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short-term repeated dose toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
a sub-chronic toxicity study (90 days) does not need to be conducted because the substance is unreactive, insoluble and not inhalable and there is no evidence of absorption and no evidence of toxicity in a 28-day 'limit test' and human exposure is limited
Justification for type of information:
The performance of a repeated dose test for toxicity by inhalation route is scientifically not justified. REACh Regulation No. 1907/2006, Annex IX, Sect. 8.6.2, Col. 2, states as follows: “8.6.2: Testing by inhalation route is appropriate if exposure on 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 inhalable size.”
Exposure to HAT ISO by inhalation is unlikely, as:
1) HAT-ISO is manufactured and formulated in closed systems. Thus, exposure via inhalation during manufacturing and formulation is unlikely. The formulated HAT-ISO product is a liquid paste.
2) Use of formulated HAT-ISO is also unlikely to result in exposure via inhalation. During use HAT-ISO is included in three-dimensional matrices of polymeric, resinous material and completely retained. Therefore, exposure to aerosols, particles or droplets of inhalable size is unlikely and inhalation practically negligible. For more details on exposure assessment see the risk assessment report in section 13. Further, physico-chemical properties of HAT ISO, including particle size determination, suggest no evidence of a significant absorption by inhalation. The substance is practically non-volatile, with vapour pressure determined below 1.6E-04 Pa at 20 °C and the mean volumetric diameter of particles was determined to be 233.7 µm. Therefore, availability of HAT ISO in air and the formation of inhalable particles are not very likely. The acute dermal toxicity testing showed no local or systemic toxicity. Neither skin nor dermal irritation tests showed signs of systemic effects by absorption through skin or mucous membranes. A 28 day oral repeated dose toxicity study in rats revealed a NOEL of 1000 mg/kg bw/day. Oral administration at dose levels up to 1000 mg/kg bw/day (limit dose) did not reveal any toxicological effects. In summary, based on exposure assessment and available toxicity tests, further repeated dose testing of HAT ISO by inhalation is scientifically not justified.

Data source

Materials and methods

Results and discussion

Applicant's summary and conclusion