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

Acute Toxicity: dermal

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:

2009

Report date:

2009

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

GLP compliance:

yes

Test type:

fixed dose 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
-CAS 18794-84-8

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Covance Research Products, Inc., Denver, PA
- Age at study initiation: 17 weeks
- Weight at study initiation: The pretest body weight range was 2.4 - 2.7 kg for males and 2.7 - 2.9 kg for females.
- Fasting period before study: No
- Housing: housed 1/cage in suspended wire cages. Paper bedding was placed beneath the cages and changed at least three times/week.
- Diet (e.g. ad libitum): Fresh PMI Rabbit Chow (Diet #5321) was provided daily
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 14.72 – 22.94 °C
- Humidity (%): 0-27%
- Air changes (per hr): Not specified
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle

IN-LIFE DATES: From: 1/6/09 To: 1/20/09

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 10 cm x 15 cm
- % coverage: 10%
- Type of wrap if used: 4 ply gauze dressing. The torso was wrapped with plastic sheeting in a semi-occlusive manner, which was secured with non-irritating tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Residual test article was removed by gently washing with distilled water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 5000 mg/kg dose
- Concentration (if solution): neat
- Constant volume or concentration used: yes/no
- For solids, paste formed: Not aplicable

VEHICLE - none

Duration of exposure:

24 hours

Doses:

5000 mg/kg

No. of animals per sex per dose:

5 males and 5 females

Control animals:

not required

Details on study design:

Dermal responses were recorded at 24 hours postdose and on days 7 and 14. Animals were observed for toxicity and pharmacological effects at 1, 2 and 4 hours postdose and once daily for 14 days. All animals were observed twice a day for mortality. Body weights were recorded pretest, weekly and at termination. All animals were examined for gross pathology. Abnormal tissues were preserved in 10% neutral buffered formalin for possible future histological examination.

Results and discussion

Preliminary study:

Not applicable

Effect levels

Effect levels 1

Sex:

female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

None observed

Clinical signs:

other: No systemic observations noted during study.

Gross pathology:

An. # Sex 24 hours Day 7 Day 14
Erythema Edema Erythema Edema Erythema Edema
H2126 M 1 0 1p 0 1e 0
H2118 M 1 0 2 2 1ef 1
H2121 M 0 0 1 2 1ef 0
H2122 M 0 0 1 2 1ef 0
H2125 M 1 0 1 2 1ef 1
H2149 F 1 0 1 1 1ef2 0
H2151 F 0 0 1p 1 1ef2 1
H2153 F 1 0 2p 2 1ef2 1
H2154 F 1 0 1 1 1ef2 0
H2155 F 0 0 1 1 1ef 0

f = flaking skin e = alopecia surrounding dose site 2 = alopecia extended down both sides and completely across the abdomen p = pale areas

Other findings:

Upon necropsy, skin abnormalities at treatment sites were noted in all animals.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Rabbit 24 hour dermal LD50 > 5000 mg/kg

Executive summary:

The acute dermal toxicity of farnesene was investigated in rabbits. The test material was applied to the shaved dorsal skin of 5 male and 5 female rabbits at 5000 mg/kg of body weight, under an occlsive dressing. 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 and pharmacological effects at 1, 2 and 4 hours postdose and once daily for 14 days. All animals were observed twice a day for mortality.

Body weights were recorded pretest, weekly and at termination. All animals were examined for gross pathology. Abnormal tissues were preserved in 10% neutral buffered formalin for possible future histological examination.

There were no deaths during the study and all animals survived the 5000 mg/kg dermal application in good health. Dermal responses were absent to very slight at 24 hours, very slight to well defined on day 7 and very slight on day 14. Additionally, pale areas, flaking skin and areas of poor hair regrowth were noted during the study. Slight body weight loss was noted on day 7 in 8/10 animals, but all returned to normal by day 14. Treated skin abnormalities were the only abnormality noted at necropsy.

The dermal LD50 of trans-ß-farnesene, in the rabbit is greater than 5000 mg/kg of body weight.