Chronic Oral Toxicity Research Articles

Assessment of the impacts of microbial plant protection products containing Bacillus thuringiensis on the survival of adults and larvae of the honeybee (Apis mellifera)

This study was aimed at evaluating the effect of a microbial pest-controlling product (MPCP) with the active substance Bacillus thuringiensis ssp. aizawai (strain: ABTS-1857) on adults and larvae of honeybees. To determine the contamination levels of Bt spores in different matrices, a colony-feeding study under semi-field conditions was performed. Furthermore, two chronic adult trials and a chronic larval study were conducted under laboratory conditions to test the effects of different concentrations of the plant protection product (PPP) on the development and mortality. Possible modifications of the chronic oral toxicity test were assessed by additional pollen feeding. Our results showed that Bt spores were detected in all matrices over the entire test duration in different concentrations, decreasing over time. The survival of adult bees and larvae was negatively affected in laboratory conditions after a chronic exposure to the MPCP depending on the tested concentrations. Moreover, the earliest sign of bee mortality, resulting from exposure to ABTS-1857, was recorded only after 96 h at the highest tested concentration. Pollen feeding to adults significantly increased the survival of the treated bees. In conclusion, the PPP with the Bt strain ABTS-1857 showed an effect on the mortality of adults and larvae under laboratory conditions. Further studies with Bt-based PPPs under realistic field conditions are necessary to evaluate the potential risk of those MPCPs on honeybees.

An in Vivo Study for the Use of Lupinus Albus (Fabaceae) in Drosophila Melanogaster Diet

Based on the oral chronic toxicity studies in humans, the daily intake of Lupinus albus L. (termiye, white lupine) with diet is recommended to be about 0.02%. The study was designed to investigate the use of lupine shells in nutrition. Dried L. albus shell was added to the artificial diet of the model organism (Drosophila melanogaster) and then lipid peroxidation, antioxidant enzyme activity, total oxidation, and total antioxidant activity were determined in the tissues obtained from the third larval phase. Changes that occurred in the larval midgut cells were examined microscopically. As the amount of shell consumption increased, malondialdehyde concentration (0.33 - 0.09 ± 0.71 nmol/ mg protein) and glutathione S transferase activity (19.91 - 14.06 ± 0.04 nmol/ mg protein/ dk) decreased statistically compared to the control. In addition to this, larval total oxidation level and total antioxidant activity also decreased (P < 0.05). No damage was detected in the larval midgut epithelial cells.

In Vivo Evaluation of the Chronic Oral Toxicity of the Marine Toxin Palytoxin.

Palytoxin (PLTX) is one of the most poisonous substances known to date and considered as an emergent toxin in Europe. Palytoxin binds to the Na+-K+ ATPase, converting the enzyme in a permeant cation channel. This toxin is known for causing human fatal intoxications associated with the consumption of contaminated fish and crustaceans such as crabs, groupers, mackerel, and parrotfish. Human intoxications by PLTX after consumption of contaminated fishery products are a serious health issue and can be fatal. Different reports have previously explored the acute oral toxicity of PLTX in mice. Although the presence of palytoxin in marine products is currently not regulated in Europe, the European Food Safety Authority expressed its opinion on PLTX and demanded assessment for chronic toxicity studies of this potent marine toxin. In this study, the chronic toxicity of palytoxin was evaluated after oral administration to mice by gavage during a 28-day period. After chronic exposure of mice to the toxin, a lethal dose 50 (LD50) of 0.44 µg/kg of PLTX and a No-Observed-Adverse-Effect Level (NOAEL) of 0.03 µg/kg for repeated daily oral administration of PLTX were determined. These results indicate a much higher chronic toxicity of PLTX and a lower NOAEL than that previously described in shorter treatment periods, pointing out the need to further reevaluate the levels of this compound in marine products.

Acute and chronic oral toxicity assessment of longan sugar extracts derived from whole fruit and from fruit pulp in rats

Ethnopharmacological relevanceLongan (Dimocarpus longan Lour.) is one of the most popular subtropical fruits. Various parts of longan, including seeds, pericarp and pulp, have long been used in traditional medicine in China, Thailand and other Asian countries. The pulp has high sugar, vitamin and mineral content as well as bioactive components. The seeds and pericarp have also been reported to contain beneficial polyphenolic compounds. Longan sugar extract from pulp (LGSP) is prepared as a conventional sugar product. Longan sugar extract from whole longan fruit (LGSW) is also offered as a health food and as a medicinal product. Aim of the studyThe objective of this study was to identify and compare potential health hazards of both LGSW and LGSP by testing for acute and chronic oral toxicity in rats. Materials and methodsIn acute toxicity testing, an oral dose (20 g/kg) of either LGSW or LGSP was administered to groups of rats. Mortality and clinical signs of toxicity were observed for 24 h, and then daily for a total of 14 days. In the chronic toxicity test, either LGSW (1, 2.5 and 5 g/kg/day) or LGSP (5 g/kg/day) was administered orally for a period of 180 days. After that treatment period, the rats in the satellite groups which received the highest doses of either LGSW or LGSP were observed for an additional 28 days. The rats then underwent clinical observation, body and organ weight measurement, hematological and biochemical analyses, and histopathological examination. ResultsIn the acute toxicity study, the oral administration of LGSP or LGSW in either pellet or syrup formulations did not cause mortality or any pathological abnormalities. In the chronic toxicity study, neither LGSW nor LGSP resulted in death or in any changes in behavior of the rats. All hematological and serum biochemical values of both the LGSW- and LGSP-treated groups were within the normal ranges. No histopathological abnormalities of any internal organs were observed. ConclusionThe safety of longan sugar extract made from whole fruit (pulp, seeds and pericarb) is comparable to that of longan sugar extract made from pulp alone.

A Chronic Toxicity Study of Oral Administration of Collagen-?® Supplement using Pregnant Rabbits

Since collagen derived products are highly used in food supplements due to its bioactive properties by influencing cellular and tissue health, flexibility with high effect of repairing and adaptation. It is necessary to carry out safety requirement of an oral chronic toxicity assessment. This study investigated the adverse effect of long term oral administration of collagen-® in pregnant rabbits. We have conducted a thirty days randomized controlled trial in pregnant rabbits. Rabbits were randomized into two groups; Group 1 (control group) were administrated with 1 ml of normal saline PO, SID while Group 2 (collagen-? group) were administered with 1 ml of collagen-?® PO, SID for one month. Bodyweight gain, viscera weight and histopathological evaluation of the individual rabbit were recorded. The results revealed that the body weight gain and visceral tissues weight in the collagen-? group were significantly lower than the control group. Moreover, various histopathological changes were recorded in heart, lungs, liver and kidneys of the collagen-? group when compared with the non-significant changes that noticed in the control group. Under the conditions of the current study, a high risk of chronic toxic effect was observed in pregnant rabbits inoculated with 1 ml of oral dose of collagen alpha supplement. This result suggests that the adverse effect of collagen derived supplements is overbalancing the benefits.

Oral Chronic Toxicity of the Safe Tetrodotoxin Dose Proposed by the European Food Safety Authority and Its Additive Effect with Saxitoxin.

Tetrodotoxin (TTX) is a potent natural toxin causative of human food intoxications that shares its mechanism of action with the paralytic shellfish toxin saxitoxin (STX). Both toxins act as potent blockers of voltage-gated sodium channels. Although human intoxications by TTX were initially described in Japan, nowadays increasing concern about the regulation of this toxin in Europe has emerged due to its detection in fish and mollusks captured in European waters. Currently, TTX is only regularly monitored in Dutch fishery products. However, the European Food Safety Authority (EFSA) has established a safety level of 44 µg/kg TTX as the amount of toxin that did not cause adverse effects in humans. This level was extrapolated considering initial data on its acute oral toxicity and EFSA remarked the need for chronic toxicity studies to further reduce the uncertainty of future toxin regulations. Thus, in this work, we evaluated the oral chronic toxicity of TTX using the safety levels initially recommended by EFSA in order to exclude potential human health risks associated with the worldwide expanding presence of TTX. Using internationally recommended guidelines for the assessment of oral chronic toxicity, the data provided here support the proposed safety level for TTX as low enough to prevent human adverse effects of TTX even after chronic daily exposure to the toxin. However, the combination of TTX with STX at doses above the maximal exposure level of 5.3 µg/kg body weight derived by EFSA increased the lethality of TTX, thus confirming that both TTX and paralytic shellfish toxins should be taken into account to assess human health risks.

Investigating combined toxicity of binary mixtures in bees: Meta-analysis of laboratory tests, modelling, mechanistic basis and implications for risk assessment

Bees are exposed to a wide range of multiple chemicals “chemical mixtures” from anthropogenic (e.g. plant protection products or veterinary products) or natural origin (e.g. mycotoxins, plant toxins). Quantifying the relative impact of multiple chemicals on bee health compared with other environmental stressors (e.g. varroa, viruses, and nutrition) has been identified as a priority to support the development of holistic risk assessment methods. Here, extensive literature searches and data collection of available laboratory studies on combined toxicity data for binary mixtures of pesticides and non-chemical stressors has been performed for honey bees (Apis mellifera), wild bees (Bombus spp.) and solitary bee species (Osmia spp.). From 957 screened publications, 14 publications provided 218 binary mixture toxicity data mostly for acute mortality (lethal dose: LD50) after contact exposure (61%), with fewer studies reporting chronic oral toxicity (20%) and acute oral LC50 values (19%). From the data collection, available dose response data for 92 binary mixtures were modelled using a Toxic Unit (TU) approach and the MIXTOX modelling tool to test assumptions of combined toxicity i.e. concentration addition (CA), and interactions (i.e. synergism, antagonism). The magnitude of interactions was quantified as the Model Deviation Ratio (MDR). The CA model applied to 17% of cases while synergism and antagonism were observed for 72% (MDR > 1.25) and 11% (MDR < 0.83) respectively. Most synergistic effects (55%) were observed as interactions between sterol-biosynthesis-inhibiting (SBI) fungicides and insecticide/acaricide. The mechanisms behind such synergistic effects of binary mixtures in bees are known to involve direct cytochrome P450 (CYP) inhibition, resulting in an increase in internal dose and toxicity of the binary mixture. Moreover, bees are known to have the lowest number of CYP copies and other detoxification enzymes in the insect kingdom. In the light of these findings, occurrence of these binary mixtures in relevant crops (frequency and concentrations) would need to be investigated. Addressing this exposure dimension remains critical to characterise the likelihood and plausibility of such interactions to occur under field realistic conditions. Finally, data gaps and further work for the development of risk assessment methods to assess multiple stressors in bees including chemicals and non-chemical stressors in bees are discussed.

Toxicological Studies of Chaturmukha Rasa, an Ayurvedic Formulation

Abstract: Objectives: Chaturmukha Rasa is aspecial, Ayurvedic mercurial preparation broadly used by local practitioners and traditional healers. This research is an endeavour to perform acute and chronic oral toxicity assessment of Chaturmukha Rasa along with an adjuvant Erandapatra (solidified aqueous extract of Ricinus communis Linn.) in wistar rats. Methods: Oral acute toxicity study was performed at 2000mg/kg orally, which was considered as limit dose. The chronic toxicity study was carried out with administration of Chaturmukha Rasa with adjuvant at three therapeutic equivalent doses i.e. TED (45mg/kg, orally), TEDx5 (225 mg/kg, orally) and TEDx10 (450 mg/kg, orally) for 90 daysand an additional recovery group of therapeutic equivalent dose×10 for 30-day observation after the treatment period. Results: The result of acute toxicity showed that drug did not create any signs and symptoms of toxicity or no mortality was shown to an oral dose of 2000 mg/ kg in rats. The results of chronic toxicity study showed that the drug even at level as high as dose of TEDx10 had no significant effect at all on haematological and body weight parameters. The drug but, at dose of TEDx10 showed mild to moderate unfavourable changes in kidney and liver. The experiential changes were not seen at the lower dose levels. Hence, it is suggested that the Chaturmukha Rasa, along with the adjuvant prepared as per the traditional method, is secure for utilization at the therapeutic dose level. Key words: Chaturmukha Rasa, Erandapatra, Ricinus communis, Bhasma, Toxicity.

EXPERIMENTAL EVALUATION OF CHRONIC ORAL TOXICITY AND LONG-TERM EFFECTS OF SOLID ROCKET FUELS COMPONENT

The chronic oral toxicity and long-term effects of the basic lead-nickel salt of phthalic acid have been investigated by long-term oral ingestion of white outbred rats. The compound at doses of 1.0 mg/kg; 0.3 mg/kg and 0.1 mg/kg have changed the physiological, behavioral, hematological, biochemical, immunological parameters, as well as the relative weight of internal organs of animals in the six months experiments. The threshold of chronic oral toxicity of the substance is set at 0.1 mg / kg.The study of long-term effects revealed the absence of its mutagenic activity both at the gene (Ames test) and chromosomal (dominant lethal method) levels. In addition, the analyzed compound did not adversely affect the reproductive function of male rats. When entering the body of females during gestation, the toxicant did not reveal embryo-lethal and teratogenic properties.However, chronic administration of the compound into the body of non-pregnant animals at a dose of 1.0 mg/kg contributed to a significant decrease relative to the control of the mass and disk diameter of the placenta, which indirectly indicated the functional inferiority of the organ. Therefore, the considered level of the substance is defined as a threshold for gonadotoxic effect.The obtained data are taken into account in developing of hygienic standard of the estimated component of solid rocket fuels in water reservoirs.

Chronic In Vivo Effects of Repeated Exposure to Low Oral Doses of Tetrodotoxin: Preliminary Evidence of Nephrotoxicity and Cardiotoxicity.

Tetrodotoxin (TTX) is one of the most potent naturally occurring neurotoxins. Initially TTX was associated with human food intoxications in Japan, but nowadays, concerns about the human health risks posed by TTX have increased in Europe after the identification of the toxin in fish, marine gastropods, and bivalves captured in European waters. Even when TTX monitoring is not currently performed in Europe, an acute oral no observable effect level (NOAEL) of 75 μg/kg has been recently established but, to date, no studies evaluating the chronic oral toxicity of TTX have been released, even when EFSA has highlighted the need for them. Thus, in this work, the chronic effects of low oral TTX doses (below the acute lethal dose 50) were evaluated following internationally adopted guidelines. The results presented here demonstrate that low oral doses of TTX have deleterious effects on renal and cardiac tissues. Moreover, alterations in blood biochemistry parameters, urine production, and urinalysis data were already detected at the oral dose of 75 µg/kg after the 28 days exposure. Thus, the data presented here constitute an initial approach for the chronic evaluation of the in vivo toxicity of tetrodotoxin after its ingestion through contaminated fishery products.

Experimental study on effect of Naga Bhasma (lead calx) on hematological and biochemical parameters

Background: In recent decade, a lot of concerns has been raised regarding heavy metal content in Ayurveda medicines, especially Bhasma (metallic calx). Naga Bhasma (lead calx) is of the metallic preparation primarily indicated in treating chronic ailments such as Kamala (jaundice), Vatarakta (gout), Grdhrasi (sciatica), Kustha (skin diseases), and Prameha (diabetes). As being a compound of lead, its chronic toxicity study was planned to find out the effect of Naga Bhasma on serum biochemical and hematological parameters. Material and method: Naga Bhasma was prepared by Parada (mercury) and Gandhaka media (NBP) and Vasa Swarasa (juice of Adhatoda vasica Linn.) as herbal media (NBH) in seven Puta (incineration cycles). Chronic oral toxicity study was carried out as per Organization for Economic cooperation and Development (OECD) 408 (90-day oral repeated dose toxicity study). Wistar strain albino rats (Rattus norvegicus) were used for the experimentation. The study was conducted at three dosage levels, therapeutically effective dose (TED) of NBP and NBH was 45 mg/kg body weight of rat, TED × 5 and TED × 10. On 91st day, blood was collected by supraorbital puncture with the help of microcapillary tubes under mild ether anesthesia for estimation of serum biochemical and hematological parameters. Observation and results: Among hematological parameters, significant decrease was observed in MCV (Mean corpuscular volume), MCH (Mean corpuscular haemoglobin), and mean corpuscular hemoglobin concentration by NBH-treated group, whereas in biochemical parameters, both test drugs significantly increased BSL (Blood Sugar Level), SGOT (Serum Glutamic-Oxaloacetic Transaminase), and serum ALP (Alkaline Phosphatise) activity. Hematological and biochemical analysis indicates that both test drugs (prepared in seven incineration cycles) were not found completely safe, especially at higher dosage where the drug affected renal and hepatic functions. Conclusion: For the safety purpose, it is suggested that Naga Bhasma prepared in less number of incineration cycles may not be used for therapeutic purpose.

Combinative Approaches of Chemistry, Pharmacology and Toxicology for the Optimal Pharmaceutical Preparation of an Anti-arthritic Chinese Medicine Formulation QFJBT

ABSTRACT ObjectiveQing Fu Juan Bi Tang (QFJBT) is an anti-arthritic Chinese medicine formula consisting of five herbs: Aconiti Lateralis Radix Praeparata (Fu Zi, 附子), Sinomenii Caulis (Qing Feng Teng, 青风藤), Astragali Radix (Huang Qi, 黄芪), Paeoniae Radix Alba (Bai Shao, 白芍) and Moutan Cortex (Mu Dan Pi, 牡丹皮), which have well-established histories of use for treatment of rheumatic and arthritic diseases. We intended to establish the optimized and standardized pharmaceutical procedures and manufacturing processes for the pilot production of QFJBT to develop it as a novel botanical drug product for treatment of rheumatoid arthritis (RA). Methods The combinative approaches of chemical assessment, toxicological and pharmacological evaluation were explored to define the pharmaceutical preparation of QFJBT. Results The optimized and standardized pharmaceutical procedures and manufacturing processes for the pilot production of QFJBT were established in terms of greatest chemical contents of bioactive constituents, potent anti-inflammatory and antinociceptive activities, and favorable safety profile. Quality analysis of the pilot product of QFJBT by high-performance liquid chromatography (HPLC) demonstrated that the chromatographic fingerprint profiles of three batches of QFJBT were basically identical and the contents of four characteristic and bioactive markers were relatively consistent. General toxicological studies showed a favorable safety profile of QFJBT. The maximum tolerated single dose of QFJBT was determined in both sexes of rats to be 33.63 g/kg body weight which is equivalent to 346 times of clinical dose. In the chronic oral toxicity study, the results of laboratory investigation showed that QFJBT at doses of 3.89, 6.80 and 9.72 g/kg body weight (equivalent to 40, 70 and 100-fold clinical doses, respectively) caused no changes in all hematological parameters and blood biochemical parameters of rats. No mortality or specific toxic responses were observed in animals after three months of repeated dosing with QFJBT. Conclusion The optimized and standardized pharmaceutical and manufacturing processes for the production of QFJBT have been successfully screened and identified through established rigorous in-process controls.

Safety Assessment of Bangle (Zingiber purpureum Rosc.) Rhizome Extract: Acute and Chronic Studies in Rats and Clinical Studies in Human.

Bangle (Zingiber purpureum Rosc.) rhizome extract (BRE) contains phenylbutenoid dimers (banglenes), which exert neurotrophic effects and possess the potential capability to regenerate hippocampal neurons in mice. The acute and chronic oral toxicities of BRE powder were evaluated in Sprague–Dawley rats. A dose of BRE powder was estimated to be higher than 2000 mg/kg containing BRE 534 mg/kg as minimum lethal dose in a single-dose oral toxicity study. The no-observed-adverse-effect-level for the BRE powder was 1000 mg/kg/day (BRE 267 mg/kg) in the 90 day oral toxicity study. Four week clinical studies of BRE tablets in humans suggested that the ingestion of BRE tablets within 850 mg/man/day (BRE 227 mg/man/day) was safe for at least 1 month and in a usual manner. The Cmax, tmax, and AUC of cis- and trans-(E)-3-(3,4-dimethoxyphenyl)-4-[(E)-3,4-dimethoxystyryl]cyclohex-1-enes (c- and t-banglenes) were calculated after the ingestion of BRE tablets (BRE 227 mg) and were 17.73 and 22.61 ng/mL, 1.8 and 1.8 h, and 71.47 and 95.53 ng/mL/h, respectively.

One size does not fit all: Caste and sex differences in the response of bumblebees (Bombus impatiens) to chronic oral neonicotinoid exposure.

Neonicotinoid insecticides have been implicated in the rapid global decline of bumblebees over recent years, particularly in agricultural and urban areas. While there is much known about neonicotinoid toxicity effects at the colony stage of the bumblebee annual cycle, far less is known about such effects at other stages critical for the maintenance of wild populations. In the present work, individual-based feeding assays were used to show that chronic consumption of the widely used neonicotinoid clothianidin at a field-realistic average rate of 3.6 and 4.0 ng/g·bee/day reduces survival of queen and male bumblebees, respectively, within a 7-day period. In contrast, worker survival was unaffected at a similar consumption rate of 3.9 ng/g·bee/day. To test the hypothesis that males have a lower tolerance for oral clothianidin exposure than workers due to their haploid genetic status, RNAseq analysis was used to compare the transcriptomic responses of workers and males to chronic intake of clothianidin at a sub-lethal dose of 0.37ng/bee/day for 5 days. Surprisingly, clothianidin consumption only altered the expression of 19 putative detoxification genes in a sex-specific manner, with 11/19 genes showing increased expression in workers. Sub-lethal clothianidin exposure also altered the expression of 40 genes associated with other major biological functions, including locomotion, reproduction, and immunity. Collectively, these results suggest that chronic oral toxicity effects of neonicotinoids are greatest during mating and nest establishment phases of the bumblebee life cycle. Chronic oral toxicity testing on males and queens is therefore required in order to fully assess the impact of neonicotinoids on wild bumblebee populations.

Safety assessment of vitacoxib: 180-day chronic oral toxicity studies

Vitacoxib, a selective COX-2 inhibitor, is approved for the relief of pain and inflammation associated with orthopedic surgery and osteoarthritis in dogs. In the current study, a chronic toxicity research was performed to evaluate the safety of vitacoxib in male and female rats for long-term. Vitacoxib was dosed orally to groups of rats for 180 days at 1.2, 6, 30 mg/kg bw/day by gavage. The chronic study oral administration of vitacoxib did not show observational or toxicological effects on the body or organ weights, food consumption, hematology and biochemistry at dose 6 mg/kg bw. However, vitacoxib (30 mg/kg) showed minor alterations to histopathology of liver, kidney and stomach related to treatment. These results provide further indication that vitacoxib is safe and well-tolerated in rats after 180 days of daily oral administration at 6 mg/kg bw and the NOAEL for both sexes was 6 mg/kg bw for 180 consecutive days.

The study of acute and chronic toxicity of the sodium-, calcium-, iron-polygalacturonate pharmacological substance in rabbits.

The purpose of this study is the assessment of the acute and chronic toxicity of pharmacological substance sodium, calcium, iron-polygalacturonate (PG Na,Ca,Fe) in rabbits as one of the stages of preclinical studies. We studied an acute and chronic oral toxicity of PG Na,Ca,Fe, which stimulates the process of hemopoiesis, in male and female rabbits of the "Chinchilla". According to the results of the study of acute toxicity of PG Na,Ca,Fe, treating with it the rabbits of both sexes in doses of 0.5-5 g/kg has no toxic effect (LD50 greater than 5 g/kg). The histostructure of studied organs of animals, treated with preparations in a dose of 5 g/kg, did not differ from that of the animals of the control group. This study allow to classify PG Na,Ca,Fe as a preparation of the 6th class with respect to harmless drugs. An estimate of the chronic toxicity of PG Na,Ca,Fe at administration of preparation in the form of boluses to rabbits in doses 0.025, 0.262 and 0.5 g/kg of the body weight demonstrated that the general condition and behavior of animals did not differ from the norm. The data of hematological and biochemical studies of blood serum and urine, electrocardiographic studies, the study of the mass coefficients of the internal organs of the experimental rabbits, treated with PG Na,Ca,Fe in the mentioned doses for 60 days, compared to those obtained in the 30-day post-observation period, did not show significant changes with respect to the control and intact group of rabbits.

Oral chronic toxicity study of geniposide in rats

Ethnopharmacological relevanceGeniposide, the major active constituent of Fructus Gardeniae (FG), has been widely used to treat various diseases in China. Aim of the studyThis chronic toxicity study was conducted to investigate the safety of geniposide. Materials and methodsGeniposide was administered to Sprague-Dawley (SD) rats of both sexes by oral gavage at dosages of 25, 50, or 100mg/kg in a volume of 10mL/kg once daily for 26 weeks. Endpoints included clinical observations, food consumption, body weights, blood biochemistry, haematology, and histomorphological observations. ResultsThe administration of geniposide did not influence animal mortality, the general conditions of the animals, body weights or food consumption. After 4 weeks of administration, significant toxicity was not observed. However, in the 13th week of the toxicity study, a few haematological parameters and some relative organ weights of male rats in the 50 and 100mg/kg geniposide groups were significantly increased. The percentage of reticulocytes (Retic %) was significantly increased in male and female rats administered 100mg/kg geniposide. In addition, two female rats in the 100mg/kg geniposide group showed slight pathological changes in hepatic and renal tissues. Furthermore, in a chronic (26 weeks) toxicity study, differences were detected in alanine aminotransferase (ALT), aspartate aminotransferase (AST), sodium (Na+), potassium (K+), white blood cell (WBC), red blood cell (RBC), and haemoglobin (HGB) levels and the relative weights of the liver and spleen in male rats administered 100mg/kg geniposide. In addition, differences were detected in Retic % and the relative weights of the liver, thymus, and kidneys in female rats administered 100mg/kg geniposide. Urinalysis results from male and female rats in the 100mg/kg geniposide group revealed noticeable changes. The histopathological structures of hepatic and renal tissues in the high-dose geniposide group exhibited serious abnormalities and pigment deposition. ConclusionGeniposide affected serum biochemistry, urinalysis, and haematological parameters as well as relative organ weights. The treatment also caused noticeable pathological abnormalities in liver and kidney tissues. Therefore, administration of a high dose of geniposide (100mg/kg) for 26 weeks could induced obvious liver and kidney damage.

Evaluation of the acute and chronic toxicity of the jiangu capsules.

Saussureae involucratae Flos is the primary component of the jiangu capsule, which also consists of 12 types of natural medicine. It is a traditional Chinese medicine used to treat a number of conditions including arthralgia, cold and sore muscles, stiff limbs, inconvenient flexion and activity limitation caused by different types of osteoarthritis. The present study was performed to assess the safety of the jiangu capsule following acute and chronic administration in mice and rats. In the acute study, mice were treated with the jiangu capsule orally at 16 g/kg/day, the highest dose, for 14 days. In the chronic oral toxicity study, rats were treated with 2, 4 and 8 g/kg/day of the jiangu capsule for 6 months. The general condition, body weight changes, food and water consumption, hematological and biochemical parameters, urinalysis, systematic anatomy and organ weights of the rats were monitored and histopathological examination was performed at the end of 3 and 6 months' daily administration, and following 14 days of withdrawal. There were no signs of toxicity in the general condition and body weight of the mice was not significantly affected by the treatment. Furthermore, necropsy findings for the animals in the acute and chronic toxicity studies demonstrated that no mortalities had occurred. The results of the current study indicate that treatment with the jiangu capsule did not induce mortality or any detectable abnormalities in mice and rats.

Evaluation of triclosan in Minnesota lakes and rivers: Part II - human health risk assessment

Triclosan, an antimicrobial compound found in consumer products, has been detected in low concentrations in Minnesota municipal wastewater treatment plant (WWTP) effluent. This assessment evaluates potential health risks for exposure of adults and children to triclosan in Minnesota surface water, sediments, and fish. Potential exposures via fish consumption are considered for recreational or subsistence-level consumers. This assessment uses two chronic oral toxicity benchmarks, which bracket other available toxicity values. The first benchmark is a lower bound on a benchmark dose associated with a 10% risk (BMDL10) of 47mg per kilogram per day (mg/kg-day) for kidney effects in hamsters. This value was identified as the most sensitive endpoint and species in a review by Rodricks et al. (2010) and is used herein to derive an estimated reference dose (RfD(Rodricks)) of 0.47mg/kg-day. The second benchmark is a reference dose (RfD) of 0.047mg/kg-day derived from a no observed adverse effect level (NOAEL) of 10mg/kg-day for hepatic and hematopoietic effects in mice (Minnesota Department of Health [MDH] 2014). Based on conservative assumptions regarding human exposures to triclosan, calculated risk estimates are far below levels of concern. These estimates are likely to overestimate risks for potential receptors, particularly because sample locations were generally biased towards known discharges (i.e., WWTP effluent).

Toxicological Studies of Rasasindura, an Ayurvedic Formulation

Rasasindura is a unique, Ayurvedic mercurial preparation widely used by practitioners. Thi investigation is an attempt to perform acute and chronic oral toxicity evaluation of Rasasindura along with an adjuvant Guduchi Ghana (solidified aqueous extract of Tinospora cordifolia Will.) in rats. Oral acute toxicity study of test drug was carried at the limit dose of 2000 mg/kg orally in rats. For chronic toxicity, Rasasindura with adjuvant was administered at therapeutic equivalent dose (45 mg/kg, orally), therapeutic equivalent dose×5 (225 mg/kg, orally), therapeutic equivalent dose×10 (450 mg/kg, orally) for 90 days and an additional recovery group of therapeutic equivalent dose×10 for 30-day observation after the treatment period. Acute toxicity result showed that drug did not produce any signs and symptoms of toxicity or mortality up to an oral dose of 2000 mg/kg in rats. Chronic toxicity results showed that Rasasindura, even at a level as high as therapeutic equivalent dose×10 level, had no significant effect whatsoever on the ponderal and hematological parameters. Although the drug produced mild to moderate adverse changes (in kidney, liver, intestine, and stomach) at therapeutic equivalent dose×10 dose level, equivalent of which are unlikely to be ever employed in a clinical trial. The observed changes were not seen at the lower dose levels as well as in the recovery study. Hence, it is suggested that the Rasasindura, along with the adjuvant prepared as per the customary method, is safe for consumption at the therapeutic dose level.