Reaction mass of ethoxylated N-oleyl-1,3-propanediamine, hydrofluorides of and ethoxylated N-palmityl-1,3-propanediamine, hydrofluorides of and ethoxylated N-stearyl-1,3-propanediamine, hydrofluorides of and olaflur

Endpoint summary

Description of key information

The LD50 of Olaflur is 929 mg/kg bw (male mice) and 608 mg/kg bw (female rats) after single oral administration.




  
  

Based on the available data (acute oral toxicity data, physico-chemical properties and data from toxicokinetic studies), the results for an acute dermal study were extrapolated using a route-to-route approach.






Based on this a dermal LD50 of > 2000 mg/kg bw (6080 mg/kg bw) was derived.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Dose descriptor:

LD50

Value:

608 mg/kg bw

Additional information

Oral

Key study

Male Carworth Farms CF-1S mice, weighing between 18 and 26 g were used in this study by Menley & James, 1969. The animals were dosed orally at 500, 625, 750, 1000, 1250, 1500 or 1750 mg/kg bw (as base) in a dose volume of 10 or 30 mL/kg bw distilled water. The 500 - 1000 mg/kg bw doses were given at 10 mL/kg bw. As the data was insufficient to calculate an LD50, additional higher doses were tested. A 30 mL/kg bw was used for these higher doses. Controls received distilled water at 10 and 30 mL/kg bw. Ten animals per dose were tested. The mice were observed for seven consecutive days for death and the LD50 with 95% Fieller confidence Limits was calculated, resulting in 929 mg/kg bw.

Key study

Female Charles River rats, weighing between 100 and 155 g, were used in this study by Menley & James, 1969.

The animals were dosed orally at 500, 625, 750 or 1000 mg/kg bw (as base) in a dose volume of 10 mL/kg bw distilled water. Controls received distilled water at 20 mL/kg bw. Ten animals per dose were tested. In general, the rats were observed for seven consecutive days for death. Due to the death of the animal dosed at 750 mg/kg bw the study was continued two additional days. No additional animals died during that period. The LD50 with 95% Fieller confidence Limits was calculated to be 608 mg/kg bw.

Dermal

No experimental study investigating the acute dermal toxicity of Olaflur is available.

However, a reliable prediction of the potential acute dermal toxicity and the respective classification and labelling of the substance is possible based on the physico-chemical properties of the test substance and data generated in other toxicological studies. Therefore, performing a new dermal toxicity study would not be in line with animal welfare ideas nor is the exposure pathway relevant to consumers or workers.

Acute dermal LD50 extrapolation:

Olaflur revealed oral LD50 values in acute studies of 929 mg/kg bw in mice and 608 mg/kg bw in rats, respectively. However, it should be noted that the observed effects are at least partially linked to local tissue damage due to the mucous membrane irritation/damaging properties of the substance and so overestimating the systemic toxicity properties.

For the route to route extrapolation taking into account the physico-chemical properties and the data from toxicokinetic studies, the following assumptions can be considered as a worst case scenario:

Oral bioavailability: 100 %

Dermal bioavailability: 10 %

Acute oral toxicity: 608 mg/kg bw

Lowest LD50 value considered although lethality at least partially is linked to local tissue damage and not to systemic toxicity.

Based on this scenario a dermal LD50 of > 2000 mg/kg bw (6080 mg/kg bw) can be calculated.

Inhalation

No studies available.

According to European Commission Regulation 1907/2006, Annex VIII, Section 8.5.2, testing the acute toxicity by inhalation route is appropriate if exposure of humans via inhalation is likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size. Olaflur is a fat-like resp. wax-like mass marketed as component of pastes or fluids only – inhalation is unlikely. Thus, the study on acute toxicity by inhalation route is not relevant and can be omitted.

Justification for classification or non-classification

Based on the results obtained in the acute toxicity studies (oral: LD50: 929 mg/kg bw (mice) and 608 mg/kg bw (rats)), Olaflur has to be classified as "harmful" with respect to acute oral toxicity taking the provisions laid down in Council Directive 67/548/EEC (DSD) and Regulation (EC) No. 1272/2008 (CLP)(GHS) into consideration. According to DSD, Olaflur has to be classified as "harmful" with Xn, R22 - harmful if swallowed. According to GHS Olaflur has to be classified as "harmful if swallowed" (H302), Cat. 4. Classification and labelling with regard to acute dermal toxicity resp. acute toxicity via inhalation is not required according to Regulation (EC) No. 1272/2008 (CLP)(GHS) and Directive 67/548/EEC (DSD).