Benzenamine, N-phenyl-, styrenated

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because exposure of humans via inhalation is not 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

other:

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING

According to REACH Annex VIII column 2, 8.5.2. Testing by the 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.
As the substance is a liquid at all relevant handling temperatures, i.e. minimum between -100°C and 400°C, no potentially inhalable particles need to be regarded.
The vapour pressure of the substance was determined to be 2.1 x 10E-4 Pa (25 °C) (OECD 104). According to the BG Bau [BG Bau 2017; Berufsgenossenschaft der Bauwirtschaft, http://www.bgbau.de/gisbau/lehrgang/a-z/dampfdru.htm, download of 2017-09-08], a vapour pressure of p < 0.01 hPa is very low, p = 1-10 hPa low and p > 10 hPa is high. The 31. BImSchV describes an organic substance as volatile if it has a vapour pressure of 0.01 kPa (i.e. 10 Pa) or more at 293.15 K. Also, according to ECHA’s guidance, substances are not available for inhalation as a gas in a relevant manner with a vapour pressure less than 0.5 kPa (i.e. 500 Pa) (or a boiling point above 150°C) [ECHA, 2008]. With a boiling point of >400°C and a vapour pressure of 2.1 x 10E-4 Pa at 25°, the registered substance has a very low vapour pressure and does not need to be regarded a volatile. Hence, the potential inhalation of the substance as a gas is not given and does not need to be regarded. Further, sufficient precautionary measures exclude the formation of droplets of inhalable size or aerosols. In consequence, exposure of humans via inhalation is not likely.

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:
According to ECHA’s guidance, moderate log P values (between -1 and 4) are favourable for absorption directly across the respiratory tract epithelium by passive diffusion. The experimentally determined LogPow is 4.64 at 22°C, lying above that value and so hindering diffusion.
However, any lipophilic compound may be taken up by micellular solubilisation. This mechanism may be of particular importance for highly lipophilic compounds (Log Pow >4), particularly those that are poorly soluble in water (1 mg/L or less) that would otherwise be poorly absorbed. Although water solubility of the registered substance is way less than 1 mg/l, exposure is practically not given.
So, the design of an OECD 403 study (5 mg/l actual concentration of respirable substances) may overestimate the actual exposure, if it would be possible anyway to convert the substance into an inhalable form.
Further, 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 similar to OECD 401: LD50 > 5000 mg/kg, LD0 ≥ 5000 mg/kg, no mortalities, no clinical symptoms on any observation day observed
Acute toxicity study similar to OECD 401, 50% solution: LD50 > 5000 mg/kg, LD0 ≥ 5000 mg/kg, no mortalities, no clinical symptoms on any observation day observed
Acute toxicity study dermal, acc. OECD 402: LD50 > 2000 mg/kg, LD0 ≥ 2000 mg/kg, no deaths occurred, no signs of systemic toxicity or dermal irritation were noted during the observation period.
Due to the lack of relevant toxicity at the application of 5000 resp. 2000 mg/kg bw test item via both the oral and dermal application route, and the fact that the LD50 values could only be determined as greater than 5000 or 2000 mg/kg, the LD50 > 2000 mg/kg bw will be further taken into account (precautionarily the lower value).
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 application route, as only the limit dose of 5000 mg/kg (2000 mg/kg via dermal route) 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 LC50inhalation > 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.