Review of mechanistic studies relevant to the potential carcinogenicity of asphalts.

Heating of asphalts to facilitate use in paving and roofing applications produces fumes containing polycyclic aromatic compounds (PAC). Regulatory organizations have suggested asphalt fumes of concern to humans due to possible carcinogenic effects but data are inadequate to classify. Two-year rodent inhalation studies and recent European epidemiology research have shown that asphalt fume alone does not pose a carcinogenic risk to humans. Dermal exposure to asphalt fume condensate have produced skin tumors in mouse skin painting studies but no skin cancer studies in humans have been reported occupationally. Mechanistic research explores underlying processes to assess relevance of findings in animals to humans. DNA adducts are useful as biological dosimeters of exposure, but DNA repair processes, lack of correlation with more definitive genotoxic and cancer results in animals and humans limits reliability as a predictor of carcinogenic hazard. Inhibition of gap junction intercellular communication and stimulation of intracellular signaling by asphalt fume condensate can relate to tumor development. Up and down-regulation of expression in genes involved in the metabolism and action of asphalt fume demonstrates intrinsic activity at the cellular level but changes were inconsistent. The relationship of reported effects on the immune system to carcinogenesis is unclear. Overall, results of mechanistic studies provide insights into biological activity from asphalt fume exposure but compositional differences, level of human exposure and detoxification processes must be considered in translating these findings to cancer risk.

Mortality studies of machining fluid exposure in the automobile industry. III: A case-control study of larynx cancer.

A case-control study of larynx cancer was conducted within a cohort of automobile workers exposed to metal working fluids, commonly referred to as machining fluids (MF). Results are based on 108 cases of larynx cancer and 5:1 matched controls. Risks associated with specific types of MF, as well as specific components of the fluids were evaluated. Based on a retrospective exposure assessment, lifetime exposures to straight and soluble fluids, grinding particulate, biocides, selected metals, sulfur, and chlorine were examined. Exposure to asbestos and acid mists at two of the three study sites was also characterized. Results suggest that straight mineral oils are associated with almost a two-fold excess in larynx cancer risk. There was also evidence of an association with elemental sulfur, commonly added to straight MF to improve the integrity of the materials under extreme pressure and heat. It is not clear whether sulfur is causally related to an excess relative risk of larynx cancer or whether the observed association is the result of unmeasured confounding by another contaminant or process feature. For example, the high stress operations that require MF enriched with sulfur are also more likely to produce polycyclic aromatic hydrocarbons (PAHs) during the process. Thus, the observed association with sulfur may be due to an association with PAH. The finding of excess risk of laryngeal cancer associated with MF is consistent with several previous reports in the literature. This is the first study, however, to distinguish straight mineral oils from other types of MF. Based on these findings, a general reduction in concentrations of straight mineral oil particulate in occupational environments would be prudent.

Consistent associations between hepatic lesions in English sole (Parophrys vetulus) and polycyclic aromatic hydrocarbons in bottom sediment.

A consistent and statistically significant association between prevalence of hepatic neoplasms in free-living sole (Parophrys vetulus) and levels of anthropogenic polycyclic aromatic hydrocarbons in bottom sediment from sites of fish capture was documented in a series of studies conducted over a period of 7 years in Puget Sound, Washington. This result strengthens the evidence supporting a causal relationship between exposure to sediment-associated hydrocarbons and development of hepatic neoplasms in this bottom-dwelling marine fish species. Prevalences of two other distinct categories of idiopathic hepatic lesions-megalocytic hepatosis and steatosis/hemosiderosis-also showed consistent, statistically significant associations with polycylic aromatic hydrocarbon concentrations in bottom sediment, and association with prevalence of a third category (putatively preneoplastic foci of cellular alteration) approached statistical significance. On the basis of other studies, megalocytic hepatosis and foci of cellular alteration are both considered to be important precursor lesions in the stepwise histogenesis of hepatic neoplasms.

Mortality among workers exposed to coal tar pitch volatiles and welding emissions: an exercise in epidemiologic triage.

The United Automobile Workers International Union has established a system of epidemiologic triage to evaluate patterns of mortality among groups of union members. In response to worker concerns, the Union examined mortality at a metal stamping plant, using a method which linked pension records with the State of Michigan computerized death registry. The observed proportion of malignant neoplasms was nearly twice that expected (95% Confidence Limits 1.36, 2.62). Two- to five-fold excess proportional mortality from cancer of the digestive organs, lung cancer, and leukemia accounted for most of the overall excess. Strong associations were found between lung and digestive organ cancer and employment as maintenance welders or millwrights in the plant (odds ratios greater than 10). High levels of six polycyclic aromatic hydrocarbons with mutagenic and carcinogenic properties were found during hot coal tar application to wood block floors, work conducted by the high-risk groups. These levels were substantially reduced following the purchase of new tar pots. The example demonstrates that epidemiologic tools can play a valuable role in occupational health decision making, but care must be taken to avoid mechanical reliance on quantitative testing and to acknowledge the important role of social and political value judgments in the establishment of responsible public policy.

[Significance of mixed function oxidases for evaluation of the harmful effects of chemicals on exposed persons]. / Znachenie na oksidazite sus smesena funktsiia za otseniavane vrednoto vuzdeistvie na khimichnite veshtestva vurkhu eksponirani litsa.

The significance of the mixed function oxidases (MFO) for hygienic toxicology is determined by the exceptional role of that enzyme system in the biotransformation of xenobiotics. On the other hand, the changes in MFO activity are some of the basic mechanisms in organism adaptation to repeated toxic exposures. An original method is elaborated for the assessment of MFO activity, used in the examinations of workers, exposed to carbon sulphide, polycyclic aromatic hydrocarbons, organic solvents, vinylchloride and styrene. Representative groups from the population, that live in a region with strongly polluted atmospheric air were studied. The results obtained reveal that the alterations in MFO activity are an early manifestation of compensatory strain of adaptive mechanisms of organisms and could be used in the diagnosis of premorbid states with chemical etiology, in checking the conformity of MAC in force, for the purposes of vocational selection, etc. The method is easy to perform and could be used for the purposes of therapeutic-diagnostic activity in some other medical specialties: gastroenterology, infectious diseases, etc.

Data from short-term tests on motor vehicle exhausts.

The mutagenicity of motor vehicle exhausts has been studied by using Salmonella typhimurium strains TA 98 and TA 100. Acetone extracts of the particulate phase and the gas phase have been tested in the presence and absence of a metabolizing system (S9). The particulate phases from medium- and heavy-duty diesel vehicles were tested. The vehicles were driven according to a modified 13 mode test, and the particulate phase was sampled at mode 6 (maximum load and intermediate engine speed) and mode 12 (10% load and rated speed). In mode 6 all vehicles gave approximately the same mutagenicity in strain TA 98 (50,000-90,000 revertants/kW-hr) as well as in TA 100 (200,000-360,000 revertants/kW-hr). A higher mutagenic effect, in some cases up to 10 times, was seen with mode 12.Light-duty vehicles of different year models were tested using different fuel/engine combinations. The vehicles were driven according to FTP 72 or ECE driving cycle. Cold starts at two different temperature levels, approx. 0 degrees C and 23 degrees C, respectively, were also compared. Based on the mutagenicity of the particulate extracts (given as revertants per km), the light-duty vehicles could be divided into three main groups. The first group, the high mutagenicity group, giving 100,000-700,000 revertants/km, consists only of diesel cars. In the medium mutagenicity group, giving between 20,000 and 100,000 revertants/km, different gasoline fuels are placed, i.e., leaded and lead-free gasoline as well as alcohol/gasoline fuels. Two other fuels, methanol (M95) and propane (LPG), constitute the low mutagenicity group, giving less than 20,000 revertants/km. Fuels from the medium effect group will produce a particulate phase with low mutagenicity if the vehicle is equipped with a three way catalyst with closed loop, or fuel injection. The cold start temperature did not change this classification, since all samples gave a somewhat higher mutagenic effect at the low temperature. With the ECE driving cycle, much lower mutagenicity was noted with the diesel cars than in the tests with the FTP-72 driving cycle, at least with tester strain TA 98. On strain TA 100 the diesel exhaust samples still showed a much higher mutagenicity than other samples. Acetone extracts of the gas phase from diesel and gasoline exhaust (trapped in ice/water condensers and CO(2)/ethanol condensers) also gave mutagenic effects. The contribution of the gas phase to the mutagenic effects seems to be more important in the absence of S9 and more important in the case of gasoline exhausts.

Role of inhalation studies with animals in defining human health risks for vehicle and power plant emissions.

Automotive vehicles and power plants using fossil fuels emit a complex array of gases and particulate material. The physical and chemical characteristics of these emissions vary markedly between sources and comprise only a portion of the contributors to air pollution exposure of people. Further, it is well recognized that a single form of self-inflicted air pollution, cigarette smoking, is the dominant cause of air pollution-induced disease. These factors minimize our potential for developing an adequate understanding of the health effects of vehicle and power plant emissions by studying only people. The alternative is to use the human data to the extent feasible and complement it with information gained in studies with macromolecules, organelles, cells, tissues and whole animals. Within this context, this paper reviews the use of inhalation studies with animals for defining human health risks of airborne materials, especially particulate materials. The major areas covered are: the fate of inhaled materials, the pathogenesis of disease induced by inhaled materials and long-term animal studies to identify late-occurring effects. Emphasis is placed on the utility of studies in whole animals as integrative models in which the multiple processes such as xenobiotic metabolism, cell injury, repair, transformation and promotion under the influence of many host factors interact in a manner that may not be directly observed in isolated cells or tissues.

Some toxic compounds produced in food by cooking and processing.

Both cooking and processing of food can produce toxic compounds in food, if the appropriate precursors are present. N-Nitrosamines, polycyclic aromatic hydrocarbons and phenolic compounds, lipid polymerisation products resulting from deep-fat frying, lipid oxidation products, Maillard-browning products and other products of protein reactions are discussed as well as their formation, concentration and control. The conclusion points out that contamination of human food is almost impossible to avoid and must be considered together with the beneficial effects of food processing on food safety, flavour, shelf-life and convenience.

Coal liquefaction: recent findings in occupational safety and health.

Some coal liquefaction materials are potentially hazardous because of similarities to materials in other related coal processes that have been associated with a high cancer risk. Limited survey data obtained by NIOSH at two coal liquefaction pilot plants have shown that workers were exposed to low concentrations of certain polynuclear aromatic hydrocarbons (PNA's) and aromatic amines, some of which are suspected carcinogens. The degree of risk incurred by such exposures cannot be determined because toxicologic data allowing for the evaluation of effects at low exposure levels are unavailable. These industrial hygiene studies are discussed as well as recent health and process aspects of this technology.

Diesel exhaust - an occupational carcinogen?

The existence of polycyclic aromatic hydrocarbons (PAH) in the particulate phase of diesel engine exhaust has raised concern about a carcinogenic effect in workers exposed to exhaust from diesel engines. Some of the PAH are carcinogenic following inhalation by experimental animals and are associated with excess cancer mortality in some occupational exposures. Studies of occupational exposure to diesel exhaust show concentrations of PAH are above ambient levels but below the very high levels in occupations with demonstrated excess cancer mortality. A critical review of the epidemiologic evidence on the carcinogenicity of workplace exposure to diesel engine exhaust is suggestive of a carcinogenic effect but the existing data are sparse and contradictory. Further epidemiologic studies of this question are needed.

Epidemics of non-infectious disease.

Epidemics of non-infectious disease are often caused by exposure to industrial products, intermediates or by-products, either in the work-place or as a result of the contamination of a wider environment. Although the prime objective of research must be the recognition of the hazard and the evaluation of its magnitude so that illness may be prevented, close collaboration of clinicians, epidemiologists and toxicologists should lead to the acquisition of much knowledge of the mechanisms by which disease is caused. Catastrophes, though always regrettable, must be seen as experiments demanding careful analysis and exploitation. Many examples of different types of problem will be selected from the numerous epidemics from the time of the Schneeberg and Joachimsthal miners to the recent concern with contamination of the environs of Seveso by dioxin.

Tissue lesions of tiger salamanders (Ambystoma tigrinum): relationship to sewage effluents.

A population of facultative neotenous tiger salamanders (A. tigrinum) inhabiting a sewage lagoon at Reese AFB, Hurlwood, Texas, was found to have an exceptionally high rate of spontaneous tissue lesions. The population is composed of an estimated 28,000 large, reproductively mature larvae that are restricted to the lagoon. Only about 17% of the population metamorphoses normally. In contrast, tiger salamanders from uncontaminated lagoons in the same general vicinity metamorphose normally; however, no neoplasms were discovered in larvae sampled from the nonsewage lagoosn. N-nitrosamine analyses of water and tissue samples of larvae were negative. Polycyclic aromatic hydrocarbon analyses revealed traces of benzo[a]pyrene in the sludge; however, perylene, a constituent of jet fuel, was found in high concentration (300 ppb). These results indicate tat preylene, which was previously found not be tumorigenic to mice and rats, should be retested as a possible agent for nonmammalian species.