Citraconic anhydride

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation, other

Remarks:

other: QSAR

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Justification for type of information:

QSAR prediction

Data source

Reference

Reference Type:

other: QSAR

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Software used
OECD QSAR Toolbox v3
DEREK NEXUS 2.0.2

Test material

Test material information

Constituent 1

Reference substance name:

Citraconic anhydride

EC Number:

210-459-0

EC Name:

Citraconic anhydride

Cas Number:

616-02-4

Molecular formula:

C5H4O3

IUPAC Name:

3-methyl-2,5-dihydrofuran-2,5-dione

Results and discussion

Any other information on results incl. tables

The results of the QSAR analysis indicate that

1. Maleic anhydride, benzene-1,2,4-tricarboxylic acid 1,2-anhydride and phthalic anhydride are potential skin and respiratory sensitizers and this agrees with experimental data.

2. Based on the similar profiles for these 4 substances, citraconic anhydride can be classified as skin Skin Sens. 1 H317) and respiratory (Resp. Sens. 1 H334) sensitizer.

Applicant's summary and conclusion

Interpretation of results:

sensitising

Remarks:

Criteria used for interpretation of results: expert judgment

Conclusions:

The results of the QSAR analysis indicate that
1. Maleic anhydride, benzene-1,2,4-tricarboxylic acid 1,2-anhydride and phthalic anhydride are potential skin and respiratory sensitizers and this agrees with experimental data.
2. Based on the similar profiles for these 4 substances, citraconic anhydride can be classified as skin Skin Sens. 1 H317) and respiratory (Resp. Sens. 1 H334) sensitizer.

Executive summary:

Software used

OECD QSAR Toolbox v3

DEREK NEXUS 2.0.2

Methods

Structures were drawn in Marvin Sketch software and used to generate the structure files (.mol) and SMILES codes, which were then checked for correctness and then used as input into the various software packages.

Results and discussion

A summary of the results of the analysis are shown in Table 1 on the next page. Table 2 shows a full human health profile of the four substances from the QSAR Toolbox. In Appendices 1 - 3 an explanation of the mechanisms of action identified in Table 1 is presented. Both QSAR Toolbox and DEREK NEXUS identify structural alerts for skin sensitization for all compounds. DEREK NEXUS identifies alerts for respiratory sensitization for all four compounds. Maleic anhydride, benzene-1,2,4-tricarboxylic acid 1,2-anhydride and phthalic anhydride are REACH Tier I registered substances and are all classified as

Resp. Sens. 1 H334: May cause allergy or asthma symptoms or breathing difficulties if inhaled.

Skin Sens. 1 H317: May cause an allergic skin reaction.

The predictions from the QSAR software agree with the measured data.

To determine whether the measured data from the three anhydrides can be read across to citraconic anhydride, parameters relevant to skin sensitization were compared for the 4 substances. Table 2 (highlighted in yellow) shows similar profiles for organic functional groups, groups of elements, chemical elements, protein binding, substance type and bioavailability (Lipinski). Additionally, Table 1 shows low values for log Kow and Log Kp (skin permeability coefficient). Based on these similar profiles, it can be concluded that experimental data (respiratory and skin sensitization) from these three anhydrides can be read across to citraconic anhydride.

For details see attached report.

Conclusions

The results of the QSAR analysis indicate that

1. Maleic anhydride, benzene-1,2,4-tricarboxylic acid 1,2-anhydride and phthalic anhydride are potential skin and respiratory sensitizers and this agrees with experimental data.

2. Based on the similar profiles for these 4 substances, citraconic anhydride can be classified as skin Skin Sens. 1 H317) and respiratory (Resp. Sens. 1 H334) sensitizer.

References

United Nations Economic Commission for Europe (UNECE). (2004). Globally Harmonized System of Classification and Labelling of Chemicals (GHS). Respiratory or Skin Sensitization, Chapter 3.4. pp. 151-158. Retrieved here Sept. 1, 2007.