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: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

09-24 May 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study conducted in compliance with OECD Guideline 423 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 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class 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:

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: 8 or 9 weeks
- Weight at study initiation: 196-217 g
- Housing: 3 animals/cage
- Diet: Food (M20, SDS), ad libitum
- Water: Tap water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Humidity: 30-70 %
- Air changes: At least 10 cycles per hour
- Photoperiod: 12 h dark / 12 h light

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME ADMINISTERED: 2.14 mL/kg bw (corresponding to 2000 mg/kg bw, according to the density of 0.936)

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

- Step 1: 3 females
- Step 2: 3 females

Control animals:

other: Study no. TAO-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 at 30 minutes, 1, 3, 4, 24 and 48 h after administration of the 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, 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:

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 clinical signs related to the administration of the test item were observed during the study.

Gross pathology:

No macroscopic abnormalities were observed at necropsy.

Other findings:

None

Any other information on results incl. tables

Table 7.2.1/1: Body weight and weight gain in grams

Female rats	D0	D2	D2-D0	D7	D7-D0	D14	D14-D0
Rf 0053	216	224	8	246	30	264	48
Rf 0054	208	219	11	236	28	245	37
Rf 0055	217	226	9	240	23	260	43
Rf 0114	196	200	4	229	33	246	50
Rf 0115	199	202	3	212	13	227	28
Rf 0116	197	201	4	223	26	247	50
Mean	205.5	212.0	6.5	231.0	25.5	248.2	42.7
Standard deviation	9.5	12.3	3.3	12.3	7.0	13.1	8.8

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 oral LD50 for Menthanyl acetate multiconstituent is higher than 2000 mg/kg bw in female 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 oral toxicity study (limit test) performed according to OECD Guideline 423 and in compliance with GLP, 6 Sprague Dawley female rats were given a single oral (gavage) dose of Menthanyl acetate multiconstituent at 2000 mg/kg bw. 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. Body weight gain of the treated animals was not affected by test item. No macroscopic abnormalities were observed at necropsy. In this study, the oral LD50 of Menthanyl acetate multiconstituent was considered to be higher than 2000 mg/kg bw in female rats.

Under the test conditions, the oral LD50 for Menthanyl acetate multiconstituent is higher than 2000 mg/kg bw in female 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).