1,4-dichloro-5,8-dihydroxyanthraquinone

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation, other

Type of information:

other: indicative assessment based on non-testing methods: QSAR, physical-chemical data, toxicological data

Adequacy of study:

other information

Data source

Reference

Reference Type:

other company data

Title:

Unnamed

Report date:

2018

Materials and methods

Principles of method if other than guideline:

Indicative assessment of potential skin sensitizing properties based on non-testing methods

Test material

Test material information

Constituent 1

Reference substance name:

1,4-dichloro-5,8-dihydroxyanthraquinone

EC Number:

220-599-4

EC Name:

1,4-dichloro-5,8-dihydroxyanthraquinone

Cas Number:

2832-30-6

Molecular formula:

C14H6Cl2O4

IUPAC Name:

1,4-dichloro-5,8-dihydroxy-9,10-dihydroanthracene-9,10-dione

Results and discussion

Any other information on results incl. tables

This indicative assessment of potential skin sensitizing properties is based on the physico-chemical properties of the substance, on Structure Activity Relationship information, and on available toxicological data. Experimental studies and/or animal studies have not been performed for this assessment.

1,4-Dichloro-5,8-dihydroxyanthraquinone shall be registered under REACH as on-site isolated intermediate (Article 17).

Substance specific and physico-chemical data provided by LANXESS:

The chlorinated anthraquinone is a red-brown solid with a molecular weight of 309 g/mole. The substance has a very low water solubility of <0.4 mg/L and a log Pow (octanol/water) of +5.23 was estimated via EPI-Suite (version 4.11). Based on these physical-chemical parameters dermal absorption is expected to be low (ECHA Guidance on Information Requirements, Chapter R7c, 2017).

Toxicological data:

The substance was shown to be not harmful after single oral uptake of high doses and only slightly irritating to rabbit’s skin and eyes. No skin irritating or skin sensitizing effects were reported in occupational settings. The substance exerted no mutagenic properties in an Ames test in Salmonella typhimurium.

In silico data:

As in silico tools for the prediction of skin sensitization the QSAR OECD Toolbox 4.0 was used. The outcome of the mechanistic/endpoint relevant profilers for skin sensitization potential is:

Protein binding alerts:

An alert for Schiff base formation was identified for 1,4-dichloro-5,8-dihydroxyanthraquinone. No protein binding was identified by the OECD Toolbox.

Protein binding potency:

not possible to classify (Remark: It could be noted that the protein-binding potency profiler only predicts the reactivity quantitatively if the protein-binding mechanism is of Michael addition-type or Nucleophilic substitution type 2.)

Specific profilers for protein binding:

No activity in the Direct Peptide Reactivity assay with regard to lysine peptide depletion and no h-CLAT activity was foreseen. With regard to DPRA Cysteine depletion the substance is out of mechanistic domain. However, for keratinocyte gene expression a very high activity was predicted.

The absence of an electrophilic (DNA-reactive) potential of 1,4-dichloro-5,8-dihydroxyanthraquinone was shown in two bacterial mutagenicity tests with negative outcome.

Discussion and conclusion:

This indicative assessment of skin sensitizing properties is based on physico-chemical, toxicological, and in silico data. Experimental studies have not been performed for this endpoint.

The substance is of low acute oral toxicity in vivo and is only slightly irritating to rabbit’s skin. In occupational settings no skin effects as skin irritation or skin sensitization were reported. The substance showed no electrophilicity in two Ames tests in vitro.

There are some inconsistent and thus equivocal results for the substance with regard to potential skin sensitization profilers in silico. However, the physico-chemical properties of the substance (solid, very low solubility in water, log Pow >5) do not indicate a relevant dermal absorption potential. There is also no relevant skin irritation potential that would facilitate penetration through the stratum corneum.

In conclusion, the limited available information with special emphasis on the physico-chemical data in this indicative evaluation does not point to a relevant skin sensitization potential in vivo.

Applicant's summary and conclusion

Conclusions:

In conclusion, the limited available information with special emphasis on the physico-chemical data in this indicative evaluation does not point to a relevant skin sensitization potential in vivo.