In vitro cytotoxicity testing for prediction of acute human toxicity

Abstract

This study was designed to compare the cytotoxic concentrations of chemicals, determined with three independent in vitro cytotoxicity testing protocols, with each other and with established animal LD50 values, and against human toxic concentrations for the same chemicals. Ultimately, these comparisons allow us to evaluate the potential of in vitro cell culture methods for the ability to screen a variety of chemicals for prediction of human toxicity. Each laboratory independently tested 50 chemicals with known human lethal plasma concentrations and LD50 values. Two of the methods used monolayer cell cultures to measure the incorporation of radiolabeled amino acids into newly synthesized proteins and cellular protein content, while the third technique used the pollen tube growth test. The latter is based on the photometric quantification of pollen tube mass production in suspension culture. Experiments were performed in the absence or presence of increasing doses of the test chemical, during an 18- to 24-h incubation. Inhibitory concentrations were extrapolated from concentration-effect curves after linear regression analysis. Comparison of the cytotoxic concentrations confirms previous independent findings that the experimental IC50 values are more accurate predictors of human toxicity than equivalent toxic blood concentrations (HETC values) derived from rodent LD50s. In addition, there were no conclusive statistical differences among the methods. It is anticipated that, together, these procedures can be used as a battery of tests to supplement or replace currently used animal protocols for human risk assessment.

Cytotoxicity of chlorhexidine digluconate to murine macrophages and its effect on hydrogen peroxide and nitric oxide induction

“…Macrophages have been used for immunocytotoxicity testing because they permit the measurement of the cytotoxic response directly in the cell culture and because of their ability to maintain immunological functions in the presence of many different chemical agents (13). The cytotoxicity of chlorhexidine has been assayed using cell lines or primary cultures of mammalian cells (6); however, there is no specific information on the toxicity of this substance to immune cells.…”

Cytotoxicity evaluation of four endodontic sealers

“…Macrophages have been used for immunocytotoxicity testing because they permit the measurement of the cytotoxic response directly in the cell culture and have the ability to maintain immunological functions in the presence of many different chemical agents (12). The effect of endodontic sealers on macrophage activity is of interest since these cells play a key role on innate and acquired immune defenses and on the pathogenesis of inflammation (13).…”

Estresse de transporte em cascudos amazônicos ornamentais Cochliodon sp. (L145) e Hypostomus sp. (L28) (LORICARIIDAE)

“…A inoculação intraperitoneal de agentes infecciosos em ratos tem sido extensivamente utilizada como modelo para análises de resposta inflamatória (SILVA et al, 1987;APPELBERG et al, 1991). AFONSO et al (1997AFONSO et al ( , 1998 Os macrófagos de rim de A. multispinis foram escolhidos, pois permitem medir a resposta citotóxica diretamente na cultura celular e pela sua capacidade para manter as funções imunológicas na presença de diferentes agentes químicos (BARILE et al, 1994). Vários fatores são capazes de estimular os macrófagos (citocinas produzidas pelo hospedeiro frente a intermediários inflamatórios produzidos por microorganismos).…”