Benzenamine, N-phenyl-, styrenated

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

short-term repeated dose toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
According to REACH Annex VIII column 1 (8.6.1), the following study for repeated dose toxicity is required: Short-term repeated dose toxicity study (28 days), one species, male and female, most appropriate route of administration, having regard to the likely route of human exposure. There is both a suitable Klimisch 1 GLP OECD 407 and 422 guideline study available, assessing the toxicological properties of styrenated diphenylamine after oral gavage over 28 days resp. 6-7 weeks. In general, the oral route is the most suitable one to assess systemic effects in humans, which is the main aim of this endpoint. The dermal or inhalative route is only scientifically relevant in case of considerable exposure, any route-specific toxicological mode of action or local effects, whereas sufficient information on the latter can be gained via irritation tests (REACH No. 8.1. or 8.2). According to REACH Annex VIII column 2 (8.6.1), 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, hence the above-mentioned criteria for the necessity of testing via inhalation route are not fulfilled.
No route-specific toxicity can be expected, and it is considered more reasonable to focus on the assessment of systemic toxicity, which can be best performed using the oral application route. In consequence, the available OECD 407 and 422 studies (oral exposure route) is sufficient to cover this endpoint, no repeated dose testing via inhalation route needs to be performed and can consequently be waived due to animal welfare.