Cyclohexanepropanol, 2,2,3,6-tetramethyl-.alpha.-propyl-

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

02-04-2007 to 30-04-2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study performed under GLP. All relevant validity criteria were met.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

inspected: August 2005; signature: November 2005

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

478-330-3

EC Name:

-

Cas Number:

95851-08-4

Molecular formula:

C16H32O

IUPAC Name:

1-[(1R,3S,6S)-2,2,3,6-tetramethylcyclohexyl]hexan-3-ol

Test material form:

liquid

Details on test material:

- Physical state: Liquid
- Storage condition of test material: approximately 4°C in the dark
- Other: clear colourless slightly viscous liquid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Remarks:

Crl : CD (SD) IGS BR

Sex:

female

Details on test animals or test system and environmental conditions:

- Rationale for alternative/additional species to rat (if applicable): Not applicable.
- Source: Recognised supplier
- Females (if applicable) nulliparous and non-pregnant: Yes.
- Rationale for use of males (if applicable): Not applicable.
- Age at study initiation: 8 - 12 weeks.
- Weight at study initiation: 208 g (300 mg/kg including sighting test; sentinel); 200 - 244 g (2000 mg/kg sighting test; sentinel); The weight variation did not exceed ±20% of the mean weight during the test.
- Fasting period before study: Overnight before dosing and three to four hours after dosing.
- Housing: Group housed in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes.
- Historical data: The laboratory has access to historical control data (HCD).
- Diet (e.g. ad libitum): Certified diet from recognised supplier, provided ad libitum (except for fasting period).
- Water (e.g. ad libitum): ad libitum (except for fasting period)
- Acclimation period: At least 5 days.
- Microbiological status when known: Not applicable.
- Method of randomisation in assigning animals to test and control groups: randomly allocated (not otherwise described)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25
- Humidity (%): 30 - 70%
- Air changes (per hr): > 15 air changes per hour
- Photoperiod: 12 h light / 12 h dark

IN-LIFE DATES: From: To: 2007-04-02 to 2007-04-30

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: For the purpose of the 300 mg/kg and 2000 mg/kg dose level, the test item was freshly prepared, as required, as a solution in arachis oil BP. Arachis oil BP was used because the test item did not dissolve/suspend in distilled water. The respective dose levels had the following characteristics: 300 mg/kg bw : concentration: 30 mg/mL and dose volume: 10 mL/kg ; 2000 mg/kg bw : concentration: 20 mg/mL and dose volume: 10 mL/kg
- Amount of vehicle (if gavage): Dose volumes were 10 mL/kg in vehicle
- Justification for choice of vehicle: Arachis oil BP was used because the test item did not dissolve/suspend in distilled water.
- Lot/batch no. (if required): Not reported.
- Purity: Not reported. BP grade utilised.

MAXIMUM DOSE VOLUME APPLIED: 10 mg/mL in vehicle.

DOSAGE PREPARATION (if unusual): Not applicable.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: In accordance with the OECD TG 420 guideline

Doses:

300 mg/kg bw (initial sighting test and main study)
2000 mg/kg bw (initial sighting test and main study)

No. of animals per sex per dose:

1 (sighting study) and 4 (main study) as applicable; total 5 per dose - based on guideline specified sequential testing strategy

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were made 0.5, 1, 2, and 4 hours after dosing and then daily for fourteen days. Morbidity and mortality checks were made twice daily. Individual body weights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.
- Necropsy of survivors performed: yes
- Clinical signs including body weight : yes. Individual body weights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.
- Other examinations performed: clinical signs, body weight

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

2000 mg/kg bw (sentinel and follow-on test): No mortality
300 mg/kg bw (sentinel and definitive test): No mortality

Clinical signs:

other: 2000 mg/kg bw (sentinel): Appeared normal throughout the study ; (follow-on test): hunched posture (5/5) and ataxia (2/5) from 4 hours until day 1. All appeared normal two days after dosing 300 mg/kg bw (sentinel and definitive test): No signs of systemic

Gross pathology:

2000 mg/kg bw (sentinel and follow-on test): No abnormalities at necropsy.
300 mg/kg bw (sentinel and definitive test): No abnormalities at necropsy.

Other findings:

- Organ weights: Not applicable.
- Histopathology: Not applicable.
- Potential target organs: Not applicable.
- Other observations: Not applicable.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study the oral LD50 was established to exceed 2000 mg/kg bw in female Sprague-Dawley CD rats. Under the conditions of this study, and according to the OECD TG 420 criteria, the LD50 cut-off value was considered to be greater than 5000 mg/kg body weight.

Executive summary:

The study was performed according to OECD TG 420 and EU Method B.1 bis Acute Toxicity (Oral) and in accordance with GLP to assess the acute oral toxicity of the test material following a single oral administration in the female Sprague-Dawley CD strain rat by the fixed dose method. The test item was administered by oral gavage in an initial sighting study at 300 mg/kg bw within a solution of arachis oil BP vehicle. No mortality and no significant toxicity was observed. Subsequently, a further sighting at 2000 mg/kg bw in arachis oil BP vehicle was conducted, demonstrating only hunched posture which resolved by day 2. Based on no mortality and no significant toxicity being observed, a further group of four fasted females was given a single oral dose of test item at a dose level of 2000 mg/kg body weight. Clinical signs and body weight development were monitored during the study and gross necropsy performed. There was no mortality during the course of the study. Clinical signs of toxicity noted treated at a dose level of 2000 mg/kg were hunched posture (5/5) and ataxia (2/5) from 4 hours until day 1. All appeared normal two days after dosing. Animals showed expected gains in bodyweight over the study period and there were no abnormalities noted at necropsy. Under the conditions of this study the oral LD50 was established to exceed 2000 mg/kg bw in the female Wistar rat. Under the conditions of this study, and according to the OECD TG 420 criteria, the LD50 cut-off value was considered to be greater than 5000 mg/kg body weight.