We examined ingestion and retention rates of microplastics (MPs) by two freshwater (Japanese medaka and zebrafish) and two marine fish species (Indian medaka and clown anemonefish) to determine their color preferences and gastrointestinal-tract retention times. In our ingestion experiments, clown anemonefish ingested the most MP particles, followed by zebrafish, and then Japanese and Indian medaka. Next, we investigated color preferences among five MP colors. Red, yellow, and green MP were ingested at higher rates than gray and blue MPs for all tested fish species. To test whether these differences truly reflect a recognition of and preference for certain colors based on color vision, we investigated the preferences of clown anemonefish for MP colors under light and dark conditions. Under dark conditions, ingestion of MP particles was reduced, and color preferences were not observed. Finally, we assessed gastrointestinal-tract retention times for all four fish species. Some individuals retained MP particles in their gastrointestinal tracts for over 24 h after ingestion. Our results show that fish rely on color vision to recognize and express preferences for certain MP colors. In addition, MP excretion times varied widely among individuals. Our results provide new insights into accidental MP ingestion by fishes.

Perfluorooctanesulfonic acid (PFOS) is a persistent anthropogenic chemical that can affect the thyroid hormone system in humans and animals. In adults, thyroid hormones (THs) are regulated by the hypothalamic-pituitary-thyroid (HPT) axis, but also by organs such as the liver and potentially the gut microbiota. PFOS and other xenobiotics can therefore disrupt the TH system at various locations and through different mechanisms. To start addressing this, we exposed adult male rats to 3 mg PFOS/kg/day for 7 days and analysed effects on multiple organs and pathways simultaneously by transcriptomics. This included four primary organs involved in TH regulation, namely hypothalamus, pituitary, thyroid, and liver. To investigate a potential role of the gut microbiota in thyroid hormone regulation, two additional groups of animals were dosed with the antibiotic vancomycin (8 mg/kg/day), either with or without PFOS. PFOS exposure decreased thyroxine (T4) and triiodothyronine (T3) without affecting thyroid stimulating hormone (TSH), resembling a state of hypothyroxinemia. PFOS exposure resulted in 50 differentially expressed genes (DEGs) in the hypothalamus, 68 DEGs in the pituitary, 71 DEGs in the thyroid, and 181 DEGs in the liver. A concomitant compromised gut microbiota did not significantly change effects of PFOS exposure. Organ-specific DEGs did not align with TH regulating genes; however, genes associated with vesicle transport and neuronal signaling were affected in the hypothalamus, and phase I and phase II metabolism in the liver. This suggests that a decrease in systemic TH levels may activate the expression of factors altering trafficking, metabolism and excretion of TH. At the transcriptional level, little evidence suggests that the pituitary or thyroid gland is involved in PFOS-induced TH system disruption.

Nanoplastic is recognized as an emerging environmental pollutant due to the anticipated ubiquitous distribution, increasing concentration in the ocean, and potential adverse health effects. While our understanding of the ecological impacts of nanoplastics is still limited, we benefit from relatively rich toxicological studies on other nanoparticles such as nano metal oxides. However, the similarity and difference in the toxicokinetic and toxicodynamic aspects of plastic and metallic nanoparticles remain largely unknown. In this study, juvenile Pacific white shrimp Litopenaeus vannamei was exposed to two types of nanoparticles at environmentally relative low and high concentrations, i.e., 100 nm polystyrene nanoplastics (nano-PS) and titanium dioxide nanoparticles (nano-TiO₂) via dietary exposure for 28 days. The systematic toxicological evaluation aimed to quantitatively compare the accumulation, excretion, and toxic effects of nano-PS and nano-TiO₂. Our results demonstrated that both nanoparticles were ingested by L. vannamei with lower egestion of nano-TiO₂ than nano-PS. Both nanoparticles inhibited the growth of shrimps, damaged tissue structures of the intestine and hepatopancreas, disrupted expression of immune-related genes, and induced intestinal microbiota dysbiosis. Nano-PS exposure caused proliferative cells in the intestinal tissue, and the disturbance to the intestinal microbes was also more serious than that of nano-TiO₂. The results indicated that the effect of nano-PS on the intestinal tissue of L. vannamei was more severe than that of nano-TiO₂ with the same particle size. The study provides new theoretical basis of the similarity and differences of their toxicity, and highlights the current lack of knowledge on various aspects of absorption, distribution, metabolism, and excretion (ADME) pathways of nanoplastics.

Mammalian polychlorinated biphenyl (PCB) metabolism has not been systematically explored with nontarget high-resolution mass spectrometry (Nt-HRMS). Here we investigated the importance of the gut microbiome in PCB biotransformation by Nt-HRMS analysis of feces from conventional (CV) and germ-free (GF) adult female mice exposed to a single oral dose of an environmental PCB mixture (6 mg/kg or 30 mg/kg in corn oil). Feces were collected for 24 h after PCB administration, PCB metabolites were extracted from pooled samples, and the extracts were analyzed by Nt-HRMS. Twelve classes of PCB metabolites were detected in the feces from CV mice, including PCB sulfates, hydroxylated PCB sulfates (OH-PCB sulfates), PCB sulfonates, and hydroxylated methyl sulfone PCBs (OH-MeSO₂-PCBs) reported previously. We also observed eight additional PCB metabolite classes that were tentatively identified as hydroxylated PCBs (OH-PCBs), dihydroxylated PCBs (DiOH-PCBs), monomethoxylated dihydroxylated PCBs (MeO-OH-PCBs), methoxylated PCB sulfates (MeO-PCB sulfates), mono-to tetra-hydroxylated PCB quinones ((OH)ₓ-quinones, x = 1–4), and hydroxylated polychlorinated benzofurans (OH-PCDF). Most metabolite classes were also detected in the feces from GF mice, except for MeO-OH-PCBs, OH-MeSO₂-PCBs, and OH-PCDFs. Semi-quantitative analyses demonstrate that relative PCB metabolite levels increased with increasing dose and were higher in CV than GF mice, except for PCB sulfates and MeO-PCB sulfates, which were higher in GF mice. These findings demonstrate that the gut microbiome plays a direct or indirect role in the absorption, distribution, metabolism, or excretion of PCB metabolites, which in turn may affect toxic outcomes following PCB exposure.

Nuclear factor-erythroid 2-related factor-2 (Nrf2) is an important modulator of cellular responses against Cd in mammalian cells. However, whether such modulation is conserved in Marsupenaeus japonicas remains unknown.In our study, the shrimps were injected with dsRNA targeting Nrf2 at 4 μg g⁻¹ body weight (b.w.) or sulforaphane (SFN) at 5 μg g⁻¹ b.w., and then were exposed to 40 mg L⁻¹ CdCl₂ for 48 h. After Nrf2 knockdown, the Cd content increased, but decreased in the SFN group. This suggested that Nrf2 could promote Cd excretion. A terminal deoxynulceotidyl transferase nick-end-labeling (TUNEL) assay revealed that the Nrf2 knockdown increased the number of apoptotic cells in M. japonicas, while SFN decreased the number of apoptotic cells. After Nrf2 knockdown, the total antioxidant capacity (T-AOC), superoxide dismutase (Sod) activity, and related gene expression decreased significantly, while the malondialdehyde (MDA) content increased remarkably. By contrast, SFN injection alleviated the oxidative stress, as evidenced by increased T-AOC, Sod activity, sod mRNA expression and a reduced MDA content. Similarly, detoxification related enzyme activities (ethoxyresorufin O-deethylase and glutathione-S-transferase (GST)) and their corresponding gene expressions (cyp3a (cytochrome P450 family 3 subfamily A) and gst) were suppressed in the ds-Nrf2 injection group, while they were elevated in the SFN group. In addition, ds-Nrf2 activated mitochondrial apoptotic pathway, as evidenced the mRNA and protein levels of caspase-3, Bcl2 associated X protein (Bax), and p53, while SFN treatment suppressed them. These results displayed that in M. japonicus Cd-induced cellular oxidative damage probably acts via the Nrf2 pathway.

Paraquat (PQ) is a toxic, organic herbicide for which there is no specific antidote. Although banned in some countries, it is still used as an irreplaceable weed killer in others. The lack of understanding of the precise mechanism of its toxicity has hindered the development of treatments for PQ exposure. While toxicity is thought to be related to PQ-induced oxidative stress, antioxidants are limited in their ability to ameliorate the untoward biological responses to this agent. Summarized in this review are data on the absorption, distribution, metabolism, excretion, and toxicity (ADME/T) of PQ, focusing on the essential roles of individual transporters and enzymes in these processes. Based on these findings, strategies are proposed to design and test specific and effective antidotes for the clinical management of PQ poisoning.

Due to the complex sources and fate of perfluoroalkyl substance (PFAS), their source apportionment in the environment remains a challenge. A data set of 11 straight-chain PFAS in 139 samples of fish in the Great Lakes was analyzed using positive matrix factorization (PMF) to investigate their primary sources, whose spatial variations were examined against the surrounding environmental factors. PMF analysis produced five fingerprints. Factor 1 (72% of Σ₁₁PFAS, dominated by PFOS) probably represented emissions from primary sources (such as consumer products) and secondary sources (precursors), and increased in average abundance from west to east across the Great Lakes. Factor 2 (13% of Σ₁₁PFAS) and factor 3 (7% of Σ₁₁PFAS), highly loaded with long-chain PFAS and PFNA, respectively, were thought to represent PVDF manufacture or processing in metal plating. They showed higher contributions in sparsely populated Lakes Superior and Huron. Factor 4 (5% of Σ₁₁PFAS, highly loaded with PFOS and PFHxS) presented hot spots near current and former air force bases, suggesting it was related to aqueous film-forming foams (AFFFs). Factor 5 (4% of Σ₁₁PFAS) contained primarily PFOS and PFOSA, which may imply metabolism of precursors (PFOSA) to PFOS in vivo. Unexpectedly, the spatial trends of the five sources all showed abnormally low values near the more urbanized Chicago and Milwaukee in Lake Michigan, which may be due to their unique wastewater and stormwater infrastructure or may arise from atmospheric transport of precursors. Our study indicated that PMF was an effective tool to identify sources of PFAS in fish despite absorption, distribution, metabolism, and excretion (ADME) processes which might alter fingerprints in fish relative to their surrounding environment.

Pharmaceutically active compounds (PhACs) have attracted increasing attention due to their large consumption volumes, high bioactivity and potential ecotoxicity. In this study, a total of 150 commonly used drugs were investigated in sediments of Jiaozhou Bay (JZB). Twenty-five target compounds were detected, of which ten were discovered for the first time in marine sediments. The range of total PhAC content was 3.62–21.4 ng/g dry weight. Ketoprofen (2.49 ng/g), oxytetracycline (1.00 ng/g) and roxithromycin (0.97 ng/g) were the preponderant PhACs. PhACs gradually decreased from east to west, and the distribution of PhACs in the sediment was controlled by the source channel, seawater dynamic process and sediment composition. The diatom, organic matter, and clay proportions in the sediments and the nutrients in the overlying water were the most important environmental factors affecting the distribution of PhACs. PhAC pollution in the sediments of the JZB exhibited an increasing trend. Coprostanol could be used as a chemical indicator of the PhAC concentration in JZB sediments. PhACs were mainly derived from direct pollution due to human fecal excretion in the eastern region. Ofloxacin, tetracycline and oxytetracycline were found to pose high or medium risks to aquatic organisms. It is necessary and urgent to improve the treatment technology of drug residues in sewage treatment plants to decrease the pollution of PhAC residues. With the continuous aging of the global population, the use of PhACs will increase rapidly, which may cause more unpredictable threats to the marine ecosystem. Therefore, the monitoring of PhACs in the marine environment needs to be strengthened, and studies on PhAC occurrence and effects must be considered a priority in global environmental research.

Data (N = 10336) from National Health and Nutrition Examination Survey for 2003–2016 for US adults aged ≥ 20 years were analyzed to evaluate the concentrations of blood and urine cadmium across the various stages of glomerular function. Estimated glomerular filtration rate (eGFR) > 90 mL/min/1.73 m2 was defined to be glomerular function stage 1 (GF-1), eGFR between 60 and 90 mL/min/1.73 m2 defined as GF-2, eGFR between 45 and 60 mL/min/1.73 m2 as GF-3A, and eGFR between 15 and 45 mL/min/1.73 m2 as GF-3B/4. Regression models stratified by GF-stages were fitted to estimate associations between the observed levels of blood and urine cadmium across stages of GF. Based on the results of stratified modes, there were consistent increases in adjusted geometric means (AGMSM) for both blood and urine cadmium from GF-1 to GF-3A although increases were not uniform from one GF stage to another. For the total population, AGMSM for blood and urine cadmium were GF-1 (0.47, 0.24), GF-2 (0.60, 0.37), GF-3A (0.72, 0.45), and GF-3B/4 (0.73, 0.45) μg/L. respectively. Although females had higher AGMSMs than males for both blood and urine cadmium, the difference in blood cadmium narrowed as kidney function deteriorated. Smokers had the steepest increases in AGMSMs for blood and urine cadmium across the stages of glomerular function and smoker-nonsmoker differences for blood cadmium narrowed as kidney function deteriorated but smoker-nonsmoker differences for urine cadmium widened as kidney function deteriorated. The important physiologic messages are that both blood and urine cadmium cease to increase from GF-3A to GF-3B/4, suggesting a new steady state based on renal failure. And, the narrowed difference in blood cadmium in smokers vs. nonsmokers suggests why this happens. Incremental exposures to cadmium are offset by excretion as renal failure progresses.