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Toxicological information

Endpoint summary

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Description of key information

Oral LD50 is 2750 mg/kg bw, using the lower value for females (similar to OECD TG 401)

Dermal LD50 is > 5000 mg/kg bw (method similar to OECD 402)

Inhalation LC50 is 7150 mg/m3 (using oral to inhalation route extrapolation)

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The acute oral toxicity is of sufficient quality and adequate for this dossier.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The information is based on a roughly route to route extrapolation and sufficiently adequate for this dossier.

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The acute dermal toxicity is of sufficient quality and adequate for this dossier.

Additional information

Acute oral toxicity

Key study: The key study for acute oral toxicity was chosen as such as it was performed according to methods similar to OECD Test Guideline 401 and under GLP conditions. Based on the results of a preliminary assay, the test substance was dosed at 3.5, 4.0, 4.5, 5.0 and 5.6 g/kg bw in the main test. Mortality was observed in all doses. The definitive 14d-LD50 values were determined to be 3.35 (2.60 - 4.32) and 2.75 (2.02 - 3.74) g/kg for male and female rats respectively, under the conditions of the test. The key value is 2750 mg/kg bw for females.

Supporting studies: Two other studies were available that were performed under the same conditions as the key study. The LD50 values established in these studies were less critical and therefore not considered key values for the endpoint. One study showed an LD50 value of >1690 mg/kg bw for males and 3450 (95% CL: 2400 - 4970) mg/kg bw for females, the other study only tested the test article in females and established a LD50 of 3643 mg/kg bw. Another study (OECD 401) was available in which a limit dose of 2000 mg/kg bw showed no deaths and therefore a LD50 of >2000 mg/kg bw was established for both males and females.

Acute dermal toxicity

Key study: In the key study, the dermal acute toxicity of the test substance, a colourless liquid, was examined (similar to OECD test guideline 402, 1987). In the preliminary assay in which two rats of each sex were dosed by application of a prepared alcoholic solution of the test substance to the skin at 5000 mg/kg bw, one animal died during the 72 hour observation period. In the main study eight male and eight female albino rats (Sprague-Dawley CD strain), weighing between 180 and 280 grams, were clipped on the day prior to dosing and the test substance, prepared in the diluent supplied, was applied onto the skin at 5000 mg/kg bw. The volume of solution administered was 0.5 ml/100 g bw. None of the male rats showed any clinical signs indicative of systemic toxicity. One of the eight female rats died on Test Day 6, but the others remained healthy throughout the study. All survivors gained weight in a normal manner. At necropsy performed on the survivors at term, none of the animals had any signs indicative of systemic toxicity. The female rat that died on Test Day 6 was examined post-mortem and there was red fluid in the intestines and congestion of the lungs. The dermal LD50 was greater than 5000 mg/kg bw, with only one death in the sixteen animals dosed.

Supporting study: Cyclacet was tested in another similar to OECD TG 402 study in which the LD50 was > 2000 mg/kg bw, the highest dose tested.

Acute inhalation toxicity

Acute inhalation toxicity is not anticipated because when the oral LD50 values are compared with the saturated vapour concentration of the esters, the result is that the inhalation LD50 values exceed the Saturated vapour concentration (SVC) and thus the inhalation LC50 cannot be reached.  

Cyclacet has an oral LD50 of 2750 mg/kg bw. Its SVC at ca. 20 oC is 167 mg/m3. This value can be calculated using vapour pressure and molecular weight (MW*VP (Pa)*1000 / 8.3 (gas constant)*293o K (20oC). The oral LD50 can be converted to an inhalation LD50 using the equation:

“Incorporated dose = concentration x respiratory volume x exposure time”, which results in

1 mg/kg bw = 0.0052 mg/l/4h (ECHA guidance on CLP, 2017). For conservative reasons the inhalation absorption is set at 100% and orally at 50%. For Cyclacet this results in 7150 mg/m3. With a maximum SVC of 167 mg/m3 the inhalation LC50 cannot be reached.

 

In case the exposure is via mists, the aerosol type of exposure needs to be considered. According to ECHA CLP guidance, the maximum exposure would be for particles 1-4um and the maximum concentration would be 2000 mg/m3 (ECHA guidance on CLP, 2017, section, 3.1.2.3.2).

The LC50 for Cyclacet is calculated as 7150 mg/m3 but the maximum dose is 2000 mg/m3 and therefore the LC50 e.g. via mists cannot be reached either.

Justification for classification or non-classification

Cyclacet does not need to be classified for acute oral, dermal and inhalation toxicity based on the information above and in accordance with EU CLP (EC 1272/2008 and its amendments).