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Description of key information

2-chlorobenzaldehyde was corrosive to the skin in a study according to OECD TG 404. 
In a study according to OECD TG 405 2-chlorobenzaldehyde was not irritating to the eye.

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:
From 18 SEP 2003 to 24 OCT 2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study (OECD TG 404)
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
other: Japanese White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Kitayama Labes Co., Ltd., Nagano, Japan (Producer, but purchased from Oriental Bioservice Kanto, Inc., Ibaraki, Japan)
- Age at study initiation: 9 to 10 weeks
- Weight at study initiation: 1.98 to 2.27 kg
- Housing: individually housed in in aluminium, automatic water-washing cages for rabbits
- Diet: pelleted feed for experimental animals Cr-3 (Clea Japan, Inc., Tokyo, Japan), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20+/-3
- Humidity (%): 50 +/- 20
- Air changes (per hr): 10 times or more
- Photoperiod (hrs dark / hrs light):12/12

IN-LIFE DATES: From: 30 SEP 2003 To: 15 OCT 2003
Type of coverage:
occlusive
Preparation of test site:
other: clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL/application site

Duration of treatment / exposure:
4
Observation period:
14 days
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 2.5 x2.5 cm² (6.25 cm²)
- Type of wrap if used: lint patch, occluded with adhesive elastic bandage and surgical tape wrapped around the trunk

REMOVAL OF TEST SUBSTANCE
- Washing (if done): after patch removal with Japanese pharmacopoeia water for injection
- Time after start of exposure: 4 h

SCORING SYSTEM: according to OECD TG 404
Irritation parameter:
erythema score
Basis:
mean
Remarks:
: individual scores (animal #1/#2/#3; mean) 1.67/2.3/4
Time point:
24/48/72 h
Score:
2.67
Max. score:
4
Reversibility:
not fully reversible within: 14 d
Remarks on result:
other: scar formation was observed in one animal
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.67
Max. score:
4
Reversibility:
fully reversible within: 10 d
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2.3
Max. score:
4
Reversibility:
fully reversible within: 14 d
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
fully reversible within: 14 d
Remarks on result:
other: scar formation
Irritation parameter:
edema score
Basis:
mean
Remarks:
: individual scores (animal #1/#2/#3; mean) 1.67/2/2
Time point:
24/48/72 h
Score:
1.89
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.67
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 5 d
Remarks on result:
other: scar formation
Irritant / corrosive response data:
Results of 4 hour occlusive exposure (score: #1/#2/#3):
- 1 hour after patch removal: no erythema occurred, but edema was already visible (score: 1/2/3). In animal #3 there was a brown macule obvious at that time, too.
- 24 h reading: eyrthema (score: 1/2/4), edema (1/2/2)
- 48 h reading: eyrthema (score: 2/2/4), edema (2/2/2)
- 72 h reading: eyrthema (score: 2/3/4), edema (2/2/2)
- day 4: eyrthema (score: 2/3/4), edema (2/2/1)
- day 5: eyrthema (score: 2/4/4), edema (1/1/0)
- day 7: eyrthema (score: 1/4/4), edema (0/0/0). In one animal (#1) exafoliation of the skin was visible.
- day 10: eyrthema (score: 0/1/1), edema (0/0/0). In two animals (#1/#2) exafoliation of the skin was visible and in animal #3 proceeded to subcutaneous hemorrhage, necrosis of the skin and scar formation.
- day 14: eyrthema (score: 0/0/0), edema (0/0/0). No effects were seen in animals #1 and #2, but in animal #3 the scar remained.
Other effects:
no other clinical signs occurred
Interpretation of results:
corrosive
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP regulation
Conclusions:
Under the conditions used in this guideline study (OECD TG 404) the test item (2-chlorobenzaldehyde) was corrosive to the skin.
Executive summary:

3 Japanes white rabbits were subjected to test the acute irritation/corrosion potential of the test item (2-chlorobenzaldehyde). According to OECD TG 404 0.5 mL of the indiluted test item were applied onto a lint patch and held at the skin under occlusive conditions for 4 hours. At the relevant readings for classification the test item revealed barely perceptible to severe erythema with slight eschar formation (mean erythema score: 2.67) and very slight to slight edema formation (mean edema score: 1.89). At the end of the observation period two animals were without any dermal reactions, but one animal still had positive dermal reactions, it showed subcutaneous hemorrhage (day 10), eschar formation (day 10) and scar formation (until day 14), which was considered to be a result of necrosis of the skin.

This well performed study which is in accordance with existing guidelines has been selected as key study (RL1).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
December 1985
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: well performed guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes
Remarks:
according to OECD parinciples
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- strain: Hy/Cr
- Source: Charles River France (Saint Aubin les Elbeuf, France)
- Weight at study initiation: mean weight on the day of treatment: 2408 g
- Housing: individually in polystyrene cages
- Diet: pelleted Rabbit Diet SOC, ad libitum
- Water: filtered tap water, ad libitum
- Acclimation period: at least seven days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 +/- 3°C
- Humidity (%): 50% +/- 30%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hrs dark/12 hrs light


- preventive treatment for coccidiosis by application of Mucoxid via drinking water

Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
Amount applied: 0.1 ml
Duration of treatment / exposure:
single exposure
Observation period (in vivo):
4 days following the day of treatment
Number of animals or in vitro replicates:
6
Details on study design:

SCORING SYSTEM:

CONJUNCTIVAE

Redness

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

Chemosis

No swelling 0
Any swelling above normal (includes nictating membranes) 1
Obvious swelling with partial eversion of lids 2*
Swelling with lids about half closed 3*
Swelling with lids more than, half closed 4*

Discharge

Absence of discharge 0
Slight discharge (does not include small amounts normally found in inner canthus) 1
Discharge with moistening of lids and hairs adjacent to lids 2
Discharge with moistening of lids and hairs on considerable area around the eye 3

IRIS

Normal 0
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) 1*
No reaction to light, haemorrhage, gross destruction
(any or all of these) 2*

CORNEA

Opacity : degree of density (area most dense taken for reading)

No ulceration or opacity 0
Scattered or diffuse areas of opacity (other than slight dulling
or normal lustre), details of Iris clearly obscured 1*
Easily discernible translucent area, details of iris slightly obscure 2*
Nacrous area, no details of Iris visible, size of pupil barely discernible 3*
Opaque cornea, iris not discernible through the opacity 4*

Area of opacity

One quarter (or less) but not zero 1
Greater than one quarter but less than a half 2
Greater than one half but less than three quarters 3
Greater than three quarters up to whole area 4

* starred figures indicate positive effect

TOOL USED TO ASSESS SCORE: no data
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
1.17
Max. score:
4
Reversibility:
fully reversible within: 5 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.67
Max. score:
4
Reversibility:
fully reversible within: 4 d
Irritation parameter:
chemosis score
Basis:
animal #2
Remarks:
#3 / #4
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 4 d
Irritation parameter:
chemosis score
Basis:
animal #5
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 4 d
Irritation parameter:
chemosis score
Basis:
animal #6
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 5 d
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 5 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.3
Max. score:
3
Reversibility:
fully reversible within: 4 d
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 3 d
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #3
Remarks:
#4 / #5
Time point:
24/48/72 h
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 4 d
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #6
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 5 d
Irritation parameter:
iris score
Remarks:
degree of congestion
Basis:
mean
Time point:
24/48/72 h
Score:
0.39
Max. score:
2
Reversibility:
fully reversible within: 5 days
Irritation parameter:
iris score
Remarks:
degree of congestion
Basis:
animal #1
Remarks:
#5
Time point:
24/48/72 h
Score:
0.67
Max. score:
2
Reversibility:
fully reversible within: 4 d
Irritation parameter:
iris score
Remarks:
degree of congestion
Basis:
animal #2
Remarks:
#3 / #4
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: no effect
Irritation parameter:
iris score
Remarks:
degree of congestion
Basis:
animal #6
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 5 d
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0.11
Max. score:
4
Reversibility:
fully reversible within: 4 days
Remarks on result:
other: degree if opacity
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 4 d
Irritation parameter:
cornea opacity score
Basis:
animal #2
Remarks:
#3 / #4 / #4 / #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effect
Irritant / corrosive response data:
Chemosis and redness of the conjunctivae were observed in all animals on day 1, 2, and 3. This effect was reversible in 5 animals on day 4 and in all animals on day 5.
Conjunctivae discharge occurred in 3 animals one hour after application, it was still observable in 2 animals on day 2 and in one animal on day 3, but was fully reversible in all animals on day 4.
Congestion of the iris was seen in 3 animals on day 2 and 3 and persisted in one animal till day 4. The effect was fully reversible in all animals on day 5.
Opacity of the cornea was observed in one animal on day 2 and day 3, but was fully reversible on day 4.

Eye irritation evaluation

CONJUNCTIVAE

 day of observation                 Animal No
 CHEMOSIS  01  02  03  04  05  06
 day 1 (1 hour)  2 2  2  2  2
 day 2  3  1  1  1  2
 day 3  2  1  1  1  2  2
 day 4  0  0  0  0  0  2
 day 5            0
 DISCHARGE            
 day 1 (1 hour)  1  1  0  0  0  1
 day 2  2  1  0  0  0  0
 day 3  1  0  0  0  0
 day 4  0  0  0  0
 day 5            0
 REDNESS            
 day 1 (1 hour)  2  2  2  2  2  2
 day 2  2  2  1  1  1  2
 day 3  2  1  1  1  2
 day 4  0  0  0  0  0  2
 day 5            0

 day of observation                 Animal No
 IRIS  01 02   03  04  05  06
 DEGREE OF CONGESTION            
 day 1 (1 hour)  0  0  0  0  0  0
 day 2  1  0  0  0  1  1
 day 3  1  0  0  0  1  1
 day 4  0  0  0  0  1
 day 5            0
 CORNEA            
 DEGREE OF OPACITY            
 day 1 (1 hour)  0  0  0  0  0  0
 day 2  1  0  0  0  0  0
 day 3  1  0  0  0  0  0
 day 4  0  0  0  0
 day 5            0
 AREA OF OPACITY            
 day 1 (1 hour)  0  0  0  0  0  0
 day 2  2  0  0  0  0
 day 3  2  0  0  0  0  0
 day 4  0  0  0  0  0  0
 day 5            0
Interpretation of results:
not irritating
Remarks:
Migrated information conclusion of the study director Criteria used for interpretation of results: EU
Conclusions:
Based on the study results, 2-chlorobenzaldehyde was not irritating to the eye.

Executive summary:

Eye irritation of 2-chlorobenzaldehyde has been investigated in New Zealand rabbits. In a study according to OECD TG 405 chemosis and redness for all animals, and discharge for three animals were observed on day 1. Congestion of iris for three animals and an opacity of cornea for one animal were observed on day 2. These reactions regressed from day 3 until day 5 and were fully reversible at the end of the observation period (day 5 post application).

This well performed study, which is in accordance with existing guidelines, has been selected as key study (RL1).

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

Additional information

In the key study 3 Japanes white rabbits were subjected to test the acute irritation/corrosion potential of the test item (2-chlorobenzaldehyde). According to OECD TG 404 0.5 mL of the indiluted test item were applied onto a lint patch and held at the skin under occlusive conditions for 4 hours. At the relevant readings for classification the test item revealed barely perceptible to severe erythema with slight eschar formation (mean erythema score: 2.67) and very slight to slight edema formation (mean edema score: 1.89). At the end of the observation period two animals were without any dermal reactions, but one animal still had positive dermal reactions, it showed subcutaneous hemorrhage, necrosis of the skin and scar formation.

Other studies on dermal irritation of 2-chlorobenzaldehyde were performed usind New Zealand white rabbits. Another guideline study (OECD TG 404) revealed differing results from the key study. In this study only a very slight erythema (one animal) and a well defined erythema (five animals) were observed 24 hours after removal of the patches. They were associated to an oedema for three animals (a very slight oedema in one animal and a slight oedema in two others). These skin reactions were fully reversible at the end of the observation period (day 5 post application). The mean scores for erythema and oedema were below the critical values for irritation.

There are two further studies of restricted reliability, which support the findings of the key study. In the first study, which was not in accordance with existing guidelines, the application of the test item to the inner ear of rabbits for 24 hours resulted in strong irritation and corrosion of the skin. Additionally, strong skin irritation has been reported for guinea pigs which received 5000 to 20000 mg/kg bw. However both studies were judged not to be reliable due to insufficient documentation and some methodological deficiencies. Due to the scar formation documented in the key study it is recommended to classify 2-chlorobenzaldehyde as corrosive to the skin.

Eye irritation of 2-chlorobenzaldehyde has been investigated in New Zealand rabbits in a study according to OECD TG 405. Chemosis and redness for all animals, and discharge for three animals were observed on day 1. Congestion of iris for three animals and an opacity of cornea for one animal were observed on day 2. These reactions regressed from day 3 to day 5 and were fully reversible at the end of the observation period (day 5 post application). Mean scores for cornea opacity, iris lesions, redness and chemosis of the conjunctivae were all below the critical values for irritation. The data of this key study are supported by data of an other study, which has been judged not to be reliable due to insufficient reporting.


Effects on skin irritation/corrosion: corrosive

Justification for classification or non-classification

According to Annex VI of the Directive 67/548/EEC and REGULATION (EC) No 1272/2008, classification as corrosive to the skin is recommended for 2-chlorobenzaldeyhde due to the fact that the positive dermal reactions were not reversible within the observation period and necrosis of the skin and scar formation were documented in one animal.

Due to only minimal irritation reactions of the eyes described in the key study 2-chlorobenzaldehyde has not to be classified for eye irritancy according to Annex VI of the Directive 67/548/EEC and REGULATION (EC) No 1272/2008.