Registration Dossier

Administrative data

Description of key information

2017 LLNA  pre-test: The observations in the OECD 429 LLNA pretests are indicative of the substances being corrosive.

Scores of =/> 3 were observed at concentrations 50, 25 and 10%

Ear swelling was greater than 25% in substance 1833500 at 25 and 50%

Body weight loss (>5%) was observed possibly indicative of systemic toxicity.

The main argument for not continuing with the main LLNA studies is the interpretation of the study director with regard to eschar formation at all concentrations tested on day 6.

Based on this observation, and in light of experience with the substance it was decided to apply a precautionary labelling of Corrosive 1C to (2-hydroxypropyl)trimethylammonium 2-ethylhexanoate.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (LLNA)
Data waiving:
study technically not feasible
Justification for data waiving:
the study does not need to be conducted because the substance is classified as skin corrosion (Category 1, 1A, 1B or 1C)
Justification for type of information:
The OECD 429 (LLNA) test guideline states that

“Dose and vehicle selection should be based on the recommendations given in references (3) and (5). Consecutive doses are normally selected from an appropriate concentration series such as 100%, 50%, 25%, 10%, 5%, 2.5%, 1%, 0.5%, etc. Adequate scientific rationale should accompany the selection of the concentration series used. All existing toxicological information (e.g. acute toxicity and dermal irritation) and structural and physicochemical information on the test substance of interest (and/or structurally related test substances) should be considered where available, in selecting the three consecutive concentrations so that the highest concentration maximises exposure while avoiding systemic toxicity and/or excessive local skinirritation(3)(25).”


.” Excessive local skin irritation is indicated by an erythema score ≥3 and/or an increase in ear thickness of≥25% on any day of measurement(26)(27). The highest dose selected for the main LLNA study will be the next lower dose in the pre-screen concentration series (see paragraph18)that does not induce systemic toxicity and/or excessive local skin irritation.”

Scores of =/> 3 were observed at concentrations 50, 25 and 10%

Ear swelling was greater than 25% in substance 1833500 at 25 and 50%

Body weight loss (>5%) was observed possibly indicative of systemic toxicity.


The main argument for not continuing with the main LLNA studies is the interpretation of the study director with regard to eschar formation at all concentrations tested on day 6.

The definition of corrosivity is not met formally “Corrosivity is defined as irreversible (14 days) damage of the epidermis and dermis following exposure to a substance up to 4 hours on skin”, because observation in the pretests ended on day 6 in the pretests.

However, the observations in the pretests are indicative of the substances being corrosive, which may well have an influence on the proliferation of lymphocytes which in turn would result in a false positive result.

Based on this observation, and in light of experience with the substance it was decided to apply a precautionary labelling of Corrosive 1C to (2-hydroxypropyl)trimethylammonium 2-ethylhexanoate.
Endpoint conclusion
Endpoint conclusion:
no study available

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification