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Unit risks used for quantitative cancer risk assessment are defined for constant lifetime exposures. The condition of temporal stability, however, usually is not fulfilled in environmental health applications. In practice, cancer risks for time-dependent exposures are often estimated by calculating lifetime average exposure, assuming a mean life expectancy of 70 years. In the present paper we discuss the question whether this is an appropriate procedure considering various variants of multi stage and epidemiological relative risk models. For this purpose, lifetime risks for time dependent exposures as calculated according to the respective model assumptions, were compared with lifetime risks estimated by the lifetime average exposure approach. As typical exposure histories in environmental health applications we studied exposures either limited to the first 5 years of life (children scenario) or limited to duration of employment (30th to 65th year of age; occupational scenario). The consideration of multistage models (Armitage-Doll- and Moolgavkar-Venzon-Knudson model) in general would not induce serious bias in risk estimation when exposures are limited to middle ages (occupational scenario). On the other hand, when exposures occur only in very young ages or only in very old ages the risk estimated by using lifetime average exposure is not comparable with the predictions of multistage models. Whereas the degree of possible underestimation is bounded by factors well below 10, the amount of possible overestimation is unbounded and may become arbitrarily high, when exposures concentrate in extreme ages. In a second part of the study we investigated different relative risk models, taking lung cancer as an example. The models differed with respect to assumptions on latent periods and moderating effects of age at exposure and age at risk. The simulations showed that the unit risk concept is appropriate for the occupational scenario. For the children scenario results strongly depend on the assumptions made. Whereas the degree of possible underestimation is acceptable, in some models the degree of possible overestimation may become arbitrarily high. Both parts of the study showed that bias induced by using lifetime average exposure is acceptable when exposures are limited to middle ages. On the other hand, the unit risk concept should not uncritically be applied to exposures limited to early childhood (e.g., in kindergartens or due to mouthing activities). Depending on the assumptions made, lifetime risk may either be moderately underestimated or grossly overestimated. Without additional knowledge on mechanisms or latency period risk estimations are of questionable value. With respect to exposures in childhood regulation should concentrate on initiating substances or substances known to have long latent periods, respectively. With respect to cancers which occur relatively frequent already in childhood specific considerations are recommended.

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We determined blood concentrations of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) in 41 female employees with previous exposure to pentachlorophenol-based wood preservatives from 10 day-care centers in the Hamburg, Germany, area. We compared the blood concentrations with estimated age-dependent reference values and analyzed the correlation between PCDD/PCDF indoor air exposure and blood concentrations. The analyses based on the PCDD congeners 1,2,3,4,7,8-, 1,2,3,6,7,8-, and 1,2,3,7,8,9-hexaCDD (hexaCDD), 1,2,3,4,6,7,8-heptaCDD (heptaCDD), octaCDD, and the 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity equivalents calculated according to the international NATO-CCMS model (I-TEQ). In comparison to the estimated reference values, the blood concentrations of hexaCDD and I-TEQ spread around the mean estimate. Data for octaCDD scattered in some cases distinctly above the upper confidence limit. Reference values for heptaCDD could not be estimated. The correlation between PCDD/PCDF indoor air exposure and PCDD/PCDF blood concentrations was examined by linear multiple regression analysis considering different exposure variables and taking confounders into account. Analyses were carried out with the total study group and with a restricted subgroup. Associations were shown between the PCDD/PCDF indoor air concentrations and blood concentrations for heptaCDD and for the I-TEQ, whereas hexaCDD showed no association. OctaCDD showed a negative association in the total study group and no association in the subgroup analysis. In summary, the analyses showed no clear association between PCDD/PCDF indoor air exposure in day-care centers and PCDD/PCDF blood levels of female employees previously exposed to wood preservatives. By contrast, the results consistently indicated a positive association between PCDD/PCDF blood concentrations and exposure to wood preservatives in private homes.

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The importance of risk communication and participation in the solution of environmental health problems has been increasingly appreciated. However, realisation is a demanding task for health departments, as practical experience is limited. Psychological processes in risk perception facilitate confounding of different levels of conflict. Therefore, risk communication and participation should be organised as a stepwise procedure which separates risk assessment, risk evaluation and risk management options. The present paper discusses problems which might emerge in each of these issues and suggests possible solutions. Risk communication aims at implementation of transparent decision making processes involving citizens. However, even when agreement in risk assessment can be achieved, arriving at a consensus in respect of decision making might fail if facts are weighted differently.

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There is much discussion on how to define an "acceptable risk" for a population typically exposed to low doses of environmental carcinogens. One proposal claims that all risks which are not "observable" should be considered acceptable (e.g. BYRD/LAVE 1987). It is demonstrated for example in cancer deaths due to environmental carcinogens that, for methodological reasons the acceptance of this criterion means the toleration of considerable health risks for society. From a preventive point of view methods of extrapolation seem to be more appropriate to handle "living with the uncertainty".

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An approximative cartographic estimation method for individual and population risk values has been developed and tested. The absolute and relative weights of multiple inhalation hazards were computed in a regionally differentiated way for the city of Hamburg (FRG).

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To study the phenomenon of cardiovascular hyperreactivity it is essential to know the impact of stimulus intensity and the effects induced by repeated exposure to a stressful situation like a mental arithmetic task. All subjects in this study were young healthy male students. Two different mental stressors were used: a mental arithmetic task with low stimulus intensity and one with high stimulus intensity characterised by more challenging instructions, a more competitive situation, and exposure to affective noise. The lower level mental test did not disclose any differences in the hemodynamic response in the subjects. Only the mental stress test with high stimulus intensity proved capable of detecting the cardiovascular hyperreactivity in normotensive subjects with familial hypertension. As hemodynamic response was attenuated during the second mental stress test if the second test was the lower stimulus test, and since repeated stress testing is necessary when prospective or intervention studies are performed, the stimulus intensity and sequence of mental stress tests had to be controlled carefully. To counteract any cardiovascular adaptation, it is suggested that the stimulus intensity of mental stress tests should slightly increase when repeatedly applied.

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The hemodynamic response to mental challenge was studied in 40 male outpatients with mild essential hypertension. The patients were treated randomly either with a beta adrenoreceptor blocker (oxprenolol) or with a calcium entry blocker (nitrendipine). Cardiovascular reactivity was evaluated with two different mental arithmetic tasks before and six months after treatment by continuously measuring systolic and diastolic pressure (ultrasonic Doppler device), heart rate (electrocardiography), and stoke volume (impedance cardiography). Patients in both treatment groups had equal decreases in arterial pressure and the same pressures at rest. In patients receiving calcium entry blockers, mental challenge provoked an increase in stroke volume and a decrease in total peripheral resistance similar to results in the pretreatment phase. In contrast, beta adrenoreceptor blockade reversed the hemodynamic response pattern to a distinct decrease in stroke volume (p less than or equal to 0.05) and an increase in total peripheral resistance (p less than or equal to 0.05). In addition, an attenuated heart rate response (p less than or equal to 0.01) and a larger increase in diastolic pressure (p less than or equal to 0.01) were found in the beta blocker group compared with the calcium entry blocker group. Although beta blockers and calcium blockers produce equal decreases in arterial pressure, beta blockers evoke an abnormal hemodynamic response to mental challenge, whereas calcium entry blockers preserve the physiologic reactivity pattern of the untreated state.

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In 100 children (63 boys and 37 girls) aged 11.3 +/- 0.6 years ambulatory blood pressure (BP) was recorded by a semi-automatic device (Remler) 9 times per year over a period of 3 years. A sex difference in systolic BP was noted from the age of 13 years on with boys having higher values by about 6 mmHg (p less than .05). This could not be explained by differences in weight. In boys parental hypertension was associated with higher systolic values independent on age (p less than .05). Genetic and hormonal factors seem to influence BP during male puberty independently from each other.

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We examined possible predictors of the recurrence of high blood pressure (BP) in patients who remained normotensive after withdrawal of drug therapy. Thirty untreated male patients with WHO stage I essential hypertension (mean age 43 +/- 6 years) were randomly allocated to oxprenolol or nitrendipine groups. Before therapy, BP at rest, during mental arithmetic (MA) and during the cold pressor (CP) test was assessed. After 6 months of effective monotherapy, all drugs were withdrawn and casual BP was followed up for 5 months. Two weeks after cessation of therapy 26% were hypertensive again, after 4 weeks 28%, after 12 weeks 48% and after 21 weeks 74%. The two therapeutic groups did not differ in their BP increase after discontinuation of therapy. Predictors for the return of high BP were age, pretreatment BP, systolic and diastolic BP increase to the CP test. Analyses of covariance for age and pretreatment BP confirmed that reactivity to the CP test was a predictor of the return of hypertension.

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Since 1981 the 'Bonn Kinderstudie' has followed blood pressure (BP) development in children. In a subset of 63 healthy boys (aged 10-12 years at the beginning of the study) we examined whether cardiovascular reactivity predicts future BP development. At a 1-year interval BP and heart rate (HR) were measured during mental arithmetic and physical exercise. Ambulatory BP was assessed nine times per year. Among different reactivity scores HR reactivity to mental stress was the most stable variable. Only reactivity of systolic BP to mental stress was different between subjects with parental hypertension and subjects with a negative family history of hypertension. After 1 year high HR reactors developed about 7 mmHg higher ambulatory systolic BP levels than low HR reactors. It is concluded that besides genetic factors HR reactivity to mental stress might indicate the disposition for developing high BP.

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Normotensives with hypertensive parents have been reported to exhibit enhanced cardiovascular reactions to mental stress. We have examined the question of why this result was not confirmed in all studies. In addition we have investigated whether appropriate tests can be performed under clinical rather than laboratory conditions. Healthy male subjects were examined. In experiment I, under laboratory conditions, a standard stress test was intensified (n = 30). In experiment II the same test was used in a simplified version which did not require special equipment (n = 19). Blood pressure, heart rate and stroke volume (by impedance cardiography) were measured. In contrast to the results with the standard test, subjects with at least one hypertensive parent exhibited enhanced responses of systolic and diastolic blood pressure and heart rate. We conclude that cardiovascular hyper-reactivity in subjects with hypertensive parents is only apparent using sufficiently intense stimuli. Although less pronounced, these differences can also be observed under clinical conditions.

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We investigate whether ambulatory BP (aBP) recording in children reflects situational variations and whether aBP depicts the impact of heightened cardiovascular reactivity under mental challenge, and gender on changes in BP. Results of 19 aBP protocols (2 to 7.30 p.m. after school; 30 min intervals) in 86 children, performed during 2 years of follow-up show that repetitive ambulatory blood pressure (aBP) recording reflects the great variability of environmental stimuli in children. Mean aBP is highly correlated with self-reported physical activity. Systolic aBP correlates with cardiovascular changes under mental arithmetic and - to a lesser degree - during bicycle exercise. Ambulatory BP recording is a sensitive method to detect the influence of hyperreactivity and gender on BP development in children at the age of 10-13 yrs.

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In 100 children of different school classes (10-12 years, participation rate ca. 50%) ambulatory blood pressure (BP) was recorded by a semi-automatic non-invasive device (Remler system). BP was measured every 1/2 h between 2 and 7.30 p.m. During each measurement the children protocolled their activity. These BP recordings were repeated five times at monthly intervals in 86 children. In the same children casual and near basal BP was determined. The mean ambulatory BP was 103/64 +/- 7/6 mm Hg. The average retest reliability of the monthly mean values was r = 0.57 for systolic and r = 0.45 for diastolic BP. The variability of BP (standard deviation) was not reproducible. Data recording failed in 32% of all single systolic and in 42% of all single diastolic BP measurements. These drop-outs were caused by inappropriate use rather than technical problems. There was a relationship between procolled activities and systolic BP. On average, ambulatory BP was lower than BP under standardized conditions. Under all conditions, children with hypertensive parents exhibited a 6 mm Hg higher systolic BP than children without a similar family history. No sex differences were found.

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Blood pressure variability under basal conditions and blood pressure reactivity to emotional stress were studied in 38 hypertensives and 13 normotensives. Systolic basal blood pressure variability correlated with systolic blood pressure reactivity. Variability increased with higher basal blood pressure. Thus in the hypertension group the blood pressure variability was greater than in the normotension group. Besides, the hypertension group showed a greater reactivity of systolic blood pressure to emotional stress, too. An influence of age on basal blood pressure, blood pressure variability, and reactivity could be evaluated; but no influence of sex on these parameters was detected. The results indicate that variability and reactivity of blood pressure can be referred to a common central nervous blood-pressure-regulating mechanism. As both parameters are increased in hypertension, a greater lability of blood pressure must be assumed. This greater lability may be attributed to a stronger neurogenic influence or to structural changes of peripheral blood vessels.

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Hemodynamic reactivity to methacholine (0,1 mg/kg bodyweight) was studied in 10 normotensives with genetic risk of hypertension (mean age: 25,4 +/- 2,6 years) in comparison with 8 controls (mean age: 25,0 +/- 2,3 yrs). Due to peripheral vasodilatation this substance led to an initial blood pressure fall which was the same in the investigated and in the control group. In the phase of counterregulation the secondary rise of blood pressure was higher in the group with family history of hypertension. As evidenced by correlation statistical analysis the increases of heart rate and cardiac output were responsible for the rise of systolic blood pressure. The hemodynamic response to methacholine in the group with genetic risk of hypertension has been attributed to a higher sympathetic reactivity.

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The hemodynamic response to emotional stress (mental arithmetic) was studied in ten borderline and ten mild hypertensives in comparison to ten age-matched normotensives. Due to emotional stress the blood pressure increased in all three groups; its rise was greater in borderline and mild hypertension. After stress, the blood pressure also remained elevated longer in the hypertensive groups. The increased blood pressure reaction was accompanied by a greater rise of heart rate and cardiac output. The increase of cardiac output correlated with the blood pressure elevation. Stroke volume changed in comparison to the pre-stress period only in the mild hypertension group. Total peripheral resistance decreased slightly in all three groups. No significant differences between the groups could be found in regard to stroke volume and total peripheral resistance. The cardiovascular hyperreactivity in early hypertension is attributed to a stronger sympathetic stimulation of the circulation. The hemodynamic pattern indicates an increased beta-adrenergic stimulation of the heart as the main pathological mechanism.

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Previous studies showed the importance of the response of blood pressure to emotional stress in essential hypertension. However, it is unclear to what extent the response of blood pressure to emotional stress is influenced by antihypertensive treatment, and especially by beta-blockers. In the present study the influence of antihypertensive treatment with either beta-blockers (beta) or diuretics (D) was compared in two series of experiments on male hypertensives, carried out after 2 weeks (beta, n = 11; D, n = 11) and 1 year of treatment (beta, n = 11; D, n = 9). One of the two drugs was randomly allocated to each patient. In the first series of experiments an ergometric exercise test was also performed (workload depending on age and body surface area, 60-100 W). The two medications caused a similar decrease in basal blood pressure. The response of blood pressure to emotional stress was also the same in both groups, and equal to that in untreated hypertensives. However, the reaction of systolic blood pressure to dynamic exercise was lower in the patients treated with beta-blockers (30.2 +/- 9.5 mm Hg) than in those treated with diuretics (42.9 +/- 12.1 mm Hg; p = 0.013). The effect of antihypertensive treatment on the reactivity of blood pressure therefore cannot comprehensively be tested by means of a single stress test. In terms of controlling the response of blood pressure to stress, beta-blockers are not generally more effective than diuretics, but only in certain situations.

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