Phenol, isopropylated, phosphate (3:1)

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation

Remarks:

other: in silico

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Study period:

3 June 2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

A DEREK prediction of sensitisation was undertaken by an experienced licensed Llasa user, using the latest version of the DEREK software, Nexus V2.0. All potential isomers of the substance are assessed. The calculation is considered appropriate for the rule base utilised, as the DEREK prediction software is fully audited by the JRC, and has an approved QMRF (see below).

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Cross-reference

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

Materials and methods

Test guideline

Qualifier:

no guideline required

Principles of method if other than guideline:

Derek for Windows assigns various levels of non-numeric likelihood to its predictions ranging from CERTAIN to CONTRADICTED, via PROBABLE, PLAUSIBLE, EQUIVOCAL, DOUBTED, IMPROBABLE, IMPOSSIBLE and OPEN. In the Derek lexicon, PLAUSIBLE indicates that the structure has activated an alert for the endpoint in question. There is sufficient information in the database to support the prediction. EQUIVOCAL – indicates that there is an equal weight of evidence for and against the proposition. OPEN – means that there is no evidence that supports or opposes the proposition.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Phenol, isopropylated, phosphate (3:1)

EC Number:

273-066-3

EC Name:

Phenol, isopropylated, phosphate (3:1)

Cas Number:

68937-41-7

Molecular formula:

CXHYO4P X and Y are variable dependant on the molecular component.

IUPAC Name:

Phenol, isopropylated, phosphate (3:1)

Details on test material:

Not applicable - in silico determination. All possible 27 isomers of the substance where assessed.

In vivo test system

Test animals

Species:

other: Not applicable - in silico modelling

Strain:

other: Not applicable - in silico modelling

Sex:

not specified

Details on test animals and environmental conditions:

Derek for Windows assigns various levels of non-numeric likelihood to its predictions ranging from CERTAIN to CONTRADICTED, via PROBABLE, PLAUSIBLE, EQUIVOCAL, DOUBTED, IMPROBABLE, IMPOSSIBLE and OPEN. In the Derek lexicon, PLAUSIBLE indicates that the structure has activated an alert for the endpoint in question. There is sufficient information in the database to support the prediction. EQUIVOCAL – indicates that there is an equal weight of evidence for and against the proposition. OPEN – means that there is no evidence that supports or opposes the proposition.

Derek Nexus contains over 70 separate alerts for skin sensitisation and a further 8 for photoallegenicity. In 2003, Hulzebos et al stated in a review of Derek for Windows 5.0 (the predecessor of Derek Nexus) that “the accuracy of prediction was around 60% for sensitisation” (Helzebos et al., 2003).

Using a later version of DEREK for Windows a review of a guinea pig archive data for compounds eliciting allergic contact dermatitis and a local lymph node assay (LLNA) data set was conducted. DEREK for windows correctly predicted 82.9% and 73% of the results from the guinea pig and LLNA data (Fedorowicz et al., 2005). New alerts are added each year to Derek software and this indicates increasing accuracy of the software with development of new versions.

Protocol adopted for processing

Knowledge base version: 11_31_05_2011. The default settings were not changed.

Species: Dog, guinea pig, hamster, human, mammal, monkey, mouse, primate, rabbit, rat and rodent

Enpoints searched: Skin sensitization

Processing constraints: The option to perceive tautomers was selected.

Results and discussion

Positive control results:

Not applicable.

Any other information on results incl. tables

Result

 

IPTPP (all isomers)

No alerts triggered for skin sensitization

  

Comment and discussion

Derek for Windows assigns various levels of non-numeric likelihood to its predictions ranging from CERTAIN to CONTRADICTED, via PROBABLE, PLAUSIBLE, EQUIVOCAL, DOUBTED, IMPROBABLE, IMPOSSIBLE and OPEN. In the Derek lexicon, PLAUSIBLE indicates that the structure has activated an alert for the endpoint in question. There is sufficient information in the database to support the prediction. EQUIVOCAL – indicates that there is an equal weight of evidence for and against the proposition. OPEN – means that there is no evidence that supports or opposes the proposition.

 

All isomers of IPTPP were analysed for skin sensitisation using Derek Nexus in a range of mammalian species. The results indicate that IPTPP does not contain any alerts for skin sensitisation.

 

Derek Nexus contains over 70 separate alerts for skin sensitisation and a further 8 for photoallegenicity. In 2003, Hulzeboset alstated in a review of Derek for Windows 5.0 (the predecessor of Derek Nexus) that “the accuracy of prediction was around 60% for sensitisation” (Helzeboset al.,2003).

 

Using a later version of DEREK for Windows a review of a guinea pig archive data for compounds eliciting allergic contact dermatitis and a local lymph node assay (LLNA) data set was conducted. DEREK for windows correctly predicted 82.9% and 73% of the results from the guinea pig and LLNA data (Fedorowiczet al., 2005). New alerts are added each year to Derek software and this indicates increasing accuracy of the software with development of new versions.

  

Conclusion

All isomers of IPTPP were analysed for skin sensitisation using Derek Nexus in a range of mammalian species. The results indicate that isomers of IPTPP do not contain any alerts for skin sensitisation and as such are unlikely to be skin sensitizers. The report is appended below for information.

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

All isomers of IPTPP were analysed for skin sensitisation using Derek Nexus in a range of mammalian species. The results indicate that isomers of IPTPP do not contain any alerts for skin sensitisation and as such are unlikely to be skin sensitizers.

Executive summary:

All isomers of IPTPP were analysed for skin sensitisation using Derek Nexus in a range of mammalian species. The results indicate that IPTPP does not contain any alerts for skin sensitisation.

 

Using a later version of DEREK for Windows a review of a guinea pig archive data for compounds eliciting allergic contact dermatitis and a local lymph node assay (LLNA) data set was conducted. DEREK for windows correctly predicted 82.9% and 73% of the results from the guinea pig and LLNA data (Fedorowiczet al., 2005). New alerts are added each year to Derek software and this indicates increasing accuracy of the software with development of new versions.

The data provided is considered to be substantial supporting evidence of the effects noted in the human exposure studies detailed in section 7.10 below. The substance is not considered to be a sensitiser on the basis of a weight of evidence approach.