[Evaluation of the new doctoral degree program at the Faculty of Medicine in Oslo 1993-98]. / Evaluering av doktorgradsprogrammet ved Det medisinske fakultet i Oslo 1993-98.

BACKGROUND: In 1993, the doctoral degree programme in the Faculty of Medicine of the University of Oslo was substantially revised to include coursework and supervision of thesis work. PhD students were expected to complete their work towards the doctorate in three years, and funding was only provided for this period. MATERIAL AND METHODS: In spring 1999, all doctoral candidates, their supervisors and members of the adjudicating committees were invited to reply to a questionnaire with the purpose of evaluating the results of the new programme over the 1993-99 period. RESULTS: Only a few doctoral students had been able to obtain their degrees in three years, the defined length of the programme. The mean age for new PhDs was 38; however, physicians obtained their PhD at a later age than the other life scientists enrolled in the programme, and the percentage of PhDs with a medical background declined from 71% in 1993-95 to 51% in 1996-98. INTERPRETATION: The doctoral programme should be extended from three to four years. More physicians should go into research soon after graduating from medical school and more openings for postdocs should be created. More time for research in the university clinics is also needed.

Assessment of historical exposures in a nickel refinery in Norway.

OBJECTIVES: The aim of the study was, on the basis of new information on nickel species and exposure levels, to generate a specific exposure matrix for epidemiologic analyses in a cohort of Norwegian nickel-refinery workers with a known excess of respiratory cancer. METHODS: A department-time-exposure matrix was constructed with average exposure to total nickel estimated as the arithmetic mean of personal measurements for periods between 1973 and 1994. From 1972 back to the start of production in 1910, exposure concentrations were estimated through retrograde calculation with multiplication factors developed on the basis of reported changes in the metallurgical process and work environment. The relative distribution of water-soluble nickel salts (sulfates and chlorides), metallic nickel, and particulates with limited solubility (sulfides and oxides) was mainly derived from speciation analyses conducted in the 1990s. RESULTS: The average concentration of nickel in the breathing zone was < or = 0.7 mg/m3 for all workers after 1978. Exposure levels for smelter and roaster day workers were 2-6 mg/m3 before 1970, while workers in nickel electrolysis and electrolyte purification were exposed to concentrations in the range of 0.15-1.2 mg/m3. The level of water-soluble nickel was of the same order for workers in the smelting and roasting departments as in some of the electrolyte purification departments. CONCLUSIONS: Compared with earlier estimates, the present matrix probably offers a more reliable description of past exposures at the plant.

Characterisation of workers' exposure in a Russian nickel refinery.

In support of a feasibility study of reproductive and developmental health among females employed in the Monchegorsk (Russia) nickel refinery, personal exposure and biological monitoring assessments were conducted. The inhalable aerosol fraction was measured and characterised by chemical speciation and particle-size distribution measurements. Unexpected findings were that: (i), pyrometallurgical working environments had significant levels of water-soluble nickel; (ii), significant exposure to cobalt occurred for the nickel workers; (iii), particles of size corresponding to the thoracic and respirable fractions appeared to be virtually absent in most of the areas surveyed. The water-soluble fraction is judged to be primarily responsible for the observed urinary nickel and cobalt concentrations. It is concluded relative to current international occupational-exposure limits for nickel in air, and because of the high nickel concentrations observed in urine, that the Monchegorsk nickel workers are heavily exposed. The implication of this finding for follow-up epidemiological work is alluded to.

Urinary nickel concentrations and selected pregnancy outcomes in delivering women and their newborns among arctic populations of Norway and Russia.

The two objectives of this study were to compare urinary nickel excretion in pregnant women and their newborns living in the Murmansk and Arkhangelsk Counties of Russia with that in comparable Norwegian populations living in Finnmark and the city of Bergen and to assess the influence on pregnancy outcome of different risk variables, specifically urinary nickel concentrations and questionnaire-based anamnestic information. Life-style information and urine samples were collected from 50 consecutive mother-infant pairs from hospital delivery departments in three Russian and three Norwegian communities. Pregnancy outcomes were verified from medical records. Urinary nickel excretion was significantly higher in the Russian communities, independent of the presence of a nickel refinery as a local environmental source. The birth weight and mean body mass index of the newborn children (BMIC) were significantly lower (p < 0.001) in the Russian groups, with or without adjustment for gestational age. A multivariate linear regression analysis indicated that maternal urinary nickel concentration had no impact on birth weight. The maternal body mass index (BMI) and maternal height were positive explanatory variables; maternal urinary creatinine is suggested as a weak negative factor. Smoking was shown to be a strong negative predictor only in the Norwegian group among whom there was a significantly higher smoking frequency (p = 0.005). The significant contribution of a country factor in the predictive model is interpreted to indicate that a number of important risk factors for low birth weight were not identified.

Correlation of urinary nickel excretion with observed 'total' and inhalable aerosol exposures of nickel refinery workers.

An investigation of the relationship between observed nickel aerosol exposures and urinary nickel excretion was undertaken at a Scandinavian nickel refinery. The goal of the study was to assess the impact of nickel aerosol speciation, the use of particle size-selective sampling instrumentation and adjustment of urinary levels for creatinine excretion on the usefulness of urinary nickel excretion as a marker for exposure. Urinary nickel measurements and paired 'total' and inhalable aerosol exposure measurements were collected each day for one week from refinery workers in four process areas. The mean observed urinary nickel concentration was 12 micrograms L-1 (11 micrograms of Ni per g of creatinine). The strongest relationships between urinary excretion and aerosol exposure were found when urinary nickel levels were adjusted for creatinine excretion and when exposure to only soluble forms of nickel aerosol was considered. No significant difference was observed between measures of 'total' and inhalable aerosol in the ability to predict urinary excretion patterns. In the light of these results, it is recommended that consideration be given to the chemical species distribution of nickel aerosol in the use of urinary nickel measurements as a screening tool for cancer risk in occupationally-exposed populations.

Urinary nickel excretion in populations living in the proximity of two russian nickel refineries: a Norwegian-Russian population-based study.

The Russian nickel refineries located in the cities of Nikel and Zapolyarny close to the Norwegian border are responsible for extensive sulfur dioxide and nickel pollution, as well as severe ecological damage in both countries. The aim of our study was to investigate human nickel exposure in the populations living on both sides of the Norwegian-Russian border. The design was a cross-sectional population-based study of adults aged 18-69 years residing in Sor-Varanger municipality, Norway, and Nikel and Zapolyarny, Russia, during 1994 and 1995. Individual exposure to nickel was assessed by measurements of nickel in urine using electrothermal atomic absorption spectrometry. For controls, urine was collected from adults in the Russian cities of Apatity and Umba (Kola Peninsula) and the Norwegian city of Tromso, all of which are locations without nearby point sources of nickel. Altogether 2,233 urine specimens were analysed for nickel. People living in Nikel had the highest concentrations (median 3.4 microg/l), followed by Umba (median 2.7 microg/l), Zapolyarny (median 2.0 microg/l), Apatity (median 1.9 microg/l), Tromso (median 1.2 microg/l), and Sor-Varanger (median 0.6 microg/l). Regardless of geographical location, the Russian study groups all had a higher urinary-nickel average than those in Norway (p<0.001). With the exception of Nikel, neither the Russian nor the Norwegian urinary-nickel levels were associated with residence location near a Russian nickel refinery. We concluded that industrial nickel pollution alone could not explain the observed discrepancy between Norway and Russia; we also discuss other possible nickel exposure sources that may account for the high urinary levels found in Russia.

Human nickel exposure in an area polluted by nickel refining: the Sør-Varanger study.

Sør-Varanger municipality in northern Norway is located close to two Russian nickel refineries that cause nickel and sulfur dioxide pollution. To investigate individual nickel exposure and possible health effects from the pollution, the authors invited all adults who were 18-69 y of age to a health survey in 1994. Urine samples were collected from 3671 participants (participation rate = 59.4%), and nickel concentrations were determined for 902 of them. Mean and median nickel concentrations were 0.9 microg/l and 0.6 microg/l, respectively. Individuals who lived in the rural areas closest to the refineries had lower nickel concentrations than individuals who lived in the more urban areas. Independent risk factors for nickel concentrations in urine were (a) being an urban dweller and (b) living close to areas with high-density traffic. The authors concluded that nickel exposure attributable to air pollution from Russian refineries was of minor importance for people who lived in Sør-Varanger.

Exposure to nickel compounds and smoking in relation to incidence of lung and nasal cancer among nickel refinery workers.

OBJECTIVES: To investigate the relation between occupational hazards among nickel refinery workers and their exposure to different forms of nickel over time and the interaction between smoking and total exposure to nickel. METHODS: The cohort consisted of 379 workers with first employment 1916-40 and at least three years of employment and 4385 workers with at least one year of employment 1946-83. Data on smoking (ever or never) were available for almost 95% of the cohort. Two analyses were used, indirect standardisation from observed and expected numbers and Poisson regression. RESULTS: During the follow up 1953-93, 203 new cases of lung cancer were observed v 68 expected (standardised incidence ratio (SIR) 3.0, 95% confidence interval (95% CI) 2.6-3.4) and 32 cases of nasal cancer were observed v 1.8 expected (SIR 18.0, 95% CI 12-25). The Poisson regression analysis showed an excess risk of lung cancer in association with exposure to soluble forms of nickel, with a threefold increase in relative risk (RR) (P < 0.001) and a multiplicative effect of smoking and exposure to nickel. The RRs were 1.1 (95% CI 0.2-5.1) for exposed workers who had never smoked and 5.1 (95% CI 1.3-20.5) for exposed workers who smoked. CONCLUSION: It is not possible to state with certainty which specific nickel compounds are carcinogenic, but a significant excess risk was found for workers exposed to soluble nickel alone or in combination with other forms of nickel. The present study suggests a multiplicative effect of smoking and nickel exposure.

Environmental pollution around nickel smelters in the Kola Peninsula (Russia).

Air pollution along the border between Norway and Russia has been recorded since 1974 in Sør-Varanger county (Norway) and since 1985 in Murmansk county (Russia). A more extensive collaboration on the environmental pollution problems in the border region was started in 1988 with the establishment of a joint pollution commission. Sulphur dioxide seems to be the most important pollutant causing both environmental damage and adverse health effects. The recommended highest 6-month mean acceptable value for Norway of 40-60 micrograms/m3 was exceeded for two Russian and one Norwegian station during the winter of 1990/91. About 5% of hourly means exceeded 350 micrograms/m3 at the most polluted Norwegian station. The highest value recorded at the nearest populated area in Norway was 2500 micrograms/m3 (The Norwegian Institute for Air Research). Standardized mortality data suggest an increase in deaths from cancer and cardiovascular disease in two cities with nickel refineries, compared to a control city. Further analysis is required to confirm this.

Congenital defects, abortion and other health effects in nickel refinery workers.

Health impairment was investigated by a thorough clinical investigation in a cross-sectional study of 821 male and 758 female workers in a nickel hydrometallurgy refining plant. The average nickel exposure levels were found to be around 0.2 mg/m3 in the electrolysis department and 0.13 mg/m3 in the electrolyte purification department. Corresponding average urinary values for nickel were 16 micrograms/l and 10 micrograms/l, respectively. The most common types of health impairment found were respiratory, skin and cardiovascular diseases. Health impairments, except for respiratory diseases, were found more often in females than in males. The design of the study does not allow comparison with a non-exposed population. Even if there are serious limitations in the statistical and sampling details of the pregnancies and new-born babies, the results suggest adverse health effects at usually accepted exposure levels to nickel. Normal pregnancies were reported in 29% of 356 pregnant nickel workers compared with 39% in 342 local construction workers. Spontaneous and threatening abortions were reported in 16% and 17% of all pregnancies in nickel-exposed workers, compared with 9% and 8%, respectively in the construction workers. Structural malformations were found in about 17% of alive-born infants with nickel-exposed mothers, compared with about 6% in the reference group. Significant increased risks of 2.9, 6.1 and 1.9 for total defects, cardiovascular defects and defects of the musculoskeletal system, respectively, were demonstrated.

Measuring strategies for the nineties. Future needs from the health point of view.

Technological progress and related social processes will determine the measuring strategies of workplace air monitoring for the nineties even if the objective is dose estimation or compliance. Expectations of the lowest possible exposure, require workplace air monitoring to be closely linked to process control in a life cycle approach. Production regularity and preventive maintenance also become important factors for strategy design. Workroom air may lose some importance as a dose estimate for the estimation of toxicological risk, as multi-factorial causes for work-related diseases become more evident and a number of syndromes of unknown aetiology become increasingly important. Cancer, cardiovascular diseases, the indoor air syndrome and multiple chemical sensitivity are given as examples. Biotechnology and the information revolution have changed the basic principles of health monitoring and surveillance. The individual worker becomes the target and the possibility of individually adjusted monitoring, surveillance and workplace design becomes important.

Acute effects and exposure to organic compounds in road maintenance workers exposed to asphalt.

Subjective symptoms and exposure to organic compounds were recorded in road repair and construction workers. Abnormal fatigue, reduced appetite, laryngeal/pharyngeal irritation, and eye irritation were recorded more often in such workers handling asphalt than in a corresponding reference group without asphalt exposure. Mean daily exposure to volatile compounds was only occasionally above 1 ppm. Mean exposure to asphalt fume was 0.358 mg/m3. There was no correlation between symptoms and total amount of volatile compounds, but a significant positive correlation was demonstrated between symptoms and some substances. The highest correlation was found for 1, 2, 4 trimethyl benzene. Symptoms increased with increasing asphalt temperature and with increasing concentrations of asphalt fumes. Amine addition did not increase the sum of symptoms, but soft asphalt seems to result in fewer symptoms than the harder types. Symptoms were not related to external factors like weather, traffic density, or specific working operations. As preventive measures, asphalt temperature should be kept below 150 degrees C, fume concentrations below 0.40 mg/m3, and if possible, the use of harder asphalt types which also require high temperatures should be avoided.

Biological monitoring of nickel.

Measurements of nickel in body fluids, excreta, and tissues from humans with occupational, environmental, and iatrogenic exposures to nickel compounds are comprehensively reviewed. Correlations between levels of human exposures to various classes of nickel compounds via inhalation, oral, or parenteral routes and the corresponding concentrations of nickel in biological samples are critically evaluated. The major conclusions include the following points: Measurements of nickel concentrations in body fluids, especially urine and serum, provide meaningful insights into the extent of nickel exposures, provided these data are interpreted with knowledge of the exposure routes, sources, and durations, the chemical identities and physical-chemical properties of the nickel compounds, and relevant clinical and physiological information, such as renal function. Nickel concentrations in body fluids should not, at present, be viewed as indicators of specific health risks, except in persons exposed to nickel carbonyl, for whom urine nickel concentrations provide prognostic guidance on the severity of the poisoning. In persons exposed to soluble nickel compounds (e.g., NiCl2, NiSO4), nickel concentrations in body fluids are generally proportional to exposure levels; absence of increased values usually indicates non-significant exposure; presence of increased values should be a signal to reduce the exposure. In persons exposed to less soluble nickel compounds (e.g., Ni3S2,NiO), increased concentrations of nickel in body fluids are indicative of significant nickel absorption and should be a signal to reduce the exposures to the lowest levels attainable with available technology; absence of increased values does not necessarily indicate freedom from the health risks (e.g., cancers of lung and nasal cavities) associated with exposures to certain relatively insoluble nickel compounds.