Registration Dossier

Administrative data

Description of key information

Skin irritation: according to the criteria established for Primary Irritation Index, 1,4-Benzenediamine, N,N'-mixed Ph and tolyl derivs. is rated “slight irritant”.
Eye irritation: according to the results of the acute eye irritation test, the 1,4-Benzenediamine, N,N'-mixed Ph and tolyl derivs. was not found irritating to the eye.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

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

Additional information

Skin irritation

2 Skin irritation studies in rabbits were available for assessment. Both studies were performed according to GLP and internationally accepted guidelines. The study by Merriman (1995) was chosen as the key study, since in this study slight signs of irritation were noted, whereas the study by Bomhard and Martins (1990) did not show any signs of skin irritation.

1,4-Benzenediamine, N,N'-mixed Ph and tolyl derivs. was subjected to a dermal irritation assessment consistent with methods described by OECD and EPA. Following application of undissolved test chemical to rabbit skin sites for a period of 4 hrs under semi-occlusive dressing, scoring for signs of irritation were made at 1, 24, 48, & 72 hrs following removal of residual chemical. The scoring system used was based upon the Draize method. Only signs of slight erythema were observed. According to criteria established for Primary Irritation Index, the chemical is rated "slight irritant", though not to such a level as to trigger classification under CLP.

Eye irritation

The key study was performed with 1,4 -benzenediamine, N,N'-mixed Ph and tolyl derivs. according to the OECD 405 test guideline. In the study the test material was not irritating to the eye (exposure period 24h). Some slight conjunctivitis was only observed 1h after application at all three animals. By day 21, all animals were free of irritation signs. The mild and transient reactions of the mucous membranes immediately following exposure of the solid test substance into the eye are considered as mechanically induced effects.

Respiratory irritation

No data regarding respiratory irritation are available for 1,4-benzenediamine, N,N'-mixed Ph and tolyl derivs. As the irritating properties of this substance when administered via the oral or dermal route are very limited, it can be assumed that the respiratory irritation potential of the substance would be likewise. Moreover, as this multi-constituent substance has a very low vapour pressure and virtually no particles of inhalable size, exposure via the respiratory route is not likely.


Effects on skin irritation/corrosion: slightly irritating

Justification for classification or non-classification

Skin irritation

In the key study used for classification and labelling (Merriman, 1995) 6 rabbits were used instead of 3. As a consequence, the “Guidance on the Application of Regulation (EC) No 1272/2008” prescribes in section 3.2.2.3.2.2 that two approaches for evaluation of the irritation effects should be used and compared in order to use the more stringent result.

Approach 1 is based on the arithmetic mean value of all animals. According to the test results, the arithmetic mean after 24/48/72 hours for erythema is below 0.5. As no signs of oedema were noted, the arithmetic mean for this effect is 0. Both values are below 2.3, i.e. no classification is warranted with regard to skin irritation.

Approach 2 is based on the average score per animal. According to the test results, the average score per animal is below 1 in all cases for erythema, and 0 for oedema. The cut-off value of 2.3 is reached for none of the test animals, i.e. no classification is warranted with regard to skin irritation.

It can thus be concluded from both approaches that 1,4-Benzenediamine, N,N'-mixed Ph and tolyl derivs. should not be classified as skin irritant according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

When comparing the recorded effects for erythema and oedema to the criteria specified in Directive 67/548/EEC (Dangerous Substances Directive), none of the 3 criteria (mean scores ≥ 2.3 or persisting inflammation, or very definite positive effect in a single animal) is fulfilled. As a consequence, classification of 1,4-benzenediamine, N,N'-mixed Ph and tolyl derivs. as corrosive or irritant to the skin is not deemed necessary.

Eye irritation

The mean scores per animal following grading at 24, 48 and 72 hours are in all cases below the cut-off values as defined in the criteria for reversible effects on the eye (Category 2). The mean values per animal for corneal opacity, iritis and conjunctival oedema are 0. The mean value for conjunctival redness is below 0.5 for all of the animals. As a consequence, no classification is warranted with regard to eye irritation category 2 of EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

When comparing the observed effects with the criteria specified in Directive 67/548/EEC (Dangerous Substances Directive), it can be concluded that these criteria (irreversible effects in at least one animal and/or a positive response in at least 2 of 3 tested animals of ≥ 3 for corneal opacity and/or > 1.5 for iritis) are not fulfilled. As a consequence, classifcation of 1,4-benzenediamine, N,N'-mixed Ph and tolyl derivs. as irritating to the eye is not deemed necessary.