| 1. |
- Broberg Palmgren, Karin, et al.
(författare)
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Influence of genetic factors on toluene diisocyanate-related symptoms: evidence from a cross-sectional study
- 2008
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Ingår i: Environmental Health. - 1476-069X. ; 7:15
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Tidskriftsartikel (refereegranskat)abstract
- Background: Toluene diisocyanate (TDI) is a highly reactive compound used in the production of, e. g., polyurethane foams and paints. TDI is known to cause respiratory symptoms and diseases. Because TDI causes symptoms in only a fraction of exposed workers, genetic factors may play a key role in disease susceptibility. Methods: Workers (N = 132) exposed to TDI and a non-exposed group ( N = 114) were analyzed for genotype (metabolising genes: CYP1A1*2A, CYP1A1*2B, GSTM1*O, GSTM3*B, GSTP1 1105V, GSTP1 A114V, GSTT1*O, MPO -463, NAT1*3, *4, *10, *11, *14, *15, NAT2*5, *6, *7, SULT1A1 R213H; immune-related genes: CCL5 -403, HLA-DQB1* 05, TNF-308, TNF-863) and symptoms of the eyes, upper and lower airways ( based on structured interviews). Results: For three polymorphisms: CYP1A1*2A, CYP1A1*2B, and TNF -308 there was a pattern consistent with interaction between genotype and TDI exposure status for the majority of symptoms investigated, although it did reach statistical significance only for some symptoms: among TDI-exposed workers, the CYP1A1 variant carriers had increased risk (CYP1A1*2A and eye symptoms: variant carriers OR 2.0 95% CI 0.68-6.1, p-value for interaction 0.048; CYP1A1*2B and wheeze: IV carriers OR = 12, 1.4-110, p-value for interaction 0.057). TDI-exposed individuals with TNF-308 A were protected against the majority of symptoms, but it did not reach statistical significance. In the non-exposed group, however, TNF -308 A carriers showed higher risk of the majority of symptoms ( eye symptoms: variant carriers OR = 2.8, 1.1-7.1, p-value for interaction 0.12; dry cough OR = 2.2, 0.69-7.2, p-value for interaction 0.036). Individuals with SULT1A1 213H had reduced risk both in the exposed and non-exposed groups. Other polymorphisms, showed associations to certain symptoms: among TDI-exposed, NAT1*10 carriers had a higher risk of eye symptoms and CCL5 -403 AG+AA as well as HLA-DQB1 *05 carriers displayed increased risk of symptoms of the lower airways. GSTM1, GSTM3 and GSTP1 only displayed effects on symptoms of the lower airways in the non-exposed group. Conclusion: Specific gene-TDI interactions for symptoms of the eyes and lower airways appear to exist. The results suggest different mechanisms for TDI- and non- TDI-related symptoms of the eyes and lower airways.
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| 2. |
- Broberg Palmgren, Karin, et al.
(författare)
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The GSTP1 Ile105 Val polymorphism modifies the metabolism of toluene di-isocyanate.
- 2010
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Ingår i: Pharmacogenetics & Genomics. - 1744-6872 .- 1744-6880. ; 20:2, s. 104-111
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Toluene di-isocyanate (TDI) is widely used in the production of polyurethane foams and paints. As TDI causes respiratory disease in only a fraction of exposed workers, genetic factors may play a key role in disease susceptibility. Polymorphisms in TDI metabolising genes may affect elimination kinetics, resulting in differences in body retention, and in its turn differences in adverse effects. OBJECTIVES: To analyze how genotype modifies the associations between (i) TDI in air (2,4-TDI and 2,6-TDI) and its metabolites toluene diamine (TDA; 2,4-TDA and 2,6-TDA) in hydrolyzed urine; and (ii) 2,4-TDA and 2,6-TDA in hydrolyzed plasma and 2,4-TDA and 2,6-TDA in urine. METHODS: Workers exposed to TDI were analyzed for 2,4-TDI and 2,6-TDI in air (N=70), 2,4-TDA and 2,6-TDA in hydrolyzed urine (N=124) and in plasma (N=128), and genotype: CYP1A1*2A, CYP1A1*2B, GSTA1-52, GSTM1O, GSTM3B, GSTP1 I105V, GSTP1 A114V, GSTT1O, MPO-463, NAT1*3, *4, *10, *11, *14, *15, NAT2*5, *6, *7, and SULT1A1 R213H. RESULTS: GSTP1 105 strongly modified the relationship between 2,4-TDA in plasma and in urine: ValVal carriers had about twice as steep regression slope than IleIle carriers. A similar pattern was found for 2,6-TDA. CYP1A1*2A, GSTM1, GSTP1, GSTT1, and MPO possibly influenced the relationship between TDA in plasma and urine. CONCLUSION: Our results show, for the first time, genetic modification on the human TDI metabolism. The findings suggest that GSTP1 genotype should be considered when evaluating biomarkers of TDI exposure in urine and plasma. Moreover, the results support earlier findings of GSTP1 105 Val as protective against TDI-related asthma.
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| 3. |
- Ekman, Eva, et al.
(författare)
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Determination of 5-hydroxythiabendazole in human urine as a biomarker of exposure to thiabendazole using LC/MS/MS.
- 2014
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Ingår i: Journal of Chromatography. B. - : Elsevier BV. - 1873-376X .- 1570-0232. ; 973, s. 61-67
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Tidskriftsartikel (refereegranskat)abstract
- Thiabendazole (TBZ) is widely used as a pre-planting and post-harvest agricultural fungicide and as an anthelminthic in humans and animals. TBZ is of toxicological concern, since adverse effects including nephrogenic, hepatogenic, teratogenic and neurological effects have been reported in mammals. Occupational exposure can occur among agricultural workers and the general public may be environmentally exposed to TBZ through the diet. The metabolite 5-hydroxythiabendazole (5-OH-TBZ) was chosen as biomarker of exposure to TBZ and a LC/MS/MS method for the quantification of 5-OH-TBZ in human urine was developed. The method includes enzyme hydrolysis, as 5-OH-TBZ is conjugated to glucuronide and sulphate in urine. Sample through put was optimised using 96-well plates for sample handling as well as for solid phase extraction (SPE). The method has excellent, within-run, between-run and between-batch precision between 4 and 9%. The limit of detection (LOD) of 0.05 and a limit of quantification (LOQ) of 0.13ng 5-OH-TBZ/mL urine enable detection in environmentally exposed populations. When applying the method in a general Swedish population, 52% had levels above LOD. The method was also applied in one oral and one dermal human experimental exposure study in two individuals. After oral exposure, the excretion of 5-OH-TBZ in urine was described by a two-compartment model and both the first rapid and the second slower elimination phase followed first-order kinetics, with estimated elimination half-life of 2h and 9-12h. The recoveries in urine were between 21 and 24% of the dose. Dermal exposure was described by a one compartment model and followed first order kinetics, with estimated elimination half-life of 9-18h. The recovery in urine was 1% of the administrated dose of TBZ. Although these studies are limited to two individuals, the data provide new basic information regarding the toxicokinetics of TBZ after oral and dermal exposure.
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| 4. |
- Faniband, Moosa, et al.
(författare)
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Biomarkers of Exposure to Pyrimethanil After Controlled Human Experiments
- 2019
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Ingår i: Journal of Analytical Toxicology. - : Oxford University Press (OUP). - 1945-2403 .- 0146-4760. ; 43:4, s. 277-283
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Tidskriftsartikel (refereegranskat)abstract
- Pyrimethanil (PYM) is a fungicide used pre- and post-harvest on many crops. It has a low acute toxicity but is of toxicological concern because of its antiandrogenic properties. The aim of the current work was to investigate some metabolism and estimate elimination kinetics of PYM in humans after experimental oral and dermal exposure. A liquid chromatography triple quadrupole mass spectrometry (LC-MS-MS) method was developed and validated for the analysis of PYM and its metabolite 4-hydroxypyrimethanil (OH-PYM) in human urine. The method was applied to analyze urine obtained from two volunteers experimentally exposed to PYM. The elimination of OH-PYM seemed to follow first-order kinetics and a two-phase excretion. After the oral exposure, the elimination half-life of OH-PYM in the rapid phase was 5 and 3 h for the female and male volunteer, respectively. In the slower phase, it was 15 h in both volunteers. After the dermal exposure, the half-life in the rapid phase was 8 h in both volunteers. In the slower phase, it was 30 and 20 h, respectively. About 80% of the oral dose was recovered as urinary OH-PYM in both volunteers. The dermal dose recovered as urinary OH-PYM was 9.4% and 19%, in the female and male volunteer, respectively. OH-PYM was mainly found as a conjugate of sulfonate and glucuronic acid. No free PYM was found. The analytical method showed good within-run, between-run and between-batch precision with a coefficient of variation between 6% and 12%. A limit of detection of 0.1 ng/mL and a limit of quantification of 0.4 ng/mL were achieved for both the analytes. The method was applied to biomonitor PYM exposure in populations in Sweden. OH-PYM was detected in nearly 50% and 96% of samples from the environmentally and occupationally exposed populations, respectively.
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| 5. |
- Littorin, Margareta, et al.
(författare)
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Analyser av pesticider i urin hos skånska kvinnor 2010
- 2013
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Såväl allmänbefolkning som vissa yrkesarbetande grupper exponeras för kemiska bekämpningsmedel (BM), allmänbefolkningen främst genom födan. Analys av exponeringsbiomarkörer för BM i t ex urin ger ett tillförlitligt mått på den aktuella kroppsbelastningen och utgör ett gott komplement till andra sätt att uppskatta befolkningens exponering. Arbets- och miljömedicin och Avd för Arbets- och miljömedicin i Lund har med Naturvårdsverkets stöd tidigare undersökt halter av BM i dygns- alternativt morgonurin hos olika befolkningsgrupper i Skåne. Nu har rester av BM undersökts i morgonurinprov från 128 kvinnor (43-60 år) i Skåne. Medelålders kvinnor är en grupp som konsumerar förhållandevis mycket frukt och grönt, den livsmedelsgrupp som bidrar mest till exponeringen för BM. Deltagarna besvarade också enkäter med frågor om livsstil och fyllde i en matdagbok.Vi undersökte rester i urinen av fungiciderna mankozeb, prokloraz och tiabendazol, herbiciderna 2,4-diklorfenoxiättiksyra och 4-klor-2-metylfenoxiättiksyra, insekticiderna klorpyrifos och flera pyretroider samt retarderingsmedlen klormekvat och mepikvat. Analysmetodernas detektionsgränser var mellan 0,1 och 1,0 ng/mL.Samtliga biomarkörer kunde påvisas. Särskilt anmärkningsvärt var den utbredda exponeringen för retarderingsmedel, för mankozeb och klorpyrifos. Metaboliten TCP från klorpyrifos låg också förhållandevis högt i jämförelse med vuxna och barn i andra länder (USA, Costa Rica, Nicaragua). Vi fann högre halt av TCP hos vegetarianer.Olika biomarkörer för BM förekom i litet högre halter när kvinnorna konsumerat relativt mycket grönsaker, frukt/bär, spannmålsprodukter, salladsblad eller kaffe dagen innan urinprovet. Till exempel var resterna av tiabendazol högre hos de kvinnor som intagit citrusfrukter eller bananer dagen innan. Frukten behandlas i producentlandet med tiabendazol inför lagring och transport. Som vi sett i tidigare undersökta grupper var ETU-halterna i urinproven högre hos de som konsumerat vin före provet. Modersubstansen mankozeb används frekvent vid vinodling.De univariata jämförelserna mellan olika undergrupper ger indikationer på samband men djupare penetration av materialet behövs för säkra slutsatser. Med hänsyn till att många analyser gjorts finns också en risk för slumpmässiga fynd. Sammantaget utgör en biologisk övervakning som denna ändå en bas för fortsatt förståelse av bekämpningsmedlens roll för miljön och oss människor.
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| 6. |
- Littorin, Margareta, et al.
(författare)
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Exponering för kemiska bekämpningsmedel hos landsbygdsbefolkning i Skåne 2010-11. : Rapport till Naturvårdsverket 2011
- 2011
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Såväl allmänbefolkning som vissa yrkesarbetande exponeras för kemiska bekämpningsmedel (BM), allmänbefolkning främst genom födan, särskilt färska frukter och grönsaker. Analys av exponeringsbiomarkörer för BM i t ex urin ger ett tillförlitligt mått på hela kroppsbelastningen och utgör ett gott komplement till andra sätt att uppskatta befolkningens exponering.Arbets- och miljömedicin i Lund har med Naturvårdsverkets stöd tidigare med hjälp av LC/MS/MS undersökt halter av BM i dygns- alternativt morgonurin hos befolkning i Skåne. Nu har exponeringen undersökts också hos 79 boende på landsbygden, som lämnat ett morgonurinprov. En mindre grupp lämnade ytterligare urinprover vid tillfällen när BM antogs ha spridits på närliggande åkrar. Deltagarna besvarade också enkäter med frågor om matvanor och livsstil.De BM som studerades var: 2,4-diklorfenoxiättiksyra (2,4-D), 3,4- dikloranilin (3,4-DKA, metabolit till anilider), 3,5-dikloranilin (3,5-DKA, metabolit till dikarboximider), etylenthiourea (ETU, metabolit till etylenbisdithiokarbamater), 4-klor-2-metylfenoxiättiksyra (MCPA), hydroxi-MCPA (HMCPA, metabolit till MCPA), 2,4,5- triklorfenoxiättiksyra (2,4,5-T), 3-fenoxibensylsyra (3-PBA, metabolit till pyretroider) samt 2,4,6-triklorfenoxiättiksyra (2,4,6-T, metabolit till prokloraz) och O,O dietyl-O-(3,5,6-triklor-2-pyridyl)thiofosfat (=triklorpyridinol=TCP, metabolit till klorpyrifos), klormekvatklorid (CCC) och mepikvat. Analysmetodernas detektionsgränser var mellan 0,1 och 1,0 ng/mL. CCC och mepikvat används i Sverige vid odling av råg och prydnadsväxter, i andra länder också till andra produkter.Nästan alla deltagare hade egen brunn och använde brunnsvattnet till dricksvatten och bostäder var mestadels belägna nära åkermark. 13% använde v b BM i yrket och 21% bejakade hemanvändning. Alla biomarkörerna kunde påvisas men för några medel i något olika frekvens jämfört med våra tidigare undersökta urbana grupper: Något lägre andel hade rester av de fungicida medlen 3,5-DKA och ETU men något högre andel av insekticidmetaboliten 3-PBA och herbiciden MCPA. Bland de nu undersökta boende på landsbygden fanns indikationer på små skillnader i urinhalter av några BM som relaterade till ålder, vinkonsumtion och kanske till boende nära besprutade åkrar.Retarderingsmedlen CCC och mepikvat undersöktes även i 100 tidigare insamlade prover från en stadsbefolkning. CCC fanns hos samtliga undersökta från landsbygd och stad och mepikvat hos nästan alla.
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| 7. |
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| 8. |
- Norén, Erika, et al.
(författare)
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Biomonitoring of organophosphorus flame retardants in a Swedish population – Results from four investigations between years 2000 - 2013
- 2017
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Flame retardants are chemical substances used in furniture, plastics, building materials, several household products and consumer goods to reduce their flammability. Their widespread use has resulted in measurable concentrations of the compounds or their residues in the environment, biota and human biological samples. The previously used brominated flame retardants were found to be persistent and to have bioaccumulative and neurotoxic potential, which raised public awareness. The use of the emerging organophosphorus compounds have increased after phasing out some brominated flame retardants. The chemical properties and health impacts of the organophosphorus flame retardants have not been studied to the same extent. The effects on public health and the environment due to the exposure from their widespread occurrence are therefore unclear.The aim of this study is to analyse exposure levels of the organophosphorus flame retardants TBP, TPP, TDCIPP and TBOEP in urine samples from a Swedish population of young men. The samples were collected through the enrolment for military service. Urine samples from year 2000, 2004, 2009 and 2013 were analysed for selected biomarkers of exposure with LC-MS/MS. The statistical analysis focused on temporal trends of the measured exposure levels.The metabolites DBP, DPP and BDCIPP were found in concentrations above LOD (0.03 – 0.1 ng/ml) in the majority of the samples, and DPP in all samples. BBOEP were only found above LOD in some samples and in very low concentrations. There was a statistically significant decreasing trend for the concentrations of DBP over time
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| 9. |
- Norén, Erika, et al.
(författare)
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Tidstrender för ftalater, bisfenoler, polyaromatiska kolväten (PAH:er) och triklosan i urinprov hos unga män och kvinnor – Resultat från fyra undersökningar mellan år 2000 - 2013
- 2017
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Befolkningen exponeras dagligen för en mängd olika miljögifter via föroreningar i utomhusmiljön, ämnen i byggnadsmaterial samt vid konsumtion av livsmedel och andra produkter. Halter av ämnen som kan medföra en risk för miljö eller hälsa mäts och kontrolleras till viss mån i miljön och i de flesta produktgrupper genom stickprov. Hur höga halter av dessa ämnen som kommer in i kroppen hos människor studeras inte lika mycket. I denna studie har halter av biomarkörer från vanligt förekommande ämnen i grupperna ftalater, bisfenoler, polyaromatiska kolväten (PAH) och triklosan analyserats i urin från unga män och kvinnor i Skåne som ett mått på exponeringen. Fokus har även varit på tidstrender genom statistisk analys av halterna vid fyra olika provtagningsår mellan år 2000 och 2013. De ämnen och utvalda biomarkörer som ingick i analysen var DEHP (MCMHP), DIDP (MCINP), DPHP (MPHHP), DINCH (MOINCH), bisfenol A (BPA), 2,2-bisfenol F (2,2-BPF), 4,4-bisfenol F (4,4-BPF), bisfenol S (BPS), fenantren (1-PH), pyren (2-OH-PH) och triklosan (TCS). Studien ska ses som ett komplement till den tidigare publicerade rapporten av Jönsson et al. (2014).Utvalda exponeringsbiomarkörer för samtliga ämnen gick att detektera i prover från alla provtagningsår utom 2,2-BPF som endast förekom i koncentrationer över LOD i enstaka urinprover år 2004 - 2013. Vanligast förekommande och högst halter var det för biomarkörerna för triklosan, bisfenol A och ftalaterna DEHP och DPHP. Dock minskade både medel- och mediankoncentrationerna av dessa ämnen över tid, med en signifikant nedåtgående trend för DEHP. Den alternativa mjukgöraren DINCH som är en ersättare för ftalater hade främst halter under LOD de första två åren men en tendens till ökning över tid med mediankoncentrationer över LOD både år 2009 och 2013. Övriga biomarkörer förekom i halter över LOD, men låga koncentrationer, och ingen tydlig trend syntes över tid.Resultatet visar en del exponeringstrender som tycks reflektera utfasning av vissa uppmärksammade ämnen. De utfasade ämnena har dock ersatts av nya snarlika ämnen, exempelvis mjukgöraren DINCH som i denna studie ser ut att öka.
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| 10. |
- Norén, Erika, et al.
(författare)
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Tidstrender för urinhalter av bekämpningsmedelsrester hos unga män – Resultat från fyra undersökningar mellan 2000 - 2013
- 2016
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The increased use of synthetic chemicals in society poses possible harmful risks for the environment and human health. There are difficulties in predicting and evaluating consequences and effects of long-time exposure of different chemicals. Biomonitoring is one way to observe the level of exposure in the human population.Agricultural pesticides are a widely used group of chemicals to which we are mainly exposed by occupation or by diet. Long-term exposure to pesticides might have a negative impact on human health, especially in children and foetuses, due to genotoxic, neurotoxic and endocrine disrupting characteristics of many pesticides.This study focuses on the exposure assessment of 14 different metabolites from about 20 pesticides in urinary samples. The pesticides and their biomarkers of exposure included in the analysis were the fungicides thiabendazole (OH-T), pyrimetanil (OH-P), tebuconazole (TEB-OH), mancozeb and several ethylenebisdithiocarbamates (ETU), propineb (PTU), the insecticides chlorpyrifos (TCP), some pyrethroid insecticides, which have the same corresponding biomarkers (3-PBA, DCCA), and some specific pyrethroid biomarkers (4F-3-PBA, CFCA), the herbicides 2,4-dichlorophenoxyacetic acid (2,4-D) and 2-methyl-4-chlorophenoxyacetic acid (MCPA) and the growth regulators chlormequat (CCC) and mepiquat (MQ). The samples were collected years 2000, 2004, 2009 and 2013 from young men in the enrolment for military service in the south of Sweden. The last year of measurement (2013) both young men and women in upper secondary school were included. All samples were analysed in 2016 with liquid chromatography-tandem mass spectrometry (LC/MS/MS). The emphasis of the statistical analysis was temporal trends between the years 2000 and 2013.The highest concentrations were found for TCP and CCC in all samples from all four years. In general, the concentrations were below the levels seen in previous studies of other Swedish populations.The only increasing trend near significance was that for TCP, although the increasing gradient was fairly low ( = 0,28). The concentrations of CCC decreased over the years, but not statistically significantly so. The biomarkers 3-PBA, 2,4-D, DCCA and MQ were detected above the limit of detection (LOD), but in fairly low concentrations in the majority of samples and without significant trends. The remaining residues were mainly below the LOD and could not be further statistically analysed.
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| 11. |
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| 12. |
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| 13. |
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| 14. |
- Berg, Lotta, et al.
(författare)
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Yttrande från SLUs vetenskapliga råd för djurskydd om djurskydd inom grisuppfödning
- 2019
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Detta yttrande svarar på följande fråga av Djurskyddet Sverige, Svenska Djurskyddsföreningen, Djurens Rätt, World Animal Protection Sverige, Compassion in World Farming Sverige och Vi Konsumenter, som vänt sig till det vetenskapliga rådet med anledning av Jordbruksverkets ändring av djurskyddsbestämmelserna för gris, Statens jordbruksverks föreskrifter och allmänna råd m ( SJVFS 2017:25) om grishållning inom lantbruket m.m., saknr. L 106: Är det förenat med bättre, likvärdig eller sämre djurvälfärd, vid en sammantagen bedömning av såväl smågrisens välfärd som suggans, om smågrisar avvänjs från suggan vid 21 dagars ålder i stället för vid 28 dagars ålder? Rådet ombads att belysa frågan utifrån ett brett perspektiv innefattande såväl psykisk som fysisk hälsa och välbefinnande.
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| 15. |
- Berg, Lotta, et al.
(författare)
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Yttrande från SLUs vetenskapliga råd för djurskydd om hållande av hund och katt
- 2018
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Detta yttrande är skrivet på uppdrag av Jordbruksverket i samband med verkets översyn av föreskrifterna för hund och katt. För att Jordbruksverkets föreskrifter ska vara väl förankrade i den senaste forskningen önskar verket inhämta underlag från det vetenskapliga rådet för djurskydd vid Sveriges lantbruksuniversitet, specifikt gällande områdena rörelsebehov, social kontakt och avvänjning.
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| 16. |
- Broström, Julia M., et al.
(författare)
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Toluene diisocyanate exposure and autotaxin–lysophosphatidic acid signalling
- 2018
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Ingår i: Toxicology and Applied Pharmacology. - : Elsevier BV. - 0041-008X .- 1096-0333. ; 355, s. 43-51
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Tidskriftsartikel (refereegranskat)abstract
- Toluene diisocyanate (TDI) is a reactive chemical used in manufacturing plastics. TDI exposure adversely affects workers' health, causing occupational asthma, but individuals differ in susceptibility. We recently suggested a role for signalling mediated by the enzyme autotaxin (ATX) and its product, lysophosphatidic acid (LPA), in TDI toxicity. Here we genotyped 118 TDI-exposed workers for six single-nucleotide polymorphisms (SNPs) in genes encoding proteins implicated in ATX–LPA signalling: purinergic receptor P2X7 (P2RX7), C–C motif chemokine ligand 2 (CCL2), interleukin 1β (IL1B), and caveolin 1 (CAV1). Two P2RX7 SNPs (rs208294 and rs2230911) significantly modified the associations between a biomarker of TDI exposure (urinary 2,4-toluene diamine) and plasma LPA; two IL1B SNPs (rs16944 and rs1143634) did not. CAV1 rs3807989 modified the associations, but the effect was not statistically significant (p = 0.05–0.09). In vitro, TDI-exposed bronchial epithelial cells (16HBE14o-) rapidly released ATX and IL-1β. P2X7 inhibitors attenuated both responses, but confocal microscopy showed non-overlapping localizations of ATX and IL-1β, and down-regulation of CAV1 inhibited the ATX response but not the IL-1β response. This study indicates that P2X7 is pivotal for TDI-induced ATX–LPA signalling, which was modified by genetic variation in P2RX7. Furthermore, our data suggest that the TDI-induced ATX and IL-1β responses occur independently.
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| 17. |
- Broström, Julia, et al.
(författare)
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Toluene diisocyanate: Induction of the autotaxin-lysophosphatidic acid axis and its association with airways symptoms.
- 2015
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Ingår i: Toxicology and Applied Pharmacology. - : Elsevier BV. - 1096-0333 .- 0041-008X. ; 287:3, s. 222-231
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Tidskriftsartikel (refereegranskat)abstract
- Diisocyanates are industrial chemicals which have a wide range of applications in developed and developing countries. They are notorious lung toxicants and respiratory sensitizers. However, the mechanisms behind their adverse effects are not adequately characterized. Autotaxin (ATX) is an enzyme producing lysophosphatidic acid (LPA), and the ATX-LPA axis has been implicated in lung related inflammatory conditions and diseases, including allergic asthma, but not to toxicity of environmental low-molecular-weight chemicals. We investigated effects of toluene diisocyanate (TDI) on ATX induction in human lung epithelial cell models, and we correlated LPA-levels in plasma to biomarkers of TDI exposure in urine collected from workers exposed to <5ppb (parts per billion). Information on workers' symptoms was collected through interviews. One nanomolar TDI robustly induced ATX release within 10min in vitro. A P2X7- and P2X4-dependent microvesicle formation was implicated in a rapid ATX release and a subsequent protein synthesis. Co-localization between purinergic receptors and ATX was documented by immunofluorescence and confocal microscopy. The release was modulated by monocyte chemoattractant protein-1 (MCP-1) and by extracellular ATP. In workers, we found a dose-response relationship between TDI exposure biomarkers in urine and LPA levels in plasma. Among symptomatic workers reporting "sneezing", the LPA levels were higher than among non-symptomatic workers. This is the first report indicating induction of the ATX-LPA axis by an environmental low-molecular-weight chemical, and our data suggest a role for the ATX-LPA axis in TDI toxicity.
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| 18. |
- Ekman, Eva, et al.
(författare)
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High-throughput method for the analysis of ethylenethiourea with direct injection of hydrolysed urine using online on-column extraction liquid chromatography and triple quadrupole mass spectrometry.
- 2013
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Ingår i: Journal of Chromatography. B. - : Elsevier BV. - 1873-376X .- 1570-0232. ; 934:Jul,5, s. 53-59
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Tidskriftsartikel (refereegranskat)abstract
- Ethylenethiourea (ETU) is of major toxicological concern, since in experimental animal studies, ETU has shown a large spectrum of adverse effects. High occupational exposure can be found among agricultural workers or during manufacturing of ethylenbisdithiocarbamates (EBDC). For the general public, sources of environmental exposure may be residues of ETU in commercial products, food and beverages. For the determination of ETU in human urine we present a high-throughput online on-column extraction liquid chromatography triple quadrupole mass spectrometry method using direct injection of hydrolysed urine samples. This method is simple, user- and environmentally friendly and all sample preparation is performed in 96-well plates. A labelled ETU internal standard was used for quantification. The method showed a good sensitivity with a limit of quantification (LOQ) of 0.5ng ETU/mL urine and the calibration curve was linear in the range 0.25-200ng ETU/mL urine. The within-run, between-run and between-batch precision was between 6% and 13%. Alkaline hydrolysis considerably increased the levels of ETU indicating a potential conjugate. The method was applied in an experimental dermal exposure study in humans, with sample concentrations ranging from 0.4 to 5.0ng ETU/mL urine. The excretion in urine was 10% of the applied dose. The elimination profile seemed to differ between the two individuals. The results show an estimated half-life of ETU between 34 and 72h. Although the experiment is limited to two individuals, the data provide valuable and new information regarding the toxicokinetics of ETU after dermal exposure.
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| 19. |
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| 20. |
- Faniband, Moosa H., et al.
(författare)
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Human experimental exposure to glyphosate and biomonitoring of young Swedish adults
- 2021
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Ingår i: International Journal of Hygiene and Environmental Health. - : Elsevier BV. - 1438-4639. ; 231
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Tidskriftsartikel (refereegranskat)abstract
- Glyphosate (GLY), N-(phosphonomethyl) glycine, is the most widely used herbicide in the world. It is a broad-spectrum herbicide, also used in crop desiccation. Agricultural workers may be occupationally exposed and general populations may be exposed to GLY mainly through diet. We studied the kinetics of GLY by measuring the parent compound and its metabolite aminomethylphosphonic acid (AMPA) in urine samples of three volunteers after an experimental oral exposure. We further examined GLY exposure by measuring GLY and AMPA in spot urine samples of 197 young adults in the general population in Scania, southern Sweden. Urine samples were analyzed using LC-MS/MS. In the experimental exposure, three healthy volunteers received an oral dose equivalent to 50% of the ADI for GLY. Urinary samples were collected up to 100 h after the exposure. The excretion of GLY to urine seemed to follow first-order kinetics and a two-phase excretion. The excretion half-life of GLY (density adjusted) was 6–9 h in the rapid phase and 18–33 h in the slower phase. The total dose recovered as unchanged GLY in the urine samples of volunteers was 1–6%. The metabolite AMPA was found to be 0.01–0.04% of the total dose of GLY. In the population of young adults, the median concentration was below 0.1 μg/L and a maximum concentration being 3.39 μg/L (density adjusted). AMPA was generally detected in lower concentrations (maximum = 0.99 μg/L). A moderate correlation (Spearman's ρ = 0.56) was observed between GLY and AMPA concentrations. Overall, the results may suggest that GLY and AMPA partly originate from separate exposures and that unchanged GLY is a more suitable biomarker of exposure.
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| 21. |
- Faniband, Moosa, et al.
(författare)
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LC-MS-MS Analysis of Urinary Biomarkers of Imazalil Following Experimental Exposures.
- 2015
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Ingår i: Journal of Analytical Toxicology. - : Oxford University Press (OUP). - 1945-2403 .- 0146-4760. ; 39:9, s. 691-697
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Tidskriftsartikel (refereegranskat)abstract
- Imazalil (IMZ) is a fungicide used in the cultivation of vegetables, such as cucumbers, in green houses or post-harvest on fruit to avoid spoilage due to fungal growth. Agricultural workers can be occupationally exposed to IMZ and the general public indirectly by the diet. The purpose of this study was to develop and validate an LC-MS-MS method for the analysis of IMZ in human urine. The method used electrospray ionization and selected reaction monitoring in the positive mode. Excellent linearity was observed in the range 0.5-100 ng/mL. The limit of detection of the method was 0.2 ng/mL, and the limit of quantitation 0.8 ng/mL. The method showed good within-run, between-run and between-batch precision, with a coefficient of variation <15%. The method was applied to analyze urine samples obtained from two human volunteers following experimental oral and dermal exposure. The excretion of IMZ seemed to follow a two-compartment model and first-order kinetics. In the oral exposure, the elimination half-life of IMZ in the rapid excretion phase was 2.6 and 1.9 h for the female and the male volunteer, respectively. In the slower excretion phase, it was 7.6 and 13 h, respectively. In the dermal exposure, the excretion seemed to follow a single-compartment model and first-order kinetics. The elimination half-life was 10 and 6.6 h for the female and the male volunteer, respectively. Although the study is limited to two volunteers, some information on basic toxicokinetics and metabolism of IMZ in humans is presented.
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| 22. |
- Julander, Anneli, et al.
(författare)
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Nickel penetration into stratum corneum in FLG null carriers—A human experimental study
- 2022
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Ingår i: Contact Dermatitis. - : Wiley. - 0105-1873 .- 1600-0536. ; 87:2, s. 154-161
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Tidskriftsartikel (refereegranskat)abstract
- Background: The filaggrin gene (FLG) plays a role in skin diseases, with the skin barrier function being impaired in FLG null carriers. The role of FLG status in relation to nickel penetration into the skin remains unclear. Objectives: To elucidate the association between FLG status and nickel penetration into stratum corneum (SC) in individuals without self-reported history of nickel allergy. Methods: Forty participants (23 FLG wt and 17 FLG null) were exposed to a nickel solution (80 μg/cm2) which was applied onto 2 × 2 cm on their left forearm. After 4 h, the area was tape-stripped with 10 consecutive tapes. Nickel in each tape was quantified using inductively coupled plasma mass spectrometry. Results: The average recovered nickel dose was 35%–48%. A tendency towards lower recovery was seen in FLG null carriers compared to FLG wt carriers, and lower recovery in those with history of skin and/or respiratory symptoms compared to those without such history. This was however not statistically significant. Conclusion: FLG null carriers had less nickel recovered by tape strips compared with FLG wt carriers and, compared with individuals without a history of skin and/or respiratory symptoms, indicating higher nickel penetration into SC for FLG null carriers, but further studies are needed.
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| 23. |
- Jönsson, Lena S, et al.
(författare)
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Influence of glutathione-related genes on symptoms and immunologic markers among vulcanization workers in the southern Sweden rubber industries.
- 2008
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Ingår i: International Archives of Occupational and Environmental Health. - : Springer Science and Business Media LLC. - 1432-1246 .- 0340-0131. ; 81:7, s. 913-919
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aim was to elucidate the role of genetic variants on symptoms of the eyes and airways, headache and nausea, as well as on immunologic markers, among vulcanization workers in the contemporary Swedish rubber industry. Polymorphisms in genes, which are involved in the defense against reactive oxygen species and metabolism of toxic substances present in the vulcanization fumes, were analyzed. METHODS: One hundred and forty-five exposed and 117 unexposed workers were included in the study. Medical and occupational histories were obtained in structured interviews. Symptoms were recorded and immunologic markers analyzed in blood. Polymorphisms in glutathione-related genes (glutamate cysteine ligase catalytic subunit (GCLC)-129, glutamate cysteine ligase modifier subunit (GCLM)-588, glutathione S-transferase alpha 1 (GSTA1)-52, GSTM1*O, GSTP1-105, GSTP1-114, and GSTT1*O) were analyzed by Taqman-based allelic discrimination and ordinary PCR. RESULTS: A protective effect of GSTA1-52 (G/A + A/A) genotype on symptoms and immunologic cells, in particular among exposed workers, was suggested. Exposed workers with GSTT1*O had increased risk of nosebleed compared to exposed workers with GSTT1*1. Exposed workers with GSTP1-105 (ile/val + val/val) had decreased levels of total immunoglobulin E (IgE) compared to exposed workers with GSTP1-105 ile/ile. GCLC-129 variant genotype demonstrated increased levels of immunologic cells among exposed workers, although statistical significance was not reached. CONCLUSION: Our data indicate that hereditary factors influence the susceptibility to symptoms and the immunologic response of workers in the rubber industry.
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| 24. |
- Jönsson, Lena S, et al.
(författare)
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Levels of 1-hydroxypyrene, symptoms and immunologic markers in vulcanization workers in the southern Sweden rubber industries.
- 2008
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Ingår i: International Archives of Occupational and Environmental Health. - : Springer Science and Business Media LLC. - 1432-1246 .- 0340-0131. ; 82, s. 131-137
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The aim of this study was to determine urinary 1-hydroxypyrene (1-HP) levels in contemporary Swedish vulcanization workers and in controls. These levels were used as an index substance for vulcanization fumes, as well as a biomarker for polycyclic aromatic hydrocarbons (PAHs). The risk of symptoms and changed levels of immunologic markers were investigated in relation to the 1-HP levels. METHODS: Included in the study were 163 exposed workers and 106 controls. Medical and occupational histories were obtained by structured interviews. Symptoms were recorded and immunologic markers analysed in blood by routine analysis methods. Levels of 1-HP were determined by liquid chromatography and fluorescence detection. RESULTS: The highest levels of 1-HP were found among exposed workers using injection and compression vulcanization and lower levels were found among exposed workers vulcanizing with salt bath, hot air, microwaves or fluid-bed. Compared to controls, exposed workers had increased risks of eye symptoms, nosebleeds, burning and dry throat, hoarseness, severe dry cough, nausea and headache. Furthermore, exposed workers had elevated levels of neutrophils and total IgG (immunoglobulin subclass G). However, only for severe dry cough an evident exposure-response relationship with urinary 1-HP levels was found. CONCLUSIONS: This work clearly shows increased levels of urinary 1-HP in Swedish vulcanization workers. Furthermore, it demonstrates an increased risk of several symptoms and elevated levels of some immunologic markers in these workers. However, no obvious exposure-response relationships were found.
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| 25. |
- Jönsson, Lena S, et al.
(författare)
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Levels of 2-thiothiazolidine-4-carboxylic acid (TTCA) and effect modification of polymorphisms of glutathione-related genes in vulcanization workers in the southern Sweden rubber industries.
- 2007
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Ingår i: International Archives of Occupational and Environmental Health. - : Springer Science and Business Media LLC. - 1432-1246 .- 0340-0131. ; 80:7, s. 589-598
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Workers in the rubber industry are exposed to a complex mixture of hazardous substances and have increased risk of developing several diseases. However, there is no up to date survey examining the exposure in the Swedish rubber industry. One of the toxic compounds in the industry is carbon disulfide (CS2), which is biotransformed to 2-thiothiazolidine- 4carboxylic acid (TTCA). TTCA is used as a biomarker of CS2 exposure, but there seem to exist inter- and intraindividual variability; which could partly be due to genetic variation. The aim of the study was to determine TTCA levels and the modifying effects of glutathione-related genes in a group of Swedish rubber workers. Methods Urine was collected from both exposed workers and controls during the last 4 h of the work shift. The level of TTCA in urine was analyzed by liquid chromatograpy tandem mass spectrometry. Genotyping of the single nucleotide polymorphisms GCLC-129, GCLM-588, GSTA1-52, GSTP1-105 and GSTP1-114 and deletions of GSTM1 and GSTT1 were performed with real-time PCR or ordinary PCR and subsequent agarose electrophoresis. Results The highest levels of TTCA were found among workers curing with salt bath, hot air, microwaves or Xuid-bed, and lower levels were found among workers curing with injection and compression molding. Furthermore, with respect to GSTM1 and GSTT1 there were statistically significant differences in TTCA-levels between genotypes among exposed workers but not among controls. The other five polymorphisms had no impact on the TTCA levels. Conclusions The present study demonstrates relatively high levels of TTCA in urine from Swedish rubber workers. Polymorphisms in GSTM1 and GSTT1 modify the levels.
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