Eula Bingham

Environmental Carcinogens: The Modifying Effect of Cocarcinogens on the Threshold Response

The acceleration of tumor production in mice by repeated application of polycyclic aromatic hydrocarbon carcinogens of high and low potency in the presence of cocarcinogenic compounds is described. Experiments exploring the concentration levels of carcinogen and cocarcinogen necessary to produce tumors demonstrate that there is a 1,000-fold increase in the enhancement of potency of low concentrations of benzo[a]pyrene and benz[a]anthracene when n-dodecane is the diluent. The effect of cocarcinogens is most obvious during exposure to low concentrations of carcinogen. The implications of this observation in the environment is discussed.

An isolated perfused lung preparation for metabolic studies

Abstract The isolated perfused lung preparation described in this report offers great potential in studying the distribution, binding, rates and pathways of metabolism of foreign compounds under conditions closely resembling those which occur in living animals. Lungs from either normal or perturbed animals may be investigated. Criteria have been developed that are necessary to insure viability and provide optimum conditions for metabolic studies.

Alveolar Macrophages: Reduced Number in Rats after Prolonged Inhalation of Lead Sesquioxide

A decreased number of alveolar macrophages was found in washings from lungs of rats inhaling small particles of lead sesquioxide for 3 to 12 months, as compared with control animals exposed to filtered air. This result contrasts with that reported by others for animals given massive exposures to various dusts for short periods of time. Because the concentrations of lead were comparable to those observed in some industrial(150 �g/m3) or urban (10 �g/m3) environmental conditions, the results may be significant in terms of human lung clearance processes after such exposures.

Metabolism of trichloroethylene by the isolated perfused lung

Abstract A technique for perfusing the isolated lung of rats and guinea pigs was developed. The main features include: constant-pressure recirculating perfusion with heparinized, autologous, whole blood; cyclic subatmospheric pressure within a temperature-controlled ventilation chamber; and ventilating gas consisting of air containing about 5% CO2. Lungs were maintained in this system for up to 3.5 hr. This system appears to be a valid technique for investigating pulmonary metabolism. Trichloroethylene was added to the gas supplied to the isolated lungs. Equilibrium was established between this gas and perfusing blood within 15 to 30 min. Trichloroethanol was evident in blood after 15 to 30 min of exposure. Chloral hydrate and trichloroethanol glucuronide were not observed. Trichloroethanol in lung tissue was estimated at about 30% of the total metabolites recovered in both rat and guinea pig preparations. Trichloroethanol production appeared to be independent of trichloroethylene concentrations and its appearance was linear over 3 hr. Trichloroacetic acid was present in smaller amounts. Pretreatment of rats with phenobarbital (75 mg/kg for 4 days) increased trichloroethanol formation significantly. Addition of ethanol to yield initial blood concentrations near 90 mg/100 ml did not affect trichloroethanol formation.

Carcinogenicity of Mineral Oils

In the mind of the public, the term mineral oil is closely associated with the highly refined white mineral oils that are used in pharmaceutical preparations and things such as tanning and baby oils. Actually mineral oil is a generic term that covers a diverse range of petroleum products. In terms of volume and use, white mineral oil constitutes a small fraction of the total production of all types of mineral oils. The anti-friction properties of mineral oils account for their predominant use as industrial and automotive lubricants. In addition to reducing friction, mineral oils have important secondary properties that make them useful for such things as heat transfer fluids, cutting oils, and corrosion inhibitors. The use of mineral oils is widespread and the potential for human exposure is high. This necessitates careful evaluation of the carcinogenic properties of the various types of mineral oils to which workers are exposed. In the occupational environment, the potential risks of exposure to fuel oils are similar to those of mineral oils, and a discussion of the hazards of mineral oils applies to fuel oils and related petroleum products. The carcinogenic properties of mineral oils were uncovered in the early 1900s by epidemiologic studies of workers in the cotton-spinning industries of the United Kingdom, Canada, and the United States (for reviews see Bingham’ and IARCZ). In these cases the source of exposure was a device known as a spinning mule, which required lubrication with mineral oil. Operators of spinning mules, called mule spinners, suffered an excess of scrota1 and skin cancer. Over the last 75 years, epidemiologic studies conducted in various industrialized countries have conclusively demonstrated excess cancer in many workers (such as machinists, who are chronically exposed to mineral oils). In addition, experimental studies involving fractionation and chemical separation and subsequent testing of fractions in experimental animals have provided important information regarding the carcinogenic potential of certain petroleum fractions and products derived thereof.

Enzymatic Changes in Alveolar Macrophages of Rats Exposed to Lead and Nickel by Inhalation

In previous inhalation studies, rats exposed to aerosol concentrations of lead oxide (Pb2O3), 150 μg/m3; lead chloride (PbCl2), 100 μg/m3; nickel oxide (NiO), 120 μg/m3; and nickel chloride (NiCl2), 109 μg/m3; significant changes were observed in the lungs and alveolar macrophages. In this study the hydroiytic enzymes, acetylesterase, acid and alkaline phos-phatases, lysozyme, and beta-glucuronidase, in alveolar macrophages and lung washout fluid from rats subjected to the inhalation of the lead and nickel aerosols were examined. Washed alveolar macrophages from animals exposed to lead and nickel aerosols were found to contain reduced quantities of the various hydrolytic enzymes (except for acetylesterase) when compared with those from control rats. On the other hand, a significant increase in enzymatic activity was noted in lung washout fluid from exposed animals. The functional efficiency of macrophages, relative enzyme changes, and the mechanism of action of metals are discussed. It is important to note that the changes observed in these studies were from animals exposed to metallic concentrations near their Threshold Limit Values.

Workplace Regulation Gone Wrong

Although the title of this presentation implies a problem, it must be pointed out that many interest groups in this country do not believe there is anything wrong. A deregulatory movement-political, well-organized, and well-funded-prefers fewer standards to cover workplaces, a smaller enforcement activity, and generally a reversion to the voluntary effort that characterized workplace safety and health activities before passage of the Occupational Safety and Health Act of 1970. Prevention of occupational disease requires control measures in the work environment that either eliminate the physical or chemical agent or reduce the level to a point where men and women can work without incurring disease. This concept of prevention is at the heart of the Occupational Safety and Health Act. A diagram of the concepts is presented in FIGURE 1. The identification of disease and contaminants responsible for the disease is the research activity of the academic community, National Institute of Occupational Safety and Health, other NIH institutes, industry, and labor. The result of such activity all too often ends after the first step: the identification of disease. However, the route to determining mechanisms of action that pinpoint the specific biochemical lesion may be a high-priority activity and consume everyone’s attention. An excellent example of this approach has been the case of lead. The ill effects of lead exposure have been recognized for several hundred years, and while there has been a relentless pursuit of the biochemical lesions and their sites of occurence, little attention was paid to control of lead in the workplace until the OSHA lead standard was promulgated in 1979. It must be admitted that the pursuit of the molecular level mechanisms of toxicity has driven the recognition that more protective standards are necessary. However, the lag between identification and control, as well as the lag between understanding certain biochemical effects and control, has meant that “prevention” did not occur for thousands of workers or their families. (Do we need to be reminded that even now there axe documented cases of children whose blood lead levels are excessive because of contamination by parental clothing?) Embodied in the Act is the notion that objective measures ensuring the control of physical and chemical agents shall be instituted. One set of “objective measures” is clearly spelled out as “Standards” in the Occupational Safety and Health Act. Included are the procedures (Enforcement) for ensuring that those standards are met. If we accept the notion that there are enormous numbers of workers still at great risk of disease, injury, and death, then it may be worthwhile to analyze the record on standards promulgation for clues regarding the factors that either promote or inhibit the promulgation of standards. This record represents only one aspect of regulation, but it provides insight into understanding what is wrong-or right-with the current approaches. Examination of the health and safety standards record of the Occupational Safety and Health Administration makes it obvious that the productivity is very