(1S,4R,4aS,9aR)-4,4a,9,9a-tetrahydro-1H-1,4-methanofluorene

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

02 April to 16 April 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted to OECD, EEC, EPA and JMAF guidelines and in compliance with GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 4

Guideline:

other: JMAFF 12 Nousan No 8147, 2000

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Certificate of Compliance from UK GLP Monitoring Authority.

Test type:

fixed dose procedure

Test material

Test material information

Constituent 1

Reference substance name:

(1R,2S,10R,11S)-tetracyclo[9.2.1.0²,¹⁰.0³,⁸]tetradeca-3(8),4,6,12-tetraene

EC Number:

700-736-9

Cas Number:

2149571-40-2

Molecular formula:

C14H14

IUPAC Name:

(1R,2S,10R,11S)-tetracyclo[9.2.1.0²,¹⁰.0³,⁸]tetradeca-3(8),4,6,12-tetraene

Details on test material:

- Name of test material (as cited in study report): MTF

- Substance type: Organic
- Physical state: Transparent liquid
- Analytical purity: ca 100%
- Lot/batch No.: M1204
- Expiration date of the lot/batch: 31 December 2015
- Storage condition of test material: rom temperature (ca 20 deg C) under nitrogen.
- Other:

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: UK
- Age at study initiation: approximately 8-12 weeks prior to dosing
- Weight at study initiation: Males: 295 - 308 g; Females 185 - 207 g
- Fasting period before study:
- Housing: individually form Days -1 until Day 11 and then group housed (5 rats of same sex) until end of study.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 Days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23 °C
- Humidity (%): 40-70%
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12 hrs dark/12 hrs light

IN-LIFE DATES: From: 02 April 2013 To: 16 April 2013

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure:50mm x 50mm
- % coverage: 10%
- Type of wrap if used: porous gauze held in place with a non-irritating dressing, and further covered by a waterproof dressing encircled firmly around the
trunk of the animal.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, weak solution of detergenr in warm water.
- Time after start of exposure: 24 hrs after start of exposure

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1.89 ml/kg bodyweight
- Concentration (if solution): 1.061 g/ml
- Constant volume or concentration used: yes

Duration of exposure:

24 hours

Doses:

2000 mg/kg bodyweight

No. of animals per sex per dose:

5 per sex

Control animals:

not required

Details on study design:

A group of ten rats (five males and five females) received a single topical application of the test substance, as supplied, at a dose level of 2000 mg/kg
bodyweight, for duration of 24 hours. The animals were retained for a 14 day observation period during which clinical signs, dermal reaction and bodyweight investigations were performed. All animals were humanely killed and examined macroscopically on Day 15, the end of the observation period.

Results and discussion

Preliminary study:

There were no deaths and no systemic response to treatment in any animal. Very slight erythema (barely perceptible) was seen in four males and five females. These reactions had resolved by Day 11. A bodyweight loss was noted for four females on Day 15. All other animals were considered to
have achieved satisfactory bodyweight gains throughout the study.
No abnormalities were noted in any animal at the macroscopic examination at study
termination on Day 15.

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths

Clinical signs:

other: Very slight erythema (barely perceptible) was seen in four males and five females. These reactions had resolved by Day 11.

Gross pathology:

No abnormalities were noted in any animal at the macroscopic examination at study termination on Day 15.

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated information

Conclusions:

The acute median lethal dermal dose (LD50) to rats of MTF was demonstrated to be greater than 2000 mg/kg bodyweight.