Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Key acute dermal irritation and eye irritation studies in rabbits were conducted with Ethyl trichloroacetate, demonstrating  irritation for skin and no irritation for eye irritation. Mean 24 -72h scores for skin were 1.1/ 4 (3') and 2.1/4 (4h) for erythema and 0.2/4 (3') and 1.4/4 (4h) for edema. Skin irritation was reversible  within 7 and 14 days, after 3 minutes and 4 hours exposure. Mean 24 -72h scores for eye were 0/4 for cornea, 0/2 for iris, 0.1/3 for conjuctival redness and 0/4 for chemosis. Findings for conjuctival redness were fully reversible wihting 48 hours. 

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
evaluation after 3 minutes and 4 hours exposure
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: raised by Hoechst AG, site Hattersheim-Kastengrund near Frankfurt am Main, Germany
- Weight at study initiation: 3.1-3.7 kg
- Diet (e.g. ad libitum): Altromin 2123 Haltüngsdiät-Kaninchen, Altromin GmbH, Lage/Lippe, ad libitum
- Water (e.g. ad libitum): deionized, chlorinated water from automatic watering, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 2°C
- Humidity (%): 55 ± 10 %
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 mL of the test substance, undiluted
Duration of treatment / exposure:
3 min or 4 h, respectively
Observation period:
72 h - extended to 7 days or 14 days
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: dorsolateral area of the trunk
- % coverage: 6.25 cm2 (2.5 X 2.5 cm)
- Type of wrap if used: cellulose adhesive plaster covered with a semi-occlusive bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Remaining test item was gently removed from the skin.
- Time after start of exposure: 3 minutes or 4 hours respectively

SCORING SYSTEM:
Numerical scores according to Draize

Erythema and Eschar
0: No erythema
1: Very slight erythema (barely perceptible)
2: Well-defined erythema
3: Moderate to severe erythema
4: Severe erythema (beet redness) to slicht eschar formation (injuries in depth)

Edema
0: No edema
1: Very slight edema (barely perceptible)
2: Slight edema (edges of area well-defined by definite raising)
3: Moderate edema ( raise approximately 1 mm)
4: Severe edema (raised more than 1 mm, extending beyond the area of exposure)
Irritation parameter:
erythema score
Basis:
mean
Remarks:
application: 3 min
Time point:
24/48/72 h
Score:
1.1
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
, application: 3 min
Time point:
24/48/72 h
Score:
2
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
, application: 3 min
Time point:
24/48/72 h
Score:
1
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
, application: 3 min
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Irritation parameter:
erythema score
Basis:
mean
Remarks:
application: 4 h
Time point:
24/48/72 h
Score:
2.1
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
, application: 4 h
Time point:
24/48/72 h
Score:
2
Max. score:
4
Remarks on result:
other: not identical with animal #1, application 3 min
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
, application: 4 h
Time point:
24/48/72 h
Score:
2.7
Max. score:
4
Remarks on result:
other: not identical with animal #2, application 3 min
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
application: 4 h
Time point:
24/48/72 h
Score:
1.7
Max. score:
4
Remarks on result:
other: not identical with animal #3, application 3 min
Irritation parameter:
edema score
Basis:
mean
Remarks:
application: 3 min
Time point:
24/48/72 h
Score:
0.2
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
, application: 3 min
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
, application: 3 min
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
, application: 3 min
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Remarks:
application: 4 h
Time point:
24/48/72 h
Score:
1.4
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
, application: 4 h
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Remarks on result:
other: not identical with animal #1, application 3 min
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
, application: 4 h
Time point:
24/48/72 h
Score:
2
Max. score:
4
Remarks on result:
other: not identical with animal #2, application 3 min
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
, application: 4 h
Time point:
24/48/72 h
Score:
1
Max. score:
4
Remarks on result:
other: not identical with animal #3, application 3 min
Irritant / corrosive response data:
At an exposure time of 3 minutes, very slight to well-defined erythema and barely perceptible edema were observed. No signs of irritation were observed 7 days after application. The skin was merely still dry, brittle or fine-to-rough scaly and in one animal small areas with brownish discoloration were observed.
At an exposure time of 4 hours well-defined to moderate erythema and edema were observed. 14 days after application, the treated skin showed no more irritation. The skin was also dry, brittle, fine-to-rough scaly and brownish.

Table 1. Mean values for observations at 24, 48 and 72 hours

 

 

Exposure

3 minutes

4 hours

Erythema and Eschar formation

All animals

1.1

2.1

Animal 1

2.0

2.0

Animal 2

1.0

2.7

Animal 3

0.3

1.7

Edema

All animals

0.2

1.4

Animal 1

0.7

1.3

Animal 2

0

2.0

Animal 3

0

1.0

 

Table 2. Individual values after 3 minutes exposure to Ethyl Trichloroacetate

Time after removal of patch

0.5-1 hour

24 hours

48 hours

72 hours

7days

14 days

Animal No.

1

2

3

1

2

3

1

2

3

1

2

3

1

2

3

1

2

3

Erythema

2

0

1

2

1

1

2

1

0

2

1

0

0

0

0

 

 

 

Edema

1

0

0

1

0

0

1

0

0

0

0

0

0

0

0

 

 

 

Skin surface

 

-dry,brittle

 

 

 

 

 

 

 

 

 

 

 

 

x

x

x

 

 

 

-fine scaly

 

 

 

 

 

 

 

 

 

 

 

 

x

x

x

 

 

 

-rough scaly

 

 

 

 

 

 

 

 

 

 

 

 

x

x

x

 

 

 

Skin discoloration

 

-small areas, brownish

 

 

 

 

 

 

 

 

 

 

 

 

x

 

 

 

 

 

 

Table 3. Individual values after 4 hours exposure to Ethyl Trichloroacetate

Time after removal of patch

0.5-1 hour

24 hours

48 hours

72 hours

7days

14 days

Animal No.

1

2

3

1

2

3

1

2

3

1

2

3

1

2

3

1

2

3

Erythema

2

2

2

2

2

2

2

3

2

2

3

1

0

1

0

0

0

0

Edema

3

3

2

2

2

2

1

2

1

1

2

0

0

1

0

0

0

0

Skin surface

 

-dry,brittle

 

 

 

 

 

 

 

 

 

 

 

x

x

x

x

 

 

 

-fine scaly

 

 

 

 

 

 

 

 

 

 

 

x

x

x

x

x

x

 

-rough scaly

 

 

 

 

 

 

 

 

 

 

 

 

x

 

 

 

x

 

Skin discoloration

 

-small areas, brownish

 

 

 

 

x

 

x

x

 

x

x

 

 

x

 

 

 

 

 

Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
According to the classification criteria of the EC Directive and taking into account all relevant toxicological findings, the test substance Ethyl trichloroacetate can be described as an irritant at an exposure time of 4 hours.
Executive summary:

Acute dermal irritation was tested in 6 New Zealand White rabbits according to OECD guideline 404. Twenty-four hours before application, a dorsolateral area of the trunk (ca. 25 cm2)of 3 rabbits was shaved. Only animals with an intact skin were used for testing.
0.5 mL undiluted test item was applied on 2.5 x 2.5 cm cellulose adhesive plaster. The plaster was fixed on the shaved area and covered with a semi-occlusive bandage. Exposure time was 3 minutes and 4 hours respectively. After exposure, the remaining test item was gently removed from the skin. Examinations were performed 30-60 minutes and 24, 48 and 72 hours after removal of the plaster. Additional examinations were done after 7 and (in 3 animals) after 14 days, because of findings after 72 hours. Erythema and edema were numerically scored after Draize. All other toxicological significant findings were recorded.

At an exposure time of 3 minutes, very slight to well-defined erythema and barely perceptible edema were observed. No signs of irritation were observed 7 days after application. The skin was merely still dry, brittle or fine-to-rough scaly and in one animal small areas with brownish discoloration were observed.

At an exposure time of 4 hours well-defined to moderate erythema and edema were observed. Mean 24 -72h scores were 1.1/ 4 (3') and 2.1/4 (4h) for erythema and 0.2/4 (3') and 1.4/4 (4h) for edema.14 days after application, the treated skin showed no more irritation. The skin was also dry, brittle, fine-to-rough scaly and brownish.

Accordingto the classification criteriaof the EC Directiveandtaking into account allrelevant toxicological findings, the test substance Ethyl trichloroacetate can be described as an irritant at an exposure time of 4 hours.

 

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
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:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: raised by Hoechst AG, site Hattersheim-Kastengrund near Frankfurt am Main, Germany
- Age at study initiation: Not provided
- Weight at study initiation: 3.3-3.9 kg
- Housing: Individual battery cages
- Diet (e.g. ad libitum): Altromin 2123 Haltungsdiät- Kaninchen, Altromin GmbH, Lage/Lippe, ad libitum
- Water (e.g. ad libitum): deionized, chlorinated water from automatic watering, ad libitum
- Acclimation period: Not provided

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 2°C
- Humidity (%):55 ± 10 %
- Air changes (per hr): Not provided
- Photoperiod (hrs dark / hrs light): 12/12

selection: intact cornea
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): undiluted

left eye treated (conjunctival sac), right eye: control
Duration of treatment / exposure:
24 h
Observation period (in vivo):
72 h
Number of animals or in vitro replicates:
3
Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The treated eyes were thoroughly washed with 37 ° C warm physiological saline.
- Time after start of exposure: 24 hours.

SCORING SYSTEM:
Numerical scores according to Draize

CORNEA
Opacity: Degree of density (area most dense taken for reading)
0 No ulceration or opacity
1* Scattered or diffuse areas of opacity (other than slight dulling of normal lustre), details of iris clearly visible
2* Easily discernible translucent area, details of iris slightly obscured
3* Nacrous area, no details of iris visible, size of pupil barely discernible
4* Opaque cornea, iris not discernible through the opacity

IRIS
0 Normal
1* Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia or injection, any of these or combination of any thereof, iris still reacting to light (sluggish reaction is positive)
2* No reaction to light, haemorrhage, gross destruction (any or all of these)

CONJUNCTIVAE
Redness:
0 Blood vessels normal
1 Some blood vessels definitely hyperaemic (injected)
2* Diffuse, crimson solour, individual vessels not easily discernible
3* Diffuse, beefy red


Chemosis:
0 No swelling
1 Any swelling above normal (including nictitating membranes
2* Definite swelling with partial eversion of lids
3* Swelling with lids about half closed
4* Swelling with lids more than half closed
* means positive effect

TOOL USED TO ASSESS SCORE: fluorescein
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Time point:
24/48/72 h
Score:
0.1
Max. score:
3
Reversibility:
fully reversible within: 48h
Remarks on result:
probability of weak irritation
Irritation parameter:
conjunctivae score
Remarks:
reddening
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 48h
Remarks on result:
probability of weak irritation
Irritation parameter:
conjunctivae score
Remarks:
reddening
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
reddening
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
There were minor irritative symptoms. 1 Hour after application in one of 3 animals slight turbidity in the cornea was seen. The conjunctivae showed redness and swelling at this time. There was small, clear discharge. 24 Hours post application in only one animal, a slight conjunctival redness was observed.
Interpretation of results:
GHS criteria not met
Conclusions:
1) "In accordance with the classification criteria of the EC Directive and taking into account all relevant toxicological findings, the substance Ethyl trichloroacetate is described as non-irritating to the eye." Dr. Rupprich, Department of Toxicology - Toxicology commercial Hoechst Aktiengesellschaft, 1983
2) "In accordance with the classification criteria of EU Directive 83/467/EEC and in consideration of all relevant toxicological findings the substance Ethyl trichloroacetate does not require labeling." Dr. Kreiling, Dr. Jung, Pharma Research Toxicology - Toxicology commercial Hoechst AG, 1996
Executive summary:

Eye irritation was tested in 3 New Zealand White rabbits according to OECD guideline 405.

24 hours before the start of the test the eyes of the animals to be treated, were examined under UV light after instillation of a drop of sodium fluorescein solution (0.01%) for damage of the cornea. Only animals without findings, were taken in the experiment.

In 3 rabbits single application of 0.1 mL of the test substance Ethyl trichloroacetate was performed into the conjunctival sac of the left eye. The untreated eye served as a control. 24 Hours after administration of the test substance, the treated eyes were thoroughly washed with 37 ° C warm physiological saline.

The assessment of the eyes was performed 1, 24, 48 and 72 hours after instillation. Damage to the cornea, iris and conjunctivae were rated numerically according to Draize. All other toxicologically significant findings were recorded. In addition, following administration of a drop of fluorescein sodium solution (0.01% by weight), the eyes were examined 24 and 72 hours after instillation of the test substance under UV light for damage of the cornea.

There were minor irritative symptoms. 1 Hour after application in one of 3 animals slight turbidity in the cornea was seen. The conjunctivae showed redness and swelling at this time. There was small, clear discharge. Mean 24 -72h scores were 0/4 for cornea, 0/2 for iris, 0.1/3 for conjuctival redness and 0/4 for chemosis. 24 Hours post application in only one animal, a slight conjunctival redness was observed.

In accordance with the classification criteria of the EC Directive and taking into account all relevant toxicological findings, the substance Ethyl trichloroacetate is described as non-irritating to the eye.

 

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In a key study (Rupprich and Weigland, 1983), acute dermal irritation of Ethyl chloroacetate was tested in 6 New Zealand White rabbits under semi-occlusive bandage for 3 minutes and 4 hours respectively. After exposure, the remaining test item was gently removed from the skin. At an exposure time of 3 minutes, very slight to well-defined erythema and barely perceptible edema were observed. Mean 24 -72h scores were 1.1/ 4 (3') and 2.1/4 (4h) for erythema and 0.2/4 (3') and 1.4/4 (4h) for edema.No signs of irritation were observed 7 days after application.

The skin was merely still dry, brittle or fine-to-rough scaly and in one animal small areas with brownish discoloration were observed.At an exposure time of 4 hours well-defined to moderate erythema and edema were observed. 14 days after application, the treated skin showed no more irritation. The skin was also dry, brittle, fine-to-rough scaly and brownish.

In a key study (Rupprich and Weigland, 1983), eye irritation was tested in 3 New Zealand White rabbits according to OECD guideline 405 into the conjunctival sac of the left eye; the untreated eye served as a control. 24 Hours after administration of the test substance, the treated eyes were thoroughly washed with 37 ° C warm physiological saline. There were minor irritative symptoms. 1 Hour after application in one of 3 animals slight turbidity in the cornea was seen. The conjunctivae showed redness and swelling at this time. There was small, clear discharge. 24 hours post application in only one animal a slight conjunctival redness was observed. Mean 24 -72h scores were 0/4 for cornea, 0/2 for iris, 0.1/3 for conjuctival redness and 0/4 for chemosis. Findings for conjuctival redness were fully reversible wihting 48 hours.


Justification for selection of skin irritation / corrosion endpoint:
Key study according to regulatory standards

Justification for selection of eye irritation endpoint:
Key study according to regulatory standards

Effects on skin irritation/corrosion: irritating

Justification for classification or non-classification

Based on the results the test substance needs to be classified for skin irritation according to the Directive 67/548/EEC, Annex VI with symbol Xi and the indication of danger “irritant”; the following risk phrase shall be assigned: R38 - Irritating to skin. According to CLP regulation (No. 1272/2008 of 16 December 2008), the test substance is classified as Category 2, with signal word 'Warning' and hazard statement: H315 - Causes skin irritation. 

For the eye, the substance does not need to be classified according to Directive 67/548/EEC, Annex VI and CLP Directive 67/548/EEC, Annex VI.