Perrine Hoet

Lung exposure to nanoparticles modulates an asthmatic response in a mouse model

The aim of this study was to investigate the modulation of an asthmatic response by titanium dioxide (TiO2) or gold (Au) nanoparticles (NPs) in a murine model of diisocyanate-induced asthma. On days 1 and 8, BALB/c mice received 0.3% toluene diisocyanate (TDI) or the vehicle acetone–olive oil (AOO) on the dorsum of both ears (20 &mgr;L). On day 14, the mice were oropharyngeally dosed with 40 &mgr;L of a NP suspension (0.4 mg·mL−1 (∼0.8 mg·kg−1) TiO2 or Au). 1 day later (day 15), the mice received an oropharyngeal challenge with 0.01% TDI (20 &mgr;L). On day 16, airway hyperreactivity (AHR), bronchoalveolar lavage (BAL) cell and cytokine analysis, lung histology, and total serum immunoglobulin E were assessed. NP exposure in sensitised mice led to a two- (TiO2) or three-fold (Au) increase in AHR, and a three- (TiO2) or five-fold (Au) increase in BAL total cell counts, mainly comprising neutrophils and macrophages. The NPs taken up by BAL macrophages were identified by energy dispersive X-ray spectroscopy. Histological analysis revealed increased oedema, epithelial damage and inflammation. In conclusion, these results show that a low, intrapulmonary doses of TiO2 or Au NPs can aggravate pulmonary inflammation and AHR in a mouse model of diisocyanate-induced asthma.

Occupational exposure to pesticides and Parkinson's disease: A systematic review and meta-analysis of cohort studies

OBJECTIVES To systematically review available cohort studies and estimate quantitatively the association between occupational exposure to pesticides and Parkinsons disease (PD). METHODS Studies were identified from a MEDLINE search through 30 November 2011 and from the reference lists of identified publications. Relative risk (RR) estimates were extracted from 12 studies published between 1985 and 2011. Meta-rate ratio estimates (mRR) were calculated according to fixed and random-effect meta-analysis models. Meta-analyses were performed on the whole set of data and separate analyses were conducted after stratification for gender, exposure characterisation, PD cases identification, geographic location, reported risk estimator and cohort study design. RESULTS A statistically significant increased risk of PD was observed when all studies were combined (mRR=1.28; 95% confidence interval [CI]: 1.03-1.59) but there was a high heterogeneity and inconsistency among studies. The highest increased risks were observed for studies with the best design, i.e. reporting PD diagnosis confirmed by a neurologist (mRR=2.56; CI: 1.46-4.48; n=4), for cohort studies reporting incidence of PD (mRR=1.95; CI: 1.29-2.97; n=3) as well as for prospective cohorts (mRR=1.39; CI: 1.09-1.78; n=6). A significant increased risk was also seen for banana, sugarcane and pineapple plantation workers (mRR=2.05; CI: 1.23-3.42; n=2). CONCLUSIONS The present study provides some support for the hypothesis that occupational exposure to pesticides increases the risk of PD.

Epidemic of liver disease caused by hydrochlorofluorocarbons used as ozone-sparing substitutes of chlorofluorocarbons.

BACKGROUND Hydrochlorofluorocarbons (HCFCs) are used increasingly in industry as substitutes for ozone-depleting chlorofluorocarbons (CFCs). Limited studies in animals indicate potential hepatotoxicity of some of these compounds. We investigated an epidemic of liver disease in nine industrial workers who had had repeated accidental exposure to a mixture of 1,1-dichloro-2,2,2-trifluoroethane (HCFC 123) and 1-chloro-1,2,2,2-tetrafluoroethane (HCFC 124). All nine exposed workers were affected to various degrees. Both compounds are metabolised in the same way as 1-bromo-1-chloro-2,2,2-trifluoroethane (halothane) to form reactive trifluoroacetyl halide intermediates, which have been implicated in the hepatotoxicity of halothane. We aimed to test whether HCFCs 123 and 124 can result in serious liver disease. METHODS For one severely affected worker liver biopsy and immunohistochemical stainings for the presence of trifluoroacetyl protein adducts were done. The serum of six affected workers and five controls was tested for autoantibodies that react with human liver cytochrome-P450 2E1 (P450 2E1) and P58 protein disulphide isomerase isoform (P58). FINDINGS The liver biopsy sample showed hepatocellular necrosis which was prominent in perivenular zone three and extended focally from portal tracts to portal tracts and centrilobular areas (bridging necrosis). Trifluoroacetyl-adducted proteins were detected in surviving hepatocytes. Autoantibodies against P450 2E1 or P58, previously associated with halothane hepatitis, were detected in the serum of five affected workers. INTERPRETATION Repeated exposure of human beings to HCFCs 123 and 124 can result in serious liver injury in a large proportion of the exposed population. Although the exact mechanism of hepatotoxicity of these agents is not known, the results suggest that trifluoroacetyl-altered liver proteins are involved. In view of the potentially widespread use of these compounds, there is an urgent need to develop safer alternatives.

Reference values and upper reference limits for 26 trace elements in the urine of adults living in Belgium.

Abstract Background: Trace elements (TEs) are ubiquitous and their potential interest for human health has been constantly expanding. Biological monitoring is generally considered to be a useful tool to assess human exposure to chemical agents in risk assessment both at occupational and environmental levels. However, the knowledge of accurate reference values, which may vary across countries or regions, is a prerequisite for correct interpretation of biomonitoring data. This study aimed at determining the reference distribution and the upper reference limit for 26 TEs (Al, As, Sb, Ba, Be, Bi, Cd, Cr, Co, Cu, In, Li, Mn, Hg, Mo, Ni, Pd, Pt, Pb, Se, Te, Tl, Sn, U, V, Zn) in the urine of the general adult population residing in Belgium. Methods: In total, 1022 adults not occupationally or extra-occupationally (mainly via hobbies, drugs) exposed to these TEs were recruited by occupational physicians and toxicologists according to an a priori selection procedure. Non-fasting spot urine samples were analyzed for 460 males and 541 females by inductively coupled plasma mass spectrometry (ICP-MS). Careful control was applied during collection, handling and analyses of the samples to avoid any contamination. Results: Globally, the results indicate that the exposure levels of the Belgian population to these TEs are low and grossly similar to those recently published by other national surveys. Conclusions: These new reference values and upper reference limits will be useful for future occupational and/or environmental surveys.

Childhood leukaemia and parental occupational exposure to pesticides: a systematic review and meta-analysis

ObjectiveTo conduct a systematic review and meta-analysis of published studies on the association between parental occupational exposure to pesticides and childhood leukaemia.MethodsStudies were identified from a MEDLINE search through 31 July 2009 and from the reference lists of identified publications. Relative risk (RR) estimates were extracted from 25 studies published between 1985 and 2008. Meta-rate ratio estimates (mRR) were calculated according to fixed and random-effect meta-analysis models. Separate analyses were conducted after stratification for study design, definition of exposure (employment in a farm/agriculture assuming exposure to pesticides versus exposure to pesticides stipulated), exposed parent, window of exposure, type of leukaemia and biocide category.ResultsNo statistically significant association between childhood leukaemia and parental occupation as farmers/agricultural workers was observed. When exposure to pesticides was stipulated, positive associations were reported for maternal exposure for all studies combined (mRR: 1.62; 95% CI: 1.22–2.16), in all exposure windows considered and for acute non-lymphocytic leukaemia (ANLL). There was no association with paternal exposure when combining all studies (mRR: 1.14; 95% CI: 0.76–1.69). However, significant increased risks were seen for paternal exposure, in some exposure windows as well as for the biocide category.ConclusionsThe strongest evidence of an increased risk of childhood leukaemia comes from studies with maternal occupational exposure to pesticides. The associations with paternal exposure were weaker and less consistent. These results add to the evidence leading to recommend minimizing parental occupational exposure to pesticides. Our findings also support the need to rely more on studies that clearly stipulate exposure to pesticides rather than those that assume pesticide exposure because of farm/agriculture employment.

Residential exposure to pesticides and childhood leukaemia: A systematic review and meta-analysis

OBJECTIVE To conduct a systematic review of published studies on the association between residential/household/domestic exposure to pesticides and childhood leukaemia, and to provide a quantitative estimate of the risk. METHODS Publications in English were searched in MEDLINE (1966-31 December 2009) and from the reference list of identified publications. Extraction of relative risk (RR) estimates was performed independently by 2 authors using predefined inclusion criteria. Meta-rate ratio estimates (mRR) were calculated according to fixed and random-effect models. Separate analyses were conducted after stratification for exposure time windows, residential exposure location, biocide category and type of leukaemia. RESULTS RR estimates were extracted from 13 case-control studies published between 1987 and 2009. Statistically significant associations with childhood leukaemia were observed when combining all studies (mRR: 1.74, 95% CI: 1.37-2.21). Exposure during and after pregnancy was positively associated with childhood leukaemia, with the strongest risk for exposure during pregnancy (mRR: 2.19, 95% CI: 1.92-2.50). Other stratifications showed the greatest risk estimates for indoor exposure (mRR: 1.74, 95% CI: 1.45-2.09), for exposure to insecticides (mRR: 1.73, 95% CI: 1.33-2.26) as well as for acute non-lymphocytic leukaemia (ANLL) (mRR: 2.30, 95% CI: 1.53-3.45). Outdoor exposure and exposure of children to herbicides (after pregnancy) were not significantly associated with childhood leukaemia (mRR: 1.21, 95% CI: 0.97-1.52; mRR: 1.16, 95% CI: 0.76-1.76, respectively). CONCLUSIONS Our findings support the assumption that residential pesticide exposure may be a contributing risk factor for childhood leukaemia but available data were too scarce for causality ascertainment. It may be opportune to consider preventive actions, including educational measures, to decrease the use of pesticides for residential purposes and particularly the use of indoor insecticides during pregnancy.

Parental occupational exposure to pesticides as risk factor for brain tumors in children and young adults: A systematic review and meta-analysis

OBJECTIVE To examine the potential association between parental occupational exposure to pesticides and the occurrence of brain tumors in children and young adults. METHODS Studies identified from a MEDLINE search through 15 January 2013 and from the reference lists of identified publications were submitted to a systematic review and meta-analysis. Relative risk estimates were extracted from 20 studies published between 1974 and 2010. Most of the retrieved studies involved farm/agricultural jobs. Summary ratio estimates (SR) were calculated according to fixed and random-effect meta-analysis models. Separate analyses were conducted after stratification for study design, exposure parameters, disease definition, geographic location and age at diagnosis. RESULTS Statistically significant associations were observed for parents potentially exposed to pesticides in occupational settings and the occurrence of brain tumor in their offspring after combining all case-control studies (summary odds ratio [SOR]: 1.30; 95%: 1.11, 1.53) or all cohort studies (summary rate ratio [SRR]: 1.53; 95% CI: 1.20, 1.95). Significantly increased risks were seen for prenatal exposure windows, for either exposed parent, for exposure defined as to pesticides as well as by occupational/industry title, for astroglial brain tumors and after combining case-control studies from North America or cohort studies from Europe. CONCLUSIONS This meta-analysis supports an association between parental occupational exposure to pesticides and brain tumors in children and young adults, and adds to the evidence leading to the recommendation of minimizing (parental) occupational exposure to pesticides. These results must, however, be interpreted with caution because the impact of work-related factors others than pesticide exposure is not known.

Base Compositions and Homologies of Deoxyribonucleic Acids of Corynebacteria Isolated From Human Leprosy Lesions and of Related Microorganisms

The deoxyribonucleic acids (DNAs) of 25 strains of leprosy-derived corynebacteria (LDC)—non-acid-fast, gram-positive bacteria independently isolated from human leprosy lesions and propagated in axenic culture—were purified and analyzed. The guanine plus cytosine content, by buoyant density determination, was 54 to 59 mol% for most LDC strains, a range that corresponds to that (50 to 60 mol%) of corynebacteria which multiply in animal cells. These values were checked by chromatographic analyses of acid digests of the DNAs. The taxonomic position of the LDC as determined by DNA base composition was confirmed by the results of the corynomycolic acid determinations of the cell walls of the LDC. The results of the hybridization of the DNAs from the LDC strains suggest the occurrence of two high-homology groups, in which most of the strains were accommodated. In contrast, little homology was observed between the DNAs of the LDC and the reference corynebacteria employed. From these data, it can be inferred that the LDC represent a homogeneous and unique cluster of organisms within the genus Corynebacterium, more specifically within the group of corynebacteria pathogenic for humans.

Development of a method to monitor low molecular mass hydrocarbons in exhaled breath of man: preliminary evaluation of its interest for detecting a lipoperoxidation process in vivo

Low molecular mass hydrocarbons, particularly ethane and pentane, have been measured in expired air of man. The air is collected into 5-10 l polyamide bags. After removal of water vapour and CO2, the hydrocarbons are concentrated on a silicagel column kept at 0 degree C. The column desorption is carried out at 290 degrees C, and the gases are analysed by gas chromatography. A slight but statistically significant increased pentane production was detected in cirrhotic patients.

Elevated blood lead levels and sources of exposure in the population of Kinshasa, the capital of the Democratic Republic of Congo

The objective of this study was to determine blood lead levels (BLLs) and the possible sources of exposure in the population of Kinshasa, the capital of the Democratic Republic of Congo. A cross-sectional survey was carried out from January to May 2008 in a representative sample of the Kinshasan population. BLL was measured in 275 individuals (53.4% women) aged 1–70 years in the urban area of Kinshasa and from 60 additional subjects in the rural area. Pb was also determined in environmental specimens (air and soil, indoor and outdoor). BLL in the study population ranged from 2.9 to 49.3 μg/dl (median, 9.9 μg/dl). The median BLL among children aged <6 years was 11.5 μg/dl (range: 3.0–37.8 μg/dl). Of these children, 71% had elevated BLL (≥10 μg/dl) and 22% had BLL ≥20 μg/dl. The proportion of elevated BLL (≥10 μg/dl) was higher for children aged <3 years than for children aged 3 to 5 years (97% vs 56%). A higher prevalence of elevated BLL was observed in urban compared with rural children (71% vs 20%). Significantly higher BLLs were also found in children whose mother consumed fired clay during pregnancy. Residential informal activities in the recycling of car batteries also contributed to elevated BLL in children. The elevated background of Pb exposure in the Kinshasan population indicates a public health issue that requires corrective actions. Pb-contaminated dust and air in childrens home is an issue of public health concern. The use of leaded gasoline and the activities of car battery recycling in certain residences appear to constitute the main sources of exposure in the city of Kinshasa. The traditional use of fired clay for the treatment of gastritis by pregnant women is another significant contributor for elevated BLL in children.