Toxicology of Metalworking Fluids

Development of Metal-Working Fluids - types and uses
Cutting and grinding fluids were similar to lubricating oils.
Shale oils and mineral oils associated with skin cancer.
Semi-synthetic and synthetic oils introduced in 1940's.
Use of refined mineral oils, particularly solvent-extracted.

Adverse Health Effects - Epidemiology and exposures
In addition to skin cancer, lung, prostate, urinary bladder
and pancreas have been indicated as cancer sites, but brain
is unlikely.

Toxicology and characteristics of components
Mineral oils
Hydroxyalkylamines
Chlorinated paraffins

Toxicology and characteristics of additives and contaminants
Biocides
Formaldehyde releasing agents
Sodium nitrite
Sulfur compounds
Polynuclear hydrocarbons - quantities and carcinogenicity
Nitrosamines - quantities and carcinogenicity

Formation of contaminants (during use)
Storage
Heating
Recycling and reformulation

Risk assessment
Dermal exposure compared with inhalation

Safety of recycled materials - contaminants (such as PCB's) in some recycled products

Standards for metalworking fluids - Government and Manufacturers

Summary

Development of Metalworking Fluids - Types and Uses

Metalworking fluids have been used since automatic metalworking machines were introduced almost a century ago. They are used to quench the hot metal at the tip of the cutting tools and to wash away the metal filings. Of course, during the cutting much of the liquid splashes and forms a mist, thereby exposing operators of the machines to them. Metalworking fluids (which are commonly called cutting oils or fluids) are expensive and are collected and recycled, and often blended with other fluids, such as lubricating oils, before re-use, thereby increasing the possibility of contamination with undetermined amounts of toxic materials.

Not only must cutting oils be sufficiently mobile to be sprayed on to the cutting tools, but they must carry away heat and they must prevent corrosion of the metal. The requirement for particular properties of the oils and more-or-less standard characteristics has resulted in a blending of the basic fluid with a number of additives including, for example, biocides which slow the growth of bacteria in those fluids that are substantially aqueous; this avoids fouling of the fluids, which are frequently used and re-used for 6 months or more.

In the beginning cutting fluids were mineral oils , particularly shale oil obtained by destructive distillation of shale, and later distillates of petroleum. From the earliest days cutting oils were known to cause dermatitis and skin tumors (cancer) were related to exposure to cutting oils (Cruickshank and Squire, 1950), including shale oils (Scott, 1922); shale oils were gradually phased out. The so-called 'mule-spinners cancer' was cancer of the scrotum (reminiscent of Pott's chimney sweeps cancer) caused by exposure to shale oil used as a lubricant on mule spindles since the middle of the 19th century; Southam and Wilson (1922) reported that 27 of 35 men with cancer of the scrotum seen in Manchester were mule spinners. Later, cancer of the scrotum and of the hands and forearms was related to exposure to cutting oils, mainly mineral oils from petroleum, more or less refined. It is very probable that polynuclear hydrocarbons in the cutting oils are the carcinogens mainly responsible for the human skin cancer associated with exposure to these oils.

As with coal tar pitch, the carcinogenic properties of cutting oils has been reproduced in experiments in animals, particularly in mice. Many types of mineral oil, including cutting oils, which contain carcinogenic polynuclear hydrocarbons have induced skin cancer in mice when painted on their backs for a prolonged period.

The tumours appear within the relatively short lifespan of the mouse (2 to 3 years), whereas humans develop skin cancer after decades of exposure to these materials. Of course, the experimental animals experience a much higher relative dose than do workers with exposure to metalworking fluids, an invariable result when comparing human latent periods for cancer development with the latent periods for cancer development in animal carcinogenesis experiments. Many, but not all, polynuclear hydrocarbons induce malignant skin tumors when painted on the backs of mice. The concentration of these compounds in petroleum is not high, but processing at high temperatures produces large quantities of polynuclear hydrocarbons containing five or six rings, among which are found the most potent carcinogens.

Partly because of the carcinogenic properties of metalworking fluids in the 1940's there were introduced synthetic and semi-synthetic cutting oils, which contained less mineral oil or no mineral oil, but contained many additives, including chlorinated paraffins, to provide the necessary physical properties. These oils were favoured for high speed operations. Another later improvement were soluble cutting oils, which contained mineral oil, fats, emulsifiers (such as triethanolamine) and additives in a water emulsion. Use of the aqueous emulsions required addition of a corrosion inhibitor, typically sodium nitrite, which introduced a different hazard, formation of nitrosamines through interaction with amines. In the 1970's it was discovered that water-based cutting oils contained substantial quantities of N-nitrosodiethanolamine, which is a member of the class of potent carcinogens called N-nitroso compounds. Although not the most potent of these carcinogens, nitrosodiethanolamine has induced tumours of many organs when administered to experimental animals (rats, mice and hamsters). Concentrations as high as 3% of nitrosodiethanolamine have been measured in undiluted cutting oils. Other nitrosamines, including a nitrosomethyloxazolidine and nitrosodi-isopropanolamine (an inducer of pancreas cancer in hamsters) have also been reported; these are carcinogenic and more potent than nitrosodiethanolamine.

Contamination of cutting oils with nitrosamines is a serious hazard, since the latter are easily absorbed through the skin (although they have not induced skin tumours in experimental animals) and exert their carcinogenic effect systemically. Recently, therefore, nitrites have been largely eliminated from metalworking fluids and other non-nitrosating corrosion inhibitors have been introduced; the toxic properties of these substitutes has not always been determined. Mineral oils from which most of the carcinogenic polynuclear hydrocarbons have been removed by solvent extraction are now widely used and certainly reduce human exposure to carcinogens from this source. Moreover, modern water-based cutting fluids are not entirely free of carcinogenic risk because nitrosamines (especially nitrosodiethanolamine) have been found in some fluids formulated without nitrite. In these cases nitrosation might have come about through contact of the amines in the fluids with nitrite used a rust preventive on the lining of a steel container (as has been noticed with other products), or through reaction of the amines with nitrogen oxides in air that contains burnt fuel vapours.

Water-based cutting fluids present other possible health risks. Because metal-working fluids are recycled for many months and contain a variety of additives, including so-called 'cutting compounds' containing sulphur or chlorine (chlorinated paraffins), bacteria of various kinds build up in them leading to increasing malodour. Even after filtering to remove metal filings and cuttings, the consistency of the fluids often changes because of chemical and bacterial actions. To suppress bacterial growth a variety of biocides are added, sometimes reaching considerable concentrations. Many of these biocides are themselves toxic - and some have not been adequately tested - and might be carcinogenic. In addition, some biocides are nitrogen compounds which might be nitrosating agents (e.g. bioban), which can give rise to nitroso-diethanolamine and other nitrosamines by reaction with amines in the fluids. Furthermore, some bacteriocides (?) are formaldehyde releasers; formaldehyde facilitates formation of nitrosamines, particularly in alkaline solution (Keefer and Roller, 1973) and participates in the formation of nitrosooxazolidines. Formaldehyde itself is carcinogenic to rats by inhalation (and potentially to humans), but has not caused tumours when ingested or applied in solution to the skin.

Such information suggests strongly that, until recently, operators of machines in which metal-working fluids were used, were exposed to a variety of toxic and carcinogenic agents. Those with the longest exposures are the most likely to develop tumours, but there were undoubtedly large differences between fluids in their carcinogenic effectiveness, depending on individual composition, recycling, storage conditions, use and other factors. While the health risk from current exposures might be low (but not absent), insufficient time has elapsed since the phasing out of the more egregiously carcinogen-contaminated fluids for the risk of cancer among long-time workers to be much reduced.

Adverse Health Effects - Exposures, Epidemiology

The earliest reported health effects following exposure to metalworking fluids were skin disorders, dermatitis, hyperkeratosis and, infrequently, skin tumours including cancer. Before the common use of petroleum-derived oils shale oil was the common lubricant and skin disorders were associated with workers' exposure to it (Scott, 1922). The effects of these oils in humans was reproduced by the formation of skin tumours in mice following repeated application of lubricating oils to the skin (Leitch, 1922, 1924). In similar experiments Twort and Twort (1931) showed that many of a large number of petroleum-derived oils were carcinogenic. Later it was discovered that the carcinogenic agents in the oils were the same group of compounds, polynuclear hydrocarbons, that were responsible for skin cancer induction by coal tar. More recent studies with cutting fluids (Jepsen et al, 1977) showed that paraffin-based oils induced skin tumors (mainly papillomas) when painted on the backs of mice, whereas a soluble oil did not; there were also toxic effects in the livers of mice treated with paraffinic oils. There are few helpful results of analysis of metalworking fluids for carcinogenic polynuclear hydrocarbons; Cathchpole et al (1971), for example, uses an indirect method which approximates benzo(a)pyrene content. Cutting oils are unlikely to be very different in their polynuclear hydrocarbon content from other heavy petroleum oils (e.g. motor oils, which contain less than 1 part per million of the benchmark carcinogen, benzo(a)pyrene (Grimmer et al, 1981a); after use, especially in diesel engines, the polynuclear hydrocarbon content is considerably increased (Grimmer et al, 1981b)

Many reports have been published from several countries of the occurrence of skin lesions, including cancers, in workers exposed to metal-working fluids for prolonged periods, cancers appearing as long as 25 years after the beginning of exposure (Emmett, 1975); cases are still being reported (Tsuji et al, 1992). Malignant melanoma has been related to exposure to cutting oils and other mineral oils in the United Kingdom (Bell et al, 1987); melanoma has been rarely caused in experimental animals (mice and hamsters) painted on the skin with polynuclear hydrocarbons in solution, and some of these carcinogens have been found in mineral oils.

There are many fewer studies and much weaker epidemiological evidence implicating metalworking fluids in the causation of other human cancers. A substantial number of these studies were without significant results. Among the human cancers other than those of the skin which have been linked with exposure to metal-working fluids have been those of lung, urinary bladder, prostate, pancreas and sino-nasal cancer. Huge numbers of machinists work in automobile factories and this provides large populations of people exposed to metal-working fluids for epidemiological studies, many of which have been conducted in the United States factories with their long history of continuous vehicle manufacture. However, results are seldom clear-cut and are often conflicting.

Tolbert et al (1992) in a survey of 30,000 workers found an association between exposure to 'straight' (i.e. non-soluble) metalworking fluids and death from rectal cancer (but not colon cancer) and to cancer of the larynx; there were slight elevations in deaths from cancer of the prostate, esophagus and pancreas, but no connection with lung cancer; stomach cancer only, but no other cancer, was slightly elevated among workers exposed to soluble cutting oils. Unlike some areas of the petroleum industry, there was no significant elevation of brain tumours (astrocytomas) among workers exposed to cutting fluids (Thomas et al, 1987). In a review of occupationally-related urinary bladder cancer, Steineck et al (1990) report "somewhat increased risks" among workers with cutting fluids, but this finding is diminished in importance by the authors' statement that non-occupational confounding is a problem in the analysis.

Silverstein et al (1988) surveyed more than 1,700 workers in bearing plants who died between 1950 and 1982 and who were exposed to grinding fluids. Those which were oil-based were associated with an elevated incidence of pancreas cancer (which has few other associations with environmental exposures) and those which were water-based were associated with elevated stomach cancer incidence.

A Canadian study (Montreal) among 3,700 cancer patients who were exposed to 12 types of petroleum-derived fluids, of which one was cutting fluids, showed that exposure to the latter was associated with excess cancer of the urinary bladder (Siemiatycki et al, 1987). Of 338 people with bladder cancer who were exposed to various amounts of cutting oils for various times, 37% were machinists, 14% were plumbers and pipefitters and 18% shaped metal or fabricated aircraft. (This does not mean that cutting fluids alone were responsible for the bladder cancer in all of them or, indeed, any of them). This analysis indicated a weaker association between exposure to cutting oils and other mineral oils with an increased incidence of lung cancer, but no association with stomach cancer. A smaller scale study from France (Lyon) shows a similar association between bladder cancer incidence and exposure among workers to cutting fluids, especially when exposure began before age 20 (Hours et al, 1994). Another study from England based on a job-exposure matrix indicated an association between exposure to cutting fluids and elevated bladder cancer in workers and a weaker association with cancer of the bronchus, the latter with no apparent dose-response (Coggon et al, 1983).

Sino-nasal cancer has been associated with exposure to cutting fluids in a case-control study in Connecticut, based on death certificates of workers who died between 1935 and 1975 (Roush et al, 1980). There was a particularly strong correlation in the case of workers older than 68 at death. No doubt inhalation of cutting oil mist was the cause of the cancers; nitrosamines, including nitrosodiethanolamine found in some cutting fluids, have induced tumours of the nasal cavity in rats, mice and hamsters, often by ingestion as well as by inhalation (Lijinsky, 1992).

Stomach cancer has been related to exposure to metal-working fluids in several studies, including that of Park et al (1994) in an automobile assembly plant. The number of cases was small but the incidence increased with longer exposures. This corroborated a previous investigation of workers in a ball bearing manufacturing plant in which there was an increase in deaths from stomach cancer associated with exposure to water-based (emulsified) cutting fluids (Park et al, 1988). In a survey of more than 2000 workers in a large U.S. plant exposed to cutting oil mists for various periods (Decoufle, 1978), there was an increase in deaths from stomach cancer among those exposed for at least 5 years and observed for more than 20 years (i.e. a latent period of more than 20 years); there was no evidence for an increase of lung cancer or other cancers, except possibly intestinal cancer. A major conclusion of a very large survey of occupational cancer among almost 300,000 U.S. veterans was that elevated risks for stomach cancer among machinists may reflect exposure to cutting oils (Blair et al, 1985).

Because of suggestions from studies of petroleum workers that there were 'clusters' of brain tumours, there have been deeper investigations of the possible relation of exposure to certain types of oils with tumours of the nervous system. Among these Carpenter et al (1988) showed a very small elevation (and non-significant) in central nervous system tumours among workers exposed to cutting oils. A similar weak correlation was reported by Thomas et al (1987) in the petroleum industry; workers exposed to cutting fluids for many years had a small increased risk of astrocytic tumours. Overall, the relation of cutting fluid exposure to nervous system tumours was not impressive.

A weak correlation between exposure to cutting oils and cancer of the rectum (but not of the colon) in Sweden was reported (Gerhardsson de Verdier et al, 1992), which confirmed earlier reports. Among these studies, however, lung cancer does not appear to be easily related to exposure to metal-working fluids, possibly because the smoking habit is so significant and confounding in the etiology of this disease. However, there have been reports that increased lung cancer incidence is associated with exposure to other types of oils (e.g. Ronnenberg et al, 1988).

Toxicology and characteristics of components

1. Mineral Oils

The most studied components of metal-working fluids are mineral oils, almost always fractional distillates of petroleum, but pyrolysates of shale until the early part of the 20th Century. They are principally paraffinic hydrocarbons (sometimes partially naphthenic) and may contain simple aromatic compounds. They vary in 'purity', freedom from toxic or carcinogenic components being very important for medicinal mineral oils, which are highly refined and processed. Like all petroleum fractions, mineral oils contain some proportion of polynuclear compounds (condensed aromatic hydrocarbons) among which are found molecules that are potent skin carcinogens; most such compounds are not carcinogenic (Lijinsky, 1991).

Mineral oils have many uses and undergo more or less refining to remove, for example, waxes (dewaxing) or aromatic compounds, by solvent refining or treatment with sulphuric acid. The resulting oils will have the characteristic boiling point, viscosity and other properties required. Mineral oils are clear liquids and are immiscible with water and most hydroxylic solvents, but they are fat-soluble.

Although they have a high boiling point, mineral oils do form aerosol mists and it is recommended that human exposure be limited to less than 5 milligrams per cubic metre in this form. When ingested they pass through the gastrointestinal tract unchanged and have no apparent effect, except on the lining of the tract itself; highly refined mineral oil is still used as a 'safe' laxative.

Many samples of mineral oils similar to those used in metal-working fluids have been carcinogenic to mouse skin, although the carcinogenic potency in general declined as the extent of refining of the oil increased. Also the carcinogenic effect increased as the oils were reused or re-cycled, particularly since oils from many sources were often blended in during re-cycling.

Oil mists were often toxic to experimental animals (dogs, rats rabbits, mice, hamsters) when inhaled (as in humans); at 100 mg/cu.m long term effects (1 or 2 years) were in the lungs, in which macrophages contained oil droplets (Wagner et al, 1964). Oral administration to rats of medicinal mineral oil (2% in the diet) for 500 days did not give rise to tumours (Schmahl and Reiter, 1953) and it was later found using radiolabelled oil that no more than 2% was absorbed, metabolised and excreted as carbon dioxide (IARC Monographs Vol. 33, pp 131-133, 1984). No lung tumours were seen in long-term inhalation experiments in animals.

It appears that the paraffins and cycloparaffins which are the main constituents of mineral oils are not carcinogenic and that such carcinogenic activity as is present in commercial mineral oils is due to impurities. When heated to high temperatures as in engines (and possibly in use on cutting tools) the carcinogenicity of the oils on mouse skin often increases, probably due to formation of carcinogenic impurities (polynuclear compounds?), so that 'used' oils are more effective than new oil.

2. Hydroxyalkylamines

Hydroxyalkylamines are used in water-based metal-working fluids, especially emulsions, because members of this class of compound are excellent emulsifying agents, the most common being triethanolamine. They have also been suggested for use in metal-working fluids because of their anti-microbial properties, propanolamines being particularly effective, compared with ethanolamines and butanolamines (Bennett et al, 1979). Hydroxyalkylamines are bases and are responsible for the alkaline Ph of water-based metal-working fluids.

The toxicity of hydroxyalkylamines (or alkanolamines) to experimental animals is low. Few have been tested for chronic toxicity and triethanolamine is the only representative of which the tests are reliable and informative. Konishi et al (1992) administered a 1% solution of triethanolamine in drinking water to mice for 1.5 years and found no significant incidence of induced tumours compared with controls. This was a more comprehensive study than two previous bioassays of triethanolamine, in which lower dose rates were used and the numbers of animals were smaller. There is no evidence that alkanolamines used in metalworking fluids present a carcinogenic risk to workers, except, as discussed later, as a precursor of highly carcinogenic N-nitroso compounds.

3. Chlorinated paraffins

Chlorinated paraffins are used in metal-working fluids to provide the desired physical characteristics (e.g. viscosity) to the fluid; other substances used for this purpose include natural fats and oils, and waxes. Chlorinated paraffins are made by adding chlorine gas to long chain paraffins until the required proportion has been incorporated. Consequently, chlorinated paraffins are rather ill-defined and are characterized as mixtures of compounds with a certain average chlorine content.

Two of these mixtures have been examined in a chronic bioassay carried out by the United States National Toxicology Program. One was a sample containing mainly C12 paraffins chlorinated to the extent of 60% by weight and the other consisted of C23 paraffins chlorinated to the extent of 43% by weight. Each was administered in corn oil solution by gavage to large groups of rats and mice for 2 years. The doses were large: 3.75 grams/kg body weight per day for rats, 5 g/kg for mice of the C23 material: 625 mg/kg for rats and 250 mg/kg for mice of the C12 material. Except for some liver inflammation in rats by the C23 material, there was no evidence of toxicity by the two types of chlorinated paraffins. However, hepatocellular tumours were induced in both rats and mice by the C12 chlorinated paraffins, as well as follicular cell tumours of the thyroid in both species and kidney tubular cell tumours in rats. Evidence for carcinogenicity of C23 chlorinated paraffins was much weaker, as indicated solely by an increased incidence of malignant lymphomas in male mice (National Toxicology Program Technical reports numbers 305 an d 308, 1986). Thus, smaller chlorinated paraffins with higher chlorine content appeared to be more strongly carcinogenic than the larger molecules; which are used in any particular metal-working fluid is information not readily available. Chlorinated paraffins are not readily absorbed through the skin. The toxicology of chlorinated paraffins was reviewed in a Canadian Priority Substances List Assessment Report in 1993.

Toxicology and characteristics of additives and contaminants

Additives

Biocides

These are substances added to water-based metal-working fluids to prevent or reduce bacterial contamination leading to foul odours and undesirable changes in characteristics of the fluids, particularly after continuous re-use. Of course, the biocides themselves must not be deleterious to the correct action of the fluids.

The list of compounds used - or suitable for use - as biocides in metal-working fluids is long (Rossmore, 1981) and will not be enumerated. Alkanolamines have already been mentioned as biocides, although their principal use in metal-working fluids is as emulsifying agents. A number of other agents are so-called 'formaldehyde releasers' and are made by reaction of formaldehyde with ammonia or amines; hexamethylenetetramine is the prototype and has long been used medicinally as a urinary tract antiseptic. A common one is hexahydro-1,3,5-tris-(2-hydroxyethyl)-triazine They are assumed to act by release of formaldehyde by hydrolysis, although this is not likely in the alkaline conditions of water-based metal-working fluids.

Formaldehyde itself is an enigma, since it is a reactive normal constituent of biological material. In solution, or in the form of formaldehyde-generating condensation products (as in biocides) formaldehyde seems not to be carcinogenic. However, when inhaled as a gas it induces tumours of the nasal cavity in rats (these are not the same as sino-nasal tumours that occur in humans). There is not yet evidence that inhalation of formaldehyde is associated with any particular cancers in humans. Since little or no free formaldehyde exists in metal-working fluids containing formaldehyde-releasing biocides, it is unlikely that the risk to workers from inhaling formaldehyde will be significant.

Other biocides include o-phenylphenol, morpholine derivatives of nitroparaffins known as Bioban(s), alkyl thiocarbamates, salts of pyridinethiol-1-oxide (Omadine) and others. Most of these compounds are not very toxic to animals and there is no evidence of their being carcinogenic (but few have been tested for carcinogenicity). One, pentachlorophenol has induced liver tumours (including hemangiosarcomas) in mice in a large scale NTP bioassay (Technical Report No. 349, 1989). Chelating agents, such as ethylenediaminetetracetic acid, have been found to increase the effectiveness of biocides. Filtering of cutting fluids (through kaolin, bentonite, chalk, etc) to remove metal 'fines' and sludge prior to re-use has frequently reduced bacteriocidal effectiveness, requiring addition of more biocide (Onyekwelu and Bennett, 1979).

Sulphur compounds

Elemental sulphur is used in some formulations of metal-working fluids and is of little toxicological significance; sulphurized fats are also used in some straight cutting fluids. The most common sulphur compounds, used in water-based metal-working fluids, are sulphonated paraffins, which are detergents and emulsifying agents. There is some suggestion that bacterial reduction to sulphides is responsible for some of the foul odour of used and recycled fluids.

There is little information about the alkylsulphonates and none about their possible carcinogenicity. However, based on studies with some such detergents, they can be expected to be non-carcinogenic although there have been suggestions long ago that they might be weak skin tumour promotors.

Sodium nitrite

Sodium nitrite is one of the oldest and cheapest corrosion inhibitors. It prevents rusting and has been widely used (as well as other nitrite salts) to line cans in which aqueous solutions are kept. Corrosion inhibitors are essential in metal-working fluids which are sprayed on the tips of cutting tools, so sodium nitrite or, in a few cases, an amine are components of most water-based cutting fluids, as much as 0.8% (Fadlallah et al, 1990).

Sodium nitrite is itself a minimal hazard to humans, since it is not absorbed through the skin, is not volatile and is not very toxic to adults (large doses cause methaemoglobinemia in infants). Of several chronic toxicity tests of sodium nitrite, in only one was there a suggestion of carcinogenic activity to the liver of rats (Lijinsky et al, 1983), but this has not been confirmed.

However, the most important toxicological effect of nitrites is their propensity to react with secondary and tertiary amino compounds to form N-nitroso compounds (Lijinsky and Epstein, 1970), which comprise the most broadly acting group of carcinogens known.

N-Nitroso compounds

N-Nitroso compounds, often loosely called nitrosamines, are the products of interaction of amines with nitrosating agents, which include nitrogen oxides as well as nitrites. Consequently, they are found wherever such reactions can take place, include metal-working fluids. Reaction with nitrite is more rapid with secondary amines than with tertiary amines, for example the emulsifying agent triethanolamine; however, diethanolamine is a common contaminant of commercial triethanolamine. This explains the frequent presence of nitrosodiethanolamine (NDELA) in water-based cutting fluids; reaction with nitrogen oxides in the air is the probable source of this nitrosamine in metal-working fluids to which nitrite has not been added (Jarvholm et al, 1991a). Sophisticated methods have been developed for the determination of NDELA , which is a non-volatile nitrosamine, in various materials and these have somewhat lower sensitivity than the gas chromatographic methods for volatile nitrosamines (Spiegelhalder et al, 1983). Among the nitrite-containing fluids concentrations of NDELA as high as 3% have been reported (Fan et al, 1977), although concentrations are usually considerably lower. Although this problem has been known for more than 15 years, metal-working fluids are still found that contain significant concentrations of nitrosamines (Keefer et al, 1990); one sample analysed in 1989 contained 650 parts per million of NDELA (Jarvholm et al, 1991b)

Nitrosation of amines usually occurs most rapidly in acidic solution (optimum approximately Ph 3.4), but was found to take place quite readily in alkaline solution in the presence of carbonyl compounds (Keefer and Roller, 1973) such as formaldehyde (which is commonly present). Since other amines, such as diisopropanolamine are used in metalworking fluids, their N-nitroso derivatives (in this case nitrosodiisopropanolamine - which induces pancreas cancer in hamsters) can be present. Another consequence of the particular composition of metal-working fluids is that cyclic nitrosamines (e.g. nitrosooxazolidines) can form from hydroxyalkylamines, such as ethanolamine, in the presence of formaldehyde (Eiter et al, 1972). This subject has been extensively discussed by Loeppky in relation to the reduction of nitrosamine contamination in cutting fluids (Loeppky et al, 1983).

The properties of nitrosamines underlie the concern for the presence of these compounds in metal-working fluids. Nitrosamines are absorbed through the skin, including nitrosodiethanolamine (Lijinsky et al, 1981) and they act systemically whatever the route of exposure, inducing tumours in certain target organs in a particular species. It cannot be predicted from one species to another which organ will be the target of a particular nitrosamine. For example, nitrosodiethanolamine induces tumours of the liver, esophagus and kidney in rats, but only tumours of the nasal cavity in hamsters (Lijinsky, 1992). Therefore, results of testing a nitrosamine in rats, mice or hamsters provide no guide to which would be the target organ(s) for tumour induction in humans. NDELA induces mainly liver tumours in rats, as do nitrosooxazolidines, but nitrosodiisopropanolamine induces tumours of the esophagus in rats and pancreas tumours in hamsters. Explanations of mechanisms by which these nitrosamines induce tumours are confusing, since NDELA is not mutagenic to bacteria with rat liver enzyme activation.

N-Nitroso compounds are highly potent carcinogens and as a group have reproduced almost every type of human cancer in some experimental animal (Lijinsky, 1992); they have been tested in more than 40 species and have induced tumours in all of them (i.e. there are no resistant species). Nitrosamines are the most effective carcinogens in tobacco smoke and assessment of the effectiveness of the nitrosamines inhaled by a heavy cigarette smoker with a high risk of developing lung cancer (approximately 20 micrograms per day per pack, or 0.3 microgram per kilogram body weight) compared with the minimal effective dose of a potent nitrosamine (diethylnitrosamine) in rats, approximately 10 to 20 microgram per kilogram per day. (Lijinsky, 1993). This comparison indicates that humans might be more susceptible to carcinogenic nitrosamines than rats or other experimental animals, and this might also be the case for other carcinogens to which humans are exposed.

Cumulative doses of as little as 2 to 5 milligrams of some nitrosamines have been sufficient to induce significant incidences of tumours in experimental animals. Nitrosodiethanolamine is somewhat less potent, because 90% or more of the applied dose of this hydrophilic compound is excreted unchanged in the urine of rats (Farrelly et al, 1987), so that the effective dose in the animal is much smaller. Nevertheless, quite small doses have been effective in inducing a high incidence of liver tumours in rats (Lijinsky and Kovatch, 1985). Nitrosodiethanolamine might represent the largest (but not necessarily the most potent) exposure of humans to an environmental carcinogen.

Polynuclear hydrocarbons

These products of pyrolysis of organic material were first isolated from coal tar pitch in the 19th century and have since been found almost ubiquitously, in air, water and soil. They are present in petroleum and, therefore, in most materials made from petroleum, including mineral oils and lubricating and metal-working fluids. The concentrations of the polynuclear hydrocarbons in these materials varies and in the case of the larger molecules, which are carcinogenic, concentrations of the order of parts per million are the rule. Nevertheless, these compounds are potent carcinogens to the skin of mice and are responsible for most of the skin-cancer causation among workers exposed to petroleum-derived metal-working fluids.

In products such as mineral oils which are fractional distillates of petroleum, polynuclear hydrocarbons containing 3 fused rings (anthracene, phenanthrene, fluorene) are the most abundant, those with 4 fused rings (chrysene, benz(a)anthracene, triphenylene, pyrene, fluoranthene) are less abundant and those with 5 or 6 fused rings are quite rare. It is among the last that the most potent carcinogens are found. Unsubstituted anthracene and phenanthrene are not carcinogenic, benz(a)anthracene and chrysene are very weak carcinogens at best, and benzo(c)phenanthrene somewhat stronger, although their derivatives with alkyl (methyl) substituents in particular positions are often quite potent carcinogens (e.g. 7,12-dimethylbenz(a)anthracene or DMBA). Some of these alkyl derivatives might or might not be present in a mineral oil; they are seldom reported.

The most potent carcinogens among the 5 and 6 ring polynuclear hydrocarbons (listed in Lijinsky, 1991) are benzo(a)pyrene - a standard reference compound - and some isomeric benzofluoranthenes (b, j and k), together with dibenz(a,h)anthracene. Benzo(e)pyrene, perylene, pentaphene and benzo(b)chrysene are inactive, while dibenz(a,c)anthracene and dibenz(a,j)anthracene are relatively weak carcinogens. Several dibenzopyrenes are potent carcinogens, especially by subcutaneous injection (they tend to be so little soluble in organic solvents that skin painting of solutions is inadequate to elicit skin tumours); benzo(g,h,i)perylene (commonly found and difficult to differentiate from benzo(a)pyrene), coronene and anthanthrene are not demonstrably carcinogenic (but they, too, are difficult to dissolve.

Not all of the above hydrocarbons have been detected in all of the mineral oils and metal-working fluids examined, although sophisticated methods (sensitivity 0.1 microgram'kg) are available for their determination (Grimmer and Boehnke, 1979).

The carcinogenic potency of polynuclear hydrocarbons is usually measured by the time taken for tumors to arise in the skin of mice painted with a solution of a hydrocarbon in a solvent such as acetone or highly purified mineral oil; the number of tumors and their malignancy are other gauges of relative potency. Whereas a cumulative dose of 0.01 to 0.1 millimole in frequent applications is needed to induce tumours by a polynuclear hydrocarbon itself, as little as few micrograms are sufficient to 'initiate' tumour formation which can then be 'promoted' by substances such as phorbol diesters in the initiation/promotion protocol described by Berenblum and Shubik (1947). If the human skin responds in the same way, very small quantities of carcinogenic polynuclear hydrocarbons as are present in metal-working fluids could be significant factors in the causation of skin tumours in exposed workers.

The risks to other organs of exposure to carcinogenic polynuclear hydrocarbons are much harder to pin down. These compounds do not induce tumours of the skin in guinea pigs and were less effective in rats, rabbits and hamsters; the mouse seems to be the most sensitive species. Inhalation experiments or those using instillation of benzo(a)pyrene in the lungs (together with ferric oxide in some cases) induced lung tumours in rats, hamsters and monkeys, but the effective doses were quite large, often 100 milligrams. Oral administration of benzo(a)pyrene in solution to mice or hamsters gave rise to tumours (mainly papillomas) of the nonglandular stomach, whereas in rats mammary tumours were induced; the doses were fairly large (IARC Monograph Number 3, 1973). It is unwise to dismiss or ignore the possible contribution of polynuclear hydrocarbons in metal-working fluids to the cancer risk of exposed workers, simply because information about their carcinogenic effectiveness is inadequate

Formation of contaminants during use of metalworking fluids

Storage

The risk of formation of carcinogenic contaminants during storage is important only in relation to nitrosamines. The processes by which nitrosamines are formed in the alkaline medium of water-based metal-working fluids are slow, whether from nitrite in the fluids, as a lining of the cans in which they are stored or from nitrogen oxides in the air. Although the yields of nitrosamines will be higher because of the higher concentrations of reactants in the undiluted fluid, compared with the material after dilution with water, the nitrosamine contamination will become severe only after prolonged storage. Recycling with addition of more reactants will increase the problem.

Heating

The biggest problem with 'straight' cutting oils is the heat created at the tip of the cutting tool, which can possibly be high enough to cause pyrolysis and formation of polynuclear hydrocarbons. The extent to which this takes place is not clear, but studies of metal-working fluids after re-use has shown an increase in the content of carcinogenic hydrocarbons. The matter is somewhat confused because the fluids studied have been recycled and reformulated before examination. Certainly, in the case of engine oil the content of polynuclear hydrocarbons has been shown to increase after use (Grimmer et al, 1981), but the temperatures in an engine are presumably higher than in metal-working; the formation of the larger polynuclear hydrocarbons increases enormously at high temperatures compared with those somewhat lower (Lijinsky and Raha, 1961).

Reformulation

Information about reformulation of metal-working fluids is fragmentary and somewhat anecdotal. It is said that most cutting fluids are recycled (for economic reasons) and that biocides are repeatedly added to water-based fluids to suppress bacterial growth.

Frequently unspecified materials, such as old lubricating oils are added to recycled metal-working fluids, thereby adding substances of unknown toxicity, such as PCB's. The manufacturers would undoubtedly prefer that fresh fluid be used each time, but it is probable that in most machine shops workers do not know the composition of the fluids with which they work.

There seems to be little concern for the safety of recycled metal-working fluids. It might be that neither workers nor managers care to know about the possible risks. The lack of control is shown by the presence of nitrosamines at considerable concentrations as well as nitrite in cutting fluids in Canada as recently as 1990 (Fadlallah et al, 1990), despite recommendations ten years earlier that the use of nitrite in these fluids should be abandoned for health reasons. It might be that the consequences of ignoring safety standards for metal-working fluids will not be discerned by increases in cancer rates for many years (because of the long latent periods), or perhaps will never be known because the additional cases will be submerged in other statistics.

Risk Assessment

It is difficult to compare the various health risks in exposure to metal-working fluids because of the lack of adequate standards for the materials used. Because of the proprietary nature of most of the fluids, which merely have to satisfy standards of physical and (sometimes) aesthetic qualities, it is not possible to compare exposures between factories and across long periods of time, possibly decades. Manufacturers change their formulations and factories change their suppliers. It is possible that the manufacturers do not know accurately what is in their materials. Variations in recycling and reformulation, coupled with sound or unsatisfactory practices in different machine shops, makes it very difficult to draw reliable conclusions about health effects related to chemical composition of metal-working fluids.

Broad and tentative conclusions are that carcinogenic effects related to metal-working fluids are not very large, considering the great number of workers engaged in machining. The most noticeable effects seem to be on the skin, the tumours being most likely related to polynuclear compounds in the petroleum-derived oils.

The relation of inhalation of oil mists to lung cancer is not well established. On the other hand, cancers of the stomach, rectum and bladder are more likely to be associated with water-based cutting fluids, either inhaled as mists or splashed on the skin resulting in absorption of the carcinogenic materials. It seems obvious that use of more standardised materials, free as far as possible from carcinogens or their precursors, to formulate the metal-working fluids, and taking care to recycle and reformulate only with well characterised additives, will reduce whatever health risks presently prevail.

Standards

Safety data sheets on cutting oils do not classify the oils as 'hazardous materials' according to the U.S. Occupational Safety and Health Administration. It is claimed that there are no ingredients classified as carcinogens by NTP, IARC or OSHA. Soap and water is recommended for cleaning splashes from the skin. Storage at moderate temperatures (i.e. no strong heat) is recommended. There are no special requirements for disposal.

There is a permissible exposure limit (PEL, set by OSHA) for mineral oil mists of 5 mg per cubic metre, average for 8 hours. Also recommended is a short term exposure limit (STEL) of 10 mg per cubic metre. A number of components and additives in metal-working fluids are mentioned by OSHA as having some toxic effects, including 'cancer in animals' in the case of formaldehyde and chlorinated paraffins; there is also a caution about mixing amines with nitrites.

In summary, there are many millions of pounds of metalworking fluids used each year. The composition of these fluids is irregular, the objective being to achieve certain physical properties appropriate to the task. Mineral oil based fluids are relatively simple in composition, with various materials (sulphur, vegetable oils, chlorinated paraffins added for hardness. Water-based fluids may contain mineral oil but they are complex mixtures designed for high-speed machining, the water being needed for cooling of the cutting tools. The aqueous fluids contain emulsifiers, corrosion inhibitors, bacteriocides and other components, which are perhaps innocuous, but can interact or change to form toxic and carcinogenic products, particularly after protracted use or storage. Control of these materials to protect the health of exposed employees is uncommon and difficult, although some less than adequate epidemiological studies indicate an association with cancer of the gastrointestinal tract, urinary bladder, skin, possibly lung and pancreas.

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