Reaction mass of cis-1-methyl-1-(4-methylcyclohexyl) ethyl acetate and trans-1-methyl-1-(4-methylcyclohexyl) ethyl acetate and cis- 4-isopropyl-1-methylcyclohexyl acetate and trans-4-isopropyl-1-methylcyclohexyl acetate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

9 - 23 May 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study conducted according to OECD Guideline 402 without any deviation.

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:

2012

Report date:

2012

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

(1r,4r)-1-methyl-4-(propan-2-yl)cyclohexyl acetate; (1s,4s)-1-methyl-4-(propan-2-yl)cyclohexyl acetate; 2-[(1r,4r)-4-methylcyclohexyl]propan-2-yl acetate; 2-[(1s,4s)-4-methylcyclohexyl]propan-2-yl acetate

EC Number:

939-728-7

Molecular formula:

C12H22O2

IUPAC Name:

(1r,4r)-1-methyl-4-(propan-2-yl)cyclohexyl acetate; (1s,4s)-1-methyl-4-(propan-2-yl)cyclohexyl acetate; 2-[(1r,4r)-4-methylcyclohexyl]propan-2-yl acetate; 2-[(1s,4s)-4-methylcyclohexyl]propan-2-yl acetate

Test material form:

gas under pressure: refrigerated liquefied gas

Details on test material:

- Name of test material (as cited in study report): Menthanyl acetate multiconstituent
- Physical state: Colourless to slightly amber liquid
- Analytical purity: 98.4 %
- Composition of test material (%):Trans para menthanyl 1 (17.0 %), trans para menthanyl 8 (28.9 %), cis para menthanyl 8 (32.5 %), cis para menthanyl 1 (20.0 %) and others (1.6 %)
- Lot/batch No.: 120922
- Purity test date: 05 July 2011
- Date of receipt: 16 April 2012
- Expiration date of the lot/batch: 04 July 2012
- Storage condition of test material: Stored at 6 ± 3 °C in darkness

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: 7 weeks; females: 8 weeks
- Weight at study initiation: Males: 221-238 g; females: 207-210 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: Food (M20, SDS), ad libitum
- Water: Tap water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19-25 °C
- Humidity: 30-70 %
- Air changes: Approximately 15 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: 2.14 mL/kg bw (corresponding to 2000 mg/kg bw according to the density of 0.936)
- 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-2012-001 (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 vital functions 1, 3, 5 and 24 h after administration of the test item and thereafter once a day until Day 14.
Bodyweight was recorded on Days 0 (prior to dosing), 2, 7 and 14.
- Necropsy of survivors performed: Yes; On Day 14, the animals were anaesthetised with sodium pentobarbital and then administered sodium pentobarbital up to a lethal dose and were subjected to a macroscopic examination.

Statistics:

None

Results and discussion

Preliminary study:

Not applicable

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortality and no clinical signs were observed.

Mortality:

No mortality was observed.

Clinical signs:

other: No systemic clinical signs related to the administration of the test item was observed.

Gross pathology:

No macroscopic abnormalities were observed at necropsy.

Other findings:

None

Any other information on results incl. tables

Table 7.2.3/1: Body weight and weight gain in grams

Male rats	D0	D2	D2-D0	D7	D7-D0	D14	D14-D0
Rm 0074	227	229	2	268	41	321	94
Rm 0075	221	223	2	267	46	333	112
Rm 0076	233	237	4	288	55	356	123
Rm 0077	238	242	4	279	41	338	100
Rm 0078	229	241	12	271	42	316	87
Mean	229.6	234.4	4.8	274.6	45.0	332.8	103.2
Standard deviation	6.4	8.2	4.1	8.8	6.0	15.7	14.4
Female rats	D0	D2	D2-D0	D7	D7-D0	D14	D14-D0
Rf 0079	208	203	-5	226	18	248	40
Rf 0080	207	217	10	235	28	250	43
Rf 0081	209	207	-2	228	19	241	32
Rf 0082	210	208	-2	228	18	248	38
Rf 0083	208	207	-1	224	16	236	28
Mean	208.4	208.4	0.0	228.2	19.8	244.6	36.2
Standard deviation	1.1	5.2	5.8	4.1	4.7	5.9	6.1

D: Day

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the test conditions, the acute dermal LD50 of Menthanyl acetate multiconstituent is higher than 2000 mg/kg bw in rats therefore it is not classified according to the Annex VI to the Directive 67/548/EEC and the 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, Sprague Dawley rats (5/sex/dose) were given a single dermal application of Menthanyl acetate multiconstituent at 2000 mg/kg bw. The test item was placed directly on dorsal area of the skin representing approximately 10 % of the total body surface of the animals. The application site was then covered with a semiocclusive 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 and no clinical signs were observed during the study. Body weight gain of the treated animals was not affected by test item. No macroscopic abnormalities were observed at necropsy. The combined dermal LD50 of Menthanyl acetate multiconstituent was considered to be higher than 2000 mg/kg bw in rats.

Under the test conditions, the acute dermal LD50 of Menthanyl acetate multiconstituent is higher than 2000 mg/kg bw in rats therefore it is not classified according to the Annex VI to the Directive 67/548/EEC and the CLP Regulation (EC) N° (1272-2008).