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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP, Guideline Study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
Farnesane

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Covance Research Products Inc., Denver, PA on 06/09/10 & 07/07/10.
- Age at study initiation: The animals were born on 02/20/10 & 03/13/10. Experimental Start date was 8/17/10
- Weight at study initiation: The pretest body weight range was 3.0 - 3.4 kg.
- Housing: The animals were identified by cage notation and a uniquely numbered metal eartag and individually housed in suspended wire bottom cages. Paper bedding was placed beneath the cages and changed at least three times/week. The animal room, reserved exclusively for rabbits on acute tests, was temperature controlled, had a 12 hour light/dark cycle, and was kept clean and vermin free.
- Diet (e.g. ad libitum): Fresh PMI Rabbit Chow (Diet #5321) was provided daily
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: None specified

IN-LIFE DATES: From: 8/17/10 To: 8/24/10

Test system

Type of coverage:
semiocclusive
Preparation of test site:
other: The day prior to application of the test article, the dorsal area of the trunk of each animal was clipped free of hair. The prepared site was approximately 10 x 10 cm and remained intact.
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml
- Concentration (if solution): Neat

Duration of treatment / exposure:
The test article was kept in contact with the skin for 4 hours at which time the wrappings and patches were removed. Residual test article was removed from the test site by gently washing with distilled water at the end of the exposure period, prior to scoring for dermal reactions.
Observation period:
The test sites were scored for dermal irritation at 60 minutes and at 24, 48 and 72 hours in all animals and on day 7 in one animal following patch removal. Body weights were recorded pretest and at termination.

Animals were observed for toxicological and pharmacological effects at each dermal observation period and observed for mortality daily. All animals were humanely sacrificed using CO2 following study termination.
Number of animals:
3 males
Details on study design:
TEST SITE
-The test article was dosed by volume, 0.5 ml/site. The test article was placed over a 2 x 3 cm gauze patch. Gentle pressure was applied to aid in the distribution of the test article over the prepared site. The patch was secured with non-irritating tape. The torso was covered with a piece of porous dressing (semi-occlusive) large enough to cover the dose site with at least 5 cm square to spare on all sides of the gauze patch. Porous, non-irritating tape was used to encircle the trunk of the animal. The test article was kept in contact with the skin for 4 hours at which time the wrappings and patches were removed. Residual test article was removed from the test site by gently washing with distilled water at the end of the exposure period, prior to scoring for dermal reactions.

SCORING SYSTEM:

Erythema & Eschar
No erythema 0
Very slight erythema (barely perceptible) 1
Well defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness) to slight eschar formation (injuries in depth) 4


Edema
No edema 0
Very slight edema (barely perceptible) 1
Slight edema (edges of area well-defined by definite raising) 2
Moderate edema (raised approximately 1.0 mm) 3
Severe edema (raised more than 1.0 mm, extending beyond the area of exposure) 4

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
Mean
Time point:
24/48/72 h
Score:
0.33
Max. score:
1
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
Mean
Time point:
24/48/72 h
Score:
0
Max. score:
1
Reversibility:
other: not applicable
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
Mean
Time point:
24/48/72 h
Score:
1.4
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
Mean
Time point:
24/48/72 h
Score:
0.33
Max. score:
1
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
Mean
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
Mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritant / corrosive response data:
At one hour following the 4 hour exposure, erythema was very slight to well defined and edema was very slight. At 24 hours, erythema was very slight to well defined and edema was absent to very slight. At 48 hours, erythema was absent to very slight and edema was absent. At 72 hours, erythema was absent to very slight (one animal) and edema was absent. Animal #H3487/M was extended to day 7. No erythema or edema was noted.



Dermal Observations, Body Weights and Systemic Observations
===============================================================================
Rabbit Eartag: H3490 H3427 H3487
Sex: M M M
Pretest Body Weight - kg: 3.4 3.0 3.1
Terminal Body Weight Day 7 - kg: 3.4 3.1 3.2

Time after patch removal Erythema & Eschar Formation

60 minutes 1 2 2
24 hours 1 2 2
48 hours 0 1 1
72 hours 0 1 0
7 days N/A 0 N/A
Edema

60 minutes 1 1 1
24 hours 0 1 0
48 hours 0 0 0
72 hours 0 0 0
7 days N/A 0 N/A
Systemic Observations

60 minutes A A A
24 hours A A A
48 hours A A A
72 hours A A A


N = Normal; N/A = Not applicable
Other effects:
There were no abnormal physical signs noted during the observation period.

All body weight changes were normal

Applicant's summary and conclusion

Interpretation of results:
other: Not classified
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Test material was not irritating per the EU CLP criteria
Executive summary:

Objective: To determine the irritant or corrosive effects, if any, of test article when applied dermally. This study was designed to comply with the standards set forth in EPA Health Effects Testing Guidelines, OPPTS Series 870.2500, final guideline, August 1998.

Method Synopsis: Since the test article was not expected to produce severe irritation or corrosion, three healthy New Zealand White rabbits (males) were dosed dermally with farnesane.

The test article (0.5ml) was applied dermally to one intact site/rabbit. The test article was kept in contact with the skin for 4 hours at which time the wrappings were removed. Erythema and edema were scored at 60 minutes and at 24, 48 and 72 hours in all animals and on day 7 in one animal (H3487/M) following patch removal. The skin was also evaluated for ulceration and necrosis or any evidence of tissue destruction at these time periods. Animals were observed for toxicological and pharmacological effects at each dermal observation period and observed for mortality daily. Body weights were recorded pretest and at termination. 

Summary: At one hour following the 4 hour exposure, erythema was very slight to well defined and edema was very slight. At 24 hours, erythema was very slight to well defined and edema was absent to very slight. At 48 hours, erythema was absent to very slight and edema was absent. At 72 hours, erythema was absent to very slight (one animal) and edema was absent. Animal #H3487/M was extended to day 7. No erythema or edema was noted.

There were no abnormal physical signs noted during the observation period. All body weight changes were normal.

Conclusion: Farnesane is not classfied as a dermal irritant according to CLP criteria.