Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
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 870.1200 (Acute Dermal Toxicity)
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): Farnesane
- CAS number: 3891-98-3
-Specific Gravity: 0.77 g/cm3 at 15 °C

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
Animals were received from Covance Research Products, Inc., Denver, PA on 08/11/10. Following an acclimation period of at least five days, five healthy male and five healthy, non-pregnant and nulliparous female New Zealand White rabbits were randomly assigned to the treatment group.

TEST ANIMALS
- Source: Covance Research Products, Inc., Denver, PA

- Age at study initiation: The animals were born on 05/01/10. First Exposure was 8/18/10

- Weight at study initiation: The pretest body weight range was 2.1 - 2.9 kg for males and
2.2 - 2.5 kg for females. The weight variation of the animals used did not exceed + 20% of the mean weight.

- Housing: The animals were identified by cage notation and a uniquely numbered metal eartag and housed 1/cage in suspended wire 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: At least 5 days

IN-LIFE DATES: From: 8/18/10 To: 9/1/10

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Site Preparation
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% of the body surface and remained intact.

Dosing
A single dose of the test article was applied to the prepared site, over a 4-ply porous gauze dressing measuring 10 x 15 cm at a dose level of 5000 mg/kg. The dose was based on the sample weight as calculated from the specific gravity. The torso was wrapped with plastic sheeting in a semi-occlusive manner, which was secured with non-irritating tape. The test article remained in contact with the skin for 24 hours at which time the wrappings were removed. Residual test article was removed by gently washing with distilled water.

- Amount(s) applied (volume or weight with unit) are summarzed below in "Results and Discussion" table

Duration of exposure:
24 hours
Doses:
5000 mg/kg
No. of animals per sex per dose:
5 males at 5000 mg/kg and 5 females at 5000 mg/kg
Control animals:
not required
Details on study design:
Five healthy male and five healthy female New Zealand White rabbits were dosed dermally with Farnesane CAS# 3891-98-3, Lot# AMD_072010 at 5000 mg/kg of body weight. The test article was kept in contact with the skin for 24 hours. Dermal responses were recorded at 24 hours postdose and on days 7 and 14. Animals were observed for toxicity, mortality and pharmacological effects at 1, 2 and 4 hours postdose and once daily for 14 days. Body weights were recorded pretest, weekly and at termination. All animals were examined for gross pathology.
Statistics:
Body weight data is summarized in "Results and Discussion"

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
0/10
Clinical signs:
One male and one female were noted with soiling of the anogenital area between days 1 and 3. There were no other abnormal physical signs noted during the observation period.


Skin reactions were absent to well defined for erythema and absent to slight for edema at 24 hours. On day 7, flaking skin was noted in one animal and no other skin reactions were noted. On day 14, skin reactions were absent.



ANIMAL # & SEX
TIME H3549 H3550 H3551 H3552 H3553 H3554 H3555 H3556 H3557 H3558
PERIODS F F F F F M M M M M
Hour 1
Hour 2
Hour 4
Day 1 T T
Day 2 T T
Day 3 T
Day 4
Day 5
Day 6
Day 7
Day 8
Day 9
Day 10
Day 11
Day 12
Day 13
Day 14

No entry indicates animal appeared normal at that observation period. T = soiling of the anogenital area
------------------------------------------------------------------------------------------------------------------------------------------
Dermal Observations


Animal #/Sex 24 hours Day 7 Day 14
Erythema Edema Erythema Edema Erythema Edema
H3549/F 2 1 0 0 0 0
H3550/F 1 1 0 0 0 0
H3551/F 2 1 0 0 0 0
H3552/F 2 0 0,f 0 0 0
H3553/F 1 1 0 0 0 0

H3554/M 1 0 0 0 0 0
H3555/M 0 0 0 0 0 0
H3556/M 2 0 0 0 0 0
H3557/M 0 2 0 0 0 0
H3558/M 2 0 0 0 0 0

f = flaking skin
Body weight:
The pretest body weight range was 2.1 - 2.9 kg for males and
2.2 - 2.5 kg for females. The weight variation of the animals used did not exceed + 20% of the mean weight. Body weight changes were normal.

Animal #/Sex Dose volume Body Weight (kg) Body Weight (kg) Body Weight (kg)
(cc) Day 0 Day 7 Day 14
H3549/F 14.9 2.3 2.6 2.6
H3550/F 13.6 2.1 2.4 2.5
H3551/F 16.2 2.5 2.8 2.9
H3552/F 18.8 2.9 3.1 3.2
H3553/F 14.9 2.3 2.5 2.6

Mean 2.4 2.7 2.8
SD 0.3 0.3 0.3

H3554/M 16.2 2.5 2.8 2.9
H3555/M 14.3 2.2 2.4 2.6
H3556/M 15.6 2.4 2.5 2.7
H3557/M 14.3 2.2 2.4 2.5
H3558/M 14.3 2.2 2.5 2.5

Mean 2.3 2.5 2.6
SD 0.1 0.2 0.2




Gross pathology:
Necropsy results were normal.

Applicant's summary and conclusion

Interpretation of results:
other: Not classified
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Dermal LD50 in rabbits > 5000 mg/Kg
Executive summary:

Objective: To determine the potential for toxicity of the test article when applied dermally. This study was designed to comply with the standards set forth in EPA Health Effects Testing Guidelines, OPPTS 870.1200, final guideline, August 1998.

 

Method Synopsis: Five healthy male and five healthy female New Zealand White rabbits were dosed dermally with farnesane CAS# 3891-98-3 at 5000 mg/Kg of body weight. The test article was kept in contact with the skin for 24 hours. Dermal responses were recorded at 24 hours post-dose and on days 7 and 14. Animals were observed for toxicity, mortality and pharmacological effects at 1, 2 and 4 hours postdose and once daily for 14 days. Body weights were recorded pretest, weekly and at termination. All animals were examined for gross pathology. 

 

Summary: All animals survived the 5000 mg/Kg dermal application.

 

One male and one female were noted with soiling of the anogenital area between days 1 and 3. There were no other abnormal physical signs noted during the observation period.

 

Skin reactions were absent to well defined for erythema and absent to slight for edema at 24 hours. On day 7, flaking skin was noted in one animal and no other skin reactions were noted. On day 14, skin reactions were absent.

 

Body weight changes were normal.

 

Necropsy results were normal.

 

Conclusion: The dermal LD50 of Farnesane CAS# 3891-98-3 is greater than 5000 mg/Kg of body weight.