Registration Dossier

Administrative data

Description of key information

Skin irritation

Key studies:
- Study in rabbits according to OECD Guideline 404 (Acute Dermal Irritation / Corrosion).
A 34.5 % aqueous solution of sodium chlorite is a non-irritant when administered by cutaneous route in rabbits.

- Study in rabbits according to EPA No. 158.81-5.
Irritation consisted of erythema (Grades 1 through 3) in all sites at 30-60 minutes and 24 hours postdose, persisting through Day 7 in two sites.
Edema (Grade 1) was observed in one site at 30-60 minutes and in two sites at 48 hours.
Other dermal effects included blanching, thickening, necrosis, sloughing, and blackened areas.
One female was found dead on Day 20 postdose. The substance is classified as Corrosive Category 1B (necrosis was observed in two animals).

- Study in rabbits according to method EPA guideline 8/22/78 (40 CFR, Part 163).
Not irritating (31% aqueous solution)


Eye irritation

Key study
-In rabbits. Guidelines for Hazardous Evaluation for Humans and Domestic Animals, Federal Register, Vol. 43, No. 163, 1978; section 163.81-5.
A 31 % aqueous solution of sodium chlorite is a severe eye irritant, based on the observed effects on the cornea, iris and conjunctiva which are not fully reversible within the observation period of 21 days.

- In-vitro ICE test: OECD Guideline 438.

The results obtained in the study performed on sodium chlorite 9% water solution lead to the category "no prediction can be made" according to current guidelines.

- In rabbits. OECD Guideline 405.

A 9% aqueous solution of sodium chlorite is determined to be irritationg to the eyes (category 2, H319), based on the moderate and totally reversible effects observed in all animals, and being the corneal opacity score > 1 in all three animals tested.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation / corrosion, other
Remarks:
In vivo study, the test was conducted in 1994 before REACH Regulation (EC) 1907/2006 entered into force.
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Source:Elevage Cunicole de Val de Selle, Prouzel, France
Sex:Male
Weight at study initiation:2.6 ± 0.2 kg
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
other: No vehicle was used as the test material is an aqueous solution
Controls:
other: Animals 02 and 03 did not receive any test substance on the left flank, and served as controls.
Amount / concentration applied:
The test substance was applied to a 6 cm2 dry hydrophilic gauze patch, which was then applied to the posterior left flank of the animals (animal No.01) or the right flank of all 3 animals.Total volume applied: 0.5 mL
Duration of treatment / exposure:
The test substance was applied in a first assay for a period of 3 minutes in animal 01. As the test substance was non corrosive, it was applied in a second assay for 4 h. The results were then confirmed on 2 additional animals (nos. 02 and 03).
Observation period:
10 days
Number of animals:
3 rabbits/group
Details on study design:
SCORING SYSTEM:Dermal irritation was evaluated for each animal according to the following scoring scale:
Erythema and eschar formation:
No erythema 0
Very slight erythema (barely perceptible)1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness) to slight eschar formation (injuries in depth)4

Oedema formation:
No oedema 0
Very slight oedema (barely perceptible) 1
Slight oedema (edges of area well-defined by definite raising) 2
Moderate oedema (raised approximately 1 millimetre) 3
Severe oedema (raised more than 1 millimetre and extending beyond area of exposure) 4

Examination time points: 1 h, 24 h, 48 h, 72 h after removal of the dressing and then daily until day 10.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: Mean score from days 2, 3 and 4
Score:
0
Remarks on result:
other: 3 minute treatment
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: Mean score from days 2, 3 and 4
Score:
1
Remarks on result:
other: 4 hour treatment
Irritation parameter:
erythema score
Basis:
animal: 2 and 3
Time point:
other: Mean score from days 2, 3 and 4
Score:
0
Remarks on result:
other: 4 hour treatment
Irritation parameter:
edema score
Basis:
animal: 1, 2 and 3
Time point:
other: Mean score from days 2, 3 and 4
Score:
0
Remarks on result:
other: 4 hour treatment
Irritant / corrosive response data:
Treatment for 3 minutes – only a dryness of the skin was observed on days 4 and 5.Treatment for 4 hours – No cutaneous reactions were observed during the study in 2 animals given the test substance for 4 h. In one animal treated with the test substance during 4 hours, very slight reversible erythema and / or dryness of the skin was noted within 9 days. No necrosis or ulceration was observed.

Table A6_1_4i-1             Table for skin irritation study

time

Erythema

Edema

average score per animal

01

1.0

0.0

02

0.0

0.0

03

0.0

0.0

reversibility: *

C

N/A

average time for reversibility

*      c :      completely reversible
     n c :      not completely reversible
        n :      not reversible

Interpretation of results:
GHS criteria not met
Remarks:
Not classified according to CLP criteria.
Conclusions:
A 34.5 % aqueous solution of sodium chlorite is a non-irritant when administered by cutaneous route in rabbits.
Executive summary:

Study in rabbits according to OECD Guideline 404 (Acute Dermal Irritation / Corrosion).

A 34.5 % aqueous solution of sodium chlorite is a non-irritant when administered by cutaneous route in rabbits.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 6 September 1984 to 27 September 1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Remarks:
No GLP but it is similar to OECD guideline n 404.
Qualifier:
according to
Guideline:
other: Environmental Protection Agency Guidelines for FIFRA and TSCA, EPA No. 158.81-5
Deviations:
not specified
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
not specified
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
New Zealand White rabbits were received from Hazleton Dutchland ,Inc., Denver. Pennsylvania. The rabbits were assigned animal numbers using a computerized randomization process. This process involved generating random numbers, assigning the random numbers to the animals, and ranking the random numbers. The rabbits were identified uniquely by individual ear tags and housed individually in elevated wire-mesh cages. Commercial rabbit ration (Purina Lab Rabbit Cho~ and tap water were available ad libitum except where noted otherwise. The rabbits were acclimated to laboratory conditions for a minimum of one week prior to initiation of treatment.
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
A 0.5 gram aliquot of the test material was introduced under a one to one and one-half-inch square gauze patch (two layers thick) which was secured in place with porous tape.
Duration of treatment / exposure:
4 hours
Observation period:
Dermal responses were graded and scored at 30-60 minutes, 24, 48, and 72 hours and on Days 4, 7, 14, and 21 according to the system· ofDraize (1959).
Number of animals:
3 males3 females
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0.83
Max. score:
2
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0.11
Max. score:
1
Reversibility:
fully reversible
Other effects:
Other dermal effects included blanching, thickening, necrosis, sloughing, and blackened areas. One female was found dead on Day 20 postdose. The animal refused food and water prior to death. This death was judged to be unrelated to compound administration.Four of the five surviving animals gained weight from initiation through termination .
Interpretation of results:
Category 1B (corrosive) based on GHS criteria
Remarks:
Equivalent to CLP criteria; necrosis has been observed in two animals
Conclusions:
Irritation consisted of erythema (Grades 1 through 3) in all sites at 30-60 minutes and 24 hours postdose, persisting through Day 7 in two sites. Edema (Grade 1) was observed in one site at 30-60 minutes and in two sites at 48 hours. Other dermal effects included blanching, thickening, necrosis, sloughing, and blackened areas. One female was found dead on Day 20 postdose, it was considered not treatment related.
Executive summary:

The purpose of this study was to evaluate the primary skin irritation potential of the test material in rabbits (3 males and 3 females) according to the Environmental Protection Agency Guidelines for FIFRA and TSCA, EPA No. 158.81-5 (similar to OECD Guideline nr.404).

0.5g aliquot of the test material was introduced under a one to one and one-half-inch square gauze patch (two layers thick) which was secured in place with porous tape.

The duration of the exposure was 4 hours. Dermal responses were graded and scored at 30-60 minutes, 24, 48, and 72 hours and on Days 4, 7, 14, and 21 according to the system· of Draize (1959).

Irritation consisted of erythema (Grades 1 through 3) in all sites at 30-60 minutes and 24 hours postdose, persisting through Day 7 in two sites.

Edema (Grade 1) was observed in one site at 30-60 minutes and in two sites at 48 hours.

Other dermal effects included blanching, thickening, necrosis, sloughing, and blackened areas.

One female was found dead on Day 20 postdose although it was considered to be not related to the treatment.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 2nd January 1985 to 22nd January 1985
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
No GLP.
Qualifier:
according to
Guideline:
other: EPA guidelines 8/22/78 (40 CFR Part 163)
Deviations:
not specified
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Adult New Zeland albino rabbits, both sexes, weights 2 kg.-rabbit
food and water ad libitum
-12 hour night-day lighting cycle
-relative humidity 40-50%
-temperature of animal room 20-25ºC
-indirect bedding of absorbent liners over pine shavings-stainless steel wire cages of USDA specifications-animal quarantine and acclimitization prior to dosing
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
not specified
Amount / concentration applied:
The dose rate was 1.67 ml (2.0 g of liquid) per kilogram bw
Duration of treatment / exposure:
The treated skin was covered for 24 hours with a gauze dressing and a plastic over-wrap which were held to theskin under a rubberized sleeve.
Observation period:
The dosing area was observed for erythema and edema at 24 hours after application and again at 72 hours.
Number of animals:
10 animals (5 male, 5 female)
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
no data
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
no data
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
no data
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
1.5
Max. score:
2
Reversibility:
no data
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
no data
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.5
Max. score:
2
Reversibility:
no data
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
1
Reversibility:
no data
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
1
Reversibility:
no data
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
1
Max. score:
1
Reversibility:
no data
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
0
Interpretation of results:
other: Not irritating according to CLP criteria.
Conclusions:
A 31 % aqueous solution is not irritating according to CLP criteria.
Executive summary:

The purpose of the study is to determine the primary irritation of the test material.

The test was performed according to method EPA guideline 8/22/78 (40 CFR, Part 163).

10 adult New Zealand albino rabbits were used (both sexes, weights 2 kg).

The dose rate was 1.67 ml (2.0 g of liquid) bw.

After 24 hours of semi-occlusive application, the dosing area was observed for erythema and edema at 24 hours after application and again at 72 hours.

The result was as follows:

Not irritating (31% aqueous solution)

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
26 April 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 438 (Isolated Chicken Eye Test Method for Identifying i) Chemicals Inducing Serious Eye Damage and ii) Chemicals Not Requiring Classification for Eye Irritation or Serious Eye Damage)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
chicken
Details on test animals or tissues and environmental conditions:
SOURCE OF COLLECTED EYES
- Source: Etablissement Brun, 33820 Etauliers, France
- Age/weight: That of spring chickens traditionally processed by a poultry alaughterhouse (i.e., approximately 7 weeks old, 1.5-2.5 kg).
- Storage, temperature and transport conditions of ocular tissue (e.g. transport time, transport media and temperature, and other conditions): The intact heads were transported from the slaughterhouse at ambient temperature in plastic boxes humidified with towels moistened with physiological saline.
- Time interval prior to initiating testing: The heads were collected on 26 April 2017 at 8:10 am and they were enucleated at 9:50 am.
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent positive control
yes, concurrent negative control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 30 µL
- Concentration (if solution): Test item us such (sodium chlorite 9% water solution)
Duration of treatment / exposure:
10 seconds
Duration of post- treatment incubation (in vitro):
240 min
Number of animals or in vitro replicates:
3
Details on study design:
SELECTION AND PREPARATION OF ISOLATED EYES
Eyelids were carefully excised and further dissected from the skull, taking care not to damage the cornea. The eyeball was pulled from the orbit by holding the nictitating membrane firmly with surgical forceps, and the eye muscles were cut. The optic nerve was left attached. The nictitating membrance and the other connective tissue were finally cut away. The enucleated eye was mounted in a stainless steel clamp with the cornea positioned vertically and it was transferred to a chamber of the superfusion apparatus (32.0-32.4 ºC). The entire cornea was supplied with the physiological saline drip (0.1-0.15 mL/min). The eyes were examined with a slit-lamp microscope to ensure that they have not been damaged during the dissection procedure. Corneal thickness was measured. Eyes with (i) a fluorescein retention scope of > 0.5, (ii) corneal opacy > 0.5, or (iii) any additional signs of damage were replaced. Moreover, individual eyes with a corneal thickness deviating more than 10% from the mean value for all eyes were rejected.

EQUILIBRATION AND BASELINE RECORDINGS
Once the eyes were examined and approved, the eyes were incubated between 45 and 56 minutes to be equilibrated. Then, a zero reference measurement was recorded for corneal thickness and opacity to serve as a baseline (i.e. time = 0). The fluorescein score determined at dissection was used as the baseline measurement for that endpoint.

NUMBER OF REPLICATES : 3

NEGATIVE CONTROL USED : Physiological saline (Dutscher Batch No. 3012316)

POSITIVE CONTROL USED: 5% Benzalkonium chloride (Sigma Batch No. BCBQ9761V)

APPLICATION DOSE AND EXPOSURE TIME : 30 µL and 10 seconds.

OBSERVATION PERIOD: 0, 30, 75, 120, 180 and 240 minutes after post-treatment rinse.

REMOVAL OF TEST SUBSTANCE
- Volume and washing procedure after exposure period: Eyes were rinsed with 20 mL of physiological saline at ambient temperature.

METHODS FOR MEASURED ENDPOINTS:
- Corneal opacity: It was calculated by using the area of the cornea that was not densely opacified for scoring.
- Damage to epithelium based on fluorescein retention: Calculated for the 30 min observation time period only.
- Swelling: measured with optical pachymeter on a slit-lamp microscope; slit-width setting: 9 1/2. equalling 0.095 mm.
- Macroscopic morphological damage to the surface: Including "pitting" of corneal epithelial cells, "loosening" of epithelium, "roughening" of the corneal surface and "sticking" of the test item to the cornea.

SCORING SYSTEM:
- Mean corneal swelling (%) : [(Corneal thickness at time I - corneal thickness at time 0) / corneal thickness at time 0] x 100.
- Mean maximum opacity score: Based on the highest mean score at any time point, an overall category score was given:
0 - No opacity
0.5 - Very faint opacity
1 - Scattered or diffuse area; details of the iris clearly visible
2 - Easily discernible translucent area; details of the iris are slightly obscured
3 - Severe corneal opacity; no specific details of the iris are visible, size of the pupil is barely discernible
4 - Complete corneal opacity; iris visible
- Mean fluorescein retention score at 30 minutes post-treatment
0 - No fluorescein retention
0.5 - Very minor single cell staining
1 - Single cell staining scattered throughout the treated area of the cornea
2 - Focal or confluent single cell staining
3 - Confluent large areas of the cornea retaining fluorescein.

DECISION CRITERIA: as indicated in the TG.
Irritation parameter:
cornea opacity score
Run / experiment:
Mean 1-3
Value:
2
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: ICE class III
Irritation parameter:
fluorescein retention score
Run / experiment:
Mean 1-3
Value:
2
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: ICE class III
Irritation parameter:
percent corneal swelling
Run / experiment:
Maximal 1-3
Value:
5
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Other effects / acceptance of results:
OTHER EFFECTS:
- Visible damage on test system: Not stated.

DEMONSTRATION OF TECHNICAL PROFICIENCY: Yes

ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: Yes (3 x I)
- Acceptance criteria met for positive control: Yes (3 x IV)

Endpoint

Eye no.

Time (min)

0

30

75

120

180

240

Corneal opacity

7

0

1

1

1

1

2

8

0

1

1

1

1

2

9

0

1

2

2

2

2

Mean

0.0

1.0

1.3

1.3

1.3

2.0

ICE class

III

Fluorescein retention

7

0.5

2

-

-

-

-

8

0.5

2

-

-

-

-

9

0.5

2

-

-

-

-

Mean

0.5

2.0

-

-

-

-

ICE class

III

Corneal thickness

7

0.59

0.64

0.64

0.65

0.65

0.66

8

0.60

0.60

0.60

0.60

0.60

0.62

9

0.64

0.64

0.64

0.64

0.64

0.64

Corneal swelling (%)

7

-

8

8

10

10

12

8

-

0

0

0

0

3

9

-

0

0

0

0

0

Mean

-

3

3

3

3

5

ICE class

I

Combination

2 x III, 1 x I

Classification

No prediction can be made

Interpretation of results:
other: No prediction can be made
Conclusions:
Results obtained under the in-vitro Isolated Chicken eye test lead to the category "no prediction can be made" since the combination of the three endpoints for the test item was 2xIII, 1xI.
Executive summary:

The in-vitro Isolated Chicken Eye test was performed according to OECD Guideline 438 (GLP study). The test item was applied at the dose of 30 µL to 3 enucleated chicken eyes during 10 seconds and then, the eyes were rinsed twice with 10 mL of physiological saline. Three eyes were treated in the same manner with a positive control and one eye with a negative control. Damages by the test item were assessed by determination of corneal swelling, opacity and fluorescein retention at 30, 75, 120, 180 and 240 minutes after treatment. The ocular reactions observed in the eyes treated with the test item were: maximal mean score of corneal opacity of 2.0, corresponding to ICE class III; mean score of fluorescein retention of 2.0, corresponding to ICE class III and maximal mean corneal swelling of 5%, corresponding to ICE class I. The combination of the three endpoints was 2xIII, 1xI, which lead to the category "no prediction can be made" as defined by the OECD guideline. Bothe the positive and negative controls were acceptable.

Endpoint:
eye irritation, other
Remarks:
In vivo study, The test was conducted in 1985 before REACH Regulation (EC) 1907/2006 entered into force.
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: No GLP statement
Qualifier:
according to
Guideline:
other: Guidelines for Hazardous Evaluation for Humans and Domestic Animals, Federal Register, Vol. 43, No. 163, 1978; section 163.81-5
Deviations:
no
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Age/weight at study initiation:
adult, 2 kg
Sex:Male and female
Vehicle:
other: No vehicle was used as the test material was an aqueous solution
Controls:
not specified
Amount / concentration applied:
Volume applied: 0.1 mL
Duration of treatment / exposure:
Exposure period:Single administration
Observation period (in vivo):
14 days
Number of animals or in vitro replicates:
9 animals/group
Details on study design:
Scoring system: Draize
Examination time points:Daily
Other investigations:For 3 out of 9 animals the eye was rinsed for 30 seconds using tap water. The eyes of the other 6 animals were not rinsed.
Gross observations were made daily under white light and under long wave ultra violet light subsequent to fluorescein staining. Corneal opacity was observed to 14 days.
Irritation parameter:
cornea opacity score
Basis:
other: 6 of 9 animals had irreversible corneal opacity
Time point:
21 d
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Irritant / corrosive response data:
Sodium chlorite was a severe eye irritant when tested with and without a 30 second rinse. Irreversible corneal damage was observed in all but 3 test animals in conjunction with iris damage and moderate to sever conjunctivitis. The formulation also produced pannus (superficial corneal vasularization) in 8 out of 9 test animals along with transient cases of adhesions, blistering, and haemorrhaging. Rinsing for 30 seconds after treatment did not alleviate the irritation response.

Table A6_1_4ii-1.           Results of eye irritation study

Cornea

Iris

Conjunctiva

redness

chemosis

score (average of animals investigated)

0 to 4

0 to 2

0 to 3

0 to4

No rinse:

Day 0

0

0

0

0

Day 1

0.5

1.7

2.2

3.3

Day 2

1.0

1.8

2.8

3.0

Day 4

2.3

1.7

2.7

2.8

Day 7

3.2

1.3

2.8

2.5

Day 14

3.3

1.0

1.7

2.0

Day 21

3.3

0.5

1.2

1.5

30 s rinse:

Day 0

0

0

0

0

Day 1

1.0

1.3

2.3

3.0

Day 2

1.3

1.3

3.0

3.0

Day 4

2.3

0.7

2.7

3.0

Day 7

2.3

1.0

2.7

2.7

Day 14

1.3

0.7

1.3

2.0

Day 21

1.3

0

0.7

1.0

Maximum average score (including area affected, max 110)

Reversibility*

average time for reversion

Give method of calculation maximum average score.

*              c :            completely reversible
                n c :        not completely reversible
                n :           not reversible

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Remarks:
According to CLP.
Conclusions:
A 31 % aqueous solution of sodium chlorite is a severe eye irritant.
Executive summary:

The aim of the study was to determine the eye irritation in rabbits due to the test material.

The test procedure was: Guidelines for Hazardous Evaluation for Humans and Domestic Animals, Federal Register, Vol. 43, No. 163, 1978; section 163.81-5. A 31 % aqueous solution of sodium chlorite is a severe eye irritant, based on the observed effects on the cornea, iris and conjunctiva which are not fully reversible within the observation period of 21 days.

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
06 June 2017 - 26 June 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
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 old
- Weight at study initiation: 2.26 kg
- Housing: Individual boxes.
- Diet (e.g. ad libitum): Ad libitum (Envigo - 2030C)
- Water (e.g. ad libitum): Ad libitum (tap water)
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23
- Humidity (%): 30-70
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 (07.00-19.00)
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): Unchanged (sodium chlorite 9% water solution)
Duration of treatment / exposure:
1 second
Observation period (in vivo):
72h (if reactions, additional observations from 7 to 21 days).
Details on study design:
SCORING SYSTEM:
Ocular examination were performed on both right and left eyes 1, 24, 48 and 72 hours following treatment.
Chemosis:
0 - No swelling
1 - Slight swelling, including the nictitating membrane
2 - Swelling with eversion of the eyelid
3 - Swelling with eyelid half-closed
4 - Swelling with eyelid more than half-closed

Discharge:
0 - No discharge
1 - Slight discharge (normal slight secretions in the inner corner no to be taken into account
2 - Discharge with moistening of the eyelids and neighbouring hairs
3 - Discharge with moistening of the eyelids and large areas around the eye

Redness:
0 - Blood vessels normal
1 - Vessels significantly more prominent than normal
2 - Vessels individually distinguishable with difficulty (Generalised red coloration)
3 - Vessels individually distinguishable with difficulty (Generalised deep red coloration)

Iris:
0 - Normal
1 - Iris significantly more wrinkled than normal, congestion, swelling of the iris which continues to react to light, even slowly
2 - No reaction to light, haemorrhage, significant damage (any or all of these characteristics)

Cornea: Degree of opacity:
0 - No modification visible either directly or after installation of fluorescein (no loss of glint or polish)
1 - Transluent areas (diffuse or disseminated), iris details clearly visible
2 - Easily identifiable transluent area, iris details slightly obscured
3 - Opalescent area, no iris details visible, pupil outline scarcely distinguishable
4 - Total cornea opacity, completely obscuring the iris and pupil

Cornea: Extent of opacity
1 - Opaque area present but covering one quarter or less
2 - Between one quarter and half
3 - Between half and three quarters
4 - Between three quarters and the entire surface
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.7
Max. score:
1
Reversibility:
fully reversible within: 72h
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.3
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.3
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.3
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.7
Max. score:
1
Reversibility:
fully reversible within: 72h
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.3
Max. score:
2
Reversibility:
fully reversible within: 72h
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.3
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritant / corrosive response data:
The ocular reactions observed during the study have been moderate and totally reversible in all animals.
- At the conjunctivae level: a moderate redness noted 1 hour after the test item installation and totally reversible on day 7, associated with a slight to moderate chemosis and noted 1 hour after the test item installation and totally reversible between days 3 and 7.
- At the iris level: an injection noted 24 hours after the test item installation in two animals and totally reversible between days 3 and 7.
- At the corneal level: a moderate opacity, noted 24 hours after the test item installation and totally reversible between days 3 and 7.

Animal nº

Weight (kg)

Time after treatment (h)

Conjunctivae

Iris

Cornea

Chemosis

Redness

Lesion

Opacity

A6506

Start: 2.25

End: 2.38

24

1

2

0

2

48

1

1

0

2

72

0

1

0

0

Mean

0.7

1.3

0

1.3

7d

0

0

0

0

A6525

Start: 2.23

End: 2.73

24

1

2

1

2

48

1

1

1

1

72

1

1

0

1

Mean

1.0

1.3

0.7

1.3

7d

0

0

0

0

A6526

Start: 2.29

End: 2.59

24

1

2

1

2

48

1

1

1

2

72

1

1

1

2

Mean

1.0

1.3

1.0

2.0

7d

0

0

0

0

Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
The test item is determined to be irritating to the eyes.
Executive summary:

An in-vivo eye irritation test was performed on the test item according to OECD Guideline 405 (GLP study). The test item was installed, as supplied, into the eye of three New Zealand rabbits at the dose of 0.1 mL. The ocular reactions observe during the study have been moderate and totally reversible in all animals. The obtained mean scores (24 -72h) for the three animals were as follows:

- Conjunctivae chemosis: 0.7, 1.0 and 1.0.

- Conjunctivae readness: 1.3, 1.3 and 1.3.

- Iritis: 0.0, 0.7 and 1.0.

- Corneal opacity: 1.3, 1.3 and 2.0.

Based on CLP Regulation (EC) 1272/2008, taking into account that all 3 tested animals had a corneal opacity > 1, the substance should be regarded as irritating to the eye category 2, H319.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation, Three Key studies:

- Study in rabbits according to OECD Guideline 404 (Acute Dermal Irritation / Corrosion).

A 34.5 % aqueous solution of sodium chlorite is a non-irritant when administered by cutaneous route in rabbits.

- Study in rabbits according to EPA No. 158.81-5.

Irritation consisted of erythema (Grades 1 through 3) in all sites at 30-60 minutes and 24 hours postdose, persisting through Day 7 in two sites. Edema (Grade 1) was observed in one site at 30-60 minutes and in two sites at 48 hours. Other dermal effects included blanching, thickening, necrosis, sloughing, and blackened areas. One female was found dead on Day 20 postdose. The substance is classified as Corrosive Category 1B (necrosis was observed in two animals).

- Study in rabbits according to method EPA guideline 8/22/78 (40 CFR, Part 163).

Not irritating (31% aqueous solution)

Eye irritation, Three key studies:

-In rabbits. Guidelines for Hazardous Evaluation for Humans and Domestic Animals, Federal Register, Vol. 43, No. 163, 1978; section 163.81-5.

A 31 % aqueous solution of sodium chlorite is a severe eye irritant, based on the observed effects on the cornea, iris and conjunctiva which were not fully reversible within the observation period of 21 days.

- In-vitro ICE test: OECD Guideline 438.

The results obtained in the study performed on sodium chlorite 9% water solution lead to the category "no prediction can be made" according to current guidelines.

- In rabbits. OECD Guideline 405.

A 9% aqueous solution of sodium chlorite is determined to be irritationg to the eyes (category 2, H319), based on the moderate and totally reversible effects observed in all animals, and being the corneal opacity score > 1 in all three animals tested.


Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: corrosive

Justification for classification or non-classification

Skin irritation: based on the observed effects (necrosis was observed in two animals after a 4 -h exposure), the substance is classified as Corrosive Category 1B.

Eye irritation: based on the observed effects on the cornea, iris and conjunctiva which are not fully reversible within the observation period of 21 days, the substance is classified as Irreversible effects on the eye, Category 1. However, as recommended in the corresponding guidance "Guidance on the Application of the CLP Criteria" since the substance is classified as skin corrosive and additional classification with H318 "Cause serious eye damage" is not indicated.