Biological monitoring of exposure to 1,5–naphthalene diisocyanate and 4,4’-methylenediphenyl diisocyanate

Objectives: Biological monitoring of occupational sensitizers, such as 1,5-naphthalene diisocyanate (NDI) and 4,4’-methylenediphenyl diisocyanate (MDI) is of high importance. In this study, 1,5-naphthalenediamine (NDA) and 4,4’-methylenedianiline (MDA) in hydrolysed urine and plasma were evaluated as biomarkers of exposure to NDI and MDI, respectively. Methods: The air exposure to NDI and MDI was monitored for 30 exposed workers at four different plants. In parallel, urinary as well as blood plasma samples were collected. Biomarker levels were determined in hydrolysed urine and plasma by means of gas chromatography–mass spectrometry. Results: Air exposure to both MDI and NDI was correlated to their corresponding urinary and plasma biomarkers. The correlation coefficients for the associations between air and biomarker levels were in the range of 0.51–0.65 and 0.53–0.96 for MDI and NDI, respectively. For NDI, but not for MDI, the significance and correlation coefficients were increased by adjusting the urinary biomarker levels for creatinine content or density. Conclusions: Biomarker and air levels of MDI and NDI were correlated, but there was a large individual variation.     

4,4′-Methylenedianiline in hydrolysed serum and urine from a worker exposed to thermal degradation products of methylene diphenyl diisocyanate elastomers

A 45-year-old mechanic employed in blowing hot air (350°–600°C) onto the surface of a polyurethane methylene diphenyl diisocyanate (MDI) conveyer belt developed dyspnoea, rhinoconjunctivitis and fever. The illness was suggestive of an MDI-associated illness, compatible with both immediate hypersensitivity and a complement-mediated immune-complex reaction. In his serum there were specific IgG and IgE antibodies against MDI and other isocyanates, and high values of circulating immune complexes. The patient's blood and urine samples were analysed for the presence of 4,4-methylenedianiline (MDA) in hydrolysed urine and plasma. MDA was derivatized to amides using pentafluoropropionic acid anhydride (PFPA). Gas chromatography-mass spectrometry determinations were made monitoring the (M-20; M = molecular mass) fragments from the MDA-PFPA and the [²H₂]MDA-PFPA derivative. The first urine sample was obtained 22 h and the last sample 114 h after start of exposure. The urine concentrations of MDA were corrected for creatinine. The half-time of MDA was 70–80 h. The first serum sample was obtained 19 h and the last sample 1967 days after the start of exposure. The half-time was 21 days, which suggests the presence of MDI/MDA plasma protein adducts in the exposed worker.     

Biomonitoring of 4,4′-methylene dianiline by measurement in hydrolysed urine and plasma after epicutaneous exposure in humans

Five healthy volunteers were dermally exposed for 1 h to 0.75–2.25 mol 4,4-methylene dianiline (MDA) dissolved in isopropanol, by use of a patchtest technique. Determination of MDA remaining in the patch units after exposure showed that a median of 28% (range 25–29%) was absorbed. By analysis of hydrolysed plasma, an initial accumulation of MDA could be shown, and then a decline. MDA was also detected in hydrolysed urine. The maximum rate of MDA excretion in urine was found 6–11 h after the onset of exposure. Within two subjects studied at three doses, the urinary excretion was proportional to the exposure. The elimination half-lives (elim-t _1/2) in plasma and urine had medians of 13 and 7 h, respectively. In eight out of nine exposures, the elim-t _1/2 was longer in plasma than in urine. Slow acetylation seemed to be associated with short elim-t _1/2 in urine. The median of total MDA amount excreted in urine during 48 h, was 33 nmol for the five subjects exposed to 0.75 mol, which corresponded to roughly 16% (range 2%–26%) of the absorbed dose while only a limited number of individuals were studied, the data still indicated that MDA in hydrolysed plasma or urine can be used for biological monitoring of occupational dermal exposure. However, the individual variation must be taken into account. Sampling should preferably be made several hours post shift. Urine is preferred before plasma at low exposures, because of its higher concentrations of MDA.     

Assessment of occupational exposure to 4,4′-methylenedianiline by the analysis of urine and blood samples

Seven workers at a work site where methylenedianiline (MDA) was used as a curing agent for an epoxy resin were studied during 4 workdays and one weekend. Internal exposure was monitored by analysis of 4,4-MDA in hydrolysed urine and blood. After acidic hydrolysis, MDA was extracted, derivatised by use of pentafluoropropionic anhydride, and determined by gas chromatography and mass spectrometry, with negative ion chemical ionization. There was wide variation of MDA concentrations in hydrolysed blood between the workers (range 10–60 nmol/l). Also, the urinary excretion rate varied considerably both between and within the individual workers (0–90 mol/h). The urinary excretion displayed some variation in relation to exposed periods. The urinary levels were linearly related to the concentrations in blood (r _s= 0.93,P = 0.02). The present results show the value of excretion of MDA in hydrolysed urine and concentrations in blood as means for the biological monitoring of MDA exposure. In this case, the exposure was probably mainly dermal, in spite of extensive protection measures.     

Exposure biomarkers and risk from gluing and heating of polyurethane: a cross sectional study of respiratory symptoms

OBJECTIVES—To define the relation between exposure to polyurethane (PUR) glue, biomarkers of exposure and effect, and work related symptoms that occur at least once a week.
METHODS—In a cross sectional study, 152 workers and 14 clerks in a factory with exposure to sprayed and heated PUR glue containing 4,4'-diphenylmethane (MDI) or 1,6-hexamethylene (HDI) di-isocyanate were examined with gas chromatography-mass spectrometry (GC-MS) for metabolites of MDI in plasma (P-MDX) and urine (U-MDX), 2,4- and 2,6-toluene di-isocyanate (TDI; P-TDX, U-TDX) and HDI in plasma and urine, specific serum IgG (S-IgG-MDI, S-IgG-HDI, and S-IgG-TDI, respectively) and IgE (S-IgE-MDI). Work related symptoms of the eyes and airways (nose or lower airways, or both), and lung function were also evaluated.
RESULTS—P-MDX was detected in 65% of the workers, U-TDX in 47%, HDX in none. Three per cent were positive for S-IgE-MDI, 33% for S-IgG-MDI, 32% for S-IgG-TDI, and 12% for S-IgG-HDI. A few clerks had metabolites, and some had antibodies. Most metabolites and immunoglobulins were slightly correlated—for example, P-MDX v S-IgG-MDI: r_s=0.21. Workers who heated glue had increased P-MDX (odds ratio (OR)=12 for a value above the median) and S-IgG-MDI (OR=3.7), sprayers P-2,4-TDX (OR=6.2) and P-2,6-TDX (OR=16). Twenty six per cent of the workers had work related symptoms of the airways, 21% from the nose, 11% from the lower airways. Spraying of glue increased the risk of work related symptoms and slightly decreased lung function. U-MDX was associated with work related symptoms from the airways (OR=3.7) and P-2,6-TDX with work related symptoms from the lower airways (OR=6.6). S-IgG-MDI was related to work related symptoms from the airways (OR=2.6).
CONCLUSIONS—There were relations between exposures to sprayed and heated PUR glue based on MDI and HDI, concentrations of metabolites of MDI and TDI in plasma and urine, specific IgG serum antibodies against MDI, TDI, and HDI, and work related symptoms.


Keywords: isocyanate; metabolites; antibodies     

Biological monitoring of workers exposed to 4,4′-methylenediphenyl diisocyanate (MDI) in 19 French polyurethane industries

OBJECTIVES: To study the range of urinary levels of 4,4'-methylenedianiline (MDA), a metabolite of methylenediphenyl diisocyanate (MDI), across factories in the polyurethane industries and to evaluate the validity of this biomarker to assess MDI occupational exposure. METHODS: Workers exposed to MDI, as well as non-occupationally exposed subjects, were studied and pre- and post-shift urine samples were collected from 169 workers of 19 French factories and 120 controls. Details on work activities and practices were collected by a questionnaire and workers were classified into three job categories. The identification and quantification of the total urinary MDA were performed by high-performance liquid chromatography with electrochemical detection (HPLC/EC). RESULTS: For all the factories, MDA was detectable in 73% of the post-shift urine samples. These post-shift values, in the range of <0.10 (detection limit)-23.60 microg/l, were significantly higher than those of the pre-shift samples. Urinary MDA levels in the control group were in the range of < 0.10-0.80 microg/l. The degree of automation of the mixing operation (polyols and MDI) appears as a determinant in the extent of exposure levels. The highest amounts of MDA in urine were found in the spraying or hot processes. The excretion levels of the workers directly exposed to the hardener containing the MDI monomer were significantly higher than those of the other workers. In addition, skin exposure to MDI monomer or to polyurethane resin during the curing step were always associated with significant MDA levels in urine. CONCLUSIONS: Total MDA in post-shift urine samples is a reliable biomarker to assess occupational exposure to MDI in various industrial applications and to help factories to improve their manufacturing processes and working practices. A biological guiding value not exceeding 7 microg/l (5 microg/g creatinine) could be proposed in France.     

Upper reference limits for biomarkers of exposure to aromatic diisocyanates

Objectives: The objectives of this study were to determine the levels of 2,4-toluenediamine, 2,6-toluenediamine, 1,5-naphthtalenediamine and 4,4-methylenediphenyldianiline in hydrolyzed urine and plasma for occupationally unexposed workers and to calculate upper reference limits (URLs). These analytes are biomarkers of exposure to 2,4-toluene diisocyanate and 2,6-toluene diisocyanate (2,4-TDI and 2,6-TDI), 1,5-naphtalene diisocyanate (NDI) and 4,4-methylenediphenyl diisocyanate (MDI), respectively. Methods: The biomarker levels were determined in urinary and plasma samples obtained from 121 occupationally unexposed workers. Based on these biomarkers levels and the biomarker levels in an occupationally exposed group of workers, URLs were calculated. The method used for these calculations was based on the receiver operator characteristic (ROC) curve method technique, and the URLs were set at the optimum of sum of sensitivity and specificity. Results: The URLs for the different diisocyanates were calculated to be in the range of 0.1–0.5 g/L. Occupationally unexposed workers had detectable biomarker levels of the diisocyanates investigated. Especially abundant was the biomarkers of MDI which were found in 97% of both urinary and plasma samples. For the other biomarkers, 0–15% of the unexposed workers had detectable levels. The detected levels were mostly close to the limit of detection (LOD), but urinary levels of biomarkers of MDI up to 60 times the LOD were found. The sensitivities and specificities for classification of the workers as occupationally exposed or not, were in the range of 88–100% and 97–100%, respectively. Conclusions: The URLs were calculated that may be applicable when screening for occupational exposure. A worker with a biomarker level above the URL will be classified as occupationally exposed. Biomarkers of aromatic diisocyanates, especially biomarkers of MDI, were present among occupationally unexposed workers, but the source and nature of the exposure is unknown.     

Exposure and nasal inflammation in workers heating polyurethane

OBJECTIVE: To test the hypothesis that exposure to thermal-degradation products of polyurethane (PUR), particularly isocyanates, induced nasal inflammation. METHODS: Thirty-eight workers -14 with a history of work-related nasal symptoms (WRS/Nose), and 15 referents without such history - exposed to sprayed and heated PUR glue, were studied with regard to biomarkers of isocyanate exposure [4,4'-diphenylmethane diisocyanate (4,4'-methylenediphenyl diisocyanate; MDI) and 2,4- and 2,6-toluene diisocyanate (TDI), determined as 4,4'-diphenylmethane (U-MDX) and 2,4- and 2,6-toluene (U-2,4 and U-2,6-TDX) diamine in hydrolysed urine and nasal lavage fluid (NAL)], inflammation [albumin; eosinophilic cationic protein (ECP); myeloperoxidase (MPO) and cells in NAL], serum IgG specific for MDI (S-IgG-MDI) and TDI (S-IgG-TDI), and nose symptoms. Nine unexposed office workers were also examined. RESULTS: The exposure to sprayed and heated PUR glue, especially when heated by gun, was associated with the presence of biomarkers of isocyanate exposure in urine; after work the levels [median (range)] in all workers were: U-MDX 0.32 (相似文献   

Concentrations of benzene in blood and S-phenylmercapturic and t,t-muconic acid in urine in car mechanics

Summary Different parameters of biological monitoring were applied to 26 benzene-exposed car mechanics. Twenty car mechanics worked in a work environment with probably high benzene exposures (exposed workers); six car mechanics primarily involved in work organization were classified as non-exposed. The maximum air benzene concentration at the work places of exposed mechanics was 13 mg/m³ (mean 2.6 mg/m³). Elevated benzene exposure was associated with job tasks involving work on fuel injections, petrol tanks, cylinder blocks, gasoline pipes, fuel filters, fuel pumps and valves. The mean blood benzene level in the exposed workers was 3.3 g/l (range 0.7–13.6 g/1). Phenol proved to be an inadequate monitoring parameter within the exposure ranges investigated. The muconic and S-phenylmercapturic acid concentrations in urine showed a marked increase during the work shift. Both also showed significant correlations with benzene concentrations in air or in blood. The best correlations between the benzene air level and the mercapturic and muconic acid concentrations in urine were found at the end of the work shift (phenylmercapturic acid concentration: r = 0.81, P < 0.0001; muconic acid concentration: r = 0.54, P < 0.05). In conclusion, the concentrations of benzene in blood and mercapturic and muconic acid in urine proved to be good parameters for monitoring benzene exposure at the workplace even at benzene air levels below the current exposure limits. Today working as a car mechanic seems to be one of the occupations typically associated with benzene exposure.     

Biomarkers of exposure, antibodies, and respiratory symptoms in workers heating polyurethane glue.

OBJECTIVES: The pathogenic basis of respiratory disorders associated with isocyanates are still obscure. One reason for this is the lack of good estimates of human exposure. In this study exposure was estimated by measurement of isocyanate metabolites in biological samples. METHODS: In a factory using isocyanate based polyurethane (PUR) glue, isocyanate concentrations in air were measured by liquid chromatography. Samples from 174 employees were analysed for metabolites of 4,4'-methylene diphenyl diisocyanate (MDI) in plasma (P-MDX) and urine (U-MDX). After hydrolysis, 4,4'-methylenedianiline was measured by gas chromatography-mass spectrometry (GC-MS). The employees were screened for work related respiratory symptoms and tested for specific immunoglobulin E (IgE) and IgG antibodies directed against isocyanate conjugated to human serum albumin. RESULTS: The time weighted isocyanate concentrations in air were low (MDI < 0.2-7; hexamethylene diisocyanate (HDI) < 0.1-0.7; 2,6-toluene diisocyanate (TDI) < 0.1 microgram/m3). All subjects had detectable P-MDX and U-MDX. There were significant associations between the estimates of exposure to thermal degradation products of an MDI based glue and P-MDX (range < or = 0.10-5.5 micrograms/l); and U-MDX (< or = 0.04-5.0 micrograms/g creatinine); in cases of heavy exposure. P-MDX and U-MDX were associated with each other (r = 0.64; P = 0.0001), work related symptoms (P-MDX: P = 0.03; Mann-Whitney U test), and serum concentrations of MDI specific IgG antibodies (r = 0.26; P = 0.0007). Unexpectedly, high P-MDX and U-MDX concentrations were also encountered in workers cutting textile (P-MDX 2.4-4.5 micrograms/l; U-MDX 0.81-3.8 micrograms/g creatinine); the reason is still unknown. Equally unexpected, there were significant negative associations between P-MDX and liver function tests. CONCLUSIONS: The results clearly show the value of biomarkers for isocyanate exposure; in particular, P-MDX is useful. Further, these results show the risk connected with thermal degradation of PUR.     

N-Methylsuccinimide in plasma and urine as a biomarker of exposure to N-methyl-2-pyrrolidone

Objective: N-Methyl-2-pyrrolidone (NMP) is a selective and powerful organic solvent. The aim of this study was to investigate whether the NMP metabolite N-methylsuccinimide (MSI) in plasma and urine can be used as a biomarker of exposure to NMP. Methods: Six healthy subjects were exposed to 10, 25, and 50 mg NMP/m³ in an exposure chamber for 8 h. The air levels were monitored by XAD-7 solid sorbent sampling, and analysed by gas chromatography (GC). Plasma and urine were sampled for two days following the exposure, and the levels of MSI were analysed by GC with mass spectrometric detection. Results: The concentration of MSI in plasma and urine rose during the exposure, and reached a peak at about 4 h after the end of the exposure. The concentration then decayed according to a one-compartment model with a half-time of approximately 8 h. About 1% of the inhaled NMP was excreted in urine as MSI. There were very close correlations between the NMP air levels and, on the one hand, the MSI concentrations in plasma collected at the end of exposure (r=0.98), or the urinary MSI concentration collected during the last 2 h of exposure (r=0.96), on the other. Conclusions: MSI in plasma or urine is applicable as a biomarker of exposure to NMP. The concentration in plasma and urine mainly reflects the exposure over one day. Received: 5 May 2000 / Accepted: 1 November 2000     

Influence of polymorphic metabolic enzymes on biotransformation and effects of diphenylmethane diisocyanate

Objectives To identify effect modification produced by genetic traits found in metabolic enzymes, to investigate how these affect the levels of different biomarkers of sprayed and thermo-degraded polyurethane (PUR) based on 4,4′-diphenylmethane diisocyanate (MDI) and to determine how associated respiratory disorders are affected. Methods Two partly overlapping groups of 141 and 158 factory employees exposed to sprayed or heated MDI-PUR glue were examined in years 0 and 2, respectively, for occurrence of polymorphisms in five genes (N-acetyltransferase NAT2 and the glutathione S-transferases GSTM1, GSTM3, GSTP1 [codon 105 and 114] and GSTT1) on the basis of the polymerase chain reaction, exposure biomarkers in plasma and urine (P- and U-MDX), by means of gas chromatography-mass spectrometry, specific serum IgG antibodies against MDI (S-IgG-MDI) by means of ELISA, total S-IgE, symptoms in the eyes, nose and lower airways as assessed by questionnaire and interview, and lung function as measured by spirometry. Results Both the GSTP1 ¹⁰⁵ isoleucine/isoleucine and GSTP1 ¹¹⁴ alanine/alanine genotypes showed higher levels of U-MDX than the other genotypes and the GSTP1 ¹¹⁴ genotype modified the P-MDX/U-MDX relationship. GSTP1 ¹⁰⁵ isoleucine/isoleucine was found to be associated with lower levels of S-IgG-MDI and fewer eye symptoms, but with an increased risk of symptoms in the airways, as well as with atopy. Presence of the GSTT1 gene resulted in somewhat lower lung function levels than did the null genotype. A slow NAT2 acetylating capacity was associated with lower P- and U-MDX and S-IgG-MDI levels, and better lung function, but a higher risk of eye and airway symptoms. Analysing the effects of combinations of the different genes provided no further information. Conclusions Although our study has clear limitations, it reveals various effect modifications produced by the GST and NAT2 genotypes. Gene-environment interactions are highly complex. Further research is needed to obtain a more comprehensive understanding of them.     

Airway symptoms and lung function in pipelayers exposed to thermal degradation products from MDI-based polyurethane.

OBJECTIVES: To study the prevalence of symptoms from the eyes and the upper and lower respiratory tract, lung function, and immunological sensitisation towards isocyanates in pipelayers exposed to thermal degradation products from methylene diphenyl diisocyanate (MDI)-based polyurethane (PUR). MATERIAL AND METHODS: 50 presently active and 113 formerly active pipelayers were examined. Also, 65 unexposed workers were investigated for comparison. The one year prevalence of symptoms and smoking history (questionnaire data), lung function (vital capacity (VC) and forced expiratory volume in one second (FEV1), and atopy (positive skin prick tests towards standard allergens) were assessed among pipelayers and controls. For the pipelayers, the presence of work related symptoms and estimates of isocyanate and welding exposure were obtained from an interview. Skin prick tests towards specific isocyanate antigens and determinations of IgE-MDI and IgG-MDI in serum were also performed. RESULTS: The prevalence of episodes (more than once a month) of irritative eye symptoms, congestion of the nose, and soreness or dryness in the throat was much higher among the PUR pipelayers than among the controls. Most of the pipelayers with symptoms reported that these had started and occurred in relation to the PUR welding tasks. Presently active pipelayers with recent high PUR exposure showed a significant reduction of FEV1 compared with the controls. The estimated reduction, adjusted for smoking, was -0.3 l (P = 0.04). There was no confounding effect of ordinary welding. None of the pipelayers showed positive skin prick reactions against the specific isocyanate antigens used, or positive IgE-MDI, and only two had increased IgG-MDI. CONCLUSIONS: The findings indicate that exposure to thermal degradation products from MDI-based polyurethane has adverse effects on the mucous membranes and airways.     

Occupational asthma follow-up — which markers are elevated in exhaled breath condensate and plasma?

Objectives

To search for optimal markers in the exhaled breath condensate (EBC), plasma and urine that would reflect the activity/severity of occupational asthma (OA) after the withdrawal from the exposure to the allergen.

Material and Methods

Markers of oxidative stress: 8-iso-prostaglandin {ie206-1} (8-isoprostane, 8-ISO), malondialdehyde (MDA), 4-hydroxy-trans-2-nonenale (HNE), cysteinyl leukotrienes (LT) and LTB₄ were determined using liquid chromatography and mass spectrometry in 43 subjects with immunological OA (49.3±11.8 years), removed from the exposure to the sensitizing agent 10.5±6.5 years ago; and in 20 healthy subjects (49.0±14.9 years). EBC was harvested both before and after the methacholine challenge test. In parallel, identical markers were collected in plasma and urine. The results were analyzed together with forced expiratory volume in one second (FEV₁), blood eosinophils, immunoglobulin E (IgE) and eosinophilic cationic protein (ECP) and statistically evaluated (Spearman rank correlation r_S, two- or one-sample t tests and alternatively Kruskal Wallis or pair Wilcoxon tests).

Results

Several parameters of lung functions were lower in the patients (FEV1% predicted, MEF25% and MEF50%, Rtot%, p < 0.001). Shorter time interval since the removal from the allergen exposure correlated with higher ECP (r_S = 0.375) and lower FEV₁%, MEF25% and MEF50% after methacholine challenge (r_S = ?0.404, ?0.425 and ?0.532, respectively). In the patients, IgE (p < 0.001) and ECP (p = 0.009) was increased compared to controls. In EBC, 8-ISO and cysteinyl LTs were elevated in the asthmatics initially and after the challenge. Initial 8-ISO in plasma correlated negatively with FEV₁ (r_S = ?0.409) and with methacholine PD₂₀ (r_S = ?0.474). 8-ISO in plasma after the challenge correlated with IgE (r_S = 0.396).

Conclusions

The improvement in OA is very slow and objective impairments persist years after removal from the exposure. Cysteinyl LTs and 8-ISO in EBC and 8-ISO in plasma might enrich the spectrum of useful objective tests for the follow-up of OA.     

Occupational exposure to cadmium and kidney dysfunction

Summary Investigations were carried out in an alkaline battery factory. The study group consisted of 102 persons and the control group of 85 persons. Cadmium in blood (Cd-B) and cadmium in urine (Cd-U), as well as ₂-microglobulin (B₂-M), retinol binding protein (RBP), amino acids in urine were determined. Exposure to cadmium was high; Cd-B and Cd-U concentrations were higher than recommended, 10 gmg/l and 10 gmg/g creat. in 65% and 56% of workers, respectively. Excretion of B₂-M and RBP in urine was higher than the accepted upper limits of 380 and 130 I g/g creat. in about 20% of the workers. A significant correlation was observed between: log Cd-U log Cd-B (r = 0.85), log B₂-M log RBP (r = 0.66), log Cd-U · log B₂- M (r = 0.52), and log Cd-U · log RBP (r = 0.55). To evaluate the admissible period of occupational exposure to cadmium, an integrated exposure index (Cd-B × years of exposure) is proposed. According to the dose-response relationship, an increase of low molecular protein excretion in urine can be expected in 10% of the cases at Cd-U amounting to 10 to 15 g/g creat. and Cd-B × years of about 300 to 400.     

Biomarkers of exposure in Monday morning urine samples as a long-term measure of exposure to aromatic diisocyanates

Purpose

Exposure to diisocyanates is a known occupational hazard. One method for monitoring occupational exposure is by analyzing biomarkers in hydrolyzed urine and plasma. The half-life of the biomarkers in plasma is about 3 weeks, and the urinary elimination is divided into one fast (hours) and one slow phases (weeks). Polymorphism in glutathione S-transferase enzymes (GST) is earlier shown to modify the metabolism. The aim of the study was to assess whether biomarkers of exposure in urine collected after two non-exposed days correlate with levels in plasma and whether they can be used as a measure for long-term exposure to aromatic diisocyanates and further whether polymorphisms in GST influenced the correlations.

Methods

Biomarkers of exposure was analyzed in urine and blood samples collected from 24 workers, exposed to at least one of toluene-, methylenediphenyl- or naphthalene diisocyanate, on a Monday morning after at least two unexposed days. Moreover, genotype was determined for 19 of the workers.

Results

The corresponding specific gravity-adjusted biomarkers in urine and plasma levels for the different diisocyanates correlated well (r between 0.689 and 0.988). When taking all samples together, the correlation coefficient was 0.926. Polymorphism in the GSTM1 genotype seemed to modify the association.

Conclusion

Urine collected after two unexposed days can possibly be used as long-term biomarker of exposure for aromatic diisocyanates.     

Prenatal molybdenum exposure and infant neurodevelopment in Mexican children

Objective

To evaluate the association between prenatal exposure to molybdenum (Mo) and infant neurodevelopment during the first 30 months of life.

Methods

We selected a random sample of 147 children who participated in a prospective cohort study in four municipalities in the State of Morelos, Mexico. The children were the products of uncomplicated pregnancies with no perinatal asphyxia, with a weight of ≥2 kg at birth, and whose mothers had no history of chronic illnesses. These women were monitored before, during, and after the pregnancy. For each of these children a maternal urine sample was available for at least one trimester of pregnancy, and urine Mo levels were determined by electrothermal atomic absorption spectrometry. Neurodevelopment was evaluated using the psychomotor (PDI) and mental development indices (MDI) of the Bayley scale. Association between prenatal exposure to Mo and infant neurodevelopment was estimated using generalized mixed effect models.

Results

The average urinary concentrations of Mo adjusted for creatinine varied between 45.6 and 54.0 µg/g of creatinine at first and third trimester, respectively. For each doubling increase of Mo (μg/g creatinine) during the third trimester of pregnancy, we observed a significant reduction on PDI (β = ?0.57 points; P = 0.03), and no effect on MDI (β = 0.07 points; P = 0.66).

Discussion

As this is the first study that suggests a potential negative association between prenatal Mo exposure and infant neurodevelopment, these results require further confirmation.     

Evaluation of occupational exposure to benzene by urinalysis

Urinary phenol determinations have traditionally been used to monitor high levels of occupational benzene exposure. However, urinary phenol cannot be used to monitor low-level exposures. New biological indexes for exposure to low levels of benzene are thus needed. The aim of this study was to investigate the relations between exposure to benzene (Abenzene, ppm), as measured by personal air sampling, and the excretion of benzene (U-benzene, ng/l),trans,trans-muconic acid (MA, mg/g creatinine), andS-phenylmercapturic acid (PMA, g/g creatinine) in urine. The subjects of the study were 145 workers exposed to benzene in a chemical plant. The geometric mean exposure level was 0.1 ppm (geometric standard deviation = 4.16). After logarithmic transformation of the data the following linear regressions were found: log (U-benzene, ng/l) = 0.681 log (A-benzene ppm) + 4.018; log (MA, mg/g creatinine) = 0.429 log (A-benzen ppm) – 0.304; and log (PMA, g/g creatinine) = 0.712 log (A-benzene ppm) + 1.664. The correlation coefficients were, respectively, 0.66, 0.58, and 0.74. On the basis of the equations it was possible to establish tentative biological limit values corresponding to the respective occupational exposure limit values. In conclusion, the concentrations of benzene, mercapturic acid, and muconic acid in urine proved to be good parameters for monitoring low benzene exposure at the workplace.     

Biological monitoring of exposure to solvents using the chemical itself in urine: application to toluene

Objective Biomonitoring of solvents using the unchanged substance in urine as exposure indicator is still relatively scarce due to some discrepancies between the results reported in the literature. Based on the assessment of toluene exposure, the aim of this work was to evaluate the effects of some steps likely to bias the results and to measure urinary toluene both in volunteers experimentally exposed and in workers of rotogravure factories. Methods Static headspace was used for toluene analysis. o-Cresol was also measured for comparison. Urine collection, storage and conservation conditions were studied to evaluate possible loss or contamination of toluene in controlled situations applied to six volunteers in an exposure chamber according to four scenarios with exposure at stable levels from 10 to 50 ppm. Kinetics of elimination of toluene were determined over 24 h. A field study was then carried out in a total of 29 workers from two rotogravure printing facilities. Results Potential contamination during urine collection in the field is confirmed to be a real problem but technical precautions for sampling, storage and analysis can be easily followed to control the situation. In the volunteers at rest, urinary toluene showed a rapid increase after 2 h with a steady level after about 3 h. At 47.1 ppm the mean cumulated excretion was about 0.005% of the amount of the toluene ventilated. Correlation between the toluene levels in air and in end of exposure urinary sample was excellent (r = 0.965). In the field study, the median personal exposure to toluene was 32 ppm (range 3.6–148). According to the correlations between environmental and biological monitoring data, the post-shift urinary toluene (r = 0.921) and o-cresol (r = 0.873) concentrations were, respectively, 75.6 μg/l and 0.76 mg/g creatinine for 50 ppm toluene personal exposure. The corresponding urinary toluene concentration before the next shift was 11 μg/l (r = 0.883). Conclusion Urinary toluene was shown once more time a very interesting surrogate to o-cresol and could be recommended as a biomarker of choice for solvent exposure.     

2-Acetylfuran,a confounder in urinalysis for 2,5-hexanedione as an n-hexane exposure indicator

Summary The apparent amount of 2,5-hexanedione, a biomarker of n-hexane exposure in occupational health, in the urine of both exposed and non-exposed subjects varied not only as a function of the pH at which the urine sample was hydrolyzed but also depending on the capillary column used for gas chromatographic (GC) analysis of the urinary hydrolyzates after extraction with dichloromethane. The formation of a compound, identified by gas chromatography-mass spectrometry (GC-MS) as 2-acetylfuran, following acid hydrolysis was a major cause of confounding effects. This compound was hardly separated from 2,5-hexanedione on a capillary column such as DB-WAX, whereas separation could be achieved on a DB-1 capillary column. 2-Acetylfuran was formed when a urine sample was heated at a pH of < 2 for hydrolysis, and the amount detected in urine did not differ between exposed and non-exposed subjects, indicating that the formation of 2-acetylfuran is independent of n-hexane exposure. When urinary hydrolysis is used, hydrolysis at a pH of < 0.5, extraction with dichloromethane, and GC analysis on a non-polar capillary column are proposed to be the best analytical conditions for 2,5-hexanedione analysis in biological monitoring of exposure to n-hexane.