Registration Dossier

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1986-10-27 to 1986-12-05
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-compliant study according to internationally accepted testing guideline OECD 406.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report Date:
1986

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
: Number of animals
Principles of method if other than guideline:
Number of tested animals: 10
Number of animals in control group: 5
GLP compliance:
yes
Type of study:
guinea pig maximisation test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
p-Chlorobenzyl chloride D
State of matter: solid

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Pirbright -White
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Guinea pig, strain: Pirbright-White
- Source: Hoechst AG, Kastengrund, SPF-Zucht
- Weight at study initiation: 317 g
- 15 ( female)

ENVIRONMENTAL CONDITIONS
- Diet: ERKA-Mischfutter Nr. 8300 für Meerschweinchen und Kaninchen (ad libitum)
- Water: tap water (ad libitum)
- Temperature: 22 °C +/- 3 °C
- Humidity: 50 % +/- 20 %
- Photoperiod (hrs dark / hrs light): 12 / 12
- Acclimation: > 5 days
- Housing: 4 animal per cage

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: induction: paraffin oil; challenge: vaseline
Concentration / amount:
1 % test substance for intradermal and epicutaneous treatment
Challenge
Concentration / amount:
1 % test substance for intradermal and epicutaneous treatment
No. of animals per dose:
10 (dose group)
5 (control groups and satellite group)
Details on study design:
RANGE FINDING TESTS:
Estimation of the concentration for epicutaneous induction and challenge treatment:
Epicutaneous application of p-chlorobenzyl chloride at concentrations of 10%, 1%, and 0.1% in vaseline (6 animals).
Dermal treatment with 10 % test item caused barley perceptible erythema and slight edema. 1 % and 0.1 % did not cause any skin reactions.
Estimation of the concentration for intradermal induction exposure:
Injection of p-chlorobenzyl chloride at concentrations of 5%, 1%, and 0.2% in paraffin oil (3 animals).
Intradermal injection of 0.2 % test item caused slight erythema and edema. 1 % and 5 % caused more severe erythema and edema. 5 % caused also hardening of the skin.
Satellite group:
Dermal treatment with 1 % test item of the animals pre-treated with Freud's adjuvans did not result in skin reactions.
Based on these results, 1 % was selected as concentration for intradermal and dermal treatemtent.


MAIN STUDY

A1. INDUCTION EXPOSURE (intradermal)
- Test group: Position 1: 2 x 0.1 mL 50 % Freunds Complete Adjuvant (FCA); Position 2: 2 x 0.1 mL 1 % in paraffin oil; Position 3: 2 x 0.1 mL 1 % in FCA
- Control group: Position 1: 2 x 0.1 mL 50 % Freunds Complete Adjuvant (FCA); Position 2: 2 x 0.1 mL paraffin oil; Position 3: 2 x 0.1 mL 50 % FCA
- Satellite group: Position 1: 2 x 0.1 mL 50 % Freunds Complete Adjuvant (FCA); Position 2: 2 x 0.1 mL paraffin oil; Position 3: 2 x 0.1 mL 50 % FCA
- Site: upper ridge (near shoulder region)
- Frequency of applications: 1
- Concentrations: 1%

A2. INDUCTION EXPOSURE (dermal)
- No. of exposures: 1
- Exposure period: 48 h
- Test group: 1% in vaseline
- Control group: vaseline
- Satellite group: vaseline
- Site: intradermal exposure sites
- Concentrations: 1%

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day of challenge: 22 (test group/control group), 15 (satellite group)
- Exposure period: 24 h
- Test group: 1% in vaseline
- Control group: 1% in vaseline
- Satellite group: 1% in vaseline
- Site: left flank
- Concentrations: 1%
- Evaluation (hr after challenge): 48 h, 72 h
Challenge controls:
see above

Results and discussion

Positive control results:
not applicable

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
1.0 % p-Chlorobenzyl chloride
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
Erythema: score 3 (mean); oedema: score 1.8 (mean, 6/10); scab: 8/10 animals
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 1.0 % p-Chlorobenzyl chloride. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: Erythema: score 3 (mean); oedema: score 1.8 (mean, 6/10); scab: 8/10 animals.
Reading:
2nd reading
Hours after challenge:
72
Group:
test group
Dose level:
1.0 % p-Chlorobenzyl chloride
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
Erythema: score 3.1 (mean); oedema: score 2 (mean, 3/10); scab: 7/10 animals
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 72.0. Group: test group. Dose level: 1.0 % p-Chlorobenzyl chloride. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: Erythema: score 3.1 (mean); oedema: score 2 (mean, 3/10); scab: 7/10 animals.
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
1.0 % p-Chlorobenzyl chloride
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
Erythema and oedema: Score 0 (mean)
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 1.0 % p-Chlorobenzyl chloride. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: Erythema and oedema: Score 0 (mean).
Reading:
2nd reading
Hours after challenge:
72
Group:
negative control
Dose level:
1.0 % p-Chlorobenzyl chloride
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
Erythema and oedema: Score 0 (mean)
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: negative control. Dose level: 1.0 % p-Chlorobenzyl chloride. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: Erythema and oedema: Score 0 (mean).
Reading:
1st reading
Hours after challenge:
48
Group:
other: satellite
Dose level:
1.0 % p-Chlorobenzyl chloride
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
Erythema and oedema: Score 0 (mean)
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group:
Reading:
2nd reading
Hours after challenge:
72
Group:
other: satellite
Dose level:
1.0 % p-Chlorobenzyl chloride
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
Erythema and oedema: Score 0 (mean)
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 72.0. Group:

Applicant's summary and conclusion

Interpretation of results:
sensitising
Remarks:
Migrated information
Executive summary:

In a guinea pig maximisation test p-chlorobenzyl chloride was tested at a challenge concentration of 1% in vaseline. The animals were induced with 1 % test item in paraffin oil and vaseline for intradermal and dermal induction, respectively. No signs of systemic toxicity were observed in the dose group during the study. All test group animals showed signs of sensitisation following challenge treatment. In the control group and satellite group, no local effects were registered after the challenge. In this study it was demonstrated that p-chlorobenzyl chloride is a dermal sensitizer.