Risk Assessment of Dietary Exposure to Organophosphorus Flame Retardants in Children by Using HBM-Data.

Due to their extensive usage, organophosphorus flame retardants (OPFRs) have been detected in humans and in the environment. Human are exposed to OPFRs via inhalation of indoor air, dust uptake or dietary uptake through contaminated food and drinking water. Only recently, few studies addressing dietary exposure to OPFRs were published. In this study, we used human biomonitoring (HBM) data of OPFRs to estimate how much the dietary intake may contribute to the total exposure. We estimated by reverse dosimetry, the daily intake of tris (2-chloroethyl) phosphate (TCEP), tris (1-chloro-2-propyl) phosphate (TCIPP), tris (1,3-dichloro-2-propyl) phosphate (TDCIPP) for children using HBM data from studies with sampling sites in Belgium, Denmark, France, Germany, Slovenia and Slovakia. For estimating the dietary exposure, a deterministic approach was chosen. The occurrence data of selected food categories were used from a published Belgium food basket study. Since the occurrence data were left-censored, the Lower bound (LB)-Upper bound (UB) approach was used. The estimated daily intake (EDI) calculated on the basis of urine metabolite concentrations ranged from 0.03 to 0.18 µg/kg bw/d for TDCIPP, from 0.05 to 0.17 µg/kg bw/d for TCIPP and from 0.02 to 0.2 µg/kg bw/d for TCEP. Based on national food consumption data and occurrence data, the estimated dietary intake for TDCIPP ranged from 0.005 to 0.09 µg/kg bw/d, for TCIPP ranged from 0.037 to 0.2 µg/kg bw/d and for TCEP ranged from 0.007 to 0.018 µg/kg bw/d (summarized for all countries). The estimated dietary intake of TDCIPP contributes 11-173% to the EDI, depending on country and LB-UB scenario. The estimated dietary uptake of TCIPP was in all calculations, except in Belgium and France, above 100%. In the case of TCEP, it is assumed that the dietary intake ranges from 6 to 57%. The EDI and the estimated dietary intake contribute less than 3% to the reference dose (RfD). Therefore, the estimated exposure to OPFRs indicates a minimal health risk based on the current knowledge of available exposure, kinetic and toxicity data. We were able to show that the dietary exposure can have an impact on the general exposure based on our underlying exposure scenarios.

Probabilistic modelling techniques in dietary exposure assessment: application on the risk assessment of cadmium for Austrian adults.

Probabilistic exposure and risk assessment of chemical hazards in the diet have increasingly gained ground in recent years as a pragmatic approach for the approximation of reality. This work presents the outcomes of a project which aimed at applying probabilistic techniques for basic modelling of chronic dietary exposure to food contaminants following EFSA guidance. These techniques, based on Monte Carlo Risk Assessment (MCRA) software and on the programming language R, were employed for the risk assessment of cadmium for Austrian adults, enabling the validation and the critical comparison of the two approaches. Harmonisation and optimisation of procedures, refinement of exposure assessment skills and confidence in the results were the main benefits. Data amount and validity were identified as critical parameters, influencing the precision of the results. Cadmium was selected as a case study due to its toxicological properties, its ubiquitous presence in food and the availability of Austrian occurrence data. Similar exposure and risk estimates were generated through MCRA and R in alternative optimistic and pessimistic exposure scenarios, suggesting low levels of concern, except for vegetarians, whose upper tail exposures are close to the established Tolerable Weekly Intake. However, as occurrence data gaps have been identified as the major element of uncertainty, the estimated exposure and risk levels are characterised as underestimated. Grains and grain-based products, potatoes and leafy vegetables are the main contributors to the intake. The results will contribute to risk management and to a future refinement of the assessment.

Toxicological approaches for the quantitative inhalation risk assessment of toxic metals from tobacco smoke: application on the deterministic and probabilistic inhalation risk assessment of cadmium for Austrian smokers.

OBJECTIVE: The objective of this study was the assessment of risks from inhalation exposure of Austrian smokers to cadmium through established toxicological approaches with emphasis on the exposure assessment component, which is challenging regarding the actual amount of metal that is inhaled and the simulation of the smoking pattern. MATERIALS AND METHODS: Exposure assessment comprised an estimation of the proportion of cadmium inhaled through smoking and actual occurrence data in tobacco products and survey smoking habits, which were integrated in alternative scenarios through a deterministic and a probabilistic Monte Carlo simulation method. Risks were characterized through the comparison of the exposure with health-based guidance values, as well as through the assessment of the excess lifetime cancer risk (ELCR), the non-cancer hazard quotient (NCHQ), and the margin of exposure (MOE). The strengths, the uncertainties, and the limitations of the different methodologies were discussed. RESULTS AND DISCUSSION: Upper exposures are close or exceed the Permitted Daily Exposure. Respiratory ELCRs are unacceptable compared to the benchmark range of 1.0E-06 to 1.0E-04. Renal and respiratory NCHQs exceed the target value of 1.0 by 3- to 17-fold. MOEs are not protective enough for cancer and non-cancer effects. The amount of cadmium that reaches the lung is a key source of uncertainty. CONCLUSION: Probabilistic estimates provide a refined capture of the actual inhalation exposure. Risk estimates and gender and age profiles are alarming, especially for young smokers. Application of toxicological approaches, combined with realistic assessment of the inhalation exposure levels, can support risk communication and management.

A tiered approach to cumulative risk assessment for reproductive and developmental toxicity of food contaminants for the austrian population using the modified Reference Point Index (mRPI).

Through our daily diet, we are exposed to a variety of food contaminants. Yet, assessing the cumulative health risk of chemical mixtures remains a challenge. Using a recently developed method, the modified Reference Point Index (mRPI), the cumulative risks posed by contaminant mixtures were assessed for their effects on reproduction and development. Since these effects can be quite diverse, a tiered approach was adopted to elucidate the risks at a more detailed level based on specific toxicological endpoints. An additional analysis was performed using the modified Maximum Cumulative Ratio (mMCR), which provides the determination of risk-dominating substances in the mixture. Our method represents a novel useful tool to screen and prioritise contaminant mixtures regarding their potential health risks. We found, that in the majority of the calculated scenarios a single substance dominates the cumulative risks. Lead was found to be the primary factor for adverse effects on reproduction and neuronal development of children. Perchlorate was identified as the most prominent risk factor for child development in generalCumulative risks of trichothecenes were dominated by deoxynivalenol. Concerning the impact on pre- and neonatal development, the co-exposure of several substances resulted in increased risks, with none of the considered contaminants dominating substantially.

Dietary exposure to furan of the Austrian population.

In the period from 2007 to 2017 furan levels of foods were analysed by the Austrian Agency for Health and Food Safety. Based on these analytical data and the Austrian consumption data the dietary exposure of children and adults to furan was estimated by using a deterministic approach. For the adult population the mean and 95th percentile dietary exposures to furan were estimated at 0.31 µg/kg bodyweight per day and at 0.72 µg/kg bodyweight per day, respectively. The mean dietary exposure of children was estimated at 0.18 µg/kg bodyweight per day and is thus only about half as high as for Austrian adults. At the 95th percentile the dietary exposure of children was estimated at 0.49 µg/kg bodyweight per day. The main contributor to the total dietary exposure for adults is coffee followed by convenience products and for children the main contributors are grain products as well as convenience products, bread and snacks. Based on the BMDL10 of 0.064 mg/kg bodyweight per day for the development of cholangiofibrosis, the MOE-calculation revealed that the current levels of dietary exposure to furan are of concern for Austrian adult high consumers. The MOE-calculation, based on the BMDL10 of 1.31 mg/kg bodyweight per day for the development of hepatocellular adenomas, indicated a health concern for Austrian children and adults.

Modified Reference Point Index (mRPI) and a decision tree for deriving uncertainty factors: A practical approach to cumulative risk assessment of food contaminant mixtures.

Risk assessment of chemical mixtures remains a challenging task in all areas of food and consumer safety. So far, no general method has been developed that is best suited to several subject areas (e.g. food contaminants, additives and supplements, plant protection products). Especially for mixtures of food contaminants sophisticated methods are typically not applicable due to a general lack of complete toxicological data sets. We developed a new approach, the modified Reference Point Index (mRPI), that combines the advantages of the Hazard Index and the Reference Point Index. Furthermore, we developed a decision tree for the determination of specific uncertainty factors that makes the mRPI an easy to use method for cumulative risk assessment even in a data poor field such as food contaminants. To further characterise the estimated cumulative risks, the Maximum Cumulative Ratio (MCR) was adapted to be applied on the mRPI, and the modified Maximum Cumulative Ratio (mMCR) was established to identify whether the risks are dominated by a single substance. We present two case studies assessing the nephrotoxic and neurotoxic risks for the Austrian population originating from food contaminant mixtures. Calculations could not rule out potential cumulative risks, yet, they seemed to be dominated by single substances.

Risk assessment of dietary exposure to perchlorate for the Austrian population.

Perchlorate is frequently found as contaminant in a variety of food. Based on analytical data of perchlorate occurrence in food products from the Austrian market, this study calculated dietary perchlorate exposure of the Austrian population for the three age classes of adults, children and infants. Furthermore, a detailed risk assessment was conducted based on the tolerable daily intake (TDI) of 0.3 µg/kg body weight/day, established by the European Food Safety Authority in 2014. Calculations of a scenario of average food consumption did not indicate elevated health risks by dietary perchlorate uptake. Exposure estimates reached only 12%, 26% and 24% of the TDI for adults, children and infants, respectively. However, in a scenario of high consumption, the TDI was exceeded by all age classes with 132%, 161% and 156%. The major cause for this exceedance is the comparatively high perchlorate contamination of spinach, but also other leaf vegetables, legumes and pineapples, leading to elevated exposure of high consumers. Our calculations reveal that the current provisional intra-Union trade reference level for perchlorate in spinach of 0.2 mg/kg, advocated by the European Commission, is not sufficient to protect high consumers against possible health risks. In order to reduce health risks to a tolerable level for all consumers, lowering of the regulatory maximum perchlorate concentrations is indicated. Moreover, a generally diversified diet can also counteract excessive exposure to perchlorate as well as to other harmful food contaminants.

Risk assessment of dietary exposure to tryptamine for the Austrian population.

Tryptamine acts as a neuromodulator and vasoactive agent in the human body. Dose-response data on dietary tryptamine are scarce and neither a toxicological threshold value nor tolerable levels in foods have been established so far. This paper reviews dose-response characteristics and toxicological effects of tryptamine as well as tryptamine contents in food, estimates dietary exposure of Austrian consumers, and calculates risk-based maximum tolerable limits for food categories. A dose without effect of 8 mg kg-1 body weight day-1 was derived from literature data. Dietary exposure via fish/seafood, beer, cheese and meat products was estimated for Austrian schoolchildren, female and male consumers, based on 543 food samples analysed in Austria 2010-15 and on food consumption data from 2008. Even worst-case estimates based on very high tryptamine contents reported in the literature did not exceed 5.9 mg kg-1 body weight day-1, and thus were below the dose without effect. Maximum tolerable levels for food commodities were calculated for high-consumption scenarios (95th percentile of female Austrian consumers). For fresh/cooked fish, preserved fish, cheese, raw sausage, condiments, sauerkraut and fermented tofu, maximum tolerable levels were 1650, 3200, 2840, 4800, 14,120, 1740 and 2400 mg kg-1, respectively. For beer, the maximum tolerable limit of 65 mg kg-1 included an uncertainty factor of 10. None of the Austrian occurrence data exceeded these levels (in fact, only 3.3% of samples demonstrated measurable amounts of tryptamine), and just one report was found in the literature on a raw fish sample exceeding the respective tolerable level. In sum, dietary intake of tryptamine should not cause adverse health effects in healthy individuals. The assessment did not take into account the combined effects of simultaneously ingested biogenic amines, and increased susceptibility to tryptamine, e.g., due to reduced monoamine oxidase activity.

Antibiotic resistance marker genes as environmental pollutants in GMO-pristine agricultural soils in Austria.

Antibiotic resistance genes may be considered as environmental pollutants if anthropogenic emission and manipulations increase their prevalence above usually occurring background levels. The prevalence of aph(3')-IIa/nptII and aph(3')-IIIa/nptIII - frequent marker genes in plant biotechnology conferring resistance to certain aminoglycosides - was determined in Austrian soils from 100 maize and potato fields not yet exposed to but eligible for GMO crop cultivation. Total soil DNA extracts were analysed by nptII/nptIII-specific TaqMan real time PCR. Of all fields 6% were positive for nptII (median: 150 copies/g soil; range: 31-856) and 85% for nptIII (1190 copies/g soil; 13-61600). The copy-number deduced prevalence of nptIII carriers was 14-fold higher compared to nptII. Of the cultivable kanamycin-resistant soil bacteria 1.8% (95% confidence interval: 0-3.3%) were positive for nptIII, none for nptII (0-0.8%). The nptII-load of the studied soils was low rendering nptII a typical candidate as environmental pollutant upon anthropogenic release into these ecosystems.

Prevalence of the aminoglycoside phosphotransferase genes aph(3')-IIIa and aph(3')-IIa in Escherichia coli, Enterococcus faecalis, Enterococcus faecium, Pseudomonas aeruginosa, Salmonella enterica subsp. enterica and Staphylococcus aureus isolates in Austria.

The aminoglycoside phosphotransferase aph(3')-IIa primarily inactivates kanamycin and neomycin, whilst aph(3')-IIIa also inactivates amikacin. The aim of this study was to determine the frequency of both resistance genes in major human pathogens to obtain their baseline prevalence in the gene pool of these bacterial populations in Austria. In total, 10 541 Escherichia coli, Enterococcus faecalis, Enterococcus faecium, Pseudomonas aeruginosa, Salmonella enterica subsp. enterica and Staphylococcus aureus isolates were collected representatively without selection bias between 2008 and 2011. Isolates were analysed by aph(3')-IIIa/nptIII- and aph(3')-IIa/nptII-specific TaqMan real-time PCR. For positive strains, MICs using Etests were performed and resistance gene sequences were determined. The overall prevalence of aph(3')-IIIa/nptIII was 1.62 % (95 % confidence interval: 1.38-1.88 %). In Escherichia coli, enterococci, Staphylococcus aureus, P. aeruginosa and Salmonella spp., the aph(3')-IIIa/nptIII prevalence was 0.47 % (0-1.47 %), 37.53 % (32.84-42.40 %), 2.90 % (1.51-5.02 %), 0 % (0-0.32 %) and 0 % (0-0.037 %), respectively. Eleven of a total of 169 carriers showed single-nucleotide polymorphisms in the resistance allele. The overall prevalence of aph(3')-IIa/nptII was 0.0096 % (0-0.046 %). Escherichia coli (0-0.70 %), enterococci (0-0.75 %), Staphylococcus aureus (0-0.73 %) and P. aeruginosa (0-0.32 %) did not carry aph(3')-IIa. A single Salmonella isolate was positive, resulting in an aph(3')-IIa prevalence of 0.013 % (0-0.058 %). aph(3')-IIIa/nptIII carriers were moderately prevalent in the strains tested except for in enterococci, which appeared to be an important reservoir for aph(3')-IIIa. aph(3')-IIa/nptII genes were detected at clinically irrelevant frequencies and played no significant role in the aminoglycoside resistance gene pool during the observation period.