Assessment of exposure to pesticides: residues in 24 h duplicate diets versus their metabolites in 24 h urine using suspect screening and target analysis.

Human biomonitoring can add value to chemical risk assessment by reducing the assumptions regarding consumption rates, residue occurrence, and processing effects and by integrating exposures from different sources (diet, household use, environmental). However, the relationship between exposure and concentration in human matrices is unknown for most pesticides. Therefore, we conducted a pilot study to gain more insight into the qualitative and quantitative relationship between dietary intake of pesticides (external exposure) and urinary excretion (reflecting internal exposure). In this cross-sectional observational study, 35 healthy consumers aged 18-65 years from the region of Wageningen, Netherlands, collected an exact duplicate portion of their diets during 24 h. On the same day, they also collected all their urine. The duplicate diets were analyzed using target screening by GC- and LC-HRMS; each duplicate diet contained at least five, up to 21, pesticide residues. The 24 h urine samples were analyzed using LC-HRMS in a suspect screening workflow. Metabolites were tentatively detected in all 24 h urine samples, ranging from six metabolites corresponding to four pesticides up to 40 metabolites originating from 16 pesticides in a single urine sample. In total, 65 metabolites originating from 28 pesticides were tentatively detected. After prioritization and additional confirmation experiments, 28 metabolites originating from 10 pesticides were identified with confidence level 1 or 2b. Next, quantitative analysis was performed for a selection of pesticides in duplicate diets and their metabolites in 24 h urine to assess quantitative relationships. In the quantitative comparisons between duplicate diet and 24 h urine, it was found that some metabolites were already present in the duplicate diet, which may give an overestimation of exposure to the parent pesticide based on measurement of the metabolites in urine. Additionally, the quantitative comparisons suggest a background exposure through other exposure routes. We conclude that suspect screening of 24 h urine samples can disclose exposure to mixtures of pesticide on the same day in the general population. However, more research is needed to obtain quantitative relationships between dietary intake and exposure.

Urinary pesticide mixture patterns and exposure determinants in the adult population from the Netherlands and Switzerland: Application of a suspect screening approach.

INTRODUCTION: Non-occupational sources of pesticide exposure may include domestic pesticide usage, diet, occupational exposure of household members, and agricultural activities in the residential area. We conducted a study with the ambition to characterize pesticide mixture patterns in a sample of the adult population of the Netherlands and Switzerland, using a suspect screening approach and to identify related exposure determinants. METHODS: A total of 105 and 295 adults participated in the Dutch and Swiss studies, respectively. First morning void urine samples were collected and analyzed in the same laboratory. Harmonized questionnaires about personal characteristics, pesticide-related activities, and diet were administered. Detection rates and co-occurrence patterns were calculated to explore internal pesticide exposure patterns. Censored linear and logistic regression models were constructed to investigate the association between exposure and domestic pesticide usage, consumption of homegrown and organic foods, household members' exposure, and distance to agricultural and forest areas. RESULTS: From the 37 detected biomarkers, 3 (acetamiprid (-CH2), chlorpropham (4-HSA), and flonicamid (-C2HN)) were detected in ≥40% of samples. The most frequent combination of biomarkers (acetamiprid-flonicamid) was detected in 22 (5.5%) samples. Regression models revealed an inverse association between high organic vegetable and fruit consumption and exposure to acetamiprid, chlorpropham, propamocarb (+O), and pyrimethanil (+O + SO3). Within-individual correlations in repeated samples (summer/winter) from the Netherlands were low (≤0.3), and no seasonal differences in average exposures were observed in Switzerland. CONCLUSION: High consumption of organic fruit and vegetables was associated with lower pesticide exposure. In the two countries, detection rates and co-occurrence were typically low, and within-person variability was high. Our study results provide an indication for target biomarkers to include in future studies aimed at quantifying urinary exposure levels in European adult populations.

Hair as a matrix to evaluate cumulative and aggregate exposure to pesticides in winegrowers.

INTRODUCTION: Vineyard is a crop where a large number of pesticides are applied; exposure to pesticides may occur in farmers and the general population living close to the treated area. This work aimed to investigate hair as a matrix for the assessment of cumulative and aggregate exposure to pesticides in potentially exposed individuals. METHODS: Twenty agricultural workers (AW), 4 agricultural worker relatives (AR), and 5 research staff members (RS) were involved in the study. Hair samples were collected before and after the application season (PRE- and POST-EXP samples) to obtain 18 paired samples. Records with the name and the quantity of applied pesticides were obtained; twenty-seven pesticides were measured in hair by solvent extraction and LC-MS/MS. RESULTS: During the study season, AW applied 14 different pesticides with median amount ranging from 12 to 7200 g. The most popular pesticides were dimethomorph, penconazole, cyazofamid, fenamidone and quinoxyfen, applied from 94 to 69% of AW. In AW, in PRE-EXP samples the majority of used pesticides was detectable (with detection rates from 6 to 88%), with median concentrations of few pg/mg hair; in the POST-EXP samples the frequency of detected values increased (from 25 to 100%), with median concentrations up to two orders of magnitude higher. In AR, most pesticides were quantifiable only in POST-EXP samples and with lower concentration in comparison with AW; in RS, in both PRE- and POST-EXP samples only a few pesticides were quantifiable with very low levels. In AW, a linear correlation (r = 0.682 on log-transformed data, p < 0.01) was found between the total amounts of applied pesticides during the season and their concentration in hair. CONCLUSION: The study shows that the majority of assessed pesticides was incorporated into hair of AW and AR. The increased frequency of detection and level at the end of the season and the correlation between pesticide in hair and the amount of applied pesticides, reinforce the use of hair for quantitative biomonitoring of cumulative exposure to pesticides.

[Revised guideline 'prevention of cot death']. / Herziene richtlijn 'preventie wiegendood'.

There are new insights into the pathogenesis of cot death ('sudden infant death syndrome'; SIDS). Based on these new insights, the Dutch Paediatric Association and the Dutch Child and Youth Health Care Physicians have drawn up a new guideline 'Prevention of cot death', which replaces the consensus statement of 1996. The 2 major differences from the old guideline are that co-sleeping of young infants in the same bed with the parents is now actively discouraged under the age of 4 months, and that the supine sleeping position is recommended from birth on. The recommendation that lying on one side can be used during the first 2 weeks of life has now been withdrawn.

Bayesian approach to peak deconvolution and library search for high resolution gas chromatography - Mass spectrometry.

A novel probabilistic Bayesian strategy is proposed to resolve highly coeluting peaks in high-resolution GC-MS (Orbitrap) data. Opposed to a deterministic approach, we propose to solve the problem probabilistically, using a complete pipeline. First, the retention time(s) for a (probabilistic) number of compounds for each mass channel are estimated. The statistical dependency between m/z channels was implied by including penalties in the model objective function. Second, Bayesian Information Criterion (BIC) is used as Occam's razor for the probabilistic assessment of the number of components. Third, a probabilistic set of resolved spectra, and their associated retention times are estimated. Finally, a probabilistic library search is proposed, computing the spectral match with a high resolution library. More specifically, a correlative measure was used that included the uncertainties in the least square fitting, as well as the probability for different proposals for the number of compounds in the mixture. The method was tested on simulated high resolution data, as well as on a set of pesticides injected in a GC-Orbitrap with high coelution. The proposed pipeline was able to detect accurately the retention times and the spectra of the peaks. For our case, with extremely high coelution situation, 5 out of the 7 existing compounds under the selected region of interest, were correctly assessed. Finally, the comparison with the classical methods of deconvolution (i.e., MCR and AMDIS) indicates a better performance of the proposed algorithm in terms of the number of correctly resolved compounds.

[The Dutch Child Health Care guideline 'early detection of congenital heart disease in the age group 0-19 years']. / De standaard 'Vroegtijdige opsporing van aangeboren hartafwijkingen 0-19 jaar' van de jeugdgezondheidszorg.

The Dutch Child Health Care guideline on the early detection of congenital heart disease was developed according to the principles for evidence-based guideline development and contains recommendations for the conduct of the examination during routine check-ups and for referral criteria. Most congenital heart diseases can be detected in the first year of life if physicians and nurses work according to this guideline. Important early times for screening are the home visit to infants at the age of two weeks by the child health nurse and the routine check-up of infants at the age of four weeks by the child health care physician. A routine cardiac screening is carried out in every child by the nurse and the physician at times specified in the basic list of professional responsibilities. A more extensive examination is carried out when indicated. Routine cardiac check-ups are recommended until the age of four, after which they should be done only when indicated on medical grounds. A feasibility study showed that physicians and nurses can apply the guideline effectively, provided that they take part in prior specific training.

Hypoglycin A Concentrations in Maple Tree Species in the Netherlands and the Occurrence of Atypical Myopathy in Horses.

BACKGROUND: Atypical myopathy (AM) in horses is caused by the plant toxin hypoglycin A, which in Europe typically is found in the sycamore maple tree (Acer pseudoplatanus). Owners are concerned about whether their horses are in danger if they graze near maple trees. HYPOTHESIS/OBJECTIVES: To measure hypoglycin A in the most common maple tree species in the Netherlands, and to determine whether concentration of toxin is a predictor of AM in horses. METHODS: A total of 278 samples of maple tree leaves, sprouts, and seeds were classified by species. Mean concentrations of hypoglycin A were compared for the type of sample, the season and the occurrence of AM in the pasture (non-AM versus AM). Statistical analysis was performed using generalized a linear model (SPPS22). RESULTS: Almost all Acer pseudoplatanus samples contained hypoglycin A, with concentrations differing significantly among sources (P < .001). Concentrations were significantly higher in seeds from the AM group than in seeds from the non-AM group (856 ± 677 and 456 ± 358 mg/kg, respectively; P = .039). In sprouts and leaves this was not the case. Acer platanoides and Acer campestre samples did not contain detectable concentrations of hypoglycin A. CONCLUSIONS AND CLINICAL IMPORTANCE: Acer platanoides and campestre seem to be safe around paddocks and pastures, whereas almost all Acer pseudoplatanus samples contained hypoglycin A. In all AM cases, Acer pseudoplatanus was found. Despite significantly higher concentration of hypoglycin A in seeds of pastures where AM has occurred, individual prediction of AM cannot be made by measuring these concentrations because of the high standard deviation.

Skin dose measurements on patients for diagnostic and interventional neuroradiology: a multicentre study.

The present study reports on the skin dose measurements on patients undergoing diagnostic and interventional neuroradiology procedures. Grids of thermoluminescence dosemeters were attached on the head of the patient. The exposure parameters of the X-ray systems and the clinical procedures were fully documented. While for the diagnostic procedure, the dose threshold of 2 Gy for deterministic effects was not reached, this situation was much different for the embolisations. For angiography of the carotid arteries, no skin doses were measured >320 mGy. For the cerebral embolisations, maximum skin doses up to 5.4 Gy were measured. Doses to the patients varied largely between different hospitals and within the same hospital for similar procedures. On the one hand, the complexity of the pathology for interventional procedures was responsible for the large variability in dose. On the other hand, large differences in clinical protocol and technical parameters of the X-ray systems, explaining the dose variations, were also observed. A correlation was found between the maximum skin dose measured on a patient and the total dose-area product (DAP) value for cerebral embolisations. This correlation makes it possible to estimate the maximum skin dose from these DAP values and to determine a trigger level. In conclusion, management of patient doses in interventional radiology requires training, specialisation and well-documented procedure guidelines.

Determination of endocrine disruptors in water after derivatization with N-methyl-N-(tert.-butyldimethyltrifluoroacetamide) using gas chromatography with mass spectrometric detection.

The combined gas chromatographic determination of a number of hydroxyl-group containing endocrine disruptors, including 4-octylphenol, 4-nonylphenol, 2,4-dichlorophenol, pentachlorophenol, 4-tert.-butylbenzoic acid, bisphenol-A, 17beta-estradiol and 17alpha-ethynylestradiol, was investigated. Derivatization, required for sensitive determination of these compounds, was carried out using N-methyl-N-(tert.-butyldimethyltrifluoroacetamide). A number of parameters affecting the derivatization reaction, like temperature, time, matrix, solvent, and amount of reagent were studied in detail. Quantitative yields were obtained for real-life extracts after optimization, but the hormones were only mono-substituted. Both solid-phase extraction (SPE) and liquid-liquid extraction were studied as extraction methods, with emphasis on SPE material and effect of pH. Recoveries and RSD for analysis of surface water samples were 58-106 and 6-16% (n=4), respectively, when using SPE, and 109-117 and 6-14% (n=6) when using liquid-liquid extraction. The method developed allows routine analysis of surface water for traces of endocrine disruptors. The limits of detection of were 4-6 ng/l but higher for the hormones.

Determination of polar organophosphorus pesticides in aqueous samples by direct injection using liquid chromatography-tandem mass spectrometry.

It was demonstrated that four out of six of the very polar organophosphorus pesticides (OPs), i.e. acephate, methamidophos, monocrotophos, omethoate, oxydemeton-methyl and vamidothion, could not be extracted from water using commonly available SPE cartridges. In addition, GC analysis on all six compounds was found to be troublesome due to their polar and thermolabile character. This initiated the development of an alternative highly sensitive and selective method for the determination of the above mentioned very polar OPs in water, based on LC-MS. Large volume (1 ml) water samples were directly injected onto an RP18 HPLC column with a polar endcapping. The latter was essential for obtaining retention and maintaining column performance under 100% aqueous conditions during the sampling. The compounds were ionized using atmospheric pressure chemical ionization and detected on a tandem mass spectrometer operated in multiple reaction-monitoring mode. The detection limits were in the range of 0.01-0.03 microg/l. Compared to conventional GC methods, the developed LC-MS procedure is very straightforward, fast and more reliable. This application demonstrates the applicability of LC-MS for analysis of polar OPs in surface, ground and drinking water, as a more favourable alternative to GC.

Determination of daminozide in apples and apple leaves by liquid chromatography--mass spectrometry.

A straightforward and efficient method was developed for the determination of intact daminozide in apples and apple leaves. After extraction with methanol and a clean-up step using a graphitized carbon cartridge, the extract was analysed by ion-trap liquid chromatography-tandem mass spectrometry (LC-MS-MS) using atmospheric pressure chemical ionisation in the positive ion mode. Recoveries for apple were 98-102% with a R.S.D. < or = 11% (n = 6) and for leaves were 112-116% with a R.S.D. < or = 18% (n = 6). The limits of detection were 0.008 and 0.02 mg/kg for apples and leaves, respectively.

Acoustic parameters of ocular tissues.

The sound velocity and the impedance of animal eyes and human eyes are measured by high frequency RF echograms (10 MHz) using a digital computer. The results are compared to literature data from 1955 to 1965, which were obtained with completely different techniques. The pig's eye appears to be a good animal model for the human eye in ultrasonic experiments. The reflectivity levels predicted from the impedance values correspond to known relative reflectivity levels obtained in clinical routine.

In vitro estimation of acoustic parameters of the liver and correlations with histology.

Freshly excised human liver specimens (77) were investigated echographically and histologically. The echography was concerned with the acoustic parameters: speed of sound, impedance, several attenuation parameters, and the texture parameters: reflectivity and the signal to noise ratio. It was found that the speed and impedance, the attenuation parameters, and the texture parameters did not correlate with each other. The major correlation between histologic parameters was found for the focal collagen content to the parenchymal content (r = -0.72). The most important correlations of the acoustic parameters to the histologic ones were: attenuation slope to the focal collagen content (r = +0.63) and the reflectivity to the water content (r = -0.55). The most significantly separating acoustic parameters in the comparison of normal livers from focal tumours were found to be the speed, the attenuation slope, the reflectivity, and the signal to noise ratio. A Fisher discriminant analysis revealed a specificity of 91% and a sensitivity of 83% of the separation of tumours from normals when the speed of sound and two parameters of the frequency dependence of the attenuation were considered.

Determination of chlormequat in pears by liquid chromotagraphy/mass spectrometry.

A straightforward and reliable method was developed for the determination of chlormequat in pears by liquid chromatography/mass spectrometry (LC/MS). Water and methanol were compared as extraction solvents. Because no significant differences in extraction efficiency or repeatability were found, water was chosen as the extraction solvent. The extracts were analyzed without cleanup by either an ion-trap liquid chromatograph/mass spectrometer in the single MS mode or a triple-quadrupole instrument in the MS/MS mode, using electrospray ionization. Both instruments were equally suitable for quantitation and confirmation of identity. Recoveries were 76-103%, and reproducibility was < or = 12%. The lowest detection limit (0.007 mg/kg) was obtained with the triple-quadrupole instrument in the MS/MS mode.

[Stereotactic radiosurgery with adjusted linear accelerator for cerebral arteriovenous malformations: preliminary results in the Netherlands]. / Stereotactische radiochirurgie met aangepaste lineaire versneller voor cerebrale arterioveneuze malformaties: eerste ervaringen in Nederland.

OBJECTIVE: To assess the effects of stereotactic radiosurgery of a cerebral arteriovenous malformation (AVM). DESIGN: Prospective. METHOD: In November 1991-December 1995 linear acceleration radiosurgery was performed on 29 patients for their 30 cerebral AVMs in the University Hospital Vrije Universiteit, Amsterdam, the Netherlands. There were 15 females and 14 males with a mean age of 37.1 years (range: 13-58). Generally one isocentre was used and 15 Gy was given to the margins of the AVM at the 80% isodose. The mean target volume was 2.4 ml (range; 0.5-8.2). After 6 months, one year and thereafter every year, neurological and MRI-controls took place, in the outpatient ward. Angiography was performed after an average of 35 months (range: 24-70) to check if the AVM had obliterated. RESULTS: Angiographic post-treatment results were available in 27 patients and MRI information in one. Angiographic obliteration occurred in 20 patients (71%). No permanent radiation-induced neurological deficit was seen, nor did any hemorrhage occur during the interval between irradiation and obliteration.

[The guideline 'Detection of visual disorders at the age of 0-19' from the Dutch Association of Child Health Care]. / De standaard 'Opsporing visuele stoornissen 0-19 jaar' van de jeugdgezondheidszorg.

The child health-care guideline 'Detection of visual disorders at the age of 0-19' draws attention to the importance of early detection of visual disorders and provides guidelines to child health-care workers for detecting disorders during routine check-ups. Children under the age of 3 are examined by the 'Early detection of visual disorders' method. Picture charts may be used for children from the age 3 onwards. From the age of 3.5 charts which follow the Snellen principle such as the Landolt-C chart should be used. Screening for refraction after the age of 7 and screening for colour blindness are not necessary. Children born before 32 weeks of pregnancy, children with a family history of visual disorders and mentally disabled children have an increased risk of visual disorders.

[Consensus prevention of crib death. CBO (Central Guidance Organization for Peer Review)]. / Consensus preventie van wiegendood. Centraal Begeleidingsorgaan voor de Intercollegiale Toetsing.

The sudden and unforeseen death of a child in the first two years, usually happening during a sleeping period, is known as cot death. As cot death is a very tragic and dramatic experience for the family, it is important to reduce its incidence. In the period between 1972 and 1987, the number of cot deaths initially increased, but during the last decade a substantial reduction could be observed. This fluctuation can be connected with the position in which the baby is put to sleep. From 1970 the prone sleeping position was strongly recommended. Since then, the number of cot death cases increased. From 1987, a causal relationship between the prone sleeping position and cot death was suspected. As a result the prone sleeping position was strongly advised against. A reduction of cot death cases was then observed. By now, the role of many other factors in cot death has been perceived. The risk of cot death is increased if these factors act at the same time. Some of these factors that promote cot death come from the child's environment and can be influenced when kept in mind. Apart from the prone or side sleeping position, heat congestion, unsafe bed material and smoking in the presence of the child substantially increase the risk of cot death. The main recommendations of the committee which drew up the Dutch consensus report on prevention of cot death are therefore aimed at avoiding the above mentioned risk factors. Continuation of research is necessary to further reduce the current number of some 50 cases of cot death which happen yearly in the Netherlands.

[Prevention of food-borne diseases in the Netherlands. Are we on the right course?]. / Preventie van door voedsel overgebrachte ziektes in Nederland. Zijn wij op de goede weg?

It is estimated that in the Netherlands several hundreds of thousands of patients are affected with food-borne diseases or poisoning each year. Though the symptoms are usually mild and mortality is low, the financial impact on society is enormous. The consumer is hardly aware of this fact and the--substantial--government efforts to achieve prevention are not very effective. In view of the present state of science, it should be possible to ensure the consumer of safe food on the market, which may be eaten without any risk after sound preparation. The origin, magnitude and effects on society of this complex problem are studied in the present review. An attempt is made to evaluate the possibilities of reducing the morbidity of food-borne diseases, regarded by the World Health Organization as the most important problem in public health after diseases of the respiratory tract in the coming decades. Particular attention is paid to the role to be played by the authorities in these efforts to reduce morbidity.

A new CoDNA-ase spot plate method for the detection of coagulase and DNA-ase activity of staphylococci.

A new method for the determination of the coagulase and DNA-ase activity of staphylococci is described. The method enables the analyst to test large numbers of strains for this microorganism without the loss of time involved in the conventional technique.

[Staphylococci in cheese made from raw milk. (author's transl)]. / Staphylococcen in kaas bereid uit rauwe melk

The presence of markedly varying numbers of coagulase-positive staphylococci per gram (less than 10(2) -- greater than 10(6)) of cheese made from raw milk is reported. In twenty cases, the strains isolated from the cheese were examined for their ability to produce toxins. Eight strains were found to produce toxin A, no toxin being isolated from cultures of the twelve other strains. In two cases, the studies were done because of food poisoning which had probably been caused by the cheese. The number of staphylococci was more than 10(6) in one case (cheese about four weeks old) and approximately 1.5 x 10(4) in another (matured cheese). Subsequent studies showed that rather large amount of enterotoxin A were present in the second cheese. The first cheese was not examined for the presence of toxin.