Cyclohex-1,4-ylenedimethanol

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 22 April 2002 to 9 May 2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study (OECD)

Data source

Reference

Reference Type:

other company data

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

1,4-cyclohexanedimethanol (CHDM)

IUPAC Name:

1,4-cyclohexanedimethanol (CHDM)

Constituent 2

Reference substance name:

Cyclohex-1,4-ylenedimethanol

EC Number:

203-268-9

EC Name:

Cyclohex-1,4-ylenedimethanol

Cas Number:

105-08-8

Molecular formula:

C8H16O2

IUPAC Name:

cyclohexane-1,4-diyldimethanol

Constituent 3

Reference substance name:

[4-(hydroxymethyl)cyclohexyl]methanol

IUPAC Name:

[4-(hydroxymethyl)cyclohexyl]methanol

Details on test material:

- Name of test material (as cited in study report): 1,4-cyclohexanedimethanol
- Substance type: pure active substance
- Physical state: White waxy solid
- Analytical purity: Min 99%
- Impurities (identity and concentrations): not available
- Composition of test material, percentage of components: 99%
- Isomers composition: not applicable
- Purity test date: not available
- Lot/batch No.: 0090
- Expiration date of the lot/batch: 31 March 2003
- Radiochemical purity (if radiolabelling): not applicable
- Specific activity (if radiolabelling): not applicable
- Locations of the label (if radiolabelling): not applicable
- Expiration date of radiochemical substance (if radiolabelling): not applicable
- Stability under test conditions: not determined
- Storage condition of test material: room temperature

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan U.K. Ltd., Bicester, Oxon, England
- Age at study initiation: approximately five to seven weeks of age
- Weight at study initiation: 90 - 107g
- Fasting period before study: overnight prior to and approximately 4 hours after dosing.
- Housing: housed in groups of three rats of the same sex in metal cages with wire mesh floors in Building F21 Room 28.
- Diet (e.g. ad libitum): Special Diet Services RM1(E) SQC expanded pellet
- Water (e.g. ad libitum): Drinking water ad libitum
- Acclimation period: five days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/- 3
- Humidity (%): 40-70
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12 hours of artificial light (06:00-18:00 GMT)

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200mg/ml in water
- Amount of vehicle (if gavage): 10ml/kg bw
- Justification for choice of vehicle:
- Lot/batch no. (if required):
- Purity:


MAXIMUM DOSE VOLUME APPLIED: 2000mg/kg bodyweight (a single dose of the test substance)

Doses:

2000mg/kg

No. of animals per sex per dose:

A group of three fasted female(U1, U2, U3) and male(U4, U5, U6) rats at each single dose.

Control animals:

no

Details on study design:

- Duration of observation period following administration: All animals were observed for 14 days after dosing.

- Frequency of observations and weighing: Mortality-at least twice daily Clinical sign- Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1. On subsequent days, animals were observed once in the morning and again at the end of the experimental day (with the exception of Day 15-morning only) Bodyweight-The bodyweight of each rat was recorded on Days 1 (prior to dosing), 8 and 5. Individual weekly bodyweight changes and group mean bodyweights were calculated.

- Necropsy of survivors performed: All animals killed on Day 15 by carbon dioxide asphyxiation. All animals were subjected to a microscopic examination which consisted of opening the cranial, thoracic and abdominal cavities. The macroscopic appearance of all examined organs was recorded.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

There were no deaths during the study.

Clinical signs:

other: Clinical signs of reaction to treatment were first noted within 30 minutes of dosing and comprised of piloerection, lethargy, abnormal gait and hunched posture seen in all rats, with partially closed eyelids, irregular respiration and pallor to the skin o

Other findings:

- Other observations:
Macroscopic pathology-No abnormalities were revealed at the macroscopic examination at study termination on Day 15.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute lethal oral dose (LD50) to rats of CHDM (1,4-cyclohexanedimethanol) was demonstrated to be greater than 2000 mg/kg bodyweight. It means there is low potential toxic effect.

Executive summary:

This study was performed to assess the acute oral toxicity oral toxicity CHDM(1,4 -cyclohexanedimethanol) to the rat. A group of three fasted female rats received a single oral gavage dose of the test substance, formulated in water for irrigation, at a dose level of 2000mg/kg bodyweight. As results at this dosage indicated the acute lethal oral dose of the rest material to be greater than 2000mg/kg bodyweight, in compliance with the study guidelines, a group of three fasted males was similarly dosed at 2000mg/kg to confirm results at this dosage and complete the study. The acute lethal oral dose (LD50) to rats of CHDM (1,4 -cyclohexanedimethanol) was demonstrated to be greater than 2000mg/kg bodyweight.