Registration Dossier

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:
2016-2018, depending on ECHA's timeline for permission. Minimum 30 months from Final Desicion
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: Amines, polyethylenepoly-, triethylenetetramine fraction. CAS 90640-67-8

CONSIDERATIONS THAT THE GENERAL ADAPTATION POSSIBILITIES OF ANNEX XI OF THE REACH REGULATION ARE NOT ADEQUATE TO GENERATE THE NECESSARY INFORMATION:
- Available GLP studies: There are no GLP-compliant studies available on reproductiv toxicity with the registered substance.
- Available non-GLP studies: There are no non-GLP studies available on reproductive toxicity with the registered substance.
- Historical human data: There are no appropriate historical human data available addressing the endpoint reproductive toxicity.
- (Q)SAR: (Q)SAR tools sufficiently addressing the endpoint reproductive toxicity are currently not available.
- In vitro methods: No validated or regulatory accepted alternative methods are available for replacing animal testing with respect to reproductive toxicity.
- Weight of evidence: There are no studies available on repeated dose toxicity with the registered substance which could be used in a weight of evidence approach.
- Grouping and read-across: There are no read-across data available on toxicity to reproduction

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:
- There is no data available on reproductive toxicity with Amines, polyethylenepoly-, triethylenetetramine fraction (CAS 90640-67-8). Validated or regulatory accepted alternative methods are not available for replacing animal testing with respect to reproductive toxicity. Furthermore, although appropriate read-across substances are available (see read across justification) for none of these substances a reproductive toxicity study is available so far.
In order to fulfil the standard information requirements, a GLP-compliant reproductive toxicity study in the rat via the oral route following OECD 443 was proposed, according to Annex IX, Column I, 8.7.2.

Data source

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 443 (Extended One-Generation Reproductive Toxicity Study)
GLP compliance:
yes (incl. certificate)
Limit test:
no
Justification for study design:
Testing Proposal for an EOGRTS without extension of Cohort 1B, without Cohorts 2A and 2B, and with Cohort 3.

Justification:

Pre-mating exposure period of 10 weeks as recommended in the draft Guideline.

Dose level setting: a top dose level will be selected which leads to minimal signs of systemic toxicity in pregnant animals, as per the draft Guideline. From earlier developmental toxicity studies with analogues, it is known that pregnant female animals may be more sensitive to systemic ethylene amine toxicity than not-pregnant females or males, therefore a range-finding study in pregnant animals will be necessary.

Extension of Cohort 1B is deemed not to be necessary since none of the triggers from Column II of Annex X are applicable.

Inclusion of Cohorts 2A / 2B is not deemed necessary, since no signs of neurotoxicity were observed in any study with the test material or its analogues. In view of the very high water solubility and very low Kow, penetration in fat-rich tissue, c.q. the developing brain and other nervous tissues, is not to be expected.

Cohort 3 is not deemed necessary since, apart from the known skin sensitisation properties, no effects on the immune system are known of TETA and other ethylene amines.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid

Test animals

Species:
rat
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
plus neutralisation with HCl to pH < 9
Details on exposure:
exposure by gavage to ensure proper dosing, neutralisation to pH < 9 will be required because of the corrosive nature of the substance.
Details on mating procedure:
according to OECD protocol
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
according to OECD protocol
Duration of treatment / exposure:
according to OECD protocol
Frequency of treatment:
according to OECD protocol
Details on study schedule:
according to OECD protocol
No. of animals per sex per dose:
according to OECD protocol

Examinations

Parental animals: Observations and examinations:
according to OECD protocol
Oestrous cyclicity (parental animals):
according to OECD protocol
Sperm parameters (parental animals):
according to OECD protocol
Litter observations:
according to OECD protocol
Postmortem examinations (parental animals):
according to OECD protocol
Postmortem examinations (offspring):
according to OECD protocol
Statistics:
to be determined.
Reproductive indices:
according to OECD protocol
Offspring viability indices:
according to OECD protocol

Results and discussion

Applicant's summary and conclusion