Results of long-term experimental studies on the carcinogenicity of ethylene-bis-dithiocarbamate (Mancozeb) in rats.

Mancozeb, an ethylene-bis-dithiocarbamate (EBDC), has been one of the most commonly used fungicides in commercial use for several decades. Nevertheless, up to now, no adequate published experimental studies on the carcinogenicity of Mancozeb have been published. Because of the importance of the compound and of the number of people potentially exposed (workers engaged in the production and use of the fungicide, people living in agricultural areas where the compound is sprayed, and people consuming polluted products), a long-term experimental study of Mancozeb was begun at the Cancer Research Center of the Ramazzini Foundation.

Results of long-term carcinogenicity bioassay on vinyl acetate monomer in Sprague-Dawley rats.

Vinyl acetate monomer (VAM) was administered in drinking water supplied ad libitum at doses of 5,000, 1,000, and 0 ppm (v/v) to 17-week-old Sprague-Dawley rats (breeders) and to 12-day embryos (offspring). Treatment lasted for 104 weeks; thereafter, animals were kept under control conditions until spontaneous death. VAM was found to cause an increase in total malignant tumors and in carcinomas and/or precursor lesions of the oral cavity, lips, tongue, esophagus, and forestomach.

Results of long-term experimental studies on the carcinogenicity of formaldehyde and acetaldehyde in rats.

Formaldehyde was administered for 104 weeks in drinking water supplied ad libitum at concentrations of 1500, 1000, 500, 100, 50, 10, or 0 mg/L to groups of 50 male and 50 female Sprague-Dawley rats beginning at seven weeks of age. Control animals (100 males and 100 females) received tap water only. Acetaldehyde was administered to 50 male and 50 female Sprague-Dawley rats beginning at six weeks of age at concentrations of 2,500, 1,500, 500, 250, 50, or 0 mg/L.

Results of long-term carcinogenicity bioassays on tert-amyl-methyl-ether (TAME) and di-isopropyl-ether (DIPE) in rats.

Tert-amyl-methyl ether (TAME) was administered by gavage in extra virgin olive oil solution at concentrations of 750, 250, or 0 mg/kg bw to groups of 100 male and 100 female Sprague-Dawley rats 8 weeks old at the start of the experiment. Di-isopropyl ether (DIPE) was administered in the same manner at the doses of 1000, 250, or 0 mg/kg body weight to groups of 100 male and 100 female Sprague-Dawley rats. TAME and DIPE were each delivered in 1-mL solution 4 days a week for 78 weeks.

Results of long-term experimental studies on the carcinogenicity of methyl alcohol and ethyl alcohol in rats.

Methyl alcohol was administered in drinking water supplied ad libitum at doses of 20,000, 5,000, 500, or 0 ppm to groups of male and female Sprague-Dawley rats 8 weeks old at the start of the experiment. Animals were kept under observation until spontaneous death. Ethyl alcohol was administered by ingestion in drinking water at a concentration of 10% or 0% supplied ad libitum to groups of male and female Sprague-Dawley rats; breeders and offspring were included in the experiment.

Ramazzini Foundation cancer program: history and major projects, life-span carcinogenicity bioassay design, chemicals studied, and results.

The Ramazzini Foundation research program was started over thirty years ago. The features of this program are: (1) systematic and integrated project design; (2) consistency over time; (3) homogeneity of approach: key members of the team remain unchanged; and (4) choice to work on new frontiers of scientific research. The program centers mainly on three projects: Project 1: experimental carcinogenicity bioassays; Project 2: experimental anticarcinogenesis assays to identify factors and active principles (compounds) capable of opposing the onset of tumors while being suitable for preventive/chemopreventive intervention; Project 3: epidemiological studies, both descriptive and analytical, on tumor incidence and mortality in persons professionally and environmentally exposed to industrial carcinogenic risks.

The International Commission on Occupational Health (ICOH) and its influence on international organizations.

The ICOH has played a key role in the development of some scientific documents and policy recommendations, but it has not always been scientifically objective, particularly in regard to asbestos and other fibers and some chemicals and pesticides. Many ICOH members are employees of corporations or consultants to industry, serving multinational corporate interests to influence public health policy in the guise of a professional scientific organization. ICOH members' conflicts of interest with the public health dominate the organization and damage the standing of the ICOH.

Mega-experiments to identify and assess diffuse carcinogenic risks.

Diffuse carcinogenic risks, that is, those of low potency involving large areas of population and sometimes all mankind, pose a serious public health problem. Controlling these risks might help to reduce the incidence of, and mortality from, cancer. Because of their low expected carcinogenic potential, these risks are difficult to expose or assess.

The scientific and methodological bases of experimental studies for detecting and quantifying carcinogenic risks.

This paper outlines the aims and potential scope of experimental research for risk identification and assessment in industrial carcinogenesis (environmental and occupational). It then reviews the basic, general, and specific requisites of a rigorously scientific nature that are required to render experiments to be more appropriate and better geared to the information they seek. A range of experimental approaches to risk assessment are illustrated by results achieved in the Cancer Research Centre of the Ramazzini Foundation (CRC/RF).

Prevention of breast cancer with tamoxifen: preliminary findings from the Italian randomised trial among hysterectomised women. Italian Tamoxifen Prevention Study.

Background: Tamoxifen is a candidate chemopreventive agent in breast cancer, although the drug may be associated with the development of endometrial cancer. Therefore we did a trial in hysterectomised women of tamoxifen as a chemopreventive.

Methods: In October, 1992, we started a double-blind placebo-controlled, randomised trial of tamoxifen in women (mainly in Italy) who did not have breast cancer and who had had a hysterectomy.

Chemoprevention trial of contralateral breast cancer with fenretinide. Rationale, design, methodology, organization, data management, statistics and accrual.

The Fenretinide (4-HPR) Breast Cancer Study is a randomized multicenter clinical trial originally designed and conducted by the investigators of the Istituto Nazionale Tumori of Milan. The study is sponsored by the National Cancer Institute of Bethesda and by the Italian National Research Council. The trial was designed to evaluate the effectiveness of the synthetic retinoid 4-HPR, at a dose of 200 mg per os every day for 5 years, in reducing the incidence of contralateral breast cancer in a population of patients previously operated on for breast cancer.

Results of three life-span experimental carcinogenicity and anticarcinogenicity studies on tamoxifen in rats.

Tamoxifen was submitted to carcinogenicity bioassays on Sprague-Dawley rats (of the colony used at the Cancer Research Center in the Castle of Bentivoglio of the European Ramazzini Foundation of Oncology and Environmental Sciences) at the dose of 3.3 mg/kg b.w.

Results of a long-term experimental study on the carcinogenicity of vinyl acetate monomer in mice.

Vinyl acetate monomer (VAM) was administered in drinking water at doses of 5,000, 1,000, and 0 ppm (v/v), to Swiss mice, 17 weeks old (breeders) or 12-day embryos (offspring) at the start of the experiment. The treatment lasted 78 weeks, and the animals were kept under control until spontaneous death. VAM has been shown to cause an increase in: (1) total malignant tumors; (2) carcinomas of the Zymbal glands, oral cavity, tongue, esophagus, and forestomach; (3) stomach tumors; (4) lung tumors; and (5) uterine tumors.

Results of long-term carcinogenicity studies of chlorine in rats.

Four groups, each of 50 male and 50 female Sprague-Dawley rats, of the colony used in the Cancer Research Center of Bentivoglio of the Ramazzini Foundation, 12 weeks old at the start of the study, received drinking water containing sodium hypochlorite, resulting in concentrations of active chlorine of 750, 500, and 100 mg/l (treated groups), and tap water (active chlorine < 0.2 mg/l) (control group), respectively, for 104 weeks. Among the female rats of the treated groups, an increased incidence of lymphomas and leukemias has been observed, although this is not clearly dose related.

Results of long-term experimental studies on the carcinogenicity of methyl tert-butyl ether.

Methyl-tert-butyl ether (MTBE) was submitted to long-term carcinogenicity bioassays on Sprague-Dawley rats. The test compound was delivered in olive oil by stomach tube (gavage), at the doses of 1000, 250, and 0 mg/kg b.w.

Results of long-term experimental carcinogenicity studies of the effects of gasoline, correlated fuels, and major gasoline aromatics on rats.

Unleaded gasoline, with high aromatic content, leaded gasoline, gasoil (diesel), kerosene, toluene, xylenes, ethylbenzene, and 1,2,4-trimethyl-benzene were submitted to long-term experimental carcinogenicity bioassays. The mixtures and the compounds were administered by stomach tube, in olive oil, once daily, 4 days weekly, for 104 weeks, to male and female Sprague-Dawley rats. The animals were kept under control until the end of the experiments.

Mesotheliomas in some selected Italian population groups.

The analysis of 335 cases of mesothelioma observed at the Ramazzini Foundation and the Bologna Institute of Oncology has shown: 1) a high percentage of correlation of these tumours with asbestos exposure; 2) a large number of population categories potentially exposed to asbestos fibres and therefore at risk of developing mesothelioma; and 3) the high risk of mesothelioma among people exposed in various circumstances to asbestos used in railroads and sugar refinery plants.

p53 gene mutation pattern in rat liver tumors induced by vinyl chloride.

Vinyl chloride (VC) induces angiosarcomas of the liver (ASL) and hepatocellular carcinomas (HCCs) in humans and rodents. We examined the presence of p53 gene mutations in ASL and HCC induced by VC in Sprague Dawley rats; 25 ASL and eight HCCs were analyzed for point mutations in exons 5-8, using PCR amplification, single-strand conformation polymorphism analysis, and direct DNA sequencing. Mutations were found in 11 (44%) of the ASL and in 1 HCC.

Ignored occupational risks of asbestos mesotheliomas.

Nine cases of asbestos mesothelioma following usually ignored asbestos exposure were reported. In these cases the asbestos exposure has been traced following a thorough medical inquiry within the hospital. Such a type of inquiry would reduce the number of mesotheliomas due to unknown causes or considered spontaneous.