
The lead registrant proposes to conduct an Extended One Generation Reproductive Toxicity (EOGRT) study (OECD 443). The study will be conducted upon the registered substance. This proposal is based upon the following information and considerations:

Available GLP studies:
The available 28 day and 90 day repeat dose toxicity studies do not include observations on the effects of the registered substance on the reproductive organs. Systemic toxic effects on reproductive organs from the registered substance cannot be conclusively disproved.
The available information on toxicity to reproduction OECD 414 conducted in the rat, and OECD 414 conducted in Rabbits does not provide sufficient information to fulfil the REACH (1907/2006), Annex IX, 8.7.3. requirement.

Available non-GLP studies:
There are no available non-GLP studies conducted on this substance examining reproductive and developmental effects.

Grouping and read-across:
There is no suitable read-across data available for this substance.

Historical human data:
There are no studies conducted on human exposure which examine the effects of this substance on reproduction and development.

QSAR:
There are currently no validated QSAR models which would examine the reproductive and developmental effects of this substance.

In vitro methods:
There are currently no validated in vitro methods which would fulfil the above endpoint requirement.

Weight of evidence:
There is no suitable weight of evidence data available for this substance.

Substance-tailored exposure driven testing:
This type of testing is considered to be not applicable for the substance and its use pattern.

Data source

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 443 (Extended One-Generation Reproductive Toxicity Study)
Version / remarks:
Two weeks pre-mating, cohorts 1A + 1B only
GLP compliance:
yes (incl. certificate)
Justification for study design:
SPECIFICATION OF STUDY DESIGN FOR EXTENDED ONE-GENERATION REPRODUCTION TOXICITY STUDY WITH JUSTIFICATIONS:

- Premating exposure duration for parental (P0) animals
The standard two week pre-mating dosing period is proposed for the study. There is no evidence from the existing OECD 414 studies and the 90 and 28 day repeat dose studies that extending the pre-mating dosing period will have an effect on the result of the main extended one generation study.

- Basis for dose level selection
Dose find studies have already been conducted for the OECD 414 in rats and the OECD 414 in rabbits. It is proposed to use the results of these existing studies to avoid additional animal testing. Doses for the main test are therefore proposed at 50, 150, and 500 mg/kg bw/day, in-line with the OECD 414 studies.

- Inclusion/exclusion of extension of Cohort 1B
Use of the substance is not expected to lead to significant exposure to consumers or professionals based upon the identified uses and exposure scenarios detailed in this dossier. The substance has not displayed genotoxic effects in somatic cells which would lead to classification as a mutagen cat. 2 or higher. The available repeat dose studies do not include evidence that the internal dose of the registered substance (or its metabolites) reaches a steady state only after an extended exposure. There is no evidence of endocrine disruption contained in any of the available information.

- Termination time for F2
Inclusion of an F2 generation is not proposed, as the registered substances does not fulfil the criteria in REACH (1907/2006), Annex IX, 8.7.3, column 2.

- Inclusion/exclusion of developmental neurotoxicity Cohorts 2A and 2B
No evidence of neurotoxicity or effects upon the brain or nervous system are reported in any of the available data.

- Inclusion/exclusion of developmental immunotoxicity Cohort 3
No evidence of immunotoxicity or effects upon the immune system are reported in any of the available data.

- Route of administration
The oral route of administration is proposed. Gavage is the preferred method of administration.

- Other considerations, e.g. on choice of species, strain, vehicle and number of animals [if applicable]
The study is proposed in the rat, as the preferred test species listed in the OECD 443 test guideline.

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage

Results and discussion

Applicant's summary and conclusion