Joint Toxic Action Research Articles

Single and Joint Action Toxicity Studies of Trace Elements in Binary Mixtures against <i>Clarias gariepinus</i> and <i>Sarotherodon melanotheron</i>

This study investigated the interactions of essential and non-essential trace elements when present in binary mixtures and resultant effects on acute toxicity in fish. The effects of four essential trace elements; Zn, Ni, Co and Cr respectively on the acute toxicities of three non-essential trace elements; Cd, Hg and Pb against Clarias gariepinus and Sarotherodon melanotheron were assessed using laboratory bioassays. The patterns of interaction of the elements affecting toxicity via antagonistic, synergistic or additive reactions were determined using the Synergistic Ratio (RA) and Concentration Addition (CA) joint action toxicity models. Single action toxicity indices showed that Hg was the most toxic element with a 96hr LC50 value of 0.0004 and 0.0003 mmol/l and Co the least toxic element with a 96hr LC50 value of 0.86 and 1.00 mmol/l, against the two fish species respectively. The SR and CA toxicity models showed that the essential trace elements (Zn, Ni, Cr and Co) reduced the toxicity of Pb against C.gariepinus as indicated by SR and RTU values < 1. Both models also showed that Zn reduced the toxicity of Pb and Hg respectively against S.melanotheron. However, the SR model showed that only Co reduced the toxicity of Cd against C.gariepinus. This study has established the possible beneficial interactions among essential trace elements and hazardous non-essential trace elements. Factors influencing such beneficial interactions including physiological processes in fish species, trace element concentrations and physicochemical parameters of exposure medium should be explored in future studies.Keywords: Essential Trace Elements; Non-essential Trace Elements; Antagonism; Toxicity

Regular time-dependent cross-phenomena induced by hormesis: A case study of binary antibacterial mixtures to Aliivibrio fischeri

Time-dependent cross-phenomenon in which the cross between the actual concentration-response curve (CRC) for mixture crosses the CRCs for reference model varies with time has been frequently reported in previous studies, expressed as a heterogeneous pattern of joint toxic action. However, the variation tendency of time-dependent cross-phenomenon is rarely addressed. In this study, the joint toxic actions of binary antibacterial mixtures (i.e., two quorum sensing inhibitors, tetracycline hydrochloride, erythromycin, and chloramphenicol with sulfonamides) were judged using independent action (IA) model to find the variation tendency of time-dependent cross-phenomenon. The results show that the time-dependent cross-phenomena of the test binary antibacterial mixtures follow a unified variation tendency and the corresponding joint toxic actions change regularly with an increase of both concentration and time. Through investigating the relationship between the stimulatory and inhibitory modes of action for the single agents and the time-dependent cross-phenomena of binary mixtures, the regular time-dependent cross-phenomena is speculated to be derived from the hormetic effects of the components in the mixtures. This study offers an advance for the variation tendency and mechanistic explanation of time-dependent cross-phenomenon, which will provide a support for the future development in the exploration of time-dependent cross-phenomenon and environmental risk assessment of pollutant mixtures.

Combined Toxicity of Nitro-Substituted Benzenes and Zinc to Photobacterium Phosphoreum: Evaluation and QSAR Analysis.

The single toxicity (IC50) of zinc (Zn) and 11 nitro-substituted benzenes to Photobacterium phosphoreum were determined, respectively. On basis of single toxicity, the joint toxicity of binary mixtures of Zn and 11 nitro-substituted benzenes at different Zn concentrations of 0.2 IC50, 0.5 IC50, and 0.8 IC50 were measured. The joint toxicity was evaluated by toxic unit (TU) and additive index (AI) methods. The results indicated that the joint toxicity was not only depending on the Zn concentrations but also on the substituted groups of nitro-substituted benzenes. The quantitative structure-activity relation (QSAR) equations were developed and the results showed that the toxicity of nitro-substituted benzenes has different joint effect at the different Zn concentrations. At the Zn concentration of 0.2 IC50, the binary joint effects were mainly antagonism and the joint toxicity was negatively related to descriptors called VE2_B(p) and TIC3. At the Zn concentration of 0.5 IC50 and 0.8 IC50, the binary joint effects were mainly antagonism and simple addition, and the joint toxicity was related to the same descriptor Eig06_ AEA(dm). It indicated that the joint toxic actions were similar when combined at the medium and high concentrations of Zn.

Exposure to cadmium and mono-(2-ethylhexyl) phthalate induce biochemical changes in rat liver, spleen, lung and kidney as determined by attenuated total reflection-Fourier transform infrared spectroscopy.

Attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy is a label-free, non-destructive analytical technique for biochemical analysis of macromolecular components within tissue samples. Cadmium (Cd) and mono-(2-ethylhexyl) phthalate (MEHP), a primary metabolite of di-(2-ethylhexyl) phthalate, are present ubiquitously in the environment and in organisms, and have adverse impacts on ecosystems and human health. Herein we employed ATR-FTIR analysis to identify biomolecular changes in rat liver, spleen, lung and kidney after prepubertal exposure to Cd and MEHP. Our results showed clear segregations between the 3mg/kg Cd-, 10mg/kg, 50mg/kg, 250mg/kg MEHP- and binary mixture-treated groups vs. the solvent control group. Following principal components analysis coupled with linear discriminant analysis, biochemical alterations associated with different doses of Cd and MEHP were attributed mainly to lipids, proteins, phosphates and carbohydrates. In addition, the ratios of lipid/protein, C=O stretching/CH2 methylene (lipid oxidation level), amide I/amide II, α-helix/β-sheet and CH3 methyl/CH2 methylene (acetylation level) in target organs were affected by these toxicants. There seems to be no dose-response effect of Cd and MEHP on target organs. We observed hardly any joint toxic action of these toxicants. This is the first study showing the application of ATR-FTIR spectroscopy to the assessment of toxicity of Cd and MEHP. Possibly, destruction of cell membrane structure and integrity could be the common mechanism of Cd and MEHP toxicity in liver, spleen, lung and kidney.

Probabilistic Integrated Human Mixture Risk Assessment of Multiple Metals Through Seafood Consumption

Inorganic arsenic (iAs), cadmium (Cd), lead (Pb), and methylmercury (MeHg) are toxic metals that cause substantial health concern and are present in various seafood items. This study linked probabilistic risk assessment to the interactive hazard index (HIINT ) approach to assess the human mixture risk posed by the dietary intake of iAs, Cd, Pb, and MeHg from seafood for different age populations, and joint toxic actions and toxic interactions among metals were also considered in the assessment. We found that, in combination, an iAs-Cd-Pb-MeHg mixture synergistically causes neurological toxicity. Furthermore, an iAs-Cd-Pb mixture antagonistically causes renal and hematological effects and additively causes cardiovascular effect. Our results demonstrated that if toxic interactions are not considered, the health risk may be overestimated or underestimated. The 50th percentile HIINT estimates in all age populations for neurological, renal, cardiovascular, and hematological effects were lower than 1; however, the 97.5th percentile HIINT estimates might exceed 1. In particular, toddlers and preschoolers had the highest neurological risk, with 0.16 and 0.19 probabilities, respectively, of neurological HIINT exceeding 1. Saltwater fish consumption was the principal contributor to the health risk. We suggest that regular monitoring of metal levels in seafood, more precise dietary surveys, further toxicological data, and risk-benefit analysis of seafood consumption are warranted to improve the accuracy of human mixture risk assessment and determine optimal consumption.

Mechanistic explanation of time-dependent cross-phenomenon based on quorum sensing: A case study of the mixture of sulfonamide and quorum sensing inhibitor to bioluminescence of Aliivibrio fischeri

Cross-phenomenon in which the concentration-response curve (CRC) for a mixture crosses the CRC for the reference model has been identified in many studies, expressed as a heterogeneous pattern of joint toxic action. However, a mechanistic explanation of the cross-phenomenon has thus far been extremely insufficient. In this study, a time-dependent cross-phenomenon was observed, in which the cross-concentration range between the CRC for the mixture of sulfamethoxypyridazine (SMP) and (Z-)-4-Bromo-5-(bromomethylene)-2(5H)-furanone (C30) to the bioluminescence of Aliivibrio fischeri (A. fischeri) and the CRC for independent action model with 95% confidence bands varied from low-concentration to higher-concentration regions in a timely manner expressed the joint toxic action of the mixture changing with an increase of both concentration and time. Through investigating the time-dependent hormetic effects of SMP and C30 (by measuring the expression of protein mRNA, simulating the bioluminescent reaction and analyzing the toxic action), the underlying mechanism was as follows: SMP and C30 acted on the quorum sensing (QS) system of A. fischeri, which induced low-concentration stimulatory effects and high-concentration inhibitory effects; in the low-concentration region, the stimulatory effects of SMP and C30 made the mixture produce a synergistic stimulation on the bioluminescence; thus, the joint toxic action exhibited antagonism. In the high-concentration region, the inhibitory effects of SMP and C30 in the mixture caused a double block in the loop circuit of the QS system; thus, the joint toxic action exhibited synergism. With the increase of time, these stimulatory and inhibitory effects of SMP and C30 were changed by the variation of the QS system at different growth phases, resulting in the time-dependent cross-phenomenon. This study proposes an induced mechanism for time-dependent cross-phenomenon based on QS, which may provide new insight into the mechanistic investigation of time-dependent cross-phenomenon, benefitting the environmental risk assessment of mixtures.

Biochemical Effects of the Toxic Interaction of Copper, Lead and Cadmium on Clarias gariepinus.

Background.The presence of heavy metals in the aquatic environment is a concern because of potential toxicity and threats to plant and animal life.Objective.The present study evaluated the joint action toxicity and biochemical effects of sublethal concentrations of copper (Cu), lead (Pb) and cadmium (Cd) against Clarias gariepinus over a period of 28 days.Methods.We procured fingerlings (weight: 5–8 g; length: 4.5–6.0 cm) and juveniles (weight: 20–25 g; length: 14.5–17.5 cm) from a commercial fish farm in Bariga, Lagos state, Nigeria. Test toxicants were selected from the analyzed heavy metals in the field based on their deviation from World Health Organization, Federal Environmental Protection Agency and United States Environmental Protection Agency standards. Fish were randomly loaded into a 4-L glass aquaria for the bioassay per toxicant concentration of two replicates and untreated control (dechlorinated tap water).Results.The derived 96 hour lethal concentration 50 (LC50) value of Cu (2.11 mg/L) was the most toxic followed by Cd (24.18 mg/L) and Pb (34.48 mg/L), which was the least toxic of the singly tested pollutants. The analysis of dose-response data of the joint action toxicity of Cu and Cd, and Cu and Pb determined 96 hour LC50 values of 1.804 mg/L and 2.15 mg/L, respectively. The interactions between the mixture of Cu:Cd conformed with the model of synergism (synergistic ratio (SR)>1 and relative toxic units (RTU)>1), while the interaction between Cu:Pb was found to be antagonistic (SR<1), with an SR value of 0.98. The biochemical effects study revealed that malondialdehyde (MDA) levels decreased significantly (P<0.05) in the exposed fish, reduced glutathione was not significant at (P<0.05), and levels of superoxide dismutase (SOD), catalase, glucose and cholesterol were significantly different (P<0.05).Discussion.The observed increased in the glutathione level in the Cu:Cd mixture and a corresponding decrease in MDA concentration in the liver of test animals revealed the ability of fish to overcome the effects of lipid peroxidation in this group because the Cu ion is displaced by Cd, and the fish were able to catalyze the breakdown of hydrogen peroxide via the Fenton reaction.Conclusions.Further studies on the joint action toxicity of heavy metals are needed in order to further determine their concentration in the local environment.Ethics Approval.Study protocols were approved by the Health Research Ethics Committee of the University of Lagos.

Single and joint action toxicity evaluation of insecticide and laundry detergent against &lt;i&gt;Poecilia reticulata&lt;/i&gt;

In laboratory bioassays, single action toxicities of an insecticide (Apicide [A]) and two laundry detergents (Persil [P] and Klin [K]) as well as their joint action toxicity studies in binary (1:1; 1:4) and triple (1:1:1) mixtures were evaluated against Poecilia reticulata (Guppy). Joint action toxicity mortality data was analyzed using Synergistic Ratio (SR), Concentration – Addition (RTU) and Isobolograms models. On the basis of 96hr LC 50 mortality data from single action studies, showed that A was the most toxic (0.00137mg/l) followed by P (0.773mg/l) and K (28.841mg/l). The joint action toxicity data showed a synergistic effect in mixtures of insecticide and detergents in all ratios (1:1, 1:4, 1:1:1) than when acting alone. In descending order of toxicity it was revealed that Apicide/persil (1:1; 0.00079mg/l)>Apicide/ Persil/Klin (1:1:1; 0.00093mg/l)>Apicide/Klin (1:1; 0.00094mg/l)>Apicide/ Persil (1:1; 0.00098mg/l)>Apicide/ Klin (1:4; 0.00106mg/l). The subjection of the 96h LC 50 values of test compound mixtures based SR and RTU showed that interaction of mixtures in various ratios (1:1, 1:4, 1:1:1) tended towards synergisms (SR>1; RTU>1) respectively. Further analysis based on the isobologram model was in conformity with RTU and SR models. The significance of this study showed the relevance of joint action toxicity studies in setting realistic safe limits in order to protect aquatic organisms. Therefore, proper disposal and management strategies for wastes should be enforced. Keywords: Bioassay, Detergent, Insecticide, Toxicity, Poecilia reticulata

Mixture risk assessment due to ingestion of arsenic, copper, and zinc from milkfish farmed in contaminated coastal areas.

Human health risks associated with the consumption of metal-contaminated fish over extended periods have become a concern particularly in Taiwan, where fish is consumed on a large scale. This study applied the interaction-based hazard index (HI) to assess the mixture health risks for fishers and non-fishers who consume the arsenic (As), copper (Cu), and zinc (Zn) contaminated milkfish from As-contaminated coastal areas in Taiwan, taking into account joint toxic actions and potential toxic interactions. We showed that the interactions of As-Zn and Cu-Zn were antagonistic, whereas As-Cu interaction was additive. We found that HI estimates without interactions considered were 1.3-1.6 times higher than interactive HIs. Probability distributions of HI estimates for non-fishers were less than 1, whereas all 97.5%-tile HI estimates for fishers were >1. Analytical results revealed that the level of inorganic As in milkfish was the main contributor to HIs, indicating a health risk posed to consumers of fish farmed in As-contaminated areas. However, we found that Zn supplementation could significantly decrease As-induced risk of hematological effect by activating a Zn-dependent enzyme. In order to improve the accuracy of health risk due to exposure to multiple metals, further toxicological data, regular environmental monitoring, dietary survey, and refinement approaches for interactive risk assessment are warranted.

Mechanism Underlying Time-dependent Cross-phenomenon between Concentration-response Curves and Concentration Addition Curves: A Case Study of Sulfonamides-Erythromycin mixtures on Escherichia coli.

Previous studies have identified a phenomenon in which the concentration-response curves (CRCs) for mixtures cross the curves for concentration addition model when predicting or judging joint toxic actions. However, mechanistic investigations of this phenomenon are extremely limited. In this study, a similar phenomenon was observed when we determined the joint toxic actions of sulfonamides (SAs) and erythromycin (ERY) on Escherichia coli (E. coli), which we named the “cross-phenomenon”, and it was characterized by antagonism in the low-concentration range, addition in the medium-concentration range, and synergism in the high-concentration range. The mechanistic investigation of the cross-phenomenon was as follows: SAs and ERY could form a double block to inhibit the bacterial growth by exhibiting a synergistic effect; however, the hormetic effect of SAs on E. coli led to antagonism in the low-concentration range, resulting from the stimulation of sdiA mRNA expression by SAs, which increased the expression of the efflux pump (AcrAB-TolC) to discharge ERY. Furthermore, this cross-phenomenon was observed to be a time-dependent process induced by the increase of both the concentration and extent of stimulation of sdiA mRNA with exposure time. This work explains the dose-dependent and time-dependent cross-phenomenon and provides evidence regarding the interaction between hormesis and cross-phenomenon.

Metabonomic analysis of the protective effect of quercetin on the toxicity induced by mixture of organophosphate pesticides in rat urine.

The present study aims to investigate the protective effect of quercetin against the joint toxic action induced by the mixture of four organophosphate pesticides (mixture-OPs) (dimethoate, acephate, dichlorvos, and phorate) at their corresponding no observed adverse effect level (NOAEL) using metabonomics. Rats were randomly divided into control, quercetin-treated, mixture-OPs-treated, and quercetin plus mixture-OPs-treated groups. Mixture-OPs and quercetin were given to the rats daily through drinking water and intragastric administration, respectively, for 90 days. The metabonomic profiles of rat urine were analyzed using ultra-performance liquid chromatography-mass spectrometry (UPLC/MS). The 14 metabolites significantly changed in the treatment groups compared with the control group, including the biomarkers of OPs exposure (dimethylphosphate, dimethyldithiophosphate, diethylphosphate) and the metabolites of quercetin (quercetin and isorhamnetina). The intensities of gentisic acid, creatinine, suberic acid, hippuric acid, uric acid, and citric acid significantly decreased, whereas the intensities of 7-methylguanine, estrone sulfate, and cholic acid significantly increased, in the mixture-OPs-treated group compared with the control group ( p < 0.01). The variation tendency of the aforementioned metabolites was significantly ameliorated in the high-dose quercetin (50 mg/(kg bw day)) plus mixture-OPs-treated group compared with the mixture-OPs-treated group ( p < 0.05). However, the intensities of these metabolites in the high-dose quercetin plus mixture-OPs-treated group were still significantly different from those of the control group ( p < 0.05). Results indicated that high dose of quercetin elicits a partial protective effect on the toxicity induced by mixture-OPs, including fatty acid and energy metabolism, antioxidant defense system, DNA damage, and liver and kidney function.

Histopathological alterations, biochemical responses and acetylcholinesterase levels in Clarias gariepinus as biomarkers of exposure to organophosphates pesticides.

Organophosphate pesticides, commonly used in large scale farming, have been found to be major contaminants in aquatic environment. Clarias gariepinus was exposed to acute and sublethal concentrations of phostoxin and DD Force to evaluate single and joint action toxicity of the organophosphates. Effects of phostoxin and DD force on antioxidant enzymes, fish organs and acetylcholinesterase levels in fingerlings and juveniles of C. gariepinus were also investigated. The lethal concentrations (96 h LC50) for phostoxin and DD Force were 0.631 and 1.759 mg/l, respectively. The results obtained from the bioassay showed that phostoxin was 2.8× more toxic than DD Force after exposure of C. gariepinus. Joint action toxicity evaluations of phostoxin and DD Force showed that the interaction between the chemicals was synergistic (RTU >1). The biochemical responses in the exposed fish differed significantly (P < 0.05) from the control fish. The result of acetylcholinesterase study revealed significant difference between acetylcholinesterase levels in the exposed fish and control, with reduction in the acetylcholineterase level in fish exposed to sublethal concentrations of phostoxin and DD Force. Haematological studies revealed an increase in WBC, RBC, PCV and platelets in the exposed fish. Histopathology of the gills showed shortened primary lamellae, loss of secondary lamellae and loss of ceratobrachial bones. In the acute toxicity studies, respiratory stress, erratic swimming and instant death of fish were observed in the exposed fish. This study reveals that changes in histopathology and acetylcholinesterase level are good biomarkers and can be successfully used to detect exposure to organophosphates pesticides in fish.

Toxicity and Some Biological Effects of Emamectin Benzoate, Novaluron and Diflubenzuron against Cotton Leafworm

Toxicity and sublethal effects of emamectin benzoate, novaluron and diflubenzuron were evaluated against the 2nd instar larvae of cotton leafworm (CLW). The joint toxic action of emamectin benzoate with novaluron or diflubenzuron was carried out. Emamectin benzoate (LC50 = 0.014 mg L-1) was 264.3 and 5707.1 times more toxic than novaluron (LC50 = 3.7 mg L-1) and diflubenzuron (LC50 = 79.9 mg L-1), respectively. Novaluron was approximately 21.6 times more toxic than diflubenzuron. After 24 hrs of exposure, all mixtures of emamectin benzoate (at LC10 or LC25) with novaluron or diflubenzuron (at LC10 or LC25) resulted in antagonistic effects with co-toxicity factors (CTFs) ranged between -25 to -700 except the mixture of emamectin benzoate at LC10 with novaluron at LC10 (CTF = 60). Mixtures of emamectin benzoate at LC10 with novaluron at LC10 and emamectin benzoate at LC25 with novaluron at LC25 resulted in potentiating effects after 48, 72 and 96 hrs of exposure. On the other hand, all mixtures of emamectinbenzoate with diflubenzuron resulted in antagonistic effects. Emamectin benzoate, novaluron and diflubenzuron at the two sublethal concentrations reduced average larval weight, average time to the pupation, %pupation, pupal mean weight and %adult emergence compared to control. Results of this study verified the lethal and sublethal effects of emamectin benzoate, novaluron and diflubenzuron on the larval stage of S. littoralis, which negatively affect some biological parameters and insect population can be negatively affected. Emamectin benzoate, novaluron and diflubenzuron can be used for S. littoralis control and in resistance management programs, because their mode of action is different from pyrethroid, carbamate and organophosphate insecticides.

Joint Toxic Action of Chlorantraniliprole with Certain Insecticides against Cotton Leafworm Larvae

Joint Toxic Action of Chlorantraniliprole with Certain Insecticides against Cotton Leafworm Larvae

Copper–zinc coergisms and metal toxicity at predefined ratio concentrations: Predictions based on synergistic ratio model

A significant number of studies have centred on the single actions of heavy metals against test animals in predicting aquatic toxicity. However, practical existence of environmental toxicants is in multiple mixtures and variable undefined ratio combinatorial concentrations. Pollution abatement approaches in setting representative safe boundaries for metal contaminants is crucial with factual data on predictively modelled exposures of organisms to multiple mixtures. In continuance of our approach to toxicity of individual heavy metals, we determined the toxicity of binary mixtures of copper and zinc at predetermined ratios against tilapia species and also evaluated the coergisms based on synergistic ratio model for effective formulations of safe limits. Orecohromis niloticus species were exposed to copper and zinc (Cu:Zn) at ratios of 1:1 and 1:2 on 96hLC50 index and mortality response analysed following the probit-log-dose regression with metal–metal interactions effectively modelled. The 96hLC50 values for Cu:Zn were calculated to be 68.898 and 51.197mg/l for ratios 1:1 and 1:2, respectively. The joint action toxicity of the metal mixtures was observed to differ from the metals acting singly against the same animal species. Synergistic coergisms were realized in most of the ratio mixtures except the antagonistic effect displayed by the combination of Cu:Zn in the ratio 1:1 when compared to the single action of copper. Biological toxicity of heavy metals however still appears uncertain, and consideration of multiple mixtures and interactions of toxicants in natural milieu is very crucial in environmental management of the existing and emerging contaminating metals.

TOXICITY OF SOME CONVENTIONAL AND NONCONVENTIONAL INSECTICIDES AGAINST COTTON LEFWORM, Spodoptera littoralis (BOISD.)

The ovicidal action of three novel compounds (emamectin benzoate, methoxyfenozide, pyridalyl) and conventional insecticide (methomyl) against (0-24, 24-48 and 48-72 hours age) eggs of Spodoptera littoralis was assessed. The toxic activity of emamectin benzoate, methoxyfenozide, pyridalyl and methomyl against 4th instar larvae of laboratory and field strains of S. littoralis were carried out. Also, the build up of resistance of each tested compound in the field strain was calculated. The joint toxic action of emamectin benzoate, methoxyfenozide and pyridalyl with tested insecticides was also studied. The obtained data revealed that emamectin benzoate gave an ovicidal activity higher than methomyl, methoxyfenozide and pyridalyl. Also, emamectin benzoate was a superior potent compound against 4th instar larvae of S. littoralis followed by methoxyfenozide, with LC50 values were 0.007 and 0.932 ppm after 72 hrs, while methomyl was the least toxic one, LC50 value was 95.60 ppm. The build up of resistance of tested compounds indicated that the resistance ratio of methoxyfenozide and methomyl were 5.9 and 5.8 fold as the laboratory strain, while the resistance ratio of emamectin benzoate and pyridalyl were 2.7 and 1.9 fold as the laboratory strain. In respect with the joint toxic action, the all mixtures of the tested insecticides showed highly antagonisms effect as calculated by the co-toxicity factors. The present study suggests that emamectin benzoate is very effective in the control of S. littoralis.

EFSA's 21st Scientific Colloquium on Harmonisation of human and ecological risk assessment of combined exposure to multiple chemicals

EFSA's 21st Scientific Colloquium on Harmonisation of human and ecological risk assessment of combined exposure to multiple chemicals

Predictive Modelling of Heavy Metal-Metal Interactions in Environmental Setting: Laboratory Simulative Approach

Aquatic ecosystem pollution by heavy metals is a global problem and requires proactive measures and techniques in tackling the scourge. Exposure to multiple contaminants in water environment now displaces the single action of pollutants and creates a challenge for complex mixture contact management. Heavy metals at individual low acting concentrations can elicit higher toxicity on interactions with other environmental toxicants. In this study, Clarias gariepinus was exposed to the mixture of zinc and copper at predetermined ratio of 1:1 and 1:2 based on 96hLC₅₀ index and binary interactive dynamics of the two metals calculated using the synergistic ratio model. Following the exposure, the 9hLC₅₀ values were 84.683 mg/l and 45.875 mg/L for ratios 1:1 and 1:2, respectively. Physiological responses such as rapid opercula movement, frequent gulping of air and neurological symptoms like jerking movements, frightening and loss of balance were observed throughout the experimental period. There were antagonistic and synergistic reactions between the metals at the two combinatorial ratios. Antagonism occurs when the metals were mixed at the ratio of 1:1 and synergism at the ratio of 1:2. We therefore recommend that joint action toxicity of metals should be taken into consideration in fixing environmental safe limits for heavy metals in order to have a complete protection of aquatic ecosystems.

Joint Action Toxicity and Biochemical effects of Binary Mixtures of Forcados Light Crude Oil and Three Dispersants against Clarias gariepinus

Laboratory-scale experiments were conducted to evaluate the joint action toxicity and biochemicaleffects of sublethal concentrations of Forcados light crude oil (FLCO) and three dispersants against Clariasgariepinus over a period of 28 days. The derived 96hrLC50 values revealed that the dispersant, DS/TT/066(0.03mL/L) was the most toxic, followed by dispersant, OC/TT/OSI (0.19mL/L), FLCO (5.06mL/L) andcrystal clear oil dispersant (CCOD = 12.06mL/L) the least toxic when acting singly. Joint action toxicityevaluations of FLCO and dispersants showed that the interaction between FLCO : DS/TT/066 and FLCO :OC/TT/OSI was synergistic (synergistic ratio (SR) > 1) with SR values of 10.5 and 3 respectively. However,for the mixture of FLCO : CCOD, the interaction was antagonistic (SR 0.05) in superoxide dismutase (SOD) and catalase (CAT) activities in all the exposed fishes compared to control animals. The observed increase in GSH and GST levels in conjunction with a decrease in MDA concentration in the liver of test animals exposed to binary mixtures of FLCO and CCOD reveals the ability of the animals to overcome the effects of lipid peroxidation in this group. Further studies on the mechanism of toxicity of these dispersants in field and laboratory assays are recommended.

Metabonomic analysis of the joint toxic action of long-term low-level exposure to a mixture of four organophosphate pesticides in rat plasma

In previously published articles, we evaluated the toxicity of four organophosphate (OP) pesticides (dichlorvos, dimethoate, acephate, and phorate) in rats using metabonomic technology at their corresponding no observed adverse effect levels (NOAELs). The results show that a single pesticide did not elicit a toxic response. The joint toxic action of four pesticides (at their corresponding NOAELs) was evaluated by metabolomic analysis of rat plasma under experimental conditions similar to those of the four single OP pesticides. The pesticides were administered daily to rats through drinking water for 24 weeks. The mixture of four pesticides showed a joint toxic action at the NOAELs of each pesticide. The 19 metabolites were statistically significantly changed in all the treated groups compared with those in the control group (p < 0.05 or p < 0.01). Exposure to OP pesticides resulted in increased lysoPC (15 : 0/0 : 0), lysoPC (16 : 0/0 : 0), lysoPC (O-18 : 0/0 : 0), lysoPC (P-19 : 1(12Z)/0 : 0), lysoPC (18 : 1(9Z)/0 : 0), lysoPC (18 : 0/0 : 0), lysoPC (20 : 4(5Z, 8Z, 11Z, 14Z)/0 : 0), lysoPE (16 : 0/0 : 0), lysoPC (17 : 0/0 : 0), 4-pyridoxic acid, glutamic acid, glycocholic acid, and arachidonic acid, as well as decreased C16 sphinganine, C17 sphinganine, phytosphingosine, indoleacrylic acid, tryptophan, and iodotyrosine in rat plasma. The results indicate that the mixture of OP pesticides induced oxidative stress, liver and renal dysfunction, disturbed the metabolism of lipids and amino acids, and interfered with the function of the thyroid gland. The present plasma results provided complementarities with our previous metabolomic analysis of the rat urine profile exposed to a mixture of four OP pesticides, and also contributed to the understanding of the mechanism of joint toxic action.