Occupational Disease Panel
ODP Report No. 15
Toronto, Ontario
In 1985, the Ontario legislature established the Industrial Disease Standards Panel to investigate and identify diseases related to work. The Panel is independent of both the Ministry of Labour and the Workers' Compensation Board. At the end of each fiscal year the WCB reimburses the Ministry for the Panel's expenditures. In 1995, the name was changed to the Occupational Disease Panel (ODP).
The Panel's authority flows from section 95 of the Workers' Compensation Act and its functions are set out as follows:
95(8)
(b) to make findings as to whether a probable connection exists between a disease and an industrial process, trade or occupation in Ontario;
(c) to create, develop and revise criteria for the evaluation of claims respecting industrial diseases; and
(d) to advise on eligibility rules regarding compensation for claims.
Decisions of the Panel are made by its members who represent labour, management, scientific, medical and community interests. Once the Panel makes a finding, the WCB is required to publish the Panel's report in the Ontario Gazette and solicit comments from interested parties. After considering the submissions the WCB Board of Directors decide if the Panel's recommendations are to be implemented, amended or rejected.
To assist with its work, the Panel has a small staff of researchers, analysts and support people. In addition to its own staff, the Panel relies heavily on the advice of outside experts in science, medicine and law, as well as input from parties of interest.
Additional copies of this publication are available by writing:
Occupational Disease Panel
69 Yonge Street, Suite 1004
Toronto, Ontario M5E 1K3
(416) 327-4156
| Panel Members | Appointment |
| Ms. Nicolette Carlan (Chair) | May 16, 1991 to May 15, 1997 |
| Mr. James Brophy | January 23, 1992 to January 22, 1998 |
| Dr. Carol Buck | June 1, 1991 to June 16, 1997 |
| Mr. Robert DeMatteo | April 7, 1993 to April 7, 1996 |
| Mr. William Elliott | November 7, 1991 to November 6, 1997 |
| Ms. Nicole Godbout | December 16, 1992 to December 15, 1995 |
| Mr. John Macnamara | November 7, 1991 to November 6, 1997 |
| Mr. Homer Seguin | May 28, 1992 to May 27, 1998 |
| Dr. Michael Wills | November 7, 1991 to November 6, 1997 |
| Staff | Title |
| Carolyn Archer | Senior Research Officer |
| Robert Chase | Medical Consultant |
| Gloria Lauris Elkholy | Policy Analyst |
| Francis Macri | Policy Analyst |
| Cara Melbye | Policy Analyst |
| Anne Rekenye | Data Entry Clerk |
| Tracy Soyka | Project Co-Ordinator |
| Salima Storey | Administrative Officer |
| Jason Tung | Industrial Hygienist |
Letter of Transmittal
Working Definitions
Chapter 1. The Panel's investigation
a) The issue and how it arose
b) The ODP mandate and terms
of reference
c) Investigations by the ODP
d) Submissions from stakeholders
e) Legal, policy and claims
experience considerations
a) Cancer of the larynx
b) Metalworking fluids/oil mists
(i) Types of metalworking fluids
(ii) Refining
a) Structuring the discussion
b) Evidentiary limitations
c) The epidemiological findings
d) Confounders: Smoking and alcohol
consumption
e) Possible cancer-causing agents
f) Consultants' and reviewers' comments
Appendix A: Present at Panel's Meeting Concerning Metalworking Fluids - January 20th, 1994
Appendix C: Metalworking Fluids/Oil Mists - Mortality/Morbidity Studies: Larynx Cancer
Appendix D: IARC Evaluations of Evidence For Carcinogenicity
Appendix E: IARC Monograph on the Overall Evaluation of the Carcinogenicity Of Mineral Oils
TABLES & FIGURES
Table 1: Adjusted ORs for Laryngeal Cancer from Case-Control Study by Eisen et al. (1994)
Figure 1: Studies of Laryngeal Cancer Among Workers Exposed to Metalworking Fluids
Figure 2: RR's for Straight Oil Exposed (Tolbert et. al., 1992)
For the purposes of this report, the Panel has adopted the following definitions:
Metalworking fluids are petroleum-based fluids used for machining and lubricating metal in manufacturing. (Exposure to petroleum-based fluids in other settings will be re-visited by the Panel in the future.) This exposure includes inhalation of oil mists which are produced as metalworking fluids are used. The discussion in this report applies to straight, soluble and semi-synthetic metalworking fluids since they are petroleum-based. Synthetic fluids with no petroleum content are not included in this investigation. Metalworking fluids are also known as metalworking oils, machining fluids/oils, cutting fluids/oils, lubricating fluids/oils, oil mists, lubricants and coolants.
Laryngeal cancer refers to primary cancer of the larynx (International Classification of Diseases, 9th Revision, code #161).
a) The issue and how it arose
On February 3, 1993, Cathy Walker, National Health and Safety Director of the Canadian Auto Workers (CAW) made a presentation to the Occupational Disease Panel (ODP) in Windsor and expressed concern about the incidence of industrial disease among autoworkers. In particular she raised concern about adverse health effects associated with the use of machining fluids that are widely used by the CAW membership.
In support of their concerns, Ms. Walker provided the Panel with recently published studies that had been conducted jointly by General Motors (GM) and the United Autoworkers (UAW). Her letter quotes the researchers as saying:
"Overall, our findings suggest a positive association of rectal cancer with straight oil; stomach cancer with soluble oils and grinding; laryngeal cancer with straight and soluble oils; lung cancer with all exposure groupings; prostatic cancer with synthetic and soluble machining fluids and with grinding; brain cancer with soluble oils; leukaemia with all exposure groupings, and pancreatic cancer with soluble oils." [67]
Ms. Walker asked that should the investigation reveal a probable connection between metalworking fluid exposure and a particular disease(s), the Panel recommend that a legal presumption be enacted in favour of allowing Workers' Compensation claims for such disease(s) from claimants with a history of metalworking fluid exposure.
Representatives of the employers were invited to attend the meeting. While they were invited to participate in the discussion, the employers thought that it was premature to comment on this issue at that time.
The Panel considered the submission, undertook some preliminary reviews and ultimately agreed to place the issue of health effects associated with metalworking fluids on its agenda.
The following Report will be limited to the Panel's findings with respect to laryngeal cancer and exposure to petroleum based metalworking fluids in the manufacturing environment.
Future reports will deal with the other possible cancer sites raised by Ms. Walker and other work environments.
b) The ODP mandate and terms of reference
Section 95 of the Workers' Compensation Act requires the ODP to investigate possible diseases and when appropriate make findings of "probable connection" between disease and work [74].
The evidence that the ODP weighs to examine whether a probable connection exists is scientific and medical in nature. Specifically, the ODP considers epidemiological studies, hygiene information, toxicological evidence about the identified contaminants and alternative causes of disease.
When the Panel evaluates this evidence, it continues to be aided by the work of Sir Austin Bradford Hill (1965). Bradford Hill argued that to infer causality, consideration should be given to the following factors(1):
1. strength of association;
2. consistency;
3. specificity;
4. temporality;
5. biological gradient;
6. biological plausibility;
7. coherence;
8. experiment; and
9. analogy.
After weighing all of the evidence, the Panel decides what, if any, connection exists between occupation and disease. If the results of the investigation do not indicate the existence of a probable connection, the Panel will also report those findings.
When a probable connection is identified, depending on the strength of the connection, the Panel may recommend that the WCB enact guidelines for adjudication of claims on a case-by-case basis or recommend the disease and the relevant exposure(s) be added to Schedule 3 or 4 of the Act.
When a worker suffers from one of the diseases listed in the "Disease" column of Schedule 3 and can show that he or she was employed in an industrial process listed in the "Process" column, Section 134 of the Act states that the disease "shall be deemed to have been due to the nature of that employment unless the contrary is proved" (emphasis added).
A conclusive presumption applies to claims for diseases listed in Schedule 4. In other words, compensation benefits are always paid when a worker contracts the disease listed in the first column and was employed in the industrial process identified in the second column.
Readers are welcome to contact the ODP to receive more detailed information about the decision-making principles used by the Panel.
c) Investigations by the ODP
After listening to the submissions of the CAW, the Panel solicited an expert review of the world literature on the health effects of metalworking fluids by Dr. Paige Tolbert of Emory University [64] as a preliminary step. Dr. Tolbert was one of the authors of the series of studies conducted as a joint venture between GM and the UAW. The choice of Dr. Tolbert was acceptable to all the parties identified by the Panel as formal stakeholders.
The Panel recognizes that metalworking fluids are used in many workplaces and the representatives of labour and management from those workplaces would be interested in participating in this discussion. However, to complete this investigation within a reasonable time frame, the Panel decided to limit the number of parties it consulted formally, while it ensured an equal and fair balance between worker and employer participation. Throughout this investigation, the Panel consulted with large groups of metalworking fluid users in the automotive industry -- GM, Chrysler and Ford -- and the union representing the workers, the CAW.
Less formal consultations with a wide range of groups and individuals also took place. A Request for Submissions, containing Dr. Tolbert's review, was published in the October 23, 1993 issue of the Ontario Gazette. No submissions were received in response.
The Panel asked the CAW, GM, Ford and Chrysler to suggest names of medical experts to provide a written appraisal of Dr. Tolbert's review. The CAW selected three experts to comment and GM, Chrysler and Ford each selected one, so that an equal number of experts were chosen by labour and management stakeholders. The Panel bore the cost of the majority of those consultations.
The experts were:
Selected by Chrysler: Dr. Philip Landrigan, Chair, Department of Community Medicine and Director of the Division of Environmental and Occupational Medicine, Mount Sinai Medical Center, New York;
Selected by Ford: Dr. Elizabeth Delzell, School of Public Health, University of Alabama at Birmingham;
Selected by General Motors: Dr. Rosemary Marchant, Worksafe Incorporated, St. Catharines, Ontario;
Selected by the Canadian Auto Workers: Dr. Susan Kennedy, University of British Columbia and Vancouver General Hospital; Dr. Jack Siemiatycki, Épidémiologiste - professeur, Université du Québec, Institut Armand-Frappier; and Dr. Rafael Moure-Eraso, Associate Professor, Work Environment Department, University of Massachusetts, Lowell.
Each of these six experts provided written comments on Dr. Tolbert's review and the subject generally. A copy of each of their reports was sent to Dr. Tolbert and the four stakeholders for additional comments.
At the Panel's meeting of January 20, 1994, Dr. Tolbert briefly presented her paper. Then the Panel heard comments from Drs. Kennedy, Delzell
and Marchant and submissions from representatives of the CAW, Ford, Chrysler and GM.
Also in attendance as observers were representatives of the Occupational Health Clinics for Ontario Workers, United Steelworkers of America, the Task Force on Occupational Disease, the WCB, the Ontario Ministry of Labour and the Workplace Health and Safety Agency. (A list of participants may be found in Appendix A.)
The Panel asked the stakeholders to address the following questions:
1) Is there agreement that metalworking fluids are not a single
substance? If so, how should the topic be divided?
2) What, if any, further investigative steps should the Panel take?
3) What conclusions can be drawn from the available evidence?
4) What medical conditions should the Workers' Compensation
Board's policies cover and how?
The Panel also received written submissions from the CAW [68] and the WCB [20].
An in-house computerized search of the world literature about metalworking fluids and laryngeal cancer specifically was conducted by ODP staff through MEDLINE, NIOSH, BIOSIS and CANCERLIT. Additional medical information and advice was sought as needed.
Each of the four stakeholders was asked to review their historical records and provide as much detail as possible about what products were used and when. Generally records do not exist for the time before the early 1980's [8, 16, 69].
The WCB was asked to provide information about the number and status of laryngeal cancer claims filed. Legal practices in other jurisdictions were also explored.
d) Submissions from stakeholders
Those stakeholders and experts present at the Panel's January, 1994 meeting agreed that the Panel should not await further original research because large and excellent quality studies of the health effects of metalworking fluid exposure were already available.
The CAW took the position that metalworking fluid exposure and laryngeal cancer, among other diseases, should be added to Schedule 3 of the Workers' Compensation Act.
Chrysler's representative said that there may be an association between straight oils and rectal, scrotal and squamous skin cancer.
Ford's representative said that the evidence does not support applying a legal presumption in favour of claims for lung, pancreatic or stomach cancers, but might support the scheduling of laryngeal, rectal and skin cancers.
The consultant chosen by GM said that the association of straight oils with skin cancer is clear, and such claims should be paid, but that use of straight oils is declining. In her opinion, the evidence about other cancers is not sufficiently clear; however, exposure should be kept low since it is known that metalworking fluids contain carcinogens.
e) Legal, policy and claims experience considerations
The Panel did not find its investigation of the statutes and policies used in other jurisdictions very informative. None of the provinces or territories in Canada have policies pertaining specifically to cancer of the larynx and metalworking fluid exposure.
All other possibly relevant evidence is detailed in Appendix B which contains:
1. policies on laryngeal cancer from other sources;
2. occupational metalworking fluid exposure guidelines in Canadian
and other jurisdiction;
3. actual occupational exposure levels.
a) Cancer of the larynx
The larynx is the organ of voice production. It is the part of the respiratory tract between the pharynx and the trachea. It consists of a framework of cartilages and elastic membranes housing the vocal folds and the muscles which control the position and tension of these elements [62].
Cancer of the larynx is a relatively rare disease with prolonged survival(2). The National Cancer Institute of Canada reported that laryngeal cancer had a 5-year survival rate of 62% among males of all ages in Quebec between 1984 and 1986 [49].
A substantial proportion of those affected will not die of the disease because curative treatment is available. The larynx can be removed, or the tumour treated with radiation. For this reason, incidence studies, which examine all cases of the disease including the non-fatal cases will have more statistical power. As well, incidence data are based upon hospital pathology reports which are widely recognized to provide more reliable data than the data obtained from death certificates [58].
Occupation and lifestyle are known and suspected to contribute to laryngeal cancer. It is well established that smoking and alcohol consumption contribute to higher rates of cancer of the larynx [57]. Most authors of studies of laryngeal cancer take smoking and alcohol use into account [1, 5, 6, 7, 15, 18, 19, 22, 26, 48, 51, 71, 80, 83].
IARC has identified sulphuric acid mist as a possible occupational exposure that can contribute to incidence of this disease [32, 61]. There is also evidence that other occupational exposures, such as nickel aerosol [44] and asbestos [24] contribute to cancer of the larynx.
b) Metalworking fluids/oil mists
Metalworking fluids are widely used in a variety of industries for cooling and lubricating both the tool and the work surfaces during metalworking operations. Such operations include turning, grinding, boring, drawing, tapping, gear shaping, reaming, rolling, hobbing(3), and band and hack sawing. The fluids are directed at the work surface in a spray or stream, and are generally collected and reused. Workers may be exposed through contact with their skin or by inhaling and swallowing the mist that is produced [64].
In 1981, US sales of lubricating oil products amounted to 7.36 million tonnes. The following pattern has been reported for US lubricant usage in 1980: 78.5% in manufacturing; 5% in mining; 1.8% in construction; and 14.7% in miscellaneous industries [30].
On the basis of the 1974 National Occupational Hazard Survey in the US, the National Institute for Occupational Safety and Health (NIOSH) estimated that about six million US workers in non-agricultural industries were exposed to mineral oils, two million to lubricating oils, one million to cutting oils and one million to motor oils.
Less information is available about Canadian usage and the number of workers exposed, but IARC reported Canadian sales of lubricating oil products of 1.4 million tonnes in 1981 [30].
(i) Types of metalworking fluids
Mineral oil is a component of all metalworking fluid types except synthetics. The degree of refining has varied widely over time, as have the types of additives used. Epidemiological data are not yet available to assess the carcinogenicity of current formulations including synthetics because a sufficient latency period has not elapsed [64].
There are basically four different types of metalworking fluids:
Straight oils: These are mineral oils with additives such as sulphurized fats and rust inhibitors. They contain no water, but water may get added inadvertently as they are used, which can allow the growth of micro-organisms and necessitate the addition of biocides. According to IARC, about 45% of fluids used as of 1984 were straight oils. They are used for applications requiring maximum lubricity. Their coolant properties are less effective than those of soluble oils;
Soluble oils: These are straight oils mixed with water as well as emulsifiers, coupling agents, rust inhibitors and biocides. They are cheaper than straight oils and have better coolant properties. According to IARC, about 50% of fluids used as of 1984 were soluble oils;
Semi-synthetic fluids: These are a hybrid of soluble petroleum-based fluids and synthetic fluids containing 15-40% mineral oils with glycols, polyols and ester lubricants;
Synthetic fluids: These are water-based fluids that contain organic chemicals, such as ethanolamines [64]. According to IARC, 4-5% of fluids used as of 1984 were synthetic or semi-synthetic [30]. IARC has not produced a monograph on synthetic fluids. This Panel investigation and Report do not cover synthetic fluids.
Straight (or "neat") oils have been in use since the nineteenth century. Soluble and synthetic fluids were introduced in the 1940's when high-speed machinery made necessary the superior cooling capabilities of water-based fluids [64].
(ii) Refining
Mineral oil-based fluids are refined from petroleum crude oils. All crude oils contain some polycyclic aromatic hydrocarbons (PAHs(4)) in varying degrees. The chemical compositions of these fluids depend both on the original crude substance and on the processes used during refining. The trend has been toward more severely refined oils with more complete removal of unwanted impurities such as PAHs.
All refining processes begin with the vacuum distillation of crude oils to light and heavy distillates. Until the 1940's, these distillates were further processed by acid refining. Mild acid refining was used to improve colour, odour and stability of petroleum-based oils by removing unstable hydrocarbons, resins and asphalt as well as sulphur, nitrogen and oxygen-containing compounds. Such treatment reduced the total aromatic content slightly but did not significantly reduce the amount of PAHs. After acid refining, the base oil underwent neutralization with caustic soda or clay absorption, or both. The last step in the refining process was "dewaxing" for optimal low-temperature flow characteristics. The base oil was treated with a dewaxing agent and then chilled, causing waxes (high molecular-weight paraffins) in the oils to crystallize so they could be filtered and removed.
Since the 1940's, acid refining has been gradually replaced by solvent refining, a process which selectively extracts and removes undesirable compounds (such as PAHs, olefins, naphthenes and paraffins) from the distillates. Controlling and increasing the degree of extraction allows highly refined oils (having few impurities such as PAHs) with selected characteristics to be produced. IARC estimated that, as of 1984, 74% of all finished lubricant capacity in the US and Canada included solvent refining as a processing step, and this is probably also true in other parts of the world.
In the 1960's, "hydrotreating" was introduced. This process is a more severe treatment of the distillates to produce a more highly refined base oil than is produced by acid refining. Hydrotreating, sometimes used in conjunction with solvent refining, converts olefins and cyclic hydrocarbons (including PAHs) to simpler straight-chain hydrocarbons in the presence of a catalyst. The severity of the treatment dictates the extent of this conversion.
Certain specialty oils with very particular specifications, such as white oils used in medicines, are still produced using fuming sulphuric acid in order to remove virtually all aromatic compounds. As hydrotreating processes are improved, acid treating will continue to be reduced to very limited uses or eliminated. Even medicinal white oils can now be produced solely by hydrotreatment [30].
a) Structuring the discussion
An extensive literature search was conducted by Dr. Tolbert. An additional search, specifically about laryngeal cancer, was conducted by the Panel staff. Numerous and general keywords describing occupation were used to ensure the inclusion of any relevant data. It was then necessary to organize this large pool of data and eliminate those studies which were not informative about the issue at hand.
The method the Panel used to evaluate the relevance of studies is explained below.
1) Studies that involved fewer than four cases of laryngeal cancer were excluded [42]. Such studies probably did not have sufficient power to identify any increase in risk which might have existed.
2) Studies in which the authors made no mention of exposure to "metalworking fluids", "oil mists", "machining fluids/oils", "cutting fluids/oils", "lubricants" or "coolants" were excluded [6, 10, 13, 19, 21, 45, 55, 71]. Although the Panel's broad literature search identified studies of workers who might have had such exposure, such as metal processors [5] or workers from a particular manufacturing complex [13], the Panel was not prepared to assume that such exposures occurred if they were not cited by the authors.
3) Studies that described the relevant exposure as simply "oil and grease" were excluded [5, 7]. For example, Cauvin et al. (1990) described exposure in this way, with most subjects being mechanics and gas pump attendants. Exposure to "oil and grease" tells little about the substances involved, their respirability or even route of entry. Gas pump attendants would likely be exposed to gas fumes which contain many substances that could be confounders. Therefore, the Panel found this study uninformative about laryngeal cancer and metalworking fluid exposure.
4) Studies that combined findings for laryngeal cancer with, for example, lung cancer as part of the broader category "respiratory system cancers" [11] were excluded. Findings for laryngeal and lung cancers can differ substantially. For example, the first GM/UAW study [14] found one group which experienced a statistically significant increase in lung cancer (among white males from plant 2(5)) but the other groups in that study showed approximately the expected rate. The second GM/UAW report studied mortality more closely, by type of metalworking fluid [65], and found a statistically significant increase in laryngeal cancer, a reduction in lung cancer deaths and an inverse dose-response trend for lung cancer. This suggests that combining results for lung and laryngeal cancers could hide a health risk.
5) Studies whose authors did not provide numerical data but only commented about laryngeal cancer were excluded [54] because the lack of data prevented the Panel from independently assessing the significance of the results.
6) Studies which combined the results for workers with widely varying possible exposures to metalworking fluids were also excluded. This is true of the large cohort study conducted by Rotimi et al. (1993) which combined results from engine plants and foundries. The extent of exposure to metalworking fluids in engine plants is significantly greater than foundries and when the disease incidence of workers in these two work sites is combined, the data becomes very unreliable. Furthermore, the small number of laryngeal cancer cases (5) further weakens the significance of the results.
7) Finally, a 1947 study by Kennaway and Kennaway was excluded. It reported lung and laryngeal cancer deaths in England and Wales that occurred between 1921 and 1938 inclusive. The metalworking fluids in use from before the turn of the century until about 1940 were mildly acid-refined mineral oil and highly carcinogenic, according to IARC [30]. Current and future claimants would have had different types of exposures. It is highly unlikely that claims will arise in the future from pre-1940 exposures, the period covered by this study.
Nine reports on seven different cohorts remained.(6) There are two mortality studies of GM workers. In addition, the Panel examined seven case-control studies of cancer incidence [1, 15, 18, 22, 51, 80, 83] and one standardized cancer incidence study [63].
Ultimately, the Panel gave considerable weight to the series of four papers on the GM cohort by Eisen and Tolbert and their colleagues [14, 15, 23, 65] for the following reasons:
the overall SMR study involved more than 45,000 automobile production workers from three plants over a 47 year period, the largest number of workers ever studied for risks associated with metalworking fluid exposure;
the study team conducted the most detailed exposure assessments(7);
the series of articles includes a further SMR analysis broken down by the type of metalworking fluid;
a nested case-control study of the incidence of laryngeal cancer over a 70 year period was conducted which used nearly five controls per case; and,
the consultants chosen by all of the identified stakeholders agreed that, for the purposes of the Panel's Report, these studies are of very high quality with exceptionally detailed exposure analyses and are sufficiently large to provide reliable results.
As mentioned above, the Panel did not rely on the GM/UAW studies alone, but examined reports on eight different groups of workers.
b) Evidentiary limitations
Most epidemiological studies do not provide findings by fluid type. The ODP wrote to all four of the designated stakeholders and asked them to check their purchasing, plant condition or other records to determine: 1) the date of the earliest records; 2) what types of metalworking fluids were used for what operations and during what time periods. The earliest record produced was from 1974, but generally records do not exist for the time before the early 1980's. The available records show that all types of fluids were used to varying extents and in various processes. No particular pattern was evident. Nor is the degree of refining known, except by the approximate time frames discussed below.
No study of the health effects of metalworking fluid exposure provides information about the degree of refining of the fluids involved. The Panel consulted Dr. Susan Woskie, one of the authors of the GM/UAW studies to see if it was possible to break down the evidence. She advised that, in the US, major changes in the refining of the petroleum oils used in metalworking fluids did not occur on a large scale until the 1980's [81]. Therefore, any analysis based on degree of refining would not be helpful.
FIGURE 1: STUDIES OF LARYNGEAL CANCER AMONG WORKERS EXPOSED TO METALWORKING FLUIDS
1a. Mortality Studies (SMRs)
1 (95% CI .58-1.66)
2 (95% CI .65-3.36)
3 (95% CI 1.03-3.05)
4 (95% CI .09-2.70)
5 (95% CI 1.26-2.98)
1c. Case-Control Studies (RRs)
1 (90% CI 0.3-7.0)
2 (90% CI 1.4-29.1)
3 (95% CI 0.9-2.1)
4 (95% CI 1.1-11.8)
5 (CI not available)
1b. Incidence Studies (SIRs)
(95% CI 30-136)
(95% CI 77-179)
1d. Case-Control Studies (ORs)
1 (95% CI .5-1.8)
2 (95% CI 0.2-4.8)
3 (95% CI 0.9-6.7)
4 (95% CI 1.0-4.7)
5 (95% CI 1.2-5.5)
6 (95% CI 0.9-5.3)
7 (95% CI 0.3-7.3)
8 (95% CI 1.3-4.9)
9 (95% CI 1.25-3.98)
c) The epidemiological findings
Mortality and Morbidity Data
The Panel and the stakeholders found the large historical cohort study, conducted at Harvard University and sponsored jointly by the UAW and GM, to be particularly instructive. The researchers had a study group of 45,000 auto production workers from 3 plants in Michigan. ( Plant I produced gear and axles, Plant II produced transmissions and Plant III manufactured steering columns).
To date three different epidemiological papers have been produced as a result of that research. A fourth paper details the exposure assessment developed to allow for the analysis contained in the second and third papers [23].
The original work was a cohort study of the complete group of 45,000 workers. The study was designed to assess cancer mortality associated with long-term exposure to machining fluids. The results of that study were indicative of but did not conclusively establish elevated laryngeal cancer risks. In Plant I the laryngeal cancer rates were 1.02 (95% CI .58- 1.66) for white males and 1.63 (95% CI .65- 3.36) for black males. The white males in Plant II had an overall SMR of 1.85 (95% CI 1.03 - 3.05). There were not a sufficient number of black workers at Plant II to conduct the same detailed analysis. For Plant III the SMR for laryngeal cancer was 0.77 (95% CI .09-2.70); however, the authors noted that low number of deaths among that group made the risk assessment unstable.
The authors of this study found the evidence of a possible excess of laryngeal cancer in Plants I and II to be sufficient to warrant further investigation [14]. As a result a second analysis was conducted. The authors decided to eliminate Plant III from the analysis because a policy at that plant meant that old employment records had been purged [66]. This second analysis showed elevated rates of laryngeal cancer among white men in each exposure group. The highest risk was among white men exposed to straight machining fluids. In that group the SMR was 2.0 (95% CI 1.3-3.0). There were too few deaths to provide any reliable data about the experience of black men. The positive association was identified in both plants [65].
Finally, the research team conducted a case-control study within the cohort of automobile workers exposed to machining fluids. The authors examined 108 cases of laryngeal cancer which were matched to 5 controls randomly selected from the large cohort but matched according to year of birth, plant, race and gender. When the data was combined from all plants the OR increased with increasing exposure to straight oils. This exposure was primarily associated with machining operations.
The increases in laryngeal cancer were not similar for grinders. According to the authors this anomaly may have occurred for three reasons. In the first instance, the particle size to which grinders are exposed is larger than that found in machining operations and could result in a differential pattern of deposits of dust particles in the respiratory system. Secondly, the authors noted straight oils were rarely used for high speed grinding. Finally, it was opined that the higher speeds in grinding could have chemically altered the composition of metalworking fluid.
In that case control study, in the highest category of metalworking fluid exposure the OR was 2.23 (95% CI 1.25-3.98). The authors concluded:
"While further work is needed in order to better specify the causal agent, these data present a compelling case for the association of straight MF exposure and larynx cancer risk, and suggest that straight MF exposures be reduced." [15]
In four other case-control studies, researchers identified statistically significant excesses of laryngeal cancer among workers exposed to metalworking fluids. In those studies the rates ranged from 2.1 - 5.6. Two other case-control studies of workers exposed to metalworking fluids showed elevated rates of cancer of the larynx; however, these results were not statistically significant.
In a 1988 cancer incidence study of Finnish metalworking fluid-exposed shipyard workers Tola et al. (1988) found elevated but not statistically significant rates (SIR 120 [95% CI 77-179]) of laryngeal cancer. In the same study the authors found machinists experienced lower than expected rates and this decrease was also not statistically significant. For that group the SIR was 69 (95% CI 30-136).
In summary the evidence shows increasing rates of laryngeal cancer among those workers with confirmed exposure to metalworking fluids. The evidence of excess levels of laryngeal cancer is less reliable statistically as the exposure data decreases in reliability.
Dose/Response data
An important factor which points to an association between the incidence of disease and exposure to a certain product is the existence of a dose/response trend. The best evidence that we have of a dose/response comes from the GM study because it has the most detailed information about exposure. In that study the authors produced the following table:
TABLE 1: Adjusted ORs for Laryngeal Cancer from Case-Control Study by Eisen et al. (1994)
As demonstrated, there is a clear progression of the incidence of disease with increasing exposure to straight oils. The same relationship is not seen for workers engaged in grinding for the reason specified in the previous sections.
The other studies available to the Panel did not have sufficient exposure data to allow for this type of analysis.
d) Confounders: Smoking and alcohol consumption
Potential confounders are variables which may be associated with exposure, and are also independent risk factors for disease. Since smoking and alcohol use are known causes of laryngeal cancer, it is important to design studies, or evaluate findings, in such a way that the effects of smoking and alcohol consumption are taken into account and do not create a spurious connection between laryngeal cancer and metalworking fluid exposure. The authors of all of the case-control studies controlled for smoking and alcohol use in their initial study designs.
The GM/UAW studies did not control for smoking or alcohol consumption in their initial data collection processes; however, the authors took these issues into account and commented as follows:
"Given the documented association between smoking, alcohol, and larynx cancer, one must address the possibility that these unmeasured covariates account for these results. To this end, lung cancer and cirrhosis deaths were treated as crude relative measures of smoking and alcohol consumption and examined in relation to exposure. Relative risks were examined across increasing exposure categories in Poisson regression models based on the entire cohort from which the subjects in this case-control study came. No evidence was found of either increasing lung cancer risk or increasing risk of cirrhosis with increasing exposure to straight MF [metalworking fluid] [Monson, 1992]. These results suggest that neither cigarette smoking nor alcohol use increased with increasing exposure to straight MF." [15](8)
THE INTERNATIONAL AGENCY FOR RESEARCH ON CANCER (IARC)
e) Possible cancer causing agents
The Panel's work has been aided by the critical reviews and evaluations conducted by IARC. It has used its unique international position to develop a system for classifying substances that has been praised for its elegant scientific criteria for selecting and evaluating published evidence on cancer. IARC is recognized worldwide as an authoritative source of information on the carcinogenicity of chemicals and complex exposures. (For a detailed description of the IARC criteria, please see Appendix D.)
Mineral oil is present in all metalworking fluids in varying amounts except in synthetic oils.
According to IARC, there is "sufficient" evidence of carcinogenicity to humans for untreated and mildly-treated mineral oils (IARC Group 1). Highly-refined mineral oils are "not classifiable" because there is insufficient evidence to date (Group 3).
IARC has distinguished mildly-refined from highly-refined mineral oil for the following reasons:
1) Highly-refined products contain smaller amounts of contaminants such as PAHs which are thought to be largely responsible for the carcinogenicity of mineral oils [64];
2) Mildly-refined mineral oils induced skin tumours in mice, rabbits and rhesus monkeys, while highly-refined mineral oils did not produce skin tumours in mice; and
3) These distinctions generally followed the same pattern in tests for mutagenicity [31].
The cancers that occurred in excess in the studies cited by IARC include: skin, especially scrotum; gastrointestinal (stomach cancer in two studies, large bowel cancer in one); sinonasal cancer; primary respiratory, upper alimentary tract and skin cancers among men with scrotal cancer; bladder cancer; lung cancer among newspaper pressmen; rectal cancer; buccal cavity and pharyngeal cancer [30].
Neither the 1984 IARC report nor its 1987 update refers to cancer of the larynx. This may be because little research about the potential association between metalworking fluids and laryngeal cancer had been published by 1987. Only three of the studies that were before the Panel were available in 1987; they are all case-control studies [18, 51, 83].
All crude petroleum oils contain some PAHs (described by IARC as contaminants) which are removed to varying degrees by the refining process. There is evidence that the PAH concentration of mineral oils increases with use, perhaps as a result of chemical reactions as they are heated [3, 64]. When used as cutting oils and heated, PAH concentration has been found to increase up to 10-fold [30]. Therefore, even if an oil is originally highly refined, a carcinogenic agent may reappear with use.
Dr. Tolbert's literature review also lists the following known or suspected carcinogens in metalworking fluids: long-chain aliphatics; sulphur; chlorinated paraffins; formaldehyde (IARC Group 2A); N-phenyl-2-naphthylamine (IARC Group 3) [31, 64]. Contaminants such as metal particles are generated in the course of metalworking operations. Particles become suspended in the fluid and concentrate with use. These contaminants may include nickel, chromium, lead, cobalt and molybdenum [64, 15, 31].
All fluid types contain additives of various purposes(9). Because the additives are commercial products, protected by patent, the formulation of these elements is unknown. They include:
1. biocides, necessary to control bacterial growth in any metalworking fluids that contain water. IARC has determined that some nitrosamines identified in metalworking fluids cause cancer in animals and could cause cancer in humans [29]. Some research has linked nitrosamines with gastric cancer [4]. The nitrosamine N-nitrosomorpholine (NMOR), which has been used as a biocide in some soluble fluids [33] induced laryngeal cancer in hamsters [29].
2. chemicals added to inhibit rust and corrosion. They may be converted into nitrosamines when they are heated during use [40]. Studies by Keefer, et al. (1990) and Monarca and colleagues (1993), among others, have shown nitrosamines to be present in both new and used metalworking fluids. NIOSH has conducted its own original analyses of 49 samples of soluble and synthetic fluids(10). It found the nitrosamine N-nitrosodiethanolamine (NDELA) to be present in 50% of samples(11) [41].
f) Consultants' and reviewers' comments
As mentioned above, Dr. Paige Tolbert provided the Panel with a review of the world literature on the overall health effects of exposure to metalworking fluids. Six other independent experts provided comments on Dr. Tolbert's review and on the subject generally.
Drs. Tolbert and Kennedy were convinced of a causal connection between metalworking fluid exposure and laryngeal cancer. Dr. Siemiatycki thought there was a weak to moderate association. Dr. Marchant said that the strongest evidence for causality is with smoking and alcohol and that occupational causes lack strong epidemiological evidence. In their reviews, Drs. Delzell, Landrigan and Moure did not comment specifically about laryngeal cancer.
The four experts who did provide comments about laryngeal cancer are quoted below.
Dr. P. Tolbert's report to the Panel supports an association:
"While machining fluid exposure did not appear to increase lung cancer risk in this cohort study, a positive association with larynx cancer was evident. A two-fold excess of larynx cancer mortality was observed among those exposed to straight oils [Tolbert et al., 1992a]. This finding was pursued in a case-control study nested within this cohort for which incident larynx cancer cases were ascertained through cancer registries and information on possible confounding exposures (such as solvents, acid mists, and asbestos) was obtained [Eisen et al., [1994]). The association of straight oil exposure with larynx cancer risk persisted; a dose-response trend was notable, with a statistically significant two-fold excess among those exposed to greater than 0.5 mg/m3-years. Another recent investigation substantiates this finding; in a registry-based case control study, Ahrens et al. [1991] observed a statistically significant association of a history of work in jobs with oil mist exposure and larynx cancer risk."
Dr. S. Kennedy agreed, saying:
"The larynx is the likely primary target organ for inhaled straight oil mists, as these aerosols tend to be made up of droplets in the size range deposited mainly in the upper airways, rather than in the deeper lungs. The epithelium of the larynx is similar to that of the skin (i.e. stratified squamous epithelium, not the respiratory epithelium found in the rest of the upper and lower airways). Cancer of the larynx is relatively uncommon, but cancers found in this organ are typical squamous carcinomas, similar to squamous cell carcinomas of the skin (14). Therefore, it is very likely that the cancer risk for this site would mimic that of skin, for this type of exposure. This strong biologic plausibility, together with the epidemiologic evidence of excess laryngeal cancers in association with straight oil exposure argues in favour of accepting cancers at this site as work-related, if a history of straight oil exposure is present."
Dr. J. Siemiatycki said:
"The summary is reasonable. I would say that the evidence for an effect on the bladder is stronger than for esophagus, pancreas, colon and sinonasal region, and that the evidence for larynx and rectum, resting essentially on one study, is not quite as strong as she implies. But we're talking about shades of grey, not blacks or whites."
Dr. R. Marchant thought that lifestyle exposures provide the strongest evidence of causation. She wrote:
"There are very few studies that report a potential relationship between cutting oil and laryngeal cancer. Only in Ahrens et al [1991] was there any control for smoking and alcohol, and in that study there was significant results for both of those exposures with only an excess risk for the occupational exposures.
"Many occupational reports for cancer of the larynx suggest that there is an increased risk for laryngeal cancer in workers exposed to asbestos, cutting oil, wood dust, grease and oil. Workers in the paper, metal, leather, food and textile industries and barbers, drivers and naphthalene cleaners have also shown an increase [Rothman et al 1980, Decoufle 1979, Morgan and Shettigara 1976, Milham 1976, Wolf 1978, Decoufle et al 1977, Wynder et al 1976]. By and large these reports do not control for lifestyle risk factors such as tobacco and alcohol, well established as causes of laryngeal cancer [Tuyns 1990, Sherman 1991]. As the occupational reports are mainly based on a few cases unconfirmed by higher order studies, the association must be considered tentative.
"In a case-control study [Flanders et al 1982], controlling for alcohol and tobacco consumption, increased odds ratios were found for workers in construction, railroad and food industries, and for grinding wheel operators, sheetmetal workers, electricians and automobile mechanics (number of cases very small in each category). Comparing heavy smokers with light or non-smokers the ratio was 6.8 90% CI ± 3.1-14.1. For alcohol users versus non-users the rate was 2.5 90% CI ± 1.6-4.0."
"Haguenoer et al [1990] in a case-control study, with controls matched for lifestyle, race, residence, gender and age found a significant association with laryngeal cancer and coal mining."
"Asbestos and related laryngeal cancer risk has been explored in case-control and cohort studies. In a review of the evidence [Liddell 1990] concludes that the findings: 'from the case-referent studies are mutually inconsistent; (2)...from the cohort studies, while not demonstrably consistent, do not indicate a major excess of laryngeal cancer mortality in cohorts of asbestos workers; and (3) exposure-response relations are unobtainable or equivocal. No experimental evidence has been proffered. Estimates of the RR of cancer of the larynx obtained from the various surveys are so divergent that it is impossible to find a merged value without violating established epidemiological principles. This disease has seldom been found among non-smoking asbestos workers and there is no evidence as to whether these few cases were also non-drinkers.' The relationship between asbestos and laryngeal cancer has been investigated by more studies and in greater depth than the potential association with other occupations or occupational exposures. Information to conclude that laryngeal cancer is caused by asbestos exposure is insufficient."
"IARC [1988] concludes that the 'occurrence of malignant tumours of the oral cavity, pharynx, larynx, esophagus and liver are causally related to the consumption of alcoholic beverages. Alcoholic beverages are carcinogenic in humans."
"The causal relationship between laryngeal cancer and cigarette smoking is well established [US Public Health Service 1964, 1982] in men. There is a strong dose response relationship [Blot 1988] and a multiplicative interaction between smoking and alcohol consumption [US Dept. of Health and Human Services 1989]. However, alcohol consumption correlates better to laryngeal cancer than tobacco consumption [Tuyns 1982] and relates to an increased risk in drinkers that are life-long non-smokers [Burch et al 1981, Elwood et al 1984, Tuyns et al 1988]."
"The strongest evidence for causality for laryngeal cancer is with smoking and alcohol. Occupational causes are very tentative and lack strong epidemiological evidence."
Smoking and alcohol use are discussed under Confounders on page 23.
THE BRADFORD HILL CONSIDERATIONS FOR EVALUATING WHETHER A PROBABLE CONNECTION TO WORK EXISTS
In 1965, Sir Austin Bradford Hill (Professor Emeritus of Medical Statistics at the University of London, England) articulated nine factors to be weighed when considering whether work has caused disease [25]. These factors are now widely accepted and are used by the Panel. They are:
1) Strength of association:
The degree of increase in the risk of disease after exposure to a substance or process (for example, a high SMR). A statistically significant increase is usually required to confirm an excess risk of disease; however, a strong association may be relevant even if statistical significance has not been shown, particularly when the failure to show statistical significance is because a small population is being studied.
2) Consistency:
Consistency is shown when several different studies produce similar findings. Consistency is particularly persuasive if the studies are of various designs, and are large and carefully conducted.
3) Specificity:
Specificity is shown when exposure to a particular substance or process is associated with one particular disease. Specificity must be weighed with caution because it does not apply if a certain substance is capable of causing more than one disease, such as lead.
4) Temporality:
Temporality means that the exposure took place before the disease occurred.
5) Dose-response (also called "biological gradient"):
A dose-response trend is shown when an increase in the exposure ("dose") corresponds with an increase in the rate of disease or death ("response"). Conversely, a dose-response trend will also
occur if the incidence of disease decreases with a corresponding decrease in the exposure.
6) Biological plausibility:
An association is biologically plausible when the suspected connection between the exposure and the disease is consistent with what we already know about biological and chemical patterns.
7) Coherence:
Coherence is shown when the evidence as a whole makes sense and is not contradicted by what we already know about the disease process. This may simply be another way of describing biological plausibility.
8) Experiment:
Experimental evidence is also relevant, if it is available. For obvious ethical reasons, scientists cannot conduct experiments on human beings, so such evidence is rarely available; however, often animal studies provide evidence about the effects of exposures.
9) Analogy:
An analogy is shown if the same exposure in another setting is also associated with an increased risk of the same disease.
As in previous discussions, the Panel's analysis is based upon the considerations articulated by Sir Austin Bradford Hill.
Strength of association:
Researchers in five studies of workers exposed to metalworking fluids reported increased rates of laryngeal cancer. Five subgroups within those cohorts experienced statistically significant increases, with SMRs, ORs or RRs ranging from 1.85 to 5.6. Two other subgroups showed some increase. This evidence establishes a strong association between metalworking fluid exposure and the development of cancer of the larynx.
Consistency:
With seven subgroups demonstrating some increases, and no statistically significant decreases found, consistency in the findings between studies of different groups of workers is established.
Specificity:
Since it is known that mineral oil exposure is associated with skin cancer, Hill's consideration regarding specificity for laryngeal cancer is not satisfied. As mentioned above, however, specificity must be weighed together with the other evidence. There are substances that are known to cause more than one type of cancer as well as non-malignant respiratory disease, such as asbestos. Data that show that a specific agent causes a specific disease is unequivocal evidence of an association; however, the fact that an agent can be associated with several cancer sites does not negate the existence of an association.
Temporality:
None of the studies present laryngeal cancer data by time since first exposure, therefore it is not possible to comment on temporality.
Dose-response:
The GM/UAW study, the only study with detailed exposure data, was also the only study that had sufficient evidence to allow for a dose-response analysis. That analysis clearly establishes increasing rates with increasing exposure to straight metalworking fluids.
Biological plausibility:
The route of entry, inhalation, suggests that an association is biologically plausible. Consultant Dr. Kennedy explained it this way:
"The larynx is the likely primary target organ for inhaled straight oil mists, as these aerosols tend to be made up of droplets in the size range deposited mainly in the upper airways, rather than in the deeper lungs. The epithelium of the larynx is similar to that of the skin (i.e. stratified squamous epithelium, not the respiratory epithelium found in the rest of the upper and lower airways). Cancer of the larynx is relatively uncommon, but cancers found in this organ are typical squamous carcinomas, similar to squamous cell carcinomas of the skin (14). Therefore, it is very likely that the cancer risk for this site would mimic that of skin, for this type of exposure. This strong biologic plausibility, together with the epidemiologic evidence of excess laryngeal cancers in association with straight oil exposure argues in favour of accepting cancers at this site as work-related, if a history of straight oil exposure is present." [37]
The Panel agrees with Dr. Kennedy that it is biologically plausible for metalworking fluid exposure to contribute to laryngeal cancer for the several reasons she has articulated. However, the Panel acknowledges that there are two differences between squamous cell carcinoma of the skin and squamous cell carcinoma of the larynx. Squamous cell carcinoma of the skin is common and rarely metastasizes, whereas squamous cell carcinoma of the larynx is rare and metastasizes more often [60]. The comparison posed by Dr. Kennedy does provide evidence of a biologically plausible connection between metalworking fluids and laryngeal cancer, but the Panel acknowledges that laryngeal and skin cancers are not entirely comparable.
On the same topic but from a different perspective, the authors of the GM study wrote:
"Considerations of biologic plausibility support a causal interpretation of the results. The larger particulate used as the basis for defining exposure in this study (>9.8 m) would be likely to deposit in the head and upper airways, and the opening of the larynx is a likely location of impaction for these larger inhaled particles. Thus, it is plausible that an irritating material present in the aerosolized straight MF would come into contact with the larynx. Chovil [1981] has suggested that chronic irritation to the vocal cords may lead to nonmalignant nodules which may then progress to malignancies in the presence of another carcinogen, and the irritating nature of these fluids has been recently documented in both human and animal studies [Kennedy et al., 1989; Schaper and Detwiler, 1991]." [15]
We also know from the information provided by IARC that metalworking fluids contain known human carcinogens, as well as some potential human cancer causing agents.
Coherence:
The evidence as a whole supports the existence of a probable connection. Most studies established increased rates of laryngeal cancer among metalworking fluid-exposed workers, some of which were statistically significant. There is strong evidence that carcinogenic agents are present in metalworking fluids and that the route of entry, inhalation, places the fluids in direct contact with the larynx. Furthermore, metalworking fluids are known to cause skin cancer when there is direct contact with skin.
Experiment:
N-nitrosomorpholine, a biocide which has commonly been added to some types of metalworking fluids, induced laryngeal cancer in hamsters.
Analogy:
Analogies with metal manufacturing industries include the statistically significant increases of laryngeal cancer found among coal miners exposed to mineral oil by Haguenoer et al.(1990) and among textile processors exposed to machining oils by Flanders et al. (1984).
The Panel's findings
On the basis of the evidence which is available and reliable the Panel is satisfied that a strong probable connection between metalworking fluids and primary cancer of the larynx exists.
The evidence establishes increased rates of laryngeal cancer among most groups of workers studied. Not only are there increases, but the majority of the studies show levels of excess double the expected, particularly when the time since first exposure is greater than 20 years. Furthermore, because cancer of the larynx is not common, the fact that these increases reached statistical significance is a strong indicator of an association. The association becomes more compelling with evidence that components of metalworking fluids are recognized human carcinogens. We also have evidence that allows us to establish a clear and unequivocal response among those workers exposed to straight oils. Finally, the consultants and researchers accept that the type of exposure, particulates measuring >9.8 m would probably be deposited in the upper airways and the opening of larynx, making the findings of the group data biologically plausible. One of the consultants reported that the concept of biological plausibility is further confirmed by the tumour type which she considers consistent with the well-established association between skin cancer and exposure to metalworking fluids.
The Panel's recommendation
The Panel recommends that occupational processes resulting in exposure to petroleum based metalworking fluids and cancer of the larynx be added to Schedule 3 of the Act. The ODP is willing, if requested by the Board, to assist in the development of a rebuttal matrix.
Due to copyright restrictions, references may not be reproduced by photocopying. All references are available at the WCB library.
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72. Workers' Compensation Act, R.S.B.C. 1979, c. 437, s. 6.
73. Workers' Compensation Act, R.S.N. 1983, c. 48, s. 79.
74. Workers' Compensation Act, R.S.O. 1990, c. W. 11.
75. Workers' Compensation Act, S.A. 1981, c. W-16, s. 1(1)(s).
76. Workers' Compensation Appeals Tribunal (Ontario) Decision No. 773/88, 19 WCATR 39 (1991; Signoroni, Jackson, Nipshagen).
77. Workers' Compensation Board (Alberta). Claims Department Policy Manual, Policy statement OCC-4, page 1, effective Feb. 23, 1987.
78. Workers' Compensation Board (Manitoba). Policy on Laryngeal Cancer, Document No. 44.20.30.60, effective June 14, 1978.
79. Workers' Compensation Board (Ontario). Operational Policy Manual. Document No. 04-04-13. May 4, 1978.
80. Wortley, P.; Vaughan, T.L.; et al. A case-control study of occupational risk factors for laryngeal cancer. British Journal of Industrial Medicine. Vol. 49(1992). p. 837-844.
81. Woskie, S.R., Assistant Professor, Work Environment Department, University of Massachusetts Lowell. [letter to C. Melbye regarding refining of metalworking fluids]. May 1, 1995.
82. Yeung, K.S., Acting Director, Medical and Occupational Disease Policy Branch, Workers' Compensation Board of Ontario. [letter to C. Melbye regarding laryngeal cancer claims]. March 20, 1995.
83. Zagraniski, R.T.; Kelsey, J.L.; et al. Occupational risk factors for laryngeal carcinoma: Connecticut, 1975-1980. American Journal of Epidemiology. Vol. 124, no. 1(1986). p.67-76.
- Mr. George Botic, Canadian Auto Workers, Toronto
- Dr. Penny Chan, Occupational Disease Task Force, Ontario Ministry of Labour
- Mr. Robert D. Chesnik, Chrysler Canada Limited
- Dr. Jianping Cui, Occupational Health Clinic for Ontario Workers, Windsor
- Dr. Elizabeth Delzell, School of Public Health, University of Alabama at Birmingham
- Mr. Pat Dugal, Canadian Auto Workers, Windsor
- Mr. Vern Edwards, Ontario Federation of Labour, Toronto
- Mr. Reimar Gaertner, Medical and Occupational Disease Policy Branch, Ontario Workers' Compensation Board
- Mr. Ron Hunter, Chrysler Canada Limited
- Dr. Susan M. Kennedy, Occupational Hygiene Programme, University of British Columbia, Vancouver, BC
- Mr. Robert Kusiak, Health Studies Unit, Ontario Ministry of Labour
- Mr. Murray Lawrence, Occupational Health Clinic for Ontario Workers, Windsor
- Dr. Henry B. Lick, Ford Motor Company
- Dr. Gary Liss, Health and Safety Policy Branch, Ontario Ministry of Labour
- Ms. Roxanne Lloyd, Workplace Health and Safety Agency
- Dr. Rosemary Marchant, Worksafe Inc., St. Catharines, Ontario
- Mr. John Perquin, United Steelworkers of America, Toronto
- Dr. Gordon R. Reeve, Ford Motor Company
- Dr. Larry M. Roslinski, Ford Motor Company
- Mr. Paul Sampara, Occupational Health Clinic for Ontario Workers, Hamilton
- Mr. Bill Simmonds, Ford Motor Company of Canada, Limited
- Mr. William Tate, Vice-President, General Motors of Canada
- Dr. Paige E. Tolbert, Environmental and Occupational Health Division, Emory University School of Public Health, Atlanta, Georgia
- Mr. Dave Triggs, Ford Motor Company
- Mr. Bruce Waechter, Ford Motor Company of Canada, Limited
- Ms. Cathy Walker, Canadian Auto Workers, Toronto
- Dr. William D. Watt, Chrysler Corporation
None of the provinces or territories in Canada have policies pertaining specifically to cancer of the larynx and metalworking fluid exposure.
Ontario
Since 1978, the Ontario WCB has had a policy (#04-04-13) stating that claims for laryngeal cancer will be accepted if the worker has had:
- 15 years exposure to nickel aerosol with 20 years latency, OR;
- 10 years exposure to asbestos dust with 20 years latency, OR;
- 7.5 years nickel aerosol and 5 years asbestos dust exposure with 15 years latency.
In 1990, the Panel published its Second Report to the Workers' Compensation Board on certain issues arising from the Report of the Royal Commission on Asbestos. It recommended that asbestos-related laryngeal cancer be added to Schedule 3. The majority of the Panel recommended that certain qualifiers (for example, at least 10 years' exposure) be included in the "Process" column. Three dissenting Panel members argued that the WCB does not have the legislative authority to include eligibility rules in the Schedule. They recommended adding laryngeal cancer to Schedule 3 with no qualifiers [28]. There has been no change in WCB policy or additions to the Schedules since that Panel Report.
The WCB reports having received 123 claims for laryngeal cancer, most of which were attributed to asbestos or nickel exposure. None of the claimants attributed their disease to metalworking fluid exposure [82].
Of four Workers' Compensation Appeals Tribunal decisions involving laryngeal cancer, only one addressed the question of how to determine work-relatedness. It granted entitlement to a nickel refinery worker after applying the benefit of doubt [76].
British Columbia
Cancer of the larynx is listed in Schedule B opposite the industrial process of work involving exposure to airborne asbestos dust. Thus, a worker with laryngeal cancer who worked with asbestos dust will be presumed to have contracted cancer as a result of employment unless the contrary is shown [72].
Alberta
The rebuttable presumption attached to Alberta's Schedule B does not apply to laryngeal cancer. The Board, however, has a policy which states: "Where a worker suffers a disease of the respiratory system due in part to occupational factors and in part to non-occupational factors, the overall disability will be presumed to be related to employment." [75, 77]
Manitoba
The Board has a policy stating that claims for laryngeal cancer will generally be accepted if the worker was exposed at work to asbestos fibres or nickel aerosol [78].
Newfoundland
One of the provisions in the Newfoundland statute may apply to laryngeal cancer in some cases. This provision states that if a worker with carcinoma was involved in fluorspar extraction, the disease is presumed to be due to employment in the mines unless the disease is traceable to another cause [73].
Other
The other provinces and territories have no policies about laryngeal cancer.
The Panel notes that Germany recognizes an association between laryngeal cancer and occupational exposure to nitrosamines, and to PAHs [34].
MINERAL OIL MIST OCCUPATIONAL EXPOSURE GUIDELINES
Ontario
Ontario's workplace exposure guidelines for mineral oil mist are prescribed in Regulation #833 under the Occupational Health and Safety Act. Two types of guidelines are used. A time-weighted average exposure value (TWAEV) is the average airborne concentration of a chemical or biological agent to which a worker may be exposed in a work day or a work week. The current TWAEV for mineral oil mist is 5 mg/m3.
The short term exposure value (STEV) is a 15-minute time-weighted average concentration which may not be exceeded at any time during a work day. The current STEV for mineral oil mist is 10 mg/m3.
It should be noted that an STEV is set on the basis of preventing the acute adverse effects which have been observed in humans or animals after high short-term exposures(12).
The Ontario Ministry of Labour's bipartite Occupational Exposure Limits Task Force recently conducted a review of the current exposure limits for 101 substances. The Task Force initially recommended lowering the current TWAEV for mineral oil mist from 5 mg/m3 to 1 mg/m3. It had also recommended lowering the current STEV for mineral oil mist from 10 mg/m3 to 3 mg/m3 [50]. Some of the other Task Force recommendations have been enacted but those pertaining to mineral oil mist have not. The Task Force members eventually agreed to maintain the current guidelines due to the potential economic impact of reducing them [52].
One of the bases for the Ontario guidelines has been the recommendations made by the American Conference of Governmental Industrial Hygienists (ACGIH). The ACGIH has revised its recommendations about mineral oil mist a number of times over the years since it first proposed a guideline in 1962. In 1984, the International Agency for Research on Cancer (IARC) published a detailed report that correlated the degree of health hazard from inhaled mineral oil mist to the extent to which the oil had been refined. The less refined the oil, the more hazardous is the inhaled mist. Later ACGIH recommendations were based on the IARC classifications.
In May of 1993, the ACGIH gave notice of its most recent intended change in recommended Threshold Limit Value (TLV) for mineral oil mist:
"On the basis of available human studies, exposure to oil mist alone has not been demonstrated to cause human health effects except at levels above 5 mg/m3. It is anticipated that this level will minimize the potential for skin and respiratory tract irritation. However, it is not possible to conclude from these limited human studies that 5 mg/m3, as a TWA [time-weighted average], is an acceptable exposure concentration for all types of oils. For oils containing toxic additives, it may be more appropriate to monitor and control exposure to the additives rather than to the oil mist."
"For products containing carcinogens, an exposure level below 5 mg/m3 would be prudent. For oils containing measurable quantities of carcinogenic PNAs(13) a TLV-TWA of 0.2 mg/m3, as the cyclohexane-soluble fraction of total suspended particulate, is recommended. This is the same as the TLV recommended for Coal Tar Pitch Volatiles. In accordance with the IARC recommendation, these oils are assigned an A1, Confirmed Human Carcinogen, designation. The oils covered by this TLV are those that are mildly solvent-refined, mildly hydrotreated, mildly acid-treated, aromatic distillate extracts, catalytically cracked oils, and untreated oils. These terms are further defined in IARC Monograph 33. Oils that have been in use may contain carcinogens produced by the usage conditions even though no carcinogens may have been present in the unused oil."
"At this time, no STEL [short-term exposure limit] is recommended until additional toxicological data and industrial hygiene experience become available to provide a better base for quantifying on a toxicological basis what the STEL should be." [2, 70]
Other jurisdictions
As of the writing of the 1984 IARC monograph which covers mineral oils, an exposure guideline of 5 mg/m3 was in use in Australia, Belgium, the German Democratic Republic, Italy, the Netherlands, Switzerland, the US and the USSR. In Japan, Finland and Sweden, the exposure guideline was 3 mg/m3 [30].
SOME ACTUAL OCCUPATIONAL EXPOSURE LEVELS
Assessments of past metalworking fluid exposures at three GM plants in the US, reported by Hallock et al. (1994), showed that the arithmetic mean exposure of all measurements taken between 1958 and 1970 was 5.42 mg/m3. Arithmetic means for different subgroups ranged from 0.59 to
20.28 mg/m3. Those findings range from far below to over four times the current Ontario TWAEV of 5 mg/m3.
After 1980, for the same operations, the arithmetic mean exposure was 1.82 mg/m3 with subgroups ranging from 0.45 to 2.79 mg/m3. The authors commented that changes in exposure levels generally corresponded with reported changes in plant environments such as installation of enclosures and local exhaust ventilation on machines [23].
| AUTHOR(S); YEAR; TYPE OF STUDY | NUMBER OF SUBJECTS | YEARS STUDIED | COMPARISON CONTROL GROUP | INDUSTRY AND GEOGRAPHICAL LOCATION | CONTROL FOR HEALTHY WORKER EFFECT | LARYNX CANCER - S.M.R.; (C.I.); number of cases; dose-response? | COMMENTS |
| Eisen, Tolbert et al.; (1992); mortality study | 46,384 males in total with a minimum 3 years of service; 10,159 deaths | 1941-1984
(43 yrs.) |
US males; local males for some analyses | 3 auto manufacturing
plants;
Michigan state, US (General Motors) |
no | Plant 1: whites: SMR 1.02 (0.58-1.66) n=16; blacks: SMR 1.63 (0.65-3.36) n=7; Plant 2: whites: SMR 1.85 (1.03-3.05) n=15; SMRs increased with longer latency; Plant 3: whites: SMR .77 (.09-2.79) n=2; no dose-response analyses | the first in a series of three GM studies; did not control for smoking or alcohol consumption in study design |
| Tolbert, Eisen et al.; (1992); mortality study | 33,619 in total with a minimum 3 years of service; 9349 deaths | 1941-1984 (43 yrs.) | US population | 2 auto manufacturing plants; Michigan state, US (General Motors) | no | elevated at both plants and in each exposure group; SMR for white males exposed to straight oils: 1.98 (1.26-2.98) n=23; rate ratio highest for those with 7.5 or more years exposure; dose-response? (RRs: 1.26; 1.02; 2.02) | a detailed exposure assessment was conducted; results for specific fluid types were provided; did not control for smoking or alcohol consumption in study design |
| Eisen et al.; (1994); nested case-control study | 108 cases with a minimum of 3 years of service | 1920-1989
(70 yrs.) |
538 controls
selected from a
cohort of 46,384
auto workers by
incidence density
sampling,
matched by year
of birth, plant,
race and gender
(ratio 1:4, 98) |
7 auto manufacturing plants in Michigan, US (GM) | yes | OR for straight oil exposure in excess of 0.5 mg/m3-years: 2.23 (1.25-3.98) n=28; dose-response shown | there was an association between sulphur and/or PAHs and laryngeal cancer; no increase in risk of lung cancer or cirrhosis which might have implicated smoking or alcohol use |
| Tola et al.; (1988); (cancer) incidence study | 12,693 males with a minimum of one year of service | 1953-1981 (29 yrs.) | local urban males | workers from 5 shipyards and 4 machine shops in south-southwestern Finland | yes | SIR among shipyard workers: 120 (77-179) n=24; among machine shop workers: 69 (30-136) n=8; no dose-response analyses | the smoking habits of this cohort roughly correspond to the average Finnish smoking habits; there was asbestos exposure but only two deaths from mesothelioma; no exposure to hexavalent chromium |
| Olsen and Sabroe; (1984); case-control study | 326 cases with laryngeal cancer and 1134 controls; (ratio 1:3.48) | 1980-1982 (2 yrs.) | members of the same sex from the municipal registry with the closest possible birth date | Denmark | no | RR for males occupationally exposed to oil: adjusted 1.4 (0.9-2.1) n=37; (unadjusted=1.6); no dose-response analyses | authors adjusted for age, sex, tobacco and alcohol consumption |
| Haguenoer et al.; (1990); case- control study | 283 cases and 566 controls; (ratio 1:2) | 1983 | patients in local general hospitals who did not have cancer | northern France | no | RR for metal work, mechanics: 1.6 (7 exposed cases; 8 exposed controls); RR for coal mining: 3.2; p<0.05; 11 exposed cases; 10 exposed controls; no dose-response analyses | controls were matched for sex, age, ethnicity, area of residence, smoking and alcohol use; the authors noted the presence of mineral oils in coal mines |
| Wortley et al.; (1992); case-control study | 235 cases and 547 controls; (ratio 1:2.33) | 1983-1987 (about 3½ yrs.) | 547 controls identified by random-digit dialling, from the same 13-county area, similar in age and sex distribution | western Washington state, US | no | OR for metalworking and plastic working machine operators: 2.6 (1.3-4.9) n=24; no dose-response; OR for metal and plastic process machine operators: 1.5 (0.3-7.3) n=4; possible dose-response for welders, cutters; dose-response not apparent for cutting oil exposure | authors controlled for smoking, alcohol, age and education |
| Ahrens et al.; (1991); case-control study | 100 male cases and 100 controls; (ratio 1:1) | 1986 | 100 males in hospital for other than smoking-related reasons | Bremen, Germany | no | OR for mineral oil exposure: 2.2 (0.9-5.3); no dose-response analysis for this exposure | adjusted for age and for amount of smoking and alcohol use |
| Zagraniski et al.; (1986); case-control study | 92 white male cases and 181 controls; (ratio 1:1.97) | 1975-1980 | 181 white male surgical patients from the same 2 hospitals without cancer or respiratory disease | New Haven, Connecticut, US | no | OR for machinists: 2.5 (1.2-5.2) 25% of cases; OR for metal grinders: 2.1 (1.0-4.7) 19.6% of cases; OR for transportation equipment manufacturing industry: 2.5 (0.9-6.7) 13% of cases; OR for shipbuilding industry: 1.0 (0.2-4.8) 5.4% of cases; OR for metal products industry: 1.0 (0.5-1.8) 47.8% of cases; no dose-response analyses | adjusted for lifetime tobacco and alcohol consumption; exposures to metals, metal dusts and cutting oils were examined but none explained the elevated risk for machinists |
| Flanders et al.; (1984); case- control study | 42 cases with a minimum of 6 mos. of service and 85 controls; (ratio 1:2.02) | 1974-1979 (5 yrs.) | 85 local hospital patients without cancer, lung disease or work-related illness | Richmond County, Georgia, US | no | RR for those with 5 or more years as textile processors: 5.6 (90% CI 1.4-29.1) n=7; RR for those with 5 or more years as mechanics, millwrights and repairmen: 1.5 (90% CI 0.3-7.0) n=6; no dose-response analyses (confidence intervals would be wider if 95% had been used) | authors controlled for age, sex, area of residence, smoking and alcohol use; authors noted that some textile workers may be exposed to machine oils; |
a) Degrees of evidence for carcinogenicity to humans and to experimental animals and supporting evidence
It should be noted that these categories refer only to the strength of the evidence that these agents are carcinogenic and not to the extent of their carcinogenic activity (potency) nor to the mechanism involved. The classification of some agents may change as new information becomes available.
(i) Human carcinogenicity data
The evidence relevant to carcinogenicity from studies in humans is classified into one of the following categories:
Sufficient evidence of carcinogenicity: The Working Group considers that a causal relationship has been established between exposure to the agent and human cancer. That is, a positive relationship has been observed between exposure to the agent and cancer in studies in which chance, bias and confounding could be ruled out with reasonable confidence.
Limited evidence of carcinogenicity: A positive association has been observed between exposure to the agent and cancer for which a causal interpretation is considered by the Working Group to be credible, but chance, bias or confounding could not be ruled out with reasonable confidence.
Inadequate evidence of carcinogenicity: The available studies are of insufficient quality, consistency or statistical power to permit a conclusion regarding the presence or absence of a causal association.
Evidence suggesting lack of carcinogenicity: There are several adequate studies covering the full range of doses to which human beings are known to be exposed, which are mutually consistent in not showing a positive association between exposure to the agent and any studied cancer at any observed level of exposure. A conclusion of "evidence suggesting lack of carcinogenicity" is inevitably limited to the cancer sites, circumstances and doses of exposure and length of observation covered by the available studies. In addition, the possibility of a very small risk at the levels of exposure studied can never be excluded.
In some instances, the above categories may be used to classify the degree of evidence for the carcinogenicity of the agent for specific organs or tissues.
(ii) Experimental carcinogenicity data
The evidence relevant to carcinogenicity in experimental animals is classified into one of the following categories:
Sufficient evidence of carcinogenicity: The Working Group considers that a causal relationship has been established between the agent and an increased incidence of malignant neoplasms or of an appropriate combination of benign and malignant neoplasms (as described on p.23) in (a) two or more species of animals or (b) in two or more independent studies in one species carried out at different times or in different laboratories or under different protocols.
Exceptionally, a single study in one species might be considered to provide sufficient evidence of carcinogenicity when malignant neoplasms occur to an unusual degree with regard to incidence, site, type of tumour or age at onset.
In the absence of adequate data on humans, it is biologically plausible and prudent to regard agents for which there is sufficient evidence of carcinogenicity in experimental animals as if they presented a carcinogenic risk to humans.
Limited evidence of carcinogenicity: The data suggest a carcinogenic effect but are limited for making a definitive evaluation because, for example, (a) the evidence of carcinogenicity is restricted to a single experiment; or (b) there are unresolved questions regarding the adequacy of the design, conduct or interpretation of the study; or © the agent increases the incidence only of benign neoplasms or lesions of uncertain neoplastic potential, or of certain neoplasms which may occur spontaneously in high incidences in certain strains.
Inadequate evidence of carcinogenicity: The studies cannot be interpreted as showing either the presence or absence of a carcinogenic effect because of major qualitative or quantitative limitations.
Evidence suggesting lack of carcinogenicity: Adequate studies involving at least two species are available which show that, within the limits of the tests used, the agent is not carcinogenic. A conclusion of evidence suggesting lack of carcinogenicity is inevitably limited to the species, tumour sites and doses of exposure studied.
(iii) Supporting evidence of carcinogenicity
The other relevant data judged to be of sufficient importance as to affect the making of the overall evaluation are indicated.
b) Overall evaluation
Finally, the total body of evidence is taken into account; the agent is described according to the wording of one of the following categories, and the designated group is given. The categorization of an agent is a matter of scientific judgement, reflecting the strength of the evidence derived from studies in humans and in experimental animals and from other relevant data.
Group 1 - The agent is carcinogenic to humans.
The category is used only when there is sufficient evidence of carcinogenicity in humans.
Group 2
This category includes agents for which, at one extreme, the degree of carcinogenicity in humans is almost sufficient, as well as agents for which, at the other extreme, there are no human data but for which there is experimental evidence of carcinogenicity. Agents are assigned to either 2A (probably carcinogenic) or 2B (possibly carcinogenic) on the basis of epidemiological, experimental and other relevant data.
Group 2A - The agent is probably carcinogenic to humans.
This category is used when there is limited evidence of carcinogenicity in humans and sufficient evidence of carcinogenicity in experimental animals. Exceptionally, an agent may be classified into this category solely on the basis of limited evidence of carcinogenicity in humans or of sufficient evidence of carcinogenicity in experimental animals strengthened by supporting evidence from other relevant data.
Group 2B - The agent is possibly carcinogenic to humans.
This category is generally used for agents for which there is limited evidence in humans in the absence of sufficient evidence in experimental animals. It may also be used when there is inadequate evidence of carcinogenicity in humans or when human data are nonexistent but there is sufficient evidence of carcinogenicity in experimental animals. In some instances, an agent for which there is inadequate evidence or no data in humans but limited evidence of carcinogenicity in experimental animals together with supporting evidence from other relevant data may be placed in this group.
Group 3 - The agent is not classifiable as to its carcinogenicity to humans due to a lack of evidence.
Agents are placed in this category when they do not fall into any other group.
Group 4 - The agent is probably not carcinogenic to humans.
This category is used for agents for which there is evidence suggesting lack of carcinogenicity in humans together with evidence suggesting lack of carcinogenicity in experimental animals. In some circumstances, agents for which there is inadequate evidence of or no data on carcinogenicity in humans but evidence suggesting lack of carcinogenicity in experimental animals, consistently and strongly supported by a broad range of other relevant data, may be classified in this group.
MINERAL OILS: UNTREATED AND MILDLY-TREATED OILS (GROUP 1) HIGHLY-REFINED OILS (GROUP 3)
A. Evidence for carcinogenicity to humans (sufficient for untreated and mildly-treated oils; inadequate for highly-refined oils)
Exposure to mineral oils that have been used in a variety of occupations, including mulespinning, metal machining and jute processing, has been associated strongly and consistently with the occurrence of squamous-cell cancers of the skin, and especially of the scrotum1. Production processes for these oils have changed over time, and with more recent manufacturing methods highly-refined products are produced that contain smaller amounts of contaminants, such as polycyclic aromatic hydrocarbons.
Excess mortality or morbidity from gastrointestinal malignancies was seen in two out of three cohort studies of metal workers (stomach cancer in two studies, large-bowel cancer in one); however, the only significant excess was for the sum of stomach cancer plus large-bowel cancer in one study. Four cases of scrotal cancer were detected in one relatively small cohort study of metal industry workers1. Among 682 turners with five or more years of exposure to mineral oils, five cases of squamous-cell carcinoma of the skin (four of the scrotum) occurred, with 0.3 expected2. In a case-control study, a relative risk of 4.9 was reported for the association of scrotal cancer with potential exposure of metal workers to mineral oils. Neither the actual levels of exposure nor the classification of the mineral oil to which the machine workers were potentially exposed was available in the reports of the epidemiological studies1.
In a case control study, an excess of sinonasal cancers was seen in toolsetters, set-up men and toolmakers1. In a series of 344 cases of scrotal cancer from 1936 to 1976, 62% had held occupations in which exposure to mineral oils was likely to have occurred. The median latent period was 34 years3.
An examination of the incidence of second primary cancers among men with scrotal cancer demonstrated excesses of respiratory, upper alimentary tract and skin cancers; when the occupations were grouped, the excess was largely confined to those with exposure to oil1.
Excesses of bladder cancer have been reported in case-control studies in several countries among machinists and engineers, who were possibly exposed to cutting oils containing aromatic amines as additives1.
With regard to printing pressmen, one of two cohort studies addressing lung cancer showed an excess and one of two proportionate mortality studies showed a small, statistically nonsignificant excess of lung cancer among newspaper pressmen but no excess among non-newspaper pressmen; the other study did not address lung cancer. One of three proportionate mortality studies on manual workers in the printing industry, not specifically addressing printing pressmen, did not show an increased lung cancer risk, whereas the other two studies found a statistically significant excess. One of two proportionate mortality studies of printing pressmen indicated a statistically significant increase of deaths from rectal cancer, and the other showed a statistically nonsignificant increase of deaths from colon cancer; the cohort study considering colorectal cancers did not show an increase occurrence. One proportionate mortality study among newspaper and other commercial printing pressmen showed a statistically significant excess of mortality from cancers of the buccal cavity and pharynx, whereas no such excess was observed in a cohort study. One case-control study indicated a statistically significant excess of cancers of the buccal cavity and pharynx. The findings regarding other malignancies were inconsistent; scrotal cancers were not mentioned. The type and amount of exposure were usually not described; exposure to both mineral oils and carbon blacks (see p. 142) would probably have been involved1.
In mortality statistics from the UK and from Washington State, USA, excesses of lung and skin cancer have been registered from jobs entailing exposure to mineral oils1.
B. Evidence for carcinogenicity to animals (sufficient for untreated and mildly-treated oils; inadequate for highly-refined oils)
Vacuum-distillate fractions, acid-treated oils, mildly-treated solvent-refined oils, mildly-treated hydrotreated oils, solvent extracts (aromatic oils) and some cutting oils produced skin tumours after repeated skin applications to mice. Similar treatment with high-boiling, catalytically-cracked oils produced skin tumours in rabbits and rhesus monkeys. Some severely solvent-refined oils did not produce skin tumours in mice. Highly-refined food-grade mineral oils did not produce skin tumours when applied to the skin of mice, although after intraperitoneal injection they produced plasma-cell neoplasms and reticulum-cell sarcomas in certain strains of mice 1. It was agreed that, in accordance with the previous evaluation, 'the significant latter finding is difficult to interpret'1.
C. Other relevant data
An increase in the frequency of chromosomal aberrations was observed in the peripheral blood lymphocytes of glass workers exposed to mineral oil mists. Urine from workers in a cold-rolling steel plant exposed to oil mists of solvent-refined oils was mutagenic to Salmonella typhimurium in the presence of an exogenous metabolic system4.
Special test protocols may be necessary to evaluate mineral oils adequately in short-term tests. Vacuum distillates from oil refining were reported to be mutagenic to S. typhimurium in the presence of an exogenous metabolic system. Positive findings were also obtained when the concentration of the exogenous metabolic system was five to ten fold that used generally. Acid-treated oils were not mutagenic to S. typhimurium in the presence of an exogenous metabolic system; solvent-refined oils were reported to be mutagenic in the presence of an exogenous metabolic system. Hydrotreated oil was reported to be mutagenic to S. typhimurium in the presence of an exogenous metabolic system, while white oils, highly-refined steel-hardening oil and solvent-refined steel-rolling oils were not. Unused crankcase oil was mutagenic to S. typhimurium in the presence of an exogenous metabolic system, while in other studies no mutagenic activity was found. Used crankcase oil from both gasoline and diesel engines was mutagenic to S. typhimurium both in the presence and absence of a metabolic system4.
Two insulation oils from highly-refined mineral-base oils induced transformation of Syrian hamster embryo cells and enhanced transformation of mouse C3H 10T1/2 cells. Unused new, re-refined and used crankcase oils induced transformation in Syrian hamster embryo cells4.
References
1 IARC Monographs, 33, 87-168, 1984
2 Järvholm, B., Fast, K., Lavenius, B. & Tomsic, P. (1985) Exposure to cutting oils and its relation to skin tumours and premalignant skin lesions on the hands and forearms. Scand. J. Work Environ. Health, 11, 365-369
3 Waldron, J.A., Waterhouse, J.A.H. & Tessema, N. (1984) Scrotal cancer in the West Midlands, 1936-76. Br. J. Ind. Med., 41, 437-444
4 IARC Monographs, Suppl. 6, 403, 1987
case-control study: A study that identifies people with a condition (usually a disease or cause of death), who are called cases, and people without that condition, who are called controls, then compares the frequency and/or severity of their exposure(s) that occurred before the condition developed. The case-control studies discussed in this Report examined the incidence of laryngeal cancer, rather than deaths caused by laryngeal cancer.
cohort study: A study that starts with a group of people who have something in common (such as a workplace or occupation), who are called a cohort. It identifies the frequency and/or severity of their exposure(s), follows them to see what disease(s) occur, in comparison to a control group that did not have the exposure(s).
95% confidence interval: See SMR, below.
confounders: Factors that can influence the results of studies (such as smoking and alcohol consumption, in this case) other than the factor under study (which is, in this case, the effect of metalworking fluid exposure).
to control for: To take into account, in the design of a study or in the analysis of its results, factors other than those being studied which could have influenced the results (confounders).
dose-response: A dose-response trend is shown when an increase in the "dose" (exposure level, intensity or duration) corresponds to an increase in the "response" (death or disease). Since detailed occupational exposure data is rarely available, most authors measure "dose" by the duration of employment.
epidemiology: The study of disease patterns in groups of people.
latency period: The period of time between the first exposure to a substance(s) and the appearance of the disease which the exposure(s) may have caused. Latency is usually measured by the time since the first employment.
odds ratio (OR): Refers to the odds ratio. This represents the likelihood that observed cases had a certain exposure, compared to the likelihood that controls had that exposure. An equal likelihood is expressed as 1.
relative risk (RR): The ratio of the risk of disease or death among exposed people as compared to the risk among unexposed people.
standardized incidence ratio (SIR): An SIR is calculated by comparing the number of cases of a disease observed among the people being studied with the number of cases of a disease that are expected based upon a comparison group of the same age and sex, during the same time period.
standardized mortality ratio (SMR): An SMR is calculated by comparing the number of deaths observed (that is, deaths that occurred) among the people being studied with the number of deaths that are expected based upon a comparison group of the same age and sex, during the same time period:
"observed" deaths }
SMR = ----------------------------------------} (x100)
"expected" deaths }
Most authors multiply the ratio by 100 to avoid using fractions, but some do not; so, an SMR of 1.98 is the same as an SMR of 198. 100 is the expected, or "normal". An SMR greater than 100 (or 1) suggests an excess risk of death or disease. Epidemiologists evaluate the statistical significance of an elevated SMR by using the 95% confidence interval, which is the range in which the true SMR would fall in 95% of cases. (In this Report, the 95% confidence interval is shown in brackets, following the SMR; "n" refers to the number of cases or deaths.)
If the lower end of the 95% confidence interval is above 100 (or 1), the likelihood that the excess of deaths or disease is caused by chance is less than 5% (or 1 out of 20). If the SMR is under 100 (or 1) and the upper end of the 95% confidence interval is under 100 (or 1), a statistically significant decrease in deaths or disease is indicated, compared to the number of deaths that would normally be expected.
statistically significant: See SMR, above.
Dear Mr. Copeland:
I enclose a copy of the Panel's "Report to the Workers' Compensation Board on the health effects of occupational exposure to petroleum-based fluids used for machining and lubricating metal in manufacturing: Cancer of the larynx".
The Panel will issue separate reports on other disease outcomes of occupational exposure to these substances in the future.
As you will see, the Panel has recommended that certain additions be made to Schedule 3 and that guidelines be developed. We would be happy to work with WCB staff to develop rebuttal criteria and guidelines, if you agree.
I would be pleased to discuss the Report with you and the Board of Directors at your convenience.
Sincerely,
Nicolette Carlan
Chair
Enclosure
1. For a brief description of these terms, please see The Bradford Hill considerations for evaluating whether a probable connection to work exists on page 32.
2. The 1983 incidence rate among men in Ontario was 7 per 100,000 population; the corresponding incidence for lung cancer was 65.4 per 100,000. Laryngeal cancer mortality in 1983 among men in Ontario was 1.8 per 100,000 compared with 54.4 per 100,000 for lung cancer mortality [9].
3. cutting gear teeth
4. PAHs (also called PNAs or polynuclear aromatic hydrocarbons) are multi-ring aromatic compounds found widely dispersed in nature. They are formed during the combustion of many organic materials (for example, diesel fuel) and high-temperature processing of crude oil, coal and coke. They also occur in tobacco smoke and grilled, smoked and fried foods [33].
5. SMR 1.16 (1.01-1.32) n=213
6. The Panel carefully considered the role of confounders such as smoking and alcohol use. Please see Confounders on page 23 for a full discussion.
7. The authors conducted a detailed investigation of past and current exposures in the three plants as follows: past exposures were estimated based on air sampling measurements, review of historic records and interviews with plant personnel. A total of 475 full-shift personal air samples were collected in major exposure groups defined by machine and coolant type. Size-selective sampling estimates included an extra thoracic fraction (particles with a mass median diameter >9.8 µm), a thoracic fraction (<9.8µm), and a respirable fraction (<3.5 µm). Quantitative exposure variables were based on the concentration of particulate in the extra thoracic fraction, since this is the size range most likely to be deposited in the throat and upper airways.[15, 23]
8. The Panel also notes that in the first SMR study of the same cohort circulatory disease was not elevated.
9. including viscosity index improvers, pour-point depressants, tackiness agents, anti-foam additives, emulsifiers, friction modifiers, anti-oxidants, anti-rust additives, metal deactivators, anti-wear and extreme-pressure additives such as sulphur, detergents/dispersants and formaldehyde-releasing biocides such as triazine [30].
10. The sampling conducted by NIOSH was prompted by reports that nitrosamines had been identified in metalworking fluids after a 1984 Environmental Protection Agency ban on the use of nitrosating agents in metalworking fluids [17].
11. mean levels of 0.64 ppm in new fluids and 0.53 ppm in used fluids; these data were presented by Dr. A. Lunsford at a conference held to address metalworking fluids issues sponsored by NIOSH and held in Cincinnati, Ohio on November 2 and 3, 1994.
12. Thus, STEVs may have little significance in estimating the risk of long-term health effects such as cancers and chronic respiratory disease.
13. PNAs = Polynuclear aromatic hydrocarbons, also known as PAHs or polycyclic aromatic hydrocarbons.