Lead Carbonate Intermediate

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro cytogenicity / chromosome aberration study in mammalian cells

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Justification for type of information:

Hypothesis for read-across: Lead (Pb) is the main component of the target substance, and considered the major driver for adverse effects based on its properties and relative quantity in the substance. For toxicity assessment the bioavailable part is relevant. From the target substance itself, Pb is poorly soluble. For read-across purpose, however, data from more soluble compounds was used. Therefore, it is considered that the used read-across data gives worst-case estimate on the adverse effects. Rationale for key study selection: the substance “Reaction product of lead chloride or lead sulphate with alkaline solution” starting material is lead chloride which is studied in this robust study summary.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

2005

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The genotoxicity of lead chloride, lead nitrate, and lead acetate was studied in Chinese hamster V79 cells. Chromosomal damage was examined using the micronucleus test and CREST analysis. Microtubule assembly/disassembly was examined using immunofluorescence staining and a turbidity assay. Effects on kinesin activity were measured using the microtubule gliding assay.

GLP compliance:

not specified

Type of assay:

in vitro mammalian cell micronucleus test

Test material

Test material information

Constituent 1

Reference substance name:

Lead Chloride

Cas Number:

12612-47-4

IUPAC Name:

Lead Chloride

Constituent 2

Reference substance name:

Lead dinitrate

EC Number:

233-245-9

EC Name:

Lead dinitrate

Cas Number:

10099-74-8

Constituent 3

Reference substance name:

Lead acetate

EC Number:

239-379-4

EC Name:

Lead acetate

Cas Number:

15347-57-6

Molecular formula:

C2H4O2.xPb

IUPAC Name:

lead(4+) tetraacetate

Results and discussion

Test results

Species / strain:

Chinese hamster lung fibroblasts (V79)

Metabolic activation:

not specified

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Any other information on results incl. tables

Lead chloride and lead acetate induced a dose-dependent increase in the frequency of micronuclei at concentrations starting at 1.1 uM lead chloride and 0.05 uM lead acetate. The CREST assay verified a predominantly aneugenic effect for both lead compounds. Microtubule damage and disruption of the microtubule network was reported with exposure to lead acetate at concentrations greater than 500 uM. In turbidity assays, lead chloride, lead nitrate, and lead acetate inhibited tubulin assembly in a dose-dependent manner at 20 uM and above. In the gliding assay, lead nitrate inhibited kinesin-driven microtubule motility in a dose-dependent manner at concentrations of 25 uM and above.

Justification for read-across: Lead (Pb) is the main component of the target substance, and considered the major driver for adverse effects based on its properties and relative quantity in the substance. For toxicity assessment the bioavailable part is relevant. From the target substance itself, Pb is poorly water soluble. For read-across purpose, however, data from more soluble compounds was used. Therefore, it is considered that the used read-across data gives worst-case estimate on the adverse effects.

See IUCLID Section 13 for Analogue approach report.

Applicant's summary and conclusion

Conclusions:

Interpretation of results:
positive

Executive summary:

The genotoxicity of lead chloride, lead nitrate, and lead acetate was studied in Chinese hamster V79 cells. Chromosomal damage was examined using the micronucleus test and CREST analysis. Microtubule assembly/disassembly was examined using immunofluorescence staining and a turbidity assay. Effects on kinesin activity were measured using the microtubule gliding assay. Lead chloride and lead acetate induced a dose-dependent increase in the frequency of micronuclei at concentrations starting at 1.1 uM lead chloride and 0.05 uM lead acetate. The CREST assay verified a predominantly aneugenic effect for both lead compounds. Microtubule damage and disruption of the microtubule network was reported with exposure to lead acetate at concentrations greater than 500 uM. In turbidity assays, lead chloride, lead nitrate, and lead acetate inhibited tubulin assembly in a dose-dependent manner at 20 uM and above. In the gliding assay, lead nitrate inhibited kinesin-driven microtubule motility in a dose-dependent manner at concentrations of 25 uM and above.