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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
September 6, 2016 - September 20, 2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
2016
Report date:
2016
Reference Type:
study report
Title:
Unnamed
Year:
2016
Report date:
2016
Reference Type:
study report
Title:
Unnamed
Year:
2016
Report date:
2017

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
2 October 2012
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
31 May 2008
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Version / remarks:
August 1998
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
TOXI-COOP ZRT.1045 Budapest, Berlini u. 47-49. Hungary

Test material

Constituent 1
Chemical structure
Reference substance name:
Reaction mass of calcium 2,6-bis(3-carboxylatopropanamido)hexanoate and isomers of calcium amino-(3-carboxylatopropanamido)hexanoate
EC Number:
947-903-4
Cas Number:
1917323-93-3
Molecular formula:
C28H42Ca3N4O16 and C10H16CaN2O5
IUPAC Name:
Reaction mass of calcium 2,6-bis(3-carboxylatopropanamido)hexanoate and isomers of calcium amino-(3-carboxylatopropanamido)hexanoate
Test material form:
other: highly viscous, semi-solid mass

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: S & K LAP Kft. 2173 Kartal, Császár út 135, HUNGARY
- Age at study initiation: Young adult rabbits
- Weight at study initiation: 2884-3118 g
- Housing: housed individually in metal cages
- Diet: ad libitum, C.HYF rabbit mixed diet produced by Cargill Takarmány Zrt., 5300 Karcag, Madarasi út 0399., Hungary
- Water: ad libitum, tap water
- Acclimation period: 5 days in first animal and 6 days in second and third animal

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 30 - 70
- Air changes (per hr): above 10 changes
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g

Duration of treatment / exposure:
The eyes of the test animals were not washed out 24 hours after the application of test item, because the test substance was removed from the eye of the test animal by physiological mechanisms and the test item did not cause immediately severe irritation or corrosion after test item application.
Observation period (in vivo):
eyes examined at 1, 24, 48 and 72 hours after the application
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: none
SCORING SYSTEM: The eye irritation scores were evaluated according to the scoring system by Draize (1977) and OECD 405 (2nd October 2012)
A. Opacity-degree of density (Area most dense taken for reading)
No uncleration or opacity: 0
Scattered or diffuse areas of opacity (other than slight
dulling of normal lustre): details of iris clearly visible: 1
Easily discernible translucent area: details of iris slightly obscured: 2
Nacreous area: no details of iris visible: size of pupil barely discernible: 3
Opaque cornea: iris not discernible through the opacity: 4

Area of cornea involved
One quarter (or less), but not zero: 1
Greater than one quarter, but less than half: 2
Greater than half, but less than three quarters: 3
Greater than three quarters, up to whole area: 4

B. Iris
Values
Normal: 0
Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia: or injection: iris reactive to light
(a sluggish reaction is considered to be an effect): 1
Hemorrhage, gross destruction, or no reaction to light: 2

C. Conjunctivae
Redness (Palpebral and bulbar)
Normal: 0
Some blood vessels hyperaemic (injected): 1
Diffuse, crimson colour, individual vessels not easily discernible: 2
Diffuse beefy red: 3
Chemosis
Normal: 0
Some swelling above normal (includes nictitating membrane): 1
Obvious swelling with partial eversion of lids: 2
Swelling with lids about half closed: 3
Swelling with lids more than half closed: 4
D. Discharge
No discharge: 0
Any amount different from normal (does not include small amounts observed in inner canthus of normal animals): 1
Discharge with moistening of the lids and hairs just adjacent to lids: 2
Discharge with moistening of the lids and hairs, on considerable area around the eye: 3

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
other: Discharge
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Other effects:
No systemic toxicity was observed on the day of the treatment and during the 72-hour observation period. The body weight of animals corresponded to their species and age. Sign of pain and distress as discharge was observed in one animal on the treatment day at first observation.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The test item, applied to the rabbits’ eye mucosa, caused slight conjunctival irritant effects which were fully reversible within 24 hours.
Executive summary:

A study according OECD TG 405, EU method B5 and EPA OPPTS 870.2400 was conducted to determine the eye irritation potential of the test item. The test item was placed into the conjunctival sac of the left eye of three New Zealand White rabbits. The untreated right eye served as control. A weight of 0.1 g of the test item was used, as a single dose. The eyes of the test animals were not washed out after the application of test item. The irritation effect of the test item was evaluated according to the Draize method.

The eyes were examined at 1, 24, 48 and 72 hours after the application. One hour after the treatment, slight conjunctival redness, chemosis and discharge were observed in animals. 24 hours after the treatment, all animals became free of symptoms. 72 hours after the treatment all animals were free of symptoms and the study was terminated.

No systemic toxicity was observed on the day of the treatment and during the 72-hour observation period. The body weight of animals corresponded to their species and age. Sign of pain and distress as discharge was observed in one animal on the treatment day at first observation.

In conclusion, the test item applied to the rabbits’ eye mucosa, caused slight conjunctival irritant effects which were fully reversible within 24 hours. According to Regulation (EC) No 1272/2008, the test item has not been classified into any category.