2,4-dichlorobenzyl alcohol

Endpoint summary

Description of key information

The test subtstance caused very slight irritation to the skin of rabbits without consequences for C&L.

The test substance caused slight irritation in the eyes of three rabbits without consequences for C&L.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1998-02-17 to 1998-02-28

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 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan UK Ltd. Bicester
- Weight at study initiation: 3.11 to 3.89 kg
- Housing: single, floor pens (min 0.6 m2)
- Diet: ad libitum, SQC TRB Rabbit Diet 9603 (pelleted) from Harlan Teklad, Bicester
- Water: ad libitum, mains water
- Acclimation period: 10 to 14 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16-22
- Humidity (%): 40-80
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

undiluted, 500 mg (treatment side was moistured with water)

Duration of treatment / exposure:

4 h

Observation period:

3 days

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure: dorsal, 30*20 mm
- Type of wrap if used: dense gauze patch, covered by a larger gauze patch and an open weave, elasticated adhesive bandage "Steroban" from Steroplast Ltd., Bredbury, UK which was wrapped firmly around the torso to secure the applied dose and patch in the correct position.

REMOVAL OF TEST SUBSTANCE
- Washing: light brushing and swabbing with moist cotton wool
- Time after start of exposure: 4 h

SCORING SYSTEM:
- Erythema and eschar Grade
No erythema: 0
Very slight erythema: 1
WelI-defined erythema: 2
Moderate erythema: 3
Severe erythema (beet redness) or eschar preventing reading of erythema: 4
- Oedema Grade
No oedema 0
Very slight oedema (barely perceptible): 1
Slight oedema (edges of area well-defined by definite raising): 2
Moderate oedema (edges raised approximately 1 mm): 3
Severe oedema (raised >1 mm and extending beyond area of exposure): 4

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0.06

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

other: 24, 48, 72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

animal #3

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

animal #4

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

animal #5

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

animal #6

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 0 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 24 h

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 1 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 24 h

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

other: 1 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

other: 24 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 48 h

Remarks on result:

other: only 3 foci affected

Other effects:

There were no signs of toxicity or ill health in any rabbit during the observation period.

Interpretation of results:

not classified

Remarks:

Migrated information

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

A study to determine the skin irritation properties of the test substance was conducted according to OECD test guideline 404 under GLP. The test substance (500 mg) was applied to the skin of 6 female rabbits for 4 h under semi-occlusive cover. The animals were observed for 72 h and sacrificed afterwards. In one animal erythema was observed directly after removal of the cover (Score 2) and after 1 h (Score 1). In another rabbit erythema was detected after 1 h (Score 1) and 24 h (Score 1 with 3 foci affected). The skin of both animals recovered completely and no effects were observed after 24 h or 48 h. The other 4 animals showed no kinds of skin irritation at any time. The mean erythema score for after 24, 48 and 72 h was 0.06 and the mean edema score was 0. Therefore the test substance was not classified for skin irritation.

 

Additional non-guideline studies in rabbits showed no irritation potential higher than the vehicle in which the test substance was applied to intact and abraded skin one or 10 times. For details please refer to IUCLID section 7.12. 

 

Eye irritation

Non-guideline studies in rabbits showed no irritation potential higher than the vehicle in which the test substance was applied, nevertheless as this study was limited in reliability due to the low contact time of 1 min reflecting not guideline conditions an in vitro turnkey study according to guideline OECD 437 and 492 was performed (BASF SE, 2018).

BCOP (OECD 437)

The potential of the test substance to cause ocular irritation or serious damage to the eyes was assessed by a single topical application of 750 μL 20% test-substance preparation to the epithelial surface of isolated bovine corneas. Three corneas were treated with the test-substance preparation for an exposure period of 4 hours. In addition to the test substance, a negative control (NC; deionized water) and a positive control (PC; 20% imidazole in deionized water) were applied to three corneas each. Corneal opacity was quantitatively measured as the amount of light transmitted through the cornea. Permeability was quantitatively measured as the amount of sodium fluorescein dye that passes across the full thickness of the cornea. Both measurements were used to calculate an In Vitro Irritancy Score of the test substance.

In addition, H&E-stained cross sections of the corneas were evaluated.

The following results were obtained in the BCOP Test: Mean In Vitro Irritancy Score 73.5 Detachment (partly) of the epithelium was noted in all test-substance treated corneas after

the washing procedure. Histological evaluation revealed changes indicating severe eye damage in all corneas treated with the test substance. The median histological irritation score was IV.

EpiOcular (OECD 492)

The potential of the test substance to cause ocular irritation was assessed by a single topical application of 50 μL bulk volume (about 22 mg) undiluted test substance to a reconstructed three-dimensional, human cornea model (EpiOcular™). Two EpiOcular™ tissues were incubated with the test substance for 6 hours followed by a 18-hour post-incubation period. Tissue destruction was determined by measuring the metabolic activity of the tissue after exposure/post-incubation by using a colorimetric test.

The following results were obtained in the EpiOcular™ eye irritation assay: The test substance is able to directly reduce MTT. Therefore, an additional MTT reduction control (freeze-killed control tissues (KC)) was introduced. The final mean viability of the tissues treated with the test substance was 1.8%.

Based on the result of these two in vitro assays the following conclusion can be drawn:

2,4-Dichlorbenzylalkohol causes ocular corrosion or severe irritation in the in vitro eye irritation test strategy under the test conditions chosen.

Justification for selection of skin irritation / corrosion endpoint:

Experimental study according to guideline and GLP.

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 (EU) No 2015/1221. As a result the substance is considered to be not classified for 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 (EU) No 2015/1221. As a result the substance is considered to cause servere eye damage (CAT 1; H318).