3,5-diethyl-1,2-dihydro-1-phenyl-2-propylpyridine

Endpoint summary

Description of key information

No evidence of dermal sensitisation

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation, other

Remarks:

in silico

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Study period:

Dec 2017

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification

Qualifier:

no guideline required

Principles of method if other than guideline:

Validated (Q)SAR of results of an OECD guideline method (LLNA, OECD 429)

GLP compliance:

no

Key result

Parameter:

other: QSAR prediction of LLNA

Remarks on result:

other: positive as a weak sensitiser, negative as a moderate or strong sensitiser

Remarks:

non-quantitative results

QPRFS:

3.2 Algorithm (OECD Principle 2):

 a. Model or submodel name: SKIN_LLNA_W(weak sensitizers (LLNA EC3<100%)

b. Model version: 1.5.2.0.587.500

c. Reference to QMRF:

d. Predicted value (model result): POSITIVE

e. Predicted value (comments): The compound is predicted to be POSITIVE. Possible outcomes are Negative, Marginal, Positive, Inconclusive and Out of Domain. The test chemical is predicted to be positive because positive structural alerts were identified.

3.2 Algorithm (OECD Principle 2):

 a. Model or submodel name:SKIN_LLNA_M(moderate sensitizers (LLNA EC3<10%)

b. Model version:1.5.2.0.189.400

c. Reference to QMRF:

d. Predicted value (model result):NEGATIVE

e. Predicted value (comments):The compound is predicted to be NEGATIVE. Possible outcomes are Negative, Marginal, Positive, Inconclusive and Out of Domain. The test chemical is predicted to be negative because no positive alert was found in it.

3.2 Algorithm (OECD Principle 2):

 a. Model or submodel name: SKIN_LLNA_X(extreme sensitizers (LLNA EC3<1%)

b. Model version: 1.5.2.0.587.600

c. Reference to QMRF:

d. Predicted value (model result): NEGATIVE

e. Predicted value (comments): The compound is predicted to be NEGATIVE. Possible outcomes are Negative, Marginal, Positive, Inconclusive and Out of Domain. The test chemical is predicted to be negative because no positive alert was found in it.

Interpretation of results:

study cannot be used for classification

Conclusions:

The substance was tested in commercial (Q)SAR models, in which the models were differentiated based on their potency: weak (required concentration of the substance is up to 100%), moderate (concentration up to 10%) and extreme (strong, concentration up to 0.1%). The substance was predicted to be a positive in the weak sensitiser model, but non-sensitising in the moderate or extreme sensitiser models.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

The substance was tested using the OECD (Q)SAR toolbox, with a finding of no structural alerts for most dermal sensitisation endpoints.

There are no known substances with similar chemical structure and data available on skin sensitisation or other toxicological findings. In vitro testing for dermal sensitisation for this substance was not feasible, as the log P > 3.5 makes the results of the OECD 442D (KeratinoSense) and OECD 442E (h-CLAT) unable to be interpreted (if negative). The OECD 442C (DPRA) showed a low degree of protein binding to Cys but not to Lys (Fleet, 2018). This substance was then placed in a LLNA protocol, but this was discontinued after animals were unable to tolerate the dose-range finding study. Commercial computer modeling was undertaken, using 3 models for the LLNA based on potency (weak, moderate and extreme), and for allergic contact dermatitis (ACD). The substance was found to be positive for weak sensitisers, consistent with and possibly measuring the same cysteine binding event as in the DPRA. No alerts were found in the models for moderate or extreme sensitisers. The substance was out of the applicability domain of the ACD model. The conclusion is that the substance is not a skin sensitiser.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

As there are no data available on skin sensitisation nor is it technically feasible to generate this data, and given that computer models examining substance substructures fail to produce predictions that the substance would be a dermal sensitiser, the criteria for classification as a skin sensitiser according to Regulation EC No. 1272/2008 are not met and the substance is not classified.