title: p-Aramid RFP do not induce chromosomal aberrations in a standardized in vitro genotoxicity assay using human lymphocytes.
abstract: Genotoxicity evaluations have been proposed as regulatory requirements for establishing German MAK values for inhaled fibrous dusts. The objective of this in vitro assay was to assess the potential for para-aramid (p-aramid) respirable-sized, fiber-shaped particulates (RFP) to induce chromosomal aberrations in cultured human peripheral blood lymphocytes without metabolic activation. The highest concentration tested in this assay was limited by the physical characteristics of p-aramid RFP. The test substance was suspended in fully supplemented RPMI culture medium with 1% Pluronic F68. All dosing was achieved using a dosing volume of 90% (900 microl/ml), and the vehicle control cultures were treated with 900 microl/ml of fully supplemented RPMI culture medium with 1% Pluronic F68. In the chromosomal aberrations assay, the treatments were either 3 or 19 h without metabolic activation. Cultures were harvested 22 h from the initiation of treatment. Replicated cultures of human whole blood lymphocytes were incubated with p-aramid RFP concentrations of 6.30, 12.6, 25.2, 50.4, 101, 201, and 401 microg/ml. Cultures treated with concentrations to 50.4 microg/ml for 3 h and 6.30, 12.6, 25.2, and 201 microg/ml for 19 h were analyzed for structural and numerical chromosomal aberrations. No significant increase in cells with chromosomal aberrations, polyploidy, or endoreduplication was observed in the cultures analyzed. The results demonstrated that p-aramid RFP was negative for inducing chromosomal aberrations in cultured human peripheral blood lymphocytes without metabolic activation. In addition, we conclude that the utility of these tests for evaluating the genotoxicity of fibrous or particulate materials is questionable.
authors.affiliation: DuPont Haskell Laboratory for Health and Environmental Sciences, Newark, DE 19711, USA. david.b.warheit@usa.dupont.com
authors.forename: D B
authors.initials: DB
authors.lastname: Warheit
authors.forename: M
authors.initials: M
authors.lastname: Donner
authors.forename: H
authors.initials: H
authors.lastname: Murli
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D006801:Humans; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000187:drug effects* / Q000648:ultrastructure; D008855:Microscopy, Electron, Scanning; D016685:Mitomycin / Q000633:toxicity; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D019384:Nucleic Acid Synthesis Inhibitors / Q000633:toxicity; D011108:Polymers / Q000633:toxicity*
chemical_list: C039578:Kevlar Aramid fibers; D009153:Mutagens; D019384:Nucleic Acid Synthesis Inhibitors; D011108:Polymers; D016685:Mitomycin