Glycerides, C16-18 and C18-unsatd. mono-, di- and tri-, citrates, potassium salts

Endpoint summary

Description of key information

The sensitizing potential of the substance was investigated in a study according to OECD 406 (Buehler). The substance concentrations for induction and challenge were 2, 25, 50, and 100 % in corn oil. Experimental animals were epidermally exposed to undiluted test substance on days 0, 7, and 14 (occlusive dermal applications for 6 hours, scoring at 30 hours after start of application). Control animals were exposed to vehicle only. On day 28 animals were challenged with undiluted test substance (occlusive dermal application for 6 hours). Evaluations were made after 24 and 48 h. Under the conditions of the test no sensitizing effects of the test substance could be observed. In addition, no clinical effects were observed. Body weight increase of the test animals was comparable to the control.

The sensitizing potential of an analogue substance was investigated in a study according to OECD 406 (GPMT). The substance concentrations for induction were 5 % (intradermal induction) and 25 % (topical induction). The concentration for topical challenge was 25 %. The vehicle for intradermal induction was liquid paraffin B.P. Petroleum jelly B.P. was used for topical induction and challenge. No animals of the test or control groups produced sensitization reactions at either the test or vehicle control sites, at the 24 or 48 h readings. No clinical signs were reported.

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:

supporting study

Study period:

1981

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study performed according to internationally accepted testing guideline, well documented, without GLP.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

Maximisation test [Magnusson B. and Kligman A. M. (1969) J. Invest. Dermatol., 52, 268-276.]

Deviations:

no

GLP compliance:

no

Type of study:

guinea pig maximisation test

Species:

guinea pig

Strain:

other: albino

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: David Hall Limited, Burton-on-Trent, Staffordshire, U. K.
- Age: 8 – 12 weeks
- Weight at study initiation: 345 – 438 g
- Housing: housed in groups of up to four in solid floor polypropylene cages furnished with softwood sawdust
- Diet (e.g. ad libitum): guines pig diet, J.Waring Ltd (feeds), Shardlow, Derbyshire
- Water (e.g. ad libitum): The drinking water was supplemented daily with vitamin C tablets
- Acclimation period: not mentioned

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3
- Humidity (%): not mentioned
- Air changes (per hr): 20
- Photoperiod (hrs dark / hrs light): 12/12

Route:

intradermal and epicutaneous

Vehicle:

other: intradermal: liquid paraffin B.P.; topical: petroleum jelly B.P.

Concentration / amount:

Intradermal Induction: 5%
Topical Induction: 25%
Topical challenge: 25%

Route:

epicutaneous, occlusive

Vehicle:

other: intradermal: liquid paraffin B.P.; topical: petroleum jelly B.P.

Concentration / amount:

Intradermal Induction: 5%
Topical Induction: 25%
Topical challenge: 25%

No. of animals per dose:

test animals: 10 (main test); 6 (range finding)
control animals: 5

Details on study design:

RANGE FINDING TESTS: Intradermal Injection: An area of 4x6 cm at the shoulder region of 2 animals were clipped. Into these areas were injected simultaneousely four 0.1 ml intradermal injections of the test material with the following concentrations: guinea pig A: 1% and guinea pig B: 5% in paraffin. Animals were observed 24, 48, 72 h and 7 days following treatment. Topical Application: The test material at two concentrations, was topically applied under an occlusive patch to four sites on the shaved flanks of each of a group of two guinea pigs. These animals had previously been intradermally injected with FDA. Following a 24 h exposure period the patches were removed and the degrees of irritancy at the test sites were evaluated for erythema immediately after removal of the patches and then at 24 and 48 h. The concentrations of the test material to be used on two further animals were chosen, applied and then evaluated after similar time intervals.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 1
- Exposure period: intradermal: 5% w/v in paraffin;
- Concentration in Freunds Complete Adjuvants (FCA): 5% in in 50% v/v FCA/paraffin
- Test group: dermal: test substance in paraffin
- Control group: paraffin
- Frequency of applications: induction on days 0 and 7
- Duration: removal of patches after 48 hours
- Concentrations: 5% w/v

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: on day 21
- Exposure period: dermal application for 24 hours
- Test groups: test substance in paraffin
- Control group: test substance in paraffin
- Site: flank-region
- Concentrations: 5% w/v
- Evaluation (hr after challenge): 24 and 48 hours after application

Positive control substance(s):

not specified

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

5%

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

no indication of skin sensitisation

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

5%

No. with + reactions:

0

Total no. in group:

5

Remarks on result:

no indication of skin sensitisation

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

5%

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

no indication of skin sensitisation

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

5%

No. with + reactions:

0

Total no. in group:

5

Remarks on result:

no indication of skin sensitisation

Reading:

other: periodically

Group:

positive control

Remarks on result:

positive indication of skin sensitisation

RESULTS OF PILOT STUDY: Guinea pig A (concentration 1%): 24, 48 and 72 h slight erythema, 7 days none. Guinea pig B, (concentration 5%): 24, 48, 72h and 7 days slight erythema.

RESULTS OF TEST

- Sensitization reaction: No animals of the test or control groups produced reactions at either the test or vehicle control sites, at the 24 or 48 h readings.

- Clinical signs: No clinical signs were reported.

- Grading system: according to the Magnusson and Kligman grading scale for the evaluation of challenge patch test reactions

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test substance is not sensitizing.

Executive summary:

The sensitizing potential of the test substance (CAS 91744-38-6, Glycerides, C16-18 mono-, di- and tri-, hydrogenated, citrates, potassium salts) was investigated in a study according to OECD Guideline No. 406 "Skin Sensitization (maximization test)”.

The following numbers of guinea pigs were used in the study: 10 (main test); 6 (range finding), control animals: 5.

The substance concentrations for induction were 5 % (intradermal induction) and 25 % (topical induction). The concentration for topical challenge was 25 %. The vehicle for intradermal induction was liquid paraffin B.P. Petroleum jelly B.P. was used for topical induction and challenge.

Animal sites were graded according to the Magnusson and Kligman grading scale for the evaluation of challenge patch test reactions.

No animals of the test or control groups produced sensitization reactions at either the test or vehicle control sites, at the 24 or 48 h readings. No clinical signs were reported.

Reference 2

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

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

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study performed according to internationally accepted testing guideline, well documented, without GLP. Read-across from analogue substance. For justification of read-across and for further details please refer to the read-across report.

Justification for type of information:

Refer to the read-across report submitted in section 13 of this IUCLID dossier

Reason / purpose for cross-reference:

read-across source

Species:

guinea pig

Strain:

other: albino

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: David Hall Limited, Burton-on-Trent, Staffordshire, U. K.
- Age: 8 – 12 weeks
- Weight at study initiation: 345 – 438 g
- Housing: housed in groups of up to four in solid floor polypropylene cages furnished with softwood sawdust
- Diet (e.g. ad libitum): guines pig diet, J.Waring Ltd (feeds), Shardlow, Derbyshire
- Water (e.g. ad libitum): The drinking water was supplemented daily with vitamin C tablets
- Acclimation period: not mentioned

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3
- Humidity (%): not mentioned
- Air changes (per hr): 20
- Photoperiod (hrs dark / hrs light): 12/12

Route:

intradermal and epicutaneous

Vehicle:

other: intradermal: liquid paraffin B.P.; topical: petroleum jelly B.P.

Concentration / amount:

Intradermal Induction: 5%
Topical Induction: 25%
Topical challenge: 25%

Route:

epicutaneous, occlusive

Vehicle:

other: intradermal: liquid paraffin B.P.; topical: petroleum jelly B.P.

Concentration / amount:

Intradermal Induction: 5%
Topical Induction: 25%
Topical challenge: 25%

No. of animals per dose:

test animals: 10 (main test); 6 (range finding)
control animals: 5

Details on study design:

RANGE FINDING TESTS: Intradermal Injection: An area of 4x6 cm at the shoulder region of 2 animals were clipped. Into these areas were injected simultaneousely four 0.1 ml intradermal injections of the test material with the following concentrations: guinea pig A: 1% and guinea pig B: 5% in paraffin. Animals were observed 24, 48, 72 h and 7 days following treatment. Topical Application: The test material at two concentrations, was topically applied under an occlusive patch to four sites on the shaved flanks of each of a group of two guinea pigs. These animals had previously been intradermally injected with FDA. Following a 24 h exposure period the patches were removed and the degrees of irritancy at the test sites were evaluated for erythema immediately after removal of the patches and then at 24 and 48 h. The concentrations of the test material to be used on two further animals were chosen, applied and then evaluated after similar time intervals.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 1
- Exposure period: intradermal: 5% w/v in paraffin;
- Concentration in Freunds Complete Adjuvants (FCA): 5% in in 50% v/v FCA/paraffin
- Test group: dermal: test substance in paraffin
- Control group: paraffin
- Frequency of applications: induction on days 0 and 7
- Duration: removal of patches after 48 hours
- Concentrations: 5% w/v

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: on day 21
- Exposure period: dermal application for 24 hours
- Test groups: test substance in paraffin
- Control group: test substance in paraffin
- Site: flank-region
- Concentrations: 5% w/v
- Evaluation (hr after challenge): 24 and 48 hours after application

Positive control substance(s):

not specified

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

5%

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

no indication of skin sensitisation

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

5%

No. with + reactions:

0

Total no. in group:

5

Remarks on result:

no indication of skin sensitisation

Reading:

other: periodically

Group:

positive control

Remarks on result:

positive indication of skin sensitisation

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

5%

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

no indication of skin sensitisation

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

5%

Total no. in group:

5

Remarks on result:

no indication of skin sensitisation

RESULTS OF PILOT STUDY: Guinea pig A (concentration 1%): 24, 48 and 72 h slight erythema, 7 days none. Guinea pig B, (concentration 5%): 24, 48, 72h and 7 days slight erythema.

RESULTS OF TEST

- Sensitization reaction: No animals of the test or control groups produced reactions at either the test or vehicle control sites, at the 24 or 48 h readings.

- Clinical signs: No clinical signs were reported.

- Grading system: according to the Magnusson and Kligman grading scale for the evaluation of challenge patch test reactions

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test substance is not sensitizing.

Executive summary:

The sensitizing potential of the test substance (CAS 91744-38-6, Glycerides, C16-18 mono-, di- and tri-, hydrogenated, citrates, potassium salts) was investigated in a study according to OECD Guideline No. 406 "Skin Sensitization (maximization test)”.

The following numbers of guinea pigs were used in the study: 10 (main test); 6 (range finding), control animals: 5.

The substance concentrations for induction were 5 % (intradermal induction) and 25 % (topical induction). The concentration for topical challenge was 25 %. The vehicle for intradermal induction was liquid paraffin B.P. Petroleum jelly B.P. was used for topical induction and challenge.

Animal sites were graded according to the Magnusson and Kligman grading scale for the evaluation of challenge patch test reactions.

No animals of the test or control groups produced sensitization reactions at either the test or vehicle control sites, at the 24 or 48 h readings. No clinical signs were reported.

Reference 3

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1996-03-26 to 1996-07-12

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study.

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

GLP compliance:

yes (incl. QA statement)

Type of study:

Buehler test

Justification for non-LLNA method:

The in vivo study data were obtained in studies performed before any in vitro sensitization tests had been validated and accepted for regulatory purposes

Species:

guinea pig

Strain:

other: Dunkin Hartley, Pirbright White

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Harlan Winkelmann GmbH, Versuchstierzucht, Borchen, Germany
- Age at study initiation: young adults, no further details mentioned
- Weight at study initiation: 257 ± 19 g
- Housing: conventional, Makrolon Type IV cages (maximum 5 animals per cage)
- Diet (e.g. ad libitum): Ssniff G4 complete feed for guinea pigs ad libitum, supplied by Ssniff Spezialfutter GmbH, Soest, Germany
- Water (e.g. ad libitum): drinking water ad libitum, supplied by Gelsenwasser, Wasserwerk, Haltern, Germany
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 - 70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 1996-03-26 To: 1996-03-29 (preliminary study)
From: 1996-06-12 To: 1996-07-12 (main study)

Route:

epicutaneous, occlusive

Vehicle:

water

Concentration / amount:

induction and challenge: 2, 25, 50 and 100 % in corn oil MEH 56

Route:

epicutaneous, occlusive

Vehicle:

water

Concentration / amount:

induction and challenge: 2, 25, 50 and 100 % in corn oil MEH 56

No. of animals per dose:

test animals: 20 (main experiment), 3 (pilot study), 3 (determination of challenge concentration)
control animals: 10

Details on study design:

RANGE FINDING TESTS:
Determination of the non-irritant concentration of the test substance with occlusive epicutaneous applications for 6 hours of test substance 5%, 25%, 50% in corn oil MEH 56 and undiluted 100% (delivery form). Reading at 30 and 54 hours after application.
Redetermination of the maximum non-irritant concentration for the challenge treatment in the 4th week with 3 additional guinea pigs which had not been treated up to this time. The concentrations and test conditions were the same as in the pilot study. This additional testing 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 approx. the same weights as the 30 animals in the challenge phase.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: occlusive dermal applications for 6 hours, scoring at 30 hours after start of application
- Test group: receiving test substance (0.3 cm³/patch)
- Control group: receiving vehicle (0.3 cm³/patch)
- Site: left flanks
- Frequency of applications: induction on days 0, 7 and 14
- Duration: 3 weeks
- Concentrations: undiluted (delivery form)

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: on day 28
- Exposure period: occlusive dermal application for 6 hours
- Test groups: receiving test substance solution and vehicle (0.3 cm³/patch each)
- Control group: receiving test substance solution and vehicle (0.3 cm³/patch each)
- Site: right flanks (front: vehicle, back: test substance solution)
- Concentrations: undiluted (delivery form)
- Evaluation (hr after challenge): 24 and 48 hours

Challenge controls:

same treatment as test group animals

Positive control substance(s):

yes

Remarks:

2-Mercaptobenzothiazole

Positive control results:

The sensitivity of the used guinea pig strain was checked from 1996-04-29 to 1996-05-30. The test compound was used as an well-known standard allergen. The maximisations method was carried out for this test. A test goup of 10 and a control group of 5 animals were used to test the sensitivity. 48 and 72 hours after challenge treatment all skin reaction were recorded:
Dermal irritation was found on the right flank of 3 of 10 test animals 48 and 72 hours after treatment with the allergen. Treatment of the test animals with the vehicle on the left flank likewise resulted in a slight or to distinct subcutaneous reaction after 48 and 72 hours in two animals.
There were no signs of irritation at these times on the skin on the left (standard allergen) and right (vehicle) flanks of the control animals.
It was necessary to pretreat the skin with 10% sodium dodecylsulphate in vaseline in order to cause slight to moderate cutaneous inflammation, because the highest allergen concentration which could be administered satisfactorily caused no dermal irritation.
On the basis of these results (30% of test animals showed evidence of delayed contact hypersensitivity), the guinea pig strain was judged to be sensitive under the test conditions described. In the maximisation method, a figure of 15% or more is regarded as positive result.

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

100%

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

no clinical effects observed

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: no clinical effects observed.

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

100%

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

no clinical effects observed

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: no clinical effects observed.

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

100%

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

no clinical effects observed

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no clinical effects observed.

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

100%

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

no clinical effects observed

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no clinical effects observed.

Reading:

other: Reliability

Group:

positive control

Remarks on result:

positive indication of skin sensitisation

Remarks:

The sensitivity of the used guinea pig strain was checked from 1996-04-29 to 1996-05-30. The test compound was used as an well-known standard allergen.

RESULTS OF PILOT STUDY

No irritant effects at any concentration of the test substance tested.

RESULTS OF TEST

- Sensitisation reaction: No sensitising effects observed.

- Clinical signs: No clinical effects observed. Body weight increase comparable to control.

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test substance is not sensitizing.

Executive summary:

The sensitizing potential of the test substance (CAS 91744-23-9) was investigated in a study according to OECD Guideline No. 406 "Skin Sensitization (maximization test)”.

The following animal numbers were used in the study: 20 (main experiment), 3 (pilot study), 3 (determination of challenge concentration), control animals: 10. The substance concentrations for induction and challenge were 2, 25, 50, and 100 % in corn oil MEH 56. 2 -Mercaptobenzothiazole served as positive control.

Experimental animals were epidermally exposed to undiluted test substance on days 0, 7, and 14 (occlusive dermal applications for 6 hours, scoring at 30 hours after start of application). Control animals were exposed to vehicle only. On day 28 animals were challenged with undiluted test substance (occlusive dermal application for 6 hours). Evaluations were made after 24 and 48 h.

Under the conditions of the test no sensitizing effects of the test substance could be observed. In addition, no clinical effects were observed. Body weight increase of the test animals was comparable to the control.

On the basis of the results with the positive control 2-mercaptobenzothiazole (30% of test animals showed evidence of delayed contact hypersensitivity), the guinea pig strain was judged to be sensitive under the test conditions described.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the findings of a reliable in vivo study conducted on the substance and a reliable in vivo study conducted on an analogue substance, classification of the substance is not justified.