Cyclohex-1,4-ylenedimethanol

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

24-hour application followed by 14-day observation period

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study conducted prior to introduction of the Good Laboratory Practices regulations. The study was conducted according to an internal Eastman Kodak Company method, developed prior to established guidelines, but according to acceptable scientific standard methods in use at the time the study was conducted. The results of this study are valid insofar as the conditions of exposure are at least as stringent as modern guidelines.

Data source

Reference

Reference Type:

other: Eastman Kodak Company Summary Report

Title:

Unnamed

Year:

1962

Report date:

1962

Materials and methods

Test guideline

Qualifier:

no guideline available

Deviations:

not specified

Principles of method if other than guideline:

Method is an in vivo study using three guinea pigs. Following depilation of the abdomen of each animal, a single dose of 5.0, 10.0, or 20.0 mL/kg bw of the test material (received as a slurry in 1-3% methanol) was applied under an occlusive cuff prepared from a pad of gauze held in place with an impervious cuff made of rubber dental dam. The cuff was wrapped securely around the torso and held in place using non-irritating tape. Animals were exposed to the test material for 24 hours, then cuffs were removed; animals were observed following removal of the cuff, and on Days 7 and 14. In addition to observations for mortality, dermal reactions and weight changes were also recorded.

GLP compliance:

no

Test type:

other: Study conducted according to an internal Eastman Kodak Company laboratory method.

Limit test:

no

Test material

Test material information

Constituent 1

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 2

Reference substance name:

[4-(hydroxymethyl)cyclohexyl]methanol

IUPAC Name:

[4-(hydroxymethyl)cyclohexyl]methanol

Constituent 3

Reference substance name:

Cyclohexane-1,4-dimethanol; 1,4-Bis(hydroxymethyl)cyclohexane; CHDM

IUPAC Name:

Cyclohexane-1,4-dimethanol; 1,4-Bis(hydroxymethyl)cyclohexane; CHDM

Details on test material:

no data

Test animals

Species:

guinea pig

Strain:

Hartley

Sex:

not specified

Details on test animals or test system and environmental conditions:

no data

Administration / exposure

Type of coverage:

occlusive

Vehicle:

other: Test material administered as a slurry in 1-3% methanol.

Details on dermal exposure:

Following depilation of each animal's abdomen, a single dose of 5.0, 10.0, or 20.0 mL/kg bw of the test material (slurry in 1-3% methanol) was applied under an occlusive cuff and wrap. After a 24 hour exposure period, the cuffs and wrappings were removed.

Duration of exposure:

24 hours

Doses:

One animal each was exposed to a single dose of 5, 10, or 20 mL/kg bw of the test substance as a slurry in 1-3% methanol.

No. of animals per sex per dose:

1 animal/dose (sex not determined)

Control animals:

no

Details on study design:

Three guinea pigs (sex, age, and initial weights not provided) were used. Following depilation of the guinea pig abdomens, a single dose of 5.0, 10.0, or 20.0 mL/kg bw of the test material (slurry in 1-3% methanol) was applied under an occlusive wrap prepared from a pad of gauze held in place with an impervious cuff made of rubber dental dam material. The cuff was wrapped securely around the torso of the guinea pig and held in place with non-irritating tape. Animals were exposed for 24 hours, then the cuffs were removed. Animals were observed following removal of the cuff, and on Days 7 and 14. In addition to observations for mortality, dermal reactions were also noted. Guinea pigs were weighed prior to administration of the test substance and at termination of the 14-day observation period.

Statistics:

no data

Results and discussion

Effect levels

Sex:

not specified

Dose descriptor:

LDLo

Effect level:

> 20 mL/kg bw

Remarks on result:

other: The dose levels used in this study are significantly higher than those used for present-day guideline studies.

Mortality:

None

Clinical signs:

other: No signs of test material absorption or systemic toxicity were noted during the study. Signs of irritation at the application site were limited to slight edema and slight erythema.

Gross pathology:

Not performed

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

1,4-Cyclohexanedimethanol was not acutely toxic by the dermal route in guinea pigs under conditions used in this study. The dermal LDLo in guinea pigs was > 20.0 mL/kg bw.

Based on an acute dermal LDLo value of > 20.0 mL/kg bw in guinea pigs, 1,4-cyclohexanedimethanol is not classified for Acute Toxicity by the dermal route under GHS. In the absence of signs of systemic toxicity and/or skin absorption, 1,4-cyclohexanedimethanol is not classified under GHS for Specific Target Organ Toxicity – Single Exposure. Based on minimal signs of irritation after an extreme exposure period of 24 hours under an occlusive wrap to depilated abdominal skin of guinea pigs, 1,4-cyclohexanedimethanol is not classifiable for Skin Irritation/Corrosion according to GHS.

Executive summary:

In an acute dermal toxicity study, 3 Hartley guinea pigs were exposed to 5, 10 or 20 mL/kg bw of 1,4-cyclohexanedimethanol (slurry in 1-3% methanol) under occlusive contact for 24 hours. Based on a specific gravity of 1.04 for the undiluted test material, the doses of 1,4-cyclohexanedimethanol administered to guinea pigs in this study were significantly higher than those used in present day protocols. Under the conditions of this study, no deaths occurred and the dermal LDLo was considered to be > 20.0 mL/kg bw. No signs of skin absorption or systemic toxicity were evident during the study. At the application sites, signs of skin irritation were limited to slight edema and slight erythema. Desquamation at the application sites was noted at the 1-week observations. At termination of the 2-week study, all animals appeared normal. A body weight gain was noted for all animals over the 2-week observation period. Based on the results of this study, 1,4-cyclohexanedimethanol presents a low toxicity hazard upon skin contact under conditions of normal use.