Fatty acids, C18-36, esters with ethylene glycol

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
Details in section 13 of IUCLID

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The source and the target substance are both esters of long-chain fatty acids and an alcohol. They are produced in a similar way, but with a slightly different starting materials. When becoming bioavailable, both source and target substances are expected undergo hydrolysis by esterases (lipases)in mammalian species. The uptake after oral administration of long-chain fatty acids after hydrolysis of the esters and their subsequent metabolism is expected to follow a similar pattern to that of dietary fatty acids, mainly associated with β-oxidation to CO2. The alcohol part of the source and the target substance differs with glycerol being the constituent of dietary fats, while ethylene glycol is not. Both alcohols are expected to be taken up via the gastro-intestinal tract, but an effect of ethylene glycol cannot be excluded.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Target: Fatty acids, C18-36 esters with ethylene glycol
Source: glyceryl laurate and glyceryl isostearate (analogue to glycerides Montan wax) , ethylene glycol (hydrolysis product)

3. ANALOGUE APPROACH JUSTIFICATION
No studies on Fatty acids, C18-36 esters with ethylene glycol are available. For glyceryl laurate, glyceryl isostearate and ethylene glycol negative sensitization studies are available that conclude that these substances show no sensitizing properties. The source substances are structural analogues of the target substance and ethylene glycol represents the hydrolysis product that differs from the hydrolysis products of both structural analogues. In addition dermal uptake of the target substance (molecular weight > 500 Da, logKow > 10) is expected to negligible. Therefore the available data
are considered representative for the target substance in a worst case approach. The target substance is considered non-sensitizing to the skin.

4. DATA MATRIX
see section 13

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

read-across source

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1996

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

GLP compliance:

no

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

Data were generated before the LLNA test became available

Species:

guinea pig

Strain:

Hartley

Sex:

female

Route:

intradermal

Vehicle:

other: olive oil/acetone (7/3)

Concentration / amount:

0.2%

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

Concentration / amount:

100%

Day(s)/duration:

not indicated

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

Concentration / amount:

100 µL at 100%

Day(s)/duration:

24 hours

No. of animals per dose:

4

Details on study design:

The test was performed according to the method of Magnusson and Kligman. A total of 19 guinea pigs were used. For sensitization, the solution for injection was prepared by mixing equal volumes of Freund's complete adjuvant and distilled water using two 5-mL glass syringes and stainless-steel syringe connector. The substance was diluted with olive oil and acetone (7: 3 v/v) at concentrations of 0.2% by weight. In the first stage of induction, 50 µL of the formulation was intradermally injected into the back skin near the neck. One week later, as the second stage of induction, a filter paper patch soaked in 0.2 mL (100%) of the formulation was placed onto the shaved back of the guinea pigs. Finally, the pure substance (100 µL and 100% each) were applied to the skin at two sites using an Eppendorf filter paper under a sealed dressing for challenge for 24 hours.

Positive control substance(s):

no

Reading:

1st reading

Group:

test chemical

Dose level:

100%

No. with + reactions:

0

Total no. in group:

4

Remarks on result:

no indication of skin sensitisation

Interpretation of results:

GHS criteria not met

Conclusions:

The substance is not sensitizing in a maximisation test

Cross-reference 2

Reason / purpose for cross-reference:

read-across source

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

not specified

Remarks:

no details provided

Principles of method if other than guideline:

Full title: Final Report of the Amended Safety Assessment of Glyceryl Laurate, Glyceryl Laurate SE, Glyceryl Laurate/Oleate, Glyceryl Adipate, Glyceryl Alginate, Glyceryl Arachidate, Glyceryl Arachidonate, Glyceryl Behenate, Glyceryl Caprate, Glyceryl Caprylate, Glyceryl Caprylate/Caprate, Glyceryl Citrate/Lactate/Linoleate/Oleate, Glyceryl Cocoate, Glyceryl Collagenate, Glyceryl Erucate, Glyceryl Hydrogenated Rosinate, Glyceryl Hydrogenated Soyate, Glyceryl Hydroxystearate, Glyceryl Isopalmitate, Glyceryl Isostearate, Glyceryl Isostearate/Myristate, Glyceryl Isostearates, Glyceryl Lanolate, Glyceryl Linoleate, Glyceryl Linolenate, Glyceryl Montanate, Glyceryl Myristate, Glyceryl lsotridecanoate/Stearate/Adipate, Glyceryl Oleate SE, Glyceryl Oleate/Elaidate, Glyceryl Palmitate, Glyceryl Palmitate/Stearate, Glyceryl Palmitoleate, Glyceryl Pentadecanoate, Glyceryl Polyacrylate, Glyceryl Rosinate, Glyceryl Sesquioleate, Glyceryi/Sorbitol Oleate/Hydroxystearate, Glyceryl Stearate/Acetate, Glyceryl Stearate/Maleate, Glyceryl Tallowate, Glyceryl Thiopropionate, and Glyceryl Undecylenate.

GLP compliance:

no

Type of study:

other: see summary

Justification for non-LLNA method:

Information on these in vivo studies was already available

Specific details on test material used for the study:

no details available

Remarks on result:

no indication of skin sensitisation

Interpretation of results:

GHS criteria not met

Conclusions:

Glyceryl esters of long-term saturated fatty acids are not sensitizing to the skin

Executive summary:

Glyceryl isostearate was evaluated in the maximization test. After induction, ten guinea pigs were challenged with 50% glyceryl isostearate in polyethylene glycol (PEG) and microcrystalline cellulose (MCC). Two additional challenges were also conducted. The first challenge yielded one and two positive reactions (all slight reactions) at 24 and 48 h, respectively. These results were confirmed by reactions observed after the third challenge.

 

The skin sensitization potential of glyceryl laurate was evaluated in the maximization test. Guinea pigs were subjected to four sensitizing injections of 2% glyceryl laurate and then challenged with intradermal injections of 0.8% glyceryl laurate and topical applications of 25% glyceryl laurate. No positive reactions were observed. In another maximization test, skin sensitization was induced in 2 of I 0 guinea pigs challenged with a 10% dilution of 20% glyceryl laurate emulsion. When a second challenge was initiated 7 days after the first, positive reactions were observed in five animals. Positive reactions were also observed in four animals challenged with a 5% dilution of 20% glyceryl laurate emulsion. Because positive reactions were also noted in the control group after the first and second challenge, the results were attributed to skin irritation (but not sensitization) effects of the test substance.

Materials and methods

Test material

Test material information

Constituent 1

Reference substance name:

Fatty acids, C18-36, esters with ethylene glycol

EC Number:

305-673-7

EC Name:

Fatty acids, C18-36, esters with ethylene glycol

Cas Number:

94944-95-3

Molecular formula:

C40H78O4/C70H138O4

IUPAC Name:

Fatty acids, C18-36, esters with ethylene glycol

Test material form:

solid

Results and discussion

In vivo (non-LLNA)

Results

Remarks on result:

not measured/tested

Remarks:

based on read-across

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the information on toxicokinetics and data on analogues and degradation products the substance is considered not sensitizing to the skin.