Registration Dossier

Administrative data

Description of key information

In a study according to OECD guidelines 404 and 405 1,4-dichlorobenzene shows no acute potential for skin irritation/corrosion and also no local risk potential for eye irritation (Märtins 1988). However, based on limited data from workplace exposure irritating effects on the mucous membranes on eyes and nose are difficult to interprete and indicate a certain irritation potential.

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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: No GLP defined.
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 3,4- 3,5 kg.
- Housing: individually
- Diet ad libitum
- Water ad libitum
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20
- Humidity (%): 50
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 / 12
Type of coverage:
semiocclusive
Preparation of test site:
other: clipped
Vehicle:
other: parafine oil
Controls:
other: the contralateral side was untreated and served as control
Amount / concentration applied:
500 mg paradichlorbenzene moistened with parafine oil on a 6 cm² skin surface.
Duration of treatment / exposure:
4 hours.
Observation period:
7 days
Number of animals:
3
Details on study design:
500 mg paradichlorbenzene moistened with parafine oil was applied on a 6 cm² skin surface of the back of 3 rabbits covered with a semiocclusive plaster for 4 hours (the contralateral side was untreated and served as control). After termination of treatment the respective areas were washed with water and observed for 7 days
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24-72 hours
Score:
>= 0.7 - <= 1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
mean
Time point:
other: total observation time
Score:
ca. 0
Max. score:
4
Irritant / corrosive response data:
Based on the observed erythema score of 1 of max 4(in 2 rabbits at 24,48,72 h and 1 rabbit at 48 and 72 h) which recovered within 7 days and no edema during the total observation time , the test substance is evaluated as slightly irritating to the skin of rabbits which do not lead to classification

No edema observed.

   Draize grade after        
   1h 24h  48h  72h  7d 
  Erythema   Erythema    Erythema    Erythema    Erythema  
Rabbit 1   1  1  1
Rabbit 2 0  1  1  0
Rabbit 3   0  1  1  0
Interpretation of results:
slightly irritating
Remarks:
Migrated information
Executive summary:

Skin irritation was tested using the OECD TG 404 in rabbits.500 mg paradichlorbenzene moistened with parafine oil was applied on a 6 cm² skin surface of the back of 3 rabbits covered with a semiocclusive plaster for 4 hours (the contralateral side was untreated and served as control). After termination of treatment the respective areas were washed with water and observed for 7 days. p-Dichlorobenzene evoked no systemic reactions but slight and passagere erythema on skin of adult rabbits (total irritation score: 0.7- 1.0 with total recovery within 7 days and no edema). These very mild skin reactions can be evaluated as no acute risk potential for skin of rabbits and do not lead to classification or labelling

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not 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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: No GLP defined.
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 3,4- 3,5 kg.
- Housing: individually
- Diet ad libitum
- Water ad libitum
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20
- Humidity (%): 50
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 / 12
Vehicle:
not specified
Controls:
other: the untreated second eye served as control
Amount / concentration applied:
100 µl (bulk volume = ca 90 mg test substance)
Duration of treatment / exposure:
24 hours
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
3
Details on study design:
Ca 90 mg ofundissolved test substance was applied into the conjunctival sac of one eye (ther other served as control) of each of 3 rabbits; lids were pressed together for one second. 24 hours later the treated eyes were rinsed with saline solution and observed for further 7 days. Eye reactions were evauated according to Draize.
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 7d
Score:
ca. 0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: not irritant or corrosive
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: 7d
Score:
ca. 0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: not irritant or corrosive
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: 7d
Score:
ca. 0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: not irritant or corrosive
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: 7d
Score:
ca. 0
Max. score:
2
Reversibility:
fully reversible
Remarks on result:
other: not irritant or corrosive
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: 7d
Score:
ca. 0
Max. score:
2
Reversibility:
fully reversible
Remarks on result:
other: not irritant or corrosive
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: 7d
Score:
ca. 0
Max. score:
2
Reversibility:
fully reversible
Remarks on result:
other: not irritant or corrosive
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 7d
Score:
ca. 0
Max. score:
3
Reversibility:
fully reversible
Remarks on result:
other: not irritant or corrosive
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: up to 48h
Score:
ca. 1
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: a reddening an swelling was observed
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: 7d
Score:
ca. 0
Max. score:
3
Reversibility:
fully reversible
Remarks on result:
other: not irritant or corrosive
Irritant / corrosive response data:
No irritating effects were observed

no irritant or corrosive effect in rabbit eye.

Interpretation of results:
not irritating
Remarks:
Migrated information
Executive summary:

Eye irritation was tested in rabbits using the OECD TG 405. Ca 90 mg of undissolved test substance was applied into the conjunctival sac of one eye (the other served as control) of each of 3 rabbits and lids were pressed together for one second. 24 hours later the treated eyes were rinsed with saline solution and observed for further 7 days. Eye reactions were evauated according to Draize.

P-dichlorobenzene had no irritating or corrosive effect in adult rabbit eyes.Therefore no local risk potential for eyes of rabbits exists

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

Additional information

Skin irritation/corrosion

Skin irritation was tested using the OECD TG 404 in rabbits.500 mg paradichlorbenzene, moistened with parafine oil, was applied on a 6 cm² skin surface of the back of 3 rabbits covered with a semiocclusive plaster for 4 hours (the contralateral side was untreated and served as control). After termination of treatment the respective areas were washed with water and observed for 7 days. p-Dichlorobenzene evoked no reactions attributable to systemic toxisitx but slight and passagere erythema on skin of adult rabbits (total irritation score: 0.7- 1.0 with total recovery within 7 days and no edema). These very mild skin reactions can be evaluated as no acute risk potential for skin of rabbits and do not lead to classification or labelling

Eye irritation

Eye irritation was tested in rabbits using the OECD TG 405. Ca 90 mg of undissolved test substance was applied into the conjunctival sac of one eye (the other served as control) of each of 3 rabbits and lids were pressed together for one second. 24 hours later the treated eyes were rinsed with saline solution and observed for further 7 days. P-dichlorobenzene had no irritating or corrosive effect in adult rabbit eyes.Therefore no local risk potential for eyes of rabbits exists

However, in workers exposed in operation involving the handling of 1,4-dichlorobenzene (58 workers, 8 hours/day, 5 days/week, for 8 months to 25 years with an average of 4.75 years), several surveys were conducted (Hollingsworth, 1956); irritation complaints appear evident at a vapour concentration between 50 and 80 ppm; irritation becomes severe at concentration greater than approximately 160 ppm and is accompanied by signs of pulmonary irritation. Certain individuals develop acquired tolerance after repeated exposures. In this old study, it was not specified if workers were exposed to others chemicals than 1,4-dichlorobenzene; moreover, concentration data are range concentrations with median values, in which peak exposure concentrations cannot be excluded (results of spot samples of atmosphere) and no clear correlation between concentration and effect can be done; no more information are available in this study to clarify the respiratory symptoms and the concentration levels (Hollingsworth, 1956).

Conclusion:

1,4-dichlorobenzene is not irritating/corrosive in animal experiments. Limited human data are difficult to interpret and indicate a certain irritation potential.


Justification for selection of skin irritation / corrosion endpoint:
the only available guideline study which is evaluated with Klimisch score 2

Justification for selection of eye irritation endpoint:
The only available animal study which is performed according to guideline and evaluated with Klimisch score 2. However, observations in humans cannot be neglected.

Effects on eye irritation: slightly irritating

Justification for classification or non-classification

Based on the considerations above p-dichlorobenzene is not classified or labelled as irritating or corrosive to the skin.

Although the results from animal experiments do not indicate irritation effects on the mucous membranes, but taking into account the observations in humans at workplace classification and labelling with R36 (irritating to the eyes) according to Directive 67/548/EEC and allocating to Category 2 (H319) of the eye irritating substances according to Regulation (EC) No1272 / 2008 should be considered.