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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
Study period:
October 12, 1991 - October 30, 1991.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
Buehler test
Justification for non-LLNA method:
not mentioned in report

Test material

Reference
Name:
Unnamed

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: BuckberG Lab Animals, Tomkins Cove, New York
- Age at study initiation: 4-6 weeks
- Weight at study initiation: 300-700 grams
- Housing: Separate isolation by test system Light cycle - 12 hours light, 12 hours dark Temperature/Relative Humidity - Every attempt
was made to maintain a temperature of 22°C ± 3°C (66-77°F) and a relative humidity of 30 to 70%.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

Study design: in vivo (non-LLNA)

Induction
Route:
epicutaneous, semiocclusive
Vehicle:
water
Concentration / amount:
300mg
Day(s)/duration:
30
Adequacy of induction:
not specified
Challenge
Route:
epicutaneous, semiocclusive
Vehicle:
water
Concentration / amount:
300mg
Day(s)/duration:
48 hours
Adequacy of challenge:
not specified
No. of animals per dose:
20 for test item, 5 for positive control, 10 for negative control
Details on study design:
RANGE FINDING TESTS: Prior to initiation of the studies, the irritation potential of each test article was determined in a dose-range-finding study. Four (4) previously unexposed animals were each exposed to four concentrations of 1.0, 10 and 50% of the test article in acetone and as received, by the technique described in site preparation. The procedure for primary challenge was used in grading the responses except that only 24 hour grades were obtained. No signs of erythema were observed at any treatment site with the exception of slightly patchy erythema in one animal treated with EtNENA as received. Therefore, the decision was made to dose the test articles in the definitive studies as received.

MAIN STUDY
All materials were applied beneath a 25 mm Hill Top Chamber1*, (Hill Top Research, Inc., Miamiville, Ohio) and covered with dental dam. The patch and dam were held in place with clips attached to the sides of the guinea pig restrainer. The patches were allowed to remain in place for six hours, after which the rubber dams and patches were removed. This procedure was performed once per week for three weeks, a total of three six hour inductions. The treated sites were examined after each dosing day and scored at 24 and 48 hours for erythema.

CHALLENGE EXPOSURE
Fourteen days after the last induction exposure, all animals were challenged in the same manner on a naive site on the left flank. The negative control animals were challenged with distilled water or 80% ethanol on the left flank and test article on the right flank. Twenty-four hours after challenge, all animals
were depilated with NeetR Hair Remover (Whitehall Laboratories, Inc., New York 10017). The depilatory was applied to the test sites and surrounding areas and removed within 30 minutes by thoroughly rinsing with water and gently patting dry. They were then returned to their cages. A minimum of two hours after depilation, test sites were graded for erythema. The scoring was repeated twenty-four hours later (48 hour grade).
Positive control substance(s):
yes

Results and discussion

Positive control results:
A positive response was elicited in the animals treated with the positive control article.

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
300 mg/site
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
not specified
Key result
Reading:
rechallenge
Hours after challenge:
48
Group:
test group
Dose level:
300 mg/site
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
not specified
Group:
negative control
Dose level:
100mg/site
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: The negative control animals were challenged with distilled water or 80% ethanol
Group:
positive control
Dose level:
0.3%
No. with + reactions:
5
Total no. in group:
5
Remarks on result:
other: DCNB in 80% ethanol

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Based upon the observations made in the Delayed Contact Hypersensitivity Study in Guinea Pigs (Buehler Assay), test articles MeNENA, EtNENA, BUNENA, BDNPA/F+DPA and BDNPA/F-DPA did not cause dermal sensitization in guinea pigs under
the conditions of this study. Dermal sensitization was elicited in the animals receiving the positive control article, 1- chloro-2,4-dinitrobenzene at a 0.3% concentration.