Concentrates of lead and zinc compounds with sulfur resulting from hydrometallurgy (hot acid leaching, super-hot acid leaching and flotation)

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Study period:

August-December 2003

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Justification for type of information:

Well-documented and corresponded to the requirements of the recommended Annex V Test Guidelines.Read-across justification:Read-across from the most critical and bioavailable constituents (lead and its compounds):Based on the mineralogical composition, lead is the main constituent in the target substance and appears in sulphate form. The target substance is a solid inorganic UVCB substance and insoluble in water. Therefore, the transformation/dissolution study (OECD guidance 29) was conducted for the target substance to focus on the most critical bioavailable constituents of the substance. According to the T/D study results, the readily soluble constituent is lead. Based on the hazard profile of lead it is also the most hazardous constituent of this substance. Therefore, and in order to avoid the unnecessary animal testing, the read-across data from the most critical constituent is used to evaluate the short-term and long-term toxicological adverse effects of the target substance. The read-across data focuses on the properties of lead sulphate and other bioavailable forms of lead.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

yes

Remarks:

There was one deviation from the study protocol which was concerned with the relative humidity (section 6.2 Husbandry). At some days of the study the relative humidity was higher than 70%.

GLP compliance:

yes (incl. QA statement)

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

The study was conducted in 2003 before the entry into force of the current legislation.

Test material

Test material information

Constituent 1

Reference substance name:

trilead dioxide phophonate

IUPAC Name:

trilead dioxide phophonate

Constituent 2

Reference substance name:

Trilead dioxide phosphonate

EC Number:

235-252-2

EC Name:

Trilead dioxide phosphonate

Cas Number:

12141-20-7

Molecular formula:

HO5PPb3

IUPAC Name:

trilead dioxide phosphonate

Details on test material:

- Name of test material (as cited in study report): ALLSTAB LP 3139 dibasic lead phosphite- Molecular formula (if other than submission substance): 2PbO x PbHPO3 x 0.5 H2O- Molecular weight (if other than submission substance): - Smiles notation (if other than submission substance): - InChl (if other than submission substance): - Structural formula attached as image file (if other than submission substance): see Fig. - Substance type: - Physical state: fine white powder- Analytical purity: 99.3%- Impurities (identity and concentrations): - Composition of test material, percentage of components: - Isomers composition: - Purity test date: - Lot/batch No.: 0210510067- Expiration date of the lot/batch: > 24 months after shipping- Radiochemical purity (if radiolabelling): - Specific activity (if radiolabelling): - Locations of the label (if radiolabelling): - Expiration date of radiochemical substance (if radiolabelling): - Stability under test conditions: - Storage condition of test material: At room temperature. Shelf Life: min. 24 months (sfter shipment), when stored in sealed containers at temperatures below 40 degrees centigrade.- Other:

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- Age at study initiation: - Weight at study initiation: males: 459-545 g; females: 416-530 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" (pelleted diet, batch no. K080) offered 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- Humidity (%): 37-76%- Air changes (per hr): 16 times/ hour and filtered adequately- Photoperiod (hrs dark / hrs light): 12 hours dark/12 hours light with light on at 7:00AMIN-LIFE DATES: From: To:

Study design: in vivo (non-LLNA)

Induction

Induction 1

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.

Induction 2

Concentration / amount:

Intradermal injection- 5% of the test articleDermal application 50% in petrolatum

Challenge

Challenge 1

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.

Challenge 2

Concentration / amount:

Intradermal injection- 5% of the test articleDermal application 50% in petrolatum

No. of animals per dose:

10 test and 5 control animals

Details on study design:

RANGE FINDING TESTS: The range finding test was performed to determine the concentration of the test article to be used in the main test. For the intradermal injection, the test article was diluted with aqua ad iniectabilia (Delta-Pharma, Pfullingen) and Freund's complete adjuvant (FCA; batch no. 62K8933; SIGMA, Steinheim) to a final concentration of 5.0%. Two animals were employed, skin reactions being recorded 48 and 72 hours after treatment. For the dermal application, the solid test article was used 50% in petrolatum. A closed patch exposure was effected by means of an occlusive bandage using cellulose swabs, Leukosilk and non-irritating tape Elastoplast, which enveloped the whole animal's trunk. Two animals were employed and skin reactions were recorded 48 and 72 hours post applicationem.MAIN STUDYA. INDUCTION EXPOSURE- No. of exposures: 3 injection sites- Exposure period: Seven days after injection, the injection sites were covered occlusively for 48 hours.- Test groups: 10- Control group: 5- Site: 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) testt article 5% in peanut oil, 3) test article 5% in aqua ad iniectabilia/FCA. Control Group: 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: Both control and test animals were subjected to a challenge exposure 14 days after the second stage of the induction.- Exposure period: 24 hours- Test groups: 10- Control group: 5- Site: 5 x 5 cm clipped skin area on each flank- Concentrations: 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 described under 6.2.1. In each case, the duration of the exposure was 24 hours under an occlusive dressing.- Evaluation (hr after challenge): 24 and 48 hours after challenge.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 described under 6.2.1. In each case, the duration of the exposure was 24 hours under an occlusive dressing.

Positive control substance(s):

yes

Results and discussion

Positive control results:

Sensitisation rate (50%) at 24 hours: 70% Sensitisation rate (50%) at 48 hours: 70%Sensitisation rate (25%) at 24 hours: 30% Sensitisation rate (25%) at 48 hours: 20%

In vivo (non-LLNA)

Results

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

50% in petrolatum

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

0 %

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: 0 %.

Any other information on results incl. tables

There were no skin reactions after the dermal application in the induction phase. No allergic skin reactions were observed in test animals after the challenge exposure 24 and 48 hours after patch removal. No findings were observed in control animals.

The sesitisation rate, i.e. the number of animals showing an alergic response expressed as a percentage of the total number of animals, was determined 24 and 48 hours after patch removal and was 0% in test animals in each case. The corresponding reaction rate in control animals was 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), the test article "ALLSTAB LP 3139 dibasic lead phosphite" can be classified as a "non-sensitiser since no allergic responses were observed in test animals after the adjuvant test according to Magnusson & Kligman.

Executive summary:

The potential skin sensitising properties of the test article "ALLSTAB LP 3139" 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 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 nthe EEC Directive 2001/59/EEC, 6 August 2001 and the Gefahrstoffverordnung (GefStoffV) of 15 November 1999 (BGB1. I, p.2233), the test article "ALLSTAB LP 3139 dibasic lead phosphite" can be classified as a "non-sensitiser" since no allergic responses were observed in test animals under the experimental conditions described.