(E)-7,11-dimethyl-3-methylenedodeca-1,6,10-triene

Acute Toxicity: oral

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

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

Test material information

Constituent 1

Reference substance name:

(E)-7,11-dimethyl-3-methylenedodeca-1,6,10-triene

EC Number:

242-582-0

EC Name:

(E)-7,11-dimethyl-3-methylenedodeca-1,6,10-triene

Cas Number:

18794-84-8

Molecular formula:

C15H24

IUPAC Name:

(E)-7,11-dimethyl-3-methylenedodeca-1,6,10-triene

Constituent 2

Reference substance name:

Farnesene

IUPAC Name:

Farnesene

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 or test system 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:

other: piloerection, wettness and staining about the urogenital area, alopecia, dark substance on nose.

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.