Sucrose and glycerol, reaction products with C12-18, C18unsatd. fatty acids

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

01-08-1989 to 03-09-1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Species:

guinea pig

Strain:

other: Pirbright

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Substrain: Bor: DHPW (SPF), white
- Age at study initiation: no data
- Weight at study initiation: 271 - 350 g
- Housing: max. 5 animals in one cage, Macrolon plastic cages IV: 20 cm high, 33 cm width, 55 cm length
- Diet: ad libitum; Ssniff-G (Alleindiät für Meerschweinchen), pellets
- Water: ad libitum; Macrolon drinking bottles, 300 mI, Fa. Becker & Co., 4629 Castrop-Rauxel
- Acclimation period: 7 days at least

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 2
- Humidity (%): 50-85
- Air changes (per hr): no data
- Photoperiod: 12/12 , Fluorescent light, 120 lux

IN-LIFE DATES: From: 01.08 1989 To: 03.09.1989

Route:

intradermal and epicutaneous

Vehicle:

water

Concentration / amount:

Range finding study:
Dermal treatment: 10%, 25%, 50%, 100% in water

Main study:
Intradermal treatment: 10 % in water and 10% in 10 % Freund's Adjuvant complete
Dermal treatment: 50 % in water
Challenge: 10 % in water

Route:

epicutaneous, occlusive

Vehicle:

water

Concentration / amount:

Range finding study:
Dermal treatment: 10%, 25%, 50%, 100% in water

Main study:
Intradermal treatment: 10 % in water and 10% in 10 % Freund's Adjuvant complete
Dermal treatment: 50 % in water
Challenge: 10 % in water

No. of animals per dose:

Range finding:
2 per dose

Main Study:
10/sex

Details on study design:

RANGE FINDING TESTS:
To exclude primary skin irritations two animals/group were treated dermally in a preliminary study under occlusiv conditions (exposure period 24 h) with the following concentrations (each 0.5 (g) ml/animal) of the sampie: 100 % (undiluted), 50%, 25% and 10% in Aqua deion.

MAIN STUDY
A. INDUCTION EXPOSURE
Intradermal treatment (on first day)

- Test groups:
1. 0.1 mL FCA in aqua deion.; 2 (by pairs)
2. 0.1 mL test article (10 %) in aqua deion.; 2 (by pairs)
3. 0.1 mL test article (10 %) in FCA 1:2; 2 (by pairs)

- Control group:
1. 0.1 mL FCA (diluted 1 : 2 in water); 2 (by pairs)
2. 0.1 mL aquq deion.; 2 (by pairs)
3. 0.1 mL aqua deion. (diluted 1 : 2 with FCA); 2 (by pairs)


First dermal treatment (after 7 days)
- Volume: 0.5 mL
- Exposure period: 48 h
- Test groups: 20
- Control group: 20
- Site: first injection were located at the craniodorsal area and the following onces were performed underneath
- Frequency of applications: 1
- Concentrations: 50% in aqua deion.

B. CHALLENGE EXPOSURE (after 22 days)
- No. of exposures: 1
- Day(s) of challenge: 3 weeks after the first intradermal treatment
- Exposure period: 24 h
- Control group: aqua deion.
- Concentrations: 10% in Aqua deion.
- Evaluation (hr after challenge): 24 h, 48 h

Positive control substance(s):

no

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

10%

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

no observations

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: no observations.

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

10%

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

no observations

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: no observations.

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

0%

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

no observations

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: no observations.

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

0%

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

no observations

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: no observations.

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: other: CLP, EU GHS (Regulation (EC) No 1272/2008) and DSD (Directive 67/548/EEC)

Conclusions:

In the study performed according to the method of B. Magnusson and A. M Kligman (OECDguidelines) the test substance GRILLOTEN LSE 65 K BATCH 801 is considered to cause no contact hypersensitivity. According to CLP, EU GHS (Regulation (EC) No 1272/2008) and to DSD (Directive 67/548/EEC), no classification and labelling is required.

Executive summary:

In a dermal sensitisation study performed according to the OECD Guideline 406 (Skin Sensitisation) with Sucroglyceride C12-18, C18unsatd. in water, young adult Pirbright white Guinea Pigs 10/sex were tested using the method of B. Magnusson and A. M Kligman. No positive control data are reported.

No skin reactions were observed in the range finding study or in the main study.

In this study, Sucroglyceride C12-18, C18unsatd. is not a dermal sensitiser.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Assessment of skin sensitisation

 

Key study on the registration substance Sucroglyceride C12-18, C18unsatd. (Evonik, 1989)

In order to assess its potential to cause skin sensitisation, Sucroglyceride C12-18, C18unsatd. was tested in an in vivo study. The test substance is a white waxy solid.

A skin sensitisation study was performed according to the OECD Guideline 406 (Skin Sensitisation), using the method of Magnusson and Kligman in an in vivo model with Pirbright white guinea pigs. In order to examine primary skin irritation, two animals/group were treated dermally in a preliminary study under occlusive conditions (exposure period 24 h) with the following concentrations (each 0.5 (g) mL/animal) of the sample: 100 % (undiluted), 50%, 25% and 10% in water. At 50% and 100%, slight erythema was observed after 24-48 h, at 25% partly very slight erythema was observed at 24 h, at 10% no primary skin irritation was noted.

In the main study, both intradermal and dermal treatment were used for induction. 0.1 mL of 10% solutions of Sucroglyceride C12-18, C18unsatd. were used for intradermal treatment performed both with aqueous solutions and dissolved in 10% Freund's Adjuvant complete. After 7 days, dermal treatment followed with 0.5 mL of a 50% solution of the test substance in water, exposure time 48 h. Group sizes for treated and control groups were 20 animals/group.

Challenge was performed after 3 weeks by topical application of a 10% solution of test substance in water, exposure time 24 h. The scoring system was comparable to the one reported in the current version of the OECD Guideline 406 (dated 17/07/1992) and scoring was performed 24 and 48 h after the challenge.

At both readings, 24 and 48 h, neither the test or the control animals showed any primary skin irritation. Consequently, no re-challenge was necessary.

The erythema scores were 0 for all treated animals at 24-48 h.

The absence of erythema proves that Sucroglyceride C12-18, C18unsatd. is not a skin sensitiser.

 

Supporting study on the read-across substance Sucroglyceride C12 (Evonik, 1989)

The read-across substance Sucroglyceride C12, a structural analogue of the registration substance, was tested in vivo for its skin sensitisation potential. The test substance is a yellowish clear waxy solid.

The study design and the preparation of the test substance were identical to the key study reported above.

At both readings, 24 and 48 h, neither the test or the control animals showed any primary skin irritation. Consequently, no re-challenge was necessary.

The erythema scores were 0 for all treated animals at 24-48 h.

The absence of erythema proves that Sucroglyceride C12 is not a skin sensitiser.

 

Supporting study on the read-across substance Stearic acid, esters with methyl α-D-glucoside (Evonik, 1990)

The read-across substance Stearic acid, esters with methyl α-D-glucoside, a structural analogue of the registration substance, was tested in vivo for its skin sensitisation potential. The test substance is a brown granular powder. Purity is 100%.

In a dermal sensitization study according to the OECD Guideline 406 (Skin Sensitisation) with Stearic acid, esters with methyl α-D-glucoside, Pirbright white guinea pigs were tested using the method of Magnusson and Kligman. Positive control substance was 2,4-Dinitrochlorobenzene.

In order to examine primary skin irritation, in a preliminary study two animals/group were treated intradermally with 5% and then dermally with 25% test substance in water.

In the main study, for intradermal induction a concentration of 5% was used. The test concentration of 25% used for dermal induction was non-irritating. However, 7 days after first intradermal induction the test site was pretreated with 10% sodium laurylsulfat in petrolatum in order to create a local irritation. 24 hours later a 25% dilution of the test substance was applied and covered by occlusive dressing for 48 h. The same non-irritating test substance concentration of 25% was used for challenge procedure.

According to OECD guideline 406, a pretreatment with sodium lauryl sulphate is recommended, if the test substance is not a skin irritant. Thus, it can be assumed that including the pretreatment with the promoter substance sodium lauryl sulphate the induction procedure was sufficient to induce a potential allergic sensitisation reaction and the study is judged as valid.

At challenge no visible changes of the treated skin sites (no erythema and no edema) were observed in test or control animals at any time point.

At both readings, 24 and 48 h, neither the test or the control animals showed any primary skin irritation. Consequently, no re-challenge was necessary.

The erythema scores were 0 for all treated animals at 24-48 h.

The absence of erythema proves that Stearic acid, esters with methyl α-D-glucoside is not a skin sensitiser.

 

Supporting study on the read-across substance Isostearic acid, esters with methyl α-D-glucoside (Evonik, 2009)

The read-across substance Isostearic acid, esters with methyl α-D-glucoside, a structural analogue of the registration substance, was tested in vivo for its skin sensitisation potential. The test substance is a yellow paste. Purity is 100%.

In a dermal sensitisation study according to OECD guideline 406 (Skin Sensitisation) with Isostearic acid, esters with methyl α-D-glucoside, Dunkin-Hartley guinea pigs were tested using the method of Magnusson and Kligman. Positive control substance was 2-Mercaptobenzothiazole.

A pilot study was performed on 4 animals per dose. The intradermal application of the 5%, 3.5% and 2% test substance in sesame oil showed medium reactions, but the 0.5% solution of the test substance in sesame oil elicited a slight reaction. Dermal application without Duhring Chambers of 100% and 75% solutions of the test substance in sesame oil showed slight reactions. Dermal application of 50% and 25% test substance in sesame oil with Duhring Chambers provoked a medium or slight reaction, respectively, whereas the 15% and 5% test substance in sesame oil with Duhring Chambers showed no reaction. The control group showed no reactions

Based on these preliminary results, in the main study (10 treated and 5 control animals per dose) for the intradermal and epicutaneous induction procedure test substance concentrations of 0.5% and 75% in sesame oil were used, respectively. The test article concentration for the challenge procedure was 15% in sesame oil.

During induction, the intradermal and the epicutaneous induction resulted in slight skin reactions in a various number of animals indicating that the chosen test substance concentrations led to slight irritation. In the control group animals no skin reaction was observed after the application of the vehicle sesame oil. Additional observations: Crust formation (diameter: 6 mm) was observed at the injection sites with FCA in the test group and the control group animals 1-2 weeks following the intradermal injection.

Upon challenge, no visible changes of the treated skin sites were observed in the test group animals 24 h and 48 h after patch removal (= grading "0"). In the control group animals also no visible signs of skin reactions were observed (= grading "0") indicating that the chosen concentration of the test substance was below the irritative dose.

Slight skin reactions were observed after induction, whereas at challenge no visible changes of the treated skin sites (no erythema and no edema) were observed in test or control animals at any time point. Consequently, no re-challenge was necessary.

The erythema scores were 0 for all treated animals at 24-48 h.

The absence of erythema proves that Isostearic acid, esters with methyl α-D-glucoside is not a skin sensitiser.

 

General evaluation of skin sensitisation

Sucroglyceride C12-18, C18unsatd. is negative in an in vivo assay performed according to the method of Magnusson and Kligman and it can be concluded that Sucroglyceride C12-18, C18unsatd. is not a skin sensitiser.

 

For skin sensitisation, the registration substance Sucroglyceride C12-18, C18unsatd. and the three read-across substances, Sucroglyceride C12, Stearic acid, esters with methyl α-D-glucoside and Isostearic acid, esters with methyl α-D-glucoside exhibit a comparable profile and are characterised by experimental results which lead to the same overall evaluation with regard to classification and labelling.

 

For the registration substance Sucroglyceride C12-18, C18unsatd. and for three read-across substances, no skin sensitisation potential is detected.

 

Based on the experimental evidence provided, Sucroglyceride C12-18, C18unsatd. does not need to be classified for skin sensitisation according to CLP, EU GHS (Regulation (EC) No 1272/2008) and according to DSD (Directive 67/548/EEC) and labelling is not required.

Migrated from Short description of key information:
Sucroglyceride C12-18, C18unsatd. does not provoke any skin reaction in a skin sensitisation test according to Magnusson and Kligman.
In support of this and using the same study design, also the three read-across substances Sucroglyceride C12 10% a.i., Stearic acid, esters with methyl α-D-glucoside and Isostearic acid, esters with methyl α-D-glucoside result not to be dermal sensitisers.

General evaluation
All studies are GLP compliant guideline studies, the key studies have a Klimisch score 1 while the Klimisch scores of the supporting studies were changed from 1 to 2 to reflect the fact that they were conducted on read-across substances.
Overall, Sucroglyceride C12 -18, C18unsatd. is not considered to be a dermal sensitiser.

Justification for selection of skin sensitisation endpoint:
Only one study on Sucroglyceride C12-18, C18unsatd. is available, the other three studies report read-across data from supporting substancees (structural analogues).

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information:

No data are available for respiratory sensitisation. This reflects the fact that inhalation is not a relevant route for exposure.

Justification for classification or non-classification

For skin sensitisation, the studies reported for the test substance and for three chemically closely related substances show that the substances do not provoke any skin reaction in sensitisation studies performed according to Magnusson and Kligman. Hence, they are graded not to be dermal sensitisers.

Consequently, unambiguous data are available to support that, according to the CLP Regulation (EC) No 1272/2008 and according to DSD (67/548/EEC), there is no need for classification of Sucroglyceride C12 -18, C18unsatd. for skin sensitisation and no labelling is required.