7-(4-ethyl-1-methyloctyl)quinolin-8-ol

Endpoint summary

Description of key information

Key studies are available for both skin and eye irritation. Studies are performed in accordance with an appropriate guideline and under the conditions of GLP.

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:

The study was conducted between 08 October 2018 and 11 October 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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:

other: EU Method B40-BIS

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Date of Inspection: 15 and 16 November 2017; Date of Signature on Certificate: 15 May 2018

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 1702-18-01/O
- Expiration date of the lot/batch: 25 March 2021

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Storage at room temperature (20 ± 5 °C); keep away from light.

Test system:

human skin model

Source species:

other: reconstituted human epidermis

Cell type:

other: reconstituted human epidermis

Cell source:

other: reconstitued human epidermis

Source strain:

other: N/A

Details on animal used as source of test system:

N/A - reconstitued human epidermis

Justification for test system used:

The test system has been validated as acceptable for this purpose

Vehicle:

unchanged (no vehicle)

Details on test system:

TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: 37 ± 1°C


REMOVAL OF TEST MATERIAL AND CONTROLS
-Volume and number of washing steps: One
- Observable damage in the tissue due to washing: None reported
- Modifications to validated SOP: N/A

MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- MTT concentration: 1 mg/mL
- Incubation time: 3 hours
- Spectrophotometer: Anthos Reader 2010 Flexi
- Wavelength: 570 nm
- Filter: N/A
- Filter bandwidth: N/A
- Linear OD range of spectrophotometer: Not reported


NUMBER OF REPLICATE TISSUES: 2

CONTROL TISSUES USED IN CASE OF MTT DIRECT INTERFERENCE N/A


NUMBER OF INDEPENDENT TEST SEQUENCES / EXPERIMENTS TO DERIVE FINAL PREDICTION:
Two



FUNCTIONAL MODEL CONDITIONS WITH REFERENCE TO HISTORICAL DATA
- Viability: Pass (2.027 +/- 0.095)
- Barrier function: Pass (5.11 hours)
- Contamination: Pass (Sterile)

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): N/A

VEHICLE
N/A

NEGATIVE CONTROL
- Amount(s) applied (volume or weight): 50 µL
- Concentration (if solution): N/A

POSITIVE CONTROL
- Amount(s) applied (volume or weight): 50 µL
- Concentration (if solution): 8M

Duration of treatment / exposure:

3 minutes and 1 hour

Duration of post-treatment incubation (if applicable):

3 hours

Number of replicates:

2

Irritation / corrosion parameter:

% tissue viability

Run / experiment:

Experiment 1 - 3 min incubation

Value:

102.4

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

no indication of irritation

Irritation / corrosion parameter:

% tissue viability

Run / experiment:

Experiment 2 - 1 hour incubation

Value:

102.1

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:

- OTHER EFFECTS:
- Visible damage on test system: None reported
- Direct-MTT reduction: No
- Colour interference with MTT: No

DEMONSTRATION OF TECHNICAL PROFICIENCY: Demonstrated. The twelve proficiency substances were correctly classified.

ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: Yes
- Acceptance criteria met for positive control: Yes
- Acceptance criteria met for variability between replicate measurements: Yes
- Range of historical values if different from the ones specified in the test guideline: N/A

Measured Values

As blank, the optical density of isopropanol was measured in 12 wells of the 96-well-plate. The measured values and their mean are given in the following table:

Absorbance values blank isopropanol (OD 570 nm)

Replicate	1	2	3	4	5	6	Mean 0.038
Absorbance	0.040	0.039	0.039	0.039	0.038	0.038
Replicate	7	8	9	10	11	12
Absorbance	0.040	0.038	0.037	0.038	0.038	0.037

The absorbance values of negative control, test item and positive control are given in the following table:

Absorbance Values (OD 570 nm)

Incubation	Negative Control		Test Item		Positive Control
	Tissue 1	Tissue 2	Tissue 1	Tissue 2	Tissue 1	Tissue 2
3 min	1.682	1.738	1.709	1.781	0.415	0.439
	1.691	1.684	1.715	1.748	0.411	0.439
	1.688	1.677	1.709	1.733	0.413	0.438
1 h	1.578	1.570	1.658	1.555	0.250	0.258
	1.546	1.563	1.630	1.539	0.250	0.257
	1.541	1.557	1.630	1.536	0.249	0.258

 

From the measured absorbances, the mean absorbance of isopropanol (given in table 8.1-a) was subtracted. The corrected mean and relative standard deviation (RSD) of the two tissues were also calculated.

Mean Absorbance Values of the 3 Minutes Experiment

Designation	Negative Control	Test Item	Positive Control
Mean – blank (tissue 1)	1.649	1.673	0.375
Mean – blank (tissue 2)	1.661	1.716	0.400
Mean of the two tissues	1.655	1.694	0.387
RSD	0.5%	1.8%	4.7%

Mean Absorbance Values of the 1 h Experiment

Designation	Negative Control	Test Item	Positive Control
Mean – blank (tissue 1)	1.517	1.601	0.211
Mean – blank (tissue 2)	1.525	1.505	0.219
Mean of the two tissues	1.521	1.553	0.215
RSD	0.4%	4.4%	2.6%

Comparison of Tissue Viability

For the test item and the positive control, the following percentage values of mean tissue viability were calculated in comparison to the mean of the negative controls:

% Tissue Viability

Test Item	Positive Control	Incubation
102.4%	23.4%	3 min
102.1%	14.2%	1 h

Interpretation of results:

GHS criteria not met

Conclusions:

The test item is considered non-corrosive to skin.
After 3 minutes treatment, the mean value of relative tissue viability of the test item was 102.4%. This value is well above the threshold for corrosivity (50%). After 1 hour treatment the mean value of relative tissue viability of the test item was 102.1%. This value is well above the threshold for corrosivity (15%).

The values of the negative control met the required acceptability criterion of mean OD ≥ 0.8 and ≤ 2.8 for both treatment intervals, thus showing the quality of the tissues.
The positive control has met the validity criterion too, thus ensuring the validity of the test system.

For these reasons, the result of the test is considered valid.

Executive summary:

One valid experiment was performed.

Two tissues of the human skin model EpiDerm^TMwere treated with the test itemfor 3 minutes and 1 hour, respectively. The test item was applied to each tissue and spread to match the tissue size.

Demineralised water was used as negative control, 8 M KOH was used as positive control.

After treatment, the respective substance was rinsed from the tissues. Then, cell viability of the tissues was evaluated by addition of MTT, which can be reduced to a blue formazan. Formazan production was evaluated by measuring the optical density (OD) of the resulting solution.

 

After treatment with the negative control, the absorbance values were within the required acceptability criterion of mean OD ≥ 0.8 and ≤ 2.8 for both treatment intervals thus showing the quality of the tissues. The OD was 1.7 (3 minutes experiment) and 1.5 (1 hour experiment).

The positive control showed clear corrosive effects for both treatment intervals. The mean relative tissue viability value was reduced to 14.2% for the 1 hour treatment.

After 3 minutes treatment with the test item, the mean value of relative tissue viability was increased to 102.4%. This value is above the threshold for corrosion potential (50%). After 1 hour treatment, mean value of relative tissue viability was increased to 102.1%. This value, too, is above the threshold for corrosion potential (15%).

 

Therefore, the test item7-(4-ethyl-1-methyloctyl)quinolin-8-olis considered non-corrosive to skin in the Reconstructed Human Epidermis (RHE) Test Method.

Reference 2

Endpoint:

skin irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

12 Nov 2018 - 16 Nov 2018

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:

28 July 2015

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.46 (In Vitro Skin Irritation: Reconstructed Human Epidermis Model Test)

Version / remarks:

06 July 2012

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Sponsor / 1702-18-01/O
- Expiration date of the lot/batch: 25 March 2021


STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room Temperature (20 ± 5 °C); Keep away from light
- Stability under test conditions: Stable
- Solubility and stability of the test substance in the solvent/vehicle:

Stability H2O: unknown; Ethanol: unknown; acetone; unknown; CH3CN: unknown; DMSO: unknown
Solubility H2O: < 0.1 g/L; Ethanol: unknown; acetone: > 1 g/L; CH3CN: unknown; DMSO: unknown

Test system:

human skin model

Source species:

human

Cell type:

non-transformed keratinocytes

Cell source:

other: not specified

Details on animal used as source of test system:

The test system is a commercially available EpiDermTM-Kit, procured by MatTek.
The EpiDermTM tissue consists of human-derived epidermal keratinocytes which have been cultured to form a multi-layered, highly differentiated model of the human epidermis. It con-sists of organized basal, spinous and granular layers, and a multi-layered stratum corneum containing intercellular lamellar lipid layers representing main lipid classes analogous to those found in vivo. The EpiDermTM tissues are cultured on specially prepared cell culture inserts.
6.4.2 Origin
EpiDermTM tissues were procured from MatTek In Vitro Life Science Laboratories, Brati-slava.
Designation of the kit: EPI-200-SIT
Day of delivery: 13. Nov. 2018
Batch no.: 28668

Justification for test system used:

Standard methodology

Vehicle:

unchanged (no vehicle)

Details on test system:

RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used: EPI-200-SIT
- Tissue batch number(s): 28668
- Delivery date: 13 Nov 2018
- Date of initiation of testing: 16 Nov 2018

TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: 37 ± 1°C
- Temperature of post-treatment incubation (if applicable): 37 ± 1°C

REMOVAL OF TEST MATERIAL AND CONTROLS
-Volume and number of washing steps: hour after the first application, the inserts were removed from the plates using sterile for-ceps and rinsed immediately in 1-minute-intervals.
After rinsing thoroughly with DPBS, each tissue was blotted with sterile cellulose tissue and then transferred into a new 6-well-plate with fresh assay medium (0.9 mL). The surface of the inserts was then carefully dried with a sterile cotton tipped swab.
- Observable damage in the tissue due to washing: No
- Modifications to validated SOP: No

MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- MTT concentration: 1 mg/ml)
- Incubation time: 3 hrs
- Spectrophotometer: Anthos Reader 2010 Flexi
- Wavelength: 570nm


NUMBER OF REPLICATE TISSUES: 3

NUMBER OF INDEPENDENT TEST SEQUENCES / EXPERIMENTS TO DERIVE FINAL PREDICTION: 3

PREDICTION MODEL / DECISION CRITERIA (choose relevant statement)
Skin irritation potential of the test item is assessed as given in the following table:
Assessment of Skin Irritation Potential
% Tissue viability Assessment UN GHS classification
≤ 50 % of negative control Corrosive/ Irritant to skin UN GHS Category 1 or 2
> 50 % of negative control Non-irritant to skin No Category

Control samples:

yes, concurrent negative control

yes, concurrent positive control

Amount/concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 30 μL

NEGATIVE CONTROL
- Amount(s) applied (volume or weight): 30 μL


POSITIVE CONTROL
- Amount(s) applied (volume or weight): 30 μL
- Concentration (if solution): 5% SDS-solu-tion

Duration of treatment / exposure:

1 hr

Duration of post-treatment incubation (if applicable):

23 hours and 25 minutes

Number of replicates:

3

Irritation / corrosion parameter:

% tissue viability

Run / experiment:

1

Value:

92.5

Negative controls validity:

valid

Positive controls validity:

valid

Irritation / corrosion parameter:

% tissue viability

Run / experiment:

2

Value:

94.7

Negative controls validity:

valid

Positive controls validity:

valid

Irritation / corrosion parameter:

% tissue viability

Run / experiment:

3

Value:

95.1

Negative controls validity:

valid

Positive controls validity:

valid

Other effects / acceptance of results:

- OTHER EFFECTS:
- Visible damage on test system:
- Direct-MTT reduction:
- Colour interference with MTT:

DEMONSTRATION OF TECHNICAL PROFICIENCY:

ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: yes,
Demanded: ≥ 0.8 and ≤ 2.8
Found: 1.6
- Acceptance criteria met for positive control: yes
Demanded: ≤ 20% of negative control
Found: 2.5%
- Acceptance criteria met for variability between replicate measurements: Yes
Demanded: ≤ 18%
Found: 2.9% (negative control) 0.3% (positive control) 1.4% (test item)

- Range of historical values if different from the ones specified in the test guideline: Values for negative control and for positive control were within the range of historical data of the test facility:

Parameter Negative Control (OD) Positive Control (% OD compared to NegativeControl)
Substance DPBS buffer Sodium Dodecyl Sulphate Solution 5%
Mean 1.793 4.5%
Standard
deviation 0.328 3.1%
Range 0.476 – 2.471 1.7 – 17.1%
Study 1.595 2.5%

Interpretation of results:

GHS criteria not met

Conclusions:

After the treatment with the test item, the mean value of relative tissue viability was reduced to 94.1%. This value is well above the threshold for skin irritation potential (50%). Test items that induce values above the threshold of 50% are considered non-irritant to skin.
Therefore, the test item 7-(4-ethyl-1-methyloctyl)quinolin-8-ol is considered non-irritant to skin in the Reconstructed human Epidermis (RhE) Test Method.

Executive summary:

Title of Study: Determination of Skin Irritation Potential of 7-(4-ethyl-1-methyloctyl)quinolin-8-ol in the Reconstructed human Epi-dermis (RhE) Test Method following EU-Method B.46 and OECD 439

Findings and Results:

One valid experiment was performed.

Three tissues of the human skin model EpiDermTM were treated with the test item for 60 minutes.

The test item was applied directly to each tissue and spread to match the tissue size (0.63 cm2; as indicated by the supplier).

DPBS-buffer was used as negative control and 5% SDS solution was used as positive control.

After treatment with the negative control, the mean absorbance value was within the re-quired acceptability criterion of 0.8 ≤ mean OD ≤ 2.8, OD was 1.6.

The positive control showed clear irritating effects. The mean value of relative tissue viability was reduced to 2.5% (required :≤ 20%).

The variation within the tissue replicates of negative control, positive control and test item was acceptable (required: ≤ 18%).

After the treatment with the test item, the mean value of relative tissue viability was reduced to 94.1%. This value is well above the threshold for skin irritation potential (50%). Test items that induce values above the threshold of 50% are considered non-irritant to skin.

Therefore, the test item 7-(4-ethyl-1-methyloctyl)quinolin-8-ol is considered non-irritant to skin in the Reconstructed human Epidermis (RhE) Test Method.

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:

weight of evidence

Study period:

26 September 2018

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 Ocular Corrosives and Severe Irritants)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU method B.47 (Bovine corneal opacity and permeability test method for identifying ocular corrosives and severe irritants)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Sponsor/1702-18-01/O
- Expiration date of the lot/batch: 25 Mar 2021
- Purity test date: 26 Mar 2018

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature (20 ± 5 °C); Keep away from light
- Stability under test conditions: Stable
- Solubility and stability of the test substance in the solvent/vehicle: Stable

Species:

cattle

Strain:

not specified

Details on test animals or tissues and environmental conditions:

SOURCE OF COLLECTED EYES
- Source: slaughterhouse Müller Fleisch GmbH, Enzstr. 2-4, 75217 Birkenfeld, Germany
- Number of animals: not specified.
- Characteristics of donor animals (e.g. age, sex, weight): The cattle were between 12 and 60 months old
- Storage, temperature and transport conditions of ocular tissue (e.g. transport time, transport media and temperature, and other conditions): The eyes were transported to the test facility in Hanks’ Balanced Salt Solution with 1% Penicillin-Streptomycin solution (Penicillin 100 U/mL, Streptomycin 100 µg/mL) in a suitable cooled container within 1 hour and 15 minutes.

Vehicle:

Hank's balanced salt solution

Controls:

yes, concurrent positive control

yes, concurrent negative control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 750 µL

Duration of treatment / exposure:

incubation time: 10 min

Duration of post- treatment incubation (in vitro):

2 hours

Number of animals or in vitro replicates:

3 replicates

Details on study design:

SELECTION AND PREPARATION OF CORNEAS : Only corneas which were free from damage were used. The corneas were excised with a scalpel and cut from the globe with a 2-3 mm ring of sclera around the outside. Each cornea was transferred to a cornea holder in which pre-warmed cMEM (32 ± 1 °C) without phenol red was filled. The holders were then incubated for 1 hour in the incubation chamber at 32 ± 1 °C.

QUALITY CHECK OF THE ISOLATED CORNEAS : After the initial incubation, the medium was completely changed and the baseline opacity for each cornea was recorded. None of the corneas showed tissue damage; therefore, all corneas were used.

NUMBER OF REPLICATES : 3

NEGATIVE CONTROL USED : HBSS

POSITIVE CONTROL USED : Dimethylformamide (undiluted)

APPLICATION DOSE AND EXPOSURE TIME : 750 µL, EXPOSURE TIME 10 MINUTES.

TREATMENT METHOD: closed chamber

POST-INCUBATION PERIOD: yes. If YES please specify duration : 2 hours.

REMOVAL OF TEST SUBSTANCE
- Number of washing steps after exposure period: the anterior chamber was rinsed with cMEM with phenol red, then with cMEM without phenol red.


METHODS FOR MEASURED ENDPOINTS:
- Corneal opacity: Opacitometer
- Corneal permeability: passage of sodium fluorescein dye measured with the aid of microtiter plate reader (OD 492 nm)

SCORING SYSTEM: In Vitro Irritancy Score (IVIS)
The IVIS of each replicate of the negative control was calculated from the following equation:
IVIS = opacity difference + (15 x corrected OD492 value)

The IVIS of each replicate of the positive control and of the test item were calculated from the following equation:
IVIS = (opacity difference – mean opacity difference of the negative control) + [15 x (OD492 – mean OD492 of the negative control)]

DECISION CRITERIA: OECD TG.

Irritation parameter:

in vitro irritation score

Run / experiment:

1

Value:

0.21

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Irritation parameter:

in vitro irritation score

Run / experiment:

2

Value:

-1.44

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Irritation parameter:

in vitro irritation score

Run / experiment:

3

Value:

0.75

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Irritation parameter:

in vitro irritation score

Run / experiment:

mean

Value:

-0.16

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: none

DEMONSTRATION OF TECHNICAL PROFICIENCY: yes

ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: yes
- Acceptance criteria met for positive control: yes

Values Negative Control

Parameter	Negative Control
	1. Rep.	2. Rep.	3. Rep.
Opacity before exposure	2.84	2.75	3.57
Opacity after exposure	5.49	5.88	4.88
Opacity Difference	2.66	3.13	1.31
Mean Opacity Difference	2.36

Rep. = Replicate

Opacity Values Test Item and Positive Control

Parameter	Test Item			Positive Control
	1. Rep.	2. Rep.	3. Rep.	1. Rep.	2. Rep.	3. Rep.
Opacity before exposure	2.54	3.53	1.49	2.01	2.54	1.33
Opacity after exposure	5.16	4.42	4.69	99.76	97.95	96.62
Opacity Difference	2.62	0.89	3.21	97.76	95.41	95.29
Opacity Difference corrected	0.25	-1.47	0.85	95.39	93.04	92.93
Mean Opacity Difference corrected	-0.12			93.79

Rep. = Replicate

Optical density at 492 nm of Negative Control, Test Item and Positive Control

Parameter	Negative Control			Test Item			Positive Control
	1. Rep.	2. Rep.	3. Rep.	1. Rep.	2. Rep.	3. Rep.	1. Rep.	2. Rep.	3. Rep.
1. Measurement	0.050	0.045	0.065	0.048	0.053	0.049	0.950	1.392	1.931
2. Measurement	0.051	0.043	0.056	0.047	0.053	0.043	0.962	1.388	1.998
3. Measurement	0.048	0.043	0.057	0.048	0.052	0.041	0.952	1.394	1.953
1. Measurement – blank	0.0070	0.0020	0.0220	0.0050	0.0100	0.0060	0.9070	1.3490	1.8880
2. Measurement – blank	0.0080	0.0000	0.0130	0.0040	0.0100	0.0000	0.9190	1.3450	1.9550
3. Measurement – blank	0.0050	0.0000	0.0140	0.0050	0.0090	-0.0020	0.9090	1.3510	1.9100
Mean of each replicate	0.0067	0.0007	0.0163	0.0047	0.0097	0.0013	0.9117	1.3483	1.9177
Mean of the 3 replicates	0.0079			--			--
Corrected	--	--	--	-0.0032	0.0018	-0.0066	0.9038	1.3404	1.9098
Corrected mean of the 3 replicates	--			-0.0027			1.3847

IVIS

Test Group	IVIS	Mean IVIS	Relative Standard Deviation IVIS
Negative Control HBSS	2.76	2.48	33.25%
	3.14
	1.55
Test Item 7-(4-ethyl-1-methyloctyl)quinolin-8-ol	0.21	-0.16	697.17%
	-1.44
	0.75
Positive Control DMF undiluted	108.95	114.56	5.61%
	113.15
	121.58

 

Note: the high relative standard deviation of the IVIS of test item is due to mathematical reasons, as the respective means are very small

Interpretation of results:

GHS criteria not met

Conclusions:

The test item 7-(4-ethyl-1-methyloctyl)quinolin-8-ol showed no effects on the cornea of the bovine eye. The calculated mean IVIS (In Vitro Irritancy Score) was -0.16.

The experiment is considered as sufficient for the classification of the test item, because all three replicates of the test item lead to the same assessment for the test item.

Executive summary:

Findings and Results:

One valid experiment was performed.

Bovine corneas were used. They were collected from slaughtered cattle that were between 12 and 60 months old. The test item 7-(4-ethyl-1-methyloctyl)quinolin-8-ol was applied onto the cornea of a bovine eye which had been previously incubated with cMEM without phenol red at 32 ± 1 °C for 1 hour and whose opacity had been measured.

The test item was incubated on the cornea for 10 minutes at 32 ± 1 °C. After removal of the test item and 2 hours post-incubation, opacity and permeability values were measured.

Hank’s Balanced Salt Solution (HBSS) was used as negative control. The negative control showed no irritating effect on the cornea and the calculated mean IVIS (In Vitro Irritancy Score) was 2.48.

Dimethylformamide (DMF) undiluted was used as positive control. The positive control induced serious eye damage on the cornea and was within two standard deviations of the current historical mean. The calculated mean IVIS was 114.56.

Under the conditions of this study, the test item 7-(4-ethyl-1-methyloctyl)quinolin-8-ol showed no effects on the cornea of the bovine eye. The calculated mean IVIS was -0.16.

According to OECD Guideline no. 437 (Oct. 2017), a substance with an IVIS ≤ 3 requires no classification 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

Justification for classification or non-classification

Eye irritation:

The test item 7-(4-ethyl-1-methyloctyl)quinolin-8-ol showed no effects on the cornea of the bovine eye. The calculated mean IVIS (In Vitro Irritancy Score) was -0.16. In accordance with Regulation (EC) No.1272/2008 (EU CLP) no classification is proposed.

Skin irritation:

Corrosion study: After 3 minutes treatment, the mean value of relative tissue viability of the test item was 102.4%. This value is well above the threshold for corrosivity (50%). After 1 hour treatment the mean value of relative tissue viability of the test item was 102.1%. This value is well above the threshold for corrosivity (15%), therefore the substance is characterised as non-corrosive. In accordance with Regulation (EC) No.1272/2008 (EU CLP) no classification is proposed.

Irritation study:

After the treatment with the test item, the mean value of relative tissue viability was reduced to 94.1%. This value is well above the threshold for skin irritation potential (50%). Test items that induce values above the threshold of 50% are considered non-irritant to skin. Therefore, the test item 7-(4-ethyl-1-methyloctyl)quinolin-8-ol is considered non-irritant to skin in the Reconstructed human Epidermis (RhE) Test Method.