Octanoic acid, monoester with 1,2-propanediol

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

All three mein 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 NEGATIVE for Bacterial Mutagenicity.

Link to relevant study records

Reference

Endpoint:

in vitro gene mutation study in bacteria

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:
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

GLP compliance:

no

Type of assay:

other: QSAR

Remarks on result:

no mutagenic potential (based on QSAR/QSPR prediction)

Consensus results for in vitro mutagenicity from statistical-based models with reliability scores, s^+/-, and weighted reliability scores, s^+/-∙w (for details, please refer to appendix)

Model	Pred result (+/-)	s^+/-	Exp result (+/-)	s^+/-·w	Pred result (+/-)	s^+/-	Exp result (+/-)	s^+/-·w
	2-hydroxypropyl octanoate				1,2 propanediol
CASE Ultra	-	1		0.2	-	2		1.2
CAESAR	-	2		1.2	-	3	-	3
ISS	-	3		2.7	-	3		2.7
SarPy	-	2		1.2	-	3	-	3
KNN	-	3		2.7	-	3		2.7
Consensus score Mutagenicity				0.00				0.00
Consensus score Non-Mutagenicity				0.53				1.00
	Propylene glycol 2-caprylate				1,3 propanediol
CASE Ultra	-	3		2.7	-	2	-	3
CAESAR	-	2		1.2	-	3		2.7
ISS	-	3		2.7	-	2		1.2
SarPy	-	2		1.2	-	3		2.7
KNN	-	3		2.7	-	3		2.7
Consensus score Mutagenicity				0.00				0.00
Consensus score Non-Mutagenicity				0.70				1.00
	Propylene-1,2-dioctanoate				Caprylic acid
CASE Ultra	-	3		2.7	-	3	-	3
CAESAR	-	3		2.7	-	3	-	3
ISS	-	3		2.7	-	3		2.7
SarPy	-	3		2.7	-	3	-	3
KNN	-	2		1.2	-	3	-	3
Consensus score Mutagenicity				0.00				0.00
Consensus score Non-Mutagenicity				0.80				1.00

CASE Ultra predictions results and probability values for chromosomal aberration, micronucleus and mouse lymphoma test

	Chromosomal aberrations,in vitro, CHL cell line		Chromosomal aberrations,in vitro, CHO cell line		Micronucleus test,in vivo, mouse		Mouse Lymphoma, activated		Mouse Lymphoma, unactivated
	Result	Prob	Result	Prob	Result	Prob	Result	Prob	Result	Prob
2-hydroxypropyl octanoate	Negative	27.2	Negative	27.6	Negative	32.5	Negative	26.7	Negative	29.4
Propylene glycol 2-caprylate	Negative	27.2	Negative	27.6	Negative	32.5	Negative	26.7	Inconclusive	52.8
Propylene-1,2-dioctanoate	Negative	27.2	Negative	27.6	Negative	32.5	Negative	26.7	Negative	29.4
1,2 propanediol	known Negative	27.2	Negative	27.6	Negative	32.5	Negative	26.7	Inconclusive	52.8
1,3 propanediol	Negative	27.2	Negative	27.6	Negative	32.5	Negative	26.7	Negative	29.4
Caprylic acid	Negative	27.2	Negative	27.6	Negative	32.5	Negative	26.7	Negative	29.4

Result of read-across assessment for mutagenicity with ToxRead

Impurity/Metabolite	Non-mutagenicity score	Mutagenicity score	Read-across assessment
2-hydroxypropyl octanoate	0.95	0.05	Non-mutagenic
Propylene glycol 2-caprylate	0.94	0.06	Non-mutagenic
Propylene-1,2-dioctanoate	1.00	0.00	Non-mutagenic
1,2 propanediol	1.00	0.00	Non-mutagenic
1,3 propanediol	1.00	0.00	Non-mutagenic
Caprylic acid	1.00	0.00	Non-mutagenic

Conclusions:

All components of the substance PGMC are considered to be non-mutagenic

Executive summary:

No alert for mutagenicityin vitroin bacterium was identified for the six query compounds with DEREK and the expert system concluded mutagenicityin vitroin bacterium is INACTIVE (Table2). Moreover, no misclassified or unclassified features were detected which indicates confidence in the predictions.

No expert alerts were identified with the rule-based expert system GT_EXPERT of CASE Ultra and the six query compounds were predicted to be NEGATIVE in the bacterial in vitro mutagenicity test forS. typhimuriumandE. coliassays (Table2).

Rule-based read-across platform ToxRead identified only structural alerts for non-mutagenicity (Table2) and predicted all query compounds to be NON-MUTAGENIC in the Ames mutagenicity test (Table5).

2-hydroxypropyl octanoate, propylene glycol 2-caprylate, propylene-1,2-dioctanoate and 1,2 propanediol have a structural alert forin vivomutagenicity in OECD Toolbox (Table2). Thein vivomutagenicity (micronucleus) alert explores the possibility that a chemical interacts with DNA and/or proteins via non-covalent binding, such as DNA intercalation or groove-binding‎[11]. The percentage of true positives for this alert was low as only 34% of the substances that generate this alert tested positive for this mutagenic pathway (i.e., 55 substances tested positive of the 163 substances with this alert in the original analysis conducted by Benigni et al.‎[12]). In another study 28 structural alerts of the six mutagenicity profiler in OECD Toolbox were found to be too inaccurate to be used as an indicator for mutagenicity, of which “Hacceptor-path3-Hacceptor” in the micronucleus profiler was the highest triggered alert. The positive predictivity of this alert was 30% (i.e. 323 substances tested positive of the 1114 with this alert)‎[13]. Thus, the presence of this alert is not necessarily a strong indicator of effects. In addition, 1,2 propanediol was reported negative in the micronucleus assay‎[14], providing sufficient information to suggest this compound is unlikely to cause mutagenicity through the alert identified by the ISS profiler forin vivomutagenicity. Further, negative prediction results for chromosomal aberration, micronucleus and mouse lymphoma test indicate all query compounds to be not clastogenic and/or aneugenic (Table4). In our expert opinion, the domain of this alert is not well defined and the alert has a very weak support for mutagenicity. That makes the alertof context for the purpose of this investigation and suggests dismissing its finding as insignificant.