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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2006
Report date:
2006

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
- Principle of test: The eye irritation potential of zinc glycinate was tested on three male Japanese albino rabbits (Kbl: JW, SPF) using the Draize method.

- Short description of test conditions: The test substance was made into a fine powder and was instilled into the right eye.
The test sample was distilled into the conjunctival sac of the right eye and the upper and lower eyelid were gently closed together for about a second. The eye was left as it was after the treatment. The left eye was used as a control without any treatment. A cone (Elizabethan collar) was used on all animals from the time right before the administration until the end of the observation to prevent any touching of the eye.
The ocular reaction was observed in intervals of 1, 24, 48 and 72 hours, as well as 4, 7, 10, 14, 18 and 21 days after the administration. Furthermore, a photograph of a representative animal was taken at each observation.

- Parameters analysed/observed: After exposure, different scores were determined: conjunctival redness, chemosis, discharge and iris hyperaemia.
Animal symptoms and their dissipations were then followed until 21 days after exposure.
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Chemical structure
Reference substance name:
Bis(glycinato-N,O)zinc
EC Number:
238-173-1
EC Name:
Bis(glycinato-N,O)zinc
Cas Number:
14281-83-5
Molecular formula:
C4H8N2O4Zn
IUPAC Name:
Zinc bis(aminoacetate)
Test material form:
solid: particulate/powder
Details on test material:
Batch number: 4002
Pourcentage of Zinc: 28.2%
Molecular Weight: 231.52
Specific details on test material used for the study:
- Appearance: White powder
- Storage Conditions: Room temperature (permissible range between 10-30°C), dark location
- Temperature: 13.8-25.2°C (actual measurement)

Test animals / tissue source

Species:
rabbit
Strain:
other: Japanese Albino (Kbl: JW)
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Kitayama Labes Co., Ltd.
- Age at study initiation: 11 weeks
- Weight at study initiation: 2.25 - 2.43 kg
- Housing: Suspension type aluminium cage (32W x 48D x 33H cm, with wire mesh cage floor, Tokiwa Kagaku Kikai Co., Ltd.)
Material was sterilized using steam and exchanged once 7 days after the arrival of the animals.
1animal per cage
- Diet (e.g. ad libitum): Solid feed for laboratory animals (LRC4, Oriental Yeast Co., Ltd.) - Free feeding - Leftovers were disposed of when exchanging the feeder and new feed was provided.
- Water (e.g. ad libitum): Tap water filtered with a 5μm filter and subsequent ultraviolet irradiation treatment - Free water feeding - Inspection of water quality was carried out periodically (twice a year) by Diamond Analysis Center Co., Ltd. (now Mitsubishi Chemical Analytech Co., Ltd.). Conformation to the criteria of the standard operating procedure manual, which were based on water supply regulations, was assured.
- Acclimation period: To confirm the good health of the animals, the general condition of each animal was observed once per day for 5 days and the weight was measured on the day of arrival and the end of quarantine. No abnormalities were found during the quarantine and acclimatization period.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Actual value 20.5-24.3°C (permissible range 19.0-25.0°C)
- Humidity (%): Actual value 44.4-72.6% (permissible range 35.0-75.0%)
- Air changes (per hr): 6-20 air changes per hour, “All Fresh Air” supply
- Photoperiod (hrs dark / hrs light): 12 hours light per day, between 7:00 and 19:00

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes
other: Left eye - without any treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1g
- Number of Doses: one
Duration of treatment / exposure:
One administrated dose
Observation period (in vivo):
21 days
Number of animals or in vitro replicates:
3 animals
Details on study design:
METHOD OF ADMINISTRATION
The test sample was distilled into the conjunctival sac of the right eye and the upper and lower eyelid were gently closed together for about a second. The eye was left as it was after the treatment. The left eye was used as a control without any treatment. A cone (Elizabethan collar) was used on all animals from the time right before the administration until the end of the observation to prevent any touching of the eye.

OBSERVATION OF OCULAR REACTION
The ocular reaction was observed in intervals of 1, 24, 48 and 72 hours, as well as 4, 7, 10, 14, 18 and 21 days after the administration. Furthermore, a photograph of a representative animal (animal number 30102) was taken at each observation.

SCORING SYSTEM
Based on the Draize criteria, a score was calculated taking into account the degree of cornea opacity and the area of clouding, the extent of damage to the iris, as well as the extent of conjunctival redness, chemosis and discharge.

TOOL USED TO ASSESS SCORE
(1) Slit lamp (SL-5, Kowa Company, Ltd.)
The slit lamp was used at each observation.
(2) UV lamp (UVL-56, Funakoshi Co., Ltd.)
From 24 hours after the administration onwards, 1 w/v% fluorescein sodium salt dye (Wako Pure Chemical Industries, Ltd., lot number SEK8296) aqueous solution was instilled into the eye of the animals. The residual dye was flushed away using Japanese Pharmacopoeia Isotonic Sodium Chloride Solution (Otsuka Pharmaceutical Factory, Inc., lot number 4G90N). Afterwards, the cornea was inspected with a UV lamp.

CLASSIFICATION OF THE EXTENT OF IRRITATION
According to the Draize scheme, the total score was calculated for each individual resulting from the weighted score of each entry on the list. Further, the mean total score was calculated for each point of observation and the highest value until 4 days after the administration was noted. This value was used to classify the extent of eye irritation using the method by Kay and Calandra.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 7/10/14/18/21 d
Score:
>= 54 - <= 75.3
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
24/48/72 h
Score:
>= 22.3 - <= 48.3
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: 48/72 h and 7/10/14/18/21 d
Score:
ca. 2
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24 h
Score:
ca. 3
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: 7/10/14/18/21 d
Score:
ca. 2
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48 h
Score:
ca. 3
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: 7/10/14/18/21 d
Score:
ca. 0
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 1
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: 10/14/18/21 d
Score:
ca. 3
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
72 h
Score:
ca. 1
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48 h
Score:
ca. 0
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: 7/10/14/18/21 d
Score:
ca. 3
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 4
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: 7/10/14/18/21 d
Score:
ca. 2
Reversibility:
not reversible
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: 48/72 h
Score:
ca. 2
Reversibility:
not reversible
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24 h
Score:
ca. 1
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: 7/10/14/18/21 d
Score:
ca. 0
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 1
Reversibility:
fully reversible
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: 10/14/18/21 d
Score:
ca. 3
Reversibility:
not reversible
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
72 h
Score:
ca. 1
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48 h
Score:
ca. 0
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
21 d
Score:
ca. 3
Reversibility:
not reversible
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 3
Reversibility:
not reversible
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
21 d
Score:
ca. 2
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 7/10/14/18 d
Score:
ca. 3
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 3
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: 7/10/14/18/21 d
Score:
ca. 0
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 1
Reversibility:
fully reversible
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 10/14/18/21 d
Score:
ca. 3
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
7 d
Score:
ca. 2
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
72 h
Score:
ca. 2
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
48 h
Score:
ca. 1
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24 h
Score:
ca. 0
Irritant / corrosive response data:
OCULAR REACTION
Until the observation 24 hours after the administration, all animals reached a score of 1 to 3 for conjunctival redness, 2 to 4 for chemosis, 2 to 3 for discharge and 1 for iris hyperaemia. A score of 1 to 2 for the cornea opacity (area of opacity: 4) was confirmed in all animals 72 hours after the administration. Amongst these symptoms, a dissipation was observed for the iris hyperaemia after 7 days in all animals. The other symptoms continued and the score for cornea opacity even increased to 3 (area of opacity: 4) in all animals after 10 days. On the day of the last observation (21 days after the administration) a dissipation of the discharge could be found in 1 animal; however, the other symptoms did not disappear. Furthermore, corneal epithelial defects, entropion, conjunctival whitening, corneal oedema and corneal vascularization were confirmed in all animals until the observation on day 4 after the administration at latest. Conjunctival deformation was observed in 2 animals after 10 days and 1 animal after 14 days. The observations 21 days after the administration also confirmed corneal epithelial defects, corneal oedema, corneal vascularization and conjunctival deformation in all animals. Entropion was confirmed in 2 and conjunctival whitening in 1 animal after 21 days.

CLASSIFICATION OF EYE IRRITATION
The average score weighted using the Draize method. The mean total score of the highest value until day 4 was 59.7 on day 4 after the administration.
As a result, the extent of the eye irritation can be classified as “extremely irritating”.
Other effects:
GENERAL CONDITION
No abnormalities were found in any animal during the observation time.

BODY WEIGHT
A slight weight decrease was found in two animals 4 days after the administration; however, an abnormal weight fluctuation with influence on the evaluation of the test results was not found.

Applicant's summary and conclusion

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
The eye irritation potential of zinc glycinate was examined.
The average score weighted using the Draize method. The mean total score of the highest value until day 4 was 59.7 on day 4 after the administration.
As a result, the extent of the eye irritation can be classified as “extremely irritating”.
Executive summary:

The eye irritation potential of zinc glycinate was examined.
The test substance was made into a fine powder and 0.1 g was instilled into the right eye.
Until the observation 24 hours after the administration, all animals reached a score of 1 to 3 for conjunctival redness, 2 to 4 for chemosis, 2 to 3 for discharge and 1 for iris hyperaemia. A score of 1 to 2 for cornea opacity (area of opacity: 4) was confirmed in all animals 72 hours after the administration, which increased to 3 (area of opacity: 4) in all animals after 10 days. Amongst these symptoms, a dissipation was observed for the iris hyperaemia after 7 days in all animals. In 1 animal the dissipation of discharge could be found after 21 days; however, the other symptoms did not disappear. Furthermore, corneal epithelial defects, entropion, conjunctival whitening, corneal oedema and corneal vascularization were confirmed in all animals until the observation on day 4 after the administration at latest. Conjunctival deformation was observed in 2 animals after 10 days and 1 animal after 14 days. The observations 21 days after the administration confirmed corneal epithelial defects, corneal oedema, corneal vascularization and conjunctival deformation in all animals. Entropion was confirmed in 2 animals and conjunctival whitening in 1 animal after 21 days. The extent of the eye irritation is classified as “extremely irritating” according to the method by Kay and Calandra.
The extent eye irritation was classified as “extremely irritating” in this test. In addition, irreversibility of the reaction in this test can be assumed, resulting from the tissue damage indicated by e.g. the conjunctival whitening and deformation in all animals.
During the observation period, a slight decrease in body weight was found in 2 animals, however this is a change found often in this type of test and is thought to be caused by the stress resulting from the series of treatments. It is thus assumed to have no influence on the test evaluation.
The zinc glycinate eye irritation in rabbits was concluded to be irreversible and the substance was extremely irritating to the eye under the conditions of this test.