MEIC Study

ACTIVTox replicates results from MEIC study

ACTIVTox hepatotoxicity kits can be used to determine both general and liver specific toxicity. The results shown below demonstrate that ACTIVTox faithfully replicates the results found in one of the largest studies of in vitro cytotoxicity.

MEIC Study

In 1989, Björn Ekwall and the Scandinavian Society for Cell Toxicology organized the Multicenter Evaluation of In Vitro Cytotoxicity (MEIC). This project was assembled with the idea of evaluating the usefulness of in vitro tests for predicting acute toxicity in humans and to determine which test might be most useful in replacing animals for such testing. The results of this landmark study were published in a series of papers (1–7) and are available here. There were several important findings from this study. The first was that in vitro tests were a reasonable approximation of in vivo findings. The second was that a series of tests utilizing human liver derived cell lines was the most predictive of acute human toxicity.

Procedure

We have used 36 of the 50 compounds referenced in the MEIC study to examine the ability of ACTIVTox to replicate the results obtained in that study. Rapidly dividing, low density cultures of ACTIVTox cells were incubated with serial dilutions of the compounds in serum containing medium for 48 hours, at which time cultures were assayed for cell growth. Each dilution was tested in triplicate wells of 96 well plates.

Figure 1. ACTIVTox IC50 versus MEIC IC50. r2=0.87

In vitro toxicity correlates with known human toxicity

Results were collected in MDL Assay Explorer for determination of IC50. Figure 1 shows the IC50 determined in ACTIVTox versus the IC50 found in the MEIC study using the three liver related cell lines. Figure 1 shows an excellent correlation between the results of the MEIC study and those found using ACTIVTox. In vitro toxicity testing is increasingly recognized as a valid surrogate for potential human toxicity.

MEIC compounds tested using ACTIVTox

1,1,1 Trichloroethane, 2,4 Dichlorophenoxyacetic acid, Acetaminophen, Amitriptyline, Amphetamine sulfate, Arsenic Trioxide, Aspirin, Atropine sulfate, Barium Nitrate, Caffeine, Chloramphenicol, Chloroform, Cupric sulfate, Diazepam, Ferrous Sulfate, Isoniazid, Lithium Sulfate, Malathion, Mercuric chloride, Nicotine, Paraquat, Pentachlorophenol, Phenobarbital, Phenol, Potassium chloride, Potassium cyanide, Propranolol, Quinidine sulfate, Sodium Fluoride, Sodium Oxalate, Thallium Sulfate, Theophylline, Thioridazine, Verapamil, Warfarin, Xylene.

MEIC References

1. Clemedson, C., et al (1996) MEIC evaluation of acute systemic toxicity. Part 1. ATLA 24,249–272.
2. Clemedson, C., et al (1996) MEIC evaluation of acute systemic toxicity. Part II. ATLA 24,273–311.
3. Clemedson, C., et al (1998) MEIC evaluation of acute systemic toxicity. Part III. ATLA 26,93–129.
4. Clemedson, C., et al (1998) MEIC evaluation of acute systemic toxicity. Part IV. ATLA 26,131–183.
5. Ekwall, B., et al (1998) MEIC evaluation of acute systemic toxicity. Part V. ATLA 26,571–616.
6. Ekwall, B., et al (1998) MEIC evaluation of acute systemic toxicity. Part VI. ATLA 26,617–658.
7. Clemedson, C., et al (2000) MEIC evaluation of acute systemic toxicity. Part VII. ATLA 28, Suppl. 1,159–200.