Cyclohex-1,4-ylenedimethanol

Endpoint summary

Description of key information

An acute oral toxicity study showed the rat LD50 was > 2000 mg/kg.

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:

From 22 April 2002 to 9 May 2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study (OECD)

Qualifier:

according to guideline

Guideline:

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

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

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)

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.

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.

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The actual finding was > 2000 mg/kg, but ">" is not an option to use.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

6-hour exposure followed by 14-day observation period

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study was 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 methods in use at the time the study was conducted.

Qualifier:

no guideline available

Deviations:

not specified

Principles of method if other than guideline:

Method is an in vivo study using a group of three rats (sex, strain, and weights not available) exposed to an atmosphere containing the test material for a period of six hours. After termination of exposure, the animals were observed for mortality and adverse clinical signs for a period of 14 days. Body weights were measured prior to exposure and at termination of the 2-week observation period.

GLP compliance:

no

Test type:

other: Study conducted according to an internal Eastman Kodak Company laboratory method, using a 6-hour inhalation exposure period to rats.

Limit test:

no

Species:

rat

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

no data

Route of administration:

inhalation

Type of inhalation exposure:

whole body

Vehicle:

other: air

Details on inhalation exposure:

Rats were exposed (whole-body) to an atmosphere containing 1.25 mg/L (calculated 212 ppm) of the test material for a period of six hours. The atmosphere was generated by heating the test material to 100 °C in a washing bottle and passing air through at a rate of 2.0 L/minute. The atmosphere generated in this manner was then passed into the chamber containing the rats.

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

6 h

Concentrations:

1.25 mg/L (calculated 212 ppm)

No. of animals per sex per dose:

3 (sex not specified)

Control animals:

no

Details on study design:

Three rats (sex, strain, and weights not available) were exposed (whole-body) to an atmosphere containing 1.25 mg/L (calculated 212 ppm) of the test material for a period of six hours. The atmosphere was generated by heating the test material to 100 °C in a washing bottle and passing air through at a rate of 2.0 L/minute. The atmosphere generated in this manner was then passed into the chamber containing the rats. Animals were observed for mortality and adverse effects for a period of 14 days. Body weights were recorded prior to exposure to the test material and at termination of the observation period.

Sex:

not specified

Dose descriptor:

LCLo

Effect level:

> 1.25 mg/L air

Exp. duration:

6 h

Remarks on result:

other: calculated atmospheric concentration of 212 ppm

Mortality:

None

Clinical signs:

other: No signs of systemic toxicity or abnormal clinical signs were noted during the study.

Body weight:

All animals gained weight over the 14-day observation period.

Gross pathology:

not performed

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

Under conditions used in this study, 1,4-cyclohexanedimethanol was not acutely toxic by the inhalation route in rats exposed to a concentration of 1.25 mg/L of air for 6 hours. This exposure level was the highest atmosphere that could be generated by heating the test material to 100 °C in a vessel and passing air through at a rate of 2.0 L/minute. Since no mortality was noted at this exposure level, the LCLo in rats was greater than 1.25 mg/L of air/6 h.

Based on an acute inhalation LCLo value > 1.25 mg/L of air/6h in rats, 1,4-cyclohexanedimethanol is not expected to be classifiable for Acute Toxicity by the inhalation route according to the UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS) or the EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation No. 1272/2008. Based on the absence of abnormal clinical signs, 1,4-cyclohexanedimethanol is not expected to be classifiable for Specific Target Organ Toxicity – Single Exposure at this exposure concentration.

Executive summary:

In an acute inhalation toxicity study, three rats were exposed to 1,4-cyclohexanedimethanol at a concentration of 1.25 mg/L of air for a period of 6 hours. Under the conditions of this study, no deaths occurred and the LCLo was considered to be greater than 1.25 mg/L. No abnormal clinical signs or signs of systemic toxicity were evident during a 14-day observation period. Based on the results of this study, 1,4-cyclohexanedimethanol is not classified for toxicity by the inhalation route at this exposure concentration.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

1 250 mg/m³ air

Quality of whole database:

Th collect value is > 1.25 mg/l, which was the saturated vapor pressure of the study. This was a 1957 study was was reoughly equivalent to an OECD 403.

Acute toxicity: via dermal route

Link to relevant study records

Reference

Reference 1

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.

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

Species:

guinea pig

Strain:

Hartley

Sex:

not specified

Details on test animals or test system and environmental conditions:

no data

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

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

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.

Reference 2

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 was conducted prior to the 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 methods in use at the time the study was conducted. The results of this study are valid for classification insofar as the conditions of exposure (24 hours under an occlusive wrap) are at least as stringent as modern guidelines.

Qualifier:

no guideline available

Deviations:

not specified

Principles of method if other than guideline:

Method is an in vivo study using two guinea pigs. Following depilation of the abdomen of each animal, a single dose of 500 or 1000 mg/kg bw of the test material, moistened with water, 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 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

Species:

guinea pig

Strain:

Hartley

Sex:

not specified

Details on test animals or test system and environmental conditions:

no data

Type of coverage:

occlusive

Vehicle:

other: The solid test material was moistened with water.

Details on dermal exposure:

Following depilation of each animal's abdomen, a single dose of 500 or 1000 mg/kg bw of the test material, moistened with water, 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 500 or 1000 mg/kg bw of the test material moistened with water.

No. of animals per sex per dose:

1 animal/dose (sex not determined)

Control animals:

no

Details on study design:

Two guinea pigs (sex, age, and initial weights not provided) were used. Following depilation of the guinea pig abdomens, a single dose of either 500 or 1000 mg/kg bw of the test material, moistened with water, 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, and 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

Sex:

not specified

Dose descriptor:

LDLo

Effect level:

> 1 000 mg/kg bw

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 after termination of exposure. Sparse hair was also noted at one and two

Gross pathology:

Not performed

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 > 1000 mg/kg bw.

Based on an acute dermal LDLo value of > 1000 mg/kg bw in guinea pigs, 1,4-cyclohexanedimethanol is not expected to be classified for Acute Toxicity by the dermal route under GHS. However, insufficient data were available in this study to provide a definitive classification. 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, 2 Hartley guinea pigs were exposed to either 500 or 1000 mg/kg bw of 1,4-cyclohexanedimethanol, moistened with water, under occlusive contact for 24 hours. Under the conditions of this study, no deaths occurred and the dermal LDLo was considered to be > 1000 mg/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 after termination of exposure. Other clinical signs were limited to sparse hair at the application sites one and two weeks after exposure. A body weight gain (26 or 37 grams) was noted for both 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.

Reference 3

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 was 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 methods in use at the time the study was conducted. The results of this study are valid for classification insofar as the conditions of exposure (24 hours under an occlusive wrap) are at least as stringent as modern guidelines.

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 250, 500, or 1000 mg/kg bw of the test material (solid moistened with water) 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 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

Species:

guinea pig

Strain:

Hartley

Sex:

not specified

Details on test animals or test system and environmental conditions:

no data

Type of coverage:

occlusive

Vehicle:

other: Test material administered as a solid moistened with water.

Details on dermal exposure:

Following depilation of each animal's abdomen, a single dose of 250, 500, or 1000 mg/kg bw of the test material (solid moistened with water) 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 250, 500, or 1000 mg/kg bw of the test substance as a solid moistened with water.

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 250, 500,or 1000 mg/kg bw of the test material (solid moistened with water) 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

Sex:

not specified

Dose descriptor:

LDLo

Effect level:

> 1 000 mg/kg bw

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 at 24 hours and desquamation at 1-week. All animals appeared normal by termination of the 14-da

Gross pathology:

Not performed

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 > 1000mg/kg bw.

Based on an acute dermal LDLo value of > 1000 mg/kg bw in guinea pigs, 1,4-cyclohexanedimethanol is not expected to be classified for Acute Toxicity by the dermal route under GHS. However, insufficient data were available in this study to provide a definitive classification. 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 250, 500, or 1000 mg/kg bw of 1,4-cyclohexanedimethanol (solid moistened with water) under occlusive contact for 24 hours. Under the conditions of this study, no deaths occurred and the dermal LDLo was considered to be > 1000 mg/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 at 24 hours and desquamation at 1 week. All animals appeared normal at termination of the 14-day study. 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.

Reference 4

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 was 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 methods in use at the time the study was conducted. The results of this study are valid for classification insofar as the conditions of exposure are at least as stringent as modern guidelines.

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 a 20% solution of the test material in a mixture of acetone and corn oil (90:10) 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 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

Species:

guinea pig

Strain:

Hartley

Sex:

not specified

Details on test animals or test system and environmental conditions:

no data

Type of coverage:

occlusive

Vehicle:

other: a 90:10 mixture of acetone and corn oil (no other data on preparation of vehicle)

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 a 20% solution of the test material in a 90:10 mixture of acetone and corn oil (no data on preparation of vehicle) 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 a 20% solution of the test substance in a 90:10 mixture of acetone and corn oil.

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 a 20% solution of the test material in a 90:10 mixture of acetone and corn oil (no data on preparation of vehicle) 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

Sex:

not specified

Dose descriptor:

LDLo

Effect level:

> 20 mL/kg bw

Remarks on result:

other: No information on how the dose levels and test results were reported.

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

Since the test material is completely soluble in water, it is unknown why the acetone/corn oil solvent was used. There was no information provided on test material purity. In the absence of additional information, a true dermal LD50 could not be determined.

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 administered a 20% solution of the test substance in a 90:10 mixture of acetone and corn oil under occluded contact for 24 hours was > 20.0 mL/kg bw.

Based on an acute dermal LDLo value of > 20.0 mL/kg bw in guinea pigs, a 20% solution of 1,4-cyclohexanedimethanol in a 90:10 mixture of acetone and corn oil is not classified for Acute Toxicity by the dermal route under GHS. In the absence of signs of systemic toxicity and/or skin absorption, a 20% solution of 1,4-cyclohexanedimethanol in a 90:10 mixture of acetone and corn oil 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, a 20% solution of 1,4-cyclohexanedimethanol in a 90:10 mixture of acetone and corn oil is not classifiable for Skin Irritation/Corrosion according to GHS.

Executive summary:

In an acute dermal toxicity study, three Hartley guinea pigs were exposed to 5, 10 or 20 mL/kg bw of a 20% solution of 1,4-cyclohexanedimethanol in a 90:10 mixture of acetone and corn oil under occlusive contact for 24 hours. Under the conditions of this study, no deaths occurred and the dermal LDLo for the mixture 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. A body weight gain was noted for all animals over the 2-week observation period. Based on the results of this study, a 20% solution of 1,4-cyclohexanedimethanol in a 90:10 mixture of acetone and corn oil is not classified for acute dermal toxicity, specific organ toxicity, or skin irritation/corrosion using the OECD GHS classification system, and therefore, presents a low toxicity hazard upon skin contact under conditions of normal use.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Quality of whole database:

For acute dermal toxicity, 4 older non-GLP studies were referenced. In all, doses range from 1 g/kg to over 20 g/kg with no signs of dermal toxicity.

Additional information

None

Justification for classification or non-classification

1,4-cyclohexanedimethanol is not classified for acute lethality by any route.