Levels of nitrate, nitrite and nitrosamines in model sausages during heat treatment and in vitro digestion - The impact of adding nitrite and spinach (Spinacia oleracea L.).

Nitrite derivatives react with endogenous precursors forming N-nitrosamines associated with development of colorectal cancer. The present study aims to investigate the formation of N-nitrosamines in sausage during processing and in vitro gastrointestinal digestion after adding sodium nitrite and/or spinach emulsion. The INFOGEST digestion protocol was used to simulate the oral, gastric, and small intestinal phases of digestion, and sodium nitrite was added in the oral phase to mimic the input of nitrite from saliva as it has shown to affect the endogenous formation of N-nitrosamines. The results show that the addition of spinach emulsion, in spite of it being a source of nitrate, did not affect the nitrite content in either batter, sausage, or roasted sausage. The levels of N-nitrosamines increased with the added amount of sodium nitrite, and further formation of some volatile N-nitrosamines was observed during roasting and in vitro digestion. In general, N-nitrosamine levels in the intestinal phase followed the same trend as in the undigested products. The results further indicate that nitrite present in saliva may cause a significant increase in N-nitrosamine levels in the gastrointestinal tract and that bioactive components in spinach may protect against the formation of volatile N-nitrosamines both during roasting and digestion.

Alteration of hepato-lipidomic homeostasis in A/J mice fed an environmentally relevant PFAS mixture.

In the present study, we have investigated liver lipid homeostasis and corresponding changes in transcript and functional product levels in A/J mice exposed to environmental relevant concentration of per- and polyfluoroalkyl substances (PFAS) mixture. Mice were fed environmentally relevant concentrations of a PFAS mixture during a period of 10 weeks. The concentrations of the 8 individual PFAS in the mixture were chosen based on measured concentrations in earthworms at a Norwegian skiing area. Our data show high liver accumulation of ∑PFAS in exposed mice, which paralleled significant elevation in body weight and hepatosomatic index (HSI) of male mice. UPC2 -MS/MS analysis in both positive and negative mode, respectively, indicated significant differences between control and exposure groups in the liver of exposed mice. Principal component analysis (PCA) of the features revealed separation of control and exposure groups in both sexes. From the significantly differential 207 lipids, only 72 were identified and shown to belong to eight different lipid classes. PCA of fatty acids (FAs) profile showed a clear separation between control and PFAS exposure groups in both female and male mice, with differential abundant levels of 5 and 4 hydrolyzed FAs, respectively. Transcript and protein analysis of genes associated with lipid homeostasis (ppar-α and ß, lxr-α and ß, rxr, fasn and srebp) showed that PFAS exposure produced sex- and individual response related alterations. Glutathione reductase (Gr) activity showed exposure-related changes in both female and male mice, compared with controls. Overall, the present study has demonstrated changes in lipid metabolism after PFAS exposure, showing that PFAS accumulation in the liver resulted to hepatotoxic effects, potential interference with membrane lipid profile and homeostasis, and oxidative stress. Given the structural similarity with FAs, interaction between PFAS and nuclear receptors such as PPARs may have severe consequences for general health and physiology in exposed animals and humans.

Do changes in persistent organic pollutants after bariatric surgery cause endocrine disruption?

BACKGROUND: Bariatric surgery results in weight loss, marked endocrine changes and the release of persistent organic pollutants (POPs). The release of POPs might cause endocrine disruption. The study aimed to explore associations between POPs and adiponectin, leptin and ghrelin in subjects undergoing bariatric surgery. METHODS: The study included 63 subjects with severe obesity (men/women: 13/50), age (years): 45.0 (8.5), and BMI (kg/m2) 39.1 (3.4). Analyses of adiponectin, leptin and ghrelin and POPs (hexachlorobenzene (HCB), dichlorodiphenyldichloroethylene (p,p'-DDE), polychlorinated biphenyl (PCB) 118 (dioxin-like compound; dl), and sum 6 PCB (PCB 28, -52, -101, -138, -153, and -180) were performed before and 12 months after bariatric surgery. RESULTS: There were significant increases in adiponectin and all POPs and a fall in leptin after surgery. The main finding was the highly significant associations between adiponectin and all POPs. The increase in HCB explained 38% of the variation in adiponectin. CONCLUSIONS: If the POP-associated increase in adiponectin is a causal effect, the release of POPs might have important clinical consequences. Adiponectin has both positive and negative clinical effects exerted by essentially unknown mechanisms. The effects of released POPs on the metabolic functions in subjects undergoing bariatric surgery deserve further evaluation.

Co-exposure to UV radiation and crude oil increases acute embryotoxicity and sublethal malformations in the early life stages of Atlantic haddock (Melanogrammus aeglefinus).

Crude oil causes severe abnormalities in developing fish. Photomodification of constituents in crude oil increases its toxicity several fold. We report on the effect of crude oil, in combination with ultraviolet (UV) radiation, on Atlantic haddock (Melanogrammus aeglefinus) embryos. Accumulation of crude oil on the eggshell makes haddock embryos particularly susceptible to exposure. At high latitudes, they can be exposed to UV radiation many hours a day. Haddock embryos were exposed to crude oil (5-300 µg oil/L nominal loading concentrations) for three days in the presence and absence of UV radiation (290-400 nm). UV radiation partly degraded the eggs' outer membrane resulting in less accumulation of oil droplets in the treatment with highest oil concentration (300 µg oil/L). The co-exposure treatments resulted in acute toxicity, manifested by massive tissue necrosis and subsequent mortality, reducing LC50 at hatching stage by 60 % to 0.24 µg totPAH/L compared to 0.62 µg totPAH/L in crude oil only. In the treatment with nominal low oil concentrations (5-30 µg oil/L), only co-exposure to UV led to sublethal morphological heart defects. Including phototoxicity as a parameter in risk assessments of accidental oil spills is recommended.

Estimated daily intake of phthalates, parabens, and bisphenol A in hospitalised very low birth weight infants.

Very low birth weight infants (VLBW, birth weight (BW) < 1500 g) are exposed to phthalates, parabens and bisphenol A (BPA) early in life. We estimated daily intake (EDI) of these excipients in 40 VLBW infants the first and fifth week of life while hospitalised. Based on urinary samples collected in 2010, EDI was calculated and compared to the tolerable daily intake (TDI) with hazard quotients (HQs) evaluated. A HQ > 1 indicates that EDI exceeded TDI with increased risk of adverse health effects. EDI was higher in VLBW infants compared to term-born infants and older children. VLBW infants born at earlier gestational age (GA), or with lower BW, had higher EDI than infants born at later GA or with higher BW. First week median EDI for BPA was higher than TDI in 100% of infants, in 75% for di(2-ethylhexyl) phthalate (DEHP), 90% for the sum of butyl benzyl phthalate (BBzP), di-n-butyl phthalate (DnBP), DEHP and di-iso-nonyl phthalate (DiNP) = ∑BBzP+DnBP+DEHP+DiNP, and in 50% of infants for propylparaben (PrPa), indicating increased risk of adverse effects. Fifth week EDI remained higher than TDI in all infants for BPA, in 75% for DEHP and ∑BBzP+DnBP+DEHP+DiNP, and 25% of infants for PrPa, indicating prolonged risk. Maximum EDI for di-iso-butyl phthalate was higher than TDI suggesting risk of adverse effects at maximum exposure. VLBW infants born earlier than 28 weeks GA had higher EDI, above TDI, for PrPa compared to infants born later than 28 weeks GA. Infants with late-onset septicaemia (LOS) had higher EDI for DEHP, ∑BBzP+DnBP+DEHP+DiNP and BPA, above TDI, compared to infants without LOS. More 75% of the infants' EDI for DEHP and ∑BBzP+DnBP+DEHP+DiNP, 25% for PrPa, and 100% of infants' EDI for BPA, were above TDI resulting in HQs > 1, indicating increased risk of adverse health effects.

Effects of an environmentally relevant PFAS mixture on dopamine and steroid hormone levels in exposed mice.

In the present study, we investigated the dopaminergic and steroid hormone systems of A/J mice fed environmentally relevant concentrations of a perfluoroalkyl substance (PFAS) mixture over a period of 10 weeks. The PFAS mixture was chosen based on measured PFAS concentrations in earthworms at a Norwegian skiing area (Trondheim) and consisted of eight different PFAS. Dietary exposure to PFAS led to lower total brain dopamine (DA) concentrations in male mice, as compared to control. On the transcript level, brain tyrosine hydroxylase (th) of PFAS exposed males was reduced, compared to the control group. No significant differences were observed on the transcript levels of enzymes responsible for DA metabolism, namely - monoamine oxidase (maoa and maob) and catechol-O methyltransferase (comt). We detected increased transcript level for DA receptor 2 (dr2) in PFAS exposed females, while expression of DA receptor 1 (dr1), DA transporter (dat) and vesicular monoamine transporter (vmat) were not affected by PFAS exposure. Regarding the steroid hormones, plasma and muscle testosterone (T), 11-ketotestosterone (11-KT) and 17ß-estradiol (E2) levels, as well as transcripts for estrogen receptors (esr1 and esr2), gonadotropin releasing hormone (gnrh) and aromatase (cyp19) were unaltered by the PFAS treatment. These results indicate that exposure to PFAS doses, comparable to previous observation in earthworms at a Norwegian skiing area, may alter the dopaminergic system of mice with overt consequences for health, general physiology, cognitive behavior, reproduction and metabolism.

High urinary concentrations of parabens and bisphenol A in very low birth weight infants.

Very low birth weight infants (VLBW; birth weight < 1500 g) are treated with pharmaceuticals and medical equipment containing parabens and bisphenol A (BPA). Parabens are used in pharmaceuticals, whereas BPA in medical equipment where concentrations are rarely reported in hospitalised VLBW infants. We measured urinary concentrations of parabens and BPA and hypothesised high and increasing concentrations in infants born at lower gestational ages (GAs), and among infants with bronchopulmonary dysplasia (BPD) and late-onset septicaemia (LOS) due to higher exposure from pharmaceuticals and medical equipment. Urinary samples were collected during the first (n = 38) and fifth (n = 36) week of life. Methylparaben, ethylparaben, propylparaben, butylparaben, and BPA concentrations were measured using ultra high-performance liquid chromatography coupled to tandem mass spectrometry. VLBW infants had very high urinary concentrations of parabens and BPA compared to term infants and older children. The Σ paraben concentration was higher than detected in previous studies on premature infants. Lower GA at birth was associated with higher concentrations of parabens and BPA. Infants born before 28 weeks GA had higher first week concentrations of propylparaben (38.6 vs. 9.05 ng/mL, p = 0.007), butylparaben (0.28 vs. 0.09 ng/mL, p = 0.05) and fifth week concentrations of BPA (15.1 vs. 6.02 ng/mL, p = 0.02) than infants born after 28 weeks GA. Infants with LOS and BPD had higher fifth week concentrations of BPA than infants without LOS and BPD (LOS: 14.2 vs. 6.77 ng/mL, p = 0.07; BPD: 18.6 vs. 7.62 ng/mL, p = 0.05).

Maternal exposure to a human relevant mixture of persistent organic pollutants reduces colorectal carcinogenesis in A/J Min/+ mice.

An increased risk of developing colorectal cancer has been associated with exposure to persistent organic pollutants (POPs) and alteration in the gut bacterial community. However, there is limited understanding about the impact of maternal exposure to POPs on colorectal cancer and gut microbiota. This study characterized the influence of exposure to a human relevant mixture of POPs during gestation and lactation on colorectal cancer, intestinal metabolite composition and microbiota in the A/J Min/+ mouse model. Surprisingly, the maternal POP exposure decreased colonic tumor burden, as shown by light microscopy and histopathological evaluation, indicating a restriction of colorectal carcinogenesis. 1H nuclear magnetic resonance spectroscopy-based metabolomic analysis identified alterations in the metabolism of amino acids, lipids, glycerophospholipids and energy in intestinal tissue. In addition, 16S rRNA sequencing of gut microbiota indicated that maternal exposure modified fecal bacterial composition. In conclusion, the results showed that early-life exposure to a mixture of POPs reduced colorectal cancer initiation and promotion, possibly through modulation of the microbial and biochemical environment. Further studies should focus on the development of colorectal cancer after combined maternal and dietary exposures to environmentally relevant low-dose POP mixtures.

Decreased plasma levels of perfluoroalkylated substances one year after bariatric surgery.

Per- and polyfluoroalkylated substances (PFASs) are classified as persistent organic pollutants (POPs), and known to be protein bound. The aim of the present study was to determine the levels of 17 different PFASs before and one year after bariatric surgery, and to assess whether weight loss and changed serum protein concentrations could be influencing factors. Plasma samples from 63 patients were analyzed for nine perfluoroalkyl carboxylic acids (PFCAs), three perfluoroalkane sulfonic acids (PFSAs), and five perfluoroalkyl sulfonamide based substances (PASF) before and after surgery. Protein determination was performed in the corresponding serum samples. Mean weight loss one year after surgery was 32.1 kg. The plasma levels of all PFASs decreased with 4-34% compared to preoperative values, and included perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), and perfluorobutane sulfonate (PFBS), which have been identified with increasing levels in the general population during recent years. Serum protein concentrations also decreased with 7-8%. Although protein levels were positively correlated with PFOA, PFBS, PFHxS and PFOS, regression analysis revealed that neither weight loss nor reductions in concentrations of serum protein could explain the decreased PFAS levels. The type of surgical procedure did not influence the changes of PFAS levels between the two sample points. A reduced food intake and alterations in absorptions of nutrients after bariatric surgery may have influenced the observed decreasing plasma levels of PFASs.

Increased levels of persistent organic pollutants in serum one year after a great weight loss in humans: Are the levels exceeding health based guideline values?

BACKGROUND: With the growing prevalence of obesity, an increased number of bariatric surgeries are being performed. Lipophilic persistent organic pollutants (POPs) are stored in adipose tissue, and an increased release of lipophilic POPs into the blood circulation may occur following rapid weight loss such as after bariatric surgery. OBJECTIVES: To evaluate and compare POP levels in serum before and after bariatric surgery, and to assess if the POP levels exceeded health based guideline values, with particular focus on women of childbearing age (WCBA). METHODS: Serum samples from 63 patients before and one year after bariatric surgery were analysed for organochlorine pesticides (OCPs); polychlorinated biphenyls (PCBs); and brominated flame retardants (BFRs). RESULTS: Mean weight loss one year after surgery was 32.1kg. The levels of all the analysed POPs in serum increased during the study period. Median levels of dichlorodiphenyldichloroethylene (p,p'-DDE), hexachlorobenzen (HCB) and PCB-153 increased from 90.2ng/g lipid weight (lw) to 158.5ng/glw, from 21.1ng/glw to 36.4ng/glw and from 48.7ng/glw to 71.5ng/glw, respectively. The highest percentage increase was observed for PCB -138, with 83.1%. BFRs were detected in low sample numbers and at low levels. Guideline values for ΣPCB6 in serum were exceeded for 5% of the participants. CONCLUSIONS: Weight loss after bariatric surgery resulted in increases of POPs levels in serum between 46.7%-83.1%. Guideline values for ΣPCB6 in serum were exceeded for 5% of the participants. For WCBA, the possible transfer of comparable levels to infants warrants further attention.