Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Toxicological information

Eye irritation

Currently viewing:

Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report date:
2010

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes

Test material

Constituent 1
Reference substance name:
CHDM-D90
IUPAC Name:
CHDM-D90
Test material form:
liquid: viscous
Details on test material:
material description: Eastman(tm) CHDM-D90

composition:
1,4-cyclohexane-dimethanol 89.5%
water 10.4%
intermediated-boiling glycols 0.1%

batch no. TP08031489
ship date 04 Feb 2010
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

Test animals / tissue source

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.

Test system

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.

Results and discussion

In vivo

Resultsopen allclose all
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.

Any other information on results incl. tables

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

Applicant's summary and conclusion

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.