Function Of Cumulative Exposure Research Articles

Estimation of the Risk of Contracting Pneumoconiosis in the UK Coal Mining Industry

This paper discusses the impact that proposed new regulations for respirable dust in UK coal mines could have on the risk of contracting pneumoconiosis in the UK coal industry. The risk of contracting pneumoconiosis is primarily a function of cumulative exposure to coal mine dust. Since the current dust regulations were introduced in the 1970s the average concentrations of dust to which miners are exposed have decreased considerably. However, working hours have increased in the last few years, leading to concerns of a potential upturn in the risk of contracting pneumoconiosis. The new regulations under discussion address the problem of excessive hours through scaling the limit values when long hours are worked. Hence, by controlling cumulative dust exposures to values below those currently encountered, the proposed new regulations are shown to lead to lower lifetime pneumoconiosis risk when compared with current conditions.

Inhibition of marine photosynthesis by ultraviolet radiation: Variable sensitivity of phytoplankton in the Weddell‐Scotia Confluence during the austral spring

To assess the potential impacts of ozone depletion on photosynthesis in the Southern Ocean, we need to know more about effects of ultraviolet radiation (UV) on phytoplankton in Antarctic waters, where, in addition to variable stratospheric ozone, temporal and regional differences in vertical mixing might influence photosynthesis and photoacclimation of phytoplankton assemblages. Toward this end, we quantified the responses to UV of Antarctic phytoplankton in the Weddell‐Scotia Confluence during the austral spring of 1993. Experimental results on spectral sensitivity of photosynthesis were fit statistically to a model that incorporated uninhibited photosynthesis as a function of photosynthetically available radiation (PAR), wavelength‐dependence of inhibition, and the kinetics of photosynthesis during exposure to UV. In contrast to previous results on UV‐induced photoinhibition in a diatom culture at 20°C natural phytoplankton from open waters of the Antarctic showed no ability to counter UV‐induced inhibition of photosynthesis during exposures of 0.5–4 h: the rate of photosynthesis declined exponentially as a function of cumulative exposure, and inhibition was not reversed during incubations for up to 3.5 h under benign conditions. The results suggest that nonlinear exposure‐response relationships are necessary for modeling UV dependent photosynthesis in the surface mixed layer of the springtime Weddell‐Scotia Confluence. Consequently, we modified our laboratory‐based model of photosynthesis and photoinhibition to describe photoinhibition as a nonlinear function of biologically weighted cumulative exposure to damaging irradiance. The model described ˜90% of the spectrally dependent experimental variation in photosynthetic rate, and yielded six biological weighting functions (BWFs) for phytoplankton in the Weddell‐Scotia Confluence. Assemblages from different stations showed substantial variability in sensitivity to UV. Tolerance of UV was generally highest in assemblages from shallower mixed layers, which presumably had experienced higher irradiance, including UV, prior to sampling. The BWFs of assemblages that seemed acclimated to low irradiance showed the highest sensitivity to UV yet seen for Southern Ocean phytoplankton. The pattern of UV sensitivity was consistent with acclimation, but also with selection against less tolerant species.

Reanalysis of lung cancer mortality in a National Cancer Institute study on mortality among industrial workers exposed to formaldehyde.

The results of an historical cohort study of mortality among individuals occupationally exposed to formaldehyde were announced in 1986 by Blair et al (JNCI 1986; 76:1071-1084). The study was a joint undertaking of the National Cancer Institute and the Formaldehyde Institute, and concluded, ". . .this large multiplant cohort study provided little evidence to suggest that formaldehyde exposure affected the mortality experience of these industrial workers." However, there were concerns by a number of workers that the design and analysis of the study had possibly masked an existing occupational hazard. Analyzing time-integrated exposure to formaldehyde without simultaneously considering length of exposure and comparing mortality of formaldehyde workers to mortality of the general population could have masked an increase in cancer risks because of the healthy worker effect. A copy of the data of the study was obtained from the principal investigator and reanalyzed. We find a significantly increased risk for all cancers and for lung cancer as a function of cumulative exposure when workers with higher levels of exposure are compared with those with little or no exposure while simultaneously considering length of exposure. When the risk ratio (RR) for lung cancer at less than or equal to 0.1 ppm cumulative exposure (CX) is taken as 1.0, the lung cancer RR for CX of 0.1 to 0.5 ppm is 1.41 (1.20 to 1.66), the RR for CX of 0.5 to 2.0 ppm is 1.73 (1.42 to 2.11), and the RR for CX greater than or equal to 2.0 is 1.70 (1.32 to 2.18). Hourly workers have a significantly higher RR than salaried workers (RR = 1.58).(ABSTRACT TRUNCATED AT 250 WORDS)

A graphical approach to the identification and estimation of causal parameters in mortality studies with sustained exposure periods

In observational cohort mortality studies with prolonged periods of exposure to the agent under study, independent risk factors for death commonly determine subsequent exposure to the study agent. For example, in occupational mortality studies, date of termination of employment is both a determinant of subsequent exposure to the chemical agent under study (since terminated individuals receive no further exposure) and an independent risk factor for death (since disabled individuals tend to leave employment). When a risk factor determines subsequent exposure and is determined by previous exposure, standard analyses that estimate age-specific mortality rates as a function of cumulative exposure can underestimate the true effect of exposure on mortality, whether or not one adjusts for the risk factor in the analysis. This observation raises the question, “Which, if any, empirical population parameter can be causally interpreted as the true effect of exposure in observational mortality studies?” In answer, we offer a graphical approach to the identification and estimation of causal parameters in mortality studies with sustained exposure periods. We reanalyze the mortality experience of a cohort of arsenic-exposed copper smelter workers using our approach and compare our results with those obtained using standard methods. We find an adverse effect of arsenic exposure on all cause and lung cancer mortality, which standard methods failed to detect. The analytic approach introduced in this paper may be necessary to control bias in any epidemiologic study in which there exists a risk factor which both determines subsequent exposure and is determined by previous exposure to the agent under study.

A new approach to causal inference in mortality studies with a sustained exposure period—application to control of the healthy worker survivor effect

In observational cohort mortality studies with prolonged periods of exposure to the agent under study, it is not uncommon for risk factors for death to be determinants of subsequent exposure. For instance, in occupational mortality studies date of termination of employment is both a determinant of future exposure (since terminated individuals receive no further exposure) and an independent risk factor for death (since disabled individuals tend to leave employment). When current risk factor status determines subsequent exposure and is determined by previous exposure, standard analyses that estimate age-specific mortality rates as a function of cumulative exposure may underestimate the true effect of exposure on mortality whether or not one adjusts for the risk factor in the analysis. This observation raises the question, which if any population parameters can be given a causal interpretation in observational mortality studies? In answer, we offer a graphical approach to the identification and computation of causal parameters in mortality studies with sustained exposure periods. This approach is shown to be equivalent to an approach in which the observational study is identified with a hypothetical double-blind randomized trial in which data on each subject's assigned treatment protocol has been erased from the data file. Causal inferences can then be made by comparing mortality as a function of treatment protocol, since, in a double-blind randomized trial missing data on treatment protocol, the association of mortality with treatment protocol can still be estimated. We reanalyze the mortality experience of a cohort of arsenic-exposed copper smelter workers with our method and compare our results with those obtained using standard methods. We find an adverse effect of arsenic exposure on all-cause and lung cancer mortality which standard methods fail to detect.

Lung changes in rats inhaling volcanic ash for one year.

Rats were exposed to 5 mg/m3 or 50 mg/m3 (respirable aerosol concentration) volcanic ash, or to 50 mg/m3 quartz, 6 h/day, 5 days/wk, for as long as 12 months. Subgroups of rats were killed at 4-month intervals to determine lesion development as a function of dose and cumulative exposure. Treatment-related lung changes comprised alveolar macrophage accumulation, interstitial reaction, peribronchiolar lymphoid hyperplasia, lymph node hyperplasia, and--in the 50 . mg/m3 ash-exposed and quartz-exposed rats--alveolar proteinosis. Some of the changes did not increase appreciably after 8 months of exposure, whereas others continued to increase as a function of cumulative exposure. Generally, there were distinct dose-response and agent-response relationships. These trends were also observed in lung weights, respiratory rates, and volumes of mediastinal lymph nodes. Like the histologic changes, the effects on these ancillary parameters also increased in the following order: sham-exposed control group, 5 mg/m3 and 50 mg/m3 ash-exposed groups, and quartz-exposed positive control group.