Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
This study was designed to comply with the standards set forth in EPA Health Effects Testing Guidelines, OPPTS Series 870.1100,December 2002 and in OECDGuidelines for the testing of Chemicals, Guideline 425 updated March 2006. The study was also conducted in accordance with Good Laboratory Practices requirements of EPA, 40 CFR 160 and 792, FDA 21 CFR 58, and the OECD, Principles on Good Laboratory Practices, 1997.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report Date:
2009

Materials and methods

Test guideline
Qualifier:
according 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
Type:
Constituent
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): trans-beta-farnesene

Test animals

Species:
rat
Strain:
other: Wistar Albino
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Ace Animals; Boyertown, Pennsylvanina USA
- Age at study initiation: 10 weeks
- Weight at study initiation: 209-218 grams
- Fasting period before study: 16-20 hours prior to dosing
- Housing: individually housed in suspended stainless steel wire bottom cages; paper bedding beneath cages with bedding changed 3x/week.
- Diet (e.g. ad libitum): PMI rat chow ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 24.38 °C
- Humidity (%): 0 - 3.6%
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark

IN-LIFE DATES: From: 12/30/2008 To: 1/19/2009

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 5000 mg/kg

- Rationale for the selection of the starting dose: Initially one animal was dosed. Since it survived, 2 additional animals were dosed.
Doses:
5000 mg/kg
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: weighing: pre-test, weekly, and at termination. Observation: Daily for toxicological effects and twice daily for mortality
- Necropsy of survivors performed: yes
- Other examinations performed: body weight and systemic toxicity

Results and discussion

Preliminary study:
First rat was dosed at 5000 mg/kg. No mortality so proceeded with dosing other rats with 5000 mg/kg
Effect levels
Sex:
female
Dose descriptor:
approximate LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
95% CL:
> 5 000
Mortality:
None observed
Clinical signs:
piloerection, wettness and staining about the urogenital area, alopecia, dark substance on nose.
Body weight:
Dose Volume and Body Weights
Dose: 5000 mg/kg
Dose Volume
An. # & Sex in cc Day 0 Day 7 Day 14
1 F 1.30 218 260 279
2 F 1.30 213 275 273
3 F 1.30 209 258 267

MEAN 213 264 273
S.D. 4.5 9.3 6.0
# 3 3 3
Gross pathology:
No findings in necropsy

Systemic Observations
DOSE 5000 mg/kg

Animal # / Sex 1/F 2/F 3/F
15 minutes
Hour 1
Hour 2
Hour 4
Day 1 R T,F,1 T,F,1
Day 2 R T,1
Day 3 2
Day 4 2
Day 5 2
Day 6 2
Day 7 2
Day 8 2
Day 9 2
Day 10 2
Day 11 2 2
Day 12 2 2,3
Day 13 2 2,3
Day 14 2 2
No entry indicates animal appeared normal at that observation period.
F = Piloerection R = wetness of the anogenital area T = soiling of the anogenital area 1 = anogenital area stained yellowish around back tail area
2 = alopecia around anogenital area 3 = dark substance on nose

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Rat Oral LD50 > 5000 mg/kg
Executive summary:

Initially, one healthy female Wistar albino rat was dosed orally with trans-ßfarnesene, (Lot# KJF-134-53-03, CAS# 18794-84-8) 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 postdose and once daily for 14 days for toxicity and pharmacological effects. All animals were observed twice daily for mortality. Body weights were recorded immediately pretest, weekly and at termination. All animals were examined for gross pathology. The potential for toxicity was based on the mortality response noted.

All three females survived the 5000 mg/kg oral dose. Instances of soiling, wetness and yellow staining of the anogenital area, piloerection, localized alopecia and chromorhinorrhea were noted during the observation period.

Body weight changes were normal in 2/3 animals. One animal lost weight during the second week of the observation period.

There were no macroscopic observations during terminal necropsy.

The LD50 of trans-ß-farnesene following oral administration to the rat was greater than 5000 mg/kg.