Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study performed according to internationally accepted testing guideline, well documented, without GLP.
Justification for type of information:
refer to category justification report provided in IUCLID section 13
Qualifier:
equivalent or similar to
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
Justification for non-LLNA method:
A non-LLNA which was conducted in 1985 with a current scientifically accepted methodology for assessing skin sensitisation potential is available. Even though the available guinea pig maximisation test (GMPT) is not the preferred method for skin sensitisation testing according to the REACH legislation (EC no 1907/2006) and CLP Regulation (EC No 1272/2008) it is still however an adequate method for skin sensitisation testing. Therefore, a LLNA is not required as adequate data from a GMPT are available (study scientifically not necessary/ other information available).
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
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
Induction: 0%; challenge: 25%
No. with + reactions:
0
Total no. in group:
6
Remarks on result:
other: Reading: 1st reading. Hours after challenge: 24.0. Group: negative control. Dose level: induction: 0%; challenge: 25%. No with. + reactions: 0.0. Total no. in groups: 5.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
induction: 5%; challenge: 25%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: induction: 5%; challenge: 25%. No with. + reactions: 0.0. Total no. in groups: 10

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:
CLP: not classified
DSD: not classified
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.

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
12 Nov 1984 - 18 Apr 1985
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP-Guideline study with acceptable restrictions. Lack of test material details, no reliability check.
Justification for type of information:
refer to category justification report provided in IUCLID section 13
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
lack of test materials details, no reliability check.
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
yes
Remarks:
lack of test materials details, no reliability check.
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
A non-LLNA which was conducted in 1985 with a current scientifically accepted methodology for assessing skin sensitisation potential is available. Even though the available guinea pig maximisation test (GMPT) is not the preferred method for skin sensitisation testing according to the REACH legislation (EC no 1907/2006) and CLP Regulation (EC No 1272/2008) it is still however an adequate method for skin sensitisation testing. Therefore, a LLNA is not required as adequate data from a GMPT are available (study scientifically not necessary/ other information available).
Species:
guinea pig
Strain:
other: Pirbright white
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Winkelmann, Borchen, Germany
- Weight at study initiation: 312 g (test group), 303 g (control group)
- Housing: 5 animals per cage in Makrolon Type IV
- Diet: Altromin Diet 3032 DK (Altromin GmbH, Lage, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 50-60
- Photoperiod (hrs dark / hrs light): 12/12
Route:
intradermal and epicutaneous
Vehicle:
other: paraffin oil (1%) for intradermal application and vaseline (50%) for epicutaneous application
Concentration / amount:
Induction:
Intradermal: 1 %
Epicutaneous: 50%

Challenge: 25%
Route:
epicutaneous, occlusive
Vehicle:
other: paraffin oil (1%) for intradermal application and vaseline (50%) for epicutaneous application
Concentration / amount:
Induction:
Intradermal: 1 %
Epicutaneous: 50%

Challenge: 25%
No. of animals per dose:
20
Details on study design:
RANGE FINDING TESTS:
3 preliminary tests were performed with 5 animals each:
Intradermal application with a concentration of 1% of test substance in vaseline induced skin irritation (definite effects, without induction of necrosis). After epidermal application with a concentration of 50% of the test substance in vaseline, this concentration was determined as the minimal irritating concentration. To be able to determine the maximum non-irritating concentration for challenge treatment, intracutaneous injections of 0.1 mL FCA bilaterally of the vertebral column were made. 2 weeks later 25% and 50% test substance concentrations were applied for 24 h under plaster-covering. A concentration of 25% was found to be the maximum non-irritating concentration.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal and epicutaneous, respectively)
- Exposure period: single injection (intradermal) and 48 h (epicutaneous)
- Test groups:
Intradermal (3 pairs of injections):
Injection 1: FCA
Injection 2: test substance in paraffin
Injection 3: test substance in a 1:1 mixture (v/v) FCA
Epicutaneous: test substance in vaseline

- Control group:
Injection 1: FCA
Injection 2: paraffin
Injection 3: parafin in a 1:1 mixture (w/v) FCA
Epicutaneous: vaseline

- Site: shoulder region (intradermal + epicutanous)
- Frequency of applications: every 7 days
- Duration: Days 0-8
- Concentrations: intradermal 1%, epicutaneous 50%

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 20
- Exposure period: 24 h
- Test groups: test substance and vehicle only
- Control group: test substance and vehicle only
- Site: cranial (vehicle) and caudal (test substance)
- Concentrations: 25%
- Evaluation (hr after challenge): 48 and 72

Positive control substance(s):
not specified
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
induction: 0%; challenge: 25%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: induction: 0%; challenge: 25%. No with. + reactions: 0.0. Total no. in groups: 20.0.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
induction: 1%; challenge: 25%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: induction: 1%; challenge: 25%. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
induction: 0%; challenge: 25%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: induction: 0%; challenge: 25%. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
induction: 1%; challenge: 25%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: induction: 1%; challenge: 25%. No with. + reactions: 0.0. Total no. in groups: 20.0.

No effects on bodyweight were observed during the study period. After intradermal injection all animals showed the expected reactions for FCA. Intradermal injections of the vehicle paraffin caused reactions as well (no further information). After removal of the epicutaneous induction patch erythemateous reaction was observed being clearly decreased 24 h later. According to the author, individual results were not given in tabulated form, as all skin examinations were negative, both at 24 and 48 h after challenge exposure.

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
DSD: not classified
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
refer to category justification report provided in IUCLID section 13
Reason / purpose:
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
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
Induction: 0%; challenge: 25%
No. with + reactions:
0
Total no. in group:
6
Remarks on result:
other: Reading: 1st reading. Hours after challenge: 24.0. Group: negative control. Dose level: induction: 0%; challenge: 25%. No with. + reactions: 0.0. Total no. in groups: 5.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
induction: 5%; challenge: 25%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: induction: 5%; challenge: 25%. No with. + reactions: 0.0. Total no. in groups: 10

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:
CLP: not classified
DSD: not classified
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.

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
refer to category justification report provided in IUCLID section 13
Reason / purpose:
read-across source
Species:
guinea pig
Strain:
other: Pirbright white
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Winkelmann, Borchen, Germany
- Weight at study initiation: 312 g (test group), 303 g (control group)
- Housing: 5 animals per cage in Makrolon Type IV
- Diet: Altromin Diet 3032 DK (Altromin GmbH, Lage, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 50-60
- Photoperiod (hrs dark / hrs light): 12/12
Route:
intradermal and epicutaneous
Vehicle:
other: paraffin oil (1%) for intradermal application and vaseline (50%) for epicutaneous application
Concentration / amount:
Induction:
Intradermal: 1 %
Epicutaneous: 50%

Challenge: 25%
Route:
epicutaneous, occlusive
Vehicle:
other: paraffin oil (1%) for intradermal application and vaseline (50%) for epicutaneous application
Concentration / amount:
Induction:
Intradermal: 1 %
Epicutaneous: 50%

Challenge: 25%
No. of animals per dose:
20
Details on study design:
RANGE FINDING TESTS:
3 preliminary tests were performed with 5 animals each:
Intradermal application with a concentration of 1% of test substance in vaseline induced skin irritation (definite effects, without induction of necrosis). After epidermal application with a concentration of 50% of the test substance in vaseline, this concentration was determined as the minimal irritating concentration. To be able to determine the maximum non-irritating concentration for challenge treatment, intracutaneous injections of 0.1 mL FCA bilaterally of the vertebral column were made. 2 weeks later 25% and 50% test substance concentrations were applied for 24 h under plaster-covering. A concentration of 25% was found to be the maximum non-irritating concentration.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal and epicutaneous, respectively)
- Exposure period: single injection (intradermal) and 48 h (epicutaneous)
- Test groups:
Intradermal (3 pairs of injections):
Injection 1: FCA
Injection 2: test substance in paraffin
Injection 3: test substance in a 1:1 mixture (v/v) FCA
Epicutaneous: test substance in vaseline

- Control group:
Injection 1: FCA
Injection 2: paraffin
Injection 3: parafin in a 1:1 mixture (w/v) FCA
Epicutaneous: vaseline

- Site: shoulder region (intradermal + epicutanous)
- Frequency of applications: every 7 days
- Duration: Days 0-8
- Concentrations: intradermal 1%, epicutaneous 50%

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 20
- Exposure period: 24 h
- Test groups: test substance and vehicle only
- Control group: test substance and vehicle only
- Site: cranial (vehicle) and caudal (test substance)
- Concentrations: 25%
- Evaluation (hr after challenge): 48 and 72

Positive control substance(s):
not specified
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
induction: 0%; challenge: 25%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: induction: 0%; challenge: 25%. No with. + reactions: 0.0. Total no. in groups: 20.0.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
induction: 1%; challenge: 25%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: induction: 1%; challenge: 25%. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
induction: 0%; challenge: 25%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: induction: 0%; challenge: 25%. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
induction: 1%; challenge: 25%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: induction: 1%; challenge: 25%. No with. + reactions: 0.0. Total no. in groups: 20.0.

No effects on bodyweight were observed during the study period. After intradermal injection all animals showed the expected reactions for FCA. Intradermal injections of the vehicle paraffin caused reactions as well (no further information). After removal of the epicutaneous induction patch erythemateous reaction was observed being clearly decreased 24 h later. According to the author, individual results were not given in tabulated form, as all skin examinations were negative, both at 24 and 48 h after challenge exposure.

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
DSD: not classified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Justification for read-across

Reliable data on the skin sensitisation potential of glycerides, C16-18 and C18-unsaturated, mono-and di-citrates (CAS 91052-16-3) are not available. The assessment was therefore based on studies conducted with analogue substances as part of a read across approach, which is in accordance with Regulation (EC) No. 1907/2006, Annex XI, 1.5. For each specific endpoint the source substance(s) structurally closest to the target substance is/are chosen for read-across, with due regard to the requirements of adequacy and reliability of the available data. Structural similarities and similarities in properties and/or activities of the source and target substance are the basis of read-across. A detailed justification for the analogue read-across approach is provided in the technical dossier (see IUCLID Section 13).

CAS 91845-19-1

The skin sensitising potential of Glycerides, C16-18 and C18-hydroxy mono- and di- was studied in guinea pigs according to the maximisation method (OECD guideline 406) and in compliance with GLP (Kästner, 1985). In three preliminary tests, suitable treatment concentrations for the main study were determined in each 5 animals. For the intradermal route, the test substance at concentrations of 1 and 10 % in paraffin was administered to the clipped skin of 5 animals. Based on the induction of moderate irritant effects on the skin but no necrosis, a test substance concentration of 1% in paraffin oil (w/w) was chosen for intradermal injections in the main study. For the cutaneous route, the test substance at 25 and 50% in vaseline was applied to the clipped skin of 5 animals for 48 h using an occlusive dressing within the preliminary experiment. Since the 50% concentration of the test substance was sufficient to cause skin irritation, this concentration was selected for topical application in the induction phase of the main experiment. For challenge exposure, intradermal injections with Freund’s adjuvant followed by epicutaneous application of 0.2 g of the test substance at concentrations of 25 and 50% in vaseline were performed in the preliminary test. After 24-h exposure under occlusive conditions, slight erythema was observed on the skin of 2/5 animals. Thus, the test substance at 25% in Vaseline was chosen for topical application in the challenge phase of the main test. In the induction phase of the main study, intradermal injections of the test substance at 1% in paraffin and/or FCA were applied into the clipped skin area of 20 females. A control group, consisting of 20 females, was injected with vehicle only and/or FCA. On Day 8, a 48-hour epicutaneous induction treatment with test substance at 50% in vaseline or vehicle only was performed in the treated or control animals on the regions of intradermal injections. On Day 22, the challenge treatment was performed by topical application of the test substance at 25% concentration in vaseline and the vehicle to all animals for 24 h. Skin reactions were evaluated 24 and 48 h after the challenge application. During the study no test substance-related clinical signs and no effects on body weight gain were observed. No cutaneous reactions were provoked by the challenge treatment with the test substance at 25% in none of the animals of the test and control groups. Therefore, the test substance had no sensitising effect in guinea pigs under the experimental conditions chosen.

CAS 91744-38-6

The sensitising potential of Glycerides, C16-18 mono-, di- and tri-, hydrogenated, citrates, potassium salts was studied in guinea pigs according to the maximisation method (OECD guideline 406) and in compliance with GLP (Collier, 1981). The following numbers of guinea pigs were used in the study: 10 (main test); 6 (range finding), control animals: 5. A concentration of 5% of the test substance was used for intradermal induction and 25% was used for topical induction. The concentration used for the topical challenge phase was 25 %. The vehicle used for intradermal induction was liquid paraffin B.P. Petroleum jelly B.P. was the vehicle used for the topical induction and challenge phases. 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. Therefore, the test substance had no sensitising effect in guinea pigs under the experimental conditions chosen.

Overall conclusion for skin sensitisation

The reliable data available for the read-across analogue substances did not show any skin sensitisation effects. Therefore, glycerides, C16-18 and C18-unsaturated, mono-and di-citrates (CAS 91052-16-3) is not considered to be a skin sensitiser.


Migrated from Short description of key information:
Skin sensitisation (GPMT): not sensitising

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 analogue concept is applied to glycerides, C16-18 and C18-unsaturated, mono-and di-citrates (CAS 91052-16-3) data will be generated from data for reference source substance(s) to avoid unnecessary animal testing. Additionally, once the analogue read-across concept is applied, substances will be classified and labelled on this basis. Therefore, based on the analogue read-across approach, the available data on skin sensitisation do not meet the classification criteria according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification