Pentachlorotoluene and pentabromotoluene: Results of a subacute and a subchronic toxicity study in the rat

Abstract

Pentachlorotoluene (PCT) and pentabromotoiuene (PBT) are environmental contaminants detected in the Great Lakes ecosystem. In view of the paucity of toxicity data and the potential for human exposure, a subacute (28 day) and a subchronic (91 day) study were conducted in the rat. In the subacute study, groups of 10 male and 10 female rats were fed the diet containing PCT or PBT at 0, 0.5, 5.0, 50 or 500 ppm for 28‐days. In the subchronic study, the group size was increased to 15, the dose levels were 0, 0.05, 0.5, 5.0, 50 and 500 ppm in the diet and the exposure period was 91 days. Growth rate and food consumption were not affected by exposure to either chemical in the subacute and subchronic study. Clinical observations revealed no abnormalities. Decreased hemoglobin was observed in female rats fed 5.0 ppm PCT and higher levels in the subacute (28 day) study. In the same study the hematocrit value and erythrocyte numbers of females fed 5.0 or 500 ppm PCT diets were significantly lower than the control. In both subacute and subchronic studies mild dose‐dependent histopathological changes were observed in the thyroid, liver and kidney of rats fed PCT and PBT diets. In general male rats were more susceptible than females to the treatment of PCT and PBT. Based on these data, it was concluded that the no observable adverse effect level for PCT was 50 ppm in the diet (3.5 mg/kg b.w./day) and that of PBT was 5.0 ppm (0.35 mg/kg b.w./day).     

The subchronic toxicity of acridine in the rat

Abstract

The subchronic toxicity of acridine was investigated in rats following dietary exposure at 0, 1, 10, 100 and 500 ppm for 13 weeks. The growth rate and food consumption were not affected by treatment and no clinical signs of toxicity were observed. There was a slight but significant decrease in spleen weight, both in absolute terms and as a percent of body weight, in the 500 ppm males and a slight increase in absolute thymus weight in the females of the same dose group. Both hepatic ethoxyresorufin O‐deethylase (EROD) and pentoxyresorufin O‐dealkylase (PROD) activities were slightly, but significantly, elevated in females in the 500 ppm dose group. No haematological or other biochemical changes were observed. Females also displayed dose‐related increases in inorganic phosphate and uric acid levels. Treatment‐related histopathological changes were seen in the thyroid, liver and kidney and included hepatic anisokaryosis and vesiculation of nuclei and glomerular adhesions, reticulin sclerosis and nuclear pyknosis in the kidney. Residue data showed a dose‐dependent accumulation of acridine in liver, kidney and adipose with the highest concentration being found in the fat of the 500 ppm dose group. Based on these data, the no observable adverse effect level of acridine was judged to be 100 ppm or 12 mg/kg bw/day.     

镉对泥鳅幼鱼的急性和亚急性毒性研究

在实验条件下研究了镉对泥鳅幼鱼的急性和亚急性毒性。试验从刚孵出的幼鱼开始,采用静水换水法。亚急性试验历时20d。镉对泥鳅幼鱼24、48h的LC50值分别为1．22、0．85mg/L。亚急性试验中,镉对泥鳅幼鱼存活有明显影响的可观察效应浓度（LOEC）最低是O．16mg/L;根据对幼鱼现存量的影响,镉对泥鳅的最低可观察效应浓度为0．08mg/L,而无可观察效应浓度（NOEC）为0．04mg/L。     

Toxicity of pirimiphos-methyl: I. The acute and subacute oral toxicity in albino rats

In an acute study, albino rats of both sexes were orally administered graded doses of Pirimiphosmethyl, and the statistically computed median lethal dose (LD-50) were 1861 and 1667 mg/kg body weight for male and female rats respectively. No treatment related changes were discernible with regard to food intake, growth, gross or histopathology of the organs. In a time-course study, the correlation between symptoms and degree of esterase inhibition was examined in rats administered the minimum lethal dose (MLD: 1000 mg/kg b.w.) of the insecticide. Time-course inhibition pattern of both cholinesterase (ChE) and non-specific carboxylesterase (NSE) activities in brain and plasma revealed maximum inhibition at 24 h post-treatment which correlated well with the intensity of symptoms. In a subacute study, groups of male rats were fed dietary Pirimiphos-methyl at 0, 10, 250, 500 and 1000 ppm for 28 days. Food consumption and growth rate were not affected throughout the experimental period. At necropsy after 28 days, no gross pathological changes were seen in any of the organs except a slight increase in liver weight at 1000 ppm. Though no statistical differences were observed in the levels of hepatic transaminases, a significant increase in serum transaminase was evident. Significant increase in the activities of hepatic ALP, beta-GLR and serum ALP were evident at 500 and 1000 ppm. Further, significant inhibition of plasma PChE was evident at 250, 500 and 1000 ppm while the degree of inhibition of brain AChE was significant only at the higher dosages. No histopathological alterations were observed in any of the organs.     

Excretion and toxicity of Cyolane in the rat

The excretion of ¹⁴C-labelled Cyolane, 24 hours after single oral application was found to be about 50% of the applied dose in urine, faeces and expired air.The activity of Acetylcholine esterase in brain, plasma and erythrocytes, and liver succinate dehydrogenase was studied for 16 weeks in 4 groups of rats after repeated orally daily doses of Cyolane, 0.9, 0.45, 0.09 and 0.045 mg/kg.It has been found that at all the dose levels there were cumulative inhibition effects in brain and blood choline esterase and liver succinate dehydrogenase till the 2nd week and then there was a recovery at low dose rates in blood choline esterase and liver succinate dehydrogenase activities. After 6 - 16 weeks the effects were nearly compensated. At higher doses almost all the rats died after 6 weeks due to the insecticide toxicity.     

Interactions of 2,2′,4,4′,5,5′-hexachlorobiphenyl and 2,3,7,8-tetrachlorodibenzo-p-dioxin in a subchronic feeding study in the rat

Female (SD) rats were fed diets containing 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB 153) in various concentrations for three months. PCB 153 had no significant effect on the body weight gain when given alone or in combination with TCDD. The increases in relative liver weights were additive. For thymic atrophy no interactive effects became apparent. PCB 153 had no effect on the EROD induction by TCDD. PROD induction by PCB 153 was diminished in the presence of TCDD. The level of TCDD in the liver was decreased by PCB 153. Increasing TCDD dosage led to an increase in PCB 153 levels.     

90-day oral toxicity of ziram: a thyrostatic and hepatotoxic study

Ziram, a dithiocarbamate fungicide, is extensively used in crop protection. Daily oral doses of ziram (5 and 25 mg kg(-1) day(-1)) for 30, 60 and 90 days produced significant mortality in male rats. The fungicide also caused a significant increase in the thyroid:body weight ratio, histological changes, and a reduced activity of thyroid (125)I uptake and protein bound (125)I. However, the animals did not show any change in the clinical enzyme profile of the liver, serum and brain. It is believed that ETU, the degradation product of ziram and a known antithyroid compound, is the causative agent for the high mortality, as well as for the pronounced thyrostatic and hepatotoxic effects found in the experimental animals.     

Research to develop a predicting system of mammalian subacute toxicity (3) construction of a predictive toxicokinetics model

A new predictive toxicokinetics model was developed to estimate subacute toxicity (target organs, severity, etc.) of non-congeneric industrial chemicals, where the chemical structures and physico-chemical properties are only available. Thus, a physiological pharmacokinetics model, which consists of blood, liver, kidney (these were experimentally found as major toxicological targets), muscle and fat compartments , was established to simulate the chemical concentrations in organs/tissues with pharmacokinetic parameters by means of Runge-Kutta-Gill algorithm. The pliarmacokinetic parameters, i.e. absorption rate, absorption ratio, hepatic extraction ratio of metabolism and renal clearance were calculated by using separately established Quantitative Structure-Pharmacokinetics Relationship equations. The developed predictive model was then applied to simulations of 43 non-congeneric industrial chemicals. The chemical concentrations in organs/tissues after single oral administration were simulated, and their maximum concentrations (Cmax's) and area tinder the concentration-time curves (AUC's) were calculated.Fast Inverse Laplace Transform was newly applied for the purpose of simulation of 28-day repeated dose toxicity.Simulated concentrations of 28 days repeated dose were, however, found to be the same as those of simple repetitions of a single administration per day because of the short half-lives of non-congeneric industrial chemicals.A comparison of subacute toxicity data with Cmax's and AUC's in a single dose scenario suggested that the organs/tissues with relatively high concentrations of tested chemical substances were the most sensitive targets within a chemical.Chemical concentrations in liver, for instance, were correlated with the severity of hepatotoxicity among the chemicals. It was also suggested that to improve and widen the present approach, data of metabolite and reactivity of non-congeneric industrial chemicals to organs/tissues, receptors, etc. should be incorporated into the model.     

Development of a three-stage system for wastewater toxicity monitoring: a design and feasibility study.

A three-stage system was developed to automate a batchwise toxicity testing protocol designed for assessing wastewater toxicity to activated sludge. The three-stage system used the luminescent bacterium Shkl. The three stages were cell storage, cell activation, and continuous toxicity testing. Shkl cells were stored in a bioreactor at 4 degrees C when the system was not in use and activated in another bioreactor for use in toxicity tests conducted in a continuous manner. The system could quickly be switched between the "off" and "on" modes, and operation of the system was easy. The stability of the system, in terms of cell density and bioluminescence in the storage and activation bioreactors, and the response of the activated cells to a metal and an organic toxicant were studied. The feasibility of the system design was demonstrated by simulating zinc toxicity episodes in synthetic wastewater. The needs for further modifications and improvements of the system were discussed.     

Toxicity of trichlorotoluene isomers: a 28-day feeding study in the rat

Groups of 10 male and 10 female rats were fed alpha,alpha,alpha-, alpha,2,6- or 2,3,6- trichlorotoluene (TCT) in their diet at 0, 0.5, 5.0, 50 or 500 ppm for 28 days. Growth rate and food consumption were not affected by treatment. No deaths occurred. Significant increases in liver weights were observed in male rats fed 5.0 and 500 ppm 2,3,6-TCT. Mild serum biochemical changes occurred in male rats. These included increased SDH activities in the groups fed 5.0 and 50 ppm alpha, alpha, alpha-TCT, and 5.0 ppm 2,3,6-TCT. Alpha, alpha, alpha-TCT at 500 ppm caused elevated LDH activities in male rats. Hepatic microsomal aminopyrine N-demethylase activities were increased in male rats fed 500 ppm alpha,2,6-TCT. Hematological parameters were not affected by treatment. Mild histological changes were seen in the liver, kidney and thyroid of treated rats. Data presented here suggest that alpha, alpha, alpha-, alpha,2,6- and 2,3,6-TCT possess a low order of oral toxicity in the rat.     

CeO2 nanoparticle fate in environmental conditions and toxicity on a freshwater predator species: a microcosm study

Environmental Science and Pollution Research - We studied the fate and toxicity of two types of CeO2 NPs (bare or citrate-coated) in environmentally relevant conditions, using large indoor...     

Sulphur in the Arctic environment (1): results of a catchment-based multi-medium study.

S-concentrations were determined in 9 different sample materials (precipitation (rain and snow), vegetation, O-, E-, B- and C- horizon pf podzols, streams water and ground water) collected in eight small catchments (10-30 km2) at different distances from major SO2 point-source emitters on the Kola Peninsula, Russia. Comparison of the results from these materials, representing different compartments of the ecosystems under varying natural conditions leads to a better understanding of sources, cycling and fate of S in the Arctic environment. More than 300,000 t of SO2 emitted annually from the Kola smelters affect the air quality over a large area. Arctic climatic conditions (cold and dry) and the remote location of the emitters results in considerably lower S-deposition values than those observed in central Europe. The pathways of atmospheric S-deposition in the terrestrial environment vary significantly from summer to winter because different compartments of the ecosystems, with a different capability to accumulate S, are active. The actual S-flux is altered by every component of the ecosystem. When estimating the total S-deposition this effect must be considered.     

Effects of a chelating resin on metal bioavailability and toxicity to estuarine invertebrates: Divergent results of field and laboratory tests

Benthic invertebrates can uptake metals through diffusion of free ion solutes, or ingestion of sediment-bound forms. This study investigated the efficacy of the metal chelating resin SIR 300™ in adsorbing porewater metals and isolating pathways of metal exposure. A field experiment (Botany Bay, Sydney, Australia) and a laboratory toxicity test each manipulated the availability of porewater metals within contaminated and uncontaminated sediments. It was predicted that within contaminated sediments, the resin would adsorb porewater metals and reduce toxicity to invertebrates, but in uncontaminated sediments, the resin would not significantly affect these variables. Whereas in the laboratory, the resin produced the predicted results, in the field the resin increased porewater metal concentrations of contaminated sediments for at least 34 days and decreased abundances of four macroinvertebrate groups, and richness in all sediments. These contrasting findings highlight the limits of extrapolating the results of laboratory experiments to the field environment.     

Identifying the cause of toxicity in an algal whole effluent toxicity study - an unanticipated toxicant

Toxicity was observed in whole effluent toxicity (WET) studies with the freshwater alga, Pseudokirchneriella subcapitata, in three consecutive monthly studies, (NOEC = 50-75%). Toxicity was not observed to Ceriodaphnia dubia or the fathead minnow, Pimephales promelas in concurrent studies. Selected toxicity identification evaluation (TIE) tests were conducted in a tiered approach to eliminate possible toxicants and progressively identify the causative agent. Filtration following alkaline adjustment (pH 10 or 11) was effective in eliminating significant growth effects and also reduced phosphate concentration. The TIE studies confirmed that the observed effluent toxicity was caused by excess ortho-phosphate in the effluent not by overstimulation or related to unfavorable N:P ratios; but due to direct toxicity. The 96-h 25% inhibition concentration (IC25) of ortho-phosphate to P. subcapitata was 3.4 mg L⁻¹ while the maximum acceptable toxicant concentration was 4.8 mg L⁻¹. This study illustrates the value of multi-species testing and also provides an example of an effective TIE using algae identifying an unanticipated toxicant.     

Chronic toxicity of diclofenac,carbamazepine and their mixture to Daphnia magna: a comparative two-generational study

Environmental Science and Pollution Research - The chronic toxicity of diclofenac (DCF) and carbamazepine (CBZ) as separate substances and in conjunction with their mixture on Daphnia magna was...     

Evaluation of effluent toxicity and ambient toxicity in a polluted lowland river

The impact of an industrial effluent containing high loads of calcium, cadmium, lead chloride and sulphate, on a river ecosystem was assessed using a combination of an effluent toxicity test, an ambient toxicity test and an ecological survey. Only this combination of techniques made it possible to discriminate between the effects of the discharge and those of the background pollution. Each of the individual techniques detected essential effects which the other failed to reveal. With the physical and chemical measurements, important increases of several components were measured at all sampling sites downstream of the discharge. With the ecological survey, however, no large changes in water quality could be determined at the sampling sites, due to the high degree of pollution present upstream of the discharge. Reproduction of Daphnia magna, exposed to sublethal effluent dilutions, was followed over two generations. The offspring of the first generation were shown to have an increased sensitivity to the effluent, compared to the first generation that was born from previously unexposed mothers. Besides the toxicity of the effluent, the acute and chronic toxicity of its main component, CaCl(2), was also determined. The results of the CaCl(2)-tests and toxicity data from literature for the suspected toxicants were transformed to Toxic Units (TU). Using the sum of the TUs we investigated the possibility of predicting effluent toxicity to Daphnia magna. Effluent toxicity was under-estimated by calculating the sum of the TUs of the individual components. Dilution of the effluent to a level at which the measured toxicant concentrations comply with European regulations still showed significant effects on Daphnia reproduction.     

Involvement of glutathione in the reduction of captan-induced in vivo inhibition of monooxygenases and liver toxicity in the rat

If given orally captan is relatively nontoxic, but it can be extremely toxic after parenteral exposure. Therefore, a single i.p. dose of captan (20 mg/kg) was given to male Sprague-Dawley rats and its effect on liver microsomal mixed function oxidases and certain serum enzymes (SDH, SGPT and SGOT) was studied. The single dose of captan caused marked depression of microsomal cytochrome P-450 and the activity of benzphetamine N-demethylase and aniline hydroxylase, and moderate elevation of the serum enzymes indicative of liver damage. However, reduced glutathione (100 mg/kg, i.p.) given prior to captan, appears to decrease the liver toxicity as measured by reduced inhibition of the microsomal enzymes and elevation of serum enzymes activity. The results suggest that glutathione and other compounds containing sulfhydryl groups may protect the subjects from captan-induced liver toxicity.     

PTFE-coated non-stick cookware and toxicity concerns: a perspective

PTFE is used as an inner coating material in non-stick cookware. This unique polymer coating prevents food from sticking in the pans during the cooking process. Such cookware is also easy to wash. At normal cooking temperatures, PTFE-coated cookware releases various gases and chemicals that present mild to severe toxicity. Only few studies describe the toxicity of PTFE but without solid conclusions. The toxicity and fate of ingested PTFE coatings are also not understood. Moreover, the emerging, persistent, and well-known toxic environmental pollutant PFOA is also used in the synthesis of PTFA. There are some reports where PFOA was detected in the gas phase released from the cooking utensils under normal cooking temperatures. Due to toxicity concerns, PFOA has been replaced with other chemicals such as GenX, but these new alternatives are also suspected to have similar toxicity. Therefore, more extensive and systematic research efforts are required to respond the prevailing dogma about human exposure and toxic effects to PTFE, PFOA, and GenX and other alternatives.     

Studies on cadmium toxicity in plants: a review

This review emphasises cadmium toxicity on plants with regards to ecological, physiological and biochemical aspects. Cadmium toxicity in plants and problems concerning tolerance and ecological performance are discussed briefly. Efforts have been made to compare the relative sensitivity of various plant groups including micro-and macro-flora. This review may help in interdisciplinary studies to assess the ecological significance of metal stress.