The U.S. National Institute for Occupational Safety and Health (NIOSH) has recently published a criteria document addressing occupational exposure to metal removal fluids ("Criteria for a Recommended Standard: Occupational Exposure to Metalworking Fluids", 1998). This NIOSH document contains an extensive compilation and review of relevant clinical case studies, surveillance data, and epidemiological studies of respiratory conditions and their association with exposure to MRF aerosols. In its discussion of the literature and data reviewed on respiratory effects, NIOSH notes:

Recent studies are not entirely consistent in documenting exposure-response relationships between MWF [metalworking fluid] aerosol exposures and respiratory symptoms and lung function effects (both acute and chronic), including clinically recognized asthma. Nevertheless, for each MWF class, frequent adverse respiratory effects have been clearly attributable to MWF aerosol concentrations in excess of approximately 0.5 mg/m3 (thoracic fraction) in most recent epidemiological studies, and to even lower aerosol concentrations in some of these studies. . . . The possibility exists that short-term peak exposures are more important determinants of at least some of the airways disorders induced by MWF aerosols (e.g., asthma), but no epidemiological studies to date have assessed MWF aerosol exposures with respect to short-term peak exposures.

Despite an impressive amount of research recently carried out on the airways effects of exposure to MWF aerosol, the potential importance of various adverse acute airways effects attributed to MWF aerosol is not entirely clear.

Theories about asthma generally explain the hyperreactivity of the airways as an exaggeration of the normal defense response of the respiratory tract. This can result from abnormal tissue reactions in the airways (both intrinsic and/or extrinsic), or from a biochemical, neurological or humoral imbalance of other normally functioning responses. Because of the diverse stimuli known to produce asthma (see below), no single current theory satisfactorily explains all types and cases.

Common precipitating factors in asthma include the following:

Allergic Stimuli: In allergic asthma, acute episodes may be precipitated by inhaled or ingested allergens. Airborne allergens such as house dusts, feathers, animal danders, insect fragments, furniture stuffing, fungal spores and various plant pollens are substances that may be inhaled. Allergenic foods like cow's milk, fish, eggs, various nuts, chocolate, shellfish and tomatoes are generally less responsible as a cause of asthma. In some people, allergens may have an additive or even synergistic effect. Allergens causing sensitivity in a person are unpredictable and variable; the response can change, and often decreases in severity from childhood to adult life.

Toxic and Irritative Stimuli: Many irritative factors in the inhaled air may induce or aggravate an asthma attack. Obvious examples are tobacco smoke, air pollutants including automobile exhaust and industrial fumes, and volatile substances such as paint or gasoline. Certain chemicals such as TDI (toluene diisocyanate) and many metals such as platinum or nickel can also provoke an attack.

Infection: although infection (viral, bacterial or fungal) is often the precipitating stimulus in infective asthma, it can also be a significant factor in allergic asthma. Bacterial sinusitis or a common cold may thus trigger an asthmatic episode, or infection may complicate an attack that began on a purely allergic basis.

Medications: Drugs may initiate acute asthma either by their direct pharmacological action or by an allergic response, such as with penicillin and vaccines.

Other Causes and Contributing Factors: Psychological and physical stress may contribute to an asthmatic episode in susceptible individuals. Similarly, trigger mechanisms such as breathing cold air, rapid changes in temperature or humidity, physical exertion or even laughing may cause an acute episode.

Chronic Bronchitis

Chronic bronchitis is associated with hyperplasia and hypertrophy of the mucus secreting glands found in a layer of cells (the submucosa) of the large cartilaginous conducting airways (trachea and bronchi). This enlargement and/or increase in the number of cells over a long duration leads to increased mucus production and secretion into the conducting airways. Chronic bronchitis also produces hyperplasia of the goblet cells and other diffuse changes in the smaller noncartilaginous airways (bronchioles) that do not contain submucus glands. It is quite likely that the diffuse changes in small airways contributes more to the obstruction and poor distribution of air to the alveoli than do the more obvious abnormalities in large airways. Of course, the chronic cough associated with chronic bronchitis is a symptom of the body's attempt to clear this excess mucus.

Chronic bronchitis is an integral part of a larger category known as chronic obstructive pulmonary disease (COPD). COPD, consisting of some combination of chronic bronchitis and emphysema, is the most common chronic disease of the lungs. Although generally present in combination, chronic bronchitis and emphysema are two distinct processes. Emphysema is a very serious obstructive lung disorder that involves gradual destruction of the septa (walls) of the respiratory bronchioles, alveolar ducts, and alveolar sacs. This pathologic process serves to greatly reduce the amount of gas exchange surface area.

Hypersensitivity Pneumonitis

Hypersensitivity pneumonitis (HP) is an inflammatory disease that affects primarily the deep lung or peripheral airways. Specifically, it is the alveoli (those areas of the lower lung where the actual exchange of oxygen and carbon dioxide occurs) and the interstitium (the tissue space separating individual alveoli) that are typically affected. HP is not the same as asthma, which involves constriction of the conducting airways leading to the lower lung. Moreover, although both diseases involve the activity of the immune system, the mechanism of action differs between the two. HP is associated with the cell-mediated response arm of the immune system, whereas asthma is more typically a manifestation of the humoral- or antibody-mediated immune response. It is also important to recognize that HP and asthma are both distinct from non-specific airway reactivity or hyper-responsiveness, which is an airway disorder that does not involve an immune-mediated response component.

The occurrence of HP is a rare phenomenon among the general population, although certain occupations and avocations have been associated with specific HP-syndromes (see table below) The most commonly recognized causes of HP are microbial agents, including bacteria, fungi and amoebae; however, animal proteins and low-molecular weight chemicals (such as isocyanates) have also been identified as potential causative agents.

Definitive diagnosis of HP is extremely difficult and often based upon the degree to which a litany of "major" and "minor" criteria have been fulfilled, with ultimate confirmation of the disease possibly requiring lung biopsy results. Development of HP involves

repeated exposure to the antigen (or causative agent)

2.  immunological reaction or sensitization to the antigen, and

3.  immune-mediated damage to the lung.

Following initial exposure to the antigen or causative agent, the time to onset of HP symptoms is extremely variable, with latency periods of weeks and years. Clinically, the disease progression has been classically divided into acute, subacute and chronic forms or stages. This delineation may be misleading, since the clinical findings often overlap and it is possible for all three forms to coexist in one individual. Nevertheless, symptoms of acute illness typically begin four to twelve hours after exposure, with the individual presenting flu-like symptoms (e.g., fever, chills, cough, malaise, myalgia or muscle pain, etc.), dyspnea (or difficulty breathing), chest tightness, tachycardia (increased heart rate), crepitant rales, alveolitis, hypoxia that worsens with exercise, and/or pulmonary function changes. The acute form of HP is generally considered reversible with proper medical care, provided that exposure to the antigen ceases. Additionally, the individual will likely exhibit exercise-induced dyspnea and cough, fatigue, anorexia, weight-loss, and/or increased sputum production. The chronic form of HP, however, portends irreversible changes, which include loss of lung function and fibrosis of the lung.

Recently, HP has emerged as a concern in the machining environment. In January, 1997, the National Institute of Occupational Safety and Health (NIOSH) convened a workshop ("Pneumonitis in the Machining Environment"), sponsored by the UAW-Chrysler National Joint Committee on Health and Safety, to exchange information regarding the occurrence of HP associated with machining environments in industry since 1991. The goals of the workshop were "to identify gaps in knowledge regarding cause, exposures, control, and prevention of this occupational lung disease; tools for addressing these knowledge gaps; and best practices for control prevention, where consensus existed." The workshop included a review of seven documented outbreaks of HP that have occurred in metal removal environments since 1991. The workshop proceedings were subsequently published by NIOSH (American Journal of Industrial Medicine, 32: 423-432, 1997). Highlights of the workshop findings may be summarized as follows:

HP is a problem in the machining environment—i.e., HP can occur in the machining environment; however, the magnitude of the problem (how often and to what extent) is presently undetermined.

The occurrence of HP seems to be associated with environments where other work-related respiratory or chest symptomology exists.

To date, HP outbreaks in machine shops have been associated with the use of water-based metalworking fluids.

HP has occurred where "atypical" or unusual microbial contaminants (i.e., mycobacteria and fungi) predominate in the machine sumps. This supports the theory of a microbiologically derived causative agent, although a chemical cause has not been eliminated.

HP has occurred in widely varying mist exposure environments, including documented exposure levels well below 0.5 mg/m3. This provides further circumstantial evidence of a non-chemical cause.

For affected individuals, return to work is possible in non-exposure jobs.

Improved standardization of acceptable diagnostic criteria is needed, but diagnosis can usually be made in the absence of lung biopsy results.

Broader dissemination to clinical health professionals, along with heightened awareness and general education of clinical health professionals, is needed regarding diagnostic criteria for HP.

A report of six biopsy-diagnosed cases of hypersensitivity pneumonitis in metal removal operations has been reported in the Morbidity and Mortality Weekly Report.

Over the years a number of studies have found an association between working with MRF and a variety of cancers, including stomach, rectal, pancreatic, laryngeal and skin. The biggest and by far the best of these studies were done at GM and Ford in cooperation with the UAW. These studies, depending on interpretation, found exposure-response associations for cancer of the larynx, esophagus, pancreas and rectum of exposed workers. Epidemiology based on smaller and earlier studies found an increase in stomach, rectal, pancreatic and laryngeal cancers associated with exposure to MRF. However, the earlier smaller studies were not supported by the results of the large GM-UAW and Ford studies which had a more rigorous design and were analytically more thorough. There are, however, multiple confounding factors that work to modify the conclusion that there were increases in stomach cancer. In a follow-up case control study of the stomach cancers at Ford more detailed information was obtained on work histories, ethnicity and a surrogate for diet, and the increase in stomach cancer was not supported.

Increased rates of esophageal and colon cancers have been reported by the GM-UAW study in relation to grinding with synthetic or soluble fluids, but data relating to exposure concentrations are not available. These studies presented data showing excess risk with a 10-20 year lag period which means that deaths which took place from 1940 to 1984 would be the result of exposures that took place in the previous 10-20 years. For the relationship between this data and exposure to synthetic or soluble MRF in grinding operations to be accepted, it should be demonstrated that the plants in this study had significant use of soluble or synthetic MRF between 1920 and 1964 with the risk due to exposure during those periods.

Straight oils and soluble fluids were the most common MRF used in the plants studied during the period 1920-1940. Synthetics started to become more common in the 1970s. When considering the significance of the GM-UAW study for laryngeal, prostate and rectal cancers, one should also take into account the change in base oil refining practices which began removing PACs around 1950. Over 60% of the deaths in the GM-UAW study came out of the oldest plant, which started operations in the 1920s and primarily used straight oils and soluble fluids. Two of the three plants in this study started operations in the 1920s. The average time from first exposure for individuals from this oldest plant was 29 years, which means that, on average, first exposure occurred prior to 1954. Among those who died, the average year of first exposure would be even earlier. Another confounding factor would be the gradual removal of nitrites from semi-synthetic and synthetic MRF starting in the middle 1970s.

Historical exposures to MRF containing non-severely refined base oils can be related to the development of laryngeal, prostate and rectal cancers. Both the Ford and GM/UAW studies found an increased incidence of pancreatic cancers in black but not white employees, and these seem related to historical grinding operations. The GM-UAW study also found some small to moderate increases of several kinds of cancers not observed in the Ford study. These findings relate to historical patterns of MRF use and exposure patterns which, for the most part, are no longer valid. What they tell us about the risk of cancer from exposure to very different modern synthetic fluids at much lower concentrations can only be speculated upon until appropriate follow-up studies have been done.

Personal filter sampling of MRF aerosol

Past techniques included simple gravimetric weighing of the filter media (i.e. – assuming that all of the collected particulate was MRF). Various extraction techniques were also used to separate the fluid mist from other particulate, such as metal fines, before attempting to calculate the MRF concentrations. The extracted fraction was then analyzed by various techniques to determine the MRF levels. These techniques included infrared spectrophotometry and secondary gravimetric techniques. Analysis for specific components of the MRF was very rarely, if ever, done. There has been a recent attempt to provide a standardized method of sampling and analysis for MRF. This method should be capable of providing equivalent results whatever the composition of the MRF or the type of operation. The method (developed by an ASTM committee and designated "ASTM Provisional Method PS 42") involves collecting the MRF on a PTFE membrane filter, and then using a combination of standardized gravimetric and solvent extraction techniques. The extraction solvent removes the fluid components and leaves the insoluble particulate on the filter, regardless of the MRF formulation. The resulting extract can be subjected to various analytical techniques to determine the total or specific components of the extracted MRF. ASTM Provisional Method PS 42 determines both total particulate matter and extractable mass metal removal fluid aerosol concentrations in a range from 0.05 to 5 mg/m3 in workplace atmospheres. Other methodologies, such as NIOSH Method 0500, may be used for estimations of total particulate matter. A direct reading instrument can be used for screening operations for further evaluation or determining locally high concentrations of aerosol. Aerosol monitors are also useful in identifying mist or particulate sources and can be useful in determining time-dependent fluctuations in mist or particulate levels Because these monitors cannot differentiate between MRF mist and dust, care must be used when evaluating areas near dry machining operations or other sources of particulate.