Reaction products of tetrabromophthalic anhydride with 2,2'-oxydiethanol and methyloxirane

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation, other

Remarks:

QSAR

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

accepted calculation method

Justification for type of information:

1. SOFTWARE: OECD QSAR Toolbox

2. MODEL (incl. version number): 4.2

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
CAS: 20566-35-2, Smiles: CC(O)COC(=O)c1c(Br)c(Br)c(Br)c(Br)c1C(=O)OCCOCCO
4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL . QMRF attached.
- Defined endpoint: skin sensitization
- Unambiguous algorithm: Read across analysis takes highest value from nearest 5 neighbours
- Defined domain of applicability: within applicability domain for all criteria log Kow, Ester structural group, protein binding OASIS, chemical elelments analysis, structure similarity subcharacterization.
- Appropriate measures of goodness-of-fit and robustness and predictivity: yes see QMRF
- Mechanistic interpretation: no structural alert

5. APPLICABILITY DOMAIN
- Descriptor domain: log Kow in range of 3.04 to 4.61
- Structural and mechanistic domains: Ester structural group
- Similarity with analogues in the training set: 11 analogs of which 10 negative
- Other considerations (as appropriate): no structural alerts, no protein binding predicted

6. ADEQUACY OF THE RESULT
The result confirms an absence of groups that could react with proteins as the first step of a skin senstization AOP. This substance represents the lowest molecular weight components and thus a worst case assessment. Higher molecular weight components are unlikely to be absorbed through the skin and reach the target layer for skin sensitization.

Data source

Reference

Reference Type:

other company data

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Principles of method if other than guideline:

- Software tool(s) used including version:
- Model(s) used: OECD Toolbox version 4.2
- Model description: see field 'Justification for non-standard information', 'Attached justification'
- Justification of QSAR prediction: see field Justification for type of information', 'Attached justification'.

GLP compliance:

no

Justification for non-LLNA method:

In silico model preferred to animal testing

Test material

Test material information

Constituent 1

Reference substance name:

Reaction products of 3,4,5,6-tetrabromobenzene-1,2-dicarboxylate with 2,2'-oxy-diethanol and 2-epoxypropane

EC Number:

616-436-5

Cas Number:

77098-07-8

Molecular formula:

Ester product of C8 H2 Br4 O4 with C4 H10 O3 and C3 H8 O2 and condensation products, thereof.

IUPAC Name:

Reaction products of 3,4,5,6-tetrabromobenzene-1,2-dicarboxylate with 2,2'-oxy-diethanol and 2-epoxypropane

Test material form:

solid

Specific details on test material used for the study:

OTHER SPECIFICS: lowest molecular weight structural component

Results and discussion

In vitro / in chemico

Results

Key result

Parameter:

other: protein binding and skin sensitization

Remarks on result:

no indication of skin sensitisation

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The QSAR prediction derived from 11 close analogs of which 10 were negative predicts that the chemical is not a skin sensitizer. In addition no protein bindign is predicted by OASIS and no structural alert for skin sensitization is identified. The substance is within the applicability domain of the model for all parameters. Based on this, it can reasonably be concluded that the substance, including higher molecular weight components that are less likely to pass the stratum corneum barrier, is not a skin sensitizer and additional testing is not considered necessary.

Executive summary:

The skin sensitization potential was modeled in silico using OECD Toolbox version 4.2. Due to the complex nature of the UVCB substance the in silico approach using the lower molecualr weight components of the substance seems a reasonable approach for a worst case assessment of the skin snsitizing potential.

The QSAR prediction derived from 11 close analogs of which 10 were negative predicts that the chemical is not a skin sensitizer. In addition no protein binding is predicted by OASIS and no structural alert for skin sensitization is identified. The substance is within the applicability domain of the model for all parameters. Based on this it can reasonably be concluded that the substance including higher molecular weight components that are less likely to pass the stratum corneum barrier is not a skin sensitizer and additional testing is not considered necessary.