Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
8/18/10 - 11/29/10
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 870.1100 (Acute Oral Toxicity)
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
GLP compliance:
yes
Test type:
up-and-down 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

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Ace Animals, Boyertown, PA on 08/03/10 & Taconic Farms, Hudson, NY
- Age at study initiation: The animals were born the week of 06/08/10 and on 06/21/10. First exposure to test subtance was on 8/31/10
- Weight at study initiation: 224 - 259 grams. The weight variation of the animals used did not exceed + 20% of the mean weight of the previously dosed animals. See body weight data summarzied in "administration/exposure" section.
- Housing/Environmental conditions: The animals were identified by cage notation and indelible body marks, and individually housed in suspended stainless steel wire bottom cages. Paper bedding was placed beneath the cages and changed at least three times per week. The animal room, reserved exclusively for rats 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 Rat Chow (Diet #5012) was freely available except for 16-20 hours prior to dosing.
- Water (e.g. ad libitum): Available ad libitum


IN-LIFE DATES: From: 8/31/10 To: 9/22/10

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
Initially, one rat dosed at 5000 mg/kg. Since the animal survived, two additional animals were dosed at 5000 mg/kg. The rats were observed at 15 minutes, 1, 2 and 4 hours post dose and once daily for 14 days for toxicity and pharmacological effects. All animals were observed twice daily for mortality.

Doses:
5000 mg/kg

No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
-Oral dosing by syringe and dosing needle
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Daily for mortality; twice daily for toxicity and pharmacoligical effects; weighed pre-test, once weekly, and at termination.
- Necropsy of survivors performed: yes
Statistics:
Animal # Dose volume (cc) Body Weight (g) Day 0 Body Weight (g) Day 7 Body Weight (g) Day 14
1 1.7 259 295 295
2 1.5 224 267 253
3 1.5 227 250 252

Mean 237 271 267
Std. Dev 19.4 22.7 24.5



Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
0/3
Clinical signs:
-A single instance of anogenital area wetness was noted during the observation period. See "Adminstration/Exposure" for summary table.

Body weight:
-Body weight changes were normal in 2/3 animals. One animal lost weight within the last week of observations. See body weight information in "Administration/Exposure" section.
Gross pathology:
Normal
Other findings:
No

Applicant's summary and conclusion

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

Initially, one healthy feamle Sprague Dawley rat was dosed orally with farnesane at 5000 mg/kg. Since the animal survived, two additional animals were dosed at 5000 mg/Kg. The rats were observed at 15 minutes, 1, 2, and 4 hours post-dose and once daily for 14 days for toxicity and pharmacological effects. All animals were oberved twice daily for mortality. Body weights were recorded immediately pre-test, weekly, and at termination. All animals were examined for gross pathology. The potential for toxicity was based on the mortality response noted. All animals survived the 5000 mg/kg oral dose. A single instance of wetness of the anogenial rae was noted during the observation period. Body weight changes wer normal in 2/3 animals. one animal lost weight within the last week of observations. Necropsy results were normal.

Conclusion: The LD50 of farnesane is greater than 5000 mg/Kg body weight in female rats.