Exo-1-methyl-4-(1-methylethyl)-7-oxabicyclo[2.2.1]heptan-2-ol

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1986-02-18 to 1986-03-20

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1986

Report date:

1986

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

GLP compliance:

yes

Type of study:

Buehler test

Justification for non-LLNA method:

A Buhler test with the test substance is available. The Buhler test has been shown to be sensitive enough to detect moderate to strong sensitisers and is thus considered suitable to address this endpoint.

Test material

Test material information

Constituent 1

Reference substance name:

(1S,2S)-1-methyl-4-(propan-2-yl)-7-oxabicyclo[2.2.1]heptan-2-ol

Cas Number:

87172-89-2

IUPAC Name:

(1S,2S)-1-methyl-4-(propan-2-yl)-7-oxabicyclo[2.2.1]heptan-2-ol

Test material form:

solid

In vivo test system

Test animals

Species:

guinea pig

Strain:

Hartley

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc., Wilmington, MA.
- Weight at study initiation: Test group: 413 +/-18; Naive control: 409 +/- 16; Positive control: 402 +/-12
- Housing: The animals were individually housed in wire-mesh cages.
- Diet: NIH Animal Feed A, Zeigler Brothers, Inc., Gardners, PA; ad libitum
- Water: Tap water; ad libitum
- Acclimation period: The animals were acclimated to the laboratory environment for at least 5 days
- Indication of any skin lesions: None

ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

No. of animals per dose:

Test group: 10 animals
Positive control: 6 animals
Naive control: 3 animals

Details on study design:

RANGE FINDING TESTS:
A test item sample was prepared at concentrations of 25, 50 and 75% w/v in mineral oil immediately prior to application and dispensed for dose administration. The test article was also dispensed neat (as received from the Sponsor). Four female guinea gips were exposed once to the test article. No dermal irritation was observed following application of the tested concentrations. Based on the range finding study the test item was dispensed as received from the Sponsor for both the induction and challenge application.

MAIN STUDY
A. INDUCTION EXPOSURE (Day 1, 8, 15)
- No. of exposures: 3
- Exposure period: 6 h; Patches were secured in place after dose administration with an overwrap of Micropore® tape, plastic wrap and a stockinette sleeve. Following the exposure period, the patches were removed and any remaining material was gently wiped off with a clean gauze.
- Test groups: 10 animals (see table 1 for details).
- Control group:
Positve control: 6 female animals were exposed to DNCB (see table 1 for details).
Naive control: 3 additional animals serve as naive controls at the challenge (see table 1 for details).
- Site: Clipped back of the animals
- Frequency of applications: Once a week
- Concentrations: 0.5 g of the test item

B. CHALLENGE EXPOSURE (Day 29)
- No. of exposures: Single application
- Day of challenge: 29
- Exposure period: 6 h; Patches were secured in place after dose administration with an overwrap of Micropore® tape, plastic wrap and a stockinette sleeve. Following the exposure period, the patches were removed and any remaining material was gently wiped off with a clean gauze.
- Test groups: 10 animals (see table 1 for details).
- Control group:
Positve control: 6 female animals were exposed to DNCB (see table 1 for details).
Naive control: 3 additional animals serve as naive controls at the challenge (see table 1 for details).
- Site: Dorsal virgin skin sites
- Concentrations: 0.5 mL

OTHER:
Daily observations and dermal response evaluation:
All animals were observed daily for signs of toxicity and overt behavioral changes. Mortality checks were conducted twice daily, at least five hours apart. The application sites were examined for erythema and edema at 24 and 48 hours post-induction and challenge applications. Erythema and edema were scored according to the Draize method.

Positive control substance(s):

yes

Remarks:

1-chloro-2,4-dinitrobenzene (DNCB)

Results and discussion

In vivo (non-LLNA)

Results

Results 1

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

0.5 g of the test item

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Edema and Erythema Score; For details see table 1

Results 2

Key result

Reading:

1st reading

Hours after challenge:

48

Group:

test chemical

Dose level:

0.5 g of the test item

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Edema and Erythema Score; For details see table 1

Any other information on results incl. tables

Daily observation and body weight:

One animal exhibited soft stools during the study. All other animals appeared normal throughout the study period.

All animals gained weight during the study.

Induction Application:

Very slight (Draize score = 1) erythema was noted for one test article-treated animal following induction application two.

DNCB-treatment caused dermal irritation which was characterized by erythema. Individual erythema scores within this treatment group increased from none (0) to well-defined (2) after three applications. Slight (1) edema was observed in two DNCB-treated animals following induction application 3.

Challenge:

No irritation was noted in the test or naive animals following the challenge application. This response was significantly greater (p<=0.05) than the response obtained after the first induction application. Slight (1) edema was also observed following the challenge application of DNCB in one of the six animals.

Table 1: Summary of Dermal Response - Edema

Group	Application	Mean Edema Score
		24 h	48 h
Test	Induction 1	0	0
	Induction 2	0	0
	Induction 3	0	0
	Challenge	0	0
Naive Control	Challenge	0 (3)	0 (3)
Positive Control
DNCB (0.1% in 70% ethanol)	Induction 1	0 (6)	0 (6)
DNCB (1.0% in 70% ethanol)	Induction 1	0 (6)	0 (6)
	Induction 2	0 (6)	0 (6)
	Induction 3	0.3±0.5 (6)	0.2±0.4 (6)
DNCB (0.1% in 70% ethanol)	Challenge	0 (6)	0.2±0.4 (6)
70% ethanol	Challenge	0 (6)	0 (6)

Values are group mean±S.D. of scores read at 24 and 48 hours post-administration for 10 animals except where indicated in ()

Table 2: Summary of Dermal Response - Erythema

Group	Application	Mean Erythema Score
		24 h	48 h
Test	Induction 1	0	0
	Induction 2	0	0.1  ±0.3
	Induction 3	0	0
	Challenge	0	0
Naive Control	Challenge	0 (3)	0 (3)
Positive Control
DNCB (0.1% in 70% ethanol)	Induction 1	0 (6)	0 (6)
DNCB (1.0% in 70% ethanol)	Induction 1	1.2±0.4 (6)	1.2±0.4 (6)
	Induction 2	1.0 ± 0 (6)	1.0±0 (6)
	Induction 3	1.8±0.4 (6)	1.8±0.4 (6)
DNCB (0.1% in 70% ethanol)	Challenge	1.7 ^a±0.5 (6)	1.5 ^a±0.5 (6)
70% ethanol	Challenge	0 (6)	0 (6)

Values are group mean±S.D. of scores read at 24 and 48 hours post-administration for 10 animals except where indicated in ()

^a Significantly different from induction application 1 (p≤0.05)

 

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this Buehler test, the test substance did not cause dermal contact sensitisation in female albino guinea pigs.