Ethane-1,2-diyl palmitate

Endpoint summary

Description of key information

Skin sensitisation: not sensitising (OECD 406)

The hazard assessment is based on the data currently available. Pursuant to ECHA decision on a compliance check CCH-D-2114546559-35-01/F new studies with the registered substance will be conducted in the future. The finalised studies will be reported in an updated dossier until 22 July 2024 and the hazard assessment will be re-evaluated accordingly.

For further details, please refer to the category concept document attached to the category object (linked under IUCLID section 0.2) showing an overview of the strategy for all substances within the glycol esters category.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Lack of test material details.

Justification for type of information:

Refer to category justification provided in the category object.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

yes

Remarks:

lack of test material details

GLP compliance:

not specified

Type of study:

Buehler test

Justification for non-LLNA method:

A non-LLNA test is available that was performed prior to the current data requirements, stipulated in Regulation (EC) No 1907/2006. In accordance with the same Regulation, the data was included to avoid unnecessary testing.

Species:

guinea pig

Strain:

other: Pirbright

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Lippische Versuchstierzucht Hagemann GmbH&Co. KG, Extertal, Germany
- Weight at study initiation: 269 g
- Housing: Groups of 2 animals in Macrolon Plastic cages III (measuring 14 x 25 x 42 cm) with Saniff bedding.
- Diet: pelleted, Alleindiät für Meerschweinchen (Plange Kraftfutterwerk Soest GmbH, Soest, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 2
- Humidity (%): 45-55
- Photoperiod (hrs dark / hrs light): 12/12

Route:

epicutaneous, occlusive

Vehicle:

water

Concentration / amount:

Preliminary study: 25, 50, 75 and 100%
Main study: 100% (test substance mixed with a few drops of water)

Route:

epicutaneous, occlusive

Vehicle:

water

Concentration / amount:

100% (with a few drops of water)

No. of animals per dose:

10 (controls), 20 (test group)

Details on study design:

RANGE FINDING TESTS:
In a preliminary test with 25, 50, 75 and 100% (w/v) of the test substance in water no irritation was noted after 6 h occlusive exposure. Therefore, the test article was applied as 100% (w/v) in a few drops of dest. water.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 h
- Test groups: test substance in dest. water
- Control group: untreated
- Site: shaved left shoulder
- Frequency of applications: every week
- Duration: Day 0-21
- Concentrations: 100%

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 35
- Exposure period: 6 h
- Test groups: test substance
- Control group: test substance
- Site: shaved right shoulder
- Concentrations: 100%
- Evaluation (hr after challenge): 24, 48 and 72 h

OTHER: 24 h after the challenge all animals were depilated with Pilca Cream (Olivin, Hamburg, Germany).

Positive control substance(s):

no

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

100%

No. with + reactions:

0

Total no. in group:

10

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

100%

No. with + reactions:

0

Total no. in group:

20

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

100%

No. with + reactions:

0

Total no. in group:

10

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

100%

No. with + reactions:

0

Total no. in group:

20

Reading:

other: 3rd reading

Hours after challenge:

72

Group:

negative control

Dose level:

100%

No. with + reactions:

0

Total no. in group:

10

Reading:

other: 3rd reading

Hours after challenge:

72

Group:

test chemical

Dose level:

100%

No. with + reactions:

0

Total no. in group:

20

Group:

positive control

Remarks on result:

other: no information available

The test substance caused no skin reactions in the preliminary and in the main study in any animal during the study period.

Interpretation of results:

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

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

The hazard assessment is based on the data currently available. Pursuant to ECHA decision on a compliance check CCH-D-2114546559-35-01/F new studies with the registered substance will be conducted in the future. The finalised studies will be reported in an updated dossier until 22 July 2024 and the hazard assessment will be re-evaluated accordingly.

For further details, please refer to the category concept document attached to the category object (linked under IUCLID section 0.2) showing an overview of the strategy for all substances within the glycol esters category.

Skin sensitisation

Data Matrix 

CAS #	Skin sensitisation
111-60-4 (b)	Not sensitising
624-03-3 (a)	RA: CAS 627-83-8
627-83-8	Not sensitising
91031-31-1	RA: CAS 627-83-8
151661-88-0	Not sensitising
29059-24-3	Not sensitising
37321-62-3	Not sensitising
68583-51-7	RA: CAS 29059-24-3 RA: CAS 853947-59-8 RA: CAS 37321-62-3
84988-75-0	RA: CAS 627-83-8 RA: CAS 853947-59-8 RA: CAS 29059-24-3
853947-59-8	Not sensitising

(a) Category members subject to registration are indicated in bold font. Only for these substances a full set of experimental results and/or read-across is given.

(b) Substances not subject to registration are indicated in normal font. Lack of data for a given endpoint is indicated by “--“.

CAS 68583-51-7

No studies are available investigating the skin sensitising properties of Decanoic acid, mixed esters with octanoic acid and propylene glycol (CAS No. 68583-51-7). In order to fulfil the standard information requirements set out in Annex VII, 8.3, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006 read-across from the structurally related category members Myristic acid, monoester with propane-1,2-diol (CAS 29059-24-3), Butylene glycol dicaprylate / dicaprate (CAS 853947-59-8) and Dodecanoic acid, ester with 1,2-propanediol (CAS 37321-62-3) was conducted.

The skin sensitising potential of the category members was investigated in Guinea pig maximisation tests according to EU method B.6 (Kästner, 1989) and according to OECD guideline 406 under GLP conditions (Mürmann, 1992a, b).

In the study with Myristic acid, monoester with propane-1,2-diol, a preliminary range finding test was conducted to evaluate the suitable concentrations for the main study for the intradermal injection and the patch testing. In the main study, 20 female Pirbright white guinea pigs were induced with a single intradermal injection of the test substance at 0.1% in Paraffin perliquid DAB 8 and an epicutaneous occlusive application of the test substance at 15% on the shoulder region 7 days later. A negative control group of 20 animals was treated with Paraffin perliquid DAB 8 only. Epicutaneous challenge exposure was conducted 20 days after the first induction for 24 h under occlusive conditions at concentrations of 2.5% and 5% of the test substance, respectively. All test and control animals showed no skin reactions after 24 and 48 h with one exception only. In one control animal, a slight redness of the skin after 48 h was apparent. No positive control data was included in the study report for reliability check (Kästner, 1989). In two studies with Butylene glycol dicaprylate / dicaprate and Dodecanoic acid, ester with 1,2-propanediol by Mürmann (1992a, b) following preliminary range finding tests, male and female Dunkin Hartley guinea pigs (20 in test group, 10 in control group) were induced with a single intradermal injection of the test substance at 10% in maize germ oil MEH56 or corn oil, respectively. Epicutaneous occlusive application of the undiluted test substance was performed 7 days later. The negative control groups were treated with maize germ oil MEH56 or corn oil, respectively. Epicutaneous challenge exposures were conducted 20 days after the first induction for 24 h under occlusive conditions. The undiluted test substance was applied on the right flank and evaluation of skin reactions was carried out 24, 48 and 72 h after application. After intradermal injection of Freund´s adjuvans and test substance or vehicle only, all test and control animals showed severe erythema and oedema after 24 h. After challenge, all test and control animals showed no skin reactions after 24, 48 and 72 h. The sensitivity of the test system was reported to be checked at regular intervals; however, the data were not included in the study reports (Mürmann, 1992a, b).

In summary, based on the available data on the skin sensitisation properties of the category members, it is concluded, that there is no evidence of sensitising properties of Decanoic acid, mixed diesters with octanoic acid and propylene glycol.

CAS 627-83-8

The skin sensitising properties of ethylene distearate were evaluated according to a Buehler test protocol similar to OECD guideline 406 in Hartley guinea pigs (Müller, 1984). The solid test material was mixed with a few drops of water and applied at a concentration of 100% for epidermal induction and challenge. The negative control group was treated with the vehicle only. No positive control data was included in the study report for reliability check. At challenge, the neat test substance induced no skin effects in the test and negative control group. No further skin reactions after induction and challenge were observed.

In addition, a sensitisation study with guinea pigs with limited details is available (Elder, 1982). Two animals were intradermally induced and challenged with 0.1% glycol distearate in a saline solution and showed no skin reactions (Elder, 1982).

In summary, based on the available data, ethylene distearate is not sensitising.

 

CAS 84988-75-0

No studies are available investigating the skin sensitising properties of Fatty acids, C14-18 and C16-18-unsatd., esters with propylene glycol. In order to fulfil the standard information requirements set out in Annex VII, 8.3, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006 read-across from the structurally related category members Myristic acid, monoester with propane-1,2-diol (CAS 29059-24-3), Butylene glycol dicaprylate / dicaprate (CAS 853947-59-8) and ethylene distearate (CAS 627-83-8) was conducted. The studies of the category members are already discussed under the CAS number 68583-51-7 and CAS number 627-83-8.

The available studies investigating the sensitisation properties of the category members consistently showed negative results. Thus, there is no evidence for sensitising properties of Fatty acids, C14-18 and C16-18-unsatd., esters with propylene glycol.

 

CAS 624-03-3

No studies are available investigating the skin sensitising properties of ethane-1,2-diyl palmitate. In order to fulfil the standard information requirements set out in Annex VII, 8.3, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006 read-across from the structurally related category member ethylene distearate (CAS 627-83-8) was conducted. The studies of the category member ethylene distearate are already discussed under the respective CAS number.

The available studies investigating the sensitisation properties of ethylene distearate consistently showed negative results. Based on the available data on skin sensitisation properties of the category member, it is concluded, that there is no evidence for sensitising properties of ethane-1,2-diyl palmitate.

Additional data

In addition, the category members Glycol Stearate (CAS 111-60-4) and Fatty acids, C18 and C18 unsatd. epoxidized, ester with ethylene glycol (CAS 151661-88-0) did not show skin sensitisation properties, as well.

Conclusion for skin sensitisation properties

In conclusion, no skin sensitisation properties of the category members Ethylene distearate (CAS 627-83-8), Myristic acid, monoester with propane-1,2-diol (CAS 29059-24-3), Butylene glycol dicaprylate / dicaprate (CAS 853947-59-8) and Dodecanoic acid, ester with 1,2-propanediol (CAS 37321-62-3) were apparent in several in vivo studies. Altogether, the available data were consistently negative and thus there is no evidence for skin sensitisation properties of any category member of the Glycol Ester group.

 

References

Agency for Toxic Substances and Disease Registry (ATSDR) (1997): Toxicological Profile for Propylene Glycol. US Department of Health and Human Services. Atlanta, US.

Agency for Toxic Substances and Disease Registry (ATSDR) (2010): Toxicological Profile for Ethylene Glycol. US Department of Health and Human Services. Atlanta, US.

Gubicza, L., Kabiri-Badr, A., Keoves, E., Belafi-Bako, K. (2000): Large-scale enzymatic production of natural flavour esters in organic solvent with continuous water removal. Journal of Biotechnology 84(2): 193-196.

Heymann, E. (1980): Carboxylesterases and amidases. In: Jakoby, W.B., Bend, J.R. & Caldwell, J., eds., Enzymatic Basis of Detoxication, 2nd Ed., New York: Academic Press, pp. 291-323.Gubicza, L. et al. (2000). Large-scale enzymatic production of natural flavour esters in organic solvent with continuous water removal. Journal of Biotechnology 84(2): 193-196.

International Programme on Chemical Safety (IPCS) (2001): Ethylene Glycol. Poisons Information Monograph. PIM 227.

Lilja, J. et al. (2005). Esterification of propanoic acid with ethanol, 1-propanol and butanol over a heterogeneous fiber catalyst. Chemical Engineering Journal, 115(1-2): 1-12.

Liu, Y. et al. (2006). A comparison of the esterification of acetic acid with methanol using heterogeneous versus homogeneous acid catalysis. Journal of Catalysis 242: 278-286.

Miller, O.N., Bazzano, G. (1965): Propanediol metabolism and its relation to lactic acid -metabolism. Annals of the New York Academy of Sciences 119, 957-973.

Radzi, S.M. et al. (2005). High performance enzymatic synthesis of oleyl oleate using immobilised lipase from Candida antartica. Electronic Journal of Biotechnology 8: 292-298.

Ritchie, A.D. (1927): Lactic acid in fish and crustacean muscle. Journal of Experimental Biology 4, 327-332.

Stryer, L. (1994): Biochemie. 2nd revised reprint, Heidelberg; Berlin; Oxford: Spektrum Akad. Verlag.

Tocher, D.R. (2003): Metabolism and Functions of Lipids and Fatty Acids in Teleost Fish. Reviews in Fisheries Science 11(2), 107-184.

WHO (2002): Ethylene Glycol: Human Health Aspects. Concise International Chemical Assessment Document 45.

Zhao, Z. (2000). Synthesis of butyl propionate using novel aluminophosphate molecular sieve as catalyst. Journal of Molecular Catalysis 154(1-2): 131-135.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

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 group concept is applied to the members of the Glycol Ester Category, data will be generated from representative reference substance(s) within the category to avoid unnecessary animal testing. Additionally, once the group concept is applied, substances will be classified and labeled on this basis.

Therefore, based on the group concept, all available data on sensitisation do not meet the classification criteria according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.