1-chloro-4-[(prop-2-yn-1-yloxy)methyl]benzene

Endpoint summary

Description of key information

Skin: 
In an in vitro skin irriation study (OECD 439) a mean tissue viability of 40.3 % was determined. 
In an in vitro skin corrosion study (OECD 431) a mean tissue viability of 114.3 % after 3 min exposure and 94.1 % after 1 h exposure to the test substance was determined. 
Eye irriation
In an in vitro eye irritation study (OECD 437) an In Vitro Irritancy score (IVIS) of 0.5 was determined. 
In an in vitro Reconstructed Human Cornealike Epithelium (RhCE) eye irritation study a tissue viablity of 65.5 % was observed. 

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

2014-12-09 to 2015-03-23

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Experimental study according to guideline and GLP

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2013

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2012

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

BASF SE, Experimental Toxicology and Ecology, 67056 Ludwigshafen, Germany

Species:

human

Details on test animals or test system and environmental conditions:

Kits used:
- EpiDerm™ 200 kit (Lot: 21607)
- Source: MatTek In Vitro Life Science Laboratories, Bratislava, Slovakia,
- containing: 24 Epi-200 tissues (reconstructed epidermis): surface 0.6 cm² cultured in Millicells® ∅ 1 cm
- Tissue for MTT reduction control: Epi-200 tissue that is killed by freezing at –20°C

Vehicle:

unchanged (no vehicle)

Controls:

other: negative, positive and MTT-reduction control

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 30 µL
- Concentration: undiluted

Duration of treatment / exposure:

1 h

Details on study design:

please refer to "Any other information on materials and methods"

Irritation / corrosion parameter:

other: other: viability

Value:

40.3

Remarks on result:

other:

Remarks:

Basis: mean. Time point: 1 h exposure, 42 h post-exposure. Reversibility: other: not applicable. Remarks: %. (migrated information)

Test substance			Tissue 1	Tissue 2	Tissue 3	Mean	SD	CV [%]
Negative control	Viable tissues	Mean OD570	2.304	2.649	2.488	2.480	0.173
		Viability [% of NC]	92.9	106.8	100.3	100.0	7.0	7.0
	KC tissues	Mean OD570	0.062	0.066	0.055	0.061	0.005
		Viability [% of NC]	2.5	2.6	2.2	2.4	0.2	8.7
Test substance	Viable tissues	Mean OD570	0.812	0.986	1.198	0.999	0.193
		Viability [% of NC]	32.7	39.8	48.3	40.3	7.8	19.4
	KC tissues	Mean OD570 corrected	0	0	0	0	0
		Viability [% of NC]	0	0	0	0	0	-
Positive control	Viable tissues	Mean OD570	0.063	0.068	0.072	0.067	0.005
		Viability [% of NC]	2.5	2.7	2.9	2.7	0.2	7.1

Negative values were set to zero for further calculation

CV=coefficient of variation

SD=standard deviation

Due to the ability of the test substance to reduce MTT directly, KC tissues were applied in parallel. However, the result of the KC did not indicate an increased MTT reduction. Thus the mean viability is given without KC correction.

Interpretation of results:

irritating

Remarks:

Migrated information

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (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:

2014-12-01 to 12015-03-23

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Experimental study according to guideline and GLP

Qualifier:

according to guideline

Guideline:

OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying Ocular Corrosives and Severe Irritants)

Version / remarks:

2013

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Commission Regulation (EU) No. 1152/2010 of 8 December 2010 Part B: Methods for the det.: Bovine Corneal Opacity and Permeability Test, Method for identifying ocular corrosives and severe irritants; Official Journal of the European Union, No. L 324 (B.47?

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

BASF SE, Experimental Toxicology and Ecology, 67056 Ludwigshafen, Germany

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 750 µL
- Concentration: undiluted

Duration of treatment / exposure:

10 min

Details on study design:

Please refer to "Any other information on materials and methods"

Irritation parameter:

in vitro irritation score

Run / experiment:

10 min exposure, 2 h post-exposure (test substance)

Value:

0.5

Irritation parameter:

in vitro irritation score

Run / experiment:

10 min exposure, 2 h post-exposure (negative control)

Value:

1.9

Irritation parameter:

in vitro irritation score

Run / experiment:

10 min exposure, 2 h post-exposure (positive control, ethanol 100 %)

Value:

63.3

Irritation parameter:

in vitro irritation score

Run / experiment:

10 min exposure, 2 h post-exposure (positive control, Dimethylformamid 100 %)

Value:

129

Opacity

Substance	Cornea No.	Initial opacity	Final opacity	Opacity change	Corrected opacity change	Mean	SD
Test substance	10	2.5	5.5	3	1.1	0.5	0.6
	11	2.8	5.1	2.3	0.5
	12	4.6	5.9	1.3	0.0
Negative control	1	1.7	2.3	0.7	NA	1.8	2.6
	2	4.4	3.4	0.0	NA
	3	4.3	9.1	4.9	NA
Ethanol (100 %)	4	5.6	36.8	31.2	29.3	32.4	3.5
	5	3.7	37.2	33.6	31.7
	6	2.1	40.1	38.0	36.2
Dimethylformamid (100 %)	7	2.2	95.9	93.7	91.8	104.0	13.2
	8	4.0	123.8	119.8	118.0
	9	2.7	106.8	104.1	102.2

 

Permeability

Substance	Cornea No.	Mean OD490	Dilution factor	Mean corrected OD490	Mean	SD
Test substance	10	0.001	1	0.001	0.001	0.001
	11	0.002	1	0.002
	12	-0.002	1	0
Negative control	1	-0.002	1	NA	0	0
	2	0	1	NA
	3	0	1	NA
Ethanol (100 %)	4	0.446	5	2.231	2.059	0.318
	5	0.338	5	1.691
	6	0.451	5	2.253
Dimethylformamid (100 %)	7	0.172	5	0.860	1.665	0.736
	8	0.461	5	2.305
	9	0.366	5	1.830

 

In Vitro Irritancy score (IVIS)

Substance	Cornea No.	Opacity per cornea	Permeability per cornea	IVIS
				per cornea	per group
					Mean	SD
Test substance	10	1.1	0.001	1.1	0.5	0.6
	11	0.5	0.002	0.5
	12	0	0	0
Negative control	1	0.7	0	0.7	1.9	2.6
	2	0	0	0
	3	4.9	0.001	4.9
Ethanol (100 %)	4	29.3	2.231	62.8	63.3	6.5
	5	31.7	1.691	57.1
	6	36.2	2.253	70.0
Dimethylformamid (100 %)	7	91.8	0.860	104.7	129.0	23.9
	8	118.0	2.305	152.5
	9	102.2	1.830	139.7

 

Interpretation of results:

other: not irritating and not corrosive

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

Weight of evidence approaches with each two in vitro studies were done to evaluate if the test substance was irritating or corrosive to the skin and irritating or corrosive to the eye.

 

Skin corrosion

The in vitro Human Skin Model Test with EpiDerm™ study according to OECD 431 was performed to assess the corrosive potential of the test substance. Independent duplicate tissues of EpiDerm™ were exposed to either the test substance, the negative control (deionised water) or the positive control (8.0 N KOH) for 3 min and 1 hour. 50 μL (dose calculation was adjusted to purity) of the test substance were dispensed directly onto duplicate EpiDermTM tissue surface. After exposure of the tissues to the test substance the mean tissue viability (corrected) was 114.3 % after 3 minutes exposure and 94.1 % after 1 h exposure. Both values did not touch the threshold for corrosivity, which is defined to be < 50% after the 3 minutes exposure and < 15% after the 1 hour exposure. Therefore, the test substance was not considered to be corrosive. In conclusion, it can be stated that in this study and under the reported experimental conditions, the test substance was non corrosive to skin and therefore has not be be classified into Category 1 according to EU CLP and UN GHS.

 

Skin irritation

The in vitro Human Skin Model Test with EpiDerm™ study according to OECD 439 was performed to assess the irritation potential of the test substance. Independent triplicate tissues of EpiDerm™ were exposed to either the test item, the negative control (PBS) or the positive control (5 % SDS in water) for 1 hour. 30 μL of the test item were dispensed directly onto triplicate EpiDermTM tissue surface, and spread to match the surface of the tissue. After exposure of the tissues to the test substance the mean tissue viability decreased to 40.3 % after 1 h exposure. This value is below the threshold for irritation, which is defined to be < 50 %. Therefore, the test substance was considered to be skin irritating. In conclusion, it can be stated that in this study and under the reported experimental conditions, the test substance was irritating to skin and therefore is classified as Category 2 according to EU CLP and UN GHS.

 

Eye irritation / corrosion

An in vitro study with fresh bovine cornea was conducted according to OECD 437 to investigate the eye irritation properties of the test substance. After a first opacity measurement of the fresh bovine corneae, the undiluted test substance, the positive and the negative controls were applied to corneae (750 µL) and incubated for 10 min at 32 °C. After the incubation phase the substances were rinsed from the corneae. The corneae were incubated for 2 h at 32 °C in incubation medium, and opacity was measured a second time. After the opacity measurements permeability of the corneae was determined by measuring spectrophotometrically the transfer of sodium fluorescein after incubation in a horizontal position for 90 minutes at 32 °C. The positive controls showed clear opacity and distinctive permeability of the corneae (mean IVIS = 63.3 for ethanol and 129 for dimethylformamid). Relative to the negative control, the test substance did not cause an increase of the corneal opacity or permeability. The calculated mean IVIS was 0.5 (threshold for serious eye damage: IVIS ≥55). According to OECD 437 the test item is not identified as corrosive or severe irritant.

An in vitro study with a three dimensional human cornea model (EpiOcular™) was conducted to investigate the eye irritation properties of the test substance. Independent duplicate tissues of EpiOcular™ were exposed to either the test substance, the negative control (deionised water) or the positive control (Methyl acetate) for 30 min followed by a 2-hours post-incubation period. 50 μL of the test substance were dispensed directly onto tissue surface. After exposure of the tissues to the test substance the mean tissue viability was 65.6 %. The values did not touch the threshold for irritation, which is defined to be ≤ 60 %. Therefore, it can be stated that in this study and under the reported experimental conditions, the test substance was non-irritant to the eye.

As one in vitro study showed that the test substance is not corrosive or severe irritating to the eye and a second in vitro study that the test substance is in general not irritating it can be concluded that the test substance is not classified as corrosive or irritating to the eye.

 

Justification for selection of skin irritation / corrosion endpoint:
The most sensitive endpoint was considered.

Justification for selection of eye irritation endpoint:
The study showed non-irritating properties of the test substance and the result was further supported by a second in vitro test.

Effects on skin irritation/corrosion: irritating

Justification for classification or non-classification

Skin irritation/corrosion

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008, as amended for the seventh time in Regulation (EC) No 2015/1221. As a result the substance is considered not classified for skin corrosion but to be classified for skin irritation in Category 2 and. H315: Causes skin irritation.

 

Eye irritation/corrosion

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008, as amended for the seventh time in Regulation (EC) No 2015/1221. As a result the substance is considered to be not classified as corrosive or irritating to the eye.