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Administrative data

Description of key information

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
LD50
Value:
5 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Dose descriptor:
LC50
Value:
160 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Dose descriptor:
LD50
Value:
9 400 mg/kg bw

Additional information

Acute toxicity: oral

The acute oral toxicity of Desmodur VP.PU 60WF14 (TDI Biuret) was low with an LD50 value exceeding 5000 mg/kg bw in rats (cut-off value) according to OECD TG 423 (Gillissen, 2010). At a test dose of 2000 mg/kg bw no animal died and no clinical signs were observed during the 14-day post observation period.

 

Acute toxicity: dermal

The results for the acute dermal toxicity have been 'read across' from TDI (justification of read-across see below). In an acute rabbit study similar to OECD TG 402 the dermal toxicity of TDI (unspecified isomers) was low with an LD50 value exceeding 9400 mg/kg bw (Wazeter et al., 1964). No mortality occured and animals appeared normal throughout the 14-day post observation period but skin irritation was noted at all dose levels (2500 to 9400 mg/kg bw) at a moderate-to-marked degree.

 

Acute toxicity: inhalation

An acute inhalation toxicity study with Desmodur VP.PU 60WF14 (TDI Biuret) according to OECD TG 403 was conducted on male and female rats, which were nose-only exposed to liquid aerosol concentrations of 75.7, 105.4, 114.9 and 177.6 mg/m3 (analytical concentrations - sum TDI-isomers) (Folkerts, 2010). The aerosol was of adequate respirability for the rats (MMAD 1.35 -1.81 µm / GSD 1.61 -2.07µm). Mortality occurred in a concentration-dependent manner at 105.4 mg/m³ and above. A particular sex-difference in susceptibility was not apparent. For both genders combined an approximate LC50 (4 hrs, aerosol) of 112 mg/m3 was calculated based on the TDI-isomers. The calculation of the LC50 value based on test substance concentration reveals an approximate LC50 of 160 mg/m3. Decreased body weights and clinical signs indicative of respiratory tract irritation were observed at 75.7 mg/m3 and above. Reflex assessment after exposure revealed reduced grip strength and abnormal righting response. Histopathology of additional males of the exposure group 114.9 mg/m3 revealed acute inflammatory findings and severe necroses of the respiratory tract. In these animals almost all histopathological findings in the nasal cavities had recovered 12 days after exposure. Early mortality appeared to be caused by acute lung edema and delayed mortality (around day 10) by inflamatoric changes in and obstruction of the respiration tract.

 

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.

Acute toxicity: oral 

Not classified under Annex I of Directive 67/548/EEC or Annex VI-1 of CLP Regulation (EC) No 1272/2008. According to Annex I of CLP Regulation (EC) No 1272/2008 no classification is required for acute oral toxicity (2,4-/2,6-TDI: LD50 > 2000 mg/kg bw; TDI Biuret: LD50 cut-off >= 5000 mg/kg bw).

Acute toxicity: dermal

Not classified under Annex I of Directive 67/548/EEC or Annex VI-1 of CLP Regulation (EC) No 1272/2008. According to Annex I of CLP Regulation (EC) No 1272/2008 no classification is required for acute dermal toxicity (2,4-/2,6-TDI: LD50 > 9400 mg/kg bw).

Acute toxicity: inhalation

2,4-/2,6-TDI vapour is classified under Annex I of Directive 67/548/EEC with R26 (very toxic by inhalation). This classification corresponds to Category 1 (fatal if inhaled) according to Annex VI-1 of CLP Regulation (EC) No 1272/2008.

Remark: For TDI Biuret the LC50 was 160 mg/m3 after a 4-hour aerosol exposure to rats. According to Annex I of CLP Regulation (EC) No 1272/2008 this LC50 value would lead to Category 2 (fatal if inhaled).

Classification of acute inhalation toxicity with regard to Specific Target Organ Toxicity - Single Exposure (STOT-SE):

Due to respiratory irritation effects 2,4-/2,6-TDI was classified under Annex I of Directive 67/548/EEC with R37 (irritating to respiratory system). This classification corresponds to STOT-SE Category 3 (may cause respiratory irritation) according to Annex VI-1 of CLP Regulation (EC) No 1272/2008.