Acetic acid, anhydride, reaction products with 1,5,10-trimethyl-1,5,9-cyclododecatriene

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

8 March 2007 - 29 March 2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

482-330-9

EC Name:

-

Cas Number:

144020-22-4

Molecular formula:

C17H26O

IUPAC Name:

1-[(1E,5Z,9Z)-2,5,10-trimethylcyclododeca-1,5,9-trien-1-yl]ethan-1-one; 1-[(1R)-2,5,10-trimethylcyclododeca-2,5,9-trien-1-yl]ethan-1-one; 1-[(1R)-4,9-dimethyl-12-methylidenecyclododeca-4,8-dien-1-yl]ethan-1-one; 1-[(1S)-2,5,10-trimethylcyclododeca-2,5,9-trien-1-yl]ethan-1-one; 1-[(1S)-4,9-dimethyl-12-methylidenecyclododeca-4,8-dien-1-yl]ethan-1-one

Test animals

Species:

other: CD (Crl:CD BR) rats

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, Kent, England.
- Females (if applicable) nulliparous and non-pregnant: Yes
- Age at study initiation: eight to twelve weeks
- Weight at study initiation: 214 to 281 g
- Fasting period before study: No
- Housing: The cages comprised a polycarbonate body with a stainless steel mesh lid and were supplied Lignocel ¾ wood flake bedding, which was changed at appropriate intervals
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: seven days
- Method of randomisation in assigning animals to test and control groups: The animals were allocated without conscious bias to cages within the treatment group. They were housed individually from Day -1 until Day 12 when they were returned to group housing (in groups of five rats of the same sex).

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 23°C
- Humidity (%): 40 to 70%
- Air: The animal room was kept at positive pressure with respect to the outside by its own supply of filtered fresh air, which was passed to atmosphere and not re-circulated.
- Photoperiod (hrs dark / hrs light): 12 hours continuous light and 12 hours continuous dark per 24 hours

Administration / exposure

Type of coverage:

occlusive

Vehicle:

other: None, administered as supplied.

Details on dermal exposure:

Very slight erythema was observed in one male (No. R2) and one female (No. R10) during Days 2 to 3 and Days 5 to 8 respectively. The female exhibiting erythema also showed eschar/scabbing on the dose site from Day 4 until Day 12. Desquamation/exfoliation was observed in a further three animals; one male (No. R4) and one female (No. R9) during Days 5 to 6 and one female (No. R8) during Days 7 to 8.

Duration of exposure:

24 hour exposure period

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 animals per sex per dose (2000 mg/kg)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing:
- Mortality: checked at least twice daily
- Clinical observations: Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1. On subsequent days, animals were observed once in the morning and again at the end of the experimental day (with the exception of Day 15 – morning only). The nature and severity, where appropriate, of the clinical signs and the time were recorded at each observation. All animals were observed for 14 days after dosing.
- Bodyweight: The weight of each rat was recorded on Days 1 (prior to dosing), 8 and 15. Individual weekly bodyweight changes and group mean bodyweights were calculated.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, dermal reactions, macroscopic pathology, and mortality.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0

Clinical signs:

other: Signs of toxicity related to dose levels: There were no deaths and no systemic response to treatment in any animal.

Gross pathology:

Effects on organs: None observed.

Other findings:

Signs of toxicity (local):
Very slight erythema was observed in one male and one female during Days 2 to 3 and Days 5 to 8 respectively. The female exhibiting erythema also showed eschar/scabbing on the dose site from Day 4 until Day 12.

Applicant's summary and conclusion

Interpretation of results:

other: not harmful according to EU CLP (1272/2008 and its amendments)

Conclusions:

The LD50 is > 2000 mg/kg bw in an OECD TG 402 test.

Executive summary:

Acute dermal toxicity in female and male rats was studied in accordance to OECD TG 402 and GLP.  A group of ten rats (five males and five females) received a single topical application of the test substance, administered as supplied, at a dosage of 2000 mg/kg bodyweight for a duration of 24 hours. All animals were killed as scheduled and examined macroscopically on Day 15, the end of the observation period. There were no deaths or clinical signs following the dose level of 2000/mg/kg bodyweight. All animals gained weight throughout the study and no macroscopic findings were evident at the macroscopic examination at termination on Day 15. Very slight erythema was observed in one male and one female. The female exhibiting erythema also showed eschar/scabbing. Desquamation/exfoliation was observed in a further three animals. The acute dermal toxicity (LD50) was determined to be >2000 mg/kg. Based on this result, the substance does not need to be classified for acute toxicity by the dermal route.