A large number of toxicity studies report abnormalities in early life-stage (ELS) fish that are described here as a sublethal toxicity syndrome (TxSnFELS) and generally include a reduced heart rate, edemas (yolk sac and cardiac), and a variety of morphological abnormalities. The TxSnFELS is very common and not diagnostic for any chemical or class of chemicals. This sublethal toxicity syndrome is mostly observed at high exposure concentrations and appears to be a baseline, non-specific toxicity response; however, it can also occur at low doses by specific action. Toxicity metrics for this syndrome generally occur at concentrations just below those causing mortality and have been reported for a large number of diverse chemicals. Predictions based on tissue concentrations or quantitative-structure activity relationship (QSAR) models support the designation of baseline toxicity for many of the tested chemicals, which is confirmed by observed values. Given the sheer number of disparate chemicals causing the TxSnFELS and correlation with QSAR derived partitioning; the only logical conclusion for these high-dose responses is baseline toxicity by nonspecific action and not a lock and key type receptor response. It is important to recognize that many chemicals can act both as baseline toxicants and specific acting toxicants likely via receptor interaction and it is not possible to predict those threshold doses from baseline toxicity. We should search out these specific low-dose responses for ecological risk assessment and not rely on high-concentration toxicity responses to guide environmental protection. The goal for toxicity assessment should not be to characterize toxic responses at baseline toxicity concentrations, but to evaluate chemicals for their most toxic potential. Additional aspects of this review evaluated the fish ELS teratogenic responses in relation to mammalian oral LD50s and explored potential key events responsible for baseline toxicity.

Bisphenol A (BPA), an endocrine-disrupting chemical that is largely produced and used in the plastics industry, causes environmental pollution and is absorbed by humans through consumption of food and liquids in polycarbonate containers. BPA exerts developmental and genetic toxicities to embryos and offsprings, but the embryotoxicity mechanism of this chemical is unclear. This study aimed to explore the toxic effect of BPA on embryonic development and elucidate its toxicity mechanism. Embryos of Xenopus laevis as a model were treated with different concentrations (0.1, 1, 10, and 20 μM) of BPA at the two-cell stage to investigate the developmental toxicity of BPA. Embryonic development and behaviors were monitored 24 h–96 h of BPA exposure. BPA concentrations greater than 1 μM exerted significant teratogenic effects on the Xenopus embryos, which showed short tail axis, miscoiled guts, and bent notochord as the main malformations. The 20 μM BPA-treated embryos were seriously damaged in all aspects and exhibited deformity, impaired behavioral ability, and tissue damage. The DNA integrity and apoptosis of the Xenopus embryos were also investigated. Exposure to BPA concentrations higher than 0.1 μM significantly induced DNA damage (p < 0.05). The 10 and 20 μM BPA-treated embryos exhibited higher levels of cleaved caspase-3 protein than the control. The ratios of bax/bcl-2 mRNA were significantly higher in the 10 μM and 20 μM-treated embryos than the ratio in the control group. Overall, data indicated that BPA can delay the early development, induce DNA damage and apoptosis, and eventually cause multiple malformations in Xenopus embryos.

Several studies highlighted the ubiquitous presence of ibuprofen and aluminum in the aquatic environment around the world and demonstrated their potential to induce embryotoxic and teratogenic defects on aquatic species individually. Although studies that evaluate developmental alterations induced by mixtures of these pollutants are scarce; and, since environmental contamination presented in the form of a mixture of toxicants with different chemical properties and toxicity mechanisms capable of generating interactions; the objective of this study was to evaluate the developmental defects, teratogenic alterations, and oxidative stress induced by individual forms and the mixture of ibuprofen (IBU) and aluminum (Al) on zebrafish embryos. Oocytes exposed to environmentally relevant concentrations of IBU (0.1–20 μg L-1) and Al (0.01–8 mg L-1) and one binary mixture. The LC50 and EC50 were obtained to calculate the teratogenic index (TI). The IBU LC50, EC50, and TI were 8.06 μg L-1, 2.85 μg L-1 and 2.82. In contrast, Al LC50 was 5.0 mg L-1with an EC50 of 3.58 mg L-1 and TI of 1.39. The main alterations observed for individual compounds were hatching alterations, head malformation, skeletal deformities, hypopigmentation, pericardial edema, and heart rate impairment. The mixture also showed significant delays to embryonic development. Moreover, oxidative stress biomarkers of cellular oxidation and antioxidant defenses at 72 and 96 hpf significantly increased. Results show that environmentally relevant concentrations of ibuprofen (IBU), aluminum (Al), and their mixture promote a series of developmental defects, teratogenic effects, and oxidative disruption on D. rerio embryos, and the interaction of both substances altered the response. In conclusion, morphological and biochemical tests are suitable tools for assessing the health risk of aquatic wildlife by exposure to individual and mixed pollutants in freshwater bodies.

Dichloromethane (DCM) is a volatile halogenated hydrocarbon with teratogenic, mutagenic and carcinogenic effects. Biodegradation is generally regarded as an effective and economical approach of pollutant disposal. In this study, a novel strain was isolated and its cytochrome P450 was heterologously expressed for DCM degradation. The isolate, Microbacterium keratanolyticum ZY, was characterized as a Gram-positive, rod-shaped and flagella-existed bacterium without spores (GenBank No. SUB8814364; CCTCC M 2019953). After successive whole-genome sequencing, assembly and annotation, eight identified functional genes (encoding cytochrome P450, monooxygenase, dehalogenase and hydrolase) were successfully cloned and expressed in Escherichia coli BL21 (DE3). The recombinant strain expressing cytochrome P450 presented the highest degradation efficiency (90.6%). Moreover, the specific activity of the recombinant cytochrome P450 was more than 1.2 times that of the recombinant dehalogenase (from Methylobacterium rhodesianum H13) under their optimum conditions. The kinetics of DCM degradation by recombinant cytochrome P450 was well fitted with the Haldane model and the value of maximum specific degradation rate was determined to be 0.7 s⁻¹. The DCM degradation might occur through successive hydroxylation, dehydrohalogenation, dechlorination and oxidation to generate gem-halohydrin, formyl chloride, formaldehyde and formic acid. The study helps to comprehensively understand the DCM dechlorination process under the actions of bacterial functional enzymes (cytochrome P450 and dehalogenase).

Disinfection means the killing of pathogenic organisms (e.g. bacteria and its spores, viruses, protozoa and their cysts, worms, and larvae) present in water to make it potable for other domestic works. The substances used in the disinfection of water are known as disinfectants. At municipal level, chlorine (Cl₂), chloramines (NH₂Cl, NHCl₂), chlorine dioxide (ClO₂), ozone (O₃) and ultraviolet (UV) radiations, are the most commonly used disinfectants. Chlorination, because of its removal efficiency and cost effectiveness, has been widely used as method of disinfection of water. But, disinfection process may add several kinds of disinfection by-products (DBPs) (∼600–700 in numbers) in the treated water such as Trihalomethanes (THM), Haloacetic acids (HAA) etc. which are detrimental to the human beings in terms of cytotoxicity, mutagenicity, teratogenicity and carcinogenicity. In water, THMs and HAAs were observed in the range from 0.138 to 458 μg/L and 0.16–136 μg/L, respectively. Thus, several regulations have been specified by world authorities like WHO, USEPA and Bureau of Indian Standard to protect human health. Some techniques have also been developed to remove the DBPs as well as their precursors from the water. The popular techniques of DBPs removals are adsorption, advance oxidation process, coagulation, membrane based filtration, combined approaches etc. The efficiency of adsorption technique was found up to 90% for DBP removal from the water.

Di(n-butyl) phthalate (DBP) is extensively used in industrial applications as plasticizer and stabilizer and its presence in the environment may present health risks for human. Previous studies have demonstrated its mutagenic, teratogenic, and carcinogenic ability. However, its effect on mammalian oocyte maturation remains unknown. In this study, we examined the effect of DBP on oocyte maturation both in vitro and in vivo. Our results showed that DBP could significantly reduce mice oocyte germinal vesicle breakdown (GVBD) and polar body extrusion (PBE) rates. In addition, oocyte cytoskeleton was damaged and cortical granule-free domains (CGFDs) were also disrupted. Finally, DBP induced early apoptosis of oocyte and granulosa cells (GCs). Collectively, these data demonstrate that DBP could reduce meiosis competence and mouse oocyte development.

Mycotoxins are secondary metabolites produced by varieties of fungi that contaminate food and feed resources and are capable of inducing a wide range of toxicity. In the current study, we investigated developmental and behavioural toxicity in zebrafish larvae after exposure to six different mycotoxins; ochratoxin A (OTA), type A trichothecenes mycotoxin (T-2 toxin), type B trichothecenes mycotoxin (deoxynivalenol - DON), and zearalenone (ZEN) and its metabolites alpha-zearalenol (α-ZOL) and beta-zearalenol (β-ZOL). Developmental defects, hatching time, and survival were monitored until 96 h post fertilisation (hpf). The EC₅₀, LC₅₀, and IC₅₀ values were calculated. Subsequently, to assess behavioural toxicity, new sets of embryos were exposed to a series of non-lethal doses within the range of environmental and/or developmental concern. Results indicated that all the tested mycotoxins were toxic, they all induced developmental defects, and with the exception of OTA, all affected hatching time. Behavioural effects were only observed following exposure to OTA and ZEN and its metabolites, α ZOL and β ZOL. These results demonstrate that mycotoxins are teratogenic and can influence behaviour in a vertebrate model.

In recent years, phosphorus-containing flame retardants (PFRs) have been frequently detected in various environmental media and biota - and in humans - as the result of steady increase in global usage of PFRs. However, studies on the potential health and ecological risks of PFRs are still scarce. In this study, we investigated the thyroid hormone-disrupting activity and ecological risk of nine frequently detected PFRs by in vitro, in vivo and in silico approaches. Results from the dual-luciferase reporter gene assay showed that tributyl phosphate (TNBP), tricresyl phosphate (TMPP), tris(2-chloroisopropyl)phosphate (TCIPP) and tris(2-chloro-1-(chloromethyl)ethyl)phosphate (TDCIPP) exerted thyroid receptor β (TRβ) antagonistic activity, with the values of RIC20 of 5.2 × 10−7, 2.7 × 10−7, 1.2 × 10−6 and 6.8 × 10−6 M, respectively. Molecular docking platform simulations suggested that the observed effects may be attributed to direct binding of PFRs to TR. Results from the T-screen assay indicated that TNBP and TMPP showed T3 antagonistic activity and thus significantly decreased the viability of GH3 cell lines in the presence of T3. The exposure assay using Xenopus tropicalis embryos revealed the potential teratogenic effect of TNBP, TMPP, TCIPP and TDCIPP. In conclusion, our studies revealed that some PFRs were potential thyroid hormone disruptors and may cause health and ecological risks. However, the mode of action of PFRs on TR remains uncertain. The correlation between the predicted affinity and the amplitude of the effect observed in cell based assay is encouraging, but not decisive. Further in vitro binding experiments of TR and PFRs are required. At the same time, the results provided here also demonstrated that multi-model approaches are of great importance to comprehensively evaluate the potential risks of emerging contaminants.

The presence of pharmaceuticals in the environment has triggered concern among the general population and received considerable attention from the scientific community in recent years. However, only a few publications have focused on anticancer drugs, a class of pharmaceuticals that can exhibit cytotoxic, genotoxic, mutagenic, carcinogenic and teratogenic effects. The present study investigated the photodegradation, biodegradation, bacterial toxicity, mutagenicity and genotoxicity of cyclophosphamide (CP) and 5-fluorouracil (5-FU). The photodegradation experiments were performed at a neutral to slight pH range (7–7.8) using two different lamps (medium-pressure mercury lamp and a xenon lamp). The primary elimination of the parent compounds was monitored by means of liquid chromatography tandem mass spectrometry (LC-IT-MS/MS). NPOC (non-purgeable organic carbon) analyses were carried out in order to assess mineralization rates. The Closed Bottle Test (CBT) was used to assess ready biodegradability. A new method using Vibrio fischeri was adopted to evaluate toxicity. CP was not degraded by any lamp, whereas 5-FU was completely eliminated by irradiation with the mercury lamp but only partially by the Xe lamp. No mineralization was observed for the experiments performed with the Xe lamp, and a NPOC removal of only 18% was registered for 5-FU after 256 min using the UV lamp. Not one of the parent compounds was readily biodegradable in the CBT. Photo transformation products (PTPs) resulting from photolysis were neither better biodegradable nor less toxic than the parent compound 5-FU. In contrast, the results of the tests carried out with the UV lamp indicated that more biodegradable and non-toxic PTPs of 5-FU were generated. Three PTPs were formed during the photodegradation experiments and were identified. The results of the in silico QSAR predictions showed positive mutagenic and genotoxic alerts for 5-FU, whereas only one of the formed PTPs presented positive alerts for the genotoxicity endpoint.

Ecotoxicological bioassays, e.g. based on Danio rerio teratogenicity (DarT) or the acute luminescence inhibition with Vibrio fischeri, could potentially lead to significant benefits for detecting on site contaminations on qualitative or semi-quantitative bases. The aim was to use the observed effects of two ecotoxicological assays for estimating the extent of a Benzene groundwater contamination plume. We used a Maximum Entropy (MaxEnt) method to rebuild a bivariate probability table that links the observed toxicity from the bioassays with Benzene concentrations. Compared with direct mapping of the contamination plume as obtained from groundwater samples, the MaxEnt concentration map exhibits on average slightly higher concentrations though the global pattern is close to it. This suggest MaxEnt is a valuable method to build a relationship between quantitative data, e.g. contaminant concentrations, and more qualitative or indirect measurements, in a spatial mapping framework, which is especially useful when clear quantitative relation is not at hand.