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: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

04-19 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 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

13 September 2013

Test type:

acute toxic class 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. 116109
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: 21 September 2013

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage Janvier Labs, Le Genest-St Isle, France.
- Age at study initiation: 9 weeks
- Weight at study initiation: 207-223 g
- Fasting period before study: Food was removed on Day 1 and then redistributed 4 h after administration of the test item.
- Housing: Animals were housed by group of three in solid bottomed clear polycarbonate cages with stainless steel mesh lid.
- 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

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 2.20 mL/kg bw

DOSE ADMINISTRATION:
- In the first and second step of the study, the test item was administered by gavage under a volume of 2.20 mL/kg bw (corresponding to 2000 mg/kg bw according to the density of 0.908) using a suitable syringe graduated fitted with an oesophageal metal canula.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6 females/dose

Control animals:

other: Study no.: TAO-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 at 30 minutes, 1, 3, 4, 24 and 48 h after administration of the item and continued during 14 days following the administration of test item. Clinical observations and mortality were recorded every day for 14 days.
Bodyweight: Animals were weighed on Days 0 (just before administering the test item), 2, 7 and 14.
- Necropsy of survivors performed: Yes; On Day 14, the animals were anesthetized 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:

female

Dose descriptor:

LD50

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Mortality:

Mortality was observed in one rat treated at 2000 mg/kg bw (1/6), 25 h and 35 minutes post-dose, during the second step of the study.

Clinical signs:

other: - Mortality was preceded by an absence or decrease in spontaneous activity, Preyer's reflex, body temperature, muscle tone and righting reflex, myosis, lacrymation, bradypnea and staggering gait were noted on Day 0. - In the surviving animals treated at 2

Gross pathology:

Macroscopic examination of dead animal revealed a thinning and a red coloration of the fore stomach.
No macroscopic abnormalities were observed in surviving animals.

Other findings:

None

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:

Category 5 based on GHS criteria

Remarks:

not classified according to the CLP Regulation (EC) N° 1272/2008

Conclusions:

The oral LD50 for dihydroterpineol multiconstituent is higher than 2000 mg/kg bw in female rats. Therefore it is not classified according to 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, groups (6 female rats/dose) of Sprague Dawley rats were given a single oral (gavage) dose of dihydroterpineol 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.

One animal was died at 2000 mg/kg bw. Mortality was preceded by an absence or decrease in spontaneous activity, Preyer's reflex, body temperature, muscle tone and righting reflex, myosis, lacrymation, bradypnea and staggering gait were noted on Day 0. Similar clinical signs were observed in the surviving animals from 30 minutes postdose and were totally reversible at 24 h post-dose. Body weight gain of the treated animals was not affected by test item. Macroscopic examination of dead animal revealed a thinning and a red coloration of the fore stomach. No macroscopic abnormalities were observed in surviving animals. In this study, the oral LD50 of test item was considered to be higher than 2000 mg/kg bw in female rats.

 

Therefore, the oral LD50 for the test item is higher than 2000 mg/kg bw in female rats therefore it is not classified according to CLP Regulation (EC) N° 1272/2008.