Trans-placental exposure of neonates to acrylamide—a pilot study

Objectives Acrylamide (AA) (CAS No 79-06-1) has most recently been identified as a food-borne toxicant generated during the heating process of starch-containing foods. It was the aim of the present study to investigate the trans-placental exposure of newborn infants to this possible human carcinogen by analysis of the specific haemoglobin adduct of AA (N-2-carbamoylethylvaline, AAV) in the blood of mothers and the corresponding umbilical cord blood of neonates as a parameter of biochemical effects.Methods We investigated the blood of 11 women advanced in pregnancy (one smoker, ten non-smokers) and the corresponding umbilical cord blood of neonates for the N-terminal haemoglobin adducts of AA (AAV) and the smoking-specific adduct of acrylonitrile (CAS No 107-13-1) (N-cyanoethylvaline, CEV). The limit of detection (LOD) was 5 pmol/g globin for AAV and 4 pmol/g globin for CEV.Results AAV could be determined in all blood samples of the mothers (median 21 pmol/g globin, range 18–104 pmol/g globin) as well as in the umbilical cord blood of neonates (median 10 pmol/g globin, range 6–43 pmol/g globin). The highest values were detected in the blood of the smoking mother and her child. CEV was detected only in the blood of the smoking mother (185 pmol/g globin) and the corresponding umbilical cord blood (69 pmol/g globin).Discussion AAV adduct levels in non-smoking mothers and neonates showed a good correlation (r=0.859). The concentration of AA adducts in the blood of neonates is approximately 50% of the adduct level found in the blood of the mother. In view of the shorter life span of neonatal erythrocytes and the lower body weight of newborn infants, the relative internal dose of AA in neonates (in microgrammes per kilogramme body weight) must be assumed to be at least equal to that of the mother. Because of the high cell-replication rates during foetal development, trans-placental exposure of neonates to AA might raise concerns. Neonates of smoking mothers take up much higher doses of AA than those of non-smoking mothers.     

Smoke and malaria: are interventions to reduce exposure to indoor air pollution likely to increase exposure to mosquitoes?

Indoor air pollution from the domestic use of biomass fuels by poor households in developing countries is known to be harmful to health, and efforts are being made to address this problem by changes in fuel type, stove technology, house design and fuel-use practices. However, anecdotal evidence suggests that smoke may play an important role by providing protection from biting insects and that efforts to reduce smoke may increase exposure, particularly to mosquitoes and malaria. This paper reviews the literature relating to the repellent effect of smoke on mosquitoes and finds that there is currently no evidence that smoke from domestic fuel use provides effective protection from mosquitoes and malaria. Given the limited number and quality of studies, this finding cannot be interpreted as conclusive. The literature relating to house ventilation and mosquito entry was also reviewed, and an association between eaves spaces and increased indoor mosquito density was noted. Additionally, literature on the effect of soot on the efficacy of insecticide-treated bed nets was considered, but no direct impact was shown. Efforts to reduce indoor air pollution remain desirable even in areas of malaria transmission.     

Is it feasible to construct a community profile of exposure to industrial air pollution?

OBJECTIVE—An epidemiological investigation to assess the validity of residential proximity to industry as a measure of community exposure.
METHODS—19 Housing estates in Teesside (population 1991: 77 330) in north east England were grouped into zones: A=near; B=intermediate; C=further from industry. With residential proximity of socioeconomically matched populations as a starting point a historical land use survey, historical air quality reports, air quality monitoring, dispersion modelling data, and questionnaire data, were examined.
RESULTS—The populations in zones A, B, and C were similar for socioeconomic indicators and smoking history. Areas currently closest to industry had also been closest for most of the 20th century. Historical reports highlighted the influence of industrial emissions to local air quality, but it was difficult to follow spatial pollution patterns over time. Whereas contemporary NO_x and benzene concentrations showed no geographical variation, dispersion modelling of emissions (116 industrial stacks, traffic, and domestic sources) showed a gradient associated with industry. The presumed exposure gradient of areas by proximity to industry (A>B>C) was evident for all of zone A and most of zones B and C.
CONCLUSIONS—It was feasible to assemble a picture of community exposure by integration of measurements from different sources. Proximity of residence was a reasonable surrogate for complex community exposure.


Keywords: exposure assessment; community exposure; industrial pollution     

Control of workers’ exposure to xylene in a pesticide production factory

Background:

Acute and chronic exposure to xylene can result in a range of negative health effects. However, xylene is widely used and emitted in the air of workplaces.

Objectives:

To evaluate xylene vapor concentrations to guide the design and evaluation of a local exhaust ventilation (LEV) system to reduce exposure in a pesticide production factory.

Method:

A real time volatile organic compound (VOC) monitor was used to determine the workers’ time-weighted average (TWA) exposure. A LEV system was designed, and then, workers’ exposure to xylene vapor was evaluated.

Results:

We found that worker’s exposure to xylene (4.7±5.5 ppm) was lower than the standards recommended by the American Conference of Governmental Industrial Hygienists (ACGIH) and the Occupational safety and health administration (OSHA). Despite the low TWA exposures, the short-term exposures for some workers were higher than STEL levels. Three canopy hoods were designed and installed with capture velocities of 0.508 m second⁻¹ and duct velocity of 10.16 m second⁻¹.

Conclusion:

We found that an exhaust ventilation system had a significantly reduced occupational exposure to xylene vapor.     

Are girls more susceptible to the effects of prenatal exposure to tobacco smoke on asthma?

BACKGROUND: Prenatal exposure to tobacco smoke through mother's smoking increases the risk of developing asthma later in life. A recent study suggested that this effect is present only in girls. We explored potential differences in susceptibility between boys and girls. METHODS: We followed all 58,841 Finnish singleton babies born in 1987 through 5 nationwide registries for 7 years and identified all cases of doctor-diagnosed asthma (ICD-9 code 493). The birth registry provided categorical information on the mother's smoking during pregnancy: no smoking (reference), low exposure (<10 cigarettes per day), and high exposure (>10 cigarettes per day). RESULTS: In girls the cumulative incidence of asthma was 0.0245 in the reference group, 0.0310 in the low maternal smoking group (risk difference = 0.0065; 95% CI = 0.0053-0.0076), and 0.0360 in the high maternal smoking group (0.0115; 0.0096-0.0133). The corresponding cumulative incidences for boys were 0.0405, 0.0501 (0.0096; 0.0089-0.0103), and 0.0522 (0.0117; 0.0091-0.0142). In logistic regression analysis adjusting for confounding, the combined effect of male sex and high maternal smoking (compared with female sex and no smoking) was 112% excess risk. This corresponded closely to what would be expected from the additive independent effects of male sex (67% excess risk) and high maternal smoking (44% excess risk). CONCLUSIONS: Effects of maternal smoking during pregnancy on the risk of developing asthma are similar in boys and girls, with no interaction on an additive scale.     

Insertion polymorphism of CYP2E1 and urinary N -methylformamide after N,N - dimethylformamide exposure in Japanese workers

Objectives: This study examined whether consideration of the *1C/*1D CYP2E1 insertion polymorphism is important for interpreting the biological monitoring of exposure to N,N-dimethylformamide (DMF) in Japanese workers. Methods: The insertion genotype, airborne DMF exposure on the last day of a work week, and NMF in urine sampled just after the last workshift of the week were determined in 44 male and female Japanese workers. Results and conclusions: The allelic frequency of this CYP2E1 polymorphism was 0.261 in this Japanese population of workers. The CYP2E1 insertion polymorphism did not contribute to NMF levels even after consideration of BMI or alcohol intake. The results indicate that CYP2E1 insertion polymorphism does not appear to be an important determinant for the interpretation of biological exposure to DMF by the measurement of urinary NMF. Received: 26 September 2000 / Accepted: 7 May 2001     

Ambient and biological monitoring of coke plant workers – determination of exposure to polycyclic aromatic hydrocarbons

OBJECTIVES: The aims of this study were to determine external and internal polycyclic aromatic hydrocarbon (PAH) exposure in a coke plant and to contribute to the evaluation of biological limit values. METHODS: Personal air sampling was carried out on a study population of 24 coke plant workers. In detail, 16 PAHs were determined, among them phenanthrene, pyrene and benzo[ a]pyrene. For the determination of internal exposure, post-shift urine samples from the workers were examined for hydroxylated metabolites of pyrene (1-hydroxypyrene, 1-OHP) and phenanthrene (1-, 2+9-, 3-, 4-hydroxyphenanthrene, 1-, 2+9-, 3-, 4-OHPhe). In both cases, approved HPLC methods were used. RESULTS: The workers were classified into three groups. The group most exposed was that on the top side of the coke oven, with a mean value of 491.2 microg/m(3) for the sum of all sixteen PAHs. The mean value at the bench side was 26.61 microg/m(3), while it was 76.18 microg/m(3) in the group of workers with no dedicated location (=complete area). Both the excretion of 1-OHP and the sum of hydroxyphenanthrenes had the highest mean levels in the top side group of workers (mean: 19.70 microg/g creatinine (crea.) and 39.18 microg/g crea.), followed by the bench-side workers (mean: 7.01 microg/g crea. and 12.95 microg/g crea.) and the whole-area workers (mean: 3.57 microg/g crea. and 8.70 micorg/g crea.). The concentrations of all urinary metabolites correlated significantly with benzo[ a]pyrene (BaP) in the air. CONCLUSIONS: According to these correlations, urinary concentrations of 8 and 11 microg 1-OHP/g crea., respectively 16 and 23 microg/g crea. for the sum of hydroxyphenanthrenes, correspond to BaP concentrations in air of 2 and 5 micorg/m(3), the German technical guiding concentration (TRK value). Our results are in line with others reported in the literature. That means that it should be possible today to define a standard of occupational hygiene and medicine in coke plants using the elimination of hydroxyphenanthrenes and hydroxypyrene in urine as markers for internal PAH exposure.     

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.     

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.     

Effects of short-term exposure to fine and ultrafine particles from indoor sources on arterial stiffness – A randomized sham-controlled exposure study

ObjectivesParticulate air pollution is linked to adverse cardiovascular effects, including arterial stiffness. The aim of the study was to investigate the effect of short-term exposure to indoor fine and ultrafine particles on augmentation index (AIx), augmentation pressure (AP), and pulse wave velocity (PWV), early signs of vascular damage.MethodsWe analyzed the association of particle emissions from typical indoor sources (candle burning - CB, toasting bread - TB, and frying sausages - FS) with changes in pulse wave analysis indices in 55 healthy adults in a randomized cross-over controlled exposure study. Particle mass concentration (PMC), size-specific particle number concentration (PNC) and lung-deposited particle surface area concentration (PSC) were measured during the 2 h exposure. AIx and AP were measured before, directly, 2, 4 and 24 h after exposure. PWV was measured directly and 24 h after exposure. We performed multiple mixed linear regression analyses of different particle metrics and AIx, AP and PWV.ResultsThe highest mean PMC was observed during FS reaching a maximum of 210 μg/m³ PM₁₀. The maximal PNC for UFP <100 nm was reached during CB with 2.3 million particles/cm³. PSC was similar across all three exposures (about 3000 μm²/cm³). Strongest associations between different particles metrics and arterial stiffness indices could be observed for UFP from CB and FS and for PMC from TB. The highest mean increase could be observed for the UFP fraction <10 nm, measured during CB, and AIx with an increase of 9.5%-points (95%-CI: 3.1; 15.9). PSC seemed to follow the pattern of PNC. PM₁₀ and PM_2.5 from TB led to clear changes in AIx with biggest increases for PM₁₀ of 5.8%-points (95%-CI: 3.2; 8.4) 2 h after exposure and for PM_2.5 of 8.1%-points (95%-CI: 2.5; 13.7) directly after exposure.ConclusionsOur study indicates effects of indoor exposure to fine and ultrafine particles on systemic arterial stiffness indices that depend on the indoor source as well as on particle metric. Differences in size-specific physical characteristics of source-specific particles might account for these differential effects. We did not observe clear and stable associations of indoor particle exposure and PWV.     

Prenatal exposure of the northern Québec Inuit infants to environmental contaminants.

The Inuit population residing in Nunavik (northern Québec, Canada) relies on species from the marine food web for subsistence and is therefore exposed to high doses of environmental contaminants such as polychlorinated biphenyls and methylmercury and to a lesser extent lead. In view of the neurotoxic properties of these substances following developmental exposure, we initiated a study on infant development in this remote coastal population. Here we report the magnitude of prenatal exposure to these contaminants and to selective nutrients in Inuit mothers and their newborns who were recruited on the Hudson Bay coast. We conducted interviews during the women's pregnancies and at 1 and 11 months postpartum and collected biological samples for mercury, lead, polychlorinated biphenyls (PCBs), and chlorinated pesticides analyses as well as selenium and N-3 polyunsaturated fatty acids (n3-PUFA). Cord blood, maternal blood, and maternal hair mercury concentrations averaged 18.5 microg/L, 10.4 microg/L, and 3.7 microg/g, respectively, and are similar to those found in the Faroe Islands but lower than those documented in the Seychelles Islands and New Zealand cohorts. Concentrations of PCB congener 153 averaged 86.9, 105.3, and 131.6 microg/kg (lipids) in cord plasma, maternal plasma, and maternal milk, respectively; prenatal exposure to PCBs in the Nunavik cohort is similar to that reported in the Dutch but much lower than those in other Arctic cohorts. Levels of n3-PUFA in plasma phospholipids and selenium in blood are relatively high. The relatively low correlations observed between organochlorine and methylmercury concentrations may make it easier to identify the specific developmental deficits attributable to each toxicant. Similarly, the weak correlations noted between environmental contaminants and nutrients will facilitate the documentation of possible protective effects afforded by either n3-PUFA or selenium against neurotoxic contaminants.     

Does body size contribute to sensitivity of bone tumor induction by radionuclide exposure?

Investigation of a possible increase in sensitivity to occurrence of radionuclide-induced skeletal malignancy with increasing body size was analyzed among 358 beagles injected as young adults with either 226Ra or monomeric 239Pu and maintained for their lifespans. Corresponding analyses were performed for about 240 other beagles injected as young adults with 90Sr, 228Ra, or 228Th. Body masses at the time of injection ranged between about 5.6 and 16 kg. Logistic regression analysis using body mass and cumulative skeletal radiation dose as the independent variables indicated that there could not be established a dependency of tumor occurrence upon body mass, although skeletal dose was found to be significantly correlated with occurrence of bone cancer. Regression analysis indicated that for any dosage group there could not be established a correlation between body mass and skeletal dose. Each dosage group having similar injected kBq kg(-1) for each nuclide was divided into 2 subgroups of equal size, one containing the less massive dogs and the other containing the more massive dogs. These subgroups within a roughly uniform value of skeletal dose-rate were compared by Fisher's Exact Test, and the less massive subgroups were combined within each nuclide for an additional, separate analysis against the combined more massive subgroups using the same method. In only one instance (the dosage group given 3607 kBq 90Sr kg(-1)) was there indicated a substantially greater tumor occurrence among dogs in the more massive subgroup (p = 0.061). However, for the group given 0.382 kBq 239Pu kg(-1) there was indicated a significant difference between subgroups, but the effect was exactly opposite to that found for the highest level 90Sr dogs in that the less massive subgroup had a higher relative tumor occurrence than the most massive (p = 0.042). For all groups with a p-value < 0.10, a possible correlation was investigated between survival and body mass at injection (since bone tumor occurrence might be a function of longevity), but a significant relationship could not be determined. No significant differences could be established between the combined more massive and the combined less massive subgroups for any radionuclide. We conclude that, for the conditions in our experiment, relative size within a species does not contribute importantly to the sensitivity (lifetime occurrence) for induction of skeletal malignancy.     

How should we assess the effects of exposure to dietary polyphenols in vitro?

Human intervention studies have provided clear evidence that dietary polyphenols (eg, flavonoids--eg, flavonols--and isoflavones) are at least partly absorbed and that they have the potential to exert biological effects. Biological activity of polyphenols is often assessed by using cultured cells as tissue models; in almost all such studies, cells are treated with aglycones or polyphenol-rich extracts (derived from plants and foods), and data are reported at concentrations that elicited a response. There are 2 inherent flaws in such an approach. First, plasma and tissues are not exposed in vivo to polyphenols in these forms. Several human studies have identified the nature of polyphenol conjugates in vivo and have shown that dietary polyphenols undergo extensive modification during first-pass metabolism so that the forms reaching the blood and tissues are, in general, neither aglycones (except for green tea catechins) nor the same as the dietary source. Polyphenols are present as conjugates of glucuronate or sulfate, with or without methylation of the catechol functional group. As a consequence, the polyphenol conjugates are likely to possess different biological properties and distribution patterns within tissues and cells than do polyphenol aglycones. Although deconjugation can potentially occur in vivo to produce aglycone, it occurs only at certain sites. Second, the polyphenol concentrations tested should be of the same order as the maximum plasma concentrations attained after a polyphenol-rich meal, which are in the range of 0.1-10 micromol/L. For correct interpretation of results, future efforts to define biological activities of polyphenols must make use of the available data concerning bioavailability and metabolism in humans.     

Worker exposure to,and absorption of,cypermethrin during aerial application of an “ultra low volume” formulation to cotton

Agricultural pilots and mixer-loaders were monitored for dermal exposure to and absorption of, the insecticide cypermethrin during aerial ultra low volume (ULV) applications in vegetable oil to cotton. Pilots were monitored for dermal exposure and mixer-loaders were monitored for exposure and systemic absorption. All mixer-loaders wore protective equipment. Potential (protected and exposed skin) exposure was 1.07 (0.26 to 2.65) mg/8 hr for pilots and 10.5 (2.50 to 23.1) mg/8 hr for mixer-loaders. Actual (exposed skin only) exposure was 0.67 (0.08 to 2.08) mg/8 hr for pilots and 2.43 (0.22 to 5.27) mg/8 hr for mixer-loaders. The exposure of pilots was predominantly of the hands, whereas that of mixer-loaders was more uniform, since their hands were protected by gloves.Absorption by mixer-loaders, determined by analysis of urinary metabolites, was 46 to 78 g cypermethrin equivalents per 3 mix-loads and 12 simulated mix-loads, respectively. This is a very small proportion of their predicted exposure levels, as measured in different mixer-loaders.This study demonstrates that exposure of pilots and mixer-loaders during aerial ULV applications of cypermethrin is minimal and that absorption of the chemical is only a very small proportion of that contacting the skin.     

Is it exposure to cigarette smoke or to smokers which increases the risk of meningococcal disease in teenagers?

BACKGROUND: Passive smoking appears to increase the risk of meningococcal disease (MD) in adolescents. Whether this effect is attributable to exposure to cigarette smoke or contact with smokers is unknown. METHODS: We conducted a prospective population-based case-control study with age, sex matched-controls in 1:1 matching. Participants were 15-19 year old with MD recruited at hospital admission in six regions (65% of the population of England) from January 1999 through June 2000, and their matched controls. Data on potential risk factors were gathered by confidential interview, including seven passive smoking variables. Factor analysis was performed to assess the dimensionality of the passive smoking exposure variables. The data were analysed with univariate and multivariate conditional logistic regression. RESULTS: 144 case-control pairs were recruited (51% male; median age 17.6). Factor analysis identified two independent factors representing passive smoking (P < 0.01), one associated with 'exposure to smoke', the other with 'smoker contact'. Only smoker contact was a significant risk factor for MD (OR = 1.8; 95% CI 1.0-3.3; P = 0.05). In multivariate analysis this factor was still associated with MD independently of potential confounders such as active smoker status and household crowding. CONCLUSION: Contact with smokers is associated with increased risk of MD in adolescents. This is more likely to be due to higher carriage rates in smokers than to exposure to smoke and emphasizes the importance of public health measures to stop smoking. In epidemiological studies that assess risk from passive smoking, exposure to smoke should be differentiated where possible from contact with smokers.     

Undergraduate medical students’ exposure to clinical ethics: a challenge to the development of professional behaviours?

CONTEXT: The objective of this research was to explore medical students' experience of challenges to their ethical knowledge and understanding in clinical practice, and to investigate their need and preference for support when faced with such challenges. METHODS: We carried out a cross-sectional survey using web-based and paper questionnaires. Questions were designed using examples of ethical challenges identified in the previous literature. The study involved 3 UK university medical schools. All incorporate ethics teaching programmes in problem-based learning curricula. Participants were 732 (30% of total) senior undergraduate medical students learning within the clinical environment. RESULTS: Students regularly experienced situations in clinical teaching settings that challenged their ethical values. Despite self-reports of good levels of confidence in their knowledge of ethical principles, medical students reported low levels of confidence in their ability to address these challenges, and perceived a need for additional support from clinical teachers. CONCLUSIONS: Complex and ethically challenging situations occur commonly in medical education. Many students feel that they do not currently access sufficient support from staff to address these. Clinical teachers were identified as the most relevant providers of guidance. The nature of medicine and its delivery makes it highly likely that medical students will come into contact with ethically challenging situations. Appropriate educational provision therefore requires medical educators to be equipped with the knowledge and the skills to engage with students' ethical concerns.