Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: dermal
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Justification for type of information:
The study does not need to be conducted because the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and no systemic effects have been observed in in vivo studies with dermal exposure (e.g. skin irritation, skin sensitsation) - [study scientifically not necessary / other information available]


JUSTIFICATION FOR DATA WAIVING
In accordance with column 2 of REACH Annex VIII, information requirement 8.5.3 (acute toxicity by dermal route) testing is not considered to be appropriate because skin contact in production and/or use is unlikely. Furthermore, in vivo acute oral toxicity studies have revealed that the substance does not require classification for STOT-SE by the oral route, in vitro skin corrosion/irritation and skin sensitisation studies do not indicate effects following dermal exposure to the substance and no systemic toxicity is predicted.


Although no dermal toxicity study was performed with thiamine hydrochloride it can be seen from the acute oral toxicity studies that the substance is of low acute toxicity. Two study reports are available for the acute oral endpoint (Bächtold Report No. 3191, 1970 and Bächtold Report No. 6474, 1976). The resulting LD50s were above 10000 mg/kg bw both in mice and in rats. As a consequence, Thiamine hydrochloride has not to be classified with regards to that endpoint.

Furthermore e request that the following points are also considered in support of the proposed waiver:-

- Usually acute oral toxicity drives the hazard classification (Moore et al., 2013).

- Based on the general accepted assumption that dermal absorption will not be higher than oral absorption, acute dermal toxicity of Thiamine hydrochloride is expected to result in a LD50 > 10000 mg/kg/bw.

- It is described in the EU Commission Regulation 2016/863 that there is scientific evidence for expecting substances that are not toxic via the oral route to be also non-toxic via the dermal route. Therefore, additional testing with dermal application is considered unlikely provide essential information for the safety assessment.

- Further testing is not warranted for animal welfare reasons.


References
Commission Regulation (EU) 2016/863 of 31 May 2016 amending Annexes VII and VIII to Regulation (EC) No 1907/2006 of the European Parliament and of the Council on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) as regards skin corrosion/irritation, serious eye damage/eye irritation and acute toxicity

Moore et al., 2013: Can acute dermal systemic toxicity tests be replaced with oral tests? A comparison of route-specific systemic toxicity and hazard classification under the Globally Harmonized System of Classification and Labelling of Chemicals (GHS), Reg Tox Pharm 66(1): 30-37

Data source

Materials and methods

Results and discussion

Applicant's summary and conclusion