Registration Dossier

Administrative data

Description of key information

Diszazo condensation red pigments were found to be non irritating to rabbit skin and eyes. Studies were performed according to or similar to OECD testing guidelines 404 and 405 and either valid or valid with restrictions. Effects were either absent or clearly below the threshold for classification and labelling.

Key value for chemical safety assessment

Skin irritation / corrosion

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

Eye irritation

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Adequate and reliable experimental data on skin and eye irritation is available for all disazocondensation red pigments with the following two exceptions: A summary report without experimental details is available for Pigment Brown 41 (Sandoz 1975) and Pigment Red 220 was tested at a laboratory which was later sued for having falsified test data.

 

As described in detail below, disazocondensation red pigments caused no adverse findings in studies performed similar to or according to OECD guideline 405. Skin irritation was tested either according to OECD guideline 404 or according to the Draized test with 24h occlusive exposure and shorter observation period and findings were absent or clearly below the threshold for classification and labeling. Findings are consistent with application of the BfR skin and eye irritation rules. It shows that for all pigments, the inclusion rule as an eye irritant are not met and that several rules for exclusion are met (eg molecular weight > 650 Da, MP > 200°C, water solubility < 4 mg/L). As for skin irritation, again several exclusion rules are met. The alert “phenols” is identified, which is a false alarm, as it is included in the inert cromophore and present in all non-irritating pigments. This is used to support the read-across for the two pigments for which no reliable data is available.

 

The following table presents an overview of the available irritation data. A detailed description is given below.

 

PBr 23

PBr 41

PR 144

PR 166

PR 214

PR 220

PR 221

PR 242

PR 262

35869-64-8

68516-75-6

5280-78-4

3905-19-9

40618-31-3

68259-05-2

71566-54-6

52238-92-3

79665-24-0

Mol. weight

850.0

844.5

828.9

794.5

863.4

925.8

925.8

930.5

781.7

Water solubility

(μg /L)

<20

0.5 – 1

11.2

<6.5

6.1

14.2

91

18.9

16.4

n-octanol solubility

(μg /L)

<20

56

21.9

<6.5

17.8

<10

24

41

55.4

Log Pow

 (calculated from solubilities)

n.a.

1.7 - 2.1

0.29

n.a.

0.47

<-0.15

-0.57

0.33

0.53

Skin and eye irritation

not irritating

K2

 not irritating K4

not irritating

K2

not irritating

K2

not irritating

K1

not irritating

K4

not irritating

K2

not irritating

K1

not irritatingK1

Method for skin irritation

Draize

 no data

Draize

Draize

OECD 404

Draize

Draize

OECD 404

OECD 404

Method for eye irritation

Comparable to OECD 405

 no data

Comparable to OECD 405

Comparable to OECD 405

OECD 405

Comparable to OECD 405

Comparable to OECD 405

OECD 405

OECD 405

 

 

 

Pigment Red 262 (CAS 79665-24-0, 782 g/mol)

Pigment Red 262 was evaluated in GLP and OECD 404 and 405 compliant studies in rabbits (RCC 1988). No indication of erythema or erythema was observed on skin. Also, no effects were observed on iris, cornea and conjunctivae. Overall, no adverse signs of toxicity were observed. Pigment Red 262 is not irritating to skin and eyes.

 

Pigment Red 166 (CAS 3905-19-9, 794.5 g/mol)

Pigment Red 166 was tested in two valid studies in rabbits performed prior to the introduction of GLP (Ciba-Geigy Ltd 1975). The eye irritation study procedure was comparable to OECD testing guideline 405. Six animals instead of 3 were used. For 3 animals substance was washed out after 30 seconds, whereas for the remaining animals eyes were not washed. In one study, the observation period was stopped after 72 hours since no effects were seen. In the other study, observations were made for 8 days, but also in this study, no adverse findings on iris, cornea or conjunctivae were noted.

The studies for skin irritation were conducted according to the Draize-Test (1959). In contrast to OECD guideline 404 the Draize-test is done under occlusive conditions, exposure time is 24 hrs, substance is applied to intact and abraded skin, and washing of substance after application is omitted. In one study, a slight to moderate edema with average Draize score of 1 was detected in 3 out of 6 animals after 24 hrs of application for the intact skin. These effects were completely reversible within 72 hrs. Pigment Red 166 is not irritating to skin and eyes.

 

 

Pigment Red 144 (CAS 5280-78-4, 829 g/mol)

Pigment Red 144 was tested in three studies in rabbits (Ciba-Geigy Ltd 1978, MBRL 1978 and HRC 1972/1973).

The eye irritation study procedure was comparable to OECD testing guideline 405. Six animals instead of 3 were used. For 3 animals substance was washed out after 30 seconds, whereas for the remaining animals eyes were not washed. None of the studies showed adverse effects on iris, cornea or conjunctivae.

The skin irritation procedure involved 24h exposure with occlusive wrapping and a three-day observation period. The duration is longer than required by the OECD guideline 404, but the observation period is shorter. The studies were performed prior to the introduction of GLP, but are reported with sufficient detail for evaluation. In two studies, no effects were observed an in one study slight (grade 1) erythyma and edema was observed. Pigment Red 144 is not irritating to skin and eyes.

 

 

 

Pigment Brown 41 (CAS 68516-75-6, 844 g/mol)

No methodical details are available for the experimental data which describes the substance as "non irritating" to rabbit skin and eyes (Sandoz 1975). As described in the beginning of this section, the substance is considered to be non irritating to skin and eyes based on read-across to the other members of the disazocondensation red pigments group. Application of the BfR skin and eye irritation rules show that for all pigments, the inclusion rule as an eye irritant are not met and that several rules for exclusion are met (eg molecular weight > 650 Da, MP > 200°C, water solubility < 4 mg/L). As for skin irritation, again several exclusion rules are met. The alert “phenols” is identified, which is a false alarm, as it is included in the inert cromophore and present in all non-irritating pigments.

 

 

 

Pigment Brown 23 (CAS 35869-64-8, 850 g/mol)

 

Pigment Brown 23 was tested in two valid studies in rabbits (Ciba-Geigy Ltd 1975) that were performed prior to the introduction in GLP. The eye irritation study followed procedures similar to OECD guideline 405. The observation was stopped after 7 days. A redness score of 1 was observed in one animal after 24 hours, but was completely reversible within 48 hours. Cornea and iris were not affected.

The skin irritation procedure involved 24h exposure with occlusive wrapping and a three-day observation period. The duration is longer than required by the OECD guideline 404, but the observation period is shorter. The study was performed prior to the introduction of GLP, but was reported with sufficient detail for evaluation. No erythema formation was observed, neither on intact skin sites nor on the abraded ones. Edema was observed in all but one animals after 24 hours on intact skin sites (one animal with edema score 2 and 4 animals each with edema score 1), and in 4/6 animals at abraded skin sites (one animal with edama score 2 and 3 animals each with edema score 1). The edema formation was completely reversible within 72 hours. Pigment Brown 23 is not irritating to skin and eyes.

 

Pigment Red 214 (CAS 40618-31-3, 863 g/mol)

Pigment Red 214 was evaluated in GLP and OECD 404 and 405 compliant studies in rabbits (RCC 1989). No indication of erythema or erythema was observed on skin. Also, no effects were observed on iris, cornea and conjunctivae. Overall, no adverse signs of toxicity were observed. Absence of irritating properties on skin and in eyes was reported in a poorly documented study (Andrysova 1978). Pigment Red 214 is not irritating to skin and eyes.

 

Pigment Red 220 (CAS 68259-05-2, 926 g/mol)

Pigment Red 220 was studied for skin and eye irritation in a study run at CRO that was known to have falsified study reports (Industrial Bio-Test Laboratories, Inc. 1972). The procedure for the eye irritation study was similar compared to OECD 405, with the following deviations: Only 1- 24-, 72-hour and 7-day scores available, 7-day observation period. Conjunctivae redness was observed in all animals (score 2) after 1 hour, in 4 animals after 24 hours (3 animals with a score of 1 and 1 animal with a score of 2), but was completely reversible within 72 hours. Chemosis was also present in all animals (5 animals with a score of 2 and 1 animal with a score of 1) after 1 hour, but was completely reversible within 24 hours. No cornea or iris reactions were observed. The skin irritation procedure involved 24h exposure with occlusive wrapping and a three-day observation period. The duration is longer than required by the OECD guideline 404, but the observation period is shorter. Slight erythema was observed at the 24h reading which was almost completely resolved at the 72h reading.

As the experimental data cannot be assigned for validity, the substance is considered to be non irritating to skin and eyes based on read-across to the other members of the disazocondensation red pigments group. Application of the BfR skin and eye irritation rules show that for all pigments, the inclusion rule as an eye irritant are not met and that several rules for exclusion are met (eg molecular weight > 650 Da, MP > 200°C, water solubility < 4 mg/L). As for skin irritation, again several exclusion rules are met. The alert “phenols” is identified, which is a false alarm, as it is included in the inert cromophore and present in all non-irritating pigments.

 

 

Pigment Red 221 (CAS 71566-54-6, 926 g/mol)

Pigment Red 221 was tested in a study in rabbits (Ciba-Geigy Ltd 1974) for both skin and eye irritation. The eye irritation study procedures were comparable to OECD testing guideline 405. Six animals instead of 3 were used. For 3 animals substance was washed out after 30 seconds, whereas for the remaining animals eyes were not washed. The study showed adverse no effects on iris, cornea or conjunctivae.

The skin irritation procedure involved 24h exposure with occlusive wrapping and a three-day observation period. A shaved, but intact site and an abraded site were treated. The duration is longer than required by the OECD guideline 404, but the observation period is shorter. The study was not performed under GLP, but is reported with sufficient detail for evaluation. Polyethylene glycol was used as vehicle. No indication of erythema or edema was observed.

Pigment Red 221 is not irritating to skin and eyes.

 

Pigment Red 242 (CAS 52238-92-3, 931 g/mol)

Pigment Red 242 was evaluated in GLP and OECD 404 and 405 compliant studies in rabbits (RCC 1988). No indication of erythema or erythema was observed on skin. Also, no effects were observed on iris, cornea and conjunctivae. Overall, no adverse signs of toxicity were observed. Pigment Red 242 is not irritating to skin and eyes.

 

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for skin or eye irritation under Regulation (EC) No. 1272/2008.