| Toxizitätsübersicht | IDENTIFICATION AND USE: Lead chromate is a yellow or orange-yellow powder. It is used as a pigment for paints and inksin oil and water colorsprinting fabricsdecorating china and porcelainin chemical analysis of organic substancesand in traffic paints. HUMAN EXPOSURE AND TOXICITY: Lead chromate is toxic by ingestion and inhalation. Although no evidence has been found that lead-chromate causes lung cancer in lead chromate workers, it cannot be unequivocally stated that heavy exposures to lead chromate does not present a cancer hazard. One possible mechanism for lead chromate-induced carcinogenesis is through centrosome dysfunction, leading to the induction of aneuploidy. Lead in lead chromate could cause possible neurotoxicity. Increasing concentrations of lead chromate induced increasing amounts of cytotoxicity and clastogenicity in human skin cells. ANIMAL STUDIES: A single sc injection of 30 mg lead chromate(VI) oxide in water to 2 groups of 40 rats gave rise to 26/40 & 27/40 sarcomas, respectively, at site of injection within 117-150 weeks. No local sarcoma occurred in 60 vehicle-treated control rats. Lead chromate induced 14 fibrosarcomas & 17 rhabdomyosarcomas at the site of injection in 31/47 rats given monthly im injections of lead chromate. In addition, 3/24 lead chromate-treated rats had renal carcinomas. No such tumors appeared in a similar group of 22 controls injected with the vehicle. No lung tumors were found in rabbits and guinea pigs after intratracheal instillation. The potential mutagenicity of lead chromate was tested by following battery of microbial tests: the Escherichia coli pola+/pola- survival testthe Salmonella/microsome his+ reversion assaythe E coli trp+ reversion test plate assaythe E coli gal+ forward mutation test& the Saccharomyces cerevisiae assay for mitotic recombination. Lead chromate was mutagenic in Salmonella & in Saccharomyces. Metabolic activation by rat liver homogenate (S9) was not required. Apparently, chromate ion is responsible for mutagenicity of lead chromate. An insoluble chromic compound, lead chromate (PbCrO4), was not cytotoxic nor mutagenic on V79 cells, probably because it is taken up by the cells very slowly. ECOTOXICITY STUDIES: Lead chromate was both cytotoxic and genotoxic to sea turtle cells. Concentrations of 0.1, 0.5, 1, and 5 ug/sq cm lead chromate induced 108, 79, 54, and 7% relative survival, respectively. Additionally, concentrations of 0, 0.1, 0.5, 1, and 5 ug/sq cm lead chromate induced damage in 4, 10, 15, 26, and 36% of cells and caused 4, 11, 17, 30, and 56 chromosome aberrations in 100 metaphases, respectively. Increasing concentrations of lead chromate induce increasing amounts of cytotoxicity and clastogenicity in sperm whale skin cells.Lead mimics other biologically important metals, such as zinc, calcium, and iron, competing as cofactors for many of their respective enzymatic reactions. For example, lead has been shown to competitively inhibit calcium's binding of calmodulin, interferring with neurotransmitter release. It exhibits similar competitive inhibition at the NMDA receptor and protein kinase C, which impairs brain microvascular formation and function, as well as alters the blood-brain barrier. Lead also affects the nervous system by impairing regulation of dopamine synthesis and blocking evoked release of acetylcholine. However, its main mechanism of action occurs by inhibiting delta-aminolevulinic acid dehydratase, an enzyme vital in the biosynthesis of heme, which is a necesssary cofactor of hemoglobin. Hexavalent chromium's carcinogenic effects are caused by its metabolites, pentavalent and trivalent chromium. The DNA damage may be caused by hydroxyl radicals produced during reoxidation of pentavalent chromium by hydrogen peroxide molecules present in the cell. Trivalent chromium may also form complexes with peptides, proteins, and DNA, resulting in DNA-protein crosslinks, DNA strand breaks, DNA-DNA interstrand crosslinks, chromium-DNA adducts, chromosomal aberrations and alterations in cellular signaling pathways. It has been shown to induce carcinogenesis by overstimulating cellular regulatory pathways and increasing peroxide levels by activating certain mitogen-activated protein kinases. It can also cause transcriptional repression by cross-linking histone deacetylase 1-DNA methyltransferase 1 complexes to CYP1A1 promoter chromatin, inhibiting histone modification. Chromium may increase its own toxicity by modifying metal regulatory transcription factor 1, causing the inhibition of zinc-induced metallothionein transcription. (A12, L16, A34, A35, A36, T4, A20, A22, L136) |
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