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Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From September 1980 to November 1980
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to standard guidelines (with deviations).

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1981
Report date:
1981

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
10 instead of 20 animals in test group
GLP compliance:
no
Type of study:
Buehler test
Justification for non-LLNA method:
The study was conducted before the requirement for LLNA as a basic study to perform in 2013.

Test material

Constituent 1
Reference substance name:
2-Propenoic acid, reaction products with pentaerythritol
EC Number:
629-850-6
Cas Number:
1245638-61-2
Molecular formula:
Not available for this UVCB.
IUPAC Name:
2-Propenoic acid, reaction products with pentaerythritol
Details on test material:
- Name of test material (as cited in study report): C-171
- Physical state: Viscous, clear liquid
- Storage condition of test material: Stored at room temperature

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Dutchland Laboratories, Inc., Denver, Pa
- Weight at study initiation: Males: 291-395 g; females: 290-362 g
- Housing: Individually in suspended stainless steel cages
- Diet (e.g. ad libitum): Purina Guinea Pig Chow containing Vit-C, ad libitum
- Water (e.g. ad libitum): Water (Elizabethtown Water Company), ad libitum
- Acclimation period: 23 d


ENVIRONMENTAL CONDITIONS
- Temperature (°F): 62-71
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: 80 % ethanol (induction phase) or acetone (challenge phase)
Concentration / amount:
Range finding test: 10, 25 and 50 % (v/v) solution in propylene glycol
Main test:
- Induction exposure: 100 % (v/v) solution in propylene glycol
- Challenge exposure: 50 % (v/v) solution in propylene glycol
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: 80 % ethanol (induction phase) or acetone (challenge phase)
Concentration / amount:
Range finding test: 10, 25 and 50 % (v/v) solution in propylene glycol
Main test:
- Induction exposure: 100 % (v/v) solution in propylene glycol
- Challenge exposure: 50 % (v/v) solution in propylene glycol
No. of animals per dose:
Range finding test: 2 animals/sex/dose
Main test: 5 animals/sex/dose
Details on study design:
RANGE FINDING TESTS: 0.2 mL of 10, 25 or 50 % (v/v) solution of C-171 in propylene glycol applied via occlusive patch to the clipped dorsal/lateral skin of animals for 6 h and observed for skin irritation scores after 6, 24 and 48 h post-application


MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: Nine
- Exposure period: 6 h
- Test groups: 100 %
- Control groups: 100 % Propylene glycol (negative control); 0.5 % 2,4-dinitrochlorobenzene (DNCB) in 80 % ethanol (positive control)
- Site: Dorsal/lateral skin, right side to midline
- Frequency of applications: 3 times/wk
- Duration: Days 0-19


B. CHALLENGE EXPOSURE
- Day of challenge: Day 33
- Exposure period: 6 h
- Test groups: 50 % test material in propylene glycol
- Control groups: 100 % Propylene glycol (negative control); 0.1 % DNCB in 80 % ethanol (positive control); 0.1 % DNCB in acetone (irritation control), 50 % C-171 (irritation control)
- Site: Dorsal/lateral skin, left side to midline
- Evaluation of response: Day 33-35; 6 (30 min after patch removal), 24 or 48 h after dosing


C. RECHALLENGE EXPOSURE
- Day of rechallenge: Day 37
- Test groups: 10 or 25 % test material in propylene glycol on site 1 & 2, respectively
- Control group: 10 or 25 % C-171 (irritation control) on site 1 & 2, respectively
- Evaluation of response: Day 37-39; 6 (30 min after patch removal), 24 or 48 h after dosing
Challenge controls:
100 % propylene glycol (negative control); 0.1 % DNCB in 80 % ethanol (positive control); 0.1 % DNCB in acetone (irritation control), 50 % C-171 (irritation control)
Positive control substance(s):
yes
Remarks:
0.1 % DNCB in 80 % ethanol

Results and discussion

Positive control results:
Animals treated with DNCB (positive control) exhibited evidence of sensitization, thus confirming the susceptibility of this group of animals to dermal sensitization.

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
50 % in propylene glycol
No. with + reactions:
5
Total no. in group:
10
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
50 % in propylene glycol
No. with + reactions:
8
Total no. in group:
10
Key result
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
25 % in propylene glycol
No. with + reactions:
1
Total no. in group:
10
Key result
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
10 % in propylene glycol
No. with + reactions:
0
Total no. in group:
10
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
100 % Propylene glycol
No. with + reactions:
0
Total no. in group:
10
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
100 % Propylene glycol
No. with + reactions:
0
Total no. in group:
10
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.1 % DNCB in 80 % ethanol
No. with + reactions:
8
Total no. in group:
10
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.1 % DNCB in 80 % ethanol
No. with + reactions:
8
Total no. in group:
10
Reading:
1st reading
Hours after challenge:
24
Group:
other: Irritation control
Dose level:
0.1 % DNCB in acetone
No. with + reactions:
0
Total no. in group:
8
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: other: Irritation control. Dose level: 0.1 % DNCB in acetone. No with. + reactions: 0.0. Total no. in groups: 8.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
other: Irritation control
Dose level:
0.1 % DNCB in acetone
No. with + reactions:
0
Total no. in group:
8
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: other: Irritation control. Dose level: 0.1 % DNCB in acetone. No with. + reactions: 0.0. Total no. in groups: 8.0.
Reading:
1st reading
Hours after challenge:
24
Group:
other: Irritation control
Dose level:
50 % test material
No. with + reactions:
6
Total no. in group:
8
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: other: Irritation control. Dose level: 50 % test material. No with. + reactions: 6.0. Total no. in groups: 8.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
other: Irritation control
Dose level:
50 % test material
No. with + reactions:
6
Total no. in group:
8
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: other: Irritation control. Dose level: 50 % test material. No with. + reactions: 6.0. Total no. in groups: 8.0.
Reading:
rechallenge
Hours after challenge:
48
Group:
other: Irritation control
Dose level:
25 % test material
No. with + reactions:
2
Total no. in group:
8
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: other: Irritation control. Dose level: 25 % test material. No with. + reactions: 2.0. Total no. in groups: 8.0.
Reading:
rechallenge
Hours after challenge:
48
Group:
other: Irritation control
Dose level:
10 % test material
No. with + reactions:
0
Total no. in group:
8
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: other: Irritation control. Dose level: 10 % test material. No with. + reactions: 0.0. Total no. in groups: 8.0.
Reading:
rechallenge
Hours after challenge:
24
Group:
test chemical
Dose level:
25 % in propylene glycol
No. with + reactions:
1
Total no. in group:
10
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: test group. Dose level: 25 % in propylene glycol. No with. + reactions: 1.0. Total no. in groups: 10.0.
Reading:
rechallenge
Hours after challenge:
24
Group:
test chemical
Dose level:
10 % in propylene glycol
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: test group. Dose level: 10 % in propylene glycol. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
rechallenge
Hours after challenge:
24
Group:
other: Irritation control
Dose level:
25 % test material
No. with + reactions:
2
Total no. in group:
8
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: other: Irritation control. Dose level: 25 % test material. No with. + reactions: 2.0. Total no. in groups: 8.0.
Reading:
rechallenge
Hours after challenge:
24
Group:
other: Irritation control
Dose level:
10 % test material
No. with + reactions:
0
Total no. in group:
8
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: other: Irritation control. Dose level: 10 % test material. No with. + reactions: 0.0. Total no. in groups: 8.0.

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this Buehler study, the test substance was not sensitising in guinea pig.
Executive summary:

A study was conducted to evaluate the skin sensitization potential of C-171in Hartley guinea pigs according to Buehler test method.

 

In the range finding test, test animals (2 animals/sex/dose) were applied with 10, 25 or 50 % (v/v) solution of the susbtance in propylene glycol. In the main study, animals (5/sex) were applied with 0.2 mL of undiluted substance via occluded patch for 6 h, thrice weekly for 3 weeks, followed by a challenge patch of 50 % (v/v) of C-171after 2 weeks of rest period. Control groups included: 100 % propylene glycol (negative control); 0.1 % 2,4-dinitrochlorobenzene (DNCB) in 80 % ethanol (positive control); 0.1 % DNCB in acetone (irritation control), 50 % test material (irritation control). The application sites were graded with irritation scores at 6 (30 min after patch removal), 24 or 48 h after challenge.

 

Results of the initial challenge (at a 50 % concentration) indicated evidence of dermal irritation. Since dermal scores greater than 2 occurred, in both test groups and irritation control animals, a second challenge, at lower concentrations (25 % and 10 %) was, therefore, performed. Although results of this challenge revealed evidence of slight irritation, incidence of response was comparable in control and treated animals. Scores of 2 or greater were exhibited by one of ten test animals and two of eight control animals dosed at 25 %; no dermal scores of 2 or greater occurred in animals treated with 10 %. Animals treated with DNCB (positive control) exhibited evidence of sensitization, thus confirming the susceptibility of this group of animals to dermal sensitization.

 

In conclusion, the test substance was not sensitising in this guinea pig skin sensitisation test (Aulette, 1981).