2-(3,7-dimethylocta-2,6-dienyl)cyclopentan-1-one

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

April 29 - May 13, 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The analog substance has a very similar chemical structure to the substance being registered. The reported substance has a C8 carbon chain with two methyl groups and two double bonds, and the analog substance has a C9 carbon chain with two methyl groups and two double bonds in the same positions.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Both the source and target substances were tested in very pure forms. The target substance was tested at 100% purity, and the source substance was tested at 99% purity with 1% tocopherol added as a preservative.

3. ANALOGUE APPROACH JUSTIFICATION
These results provide further justification that the target substance is non-toxic.

4. DATA MATRIX
Acute oral LD50 of target substance: > 5,000 mg/kg bw.
Acute oral LD50 of source substance: > 5,000 mg/kg bw.
Acute dermal LD50 of source substance: > 5,000 mg/kg bw.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

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:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-(3,7-dimethyl-2,6-nonadien-1-yl)-cyclopentane

Cas Number:

1206769-45-0

Molecular formula:

C16H26O

IUPAC Name:

2-(3,7-dimethyl-2,6-nonadien-1-yl)-cyclopentane

additive 1

Reference substance name:

3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H-benzopyran-6-ol

EC Number:

233-466-0

EC Name:

3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H-benzopyran-6-ol

Cas Number:

10191-41-0

Molecular formula:

C29H50O2

IUPAC Name:

2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)chroman-6-ol

Test material form:

liquid

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
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: Born on January 2, 2010
- Weight at study initiation: 2.3-2.8 kg males, 2.6-2.9 females
- Housing: individually in suspended wire cages
- Diet (e.g. ad libitum): PMI Rabbit Chow ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): temperature controlled
- Photoperiod (hrs dark / hrs light): 12 hrs light/12 hrs dark

IN-LIFE DATES: From: April 29, 2010 To: May 13, 2010

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal area of the trunk
- % coverage: 10% of body area
- Type of wrap if used: gauze dressing with semi-occlusive plastic sheeting

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, with water
- Time after start of exposure: 24 hrs

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 12.8 - 16.1 mL to create dose of 5,000 mg/kg bw
- Concentration (if solution): 100%

Duration of exposure:

24 hrs

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Toxicity and pharmacological effects - 1, 2, and 4 hrs postdose, and daily until 14 days; mortality - twice daily; Weighings - pretest, day 7 and day 14.
- Necropsy of survivors performed: yes
- Other examinations performed: gross pathology

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:

None

Clinical signs:

other: All animals showed skin reactions by 24 hrs after exposure, with erythema scores of up to 3 and edema scores of up to 2. By day 7, one animal showed no signs of skin irritation, but all other animals showed signs of irritation such as cracking skin, flak

Gross pathology:

Normal except for skin abnormalities.

Any other information on results incl. tables

Dermal Observations

Animal	Erythema – 24 hrs	Edema – 24 hrs	Erythema – Day 7	Edema – Day 7	Erythema – Day 14	Edema – Day 14
H3245	2	1	Eschar, flaking skin, cracking skin	1	Poor hair regrowth, flaking skin	0
H3246	2	1	0	0	Flaking skin	0
H3247	2	2	Eschar, flaking skin, cracking skin	0	Flaking skin, poor hair regrowth, shiny areas	0
H3249	2	1	>4 moderate eschar, cracking skin, flaking skin	2	Flaking shin, poor hair regrowth	0
H3250	2	0	Cracking skin, flaking skin, eschar	1	Flaking skin, poor hair regrowth	0
H3272	3	1	Cracking skin, flaking skin, eschar	0	Flaking skin, poor hair regrowth	0
H3273	2	2	Cracking skin	0	Flaking skin, poor hair regrowth, shiny areas	0
H3274	2	1	Cracking skin, flaking skin	0	Flaking skin	0
H3275	2	0	Cracking skin, flaking skin	0	Flaking skin	0
H3276	2	1	Flaking skin	0	Flaking skin	0

 

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute dermal LD50 of methyl apritone in rabbits is > 5000 mg/kg bw.

Executive summary:

The dermal toxicity of methyl apritone was determined by exposing 10 rabbits to 5000 mg/kg bw of the substance for 24 hrs. After 24 hrs of exposure, the test substance was removed, and the animals observed for 14 days. Although signs of skin irritiation were noted, no animals died during the study. The acute dermal LD50 of the substance is therefore > 5000 mg/kg bw.