Cyclohexane, 5-isocyanato-1-(isocyanatomethyl)-1,3,3-trimethyl-, homopolymer, 3,5-dimethyl-1H-pyrazole-blocked

Endpoint summary

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating conc.

Value:

4 953 mg/m³ air

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

An acute oral toxicity study according to OECD TG 423 (Acute Toxic Class Method) is available for the substance. This study was conducted on 6 female rats (3 per step), receiving each a single dose of 2000 mg/kg of the substance formulated in polyethylene glycol.

No mortalities, no clinical signs, no effects on body weight or body weight gain and no particular findings at necropsy were observed. Therefore, according to the flow chart of the OECD TG 423, Annex 2d, the LD50 cut off is 5000 mg/kg bw, and the discriminating dose is 2000 mg/kg.

 

A study on the acute inhalation toxicity of the test item has been conducted in accordance with OECD TG 403 and also with OECD GD 39. In that study a group of male and female rats was nose-only exposed to the dust aerosol of the test item at the maximum technically attainable concentration of 4953 mg/m³. Rats of the control group were exposed to clean air under otherwise identical circumstances.

The respirability of the aerosol was in compliance with test guidelines: MMAD 4.19 µm, GSD 2.78. Such an aerosol is respirable for rats (Mass < 3 µm aerodynamic diameter was 37 %). All rats exposed to 4953 mg/m³ showed unspecific clinical signs after exposure (e.g. bradypnea, dyspnea, motility reduced, atony, tremor, piloerection, cyanosis, serous nasal discharge). Significant decreased body temperatures and incremental body weights, compared to controls, were found at 4953 mg/m³. There is evidence of recovery regarding absolute and incremental body weights during the two week postexposure period. Mortality did not occur during the course of the study. Necropsy did not reveal any macroscopic findings at 4953 mg/m³. Reflex measurement revealed no neurotoxic findings.

The LC50 (4 h, both sexes) was therefore concluded to be > 4953 mg/m³ (maximum technically attainable concentration).

 

No acute dermal toxicity study is available for the substance. However, an assessment of acute dermal toxicity is possible based on the weight of evidences.

The substance has a molecular weight of about 955 g/mol (UVCB), which is in a range that does not favour penetration through the skin after dermal exposure. Furthermore, the substance is practically unsoluble in water and has a high lipophilicity (log Pow 8.6; Neuland 2016). Thus dermal absorption is assumed to be very low.

Experimental evidence leads to the conclusion that the substance is practically non-toxic after acute oral exposure (LD50 > 2000 mg/kg). In the respective study no mortalities, clinical signs, effects on body weight or particular findings at necropsy were observed.

No specific toxicity or signs indicating systemic toxicity are revealed from the acute inhalation toxicity study. Also the data for skin sensitisation (LLNA) give no indication for systemic availability, since no potential for skin sensitisation was found. Additionally, in vitro data does not lead to the conclusion of a skin irritant effect which could have an impairment on the protective function of the epidermidis.

Taken together, systemic availability after dermal exposure is not expected to be higher than after oral exposure. With that conclusion, the oral LD50 > 2000 mg/kg and no overt signs of toxicity after oral exposure, it is not expected that an acute dermal toxicity study would reveal adverse systemic effects and thus a positive hazard conclusion. Local effects, on the other hand, are assessed by the respective skin irritation/corrosion studies.

Therefore, an assessment on acute dermal toxicity can be done based on weight of evidences, which is in line with the recent amendment to REACH Annex VIII (8.5.3) (Reg. (EU) 2016/863) that considers toxicity testing by the dermal route as not needed if a substance does not meet the criteria for classification as acute toxic by the oral route, and with further publications.[1][2]

[1] Moore, Regulatory Toxicology and Pharmacology, 2013, 66, 30-37

[2] Creton, St. et al, Critical reviews in Toxicology, 2010, Vol. 40 No.1, pages 50-83

Justification for classification or non-classification

According to Regulation (EC) No 1272/2008, Annex I, no classification is warranted for acute oral and dermal toxicity.

With the expectation that systemic availability after dermal exposure will not be higher than after oral exposure and the low acute oral toxicity (LD50 > 2000 mg/kg) it can be concluded, that no adverse effects after acute dermal exposure will occur.

 

According to Regulation (EC) No 1272/2008, Annex I, no classification is warranted for acute inhalation toxicity.

The LC50 in the acute inhalation toxicity study (4 h, rats) was > 4953 mg/m³. This was the maximum technically achievable concentration of the substance. At this concentration no mortality occurred and only unspecific clinical signs were observed.