Registration Dossier

Administrative data

Description of key information

acute oral toxicity: LD50 > 1500 mg/kg bw
acute inhalation toxicity: LC50 > 2379 mg/m³

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
1 500 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating conc.
Value:
2 379 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

An acute oral toxicity study according to OECD TG 423 was conducted with a limit dose of 2000 mg/kg test item administered to 3 male and 3 female rats. The content of the substance in the test item was 75 %, therefore the actual limit dose based on active ingredient was 1500 mg/kg bw.

No animal died in the course of the study and no clinical signs were observed after administration of the test item. Body weight development was not affected. The animals sacrificed at the end of study showed no noticeable gross pathological findings. The LD50 was estimated to be > 2000 mg/kg bw for the test item, correlating to > 1500 mg/kg bw for the active ingredient.

A study on the acute inhalation toxicity of the substance was conducted in rats in accordance with OECD TG 403. Two groups of rats were nose-only exposed to the liquid aerosol of the substance at 0 (vehicle control) and 2379 mg/m³ (maximum technically achievable concentration). The aerosol was generated using the solvent ethyl acetate as vehicle. As the vehicle evaporates instantly after aerosolisation of the liquid test article, rats were in fact exposed to a dry powder aerosol. The respirability of the aerosol was adequate, i.e. the average MMAD was 1.96 µm (GSD 2.2).

Mortality did not occur up to the maximum concentration of 2379 mg/m³, thus the LC50 was > 2379 mg/m³. The lead pathodiagnostic effects were borderline irregular and laboured breathing patterns which lasted up to postexposure day 7. No substance specific toxicity and in particular no indications of systemic toxicity were observed. Of note is that the test substance as a resin-like solid molten-mass of no dustiness had to be dissolved in ethyl acetate to allow the aerosolization. As a result of this process of dissolution, the test article became sticky and glue-like. Most of the observations made appeared to be related to the physical glue-like properties of this dissolution. Due to the lack of any apparent test article specific toxicity higher concentrations were considered to be scientifically not justified.

Additionally, a pulmonary irritant potency study was conducted according to OECD TG 403/TRGS 430 in order to analyse the concentration- and time-course of bronchoalveolar lavage (BAL) parameters following a single 6 hours inhalation exposure to the substance. In this study rats were nose-only exposed to the test substance aerosol of an adequate respirability (MMAD 0.86 µm, GSD 2.3). Interim sacrifices were performed on postexposure days 1 (one day postexposure), 3, and 7, when also lungs were examined by bronchoalveolar lavage.

At 48.7 mg/m³ the exposure was tolerated without specific effects while at 233.8 mg/m³ most of the rats experienced mild and transient (up to the first postexposure day) irregular breathing patterns, minimal hypothermia and transiently decreased body weights. Bronchoalveolar lavage did not reveal any clear concentration-time profile suggestive of acute pulmonary irritation. Lung weights were mildly but consistently elevated at 233.8 mg/m³. According to the author, increased gamma-glutamyltransferase appeared to be related to restorative functions and was not necessarily causal for evidence of pulmonary injury.

In summary, the findings suggested that the test substance did not elicit any pathodiagnostic significant pulmonary irritation at concentrations up to 233.8 mg/m³ and above. The exposure level considered to be the NOAEL was 48.7 mg/m³. 

 

No data on acute dermal toxicity are available for the substance. However, according to Commission Regulation (EU) 2016/863 of May 2016 acute toxicity testing by the dermal route (Annex VII, point 8.5.3., column 2) ‘does not need to be conducted if the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and no systemic effects have been observed in in vivo studies with dermal exposure'. The registered substance conforms with the requirements given above.


Justification for selection of acute toxicity – oral endpoint
Only one study available

Justification for selection of acute toxicity – inhalation endpoint
Only one LC50-study available

Justification for classification or non-classification

Based on the available study no classification on acute oral toxicity according to Regulation (EC) No 1272/2008, Annex I is concluded. Although the maximum oral dose of the substance tested was 1500 mg/kg (commercial product with 75 % content of the active ingredient) and thus below the limit for non-classification of 2000 mg/kg, it can be assumed that the LC50 is higher than 2000 mg/kg bw, as no effects at all were noted at the maximum dose tested.

No classification is warranted for acute inhalation toxicity according to Regulation (EC) No 1272/2008, Annex I. The LC50 found in the study was > 2379 mg/m³. No mortality occurred at 2379 mg/m³, which was the maximum technically achievable concentration. Moreover, due to the lack of any apparent test article specific toxicity higher concentrations were considered to be scientifically not justified.

According to Commission Regulation (EU) 2016/863 of May 2016 acute toxicity testing by the dermal route (Annex VII, point 8.5.3., column 2) ‘does not need to be conducted if the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and no systemic effects have been observed in in vivo studies with dermal exposure'. The registered substance conforms with the requirements given above. Therefore, it can be concluded for acute dermal toxicity that the available information is conclusive for non-classification.