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Administrative data

Description of key information

The irritation potential of TBEP has been examined for both skin and eye irritation by in vivo studies in rabbits.
For skin irritation, a weight of evidence approach has been taken, using the studies of reliability 1 or 2. These studies are a Rel 1 study by Roth (2000), and studies of Rel. 2 by Picirillo (1981), Wolfe (1979) and Lewis (1979).
For eye irritation, a GLP-compliant guideline study (Rel. 1) by Clariant (Roth, 2000) has been chosen as key study. Supporting studies of Rel. 2 are Picirillo (1981), Wolfe (1979) and Gabriel (1980).
There are no data indicating that TBEP is irritating to the respiratory system.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

Skin irritation/corrosion:

There are six valid unpublished reports of in vivo studies in rabbits available for evaluation of this endpoint. Since the results of the studies are not totally consistent, a weight of evidence approach has been used for assessment of this endpoint.

In a GLP study (Roth, 2000) following the OECD guideline 404 (Rel 1) using 3 rabbits, mean scores for 24/48/72 hours were 1.66 for erythema and 0.66 for oedema. The individual erythema values were 0.00, 2.66 and 2.33. On the basis of the erythema results from two rabbits, the study concluded that TBEP was irritating to the skin.

In a Draize test (Picirillo, 1981) (Rel 2) using 6 rabbits exposed for 24 hours, no oedema was reported. The maximum individual erythema score at 24 or 72 hours was 2. The primary irritation index of 1.1 gave the conclusion that TBEP was a mild irritant. In two other studies using a similar protocol (Wolfe, 1979; Gabriel, 1980) (Rel 2) no oedema was reported and only one of six rabbits showed very slight (score 1) erythema at 24 and 72 hours. The primary irritation index in each study was 0.21. In a third study using a similar protocol (Bullock, 1972), thePDIIwas higher (3.17), however the mean score excluding abraded sites was 1.42 (mild irritant).

In a DOT corrosion study (Lewis, 1981) (Rel 2), no oedema was reported and only one out of six rabbits showed very slight (score 1) erythema at 48 hours, resolved by 7 days.

Overall, the studies demonstrate that TBEP has no corrosive properties. It is at least mildly and at most moderately irritating to rabbit skin. The available studies are considered sufficient to fulfill this endpoint.

Eye irritation:

In a GLP study (Roth, 2000) following the OECD guideline 405 (Rel 1) using 3 rabbits, mean scores for 24/28/72 hours were 1.89 for conjunctival redness, 1.56 for conjunctival chemosis, 0.67 for corneal opacity and 0.22 for iritis. On the basis of these results, the study concluded that TBEP was not irritating to the eye.

In a Draize test (Picirillo, 1981) (Rel 2) using 6 rabbits, no corneal opacity was reported. Total mean scores at each observation time were 3.1 (24h); 1.8 (48h); 1.1 (72h); 0.8 (96h); 0.8 (7days). In another study using a similar protocol (Wolfe, 1979) (Rel 2) no corneal opacity or iritis was reported. Total mean scores were: 2.3 (24h); 0.3 (48h) and 0 (72h). For both these studies it was concluded that TBEP was a mild eye irritant. No irritation was reported in a further study (Gabriel, 1980).

All these studies demonstrate that TBEP is not a significant eye irritant. The available studies are sufficient to fulfil this endpoint.

Respiratory Irritation.

There are no data indicating that TBEP is irritating to the respiratory system.


Effects on skin irritation/corrosion: slightly irritating

Effects on eye irritation: slightly irritating

Justification for classification or non-classification

Skin:

The threshold for classification of a substance as irritating to the skin according to the criteria ofAnnex VI Directive 67/748/EEC(R38) is overall mean score for ethythema or oedema at 24/48/72 hours ≥ 2 or mean score for 2/3 animals for 24/48/72 hours ≥ 2. According to the criteria ofEU/GHS the threshold for Irritant Cat. 2 is mean score for 2/3 animals for 24/48/72 hours ≥ 2.3.

 Although the most recent GLP-compliant study concluded TBEP as irritating to skin, the result was close to the classification threshold, particularly by GHS criteria. The results of three older studies for which the exposure time was 24 rather than 4 hours all reported TBEP as a mild irritant, clearly not fulfilling the criteria for classification.

 Taking the results of these studies together, the weight of evidence indicates that TBEP has some potential for skin irritation, but insufficient to require classification for this endpoint.

 TBEP is therefore not classified for skin irritation according to the criteria of Annex VI Directive 67/748/EECor EU GHS.

 

Eye:

The threshold for classification of a substance as irritating to the eye according to the criteria ofAnnex VI Directive 67/748/EEC(R36) is mean score 24/48/72 hours is ≥ 2 for corneal opacity, ≥ 1 for iritis, ≥ 2.5 for conjunctival redness and ≥ 2 for conjunctival oedema. According to the criteria ofEU/GHS the threshold for Irritant Cat. 2 is mean score for 2/3 animals for 24/48/72 hours ≥ 1 for corneal opacity or iritis, or ≥ 2 for conjunctival redness or oedema.

 The scores for TBEP in the key and supporting studies are below the thresholds for all these criteria.

 TBEP is therefore not classified for eye irritation according to the criteria of Annex VI Directive 67/748/EECor EU GHS.

Respiratory System:

There are no data indicating that TBEP is irritating to the respiratory system.

TBEP is therefore not classified for respiratory irritation according to the criteria of Annex VI Directive 67/748/EECor EU GHS.