Toxicity of 20 Chemicals from the MEIC Programme Determined by Growth Inhibition of L-929 Fibroblast-like Cells

Abstract

The Multicentre Evaluation of In vitro Cytotoxicity (MEIC) programme is an international project aimed at evaluating the relevance of in vitro tests in predicting human toxicity. We have screened 20 chemicals (MEIC codes 31-50) from the programme, by using a cytotoxicity test based on growth inhibition of the mouse fibroblast-like L-929 cell line. Inhibition of cell growth was determined by the neutral red uptake method, which is well established and is used for screening the cytotoxicity of chemicals and plastics for pharmaceuticals and medical devices. The concentrations causing 50% inhibition of cell growth after a 72-hour exposure period varied from 3.1μM for hexachlorophene, to 1.4mM for caffeine. This is within the same range as results recently obtained with five other cell models. However, with some chemicals (chloroform, carbon tetrachloride and dichloromethane), no reliable results were obtained. These substances could not be dissolved in a reproducible way in any of the solvents used and, furthermore, they were highly volatile, which led to difficulties in maintaining the concentrations.

Keywords

MEIC cytotoxicity inhibition of cell growth L-929 cells

Get full access to this article

View all access options for this article.

References

Clemedson

(1996). MEIC evalution of acute systemic toxicity. ATLA 24, Suppl. 1, 251–311.

Kjellstrand

, and Boberg

(1991). Toxicity testing of polymer materials for use in haemodialysis. Toxicology in Vitro 5, 443–448.

Kjellstrand

, and Boberg

(1991). Testing of polymer materials: what methods should be used? ATLA 19, 222–225.

Kjellstrand

, Boberg

, & Rydhög

(1994). Toxicity testing of polymer materials for dialysis equipment: is there any need for in vivo testing? Cell Biology and Toxicology 10, 137–142.

The International Organization of Standardization. (1992). ISO 10993–5: Biological Evaluation of Medical Devices, Part 5. Test for Cytotoxicity: In Vitro Methods, pp. 1–7.

Barile

F.A.

, Alexander

, and Sookhoo

(1995). Potential of human lung cells for predicting acute cytotoxicity. ATLA 23, 461–468.

Shrivastava

, Delomenie

, Chevalier

, John

, Ekwall

, Walum

, and Massingham

(1992). Comparison of in vivo acute lethal potency and in vitro cytotoxicity of 48 chemicals Cell Biology and Toxicology 8, 157–170.

Romert

, Jansson

, and Jensen

(1994). The cytotoxicity of 50 chemicals from the MEIC study determined by growth inhibition of Ascites Sarcoma BP8 cells: a comparison with acute toxicity data in man and rodents. Toxicology Letters 71, 39–46.

Borenfreund

, and Peurner

J.A.

(1985). Toxicity determined in vitro by morphological alterations and neutral red absorption. Toxicology Letters 24, 119–124.

10.

Borenfreund

, Babich

, & Martin-Alguacil

(1988). Comparison of two in vitro toxicity assays: the neutral red (NR) and tetrazolium MTT tests. Toxicology in Vitro 2, 1–6.

11.

Smith

L.M.

, Clothier

R.H.

, Hillidge

, & Balls

(1992). Modification of the FRAME kenacid blue method for cytotoxicity tests on volatile materials. ATLA 20, 230–234.

12.

Autian

(1977). Toxicological evaluation of bio-materials: primary acute toxicity screening program. Artificial Organs 1, 53–60.

13.

Wilsnack

R.E.

(1976). Quantitative cell culture biocompatibility testing of medical devices and correlation to animal tests. Biomaterials, Medical Devices and Artificial Organs 4, 235–261.