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Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vitro
Remarks:
in silico
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Study period:
Not applicable
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: OECD agreed method. No explicit domain available.
Justification for type of information:
QSAR prediction: migrated from IUCLID 5.6
Qualifier:
according to guideline
Guideline:
other: REACH guidance on QSARs R.6, May 2008
Principles of method if other than guideline:
Danish EPA DB was used, via the OECD QSAR Toolbox (v.3.0), to predict whether diisodecyl sebacate is a skin sensitiser from its chemical
structure
GLP compliance:
no
Remarks:
Not required
Key result
Remarks on result:
no indication of skin sensitisation
Remarks:
QSAR produced qualitative result

No explicit domain available. Predictions and domain results are pre-calculated and stored in database.
In domain.

In an MC4PC five-fold 2 * 50 % cross-validation performed on this model by DK National Food Institute:

Sensitivity was 69.9%

Specificity was 95.4%

Concordance was 90.7%

Interpretation of results:
other: Negative
Remarks:
Criteria used for interpretation of results: other: QSAR method
Conclusions:
Diisodecyl sebacate was not predicted to be a skin sensitiser by the Danish EPA DB, used via the OECD QSAR Toolbox (v.3.0).
Executive summary:

The potential for diisodecyl sebacate (DIDS) to act as a skin sensitiser was assessed using the Danish EPA DB, via the OECD QSAR Toolbox (v.3.0) (OECD, 2012).

From its structure, DIDS was not expected to be a skin sensitiser.

The REACH guidance suggests that QSAR results may be considered for this endpoint as part of an integrated testing strategy (ECHA, 2012a).

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

No relevant data on the potential for DIDS to cause skin sensitisation were identified in humans or laboratory animals.

DIDS was predicted not to be a skin sensitiser from its structure using the Danish EPA DB model via the OECD QSAR Toolbox (v.3.0). Additionally, no structural alerts for protein binding were identified (by OASIS v.1.1 or OECD) (OECD, 2012).

Relevant read-across data:

A lack of strong skin sensitising potential was seen for DIDA in a pre-GLP study similar to guideline studies. Four guinea pigs given three daily undiluted applications exhibited no reactions indicative of sensitisation when challenged four days later (Conning, 1970).

Reactions indicative of sensitisation were not seen in a limited skin sensitisation study on a group of two to four rabbits treated with undiluted DOS once, then 2-wk later [this study is considered limited due to the single induction application and the small number of animals tested]. In humans, DOS produced no reactions indicative of sensitisation when applied neat to the skin of 15-30 subjects for 48 hr, then again 2 wk later [again, this study is limited as only a single induction application] (Mallette and Von Haam, 1952a,b).

References

Mallette FS and von Haam E (1952). Studies on the toxicity and skin effects of compounds used in the rubber and plastics industries. I. Accelerators, activators, and antioxidants. AMA Archives of Industrial Hygiene and Occupational Medicine 5, 311-317.

Mallette FS and von Haam E (1952b). Studies on the toxicity and skin effects of compounds used in the rubber and plastics industries. II. Plasticizers. AMA Archives of Industrial Hygiene and Occupational Medicine 6, 231-236.


Migrated from Short description of key information:
No relevant data on the potential for DIDS to cause skin sensitisation were identified in humans or laboratory animals. No skin sensitising potential was predicted for DIDS in the OECD Toolbox (OECD, 2012) and a lack of strong skin sensitising potential was seen for DIDA in a limited guinea pig maximisation test (Conning, 1970). Limited in vivo studies on DOS (including in human subjects) also suggest a lack of skin sensitising potential.

Justification for selection of skin sensitisation endpoint:
No test data available on DIDS, but reliable predictions.

Respiratory sensitisation

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

No relevant data on the potential for DIDS to cause respiratory sensitisation were identified in humans or laboratory animals. However, DIDS is not expected to be a respiratory sensitiser based on its lack of skin sensitising potential. In addition, DIDS is unlikely to vaporise due to its low volatility and high boiling point, limiting the possibility for respiratory exposure during normal conditions of use.

The lack of skin sensitisation potential predicted for DIDS, and seen in a limited guinea pig maximisation study with DIDA, along with their low volatility suggests that such effects are unlikely to occur.


Migrated from Short description of key information:
No relevant data on the potential for DIDS to cause respiratory sensitisation were identified in humans or laboratory animals. The lack of skin sensitisation potential predicted for DIDS, and seen in a limited guinea pig maximisation study with DIDA, along with their low volatility suggests that such effects are unlikely to occur.

Justification for classification or non-classification

DIDS was predicted not to be a sensitiser in the QSAR analysis, and limited in vivo studies with DIDA and DOS indicate that these closely-related substances lack strong sensitising potential. On this basis, DIDS does not warrant classification as a skin or respiratory sensitiser according to the EU CLP or DSD criteria.