Registration Dossier

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Administrative data

Description of key information

Skin Corrosion - In vitro

Key value determined in a GLP accredited laboratory study using a human skin model, performed in accordance with OECD Guideline 431 and EU Method B.40 Bis.  

Lowinox® 22IB46 is not corrosive in the in vitro skin corrosion test under the experimental conditions described in the report.

Eye Irritation - In Vivo

Key value determined in a GLP accredited laboratory study, in New Zeland White rabbits, performed in accordance with OECD Guideline 405, EU Method B.5 and US EPA Procedure EPA OPPTS 870.2400.

Instillation of the test item resulted in irritation of the conjunctivae, which consisted of redness, chemosis and discharge. The irritation had completely resolved within 24 hours in all animals.

Based on the results, Lowinox® 22IB46 does not have to be classified.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin corrosion: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
14 March 2016 to 18 March 2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Study performed in accordance with OECD & EU test guidelines in compliance with GLP and reported with a valid GLP certificate.
Qualifier:
according to guideline
Guideline:
OECD Guideline 431 (In Vitro Skin Corrosion: Reconstructed Human Epidermis (RHE) Test Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.40 (In Vitro Skin Corrosion: Transcutaneous Electrical Resistance Test (TER))
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test system:
human skin model
Source species:
human
Cell type:
non-transformed keratinocytes
Cell source:
other: Normal human-derived epidermal keratinocytes
Source strain:
other: EpiDerm Reconstructed Human Epidermis, EPI-200, EPI-212, LOT: 23662
Details on animal used as source of test system:
EpiDerm Skin Model (EPI-200, Lot no.: 23662 kit DD and EE).The model consists of normal, human-derived epidermal keratinocytes which have been cultured to form a multilayered, highly differentiated model of the human epidermis. It consists of organized basal, spinous and granular layers, and a multi-layered stratum corneum containing intercellular lamellar lipid layers arranged in patterns analogous to those found in vivo. The EpiDerm tissues (surface 0.6 cm²) were cultured on polycarbonate membranes of 10 mm cell culture inserts.
Source: MatTek Corporation, Ashland MA, U.S.A.
Tissues: On the day of receipt the tissues were kept on agarose and stored in the refrigerator. On the next day, at least one hour before starting the assay the tissues were transferred to 6-well plates with 0.9 ml DMEM medium.
Justification for test system used:
Recommended test system in international guidelines (OECD and EC).
Vehicle:
unchanged (no vehicle)
Details on test system:
Reference items
Negative control: Milli-Q water (Millipore Corp., Bedford, Mass., USA).
Positive control: Potassium hydroxide (KOH; Merck, Darmstadt, Germany), an 8.0 normal solution was prepared.
Test item preparation: No correction was made for the purity/composition of the test item. The solid test item was applied directly on top of the skin tissue. Lowinox® 22IB46 was spread to match the size of the tissue.
Control samples:
yes, concurrent negative control
yes, concurrent positive control
yes, concurrent MTT non-specific colour control
Amount/concentration applied:
32.8 to 34.4 mg
Duration of treatment / exposure:
3 minutes & 1 hour
Duration of post-treatment incubation (if applicable):
Not applicable
Number of replicates:
2 tissues per test group (3 minutes exposure, 1 hour exposure, negative control, positive control).
Species:
other: Human
Strain:
other: EpiDerm Skin Model (EPI-200, Lot no.: 23662 kit DD and EE).
Details on test animals or test system and environmental conditions:
Environmental conditions: All incubations, with the exception of the test item incubation of 3 minutes at room temperature, were carried out in a controlled environment, in which optimal conditions were a humid atmosphere of 80 - 100% (actual range 67 - 86%), containing 5.0 ± 0.5% CO2 in air in the dark at 37.0 ± 1.0°C (actual range 36.3 - 37.3°C). Temperature and humidity were continuously monitored throughout the experiment. The CO2 percentage was monitored once on each working day. Temporary deviations from the temperature, humidity and CO2 percentage may occur due to opening and closing of the incubator door. Based on laboratory historical data these deviations are considered not to affect the study integrity.
Type of coverage:
open
Preparation of test site:
other: See details on Study Design
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent positive control
yes, concurrent negative control
Duration of treatment / exposure:
32.8 to 34.4 mg
Observation period:
3 minutes & 1 hour
Number of animals:
2 tissues per test group (3 minutes exposure, 1 hour exposure, negative control, positive control).
Details on study design:
Test for the interference of the test item with the MTT endpoint: A test item may interfere with the MTT endpoint if it is coloured and/or it is able to directly reduce MTT. The cell viability measurement is affected only if the test item is present on the tissues when the MTT viability test is performed.

Test for colour interference by the test item: Lowinox® 22IB46 was checked for possible colour interference before the study was started. Some non-coloured test items may change into coloured items in aqueous conditions and thus stain the skin tissues during the 1-hour exposure. To assess the colour interference, at least 25 mg of Lowinox® 22IB46 or 50 μl Milli-Q water as a negative control were added to 0.3 ml Milli-Q water. The mixture was incubated for approximately 1 hour at 37.0 ± 1.0°C in the dark. At the end of the exposure time the mixture was shaken and it was checked if a blue / purple colour change was observed.

Test for reduction of MTT by the test item: Lowinox® 22IB46 was checked for possible direct MTT reduction before the study was started. To assess the ability of the test item to reduce MTT, at least 25 mg of Lowinox® 22IB46 was added to 1 ml MTT (Sigma, Zwijndrecht, The Netherlands) solution (1 mg/ml) in phosphate buffered saline. The mixture was incubated for approximately 1 hour at 37.0 ± 1.0ºC. A negative control, sterile Milli-Q water was tested concurrently. At the end of the exposure time it was checked if a blue / purple colour change or a blue / purple precipitate was observed.

Application/Treatment of the test item: The skin tissues were kept in the refrigerator the day they were received. The next day, at least 1 hour before the assay was started the tissues were transferred to 6-well plates containing 0.9 ml DMEM medium per well. The level of the DMEM medium was just beneath the tissue. The plates were incubated for approximately 2 hours at 37.0 ± 1.0ºC. The medium was replaced with fresh DMEM medium just before Lowinox® 22IB46 was applied. The test was performed on a total of 4 tissues per test item together with a negative control and positive control. Two tissues were used for a 3-minute exposure to Lowinox® 22IB46 and two for a 1-hour exposure. The skin was moistened with 25 μl Milli-Q water (Millipore Corp., Bedford, Mass., USA) to ensure close contact of the test item to the tissue and 32.8 to 34.4 mg of the solid test item was added into the 6-well plates on top of the skin tissues. The remaining tissues were treated with 50 μl Milli-Q water (negative control) and with 50 μl 8N KOH (positive control), respectively. After the exposure period, the tissues were washed with phosphate buffered saline (Invitrogen Corporation, Breda, The Netherlands) to remove residual test item. Rinsed tissues were kept in 24 well plates on 300 μl DMEM medium until 6 tissues (= one application time) were dosed and rinsed.

Cell viability measurement: The DMEM medium was replaced by 300 μl MTT-medium and tissues were incubated for 3 hours at 37°C in air containing 5% CO2. After incubation the tissues were washed with PBS and formazan was extracted with 2 ml isopropanol (MatTek corporation) over night at room temperature. The amount of extracted formazan was determined spectrophotometrically at 570 nm in triplicate with the TECAN Infinite® M200 Pro Plate Reader. Cell viability was calculated for each tissue as percentage of the mean of the negative control tissues. Skin corrosion potential of the test item was classified according to remaining cell viability following exposure of the test item with either of the two exposure times.
Irritation / corrosion parameter:
% tissue viability
Run / experiment:
3-minute application, mean tissue viability
Value:
98
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other:
Remarks:
Not considered to be corrosive
Irritation / corrosion parameter:
% tissue viability
Run / experiment:
1-hour application, mean tissue viability
Value:
90
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Other effects / acceptance of results:
The mean tissue viability obtained after 3-minute and 1-hour treatments with Lowinox® 22IB46 compared to the negative control tissues. Skin corrosion is expressed as the remaining cell viability after exposure to the test item. The relative mean tissue viability obtained after the 3-minute and 1-hour treatments with Lowinox® 22IB46 compared to the negative control tissues was 98% and 90% respectively. Because the mean relative tissue viability for Lowinox® 22IB46 was not below 50% after 3 minutes treatment and not below 15% after 1 hour treatment Lowinox® 22IB46 is considered to be not corrosive.
Lowinox® 22IB46 was checked for colour interference in aqueous conditions and possible direct MTT reduction by adding the test item to MTT medium. Because the solutions did not turn blue / purple nor a blue / purple precipitate was observed it was concluded that Lowinox® 22IB46 did not interfere with the MTT endpoint.

Mean absorption in the in vitro skin corrosion test with Lowinox® 22IB46

 

3-minute application

1-hour application

 

A (OD570)

B (OD570)

Mean

(OD570)

SD

A (OD570)

B (OD570)

Mean

(OD570)

SD

Negative control

1.720

1.832

1.776

±

0.079

1.971

1.891

1.931

±

0.057

Lowinox® 22IB46

1.765

1.704

1.734

±

0.043

1.752

1.717

1.734

±

0.025

Positive control

0.185

0.185

0.185

±

0.000

0.202

0.122

0.162

±

0.056

SD = Standard deviation

Duplicate exposures are indicated by A and B.

In this table the values are corrected for background absorption (0.0418). Isopropanol was used to measure the background absorption.

Mean tissue viability in the in vitro skin corrosion test with Lowinox® 22IB46

 

3-minute application

viability (percentage of control)

1-hour application

viability (percentage of control)

Negative control

100

100

Lowinox® 22IB46

98

90

Positive control

10

8

 

Coefficient of Variation between tissue replicates

 

3 minute

1 hour

Negative control

6.1

4.1

Lowinox® 22IB46

3.4

2.0

Positive control

0.1

39

CV (%) = 100 - [(lowest OD570/highest OD570) x 100%]

INDIVIDUAL OD MEASUREMENTS AT 570 NM

 

3-minute application (OD570)

A B

1-hour application (OD570)

A B

Negative control

 

OD570measurement 1

1.7293

1.8643

2.0186

1.9594

OD570measurement 2

1.7764

1.8906

2.0188

1.9330

OD570 measurement 3

1.7795

1.8673

2.0018

1.9065

Lowinox® 22IB46

 

OD570 measurement 1

1.8329

1.7691

1.8182

1.7949

OD570measurement 2

1.7870

1.7502

1.7930

1.7290

OD570measurement 3

1.7997

1.7185

1.7706

1.752

Positive control

 

OD570measurement 1

0.2320

0.2262

0.2617

0.1636

OD570measurement 2

0.2217

0.2293

0.2356

0.1650

OD570measurement 3

0.2276

0.2263

0.2332

0.1635

OD = Optical density

Duplicate exposures are indicated by A and B.

HISTORICAL CONTROL DATA FOR IN VITRO SKIN CORROSION STUDIES

 

Negative control

Positive control

Positive control

 

3-minute treatment

(OD570)

1-hour treatment

(OD570)

3-minute treatment

(OD570)

1-hour treatment

(OD570)

3-minute treatment

(% viability)

1-hour treatment

(% viability)

Range

1.324 – 2.615

1.361 – 2.352

0.172 – 0.56

0.057 – 0.277

6 – 22

3 – 12

Mean

1.86

1.86

0.18

0.13

10.67

7.17

SD

0.24

0.22

0.10

0.05

3.9

2.36

n

65

67

64

61

30

30

SD = Standard deviation

n = Number of observations

The above mentioned historical control data range of the controls were obtained by collecting all data over the period of December 2012 to December 2015.

Interpretation of results:
GHS criteria not met
Conclusions:
It is concluded that this test is valid and that Lowinox® 22IB46 is not corrosive in the in vitro skin corrosion test under the conditions of this study.
Executive summary:

The objective of this study was to evaluate Lowinox® 22IB46 for its ability to induce skin corrosion. For this purpose Lowinox® 22IB46 was topically applied on a human three dimensional epidermal model. The possible corrosive potential of Lowinox® 22IB46 was tested through topical application for 3 minutes and 1 hour.

 

The study procedures described in this report were based on the most recent OECD and EC guidelines:

- Organisation for Economic Co-operation and Development (OECD), OECD Guidelines for Testing of Chemicals, Guideline no. 431: In Vitro Skin Corrosion: reconstructed human epidermis (RHE) test method (adopted 26 September 2014).

- European Community (EC). Commission regulation (EC) No. 440/2008, Part B: Methods for the Determination of Toxicity and other health effects, Guideline B.40 BIS: "In Vitro Skin Corrosion: Human Skin Model Test". Official Journal of the European Union No. L142, 31 May 2008.

 

Batch WB44L0016 of Lowinox® 22IB46 was a white to cream coloured powder with a purity of 99.7%. Skin tissue was moistened with 25 μl of Milli-Q water and at least 25 mg of Lowinox® 22IB46 was applied directly on top of the skin tissue.

 

The positive control had a mean relative tissue viability of 10% after 3 minutes exposure. The absolute mean OD570(optical density at 570 nm) of the negative control tissues was within the laboratory historical control data range. In the range of 20 - 100% viability the Coefficient of Variation between tissue replicates was < 7%, indicating that the test system functioned properly.

 

Skin corrosion is expressed as the remaining cell viability after exposure to the test item after 3 minutes and 1 hour. The relative mean tissue viability obtained after 3-minute and 1-hour treatments with Lowinox® 22IB46 compared to the negative control tissues was 98% and 90%, respectively.

 

Because the mean relative tissue viability for Lowinox® 22IB46 was not below 50% after the 3-minute treatment and not below 15% after the 1-hour treatment Lowinox® 22IB46 is considered to be not corrosive.

 

It is concluded that this test is valid and that Lowinox® 22IB46 is not corrosive in thein vitroskin corrosion test under the experimental conditions of this study.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
13 May 2016 to 29 May 2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
Deviations from the maximum daily mean relative humidity occurred.
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
Deviations from the maximum daily mean relative humidity occurred.
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Deviations:
yes
Remarks:
Deviations from the maximum daily mean relative humidity occurred.
GLP compliance:
yes
Specific details on test material used for the study:
Chemical name (IUPAC), synonym or trade name: 2,2’-(2-methylpropylidene)bis[4,6-xylenol]
CAS Number: 33145-10-7
pH (1% in water, indicative range): 8.0 – 7.2 (determined by Charles River Den Bosch)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Species: Albino rabbit, New Zealand White, (SPF-Quality). Recognized by international guidelines as the recommended test system (e.g. EC, OECD)
Source: Charles River France, L’Arbresle, France
Number of animals: 3 Females.
Age and body weight: At start of dosing, the animals were between 12 and 24 weeks old and body weights were at least 1.5 kg.
Identification: Earmark.
Health inspection: At least prior to dosing. It was ensured that the animals were healthy and that the eyes were free from any abnormality.
Conditions: Environmental controls for the animal room were set to maintain 18 to 24°C, a relative humidity of 40 to 70%, at least 10 air changes/hour, and a 12-hour light/12-hour dark cycle: the photoperiod was between 07:00 and 19:00 hrs daily. Any variations to these conditions were maintained in the raw data and had no effect on the outcome of the study.
Accommodation: Animals were individually housed in labeled cages with perforated floors (Ebeco, Germany, dimensions 67 x 62 x 55 cm) and shelters (Ebeco, Germany, dimensions 40 x 32 x 23 cm).
Acclimatization period was at least 5 days before start of treatment under laboratory conditions.
Diet: Pelleted diet for rabbits (Global Diet 2030 from Harlan Teklad®, Mucedola, Milanese, Italy) approximately 100 grams per day. Hay (TecniLab-BMI BV, Someren, The Netherlands) and wooden sticks (Swedish aspen wood, Bioservices, Uden, The Netherlands) were available during the study period.
Water: Free access to tap water.
Diet, water, bedding and cage enrichment evaluation for contaminants and/or nutrients was performed according to facility standard procedures. There were no findings that could interfere with the study.
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
Animals were treated by instillation of, on average, 25.9 mg (range 25.8 – 25.9 mg) of the test item (a volume of approximately 0.1 mL).
Duration of treatment / exposure:
Single dose, exposure time 1 hour.
Observation period (in vivo):
24 hour observation period
Number of animals or in vitro replicates:
The study was performed in a stepwise manner and was started by treatment of a single rabbit (sentinel). The two other animals were treated in a similar manner one week later, after considering the degree of eye irritation observed in the first animal.
Details on study design:
Weight of Evidence: Analysis In the interest of animal welfare and to minimize any testing likely to produce severe responses in animals, a weight of evidence analysis was performed, prior to the start of this in vivo eye irritation study in the rabbit. As recommended in the test guidelines, all available information was evaluated (e.g. existing human and animal data, literature, item data supplied by the Sponsor, analysis of structure activity relationships (SAR), physicochemical properties and reactivity (pH, buffering capacity) and in vitro, ex vivo and in vivo tests) to determine the need for in vivo eye testing.
Based on the available information, it was concluded that there was the need to perform this in vivo eye irritation study in rabbit in order to establish the possible eye irritating properties of the test item.

Pre-emptive Pain Management: One hour prior to instillation of the test item, buprenorphine (Buprenodale®, Dechra Ltd., Stoke-on-Trent, United Kingdom) 0.01 mg/kg was administered by subcutaneous injection in order to provide a therapeutic level of systemic analgesia. Five minutes prior to instillation of the test item, two drops of the topical anaesthetic alcaine 0.5% (SA Alcon-Couvreur NV, Puurs, Belgium) were applied to both eyes.
Treatment: Animals were treated by instillation of, on average, 25.9 mg (range 25.8 – 25.9 mg) of the test item (a volume of approximately 0.1 mL), in the conjunctival sac of one of the eyes after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second to prevent loss of the test item. The other eye remained untreated and served as the reference control. Immediately after the 1 hour observation, the treated eye was rinsed with approximately 50 mL tepid tap water, using a velocity of flow which did not affect the eye, to remove any visible residual test item. For reference control the other eye was also rinsed. In order to provide a continued level of systemic analgesia, buprenorphine 0.01 mg/kg and meloxicam (Metacam®, Boehringer Vetmed GmbH, Ingelheim/Rhein, Germany) 0.5 mg/kg were administered by subcutaneous injection. Immediately after the 24-hour observation, a solution of 2% fluorescein (Merck, Darmstadt, Germany) in water (adjusted to pH 7.0) was instilled into both eyes of each animal to quantitatively determine corneal epithelial damage. Any bright green stained area, indicating epithelial damage, was estimated as a percentage of the total corneal area. After the final observation, the animals were sacrificed by intra-venous injection of Euthasol® 20% (AST Farma BV, Oudewater, The Netherlands).
Observations
Mortality/Viability: Twice daily.
Toxicity: At least once daily.
Body Weight: Day of treatment (prior to instillation) and after the final observation.
Irritation: The eyes of each animal were examined approximately 1, 24, 48 and 72 hours after instillation of the test item. The irritation scores and a description of all other (local) effects were recorded. The irritation was assessed according to the following numerical scoring system. (see Any other information for details).
Necropsy: No necropsy was performed according to study plan.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Remarks:
see Irritant/corrosive data
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Remarks:
see Irritant/corrosive date
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
Irritation: Instillation of approximately 26 mg of Lowinox® 22IB46 (a volume of approximately 0.1 mL) into one eye of each of three rabbits resulted in irritation of the conjunctivae, which consisted of redness, chemosis and discharge.
The irritation had completely resolved within 24 hours in all animals. No iridial irritation or corneal opacity were observed, and treatment of the eyes with 2% fluorescein 24 hours after test item instillation revealed no corneal epithelial damage.
Corrosion: There was no evidence of ocular corrosion.
Other effects:
Colouration / Remnants: Remnants of the test item were present in the eye on Day 1. Toxicity / Mortality No signs of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Individual Eye Irritation Scores

Animal

Time after dosing

Cornea

Iris

Conjunctivae

Comments

Opacity

(0-4)

Area

(0-4)

Flour area (%)2

(0-2)

Redness

(0-3)

Chemosis

(0-4)

Discharge

(0-3)

821

1 hour

24 hours

48 hours

72 hours

0

0

0

0

0

0

0

0

0

0

0

0

0

1

0

0

0

1

0

0

0

1

0

0

0

b

-

-

-

93

1 hour

24 hours

48 hours

72 hours

0

0

0

0

0

0

0

0

0

0

0

0

0

1

0

0

0

1

0

0

0

1

0

0

0

b

-

-

-

94

1 hour

24 hours

48 hours

72 hours

0

0

0

0

0

0

0

0

0

0

0

0

0

1

0

0

0

1

0

0

0

1

0

0

0

b

-

-

-

1Sentinel,2Green staining after fluorescein treatment (percentage of total corneal area)

Comments:

b – Remnants of the test item in the eye.

 

Mean Value Eye Irritation Scores

Animal

Mean 24,48 and 72 hours

Corneal opacity

Iris

Conjunctivae

Redness

Chemosis

82

93

94

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

 

Animal Specifications

Animal

Sex

Age at start (weeks)

Body weights (grams)

Prior to application

At termination

82

93

94

F

F

F

22

23

23

3620

3671

4154

3752

3688

4295

 

Interpretation of results:
other: No classified
Conclusions:
Based on the results, Lowinox® 22IB46 does not have to be classified and has no obligatory labelling requirement for eye irritation according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2015) (including all amendments) and EC criteria for classification and labelling requirements for dangerous items and preparations (Council Directive 67/548/EEC) (including all amendments).
Executive summary:

Acute eye irritation/corrosion study with Lowinox® 22IB46 in the rabbit.

 

The study was carried out based on the guidelines described in:

OECD No.405 (2012) "Acute Eye Irritation / Corrosion"

EC, No 440/2008, B5: "Acute Toxicity: Eye Irritation/Corrosion"

EPA, OPPTS 870.2400 (1998): "Acute Eye Irritation"

JMAFF Guidelines (2000), including the most recent revisions.

 

Single samples of approximately 26 mg of Lowinox® 22IB46 (a volume of approximately 0.1 mL) were instilled into one eye of each of three rabbits. Observations were made 1, 24, 48 and 72 hours after instillation.

 

Instillation of the test item resulted in irritation of the conjunctivae, which consisted of redness, chemosis and discharge. The irritation had completely resolved within 24 hours in all animals.

 

Remnants of the test item were present in the eye on Day 1.

 

Based on the results, Lowinox® 22IB46 does not have to be classified and has no obligatory labelling requirement for eye irritation according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2015) (including all amendments) and EC criteria for classification and labelling requirements for dangerous items and preparations (Council Directive 67/548/EEC) (including all amendments).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for selection of skin irritation / corrosion endpoint:
Report was conducted in accordance to GLP in line with recognised OECD test guidelines

Justification for selection of eye irritation endpoint:
Report was conducted in accordance to GLP in line with recognised OECD test guidelines

Justification for classification or non-classification

Skin Irritation / Corrosion

Based on the results, Lowinox® 22IB46 does not have to be classified and has no obligatory labelling requirement for skin irritation/corrosion according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2015) (including all amendments) and EC criteria for classification and labelling requirements for dangerous items and preparations (Council Directive 67/548/EEC) (including all amendments).

Eye Irritation

Based on the results, Lowinox® 22IB46 does not have to be classified and has no obligatory labelling requirement for eye irritation according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2015) (including all amendments) and EC criteria for classification and labelling requirements for dangerous items and preparations (Council Directive 67/548/EEC) (including all amendments).