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Co-exposure with fullerene may strengthen health effects of organic industrial chemicals.

ABSTRACT: In vitro toxicological studies together with atomistic molecular dynamics simulations show that occupational co-exposure with C60 fullerene may strengthen the health effects of organic industrial chemicals. The chemicals studied are acetophenone, benzaldehyde, benzyl alcohol, m-cresol, and toluene which can be used with fullerene as reagents or solvents in industrial processes. Potential co-exposure scenarios include a fullerene dust and organic chemical vapor, or a fullerene solution aerosolized in workplace air. Unfiltered and filtered mixtures of C60 and organic chemicals represent different co-exposure scenarios in in vitro studies where acute cytotoxicity and immunotoxicity of C60 and organic chemicals are tested together and alone by using human THP-1-derived macrophages. Statistically significant co-effects are observed for an unfiltered mixture of benzaldehyde and C60 that is more cytotoxic than benzaldehyde alone, and for a filtered mixture of m-cresol and C60 that is slightly less cytotoxic than m-cresol. Hydrophobicity of chemicals correlates with co-effects when secretion of pro-inflammatory cytokines IL-1? and TNF-? is considered. Complementary atomistic molecular dynamics simulations reveal that C60 co-aggregates with all chemicals in aqueous environment. Stable aggregates have a fullerene-rich core and a chemical-rich surface layer, and while essentially all C60 molecules aggregate together, a portion of organic molecules remains in water.

SUBMITTER: Lehto M

PROVIDER: S-EPMC4256445 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Co-exposure with fullerene may strengthen health effects of organic industrial chemicals.

Lehto Maili M Karilainen Topi T Róg Tomasz T Cramariuc Oana O Vanhala Esa E Tornaeus Jarkko J Taberman Helena H Jänis Janne J Alenius Harri H Vattulainen Ilpo I Laine Olli O

PloS one 20141204 12

In vitro toxicological studies together with atomistic molecular dynamics simulations show that occupational co-exposure with C60 fullerene may strengthen the health effects of organic industrial chemicals. The chemicals studied are acetophenone, benzaldehyde, benzyl alcohol, m-cresol, and toluene which can be used with fullerene as reagents or solvents in industrial processes. Potential co-exposure scenarios include a fullerene dust and organic chemical vapor, or a fullerene solution aerosolize ...[more]

PMID: 25473947

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Project description:General population human biomonitoring programs such as the National Health and Nutrition Examination Survey (NHANES) in the United States suggest that chemical exposures are common. Exposures during childhood may affect health later in life, but biomonitoring data in NHANES among pre-school aged children are limited.A convenience group of 122 3-5year old American boys and girls were recruited in 2013 for a pilot study to assess the feasibility of collecting urine from young children and analyzing it for select chemical exposure biomarkers for future NHANES. Children were primarily Hispanic (64.8%); the remainder was divided between non-Hispanic black, and non-Hispanic white and "other." We measured 52 urinary biomarkers: 13 phthalates and one non-phthalate plasticizer, five phenols and four parabens, 10 polycyclic aromatic hydrocarbons (PAHs), and 19 pesticides. For each biomarker, we calculated descriptive statistics. We also calculated the number of biomarkers detected within each child, and performed principal components analysis (PCA).NHANES staff obtained permission to attempt collection of 60mL urine from 3 to 5year olds who participated in the 2013 NHANES health examination; 83% of children successfully provided the target volume. We detected 24 individual biomarkers of pesticides, phenols and parabens, phthalates/non-phthalate plasticizers, and PAHs in 95-100% of children. The median number of biomarkers detected was 37: nine pesticides, five phenols and parabens, 13 phthalates and non-phthalate plasticizers, and 10 PAHs. Biomarkers concentrations appear to be similar to national estimates among 6-11year old children from previous NHANES. PCA suggested high within-class correlations among biomarkers.These young children successfully adhered to the collection protocol and produced enough urine for the quantification of environmental biomarkers currently being measured in NHANES participants 6 years of age and older. Using the same analytical methods employed for the analysis of samples collected from older NHANES participants, in this sample of pre-school aged children we detected multiple chemicals including plasticizers, combustion products, personal-care product chemicals, and pesticides. Starting with NHANES 2015-2016, the NHANES biomonitoring program will include urinary biomarkers for 3-5year old children to provide exposure data to select chemicals at the national level among this age group.

Project description:Environmental and occupational exposure to industrial chemicals has been linked to toxic and carcinogenic effects in animal models and human studies. However, current toxicology testing does not thoroughly explore the endocrine disrupting effects of industrial chemicals, which may have low dose effects not predicted when determining the limit of toxicity. The objective of this study was to evaluate the endocrine disrupting potential of a broad range of chemicals used in the petrochemical sector. Therefore, 139 chemicals were classified for reproductive toxicity based on the United Nations Globally Harmonized System for hazard classification. These chemicals were evaluated in PubMed for reported endocrine disrupting activity, and their endocrine disrupting potential was estimated by identifying chemicals with active nuclear receptor endpoints publicly available databases. Evaluation of ToxCast data suggested that these chemicals preferentially alter the activity of the estrogen receptor (ER). Four chemicals were prioritized for in vitro testing using the ER-positive, immortalized human uterine Ishikawa cell line and a range of concentrations below the reported limit of toxicity in humans. We found that 2,6-di-tert-butyl-p-cresol (BHT) and diethanolamine (DEA) repressed the basal expression of estrogen-responsive genes PGR, NPPC, and GREB1 in Ishikawa cells, while tetrachloroethylene (PCE) and 2,2'-methyliminodiethanol (MDEA) induced the expression of these genes. Furthermore, low-dose combinations of PCE and MDEA produced additive effects. All four chemicals interfered with estradiol-mediated induction of PGR, NPPC, and GREB1. Molecular docking demonstrated that these chemicals could bind to the ligand binding site of ER?, suggesting the potential for direct stimulatory or inhibitory effects. We found that these chemicals altered rates of proliferation and regulated the expression of cell proliferation associated genes. These findings demonstrate previously unappreciated endocrine disrupting effects and underscore the importance of testing the endocrine disrupting potential of chemicals in the future to better understand their potential to impact public health.

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Co-exposure with fullerene may strengthen health effects of organic industrial chemicals.

Publications

Co-exposure with fullerene may strengthen health effects of organic industrial chemicals.

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