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Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non GLP defined.
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
not specified
Type of study:
guinea pig maximisation test
Species:
guinea pig
Strain:
Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 460 g
- Housing: individually
- Diet ad libitum
- Water ad libitum
- Acclimation period: 11 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.5
- Humidity (%): 55
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12/ 12
Route:
intradermal and epicutaneous
Vehicle:
other: peanut oil, vaseline, 1,2-propylene glycol. 95 % Ethanol
Concentration / amount:
INTRADERMALE INDUKTION
--Test substance: 0.1 % P-dichlorobenzene in peanut oil.
control group: peanut oil
--positve substance(2,4-Dichloronitrobenzene): 0.02 % in 1,2-propylene glycol
control group: propylene glycol
EPIKUTANE INDUKTION
--test substance :25 % p-dichlorobenzene in vaseline
control group: vaseline
--positive substance (2,4 dichloronitrobenzene)0.05 % in 95% Ethanol
control group: 95 % ethanol
EPIKUTANE CHALLENGE
--testsubstance and control group 25 % p-dichlorobenzene in vaseline
--positive substance and control group 0.05 2,4-dinitrochlorobenzene in 95 % ethanol
Route:
epicutaneous, semiocclusive
Vehicle:
other: peanut oil, vaseline, 1,2-propylene glycol. 95 % Ethanol
Concentration / amount:
INTRADERMALE INDUKTION
--Test substance: 0.1 % P-dichlorobenzene in peanut oil.
control group: peanut oil
--positve substance(2,4-Dichloronitrobenzene): 0.02 % in 1,2-propylene glycol
control group: propylene glycol
EPIKUTANE INDUKTION
--test substance :25 % p-dichlorobenzene in vaseline
control group: vaseline
--positive substance (2,4 dichloronitrobenzene)0.05 % in 95% Ethanol
control group: 95 % ethanol
EPIKUTANE CHALLENGE
--testsubstance and control group 25 % p-dichlorobenzene in vaseline
--positive substance and control group 0.05 2,4-dinitrochlorobenzene in 95 % ethanol
No. of animals per dose:
24 female guinea pigs: test subjects.
24 female guinea pigs: negative control group.
10 female guinea pigs: positive control group (2,4-dinitroclorobenzene).
10 female guinea pigs: control group
10 female guinea pigs: negative control group (2,4-chlorodinitrobenzene).
Details on study design:
experimental day 0: intradermal induction
experimental day 7: epidermal induction
experimental day 21 epidermal challenge
experimental day 23: evaluation of the skin in test animals and control animals
Challenge controls:
yes
Positive control substance(s):
yes
Remarks:
2,4-dinitrochlorobenzene
Positive control results:
24 hours post application of the challenge 9/10 animals treated with 2,4 dinitrochlorobenzene showed positive reactions
48 hours post application of the challenge 10/10 animals treated with 2,4-dinitrochlorobenzene showed marked reactions.
In the respective control group no skin reaction was observed
Reading:
other: reading
Hours after challenge:
48
Group:
test group
Dose level:
25 % in vaseline
No. with + reactions:
5
Total no. in group:
24
Clinical observations:
no mortality, reduction of mean bodyweight when compared to the respective control
Remarks on result:
other: see Remark
Remarks:
Reading: other: reading. . Hours after challenge: 48.0. Group: test group. Dose level: 25 % in vaseline. No with. + reactions: 5.0. Total no. in groups: 24.0. Clinical observations: no mortality, reduction of mean bodyweight when compared to the respective control .
Reading:
other: reading
Hours after challenge:
48
Group:
test group
Dose level:
25 % in vaseline
No. with + reactions:
4
Total no. in group:
5
Clinical observations:
evaluated as sensitized (16.4 %)
Remarks on result:
other: Reading: other: reading. . Hours after challenge: 48.0. Group: test group. Dose level: 25 % in vaseline. No with. + reactions: 4.0. Total no. in groups: 5.0. Clinical observations: evaluated as sensitized (16.4 %).
Reading:
other: reading
Hours after challenge:
24
Group:
negative control
Dose level:
vasiline only
No. with + reactions:
3
Total no. in group:
24
Clinical observations:
slight redness of the skin in control animals was evaluated as unspecific reaction
Remarks on result:
other: see Remark
Remarks:
Reading: other: reading. . Hours after challenge: 24.0. Group: negative control. Dose level: vasiline only. No with. + reactions: 3.0. Total no. in groups: 24.0. Clinical observations: slight redness of the skin in control animals was evaluated as unspecific reaction.
Reading:
other: reading
Hours after challenge:
48
Group:
negative control
Dose level:
vaseline only
No. with + reactions:
1
Total no. in group:
24
Clinical observations:
evaluated as sensized animal
Remarks on result:
other: Reading: other: reading. . Hours after challenge: 48.0. Group: negative control. Dose level: vaseline only. No with. + reactions: 1.0. Total no. in groups: 24.0. Clinical observations: evaluated as sensized animal.

A Magnusson and Klingman test on guinea pigs (EEC method, 24 controls, 24 test animals, at induction concentrations of 0.1% intradermally and 25% topically and at challenge concentrations of 25% in petrolatum, positive controls used) demonstrates a rather weak potential for sensitization. At 0.1% intradermally in pre-test, slight irritation was observed in animals. The maximum non-irritating concentration was greater than 25% after topical application because at 25% in petrolatum, no irritation was observed in a pre-test; Sodium Lauryl Sulfate was not applied. Five of the 24 animals in the 1,4-paradichlorobenzene group had positive skin reactions after the challenge exposure. As a positive skin reaction was also detected in one of 24 animals in the negative control group, a total of four of 24 animals in the test group was regarded as sensitized (16,7%). According to the scheme of Magnusson and Klingman the sensitizing potential of 1,4-dichlorobenzene is therefore rated as mild.. No histological examination was conducted (Bornatowicz 1995).

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

According to OECD TG 406 the Guinea Pig Maximization Test according to Magnusson and Klingman was carried out to reveal a possible sensitizing potential of Paradichlorobenzene. Five of the 24 animals in the Paradichlorobenzene-group had positive skin reactions after the challenge exposure. As a positive skin reaction was also detected in one of 24 animals in the negative control group, a total of four of 24 animals in the test group was regarded as sensitized, i.e., 16,7%.

According to the gading and evaluating system given by Magnusson and Klingman the sensitizing potential of Paradichlorobenzene is therefore rated to be mild. The concurrent positive control substance induced clear reaction in all animals.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

According to OECD TG 406 the Guinea Pig Maximization Test according to Magnusson and Kligman was carried out to reveal a possible sensitizing potential of Paradichlorobenzene. Five of the 24 animals in the paradichlorobenzene-group had positive skin reactions after the challenge exposure. As a positive skin reaction was also detected in one of 24 animals in the negative control group, a total of four of 24 animals in the test group was regarded as sensitized, i.e., 16,7%.

According to the grading and evaluating system given by Magnusson and Kligman the sensitizing potential of Paradichlorobenzene is rated to be mild. The concurrent positive control substance induced clear reaction in all animals (Bornatovitc1995)

In addition, the skin sensitizing potential of p-dichlorobenzene was tested in the "open epicutan test" according to Klecak and under GLP conditions. The animals were pretreated with 1, 3, 10 and 30% solution of Paradichlorobenzene in paraffine oil , controls were treated with parafine oil only (all groups 20 times during 4 weeks). Challenges with 1, 3, 10 and 30% solutions in paraffine oil induced no skin hypersensivity response neither in the test groups nor in control animals.

Overall, there is a case for stating that 1,4 dichlorobenzene has a very weak sensitization potential given the animal data and only questionable human case (see Nalbandian 1965) reported despite the widespread use of 1,4 -dichlorbenzene for many years in occupational settings and consumer settings and the possible direct handling use. In animals the open epicutaneous test gave a negative result but for the maximization study interpretation of the results is difficult. Thus , there is no sufficient argument to classify 1,4 -dichlorobenzene as a sensitizer or to request an animal study (EU-RAR 2004)

Migrated from Short description of key information:
A Magnusson and Klingman test on guinea pigs (EEC method, 24 controls, 24 test animals, , positive controls used) demonstrates a rather weak potential for sensitization (4/24 animals positive) (Bornatowicz 1995).
An open epicutaneous test (Klecak) on guinea pigs (8 controls, 8 test animals treated at concentrations of 30, 10, 3 and 1% in paraffin oil) did not reveal any signs of sensitisation on days 32 and 46. Signs of irritation were observed at induction (Schmidt 1985).

Justification for selection of skin sensitisation endpoint:
This is the only study according to OECD TG 406 and is carefully reported although GLP conditions are not mentioned. Therefore , the study was evaluated with Klimisch score 2

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the considerations on skin sensitization potential of p-dichlorobenzene no classification or labelling according to EU directive 67/548/EEC or Regulation (EC) No 1272, 2008 is required