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The polychlorinated compounds captafol (CPL) and 2,6-dichloroisonicotinic acid (INA) are able to protect plants acting as a fungicide or an inductor of plant resistance, respectively. At the same time, CPL and INA are dangerous for the respiratory organisms, i.e. mammalians, bacteria, and fungi. The high electron-withdrawing ability of these compounds enables them to serve as unnatural electron acceptors in the cellular ambient near to electron transport pathways located in the thylakoid membrane of chloroplasts or in the mitochondrial respiratory chain. Low-energy electron attachment to CPL and INA in vacuo leads to formation of many fragment species mainly at thermal electron energy as it is shown using dissociative electron attachment spectroscopy. On the basis of the experimental findings, assigned with the support of density functional theory calculations it is suggested that the different bioactivity of CPL and INA in respiratory and photosynthetic organisms is due to the interplay between the dissociative electron attachment process and the energies of electrons leaked from the electron transport pathways.

A novel method was developed for the determination of captan, folpet, and captafol in apples by dispersive liquid-liquid microextraction (DLLME) coupled with gas chromatography-electron capture detection (GC-ECD). Some experimental parameters that influence the extraction efficiency, such as the type and volume of the disperser solvents and extraction solvents, extraction time, and addition of salt, were studied and optimized to obtain the best extraction results. Under the optimum conditions, high enrichment factors for the compounds were achieved ranging from 824 to 912. The recoveries of fungicides in apples at spiking levels of 20.0 microg kg(-1) and 70.0 microg kg(-1) were 93.0-109.5% and 95.4-107.7%, respectively. The relative standard deviations (RSDs) for the apple samples at 30.0 microg kg(-1) of each fungicide were in the range from 3.8 to 4.9%. The limits of detection were between 3.0 and 8.0 microg kg(-1). The linearity of the method ranged from 10 to 100 microg kg(-1) for the three fungicides, with correlation coefficients (r (2)) varying from 0.9982 to 0.9997. The obtained results show that the DLLME combined with GC-ECD can satisfy the requirements for the determination of fungicides in apple samples.

Possible modifying effects of pesticide mixtures on tumorigenesis were investigated with medium-term carcinogenesis protocols for rapid detection of carcinogenic agents using male F344 rats. In the 8-wk liver model, administration of 20 pesticides (19 organophosphorus compounds and one organochlorine), added to the diet each at acceptable daily intake (ADI) levels, did not enhance rat liver preneoplastic lesion development initiated by diethylnitrosamine. In contrast, a mixture of these 20 pesticides at 100 times the ADI significantly increased the number and area of liver lesions. In the second experiment using a multi-organ carcinogenicity protocol of 28 wk, mixtures of 40 pesticides (high production examples) or 20 pesticides (suspected carcinogens) added to the diet at their respective ADI levels did not modulate carcinogenesis in any organ initiated by five known potent carcinogens in combination. These results thus provide direct support for the safety factor (usually 100) approach using ADI values for the quantitative risk evaluation of pesticides.

Cytotoxic and cell-transforming activities of the three fungicides, captan, captafol and folpet, have been studied in an experimental in vitro model by exposing BALB/c 3T3 cells to the chemicals with or without S-9 mix-induced bioactivation. Cytotoxicity of the three compounds was reduced in the presence of the metabolizing system. Each assayed pesticide displayed cell-transforming ability in the presence of the metabolizing system. The relative efficiency was: captafol > captan > folpet. Cell transformation was considered to be due to carcinogenesis-promoting activity. These data, obtained in a medium-term (6-8 weeks) experimental model, contribute to a better understanding of the action of the three pesticides in the multistep carcinogenesis process and provide more information concerning the oncogenic risk of these xenobiotic compounds for humans.

Early life-stage survival, motility, and growth toxicity tests were carried out on common carp (Cyprinus carpio L.) endotrophic embryo, with two reference molecules (captafol and DNOC), from fertilization to the end of the first two-thirds period of mortalities by starvation. Thirteen days duration exposure was performed in daily renewed medium, at 24.5 degrees C, in standard synthetic water, at three pHs (6.9, 7.8, 9.0), in the presence of 10 mM/liter nontoxic pH buffer. Nominal concentrations of toxicants were 0.0, 0.25, 0.5, 1.0, and 2.0 mg/liter. Toxic effects on survival, motility, and growth decreased with increasing pH. From pH 6.9 to 9.0, the "no-observed-effect concentrations" differed by a factor greater than 8. Motility and growth cannot be considered, at population level, as true sublethal embryo-larval toxicity criteria. The toxicological interpretation of these results is discussed. They confirm the need of multifactorial methods for toxic risks and effects assessment on fish early life stages in the environment.

The mutagenic activity of captan and captafol was tested using Ames strains and strains showing an SOS response. Captafol was mutagenic in S. typhimurium strain TA102 (uvr+) and captan in strain TA104 (uvrB). Both captan and captafol elicit damages in DNA recognized by correndonuclease II, as shown by the repair test, and induced the SOS repair system in E. coli PQ37 (uvrA) strain. Only captafol induced the SOS system in PQ35 (uvr+). The lack of induction of beta-galactosidase at nonpermissive temperature in E. coli MD332 (dnaCs uvrA) strain showed that neither chemical was able to produce DNA breaks. In V79 Chinese hamster fibroblasts higher induction of c-mitosis by captafol than by captan (22% and 15% over the control, respectively) was accompanied by a higher decrease in nonprotein sulfhydryl groups, mainly GSH (41% and 77%, respectively). The content of protein sulfhydryl groups was decreased by either fungicide to a similar extent.

In a development trial for an initiation bioassay system, 7 known carcinogens and 1 suspected carcinogen were examined. In experiment 1, group 1 animals were initially subjected to partial hepatectomy (PH) 12 h before administration of diethylnitrosamine, 2-amino-3-methylimidazo[4,5-f]-quinoline (IQ), captafol, alpha-hexachlorocyclohexane or diethylstilbestrol (DES), then 2 weeks later underwent a promotion procedure comprising administration of phenobarbital (0.05% in diet) for 8 weeks and D-galactosamine (300 mg/kg, i.g.) at week 3. Group 2 received the promotion protocol alone as in group 1. Initiating potential was assayed on the basis of significant increase in values of preneoplastic placental form glutathione S-transferase-positive (GST-P+) foci of more than 3 cells in cross section at week 10. Numbers and areas of GST-P+ foci in group 1 given IQ, captafol and DES were significantly increased as compared to group 2, confirming the validity of the protocol as an initiation assay. In Experiment 2, group 1 rats were subjected to PH and 12 h later received a suspected carcinogenic mixture of opium pyrolysate (OP) or carcinogenic pesticide p,p'-dichloro-diphenyltrichloroethane or hexachlorobenzene. Application of a modified promotion procedure comprising cholic acid (0.15%) and carbon tetrachloride (1 ml/kg, i.g.) revealed significant initiation potential for OP. Overall the results indicate that the current protocols may be useful for detection of the initiation potential of carcinogens irrespective of their mutagenicity.

Captafol was administered at dietary levels of 0 (control), 750 and 1,500 parts per million (ppm) to groups of 50 male and 50 female F344/DuCrj rats for 104 weeks, and then all animals were maintained without captafol for a further 8 weeks, and killed in week 113. Renal cell carcinoma was found in eight of 50 male rats treated with 1,500 ppm and in one of 50 male rats treated with 750 ppm of captafol. The incidences of renal adenomas, including micro-adenomas, and basophilic altered cell tubules were significantly higher in both sexes treated with captafol than in controls, and the increases were apparently dose-dependent except that of adenomas in females. The incidences of neoplastic and preneoplastic lesions of the kidney in captafol-treated animals were higher in males than in females. Captafol also induced hepatocellular carcinomas in four of 50 female rats in the 1,500 ppm group. The incidences of hyperplastic (neoplastic) nodules and foci of cellular alterations in the liver were also significantly increased in both sexes treated with captafol, the increases being dose-dependent. In conclusion, captafol induced renal cell carcinomas in male rats and hepatocellular carcinomas in female rats.