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1.
J Agric Food Chem ; 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38886165

ABSTRACT

Understanding the transfer of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in farm animals is essential for ensuring food safety, but such information for suckler ewes (Ovis aries) has been lacking. This work quantifies the accumulation, tissue distribution, and depuration kinetics of PCDD/Fs in these animals. Six suckler ewes (EXP group) were exposed to PCDD/Fs through contaminated hay (2.3-12.7 ng toxic-equivalent kg-1 dry matter) and then allowed to depurate by switching to noncontaminated hay from 29 days of lactation. Four control ewes were fed continuously with noncontaminated hay. At different time points covering depuration, weaning and slaughter, PCDD/F analysis of milk (three time points), blood and sternal adipose tissue (five time points), Longissimus thoracis muscle, liver, and empty body homogenate at slaughter (188 days of depuration) was performed. A relevant PCDD/F bioaccumulation was observed from oral intake in milk and adipose tissue (biotransfer factors of 1.24 and 1.06 day kg-1 lipids for the sum toxic-equivalent, respectively) in the EXP ewes, especially for penta- and hexa-chlorinated congeners. The EXP ewes' adipose tissue started at 10-fold the EU maximum level (ML) and showed depuration below the ML after 130 days. Specific PCDD/F accumulation in the ewe liver was observed, especially for dibenzofurans. These toxicokinetic data can inform recommendations to ensure the chemical safety of sheep food products.

2.
Environ Int ; 180: 108218, 2023 10.
Article in English | MEDLINE | ID: mdl-37820422

ABSTRACT

With increasing global focus on planetary boundaries, food safety and quality, the presence of per- and polyfluoroalkyl substances (PFAS) in the food chain presents a challenge for the sustainable production and supply of quality assured food. Consumption of food is the primary PFAS exposure route for the general population. At contaminated sites, PFAS have been reported in a range of agricultural commodities including cattle. Consumer exposure assessments are complicated by the lack of validated modelling approaches to estimate PFAS bioaccumulation in cattle. Previous studies have shown that PFAS bioaccumulation in livestock is influenced by environmental, spatial and temporal factors that necessitate a dynamic modelling approach. This work presents an integrated exposure and population toxicokinetic (PopTK) model for cattle that estimates serum and tissue concentrations of PFAS over time. Daily exposures were estimated from intakes of water, pasture, and soil, and considered animal growth, seasonal variability (pasture moisture content and temperature) and variable PFAS concentrations across paddocks. Modelled serum and tissue estimates were validated against monitoring data from Australian and Swedish cattle farms. The models were also used to develop and test practical management options for reducing PFAS exposure and to prioritise remediation for farms. Model outputs for exposure management scenarios (testing cattle rotation and targeted supplementation of feed and water) showed potential for marked reductions in consumer exposures from cattle produce.


Subject(s)
Alkanesulfonic Acids , Drinking Water , Fluorocarbons , Humans , Cattle , Animals , Body Burden , Australia , Food Safety , Drinking Water/analysis
4.
J Agric Food Chem ; 71(36): 13495-13507, 2023 Sep 13.
Article in English | MEDLINE | ID: mdl-37652440

ABSTRACT

Dioxin-like polychlorinated biphenyls (dl-PCBs) as well as polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) are a major concern for food safety, especially in fat-containing foods of animal origin, such as milk. Due to the lipophilic character of PCDD/Fs and PCBs, it is of special interest to explore whether the metabolic state of high-yielding cows influences the transfer rates into milk. Five German Holstein cows were orally exposed to a mixture of 17 PCDD/Fs, 12 dl-PCBs, and 6 non-dioxin-like PCBs (ndl-PCBs) for two dosing periods of 28 days each. The first period covered the negative energy balance (NEB) after calving, while the second period addressed the positive energy balance (PEB) in late lactation. Each dosing period was followed by a depuration period of around 100 days. During the NEB phase, the transfer rates of 14 PCDD/Fs and 7 dl-PCBs quantified were significantly (p ≤ 0.1) higher compared to the PEB phase, indicating an influence of the metabolic state on the transfer. Furthermore, the congener-specific transfer rates (0.3-39%) were in the range of the results from former studies. This indicates that the milk yield of the exposed cows is not the only determining factor for the transfer of these congeners into milk.


Subject(s)
Polychlorinated Biphenyls , Polychlorinated Dibenzodioxins , Female , Cattle , Animals , Milk , Dibenzofurans , Lactation
5.
Sci Total Environ ; 892: 164539, 2023 Sep 20.
Article in English | MEDLINE | ID: mdl-37268128

ABSTRACT

Non-dioxin-like polychlorinated biphenyls (ndl-PCBs) are persistent environmental pollutants that accumulate in the tissues of exposed animals and humans. Contaminated feed can lead to ndl-PCB contaminated food of animal origin; such foods are the main route of human exposure. Therefore, predicting ndl-PCB transfer from feed into animal products is important for human health risk assessment. Here, we developed a physiologically based toxicokinetic model describing the transfer of PCBs-28, 52, 101, 138, 153 and 180 from contaminated feed into the liver and fat of fattening pigs. The model is based on a feeding study with fattening pigs (PIC hybrids) that were temporarily fed contaminated feed containing known concentrations of ndl-PCBs. Animals were slaughtered at different ages, and ndl-PCB concentrations in muscle fat and liver were determined. The model accounts for animal growth and excretion via the liver. Based on their elimination speed and half-lives, they can be categorized into fast (PCB-28), intermediate (PCBs 52 and 101) and slow (PCBs 138, 153 and 180). Using a simulation with realistic growth and feeding patterns, the following transfer rates were found: 10 % (for fast), 35-39 % (intermediate) and 71-77 % (slow eliminated congeners). Using the models, the highest level of 3.8 µg/kg dry matter (DM) was calculated for any sum of ndl-PCBs in pig feed to ensure that the current maximum levels in pork meat and liver (40 ng/g fat) are not be exceeded. The model is included in the Supplementary Material.


Subject(s)
Dioxins , Polychlorinated Biphenyls , Polychlorinated Dibenzodioxins , Swine , Animals , Humans , Polychlorinated Biphenyls/toxicity , Toxicokinetics
6.
Environ Toxicol Pharmacol ; 99: 104106, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36907369

ABSTRACT

Polychlorinated biphenyls (PCBs) are persistent environmental pollutants that accumulate in tissues of exposed animals and humans. This case report refers ton=3 dairy cows accidentally exposed to non-dioxin-like PCBs (ndl-PCBs) of unknown origin on a German farm. At study start they had a cumulative total of 122-643 ng/g fat in milk and 105-591 ng/g fat in blood, consisting mainly of PCBs 138, 153, and 180. Two cows calved during the study and their calves were raised on their mothers' milk, resulting in cumulative exposure until slaughter. A physiologically based toxicokinetic model was developed to describe the fate of ndl-PCBs in the animals. The toxicokinetic behavior of ndl-PCBs was simulated in individual animals, including transfer of contaminants into calves via milk and placenta. Both the simulations and experimental data indicate that contamination via both routes is significant. In addition, the model was used to estimate kinetic parameters for risk assessment.


Subject(s)
Benzofurans , Environmental Pollutants , Polychlorinated Biphenyls , Humans , Pregnancy , Female , Cattle , Animals , Polychlorinated Biphenyls/toxicity , Toxicokinetics , Environmental Pollutants/toxicity , Environmental Pollutants/analysis , Milk/chemistry
7.
Nutr Res Rev ; 36(2): 448-470, 2023 Dec.
Article in English | MEDLINE | ID: mdl-36089770

ABSTRACT

Polychlorinated dibenzo-para-dioxins (PCDDs) and dibenzofurans (PCDFs) (collectively and colloquially referred to as 'dioxins') as well as polychlorinated biphenyls (PCBs) are persistent and ubiquitous environmental contaminants that may unintentionally enter and accumulate along the food chain. Owing to their chronic toxic effects in humans and bioaccumulative properties, their presence in feed and food requires particular attention. One important exposure pathway for consumers is consumption of milk and dairy products. Their transfer from feed to milk has been studied for the past 50 years to quantify the uptake and elimination kinetics. We extracted transfer parameters (transfer rate, transfer factor, biotransfer factor and elimination half-lives) in a machine-readable format from seventy-six primary and twenty-nine secondary literature items. Kinetic data for some toxicologically relevant dioxin congeners and the elimination half-lives of dioxin-like PCBs are still not available. A well-defined selection of transfer parameters from literature was statistically analysed and shown to display high variability. To understand this variability, we discuss the data with an emphasis on influencing factors, such as experimental conditions, cow performance parameters and metabolic state. While no universal interpretation could be derived, a tendency for increased transfer into milk is apparently connected to an increase in milk yield and milk fat yield as well as during times of body fat mobilisation, for example during the negative energy balance after calving. Over the past decades, milk yield has increased to over 40 kg/d during high lactation, so more research is needed on how this impacts feed to food transfer for PCDD/Fs and PCBs.


Subject(s)
Benzofurans , Dioxins , Polychlorinated Biphenyls , Polychlorinated Dibenzodioxins , Female , Animals , Cattle , Humans , Polychlorinated Dibenzodioxins/analysis , Milk/chemistry , Polychlorinated Biphenyls/analysis , Dioxins/analysis , Dibenzofurans/analysis , Benzofurans/analysis
8.
Nutr Res Rev ; 36(2): 484-497, 2023 Dec.
Article in English | MEDLINE | ID: mdl-36345910

ABSTRACT

Understanding the transfer of polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) as well as polychlorinated biphenyls (PCBs) from oral exposure into cow's milk is not purely an experimental endeavour, as it has produced a large corpus of theoretical work. This work consists of a variety of predictive toxicokinetic models in the realms of health and environmental risk assessment and risk management. Their purpose is to provide mathematical predictive tools to organise and integrate knowledge on the absorption, distribution, metabolism and excretion processes. Toxicokinetic models are based on more than 50 years of transfer studies summarised in part I of this review series. Here in part II, several of these models are described and systematically classified with a focus on their applicability to risk analysis as well as their limitations. This part of the review highlights the opportunities and challenges along the way towards accurate, congener-specific predictive models applicable to changing animal breeds and husbandry conditions.


Subject(s)
Benzofurans , Polychlorinated Biphenyls , Polychlorinated Dibenzodioxins , Female , Animals , Cattle , Humans , Polychlorinated Dibenzodioxins/toxicity , Polychlorinated Dibenzodioxins/analysis , Polychlorinated Dibenzodioxins/metabolism , Milk/chemistry , Polychlorinated Biphenyls/toxicity , Polychlorinated Biphenyls/analysis , Polychlorinated Biphenyls/metabolism , Dibenzofurans , Toxicokinetics , Dibenzofurans, Polychlorinated , Benzofurans/analysis , Benzofurans/metabolism , Risk Assessment
9.
J Agric Food Chem ; 70(42): 13754-13764, 2022 Oct 26.
Article in English | MEDLINE | ID: mdl-36241171

ABSTRACT

Non-dioxin-like polychlorinated biphenyls (ndl-PCBs) are a subclass of persistent bioaccumulative pollutants able to enter the food chain. Toxicokinetic models for the transfer of the six ndl-PCB congeners (PCBs 28, 52, 101, 138, 153, and 180) from contaminated feed and soil into chicken eggs and meat are presented. Three independent controlled feeding study datasets were used to estimate the model parameters and four studies for evaluating the model performance. The yolk deposition of ndl-PCBs is modeled in a novel way that mimics the physiology of yolk growth and development, resulting in improved prediction of the experimental data without introducing an ad hoc time delay between ovulation and oviposition. Using the models, the highest level of 2.4 µg/kg dry matter (DM) was calculated for the sum of ndl-PCBs in laying hen feed to ensure that the current maximum levels in meat and eggs (40 ng/g fat) will not be exceeded. It is also shown how this highest level in feed should be adapted in case soil, in addition to feed, is also a source of ndl-PCBs for free-range chickens.


Subject(s)
Dioxins , Environmental Pollutants , Polychlorinated Biphenyls , Polychlorinated Dibenzodioxins , Animals , Female , Polychlorinated Biphenyls/toxicity , Polychlorinated Biphenyls/analysis , Dioxins/analysis , Chickens , Soil , Toxicokinetics , Food Contamination/analysis , Polychlorinated Dibenzodioxins/analysis , Eggs/analysis , Environmental Pollutants/toxicity , Environmental Pollutants/analysis
10.
J Agric Food Chem ; 70(37): 11749-11758, 2022 Sep 21.
Article in English | MEDLINE | ID: mdl-36068017

ABSTRACT

Lupin varieties with a low content of quinolizidine alkaloids (QAs) like blue sweet lupin (BSL) have long been used as a protein source for dairy cows. A health concern for humans may arise from the transfer of acute toxic QAs from feed into cow's milk. This study is the first to quantify the transfer of QAs from BSL into cow's milk with experimental and modeling methods. Four lactating dairy cows were subjected to two 7 day feeding periods with 1 and 2 kg/d BSL, respectively, each followed by a depuration period. BSL contained 1774 mg/kg dry matter total QAs. Individual milk samples were taken twice daily and QA contents in feed and milk determined with liquid chromatography-tandem mass spectrometry. Transfer of QAs into the milk was already seen with the administration of 1 kg/d BSL, with differences in transfer rates (TRs) between individual QAs. A toxicokinetic model was derived to quantify and predict QA feed-to-food transfer. For the four most prominent QAs, our model shows an α-half-life of around 0.27 d. TRs were obtained for six QAs and were between 0.13 (sparteine) and 3.74% (multiflorine). A toxicological assessment of milk containing QAs as measured in this study indicated a potential health concern.


Subject(s)
Alkaloids , Lupinus , Sparteine , Alkaloids/metabolism , Animal Feed/analysis , Animals , Cattle , Diet , Female , Humans , Lactation , Lupinus/metabolism , Milk/chemistry , Sparteine/analysis , Sparteine/metabolism
11.
Nat Food ; 3(11): 921-932, 2022 11.
Article in English | MEDLINE | ID: mdl-37118216

ABSTRACT

The industrial hemp sector is growing and, in recent years, has launched many novel hemp-derived products, including animal feed. It is, however, unclear to what extent individual cannabinoids from industrial hemp transfer from the feed into products of animal origin and whether they pose a risk for the consumer. Here we present the results of a feeding experiment with industrial hemp silage in dairy cows. Hemp feeding included changes in feed intake, milk yield, respiratory and heart rates, and behaviour. We combined liquid chromatography-tandem mass spectrometry-based analyses and toxicokinetic computer modelling to estimate the transfer of several cannabinoids (Δ9-tetrahydrocannabinol (Δ9-THC), Δ8-THC, Δ9-tetrahydrocannabinolic acid, Δ9-tetrahydrocannabivarin, 11-OH-Δ9-THC, 11-nor-9-carboxy-Δ9-THC, cannabidiol, cannabinol and cannabidivarin) from animal feed to milk. For Δ9-THC, which has a feed-to-milk transfer rate of 0.20% ± 0.03%, the acute reference dose for humans was exceeded in several consumer groups in exposure scenarios for milk and dairy product consumption when using industrial hemp to feed dairy cows.

12.
Environ Sci Technol ; 55(16): 11080-11090, 2021 08 17.
Article in English | MEDLINE | ID: mdl-34342440

ABSTRACT

Non-dioxin-like polychlorinated biphenyls (ndl-PCBs) are a subclass of persistent bioaccumulative pollutants able to enter the food chain. We investigated the transfer of ndl-PCBs from contaminated feed into meat and liver of fattening chickens. A total of 48 chicks were divided into five treatment and one control groups. Treated animals were fed with contaminated diets (11.7 ± 0.4 µg/kg sum of indicator ndl-PCBs; 88% dry matter (DM)) before slaughter for different subperiods of time: 16, 23, 28, 32, and 36 days for groups 1-5, respectively. One day after the end of each subperiod, three animals per group were slaughtered to determine the congener-specific ndl-PCB content. All remaining animals were fed the control feed until slaughter on day 37 to probe depuration. We used these data to generate congener-specific physiologically based toxicokinetic (PBTK) models for indicator ndl-PCBs. The models show that PCBs 28, 138, 153, and 180 form a more slowly eliminated cluster (with an observed transfer rate into meat over 74% and observed half-lives over 8.7 days) than PCBs 52 and 101 (with a transfer rate under 13% and half-lives under 2.6 days). Our simulations show that ndl-PCB levels in feed lower than 3.9 (long 56-day) or 4.4 µg/kg (short 37-day fattening period) would be necessary to ensure the current maximum level in muscle meat (fat basis), according to EU Regulations 1881/2006 and 1259/2011. The PBTK models are made available in the Python and Food Safety Knowledge Exchange formats.


Subject(s)
Dioxins , Polychlorinated Biphenyls , Polychlorinated Dibenzodioxins , Animals , Chickens , Meat/analysis , Polychlorinated Biphenyls/analysis
13.
PLoS One ; 16(7): e0254301, 2021.
Article in English | MEDLINE | ID: mdl-34314433

ABSTRACT

BACKGROUND: During food or feed contamination events, it is of utmost importance to ensure their rapid resolution to minimize impact on human health, animal health and finances. The existing Rapid Alert System for Food and Feed (RASFF) is used by the European Commission, national competent authorities of member countries and the European Food Safety Authority to report information on any direct or indirect human health risk arising from food or feed, or serious risks to animal health or the environment in relation to feed. Nevertheless, no methods exist to to collectively evaluate this vast source of supply chain information. METHODS: To aid in the extraction, evaluation and visualization of the data in RASFF notifications, we present the Rapid Alert Supply Network Extractor (RASNEX) open-source tool available from https://doi.org/10.5281/zenodo.4322555 freely. Among RASNEX's functions is the graphical mapping of food and feed supply chain operators implicated in contamination events. RASNEX can be used during ongoing events as a support tool for risk analysis using RASFF notifications as input. RESULTS: In a first use case, we showcase the functionality of RASNEX with the RASFF notification on a 2017/2018 contamination event in eggs caused by the illegal use of fipronil. The information in this RASFF notification is used to visualize nine different flows of main and related food products. In a second use case, we combine RASFF notifications from different types of food safety hazards (Salmonella spp., fipronil and others) to obtain wider coverage of the visualized egg supply network compared to the first use case. Actors in the egg supply chain were identified mainly for Italy, Poland and Benelux. Other countries (although involved in the egg supply chain) were underrepresented. CONCLUSIONS: We hypothesize that biases may be caused by inconsistent RASFF reporting behaviors by its members. These inconsistencies may be counteracted by implementing standardized decision-making tools to harmonize decisions whether to launch a RASFF notification, in turn resulting in a more uniform future coverage across European food and feed supply chains with RASNEX.


Subject(s)
Consumer Product Safety/legislation & jurisprudence , Food Contamination/prevention & control , User-Computer Interface , Animals , Chickens , Eggs/analysis , Eggs/microbiology , European Union , Food Chain , Food Contamination/analysis , Humans , Insecticides/analysis , Pyrazoles/analysis , Salmonella/pathogenicity
14.
ALTEX ; 38(3): 398-418, 2021.
Article in English | MEDLINE | ID: mdl-33330944

ABSTRACT

Undesirable substances in feed can transfer into foods of animal origin after ingestion by livestock animals. These contaminants in food may threaten consumer health. Commonly, feeding trials are conducted with animals to assess the transfer of undesirable substances into animal tissues or milk. Such feeding trials explore the effects of the various physiological systems (e.g., ruminant and non-ruminant gastro-intestinal tracts) as well as different livestock production intensities on transfer. Using alternative methods to mimic the complex physiological processes of several organs is highly challenging. This review proposes a potential cascade of in vitro and ex vivo models to investigate the transfer of contam­inants from feed into foods of animal origin. One distinct challenge regarding the models for ruminants is the simulation of the forestomach system, with the rumen as the anaerobic fermentation chamber and its epithelial surfaces for absorption. Therefore, emphasis is placed on in vitro systems simulating the rumen with its microbial ecosystem as well as on ex vivo systems to replicate epithelial absorption. Further, the transfer from blood into milk must be evaluated by employing a suitable model. Finally, in silico approaches are introduced that can fill knowledge gaps or substitute in vitro and ex vivo models. Physiologically-based toxicokinetics combines the information gained from all alternative methods to simulate the transfer of ingested undesirable substances into foods of animal origin.


Subject(s)
Ecosystem , Ruminants , Animals , Fermentation , Rumen
15.
J Agric Food Chem ; 68(45): 12539-12548, 2020 Nov 11.
Article in English | MEDLINE | ID: mdl-33121240

ABSTRACT

A feeding study was performed to examine the bioaccumulation of per- and polyfluoroalkyl substances (PFAS) in laying hens' tissues and plasma and feed-to-egg transfer rates and half-lives. A 25 day exposure was followed by a 42 day depuration period. A target analysis revealed substantial amounts of the precursors N-methyl and N-ethyl perfluorooctane sulfonamidoacetic acid (Me- and EtFOSAA), perfluorooctane sulfonamidoacetic acid (FOSAA), and perfluorooctane sulfonamide (FOSA). In tissues and eggs, the highest bioaccumulation was found for PFHxS, PFHpS, PFOS, and PFOA. Low levels of PFHxS (all samples), PFOS, and FOSAA (in yolk) were measurable even after the depuration period. The egg elimination half-lives of PFOS and aforementioned precursors were estimated to be 4.3 days, while the transfer rates of PFOS and all precursors taken together were 0.99. The transfer rate of PFOA was around 0.49. PFHxS and PFHpS showed apparent transfer rates of >100%, which is hypothesized to indicate the presence of precursors.


Subject(s)
Alkanesulfonic Acids/chemistry , Animal Feed/analysis , Chickens/metabolism , Eggs/analysis , Environmental Pollutants/chemistry , Fluorocarbons/chemistry , Food Contamination/analysis , Alkanesulfonic Acids/metabolism , Animals , Environmental Pollutants/metabolism , Female , Fluorocarbons/metabolism , Toxicokinetics
16.
J Agric Food Chem ; 68(45): 12527-12538, 2020 Nov 11.
Article in English | MEDLINE | ID: mdl-33121246

ABSTRACT

The group of per- and polyfluoroalkyl substances (PFAS) comprises thousands of chemicals, which are used in various industrial applications and consumer products. In this study, a feeding experiment with laying hens and feed grown on a contamination site was conducted, and PFAS were analyzed in the feed and eggs to assess the transfer of PFAS into eggs. A targeted analysis of perfluoroalkyl acids (PFAAs) and different sulfonamides was performed. Additionally, the total oxidizable precursor (TOP) assay was modified by fully oxidizing small amounts of the samples instead of oxidizing their extracts in order to overcome potential losses during extraction. Targeted analysis showed the presence of known PFAAs and four sulfonamides in the feed and egg yolk samples. In the plant-based feed, short-chain PFAAs, methyl and ethyl perfluorooctane sulfonamidoacetic acid (Me- and EtFOSAA), and perfluorooctane sulfonic acid (PFOS) were the most abundant PFAS. In the eggs, PFOS, FOSAA, and its alkylated homologues showed the highest concentrations. The TOP assay revealed the presence of substantial amounts of precursors with different chain lengths from C4 to C8. The highest relative increase of PFOA after oxidation was observed in egg yolk from the end of the exposure period (828%). The results of this study demonstrate the transfer of PFAAs and their precursors into hens' eggs and emphasize the contribution of (known and unidentified) precursors to the overall PFAS burden in edible products. The modified TOP assay approach was shown to be a powerful tool to better assess the total burden of samples with PFAS.


Subject(s)
Alkanesulfonic Acids/analysis , Animal Feed/analysis , Chickens/metabolism , Eggs/analysis , Environmental Pollutants/analysis , Fluorocarbons/analysis , Food Contamination/analysis , Alkanesulfonic Acids/metabolism , Animals , Environmental Pollutants/metabolism , Female , Fluorocarbons/metabolism , Oxidation-Reduction
17.
Arch Toxicol ; 94(1): 187-196, 2020 01.
Article in English | MEDLINE | ID: mdl-31728592

ABSTRACT

Tetrachlorodibenzo-p-dioxin (TCDD) is a ubiquitous, toxic, persistent and bioaccumulative organic pollutant. TCDD can potentially enter the food chain through contaminated food of animal origin as a consequence of feed contamination. Prediction of the TCDD transfer from feed into animal products is thus important for human health risk assessment. Here, we develop several physiologically based toxicokinetic (PBTK) models of TCDD transfer from contaminated feed into growing pigs (Sus scrofa) exposed to doses ranging from 24.52 to 3269.25 ng of TCDD. We test the consequences of explicit dose-dependent absorption (DDA) versus the indirect effects of a self-induced liver metabolism (SIM). The DDA and SIM models showed similar fit to experimental data, although currently it is not possible to unequivocally make statement on a mechanistic preference. The performance of both toxicokinetic models was successfully evaluated using the 1999 Belgian case of contaminated fats for feeding. In combination with toxicokinetic models of other dioxin congeners, they can be used to formulate maximum allowance levels of dioxins in feedstuffs for pigs. Additionally, the implementation of in silico-predicted partition coefficients was explored as a useful alternative to predict TCDD tissue distribution in low-dose scenarios without recurring to animal experiments.


Subject(s)
Animal Feed/adverse effects , Models, Theoretical , Polychlorinated Dibenzodioxins/pharmacokinetics , Animals , Body Weight/drug effects , Computer Simulation , Dietary Exposure/adverse effects , Dose-Response Relationship, Drug , Environmental Pollutants/pharmacokinetics , Environmental Pollutants/toxicity , Half-Life , Humans , Polychlorinated Dibenzodioxins/toxicity , Rats , Swine , Tissue Distribution , Toxicokinetics
18.
Arch Toxicol ; 92(3): 1089-1097, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29143854

ABSTRACT

Pyrrolizidine alkaloids (PA) are secondary metabolites of certain flowering plants. The ingestion of PAs may result in acute and chronic effects in man and livestock with hepatotoxicity, mutagenicity, and carcinogenicity being identified as predominant effects. Several hundred PAs sharing the diol pyrrolizidine as a core structure are formed by plants. Although many congeners may cause adverse effects, differences in the toxic potency have been detected in animal tests. It is generally accepted that PAs themselves are biologically and toxicologically inactive and require metabolic activation. Consequently, a strong relationship between activating metabolism and toxicity can be expected. Concerning PA susceptibility, marked differences between species were reported with a comparatively high susceptibility in horses, while goat and sheep seem to be almost resistant. Therefore, we investigated the in vitro degradation rate of four frequently occurring PAs by liver enzymes present in S9 fractions from human, pig, cow, horse, rat, rabbit, goat, and sheep liver. Unexpectedly, almost no metabolic degradation of any PA was observed for susceptible species such as human, pig, horse, or cow. If the formation of toxic metabolites represents a crucial bioactivation step, the found inverse conversion rates of PAs compared to the known susceptibility require further investigation.


Subject(s)
Microsomes, Liver/drug effects , Pyrrolizidine Alkaloids/pharmacokinetics , Animals , Biotransformation , Cattle , Female , Goats , Horses , Humans , Male , Microsomes, Liver/metabolism , Pyrrolizidine Alkaloids/toxicity , Rabbits , Rats , Sheep , Species Specificity , Swine
19.
J Agric Food Chem ; 62(28): 6861-70, 2014 Jul 16.
Article in English | MEDLINE | ID: mdl-24892814

ABSTRACT

The transfer of a mixture of perfluoroalkyl acids (PFAAs) from contaminated feed into the edible tissues of 24 fattening pigs was investigated. Four perfluoroalkyl sulfonic (PFSAs) and three perfluoroalkyl carboxylic acids (PFCAs) were quantifiable in feed, plasma, edible tissues, and urine. As percentages of unexcreted PFAA, the substances accumulated in plasma (up to 51%), fat, and muscle tissues (collectively, meat 40-49%), liver (under 7%), and kidney (under 2%) for most substances. An exception was perfluorooctanesulfonic acid (PFOS), with lower affinity for plasma (23%) and higher for liver (35%). A toxicokinetic model is developed to quantify the absorption, distribution, and excretion of PFAAs and to calculate elimination half-lives. Perfluorohexanoic acid (PFHxA), a PFCA, had the shortest half-life at 4.1 days. PFSAs are eliminated more slowly (e.g., half-life of 634 days for PFOS). PFAAs in pigs exhibit longer elimination half-lives than in most organisms reported in the literature, but still shorter than in humans.


Subject(s)
Animal Feed , Carboxylic Acids/pharmacokinetics , Fluorocarbons/pharmacokinetics , Food Contamination , Sulfonic Acids/pharmacokinetics , Sus scrofa/metabolism , Animal Feed/analysis , Animals , Carboxylic Acids/analysis , Carboxylic Acids/toxicity , Female , Fluorocarbons/analysis , Fluorocarbons/toxicity , Food Safety , Half-Life , Male , Meat/analysis , Sulfonic Acids/analysis , Sulfonic Acids/toxicity , Toxicokinetics
20.
Chemosphere ; 93(3): 474-9, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23871594

ABSTRACT

When food producing animals are contaminated with PCDD/F congeners, information on the contaminant's concentration in the bodies of the animals at time of slaughter is needed for risk management purposes. We have developed a mathematical model for the kinetics of PCDD/Fs in growing pigs in case of contaminated feed fed for a limited duration of time. This model allows the prediction of concentrations in body fat. It considers absorption fractions of PCDD/Fs, clearance by metabolism, dilution by growth and excretion through fecal fat. The model parameters were calibrated by fitting the model to experimental data. On the basis of this toxicokinetic model a probabilistic model has been constructed. The probabilistic model handles the parameters with appropriate probability distributions and Monte-Carlo simulation technique, providing for realistic situations with many animals and a range of contaminations and feeding intervals. We applied the new model to describe the German dioxin incident of winter 2010/2011 and discuss its viability as decision tool. The approach demonstrated here is a showcase how a risk assessment in the case of contaminated feeding can be performed.


Subject(s)
Dioxins/metabolism , Dioxins/toxicity , Environmental Exposure , Environmental Monitoring/methods , Environmental Pollutants/metabolism , Environmental Pollutants/toxicity , Sus scrofa/metabolism , Adipose Tissue/metabolism , Animal Feed/analysis , Animals , Dioxins/analysis , Environmental Pollutants/analysis , Food Contamination , Models, Biological , Models, Statistical , Monte Carlo Method , Pharmacokinetics , Risk Assessment , Sensitivity and Specificity
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