Reaction mass of 2-(cis-4-methylcyclohexyl)propan-2-ol and 2-(trans-4-methylcyclohexyl)propan-2-ol and cis-1-methyl-4-(propan-2-yl)cyclohexanol and trans-1-methyl-4-(propan-2-yl)cyclohexanol

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

04-18 February 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other 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)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

13 September 2013

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

cis-α,α,4-trimethylcyclohexanemethanol

EC Number:

230-795-1

EC Name:

cis-α,α,4-trimethylcyclohexanemethanol

Cas Number:

7322-63-6

Molecular formula:

C10H20O

IUPAC Name:

cis-2-(4-methylcyclohexyl)propan-2-ol

Constituent 2

Reference substance name:

trans-α,α,4-trimethylcyclohexanemethanol

EC Number:

225-844-9

EC Name:

trans-α,α,4-trimethylcyclohexanemethanol

Cas Number:

5114-00-1

Molecular formula:

C10H20O

IUPAC Name:

trans-2-(4-methylcyclohexyl)propan-2-ol

Constituent 3

Reference substance name:

cis-4-isopropyl-1-methylcyclohexanol

Cas Number:

3901-95-9

Molecular formula:

C10H20O

IUPAC Name:

cis-4-isopropyl-1-methylcyclohexanol

Constituent 4

Reference substance name:

trans-4-isopropyl-1-methylcyclohexanol

Cas Number:

3901-93-7

Molecular formula:

C10H20O

IUPAC Name:

trans-4-isopropyl-1-methylcyclohexanol

impurity 1

Reference substance name:

Non identified impurities

Molecular formula:

Not applicable

IUPAC Name:

Non identified impurities

Test material form:

liquid

Details on test material:

Batch No. MP8 du 29/10/2013
Purity: 98.8% (sum of the 4 main constituents)
Name of the test item (as cited in the study report): DIHYDROTERPINEOL MULTICONSTITUENT
IUPAC Name of the test item: Reaction mass of cis-2-(4-methylcyclohexyl) propan-2-ol and trans-2-(4-methylcyclohexyl) propan-2-ol and
cis- 4-isopropyl-1-methylcyclohexanol and trans- 4-isopropyl-1-methylcyclohexanol
Synonym: Reaction mass of cis-α,α-4-trimethyl-cyclohexanemethanol and trans-α,α-4-trimethyl-cyclohexanemethanol and cis-1-methyl-4-(1-methylethyl)-cyclohexanol and trans-1-methyl-4-(1-methylethyl)-cyclohexanol
Physical state: colourless – slightly amber liquid
Storage Conditions: +2°C to +8°C, under nitrogen and protected from light
Expiry Date: 28 October 2015

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: Males: 8 weeks; Females: 9 weeks
- Weight at study initiation: Males: 288-336 g; Females: 198-248 g
- Housing: Animals were housed in solid-bottomed clear polycarbonate cages with a stainless steel mesh lid; During the treatment, the animals were kept in individual cages and after the removal of the patch on Day 1, the animals were put into their cage by group of 5.
- Diet: Foodstuff (SAFE, A04), ad libitum
- Water: Drinking water (tap water from public distribution system), ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19-25 °C
- Humidity: 30-70 %
- Air changes: Approximately 13 changes/h
- Photoperiod: 12 h dark / 12 h light

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

Approximately 24 h before the treatment, fur was removed from the dorsal area of the trunk of the test animals by clipping.

TEST SITE
- Area of exposure: Dorsal area of the trunk
- % coverage: Approximately 10 % of the body surface area
- Type of wrap if used: Test material was applied by topical application, under porous gauze dressing.

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Dose volume: 2.20 mL/kg bw (corresponding to 2000 mg/kg bw according to the density of 0.908)
- 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:

other: Study no.: TAD-2014-001 (no treatment related changes were observed)

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical signs and mortality: Animals were observed for any behavioural or toxic effects on the major physiological functions at 1, 3 and 5 h post dose and thereafter every day for 14 days. Clinical observations and mortality were recorded every day for 14 days.
- The integrity of the skin on the application site was noted.
Bodyweight was recorded on Days 0 (just before administering test item), 2, 7 and 14.
- Necropsy of survivors performed: Yes; On Day 14, the animals were anaesthetised with sodium pentobarbital and administration continued to fatal levels and macroscopic examination was performed.

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.

Mortality:

No mortality was observed.

Clinical signs:

other: Neither cutaneous reactions nor systemic clinical signs related to the administration of the test item were observed.

Gross pathology:

No macroscopic abnormalities were observed at necropsy.

Other findings:

None

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute dermal LD50 of dihydroterpineol multiconstituent is higher than 2000 mg/kg bw in rats. Therefore it is not classified according to GHS and CLP Regulation (EC) N° 1272/2008.

Executive summary:

In an acute dermal toxicity study (limit test) performed according to OECD Guideline 402 and in compliance with GLP, a group of Sprague Dawley rats (5/sex/dose) were given a single dermal application of dihydroterpineol multiconstituent at 2000 mg/kg bw. The test item was applied on dorsal area of the trunk representing approximately 10 % of the total body surface area of the animals. The test site was then covered by a semi-occlusive dressing for 24 h. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and were all sacrificed for macroscopic examination.

No mortality was observed. Neither cutaneous reactions nor systemic clinical signs related to the administration of the test item were observed. Body weight gain of the treated animals was not affected by the test item. No macroscopic abnormalities were observed at necropsy. The combined dermal LD50 of the test item was considered to be higher than 2000 mg/kg bw in rats.

The acute dermal LD50 of dihydroterpineol multiconstituent is higher than 2000 mg/kg bw in rats therefore it is not classified according to CLP Regulation (EC) N° 1272/2008.