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Toxicological information

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented study report which meets basic scientific principles

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report Date:
1985

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: Modified Buehler (Ritz and Buehler, 1980)
GLP compliance:
yes
Type of study:
Buehler test
Justification for non-LLNA method:
This substance has been demonstrated to be a non-sensitizer in a guideline compliant studies, therefore potency data as generated in an LLNA is not needed.

Test material

Reference
Name:
Unnamed
Type:
Constituent

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Kingston, Stone Ridge, New York
- Age at study initiation: not reported
- Weight at study initiation: 426 - 632 g
- Housing: 1/cage in wire mesh cages
- Diet (e.g. ad libitum): ad libitum, Purina guinea pig chow
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 14 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 70 to 75 degrees C
- Humidity (%): 48-66%
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12 hours light / 12 hours dark


IN-LIFE DATES: From: August 20, 1984 To: September 26, 1984

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: ethanol
Concentration / amount:
0.4 mL of a 3.0% w/v ethanol solution induction
0.4 mL of a 1.0% w/v in acetone challenge
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: ethanol
Concentration / amount:
0.4 mL of a 3.0% w/v ethanol solution induction
0.4 mL of a 1.0% w/v in acetone challenge
No. of animals per dose:
30
Details on study design:
RANGE FINDING TESTS: Range finding skin irritation tests were conducted on 16 naive guinea pigs to determine the slightly irritating concentration (SIC) to be used for induction and the highest non-irritating concentration (HNIC) to be used for challenge. Eight concentrations: 50%, 25%, 12.5%, 6.0%, 3.0%, 1.0%, 0.5% and 0.25% w/v test material in absolute ethanol and the same concentrations in acetone were applied to the skin sites. The application sites were changed among the guinea pigs for each of the above concentrations to minimize any site-to-site variation in irritation response.

The range-finding primary skin irritation tests results on 32 naïve guinea pigs were 3% in absolute ethanol for induction and 1% in acetone for challenge.
RESULTS OF TEST -
Sensitization reaction:
Induction Incidence Irritation/Sensitization
24 hr 48 hr
3% (w/v) in ethanol 0/10 (0.2) 0/10 (0.1)

Challenge
1% in acetone 15/19 (1.4) 10/19 (0.7)

Note: the value in parenthesis represents the mean dermal score (i.e., the intensity of the irritation response) - Clinical signs: At a challenge concentration of 1% test material in acetone, 15 of the 19 guinea pigs induced with test material responded with erythema of grade 1 or greater while none of the non-induced guinea pigs responsed with erythema of grade 1 or greater.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 10
- Exposure period: three 6 hr periods per week for 3.5 consecutive weeks
- Test groups: 19 guinea pigs
- Control group: yes; receiving SHAM treatment during induction
- Site: back of the guinea pigs
- Frequency of applications: 10 applications over a 3.5 week period
- Duration: 6-hr
- Concentrations: 3.0%


B. CHALLENGE EXPOSURE- after a two-week rest period
- No. of exposures: 1
- Day(s) of challenge: 48 hours
- Exposure period: approximately 24 hours after the challenge application, the backs of the guinea pigs were depliated with NEET(R) lotion hair remover. The depilatory was liberally applied to the clipped application sites and allowed to remain on the animlas for approximately 20 minutes. The animals were then rinsed with lukewarm running tap water, blotted dry, and then returned to their cages.
- Test groups: 19 treated guinea pigs from the induction group and a group of 10 naive guinea pigs
- Control group: yes, from induction group
- Site: back of the guinea pigs
- Concentrations: 1.0% w/v test material
- Evaluation (hr after challenge):


OTHER: No rechallenge
Challenge controls:
Non-induced challenge controls
Positive control substance(s):
no

Results and discussion

Positive control results:
Not applicable

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
1.0% w/v in acetone
No. with + reactions:
15
Total no. in group:
19
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 1.0% w/v in acetone. No with. + reactions: 15.0. Total no. in groups: 19.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
1.0% w/v in acetone
No. with + reactions:
10
Total no. in group:
19
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 1.0% w/v in acetone. No with. + reactions: 10.0. Total no. in groups: 19.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
1.0% w/v in acetone
No. with + reactions:
0
Total no. in group:
19
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 1.0% w/v in acetone. No with. + reactions: 0.0. Total no. in groups: 19.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
1.0% w/v in acetone
No. with + reactions:
0
Total no. in group:
19
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 1.0% w/v in acetone. No with. + reactions: 0.0. Total no. in groups: 19.0.

Applicant's summary and conclusion

Interpretation of results:
sensitising
Conclusions:
Under these test conditions, the test material produced DCH in guinea pigs induced with the test material.
Executive summary:

The delayed contact hypersensitivity *DCH potential of the test material was tested in young adult outbred Hartley guinea pigs (GP). Ten induction doses (0.4 ml) of 3.0% (W/V) test material in absolute ethanol were applied to the backs of an induction group of 9 male and 10 female GP for three 6 -hr periods per week for 3.5 consecutive weeks. Two weeks after the last induction treatment, the 19 GP in the induction group and a group of 10 naive control GP were each "challenged" with 0.4 ml of a 1.0% (W/V) solution of test material in acetone. Erythema reactions were scored at 24 and 48 hours after the challenge exposure. At a challenge concentration of 1.0% (W/V) test material in acetone, 15 of 19 test material induced GP responded with an erythema reaction of grade 1 or greater while no grade 1 or greater reactions were observed in the 10 non-induced controls. Under these test conditions, the test material produced DCH in guinea pigs induced with the test material.