Cyclopropanecarboxylic acid, 2-[1-(3,3-dimethylcyclohexyl)ethoxy]-2-methylpropyl ester

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

14-05-2004 to 06-07-2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study performed under GLP. All relevant validity criteria were met.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

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

GLP compliance:

yes (incl. QA statement)

Remarks:

inspected: November 2002 ; signature: March 2003.

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

460-490-0

EC Name:

-

Cas Number:

477218-42-1

Molecular formula:

C18H32O3

IUPAC Name:

2-[(1S)-1-[(1R)-3,3-dimethylcyclohexyl]ethoxy]-2-methylpropyl cyclopropanecarboxylate; 2-[(1S)-1-[(1S)-3,3-dimethylcyclohexyl]ethoxy]-2-methylpropyl cyclopropanecarboxylate

Test material form:

liquid

Details on test material:

Physical state: Liquid
- Storage condition of test material: at room temperature (range of 20 ± 3 °C), light protected.
- Other: colourless liquid

Test animals

Species:

rat

Strain:

Wistar

Remarks:

HanBrl: WIST (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Recognised supplier.
- Females (if applicable) nulliparous and non-pregnant: Not specified.
- Age at study initiation: ca. 8 weeks age (males); ca. 12 weeks age (females)
- Weight at study initiation: 230 – 251 g (males); 197 – 215 g (females)
- Fasting period before study: Not applicable
- Housing: during acclimation and observation period: group housed by sex; during exposure: individually housed in polycarbonate cages furnished with softwood bedding.
- Diet (e.g. ad libitum): Certified diet from recognised supplier, ad libitum.
- Water (e.g. ad libitum): Community tap water, ad libitum.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25 °C (22 ± 3 °C)
- Humidity (%): 30 - 70% (values above 70% possible during cleaning process).
- Air changes (per hr): 10-15 air changes per hour
- Photoperiod: automatically controlled cycle of 12 h light / 12 h dark; music during daytime light period.

IN-LIFE DATES: From: To: 07-05-2004 to 28-05-2004

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Not specified the day before treatment the backs were clipped free of hair.
- % coverage: Approximately 10% of total body surface
- Type of wrap if used: The area of application was covered by a semi-occlusive dressing and wrapped with a piece of elastic self-adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): After the 24-hour contact period the bandage was carefully removed and the treated skin flushed with lukewarm tap water and dried with disposable paper towels.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg (or dose volume 2.073 mL/kg)
- Concentration (if solution): See below.
- Constant volume or concentration used: 2.07 mL volume /kg bw used, providing a consistent dose level of 2000 mg/kg bw test item.

Duration of exposure:

24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 per sex per dose (5 male/5 female)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations and mortality checks were conducted daily during the acclimatisation period, then at approximately 1, 2, 3 and 5 hours after administration on test day 1; Subsequent observations occured twice daily for days 2 to 15. Body weights were measured on test days 1 (prior to administration), 8 and 15. Local effects were examined twice daily days 2 to 15 after the completion of the 24-hour exposure period. Full details on the scoring and criteria (appears consistent with Draize for Erythema) are given in the full study report.
- Necropsy of survivors performed: yes

Statistics:

No statistical analyses were performed.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed.

Clinical signs:

other: - Clinical observations: None reported. - Dermal reactions: Slight scales were observed in all male animals from test day 5 or 6 to 8 and persisted in one animal up to day 10 and two animals up to day 11. Slight crusts were noted in one animal from test d

Gross pathology:

No abnormalities were noted at necropsy.

Other findings:

- Organ weights: Not reported.
- Histopathology: Not reported. No macropathological abnormalities.
- Potential target organs: Not applicable.
- Other observations: Not applicable.

Any other information on results incl. tables

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study the dermal LD50 was established to exceed 2000 mg/kg bw in male/female Wistar ras. Applicant assessment indicates under the conditions of this study, and according to the GHS criteria, the LD50 cut-off value was considered to be greater than 5000 mg/kg body weight on the basis of absence of significant clinical toxicological effects and/or bodyweight increases in all males/females.

Executive summary:

The study was performed according to OECD TG 402 and EU Method B.3 Acute Toxicity (Dermal) and in accordance with GLP to assess the acute dermal toxicity of the test item in the HanBrl: WIST (SPF) strain rat. A group of ten animals (five males and five females) was given a single, 24 hour semi-occluded dermal application of the undiluted test item to intact skin at a dose level of 2000 mg/kg body weight. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy. There was no mortality during the study. There were no signs of system toxicity or abnormalities on necropsy. It was considered there was no toxicologically significant effects on bodyweight. All males/females gained bodyweight during the study. No signs of dermal irritation were noted (score 0) up to day 14 in all females, and slight (score = 1) transient signs of dermal irritation were observed in males, with no signs of dermal irritation observed by the conclusion of the study. The dermal LD50 was established to exceed 2000 mg/kg bw in male/female HanBrl: WIST (SPF) rat. Applicant assessment indicates under the conditions of this study, and according to the GHS criteria, the LD50 cut-off value was considered to be greater than 5000 mg/kg body weight on the basis of absence of significant clinical toxicological effects and/or bodyweight increases in all males/females.