Trimethyl orthoacetate

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Justification for type of information:

The registrant concludes further that testing is scientifically not necessary and would not reveal any additional information which cannot be derived from other available acute toxicity data, so that testing can be omitted due to animal welfare:
There are no signs of toxicity obvious via the oral or dermal route. There is no study available fulfilling the criteria of an OECD 403 study (and required) for the acute inhalation toxicity of the test item; however, there is other information on acute toxicity in rats available:
Acute toxicity study oral, according to OECD 401 (GLP): LD50 > 2000 mg/kg, LD0 ≥ 2000 mg/kg, no mortalities, no signs of systemic toxicity were observed during the observation period, none of the male or female animals showed cutaneous reactions in the form of erythema or oedema in the area of application during the observation period, the changes in bodyweight were normal for all the animals and dissection at the end of the test revealed no evidence of gross changes in organs related to the test substance.
Acute toxicity study dermal, according to OECD 402: LD50 > 2000 mg/kg, LD0 ≥ 2000 mg/kg, no mortalities, no signs of systemic toxicity were observed during the observation period, none of the male or female animals showed cutaneous reactions in the form of erythema or oedema in the area of application during the observation period, the changes in bodyweight were normal for all the animals and dissection at the end of the test revealed no evidence of gross changes in organs related to the test substance.
Due to the lack of relevant toxicity at the application of 2000 mg/kg bw test item via both the oral and dermal application route, the LD50 > 2000 mg/kg bw will be further taken into account.
According to OECD guideline 403 (Acute inhalation toxicity), the concentration of respirable particles for limit testing is 5 mg/L over 4 h. Taking into account for rats a standard respiratory volume of 0.2 l/min and average body weight of 250 g (Guidance on information and requirements and chemical safety assessment, chapter R.8: Characterisation of dose [concentration]-response for human health, Version 2.1, November 2012, ECHA, http://echa.europa.eu/web/guest/guidance-documents/guidance-on-information-requirements-and-chemical-safety-assessment), a total respiratory volume of 48 litre over 4 h can be assumed. This would result in a total dose of 240 mg per rat, which is equivalent to 960 mg/kg bw.
Assuming in a worst-case scenario, although not relevant based on the phys.-chem. properties of the substance, that this total dose will be absorbed to 100%, and assuming furthermore that the orally applied amount is only absorbed to 50%, this dose would correspond to an oral dose of 1920 mg/kg bw. This is below the limit dose in oral and dermal tests and also below the actual LD50 via the oral and dermal application route, as only the limit dose of 2000 mg/kg was tested and led to no deaths or signs of toxicity in all dosed animals.
Hence, it can be reasonably assumed that an additional acute toxicity test via the inhalation route would reveal an LC50 inhalation > 5 mg/l.

So, in summary, it can be reasonably assumed that an additional testing for acute inhalation toxicity would not reveal any further relevant information and consequently, testing can be omitted due to animal welfare.