Registration Dossier

Administrative data

Description of key information

Pigment Red 220 is assessed as having not skin sensitizing potential based on the result of a human patch test study and reliable data from five structual analogues.

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Adequate and reliable experimental data on skin sensistization is available for five disazocondensation red pigments. This consists of overall four LLNA studies, one GPMT and one HRIPT. 

As previously discussed in the section for acute dermal toxicity, the pigments are large and bulky substances for which skin permeability is predicted to be very low or absent which makes a hazard for skin sensitization unlikely. Also, none of the pigment damages the skin via irritation, so that facilited uptake does not need to be considered.

To support the read-across to the non-tested pigments, the OECD QSAR Toolbox v2.3 was used to screen for structural alerts for protein binding. It should be noted that to our experience, the prediction of the OECD QSAR Toolbox overestimates the reactivity in highly conjugated systems. In this case, it identifies the alert “Amides” with the OASIS module and the alert “Acetates” with the OECD module for all disazocondensation red pigments, including the ones which were shown to be non-sensitizing in valid studies. For Pigment Red 220, it identifies in addition the alert of an a-haloalkane (OASIS) or alkyl halide (OECD); however this pigment belongs to the ones that were found to be non sensitising in the LLNA. As all alerts are presented in the proven non-sensitizing disazocondensation red pigments they are considered to be a false alarm. Most importantly, no additional alert was identified for the non-tested substances. Therefore, read-across for skin sensitization is justified.

 

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 sensitzation

 

 

not sensitizing

LLNA

K1

 

not sensitizing

LLNA

K1

not sensitizing

HRIPT

K2

not sensitizing

GMPT

K2

not sensitizing

LLNA

K1

 

 

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

Pigment Red 144 was tested in two Local Lymph Node assays according to GLP (RCC 2007, Synthesia 2009). The study by RCC followed OECD testing guideline 429 without deviations. The study by Synthesia was performed with the non-radioactive version which uses lymph node cell count as the indicator. Animals exposed to test substance showed no pathological skin reactions and no other negative clinical symptoms of intoxication throughout the experiment. There was no significant difference in body weight increment of all groups in comparison to the vehicle control. There were no clinical observations attributable to the treatment with test substance. The test substance showed a tendency to increase ear weight at the highest dose level but not paired with lymph node hyperplasia. Residues of the test substance on the ears caused this increased weight.

 

The study at RCC resulted in simulation indeces of 1.53, 1.43, and 2.37 at concentrations of 2.5, 5, and 10% in dimethylformamide. A pre-test showed that DMF was the best suited solvent and that higher concentrations could not be achieved. No symptoms of local toxicity at the ears of the animals and no systemic findings were observed during the study period. Due to the colour of the test item iritation of the ear skin could both be observed at the mid and high dose. The body weight of the animals, recorded prior to the first application and prior to treatment with 3HTdR, was within the range commonly recorded for animals of this strain and age. Pigment Red 144 is therefore non sensitizing on skin.

 

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

 

Pigment Red 214 was tested in a Local Lymph Node assays according to GLP and OECD testing guideline 429 (RCC 2005). Concentrations of 5, 10, and 15 % (w/v) in acetone/olive oil (4:1) were applied. Higher concentrations were technically not feasible as shown in a pre-test. Simulation indices were 0.9, 0.9, and 1.3 proving absence of a skin senstising potential. No deaths occurred during the study period. No symptoms of local toxicity at the ears of the animals and no systemic findings were observed during the study period. Reddening of the ears could not be determined since the ears were dyed red by the test item. However, no other signs of local irritation such as swelling of the ears could be observed. The body weight of the animals, recorded prior to the 1st application and prior to necropsy, was within the range commonly recorded for animals of this strain and age.

 

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

Pigment Red 220 was studied in a patch test with 200 volunteers in 1974 (FDRL 1974). The test item is described as a composite of two pigments and one of them is Pigment Red 220. The composite was applied at a concentration of 20% onto a patch of 3 x 3 cm with occlusive wrapping. To determine if the test material is capable of irritating the skin of humans under controlled test conditions; and, if so, to classify the test material as a primary irritant, fatiguing agent, and/or sensitizer on the basis of visible clinical responses, the test material was applied under occlusion for a series of effective contact periods of two days duration. The patches were then removed, the contact sites examined, and the reactions, if any, were graded and recorded. The following scoring, system was used to grade skin reactions: 0 = No reactions; 1+ = Slight erythema; 2+ = Marked erythema; 3+ = Marked erythema, edema, with or without a few vesicles; 4+ = Marked erythema, edema, with vesicles and oozing. If no reactions occurred, the test material was re-applied immediately for another forty-eight-hour period, and the cycle repeated for 3 more weeks, so that a series of 8 48-hour applications were completed. A challenge was then performed 2 week later and the skin reaction examined 24 and 48 hours thereafter. Under the test conditions, the test substance tested as a 20% composite, was not capable of eliciting visible skin changes consistent with the criteria deemed characteristic of a primary irritant or sensitizer. It did elicit skin changes consistent with those of a mild fatiguing agent in 1 out of 200 subjects. In the opinion of the investigator this composite material may be considered safe to use in contact with the skin insofar as primary irritation or sensitization is concerned if the conditions of contact do not exceed those of the test procedure.

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

 

Pigment Red 221 was tested in a GLP compliant guinea pig maximization test following OECD testing guideline 406 (Ciba-Geigy Ltd 1986a). A concentration of 1% was used for intradermal application in a sesame oil and saline adjuvant mixture. 30% was used for epidermal application (Induction) in vaseline. For challenge exposure, 10% in vaseline was applied. The test was performed on 10 male and 10 female guinea pigs per group. At the concentration of 10% in vaseline, Pigment Red 221 did neither

induce edema nor erythema reactions after epidermal challenge application and was therefore found to be non skin sensitizing.

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

Pigment Red 242 was tested in a Local Lymph Node assays according to GLP and OECD testing guideline 429 (RCC 2005). Concentrations of 7.5, 15, and 30 % (w/v) in acetone/olive oil (4:1) were applied. Higher concentrations were technically not feasible as shown in a pre-test. Simulation indices were 0.8, 0.7, and 0.5 proving absence of a skin sensitising potential.

 


Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

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 sensitization under Regulation (EC) No. 1272/2008.