Gunnar Skarping

Urinary cotinine in children and adults during and after semiexperimental exposure to environmental tobacco smoke

Urinary cotinine (U-cotinine) as a biomarker of environmental tobacco smoke exposure was evaluated in 14 children (age 4-11 y) and in 7 adults who were exposed to environmental tobacco smoke at an air nicotine level of 110 mg/m3 for 2 h in a bus. Nicotine in air and U-cotinine were measured by gas chromatography/mass spectrometry before, during, and after the experiment. U-cotinine rose rapidly to a maximum after a median of 6 h following the end of exposure; remained at an apparent plateau for half a day; and then decreased exponentially, with a mean half-time of 19 h (95% confidence interval 18-20 h; no significant difference between children and adults). The maximum U-cotinine was higher in the children (mean = 22 mg/l) than in the adults (13 mg/l; p = .005); decreased with age among the children (r = -.74; p = .002); and increased as the estimated inhaled nicotine dose increased. Therefore, the findings of the present study showed that young children had higher U-cotinine than adults at the same experimental environmental tobacco smoke exposure, probably because they had a higher relative nicotine dose because of a higher relative ventilation rate, and possibly also because of metabolic differences; the elimination rate did not differ. The long half-time makes U-cotinine a good biomarker of environmental tobacco smoke exposure; the time of sampling is not very critical. Dilution-adjusted concentrations should be employed, and in children, preferably by density correction. A certain urinary cotinine level indicates a lower environmental tobacco smoke exposure in a small child than in an adult.

Exposure to Environmental Tobacco Smoke in the Household and Urinary Cotinine Excretion, Heavy Metals Retention, and Lung Function

The relationship between urinary levels of cotinine (U-cotinine) and arsenic (U-As), blood levels of cadmium (B-Cd), blood levels of lead (B-Pb), lung function, and questionnaire data on smoking habits were studied in 107 parents and their 46 children (7-10 y of age). There was a statistically significant relationship between the reported amount of tobacco smoked and U-cotinine levels. Nonsmokers who were married to persons who smoked had three times higher U-cotinine levels than nonsmokers whose spouses did not smoke. There was a significant association between the number of parents who smoked in the family and the U-cotinine levels of children. If only one parent smoked, maternal smoking was of greater importance than paternal smoking. There was also an association between U-cotinine and B-Cd. A study of lung function in the children revealed that vital capacity and functional residual capacity (corrected for sex, age, and height) increased as the number of parents who smoked increased. Therefore, the present study showed that (1) U-cotinine was a useful index of active smoking and environmental tobacco smoke exposure in adults and children, (2) U-cotinine was associated with the blood concentration of cadmium, and (3) environmental tobacco smoke exposure was associated with changes in lung function of children.

Assessment of environmental tobacco smoke exposure in children with asthmatic symptoms by questionnaire and cotinine concentrations in plasma, saliva, and urine

To validate a detailed questionnaire for assessment of environmental tobacco smoke (ETS) exposure by the biomarker cotinine in various media, a population-based study in the urban area of Malmö, Sweden was performed in children aged 8-13 years with and without asthmatic symptoms. There were strong correlations between urinary and saliva cotinine concentrations and also, though to a lesser extent, between these media and plasma. Even a detailed questionnaire gave only a rough picture of the ETS exposure, as indicated by the biomarkers. In a multivariate model, the most significant questionnaire-derived predictor of the cotinine levels was the maternal smoking habits; other questionnaire variables gave only a minimal explained variance. Children with a history of asthmatic symptoms had statistically significantly lower median cotinine levels in urine and saliva compared to referent children, most likely because of the antismoking information to their parents. This should be considered in epidemiological studies of ETS risks.

Passive smoking and childhood asthma. Urinary cotinine levels in children with asthma and in referents

Passive exposure to tobacco smoke was assessed in children with asthma (age 3‐15) and in referents. There was statistically significantly (P < 0.0005) higher excretion of the nicotine metabolite, cotinine, in the urine of 49 children with asthma (geometric mean 10 ng/ml) compared with 77 referents (4.8 ng/ml). Maternal smoking was statistically significantly more prevalent among the asthmatics than among the referents (relative risk = RR = 2.6, 95% Cl = 1.2‐5.3). In conclusion, the exposure to environmental tobacco smoke in asthmatic children was higher than among healthy children, indicating that passive smoking may be a predisposing and/or aggravating factor for childhood asthma.

Trace analysis of amines and isocyanates using glass capillary gas chromatography and selective detection : I. Determination of aromatic amines as perfluoro fatty acid amides using electron-capture detection

Abstract A method for the trace analysis of aromatic amines is presented. It involves derivatization of the amines to the corresponding amides by reaction with a perfluorofatty acid anhydride. The amides were separated by glass capillary gas chromatography, picogram amounts were quantitated using on-column injection and nitrogen-selective detection with a Varian thermionic specific detector. The method was applied to amines of interest from work environment health aspects and to polyurethane pyrolysis products. Detection limits were of the order 10–20 pg amine. Comparison with a recent gas chromatographic amine analysis method from this laboratory utilizing electron-capture detection was made, and differences between the two detection methods are discussed.

Determination of complex mixtures of airborne isocyanates and amines. Part 1. Liquid chromatography with ultraviolet detection of monomeric and polymeric isocyanates as their dibutylamine derivatives

An LC–UV method using dibutylamine (DBA) as derivatization reagent for airborne monomeric and polymeric isocyanates is presented. Isocyanates were collected in impingers containing 0.01 mol l–1 DBA in 10 ml of toluene. Stable isocyanate–DBA (urea) derivatives were rapidly formed in the sampling solution and the reaction was completed within 10 s. After evaporation of the solvent and excess reagent, the urea derivatives were analysed using reversed-phase LC–UV at 240 nm. Linear calibration graphs were obtained for toluene 2,4-and 2,6-diisocyanate (TDI) and methylene diphenyl-4,4′-diisocyanate (MDI) in the range 0.4–20 nmol ml–1. The overall precision for a DBA solution spiked at concentrations of 540 µg l–1 of 2,4-TDI, 540 µg l–1 of 2,6-TDI and 520 µg l–1 of 4,4′-MDI were found to be 1.1, 5.0 and 3.0%(n= 6), respectively. The detection limit was 0.5–0.8 µg m–3 for a 15 l air sample. Ratio chromatograms between λ1= 240 nm and λ2= 254 nm demonstrated an increased selectivity. Interferences from morpholine, ethanol, phenol, toluene-2,4-and 2,6-diamine, 4,4′-methylenedianiline and water were studied by spiking the sampling solution with 6.2 µmol of each chemical, corresponding to an air concentration of 10 ppm. No losses of the urea derivatives were found. Air samples of TDI were simultaneously collected with impingers containing 9-(N-methylaminomethyl)anthracene (n= 10) and DBA (n= 10). No significant differences between the results obtained with the two methods were observed. Sampling of isocyanates in the work environment based on derivatization with DBA was demonstrated to be a robust method. DBA is especially well suited for the determination of complex mixtures of airborne isocyanates.

Poor correlation between stated and found concentrations of diphenylmethane-4,4′-diisocyanate (4,4′-MDI) in petrolatum patch-test preparations

Diphenylmethane diisocyanate (MDI) is widely used in its polymeric form in the manufacturing of polyurethane products. Previous reports on MDI‐related contact allergy have shown a pattern, where patients seem to react to their own MDI‐based work material but not to commercial patch‐test preparations, which contain 4,4′‐MDI. Therefore, we performed chemical analyses of 14 commercial test preparations of 4,4′‐MDI obtained from 8 European and 4 American dermatology departments as well as 2 preparations from 2 major European suppliers of patch‐test allergens. A new method for monitoring 4,4′‐MDI in petrolatum preparations was developed and the determination of 4,4′‐MDI as the MDI‐dibutylamine derivative using liquid chromatography‐mass spectrometry was performed. None of the preparations obtained from the dermatology departments contained more than 12% of the concentration stated on the label. In most cases, 4,4′‐MDI content was only a few percentages or less of the concentration stated. 7 of the 14 preparations were analysed before the expiry date. Yet, only 1 of them, a preparation directly obtained from the supplier, came close to the concentration stated on the label. Thus, using these preparations, patients will be tested with a lower concentration than intended, leading to possible false‐negative reactions.

Capillary gas chromatographic method for the determination of complex mixture of isocyanates and amines

Abstract A capillary gas chromatographic method using nitrogen-selective detection was developed for the analysis of complex mixtures of isocyanates and amines in air. The isocyanate group was converted directly in the air sampling step into urethane by reaction with ethanol using potassium hydroxide as a catalyst. The amine group was converted into an amide using pentafluoropropionic anhydride in an extractive derivatization procedure. The complex pattern of air pollutants after thermal degradation of a polyurethane polymer, based on toluene diisocyanate (TDI) and 3,3′-dichloro-4,4′-diaminodiphenylmethane (MOCA), was investigated. Substantial amounts of amines, isocyanates and aminoisocyanates, molecules containing both an amine and an isocyanate group, were found. Consideration must be given to these findings when using current methods for isocyanate and amine determination. The detection limits for isocyanates, amines and aminoisocyanates, essentially depending on the nitrogen content of the molecule, were about equal and in the order of 40–80 fmol.

Airborne thermal degradation products of polyurethanecoatings in car repair shops

A methodology for workplace air monitoring of aromatic and aliphatic, mono- and polyisocyanates by derivatisation with di-n-butylamine (DBA) is presented. Air sampling was performed using midget impinger flasks containing 10 ml of 0.01 mol l(-1) DBA in toluene and a glass-fibre filter in series after the impinger flask, thereby providing the possibility of collecting and derivatising isocyanates in both the gas and particle phases. Quantification was made by LC-MS, monitoring the molecular ions [MH]+. Air samples taken with this method in car repair shops showed that many different isocyanates are formed during thermal decomposition of polyurethane (PUR) coatings. In addition to isocyanates such as hexamethylene (HDI), isophorone (IPDI), toluene (TDI) and methylenediphenyl diisocyanate (MDI), monoisocyanates such as methyl (MIC), ethyl (EIC), propyl (PIC), butyl (BIC) and phenyl isocyanate (PhI) were found. In many air samples the aliphatic monoisocyanates dominated. During cutting and welding operations, the highest levels of isocyanates were observed. In a single air sample from a welding operation in a car repair shop, the highest concentrations found were: MIC, 290; EIC, 60; PIC, 20; BIC, 9; PhI, 27; HDI, 105; IPDI, 39; MDI, 4; and 2,4-TDI and 2,6-TDI 140 microg m(-3). Monitoring the particle size distribution and concentration during grinding, welding and cutting operations showed that ultrafine particles (< 0.1 microm) were formed at high concentrations. Isocyanates with low volatility were mainly found in the particle phase, but isocyanates with a relatively high volatility such as TDI, were found in both the particle and gas phases.

Toxicokinetics of 2,4- and 2,6-toluenediamine in hydrolysed urine and plasma after occupational exposure to 2,4- and 2,6- toluene diisocyanate.

OBJECTIVES: To assess the toxicokinetics of 2,4- and 2,6- toluenediisocyanate (TDI) in chronically exposed subjects. METHODS: Blood and urine, from 11 workers at two flexible foam polyurethane production plants, were sampled. By gas chromatography-mass spectrometry (GC-MS) 2,4- and 2,6-toluene diamine (TDA) were measured as pentafluoropropionic anhydride (PFPA) derivatives after acidic hydrolysis of plasma (P-TDA, ng/ml) and urine (U-TDA, microgram/h). RESULTS: In one of the plants the P-2,4-TDA concentrations were 0.4-1 ng/ml before a four to five week holiday and 0.2-0.5 ng/ml afterwards. The corresponding values for P-2,6-TDA were 2-6 and 0.5-2 ng/ml respectively. In the other plant the P-2,4-TDA concentrations were 2-23 ng/ml before the holiday and 0.5-6 ng/ml afterwards and the P-2,6-TDA concentrations were 7-24 ng/ml before and 3-6 ng/ml afterwards. The P-2,4-TDA concentrations were 2-24 ng/ml before a 12 day holiday, and 1-14 ng/ml afterwards. The corresponding values for P-2,6-TDA were 12-29 and 8-17 ng/ml, respectively. The urinary elimination rates (U-TDA, microgram/h) for 2,4-TDA before the holiday were 0.04-0.54 and 0.02-0.18 microgram/h afterwards. The corresponding values for 2,6-TDA were 0.18-0.76 microgram/h before and 0.09-0.27 microgram/h after the holiday. The half life in urine ranged between 5.8 and 11 days for 2,4- and 2,6-TDA. The differences in exposure were reflected by the P-TDA concentrations. The mean half life in plasma was 21 (range 14-34) days for 2,4-TDA and 21 (16-26) days for 2,6-TDA. The TDI air concentrations varied between 0.4 and 4 micrograms/m3 in one plant and in the other between 10 and 120 micrograms/m3. CONCLUSIONS: The half life in plasma of chronically exposed workers for 2,4-and 2,6-TDA was twice as long as for volunteers with short term exposure. An indication of a two phase elimination pattern in urine was found. The first phase was related to the more recent exposure and the second, much slower one was probably related to release of TDA in urine from TDI adducts in the body.