Cyclohexanol, 4-(1,1-dimethylethyl)-, trans-

Endpoint summary

Description of key information

Acute oral toxicity: LD50 > 2000 mg/kg bw (EU method B.1 bis; GLP compliant).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2008-04-07 to 2008-04-30

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Minor deviations from the guidelines OECD 420 (2001) and EU Method B.1 bis (2008): - the stability of the test material were missing in the study report. - source of the diet was not stated.

Qualifier:

equivalent or similar to guideline

Guideline:

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

Version / remarks:

2008

Deviations:

yes

Remarks:

please refer to "Rationale for reliability incl. deficiencies" above

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2001-12-17

Deviations:

yes

Remarks:

please refer to "Rationale for reliability incl. deficiencies" above

GLP compliance:

yes (incl. QA statement)

Remarks:

signed 2007-10-15

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, Kent, UK
- Age at study initiation: eight to twelve weeks of age
- Weight at study initiation: 207 - 228 g
- Fasting period before study: an overnight fast immediately before dosing and for approximately three to four hours after dosing
- Housing: the animals were housed in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet (ad libitum; for exception please refer to "Fasting period before study" above): Certified Rat and Mouse Diet
- Water (ad libitum; for exception please refer to "Fasting period before study" above): mains drinking water
- Acclimation period: at least five days

The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

ENVIRONMENTAL CONDITIONS
- Temperature: 19 to 25°C
- Relative humidity: 30 to 70%
- Air changes: at least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

DMSO

Details on oral exposure:

VEHICLE
- Justification for choice of vehicle: dimethyl sulphoxide was used because the test material did not dissolve/suspend in distilled water or arachis oil BP.

DOSAGE PREPARATION: for the purpose of the study the test material was freshly prepared, as required, as a solution in dimethyl sulphoxide.

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.
- concentration: 200 mg/mL

PROCEDURE:
Using the available information on the toxicity of the test material, 2000 mg/kg was chosen as the starting dose. One female rat was dosed with this dose level (sighting study).
In the absence of mortality at a dose level of 2000 mg/kg, an additional group of four animals was treated with the same dose level (main study).

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 female rats (incl. 1 female rat from the sighting study)

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 subsequently once daily for fourteen days. Morbidity and mortality checks were made twice daily.
Individual bodyweights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.
- Necropsy of survivors performed: yes; at the end of the observation period the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Statistics:

An estimate of the acute oral median lethal dose (LD50) of the test material was made.

Preliminary study:

One female rat was tested at the dose level of 2000 mg/kg.
Results:
- no death
- hunched posture was noted during the day of dosing and persisted up to three days after dosing. The animal appeared normal four days after dosing.
- the animal showed expected bodyweight gain over the observation period.
- no abnormalities were noted at necropsy.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths.

Clinical signs:

other: Main study: Hunched posture was noted in all animals during the day of dosing. Animals appeared normal one day after dosing.

Gross pathology:

Main study:
No abnormalities were noted at necropsy.

Other findings:

no other findings

Interpretation of results:

not classified

Conclusions:

The acute oral median lethal dose (LD50) of the test material in the female Sprague-Dawley CD strain rat was estimated to be greater than 2000 mg/kg bodyweight.
According to the EC-Commission directive 67/548/EEC and its subsequent amendments, the test substance is not classified as acute toxic via the oral route.
According to the EC-Regulation 1272/2008 and its subsequent amendments, the test item is not classified as acute toxic via the oral route.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The conducted study is considered reliable according to Klimisch Score 1.

Additional information

Acute oral toxicity

One fully reliable animal study (EU method B.1 bis; GLP compliant; 2008) was considered. The LD50 was determined to be greater than 2000 mg/kg bw.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008.

 

Oral Toxicity:

Reference Bradshaw (2008) is considered as the key study for acute oral toxicity and will be used for classification. The LD50 was determined to be greater than 2000 mg/kg bw. Thus, according to regulation (EC) 1272/2008 (CLP), as amended for seventeenth time in Regulation (EU) No 2021/849.

 

Specific target organ toxicant (STOT) - single exposure: oral

The classification criteria according to regulation (EC) 1272/2008 as specific target organ toxicant (STOT) – single exposure, oral are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value, oral for a Category 1 classification (C ≤ 300 mg/kg bw) and at the guidance value, oral for a Category 2 classification (2000 mg/kg bw ≥ C > 300 mg/kg bw) in addition to these effects which were responsible for the death of the animals. No classification required.