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Administrative data

Description of key information

A Buehler test with the amine part did not show sensitization to the skin of guinea pigs (Dow 1997). For the acid part two maximisation tests showed no sensitization (1984 and 1985)

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:
other: the tested substance is the acid part of the compound
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
according to
Guideline:
other: Magnusson, B., and Kligman, A.M. (1969). The identification of contact allergens by animal assay. The guinea-pig maximization test. J. Invest. Dermat., 52, 268-276.
Principles of method if other than guideline:
an LLNA study does not need to be conducted because adequate data assessed with a different method at an earlier date is available
GLP compliance:
not specified
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
an LLNA study does not need to be conducted because adequate data assessed with a different method at an earlier date is available
Species:
guinea pig
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Porcellus Ltd., UK
- Weight at study initiation: 432-623 g
- Housing: 2-3 per cage of single sex, stainless steel cages with mesh floors, identified with colored body dye
- Diet (e.g. ad libitum): SG1 with vitamin C supplement, ad libitum
- Water (e.g. ad libitum): filtered tap water, ad libitum
- Acclimation period: 2 weeks

IN-LIFE DATES: From: September 5, 1983 To: October 21, 1983
Route:
intradermal and epicutaneous
Vehicle:
corn oil
Concentration / amount:
intradermal induction: 0.05% m/v in corn oil
topical induction: 5% in corn oil
topical challenge: 2.5% in corn oil
Route:
epicutaneous, occlusive
Vehicle:
corn oil
Concentration / amount:
intradermal induction: 0.05% m/v in corn oil
topical induction: 5% in corn oil
topical challenge: 2.5% in corn oil
No. of animals per dose:
10 animals per sex in test group
5 animals per sex in control group
Details on study design:
RANGE FINDING TESTS: The dorsal areas of two male and two females were closely short and shaved with an electric razor. 0.1 ml of several test dilutions were then injected. The concentrations tested were 0.05, 0.1, 0.5, and 1.0 %(m/v) of test substance in corn oil. These animals were observed for the next few days for toxicity. An additional two males and two females were exposed to 0.3 ml of 2.5, 5.0, 10.0, 20.0, and 50.0% of test substance in corn oil dermally for 24 hrs. At 24 and 48 hrs the animals were examined for signs of skin irritation.


MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: two
- Test groups: The test group was first exposed by intradermal injection in the shoulder region. They were each given two injections of 0.1 ml each of Freund's complete adjuvant (FCA), 0.05% test substance in corn oil, and 0.05% of test substance in 50:50 FCA/corn oil. One week later, these same animals were given a dermal induction. The same area of skin was shaved. 0.3 ml of 5% test substance in corn oil was applied to a 4x4 cm2 patch of filter paper. This was applied to the skin and covered with Sleek dressing, which was then covered with Poroplast elastic adhesive bandage. Exposure was for 48 hrs.
- Control group: Control animals were treated in similar fashion with vehicle only.


B. CHALLENGE EXPOSURE
- No. of exposures: one
- Day(s) of challenge: two weeks after the topical induction
- Exposure period: 24 hrs
- Test groups: 0.1 ml of 2.5% test substance in corn oil was placed on a 3x3 cm2 piece of filter paper. A similarly sized piece of adhesive tape was used to cover it, and secured with Poroplast elastic adhesive bandage. Patches were removed after 24 hrs.
- Control group: Control group was exposed in a similar fashion.
- Site: flank
- Evaluation (hr after challenge): Sites were evaluated immediately after removal, and at 24 and 48 hrs after removal. Sites were scored using the Draize scale.

Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
2.5% in corn oil
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: 2.5% in corn oil. No with. + reactions: 0.0. Total no. in groups: 20.0.
Key result
Reading:
2nd reading
Hours after challenge:
24
Group:
test group
Dose level:
2.5% in corn oil
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 24.0. Group: test group. Dose level: 2.5% in corn oil. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
2.5% in corn oil
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 2.5% in corn oil. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
2.5% in corn oil
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 2.5% in corn oil. No with. + reactions: 0.0. Total no. in groups: 10.0.

No animals showed a positive response at the 24 and 48 hr readings.

Results of Skin Sensitisation Study

Animal

0 hrs after challenge

24 hrs after challenge

48 hrs after challenge

Test Group

2908 M

0

0

0

2909 M

0

0

0

2910 M

0

0

0

2941 M

0

0

0

2943 M

0

0

0

2934 F

1

0

0

2935 F

0

0

0

2936 F

0

0

0

2977 F

0

0

0

2978 F

0

0

0

2918 M

0

0

0

2919 M

0

0

0

2920 M

1

0

0

2945 M

0

0

0

2946 M

1

0

0

2937 F

0

0

0

2938 F

0

0

0

2940 F

0

0

0

3001 F

1

0

0

3003 F

0

0

0

Control Group

2947 M

0

0

0

2948 M

0

0

0

2950 M

0

0

0

3024 M

0

0

0

2961 F

0

0

0

2963 F

0

0

0

2964 F

0

0

0

3004 F

0

0

0

3005 F

0

0

0

 

Interpretation of results:
GHS criteria not met
Conclusions:
The test substance is not sensitising to skin.
In a guinea-pig maximization test none of the test animals showed positive responses at 24 or 48 hours after removal of the challenge patches. The test material showed no sensitizing potential in guinea pigs.
Executive summary:

A group of 10 male and 10 female guinea pigs were used to determine the potential of the test substance to be sensitising to skin. The animals were first given an intradermal induction of 0.05% of test substance in corn oil. One week later, they were given a dermal induction of 5% test substance in corn oil. A group of 5 male and 5 female guinea pigs were used as controls. These animals were treated in a similar fashion with vehicle only. Two weeks after the dermal induction, a challenge was performed via dermal exposure to 2.5% test substance in corn oil. The control group was exposed as well. The animals were exposed for 24 hrs. Skin irritation readings were made at 24 and 48 hrs after the end of exposure. No positive responses were seen in either the test or control group. The test substance is not sensitising to skin.

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
other: the tested substance is the acid part of the compound
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
Directive 179/831 Annex, Part B.
GLP compliance:
not specified
Type of study:
other: Guinea pig maximization test
Justification for non-LLNA method:
an LLNA study does not need to be conducted because adequate data assessed with a different method at an earlier date is available
Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 6-8 weeks
- Weight at study initiation: 200-350 g
- Housing: Makrolon cages, 5 per cage
- Diet (e.g. ad libitum): 8GP17 guinea pig food, ad libitum
- Water (e.g. ad libitum): ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2 degree C
- Humidity (%): 60 +/- 20%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 hrs light/12 hrs dark
Route:
other: intracutaneously and epicutaneously
Vehicle:
water
Concentration / amount:
Induction concentration was 25% in water and Freund's Adjuvant; the challenge concentration was 12.5% in deionized water
Route:
other: no data
Vehicle:
water
Concentration / amount:
Induction concentration was 25% in water and Freund's Adjuvant; the challenge concentration was 12.5% in deionized water
No. of animals per dose:
10 male and 10 female
Details on study design:
Induction
Induction was first done by intradermal injection. Test animals were injected with 0.1 ml Freund Complete Adjuvant (FCA), 0.1 ml of 25% test substance in water, and 0.1 ml test substance in FCA in water (final concentration 25%). Control group was treated in a similar manner with only FCA and water. On day 7, a second, epicutaneous challenge was done. 0.5 ml of test susbtance (25%) was placed on gauze, and then placed on the animals. The animals were than bandaged, and the test substance remained in contact for 48 hrs. Control animals were exposed to vehicle only.

Challenge
0.2 ml of 12.5 % test article was placed on gauze, which was then placed on the test and control animals. Gauze containing only vehicle was placed on the left flank. The exposure lasted 24 hrs. Observations for irritation were made at 24 and 48 hrs after the end of exposure. Skin was scored for irritation using the Draize scale.
Positive control substance(s):
not specified
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
0.2 ml of 12.5% test solution
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no positive responses were observed
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.2 ml of 12.5% test solution. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: no positive responses were observed.
Key result
Reading:
2nd reading
Hours after challenge:
72
Group:
test group
Dose level:
0.2 ml 12.5% test solution
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: test group. Dose level: 0.2 ml 12.5% test solution. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
72
Group:
negative control
Dose level:
0.2 ml 12.5% test solution
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 72.0. Group: negative control. Dose level: 0.2 ml 12.5% test solution. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
72
Group:
negative control
Dose level:
0.2 ml 12.5% test solution
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: negative control. Dose level: 0.2 ml 12.5% test solution. No with. + reactions: 0.0. Total no. in groups: 10.0.
Interpretation of results:
GHS criteria not met
Conclusions:
The test substance is not sensitizing to skin.
Executive summary:

This test determined the potential of the test substance to be sensitizing to skin. 10 male and 10 female guinea pigs were given intradermal injections of 25% test solution. Control animals (5 male and 5 female) were given injections of vehicle only. One week later, a second induction was done by dermal exposure to 25% test solution for 24 hrs. Control animals were again exposed to vehicle only. On day 21, the challenge exposure was performed. All animals were exposed to 12.5% test solution dermally. Exposure was for 24 hrs, with observations made at 48 and 72 hrs after the start of exposure. No positive reactions were noted. The test substance is not sensitizing.

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
other: the tested substance is the amine part of the compound
Adequacy of study:
key study
Study period:
1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to test guidelines and in accordance with GLP
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
Buehler test
Justification for non-LLNA method:
an LLNA study does not need to be conducted because adequate data assessed with a different method at an earlier date is available
Species:
guinea pig
Strain:
Hartley
Sex:
male
Details on test animals and environmental conditions:
Male Hartley albino guinea pigs were used. Animals were clipped free of hair, on the left and right side (and may have been clipped on their back), the day prior to dosing.
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
Induction 50 % other: occluded with Hill TopChambersChallenge 50 % other: occluded with Hill Top Chambers
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
Induction 50 % other: occluded with Hill TopChambersChallenge 50 % other: occluded with Hill Top Chambers
No. of animals per dose:
10
Details on study design:
Screen PhaseA preliminary skin irritation screen was conducted in order to determine a slightly irritating dose, if obtainable, as well as to establish the highest non-irritating concentration of the test material. Male Hartley albino guinea pigs were clipped free of hair, on the left and right side (and may have been clipped on their back), the day prior to dosing. A single application of 0.4 ml of 1, 10, 25, and 50% dose solutions of Diisopropanolamine (diluted with distilled water) was topically applied to the skin of guinea pigs for six hours in Hill Top Chambers (25 mm Hill Top Chamber, Hill Top Research Inc., Cincinnati, OH). The following day the application sites were depilated prior to scoring. Skin irritation readings were recorded approximately 24 and 48 hours after test material removal. Induction PhaseThe left side of ten male Hartley albino guinea pigs per treatment group were clipped free of hair the day prior to dosing. A single aliquot of 0.4 ml of 50% Diisopropanolamine (diluted with distilled water) was applied to the left side of ten male guinea pigs in Hill Top Chambers. A single aliquot of 0.4 ml of 10% DER 331 (CAS# 1675-54-3) epoxy in dipropylene glycol monomethyl ether (DPGME) was used as a positive control and applied in Hill Top Chambers to another group of ten male guinea pigs on weeks 1 and 2. On week 3, a single aliquot of 0.4 ml of 7.5% DER 331 in DPGME was applied to the positive control group. The chamber was secured with Vetrap which was held in place with Elastikon and removed after approximately a six hour exposure period. Observation for erythema/edema were recorded the following day. The animals were clipped and the respective groups were treated with the test material or positive control in the same manner at weekly intervals for a total of three consecutive weeks.Challenge PhaseApproximately two weeks after the last induction application, the right side of the animals was clipped free of hair. The test material, a single aliquot of 0.4 ml of 50% Diisopropanolamine or 5% DER331 (positive control material) in DPGME, was applied to the right side of the guinea pigs in the same manner as in the induction phase. (Note- No data on naive animals was found in the study file.) The test material was removed after approximately a six-hour exposure period. The following day the challenge application sites were depilated prior to scoring. The application sites were observed and graded for sensitization response or irritation approximately 24 and 48 hours after the challenge application. The animals were observed at random, such that treatment group and naive animals were unknown. A material is considered a sensitizer if a positive response (erythema and/or edema scored to be 1.0 or greater) is observed following 48 hours after dosing in two or more of the challenge animals with no evidence of irritation in the naive animals.
Positive control substance(s):
yes
Remarks:
DER 331 (CAS# 1675-54-3)
Statistics:
No statistics conducted
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
50%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none reported
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none reported.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
50%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none reported
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none reported.
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
10% DER331
No. with + reactions:
9
Total no. in group:
10
Clinical observations:
none reported
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: 10% DER331. No with. + reactions: 9.0. Total no. in groups: 10.0. Clinical observations: none reported.
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
10% DER 331
No. with + reactions:
9
Total no. in group:
10
Clinical observations:
none reported
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: positive control. Dose level: 10% DER 331. No with. + reactions: 9.0. Total no. in groups: 10.0. Clinical observations: none reported.

DIPA did not cause delayed contact hypersensitivity in guinea pigs

Interpretation of results:
GHS criteria not met
Conclusions:
The 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. Ten male Hartley albino guinea pigs received three dermal applications of 0.4 ml of 50% of the test substance in distilled water) during the three-week induction period. The animals received one application of 0.4 ml of 50% of the substance during the challenge application two weeks after the last induction application. The condition of the test sites was assessed approximately 24 and 48 hours after the challenge application. Challenge application with 0.4 ml of 50%of the substance did not cause erythema at the test site in any of the animals at the 48 hour read. Therefore, under the conditions of this study, the test substance did not cause delayed contact hypersensitivity in guinea pigs.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

The representative substances for the compound did not show any effects. Therefore the compound is considered non-sensitizing.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the outcome of the studies on the components, no classification for sensitization is necessary for the salt according to CLP (Regulation EC No 1272/2008)

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