4,8-dicyclohexyl-6-hydroxy-2,10-dimethyl-12H-dibenzo[d,g][1,3,2]dioxaphosphocin

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 a suitable Klimisch 1 GLP OECD 407 guideline study available, assessing the toxicological properties of 4,8-dicyclohexyl-6-hydroxy-2,10-dimethyl-12H-dibenzo[d,g][1,3,2]dioxaphosphocin after oral gavage over 28 days. 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.
The vapour pressure of the substance, extrapolated from experimental data is 4.3×10^-7 hPa at 20 °C, 6.2×10^-7 hPa at 25 °C and 3.5× 10^-6 hPa at 50 °C.
So, the exposure to 4,8-dicyclohexyl-6-hydroxy-2,10-dimethyl-12H-dibenzo[d,g][1,3,2]dioxaphosphocin via inhalation of vapour can be disregarded as no vapour will be formed during handling. As it is a solid, no droplets of inhalable size will be formed. Also, the substance is not distributed as e.g. aqueous solution, so the formation of inhalable droplets or aerosols can furthermore be excluded. There are no particles of inhalable size formed because the substance is manufactured and used in a non solid/granular form (pastilles). So, direct dust exposure is excluded during handling, hence not fulfilling the above-mentioned criteria for the necessity of testing via inhalation route.
Further, 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 study (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.