Objectives and interpretations.
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Decision Trees↗
Biomedical subjects
G M Paddle
Publications and source records attributed to G M Paddle.
Mortality of employees in plants manufacturing 4,4'-bipyridyl.
A historical-prospective cohort study was conducted of 729 male employees of plants manufacturing 4,4'-bipyridyl. The cohort was studied because employment in some of the plants had been linked to malignant and nonmalignant skin lesions attributed to exposure to tarry by-products. The overall mortality experience of the cohort did not show any statistically significant findings. More-detailed analysis of subdivision of the cohort gave results that justified further inquiry into lung cancer incidence. A nested case-referent study did not indicate that any occupational factor other than employment in a bipyridyl plant was related to the incidence of lung cancer. The epidemiologic, toxicologic, and industrial hygiene information was assessed, and it was concluded that there was no evidence of a plausible occupational hazard of lung cancer to the bipyridyl workers, but that a follow-up of the cohort after an interval of five years should be undertaken.
Cohort Studies↗
Better quality studies through review of protocols.
The importance of a protocol is well recognized by scientists whose work is governed by good laboratory practices. Epidemiologists have used protocols for many years but have not always reaped the full benefits. Until relatively recently, there has been little consensus among epidemiologists about what constitutes a good protocol and, consequently, expectations of the pre-study review process may not be fulfilled. This paper examines some of the benefits to be derived from a good protocol and the importance of prestudy review. Our experience suggests that peer review cannot substitute for a competent principal investigator supported by a strong study management team. If such a study management team exists, the most important contribution of the external peer reviewer should be to ensure the impartiality of the study.
Clinical Protocols↗
Does formaldehyde cause nasopharyngeal cancer in man?
Formaldehyde is a widely used industrial chemical, which also has uses in consumer products, and hence large numbers of people are exposed to it. It is also an endogenous metabolite with measurable levels in body fluids and tissues. The reports of its carcinogenicity to rats have raised concern about its potential to cause a carcinogenic response in exposed populations. This letter reviews the information on the carcinogenicity of formaldehyde, particularly to the upper respiratory tract, in animals and man.
Adenoma↗
Vinyl chloride: an assessment of the risk of occupational exposure.
There is little doubt that exposure to high levels of VCM as a consequence of occupation can result in an increased incidence of ASL. A review of 20 epidemiological studies involving about 45,000 workers occupationally exposed to VCM showed that neoplasms of the liver showed an increase in incidence in the majority of studies. For brain cancer the association between exposure to VCM and an increased incidence was less clear because of the lower relative risk. Neoplasms of the respiratory tract, digestive system, lymphatic and haemopoietic system, buccal cavity, and pharynx, cardiovascular system and colon/stomach were reported to show an increased incidence in one or more studies, but to show no increase, or in some cases a decrease, in incidence in other studies. In view of the increased incidence of breast neoplasms in rodents exposed to VCM, the studies of Chaizze et al. (1980), who did not confirm these findings in humans, are of importance. The register of ASL cases now contains records of 99 persons with confirmed ASL and occupational exposure to VCM. The average latent period between first exposure to VCM and death from ASL is 21.9 years. The majority of cases occurred in autoclave workers, who are recognized as having been exposed to extremely high levels. Although precise estimates of exposure are not available for the periods of most interest, the pattern of cases roughly suggests that extremely high exposures were necessary for the induction of ASL. For example, ASL cases tended to occur in larger numbers in some plants than in others, a finding that can be explained most easily by differences in exposure patterns. There is an extensive series of animal studies on the carcinogenicity of VCM. Some of these precede the epidemiological studies confirming the association between VCM exposure and ASL in man. ASL and neoplasms of a number of other organs have been induced in laboratory rodents by VCM. Estimation of the exposure levels likely to cause a lifetime risk of ASL of 10(-6) on the basis of these data give extremely low levels (down to 3.9 X 10(-7) ppb) which appear to be unrealistic estimates for man. Part of the reason for this is that laboratory studies have shown that VCM is metabolized in the liver (and elsewhere in the body) to the reactive metabolites chloroethylene oxide and chloroacetaldehyde. The rate of conversion is limited at high levels of exposure giving inaccurate estimates of the slope of the dose-response relationship.(ABSTRACT TRUNCATED AT 400 WORDS)
Air Pollutants, Occupational↗
Sixteen year follow up of workers in an explosives factory.
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Adolescent↗
Chromosomal analyses in vinyl chloride-exposed workers.
Chromosomal morphology from cultured peripheral lymphocytes was studied in 81 men; 57 of the men were employed on plants manufacturing vinyl chloride or polyvinylchloride, 19 were on-site controls and 5 were off-site controls. There was a significant increase in chromosomal abnormalities in the exposed workers when compared with the controls. The greatest statistically significant increase in total B and total C cells occurred in autoclave operators, with smaller increases in other job categories. The increase in chromosomal aberrations was correlated with the length of exposure and with a history during the year prior to sampling (1973--1974) of exposure to excursion levels of vinyl chloride. Information on smoking habits was obtained 18 months after blood sampling and a positive correlation between these and total C cell abnormalities was found. There was no positive correlation with various other parameters (bilirubin, platelets, gamma-glutamyltranspeptidase, alkaline phosphatase, alanine transaminase and aspartate transaminase). It was not possible to estimate which of the three parameters (smoking history, length of employment or exposure to excursion levels) was the most important.
Chromosomes↗