2-hydroxypropyl [(1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl] carbonate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1993-10-25 to 1993-11-17

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

1987-02-24

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Version / remarks:

1984

GLP compliance:

yes (incl. QA statement)

Remarks:

signed 1992-06-11

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1-[({[(1R,2S,5R)-5-methyl-2-(propan-2-yl)cyclohexyl]oxy}carbonyl)oxy]propan-2-ol

EC Number:

607-858-0

Cas Number:

260781-16-6

Molecular formula:

C14H26O4

IUPAC Name:

1-[({[(1R,2S,5R)-5-methyl-2-(propan-2-yl)cyclohexyl]oxy}carbonyl)oxy]propan-2-ol

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: approx. five to eight weeks old
- Weight at study initiation: males: 154 - 165 g; females: 140 - 154 g
- Fasting period before study: overnight fast immediately before dosing and for approximately two hours after dosing
- Housing: housed in groups of up to five by sex in solid floor polypropylene cages furnished with woodflakes.
- Diet (ad libitum, except of fasting period): Rat and Mouse Expanded Diet No. 1
- Water (ad libitum, except of fasting period): mains drinking water
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 - 22 °C
- Relative humidity: 44 - 61 %
- Air changes: approx. 15 changes/hour
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

arachis oil

Remarks:

B.P.

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg
The volume administered to each animal was calculated according to its fasted bodyweight at the time of dosing.

DOSAGE PREPARATION: test material was freshly prepared as a solution at the appropriate concentrations in the vehicle

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 males / 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days

- Frequency of observations and weighing:
death and overt signs of toxicity: 0.5, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days
individual bodyweights: prior to dosing on Day 0 and on Days 7 and 14

- Necropsy of survivors performed: yes, at the end of the study the animals were sacrificed and subjected to gross pathological examination.

Statistics:

Using the mortality data obtained, an estimate of the acute oral median lethal dose (LD50) of the test material was made.

Results and discussion

Preliminary study:

A range-finding study was conducted in rats (1 male / 1 female) at a dose level of 2000 mg/kg. Death and overt signs of toxicity were recorded 0.5, 1, 2 and 4 hours after dosing and subsequently once daily for 5 days. Individual body weights were recorded on the day of dosing to allow calculation of individual treatment volumes. No necropsies were performed.
There were no deaths or clinical signs of toxicity.
Based on this results, a dose level of 2000 mg/kg bw was selected for the main study.

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths.

Clinical signs:

other: Ataxia was noted in two males two and four hours after dosing. All other animals appeared normal throughout the study.

Gross pathology:

No abnormalities were noted at necropsy.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

LD50 (male and female rats) > 2000 mg/kg bw
According to the Regulation (EC) No 1272/2008 and subsequent adaptations, the substance is not acutely toxic via the oral route.

Executive summary:

The acute oral toxicity of the substance was investigated according to the OECD guideline 401 (1987). Five male and five female Sprague-Dawley rats received a single dose of 2000 mg/kg bw in arachis oil B.P. by gavage. Clinical signs, mortality, and body weight were recorded. All animals were subjected to gross necropsy.

Mortality or abnormalities at necropsy were not observed during the study. Ataxia was noted in two males two and four hours after dosing. All other animals appeared normal throughout the study. Lastly, all animals showed expected gain in body weight during the study.

Thus, the LD50 was considered to be greater than 2000 mg/kg bw for male and female rats. According to the Regulation (EC) No 1272/2008 and subsequent adaptations, the substance is not acutely toxic via the oral route.