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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From third of September to twenty seventh of September 1996
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study. No restrictions or deviations to the guideline observed
Justification for type of information:
Study was equivalent to a LLNA study and followed the OECD guideline 406. GLP guideline study. No restrictions or deviations to the guideline observed

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The study was performed accordingly to OECD 406.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): benzoyl chloride - CAL 5565/96
- Physical state: colourless liquid
- Analytical purity: 99.97 %
- Impurities (identity and concentrations): benzyl chloride 0.01 % and benzl chloride 0.01 %
- Composition of test material, percentage of components:
- Isomers composition:
- Purity test date: 1996.07.02
- Lot/batch No.: batch C 650
- Expiration date of the lot/batch: July 1997
- Stability under test conditions:
- Storage condition of test material: in dark at room temperature
No other data

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, St-Aubin-Les-Elbeuf, France
- Weight at study initiation: between 313 and 408 grams
- Housing: in individual propylene cage
- Diet (e.g. ad libitum): complete pelleted diet UAR 106
- Water (e.g. ad libitum): tap water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
According to OECD standards

IN-LIFE DATES: From: 1996.09.03 To: 1996.09.27

No further information

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: mineral oil
Concentration / amount:
The concentration of test substance up to 5 % of allergen used for each induction exposure has been well-tolerated systemically and was the highest non-irritant dose. This appropriate concentration was determined from a pilot study using three FCA pre-treated animals.
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: mineral oil
Concentration / amount:
The concentration of test substance up to 5 % of allergen used for each induction exposure has been well-tolerated systemically and was the highest non-irritant dose. This appropriate concentration was determined from a pilot study using three FCA pre-treated animals.
No. of animals per dose:
20 animals for the dosed group and 10 for the control group
Details on study design:
The study was performed accordingly to OECD 406.
Olive oil (Cooper - batch 12616-81722) and/or mineral oil (Sigma - batch 85H 1102) were chosen as the vehicles for benzoyl chloride depending the concentration wanted.
The maximal non irritant concentration was established in a range finding study accordingly to the OECD 406 study design on three extra guinea-pigs.
Challenge controls:
Performed accrodingly to OECD 406 with olive oil and/or mineral oil as the vehicles
Positive control substance(s):
yes
Remarks:
2-mercapto benzothiazole

Results and discussion

Positive control results:
Highly sensitizing for guinea pig female, 70 % of reactive animals at the reading 48 hours - class 4 when it was used diluted at 5 % and 2 % with mineral oil

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0
No. with + reactions:
3
Total no. in group:
10
Clinical observations:
Weight growth satisfactory and no mortality observed
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0. No with. + reactions: 3.0. Total no. in groups: 10.0. Clinical observations: Weight growth satisfactory and no mortality observed.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
5 % and 2 % benzoyl chloride
No. with + reactions:
18
Total no. in group:
20
Clinical observations:
Weight growth satisfactory and no mortality observed
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 5 % and 2 % benzoyl chloride. No with. + reactions: 18.0. Total no. in groups: 20.0. Clinical observations: Weight growth satisfactory and no mortality observed.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
Weight growth satisfactory and no mortality observed
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: Weight growth satisfactory and no mortality observed.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
5 % and 2 % benzoyl chloride
No. with + reactions:
19
Total no. in group:
20
Clinical observations:
Weight growth satisfactory and no mortality observed
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 5 % and 2 % benzoyl chloride. No with. + reactions: 19.0. Total no. in groups: 20.0. Clinical observations: Weight growth satisfactory and no mortality observed.

Applicant's summary and conclusion

Interpretation of results:
sensitising
Remarks:
Migrated information
Conclusions:
In the test conditions, the authors established that benzoyl chloride should be considered as sensitizing by contact with the skin to female Guinea-pigs according to the criteria of the EU directive 67/548/EEC since 90 % of the test animals exhibited skin sensitization responses.
Executive summary:

In this study, the authors tested the sensitizing potential to the skin of benzoyl chloride (CAS n° 98 -88 -4) on Guinea pigs (Hartley) in a maximization tests according to the OCED guideline n°406 in a GLP compliant laboratory. The tested animals weighed between 313 and 408 grams initially. Benzoyl chloride skin sensitizing potential was tested at 2 and 5 % after a determination of the maximal non irritant concentration to the skin on three FCA pre-treated animals. No deviations or restrictions to the OECD guideline are noted. All observations and determinations were performed accordingly to the OECD guideline.

Hence, in the test conditions, the general state of health of all guinea-pigs remained satisfactory throughout the study period. The weight gain was normal and no mortality was observed. For the challenge exposure, benzoyl chloride diluted at 5 % and 2 % with mineral oil were retained from the range finding study.

Furthermore, in the control group, 24 hours after the patch removal, a slight cutaneous reaction reversible in less than 24 hours was noted in three and two animals respectively. For the tested group, the application of benzoylchloride induced the formation of a slight to well defined eryhtemae in 90 % of the animals. This reaction persisted 48 hours after patch removal.

Thus, in the test conditions, benzoyl chloride should be considered as sensitizing by contact with the skin according to the criteria of the EU directive 67/548/EEC since 90 % of the test animals exhibited skin sensitization responses.

This study is fully compliant to the OECD requirements and well described. This study is then considered as reliable without restrictions.