Toxicokinetics may help assessing the risk of metal-contaminated soils by quantifying the development of internal metal concentrations in organisms over time. This study assessed the toxicokinetics in Enchytraeus crypticus of non-essential (Pb and Cd) and essential elements (Zn and Cu) in metal-contaminated field soils from a mining area, containing 3.49–24.3 mg Cd/kg dry soil, 433–1416 mg Pb/kg dry soil, 15.7–44.9 mg Cu/kg dry soil and 1718–6050 mg Zn/kg dry soil. Three different uptake-elimination patterns in E. crypticus were found. Both essential elements (Zn and Cu) showed fast increasing internal concentrations reaching equilibrium within 2 d in the uptake phase, without hardly any elimination after transfer to clean soil. The non-essential Cd showed a slow linear accumulation and excretion with body concentrations not reaching steady state within 21 d. Internal Pb concentrations, however, reached equilibrium within 7 d in the uptake phase. Longer exposure times in ecotoxicological tests, therefore, are required for elements like Cd. Porewater pH and dissolved organic carbon (DOC) levels were the dominant factors controlling Cd uptake from the test soils. The 21-d body Cd and Pb concentrations were best explained from 0.01 M CaCl₂-extractable soil concentrations. Steady-state Cu and Zn body concentrations were independent of soil exposure concentrations. Bioaccumulation factors (BAF) were low for Pb (<0.1 kgₛₒᵢₗ/kgwₒᵣₘ), but high for Cd at 1.78–24.3 kgₛₒᵢₗ/kgwₒᵣₘ, suggesting a potential risk of Cd biomagnification in the terrestrial food chain of the mining area ecosystem.

Veterinary pharmaceuticals, including antibiotics, are emerging contaminants of concern worldwide. Avian scavengers are exposed to pharmaceuticals through consumption of livestock carcasses used for feeding wildlife for conservation purposes at supplementary feeding stations. Here we tested the hypothesis that griffon vultures (Gyps fulvus) would be more exposed to antibiotics (i.e., quinolones) when feeding on livestock carcasses from intensive farming than when they rely on carcasses from extensive farming or wild animals. We sampled 657 adult griffon vultures captured between 2008 and 2012. In addition, we sampled tissues from domestic livestock supplied at feeding stations in the study area between 2009 and 2019; pig (n = 114), sheep (n = 28), cow (n = 1) and goat (n = 2). Samples were analysed by liquid chromatography with electrospray ionization mass spectrometry (LC-ESI-MS). Quinolones were detected in plasma from 12.9% of the griffon vultures analysed. Quinolone prevalence in griffon vultures varied significantly among feeding stations but was also affected by the total amount of carcasses supplemented, especially the mass of pig carcasses. These results aligned with a 21.1% quinolone prevalence in pig carcasses sampled at feeding stations, wherein enrofloxacin and ciprofloxacin levels of up to 3359 ng/g and 1550 ng/g, respectively, were found. Given enrofloxacin pharmacokinetics in pig tissues, 5.3% of the analysed pigs may have died no more than one day after treatment. Quinolone presence in vultures was negatively associated with blood lead levels, which mostly originates from lead ammunition and indicates a higher consumption of game animal carcasses. Carcass disposal for feeding avian scavengers must always assess and manage the risks posed by veterinary pharmaceuticals, especially when livestock provided may have died soon after treatment.

Phthalates are plasticizers in various products and regarded as endocrine disruptors due to their anti-androgen effects. Environmental occurrence and toxicities of parent phthalates have been widely reported, while the current state of knowledge on their metabolites is rarely summarized. Based on the available literature, the present review mainly aims to 1) characterize the potential metabolites of phthalates (mPAEs) using the pharmacokinetics evidences acquired via animal or human models; 2) examine the molecular and cellular mechanism involved in toxicity for mPAEs; 3) investigate the exposure levels of mPAEs in different human specimens (e.g., urine, blood, seminal fluid, breast milk, amniotic fluid and others) across the globe; 4) discuss the models and related parameters for phthalate exposure assessment. We suggest there is subtle difference in toxic mechanisms for mPAEs compared to their parent phthalates due to their alternative chemical structures. Human monitoring studies performed in Asia, America and Europe have provided the population exposure baseline levels for typical phthalates in different regions. Urine is the preferred matrix than other specimens for phthalate exposure study. Among ten urinary mPAEs, the largest proportions of di-(2-ethylhexyl) phthalate (DEHP) metabolites (40%), monoethyl phthalate (mEP) (43%) and DEHP metabolites/mEP (both 29%) were observed in Asia, America and Europe respectively, and mono-5-carboxy-2-ethypentyl phthalate was the most abundant compounds among DEHP metabolites. Daily intakes of phthalates can be accurately calculated via urinary mPAEs if the proper exposure parameters were determined. Further work should focus on combining epidemiological and biological evidences to establish links between phthalates exposure and biological phenotypes. More accurate molar fractions (FUE) of the urinary excreted monoester related to the ingested diesters should be collected in epidemiological or pharmacokinetic studies for different population.

Chronic toxicity of copper (Cu) at sublethal levels is associated with ionoregulatory disturbance and oxidative stress. These factors were considered in a toxicokinetic-toxicodynamic model in the present study. The ionoregulatory disturbance was evaluated by the activity of the Na⁺/K⁺-ATPase enzyme (NKA), while oxidative stress was presented by lipid peroxidation (LPO) and glutathione-S-transferase (GST) activity. NKA activity was related to the binding of Cu²⁺ and Na ⁺ to NKA. LPO and GST activity were linked with the simulated concentration of unbound Cu. The model was calibrated using previously reported data and empirical data generated when zebra mussels were exposed to Cu. The model clearly demonstrated that Cu might inhibit NKA activity by reducing the number of functional pump sites and the limited Cu-bound NKA turnover rate. An ordinary differential equation was used to describe the relationship between the simulated concentration of unbound Cu and LPO/GST activity. Although this method could not explain the fluctuations in these biomarkers during the experiment, the measurements were within the confidence interval of estimations. Model simulation consistently shows non-significant differences in LPO and GST activity at two exposure levels, similar to the empirical observation.

The scale of variation in species sensitivity to toxicants has been theoretically linked to mode of action. Specifically, it has been proposed there will be greater variations for chemicals with a putative specific biological target than for toxicants with a non-specific narcotic mechanism. Here we test the hypothesis that mode of action is related to variation in sensitivity in a specifically designed experiment for species from a single ecologically important terrestrial taxa, namely earthworms. Earthworm toxicity tests were conducted with five species for four chemicals, providing a series of increasingly complex modes of action: a putative narcotic polycyclic aromatic hydrocarbon (fluoranthene), and three insecticides (chlorpyrifos, cypermethrin, imidacloprid) with known neuronal receptor targets. Across all the chemicals, the standard epigeic test species Eisenia fetida and Lumbricus rubellus, were generally among the two least sensitive, while the endogenic Aporrectodea caliginosa and Megascolecidae Amynthas gracilis were generally more sensitive (never being among the two least sensitive species). This indicates a potential for bias in the earthworm ecotoxicology literature, which is dominated by studies in epigeic Lumbricidae, but contains few endogeic or Megascolecidae data. Results confirmed the lowest range of variation in sensitivities for effects on reproduction was for fluoranthene (2.5 fold). All insecticides showed greater variation for species sensitivity (cypermethrin: 7.5 fold, chlorpyrifos: 10.3 fold, imidacloprid: 31.5 fold) consistent with the specific mechanisms of the pesticides. Difference in toxicodynamics, based on mode of action specificity and receptor complexity was reflected in the magnitude of sensitivity variation. However, measurements of tissue concentrations also indicated the potential importance of toxicokinetics in explaining species sensitivity variations for chlorpyrifos and cypermethrin.

Toxicokinetic studies appertain to the fundamental research of soil bioavailability. However, the research outcomes of aspects influencing uptake and elimination of hydrophobic organic compounds have not been summarized so far. In our review, a recapitulation of available toxicokinetic data (i.e. experimental conditions, if the steady state was reached, uptake and elimination rate constants, and bioaccumulation factors) is presented in well-arranged tables. Further, toxicokinetic models are overviewed in the schematic form. In the review, the required information could be quickly found and/or the experimental gaps easily identified. Generally a little is known about the effects of soil properties other than soil organic matter. Limited or no data are available about soil treatment, food supply during laboratory exposure, and metabolization in oligochaeta. The impact of these factors might be important especially for arable soils with typically low organic matter content but high consequences on humans. Besides these circumstances, other uncertainties between published studies have been found. Firstly, the scientific results are provided in heterogenous units: bioaccumulation factors as well as the rate constants are reported in dry or wet weight of soil and earthworms. The steady state is another critical factor because the time to reach the equilibrium is influenced not only by soil and compound characteristics but for example also by aging. Nevertheless, toxicokinetic studies bring irreplaceable information about the real situation in soil and our review help to define missing knowledge and estimate the scientific priorities.

This work aimed at predicting the toxic effects of phenolic compounds in Ba River on the health of female sharpbelly (Hemiculter lucidus) by the de novo transcriptomic analysis of the liver. Sharpbelly, a native fish living in freshwater ecosystem of East Asia, were sampled upstream, near, and downstream of a wastewater discharge to the Ba river. Based on the occurrence of bisphenol A (BPA), nonylphenol (NP), and 4-tert-octylphenol (4-t-OP) in the water and fish sampled from each site, up-, mid-, and down-stream were interpreted as control, high, and low treatment groups, respectively. In the mid-stream group the Fulton’s condition factor (CF) and body weight were remarkably increased by approximate 20%; the gonado-somatic index (GSI) and hepatosomatic index (HSI) in mid-stream fish showed a similar increasing trend but lacking of statistical difference. Exposure to wastewater effluent caused 160 and 162 differentially expressed genes (DEGs) in up-mid and down-mid stream groups, respectively. Two sets of DEGs were primarily enriched in the signaling pathways of drug metabolism, endocrine system, cellular process, and lipid metabolism in the mid-stream sharpbelly, which may alter the fish behavior, disrupt the reproductive function, and lead to hypothyroidism, hepatic steatosis, etc. Taken together, our results linked the disrupted signaling pathways with activities of phenolic compounds to predict the potential effects of wastewater effluent on the health of wild fish.

The abnormality in thyroid hormone modulation in developmental fish, vulnerable to per- and polyfluorinated substances, is of particular concerns for the alternative substances. Juvenile rare minnows, were exposed to chlorinated polyfluoroalkyl ether sulfonates (Cl-PFESAs), the novel alternatives to perfluorooctane sulfonate (PFOS), for 4 weeks followed by 12 weeks of depuration. Half lives were determined to be 33 d, 29 d, and 47 d for total Cl-PFESAs, C8 Cl-PFESA and C10 Cl-PFESA, respectively. Preliminary toxicity test suggested that Cl-PFESAs are moderately toxic to Rare minnow with a LC50 of 20.8 mg/L (nominal concentration） after 96 h of exposure. In the chronic toxicity test, fishes were exposed to Cl-PFESAs at geometric mean measured concentrations of 86.5 μg/L, 162 μg/L and 329 μg/L. In juvenile fishes exposed to Cl-PFESAs for 4 weeks, gene profile sequencing analysis identified 3313 differentially expressed genes, based on which pathways regulating thyroid hormone synthesis and steroid synthesis were enriched. Both whole body total and free 3,5,3′-triiodothyronine (T3) levels were significantly increased. mRNA expression of genes regulating thyroid hormone synthesis (corticotropin-releasing hormone (CRH), thyroid-stimulating hormone (THS), sodium/iodide symporter (NIS), thyroglobulin (TG), and thyroid peroxidase (TPO), transport (transthyretin,TTR), deiodinase (Dio1, Dio2) and receptor (TRα and TRβ) were decreased. Uridinediphosphate glucoronosyl-transferases (UGT1A) gene, regulating THs metabolism, was also decreased. In adult fish, thyroid hormone and genes expression in hypothalamic-pituitary-thyroid axis remained at disturbed levels after 12 weeks of depuration without exposure. Chronic developmental exposure to Cl-PFESAs caused persistent thyroid hormone disrupting effects in fish, highlighting a necessity of comprehensive ecological risk assessment.

Prothioconazole (PTC) is a widely used triazolinthione fungicide with low toxicity and short residual period. However, its desulfurization metabolite, prothioconazole-desthio (PTC-d), is more persistent and has higher toxicity in terrestrial animals. In this study, the toxicokinetics (TK) and tissue distribution of PTC and PTC-d in Chinese lizards (Eremias argus) were measured following single oral dose (100 mg kg⁻¹ body weight) treatments. TK parameters indicated that PTC was more rapidly absorbed than PTC-d, as indicated by its shorter time to reach peak concentrations in most tissues. Furthermore, the relative bioavailability of PTC in lizards was lower than that of PTC-d. Compared with PTC, PTC-d preferentially accumulated in lizards, as reflected by longer half-life of PTC-d. During the distribution process, PTC-d generated in vivo was transported from other tissues and was deposited in the skin and tail, where PTC-d may be excreted by exuviation or tail detachment. Preferential enrichment of S-enantiomer of both PTC and PTC-d were observed in all tissues. Hepatic cytochrome P450 gene expression measurement revealed that cyp1a5 and cyp3a28 exhibited the strongest responses in both treatment groups. In addition, the opposite responses of cyp2k4 in different treatment groups may indicate that this enzyme caused differences in the rates of metabolism of the two chemicals. This study compared the TK profile of PTC and its desulfurization metabolite PTC-d in lizards and demonstrated that the desulfurization of PTC could increase its ecological risk due to the higher bioavailability and persistence of PTC-d.

Various crustaceans are farmed using aquaculture, and food deprivation or fasting can occur due to changing of environmental or management strategies. However, the molecular mechanisms underlying responses to starvation in crustaceans remain unclear. To address this, 12 hepatopancreas transcriptomes were compared for oriental river prawn (Macrobrachium nipponense) from four fasting stages (0, 7, 14 and 21 d). Gene Ontology functional annotation and Kyoto Encyclopaedia of Genes and Genomes pathway enrichment analysis of differentially expressed genes were subsequently performed. During the early stages of starvation (0–7 d), drug metabolism via the cytochrome P450 pathway and metabolism of xenobiotics by the cytochrome P450 pathway were enriched, suggesting that they metabolised compounds generated under starvation stress. As starvation proceeded (7–14 d), the retinol (vitamin A) metabolism pathway was activated, based on three up-regulated genes (CYP3, ADH and UGT), along with the two p450 pathways. Meanwhile, vitamin A was gradually consumed. As acute starvation was reached (14–21 d), vitamin A deficiency decreased the mRNA expression levels of IGF-I that is involved in the mTOR signalling pathway, which ultimately affected the growth and development of M. nipponense. Our results implicate drug/xenobiotic metabolism by cytochrome P450s in adaptation to starvation stress. Furthermore, metabolic cascades (CYP and retinol pathways) and growth (mTOR signalling) pathways are clearly triggered in crustaceans during starvation. The findings expand our understanding of the genes associated with hepatopancreas functioning in M. nipponense, and the underlying molecular mechanisms that govern the responses of crustaceans to starvation stress.