6-amino-1,3-dimethyluracil

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

sub-chronic 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 IX column 1 (8.6.2), the following study for repeated dose toxicity is required: Sub-chronic toxicity study (90-day), one species, rodent, 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 408 guideline study available, assessing the toxicological properties of 1,3-Dimethyl-4-aminouracil after oral application in feed over 90 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 IX column 2 (8.6.2), 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.
The substance melts at 299°C, the boiling point could not be determined with the most sensitive method, i.e. vapour pressure measurement by effusion method, weight loss, according to OECD Guideline for the Testing of Chemicals 104. It could not be determined because the vapour pressure is too low. The vapour pressure itself was determined as very low, i.e. 1 * 10exp(-7) hPa at 25°C (calculated using the Modified Watson Correlation, OECD 104, GLP). So, the exposure to 1,3-dimethyl-4-aminouracil via inhalation of vapour can be disregarded as no vapour will be formed during handling. Also, the substance is a solid, so the formation of inhalable droplets or aerosols can furthermore be excluded.
The particles of 1,3-Dimethyl-4-aminouracil form various size agglomerates. The measurement of the single particles was not possible. The amount of test item with a particle size below 250 µm was only about 2 %. This amount is too small and not relevant for the particle size distribution. The main agglomerate size was found in the range of 250 µm to 2000 µm. 50 % of the test item agglomerates exceeded 500 µm. 0.00% were < 75µm. According to ECHA’s guidance on data requirements Chapter R.7c, In humans, particles with aerodynamic diameters below 100 μm have the potential to be inhaled. Particles with aerodynamic diameters below 50 μm may reach the thoracic region and those below 15 μm the alveolar region of the respiratory tract. As obvious, only less than 2% of the particles in general have the potential to be inhaled, and none of the particles have the potential to reach the part of the lung in which no ciliary clearance occurs. Also, direct dust exposure is excluded during handling, hence not fulfilling the above-mentioned criteria for the necessity of testing via the inhalative route.
In consequence, the available OECD 408 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.