Dynamic exposure and body burden models for per- and polyfluoroalkyl substances (PFAS) enable management of food safety risks in cattle.

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.

Experimental Study on the Transfer of Polychlorinated Biphenyls (PCBs) and Polychlorinated Dibenzo-p-dioxins and Dibenzofurans (PCDD/Fs) into Milk of High-Yielding Cows during Negative and Positive Energy Balance.

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.

Toxicokinetic modelling of the transfer of non-dioxin like polychlorinated biphenyls from feed into edible tissues of pigs.

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.

Transfer and toxicokinetic modeling of non-dioxin-like polychlorinated biphenyls (ndl-PCBs) into accidentally exposed dairy cattle and their calves - A case report.

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.

Transfer of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and polychlorinated biphenyls (PCBs) from oral exposure into cow's milk - part II: toxicokinetic predictive models for risk assessment.

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.

Transfer of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and polychlorinated biphenyls (PCBs) from oral exposure into cow's milk - Part I: state of knowledge and uncertainties.

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.

Investigations on the Transfer of Quinolizidine Alkaloids from Lupinus angustifolius into the Milk of Dairy Cows.

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.