isostearic acid monoisopropanolamide

Endpoint summary

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:

key study

Study period:

From March 16, 1999 to April 28, 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Deviations:

no

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

The purpose of this skin sensitization study was to assess the allergenic potential of the test substance when administered to the skin of albino guinea pigs. This study should provide a rational basis for risk assessment of the sensitizing potential of the test article in man. The sensitivity and reliability of the experimental technique employed was assessed by use of 2-mercaptobenzothiazole which is recommended by OECD 406 Guidelines and is known to have moderate skin sensitization properties in the guinea pig strain.

Species:

guinea pig

Strain:

Himalayan

Remarks:

Ibm: GOHI; SPF-quality guinea pigs (synonym: Himalayan spotted)

Sex:

male

Details on test animals and environmental conditions:

Source: RCC Ltd Biotechnology & Animal Breeding Division CH-4414 Füllinsdorf / Switzerland
Age when treated: 4-6 weeks
Weight: 314-405 g
Temperature: 20-28 °C and relative humidity: 32-84%
Light period: 12 hour light/dark cycle
Diet: pelleted Standard Nafag Ecosan 845 25W4,ad libitum
Water: community tap water, ad libitum

Route:

intradermal

Vehicle:

water

Remarks:

bi-distilled

Concentration / amount:

1) 1:1 (v/v) mixture of Freunds Complete Adjuvant and physiological saline.
2) The test substance, at 5% in bi-distilled water.
3) The test substance at 5% in a 1:1 (v/v) mixture of Freunds Complete Adjuvant and physiological saline.
(control animals: without the test substance)

Day(s)/duration:

Dermal reactions were assessed 24 hours later

Adequacy of induction:

highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically

Route:

epicutaneous, occlusive

Vehicle:

water

Remarks:

bi-distilled

Concentration / amount:

Four intradermal injections (0.1 mL/site) of a 1:1 (v/v) mixture of Freund’s Complete
Adjuvant/physiological saline were made into the shaved neck of two guinea pigs. One week later both flanks of each of the guinea pigs were clipped and shaved just prior to the application. Thereafter 4 patches of filter paper (3 x 3 cm) were saturated with the test substance at A = 100%, B = 75%, C = 50% and D = 25% and applied to the clipped and shaved flanks. The volume of test substance preparation applied was approximately 0.3 mL. The patches were covered by a strip of aluminum foil and firmly secured by elastic plaster wrapped around the trunk and covered with impervious adhesive tape.

Day(s)/duration:

24h

Adequacy of induction:

highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically

Route:

epicutaneous, occlusive

Vehicle:

water

Remarks:

bi-distilled

Concentration / amount:

The test and control guinea pigs were challenged two weeks after the epidermal induction application. Hair was clipped and shaved from a 5 x 5 cm area on the left and right flank of each guinea pig just prior to the application. Two patches (3 x 3 cm) of filter paper were saturated with the test substance at the highest non-irritating concentration of 1% (left flank) and the vehicle only (bi-distilled water applied to the right flank) using the same method as for the epidermal application. The volume of test substance preparation and vehicle applied was approximately 0.2 mL. The dressings were left in place for 24 hours. Twenty-one hours after removal of the dressing the test sites treated with the test substance were depilated as described in the epidermal pretest.
The reaction sites were assessed approximately 24 and 48 hours after removal of the bandage for erythema and oedema according to the method of Magnusson and Kligman.

Day(s)/duration:

24h

Adequacy of challenge:

highest non-irritant concentration

No. of animals per dose:

10 (test) and 5 (control) male albino guinea pigs

Details on study design:

In order to assess the cutaneous allergenic potential of the test substance, the maximization-test was performed in 15 (10 test and 5 control) male albino guinea pigs, in accordance with OECD Guideline No. 406 and the Directive 96/54/EEC, B.6. The intradermal induction of sensitization in the test group was performed with a 5% dilution of the test substance in bi-distilled water and in an emulsion of Freunds Complete Adjuvant (FCA) / physiological saline. The epidermal induction of sensitization was conducted under occlusion with the undiluted test substance one week after the intradermal induction. The animals of the control group were intradermally induced with bi-distilled water and FCA/physiological saline and epidermally induced with bi-distilled water under occlusion. Two weeks after epidermal induction the control and test animals were challenged by epidermal application of the test substance at 1% in bi-distilled water and bi-distilled water alone under occlusive dressing. Cutaneous reactions were evaluated at 24 and 48 hours after removal of the dressing.

Challenge controls:

Negative control: vehicle alone

Positive control substance(s):

yes

Remarks:

2-mercaptobenzothiazole

Positive control results:

2-mercaptobenzothiazole:
90% (at the 24-hour reading) and 100% (at the 48-hour reading) of the animals of the test group were observed with very slight to moderate/severe erythematous reactions after treatment with a non-irritant test substance concentration of 10% in mineral oil. No skin reactions were observed in the control group. A response of at least 30% positive animals is considered positive “R43”: may Cause sensitization by skin contact according to the “Commission Directive 96/54/EEC, July 30, 1996 adapting to technical progress for the 22nd time Council Directive 67/548/EEC on the approximation of the laws, regulations and administrative provisions relating to the classification, packaging and labelling of dangerous substances”. Therefore, the positive control substance applied at a concentration of 10% in mineral oil was considered to be an extreme sensitizer when used under the described test conditions.

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

1%

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

No adverse effects

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

1%

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

No adverse effects

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

positive control

Dose level:

10% in mineral oil

No. with + reactions:

9

Total no. in group:

10

Clinical observations:

very slight to moderate/severe erythematous reactions

Remarks on result:

positive indication of skin sensitisation

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

positive control

Dose level:

10% in mineral oil

No. with + reactions:

10

Total no. in group:

10

Clinical observations:

very slight to moderate/severe erythematous reactions

Remarks on result:

positive indication of skin sensitisation

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

Bi-distilled water

No. with + reactions:

0

Total no. in group:

5

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

Bi-distilled water

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

no indication of skin sensitisation

Skin effects after intradermal induction (on test day 1):

The expected and common findings were observed in the control and test group after the different applications using FCA intradermally and consisted of erythema, oedema, necrotizing dermatitis, encrustation and exfoliation of encrustation.

Skin effects after epidermal induction (on test day 8):

Control group: No erythematous or oedematous reaction was observed in the animals treated with bi-distilled water only.

Test group: Discrete/patchy erythema was observed in all surviving test animals at the 24-hour reading after treatment with the undiluted test substance. One animal still showed the same skin effect at the 48-hour reading.

Skin effects after the challenge (on test day 22):

Control group: No skin reactions were observed in the animals when treated with either bi-distilled water only or when treated with the test substance at 1% in bi-distilled water.

Test group: No skin reactions were observed in the animals when treated with either bi-distilled water only or when treated with the test substance at 1% in bi-distilled water.

Viability/mortality/macroscopic findings:

One animal of the test group was found dead on test day 10 (i.e., day of removal of the dressing in the epidermal induction phase). At necropsy, no findings were noted. The cause of death could not be established. The death was considered to be spontaneous and treatment-unrelated.

Clinical signs, systemic:

No signs of systemic toxicity were observed in the animals.

Body weights:

One animal of the control group showed a loss of body weight (4.6%) between the treatment start and the end of the study. The body weight of the other animals was within the range commonly recorded for animals of this strain and age.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the study conditons, the test substance was not considered to be a skin sensitizer.

Executive summary:

A study was conducted to evaluate the skin sensitisation potential of the test substance, isoC18 MIPA (94.1% active), according to OECD Guideline 406 and EU Method B.6, in compliance with GLP. The test was performed in 15 (10 test and 5 control) male albino guinea pigs. The intradermal induction of sensitization was performed with a 5% dilution of the test substance in bi-distilled water and in an emulsion of Freunds Complete Adjuvant (FCA) / physiological saline. The epidermal induction of sensitization was conducted under occlusion with the undiluted test substance one week later. The animals of the control group were intradermally induced with bi-distilled water and FCA/physiological saline and epidermally induced with bi-distilled water under occlusion. Two weeks after epidermal induction, the control and test animals were challenged by epidermal application of the test substance at 1% in bi-distilled water and bi-distilled water alone under occlusive dressing. Cutaneous reactions were evaluated at 24 and 48 h after removal of the dressing. The expected and common findings were observed in the control and test group after the different applications using FCA intradermally (on test day 1) and consisted of erythema, oedema, necrotizing dermatitis, encrustation and exfoliation of encrustation. After epidermal induction (Day 8), no erythematous or oedematous reaction was observed in the animals treated with bi-distilled water only (control group). Discrete/patchy erythema was observed in all surviving test animals (treated group) at the 24 h reading after treatment with the undiluted test substance. One animal still showed the same skin effect at the 48 h reading. Following challenge (Day 22), no skin reactions were observed in the animals when treated with either bi-distilled water only (control group) or when treated with the test substance at 1% in bi-distilled water (treated group). Under the study conditons, the test substance was not considered to be a skin sensitizer (Arcelin, 1999).

Reference 2

Endpoint:

skin sensitisation: in vitro

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Justification for non-LLNA method:

The in vivo study was conducted before the requirement for the LLNA studies was published officially.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

A study was conducted to evaluate the skin sensitisation potential of the test substance, isoC18 MIPA (94.1% active), according to OECD Guideline 406 and EU Method B.6, in compliance with GLP. The test was performed in 15 (10 test and 5 control) male albino guinea pigs. The intradermal induction of sensitization was performed with a 5% dilution of the test substance in bi-distilled water and in an emulsion of Freunds Complete Adjuvant (FCA) / physiological saline. The epidermal induction of sensitization was conducted under occlusion with the undiluted test substance one week later. The animals of the control group were intradermally induced with bi-distilled water and FCA/physiological saline and epidermally induced with bi-distilled water under occlusion. Two weeks after epidermal induction, the control and test animals were challenged by epidermal application of the test substance at 1% in bi-distilled water and bi-distilled water alone under occlusive dressing. Cutaneous reactions were evaluated at 24 and 48 h after removal of the dressing. The expected and common findings were observed in the control and test group after the different applications using FCA intradermally (on test day 1) and consisted of erythema, oedema, necrotizing dermatitis, encrustation and exfoliation of encrustation. After epidermal induction (Day 8), no erythematous or oedematous reaction was observed in the animals treated with bi-distilled water only (control group). Discrete/patchy erythema was observed in all surviving test animals (treated group) at the 24 h reading after treatment with the undiluted test substance. One animal still showed the same skin effect at the 48 h reading. Following challenge (Day 22), no skin reactions were observed in the animals when treated with either bi-distilled water only (control group) or when treated with the test substance at 1% in bi-distilled water (treated group). Under the study conditons, the test substance was not considered to be a skin sensitizer (Arcelin, 1999).

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the results of a guinea pig maximisation study, the test substance does not warrant classification for sensitization according to CLP (EC 1272/2008) criteria.