Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information

Data regarding effects on fertility are not available. A data waiver is claimed.

A grouping of substances and read-across approach according to Regulation (EC) No 1907/2006 (REACH), Annex XI 1.5 and following ECHA Read-Across Assessment Framework, RAAF (2015) is accomplished for five blocked diisocyanate oligomers (also for the test substance isophorone diisocyanate, oligomeristion product, blocked with hexahydro-2H-azepin-2 -one).

An updated outline of a grouping-strategy based on read-across of the available toxicological data for these five blocked diisocyanate oligomers is attached to the endpoint summaries for 'Repeated dose toxicity' and 'Toxicity to reproduction' in IUCLID as a separate document.

Link to relevant study records

Referenceopen allclose all

Endpoint:
screening for reproductive / developmental toxicity
Data waiving:
other justification
Justification for data waiving:
other:
Reproductive effects observed:
not specified
Endpoint:
extended one-generation reproductive toxicity - basic test design (Cohorts 1A, and 1B without extension)
Data waiving:
other justification
Justification for data waiving:
other:
Reproductive effects observed:
not specified
Effect on fertility: via oral route
Endpoint conclusion:
no study available
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

Data regarding effects on fertility are not available. A data waiver is claimed.

A grouping of substances and read-across approach according to Regulation (EC) No 1907/2006 (REACH), Annex XI 1.5 and following ECHA Read-Across Assessment Framework, RAAF (2015) is accomplished for five blocked diisocyanate oligomers (also for the test substance isophorone diisocyanate, oligomeristion product, blocked with hexahydro-2H-azepin-2 -one).

Based on this grouping and read-across strategy a category was established with the registered substance and four other structually similar chemicals. Pilot inhalation toxicity studies with 2 week exposure were conducted in rats with all five category members. Thereafter, GLP-conform and Guideline-compliant 90-day subchronic inhalation toxicity studies in rats were performed with two of the category members on request of ECHA. In all of these studies portal-of-entry toxicity (local effects in the respiratory tract) was observed at doses below the Guidance value of 20 mg/m³. Thus,classification with STOT RE 1 (H372) is applicable for all members of the category with regard to local effects in the respiratory tract after inhalative exposure. As no test substance related adverse systemic toxicity could be seen in the pilot and subchronic (90-day) inhalation toxicity studies or in any of the other available toxicological studies with the category members, no hazard is anticipated with regard to systemic effects. There is no indication for systemic availability and a mode of action related to portal of entry particle toxicity is confirmed, thus, there is sufficient weight of evidence that these substances have not a reproductive or developmental toxicity potential and further testing on vertebrate animals for that property shall be omitted. Considering this, waiving of an extended-one-generation reproductive toxicity study (OECD 443), waiving of a screening test according to OECD 421/422, as well as waiving of developmental toxicity studies (OECD 414) in rats and/or in a second species is considered appropriate.

Update of grouping and read-across strategy of December 2018:

For a detailed discussion of the outcome of the testing strategy and for justification of the grouping and read across of 5 blocked diisocyanate oligomers according to regulation No. 1907/2006 (REACH), Annex XI, 1.5 and following ECHA RAAF (2015) see the document attached to the endpoint summaries for ‘Repeated Dose Toxicity’ and ‘Toxicity to reproduction’ in IUCLID. This document also addresses waiving of reproduction toxicity studies. Overall, based on this justification REACH requirements for repeated dose toxicity as well as for reproductive toxicity can be fulfilled by grouping of substances and read across approach.

Note: The first outline of a grouping-strategy was prepared in May 2013 based on read-across of the available toxicological data for 4 blocked diisocyanate oligomers at that time. In the meantime, the group was enlarged to 5 blocked diisocyanate oligomers and 90-day inhalation toxicity studies have been performed for two of the category members on request of ECHA. The updated document refers to the REACH requirements according to Annex VIII - X (10 - > 1000 tonnes/a).



Justification for selection of Effect on fertility via oral route:
Data regarding effects on fertility are not available. A data waiver is claimed.

Justification for selection of Effect on fertility via inhalation route:
Data regarding effects on fertility are not available. A data waiver is claimed.

Justification for selection of Effect on fertility via dermal route:
Data regarding effects on fertility are not available. A data waiver is claimed.

Effects on developmental toxicity

Description of key information

No developmental toxicity studies are available for the test substance. A data waiver is claimed.

A grouping of substances and read-across approach according to Regulation (EC) No 1907/2006 (REACH), Annex XI 1.5 and following ECHA Read-Across Assessment Framework, RAAF (2015) is accomplished for five blocked diisocyanate oligomers (also for the test substance isophorone diisocyanate, oligomeristion product, blocked with hexahydro-2H-azepin-2 -one).

An updated outline of a grouping-strategy based on read-across of the available toxicological data for these five blocked diisocyanate oligomers is attached to the endpoint summaries for 'Repeated dose toxicity' and 'Toxicity to reproduction' in IUCLID as a separate document.

Link to relevant study records

Referenceopen allclose all

Endpoint:
developmental toxicity
Data waiving:
other justification
Justification for data waiving:
other:
Abnormalities:
not specified
Developmental effects observed:
not specified
Endpoint:
developmental toxicity
Data waiving:
other justification
Justification for data waiving:
other:
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

No developmental toxicity studies are available for the test substance. A data waiver is claimed.

A grouping of substances and read-across approach according to Regulation (EC) No 1907/2006 (REACH), Annex XI 1.5 and following ECHA Read-Across Assessment Framework, RAAF (2015) is accomplished for five blocked diisocyanate oligomers (also for the test substance isophorone diisocyanate, oligomeristion product, blocked with hexahydro-2H-azepin-2 -one).

Based on this grouping and read-across strategy a category was established with the registered substance and four other structually similar chemicals. Pilot inhalation toxicity studies with 2 week exposure were conducted in rats with all five category members. Thereafter, GLP-conform and Guideline-compliant 90-day subchronic inhalation toxicity studies in rats were performed with two of the category members on request of ECHA. In all of these studies portal-of-entry toxicity (local effects in the respiratory tract) was observed at doses below the Guidance value of 20 mg/m³. Thus,classification with STOT RE 1 (H372) is applicable for all members of the category with regard to local effects in the respiratory tract after inhalative exposure.As no test substance related adverse systemic toxicity could be seen in the pilot and subchronic (90-day) inhalation toxicity studies or in any of the other available toxicological studies with the category members, no hazard is anticipated with regard to systemic effects. There is no indication for systemic availability and a mode of action related to portal of entry particle toxicity is confirmed, thus, there is sufficient weight of evidence that these substances have not a reproductive or developmental toxicity potential and further testing on vertebrate animals for that property shall be omitted.Considering this, waiving of an extended-one-generation reproductive toxicity study (OECD 443), waiving of a screening test according to OECD 421/422, as well as waiving of developmental toxicity studies (OECD 414) in rats and/or in a second species is considered appropriate.

Update of grouping and read-across strategy of December 2018:

For a detailed discussion of the outcome of the testing strategy and for justification of the grouping and read across of 5 blocked diisocyanate oligomers according to regulation No. 1907/2006 (REACH), Annex XI, 1.5 and following ECHA RAAF (2015) see the document attached to the endpoint summaries for ‘Repeated Dose Toxicity’ and ‘Toxicity to reproduction’ in IUCLID. This document also addresses waiving of reproduction toxicity studies.Overall, based on this justification REACH requirements for repeated dose toxicity as well as for reproductive toxicity can be fulfilled by grouping of substances and read across approach.

Note: The first outline of a grouping-strategy was prepared in May 2013 based on read-across of the available toxicological data for 4 blocked diisocyanate oligomers at that time. In the meantime, the group was enlarged to 5 blocked diisocyanate oligomers and 90-day inhalation toxicity studies have been performed for two of the category members on request of ECHA. The updated document refers to the REACH requirements according to Annex VIII - X (10 - > 1000 tonnes/a).


Justification for selection of Effect on developmental toxicity: via oral route:
No developmental toxicity/teratogenicity studies are available. A data waiver is claimed.

Justification for selection of Effect on developmental toxicity: via inhalation route:
No developmental toxicity/teratogenicity studies are available. A data waiver is claimed.

Justification for selection of Effect on developmental toxicity: via dermal route:
No developmental toxicity/teratogenicity studies are available. A data waiver is claimed.

Justification for classification or non-classification

No indication of test substance related adverse systemic toxicity and thus of bioavailability became obvious in the subchronic inhalation study. This result is in line with observations obtained in subacute and acute inhalation toxicity studies with the registered substance that also revealed no test substance related adverse systemic toxicity. Therefore, no hazard is anticipated with regard to systemic effects anda data waiver is claimed for reproductive toxicity studies.

Consequently, classification for toxicity to reproduction and for developmental toxicity according to the criteria of EC Regulation 1272/2008 is not warranted.