Bladder cancer incidence and exposure to polycyclic aromatic hydrocarbons among asphalt pavers

Objectives

To investigate the association between exposures to polycyclic aromatic hydrocarbons (PAH) that arises during asphalt paving, and risk of bladder cancer.

Methods

7298 men included in the historical cohort were first employed between 1913 and 1999 in companies applying asphalt in Denmark, Norway, Finland and Israel. The minimal duration of employment for inclusion in the cohort was two seasons of work. Occupational histories were extracted from personnel files. A follow‐up for cancer incidence was conducted through national cancer registries. The authors estimated exposures to benzo(a)pyrene as a marker for 4–6 ring PAH. Exposures were reconstructed by using information about changes in asphalt paving technology in each company over time, the modelled relation between production characteristics and exposure levels, and job histories. Relative risks and associated 95% confidence intervals were estimated using Poisson regression.

Results

48 bladder cancers among asphalt paving workers were detected; of these, 39 cases were exposed at least 15 years before the diagnosis. Cumulative exposure to PAH was not associated with the incidence of bladder cancer. The association with average exposure became stronger when 15‐year lag was considered, revealing a twofold increase in relative bladder cancer risk in the two higher exposure categories. There was an indication of exposure‐response association with lagged averaged exposure. Risk estimates were adjusted for age, country, duration of employment and calendar period, did not show heterogeneity among countries and did not materially change when re‐estimated after excluding non‐primary cancers from follow‐up. Previously conducted sensitivity analysis indicates that confounding by cigarette smoking is an unlikely explanation for the observed exposure‐response trends.

Conclusions

The authors were unable to control for all possible sources of confounding and bias. The results do not allow conclusion on the presence or absence of a causal link between exposures to PAH and risk of bladder cancer among asphalt workers.Bladder cancer is currently the seventh most common cancer worldwide, with 273 000 new cases and more than 108 000 deaths estimated to have occurred in the year 2002.¹ The most important risk factor is cigarette smoking, which accounts for approximately 65% of male and 30% of female cases in developed countries. Occupational exposures to polycyclic aromatic hydrocarbons (PAH), polychlorinated biphenyls, aromatic amines, formaldehyde, asbestos and solvents have been associated with increased bladder cancer risk.² While high PAH exposure associated with these settings (in μg/m³ in air) has been linked to bladder cancer risk, it is unclear whether lower PAH exposures (in ng/m³ in air), such as those observed in the asphalt industry^3,4 confer risk as well. A recent meta‐analysis of 11 case‐control studies, conducted from 1976–96 in six European countries and comprising 3346 incident bladder cancers and 6840 controls, attributed a 23% increase in bladder cancer risk among men to PAH exposure (odds ratio (OR) for the highest exposure tertile 1.23, 95% CI 1.07 to 1.4).⁵ It was estimated that 4.3% of bladder cancers in men can be attributed to occupational PAH exposure.⁵The cohort of European asphalt workers, coordinated by the International Agency for Research on Cancer, was originally assembled to study the risk of lung cancer following exposure to bitumen fume. However, it evolved into a very rich resource for studying focused (bitumen and cancer) and broad aetiological questions (PAH and lung cancer, cardiorespiratory diseases). The key findings from the cohort study include observations of increased lung cancer mortality with increasing bitumen fume exposure among asphalt pavers (a subcohort for which the best exposure estimates were available),⁶ positive associations of exposure to PAH among asphalt pavers with the risk of death from obstructive lung⁷ and ischaemic heart disease,⁸ lack of increased risk for fatal occupational injuries among asphalt workers in the cohort⁹ and an indication that lung and bladder cancer incidence may be increased in the subcohorts from Nordic countries.¹⁰ More specifically, although no overall increased incidence of bladder cancer was observed (standardised incidence ratio on 112 cases of 0.91 (95% CI 0.75 to 1.10), there was a tendency for higher risk with longer time since first employment, with a relative risk (RR) of 1.85 (95% CI 0.90 to 3.78) for more than 30 years vs 1–14 years (p value for trend 0.1, 22 cases).¹⁰ The main limitations of these analyses were that (a) they did not include incident bladder cancer cases available across the national subcohorts, (b) data on cigarette smoking, a major potential confounder, was not available, and (c) lack of exposure‐response analysis that uses job‐exposure matrix that we constructed for the cohort.¹¹ In this paper, we aim to overcome two of these limitations by investigate the association between PAH exposure and bladder cancer incidence among asphalt pavers using quantitative exposure indices and by including eligible incident bladder cancers from the entire international cohort.     

Dermal exposure to polycyclic aromatic hydrocarbons among primary aluminium workers.

Large amounts of PAH's are released in the electrode production departments of pre-bake cell aluminium reduction plants. Emission sources are mixing, shaping and baking of the anode (paste plant and bake oven) and pot relining operations. A study was performed to quantify the importance of dermal uptake of PAH's among exposed workers. Twenty workers in the anode production departments (paste plant (N = 8) and bake oven (N = 5)) and the pot relining department (N = 7) volunteered for the study. Monitoring was performed over a period of 5 consecutive days using personal air sampling, dermal contamination sampling and biological monitoring. Pyrene concentrations measured in the respirable air samples, ranged up to 320 micrograms/m3. Dermal contamination of pyrene was monitored at three skin sites (wrist, jaw/neck and groin) using exposure pads as pseudo-skin. The skin contamination with pyrene ranged up to 375 ng/cm2. Contamination of the groin skin site, although covered by work clothes ranged up to 106 ng/cm2. The concentration of 1-hydroxypyrene in pre and post-shift urine ranged up to 27 mumol/mol creatinine and showed an increase during the day and a decrease during the night. Pyrene in air and pyrene on the skin were tested for significance of correlation with urinary 1-hydroxypyrene in samples taken at several moments: end-of-shift, pre-shift next morning and weekly increase. The correlation coefficients between dermal contamination and urinary 1-hydroxypyrene were equal or higher than the correlation coefficient between pyrene air concentration and urinary 1-hydroxypyrene. The total skin contamination in exposed workers is estimated to be more than three times higher than the intake via the respiratory tract. The contribution of dermal exposure to the total PAH body burden of exposed workers therefore appears to be significant.     

Evaluation of worker exposure to polycyclic aromatic hydrocarbons

A sampling and analytical method was selected to determine the physical and chemical nature of worker exposure to polycyclic aromatic hydrocarbons (PAH). It consists of filter and sorbent tube sampling followed by benzene extraction and analysis of 12 different PAHs with a gas chromatograph connected to a mass spectrometer. This method has undergone extensive field trials. Sampling temperature, inorganic and organic interferences have an effect on the results as they do on the standard gravimetric method of benzene-solubles. A combination of the gravimetric method and the particulate and gaseous concentration profile of 12 PAHs is necessary to obtain an informative evaluation of worker exposure. This approach was used to demonstrate that workers in paving and roofing operations and on some worksites in the steel and silicon carbide industries show an exposure profile that suggests minimal health risk and is largely different from the exposure of workers in aluminum refineries, refractory brick laying and most other worksites in the silicon carbide industry.     

Environmental exposure of small children to polycyclic aromatic hydrocarbons

Objectives: The aim of the study was to assess the intake (by various routes of exposure) of polycyclic aromatic hydrocarbons (PAH) by children living in a Czech city, and its effect on excretion of 1-hydroxypyrene (1-OHP) in summer and winter periods. Methods: Four groups of children (3–6 years old) were chosen: (1) two groups from a kindergarten situated in the city center with a higher traffic density (“polluted” area); (2) two groups from a kindergarten situated in a green zone of the same city (“non-polluted” area). Food consumption was recorded in all children and PAH intake from foodstuffs was estimated. Ambient air samples were collected from the playground and inside the kindergartens. Soil samples were collected too. Morning and evening urine samples were collected during sampling days. Results: In both seasons, the mean outdoor total PAH concentration (sum of 12 individual PAH) in the “polluted” area was approximately three-times higher than that in the “non-polluted” area. Indoor concentration in the “polluted” area was more than six-times higher than that in the “non-polluted” area in summer, and almost three-times higher in winter. The same trend was observed for pyrene and for the sum of carcinogenic PAH. The contribution to the total pyrene absorbed dose from food consumption was much more important than that from inhalation and from ingestion of soil dust. Significantly higher urinary concentrations of 1-OHP (evening samples) were found in children from the “polluted” kindergarten in both seasons. The number of significant relationships between 1-OHP and pyrene absorbed dose was weak. Conclusions: Food seems to be the main source of total pyrene and total PAH intake in small children, even under relatively higher air PAH exposure in the city. Estimated pyrene ingestion from soil had a negligible contribution to the total pyrene absorbed dose. Urinary 1-OHP seems to be an uncertain (non-sensitive) marker of the environmental inhalation exposure to pyrene (PAH) if the pollution of air by pyrene (PAH) is not excessive and the pyrene (PAH) dose by this route is much less than by ingestion. Usefulness of the urinary 1-OHP as an indicator of overall environmental exposure to PAH needs further investigation. Received: 18 September 2000 / Accepted: 20 February 2001     

Health risks of residential exposure to polycyclic aromatic hydrocarbons

A disease prevalence study and follow-up health surveillance were conducted among residents of an African-American community situated at the site of a former creosote wood-treatment facility contaminated with polycyclic aromatic hydrocarbons. Household interviews were conducted among 214 residents living around the hazardous waste site (target population) and 212 comparison residents in a neighborhood 2.4 km away from the site. Target area residents reported a higher prevalence of skin rashes than comparison residents (relative risk [RR] = 5.7; 95% confidence interval [CI] = 3.0, 10.9). The prevalence of reported rashes increased with increasing levels of anthracene detected in yards (test for linear trend, p = 0.02). With adjustment for environmental worry, reports of chronic bronchitis and difficulties becoming pregnant did not differ significantly between target and comparison residents (p > 0.05).     

Dermal exposure assessment of polycyclic aromatic hydrocarbons: in vitro percutaneous penetration from lubricating oil

Objectives: Percutaneous penetration of polycyclic aromatic hydrocarbons (PAHs) is affected by various factors connected to exposure conditions. The nature of the matrix, such as that of oil, can strongly affect their percutaneous penetration. Risk assessment should consider these effects. We examined the effect of matrix on percutaneous penetration of PAHs, particularly that of lubricating oil. Methods: The test apparatus consisted of an in vitro static diffusion cell system using full-thickness monkey (Cercopithecus aetiops) skin as the membrane and saline solution with gentamycin sulfate and 4% bovine serum albumin as receptor fluid. Chemical analysis of PAHs in the samples obtained from cells was carried out by inverse-phase HPCL, and the results were read by spectrofluorimetry. Results: Comparing the penetration of 13 PAHs from a lubricating oil and from acetone solution with artificial sweat resulted in a significantly slower passage from the oil matrix for acenaphthene, anthracene, phenanthrene, fluoranthene, naphthalene, pyrene, fluorene (Mann-Whitney U test, P < 0.05). No significant differences in the passage were found for chrysene because, in the test with oil, its concentration was very often below the detection limit. For benzo[a]anthracene, benzo[b]fluoranthene, benzo[k]fluoranthene, and benzo[a]pyrene it was possible to demonstrate a passage through the skin only when compounds were applied in acetone solution with artificial sweat. Conclusions: The results of the study suggest the necessity of dermal penetration data relevant for risk assessment, obtained under experimental conditions similar to the real exposure conditions. Received: 7 January 1999 / Accepted: 10 July 1999     

Dermal exposure assessment of polycyclic aromatic hydrocarbons: in vitro percutaneous penetration from coal dust

To understand the dermal uptake of chemicals bound to soil and dust, information on the neat substance is helpful but does not seem sufficient. Because of its content of polycyclic aromatic hydrocarbons (PAHs) coal is suspected to be carcinogenic. However, experimental carcinogenity studies on coal dust never succeeded in demonstrating a higher incidence of cancer in treated animals. The aim of the study was to assess dermal penetration through human skin of PAHs from coal dust. A sample of coal dust was grinded and sieved, using the particle size of < 30 microm. An in vitro static diffusion cell system validated by in vitrolin vivo comparison has been used to study dermal penetration through human skin of PAHs from coal dust compared with their percutaneous absorption as pure compounds. No percutaneous penetration of PAHs was observed in the cells where coal dust was applied, while dermal penetration was demonstrated for PAHs applied in an acetone solution. Results agree with the literature that PAHs are poorly absorbed through the skin from solids. Dermal risk assessment of PAHs should take into account not only the degree and the extent of skin contamination, but also their bioavailability, which is heavily influenced by the physico-chemical characteristics of the matrix.     

Acute symptoms associated with asphalt fume exposure among road pavers

BACKGROUND: Although asphalt fume is a recognized irritant, previous studies of acute symptoms during asphalt paving have produced inconsistent results. Between 1994 and 1997, the National Institute for Occupational Safety and Health (NIOSH) evaluated workers at seven sites in six states. METHODS: NIOSH (a) measured exposures of asphalt paving workers to total (TP) and benzene-soluble particulate (BSP), polycyclic aromatic compounds, and other substances; (b) administered symptom questionnaires pre-shift, every 2 hr during the shift, and post-shift to asphalt exposed and nonexposed workers; and (c) measured peak expiratory flow rate (PEFR) of asphalt paving workers when they completed a symptom questionnaire. RESULTS: Full-shift time-weighted average exposures to TP and BSP ranged from 0.01 to 1.30 mg/m(3) and 0.01 to 0.82 mg/m(3), respectively. Most BSP concentrations were <0.50 mg/m(3). Asphalt workers had a higher occurrence rate of throat irritation than nonexposed workers [13% vs. 4%, odds ratio (OR) = 4.0, 95% confidence interval (CI): 1.2-13]. TP, as a continuous variable, was associated with eye (OR = 1.34, 95% CI: 1.12-1.60) and throat (OR = 1.40, 95% CI: 1.06-1.85) symptoms. With TP dichotomous at 0.5 mg/m(3), the ORs and 95% CIs for eye and throat symptoms were 7.5 (1.1-50) and 15 (2.3-103), respectively. BSP, dichotomous at 0.3 mg/m(3), was associated with irritant (eye, nose, or throat) symptoms (OR = 11, 95% CI: 1.5-84). One worker, a smoker, had PEFR-defined bronchial lability, which did not coincide with respiratory symptoms. CONCLUSIONS: Irritant symptoms were associated with TP and BSP concentrations at or below 0.5 mg/m(3).     

Cancer risk due to occupational exposure to polycyclic aromatic hydrocarbons

Polycyclic aromatic hydrocarbons (PAHs) demonstrate carcinogenic activity in animal models. Although some epidemiologic studies have implicated PAHs as risk factors for human cancer, the evidence reported to date has not been consistent. The purpose of this report is to describe the associations between occupational exposure to PAHs in the workplace and each of 14 types of cancer. A population-based, case-control study was carried out in Montreal to investigate associations between a large variety of environmental and occupational exposures on the one hand, and several types of cancer on the other. A detailed job history was obtained from each subject along with information on a number of potential confounders. Each job history was reviewed by a team of experts, who used this information to construct a corresponding history of occupational exposures. Among the PAH exposures considered were benzo(a)pyrene (B(a)P) and five categories of PAHs defined on the basis of the source material, namely, wood, petroleum, coal, other sources, and any source. Altogether, 3,730 cancer patients and 533 population controls were interviewed and their job exposure histories coded. For each of 14 types of cancer analyzed, three control groups were available: other cancer patients, population controls, and the pooled set of cancer and population controls. The associations between 14 cancer types and 6 PAH exposures were analyzed using logistic regression methods. For most types of cancer evaluated, there was no evidence of excess risk due to PAHs at the levels encountered in the occupations in which PAH exposure has been prevalent in the Montreal area. For a few cancer sites–the esophagus, the pancreas, and the prostate gland–there were suggestions of excess risk; these observations are noteworthy hypotheses for further investigation. For lung cancer, there appeared to be an increased risk due to PAHs among nonsmokers and light smokers, but not among heavy smokers.     

Mortality from obstructive lung diseases and exposure to polycyclic aromatic hydrocarbons among asphalt workers

Work in the asphalt industry has been associated with nonmalignant respiratory morbidity and mortality, but the evidence is not consistent. A historical cohort of asphalt workers included 58,862 men (911,209 person-years) first employed between 1913 and 1999 in companies applying and mixing asphalt in Denmark, Finland, France, Germany, Israel, the Netherlands, and Norway. The relations between mortality from nonmalignant respiratory diseases (including the obstructive lung diseases: chronic bronchitis, emphysema, and asthma) and specific chemical agents and mixtures were evaluated using a study-specific exposure matrix. Mortality from obstructive lung diseases was associated with the estimated cumulative and average exposures to polycyclic aromatic hydrocarbons and coal tar (p values of the test for linear trend = 0.06 and 0.01, respectively). The positive association between bitumen fume exposure and mortality from obstructive lung diseases was weak and not statistically significant; confounding by simultaneous exposure to coal tar could not be excluded. The authors lacked data on smoking and full occupational histories. In conclusion, exposures to polycyclic aromatic hydrocarbons, originating from coal tar and possibly from bitumen fume, may have contributed to mortality from obstructive lung diseases among asphalt workers, but confounding and bias cannot be ruled out as an explanation for the observed associations.     

职业多环芳烃暴露人群尿中生物标志物浓度水平

多环芳烃类化学物质因为其被熟知的致癌性而一直备受关注, 近来越来越多的学者意识到单一的接触生物标志物并不能完全代表暴露者体内的暴露水平。本研究就1999年以后15年间报道的职业环境中接触多环芳烃类物质的工人尿中接触生物标志物进行综述, 重点对其浓度水平进行描述, 为职业环境中多环芳烃类化学物质暴露的生物学检测提供理论依据。     

Exposure to polycyclic aromatic hydrocarbons among Dutch children.

We determined the urinary 1-hydroxypyrene (1-HP) concentration and the creatinine-adjusted 1-HP concentration in 644 randomly selected Dutch children, aged 1-6 years and living in five areas with roughly different levels of polycyclic aromatic hydrocarbons (PAHs) in soil and ambient air. The presence of other factors that might influence the exposure to PAHs was studied using a questionnaire. To evaluate the reliability of a single urinary 1-HP determination, measurements were repeated after 3 weeks for approximately 200 children. The mean urinary 1-HP content of the total study population was 2.06 nmol/l. This varied from 1.58 nmol/l in the reference area (Flevoland) to 2.71 nmol/l in the valley of the Geul. Only indoor sources of PAHs showed a small, positive association with urinary 1-HP. The urinary 1-HP concentrations of children from the valley of the Geul were higher (p < 0.01) and those of children from a suburb of Amsterdam were lower (p < 0.01) than those of children from the reference area. The possible ambient environment-related differences were probably too small to be detected in the variations of the intake of PAHs from the daily diet. The reliability of a single 1-HP measurement was low. Similar results were obtained with the creatinine-adjusted data. In one neighborhood built on coal-mine tailings, the urinary 1-HP content in children was weakly but positively associated with the PAH content in the upper soil layer of the garden of their homes. However, this association was not found for the children from the other neighborhood built on coal-mine tailings and with similar PAH levels in soil.     

重庆市某区小学女生多环芳烃内暴露水平及其与青春发动时相的关系

目的建立同时测定尿中4种多环芳烃(PAHs)代谢物的检测方法,研究重庆市某区女童青春发动时相提前与体内多环芳烃暴露水平的关系。方法研究对象采用目的性抽样,对重庆市某区4所小学1~4年级女生进行一般情况的问卷调查、生长发育的体格检查、并收集尿液,采用高效液相色谱-质谱联用法(HPLC-MS)对样品中4种PAHs代谢物进行定性和定量检测。结果 4种PAHs代谢物标准曲线相关性高,方法检出限为0.1 ng/mL。研究共调查女童737名,青春发动时相提前组209人,正常组528人。尿液检测结果显示4种PAHs代谢物检出率为100%,4种代谢物的检出浓度范围分别为1-羟基芘0.01~4.77 ng/mL,2-羟基萘0.15~50.00ng/mL,2-羟基芴0.06~12.59 ng/mL及9-羟基菲0.29~23.17 ng/mL。青春发动时相提前组和正常组在2-羟基芴(Z=-1.996)和9-羟基菲(Z=-3.161)暴露水平上差异具有统计学意义(P<0.05),控制了肥胖因素后,青春发动时相提前组9-羟基菲(Z=-3.012)暴露水平仍高于正常组(P<0.05)。结论该方法适用于4种PAHs代谢物的同时检测,研究地区女童青春发育早期均有PAHs暴露,且PAHs暴露可能是女童青春发动时相提前的因素之一。     

Biomarkers of exposure to polycyclic aromatic hydrocarbons from environmental air pollution

Metabolites of pyrene and DNA adducts have been used as biomarkers of high level exposure to polycyclic aromatic hydrocarbons (PAHs). A systematic review was performed to evaluate whether these biomarkers are also valid markers of low level environmental exposure to PAHs. Thirty five studies were identified with more than 10 subjects that evaluated environmental air pollution to PAHs in relation to metabolites of PAHs, mainly hydroxypyrene (1-OHP), PAH-DNA adducts, or protein adducts. PAH metabolites and, to a less extent, PAH-DNA adducts correlated well at the group level with exposure to B(a)P even at low levels of air pollution. The use of these biomarkers should be more widely implemented in combination with more traditional techniques for the assessment of general population exposure to PAHs from ambient air pollution.     

International studies of prenatal exposure to polycyclic aromatic hydrocarbons and fetal growth

OBJECTIVES: Polycyclic aromatic hydrocarbons (PAHs) are ubiquitously distributed human mutagens and carcinogens. However, lack of adequate air monitoring data has limited understanding of the effects of airborne PAHs on fetal growth. To address this gap in knowledge, we examined the association between prenatal exposure to airborne PAHs and birth weight, birth length, and birth head circumference, respectively, in Krakow, Poland, and New York City (NYC). METHODS: The parallel prospective cohort studies enrolled nonsmoking, healthy, and nonoccupationally exposed women and their newborns. Personal air monitoring of pregnant women was conducted over 48 hr. To control for maternal environmental tobacco smoke (ETS) exposure, we excluded those with umbilical cord plasma cotinine concentrations > 25 ng/mL. Mean cord plasma cotinine concentrations in both ethnic groups were 相似文献   

Biological monitoring and biochemical effect monitoring of exposure to polycyclic aromatic hydrocarbons

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous carcinogenic substances to which man is exposed in the environment and at certain workplaces. Estimation of the resulting health risk is therefore of great occupational-medical and environmental-medical importance. Determination of the DNA and protein adducts of PAHs is the most suitable way of estimating this risk. The analytical methods used thus far, above all, ³²P postlabeling, immunoassays, and synchronous fluorescence spectroscopy, are, however, too nonspecific; therefore, the results lack accuracy and are not comparable with one another. Only the use of very specific methods of instrumental analysis [above all, high-performance liquid chromatography (HPLC) and gas chro- matography/mass spectrometry (GC/MS)] can counteract this deficit. However, these methods can successfully be used mainly to determine the protein adducts of PAHs. Hemoglobin adducts, for example, do not have repair mechanisms like DNA adducts. They therefore occur in higher concentrations and can thus be analytically detected more easily. At present, mainly the monohydroxylated metabolites of PAHs are being determined in urine with great success. Using specific enrichment methods and HPLC with fluorescence detection it is even possible today to determine the internal PAH exposure of the general population. The detection limits lie in the lower nanogram-per-liter range. In view of the importance of this group of substances, determination of PAH adducts and the detection of their metabolites in urine will remain at the center of future occupational-medical and environmental-medical/toxicological research. In general, the lack of reference substances must be lamented. Received: 21 May 1997 / Accepted: 17 July 1997     

Elimination of 1-hydroxypyrene after human volunteer exposure to polycyclic aromatic hydrocarbons

The aim of this study was to estimate the kinetics of 1-hydroxypyrene (1-HP) elimination after inhalation exposure to polycyclic aromatic hydrocarbons (PAHs). Samples of inhaled and exhaled air were collected on glass fiber filters backed with tubes filled with Amberlit XAD-2 resin. The filters were extracted by cyclohexane and Amberlit – by acetonitrile. Extracts for the determination of pyrene and benzo[a]pyrene (B[a]P) concentrations were analyzed by high-performance liquid chromatography (HPLC). 1-Hydroxypyrene in urine was determined after its preconcentration on a C-18 column (solid phase extraction method) using the same analytical technique. Five male volunteers were exposed for 6 h (two times, with a 1-month interval) to a PAH mixture at an aluminium plant. The volunteers were breathing at rest through facial mask equipped with a 1000-ml compensation container which allows collection of the exhaled air. Inhaled air samples were collected in the breathing zone of each volunteer. Urine samples were collected until the 71st hour after the onset of exposure. The average respiratory retention of pyrene was found to be 61%. The 1-HP elimination process could be described by one-compartment model with the half-live of 9.8 hour (95% CI 7.9–11.7 h). The simulation of 1-HP elimination in urine during a working week (4 days) indicates that the balance between absorption and elimination is achieved at the end of the second day. Received: 29 July 1996 / Accepted: 21 February 1997