Potential carcinogenic effects of world trade center dust after intratracheal instillation to Sprague-Dawley rats: first observation.

BACKGROUND: More than 10 years have passed since the terrorist attack on the New York City World Trade Center on September 11, 2001. It is well known that long-term carcinogenic bioassays on rodents can predict the potential carcinogenic effects of chemical and physical agents for humans. OBJECTIVE: A life-span carcinogenicity bioassay was conducted on Sprague-Dawley rats at the CMCRC of the Ramazzini Institute to test the potential carcinogenic effects of settled dust collected at the WTC immediately after the terrorist attack. METHODS: The WTC material tested is a complex mixture of coarse particles (95%) contain pulverized cement, glass fibres, asbestos, lead, polycyclic aromatic hydrocarbons (PAH(S) ), polychlorinated biphenyls (PCB(S) ) and polychlorinated furans, and dioxin. The test matter was suspended in sterile saline and administered by intratracheal instillation (IT) to 8-week-old Sprague-Dawley rats (100 animals/sex), 3-4 days/week for 4 weeks. A group of 200 male and female rats served as controls. The animals were kept under observation until natural death. RESULTS: Histopathological evaluation of the lungs (target organ) of instilled control and treated male and female rats, did not show any significant increased incidence of lung tumors. Two hemangiomas (one with endothelial atypia) and one hemangiosarcoma were found in the lungs of treated males. Moreover a modest increased incidence of terminal bronchiolar hyperplasia (TBH) and squamous metaplasia occurred in the lung of treated males and females compared to the controls. CONCLUSION: Hemangioma and hemangiosarcoma are extremely rare tumors in the lung of our colony and we believe they are caused by WTC dust.

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). The paper ends with a call for closer relations and integration among experimental, epidemiologic, and biostatistical studies.

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. Epidemiologic investigation is of limited use in this field and yields its data too late to be useful. Experimental studies offer the only possible approach for assessing such risks. To increase experimental sensitivity and consistency of results, mega-experiments must be designed. That is, experiments that use a large number of animals with a well-known basic tumorigram, that extend the exposure and the biophase for as long as possible, that carefully observe the effects, and that are performed with suitable standardized methods. In the last 15 years the Ramazzini Foundation, in its Cancer Research Center at Bentivoglio, has conducted or planned five mega-experiments. Initial results indicate the great potential of these methods for identifying and assessing diffuse risks.

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. With varying degrees of evidence, all the tested materials were found to increase the total number of malignant tumors and of some site-specific tumors. They must therefore be considered carcinogenic. On the basis of our results the rank of carcinogenic potency of the tested aromatic hydrocarbons increases in the following order: 1,2,4-trimethylbenzene, ethylbenzene, xylenes, toluene (benzene).

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. to groups of 60 males and 60 females, once daily, 4 times weekly, for 104 weeks. All animals were kept under control until spontaneous death. MTBE was found to cause in males an increased incidence of Leydig cell testicular tumors in the group treated with the higher dose, and in females a dose-related increase of leukemias, an increase of dysplastic proliferations of lymphoreticular tissues, and also an increase of uterine sarcomas at the lower tested dose. On the basis of the presented data, MTBE must be considered a potential carcinogen.

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. Moreover, sporadic cases of some tumors, the occurrence of which is extremely unusual among the untreated rats of the colony used (historical controls), were detected in chlorine-exposed animals. The results of this study confirm the results of the experiment of the United States National Toxicology Program (1991), which showed an increase of leukemia among female Fischer 344/N rats following the administration of chlorine (in the form of sodium hypochlorite and chloramine) in their drinking water. The data here presented call for further research aimed at quantifying the oncogenic risks related to the chlorination of drinking water, to be used as a basis for consequent public health measures.

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. A slight increase of hepatomas has been observed among male mice offspring treated with the higher dose. On the basis of these data VAM must be considered a multipotential carcinogen.

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. The role of the hospitals as a primary source of epidemiological information is stressed.

Methyl-tertiary-butyl ether (MTBE)--a gasoline additive--causes testicular and lymphohaematopoietic cancers in rats.

In the framework of a series of experiments conducted to evaluate the carcinogenic effects of oxygenated gasoline additives, MTBE was analyzed in an oral lifetime carcinogenicity study using 8-week-old male and female Sprague-Dawley rats. These experiments were part of a large research project on gasoline carcinogenicity performed at the Bentivoglio (BT) Castle Cancer Research Center of the Ramazzini Foundation and of the Bologna Institute of Oncology, MTBE, dissolved in oil, was administered by stomach tube at the doses of 1000, 250, or 0 mg/kg b.w., once daily, four days weekly, for 104 weeks. The animals were maintained until natural death. The last animal died 166 weeks after the start of the experiment, i.e., at 174 weeks of age. Under the tested experimental conditions, MTBE was shown to cause an increase in Leydig interstitial cell tumors of the testes and a dose-related increase in lymphomas and leukemias in female rats.

Long-term carcinogenicity bioassays on industrial chemicals and man-made mineral fibers, at the Bentivoglio (BT) laboratories of the Bologna Institute of Oncology: premises, programs, and results.

After having stressed the need of primary prevention in the strategy for cancer control, the crucial role of the long-term carcinogenicity bioassays in providing scientific support to primary prevention has been focused. The state-of-the-art, the present inadequacies, the necessity of implementation, and the perspectives of the long-term carcinogenicity bioassays have been briefly reviewed. The performed and ongoing programs of carcinogenicity bioassays at the Bentivoglio (BT) Laboratories of the Bologna Institute of Oncology have been presented, together with the currently available results on several compounds of industrial and commercial relevance.

Xanthine oxidase status in ethanol-intoxicated rat liver.

The status of xanthine oxidase in ethanol-induced liver injury has been investigated in the rat, by acute and chronic ethanol treatments. A 38% increase of the enzyme O-form was observed after repeated ethanol administration. Chronic intoxication caused a significant decrease of total xanthine oxidase activity after both prolonged ethanol feeding and life span ethanol ingestion. The intermediate D/O-form of xanthine oxidase (that can act either as an oxidase or as a dehydrogenase, being able to react with O2 as well as with NAD+ as electron acceptor) increased 5.5-fold after prolonged ethanol feeding.

Formaldehyde: an experimental multipotential carcinogen.

Male and female Sprague-Dawley rats of different ages at the start of the experiments (12 day embryos, and 7 and 25 weeks old) were administered fromaldehyde in drinking water at different doses (2,500 or 1,500, 1,000, 500, 100, 50, 10, 0 ppm). An increased incidence of leukemias and of gastro-intestinal tumors was observed in formaldehyde treated rats. Gastro-intestinal tumors are exceptionally rare in the rats of the colony used. These results, together with the ones obtained by other Authors on rats exposed by inhalation to formaldehyde, indicate that this compound is an experimental multipotential carcinogen. The experimental results presented in this report give scientific support to the epidemiological observation of a higher incidence of leukemias and of gastro-intestinal cancers among the people occupationally exposed.

[Menopause in a sample of women from Bassa Modenese (Italy): its secular trends and connections with labor force activity]. / La menopausa in un campione di donne della Bassa Modenese (Italia): la sua evoluzione nel tempo e la sua connessione con l'attivita lavorativa.

PIP: Comparisons are made among women in Bassa Modenese, Italy, concerning age at menarche and menopause, length of reproductive period, and need for hysterectomy. The impact of employment status and occupation on the timing of these physiological events is considered. (SUMMARY IN ENG AND FRE)^ieng