Zinc isodecyl phosphorodithioate

Endpoint summary

Description of key information

The test item was found to be non-corrosive in an OECD 431 in vitro skin corrosion study, and non-irritant in an OECD 439 in vitro skin irritation study. A BCOP assay following OECD guideline 437 has also been conducted with the test item and based on the result from this study it is not considered to be an eye irritant.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin corrosion: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

14 August 2017 to 18 August 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 431 (In Vitro Skin Corrosion: Human Skin Model Test)

Version / remarks:

Adopted 29 July 2016

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test system:

human skin model

Source species:

human

Cell type:

non-transformed keratinocytes

Cell source:

other: Keratinocyte strain 00267

Source strain:

other: All cells used to produce EpiDerm tissue are purchased or derived from tissue obtained from accredited institutions, from the donor or the donor's legal next of kin for use of the tissues or derivatives of the tissue for research purposes

Details on animal used as source of test system:

Not applicable

Justification for test system used:

The test is based on the experience that corrosive chemicals show cytotoxic effects following short-term exposure to the stratum corneum of the epidermis. The test is designed to predict and classify the skin corrosion potential of a test item by assessment of its effect on a three-dimensional human epidermis model.

Vehicle:

unchanged (no vehicle)

Details on test system:

RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used: EpiDerm Skin Model (EPI-200)
- Source: MatTek Corporation, USA
- Tissue batch number(s): Lot no. 26767
- Production date: Certificate of analysis dated 16th August 2017
- Date of initiation of testing: One day after receipt of the tissues

TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: All incubations, with the exception of the test item incubation of 3 minutes at room temperature, were carried out in a controlled environment at 37.0 ± 1.0°C (actual range 36.8 - 37.5°C).
- Temperature of post-treatment incubation (if applicable): 37.0°C

REMOVAL OF TEST MATERIAL AND CONTROLS
-Volume and number of washing steps: After the exposure period, the tissues were washed with phosphate buffered saline to remove residual test item.
- Observable damage in the tissue due to washing: None noted
- Modifications to validated SOP: None

MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- MTT concentration: 5 mg/ml diluted (1:5) with MTT diluent (supplemented DMEM).
- Incubation time: 3 hours
- Spectrophotometer: TECAN Infinite® M200 Pro Plate Reader
- Wavelength: 570nm

NUMBER OF REPLICATE TISSUES: 2

PREDICTION MODEL / DECISION CRITERIA
- The test substance is considered to be corrosive to skin if the viability after 3 minutes exposure is less than 50%, or if the viability after 3 minutes exposure is greater than or equal to 50 % and the viability after 1 hour exposure is less than 15%.
- The test substance is considered to be non-corrosive to skin if the viability after 3 minutes exposure is greater than or equal to 50% and the viability after 1 hour exposure is greater than or equal to 15%.

Control samples:

yes, concurrent negative control

yes, concurrent positive control

Amount/concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 50 μl
- Concentration (if solution): Test material was applied neat.

NEGATIVE CONTROL
- Amount(s) applied (volume or weight): 50 μl
- Concentration (if solution): Milli-Q water, concentration not applicable.

POSITIVE CONTROL
- Amount(s) applied (volume or weight): 50 μl
- Concentration (if solution): Potassium hydroxide, 8.0 normal solution

Duration of treatment / exposure:

3 minutes and 1 hour

Duration of post-treatment incubation (if applicable):

3 hours

Number of replicates:

Two test replicates each for the 3 minute and 1 hour exposures

Irritation / corrosion parameter:

% tissue viability

Run / experiment:

3 minute exposure

Value:

81

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: No indication of skin corrosion

Irritation / corrosion parameter:

% tissue viability

Run / experiment:

60 minute exposure

Value:

84

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: No indication of skin corrosion

Other effects / acceptance of results:

ACCEPTANCE OF RESULTS:
The quality criteria to deem the results of the assay to be considered acceptable are:

Negative Control

The absolute OD570 of the negative control treated tissues in the MTT-test is an indicator of tissue viability obtained in the testing laboratory after the shipping and storing procedure and under specific conditions of the assay. The mean OD570 of the two negative control tissues should be ≥ 0.8 and ≤ 2.8 for each exposure time. The mean OD570 of the negative control was within this range and within the historical control range, therefore this criterion was met.

Positive Control

Potassium Hydroxide 8.0N solution was used as a positive control. An assay meets the acceptance criterion if the mean relative tissue viability of the 60 minute positive control is <15%. The mean relative tissue viability was 6.4% therefore this criterion was met.

Table 1 Mean Absorption in thein vitroSkin Corrosion Test with the test item

	3-minute application					1-hour application
	A (OD570)	B (OD570)	Mean (OD570)		SD	A (OD570)	B (OD570)	Mean (OD570)		SD
Negative control	2.030	2.037	2.034	±	0.005	2.061	1.950	2.006	±	0.078
Test item	1.678	1.608	1.643	±	0.050	1.615	1.764	1.690	±	0.106
Positive control	0.149	0.179	0.164	±	0.021	0.141	0.114	0.128	±	0.019

SD = Standard deviation

Duplicate exposures are indicated by A and B.

In this table the values are corrected for background absorption (0.0430). Isopropanol was used to measure the background absorption.

Table 2  Mean Tissue Viability in thein vitroSkin Corrosion Test with the test item

	3-minute application viability (percentage of control)	1-hour application viability (percentage of control)
Negative control	100	100
Test item	81	84
Positive control	8.1	6.4

Table 3 data interpretation and sub-categorisation of test items

Viability measured after 3-minutes and 1 hour	Prediction to be considered
Step 1
< 50% after 3 minute exposure	Corrosive
≥ 50% after 3 minute exposure AND < 15% after 1 hour exposure	Corrosive
≥ 50% after 3 minute exposure AND ≥ 15% after 1 hour exposure	Non-corrosive
Step 2 (for substances/mixtures identified as Corrosive in step 1)
< 25% after 3 minute exposure	Optional Sub-category 1A
≥ 25% after 3 minute exposure	A combination of optional Sub-categories 1B and 1C

Interpretation of results:

GHS criteria not met

Conclusions:

The test item is a not corrosive based on the results from an OECD guideline 431 study.

Executive summary:

The skin corrosion potential of the test item was assessed in an in vitro skin corrosion study.The study is assigned a reliability score of 1 (reliable without restrictions) as it followed OECD Guideline 431: In Vitro Skin Corrosion: Reconstructed Human Epidermis (RHE) Test Method and as it is compliant with GLP. 50 µL of the test item was applied undiluted to the EpiDerm tissue for 3 minutes and 1 hour. Negative and positive controls were also tested. All validity criteria for the study were met. The test item had a mean tissue viability of 81% after a 3-minute application and a mean tissue viability of 84% after a 1-hour application. The test item is therefore non-corrosive to the skin.

Reference 2

Endpoint:

skin irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

26 September 2017 - 2 October 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)

Version / remarks:

Adopted 28 July 2015

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: EC Guideline No. 440/2008. Part B: Methods for the Determination of Toxicity and other health effects, Guideline B.46 "In vitro Skin Irritation: Reconstructed Human Epidermis Model Test"

Version / remarks:

Amended by EC No. 640/2012 OJ No. L193, 20 July 2012

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test system:

human skin model

Source species:

human

Cell type:

non-transformed keratinocytes

Cell source:

other: Reconstructed epidermis of normal human keratinocytes, originating from adult donors

Source strain:

other: Strains 09-KERA-007 + 09-KERA-010

Justification for test system used:

The test is based on the experience that irritant chemicals show cytotoxic effects following short term exposure to the stratum corneum of the epidermis. The test is designed to predict and classify the skin irritation potential of a test item by assessment of its effect on a three dimensional human epidermis model (1-10).

Vehicle:

unchanged (no vehicle)

Details on test system:

RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used: EPISKIN Small model (EPISKIN-SMTM)
- Tissue batch number(s): 17-EKIN-039
- Expiration date: October 2nd 2017
- Shipping date: September 26th 2017
- Date of initiation of testing: 26th September 2017

TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: Exposure period of 15 ± 0.5 minutes at room temperature
- Temperature of post-treatment incubation (if applicable): All incubations, with the exception of the test item incubation of 15 minutes at room temperature, were carried out at 37.0 ± 1.0°C (actual range 36.4 - 37.1°C).

REMOVAL OF TEST MATERIAL AND CONTROLS
-Volume and number of washing steps: The tissues were washed with phosphate buffer saline to remove residual test item after the 15 minutes exposure period.
- Observable damage in the tissue due to washing: Not specified.
- Modifications to validated SOP: None

MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- MTT concentration: 0.3 mg/mL (3 mg/ml in PBS diluted (10x) in Assay medium)
- Spectrophotometer: TECAN Infinite® M200 Pro Plate Reader.
- Wavelength: 570 nm

NUMBER OF REPLICATE TISSUES: 3

CONTROL TISSUES USED IN CASE OF MTT DIRECT INTERFERENCE
- No. of replicates: 3

PREDICTION MODEL / DECISION CRITERIA

-The test substance is considered to be an irritant to skin if the relative mean tissue viability after a 15-minute exposure period followed by the 42-Hour post-exposure incubation period is less than 50% of the mean viability of the negative controls.
-The test substance is considered to be non-irritant to skin if the relative mean tissue viability after a 15-minute exposure period followed by the 42-Hour post-exposure incubation period is greater than 50% of the mean viability of the negative controls.

Control samples:

yes, concurrent negative control

yes, concurrent positive control

Amount/concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 25 μL
- Concentration (if solution): Applied neat, concentration not specified.

NEGATIVE CONTROL
- Amount(s) applied (volume or weight): 25 μL phosphate buffered saline
- Concentration (if solution): Not applicable

POSITIVE CONTROL
- Amount(s) applied (volume or weight): 25 μL Sodium dodecyl sulfate in PBS
- Concentration (if solution): 5% w/v aqueous solution

Duration of treatment / exposure:

15 Minutes

Duration of post-treatment incubation (if applicable):

Subsequently the skin tissues were incubated for 42 hours at 37°C.

Number of replicates:

3 test replicates.

Irritation / corrosion parameter:

% tissue viability

Run / experiment:

Mean

Value:

87

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

no indication of irritation

Other effects / acceptance of results:

ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: The negative control value from the study had a mean relative tissue viability of 100% and a mean OD570 of 1.028 which is within the historic control data range.
- Acceptance criteria met for positive control: The mean relative tissue viability of the positive control was ≤50% (11%) and the mean OD570 was 0.118 which is within the historic control data range.
- Acceptance criteria met for variability between replicate measurements: The standard deviation for the negative control was within the acceptance criteria of ≤18 for the percentage viability (5.1%). The standard deviation for the positive control was within the acceptance criteria of ≤18 for the percentage viability (6.3%).

All validity criteria were met.

Table1- Mean Absorption in the In Vitro Skin Irritation Test with (Zinc, bis(O,O-diisodecyl phosphorodithioato-.kappa.S,.kappa.S')

	A (OD570)	B (OD570)	C (OD570)	Mean (OD570)		SD
Negative control	0.978	1.082	1.025	1.028	±	0.052
Test item	0.930	0.927	0.816	0.891	±	0.065
Positive control	0.090	0.161	0.102	0.118	±	0.038

OD = optical density

SD = Standard deviation

Triplicate exposures are indicated by A, B and C.

Table 2 -Mean Tissue Viability in the In Vitro Skin Irritation Test with (Zinc, bis(O,O-diisodecyl phosphorodithioato-.kappa.S,.kappa.S')

	Mean tissue viability (percentage of control)	Standard deviation (percentage)
Negative control	100	5.1
(Zinc, bis(O,O-diisodecyl phosphorodithioato-.kappa.S,.kappa.S')	87	6.3
Positive control	11	3.7

 Historical control data for In Vitro Skin Irritation Studies

	Negative control (absorption; OD570)	Positive control (absorption; OD570)
Range	0.676 – 1.336	0.036 – 0.549
Mean	1.01	0.16
SD	0.16	0.10
n	155	154

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 November 2013 to November 2016.

Interpretation of results:

GHS criteria not met

Conclusions:

In conclusion, the test item is a non irritant according to the OECD guideline 439.

Executive summary:

The study is assigned a reliability score of 1 (reliable without restrictions) as it followed OECD Guideline 439: In Vitro Skin irritation: Reconstructed Human Epidermis (RHE) Test and as it is compliant with GLP. 25 µL of the test item was applied undiluted to the EpiSkin tissue for 15 minutes followed by a 42 hour post-exposure incubation period. Negative and positive controls were also tested. The positive control had a mean cell viability of 11% after 15 ± 0.5 minutes exposure. The absolute mean OD570 (optical density at 570 nm) of the negative control tissues was within the laboratory historical control data range. The standard deviation value of the percentage viability of three tissues treated identically was < 7%. Therefore, all validity criteria were met.

 

The substance under test conditions had a mean tissue viability of 87% compared to the negative control. This value is above the threshold for irritancy (≤50%). This concludes the test item is not a skin irritant.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

15 August 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying i) Chemicals Inducing Serious Eye Damage and ii) Chemicals Not Requiring Classification for Eye Irritation or Serious Eye Damage)

Version / remarks:

Adopted July 26 2013

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

cattle

Strain:

not specified

Details on test animals or tissues and environmental conditions:

SOURCE OF COLLECTED EYES
- Source: Slaughterhouse (Vitelco’s, Hertogenbosch, The Netherlands)
- Number of animals: Not specified.
- Characteristics of donor animals (e.g. age, sex, weight): Young cattle.
- Storage, temperature and transport conditions of ocular tissue (e.g. transport time, transport media and temperature, and other conditions): Eyes were collected and transported in physiological saline in a suitable container under cooled conditions.
- Time interval prior to initiating testing: 1 hour
- indication of any existing defects or lesions in ocular tissue samples: The eyes were checked for unacceptable defects by removing them from the physiological saline and holding them up to the light. Those exhibiting defects were discarded.
- Indication of any antibiotics used: Not applicable.

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): 750 µL was introduced onto the epithelium of the cornea
- Concentration (if solution): Test material was tested neat.

Duration of treatment / exposure:

The test consisted of topical application of the test item on the epithelium of the bovine cornea for 10 minutes. After exposure the cornea was thoroughly rinsed to remove the test item and incubated for 2 hours with fresh medium followed by opacity measurement and the permeability of the corneas was determined after a 90 minutes incubation period with sodium fluorescein.

Duration of post- treatment incubation (in vitro):

90 +- 5 minutes at 32 +-1°C

Number of animals or in vitro replicates:

Three test replicates

Details on study design:

SELECTION AND PREPARATION OF CORNEAS
Preparation: The eyes were checked for defects such as opacity, scratches, pigmentation and neovascularization by removing them from the physiological saline and holding them in the light. The isolated corneas were then stored in a petri dish with Earle’s Minimum Essential Medium (cMEM) containing 1% (v/v) L-glutamine and 1% (v/v) Foetal Bovine Serum. The isolated corneas were mounted in a corneal holder. The anterior half of the holder was positioned on top of the cornea and tighten with screws. The compartments of the corneal holder were filled with cMEM at 32 +/- 1 °C.
Selection: The corneas were incubated for a minimum of 1 hour at 32 +/-1 °C. The opacity of each cornea was read against a cMEM filled chamber, and the initial opacity reading thus determined was recorded. Corneas that had an initial opacity reading higher than 7 were not used. Three corneas were selected at random for each treatment group.

QUALITY CHECK OF THE ISOLATED CORNEAS
The eyes were checked for defects such as opacity, scratches, pigmentation and neovascularization by removing them from the physiological saline and holding them in the light. The opacity of each cornea was read against a cMEM filled chamber, and the initial opacity reading thus determined was recorded. Corneas that had an initial opacity reading higher than 7 were not used.

NUMBER OF REPLICATES: 3

NEGATIVE CONTROL USED: Physiological saline

SOLVENT CONTROL USED (if applicable): Not applicable

POSITIVE CONTROL USED: Ethanol

APPLICATION DOSE AND EXPOSURE TIME: 750 μl of test item was applied to the epithelium of the bovine cornea for 10 minutes.

TREATMENT METHOD: Closed chamber

POST-INCUBATION PERIOD: 90 minutes

REMOVAL OF TEST SUBSTANCE
- Number of washing steps after exposure period: Not specified

POST-EXPOSURE INCUBATION: 2 hours

METHODS FOR MEASURED ENDPOINTS:
- Corneal opacity: The opacity of a cornea was measured by the diminution of light passing through the cornea.
The light was measured as illuminance (I = luminous flux per area, unit: lux) by a Opacitometer.

- Corneal permeability: Microtiter plate reader (OD490)
- Others (e.g, pertinent visual observations, histopathology): Not specified.

SCORING SYSTEM: In Vitro Irritancy Score (IVIS)
In vitro irritancy score (IVIS) = mean opacity value + (15 x mean OD490 value)

In vitro score range UN GHS
≤ 3 No Category
> 3; ≤ 55 No prediction can be made
>55 Category 1

DECISION CRITERIA: please specify if the decision criteria as indicated in the TG was used.
The decision criteria for the IVIS cut-off values for identifying test chemicals as inducing serious eye damage was used for the study.

Irritation parameter:

in vitro irritation score

Run / experiment:

1

Value:

2.1

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Irritation parameter:

in vitro irritation score

Run / experiment:

2

Value:

-0.8

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Irritation parameter:

in vitro irritation score

Run / experiment:

3

Value:

1.6

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Irritation parameter:

in vitro irritation score

Run / experiment:

Mean

Value:

1

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Irritation parameter:

cornea opacity score

Run / experiment:

Mean

Value:

0.5

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Irritation parameter:

other: Permeability

Run / experiment:

Mean

Value:

0.03

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

A summary of Opacity, Permeability and In Vitro Scores

Treatment	Mean Opacity	Mean Permeability	Mean In vitro Irritation Score
Negative control	-0.1	-0.005	-0.2
Positive control (Ethanol)	27	0.802	39
Test item	0.5	0.030	1.0

Historical control data for the BCOP Studies

Negative Control				Positive control
	Opacity	Permeability	In vitro Irritancy Score	In vitro Irritancy Score
Range	-2.9-3.0	-0.016-0.042	-2.8-3.0	34.7-78.2
Mean	0.08	0.01	0.17	56.01
SD	1.04	0.01	1.14	12.51
n	84	77	78	55

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 August 2014 to August 2017.

Interpretation of results:

GHS criteria not met

Conclusions:

The test item is not an eye irritant under the conditions of the bovine corneal opacity and permeability test guideline.

Executive summary:

The study is assigned a reliability score of 1 (reliable without restrictions) as it followed OECD Guideline 437: Bovine Corneal Opacity and Permeability Test Method and is also compliant with GLP. 750 µL of the undiluted test item was applied directly on top of the corneas for 10 minutes.

The positive control mean in vitro irritancy score (39) was within two standard deviations of the current historical positive control mean. The negative control values for opacity and permeability were less than the upper limits of the laboratory historical range. The validity criteria for the study were therefore met.

The test item induced an In vitro irritancy score of less than 3, which concludes no classification is required for eye irritation or serious eye damage.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Eurlings (2017a) assessed the skin corrosion potential of the test item in an in vitro skin corrosion study.The study is assigned a reliability score of 1 (reliable without restrictions) as it followed OECD Guideline 431: In Vitro Skin Corrosion: Reconstructed Human Epidermis (RHE) Test Method and as it is compliant with GLP. 50 µL of the test item was applied undiluted to the EpiDerm tissue for 3 minutes and 1 hour. Negative and positive controls were also tested. All validity criteria for the study were met. The test item had a mean tissue viability of 81% after a 3-minute application and a mean tissue viability of 84% after a 1-hour application. The test item is therefore non-corrosive to the skin.

Groot (2017) is assigned a reliability score of 1 (reliable without restrictions) as it followed OECD Guideline 439: In Vitro Skin irritation: Reconstructed Human Epidermis (RHE) Test and as it is compliant with GLP. 25 µL of the test item was applied undiluted to the EpiSkin tissue for 15 minutes followed by a 42 hour post-exposure incubation period. Negative and positive controls were also tested. The positive control had a mean cell viability of 11% after 15 ± 0.5 minutes exposure. The absolute mean OD570 (optical density at 570 nm) of the negative control tissues was within the laboratory historical control data range. The standard deviation value of the percentage viability of three tissues treated identically was < 7%. Therefore, all validity criteria were met.

 

The substance under test conditions had a mean tissue viability of 87% compared to the negative control. This value is above the threshold for irritancy (≤50%). This concludes the test item is not a skin irritant.

For the assessment of eye irritation potential, Eurlings (2017b) is assigned a reliability score of 1 (reliable without restrictions) as it followed OECD Guideline 437: Bovine Corneal Opacity and Permeability Test Method and is also compliant with GLP. 750 µL of the undiluted test item was applied directly on top of the corneas for 10 minutes.

The positive control mean in vitro irritancy score (39) was within two standard deviations of the current historical positive control mean. The negative control values for opacity and permeability were less than the upper limits of the laboratory historical range. The validity criteria for the study were therefore met.

The test item induced an In vitro irritancy score of less than 3, which concludes no classification is required for eye irritation or serious eye damage.

Justification for classification or non-classification

Based on the results from Klimisch 1 studies following OECD guidelines 431 and 439, the test item is not corrosive to the skin and does not require classification as a skin irritant.

An OECD 437 in vitro BCOP assay has also been conducted with the test item and this confirms that the test item does not require classification as an eye irritant.