Registration Dossier

Administrative data

Endpoint:
skin sensitisation: in vitro
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because the available information indicates that the substance should be classified for respiratory sensitisation or corrosivity
Cross-reference
Reason / purpose:
data waiving: supporting information
Reference
No valid data could be identified for assessment of the skin irritating potential of isobutyric acid.
To compensate for this lack of data, information resulting from valeric acid as supporting substance is used as substitute.
For eye irritation, a valid study is available.
Skin irritation / corrosion (supporting substance valeric acid)
Valeric acid was demonstrated to be corrosive in a primary skin irritation study according to OECD TG 404 (Hoechst AG, 1983).
Eye irritation (isobutyric acid)
Isobutyric acid was demonstrated to be corrosive in a valid primary eye irritation test similar to OECD TG 405 (BASF, 1974).
Endpoint conclusion:
adverse effect observed (corrosive)
Endpoint conclusion:
adverse effect observed (irreversible damage)
Endpoint conclusion:
no study available

Skin irritation / corrosion

 

For isobutyric acid, no valid studies concerning skin irritation / corrosion could be identified. There are only publications of low reliability (RL3 or 4).

 

To assess the skin irritation / corrosion potential of isobutyric acid, data for valeric acid as supporting substance will be used based on following reasons.

 

Valeric acid is closely related to isobutyric acid. Both substances are short chain carboxylic acids differing in the length of their carbon chain by only one carbon atom (C5 and C4). Physical and chemical properties will be quite similar. The reactive group of both substances is the carboxylic acid function, which plays the key role in causing irritating / corrosive effects. Short chain carboxylic acids up to C6 are known to be corrosive. For longer chain carboxylic acids, the irritating potential will decrease. C4 and C5 carboxylic acids will cause similar irritating / corrosive effects. Thus, it is justified to use valeric acid as supporting substance in the evaluation of irritation / corrosion potential of isobutyric acid.

 

Supporting substance valeric acid

 

The irritation / corrosion potential of valeric acid was studied in a valid primary skin irritation test (Hoechst AG, 1983)

 

Hoechst AG, Rupprich 1983

 

In a primary dermal irritation study according to OECD TG 404, 3 New Zealand White rabbits were exposed dermally to single doses of 0.5 ml of undiluted valeric acid for a one-hour period. Animals then were observed for 14 days. Skin reactions were scored according to OECD TG 404 (method of Draize).

 

In this study, valeric acid was corrosive to the rabbit's skin after a one-hour contact period, as evidenced by severe skin lesions and scar formation, which persisted until the end of the 14-days observation period (Hoechst AG, 1983).

 

Corrosion / irritation potential of isobutyric acid

 

Based on the result for valeric acid, isobutyric acid is assessed also to be corrosive.

 

Eye irritation

 

For the assessment of the eye irritating potential of isobutyric acid, one valid study is available (BASF AG, 1974). In the study of Smyth (1962), the method and the scoring system used are greatly different from actual guideline requirements. Thus, results are not suited to assess the irritation / corrosion potential or the tested substances.

 

The BASF study (pre-guideline study) bears some deviations from actual test guidelines (amount of test substance, observation period, time of irritation score readings). Nevertheless, the data are assessed to be sufficiently valid to represent the eye damaging potential of isobutyric acid, as the correct amount of test substance would result in even more pronounced effects. Using available results conforms to the tiered testing and evaluation strategy for eye irritation / corrosion and further testing can be avoided.

 

BASF AG 1974

 

In a primary eye irritation test, 50 µL of isobutyric acid (purity 99%) was instilled into the conjunctival sac of one eye each of two male Vienna White rabbits. Animals then were observed for 8 days. The original irritation readings were converted to the Draize score at a later date. Readings were taken 24 h, 48 h and 8 d after application of test substance.

 

The treated eyes showed severe opacity and chemosis, which persisted until the end of the observation period (8 d). Iritis developed over time with highest scores (2) at day 8.

 

In this study, isobutyric acid was tested to be corrosive to the rabbit's eye based on the irreversibility of the effects observed.


Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: corrosive

Data source

Materials and methods

Results and discussion

Applicant's summary and conclusion