Motor development following in utero exposure to organochlorines: a follow-up study of children aged 5-9 years in Greenland, Ukraine and Poland.

BACKGROUND: Prior studies on the association between prenatal exposure to polychlorinated biphenyls (PCBs) and dichlorodiphenyldichloroethylene (DDE) and child motor development have found contradicting results. Using data collected in the INUENDO cohort in Kharkiv (Ukraine), Warsaw (Poland) and Greenland (N = 1,103) between the years 2002 and 2012, we examined relations of prenatal exposure to 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE) and 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) on motor development and developmental milestones; crawling, standing-up and walking. METHODS: CB-153 and p,p'-DDE were measured in maternal blood in second or third trimester of pregnancy. Motor development was measured in terms of the parentally assessed screening tool Developmental Coordination Disorder Questionnaire 2007 and developmental milestones were assessed via retrospective parental reports of child age at the first time of crawling, standing-up and walking. RESULTS: We saw no associations between tertiles of CB-153 and p,p'-DDE or log-transformed exposures and retrospective reports of the developmental milestones crawling, standing-up and walking in infancy or the motor skills measured as developmental coordination disorder at young school age. CONCLUSIONS: In utero exposure to CB-153 and p,p'-DDE was not associated with parentally retrospectively assessed developmental milestones in infancy or parentally assessed motor skills at young school age. The use of a more sensitive outcome measure may be warranted if subtle effects should be identified.

Temporal trends of phthalate exposures during 2007-2010 in Swedish pregnant women.

BACKGROUND: The general population is exposed to phthalates, a group of chemicals with strong evidence for endocrine disrupting properties, commonly used in a large number of consumer products. Based on published research and evidence compiled by environmental agencies, certain phthalate applications and products have become restricted, leading to an increasing number of "new generation compounds" coming onto the market during recent years replacing older phthalates. Some examples of such newer compounds are di-iso-nonyl phthalate (DiNP), di-iso-decyl phthalate (DiDP), and most recently di-isononyl-cyclohexane-1,2-dicarboxylate (DiNCH). OBJECTIVES: In order to evaluate temporal trends in phthalate exposure, first trimester urinary biomarkers of phthalates were measured in the Swedish SELMA study over a period of 2.5 years (2007-2010). METHODS: We collected first morning void urine samples around week 10 of pregnancy from 1651 pregnant women. Spot samples were analyzed for 13 phthalate metabolites and one phthalate replacement and least square geometric mean (LSGM) levels of the metabolites were compared between the sampling years when adjusted for potential confounders. RESULTS: All 14 metabolites were detectable in more than 99% of the SELMA subjects. The levels were generally comparable to other studies, but the SELMA subjects showed slightly higher exposure to butyl-benzyl phthalate (BBzP) and di-butyl phthalate (DBP). Di-ethyl-hexyl phthalate (DEHP) metabolites levels decreased while DiNP, DiDP/di-2-propylheptyl phthalate (DPHP), and DiNCH metabolites levels increased during the sampling period. CONCLUSIONS: Urinary metabolite levels of the older phthalates and more recently introduced phthalate replacement compound changed during the short sampling period in this Swedish pregnancy cohort. Our results indicate that replacement of phthalates can make an impact on human exposure to these chemicals. During this particularly vulnerable stage of life, phthalate exposures are of particular concern as the impacts, though not immediately noticeable, may increase the risk for health effects later in life.

Symptoms and immunologic markers among vulcanization workers in rubber industries in southern Sweden.

OBJECTIVES: The aim of this study was to estimate the risk of symptoms and the possible derangement of levels of immunologic markers for contemporary Swedish rubber workers. Furthermore, the relation between exposure and these biomarkers of response was examined using urinary levels of 2-thiothiazolidine-4-carboxylic acid (TTCA), which reflect the exposure. METHODS: Included in the study were 166 exposed workers and 117 controls. Medical and occupational histories were obtained in structured interviews. Symptoms were recorded, and immunologic markers were analyzed in blood. Urinary levels of TTCA were determined by liquid chromatography tandem mass spectrometry. RESULTS: Compared with the controls, the exposed workers had increased risks of eye symptoms [odds ratio (OR) 3.0], nose bleeds (OR 4.0), burning and dry throat (OR 3.0), hoarseness (OR 2.4), severe dry cough (OR 3.8), nausea (OR 4.3), and headache (OR 2.5). When the exposed workers were divided into three groups according to the TTCA levels, the highest risks were observed among the exposed workers with intermediate TTCA levels. Furthermore, the exposed workers in all of the TTCA subgroups had elevated concentrations of total immunoglobulin G when compared with the controls. Elevated concentrations of leukocytes, neutrophils, and eosinophils were observed in the group with high TTCA levels. CONCLUSIONS: This work shows an increased risk of several symptoms and elevated levels of some immunologic markers among exposed workers in Swedish rubber industries. In addition, relationships between urinary levels of TTCA and some biomarkers of response were reported.

Phthalates, non-phthalate plasticizers and bisphenols in Swedish preschool dust in relation to children's exposure.

Children are exposed to a wide range of chemicals in their everyday environments, including the preschool. In this study, we evaluated the levels of phthalates, non-phthalate plasticizers and bisphenols in dust from 100 Swedish preschools and identified important exposure factors in the indoor environment. In addition, children's total exposure to these chemicals was determined by urine analysis to investigate their relation with dust exposure, and to explore the time trends by comparing with children who provided urine fifteen years earlier. The most abundant plasticizers in preschool dust were the phthalates di-isononyl phthalate (DiNP) and di-(2-ethylhexyl) phthalate (DEHP) with geometric mean levels of 450 and 266µg/g dust, respectively, and the non-phthalate plasticizers bis(2-ethylhexyl) terephthalate (DEHT) and diisononylcyclohexane-1,2-dicarboxylate (DiNCH) found at 105 and 73µg/g dust, respectively. The levels of several substitute plasticizers were higher in newer preschools, whereas the levels of the strictly regulated phthalate di-n-butyl phthalate (DnBP) were higher in older preschools. The presence of foam mattresses and PVC flooring in the sampling room were associated with higher levels of DiNP in dust. Children's exposure from preschool dust ingestion was below established health based reference values and the estimated exposure to different phthalates and BPA via preschool dust ingestion accounted for 2-27% of the total exposure. We found significantly lower urinary levels of BPA and metabolites of strictly regulated phthalates, but higher levels of DiNP metabolites, in urine from the children in this study compared to the children who provided urine samples fifteen years earlier.

Intra-individual variations and time trends 1991-2001 in human serum levels of PCB, DDE and hexachlorobenzene.

BACKGROUND: An important question is whether human serum levels of persistent organic pollutants has continued to decrease during the last decades. The aim of this study was to assess intra-individual variations over time of serum levels of 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153), 1,1-dichloro-2,2-bis(4-chlorophenyl)-ethene (p,p'-DDE) and hexachlorobenzene (HCB), considering the impact of a number of possible determinants. METHODS: Blood samples were drawn for the same 39 subjects in 1991 and 2001. Interviews were made at both occasions. Lipid adjusted serum concentrations of CB-153, p,p'-DDE and HCB were determined in both sets of blood samples using gas chromatography-mass spectrometry. The fatty acid composition of the serum lipids was analyzed by means of gas-liquid chromatography. RESULT: The CB-153 concentrations in serum had averagely decreased with 34% in between 1991 and 2001 (p<0.001). Of individual determinants only increasing BMI was associated with decreasing CB-153 levels (beta=-1.0, 95% CI -1.8, -0.2, p=0.01), explaining 13% of the variation. The average decrease of p,p'-DDE was 55%, and could only weakly be associated with a relative increase of BMI (beta=-1.0, 95% CI -2.3, 0.2, p=0.09), explaining only 5% of the variation. The average decrease of HCB was 53%, and was associated only with high fish consumption in 1991, explaining 12% of the variation. CONCLUSIONS: The results support a continuing decrease in human body burdens of PCBs, DDE and HCB during the 1990s. The explanatory factors relative change of BMI and fish consumption explained only a minor part of the time-related variations in serum levels.

Tobacco smoking during pregnancy and risk of adverse behaviour in offspring: A follow-up study.

OBJECTIVES: This study examines associations between prenatal exposure to tobacco smoking and adverse behaviour in the offspring. METHODS: We included 1016 pregnant women from Greenland and Ukraine (526 from Greenland and 490 from Ukraine). Serum cotinine measurements were used to identify smoking pregnant women. When the children were from five to nine years of age, the parents assessed the child's behaviour using the Strength and Difficulties Questionnaire (SDQ). RESULTS: Overall, smoking in pregnancy was not associated with a higher probability of adverse behaviour assessed by the total SDQ score. However, in the crude analysis smoking was associated with a higher mean difference of SDQ-total score. In Greenland the SDQ-total mean difference (MD) was (MD (95% CI)=1.31 points (0.42; 2.19)) and in Ukraine (MD (95% CI)=0.18 points (-1.2; 0.91)), whereas the adjusted mean differences were statistically non-significant. CONCLUSIONS: In utero exposure to tobacco smoking was not associated with a significant higher risk of adverse behaviour in the offspring, but elevated risk of adverse behaviour among children prenatally exposed to smoking cannot be excluded.

Sphingolipids in human ileostomy content after meals containing milk sphingomyelin.

BACKGROUND: Sphingomyelin occurs in modest amounts in the diet, in sloughed mucosal cells, and in bile. It is digested by the mucosal enzymes alkaline sphingomyelinase and ceramidase. In humans, alkaline sphingomyelinase is also secreted in bile. The digestion of sphingomyelin is slow and incomplete, which has been linked to the inhibition of cholesterol absorption and colonic carcinogenesis. OBJECTIVE: We evaluated whether the supply of moderate amounts of milk sphingomyelin increases the exposure of the colon to sphingomyelin and its metabolites. DESIGN: Two experimental series were performed. In experiment A, we measured the content of sphingomyelin and ceramide in human ileostomy content by HPLC during 8 h after consumption of a test meal containing 250 mg milk sphingomyelin. In experiment B, we measured the molecular species of sphingomyelin and ceramide by HPLC-tandem mass spectrometry after doses of 50, 100, or 200 mg sphingomyelin. RESULTS: In experiment A, the average increase in ileostomy content of ceramide plus sphingomyelin amounted to 19% of the fed dose of sphingomyelin. In experiment B, the output of C-22:0-sphingomyelin, C-23:0-sphingomyelin, C-24:0-sphingomyelin, and sphingosine increased significantly, and palmitoyl-sphingomyelin increased proportionally less. Outputs and concentrations of palmitoyl-ceramide and sphingosine showed great individual variation, and stearoyl-sphingomyelin and stearoyl-ceramide did not increase after the meals. Although the output of long-chain sphingomyelin species increased significantly, the data indicated that >81% of all measured sphingomyelin species had been digested. CONCLUSIONS: Humans digest and absorb most of the sphingomyelin in normal diets. The amount of sphingolipid metabolites to which the colon is exposed can, however, be influenced by realistic amounts of dietary sphingomyelin.