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Diss Factsheets

Administrative data

Description of key information

Mice. Not sensitizing. OECD 429, Reliability = 1

Guinea pig. Not sensitizing. OECD 406; Reliability = 1

Guinea pig, Sensitizing, OECD 406, Reliability = 1

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:
supporting study
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:
EPA OPP 81-6 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
Buehler test
Specific details on test material used for the study:
- Substance ID: TSN 100097
- Name of substance: XDE-795
- Lot number: DECO-97-152-1
- Purity: 97.4%
Species:
guinea pig
Strain:
Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories Inc., Kingston, New York
- Age at study initiation: Approximately 5 weeks
- Weight at study initiation: 374.0 ± 13.1 g
- Housing: Five animals per cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: At least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 40-70
- Air changes (per hr): 15 times
- Photoperiod (hrs dark / hrs light): 12/12
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
A single 0.4 g of neat test substance moistened with 0.1 mL of distilled water
Day(s)/duration:
6 h
Adequacy of induction:
other: non-irritating dose during the screen phase
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
A 0.4 g aliquot of neat test substance moistened with 0.1 mL of distilled water (approximately two weeks after last induction application)
Day(s)/duration:
6 h
Adequacy of challenge:
highest non-irritant concentration
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
Five naive animals received a 0.4 g aliquot of neat test substance moistened with 0.1 mL of distilled water
Day(s)/duration:
6 h
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
10 for induction and challenge and 5 naive animals for challenge
Details on study design:
SCREEN PHASE: A preliminary skin irritation screen was conducted in order to determine a slightly irritating dose as well as to establish the highest non-irritating concentration of the test material. Guinea pigs were clipped free of hair, on the left and right side, the day prior to study initiation. Single application of 0.4 g of neat test substance moistened with 0.1 ml of distilled water was topically applied to the skin of guinea pigs for six hours, in up to two application sites per animal. The following day the application sites were depilated with Neet hair cream remover. Skin irritation readings were recorded approximately 24 and 48 after test substance removal.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 hours
- Test groups: 1
- Control group: 1
- Site: Left side
- Frequency of applications: Once weekly
- Duration: Three consecutive weeks
- Concentrations: Neat test substance moistened with 0.1 mL of distilled water

B. CHALLENGE EXPOSURE
- No. of exposures: 1 after last induction application and 1 application to naive animals
- Days of challenge: Approximately two weeks after the last induction application
- Exposure period: 6 hours
- Test groups: 2
- Control group: 2
- Site: Right side
- Concentrations: Neat test substance moistened with 0.1 mL of distilled water
- Evaluation (hr after challenge): 24 and 48
Positive control substance(s):
yes
Remarks:
10% solution of DER 331 epoxy resin in dipropylene glycol monomethyl ether
Positive control results:
Challenge application with the positive control caused slight to moderate erythema, considered to reflect a hypersensitivity response at the test site, on seven of ten animals. No effect was noted in the corresponding naive control animals, at the 48 hour read.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
other: Naive test substance animals
Dose level:
100%
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:
other: Naive test substance animals
Dose level:
100%
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
10%
No. with + reactions:
7
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
10%
No. with + reactions:
7
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
other: Naive positive control animals
Dose level:
10%
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:
other: Naive positive control animals
Dose level:
10%
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Interpretation of results:
GHS criteria not met
Conclusions:
Test substance did not cause delayed contact hypersensitivity in guinea pigs
Executive summary:

The test substance was evaluated for dermal sensitization potential using the Buehler method following OECD guideline 406 and US EPA guideline 81-6. Ten male Hartley albino guinea pigs received three dermal applications of 0.4 g of test substance during the three-week induction period. Guinea pigs were given a challenge application of 0.4 g of test substance two weeks after the last induction application. At the challenge phase, five naive animals also received a 0.4 g dermal application of test substance. The condition of the test sites was assessed approximately 24 and 48 hours after the challenge application. Challenge application with 0.4 g of test substance caused no erythema at the test site in the ten animals and none of the naive animals showed any evidence of irritation. An additional ten male Hartley albino guinea pigs received three dermal applications of 0.4 ml of a 10% solution of DER 331 epoxy resin, in dipropylene glycol monomethyl ether, which were run concurrently as a positive control. Challenge application with 0.4 ml of 10% DER 331 caused slight to moderate erythema at the test site in seven out of ten animals, while none of the DER 331 naive animals showed any evidence of irritation, at the 48-hour read. The animals were in apparent good health and gained weight over the study period. Therefore, under the conditions of this study, test substance did not cause delayed contact hypersensitivity in guinea pigs.

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
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:
LLNA test was also conducted (see Report 243491). Results of the LLNA test were negative. The results of this guinea pig maximazation test were positive and were therefore chosen as a key study along with the LLNA test. This study was conducted in 1995 whereas the LLNA test was conducted in 2007.
Specific details on test material used for the study:
- Name of substance: XDE-795 Technical
- Lot No.: RMM 2008
- Purity: 97.5%
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Route:
intradermal
Vehicle:
other: purified water
Concentration / amount:
0.1 mL of Freunds complete adjuvant (FCA)
Day(s)/duration:
single injection at least five days before topical application
Route:
epicutaneous, occlusive
Vehicle:
propylene glycol
Concentration / amount:
First induction: 1% w/v
Sencond induction: 50% w/v
Day(s)/duration:
48 hours
Adequacy of induction:
highest technically applicable concentration used
No.:
#1
Route:
intradermal
Vehicle:
other: purified water
Concentration / amount:
0.1 mL FCA
Day(s)/duration:
single injection at least 20 days before topical challenge
No.:
#2
Route:
epicutaneous, occlusive
Vehicle:
propylene glycol
Concentration / amount:
10, 50% w/v
Day(s)/duration:
24 hours
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
Test group: 10 per sex per dose
Congrol group: 5 per sex per dose
Challenge controls:
Propylene glycol, 10 and 50% w/v test substance in propylene glycol
Positive control substance(s):
no
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0
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:
0
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
50% w/v
No. with + reactions:
18
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
50% w/v
No. with + reactions:
16
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
10% w/v
No. with + reactions:
6
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
10% w/v
No. with + reactions:
8
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Group:
positive control
Remarks on result:
not measured/tested
Interpretation of results:
Category 1B (indication of skin sensitising potential) based on GHS criteria
Conclusions:
Repeated administration of the test substance caused delayed contact hypersensitivity in guinea pigs
Executive summary:

The potential of the test substance to cause delayed contact hypersensitivity in the guinea-pig was assessed by the Magnusson-Kligman Maximisation Test following OECD guideline 406.

The closely-clipped dorsa of ten male and ten female Dunkin-Hartley guinea-pigs were subject to intradermal injections of Freund’s Complete Adjuvant, 1% w/v test substance in propylene glycol and 1% w/v test substance in the adjuvant on Day 1. On Day 7, the same area was treated with sodium lauryl sulphate to enhance the dermal penetration of the following dose. On Day 8, 50% w/v test substance in propylene glycol was applied topically and the test site was covered by an occlusive dressing for 48 hours. The same induction procedures were carried out on a contemporaneous control group of five male and five female animals, except that the test material was replaced by vehicle in all doses.

On Day 22, all animals were challenged by occluded topical application of propylene glycol to the left flank and 50% w/v test substance and 10% w/v test substance in propylene glycol to two sites on the right flank. The occlusive dressings were removed on the following day and the condition of the test sites was assessed approximately 24 and 48 hours later.

Intradermal injection of 1% w/v test substance in propylene glycol caused moderate erythema, eschar and occasional pallor, while intradermal injection of 1% w/v test substance in propylene glycol in FCA caused slight or moderate erythema and pallor. Intradermal injection of FCA alone caused moderate erythema in all animals. Topical induction application of 50% w/v test substance in propylene glycol caused barely perceptible or slight erythema, exfoliation and occasional eschar.

Challenge application of 50% w/v test substance in propylene glycol gave rise to a significant response (slight erythema or a more marked reaction) in eighteen test animals and no controls. Challenge application of 10% w/v test substance in propylene glycol gave rise to a significant response in nine test animals and no controls. Challenge application of propylene glycol alone caused no significant response.

It is concluded that, under the conditions of this study, repeated administration of test substance in propylene glycol caused delayed contact hypersensitivity in guinea-pigs, and is classified as a dermal sensitizer.

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2600 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)
Deviations:
no
GLP compliance:
yes
Type of study:
mouse local lymph node assay (LLNA)
Specific details on test material used for the study:
- Substance ID: TSN 105644
- Name of substance: XDE-175 (85:15)
- Lot No.: F50-E1662-86
- Purity: 86.3% as the sum of XDE-175-J and XDE-175-L with 73.0% XDE-175-J and 13.3% XDE-175-L
Species:
mouse
Strain:
CBA:J
Sex:
female
Vehicle:
acetone/olive oil (4:1 v/v)
Concentration:
5, 25, and 75%
No. of animals per dose:
6
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
Key result
Parameter:
SI
Value:
0.8
Variability:
0.3
Test group / Remarks:
5%
Key result
Parameter:
SI
Value:
1.2
Variability:
0.6
Test group / Remarks:
25%
Key result
Parameter:
SI
Value:
2.2
Variability:
1.1
Test group / Remarks:
75%
Parameter:
SI
Value:
7.2
Variability:
3.7
Test group / Remarks:
30% HCA (positive control)
Parameter:
SI
Value:
1
Variability:
0.5
Test group / Remarks:
4:1 acetone:olive oil (Vehicle control)
Interpretation of results:
GHS criteria not met
Conclusions:
Not a sensitizer in the mouse LLNA
Executive summary:

The Local Lymph Node Assay (LLNA) was conducted to assess the potential of test substance to cause contact sensitization by measuring the lymphocyte proliferative responses from auricular lymph nodes following topical application of the test substance to the mouse ear, following OECD guideline 429 and U.S. EPA OPPTS 870.2600.

In the screening study, three daily topical applications of 1%, 5%, 25%, 50%, 75%, or 90% test substance were given to one animal at each dose level. Erythema was absent in the mice treated with 1%, 5%, 25%, 50%, and 75%, while the mouse treated with 90% demonstrated slight erythema on day 3, which resolved by day 6. Body weights were unaffected in all mice, except the mouse treated with 90% test substance, which lost 1.8 grams of body weight. Results from this study were used to determine the dosing concentrations for test substance in the LLNA.

In the LLNA study, six female mice/group received 5%, 25%, or 75% of test substance, or vehicle (4:1 acetone:olive oil), on days 1-3. On day 6, uptake of 3H-thymidine into the auricular lymph nodes draining the site of chemical application was measured five hours post administration. Proper conduct of the LLNA was confirmed via a positive response using 30% α-hexylcinnamaldehyde (HCA), a moderate contact sensitizer, which elicited proliferation that was 7.2 in comparison to vehicle-treated mice.

Erythema was absent in the mice treated with 5% and 25% test substance, while the mice dosed with 75% demonstrated slight erythema on day 3, which persisted through day 6. Body weights were unaffected in all dose groups.

The test substance elicited proliferative responses with stimulation indices (SI) that were respectively 0.8, 1.2 and 2.2 in comparison to the vehicle-treated mice. The test substance did not demonstrate dermal sensitization potential in the mouse LLNA as the lymph nodes draining the area of topical application did not demonstrate a 3-fold proliferation when compared to vehicle-treated mice.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

When tested in the local lymph node assay (LLNA) in mice, the test substance elicited proliferative responses with stimulation indices (SI) that were 0.8, 1.2, and 2.2 in comparison to the vehicle-treated mice. The test substance did not demonstrate dermal sensitization potential in the mouse LLNA as the lymph nodes draining the area of topical application did not demonstrate a 3-fold proliferation when compared to the vehicle-treated mice. The positive control substance, α-hexylcinnamaldehyde (HCA), elicited proliferation that was 7.2 in comparison to the vehicle-treated mice.

The dermal sensitization potential of the test substance was also evaluated in guinea pigs by the Buehler method in male Hartley albino guinea pigs. The positive control substance, DER 331 epoxy resin, caused slight to moderate erythema in seven out of 10 animals during the challenge application. Challenge application of the test substance did not produce any erythema at the test substance. Under the conditions of this study, the test substance did not possess skin sensitising potential. When tested in another guinea pig study conducted according to the Magnusson-Kligman Maximisation test, repeated administration of the test substance in propylene glycol caused delayed hypersensitivity.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

The test substance was negative for skin sensitization when tested in guinea pigs by the Buehler method and in mice when tested in the LLNA test. However, the test substance caused delayed hypersenisitivity in the guinea pig Magnusson-Kligman Maximisation test and a positive patch test in humans has been reported. Based on the results of the Magnusson-Kligman Maximisation test, the substance is classified as Category 1B for skin sensitisation according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.