Biological monitoring of isocyanates and related amines

Summary Five men were exposed to toluene diisocyanate (TDI) atmospheres for 7.5 h. The TDI atmospheres were generated by a gas-phase permeation method, and the exposures were performed in an 8-m3 stainless-steel test chamber. The mean air concentration of TDI was ca. 40 g/m³, which corresponds to the threshold limit value (TLV) of Sweden. The inhaled doses of 2,4- and 2,6-TDI were ca. 120 g. TDI in the test chamber air was determined by an HPLC method using the 9-(N-methyl-aminomethyl)-anthracene reagent and by a continuous-monitoring filter-tape instrument. After hydrolysis of plasma and urine, the related amines, 2,4- and 2,6-toluenediamine 2,4-, and 2,6-TDA), were determined as pentafluoropropionic anhydride (PFPA) derivatives by capillary gas-chromatography using selected ion monitoring (SIM) in the electron-impact mode. The urinary elimination of the TDAs showed a possible biphasic pattern, with rapid first phases for 2,4-TDA (mean t _1/2 for the concentration in urine, 1.9 h) and for 2,6-TDA (mean t _1/2 for the concentration in urine, 1.6 h). The cumulative amount of 2,4-TDA excreted in urine within 28 h ranged from 8% to 14% of the estimated dose of 2,4-TDI, and the cumulative amount of 2,6-TDA in urine ranged from 14% to 18% of the 2,6-TDI dose. The average urinary level of 2,4-TDA was 5 g/l in the 6 to 8-h sample (range 2.8–9.6 g/l), and the corresponding value for 2,6-TDA was 8.6 g/l (range, 5.6–16.6 g/l). Biological monitoring of exposure to 2,4- and 2,6-TDI by analysis of 2,4- and 2,6-TDA in urine is feasible.     

Biological monitoring of isocyanates and related amines

Summary Two men were exposed to toluene diisocyanate (TDI) atmospheres at three different air concentrations (ca. 25, 50 and 70g/m³) . The TDI atmospheres were generated by a gas-phase permeation method, and the exposures were performed in an 8-m³ stainless-steel test chamber. The effective exposure period was 4h. The isomeric composition of the air in the test chamber was 30% 2,4-TDI and 70% 2,6-TDI. The concentration of TDI in air of the test chamber was determined by an HPLC method using the 9-(N-methyl-amino-methyl)-anthracene reagent and by a continuous-monitoring filter-tape instrument. Following the hydrolysis of plasma and urine, the related amines, 2,4-toluenediamine (2,4-TDA) and 2,6-toluenediamine (2,6-TDA), were determined as pentafluoropropionic anhydride (PFPA) derivatives by capillary gas chromatography using selected ion monitoring (SIM) in the electron-impact mode. In plasma, 2,4- and 2,6-TDA showed a rapid-phase elimination half-time of ca. 2–5 h, and that for the slow phase was > 6 days. A connection was observed between concentrations of 2,4- and 2,6-TDI in air and the levels of 2,4- and 2,6-TDA in plasma. The cumulated amount of 2,4-TDA excreted in the urine over 24 h was ca. 15%–19% of the estimated inhaled dose of 2,4-TDI, and that of 2,6-TDA was ca. 17%–23% of the inhaled dose of 2,6-TDI. A connection was found between the cumulated (24-h) urinary excretion of 2,4- and 2,6-TDA and the air concentration of 2,4- and 2,6-TDI in the test chamber. A connection was also observed between the rate of urinary excretion of 2,4- and 2,6-TDA over the last 2h of exposure and the air concentration of 2,4- and 2,6-TDI in the test chamber. Biological monitoring of exposure to monomeric 2,4- and 2,6-TDI by the analysis of 2,4- and 2,6-TDA in biological media is feasible. A method based on 24-h urine sampling and determination levels of 2,4- and 2,6-TDA in hydrolysed urine is recommended. However, exposure to TDI is often associated with aerosols containing polymeric TDI, and we do not know whether analysis of TDA in urine can also be used as a marker of exposure to TDI prepolymers.     

Biological monitoring of isocyanates and related amines

Summary 1,6-Hexamethylene diamine (HDA), used as raw material in industrial manufacturing operations, was orally administered to six healthy volunteers. After acid hydrolysis of the urine by hydrochloric acid, HDA and the metabolite 6-aminohexanoic acid were quantified. HDA was determined as an ethyl-chloroformate derivative by capillary gas chromatography using thermionic specific detection (TSD), and 6-aminohexanoic acid was quantified by ion chromatography using the ninhydrin reaction. In nonhydrolysed urine, monoacetylated HDA (N-acetyl-1,6-hexamethylene diamine) and HDA, were verified as heptafluorobutyric anhydride derivatives by gas chromatography-mass spectrometry (GC-MS), in a chemical ionization mode using isobutane and ammonia as reagent gases. In hydrolysed urine, a mean of 0.28 mg (range 1–6%) of the administered dose (8.2 mg) was recovered as HDA, and a mean of 0.8 mg (range < 1–27%) as 6-aminohexanoic acid. The urinary excretion of both the determined compounds was rapid, and the principal part (> 90%) of the elimination was completed within 10 h. There was a considerable inter-individual variation in the excreted amounts, but the intra-individual variation in the excretion of HDA was limited. The subjects N-acetylator phenotype was determined by a dapsone test. Three slow acetylators excreted lower amounts (mean 2% of given dose) of HDA than three rapid ones (mean 5%).     

Test chamber exposure of humans to 1,6-hexamethylene diisocyanate and isophorone diisocyanate

An isocyanate generation apparatus was developed and stable isocyanate atmospheres were obtained. At a concentration of 5 g 1,6-hexamethylene diisocyanate (HDI) per m³ the precision was found to be 7% (n = 5). Three volunteers were each exposed to three different concentrations of HDI (11.9, 20.5, and 22.1 g/m³) and three concentrations of isophorone diisocyanate (IPDI) (12.1, 17.7, and 50.7 g/m³), in an exposure chamber. The duration of the exposure was 2 h. Urine and blood samples were collected, and hydrolysed under alkaline conditions to the HDI and IPDI corresponding amines, 1,6-hexamethylene diamine (HDA) and isophorone diamine (IPDA), determined as their pentafluoropropionic anhydride amides (HDA-PFPA and IPDA-PFPA). The HDA-and IPDA-PFPA derivatives were analysed using liquid chromatography mass spectrometry with thermospray monitoring negative ions. When working up samples from the exposed persons without hydrolysis, no HDA or IPDA was seen. The average urinary excretion of the corresponding amine was 39% for HDI and 27% for IPDI. An association between the estimated inhaled dose and the total excreted amount was seen. The average urinary elimination half-time for HDA was 2.5 h and for IPDA, 2.8 h. The hydrolysis condition giving the highest yield of HDA and IPDA in urine was found to be hydrolysis with 3 M sodium hydroxide during 4 h. No HDA or IPDA could be found in hydrolysed plasma (< ca 0.1 g/l).     

Urinary Hexane Diamine to Assess Respiratory Exposure to Hexamethylene Diisocyanate Aerosol: A Human Inhalation Study

Abstract

The use of urinary hexane diamine (HDA) as a biomarker to assess human respiratory exposure to hexamethylene diisocyanate (HDI) aerosol was evaluated. Twenty-three auto body shop workers were exposed to HDI biuret aerosol for two hours using a closed exposure apparatus. HDI exposures were quantified using both a direct-reading instrument and a treated-filter method. Urine samples collected at baseline, immediately post exposure, and every four to five hours for up to 20 hours were analyzed for HDA using gas chromatography and mass spectrometry. Mean urinary HDA (μg/ g creatinine) sharply increased from the baseline value of 0.7 to 18.1 immediately post exposure and decreased rapidly to 4.7, 1.9 and 1.1, respectively, at 4,9, and 18 hours post exposure. Considerable individual variability was found. Urinary HDA can assess acute respiratory exposure to HDI aerosol, but may have limited use as a biomarker of exposure in the workplace.     

Biological monitoring of isocyanates and related amines

1,6-Hexamethylene diamine (HDA), used as raw material in industrial manufacturing operations, was orally administered to six healthy volunteers. After acid hydrolysis of the urine by hydrochloric acid, HDA and the metabolite 6-aminohexanoic acid were quantified. HDA was determined as an ethyl-chloroformate derivative by capillary gas chromatography using thermionic specific detection (TSD), and 6-aminohexanoic acid was quantified by ion chromatography using the ninhydrin reaction. In nonhydrolysed urine, monoacetylated HDA (N-acetyl-1,6-hexamethylene diamine) and HDA, were verified as heptafluorobutyric anhydride derivatives by gas chromatography-mass spectrometry (GC-MS), in a chemical ionization mode using isobutane and ammonia as reagent gases. In hydrolysed urine, a mean of 0.28 mg (range 1-6%) of the administered dose (8.2 mg) was recovered as HDA, and a mean of 0.8 mg (range less than 1-27%) as 6-aminohexanoic acid. The urinary excretion of both the determined compounds was rapid, and the principal part (greater than 90%) of the elimination was completed within 10 h. There was a considerable inter-individual variation in the excreted amounts, but the intra-individual variation in the excretion of HDA was limited. The subjects N-acetylator phenotype was determined by a dapsone test. Three slow acetylators excreted lower amounts (mean 2% of given dose) of HDA than three rapid ones (mean 5%).     

Biological monitoring of TDI-derived amines in polyurethane foam production

BACKGROUND: Toluene diisocyanate (TDI) is used in industry in the production of flexible polyurethane foam, commonly a mixture of the 2,4- and 2,6- isomers. The production process may lead to exposure to diisocyanates which are associated with respiratory disease. A method has been available for the determination of TDI biomarkers in urine for some years. AIMS: To explore the usefulness of urinary toluenediamine (uTDA) in assessing whether dermal absorption of diisocyanates makes a significant contribution to a worker's total exposure. METHODS: Twenty-six workers took part in the study. Thirteen workers whose duties brought them into physical contact with uncured polyurethane foam during their shift (handlers) were compared to a control group of 13 workers in the same block plant environment had no physical contact with uncured foam on the day that sampling took place (non-handlers). Creatinine-adjusted uTDA levels in the two groups were compared across a work shift. RESULTS: Both groups of workers were exposed to similar levels of airborne TDI. Ten handlers were found to have TDA in post-shift urine samples above detection limits compared with two non-handlers (P < 0.05). No clear relationship was found between the level of airborne TDI exposure and post-shift uTDA. CONCLUSIONS: uTDA provides a useful indication of the contribution which skin absorption makes to total TDI exposure. The results suggest that skin protection when handling uncured polyurethane foam may not receive sufficient consideration.     

Biological monitoring of occupational exposure to toluene diisocyanate

Summary The study validated the use of urinary toluene diamine (TDA) in postshift samples as an indicator of preceding 8-h exposure to toluene diisocyanate (TDI). Nine workers exposed in TDI-based polyurethane foam production were studied. Their exposure levels varied in 8-h time-averaged samples from 9.5 to 94 g/m³. The urinary TDA concentrations varied from 6.5 to 31.7g/g creatinine and they were linearly related to the atmospheric TDI levels. Approximately 20% of TDI is metabolized to diamines but their specificity is remarkable to the extent that by analysis for the 2,4- and 2,6-diamino isomers an idea of the percutaneous absorption may be had.     

Urinary hexane diamine as an indicator of occupational exposure to hexamethylene diisocyanate

The occupational exposure of 19 men to hexamethylene diisocyanate (HDI) vapour was monitored during one 8-h shift. It ranged from 0.30 to 97.7 μg/m³. This was compared with the urinary output of hexane diamine (HDA) liberated by acid hydrolysis from its conjugates in post-shift samples. The excretion varied from 1.36 to 27.7 μg/g creatinine, and there was a linear association of HDI air concentration with urinary HDA excretion. The validity of the urinary analysis was confirmed by simultaneous blind analysis in another laboratory. The results had an excellent linear concordance. Thus, it seems that while the gas chromatographic-mass spectrometric detection method requires sophisticated apparatus, the results are very useful to occupational health practices. A biological exposure index limit of 19 μg HDA/g creatinine in a post-shift urine specimen is proposed as an occupational limit level of HDI monomer (time-weighted average=75 μg/m³). Most importantly, biological monitoring of HDA is sensitive enough to be used at and below the current allowable exposure limit levels.     

Biological monitoring of hexachloroethane

A small group (n=12) of military white smok munition workers provided blood plasma during a production break (S I) and after five weeks' production (S II) of a hexachloroethane (HCE)/titanium dioxide formula. Plasma was also obtained from a sex and age matched control group (n=12) and a group (n=13) of previously HCE-exposed workers, respectively. HCE in plasma (P-HCE) was determined with gas chromatography and electron capture detection. No HCE was found in the plasma samples from the two control groups. In the HCE exposed group the mean (± SD) P-HCE level increased almost two orders of magnitude from S I (0.08 t 0.14 g/l) to S 11(7.30 ± 6.04g/l) despite efforts to minimize the internal dose. Biological monitoring of HCE could be useful in occupational hygiene.     

Biological monitoring of workers exposed to ethylbenzene and co-exposed to xylene

Objective: Ethylbenzene is an important constituent of widely used solvent mixtures in industry. The objective of the present study was to provide information about biological monitoring of occupational exposure to ethylbenzene, and to review the biological limit values corresponding to the threshold limit value of ethylbenzene. Methods: A total of 20 male workers who had been exposed to a mixture of ethylbenzene and xylene, through painting and solvent mixing with commercial xylene in a metal industry, were recruited into this study. Environmental and biological monitoring were performed during an entire week. The urinary metabolites monitored were mandelic acid for ethylbenzene and methylhippuric acid for xylene. Correlations were analyzed between urinary metabolites and environmental exposure for ethylbenzene and xylene. The interaction effects of a binary exposure to ethylbenzene and xylene were also investigated using a physiologically based pharmacokinetic (PBPK) model. Results: The average environmental concentration of organic solvents was 12.77 ppm for xylene, and 3.42 ppm for ethylbenzene. A significant correlation (R²=0.503) was found between environmental xylene and urinary methylhippuric acid. Urinary level of methylhippuric acid corresponding to 100 ppm of xylene was 1.96 g/g creatinine in the worker study, whereas it was calculated as 1.55 g/g creatinine by the PBPK model. Urinary level of mandelic acid corresponding to 100 ppm of ethylbenzene was found to be 0.7 g/g creatinine. PBPK results showed that the metabolism of ethylbenzene was highly depressed by co-exposure to high concentrations of xylene leading to a non-linear behavior. Conclusions: At low exposures, both methylhippuric acid and mandelic acid can be used as indicators of commercial xylene exposures. However at higher concentrations mandelic acid cannot be recommended as a biological indicator due to the saturation of mandelic acid produced by the co-exposure to xylene. Received: 6 March 2000 / Accepted: 10 June 2000     

Biological monitoring of environmental and occupational exposure to mercury

Summary Biological monitoring was used to assess mercury exposure from occupational and environmental sources in a group of chloralkali workers (n = 89) and in a control group (n = 75). In the control group, the median value for blood mercury (B-Hg) was 15 nmol/l, that for serum mercury (S-Hg) was 4 nmol/l and that for urinary mercury (U-Hg) was 1.1 nmol/mmol creatinine. Corresponding levels in the chloralkali group were 55 nmol/l, 45 nmol/l and 14.3 nmol/mmol creatinine, respectively. In the control group, there were statistically significant relationships between fish consumption and both B-Hg and S-Hg values (P < 0.001), whereas U-Hg correlated best with the individual amalgam burden (P < 0.01). In the chloralkali group, the mercury levels in blood and urine were significantly related to the type of work (P < 0.001) but not to the length of employment, to fish consumption or to the quantity of dental amalgam fillings. In both groups there were poor correlations between smoking or alcohol intake and the mercury levels in blood and urine. The results strongly suggest that fish is an important source of methylmercury exposure and that amalgam fillings are probably the most important source of inorganic mercury exposure among occupationally unexposed individuals. In the chloralkali group, mercury exposure from fish and amalgam was overshadowed by occupational exposure to inorganic mercury.     

Biological monitoring of 2,4-dichlorophenoxyacetic acid-exposed workers in agriculture and forestry

Summary This is a report on the application of a radioimmunossay (RIA) for the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) in biological monitoring of occupationally exposed sprayers. Urinalysis was conducted on two workers involved in spraying 2,4-D sodium salt solution with car mounted ground rigs in agriculture and on the pilot and the mixer-loader of a helicopter crew applying 2,4-D dimethylamine salt for brush control in forestry. All sprayers showed detectable quantitities of 2,4-D in morning urine samples voided over 4 or 6 days in the post-spraying period. The highest 2,4-D urinary concentrations of about 2.5 ppm could be measured in a car driver on the 3 day after exposure. The 2,4-D level in urine was much lower in forestry workers, with 0.365 ppm for the mixer-loader and 0.052 ppm for the pilot on the 1 day after spraying. Urinary 2,4-D concentrations in the agricultural study were adjusted for endogenous creatinine and, when normalized for body weight, resulted in a total 2,4-D uptake of about 5.7 or 84.9 /kg body wt. for a single spraying operation. Thus, the calculated absorbed dose was less than the NOAEL (no observed adverse effect level) of 10 mg/kg body weight per day by a large margin of safety. Further, the calculated amounts excreted seemed to be sufficiently reliable to be used for assessing the risk of human exposure to 2,4-D. However, more studies are desirable for confirmation of the association of urinary 2,4-D and creatinine excretion. Clearance occurs with a 12-h to 22-h half-life.     

低浓度MDI、TDI对作业工人部分免疫功能影响的研究

目的　观察低浓度二苯基甲烷二异氰酸酯 (MDI)、甲苯二异氰酸酯 (TDI)对机体免疫系统的作用。方法　将接触MDI或TDI的工人分为MDI接触组 (Ⅰ、Ⅱ )、TDI接触组 (Ⅲ ) ,未接触过MDI、TDI的工人为对照组。各组均测定血清IgG、IgA、IgM、IgE和白介素 2受体 (IL 2R)浓度。同时MDI组、对照组测定血清中MDI特异性IgG、IgE水平和尿中MDA浓度。结果　MDI (Ⅰ )组的IgG、IgA均值明显低于对照组 (P <0 0 1)。TDI (Ⅲ )组的IgG、IgA、IgM均值明显高于对照组 ,且IL 2R水平明显升高 (P <0 0 1)。MDI接触组 (Ⅰ、Ⅱ )血清中MDI特异性IgG、IgE的阳性率随作业工龄的延长而增高 ,尿中MDA含量与血清中MDI特异性IgG水平有很好的相关性。结论　长期接触低浓度的MDI、TDI,多数人虽无明显的过敏症状 ,但机体免疫功能受到不同影响。血清MDI特异性IgG是接触人群的敏感生物标志物     

Biological monitoring and exposure to mercury

Occupational health professionals' interest in controlling mercury (Hg) exposure, and the use of biological monitoring in this context, has been ongoing for a number of years. Evidence from urinary Hg results in a number of UK firms who have undertaken some form of biological monitoring or occupational health surveillance suggest that exposure has decreased over the last 10-15 years. This decrease precedes the establishment in the UK of an advisory biological monitoring guidance value (HGV) for urinary Hg and the production of updated medical guidance from the Health & Safety Executive on Hg exposure (MS12 1996). This latter document recommends a urinary sampling interval for urinary Hg of between 1 and 3 months, which is consistent with the reported toxicokinetics of Hg excretion, but we highlight that urinary Hg represents integrated exposure over many previous months. Mercury is a recognized nephrotoxin and MS12 1996 mentions the use of regular dipstick protein estimations. We review our experience of investigating proteinuria and enzymuria in a large-scale cross-sectional occupational study. The incidence of Hg-induced renal disease is probably very rare at current exposure levels. Therefore acceptance of a high false-positive rate of proteinuria not related to Hg exposure needs to be considered in any urinary protein testing regime of Hg workers. The establishment of an HGV for urinary Hg has raised questions about the uncertainty associated with a urinary Hg result, including factors such as diurnal variation, whether urine correction by creatinine or specific gravity is preferable and the possibility of non-occupational sources of Hg contributing significantly towards breaching the HGV. Correction of urinary Hg results by creatinine or specific gravity and the use of a fixed sampling time, such as the beginning or end of the day, substantially reduce the uncertainty in a urinary Hg measurement. But even with good laboratory precision, an individual with a true urinary Hg excretion of 20 nmol/mmol creatinine could supply urine samples of between 14 and 26 nmol/mmol creatinine. The influence of dietary sources in the UK contributing to urinary Hg values approaching or exceeding the HGV is unlikely. The use of tribal or ethnic cosmetics and remedies needs to be considered if a urinary Hg result looks inappropriately high, as some such preparations have been found to contain Hg and can be absorbed through the skin. The ability of excessive chewers or teeth grinders who have a large number of dental amalgam fillings to breach the urinary HGV in the absence of substantial occupational Hg exposure has been reported in a few Scandanavian studies. We report here a likely case of this phenomenon. Since the establishment of the HGV, our biological monitoring Hg data from a number of industry sectors using inorganic or metallic Hg have suggested that a minority of samples (13%) are still greater than the HGV.     

Assessment and control of exposures to polymeric methylene diphenyl diisocyanate (pMDI) in spray polyurethane foam applicators

In this work we characterize personal inhalation and dermal exposures to diphenyl methane diisocyanate (MDI) and other species in polymeric MDI (pMDI) formulations during spray polyurethane foam (SPF) insulation at 14 sites in New England. We further assess the adequacy of current workplace practices and exposure controls via comparative urinary biomonitoring of the corresponding methylene diphenyl diamine (MDA) pre- and post-shift. MDI and pMDI are potent dermal and respiratory sensitizers and asthmagens, strong irritants of the skin, eyes, and the respiratory tract, and may cause skin burns. This study is the first comprehensive report to-date on the work practices, inhalation and dermal exposures to isocyanates and effectiveness of existing controls during SPF applications.Breathing zone exposures to 4,4′ MDI (n = 31; 24 sprayers, 7 helpers) ranged from 0.9 to 123.0 μg/m3 and had a geometric mean (GM) of 13.8 μg/m3 and geometric standard deviation (GSD) of 4.8. Stationary near field area samples (n = 15) were higher than personal exposures: GM, 40.9 (GSD, 3.9) μg/m3, range 1.4–240.8 μg/m3. Sixteen percent of personal air samples and 35% of area samples exceeded the National Institute for Occupational Health and Safety's (NIOSH) full shift recommended exposure limit (REL) of 50 μg/m3, assuming zero exposure for the unsampled time. 4,4′ MDI load on the glove dosimeters had a GM of 11.4 (GSD 2.9) μg/glove pair/min, suggesting high potential for dermal exposures. Urinary MDA had a GM of 0.7 (GSD, 3.0) μmol MDA/mol creatinine (range, nd-14.5 μmol MDA/mol creatinine). Twenty-five % of urine samples exceeded the Health and Safety Executive (HSE) biological monitoring guidance value (BMGV) of 1 μmol MDA/mol creatinine. We further report on field observations regarding current exposure controls, discuss implications of these findings and opportunities for improving work practices to prevent isocyanate exposures during SPF insulation.     

Determination of toluene diisocyanate in air by HPLC and band-tape monitors

Summary An improved HPLC method was developed for determining the atmospheric concentration of toluene diisocyanate (TDI). 1-(2-pyridyl)-piperazine in toluene was used as reagent absorber solution together with reversed phase chromatography and a simple efficient buffer system (0.1 trifluoroacetic acid - acetonitrile, 85:15%) in an isocratic elution mode. The values for atmospheric TDI concentration obtained with two continuous band-tape monitors were checked using the values from HPLC as reference. Under identical experimental conditions the two instruments (both model 7005) gave readings varying by more than 100%. At low humidity the band-tape values were considerably lower than the HPLC values. At an absolute humidity of 11.7 gH₂O/m³ (58% relative humidity) the value from instrument 1, but not instrument 2, agreed with those from HPLC. The values obtained with band-tape divices in the continuous monitoring of TDI concentration in places of work, or epidemiological studies, should be assessed with caution. HPLC offers a useful reference method for monitoring the accuracy of such devices.     

Biological monitoring of styrene exposure and possible interference of acetone co-exposure

 The object of this study is the evaluation of some of the toxicokinetic effects of exposure to low concentrations of styrene, and the possible influence of simultaneous exposure to acetone. To this end we studied 19 workmen simultaneously exposed to both solvents. During a week of 4-h work shifts, the workmen underwent daily personal environmental monitoring and the collection of urine samples, at both the beginning and the end of the work period, for the determination of mandelic acid (MA) and phenylglyoxylic acid (PGA). The presence of the solvents in the atmosphere was evaluated using passive personal monitoring and gas chromatography. Average exposure to styrene and acetone were respectively 72.2 mg/m³ and 225.7 mg/m³. MA and PGA were quantified by high-performance liquid chromatography (HPLC). The daily urinary concentration averages, both at commencement and at the end of work shifts, of both the metabolites studied and of the sum of the two, were in statistically significant linear correlation with the average daily styrene exposure. Concentrations of MA and PGA in urine samples collected at the start of the work shift averaged 61.5 mg/g creatinine and 45.2 mg/g creatinine respectively, representing 41% and 72% of those at the end of the work shift which were 148.3 and 62.6 mg/g creatinine, respectively. With equal exposure to styrene, the average urinary concentrations of MA and PGA at both the beginning and end of the work shift increased significantly (P<0.001) during the working week. Moreover, we found that with equal exposure to styrene, urinary excretion of MA, PGA and MA+PGA at the end of the shift was inversely correlated with the intensity of acetone exposure (r=0.4659, 0.3410 and 0.4542 respectively, P<0.001). In conclusion, these results express slower urinary kinetics of styrene metabolites than is usually described in the literature, and favor a tendency to accumulate MA and PGA in the organism as a consequence of the retardation of urinary excretion kinetics. Acetone apparently represents one of the determining factors in this interference. Received: 3 July 1996/Accepted: 20 September 1996     

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     

Biological monitoring of exposure to pyrethrins and pyrethroids in a metropolitan population of the Province of Quebec, Canada

Pyrethroid and pyrethrins are neurotoxic insecticides widely used to control agricultural and domestic insect pests. The general population is potentially chronically exposed through food consumption, but the actual exposure is poorly documented in Canada. This study aimed at obtaining an indication of the absorption of those insecticides in residents of Montreal Island, the largest metropolitan area of the Province of Quebec, Canada. We randomly recruited 120 adults and 120 children aged 18–64 and 6–12 years old, of which 81 adults and 89 children completed the study. The absorption of pyrethroids and pyrethrins was assessed through measurements of six urinary metabolites: chrysanthemum dicarboxylic acid (CDCA), cis- and trans-2,2-(dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acids (cDCCA and tDCCA), cis-2,2-(dibromovinyl)-2,2-dimethylcyclopropane carboxylic acid (DBCA), 3-phenoxybenzoic acid (PBA) and 4-fluoro-3-phenoxybenzoic acid (FPBA). Metabolites were determined in 12-h urine collections for children and 2-consecutive 12-h collections for adults, and were analyzed by gas-chromatography/mass spectrometry. In both adults and children, the relative distribution of the various metabolites was as follows: tDCCA>PBA>cDCCA>CDCA>DBCA>FPBA. In adults, median (95th percentiles) cumulative amounts of these metabolites were 12.0 (231.1), 8.2 (177.9), 5.0 (110.1), 0.3 (8.2), 0.1 (4.7) and 0.1 (0.5) pmol/kg bw, respectively, in nighttime 12-h urine collections. Corresponding values in children were 12.6 (207.7), 10.2 (73.2), 5.1 (59.6), 2.1 (14.2), 0.1 (4.9) and 0.1 (0.8) pmol/kg bw. The main metabolites observed are indicative of exposure mainly to permethrin and cypermethrin and amounts absorbed are in the same range in adults and children. The distribution levels of the main metabolites in our sample also appeared similar to those reported in the US population.