Anna Axmon

Lack of human exposure data is frequently reported as a critical gap in risk assessments of environmental pollutants, especially regarding "new" pollutants. The objectives of this study were to assess serum levels of the persistent 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153), hydroxylated polychlorinated biphenyl metabolites (OH-PCBs), polybrominated diphenyl ethers (PBDEs), and hexabromocyclodode-canes (HBCDDs) in a group of Swedish middle-aged and elderly women expected to be relatively highly exposed, and to evaluate the impact of potential determinants (e.g., fish intake, age) for the inter-individual variation, as well as to investigate the association between these pollutants and bone density. No associations were found between bone mineral density or biochemical markers of bone metabolism and the analyzed environmental pollutants. Relatively high levels of CB-153 (median 260 ng/g fat) and sigma 3-OH-PCBs (median 1.7 ng/mL serum), and low concentrations of sigma6PBDEs (median 3.6 ng/g fat) were determined. Total level of HBCDDs in serum was quantified by gas chromatography with mass spectrometric detection (median 0.5 ng/g fat). HBCDD diastereomeric and enantiomeric patterns were determined by liquid chromatography with mass spectrometric detection. The dominating stereoisomer was (-)alpha-HBCDD, but 1-3% of gamma-HBCDD was also detected in the serum samples.

The purpose of this study was to assess the association between 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) in plasma, a biomarker of exposure to polychlorinated biphenyls (PCB), and time to pregnancy (TTP) in a group of women with a varying dietary exposure to PCB. For 121 Swedish east coast fishermen's wives (median year of birth 1956, range 1945-1968), information on selt-reported TTP for the first planned pregnancy (median 2 mo, range 0-48) and CB-153 concentrations from blood samples drawn in 1995 (median 144 ng/g lipid, range 16-566) were available. Each woman's CB-153 concentration in plasma at the time immediately preceding her pregnancy was estimated, taking into account reduction of body burden of CB-153 due to lactation, the yearly reduction of PCB in Baltic Sea fish, as well as the biological half-life of CB-153. Based on the estimated CB-153 concentrations, subjects were categorized into tertiles as low (37-206 ng/g lipid), medium (207-330 ng/g lipid), and high (331-,1036 ng/g lipid) exposure groups. TTP in the medium- and high-exposure groups were then compared to TTP in the low-exposure group by estimating the corresponding success rate (i.e., the number of pregnancies per person month) ratios (SuRR) using discrete Cox regression, taking into account essential confounders. No obvious association between estimated CB-153 concentration and TTP was observed (medium vs. low: SuRR 0.77 [95% CI 0.47-1.28] and high vs. low: SuRR 0.95 10.74-1.23]). The present data give no support for a negative association between the plasma CB-153 concentrations observed in the present study and TTP. It should, however, be borne in mind that the study group was rather small and mainly included relatively young women, likely to have been only moderately exposed.

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 (CS(2)), which is biotransformed to 2-thiothiazolidine-4-carboxylic acid (TTCA). TTCA is used as a biomarker of CS(2) 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. 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. The highest levels of TTCA were found among workers curing with salt bath, hot air, microwaves or fluid-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. The present study demonstrates relatively high levels of TTCA in urine from Swedish rubber workers. Polymorphisms in GSTM1 and GSTT1 modify the levels.

It is usually assumed that musculoskeletal pain is associated with both the physical workload and the psychosocial work environment, as well as with personal and lifestyle factors. This study aims to ascertain the prevalence of musculoskeletal pain in women with varying or different occupational exposures, and to explore the associations between musculoskeletal pain and the occupational and personal factors. A questionnaire on physical, psychosocial and individual factors was answered by 1591 women in five occupational groups with contrasting occupational exposures (teachers, anaesthetic, theatre, and assistant nurses, and sonographers). The outcome measure was musculoskeletal pain (in a new model based on frequency and intensity of complaints the preceding year) from the neck, shoulders, hands, lower back and feet. Neck pain was equally frequent among teachers, assistant nurses and sonographers, and less frequent in anaesthetic and theatre nurses. The sonographers experienced the highest prevalence of shoulder pain, while the assistant nurses were the most affected in the wrists and hands, lower back, and feet. The teachers reported the highest scores in most of the psychosocial dimensions. The theatre nurses scored highest in strenuous work postures and movements (mechanical exposure index, MEI), and the assistant nurses in physical activity and lifting (physical exposure index, PHYI). Multivariable models in the total population showed that both the physical workload and the psychosocial work environment were associated with pain in all body regions, though different factors affected different regions. Pain in the neck, shoulders, hands and lower back was strongly associated with a high MEI and high job demands, while pain in the feet was associated with a high PHYI and a high BMI. A young age was associated with pain in the neck, and an older age was associated with pain in the hands and feet. Lack of time for personal recovery was associated with pain in the shoulders and lower back. The occupational groups were affected differently and need different protective measures. For the teachers, the psychosocial work environment should be improved. The surgical staff and sonographers require measures to mitigate lifting and constrained postures.

The aim of this study was twofold: (i) to evaluate the air levels of N-nitrosamines in the Swedish rubber industry and (ii) to estimate the risk of symptoms and changed levels of immunologic markers in relation to these levels. Using adsorption tubes, we collected samples of N-nitrosamines in the breathing zone of 96 rubber workers and analyzed them with liquid chromatography tandem mass spectrometry. Of these 96 workers, 66 were included in a medical examination and blood analysis together with an additional 106 rubber workers and 118 unexposed subjects. Medical and occupational histories were obtained in structured interviews, symptoms were recorded and immunologic markers analyzed in blood. The sum of N-nitrosamines ranged from less than the limit of detection to 36 microg/m (3)and differed with the vulcanization (ie, curing process) method used. Workers vulcanizing with a salt bath had the highest levels (median 4.2 microg/m (3)). Compared to the unexposed subjects, the rubber workers had an increased risk of nosebleeds, eye and throat symptoms, hoarseness, cough, nausea, headache, and changed levels of eosinophils and total immunoglobulin G (IgG). However, we found no clear exposure-response relationship with the symptoms or the immunologic markers studied. High levels of N-nitrosamines were found and must be lowered considerably in order to decrease the risk of cancer. There is a need for an occupational exposure limit for N-nitrosamines in Sweden. The lack of exposure-response relationships with the subacute symptoms examined in this study may be due to a healthy-worker selection or to the possibility that the symptoms are caused by an exposure not co-varying with N-nitrosamines.

Cadmium (Cd) is a human toxicant and carcinogen. Genetic variation might affect long-term accumulation. Cd is absorbed via iron transporters. We evaluated the impact of iron homeostasis genes [divalent metal transporter 1 (SLC11A2), transferrin (TF), transferrin receptors (TFR2 and TFRC), and ferroportin (SLC40A1)] on Cd accumulation. Subjects were nonsmoking women living in the Argentinean Andes [n = 172; median urinary Cd (U-Cd) = 0.24 µg/L] and Bangladesh (n = 359; U-Cd = 0.54 µg/L) with Cd exposure mainly from food. Concentrations of U-Cd and Cd in whole blood or in erythrocytes (Ery-Cd) were measured by inductively coupled plasma mass spectrometry. Fifty polymorphisms were genotyped by Sequenom. Gene expression was measured in whole blood (n = 72) with Illumina DirectHyb HumanHT-12 v4.0. TFRC rs3804141 was consistently associated with U-Cd. In the Andean women, mean U-Cd concentrations were 22% (95% CI: -2, 51%), and they were 56% (95% CI: 10, 120%) higher in women with GA and AA genotypes, respectively, relative to women with the GG genotype. In the Bangladeshi women, mean U-Cd concentrations were 22% (95% CI: 1, 48%), and they were 58% (95% CI: -3, 157%) higher in women with GA and AA versus GG genotype, respectively [adjusted for age and plasma ferritin in both groups; ptrend = 0.006 (Andes) and 0.009 (Bangladesh)]. TFRC expression in blood was negatively correlated with plasma ferritin (rS = -0.33, p = 0.006), and positively correlated with Ery-Cd (significant at ferritin concentrations of < 30 µg/L only, rS = 0.40, p = 0.046). Rs3804141 did not modify these associations or predict TFRC expression. Cd was not consistently associated with any of the other polymorphisms evaluated. One TFRC polymorphism was associated with urine Cd concentration, a marker of Cd accumulation in the kidney, in two very different populations. The consistency of the findings supports the possibility of a causal association.

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 TDI on ATX induction in human lung epithelial cell models, and we correlated LPA-levels in plasma to biomarkers of toluene diisocyanate (TDI) exposure in urine collected from workers exposed to<5p.p.b.(parts per billion). Information on workers' symptoms was collected through interviews. One nM 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 a 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.

We aimed to follow diary-registered symptoms from eyes and airways in mild steel welders and relate them to different exposure measures. Furthermore, we would clarify the influence of possible effect modifiers. Non-smoking welders with (N = 74) and without (N = 32) work-related symptoms the last month were enroled. Symptoms and work tasks each day for three two-week periods during 1 year were obtained. Respirable dust (RD) was measured 1 day each period for each worker. The personal daily exposure was assessed as: (1) days at work, (2) welding time and (3) estimates of RD from welding and grinding, calculated from diary entries and measurements. Only 9.2 % of the particle measurements exceed the Swedish occupational exposure limit (OEL; 5 mg/m(3)). Days at work increased the risk of symptoms studied: eyes: 1.79 (1.46-2.19), nasal: 2.16 (1.81-2.58), dry cough: 1.50 (1.23-1.82) and wheezing and/or dyspnoea: 1.27 (1.03-1.56; odds ratio, 95 % confidence interval). No clear dose-response...

Hairdressing work is classified as carcinogenic based on excess risk for bladder cancer. We aimed at evaluating if current hairdressers are exposed to established/suspected bladder carcinogens (aromatic amines) and indicate possible sources of exposure. Hairdressing salons listed in the telephone book were contacted for personal visits, 295 hairdressers were recruited (an estimated half of the eligible invited subjects). For comparison we included 32 consumers and 60 controls employed at our hospital. The study was restricted to female non-smokers. Questionnaires including frequency of performed work tasks were filled in by the hairdressers, and all subjects reported personal hair dye use, and exposure to environmental tobacco smoke. Blood samples were taken for analysis (gas chromatography-tandem mass spectrometry; GC-MS/MS) of ortho (o)-, meta (m)-, and para (p)-toluidine; 2-, 3-, and 4-ethylaniline, 2,3- and 3,4-dimethylaniline as haemoglobin adducts. Adduct concentrations did no...

Carcinogenic aromatic amines derived from hair dyes have recently received new attention. One of these is ortho (o)-toluidine, which is classified as carcinogenic to humans. To clarify exposure of hairdressers to potentially carcinogenic aromatic amines, including o-toluidine. We measured eight potentially carcinogenic aromatic amines in the blood of 295 hairdressers, 32 users of hair dyes and 60 controls. The study was restricted to female non-smokers. Lifestyle data were collected for all participants using self-administered questionnaires. Blood samples were taken for analysis of ortho-, meta (m)- and para (p)-toluidine; 2-, 3- and 4-ethylaniline, 2,3- and 3,4-dimethylaniline as haemoglobin adducts. The samples were analysed with gas chromatography-tandem mass spectrometry. Generally, adduct concentrations were in the range of 0-200 pg/g haemoglobin. A comparison of the adduct concentrations found in hairdressers, consumers and controls showed no statistically significant differe...

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. 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 I105V, 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). 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-exp...

Dietary POP exposure have shown negative effects on sperm motility and sperm chromatin integrity, as well as an increased proportion of Y-chromosome bearing sperms. However, it has been suggested that in epidemiological studies investigating persistent organochlorine pollutant (POP)-toxicity, other pollutants occurring simultaneously may carry an increased risk of effects, which may obscure a clear interpretation of the role of POP toxicity. One such pollutant is methyl mercury (MeHg), which has been found in fatty fish from the Baltic Sea and as a consequence men with a high consumption of such fish has been found to have twice the MeHg levels compared to men with a low fish consumption. The aim of the present study was to assess if exposure to MeHg affects male reproductive function, assessed by measuring human sperm motility, sperm concentration, total sperm count, sperm chromatin integrity and the proportion of Y-chromosome bearing sperms. Secondly we also investigated a possibl...

Exposure to diesel exhaust causes inflammatory responses. Previous controlled exposure studies at a concentration of 300 μg/m(3) of diesel exhaust particles mainly lasted for 1 h. We prolonged the exposure period and investigated how quickly diesel exhaust can induce respiratory and systemic effects. Eighteen healthy volunteers were exposed twice to diluted diesel exhaust (PM1 ~300 μg/m(3)) and twice to filtered air (PM1 ~2 μg/m(3)) for 3 h, seated, in a chamber with a double-blind set-up. Immediately before and after exposure, we performed a medical examination, spirometry, rhinometry, nasal lavage and blood sampling. Nasal lavage and blood samples were collected again 20 h post-exposure. Symptom scores and peak expiratory flow (PEF) were assessed before exposure, and at 15, 75, and 135 min of exposure. Self-rated throat irritation was higher during diesel exhaust than filtered air exposure. Clinical signs of irritation in the upper airways were also significantly more common after...

The aim of this study was twofold: (i) to evaluate the air levels of N-nitrosamines in the Swedish rubber industry and (ii) to estimate the risk of symptoms and changed levels of immunologic markers in relation to these levels. Using adsorption tubes, we collected samples of N-nitrosamines in the breathing zone of 96 rubber workers and analyzed them with liquid chromatography tandem mass spectrometry. Of these 96 workers, 66 were included in a medical examination and blood analysis together with an additional 106 rubber workers and 118 unexposed subjects. Medical and occupational histories were obtained in structured interviews, symptoms were recorded and immunologic markers analyzed in blood. The sum of N-nitrosamines ranged from less than the limit of detection to 36 microg/m (3)and differed with the vulcanization (ie, curing process) method used. Workers vulcanizing with a salt bath had the highest levels (median 4.2 microg/m (3)). Compared to the unexposed subjects, the rubber workers had an increased risk of nosebleeds, eye and throat symptoms, hoarseness, cough, nausea, headache, and changed levels of eosinophils and total immunoglobulin G (IgG). However, we found no clear exposure-response relationship with the symptoms or the immunologic markers studied. High levels of N-nitrosamines were found and must be lowered considerably in order to decrease the risk of cancer. There is a need for an occupational exposure limit for N-nitrosamines in Sweden. The lack of exposure-response relationships with the subacute symptoms examined in this study may be due to a healthy-worker selection or to the possibility that the symptoms are caused by an exposure not co-varying with N-nitrosamines.

This study attempted to determine whether musculoskeletal health is influenced by mouse-intensive computer work. The neck-upper limbs of 148 air-traffic controllers (71 women, 77 men) with demanding computer work were examined before (baseline) and a median of 20 months after (follow-up) a change from varied computer work to a mouse-based system, causing a significant change in the physical exposure of the workers (eg, lower variation of work postures and less rest in the forearm extensor muscles, as assessed by technical measurements). Complaints (according to a Nordic questionnaire), diagnoses (standardized physical examination), and psychosocial work environment (Copenhagen Psychosocial Questionnaire) were recorded. The air traffic controllers had consistently higher prevalences of disorders in the elbows-hands in the follow-up than at the baseline (complaints 30% versus 18%, P=0.03; diagnoses 10% versus 3.4%, P=0.02). The predominance of right-arm disorders was more pronounced in the follow-up than at the baseline. For the neck-shoulders-upper back, there was no consistent difference between the baseline and follow-up values; disorders increased significantly among the "young" controllers (< or =37 years), but not among the "older" ones. Perceived decision latitude decreased, while social support increased, but these changes did not explain the disorders that appeared in the elbows-hands. Intensive mouse-based computer work, with constrained posture and little rest in the forearm muscles, was associated with an increased risk of disorders in the elbows-hands. This finding should be considered for similar technological developments in other settings.

Exposure to diisocyanates is a well known occupational hazard. The objective of this study was to determine the possibility of an association between low exposure to toluene diisocyanate (TDI) (airborne isocyanates and biomarkers of isocyanates in plasma and urine) and symptoms of the eyes and upper and lower airways. Altogether 136 workers occupationally exposed to TDI and 118 unexposed employees were studied. A physician compiled thorough medical and occupational histories and registered symptoms, total and work-related, of the eyes, nose, and lower airways. The exposure was assessed with personal air measurements and with biomarkers of exposure in plasma and urine. The average exposure in the ambient air at the workplace of the exposed participants was below 1 ppb. Compared with the unexposed group, the exposed workers reported more total symptoms of the eyes and lower airways, as well as nose bleeding. A similar pattern, with even higher odds ratios, was observed for work-related symptoms. However, only eye symptoms proved to be significantly associated with the exposure, notably with all of the exposure measures. The risk was more pronounced for exposure to 2,4-TDI than for exposure to 2,6-TDI. Even very low exposure to TDI is related to negative health effects on exposed workers. Clear dose-response relationships were observed between three different measures of exposure and symptoms of the eyes.

The purpose of the study was to assess the effect of exposure to presistent organochlorine compounds through the consumption of fatty fish from the Baltic Sea on human fertility. Information on time to pregnancy, miscarriages, and subfertility was collected retrospectively by self-administered questionnaires in two cohorts of fishermen's sisters from the Swedish east coast, by the Baltic Sea, and the west coast, where fish are less contaminated. Along with cohort affiliation, fish consumption and growing up in a fishing village or fisherman's family were used as measures of exposure within the eastcoast cohort (ie, the exposed cohort). There was no support for a negative effect of the consumption of fatty Baltic Sea fish on time to pregnancy, miscarriages, or subfertility. On the contrary, some evidence pointed towards a protective effect of fatty fish consumption within both cohorts. No evidence of reduced fertility was found for women who could be assumed to have a high lifetime consumption of fatty fish contaminated by persistent organochlorine compounds. A possible explanation for this finding is that a positive effect of some of the constituents in fatty fish could be strong enough to disguise the hazardous effects of exposure to persistent organochlorine compounds.