Isooctadecyl pivalate

Endpoint summary

Description of key information

Skin sensitisation (in chemico/in vitro): not sensitising

Skin sensitisation (GPMT): not sensitising (read-across)

Skin sensitisation (QSAR): not sensitising

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Reference 1

Endpoint:

skin sensitisation: in chemico

Remarks:

QSAR prediction

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

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

Principles of method if other than guideline:

Calculation based on OECD QSAR Toolbox v3.3. QSAR prediction of the skin sensitisation potential of the test substance. The presence of protein binding alerts that may indicate a skin sensitising potential is assessed.

GLP compliance:

no

Run / experiment:

other:

Parameter:

other: QSAR prediction

Remarks on result:

no indication of skin sensitisation

The predicted skin sensitisation potential of representative constituents of Isooctadecyl pivalate, assessed as protein binding potential, was modelled in the OECD QSAR Toolbox v3.3. The test substance falls within the model applicability domain for the database OASIS v1.3. No alerts were found.

Therefore, Isooctadecyl pivalate is not expected to have a skin sensitising potential.

Interpretation of results:

other: not predicted to have skin sensitising potential

Conclusions:

The result was negative, however, the result of this QSAR prediction cannot be used on its own for the classification of a substance.

Reference 2

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Remarks:

Summary of available data used for the endpoint assessment of the target substance

Adequacy of study:

weight of evidence

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

50%

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

none

Remarks on result:

other: Source: CAS 163961-32-8

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

75%

No. with + reactions:

1

Total no. in group:

10

Clinical observations:

none

Remarks on result:

other: Source: CAS 163961-32-8

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

50%

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

none

Remarks on result:

other: Source: CAS 163961-32-8

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

75%

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

none

Remarks on result:

other: Source: CAS 163961-32-8

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

50%

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

none

Remarks on result:

other: Source: CAS 163961-32-8

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

75%

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

none

Remarks on result:

other: Source: CAS 163961-32-8

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

50%

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

none

Remarks on result:

other: Source: CAS 163961-32-8

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

75%

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

none

Remarks on result:

other: Source: CAS 163961-32-8

Group:

positive control

Remarks on result:

positive indication of skin sensitisation

Remarks:

Reliability checks had been performed 2 times a year with 10 test and 5 control animals using alpha-hexylcinnamaldehyde and 2-Mercaptobenzothiazole as positive control substances confirming the sensititvity of the used animal strain.

Applying a Weight of Evidence approach, the available results of the Guinea pig maximisation test performed with the source substances CAS 163961-32-8, CAS 110-27-0 and CAS 91031-48-0 were taken into account, respectively. In these studies, no skin sensitising properties were determined.

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008

Conclusions:

Based on the results of the available skin sensitisation study with the source substances CAS 163961-32-8, CAS 110-27-0 and CAS 91031-48-0, no skin sensitising properties were determined. Applying the read-across approach, similar results are expected for the target substance CAS 58958-60-4.

Reference 3

Endpoint:

skin sensitisation: in chemico

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

10 Mar - 10 Apr 2018

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Relative peptide concentration is measured fluorometric ally and not by high-performance liquid chromatography (HPLC) as recommended in the guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 442C (In Chemico Skin Sensitisation: Direct Peptide Reactivity Assay (DPRA))

Version / remarks:

adopted Feb 2015

Deviations:

yes

Remarks:

Relative peptide concentration is measured fluorometric ally and not by high-performance liquid chromatography (HPLC) as recommended in the guideline

GLP compliance:

yes

Type of study:

direct peptide reactivity assay (DPRA)

Details on the study design:

TEST SYSTEM
- Supplier: JPT Peptide Technologies
- Cysteine-containing peptide:
Alternative name: Ac-RFAACAA-OH (Ref. 30793_1)
Batch number: 111016HS_MHe_W0918
Molecular weight: 751.3 g/L
- Lysine-containing peptide:
Alternative name: Ac-RFAAKAA-OH (Ref. 30793_2)
Batch number: 120514HSDW_W0918
Molecular weight: 776.4 g/L

TEST METHOD
The direct peptide reactivity test is proposed to estimate the skin sensitisation potential of a test item by quantifying its reactivity towards proteins using 2 model synthetic peptides containing either cysteine or lysine. The peptide reactivity of the test item is expressed as cysteine and lysine peptide percent depletion values following 24 h incubation with the test item. Relative peptide concentration is measured by spectrofluorometric assay methods.
Cysteine peptide depletion:
- Device: microplate spectrofluorimeter
- Wavelength: 485/535 nm
- Reagent: Sensolyte® 520 Thiol Quantitation Assay "Fluorimetric" kit (AnaSpec Inc.) labeled with a quencher (QXL™520) and a fluorophore 5-FAM
Lysine peptide depletion:
- Device: fluorescence plate reader
- Wavelength: 360/465 nm
- Reagent: fluorescamine

VEHICLE CONTROL
- Substance: isopropanol (lysine) and phosphate buffer pH 7.5 (cysteine)

CONTROLS
Three reference controls were included:
- test item control: wells containing only test item without peptide
- peptide control: wells containing only peptide without test item
- solvent control: wells containing only the solvent of the test item and the peptide, respectively
Standard calibration curve was generated for both peptides:
Peptide standards were prepared in phosphate buffer (pH 7.5) for cysteine peptide and phosphate buffer (pH 10.0) for lysine peptide, using serial dilution standards of the peptide stock solutions (400 µM for cysteine and 200 µM for lysine). A blank with the dilution buffer was also included.

POSITIVE CONTROL
- Substance: cinnamic aldehyde (2 mM); p-phenlylenediamine (2 mM)

TEST SUBSTANCE PREPARATION
The test substance was prepared as a 100 mM preparation in isopropanol (lysine) or phosphate buffer (cysteine). For the assay a 2 mM solution was used for both peptides.

PEPTIDE STOCK SOLUTION PREPARATION
Cysteine-containing peptide:
- Solvent: phosphate buffer (pH 7.5)
- Concentration: 400 µM
Lysine-containing peptide:
- Solvent: isopropanol
- Concentration: 200 µM

INCUBATION CONDITIONS
- Duration of treatment / exposure: 24 h

NUMBER OF REPLICATES
for each peptide in triplicates for treatment and control

EVALUATION CRITERIA
The prediction criteria were chosen according to Jeong et al., Toxicology in vitro 27(2013): 264-271:
A cysteine peptide depletion ≥ 10% is considered to be positive and < 10% is considered to be negative.
A lysine peptide depletion ≥ 20% is considered to be positive and < 20% is considered to be negative.

ACCEPTANCE CRITERIA
The assay is valid if:
- the peptide depletion ratio of the positive control p-phenylenediamine is superior or equal to the cut-off value for both cysteine and lysine peptides;
- the peptide depletion ratio of the positive control cinnamaldehyde is superior or equal to the cut-off value for both cysteine and lysine peptides;
- the linearity of the calibration curve with cysteine and lysine peptides is established (r² > 0.958);
- the mean percent peptide depletion value of the three replicates for the positive control p-phenylenediamine and for the positive control cinnamaldehyde should be within ± 2.5 standard deviations (SD) of the historical mean established by the laboratory for the cysteine peptide and for the lysine peptide;
- the mean peptide concentration of the three replicates for the negative control should be 200 ± 24 μM for the cysteine peptide, and 100 ± 12 μM for the lysine peptide.

Positive control results:

The positive controls p-phenylenediamine and cinnamaldehyde showed high reactivity towards the synthetic peptides. The mean peptide depletion of p-phenylenediamine was 76.5% for the cysteine peptide and 94.3% for the lysine peptide. The mean peptide depletion of cinnamaldehyde was 57.0% for the cysteine peptide and 45.5% for the lysine peptide.

Key result

Run / experiment:

other: cysteine run

Parameter:

other: mean peptide depletion (%)

Value:

0

Vehicle controls validity:

valid

Negative controls validity:

not examined

Positive controls validity:

valid

Remarks on result:

other: unit : %

Key result

Run / experiment:

other: lysine run

Parameter:

other: mean peptide depletion (%)

Value:

12.8

Vehicle controls validity:

valid

Negative controls validity:

not examined

Positive controls validity:

valid

Remarks on result:

other: unit : %

Other effects / acceptance of results:

ACCEPTANCE CRITERIA
- Both positive controls met the acceptance criteria, since the values for mean peptide depletion were higher than the cut-off values for both cysteine and lysine peptides.
- The criteria for linearity of the calibration curve with cysteine and lysine peptides were fulfilled, since r² = 0.9981 for cysteine and r² = 0.9985 for lysine were higher than 0.958.
- The mean percent peptide depletion value of the three replicates for both positive controls were within ± 2.5 SD of the historical mean established by the laboratory for both peptides (please see Table 3 under 'any other information on results incl. tables').

Table 1: Results of the cysteine depletion

	Negative control		p-phenylenediamine		Cinnamaldehyde		Test substance
Cysteine peptide assay	without peptide	with peptide	without peptide	with peptide	without peptide	with peptide	without peptide	with peptide
FI 1	1986	30366	1834	8911	1920	14385	2237	31906
FI 2	1907	31841	1768	8795	1887	14542	2164	31831
FI 3	1933	31067	1775	8255	1899	14339	2185	32251
Mean	1942	31091	1792	8654	1902	14422	2195	31996
SD	40	738	36	350	17	106	38	224
FI corr (FI with peptide - FI without peptide)	-	29149	-	6861	-	12520	-	29801
Peptide depletion (%)	-	-	-	76.5	-	57.0	-	0

FI: fluorescence intensity

Table 2: Results of the lysine depletion

	Negative control		p-phenylenediamine		Cinnamaldehyde		Test substance
Lysine peptide assay	without peptide	with peptide	without peptide	with peptide	without peptide	with peptide	without peptide	with peptide
FI 1	1498	31178	1273	2824	1588	17892	1494	27613
FI 2	1478	31720	1300	3067	1578	17816	1499	27519
FI 3	1500	31403	1280	3039	1546	17989	1483	27698
Mean	1492	31434	1284	2977	1571	17899	1492	27610
SD	12	272	14	133	22	87	8	89
FI corr (FI with peptide - FI without peptide)	-	29942	-	1692	-	16328	-	26118
Peptide depletion (%)	-	-	-	94.3	-	45.5	-	12.8

FI: fluorescence intensity

Table 3: Historical control data

	p-phenylenediamine		cinnamaldehyde
	Cysteine	Lysine	Cysteine	Lysine
mean	67.7	47.4	88.7	94.2
standard deviation	7.68	7.01	6.69	3.17
min	48.5	29.9	71.9	86.3
max	86.9	65.0	105.4	102.1

Interpretation of results:

other: no skin sensitising potential based on the key event "protein reactivity"

Conclusions:

Under the conditions of the test, the test substance showed no reactivity towards selected proteins. The result does not allow for the non-classification or classification as skin sensitiser of the test substance and therefore further evaluation and/or data generation is required.

Reference 4

Endpoint:

skin sensitisation: in vitro

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

18 - 26 Sep 2018

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

other: OECD Guideline 442E (In Vitro Skin Sensitisation: Human Cell Line Activation test (h-CLAT))

Version / remarks:

adopted in Oct 2017

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: ECVAM DB-ALM protocol No. 158

Version / remarks:

2014

Deviations:

no

GLP compliance:

yes

Type of study:

activation of dendritic cells

Details on the study design:

TEST CELL LINE
- Source: THP-1 cells, procured from American Type Culture Collection, Lot No.: 61714305
- Passage number: 14 and 15

CELL CULTURE CONDITIONS
- Type and identity of media: RPMI-1640 with GlutaMAX™-1 and HEPES, and supplemented with 10% fetal bovine serum, 0.05 mM 2-mercaptoethanol and penicillin/streptomycin/amphotericin B
- Temperature (°C): 37 ± 1
- CO2 (%): 5.0 ± 1

CONTROLS
Negative control
- Substance: lactic acid
Vehicle control
- Substance: ethanol
Positive control
- Substance: 4 µg/mL 2,4-dinitrochlorobenzene (DNCB) and nickel sulphate

EXPOSURE CONDITIONS
- Exposure duration: 24 h

TEST CONCENTRATIONS: In the dose range finding assay the following concentrations 0.30, 0.40, 0.53, 0.71, 0.95, 1.27, 1.69, 2.25 and 3 mg/mL were tested to determine the cytotoxic potential of the test substance. Based on the results of the dose range finding assay, the following concentrations 0.48, 0.58, 0.69, 0.83, 1.0 and 1.2 mg/mL were used for the measurement of the expression levels of CD86/CD54.

NUMBER OF REPLICATIONS: triplicate measurements in two independent experiments

CYTOTOXICITY
- Method: Cytotoxicity was determined by measuring direct resazurin reduction
Viability (%) = corrected mean fluorescence intensity (treated wells) / corrected mean fluorescence intensity (control wells)

IMMUNOSTAINING
- Method: After 24 h of exposure with the test substance, the positive or the vehicle control, the cells were stained with anti-human CD86 and anti-human CD54 for 3 h. Thereafter, cells were washed and an alcaline phosphatase-conjugated anti-IgG is added for 2 h. The absorbance of the samples was measured at 405 nm after treatment of the samples with p-nitrophenyl phosphate substrate.
CD86/CD54 (%) = [corrected mean optical density (CD86/CD54) / Viability ] x 100

EVALUATION CRITERIA
Based on CD86/CD54 expression measurement, the aswsay is considered positive if at least one of the following conditions is met, otherwise the assay is considered negative:
- the [CD86(%)] value is equal to or greater than 150% at any tested concentration (with cell viability ≥ 50%).
- the [CD54(%)] value is equal to or greater than 200% at any tested concentration (with cell viability ≥ 50%).

ACCEPTANCE CRITERIA
- the cell viabilities of medium and solvent/vehicle controls are higher than 90%.
- both CD86 and CD54 expression in the positive control are over the positive criteria (CD86(%) ≥ 150 and CD54(%) ≥ 200) and cell viability should be more than 50%.
- the CD86(%) and CD54(%) in the DMSO solvent control does not exceed the positive criteria (CD86(%) ≥ 150 and CD54(%) ≥ 200).
- the cell viability of the test substance at more than four tested doses is ≥ 50%.

Key result

Run / experiment:

other: concentration range from 0.48 mg/mL to 1.2 mg/mL

Parameter:

other: CD86(%)

Value:

82

Vehicle controls validity:

valid

Negative controls validity:

not examined

Positive controls validity:

valid

Remarks on result:

no indication of skin sensitisation

Key result

Run / experiment:

other: concentration range from 0.48 mg/mL to 1.2 mg/mL

Parameter:

other: CD54(%)

Value:

93

Vehicle controls validity:

valid

Negative controls validity:

not examined

Positive controls validity:

valid

Remarks on result:

no indication of skin sensitisation

Other effects / acceptance of results:

ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control:
The cell viabilities of medium and solvent/vehicle controls were > 97%, and thus higher than 90%.
- Acceptance criteria met for positive control:
Both CD86 and CD54 expression in the positive control were 400 and 340%, respectively, and thus are over the positive criteria (CD86(%) ≥ 150 and CD54(%) ≥ 200). The cell viability was 85% and thus more than 50%.

Table 1: Results of the CD86 assay

CD86	Medium control	Vehicle control	Positiv control	0.48 mg/mL	0.58 mg/mL	0.69 mg/mL	0.83 mg/mL	1.00 mg/mL	1.2 mg/mL
Optical density	0.284	0.278	0.767	0.249	0.264	0.268	0.278	0.300	0.311
	0.275	0.277	0.708	0.253	0.267	0.275	0.284	0.309	0.324
	0.299	0.278	0.703	0.244	0.272	0.276	0.287	0.312	0.309
Mean	0.286	0.277	0.726	0.248	0.267	0.273	0.283	0.307	0.315
CD86(%)	100	100	400	82	93	97	102	116	120
Viability (%)	100	100	85	101	102	101	102	101	101

Table 2: Results of the CD54 assay

CD54	Medium control	Vehicle control	Positiv control	0.48 mg/mL	0.58 mg/mL	0.69 mg/mL	0.83 mg/mL	1.00 mg/mL	1.2 mg/mL
Optical density	0.329	0.313	0.762	0.328	0.314	0.320	0.303	0.310	0.322
	0.321	0.328	0.729	0.329	0.323	0.311	0.322	0.317	0.304
	0.306	0.327	0.666	0.330	0.311	0.321	0.305	0.304	0.324
Mean	0.319	0.323	0.719	0.329	0.316	0.317	0.310	0.310	0.317
CD54(%)	100	100	333	102	95	97	93	93	96
Viability (%)	100	100	85	101	102	101	102	101	101

Interpretation of results:

other: no skin sensitising potential based on the key event "activation of dentritic cells"

Conclusions:

Under the conditions of the test, it can be concluded, that the test substance is no sensitiser in the human Cell Line Activation Test (h-CLAT). The result does not allow for the non-classification or classification as skin sensitiser of the test substance and therefore further evaluation and/or data generation is required.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

The skin sensitizing potential of Isooctadecyl pivalate (CAS 58958-60-4) was evaluated in a combination of non-animal methods (in silico, in chemico and in vitro) with the target substance and in vivo data with structurally similar analogue (source) substances. A detailed justification for the analogue read across approach is provided in the technical dossier (see IUCLID section 13).

QSAR predictions:

The potential for Isooctadecyl pivalate to be a skin sensitiser was predicted in the QSAR OECD Toolbox 3.3 (Nordheim, 2016). As only mono-constituents can be used in the prediction model, representative constituents were selected for the UVCB substance Isooctadecyl pivalate. The result for the components is considered to be representative of the target substance. There were no alerts for skin sensitisation potential, estimated based on protein binding potential, in the database OASIS v1.3 (Protein binding alerts for skin sensitization).

In chemico/in vitro

The skin sensitising potential of the test substance was assessed in a Direct Peptide Reactivity Assay performed similar to OECD guideline 442C and in compliance with GLP (BIO-HC, 2018). The peptide reactivity of the test item is expressed as cysteine and lysine peptide percent depletion values following 24 h incubation with the test item. Relative peptide concentration is measured by spectrofluorometric assay methods. Reference controls (solvent, single peptide and single test item solutions) and positive controls (p-phenylenediamine and cinnamaldehyde) were included. The mean depletion was 0% of the cysteine peptide and 12.8% of the lysine peptide. Under the conditions of the test, the test substance showed no reactivity towards the cysteine and the lysine peptide. The result does not allow for the non-classification or classification as skin sensitiser of the test substance and therefore further evaluation and/or data generation is required.

In the in vitro human cell line activation (h-CLAT) study on THP-1 cells, the skin sensitising potential of the test substance was determined similar to OECD 442E and in compliance with GLP (BIO-HC, 2018). Based on the obtained results, the test substance did not increase the expression of cell surface markers CD54 and CD86 associated with the process of activation of monocytes and dendritic cells. Thus, the h-CLAT prediction is considered negative. The result does not allow for the non-classification or classification as skin sensitiser of the test substance and therefore further evaluation and/or data generation is required.

Animal data

CAS 163961-62-8

Fatty acids, C16-18 and C18-unsatd., branched and linear, Bu esters was tested for its skin sensitisation potential in a Guinea pig maximization test according to OECD guideline 406 and under GLP conditions (Safepharm, 2002). In the induction phase of the main study, intradermal injections of the test substance at 1% in arachis oil BP and/or FCA were made in the clipped skin area of 10 Dunkin-Hartley guinea pigs (males). A control group, consisting of 10 males, was injected with vehicle only and/or FCA. On Day 8, a 48-hour epicutaneous induction treatment with undiluted test substance or vehicle only was performed in the treated or control animals on the regions of intradermal injections. On Day 22, the challenge treatment was performed by topical application of the test substance at 50% and 75% concentration in arachis oil BP and the vehicle to all animals for 24 h. Skin reactions were evaluated 24 and 48 h after the challenge application. No test substance-related clinical signs and no effects on body weight gain were observed during the study. Following the challenge, discrete erythema was observed in 1/10 animals in the treatment group during the first reading. The same animal showed desquamation at the challenge site during the second reading. As no erythema was observed during the second reading, the reaction was not considered to indicate skin sensitisation. A reliability check with positive controls was performed by the laboratory 2 times per year with alpha-hexylcinnamaldehyde and 2-Mercaptobenzothiazole, confirming the validity of the test method. The test substance had no sensitising effect in guinea pigs under the experimental conditions.

CAS 110-27-0

A Guinea pig maximisation test was performed with Isopropyl myristate according to OECD guideline 406 (Henkel, 1984). 19 treatment and 15 control animals (Pirbright-Hartley guinea pigs) were induced intradermally with 5% test substance in 2% Carboxymethylcellulose and 0.5% Cremophor on both sides of the spine with and without Freud's complete adjuvant. On Day 8 the 48-h epidermal induction was performed with 5% test substance On Day 22, the challenge treatment was performed by topical application of the test substance at 25% (in 2% Carboxymethylcellulose and 0.5% Cremophor) and the vehicle to all animals for 24 h. Skin reactions were evaluated 24 and 48 h after the challenge application. Following the challenge, no skin effects were observed in any animal. No positive control was included in the study report. The test substance had no sensitising effect in guinea pigs under the experimental conditions. 

CAS 91031-48-0

Fatty acids, C16-18, 2-ethylhexyl esters (CAS 91031-48-0) was tested for its skin sensitisation potential in a Guinea pig maximization test according to OECD guideline 406 and under GLP conditions (CIT, 1991). 20 test and 10 control animals (Dunkin-Hartley guinea pigs) were induced intradermally with the test substance in a 25% dilution in paraffin oil. On Day 7 10% SDS was applied to the test site to induce skin irritation. On Day 8 the epidermal induction was performed with the undiluted test substance, as this concentration was found to be slightly irritating in the range finding test. 12 days after the last induction treatment the animals were challenged with a 50% test substance solution in paraffin oil. 24 and 48 hours after the challenge exposure ended, no indications of a skin sensitising potential of the test substance was observed in any animal. No positive control was included in the study report. The test substance was not skin sensitising under the conditions of this study.

 

Overall conclusion for skin sensitisation

A weight-of-evidence approach was applied to assess the skin sensitising potential of the target substance Isooctadecyl pivalate. The OECD QSAR Toolbox did not predict protein binding indicative for sensitising properties by the constituent 2 and constituent 3 of the target substance. Based on the results of the in chemico/in vitro tests, the target substance showed no reactivity towards the cysteine and the lysine peptide and did not increase the expression of cell surface markers CD54 and CD86. Thus, 2 out of 3 key events were negative and the target substance was considered to be no skin sensitizer. This result is further supported by available data from analogue substances. The GPMT studies performed with three source substances were negative. Taking into account the available information, Isooctadecyl pivalate is not expected to be skin sensitising.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the data on the target substance and the analogue read across approach, the available data on skin sensitisation do not meet the classification criteria according to Regulation (EC) 1272/2008 and are therefore conclusive but not sufficient for classification.