(2E)-2-methyl-3-(4-methylphenyl)prop-2-en-1-ol

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

06-10-2011 to 20-10-2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

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

Justification for type of information:

Information as to the availability of the in vivo study is provided in 'attached justification'.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

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

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000

Deviations:

no

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

(2E)-2-methyl-3-(4-methylphenyl)prop-2-en-1-ol

EC Number:

700-548-7

Cas Number:

56138-10-4

Molecular formula:

C11H14O

IUPAC Name:

(2E)-2-methyl-3-(4-methylphenyl)prop-2-en-1-ol

Details on test material:

- Physical state: Waxy solid at temperature < 23°C and liquid at temperature > 23°C
- Storage condition of test material: In refrigerator (2-8°C) in the dark under nitrogen
- Other: white waxy solid at temperature < 23°C and clear colourless liquid at temperature > 23°C

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Crl:WI (Han)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Recognised supplier
- Age at study initiation: approximately 10 weeks.
- Weight at study initiation: Female: 194 - 210 g ; Male: 292 – 312 g ; The weight variation did not exceed +/- 20% of the mean weight per sex at the start of treatment.
- Fasting period before study: Not applicable.
- Housing: Individually housed in Makrolon cages furnished with sterilized sawdust and paper cage enrichment.
- Diet (e.g. ad libitum): Certified diet from recognised supplier, provided ad libitum.
- Water (e.g. ad libitum): ad libitum.
- Acclimation period: At least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.0 ± 3.0 (actual: 19.4 to 21.2°C)
- Humidity (%): 40 to 70 (actual: 44 – 73%) - deviation had no impact on the study
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12 hours light/dark

IN-LIFE DATES: 06-10-2011 to 20-10-2011

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Remarks:

The test item was a liquid at the time of dosing and could be applied as such

Details on dermal exposure:

TEST SITE
- Area of exposure: The day before treatment the back and flanks were clipped free of hair. Dorsal area application.
- % coverage: Approximately 10% of total body surface
- Type of wrap if used: The area of application was covered piece of surgical gauze was placed over the treatment area and occluded with a piece of aluminium foil and elastic bandage affixed with micropore tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The treated skin and surrounding hair wiped with cotton wool moistened with water to remove any residual test item
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): dose volume: 1.98 mL/kg bodweight.
- Concentration (if solution): 2000 mg/kg
- Constant volume or concentration used: Not applicable.

VEHICLE
- Amount(s) applied (volume or weight with unit): Not applicable.

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

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

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: Clinical observations and mortality checks were conducted at approximately 0.5, 1, 2, and 4 hours and subsequently once daily for 15 days. Local effects were examined once daily for 15 days after the completion of the 24-hour exposure period. Full details on the scoring and criteria are given in the full study report. Individual bodyweights were recorded prior to application of the test item on Day 0 and on Days 8 and 15.
- 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: No signs of systemic toxicity were noted during the observation period. Chromodacryorrhoea (Snout) (score = 1) was noted in two females on day 1. - Dermal reactions: Focal erythema (score = 1) (Days 2 and 3) and scales (score = 1)

Gross pathology:

No abnormalities were noted at necropsy.

Applicant's summary and conclusion

Interpretation of results:

not classified

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 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.

Executive summary:

The study was performed according to OECD TG 402, EU Method B.3 Acute Toxicity (Dermal), US EPA OPPTS 870.1100 and Japanese JMAFF guidelines in accordance with GLP to assess the acute dermal toxicity of the test item in the Wistar strain rat. A group of ten animals (five males and five females) was given a single, 24 hour, 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. Clinical signs and/or local effects consisted of chromodacryorrhoea in two females on Day 1. Whereas, focal erythema (Days 2 and 3) and scales (between Days 4-7) were observed on the treated skin-area of two males and one female. The body weight gain during the observation period was within the expected range. Under the conditions of this study, the dermal LD50 was established to exceed 2000 mg/kg bw in male/female Wistar 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.