Reaction mass of potassium;sodium;2-[bis[2-[bis(carboxymethyl)amino]ethyl]amino]acetate;copper and potassium;sodium;2-[2-[bis(carboxymethyl)amino]ethyl-(2-hydroxyethyl)amino]acetate;copper

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

October 2nd, 2012.

Deviations:

yes

Remarks:

Deviations are considered as without impact on the conclusion of the study.

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

dicopper(2+) 2-({2-[bis(carboxymethyl)amino]ethyl}(2-hydroxyethyl)amino)acetate 2-[bis({2-[bis(carboxymethyl)amino]ethyl})amino]acetate

EC Number:

915-008-8

IUPAC Name:

dicopper(2+) 2-({2-[bis(carboxymethyl)amino]ethyl}(2-hydroxyethyl)amino)acetate 2-[bis({2-[bis(carboxymethyl)amino]ethyl})amino]acetate

Test material form:

solid

Remarks:

solid with lumps

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Hypharm (F-49450 La Renaudiere)
- Age at study initiation: 12 weeks
- Weight at study initiation: 2.01 - 2.36 kg
- Housing:
Each animal was kept in an individual box installed in conventional air conditioned animal husbanding:
- Diet (e.g. ad libitum):
Drinking water (tap-water from public distribution system) and foodstuff (ENVIGO – 2030C) were supplied ad libitum.
Microbiological and chemical analyses of the water were carried out once every six months by Bureau Veritas – Eurofins (FRANCE).
- Water (e.g. ad libitum):
Drinking water (tap-water from public distribution system) and foodstuff (ENVIGO – 2030C) were supplied ad libitum.
Microbiological and chemical analyses of the water were carried out once every six months by Bureau Veritas – Eurofins (FRANCE).
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
The temperature and relative humidity of the main test were controlled to remain within target ranges of 17°C to 23°C and 30% to 70%, respectively.
The rate of air exchange was at least ten changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (07.00 to 19.00) and twelve hours darkness.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1g

Duration of treatment / exposure:

0.1 g of the test item was instilled, as supplied, into the conjunctival sac of one eye after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second in order to prevent loss of the test item.

Observation period (in vivo):

Ocular examinations were performed on both right and left eyes 1 hour, 24, 48 and 72 hours following treatment

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no washing

SCORING SYSTEM:
See "any other information on materials and methods"

TOOL USED TO ASSESS SCORE: not specified

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Results 2

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.7

Max. score:

1

Reversibility:

fully reversible within: 72 h

Results 3

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

not fully reversible within: 72 h

Results 4

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.3

Max. score:

1

Reversibility:

fully reversible within: 48 hours

Results 5

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.3

Max. score:

2

Reversibility:

not fully reversible within: 72 hours

Results 6

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

not fully reversible within: 72 hours

Results 7

Irritation parameter:

iris score

Remarks:

lesion

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Results 8

Irritation parameter:

iris score

Remarks:

lesion

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.7

Max. score:

1

Reversibility:

fully reversible within: 72 hours

Results 9

Irritation parameter:

iris score

Remarks:

lesion

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.7

Max. score:

1

Reversibility:

not fully reversible within: 72 h

Results 10

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Results 11

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

not fully reversible within: 72 hours

Results 12

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.3

Max. score:

2

Reversibility:

not fully reversible within: 72 hours

Irritant / corrosive response data:

The ocular reactions observed during the study have been slight to important and totally reversible in all animals:
- at the conjunctivae level: a moderate redness noted 1 hour after the test item instillation and totally
reversible between days 2 and 7; associated with a moderate to important chemosis noted 1 hour
after the test item instillation and totally reversible between days 1 and 7.
- at the iris level: an injection noted 24 hours after the test item instillation and totally reversible on
day 3 in two animals.
- at the corneal level: a slight to moderate opacity, noted 24 hours after the test item instillation in
two animals and totally reversible between days 7 and 14.

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

The results obtained, under these experimental conditions, enable to conclude that the test item Reaction mixture of CuDTPA and CuHEEDTA has to be classified in category 2 “Irritating to eyes” in accordance with the Regulation EC No. 1272/2008 on classification, labelling and packaging of substances and mixtures.
The signal word “Warning” and hazard statement H319 “Causes serious eye irritation” are required.

Executive summary:

The test item Reaction mixture of CuDTPA and CuHEEDTA was instilled, as supplied, into the eye of three New Zealand rabbits at the dose of 0.1 g. The experimental protocol was established on the basis of the official method as defined in the O.E.C.D. Test Guideline No. 405 dated October 2nd, 2012.

The ocular reactions observed during the study have been slight to important and totally reversible in all animals:

• -  at the conjunctivae level: a moderate redness noted 1 hour after the test item instillation and totally

  reversible between days 2 and 7; associated with a moderate to important chemosis noted 1 hour

  after the test item instillation and totally reversible between days 1 and 7.

• -  at the iris level: an injection noted 24 hours after the test item instillation and totally reversible on

  day 3 in two animals.

• -  at the corneal level: a slight to moderate opacity, noted 24 hours after the test item instillation in

  two animals and totally reversible between days 7 and 14.

  In conclusion, the results obtained, under these experimental conditions, enable to conclude that the test item Reaction mixture of CuDTPA and CuHEEDTA has to be classified in category 2 “Irritating to eyes” in accordance with the Regulation EC No. 1272/2008 on classification, labelling and packaging of substances and mixtures.

  The signal word “Warning” and hazard statement H319 “Causes serious eye irritation” are required.