Registration Dossier

Toxicological information

Toxicity to reproduction

Currently viewing:

Administrative data

Endpoint:
reproductive toxicity, other
Remarks:
A testing strategy for reproduction toxicity testing is proposed.
Type of information:
experimental study planned
Study period:
Start within 12 months after obtaining the results of the proposed 90-day study and the agreement of ECHA.
Justification for type of information:
TESTING PROPOSAL ON VERTEBRATE ANIMALS
NON-CONFIDENTIAL NAME OF SUBSTANCE:
- Name of the substance on which testing is proposed to be carried out: 7-ACT.

CONSIDERATIONS THAT THE GENERAL ADAPTATION POSSIBILITIES OF ANNEX XI OF THE REACH REGULATION ARE NOT ADEQUATE TO GENERATE THE NECESSARY INFORMATION:
- Available GLP studies: No GLP-study is available.
- Available non-GLP studies No non-GLP-study is available.
- Historical human data: No historical human data are available.
- (Q)SAR: No reliable and recognized QSAR-tools are available for this toxicity endpoint.
- In vitro methods: No reliable and recognized in vitro methods are available for this toxicity endpoint.
- Weight of evidence: No WoE-approach is available for this toxicity endpoint.
- Grouping and read-across: No grouping and read-across approach is available for this toxicity endpoint.
- Substance-tailored exposure driven testing: The adaption rules are not applicable for this substance.
- Approaches in addition to above: No adequate approach is known.
- Other reasons: No other reason is known.

CONSIDERATIONS THAT THE SPECIFIC ADAPTATION POSSIBILITIES OF ANNEXES VI TO X (AND COLUMN 2 THEREOF) OF THE REACH REGULATION ARE NOT ADEQUATE TO GENERATE THE NECESSARY INFORMATION:
- The adaptation possibilities are met by using a testing strategy, as proposed below, to save animals and animal experiments.

FURTHER INFORMATION ON TESTING PROPOSAL IN ADDITION TO INFORMATION PROVIDED IN THE MATERIALS AND METHODS SECTION:
- Details on study design / methodology proposed:
The intention is, to save animals and animal experiments, by 1) not performing a screening reproduction toxicity test (OECD 421) and in addition an EOGRTS (OECD 443), but to perform only one of the 2 tests. 2) By performing, if the conditions of the adaptation rules of the Annex IX are met, only the OECD 421 screening test, which uses less animals than the OECD 443 EOGRTS. If the conditions of the Annex IX are not met, an EOGRTS will be proposed instead of the OECD 421 test. The decisions on the selection of one of the 2 tests can only be made after obtaining the results of the 90-day toxicity study, which is also proposed to be performed, because, according to Annex IX, the need to perform an EOGRTS depends on indications of "adverse effects on reproductive organs or tissues or other concerns in relation with reproductive toxicity", which can only be obtained from the proposed 90-day study, because other sources are not available. Therefore the following testing strategy is proposed and will be followed:
1. The 90-day toxicity study according to OECD 408 will be performed (after decision of ECHA).
2. If the results of this OECD 408 study indicate adverse effects on reproductive organs or tissues, the OECD 443 EOGRTS will be started in its basic test design (cohorts 1A and 1B without extension to include a F2 generation), one species.
3. If the results of this OECD 408 study indicate no adverse effects on reproductive organs or tissues, the OECD 421 reproduction toxicity screening test will be started.
Cross-reference
Reason / purpose:
reference to other study

Data source

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)
Version / remarks:
newest
Qualifier:
according to
Guideline:
OECD Guideline 443 (Extended One-Generation Reproductive Toxicity Study)
Version / remarks:
newest
GLP compliance:
yes
Justification for study design:
The intention is, to save animals and animal experiments, by 1) not performing a screening reproduction toxicity test (OECD 421) and in addition an EOGRTS (OECD 443), but to perform only one of the 2 tests. 2) By performing, if the conditions of the adaptation rules of the Annex IX are met, only the OECD 421 screening test, which uses less animals than the OECD 443 EOGRTS. If the conditions of the Annex IX are not met, an EOGRTS will be proposed instead of the OECD 421 test. The decisions on the selection of one of the 2 tests can only be made after obtaining the results of the 90-day toxicity study, which is also proposed to be performed, because, according to Annex IX, the need to perform an EOGRTS depends on indications of "adverse effects on reproductive organs or tissues or other concerns in relation with reproductive toxicity", which can only be obtained from the proposed 90-day study, because other sources are not available. Therefore the following testing strategy is proposed and will be followed:
1. The 90-day toxicity study according to OECD 408 will be performed (after decision of ECHA).
2. If the results of this OECD 408 study indicate adverse effects on reproductive organs or tissues, the OECD 443 EOGRTS will be started in its basic test design (cohorts 1A and 1B without extension to include a F2 generation), one species.
3. If the results of this OECD 408 study indicate no adverse effects on reproductive organs or tissues, the OECD 421 reproduction toxicity sceening test will be started.

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Sex:
male/female

Administration / exposure

Route of administration:
oral: feed
Details on mating procedure:
According to the guideline.
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
According to the guideline.
Frequency of treatment:
Daily, once.
No. of animals per sex per dose:
According to the guideline.
Control animals:
yes, concurrent no treatment
Details on study design:
According to the guideline.
Positive control:
no

Examinations

Parental animals: Observations and examinations:
According to the guideline.
Oestrous cyclicity (parental animals):
According to the guideline.
Sperm parameters (parental animals):
According to the guideline.
Litter observations:
According to the guideline.
Postmortem examinations (parental animals):
According to the guideline.
Postmortem examinations (offspring):
According to the guideline.

Results and discussion

Applicant's summary and conclusion