Cyclohex-1,4-ylenedimethanol

Endpoint summary

Description of key information

CHDM is not irritating to rabbit skin but is corrosive to rabbit eyes

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

15 May 2002 - 29 May 2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study (OECD)

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Highgate Farm, Market Rasen, Lincolnshire, England.
- Age at study initiation: At least 8 weeks
- Weight at study initiation: 3.03kg - 3.63kg
- Housing: housed individually in stainless steel cages with perforated floors at the Eye Research Centre, Eye, Suffolk, IP23 7PX.
- Diet (e.g. ad libitum): Special Diet Services STANRAB (P) SQC pellet
- Water (e.g. ad libitum): Drinking water ad libitum
- Acclimation period: At leat 18 days
-Identification: Each animal was identified by a numbered tag placed through the edge of one ear. This identification was unique within the Department throughout the duration of the study. Each cage was identified by a coloured label displaying the study number, animal number, phase of study and initials of the study Director and Home Office licensee.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 15- 23
- Humidity (%): 40 - 70
- Photoperiod (hrs dark / hrs light): 12 hours of artificial light (06:00-18:00 GMT)

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5g of the test substance
- Concentration (if solution): not applicable

Duration of treatment / exposure:

three exposures (of three minutes, one or four hours duration)

Observation period:

at approximately 1, 24, 48, 72 hours after administration

Number of animals:

three animals used.

Details on study design:

TEST SITE
- Area of exposure: 2-ply 25mm x 25mm
- % coverage: 100
- Type of wrap if used: Tubigrip elasticated bandage dressing
-Application site: dorsolumbar region og each rabbit

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Washed with lukewarm water (30-40 degrees) to remove any residual test substance
- Time after start of exposure: at end of exposure period

SCORING SYSTEM:



No erythma and eschar 0
Very slight erythema (barely perceptibla) 1
Well-defined erythema 2
Moderate to severe erythema 3
Servere drythema (beet redness) or eschar formation (injuries in depth) 4



No erythma 0
Very slight erythema (barely perceptibla) 1
Slight oedema (edges of area well-defined by definite rasing) 2
Moderate oedema (edges raised approximately 1 millimetre) 3
Servere oedema (raised more than 1 millimetre and extending beyond the area of exposure) 4

Irritation parameter:

erythema score

Basis:

animal: 3976

Time point:

other: 24, 48, and 72 hours

Score:

0

Irritation parameter:

erythema score

Basis:

animal: 3977

Time point:

other: 24, 48, and 72 hours

Score:

0

Irritation parameter:

erythema score

Basis:

animal: 3998

Time point:

other: 24, 48, and 72 hours

Score:

0

Irritation parameter:

edema score

Basis:

animal: 3976

Time point:

other: 24, 48, and 72 hours

Score:

0

Irritation parameter:

edema score

Basis:

animal: 3977

Time point:

other: 24, 48, and 72 hours

Score:

0

Irritation parameter:

edema score

Basis:

animal: 3998

Time point:

other: 24, 48, and 72 hours

Score:

0

Irritant / corrosive response data:

No dermal irritation was observed in any animal throughout the duration of the study.

Other effects:

There was no sign of toxicity or ill health in any rabbit during the observation period

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Since there was no skin irritation, it can be conclued that CHDM has no dermal toxic effect.

Executive summary:

A study was performed to assess the skin irritation potential of CHDM to the rabbit. Three rabbits received a single four, semi-occlusive, dermal administration of approximately 0.5 g of the test substance as supplied and were observed for four days. No dermal irritation was observed in any animal throughout the duration of the study.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes

Specific details on test material used for the study:

Identity: SKYCHDM (1,4-cyclohexanedimethanol)
Chemical name: CHDM (1,4-cyclohexanedimethanol)
Intended use: PET Bottle, Film and Sheet , Coating, Adhesive, Fabric Softener
Appearance: White waxy solid
Storage conditions: Room temperature
Lot number: SEK 018/023580
Expiry: 31 March 2003
Purity: Min. 99.0%
Date received: 5 Apri12002

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

New Zealand White rabbits were received from Covance Research Products, Inc., Denver, PA on 01/13/10, 02/12/10 & 02/17/10 and acclimated for at least five days. Only animals in apparent good health were made available for study assignment. Prior to being selected for this study, both eyes of each animal were examined according to the Draize technique for any evidence of irritation or abnormalities of the cornea, iris and/or conjunctiva. A Mini-Maglite® flashlight equipped with a high intensity bulb was used to aid in the examination. Five rabbits (1 male- 4 females), free from evidence of ocular irritation or abnormalities, were assigned to this study without conscious bias.

The animals were born on 10/03/09, 1 0/17/09 & 11/07/09. The pretest body weight range was 2.5- 3.4 kg. The animals were identified by cage notation and a uniquely numbered metal eartag. The animals were housed 1/cage in suspended cages. Paper bedding was placed beneath the cages and changed at least three times/week. Fresh PMI Rabbit Chow (Diet #5321) was provided daily. Water was available ad libitum. The animal room, reserved exclusively for rabbits on acute tests, was temperature controlled, had a 12-hour light/dark cycle and was kept clean and vermin free.

Vehicle:

water

Controls:

no

Amount / concentration applied:

The test article concentrations (0.1 ml) were placed by syringe into the conjunctival sac that was formed by gently pulling the lower eyelid away from the eye. After instillation, the lids were held together for approximately one second to insure adequate distribution of the test article. One eye of each rabbit was dosed. The contralateral eye served as a control. Using a Mini-Maglite® flashlight equipped with a high intensity bulb, the treated eye of each rabbit was examined for irritation of the cornea, iris and conjunctiva.

Duration of treatment / exposure:

one application per rabbit

Observation period (in vivo):

100% concentration
The eye was examined pretest and scored at 1, 24, 48, 72 hours and again on days 7, 14 and 21. Sodium fluorescein dye procedures were used up to day 21.

50% concentration
The eye was examined pretest and scored at 1, 24, 48, 72 hours and again on day 7. Sodium fluorescein dye procedures were used up to day 7.

35% concentration
The eyes were examined pretest and scored at 1, 24, 48 and 72 hours. Sodium fluorescein dye procedures were inadvertently not performed.

Details on study design:

The control eyes were observed at the same time periods. The sodium fluorescein dye procedures were performed with the aid of an ultraviolet light source. Ocular reactions were graded according to the numerical Draize technique. Additional signs were described.

Body weights were recorded pretest and at termination.

Observations for toxicity, mortality and pharmacological effects were recorded at each ocular observation period. All animals were humanely sacrificed using C02 following study termination.

Analysis of Data
The primary eye irritation score for each rabbit was calculated from the weighted Draize scale.

Eye irritation is the production of reversible changes in the eye following application of the test article to the anterior surface of the eye. ·

Eye corrosion is the production of irreversible tissue damage to the eye following application of the test article to the anterior surface of the eye.

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

(100% concentration)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

iris score

Basis:

mean

Remarks:

(100% concentration)

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Remarks:

erythema

Basis:

mean

Remarks:

(100% concentration)

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 21 days

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

(100% concentration)

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

fully reversible within: 21 days

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

(100% concentration)

Time point:

other: 7d, 14d

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 21 days

Irritation parameter:

cornea opacity score

Basis:

animal #2

Remarks:

(50% concentration)

Time point:

other: 1h, 24h, 48h, 72h, 7d

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

iris score

Basis:

animal #2

Remarks:

(50% concentration)

Time point:

other: 1h, 24h, 48h, 72h, 7d

Score:

0

Max. score:

2

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Remarks:

erythema

Basis:

animal #2

Remarks:

(50% concentration)

Time point:

other: 1h, 24h, 48h, 72h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

animal #2

Remarks:

(50% concentration)

Time point:

other: 1h, 24h, 48h, 72h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 7days

Irritation parameter:

cornea opacity score

Basis:

animal #3

Remarks:

(35% concentration)

Time point:

other: 1h, 24h, 48h, 72h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

iris score

Basis:

animal #3

Remarks:

(35% concentration)

Time point:

other: 1h, 24h, 48h, 72h

Score:

0

Max. score:

2

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Remarks:

erythema

Basis:

animal #3

Remarks:

(35% concentration)

Time point:

other: 1h, 24h, 48h, 72h

Score:

0

Max. score:

3

Reversibility:

fully reversible

Irritation parameter:

chemosis score

Basis:

animal #3

Remarks:

(35% concentration)

Time point:

other: 1h, 24h, 48h, 72h

Score:

0

Max. score:

3

Reversibility:

fully reversible

Irritation parameter:

cornea opacity score

Basis:

animal #4

Remarks:

(35% concentration)

Time point:

other: 1h, 24h, 48h, 72h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

iris score

Basis:

animal #4

Remarks:

(35% concentration)

Time point:

other: 1h, 24h, 48h, 72h

Score:

0

Max. score:

2

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Remarks:

erythema

Basis:

animal #4

Remarks:

(35% concentration)

Time point:

other: 1h, 24h, 48h, 72h

Score:

0

Max. score:

3

Reversibility:

fully reversible

Irritation parameter:

chemosis score

Basis:

animal #4

Remarks:

(35% concentration)

Time point:

other: 1h, 24h, 48h, 72h

Score:

0

Max. score:

3

Reversibility:

fully reversible

Irritation parameter:

cornea opacity score

Basis:

animal #5

Remarks:

(35% concentration)

Time point:

other: 1h, 24h, 48h, 72h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

iris score

Basis:

animal #5

Remarks:

(35% concentration)

Time point:

other: 1h, 24h, 48h, 72h

Score:

0

Max. score:

2

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Remarks:

erythema

Basis:

animal #5

Remarks:

(35% concentration)

Time point:

other: 1h, 24h, 48h, 72h

Score:

0

Max. score:

3

Reversibility:

fully reversible

Irritant / corrosive response data:

100% Concentration - Corneal opacity persisted to day 21. There was no iritis noted during the observation period. Conjunctival irritation cleared by day 21. The control eye appeared normal at all observation periods. There were no abnormal physical signs noted during the observation period. Body weight increased during the observation period.

50% Concentration - There was no corneal opacity or iritis noted at any observation period. Conjunctival irritation cleared by day 7. The control eye appeared normal at all observation periods. There were no abnormal physical signs noted during the observation period. Body weight remained
the same.

35% Concentration -There was no corneal opacity, iritis or conjunctival irritation noted at any observation period in the treated or control eyes. However, there was discharge noted at 1 hour in 2/3 eyes which cleared by 24 hours. There were no abnormal physical signs noted during the observation period. Body weight increased in two animals and remained the same in one animal.

Dose Concentration: 100%
An.#/Sex	Item	Tissue	Reading	1 Hour	24Hour	48 Hours	72 Hours	Day 7	Day 14	Day 21
H3041/F	A	Cornea	Opacity	0	0	2	2	2	2	2
	B		Area	0	0	1	1	1	1	1
		1. Total=(AxB)x5		0	0	10	10	10	10	10
	C	Iris		0	0	0	0	0	0	0
		2. Total=Cx5		0	0	0	0	0	0	0
	D	Conjunctiva	Redness	2	2	2	2	2	2	0
	E		Chemosis	3	3	3	3	2	2	0
	F		Discharge	3	2	2	2	2	2	0
		3. Total=(D+E+F)x2		16	14	14	14	12	12	0
		Total=l+2+3		16	14	24	24	22	22	10
	Systemic	Observations		A	A	A	A	A	A	A
	Sodium	Fluorescein			2	2	1	1	1	0
Dose Concentration: 50%
An.#/Sex	Item	Tissue	Reading
H3043/F	A	Cornea	Opacity	0	0	0	0	0
	B		Area	0	0	0	0	0
		1. Total=(AxB)x5		0	0	0	0	0
	C	Iris		0	0	0	0	0
		2. Total=Cx5		0	0	0	0	0
	D	Conjunctiva	Redness	2	2	2	2	0
	E		Chemosis	2	2	2	2	0
	F		Discharge	3	3	2	1	0
		3. Total=(D+E+F)x2		14	14	12	10	0
		Total=l+2+3		14	14	12	10	0
	Systemic	Observations		A	A	A	A	A
	Sodium	Fluorescein			2	1	1	0
Dose Concentration: 35%
An.#/Sex	Item	Tissue	Reading
H3046/M	A	Cornea	Opacity	0	0	0	0
	B		Area	0	0	0	0
		1. Total=(AxB)x5		0	0	0	0
	C	Iris		0	0	0	0
		2. Total=Cx5		0	0	0	0
	D	Conjunctiva	Redness	0	0	0	0
	E		Chemosis	0	0	0	0
	F		Discharge	2	0	0	0
	3	3. Total=(D+E+F)x2		4	0	0	0
		Total=l+2+3		4	0	0	0
	Systemic	Observations		A	A	A	A
	Sodium	Fluorescein			n/a	n/a	n/a
Dose Concentration: 35%
An.#/Sex	Item	Tissue	Reading
H3906/F	A	Cornea	Opacity	0	0	0	0
	B		Area	0	0	0	0
		1. Total=(AxB)x5		0	0	0	0
	C	Iris		0	0	0	0
		2. Total=Cx5		0	0	0	0
	D	Conjunctiva	Redness	0	0	0	0
	E		Chemosis	0	0	0	0
	F		Discharge	0	0	0	0
		3. Total=(D+E+F)x2		0	0	0	0
		Total=l+2+3		0	0	0	0
	Systemic	Observations		A	A	A	A
	Sodium	Fluorescein			n/a	n/a	n/a
Dose Concentration: 35%
An.#/Sex	Item	Tissue	Reading
H3907/F	A	Cornea	Opacity	0	0	0	0
	B		Area	0	0	0	0
		1. Total=(AxB)x5		0	0	0	0
	C	Iris		0	0	0	0
		2. Total=Cx5		0	0	0	0
	D	Conjunctiva	Redness	0	0	0	0
	E		Chemosis	0	0	0	0
	F		Discharge	2	0	0	0
		3. Total=(D+E+F)x2		4	0	0	0
		Total=l+2+3		4	0	0	0
	Systemic	Observations		A	A	A	A
	Sodium	Fluorescein			n/a	n/a	n/a

Interpretation of results:

Category 1 (irreversible effects on the eye)

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

The test article (CHDM-D90; 90% 1 ,4-Cyclohexanedimethanol in water) at a 100% concentration is corrosive in one rabbit eye. At a 50% concentration, CHDM-D90 is an ocular irritant in one rabbit eye. At a 35% concentration, CHDM-D90 is not an ocular irritant in three rabbit eyes.

Executive summary:

The potential eye irritancy of 1,4 -cyclohexanedimethanol 90% in water (CHDM-D90) was evaluated in rabbits. Initially, one healthy New Zealand White rabbit (female) free from evidence of ocular irritation and corneal abnormalities was dosed with CHDM-D90 at a dose concentration of 100%. Since the results were corrosive in the initial animal and in consultation with the Sponsor, an additional animal (female) was added to the study. The animal was dosed in the same manner as the initial animal at a 50% concentration. Since irritation was noted in the second animal, the Sponsor was consulted and an additional three (1 male-2 females) rabbits were added to the study and dosed in the same manner as the first two animals at a 35% concentration.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

None

Justification for classification or non-classification

CHDM is classified as a category 1 eye irritant due to irreversible damage to the eyes of test subjects. There is no classification for skin irritation as no dermal effects were observed.