Dodecanoic acid, ester with 1,2,3-propanetriol

Endpoint summary

Description of key information

Skin sensitisation (read across Buehler, GPMT): not sensitising

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Reference 1

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

23 Mar 1993 - 30 Apr 1993

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

No details on positive control (reliability check) given.

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

(1992)

Deviations:

yes

Remarks:

lack of details on positive control (reliability check) data

GLP compliance:

yes

Type of study:

Buehler test

Justification for non-LLNA method:

The Buehler Test was performed prior to the amendment of Regulation (EC) No 1907/2006 in which the Local Lymph Node Assay is given as the first-choice in vivo study.

Species:

guinea pig

Strain:

other: Dunkin Hartley, Pirbright White Bor: DHPW

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Winkelmann, Borchen, Germany
- Age at study initiation: young adult
- Weight at study initiation: 401 ± 29 g
- Housing: conventional, 5 animals per cage in Makrolon Type IV
- Diet: Ssniff G 4 - Complete feed for guinea pigs (Ssniff, Spezialfutter GmbH, Soest, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

Concentration / amount:

100%

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

Concentration / amount:

100%

No. of animals per dose:

20

Details on study design:

RANGE FINDING TESTS:
A preliminary test was conducted in order to establish a non-irritant test substance concentration which could be used in the main test. Amounts of 0.4 mL of test substance preparations (25, 50 and 75% (w/w) in corn oil) and the undiluted test substance were applied to the skin of 4 animals under occlusive conditions. Exposure duration was 6 h, after which the patches were removed and the areas of application were wiped off with corn oil and a cellulose swab. Dermal reactions were assessed directly after patch removal and 24 and 48 h post-application according to the Draize scoring system for erythema and edema.
The mean erythema and edema scores out of all 4 animals over 6, 24 and 48 h post-application were both 0.0. Thus, no primary dermal irritation was observed on the skin of the treated animals up to a test substance concentration of 100% at any reading time point. Therefore, the main study was performed using the undiluted test substance.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 h
- Test groups: test substance
- Control group: corn oil
- Site: left flank
- Frequency of applications: every 7 days
- Duration: Days 0-14
- Concentrations: 100%

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 28
- Exposure period: 6 h
- Test groups: test substance
- Control group: test substance
- Site: right flank
- Concentrations: 100%
- Evaluation (hr after challenge): 6, 24, 48 and 72 h after application of the test substance.

Positive control substance(s):

not specified

Remarks:

Sensitivity of the guinea pig strain to standard allergens such as 1-chloro-2,4-dinitrobenzene is checked at regular intervals.

Positive control results:

The sensitivity of the guinea pig strain used to reaction and effect of the known sensitiser 1-chloro-2,4-dinitrobenzene was stated to be checked at regular intervals (no further details provided).

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

100%

No. with + reactions:

0

Total no. in group:

10

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

100%

No. with + reactions:

0

Total no. in group:

20

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

100%

No. with + reactions:

0

Total no. in group:

10

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

100%

No. with + reactions:

0

Total no. in group:

20

Group:

positive control

Remarks on result:

not measured/tested

No test substance-related systemic effects were observed in the test or control animals. Body weight development was likewise not affected.

Interpretation of results:

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

Reference 2

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

11 May - 10 Sep 1998

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

adopted in 1992

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Version / remarks:

adopted in 1996

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Ministerium für Umwelt, Raumordnung und Landwirtschaft des Landes Nordrhein-Westfalen, Düsseldorf, Germany

Type of study:

Buehler test

Justification for non-LLNA method:

The Buehler Test was performed prior to the amendment of Regulation (EC) No 1907/2006 in which the Local Lymph Node Assay is given as the first-choice in vivo study.

Species:

guinea pig

Strain:

other: Dunkin-Hartley, Pirbright White Hsd/Poc:DH

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Harlan Winkelmann GmbH, Borchen, Germany.
- Age at study initiation: young adults
- Weight at study initiation: < 500 g
- Housing: maximum 5 animals per cage in Type IV Makrolon cages.
- Diet: Ssniff G 4 diet in pellet form (laboratory standard guinea pig dietdiet, Ssniff Spezialfutter GmbH, Soest, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30-70 (temporary deviations were caused by cleaning the animal room)
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Route:

epicutaneous, occlusive

Vehicle:

petrolatum

Concentration / amount:

50%

Route:

epicutaneous, occlusive

Vehicle:

petrolatum

Concentration / amount:

50%

No. of animals per dose:

10 (controls), 20 (in test groups)

Details on study design:

RANGE FINDING TESTS:
In a preliminary miscibility test, a test substance concentration of 50% (w/w) was determined as the highest concentration which was easily miscible and well applicable.
In a preliminary skin irritation test with 3 female animals, test substance formulations of 10, 20, 30 and 50% were topically applied to the flank under occlusive conditions for 6 h. The maximum non-irritant concentration of 50% was used for challenge.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 h
- Test groups: test substance in vehicle
- Control group: vehicle
- Site: left flank
- Frequency of applications: every 7 days
- Duration: Days 0-14
- Concentrations: 50% test substance in vaseline

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 28
- Exposure period: 6 h
- Test groups: test substance in vehicle and vehicle only
- Control group: test substance in vehicle and vehicle only
- Site: posterior right flank (test substance) and anterior right flank (vehicle)
- Concentrations: 50% test substance in vaseline
- Evaluation (hr after challenge): 24 and 48 h after test substance removal with corn oil.

Challenge controls:

In the 4th week of the test, 3 additional animals (accompanying group), kept under the same conditions, but without treatment, were used to re-determine the maximum non-irritant concentration for the challenge treatment.
This additional determination of the challenge concentration was carried out because it was suspected that the sensitivity of the skin changed as the weight of the animals increased. This ensured that the challenge concentration was determined on animals which had approximately the same weight as the 30 animals in the challenge phase. In this test, the concentrations administered and the experimental conditions corresponded to those of the preliminary test.
The determination of the challenge concentration in the 4th week of the test on 3 untreated animals of the same age led to no signs of dermal irritation in any animal 24 and 48 h post-application of formulations containing 10, 20, 30 and 50% test substance in vehicle.
On the basis of these results and the results of the induction period, the 50% test substance in vehicle was administered for the challenge treatment in the main test.
Since this test was conducted with untreated animals approximately at the same time as the challenge application, it can be considered as a challenge control test.

Positive control substance(s):

yes

Remarks:

α-hexylcinnamaldehyde

Positive control results:

The positive control substance α-hexylcinnamaldehyde (100% induction, 50% challenge concentration) induced positive reactions in 10/20 and 9/20 animals at 24 and 48 h after challenge, respectively. Thus, the reliability criteria for the Buehler test (≥ 15% positive response) were met.

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

induction and challenge: 50%

No. with + reactions:

0

Total no. in group:

10

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

induction and challenge: 50%

No. with + reactions:

0

Total no. in group:

20

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

positive control

Dose level:

induction: 100%; challenge: 50%

No. with + reactions:

10

Total no. in group:

20

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

induction and challenge: 50%

No. with + reactions:

0

Total no. in group:

10

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

induction and challenge: 50%

No. with + reactions:

0

Total no. in group:

20

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

positive control

Dose level:

induction: 100%; challenge: 50%

No. with + reactions:

9

Total no. in group:

20

Interpretation of results:

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

Reference 3

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

12 Nov 1984 - 18 Apr 1985

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

Lack of test material details, no reliability check.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

(1992)

Deviations:

yes

Remarks:

lack of test materials details, no reliability check.

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Deviations:

yes

Remarks:

lack of test materials details, no reliability check.

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

The Guinea Pig Maximisation Test was performed prior to the amendment of Regulation (EC) No 1907/2006 in which the Local Lymph Node Assay is given as the first-choice in vivo study.

Species:

guinea pig

Strain:

other: Pirbright white

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Winkelmann, Borchen, Germany
- Weight at study initiation: 312 g (test group), 303 g (control group)
- Housing: 5 animals per cage in Makrolon Type IV
- Diet: Altromin Diet 3032 DK (Altromin GmbH, Lage, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 50-60
- Photoperiod (hrs dark / hrs light): 12/12

Route:

intradermal and epicutaneous

Vehicle:

other: paraffin oil for intradermal application and vaseline for epicutaneous application

Concentration / amount:

1% for intradermal application and 50% for epicutaneous application

Route:

epicutaneous, occlusive

Vehicle:

other: vaseline

Concentration / amount:

25%

No. of animals per dose:

20

Details on study design:

RANGE FINDING TESTS:
3 preliminary tests were performed with 5 animals each:
Intradermal application with a concentration of 1% of test substance in vaseline induced skin irritation (definite effects, without induction of necrosis). After epidermal application with a concentration of 50% of the test substance in vaseline, this concentration was determined as the minimal irritating concentration. To be able to determine the maximum non-irritating concentration for challenge treatment, intracutaneous injections of 0.1 mL FCA bilaterally of the vertebral column were made. 2 weeks later 25% and 50% test substance concentrations were applied for 24 h under plaster-covering. A concentration of 25% was found to be the maximum non-irritating concentration.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal and epicutaneous, respectively)
- Exposure period: single injection (intradermal) and 48 h (epicutaneous)
- Test groups:
Intradermal (3 pairs of injections):
Injection 1: FCA
Injection 2: test substance in paraffin
Injection 3: test substance in a 1:1 mixture (v/v) FCA
Epicutaneous: test substance in vaseline

- Control group:
Injection 1: FCA
Injection 2: paraffin
Injection 3: parafin in a 1:1 mixture (w/v) FCA
Epicutaneous: vaseline

- Site: shoulder region (intradermal + epicutanous)
- Frequency of applications: every 7 days
- Duration: Days 0-8
- Concentrations: intradermal 1%, epicutaneous 50%

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 20
- Exposure period: 24 h
- Test groups: test substance and vehicle only
- Control group: test substance and vehicle only
- Site: cranial (vehicle) and caudal (test substance)
- Concentrations: 25%
- Evaluation (hr after challenge): 48 and 72

Positive control substance(s):

not specified

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

induction: 0%; challenge: 25%

No. with + reactions:

0

Total no. in group:

20

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

induction: 1%; challenge: 25%

No. with + reactions:

0

Total no. in group:

20

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

induction: 0%; challenge: 25%

No. with + reactions:

0

Total no. in group:

20

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

induction: 1%; challenge: 25%

No. with + reactions:

0

Total no. in group:

20

Group:

positive control

Remarks on result:

not measured/tested

No effects on bodyweight were observed during the study period. After intradermal injection all animals showed the expected reactions for FCA. Intradermal injections of the vehicle paraffin caused reactions as well (no further information). After removal of the epicutaneous induction patch erythemateous reaction was observed being clearly decreased 24 h later. According to the author, individual results were not given in tabulated form, as all skin examinations were negative, both at 24 and 48 h after challenge exposure.

Interpretation of results:

study cannot be used for classification

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information:

No data on the skin sensitisation of Dodecanoic acid, ester with 1,2,3-propanetriol (CAS 37318-95-9) are available. The assessment was therefore based on QSAR modelling and studies conducted with analogue (source) substances as part of a read across approach, which is in accordance with Regulation (EC) No. 1907/2006, Annex XI, 1.5. For each specific endpoint the source substance(s) structurally closest to the target substance is/are chosen for read-across, with due regard to the requirements of adequacy and reliability of the available data. Structural similarities and similarities in properties and/or activities of the source and target substance are the basis of read-across. A detailed justification for the analogue read-across approach is provided in the technical dossier (see IUCLID Section 13).

Skin sensitisation

QSAR predictions

 

CAS 37318-95-9

The potential for Dodecanoic acid, ester with 1,2,3-propanetriol to be a skin sensitiser was predicted in the QSAR OECD Toolbox v3.4 (WoE, 2017). The prediction for skin sensitisation potential in the profiler “Skin sensitisation (Danish EPA DB)” was negative.

 

In vivo

CAS No. 620-67-7

The skin sensitisation potential of Propane-1,2,3-triyl trisheptanoate was studied in female guinea pigs according to the non-adjuvant Buehler method (OECD guideline 406) and under conditions of GLP (WoE, 1993). A preliminary test in 4 animals was performed with the test substance at 25, 50 and 75% (w/w) in corn oil in order to determine a non-irritant concentration for topical application in the main assay. Since no primary irritation was observed at any test concentration after a 6-h exposure, the undiluted test substance was chosen for both the induction and challenge treatment. In the induction phase, the undiluted test substance was applied to the clipped skin of the left flank of 20 animals using an occlusive dressing. The induction phase consisted of three consecutive topical applications for period of 6 h, performed at intervals of 7 days. A control group of 10 animals was treated with corn oil. For the challenge exposure on Day 28, the undiluted test substance was applied for 6 h to the clipped skin of the right flank of all animals. Skin reactions were evaluated 6, 24, 48 and 72 h after application. None of the treated animals of the test and control group showed any symptoms of dermal irritation after the challenge treatment. No test substance-related systemic effects and no effects on body weights were observed in the test or control animals. The regularly performed reliability test with the positive control 1-chloro-2,4-dinitrobenzene showed the expected results. Based on the results, the test material had no skin sensitising effect in guinea pigs under the experimental conditions chosen.

CAS No. 555-43-1

Glycerol tristearate was investigated in male and female guinea pigs in a GLP-conform Buehler test according to OECD guideline 406 (WoE, 1998). In a preliminary skin irritation test with 3 female animals, test substance formulations of 10, 20, 30 and 50% in petrolatum were topically applied to the flank under occlusive conditions for 6 h in order to establish a non-irritant concentration for induction. The concentration for challenge exposure was determined in a further 4-week test on 3 animals using the same concentrations. The maximum non-irritant concentration of 50% was used for topical application in the induction and challenge phase of the main assay. In the induction phase, the test substance at concentrations of 50% in petrolatum was applied to the clipped skin of the left flank of 20 animals using an occlusive dressing. The induction phase consisted of three consecutive topical applications for a period of 6 h each, performed at intervals of 7 days. A control group of 10 animals was treated with the vehicle. For the challenge exposure on Day 28, the test substance at 50% concentration in petrolatum and the vehicle only was applied for 6 h to the clipped skin of the posterior and anterior right flank of all animals, respectively. Skin reactions were evaluated 24 and 48 after application. None of the treated animals of the test and control group showed symptoms of dermal irritation after challenge treatment. No test substance-related systemic effects and no effects on body weights were observed in the test or control animals. The positive control substanceα-hexyl cinnamic aldehyde showed the expected results thereby confirming the reliability of the study. Based on these results and the experimental conditions chosen, the test substance had no skin sensitising effect in guinea pigs.

CAS No. 91845-19-1

The skin sensitising potential of Glycerides, C16-18 and C18-hydroxy mono- and di- was studied in guinea pigs according to the maximisation method (OECD guideline 406) and in compliance with GLP (WoE, 1985). In three preliminary tests, suitable treatment concentrations for the main study were determined in 5 animals. For the intradermal induction, the test substance at concentrations of 1 and 10 % in paraffin was administered by intradermal injection to 5 animals. Based on the induction of moderate irritant effects on the skin but no necrosis, a test substance concentration of 1% in paraffin oil (w/w) was chosen for intradermal injections in the main study. For the epicutaneous induction, the test substance at 25 and 50% in vaseline was applied to the clipped skin of 5 animals for 48 h using an occlusive dressing within the preliminary experiment. Since the 50% concentration of the test substance was sufficient to cause skin irritation, this concentration was selected for topical application in the induction phase of the main experiment. To determine the challenge concentration, intradermal injections with Freund’s adjuvant followed by epicutaneous application of 0.2 g of the test substance at concentrations of 25 and 50% in vaseline were performed in the preliminary test. After 24-h exposure under occlusive conditions, at 50% solution slight erythema was observed on the skin of 2/5 animals. Therefore, the test substance at 25% in Vaseline was chosen for topical application in the challenge phase of the main test. In the induction phase of the main study, intradermal injections of the test substance at 1% in paraffin and/or FCA were made at the clipped test site of 20 females. A control group, consisting of 20 females, was injected with vehicle only and/or FCA. On Day 8, a 48-hour epicutaneous induction treatment with test substance at 50% in vaseline or vehicle only under occlusive conditions was performed in the treated or control animals on the same skin area as for the intradermal injections. On Day 22, the challenge treatment was performed by topical application of the test substance at 25% concentration in vaseline and the vehicle to all animals for 24 h under occlusive conditions. Skin reactions were evaluated 24 and 48 h after the challenge application. During the study no test substance-related clinical signs and no effects on body weight gain were observed. No cutaneous reactions were caused by the challenge treatment with the test substance at 25% in any of the animals of the test and control groups. Therefore, the test substance had no sensitising effect in guinea pigs under the experimental conditions chosen.

 

Conclusion

A weight-of-evidence approach was applied to assess the skin sensitising potential of the target substance Dodecanoic acid, ester with 1,2,3-propanetriol (CAS 37318-95-9). In vivo studies in animals (GPMT and Buehler test) performed with 3 source substances all gave negative results. The OECD QSAR Toolbox did not predict skin sensitising properties for the target substance. Therefore, Dodecanoic acid, ester with 1,2,3-propanetriol is not expected to be skin sensitising.

Justification for classification or non-classification

According to Article 13 of Regulation (EC) No. 1907/2006 "General Requirements for Generation of Information on Intrinsic Properties of substances", information on intrinsic properties of substances may be generated by means other than tests e.g. from information from structurally related substances (grouping or read-across), provided that conditions set out in Annex XI are met. Annex XI, "General rules for adaptation of this standard testing regime set out in Annexes VII to X” states that “substances whose physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity may be considered as a group, or ‘category’ of substances. This avoids the need to test every substance for every endpoint". Since the analogue concept is applied to Dodecanoic acid, ester with 1,2,3-propanetriol (CAS 37318-95-9), data will be generated from data for reference source substance(s) to avoid unnecessary animal testing. Additionally, once the analogue read-across concept is applied, substances will be classified and labelled on this basis.

Therefore, based on 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.