3,4,5,6-tetrachloro-2-(1,4,5,8-tetrabromo-6-hydroxy-3-oxoxanthen-9-yl)benzoic acid

Endpoint summary

Description of key information

Skin sensitisation:

The sensitization potential of D&C Red 28 was determined by performing patch tests on humans.9 patients were tested with the dye. No reactions were reported by all the patients. Thus, according to the CLP classification criteria the substance 3,4,5,6-tetrachloro-2-(1,4,5,8 -tetrabromo-6-hydroxy-3-oxoxanthen-9-yl)benzoic acid (D&C Red 28) can be considered as a non- sensitizer in humans.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

Data is from peer-reviewed journal

Qualifier:

no guideline available

Principles of method if other than guideline:

The sensitization potential of D&C Red 28 was determined by performing patch test on humans.

GLP compliance:

not specified

Type of study:

patch test

Justification for non-LLNA method:

not specified

Specific details on test material used for the study:

Name of test material (as cited in study report): D&C Red 28 also known as Phloxine B
Molecular formula: C20H4Br4Cl4O5.2Na
Molecular weight: 829.6388 g/mol
Substance type: Organic
Physical state: Solid

Species:

other: Humans

Strain:

other: Not applicable

Sex:

not specified

Details on test animals and environmental conditions:

no data

Route:

epicutaneous, occlusive

Vehicle:

petrolatum

Concentration / amount:

2% in Petrolatum

Route:

other: no data

Vehicle:

petrolatum

Concentration / amount:

2% in Petrolatum

No. of animals per dose:

9 patients

Details on study design:

OTHER: The dye was applied in Finn Chambers and read first at 2 or (more commonly) 3 days and again at 4–7 days.The reactions of the patients were graded as ?+. + and ++ categories.

Positive control substance(s):

not specified

Key result

Reading:

1st reading

Group:

test chemical

Dose level:

2%

No. with + reactions:

0

Total no. in group:

9

Clinical observations:

non sensitising

Remarks on result:

no indication of skin sensitisation

Table 1:  Patch test results

 

Chemical	No of patients tested	?+	+	++
D&C Red 28 (1% in pet.)	9	0	0	0

Interpretation of results:

other: not sensitising

Conclusions:

The sensitization potential of D&C Red 28 was determined by performing patch tests on humans.9 patients were tested with the dye. No reactions were reported by all the patients. Thus, according to the CLP classification criteria the substance 3,4,5,6-tetrachloro-2-(1,4,5,8 -tetrabromo-6-hydroxy-3-oxoxanthen-9-yl)benzoic acid (D&C Red 28) can be considered as a non- sensitizer in humans.

Executive summary:

The sensitization potential of D&C Red 28 was determined by performing patch tests on humans.  

The dye was applied in Finn Chambers and read first at 2 or (more commonly) 3 days and again at 4–7 days.

The reactions of the patients were graded as ‘?+ ‘ , ‘+’ and ‘++’ categories. 

9 patients were tested with the dye. No reactions were reported by all the patients. 

The substance 3,4,5,6-tetrachloro-2-(1,4,5,8-tetrabromo-6-hydroxy-3-oxoxanthen-9-yl)benzoic acid (D&C Red 28) can be considered as a non- sensitizer in humans.  

The CLP classification for the test chemical is ‘Not Classified’.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin sensitisation:

Various studies has been investigated for the test chemical 3,4,5,6-tetrachloro-2-(1,4,5,8-tetrabromo-6-hydroxy-3-oxoxanthen-9-yl)benzoic acid (CAS Number: 18472-87-2) to observe the potential for skin sensitization to a greater or lesser extent along with the study available on structurally similar read across substance Disodium 2-(2,4,5,7-tetraiodo-6-oxido-3-oxoxanthen-9-yl)benzoate (Erythrosine) (CAS No. 16423-68-0). The studies are summarized as below:

The sensitization potential of D&C Red 28 was determined by performing patch tests on humans.  

The dye was applied in Finn Chambers and read first at 2 or (more commonly) 3 days and again at 4–7 days.

The reactions of the patients were graded as ‘?+ ‘ , ‘+’ and ‘++’ categories. 

9 patients were tested with the dye. No reactions were reported by all the patients. 

The substance 3,4,5,6-tetrachloro-2-(1,4,5,8-tetrabromo-6-hydroxy-3-oxoxanthen-9-yl)benzoic acid (D&C Red 28) can be considered as a non- sensitizer in humans.  

The CLP classification for the test chemical is ‘Not Classified’.

Further, Mouse Local Lymph Node Assay (LLNA) was performed to evaluate the skin sensitizing potential of the test substance 3,4,5,6-tetrachloro-2-(1,4,5,8-tetrabromo-6-hydroxy-3-oxoxanthen-9-yl)benzoic acid (Acid Red 92) (CAS No. 18472-87-2) on female CBA/J mouse.

Acid Red 92 was tested in different concentrations (0.5, 1.5, 3.0, 7.0 % (w/v)) in DMSO (vehicle). On days 0, 1 and 2 the animal received 25 μl of the test item formulation, positive control or vehicle on the dorsal surface of each pinnae. Each dose was tested on one animal group, which consisted of 5 animals.

Morbidity/mortality checks were performed twice daily. Clinical examinations were performed daily. Individual body weights were recorded on days - 1 and 5. All animals were sacrificed on day 5 for assessment of cell proliferation.

No mortality was observed during the study. There were no treatment-related clinical signs. There were no treatment-related effects on body weight or body weight gains. The positive control (p-phenylenediamine) induced a positive response, as it elicited at least a 3 -fold increase in isotope incorporation relative to the vehicle. The mean stimulation index was 3.9 at the concentration of 1%.

The test substance induced a negative response, as it did not elicit at least a 3-fold increase in isotope incorporation relative to the vehicle. The mean stimulation indices were 0.9, 1.3, 1.5 and 1.9 at the concentrations of 0.5 %, 1.5%, 3.0% and 7.0%, respectively.

Based on these results, the test substance 3,4,5,6-tetrachloro-2-(1,4,5,8-tetrabromo-6-hydroxy-3-oxoxanthen-9-yl)benzoic acid (Acid Red 92) (CAS No. 18472-87-2) is not a skin sensitizer under the defined experimental conditions. The experimental conditions used in this study have been stricter than use conditions. Thus, according to CLP criteria it is therefore concluded that 3,4,5,6-tetrachloro-2-(1,4,5,8-tetrabromo-6-hydroxy-3-oxoxanthen-9-yl)benzoic acid (Acid Red 92) (CAS No. 18472-87-2) does not pose a sensitizing risk to consumers when used as intended.

Hence, based on the above mentioned studies for target substance 3,4,5,6-tetrachloro-2-(1,4,5,8-tetrabromo-6-hydroxy-3-oxoxanthen-9-yl)benzoic acid (CAS Number: 18472-87-2), no skin reactions indicative of sensitisation were found. Thus, it infers that 3,4,5,6-tetrachloro-2-(1,4,5,8-tetrabromo-6-hydroxy-3-oxoxanthen-9-yl)benzoic acid (CAS Number: 18472-87-2) is not classified as skin snsitiser as per CLP regulation.

Justification for classification or non-classification

According to Regulation (EC) 1272/2008 and based on the human and animal studies, it is concluded that the substance 3,4,5,6-tetrachloro-2- (1,4,5,8 -tetra bromo-6-hydroxy-3-oxoxanthen-9-yl)benzoic acid (CAS Number: 18472-87-2) is not classified as skin sensitizer.