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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
August-December 2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well-documented and corresponded to the requirements of the recommended Annex V Test Guidelines.
Justification for data waiving:
other:

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2003

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
Two deviations: No. 1 section 6.1 Animal Specification - Four control animals were used, since one of the male control animals died during the acclimatisation period. No.2: section 6.2 Husbandry - On some days the relative humidity was higher than 70%.
GLP compliance:
yes (incl. certificate)
Type of study:
guinea pig maximisation test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): LITHARGE lead oxide
- Molecular formula (if other than submission substance): PbO
- Physical state: fine, yelllow powder
- Analytical purity: 99.8% lead (II) oxide
- Composition of test material, percentage of components: PbO: 99.8; metallic Pb: <0.01; Pb3O4: 0.003; Cu:<0.0001: Fe: 0.0008
- Lot/batch No.: 210213
- Expiration date of the lot/batch: May 2005
- Storage condition of test material: At room temperature

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: pirbright white
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland GmbH
- Weight at study initiation: males 461-492 g; females: 405-484 g
- Housing: The guinea pigs were kept in collective housing up to a maximum of 5 animals per cage in a battery of cages, equipped with a paper disposal system.
- Diet (e.g. ad libitum): 2040 Teklad Global Guinea Pig Diet offerred ad libitum.
- Water (e.g. ad libitum):Tap water as for human consumption was continuously available ad libitum via drinking nipples.
- Acclimation period: 19 days (range finding); 22 days (main test)


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3 degrees centigrade. Maximum and minimum temperature and humidity were monitored daily.
- Humidity (%): The relative humidity was kept between 37 and 76%.
- Air changes (per hr): 16 times per hour and filtered adequately.
- Photoperiod (hrs dark / hrs light): 12 hrs dark/ 12 hrs light with light on at 7:00 AM.

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: For the intradermal injection, the test article was diluted with aqua ad iniectabilia and Freund's complete adjuvant to a final concentration of 5%. For the dermal application, the solid test article was used as 50% formulation in petrolatum.
Concentration / amount:
Intradermal injection- 5% of the test article
Dermal application 50% in petrolatum
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: For the intradermal injection, the test article was diluted with aqua ad iniectabilia and Freund's complete adjuvant to a final concentration of 5%. For the dermal application, the solid test article was used as 50% formulation in petrolatum.
Concentration / amount:
Intradermal injection- 5% of the test article
Dermal application 50% in petrolatum
No. of animals per dose:
10 test and 4 control animals
Details on study design:
RANGE FINDING TESTS: Two animals were employed and skin reactions were recorded 48 and 72 hours post applicationem. For the both the intradermal injection and the dermal application. For the intradermal injection, the test article was diluted with aqua ad iniectabilia and Freund's complete adjuvant to a final concemtration of 5%. Two animals were employed, skin reactions being recorded 48 and 72 hours after treatment. For the dermal application, the solid test article was used as 50% formulation in petrolatum. A closed patch exposure was effected by means of an occlusive bandage using cellulose swabs and non-irritating tape which enveloped the whole animal's trunk.


MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: Seven days after injections, the injection sites were covered occlusively for 48 hours.
- Test groups: 10
- Control group: 4
- Site: Injections were made in the clipped intracapsular region on either side of the spine
- Frequency of applications: Three pairs of intradermal injections (0.1 ml)
- Duration: Seven days later, the previous injection sites were covered occlusively for 48 hours with a patch carrying the test article (50%) or, in control animals, the control article petrolatum.
- Concentrations: Test Group 1) FCA 50% (v/v) diluted in aqua ad iniectabilia, 2) test article 5% in peanut oil, 3) test article 5% in aqua ad iniectabilia/F CA. Control group: 1) FCA 50% (v/v) diluted in aqua ad iniectabilia, 2) peanut oil, 3) peanut oil 50% (v/v) diluted in FCA.


B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 14 days after the second stage of the induction
- Exposure period: 24 hours
- Test groups: 10 test animals
- Control group: 4 control animals
- Site: The challenge test was performed on a 5 x 5 cm clipped skin area on each flank.
- Concentrations: The challenge test was applied at the concentration of 50% to the left flank and the control article petroleum to the right in a volume of 0.5 g using the patch tehnique.
- Evaluation (hr after challenge): 24 and 48 hours after patch removal the appearance of the challenge and re-challenge skin sites was observed and skin responses were graffed on the basis of the classification system according DRAIZE. The animals were weighed before treatment and at the end of the study. All findings were recorded with respect to duration and severity on special report forms.


OTHER:
Challenge controls:
Both control and test animals were subjected to a challenge exposure 14 days after the second stage of the induction. The challenge test was performed on a 5 x 5 cm clipped skin area on each flank. The test article was applied at the concentration of 50% to the left flank and the control article petrolatum to the right in a volume of 0.5 g using the patch technique. In each case, the duration of the exposure was 24 hours under an occlusive dressing.
Positive control substance(s):
yes

Study design: in vivo (LLNA)

Vehicle:
other: 4-aminobenzoic acid ethyl ester (benzocaine)
Concentration:
50 and 25% in vaseline
No. of animals per dose:
10
Details on study design:
The sensitivity of the test system and the reliability of the experimental technique is assessed at least every 6 months by use of "4-aminobenzoic acid ethyl ester (benzocaine) which is known to induce skin sensitisation in guinea pigs. This test was conducted as a Magnusson & Kliggman test according to the OECD Guideline for Testing of Chemicals, OECD 406, 17 July 1992 and to the EEC Directive 2001/59/EEC, 6 August 2001. The last test
with acceptable levels of responses to this substance was performed from April 8 to 2 May 2003.

Results and discussion

Positive control results:
Sensitisation rate 50% at 24 h: 70% Sensitisation Rate 50% at 48 h: 70%
Sensitisation rate 25% at 24 h: 30% Sensitisation Rate 25% at 48 h: 20%

In vivo (non-LLNA)

Results
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
50% in petrolatum
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 50% in petrolatum. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: None.

Any other information on results incl. tables

No allergic skin reactions occurred in test animals 24 and 48 hours after the end of the challenge procedure. The sensitisation rate was 0%. No findings were observed in control animals (reaction rate :0%).

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
According to the EEC Directive 2001/59/EEC, 6 August 2001 and the Gefahrstoffverordnung (GefStoffV) of 15 November 1999 (BGB1. I, p. 2233) testconditions described, the test article "LITHARGE lead oxide" can be classified as a "non-sensitiser" since no allergic responses were observed in test animals under the experimental conditions described.
Executive summary:

The potential skin sensitising properties of the test article "LITHARGE lead oxide" were assessed in the guinea pig maximisation sensitisation test carried out as an adjuvant test according to the Magnusson & Kligman Maximisation test method, using 10 test and 5 control animals in the main test. Following the induction exposure to the test article (50% in petrolatum) or the vehicle petrolatum (control article), the animals of both groups were subjected two weeks later to a challenge exposure with the test article (50% in petrolatum) as well as the control article. Responses to the challenge procedure were evaluated 24 and 48 hours after the end of the exposure period.

Results: -No allergic skin reactions occurred in test animals 24 and 48 hours after the end of the challenge procedure. The sensitisation rate was 0%

-No findings were observed in control animals (reaction rate:0%).

Evaluation: According to the EEC Directive 2001/59/EEC, 6 August 2001 and the Gefahrstoffverordnung (GefStoffV) of 15 November 1999 (BGB1. I, p.2233) test conditions described, the test article "LITHARGE lead oxide" can be classified as a "non-sensitiser" since no allergic responses were observed in test animals under the experimental conditions described.

These results can be assigned to trilead bis(carbonate) dihydroxide since a read across based on a grouping of substances (Pb substances) is applied.