[Report of the "Health and Environment" commission of the National Academy of pharmacy. Carbon monoxide and environmental health: are carbon monoxide levels in urban areas a health hazard?]. / Le monoxyde de carbone CO et la santé environnementale: CO est-il nocif aux concentrations urbaines actuelles?

In an urban environment, carbon monoxide is produced by incomplete combustion, particularly in motor vehicles. Air pollution caused by CO produced by motor vehicles is controlled by legislation. Legal regulations have considerably lowered emission levels authorized for new vehicles and total CO emission levels. CO levels in the environment (urban environment in general and zones close to motorways) have thus declined. CO remains a public health concern both as a pollutant and as an indicator of air quality. We recall here the more recent approaches used to assess CO-related hazards developed by the Environmental Protection Agency in the United States and pertinent conclusions backing up previously defined reference levels. We then report recent French data concerning CO emission, environmental levels and evaluation procedures for different situations of human exposure: geographical situations, mode of transportation, police force, air sentinels. The third part of this article is devoted to biological data (interaction between CO and hemo-proteins, CO neurotransmitter?) and epidemiological data (serial surveys). The discussion centers on the limitations of epidemiological data and on the difficulty in evaluating hazards solely on the basis of a carboxyhemoglobin threshold. This latter point is particularly important because carboxyhemoglobin is only one of many indicators of air quality. Finally recommendations are proposed concerning weather-related aspects, evaluation of human exposure, and ways of improving biological and epidemiological data.

Air pollution and health: correlation or causality? The case of the relationship between exposure to particles and cardiopulmonary mortality.

Many epidemiologic studies have observed, in different contexts, a slight short-term relationship between particles in air and cardiopulmonary mortality, even when air quality standards were respected. The causality of this relationship is important to public health because of the number of people exposed. Our aim was to make a critical assessment of the arguments used in 15 reviews of published studies. We explain the importance of distinguishing validity from causality, and we systematically analyze the various criteria of judgment within the context of ecologic time studies. Our conclusion is that the observed relationship is valid and that most of the causality criteria are respected. It is hoped that the level of exposure of populations to these particles be reduced. In Europe, acting at the root of the problem, in particular on diesel emissions, will also enable the reduction of levels of other pollutants that can have an impact on health. In the United States, the situation is more complicated, as particles are mainly secondary. It is also essential to continue with research to become better acquainted with the determinants of personal global exposures and to better understand the toxic role of the various physicochemical factors of the particles.

[Short-term modeling of the effect of air pollution on health. Example: SO2 and total mortality, Paris 1987-1999]. / Modélisation des liens à court terme entre la pollution atmosphérique et la santé. Un exemple: SO2 et mortalité totale, Paris, 1987-1990.

Since 1990, many epidemiological time series studies have provided evidence that ambient air pollution levels have adverse health effects. The ERPURS study (Evaluation des Risques de la Pollution Urbaine pour la Santé) has permitted to quantify this impact in the Paris region. This study was based on an ecological time series approach. We present, step by step, the method used, illustrated by an example: association between SO2 levels and total mortality (excluding external causes), 1987-1990. Mortality modelling has taken trend into account by a linear term, seasons by trigonometrics functions sum, day of the week effects by 6 dummy variables, temperature peak by a dummy variable, influenza epidemics by appropriate variables, mean temperature by linear and quadratic terms, relative humidity by a linear term. SO2 1 day lag was introduced in the model by a linear term. The central issue is the control of seasonal variations and long term trend. An inadequate control can lead to some spurious results. The relationship between mortality and weather variables is generally nonlinear. The use of statistical and graphical diagnostics, are necessary at each step. Time series analysis are important tools to study short term relationship between air pollutants and health indicators. The method applied in the ERPURS study is only one of the possible approaches. Whatever the method used, it is important to understand the underlying process of the data and to control for confounding factors with the appropriate method for the temporal structure of the data.

Air pollution and doctors' house calls: results from the ERPURS system for monitoring the effects of air pollution on public health in Greater Paris, France, 1991-1995. Evaluation des Risques de la Pollution Urbaine pour la Santé.

This study examines short-term relationships between doctors' house calls and urban air pollution in Greater Paris for the period 1991-1995. Poisson regressions using nonparametric smoothing functions controlled for time trend, seasonal patterns, pollen counts, influenza epidemics, and weather. The relationship between asthma visits and air pollution was stronger for children. A relative risk (RRP95/P5) of 1.32 [95% confidence interval (CI) = 1.17-1.47)] was observed for an increase from the 5th to the 95th percentile (7-51 micrograms/m3) in daily concentrations of black smoke (BS). The risks for 24-hr sulfur dioxide and nitrogen dioxide levels were in the same range. Cardiovascular conditions, considered globally, showed weaker associations than angina pectoris/myocardial infarction, for which RRP95/P5 was 1.63 (95% CI = 1.10-2.41) in relation to ozone ambient levels. Eye conditions were exclusively related to ozone (RRP95/P5 = 1.17, 95% CI 1.02-1.33). Asthma visits and ozone showed an interaction with minimum temperature: an effect was observed only at 10 degrees C or higher. In two-pollutant models including BS with, successively, SO2, NO2, and O3, only BS and O3 effects remained stable. Along with mortality and hospital admissions, house call activity data, available on a regular basis, may be a sensitive indicator for monitoring health effects related to air pollution.

Use of Salmonella typhimurium TA 98, YG 1024 and YG 1021 and deconjugating enzymes for evaluating the mutagenicity from smokers' urine.

Four smokers were chosen for their different smoking habits, and their declared cigarette consumption confirmed by urinary measurement of nicotine and its metabolites. The promutagenicity of their urine was evaluated by the Ames test, modified according to Kado et al. (Mutation Res., 31 (1983)25-32) after extraction on XAD2 Amberlite resin. The different Salmonella typhimurium strains TA 98, YG 1021 and YG 1024 were compared to determine the presence of amino aromatic compounds in the urine of smokers of blond and black tobacco. The strain YG 1024 shows higher mutagenicity than TA 98 for extracts from the smoker's urine and more particularly from black tobacco smokers. In addition, the pretreatment of urine by external enzymatic systems (beta-glucuronidase or arylsulfatase) reveals the presence in the urine of glucurono- and sulfoconjugated forms of promutagens, including amino aromatic compounds.

[Urban atmospheric pollution: sources, pollutants and evolution]. / La pollution atmosphérique urbaine: sources, polluants et évolution.

(Sub) urban air pollution (AP) is one of the most common and important forms of AP. This paper shortly gives some informations about the main sources of AP (mainly car traffic), the essential determinants of AP (emissions, meteorology, ..), the complexity of effluents and emissions (leading to the choice of AP indicators), the notion of exposition, and the recent evolution of environmental concentrations of air pollutants. Important progress were made towards emissions of industrial and heating sources, with a substantial decrease of SO2 and particulates air concentrations; but despite a marked improvement of fuels quality and of unitary vehicles emissions (and a correlated decrease in Pb and CO emissions) car pollution remains important in terms of photo-oxidant air pollution (CO, NOx, COV, O3); the good use of car in urban area must be reconsidered.

[Are nitrogen oxides major atmospheric pollutants?]. / Les oxydes d'azote: des polluants atmosphériques majeurs?

Nitrogen oxides (N2O, NO and NO2) are at different levels important molecules in biological, ecological and public health terms. They are implicated in several fundamental planetary equilibria: climate and greenhouse effect, stratospheric and tropospheric ozone. NO is a very important cellular bio-mediator considered as weakly toxic for the pulmonary function, as N2O. The main toxicological questions are coming from NO2 whose toxicity has been studied with experimental (cellular, animal and human models) and epidemiological approaches. Its pulmonary toxicity appears relatively weak in animal and healthy human for concentrations in the order of 0.5-11 ppm or more. But NO2 nocivity must be considered for several reasons: first the inter-individual variability of the human response, second the increased sensitivity of asthmatics, chronic obstructive pulmonary population but also children and women, third the increased toxicity of NO2 associated with other (allergenic or not) aerocontaminants. These results lead to apply to NO2 a caution principle in indoor or outdoor air pollution; in the second case, WHO and European Union defined references values.

Ventilation system, indoor air quality, and health outcomes in Parisian modern office workers.

A cross-sectional study was carried out to determine the effect on health of exposure to different types of ventilation, taking indoor environmental measurements (IEMs) of major contaminants and aeroallergens into account. Three buildings ventilated with heating, ventilating, and air conditioning (HVAC), fan coil units (FCUs), and natural ventilation were selected. One thousand one hundred forty-four workers answered health questionnaires. After adjusting for potential confounders, HVAC and FCU systems were related to a slightly higher risk of nonspecific symptoms (compared with natural ventilation), short-term throat irritation, work-related nasal discharge, nasal blockage on awakening, migraine, and usual coughing induced by cold air. Studying the potential effects of environmental contaminants and aeroallergens on health outcomes, taking the floor and type of ventilation into account, did not explain the observed excess of nonspecific symptoms.

Urinary promutagens of smokers: comparison of concentration methods and relation to cigarette consumption.

Different extraction techniques can be used to concentrate the promutagens of cigarette smokers' urine before evaluation of their mutagenic potency by Ames test. In this study, three solid adsorbents, C18, XAD2 and CN were compared for their ability to concentrate the promutagens of smokers' urine prior to acetone elution. C18 extracts were observed to have a higher promutagenicity than XAD2 and CN extracts. The mutagenicity of smokers' urine depended on the smoking habits, and a strong correlation was observed between urinary promutagenicity, daily cigarette consumption, and the tobacco type (black or blond). Smokers of black tobacco had a higher urinary genotoxicity than smokers of blond tobacco, after taking into account the level of tobacco consumption. Urinary promutagenicity did not appear to depend on the tar level of cigarettes.

Short term respiratory health effects of ambient air pollution: results of the APHEA project in Paris.

STUDY OBJECTIVE: To quantify the short term respiratory health effects of ambient air pollution in the Paris area. DESIGN: Time series analysis of daily pollution levels using Poisson regression. SETTING: Paris, 1987-92. MEASUREMENTS AND MAIN RESULTS: Air pollution was monitored by measurement of black smoke (BS) (15 monitoring stations), sulphur dioxide (SO2), nitrogen dioxide (NO2), particulate matter less than 13 microns in diameter (PM13), and ozone (O3) (4 stations). Daily mortality and general admissions to public hospitals due to respiratory causes were considered. The statistical analysis was based on a time series procedure using linear regression modelling followed by a Poisson regression. Meterological variables, epidemics of influenza A and B, and strikes of medical staff were included in the models. The mean daily concentration of PM13 and daily 1 hour maximum of SO2 significantly affected daily mortality from respiratory causes. An increase in the concentration of PM13 of 100 micrograms/m3 above its 5th centile value increased the risk of respiratory death by 17%. PM13 and BS were also associated with hospital admissions due to all respiratory diseases (4.1% increased risk when the BS level exceeded its 5th centile value by 100 micrograms/m3). SO2 levels consistently influenced hospital admissions for all respiratory diseases, chronic obstructive pulmonary disease, and asthma. Asthma was also correlated with NO2 levels. CONCLUSIONS: These results indicate that even though the relative risk is weak in areas with low levels of pollution, ambient air pollution, and especially particulate matter and SO2, nonetheless require attention because of the number of people exposed and the existence of high risk groups.

Urban air pollution is still a public health problem in Paris.

By correlating data obtained from environmental indicators and health indicators over a five-year period, a system for measuring the effects of air pollution on health has been established and tested. Rises in air pollution levels do appear to be accompanied by increases in the relevant health problems.

Mortality amongst Paris fire-fighters.

This paper is the first mortality cohort study undertaken in France to examine the association between fire-fighting and cause of death. The cohort investigated in this study consisted of 830 male members of the Brigade des sapeurs-pompiers de Paris (BSPP). These professional had served for a minimum of 5 years on 1 January 1977. They were monitored for a 14 year period, finishing 1 January 1991. When compared to the average French male, the Paris fire-fighters were found to have a far lower overall mortality (SMR = 0.52 [0.35-0.75]). None of the cause specific SMRs were significantly different from unity. However a greater number of deaths than expected was observed for genito-urinary cancer (SMR = 3.29), digestive cancer (SMR = 1.14), respiratory cancer (SMR = 1.12) and 'cerebrovascular disease' (SMR = 1.16). The low overall SMR observed was consistent with the healthy worker effect. As for cause specific SMRs, they will be confirmed or invalidated by a further analysis as the follow-up of this cohort is being carried on.

Smokers' behaviour and exposure according to cigarette yield and smoking experience.

The influence of cigarette yield and length of smoking experience on smoking behaviour and biomarker levels was sought in 108 smokers who have never changed cigarette class. Smoking parameters carboxyhaemoglobin percentage (COHb), urinary nicotine, and its metabolites, mutagens, and thioethers were measured. Cigarette yield does not affect daily consumption or smoke volume puffed per cigarette. But the inhalation depth increases with decreasing cigarette yield and with length of smoking habit. The COHb level after the first cigarette in the morning increases significantly with CO cigarette yield and length of smoking experience. In the evening, only the cigarette yield has an effect on COHb level. Biomarker levels excreted in urine are generally lower for females than for males. They tend to increase with smoking history. Only COHb level and total urinary nicotine metabolites (Barlow index) are weakly correlated with cigarette yield. The absence of significant differences due to cigarette class in urinary biomarkers can be explained by changes in inhalation depth, individual differences of metabolism, and limited specificity of some markers (mutagens, thioethers).

Structure-mutagenicity relationships in series of 11H-indolo[3,2-c]quinoline-1,4-diones, tetrahydro-11H-indolo[3,2-c]quinoline-1,4-diones and 11H-pyrido[3',4':4,5]pyrrolo[3,2-c]quinoline-1,4-diones with leukemia cytotoxic properties. Relations with topoisomerase I inhibiting properties.

Six heterocyclic quinones with topoisomerase I inhibiting properties and cytotoxic activities on L1210 leukemia cells were studied for their mutagenicity in four strains of Salmonella typhimurium. The tested compounds are 3-methoxyindolo[3,2-c]quinoline-1,4-diones and their derivatives in which the common pyrroloquinoline nucleus is annelated either with a benzene or a cyclohexane on a pyridine ring. Almost all quinones were found to be direct-acting mutagens at different levels in all strains, mainly TA97a and TA98. Relations were established between their structure and their mutagenic activities. The mutagenicity was found to be influenced (i) by the nature of the fourth nucleus: the pyridinic compounds were the most active, the non-aromatic ones were practically inactive; (ii) by the presence of a methyl group in the 6-position that decreased the mutagenicity. Then, the mutagenic properties were compared with the topoisomerase I inhibiting property that is one of the possible mechanisms of action for these cytotoxic quinones. The results indicated a correlation between mutagenicity and enzyme inhibiting properties.

Bladder cancer and black tobacco cigarette smoking. Some results from a French case-control study.

A retrospective study was planned in the Hérault (Mediterranean) region of France where bladder cancer mortality and incidence rates are high. In the present paper, variations in bladder cancer risk according to various smoking-related variables, in particular time of exposure and type of tobacco, are examined. This case-control study with 219 male incident cases and 794 male population controls randomized from electoral rolls was carried out in 1987-89. Trained interviewers obtained information on demographics, dietary habits (coffee, alcohol, artificial sweeteners, vegetables, spices, etc.), occupational exposures and detailed history of tobacco smoking (average number of cigarettes per day, number of years of smoking, age at which they began and/or quitted smoking, use of filter-tip and type of tobacco). The odds ratio (OR) for cigarette smokers versus non-smokers was greater than 5. Results for number of cigarettes daily, duration of smoking and lifetime smoking showed a highly significant dose-response relationship, which was confirmed when these variables were treated as continuous in a logistic regression model. Eighty-eight percent of the smokers used black tobacco. Quitting smoking did not result in a significant reduction in bladder cancer risk. Higher risks were associated with starting to smoke at an early age (OR before age 13 versus after age 21 = 3.42; 95% CI 1.07-10.9) and with black tobacco smoking (OR black versus blond = 1.63; 95% CI 0.73-3.64). Results suggest that black tobacco may be more harmful than blond tobacco and may have an early non-reversible role in bladder carcinogenesis.

Relative importance of risk factors in bladder carcinogenesis: some new results about Mediterranean habits.

In the Mediterranean region of France where bladder cancer mortality and incidence are high, a case-control study with 219 male incident cases and 794 randomized, male population-controls was carried out in 1987-89 to investigate bladder cancer risk factors and more specifically, regional factors. A stepwise logistic regression was applied to the data. This investigation confirms the role of tobacco and of certain occupational exposures in bladder carcinogenesis. There was a significant dose-response relationship with lifelong coffee drinking and alcohol consumption; however the risk estimates were only significantly elevated for the heaviest drinkers. The intake of saccharin was not associated with risk of bladder cancer. Infrequent consumption of carrots, spinach, and marrows conferred an increased risk, suggesting a protective effect of vitamin A. Finally, this investigation results in some new hypotheses. The study of residences and birthplaces has revealed a lower risk for those who have lived in a non-Mediterranean area and a higher risk for those born in a Mediterranean area. These features might be explained by some Mediterranean dietary habits, such as a high consumption of spices (odds ratio = 3.64, 95 percent confidence interval = 2.21-5.98).

Health effects of attending a public swimming pool: follow up of a cohort of pupils in Paris.

OBJECTIVES: This study aimed to determine the health effects of attending a well-kept school swimming pool maintained according to French public health regulations. METHODS: This prospective month long study was carried out on a randomised sample of pupils aged 5 to 18 years who attended a private French school with two swimming pools. The children surveyed, helped by their parents, had to fill in questionnaires about their bathing habits and symptoms during the survey period. Inspections of the pool complex were made and these included physicochemical and bacteriological analyses of the pools' water. PARTICIPATION: The response rates achieved were 70% at primary and middle school levels but only 25% in the high school pupils. Because of this older teenagers were excluded from the final analysis (of 246 children). RESULTS: Compared with non-bathers, bathers experienced fatigue and eye irritation significantly more often (p < 0.001). The eyes were red (38% of bathers) and/or watery (16%) after swimming but this resolved spontaneously within 24 hours. Bathing behaviour (bath duration, head immersion, wearing swimming goggles) did not affect these incidence rates noticeably. There were no differences between bathers and non-bathers with regard to other symptoms, especially otolaryngological ones. This survey does not allow definite conclusions to be made about verrucas because 22% of non-bathers were exempted from swimming because of verrucas that they might have caught previously in a pool. CONCLUSIONS: Except for verrucas, the methodology was adequate and daily self reporting of symptoms was feasible. This college largely recruits pupils from higher social classes and is not therefore representative of schools in Paris.