Organic mercury has been an environmental problem for many years. In spite of the high toxicity of organic mercury compounds and their accumulation ability in living organisms, the spreading in the environment has been steadily increased by human activities. In this study, the two organic mercuries, methyl mercury cloride (MMC) and methoxyethyl mercury cloride (MO), have been tested for mutagenicity in mammalian cells by use of the Chinese hamster cell line V 79-4 with two genetic markers: the locus azafor nucleic acid synthesis and the locus ouaconcerning the cell membrane. High toxic effects were obtained by MMC and by MO, beside a certain low mutagenicity in both of the tested loci; MO being slightly more mutagenic than MMC. The very narrow dose response curves were found to lie close to the threshold values for toxicity. Since the two tested mercury compounds had lower threshold values in the mutagenicitytests with V 79 cells than in toxicity tests with four different materials (Allium.human lymphocytes, E. coliK39 (ks) and V 79 cells), the mutagenicity test may generally be the more sensitive tool to evaluate biological effects of chemical compounds.

HereditasVolume 64, Issue 1 p. 142-146 Open Access The effect of two organic mercury compounds on human leukocytes in vitro Geirid Fiskesjö, Geirid Fiskesjö Institute of Genetics, University of Lund, S-223 62 Lund, SwedenSearch for more papers by this author Geirid Fiskesjö, Geirid Fiskesjö Institute of Genetics, University of Lund, S-223 62 Lund, SwedenSearch for more papers by this author First published: February 1970 https://doi.org/10.1111/j.1601-5223.1970.tb02283.xCitations: 15AboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume64, Issue1February 1970Pages 142-146 ReferencesRelatedInformation

HereditasVolume 69, Issue 1 p. 135-138 Open Access The effect of two mercury compounds on lysogenic E. coli K39 (Λ) Geirid Fiskesjö, Corresponding Author Geirid FiskesjöInstitute of Genetics S-223 62 Lund, SwedenSearch for more papers by this author Geirid Fiskesjö, Corresponding Author Geirid FiskesjöInstitute of Genetics S-223 62 Lund, SwedenSearch for more papers by this author First published: December 1971 https://doi.org/10.1111/j.1601-5223.1971.tb02426.xCitations: 2AboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Literature cited Fiskesjö, G. 1969. Some results from Allium tests with organic mercury halogenides. Hereditas 62: 314– 322. Fiskesjö, G. 1970. The effect of two organic mercury compounds on human leukocytes in vitro. Mutat. Res. 64: 142– 146. Ramel, C. 1969. Genetic effects of organic mercury compounds. I. Cytological investigations on Allium roots. Mutat. Res. 61: 208– 230. Weigle, J. J. and Delbrück, M. 1951. Mutual exclusion between an infecting phage and a carried phage. J. Bacteriol. 62: 301– 318. Zetterberg, G. 1969. Induction of lysogenic Escherichia coli with analogs of triethylenephosphoramide, TEPA. Hereditas 63: 473. Citing Literature Volume69, Issue1December 1971Pages 135-138 ReferencesRelatedInformation

HereditasVolume 102, Issue 1 p. 99-112 Open Access The Allium test as a standard in environmental monitoring GEIRID FISKESJÖ, Corresponding Author GEIRID FISKESJÖ Institute of Genetics, University of Lund, Sweden*Institute of Genetics, University of Lund, S-223 62 Lund. SwedenSearch for more papers by this author GEIRID FISKESJÖ, Corresponding Author GEIRID FISKESJÖ Institute of Genetics, University of Lund, Sweden*Institute of Genetics, University of Lund, S-223 62 Lund. SwedenSearch for more papers by this author First published: March 1985 https://doi.org/10.1111/j.1601-5223.1985.tb00471.xCitations: 41AboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Abstract The Allium test is suggested as a standard in environmental monitoring, e. g. as a part of a test battery. Background, the method including suggested parameters for standard use, results from various application areas and comparisons with a number of other test systems are presented. The Allium test is a short-term test with many advantages: low cost, ease to handle, good chromosome conditions for the study of chromosome damage or disturbance of cell division including the evaluation of risks of aneuploidy. The ability of the root cells to activate promutagens (the MFO-system) further widens the application areas of the Allium test. The use of series of onions for each concentration of the test chemical allows statistical considerations, and from growth curves Effect-Concentration values are obtained. The Allium test is, lastly, a sensitive test showing good correlation to other test systems. Thus, positive results in the Allium test should be considered as a warning and also an indication that the tested chemical may be a risk to human health and to our environment. Literature cited Clarkson, D. T. 1965. The effect of aluminium and some other trivalent metal cations on cell division in the root apices of Allium cepa. Ann. Bot. N. S. Vol. 29, No. 114: 309– 315. Fiskesjü, G. 1969. Some results with Allium tests with organic mercury halogenides. Hereditas 62: 314– 322. Fiskesjö, G. 1975. Rapport om ett biologiskt test (Alliumtest) utfört tried vatten fr˚n Braån och Höje å i SkÅne. Vatten 31: 304– 316. Fiskesjö, G. 1978. Dags införa övre gräns för koppar i dricksvatten. Miljöaktuellt nr. 8/78: 3. Fiskesjö, G. 1979. Mercury and selenium in a modified Allium test. Hereditas 91: 169– 178. Fiskesjö, G. 1981a. Allium test on copper in drinking water. Vatten 37: 232– 240. Fiskesjö, G. 1981b. Alliumtest på 10 industriers avloppsvatten. Report to the National Swedish Environmental Protection Board, 9 p. Fiskesjö, G. 1981c. Alliumtest pÅ fenol, anisol, Na-laurylsulfat och kopparsulfat. Rapport nr. 28, Nordforsk (Ekotoxikologiska metoder för akvatisk miljö). 11 p. Fiskesjö, G. 1981d. Benzo(a)pyrene and N-methyl-N-nitro-N-nitrosoguanidine in the Allium test. Hereditas 95: 155– 162. Fiskesjö, G. 1982a. Metalljoner i Alliumtestet I. (Cd, Be, Li). Annual Report to the National Swedish Environmental Protection Board, 22 p. Fiskesjö, G. 1982b. Evaluation of short-term tests for toxicity and mutagenicity with special reference to mercury and selenium.— Ph. D.-thesis, Inst. of Genetics, Univ. of Lund, Sweden. Fiskesjö, G. 1983a. Metalljoner i Alliumtestet II. (Cu, Ni, Al, Mn and Hg). Annual report to the National Swedish Environmental Protection Board. 27 p. Fiskesjö, G. 1983b. Nucleolar dissolution induced by aluminium in root cells of Allium. Physiol. Plant. 59: 508– 511. Fiskesjö, G., Lassen, C. and Renberg, L. 1981. Chlorinated phenoxyacetic acids and chlorophenols in the modified Allium test. Chem. Biol.-Interactions 34: 333– 344. Gerstner, H. B. and Huff, J. F. 1977. Clinical toxicology of mercury. J. Toxicol. Environ. Health, 2: 491– 526. Granmo, Å. 1984. Biological tests of waste waters from Stenungsund. Report to the National Swedish Environmental Protection Board SNV PM 1845 (Swedish; English summary), 134 p. Huberman, E. and Sachs, L. 1976. Mutability of different genetic loci in mammalian cells by metabolically activated carcinogenic polycyclic hydrocarbons. Proc. Natl. Acad. Sci. USA 73: 188– 192. Kihlman, B. A. 1966. Actions of Chemicals on Dividing Cells.— Prentice-Hall, Englewood Cliffs , New Jersey . Kihlman, B. 1971. Root tips for studying the effects of chemicals on chromosomes.—In Chemical Mutagens (Ed. A. Hollaender). Plenum Press, New York , p. 489– 514. Kallqvist, T. and Ormerod, K. 1981. Ringtest med 48 mikrobielle toksikologiske metoder. Rapport nr. 25, Nordforsk, (Ekotoxikologiska metoder för akvatisk miljö). 57 p. Levan, A. 1938. The effect of colchicine on root mitoses in Allium. Hereditas 24: 471– 486. Levan, A. 1945. Cytological reactions induced by inorganic salt solutions. Nature 156: 751. Levan, A. and Östergren, G. 1943. The mechanism of c-mitotic action. Observations of the naphtalene series. Hereditas 29: 381– 443. Linnainmaa, K., Meretoja, T., Sorsa, M. and Vainio, H. 1978. Cytogenetic effects of styrene and styrene oxide on human lymphocytes and Allium cepa. Scand. J. Work. Environ. Health 4: 156– 162. Panel on Mercury. 1978. An Assessment of Mercury in the Environment. Environmental Studies Board, Commission on Natural Resources, National Research Council, National Academy of Sciences, Washington D. C. Ramel, C. 1969. Genetic effects of organic mercury compounds. I. Cytological investigations on Allium roots. Hereditas 61: 208– 230. Royal Swedish Academy of Sciences. 1973. Evaluation of genetic risks of environmental chemicals. (Ambio Special Report), Ambio 3. Serres, F. J. DE 1978. Introduction: Utilization of higher plant systems as monitors of environmental mutagens. Environ. Health Perspect. 27: 3– 6. Solyom, P. 1982. Biological characterization of drainage water from BT Kemi AB. Report to the county Administration in Malmöhus County. IVL report 1982–10–29. Stich, H. F., Lam, P., Lo. L. W., Koropatnick, D. J. and San, H. C. 1975. The search for relevant short-term bioassays for chemical carcinogens: The tribulation of a modern sisyphus. Can. J. Genet. Cytol. 17: 471– 492. Vig, B. K. 1978. Somatic mosaicism in plants with special reference to somatic crossing over. Environ. Health Perspect. 27: 27– 36. World Health Organization 1971. International Standards for Drinking Water (Geneva 1971, Third ed.). Citing Literature Volume102, Issue1March 1985Pages 99-112 ReferencesRelatedInformation

Root growth and cytology of germinating seeds of Norway spruce (Picea abies L. Karst.), beech (Fagus sylvatica L.), and oak (Quercus robur L.) were investigated after various Al-treatments. In spruce, concentrations of 10 × 1-2M Al and higher caused c-mitotic effects in dividing cells; concentrations of 5 × 10-2M Al caused severe growth restrictions; 5 × 10-3M Al and higher caused bending of roots and browning of root tips; 1 × 10-3M Al also caused browning of root tips after prolonged treatment (more than 10 days). Certain structures, here called ‘Al-structures’ were observed, mainly in the root cap cells of spruce. The structures are vacuole-like and are often located in the cytoplasm, one on each side of the nucleus. The Al-structures appear as a sort of membrane-bound vacuoles, which do not stain with orcein. The structures were similar to those previously found in Allium cepa, and seem to be formed at least partly from material extruded from the nucleus. In beech and oak, similar but less distinct structures seem to occur. Whether the Al-structures contain Al or not remains to be shown.

Small bulbs of Allium cepa L. were cultivated for two days at various distances from a video display unit (computer or TV set). No effects could be observed on root growth or on the progress of normal mitosis in root tip cells. However, in a first experiment using colchicine-treated material, metaphase chromosomes with elongated centromeres were observed in a frequency which seemed to be inversely related to the distance of the onions from the screen. In a repeated, more comprehensive experiment, this relationship could not be confirmed. Instead, the occurrence of elongated centromeres was probably due to methodological variations. Thus, no biological damage could be demonstrated when root tips of ANium cepa were grown in front of video display units.

The Multicenter Evaluation of In Vitro Cytotoxicity (MEIC) programme was set up to evaluate the relevance for human acute toxicity of in vitro cytotoxicity tests. At the end of the project in 1996, 29 laboratories had tested all 50 reference chemicals in 61 cytotoxicity assays. Five previous articles have presented the in vitro data and the human database to be used in the evaluation. This article presents three important parts of the final evaluation: a) a comparison of rat and mouse oral LD50 with human acute lethal doses for all 50 chemicals; b) a display of the correlations between IC50 (concentration causing 50% inhibition) values from all 61 assays and three independent sets of human acute lethal blood concentrations, i.e. clinical lethal concentrations, forensic lethal concentrations, and peak concentrations; and c) a series of comparisons between average IC50 values from ten human cell line 24-hour assays and human lethal blood concentrations. In the latter comparisons, results from correlations were linked with known human toxicity data for the chemicals, to provide an understanding of correlative results. This correlative/mechanistic approach had the double purpose of assessing the relevance of the in vitro cytotoxicities, and of testing a series of hypotheses connected with the basal cytotoxicity concept. The results of the studies were as follows. Rat LD50 predictions of human lethal dosage were only relatively good (R 2 = 0.61), while mouse LD50s gave a somewhat better prediction (R 2 = 0.65). Comparisons performed between IC50 values from the 61 assays and the human lethal peak concentrations demonstrated that human ceil line tests gave the best average results (R 2 = 0.64), while mammalian and fish cell tests correlated less well (R 2 = 0.52–0.58), followed by non-fish ecotoxicological tests (R 2 = 0.36). Most of the 61 assays underpredicted human toxicity for digoxin, malathion, carbon tetrachloride and atropine sulphate. In the correlative/mechanistic study, the 50 chemicals were first separated into three groups: A = fast-acting chemicals with a restricted passage across the blood–brain barrier; B = slow-acting chemicals with a restricted passage across the blood–brain barrier; and C = chemicals which cross the blood–brain barrier freely, while inducing a non-specific excitation/depression of the central nervous system (CNS). The IC50 values for chemicals in group C were divided by a factor of ten to compensate for a hypothetical extra vulnerability of the CNS to cytotoxicity. Finally, the average human cell line IC50 values (24-hour IC50 for groups A and C, and after 48-hour for group B) were compared with relevant human lethal blood concentrations (peak concentrations for groups A and C, and 48-hour concentrations for group B). As a result, in vitro toxicity and in vivo toxicity correlated very well for all groups (R 2 = 0.98, 0.82 and 0.85, respectively). No clear overprediction of human toxicity was made by the human cell tests. The human cell line tests underpredicted human toxicity for only four of the 50 chemicals. These outlier chemicals were digoxin, malathion, nicotine and atropine sulphate, all of which have a lethal action in man through interaction with specific target sites not usually found in cell lines. Potassium cyanide has a cellular human lethal action which cannot be measured by standard anaerobic cell lines. The good prediction of the human lethal whole-blood concentration of this chemical was not conclusive, i.e. was probably a “false good correlation”. Another two chemicals in group C resulted in “false good correlations”, i.e. paracetamol and paraquat. The comparisons thus indicated that human cell line cytotoxicities are relevant for the human acute lethal action for 43 of the 50 chemicals. The results strongly support the basal cytotoxicity concept, and further point to the non-specific CNS depression being the obligatory reaction of humans to cytotoxic concentrations of chemicals, provided that the chemicals are able to pass the blood–brain barrier.

Results from tests on the Multicentre Evaluation of In Vitro Cytotoxicity (MEIC) reference chemicals 31-50 in 67 different in vitro toxicity assays are presented in this paper as a prerequisite to in vitro/in vivo comparisons for all MEIC in vitro toxicity data in forthcoming papers, i.e. the final MEIC evaluation of the relevance of the tests. With the aim of increasing knowledge about the relative significance of some in vitro methodological factors, the strategies and methods Df the preceding parts in the MEIC series (Parts II and III) were again employed to enable comparative cytotoxicity analysis of the new in vitro results presented in this paper. A principal components analysis (PCA) of the results from tests of the 20 chemicals in 67 assays demonstrated a dominating first component describing as much as 74% of the variance in the toxicity data, indicating a similar ranking of the cytotoxicities of the chemicals in most of the tests. The influence on the general variability of the results of a few, key methodological factors was also evaluated by using linear regression comparisons of the results of all pairs of methods available in the study, i.e. methods which were similar in all respects except for the factor being analysed. Results from this "random probe" analysis were: a) the cytotoxicities of 11 of the 20 chemicals increased considerably with exposure time (> 10 times over 4-168 hours); b) in general, human cell line toxicity was well predicted by cytotoxicity in animal cells; c) prediction of human cell line toxicity by most ecotoxicological tests was only fairly good; d) 14 comparisons of similar assays with different cell lines showed similar toxicities (mean R-2 = 0.83); e) nine comparisons of similar assays employing different primary cultures and cell lines shared similar toxicities (mean R-2 = 0.71); and f) 16 comparisons of similar assays with different growth/viability endpoints showed similar toxicities (mean R-2 = 0.71). Results b, d, e and f must contribute to the PCA-documented high general similarity of the in vitro toxicity data. Results a and c, together with factors which were not analysed, such as different protocols and interlaboratory variability of tests, could explain the 26% dissimilarity. To provide background information to the planned final MEIC evaluation of the relevance of the 61 methods in which all 50 chemicals have been tested, an additional PCA was made of the 50 chemical-61 assay in vitro database (from Parts II and III and the present paper). This supplementary PCA demonstrated an 80% similarity of results. Compared with the previous analysis of the tests of the first 30 MEIC reference chemicals (MEIC Part III), the present analysis of the tests of the last 20 MEIC chemicals indicates a somewhat higher variation in the results. Correspondingly, some deviating endpoint measurements and cell line responses were demonstrated by the pairwise comparisons in the present study. As a result, the analysis revealed a high correlation (R-2 = 0.73) between the average human cell line toxicity and the results from a new protein denaturation test. These preliminary results suggest that intracellular protein denaturation may be a frequently occurring mechanism in basal cytotoxicity.

The aluminum and calcium distributions in the root tips of aluminum-intoxicated onions, Allium cepa L., were mapped using PIXE (particle-induced X-ray emission) microanalysis. Not enough aluminum was present to have replaced, atom-for-atom, more than a minor fraction of the calcium. Furthermore, no inverse relationship between variations in aluminum and calcium concentrations was observed for pairs of adjacent 30-μm-diameter regions. Our observations, therefore, do not support the hypothesis that aluminum substantially reduces the quantity of bound calcium by competing with calcium for binding sites. Instead we suggest that reductions in calcium content are a non-local and indirect consequence of aluminum-intoxication. We found that aluminum accumulates almost exclusively in a surface layer. Observations of wounded roots indicated that exposed internal tissue binds aluminum avidly, so we contend that the surface accumulation pattern indicates that little aluminum penetrates into the interior of the root. We argue that aluminum does not directly inhibit growth in the interior of the apical root meristem because root growth rate was unaffected by root cap removal which should greatly increase the aluminum concentration in the exposed interior region. We hypothesize that growth inhibition in the interior of the meristem is mediated by a signal initiated or disrupted by excess aluminum in the periphery of the meristem.

The multicentre evaluation of in vitro cytotoxicity (MEIC) study is a programme designed to evaluate the relevance of in vitro toxicity tests for predicting human toxicity, and is organised by the Scandinavian Society for Cell Toxicology. The project started in 1989 and is scheduled to be finished by June 1996. MEIC is a voluntary effort by international laboratories to test the same 50 reference chemicals in their own in vitro toxicity systems. At present, 31 laboratories have submitted results for the first 30 reference chemicals from a total of 68 in vitro cytotoxicity tests. In the definitive evaluation of the MEIC programme, these in vitro results will be compared with human lethal blood concentrations and other relevant acute systemic toxicity data, and the results will be published as a series of articles. This paper, which is the first article in this series, describes and analyses the methodologies used in the 68 tests. The origins and purities of the test chemicals, the biological systems and the toxicity endpoints are also discussed. Since MEIC is not centrally directed, the selection of tests was entirely dependent on the preferences of the individual laboratories. Thus, the collection of tests is not representative of the full range of existing in vitro toxicity tests. In our study, basal cytotoxicity tests and ecotoxicological tests are prevalent, while tests for toxicity to primary cultures of differentiated cells, measured by organotypic toxicity endpoints, are clearly under-represented.

Results from tests of the first 30 MEIC reference chemicals in 68 different toxicity assays are presented as a prerequisite to subsequent in vitro/in vivo comparisons of acute toxicity data. A comparative cytotoxicity study was also carried out. Firstly, the variability of all of the results was analysed by using principal components analysis (PCA), analyses of variance (ANOVAs) and pairwise comparisons of means according to Tukey's method. The first PCA component described 80% of the variance of all of the cytotoxicity data. Tukey's ANOVA indicated a similar sensitivity for the assays, of approximately 80%. Secondly, the influence of five major methodological components on the general variability of the results was evaluated by linear regression and ANOVA linear contrast analyses. The findings were that: a) the toxicity of many chemicals increased with exposure time; b) in general, human cytotoxicity was predicted well by animal cytotoxicity tests; c) this prediction was poor for two chemicals; d) the prediction of human cytotoxicity by the ecotoxicological tests was only fairly good; e) one organotypic endpoint used, i.e. contractility of muscle cells, gave different results to those obtained according to viability/growth toxicity criteria; f) twelve comparisons of similar test systems involving different cell types (including highly differentiated cells) showed similar toxicities regardless of cell type; and g) nine out of ten comparisons of test systems with identical cell types and exposure times revealed similar toxicities, regardless of the viability or growth endpoint measurement used. Factors b, f and g must be the main causes of the remarkable similarity between the total results, while factors a, c, d and e, together with other minor factors that were not analysed, contributed to the 20% dissimilarity. The findings strongly support the basal cytotoxicity concept, and will facilitate future in vitro toxicity testing.

The Allium test provides a rapid screening procedure for chemicals, pollutants, contaminants, and so on that may represent environmental hazards. Root growth inhibition and adverse effects on chromosomes provide an indication of likely toxicity.

After joining the MEIC (multicentre evaluation of in vitro cytotoxicity) programme, and submitting the first ten compounds of the programme to the Allium test, we found that this test correlates well with several other tests (e.g. MIT-24 cell test, and tests with mice, rats or humans in vivo). The compounds tested were paracetamol, acetylsalicylic acid, iron sulphate, diazepam, amitriptyline, digoxin, ethylene glycol, methanol, ethanol and isopropanol. Among them, paracetamol turned Out to induce chromosome breakage in the meristems of Allium cepa root tips. This is the same qualitative response to paracetamol as that obtained previously in human lymphocytes in vivo and in vitro. The present results indicate that the eukaryotic higher plants may serve as highly useful test systems for biological risk evaluation.

The common onion Allium cepa L. (2n = 16) makes a very convenient test system for estimating harmful effects of chemicals on biological materials. Because of its excellent chromosome conditions, the Allium material has been widely exploited for such purposes since it was first introduced as a test system by A. Levar in 1938. The Allium test has later been extended to monitoring environmental risk factors as well. When wastewater from a chemical factory in southern Sweden caused severe pollution of an adjacent river, the growth restriction on Allium roots was taken as a measure of the degree of pollution in the river, and the result of the Allium test was admitted as evidence in a lawsuit against the factory. The Allium test has shown good correlation with other test systems, involving general toxicity (root growth) and genotoxicity (chromosome aberrations). Living material of Allium is easily stored and handled. It is inexpensive and assures very clear chromosomes. An Allium test takes a relatively short time to carry through: 2 days for chromosome preparations and 3–4 days for measurement of the root growth. From the growth curves, EC (effect concentration) values are obtained. © 1993 John Wiley & Sons, Inc.

After joining the MEIC (multicentre evaluation of in vitro cytotoxicity) programme, and submitting the first ten compounds of the programme to the Allium test, we found that this test correlates well with several other tests (e.g. MIT-24 cell test, and tests with mice, rats or humans in vivo). The compounds tested were paracetamol, acetylsalicylic acid, iron sulphate, diazepam, amitriptyline, digoxin, ethylene glycol, methanol, ethanol and isopropanol. Among them, paracetamol turned out to induce chromosome breakage in the meristems of Allium cepa root tips. This is the same qualitative response to paracetamol as that obtained previously in human lymphocytes in vivo and in vitro. The present results indicate that the eukaryotic higher plants may serve as highly useful test systems for biological risk evaluation.

Estimating the toxicity to humans of chemicals by testing on human subjects is not considered to be ethically acceptable, and toxicity testing on laboratory animals is also questionable. Therefore, there is a need for alternative methods that will give estimates of various aspects of human toxicity. Batteries of in vitro tests, together with physicochemical and toxicokinetic data, analysed by efficient data analytical methods, may enable analogy models to be constructed that can predict human toxicity. It may be possible to model non-specific toxicity relating to lipophilicity, or basal cytotoxicity, for a series of diverse compounds with large variation in chemical structure and physicochemical properties. However, local models for a series of similar compounds are generally expected to be more accurate, as well as being capable of modelling more-specific interactions. Analogy models for the prediction of human toxicity are discussed and exemplified with physicochemical and cytotoxicity data from the first ten chemicals in the multicenter evaluation of in vitro cytotoxicity (MEIC) project.