Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

Desmodur VP.PU 60WF14 (TDI Biuret) was investigated in the modified local lymph node assay (LLNA-IMDS) on female mice according to OECD TG 429 (Vohr, 2010). Concentrations of 0 (vehicle control), 2, 10 and 50% formulated in acetone/olive oil (4:1) were tested. The results show that Desmodur VP.PU 60WF14 has a strong sensitizing potential in mice after dermal application. Compared to vehicle treated animals there was a significant increase regarding the weights of the draining lymph nodes and the cell counts in all dose groups. The corresponding cell count indices were 4.29, 4.66 and 3.67 exceeding the "positive level" of index 1.4. A significant increase compared to vehicle treated animals regarding ear swelling and ear weights was detected in all dose groups. An increase in this parameter would point to an acute irritant (inflammatory) response. However, such an irritant property can also be combined with a strong skin sensitizing potential of a test compound.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

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

At the present time, it is not possible to define reliable exposure-response relationships with regard to the risk of sensitisation for TDI (or indeed for any other known respiratory sensitiser). While thresholds are presumed to exist for induction of respiratory sensitisation, this complex aspect has not been adequately investigated in animal models. There is some evidence that respiratory sensitisation in man is associated with short duration higher level exposures (eg accidental exposures) which suggests a threshold for induction. Animal data support the hypothesis that respiratory hypersensitivity may be induced by skin contact and this possibility has not been excluded in studies involving humans. It is likely that any significant skin exposure to TDI will involve a concomitant respiratory exposure, and discrimination of the contribution of the different exposure routes is unlikely to be resolved in humans.

 

Nevertheless, the existing data and human experience do lead to the conclusion that if the exposure concentrations of TDI are kept below 0.01 to 0.02 ppm, generally no new cases of TDI asthma are observed.

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.

 

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.

 

Skin sensitisation

2,4-/2,6-TDI is classified under Annex I of Directive 67/548/EEC with R43 (may cause sensitization by skin contact). This classification corresponds to Category 1 (may cause an allergic skin reaction) according to Annex VI-1 of CLP Regulation (EC) No 1272/2008. A modified local lymph node assay (LLNA-IMDS) in mice with Desmodur VP.PU 60WF14 (TDI Biuret) confirms this classification.

 

Respiratory sensitisation

2,4-/2,6-TDI is classified under Annex I of Directive 67/548/EEC with R42 (may cause sensitization by inhalation). This classification corresponds to Category 1 (may cause allergy or asthma symptoms or breathing difficulties if inhaled) according to Annex VI-1 of CLP Regulation (EC) No 1272/2008.