2-(3,3-dimethylcyclohex-1-enyl)-2,5,5-trimethyl-1,3-dioxane

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Between 22 July and 05 August, 2015.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP study conducted in compliance with OECD Guideline No. 402 with minor deviation: a relative humidity higher than 70% was registered. The maximum value measured was 71%. This deviation is considered as without impact on the conclusion of the study.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

24 February 1987.

Deviations:

yes

Remarks:

A relative humidity higher than 70% was registered. The maximum value measured was 71%. This deviation is considered as without impact on the conclusion of the study.

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

A relative humidity higher than 70% was registered. The maximum value measured was 71%. This deviation is considered as without impact on the conclusion of the study.

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

Inspected on 2013-06-3&4 / Signed on 2013-09-13.

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-(3,3-dimethylcyclohex-1-en-1-yl)-2,5,5-trimethyl-1,3-dioxane

EC Number:

815-500-1

Cas Number:

1853175-99-1

Molecular formula:

C15 H26 O2

IUPAC Name:

2-(3,3-dimethylcyclohex-1-en-1-yl)-2,5,5-trimethyl-1,3-dioxane

Test material form:

liquid

Details on test material:

- Physical state: Liquid
- Storage condition of test material: room temperature, darkness.

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage JANVIER (539040 Le Genest St Isle-France)
- Age at study initiation: 7 weeks (males) and 8 weeks (females)
- Weight at study initiation: 231 - 255 g (males) and 206 - 219 g (females).
- Housing: Animals were housed individually during the 24 h exposure period and in groups of five by sex for the remainder of the study in solid-bottomed clear polycarbonate cages with a stainless steel mesh lid.
- Diet: foodstuff (SAFE - A04), ad libitum
- Water: tap-water (from public distribution), ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19-25 °C
- Humidity: 30-70 %
- Air changes: at least 10 changes/h
- Photoperiod: 12 h dark / 12 h light

IN-LIFE DATES: from 22 July to 05 August, 2015.

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Back and flank area
- % coverage: approximately 10% of the total body surface area.
- Type of wrap if used: A piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self-adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): none reported.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw administered under a volume of 2.11 mL/kg bw, during 24 hours.
- Constant volume or concentration used: Yes

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for mortality or clinical signs of toxicity at 1, 3 and 5 h after dosing and subsequently once daily for 14 days. Individual bodyweights were recorded prior to application of the test material on Day 0 and on Days 7 and 14.
- After removal of the dressings and subsequently once daily for fourteen days, the test sites were examined for evidence of primary irritation and scored according to the Draize scale.
- Necropsy of survivors performed: Yes; at the end of the study animals were anaesthetised with sodium pentobarbitol and administration continued to fatal levels. After, they subjected to gross necropsy.

Statistics:

None

Results and discussion

Preliminary study:

Not applicable

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No mortality was observed.

Mortality:

No mortality was observed.

Clinical signs:

other: - No signs of systemic toxicity were noted during the observation period. - Dermal reactions: slight erythema was noted on the treated area in females of treated group, 48 h post dose. The skin recovered a normal aspect on day 5.

Gross pathology:

The macroscopic examination of the animals at the end of the study did not reveal treatment- related changes.

Other findings:

None

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the test conditions, the dermal LD50 Combined for test substance is higher than 2000 mg/kg bw in rats. Therefore, the substance is not classified according to the annex I of the Regulation EC No. 1272/2008 (CLP) and to the GHS.

Executive summary:

In an acute dermal toxicity study (limit test) performed according to OECD Guideline No. 402 and in compliance with GLP, a group of Sprague Dawley rats (5/sex) was given a single dermal application of the test material to intact skin of the back and flank area at a dose level of 2000 mg/kg bw. Test sites were covered with a semi-occlusive dressing for 24 h. Animals were observed for mortality, clinical signs and bodyweights for 14 days and at the end of the study the surviving animals were sacrificed for macroscopic examination. Skin irritation was assessed and scored according to the Draize scale at 24 h after removal of the dressings and then daily for 14 days. 

No mortality or systemic toxicity was observed. Slight erythema was noted on the treated area in females of treated group, 48 h post dose. The skin recovered a normal aspect on day 5. All animals showed gains in body weight over the observation period. No abnormalities were noted at necropsy.

 

Dermal LD50 Combined > 2000 mg/kg bw

 

Under the test conditions, the test material is not classified according to the annex I of the Regulation EC No. 1272/2008 (CLP) and to the GHS. 

This study is considered as acceptable and satisfies the requirement for acute dermal toxicity endpoint.