Octanoic acid, monoester with 1,2-propanediol

Endpoint summary

Description of key information

All three main components of the substance PGMC, namely 2-hydroxypropyl octanoate, propylene glycol 2-caprylate, propylene-1,2-dioctanoate, 1,2 propanediol, 1,3 propanediol and caprylic acid are considered NON-SENSITISER.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vitro

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

2021

Reliability:

1 (reliable without restriction)

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

Justification for type of information:

1. SOFTWARE
Various tools, inter alia CASE Ultra, DEREK Nexus, OECD Toolbox, ToxRead, Toxtree, VEGA

2. MODEL (incl. version number)

Model Version Approach
CASE Ultra 1.8.0.2 Statistical/Expert
DEREK Nexus 6.0.1 Expert
OECD (Q)SAR Toolbox 4.4.1 Expert/Read-across
ToxRead 0.23beta Read-across
Toxtree 3.1.0 Expert
VEGA 1.1.5_b36 Hybrid

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
Main components of the substance:

1) CCCCCCCC(=O)OCC(C)O
2) CCCCCCCC(=O)OC(C)CO
3) CCCCCCCC(=O)OCC(C)OC(=O)CCCCCCC

Impurities (=educts) of the substance
4) CC(O)CO
5) OCCCO
6) CCCCCCCC(=O)O

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
See attached QMRF/ QPRF Report

5. APPLICABILITY DOMAIN
See attached QMRF/ QPRF Report

6. ADEQUACY OF THE RESULT
See attached QMRF/ QPRF Report

Reason / purpose for cross-reference:

reference to same study

Principles of method if other than guideline:

- Principle of test:, Short description of test conditions, Parameters analysed / observed:
CASE Ultra LLNA
CASE Ultra Non- LLNA
CAESAR
IRFMN/JRC

Consensus score for being sensitizer and non-sensitizer

GLP compliance:

no

Justification for non-LLNA method:

QSAR study

Details of test system:

other: QSAR modelling

Details on the study design:

- Prediction model used:
CASE Ultra LLNA
CASE Ultra Non- LLNA
CAESAR
IRFMN/JRC

Remarks on result:

no indication of skin sensitisation

Remarks:

QSAR prediction

Outcome of the prediction model:

negative [in vitro/in chemico]

Consensus results for skin sensitisation from statistical-based models with reliability score s^+/-and weighted reliability score s^+/-·w (see, appendix) and available study results from training sets of models

Model	Pred result (+/-)	s^+/-	Exp result (+/-)	s^+/-·w	Pred result (+/-)	s^+/-	Exp result (+/-)	s^+/-·w
	2-hydroxypropyl octanoate				1,2 propanediol
CASE Ultra LLNA	-	3		2.7	-	3	-	3
CASE Ultra Non- LLNA	-	2		1.2	-	2	-	3
CAESAR	+	2		1.2	-	3	-	3
IRFMN/JRC	-	2		1.2	-	3	-	3
Consensus score Sensitiser				0.10				0.00
Consensus score Non-Sensitiser				0.43				1.00
	Propylene glycol 2-caprylate				1,3 propanediol
CASE Ultra LLNA	-	3		2.7	-	1		0.2
CASE Ultra Non- LLNA	Inconclusive				-	2		1.2
CAESAR	+	2		1.2	-	3		2.7
IRFMN/JRC	-	2		1.2	+	1		0.2
Consensus score Sensitiser				0.13				0.02
Consensus score Non-Sensitiser				0.43				0.34
	Propylene-1,2-dioctanoate				Caprylic acid
CASE Ultra LLNA	-	2		1.2	Inconclusive
CASE Ultra Non- LLNA	-	1		0.2	-	2	-	3
CAESAR	+	3		2.7	-	3	-	3
IRFMN/JRC	+	3		2.7	-	3	-	3
Consensus score Sensitiser				0.45				0.00
Consensus score Non-Sensitiser				0.12				1.00

Interpretation of results:

GHS criteria not met

Conclusions:

All three main consitutents of PGMC, namely 2-hydroxypropyl octanoate, propylene glycol 2-caprylate, propylene-1,2-dioctanoate, 1,2 propanediol, 1,3 propanediol and caprylic acid are considered NON-SENSITISER. Also all impurities are considered NON-SENSITISER.

Executive summary:

Skin Sensitisation

No alert for skin sensitisation was identified for the six query compounds with DEREK and the expert system concluded skin sensitisation in mammal is NON-SENSITISER (Table2). Moreover, no misclassified or unclassified features were detected which indicates confidence in the predictions.

None of the six query compounds triggered an alert from the protein binding profiler for skin sensitisation in OECD Toolbox. Negative study results for skin sensitisation of 1,2 propanediol, 1,3 propanediol and caprylic acid were included in the OECD Toolbox database. Read-across was performed for 2-hydroxypropyl octanoate, propylene glycol 2-caprylate and propylene-1,2-dioctanoate. According to the profiling result, 2-hydroxypropyl octanoate may act as prohapten with one metabolite triggering a structural alert for ketones which could interact with proteins via nucleophilic addition (see,Figure3). The profiler refers to a 3rd party expert stating that simple ketones are usually too weakly reactive to sensitise unless log K_owis very high and which was taken into account in the TIMES SS model by defining a threshold of log K_ow> 4 for weak skin sensitizers. This is substantiated by the category members used for read-across. All four analogues are likely to be subject of biotic transformation to simple ketones and have a log K_ow< 4, except 2-undecanol which is reported to be a weak sensitiser, while another study result indicates the substance to be not sensitising. This indicates that the log K_owof 2-hydroxypropyl octanoate and its ketone metabolite respectively, is too low to sensitise.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)