Registration Dossier

Administrative data

Endpoint:
specific investigations: other studies
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: scientific assessment based on original toxicological data

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report Date:
2008

Materials and methods

Principles of method if other than guideline:
Comparative assessment of the toxicologic properties of HDI Trimer asym. (HDI oligomers, iminooxadiazindione, CAS-no. 28182-81-2) and HDI Trimer (HDI oligomers, isocyanurate, CAS-no. 28182-81-2). Document for verification of read-across.

Test material

Reference
Name:
Unnamed
Type:
Constituent

Results and discussion

Details on results:
For details on results see attached document.

Applicant's summary and conclusion

Conclusions:
Comparative assessment of the toxicologic properties of HDI Trimer asym. (HDI oligomers, iminooxadiazindione, CAS-no. 28182-81-2) and HDI Trimer (HDI oligomers, isocyanurate, CAS-no. 28182-81-2). Document for verification of read-across.
Executive summary:

Cited from summary of report: "Desmodur® N3300 & Desmodur® XP 2410 are both alicyclic, HDI-based homopolymers. Previous studies addressing the acute pulmonary irritation potency of the aerosol have shown that the principle mode of action is confined to ‘pulmonary irritation’ which resembles the site of the initial deposition of aerosol. Comparative acute and subchronic 13-week inhalation studies have demonstrated that the subchronic NOAEC is contingent on the acute NOAEC. The latter can be best and most sensibly quantified by systematic studies addressing the time-course and concentration-response relationship of protein in bronchoalveolar lavage fluid (BALF). The scientific rationales have been published in detail elsewhere (Pauluhn, Toxicol Sci. 58: 173-181, 2000; Inhalation Toxicology 14: 287-301, 2002; Archives of Toxicology 78: 243-251, 2004, Inhalation Toxicology 16: 159-175, 2004; Journal of Applied Toxicology 24: 231-247, 2004; Pauluhn and Mohr, Inhalation Toxicology 13: 513-532, 2001). With regard to species-sensitivity the rat appears to be the species of choice (Pauluhn, Toxicology. 247:33-45, 2008). The comparison of the exposure characteristics of both Desmodur® N3300 & Desmodur® XP 2410 was essentially similar. The time-course of BAL-protein changes as well as the concentration-response relationship were also similar. The increase in BAL-protein at the lowest tested concentration of 3-4 mg/m³ as well as the extrapolation non-irritation threshold concentration (2 mg/m³) were essentially identical. At about 10-times higher concentrations Desmodur® XP 2410 aerosol appeared to be slightly more irritant. In summary, the basic toxicological mechanisms and toxic potencies of Desmodur® N3300 & Desmodur® XP 2410 appear to be indistinguishable. As long as subtle differences exist they appear within of the resolution of this bioassay. Due to the confluence of critical toxicity data in the MOAEC-range it does not appear to scientifically justified to consider the toxic potencies of Desmodur® N3300 & Desmodur® XP 2410 to be different. Accordingly, due to animal welfare reasons as well the availability of data the inhalation toxicity data generated for Desmodur® N3300 should also be valid for Desmodur® XP 2410."