The German view: Effects of nitrogen dioxide on human health – derivation of health-related short-term and long-term values

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Abstract

The presented overview concerning health relevant effects caused by nitrogen dioxide (NO2) resumes the current state of results from animal experiments and human studies (epidemiology and short-term chambers studies).

NO2 concentrations applied in animal experiments were mostly considerably higher than in ambient air. Therefore, short- and long-term limit values were derived from human data. Experimental studies conducted with humans demonstrate effects after short-term exposure to concentrations at or above 400 μg NO2/m3. Effects on patients with light asthma could not be observed after short-term exposure to concentrations below 200 μg/m3. On basis of epidemiological long-term studies a threshold below which no effect on human health is expected could not be specified.

Two short-term limit values have been proposed to protect public health: a 1-h value of 100 μg/m3 and a 24-h mean value of 50 μg/m3. Due to the limitations of epidemiological studies to disentangle effects of single pollutants, a long-term limit value cannot be easily derived. However, applying the precautionary principle, it is desirable to adopt an annual mean of 20 μg NO2/m3 as a long-term mean standard to protect public health.

Introduction

The Commission on Air Pollution Prevention (= Kommission Reinhaltung der Luft, KRdL) of VDI (Verein Deutscher Ingenieure=Association of German Engineers) has been commissioned by the Federal Ministry for Environment, Nature Conservation and Nuclear Safety (BMU) to give a report on the effects of nitrogen oxides on human health. The study group “Effects of Nitrogen Oxides on Human Health” of the KRdL presented its report “Evaluation of health effects of nitrogen monoxide and nitrogen dioxide” to the BMU in May 2003. The summarized and updated results of this report are presented here and compared to an assessment of the effect-relevant aspects of nitrogen dioxide (NO2) issued by a WHO study group in January 2003 (WHO, 2003).

Section snippets

Sources of nitrogen oxides in Germany

Based on calculations of the total load of nitrogen oxides (NOs), an environmental input of 1600 kt/year is assumed (UBA, 2002). The major groups of nitrogen oxide emitters in Germany are shown in Fig. 1. The traffic-associated input clearly dominates, whereas emissions from power plants, industrial heating facilities and other industrial sources (e.g., the chemical industry) add up to approximately one-third of the total amount. Since traffic emissions occur mainly in close proximity to the

Ambient air pollution by nitrogen oxides

The ambient air pollution caused by NO and NO2 depends on the respective surroundings. Since car traffic is a major source of ambient NOx, high nitrogen oxide concentrations are measured alongside roads with high traffic density (Table 1).

Whereas NO concentrations at monitoring stations close to industrial plants do not vary significantly from urban background, high annual NO2 means of more than 40 μg/m3 are almost exclusively detected along traffic arteries. Differences are even more pronounced

Symptoms caused by NO2

NO2 is a strong respiratory irritant. Like other gases with low to moderate solubility in water (e.g., ozone), NO2 reaches deeper regions of the respiratory tract. The bronchotracheal and alveolar regions are the predominating sites of action (Chitano et al., 1995).

The odour is pungently stifling. The threshold range of olfactory perception is between 200 and 410 μg/m3 according to several authors (Feldman, 1974; Henschler et al., 1960; Shalamberidze, 1967). Adaptation and consequent reduction

Toxicokinetics and mechanism of action

NO2 is almost completely absorbed in the respiratory tract (80–90%; Berglund et al., 1993). NO2 is partially taken up in the upper part of the respiratory system. For nasal respiration the absorption fraction amounts to approximately 40% at the most, depending on species and ventilation rate (Yokoyama, 1968; Kleinman and Mautz, 1987). Sixty per cent or more is absorbed in deeper regions (terminal bronchioles and alveolar region; Mücke and Wagner, 1998). An increase in respiratory frequency

Results from animal experiments

A large number of studies on the effects of NO2, especially on the respiratory tract are available. These studies used various animal models and experimental methods, and aimed at different biological end points. Results are therefore quite heterogeneous.

As far as the quantitative assessment of NO2 effects is concerned, studies carried out in recent years essentially confirm previous findings. Regarding the inhalative effects of NO2, a distinction between bronchotracheal and alveolar regions

Results from human studies

The quantification of NO effects on human health is based on results from epidemiological studies and experiments using inhalation chambers.

Epidemiological studies

In epidemiological studies the extent of air pollution is characterized by measuring individual pollutants such as NO2, SO2, CO, inhalable particles, etc. But not only the measured compounds contribute to “air pollution”, which represents a rather complex mixture. An individual substance therefore serves as indicator substance of this mixture. The concentrations of individual pollutants often display similar temporal courses and spatial distributions, because these substances are often emitted

Short-term effects

Short-term effects of ambient-air NOs are often analysed on the basis of register studies, which make use of NO values measured daily at official monitoring sites. These are correlated with the number of mortalities or number of hospital admissions per day.

Mortality

The correlation between airborne ambient NO2 levels and overall mortality (without violent deaths) in the population has been analysed in a large number of studies. Most of the publications indicate that increasing NO2 in ambient air coincides with a rise in mortality (Kinney and Ozkaynak, 1991; Saldiva et al., 1994; Anderson et al., 1996; Sunyer et al., 1996; Wietlisbach et al., 1996; Touloumi et al., 1997; Medina et al., 1997a; Morgan et al., 1998a; Burnett et al., 1998; Michelozzi et al.,

Hospital admissions and emergency consultations

Several studies indicate a correlation between increasing levels of NO2 in ambient air and a rising number of hospital admissions and emergency consultations related to respiratory diseases (Medina et al., 1997a, Medina et al., 1997b; Morgan et al., 1998b; Atkinson et al., 1999a, Atkinson et al., 1999b; Hagen et al., 2000; Tolbert et al., 2000). Atkinson et al. (1999a) for example found a significant rise of 1.6% in emergency hospital admissions due to respiratory diseases recorded in London

Deterioration of respiratory findings and pulmonary function

Several panel studies on asthmatic children revealed correlations between respiratory symptoms or pulmonary function values, and short-term variations of airborne pollutant levels. Most studies used particulate matter as indicators, but some data for NO2 are also available. Studies carried out in California showed that more and stronger medical complaints were recorded on days with higher air pollution, whereas an effect on PEF (peak expiratory flow) could not be clearly demonstrated (Delfino

Mortality

So far, only a few cohort studies investigated the association between mortality or life expectancy and long-term ambient NO2 pollution.

  • (1)

    The Adventist study of more than 6000 non-smoking individuals in California: no association of overall mortality with long-lasting NO2 exposure was found (Abbey et al., 1993). By contrast, mortality due to lung cancer was found to be increased with a relative risk of 2.8 (1.1–6.9) for females, and with a non-significant risk 1.8 (0.93–3.57) for males per

Pulmonary function and bronchial responsiveness

Healthy subjects display no adverse effect on pulmonary function during 1-h exposure to NO2 concentrations of 1–2 mg/m3 (Berglund et al., 1993; Strand et al., 1997; Blomberg et al., 1999). By contrast, for individuals suffering from asthma or COPD a deterioration in pulmonary function must be expected at concentrations of 500 μg/m3 or above (Strand, 1996, Strand, 1997; Morrow et al., 1992; Magnussen et al., 1994).

Several studies indicate an enhanced effect of NO2 during simultaneous exposure to

Derivation of health-related long-term and short-term limit values

In general, NO2 concentrations applied in animal experiments are considerably higher than values currently measured in ambient air. Based on these findings and considering appropriate safety factors, the derivation of health-related limit values for short-term and long-term NO2 exposures would on principle be possible. However, given the substantially better data concerning NO2 effects on humans, our study group has preferred to derive health-related short-term and long-term limit values from

Short-term effects

For the enhancing effect of non-specific stimuli the no-observed-adverse-effect level (NOAEL) was at NO2 concentrations of approximately 200 μg/m3 for asthmatics (for an exposure time of 30 min). According to the results of exposure experiments, the range of 400–500 μg NO2/m3 can be considered as the lowest effect concentration (LOAEL).

For obvious reasons, experimental studies on the acute effects of NO2 can be carried out with only relatively small numbers of test subjects under laboratory

Long-term effects

Long-term effects of NO2 on humans can only be assessed on the basis of epidemiological studies where population groups were analysed under real living conditions. The derivation of health-related long-term values for individual substances from epidemiological data is complicated by two major methodical features, namely the already mentioned indicator of mixtures and the issue of effect thresholds:

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    Indicator substances: As discussed above the effects of air pollution related to indicator

“Health aspects of air pollution with particulate matter, ozone and nitrogen dioxide” – commentary to the report of the WHO (2003)

In connection with the revision of EU Directive 1999/30/EG a study group of the integrated environmental activity programme “Clean Air for Europe” (CAFE) asked the WHO to provide answers to a catalogue of environmental and health-relevant issues with reference to the pollutants particulate matter (PMx), ozone and NO2. The WHO study group issued its report “Health Aspects of Air Pollution with Particulate Matter, Ozone and Nitrogen Dioxide” in January 2003 providing the requested answers (WHO,

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