[No public or meaningful name is available]

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

17-09-2014 to 01-10-2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

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:

2014

Report date:

2014

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 (incl. QA statement)

Remarks:

inspected: March 2013 ; signature: May 2013

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of (4RS,4aRS,8RS,8aRS)-4-ethyl-8-methyloctahydronaphthalen-1(2H)-one and (4RS,4aSR,8SR,8aRS)-4-ethyl-8-methyloctahydronaphthalen-1(2H)-one and (4RS,4aSR,8SR,8aSR)-4-ethyl-8-methyloctahydronaphthalen-1(2H)-one

Molecular formula:

C13H22O

IUPAC Name:

Reaction mass of (4RS,4aRS,8RS,8aRS)-4-ethyl-8-methyloctahydronaphthalen-1(2H)-one and (4RS,4aSR,8SR,8aRS)-4-ethyl-8-methyloctahydronaphthalen-1(2H)-one and (4RS,4aSR,8SR,8aSR)-4-ethyl-8-methyloctahydronaphthalen-1(2H)-one

Test material form:

liquid

Specific details on test material used for the study:

- Physical state: Liquid
- Storage condition of test material: In refrigerator (2-8°C) in the dark
- Other: clear colourless liquid

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: 199 - 212 g ; Male: 302 – 318 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
- Humidity (%): 40 to 70
- Air changes (per hr): typically, at least 15
- Photoperiod (hrs dark / hrs light): 12 hours light/dark

IN-LIFE DATES: 17-09-2014 to 01-10-2013

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

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 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 bodyweight.
- 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 periodically on day one and subsequently once daily for 15 days. 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:Lethargy, hunched posture, piloerection, chromodacryorrhoea and/or ptosis were noted among all animals between Days 1 and 8. Swelling, general erythema, and/or dryness were noted on the treated skin area of all animals between Days

Gross pathology:

No significant abnormalities were noted at necropsy. Pelvic dilation of the right kidney was found in female 10 at necropsy. This was considered a background finding.

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.

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. Lethargy, hunched posture, piloerection, chromodacryorrhoea and/or ptosis were noted among all animals between Days 1 and 8. Swelling, general erythema, and/or dryness were noted on the treated skin area of all animals between days 2 and 6. Scales were noted on the treated skin of several animals between Days 7 and 13. Some of observations (such as piloerection and hunched posture) may (in part) be related/secondary to the burden of dermal treatment and/or observed skin lesions, rather than being primary signs of toxicity. The clinical signs observed fully recovered by Day 14 of the observation period. 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.