The role of asbestos fiber dimensions in the prevention of mesothelioma.

A recent interpretation of the pathogenetic role of asbestos fiber size in the development of mesothelioma and in the possibility of mesothelioma prevention needs clarification. This point of view is based on a biased interpretation of the literature. Epidemiologic, experimental, and molecular evidence suggests that the arguments for the role of fiber size relative to dose, dose-response effect, and genetic susceptibility are scientifically unsound. Their proponent also states that means available in the past for the implementation of dust-control measures and/or personal protective equipment would not have contributed to reducing the frequency of mesothelioma among exposed subjects, an argument again based on invalid assumptions.

Cadmium-induced cancers in animals and in humans.

Discovered in the early 1800s, the use of cadmium and various cadmium salts started to become industrially important near the close of the 19th century, rapidly thereafter began to flourish, yet has diminished more recently. Most cadmium used in the United States is a byproduct from the smelting of zinc, lead, or copper ores, and is used to manufacture batteries. Carcinogenic activity of cadmium was discovered first in animals and only subsequently in humans. Cadmium and cadmium compounds have been classified as known human carcinogens by the International Agency for Research on Cancer and the National Toxicology Program based on epidemiologic studies showing a causal association with lung cancer, and possibly prostate cancer, and studies in experimental animals, demonstrating that cadmium causes tumors at multiple tissue sites, by various routes of exposure, and in several species and strains. Epidemiologic studies published since these evaluations suggest that cadmium is also associated with cancers of the breast, kidney, pancreas, and urinary bladder. The basic metal cationic portion of cadmium is responsible for both toxic and carcinogenic activity, and the mechanism of carcinogenicity appears to be multifactorial. Available information about the carcinogenicity of cadmium and cadmium compounds is reviewed, evaluated, and discussed.

Identification of carcinogenic agents and primary prevention of cancer.

During the annual Ramazzini Days, the Mayor of Carpi confers the Ramazzini Award on scientists deemed by the Collegium Ramazzini to have made outstanding contributions to furthering the aims of Bernardino Ramazzini in safeguarding public health. Dr. Lorenzo Tomatis was the Ramazzini Award recipient in 2005, and the presentation of the award was a highlight of the Symposium. The Ramazzini Lecture given by Dr. Tomatis follows.

Role of experimental and epidemiological evidence of carcinogenicity in the primary prevention of cancer.

Experimental chemical carcinogenesis, which included long-term tests in experimental animals,had a dominating role in cancer research between the 1920s and the late 1960s. Two events marked a certain decline of confidence in the ability of experimental results to predict human risks: the incapacity of developing methods to identify agents acting on the different steps of the carcinogenesis process, and the incapacity to reproduce experimentally the strong evidence of carcinogenicity of tobacco smoke provided by epidemiological studies. It was at that time that epidemiologists and biostatisticians developed criteria for assessing the causation of chronic-degenerative diseases relying primarily on epidemiological evidence. In 1969 the International Agency for Research on Cancer (IARC) did initiate a programme for identifying the cause of cancer with the aim of promoting the primary prevention of cancer. The programme is focused on the evaluation of the carcinogenicity of environmental agents on the basis of both the experimental and epidemiological evidence and, since the 1990s, a balanced use of the new tools provided by advances in toxicology, molecular biology and genetics. A strong point of the IARC programme is that in the absence of adequate human data it is reasonable and prudent to regard agents for which there is sufficient experimental evidence of carcinogenicity as if they were carcinogenic to humans.

[The role of asbestos fibre dimensions in the pathogenesis and prevention of mesothelioma]. / Il ruolo della dimensione delle fibre di amianto nella patogenesi e nella prevenzione del mesotelioma.

The particular point of view, recently published by Gerolamo Chiappino, on the pathogenetic role of asbestos fibres size in the origin of mesothelioma and on the possibility of mesothelioma prevention until the middle of the '80s needs to be critically clarified. The suggestion of an exclusive role of ultrashort and ultrathin fibres in the origin of mesothelioma is based on a biased interpretation of the literature. A review of the epidemiological, experimental, and molecular literature suggests that Chiappino's statements on the role of dose, dose-response effect, and genetic susceptibility are scientifically unsound Chiappino states that, in the past, in the workplaces where use and exposure to asbestos were not stopped, any reduction in the intensity of exposure by means of dust control measures or personal protective equipment would not have contributed to reduce the frequency of mesothelioma. In the authors' opinion the underlying assumptions are invalid.

Business bias: how epidemiologic studies may underestimate or fail to detect increased risks of cancer and other diseases.

In spite of claiming primary prevention as their aim, studies of potential occupational and environmental health hazards that are funded either directly or indirectly by industry are likely to have negative results. The authors present three common scenarios in which faulty design of epidemiologic studies skews results, and list 15 study design flaws that lead to results that are dangerously misleading with regard to both the evaluation and the improvement of public health.

Maternal effects and cancer risk in the progeny of mice exposed to X-rays before conception.

To investigate in an animal model whether preconceptual X-ray exposure leads to an altered tumor rate and spectrum in the offspring, a transgeneration carcinogenesis study was carried out. Female mice received X-ray irradiation (2 x 2 Gray) 2 weeks prior to mating with untreated males. After weaning, half of the descendants were exposed for 6 months to the immunomodulating and tumor-promoting compound cyclosporine A (CsA) by diet, the others remained untreated. The animals were maintained for their entire lifespan, terminal sacrifices were carried out after 28 months. Complete autopsy was performed, and three protocol organs (lung, liver and spleen) were examined histologically, together with any suspicious lesions in other organs. Fertility and the lifetime of the maternal mice were reduced by the X-ray irradiation, and their incidence of lung and liver tumors was increased as compared to non-irradiated mice. The descendants of all groups revealed comparable body weights and mortality rates. The incidence of hematopoietic/lymphoreticular tissue tumors increased in the female hybrids by 6 months of CsA-treatment. A higher incidence of lung and liver tumors in the sham-treated male progeny of irradiated mothers was detected, pointing to a possible germ cell-transmitted alteration initiated by the preconceptual maternal X-ray exposure.

Dichlorodiphenyltrichloroethane (DDT): ubiquity, persistence, and risks.

Due to uncontrolled use for several decades, dichlorodiphenyltrichloroethane (DDT), probably the best known and most useful insecticide in the world, has damaged wildlife and might have negative effects on human health. This review gives a brief history of the use of DDT in various countries and presents the results of epidemiologic and experimental studies of carcinogenesis. Even though its use has been prohibited in most countries for ecologic considerations, mainly because of its negative impact on wildlife, it is still used in some developing countries for essential public health purposes, and it is still produced for export in at least three countries. Due to its stability and its capacity to accumulate in adipose tissue, it is found in human tissues, and there is now not a single living organism on the planet that does not contain DDT. The possible contribution of DDT to increasing the risks for cancers at various sites and its possible role as an endocrine disruptor deserve further investigation. Although there is convincing experimental evidence for the carcinogenicity of DDT and of its main metabolites DDE and DDD, epidemiologic studies have provided contrasting or inconclusive, although prevailingly negative, results. The presence and persistence of DDT and its metabolites worldwide are still problems of great relevance to public health. Efficient pesticides that do not have the negative properties of DDT, together with the development of alternative methods to fight malaria, should be sought with the goal of completely banning DDT.

Primary prevention protects public health.

It is widely accepted that epidemiological data provide the only reliable evidence of a carcinogenic effect in humans, but epidemiology is unable to provide early warning of a cancer risk. The experimental approach to carcinogenicity can ascertain and predict potential cancer risks to humans in time for primary prevention to be successful. Unfortunately, only in rare instances were experimental data considered sufficiently convincing per se to stimulate the adoption of preventive measures. The experimental testing of environmental agents is the second line of defense against potential human carcinogens. The first line is the testing of synthesized agents, be these pesticides, medical drugs, or industrial chemical/physical agents, at the time of their development. We do not know, however, how many substances have been prevented from entering the environment because most tests are carried out by commercial or private laboratories and results are rarely released. A better understanding of the mechanisms underlying the sequence of events of the carcinogenesis process will eventually lead to a more accurate characterization and quantification of risks. However, the ways that mechanistic data have been used lately for evaluating evidence of carcinogenicity have not necessarily meant that the evaluations were more closely oriented toward public health. A tendency has surfaced to dismiss the relevance of long-term carcinogenicity studies. In the absence of absolute certainty, rarely if ever reached in biology, it is essential to adopt an attitude of responsible caution, in line with the principles of primary prevention, the only one that may prevent unlimited experimentation on the entire human species.

The IARC monographs program: changing attitudes towards public health.

From its outset, the International Agency for Research on Cancer's (IARC's) program for the evaluation of carcinogenic risks for humans had to resist strong direct and indirect pressures from various sources to protect its independence. External experts for Monographs working groups were selected on the basis of competence and the absence of conflicts of interest. The IARC did not use unpublished or confidential data, so readers could access the original information and thus follow the groups' reasoning. The strength of the original program lay in its scientific integrity and its transparency. Since 1994, however, the IARC appears to have attributed less importance to public health-oriented research and primary prevention, and the Monographs program seems to have lost some of its independence. Criteria for evaluating carcinogenicity related to mechanism(s) of action are not necessarily used as originally intended, to ensure better protection of public health. Evidence for carcinogenicity provided by the results of experimental bioassays has been disregarded on the basis of only suggested mechanistic hypotheses. If tests show those hypotheses to be incorrect, or if they do not account adequately for the wide range of susceptibility in humans, serious consequences for public health may follow.

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. Official recognition of the ICOH compromises the credibility of the WHO and the ILO. It is inappropriate for the ICOH to continue to receive WHO and ILO recognition unless the ICOH is recognized as an industry organization.