90 Kappas, A., and M. Markaki, National Research Center "Democritus", Athens (Greece)

Genetic activity of herbicides in Salmonella typhimurium and Aspergillus nidulans

The plant growth-regulating hormones indole- 3-acetic acid (IAA) and indole-3-butyric acid (IBA) have been found to greatly increase mitotic segre- gation in Aspergillus nidulans by mitotic crossing- over and non-disjunction (Kappas, A. (1983) Carcinogenesis, 4, 1409-1411). A variety of widely used herbicides, the chlorophenoxy compounds, show a plant hormone-like activity at low con- centrations whereas at high concentrations they are phytotoxic. The purpose of this work was to find whether these herbicides show similar recom- binogenic effects and also whether plant growth regulators and herbicides of similar activity are mutagenic in the Ames test. IAA, IBA and the herbicides 2,4-dichlorophenoacetic acid (2,4-D), 2,4-(dichlorophenoxy)butyric acid (2,4-DB) and 4-chloro-2-methylphenoxyacetic acid (MCPA) were tested in the Ames test for point mutations, whereas the herbicides were also tested in Asper- gillus.

IAA, IBA and 2,4-DB at a range of concentra- tions from 5 to 5000 /~g/plate were found nega- tive in the TA97, TA98, TA100, TA1535 and TA1538 strains of Salmonella typhimurium with and without an $9 mix. 2,4-D and MCPA were shown weak mutagens at concentrations between 250 and 750 /~g/plate in strain TA97 and only after metabolic activation. The latter two com- pounds were also found to increase the mitotic segregants in a properly marked diploid strain of A. nidulans at concentrations from 1 to 10/~g/ml for 2,4-D and 300 to 500/~g/ml for MCPA. In the case of 2,4-D this increase was only observed when an $9 mix was added to the medium. In both cases analysis of the segregants showed that they were formed by mitotic crossing-over.

(Supported by grant ENV-561-GR(B) from the EEC.)

APPLIED MUTAGENESIS II (industrial, pharmaceutical, therapeutical)

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91 Rossi, F., R. Vellosi, R. Del Carratore, E. Morichetti and G. Bronzetti, Istituto di Muta- genesi e Differenziamento CNR, Via Svezia 10, 56100 Pisa (Italy)

Relationship between metabolism and genetic ef- fects of 5 chlorinated ethanes

The genetic activity of 5 chlorinated ethanes widely used in industrial processes such as 1,1-di- chloroethane (1,1-DCE), 1,2-dichloroethane (1,2- DCE), 1,1,1-trichloroethane (1,1,1-TCE), 1,1,2-tri- chloroethane (1,1,2-TCE) and 1,1,2,2-tetrachloro- ethane (1,1,2,2-TeCE) was tested using the D7 yeast strain of Saccharomyces cerevisiae with and without metabolic activation ($9). Chlorinated ethanes are enzymatically transformed by cyto- chrome P-450 into different metabolites which could be genetically active. This is the reason why the 5 molecules were studied using D7 cells in logarithmic growth phase containing high level of cytochrome P-450.

Results obtained show the relevance of meta- boric activation in the induction of genetic activity as shown comparing the results obtained with stationary or logarithmic growth-phase cells.

3 out of the 5 chemicals examined were found to exert weak genotoxic activity.

(The present work is a part of an interdisci- phnary program supported by AIRC, involving the following research institutes: Institute of Mutagenesis and Diff. CNR Pisa (Responsible G. Bronzetti), Institute of Pharmacology, University of Bologna (Res. G. Cantelli-Forti), National In- stitute of Health, Rome (Res. A. Carere), Univer- sity Cancer Institute of Bologna (Res. G. Prodi and S. Grilli), Cancer Institute of Genoa (Res. S. Parodi).)

92 Hooftman, R.N., W.K. de Raat and P.B. Davis, Division of Technology for Society TNO, Postbox 217, 2600 AE Delft (The Netherlands)

The in vitro cytotoxicity and genotoxicity of weld- ing fumes

The in vitro cytotoxicity and genotoxicity of welding fume particles from different welding

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processes were investigated as part of a study on the biological effect of welding fumes. Welding fume particles from different stainless steel weld- ing processes were compared with fume particles from mild steel welding processes. The contribu- tion of Cr 6+ to the effect of welding fumes has been investigated by testing Cr 6+ (from K2CrO4). The following welding processes were applied: MMA/SS, MMA/MS, MMA/CI , M I G / S S and M I G / M S *

The in vitro tests applied were the Ames test, chromosome aberration test, H G P R T test, and cytotoxicity test with bovine alveolar macro- phages. The stainless steel welding fume particles induced genotoxic effects in all test systems, with the exception of the HGPRT test. The effects of MM A/S S (containing soluble Cr) were more pro- nounced than those of M I G / S S (containing Cr mainly as insoluble Cr). The M M A / M S was only slightly positive, the M I G / M S was negative, in the different test systems. M M A / C I was only positive in the SCE test. Cr 6+ was strongly posi- tive in all test systems with the exception of the H G P R T test. It seems that Cr 6+ plays an im- portant role in the genotoxicity and cytotoxicity of welding fumes, a contribution from other sub- stances to the effects cannot be excluded.

The results of these investigations indicate that the Ames test, the SCE test, the chromosome aberration test and the test with alveolar macro- phages, but not the H G P R T test, are sensitive systems for the in vitro study of welding fumes.

(These investigations have been supported by the Commission of the European Communities D G XIX 1A-5 (contract 7248/22/020) and by the Directorate General for Environmental Hygiene of the Dutch Ministry of Housing, Physical Plan- ning and Environment.)

* MMA, manual metal arc welding process; MIG, metal inert gas welding process; MS, mild steel (not containing Cr and Ni); SS, stainless steel (containing Cr and Ni); Ci = cast iron (containing Ni).

Trabucchi", University of Milan, and 2 Agusta S.p.A., Safety Department (Italy)

Cytogenetic study of a new resin composite for aerospace use

The evaluation of the potential health risk of a new resin composite (199-45), used in the aero- space industry was carried out by genotoxicity test with human lymphocytes " in vitro". The resin composite was made up of a mixture of tetra- glycidyl-methyl-dianiline, epoxy novolac, urea compounds and diaminodiphenylsulfone as cata- lyst.

Blood from 2 male and 2 female donors, non- smokers, free from pharmacological treatment for at least 6 months, without chromosome fragility and recent viral infections (M.A. Stenchever et al., 1976), was incubated for 4 h with increasing doses of the resin composite for determination of cyto- toxicity.

A dose of 300 /~g/ml was found to produce approx. 30% toxicity. The lymphocytes of the donors were therefore treated for 4 h at the follow- ing doses: 10, 100, 150 and 300/~g/mi (bleomycin was utilized as positive control). The cultures were incubated for 72 h at 37 °C to obtain chromosome preparations.

A chromosome analysis carried out with an image computerized analyzer (IBAS II-ZEISS- KONTRON), of 100 samples /donor showed a high number of chromosome aberrations of seri- ous biological significance, such as breaks, chro- mosome fragments, rings, dicentrics, similar in type and frequency to those obtained with the known mutagen bleomycin. A reduction in the total number of cells was also observed.

(This work was carried out within the oriented project "Medicina Preventiva e Riabilitativa", SP5 "Rischio Tossicologico" of the National Research Council.)

93 Rizzi, R. 1, E. Piatti 1, E. Chiesara 1, G.L. Marasi 2 and G. Zanon 2, 1 Dept. of Pharmacology, Chemotherapy and Medical Toxicology "E.

94 Mtiller, L., S. Madle and R. Bass, Federal Health Office, Institute for Drugs, Seestr. 10, D-1000 Berlin 65 (F.R.G.)