Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Additional information

Since no data on fertility are available for TDI Biuret, such data have been 'read across' from TDI (justification of read-across see below).

The toxicity on fertility of TDI was investigated in a two generation study in rats (Tyl et al. 1989). The study was performed in accordance to the OECD 416 guildeline under GLP. Vapor atmospheres of 0.02, 0.08 or 0.3 ppm did not effect any of the reproduction parameters which were evaluated. The only signs of toxicity were transient irritations of the upper respiratory tract. Therefore, under the conditions of this study, there was no evidence of effects on reproduction at the highest exposures tested which was 0.3ppm.

 

Justification of read-across from supporting substance (2,4-/2,6-TDI to TDI Biuret)

The 80:20 mixture of 2,4-/2,6-TDI (CAS No. 26471-62-5) is the monomeric component of the oligomeric TDI Biuret. The examination of the material balance of Desmodur VP.PU 60WF14 (TDI Biuret) yielded amounts of 42 % 2,4-TDI, 13.7 % 2,6-TDI and ca. 44 % TDI Biuret (Currenta, 2009). Thus, TDI Biuret contains ca. 56 % of a 80:20 mixture of 2,4-/2,6-TDI.

With regard to the toxicological comparability of TDI Biuret and 2,4-/2,6-TDI acute inhalation toxicity studies in rats revealed 4-hour LC50 values (aerosol) of 112 mg/m3 for TDI Biuret (based on sum of TDI isomers) and 107 mg/m3 for 2,4-/2,6-TDI (Folkerts, 2010). All qualitative cornerstones of TDI-induced respiratory tract injury were essentially identical. This included the typical delayed-onset mortality, likely as a result of a bronchiolitis obliterans. Of note is the over-proportional presence of TDI vapor relative to the TDI Biuret after inhalation exposure. This is consistent with the higher vapor pressure of TDI. In summary, the similarities of LC50s in the presence of TDI Biuret up to analytically verified breathing zone concentrations of 112 mg TDI Biuret/m3 demonstrates that the inhalation toxicity of TDI per se isnot affected to any appreciable extent by the presence of TDI Biuret aerosol. This means, modulating factors due to physicochemical interactions (partitioning of the vapor phase with the liquid aerosol phase) were not apparent as this would have lead to a more immediate onset of mortality (immediate acute lung edema rather that delayed bronchiolitis obliterans). Overall, these data demonstrate that the acute inhalation toxicity of TDI Biuret is negligible relative to TDI and any dependence of acute hazards on specific use patterns (vapor vs. aerosol) cannot be envisaged(expert opinion of Prof. J. Pauluhn: Desmodur VP.PU 60 WF14 (TDI Biuret): Comparison of acute inhalation toxicities of TDI Biuret and TDI, dated Sep. 3, 2010; complete expert opinion attached in IUCLID chapter 7 “Endpoint summary: Toxicological information”).

In addition, the toxicity profiles of TDI Biuret and 2,4-/2,6-TDI also show a high degree of consistency regarding the endpoints acute oral toxicity, skin irritation, eye irritation, skin sensitization and genotoxicity in vitro.

Therefore, based on all available data the test results obtained for 2,4-/2,6-TDI can be transferred to TDI Biuret and based on such a read-across further testing of TDI Biuret is not required. This approach is in accordance with Annex XI, section 1.5 of the REACH Regulation (EC) No 1907/2006.


Short description of key information:
No effects on fertility in a 2-Gen study. (OECD-guideline 416, GLP).

Effects on developmental toxicity

Description of key information
No effects on development in a developmental toxicity study. (OECD-guideline 414, GLP).
Additional information

Since no data on developmental toxicity / teratogenicity are available for TDI Biuret, such data have been 'read across' from TDI (justification of read-across see below).

Developmental toxicity of TDI was investigated by exposing mated female rats to TDI vapors of 0.02, 0.1, 0.5 ppm (Tyl, 1988). The study was performed in accordance to the OECD guildeline 414 under GLP. No embryotoxicity or teratogenicity was observed at any exposure concentration employed. Exposure to toluene diisocyanate vapour by inhalation during organogenesis in rats resulted primary in irritation of the respiratory tract at the highest tested dose level (0.5 ppm). Most likely secondary to this irritation maternal toxicity and minimal fetotoxicity were observed (decreased food consumtion and bw).

 

Justification of read-across from supporting substance (2,4-/2,6-TDI to TDI Biuret)

The 80:20 mixture of 2,4-/2,6-TDI (CAS No. 26471-62-5) is the monomeric component of the oligomeric TDI Biuret. The examination of the material balance of Desmodur VP.PU 60WF14 (TDI Biuret) yielded amounts of 42 % 2,4-TDI, 13.7 % 2,6-TDI and ca. 44 % TDI Biuret (Currenta, 2009). Thus, TDI Biuret contains ca. 56 % of a 80:20 mixture of 2,4-/2,6-TDI.

 

With regard to the toxicological comparability of TDI Biuret and 2,4-/2,6-TDI acute inhalation toxicity studies in rats revealed 4-hour LC50 values (aerosol) of 112 mg/m3 for TDI Biuret (based on sum of TDI isomers) and 107 mg/m3 for 2,4-/2,6-TDI (Folkerts, 2010). All qualitative cornerstones of TDI-induced respiratory tract injury were essentially identical. This included the typical delayed-onset mortality, likely as a result of a bronchiolitis obliterans. Of note is the over-proportional presence of TDI vapor relative to the TDI Biuret after inhalation exposure. This is consistent with the higher vapor pressure of TDI. In summary, the similarities of LC50s in the presence of TDI Biuret up to analytically verified breathing zone concentrations of 112 mg TDI Biuret/m3 demonstrates that the inhalation toxicity of TDI per se isnot affected to any appreciable extent by the presence of TDI Biuret aerosol. This means, modulating factors due to physicochemical interactions (partitioning of the vapor phase with the liquid aerosol phase) were not apparent as this would have lead to a more immediate onset of mortality (immediate acute lung edema rather that delayed bronchiolitis obliterans). Overall, these data demonstrate that the acute inhalation toxicity of TDI Biuret is negligible relative to TDI and any dependence of acute hazards on specific use patterns (vapor vs. aerosol) cannot be envisaged(expert opinion of Prof. J. Pauluhn: Desmodur VP.PU 60 WF14 (TDI Biuret): Comparison of acute inhalation toxicities of TDI Biuret and TDI, dated Sep. 3, 2010; complete expert opinion attached in chapter 7 “Endpoint summary: Toxicological information”).

In addition, the toxicity profiles of TDI Biuret and 2,4-/2,6-TDI also show a high degree of consistency regarding the endpoints acute oral toxicity, skin irritation, eye irritation, skin sensitization and genotoxicity in vitro.

Therefore, based on all available data the test results obtained for 2,4-/2,6-TDI can be transferred to TDI Biuret and based on such a read-across further testing of TDI Biuret is not required. This approach is in accordance with Annex XI, section 1.5 of the REACH Regulation (EC) No 1907/2006.

Justification for classification or non-classification

According to CLP Regulation (EC) No 1272/2008 the classification of 2,4-/2,6-TDI (CAS No 26471-62-5) was considered for the classification of TDI Biuret since TDI Biuret contains >= 50 % of 2,4-/2,6-TDI.

 

Toxicity to reproduction (fertility, developmental toxicity / teratogenicity)

2,4-/2,6-TDI is not classified under Annex I of Directive 67/548/EEC. According to Annex I of CLP Regulation (EC) No 1272/2008 no classification is required for toxicity to reproduction.