Toxicological studies on 2,4,6-tribromoanisole

TBA, or 2,4,6-tribromoanisole, is a musty-smelling metabolite of 2,4,6-tribromophenol that is used as a flame retardant and an antifungal agent for wooden pallets and packaging materials. The compound can impart its peculiar, often offensive, odor on product packaging to the concern of consumers for the safety of the package contents. These studies were conducted to evaluate the safety of TBA to humans ingesting products tainted with TBA. In addition to the 28-day oral study, a bacterial reverse mutation study was conducted, and confirmed that TBA was not mutagenic. To evaluate oral safety, TBA was evaluated in single dose and 5-day and 4-week repeated dose oral toxicity studies in rats. The test article, administered in single gavage doses of 2000, 5000 and 7500 mg/kg body weight (bw), in 5 daily repeated doses of 1000, 2000 or 3000 mg/kg bw/day or in 28 daily oral gavage doses of 0 001, 0.01, 100, and 1000 mg/kg bw/day did not result in any deaths. Also, the single and repeat dose studies resulted in no significant differences between control and treated groups on body weight gain, food consumption, clinical observations, blood biochemical values, and hematology findings. Treatment-related adverse findings were only detected in male rats during repeated dose studies and were associated with high plasma concentrations of TBA. The test article-related finding of hyaline droplets in the cortical tubular epithelium of kidneys was associated with increases in α_2μ-globulin content in the kidneys as indicated by the intensity of immunohistochemical staining. These findings were correlated with an increased weight of kidneys in males administered 1000 mg/kg bw/day for 28 days. Chemical induction of hyaline droplets containing α_2μ-globulin in the renal proximal tubule is a process unique to the male rat and is not relevant for human risk assessment. Findings of increased liver weight with minimal centrilobular to diffuse hepatocellular hypertrophy in males treated with TBA at 1000 mg/kg bw/day for 28 days were considered to be an adaptive metabolic response to xenobiotic administration. The increased volume of urine, noted in both males and females treated with 1000 mg/kg bw/day was considered adaptive and necessary to excrete the high xenobiotic burden resulting from TBA administration. TBA appeared to be highly bioavailable since high concentrations of TBA were detected in plasma, at 1, 4 and 8 h after administration of TBA at 100 and 1000 mg/kg bw for 1 and 28 days. Levels were dose-related but did not clarify the course of TBA elimination with time after administration. These studies indicate that TBA, administered orally to rats, produced male rat-specific, treatment-related toxicity at the highest orally administered dose in repeated dose (5-day at 3000 mg/kg bw and 28-day at 1000 mg/kg bw) studies. Therefore, the NOAEL for the 28-day oral study was determined to be 1000 mg/kg bw/day for the rat.     

Safety assessment of a solid lipid curcumin particle preparation: Acute and subchronic toxicity studies

Curcumin, a polyphenol, is obtained from turmeric, the ground rhizomes of Curcuma longa L. Extensive research over the past half century has revealed several health benefits of curcumin. The objective of the present study was to investigate potential adverse effects, if any, of a novel solid lipid curcumin particle (SLCP) preparation in rats following acute and subchronic administration. The oral LD₅₀ of the preparation in rats as well as in mice was found to be greater than 2000 mg/kg body weight (bw). In the subchronic toxicity study, Wistar rats (10/sex/group) were administered via oral gavage 0 (control), 180, 360, and 720 mg/kg bw/day of SLCP preparation for 90 days. Administration of the curcumin preparation did not result in any toxicologically significant treatment-related changes in clinical (including behavioral) observations, ophthalmic examinations, body weights, body weight gains, feed consumption, and organ weights. No adverse effects of the curcumin preparation were noted on the hematology, serum chemistry parameters, and urinalysis. Terminal necropsy did not reveal any treatment-related gross or histopathology findings. Based on the results of this study, the No Observed-Adverse-Effect Level (NOAEL) for this standardized novel curcumin preparation was determined as 720 mg/kg bw/day, the highest dose tested.     

Dose-response assessment of nephrotoxicity from a twenty-eight-day combined-exposure to melamine and cyanuric acid in F344 rats

The adulteration of pet food with melamine and derivatives, including cyanuric acid, has been implicated in the kidney failure and death of cats and dogs in the USA and other countries. In a previous 7-day dietary study in F344 rats, we established a no-observed-adverse-effect level (NOAEL) for a co-exposure to melamine and cyanuric acid of 8.6 mg/kg bw/day of each compound, and a benchmark dose lower confidence limit (BMDL) of 8.4-10.9 mg/kg bw/day of each compound. To ascertain the role played by the duration of exposure, we treated F344 rats for 28 days. Groups of male and female rats were fed diet containing 0 (control), 30, 60, 120, 180, 240, or 360 ppm of both melamine and cyanuric acid. The lowest dose that produced histopathological alterations in the kidney was 120 ppm, versus 229 ppm in the 7-day study. Wet-mount analysis of kidney sections demonstrated the formation of melamine cyanurate spherulites in one male and two female rats at the 60 ppm dose and in one female rat at the 30 ppm dose, establishing a NOAEL of 2.1 mg/kg bw/day for males and < 2.6 mg/kg bw/day for females, and BMDL values as low as 1.6 mg/kg bw/day for both sexes. These data demonstrate that the length of exposure is an important component in the threshold of toxicity from a co-exposure to these compounds and suggest that the current risk assessments based on exposures to melamine alone may not reflect sufficiently the risk of a co-exposure to melamine and cyanuric acid.     

Safety assessment of N-acetyl-l-threonine

N-acetyl-l-threonine (NAT) is a dietary constituent that has been identified at low concentrations (<1 μg/g fresh weight) in numerous foods. The current paper reports the outcome of toxicology studies conducted to assess the effects of NAT. No evidence of mutagenicity or genotoxicity was observed in in vitro bacterial or in vivo mammalian studies. No mortalities or evidence of adverse effects were observed in Sprague–Dawley (SD) rats following acute oral administration of 2000 mg of NAT/kg of body weight (kg of bw). A 28-day repeated dose toxicity study was conducted in SD rats by incorporating NAT into diets at concentrations targeting up to 1000 mg of NAT/kg of bw/day. All rats survived until scheduled sacrifice and no biologically significant differences were observed in any of the NAT treatment groups for body weights, feed consumption, clinical signs, behavioral, ophthalmology, hematology, coagulation, clinical chemistry, organ weights, or gross or microscopic changes. Based on these results, NAT does not represent a risk for mutagenicity or genotoxicity, is not acutely toxic, and the no-observed-adverse-effect-level (NOAEL) for systemic toxicity from repeated dose dietary exposure to NAT is 848.5 and 913.6 mg/kg of bw/day for male and female SD rats, respectively.     

Safety assessment of AGPC as a food ingredient

α-Glycerylphosphorylcholine (AGPC) is a semi-synthetic derivative of lecithin. Following oral administration, it is converted to phosphatidylcholine, a metabolically active form of choline that is able to reach cholinergic synaptic endings where it increases acetylcholine synthesis and release. A series of studies were conducted to demonstrate the safety of AGPC. The oral LD50 was equal to or greater than 10,000 mg/kg in rats and mice. Deaths were preceded by convulsions in some animals. Dosing of dogs with up to 3000 mg/kg AGPC resulted only in reduced activity. Sub-chronic and chronic oral toxicity studies in rats (up to 1000 mg/kg/day) and beagles (up to 300 mg/kg/day) produced symptomology primarily consisting of reduced activity; slight decreases in food consumption and body weight gain; and slight reduction in liver weight, paralleled by significant decreases in plasma triglycerides, bilirubin, and alkaline phosphatase. There were no histopathological correlates. The in vivo and in vitro assays clearly indicated that AGPC was devoid of mutagenic activity. Based on these results, AGPC is not genotoxic in vitro or in vivo, exhibits low acute oral toxicity and, has an oral NOAEL of 150 mg/kg bw/day following 26 weeks oral exposure.     

Propetamphos-induced changes in haematological and biochemical parameters of female rats: Protective role of propolis

The present study was conducted to investigate the effectiveness of propolis in alleviating the toxicity of propetamphos on haematological and biochemical parameters in rats. Twenty-four female Wistar–Albino rats (200–250 g) were randomly divided into four equal groups of six rats each. As normal drinking water was given to the control group, propolis (100 mg/kg bw/day), propetamphos (15 mg/kg bw/day), and propolis (100 mg/kg bw/day) with propetamphos (15 mg/kg bw/day) combinations were given to the other three groups by adding to drinking water for 28 days, respectively.     

General 4-week toxicity study with EMS in the rat

In this subacute toxicity study, ethyl methanesulfonate (EMS) was administered daily by oral gavage to SPF-bred Wistar rats of both sexes at dose levels of 20, 60 and 180/120 mg/kg body weight (bw)/day for a period of 28 days (for 19 days in the high-dose group). A control group was treated similarly with the vehicle, bidistilled water, only. The groups comprised 10 animals per sex, which were sacrificed after 28 days, respectively 19 days in the high-dose group, of treatment. Additional five rats per sex and group were treated accordingly and then allowed a 14 days treatment-free recovery period. Additional six rats per sex and group (three rats per sex in the control group) were treated accordingly and used for hemoglobin adduct analysis after EMS exposure. All animals survived until their scheduled necropsy. Treatment with EMS had a direct dose-dependent effect on food consumption and consequently on body weight at doses ≥20 mg/kg bw/day in male rats and at ≥60 mg/kg bw/day in females rats. Hence, treatment with the high dose of 180 mg/kg bw/day had to be interrupted for 9 days after which, the animals were re-dosed at 120 mg/kg bw/day. This dose was also poorly tolerated over the remaining two treatment weeks causing again a marked reduction in food consumption and body weight. A dose of 60 mg/kg bw/day was moderately tolerated over 4 weeks treatment with mean daily food consumption and body weight distinctly lower than in controls. Primary targets of systemic toxicity were the hematopoietic system, thymolymphatic system and sexual organs. Characteristic changes in hematology parameters were decreased red blood cell counts, hematocrit, and hemoglobin concentration. White blood cell counts were also decreased due to reduced lymphocyte and granulocyte populations of each fraction. The corresponding histopathology findings were fatty atrophy of bone marrow and minimal hypocellularity of the white pulp of the spleen. Similarly, treatment with EMS caused an involution of the thymolymphatic system characterized by decreased organ weight of thymus, lymph nodes, and spleen microscopically associated with atrophy of the thymus and hypocellularity of Peyer's patches, lymph nodes and the white pulp of the spleen. The effects on sexual organs included lower organ weight/reduced size for testes, epididymides, seminal vesicles, prostate, and uterus. Tubular atrophy, single cell necrosis of the germ cells and in epididymides reduced spermatozoa were recorded microscopically. The described findings occurred at doses of 60 and 180/120 mg/kg bw/day and were dose-dependent with regard to incidence and severity. Other target organs were the pancreas (acinar cell vacuolation), thyroid gland (follicular cell hypertrophy), and salivary gland (secretory depletion of convoluted ducts). The systemic exposure to EMS was monitored by hemoglobin ethylvaline adduct measurement. The concentration of hemoglobin ethylvaline adducts was linear with the dose and accumulated 11–26-fold over the treatment period. In summary, decreases in food consumption and body weight were the dose-limiting effects of treatment with EMS. Organ toxicity was characterized by depression of cell proliferation (hematopoiesis and spermatogenesis) and changes suggestive of reduced metabolism and/or physiological imbalances (e.g. thymolymphatic system and thyroid gland) without signs of inflammatory or necrotic lesions. For some findings, especially the effects on the thymolymphatic system and sexual organs, it cannot be excluded that starvation-like condition contributed to the occurrence of such changes. The low dose of 20 mg/kg bw/day was basically free of adverse effects despite of a clear evidence for hemoglobin adducts.     

Safety assessment of methanol extract of red dragon fruit (Hylocereus polyrhizus): Acute and subchronic toxicity studies

Recently, the fruits of Hylocereus polyrhizus, known as red dragon fruit, have received much attention from growers worldwide. However, there is little toxicological information regarding the safety of repeated exposure to these fruits. The present study evaluated the potential toxicity of a methanol extract of H. polyrhizus fruit after acute and subchronic administration in rats. In the acute toxicity study, single doses of fruit extract (1250, 2500 and 5000 mg/kg) were administered to rats by oral gavage, and the rats were then monitored for 14 days. In the subchronic toxicity study, the fruit extract was administered orally to rats at doses of 1250, 2500 and 5000 mg/kg/day for 28 days. There was no mortality or signs of acute or subchronic toxicity. There was no significant difference in body weight, relative organ weight or hematological parameters in the subchronic toxicity study. Biochemical analysis showed some significant changes, including creatinine, globulin, total protein and urea levels. No abnormality of internal organs was observed between treatment and control groups. The lethal oral dose of the fruit extract is more than 5000 mg/kg and the no-observed-adverse-effect level (NOAEL) of the extract for both male and female rats is considered to be 5000 mg/kg per day for 28 days.     

Effects of the food contaminant semicarbazide following oral administration in juvenile Sprague–Dawley rats

Semicarbazide (SEM) is an azodicarbonamide by-product present in glass jar packaged foods including babyfoods, in bleaching steps and flour treatment. Experimental data showed SEM acting as osteolathyrogen agent, but few toxicological data are available in susceptible life-stages. This study aimed to evaluate effects of SEM oral administration for 28 days at 0, 40, 75, 140 mg/kg bw day during the juvenile period in Sprague–Dawley rats. Histopatological examinations of: epiphyseal cartilage – potential target of SEM lathyrogen action - testes, ovary, uterus, thyroid, thymus, spleen, adrenals, representative of the main developing organs relevant to juvenile toxicity, and neurobehavioural tests in males, were performed. Mortality at high and mid dose levels and significantly decreased body weight gain were observed in males even at the lowest dose. Lack of mineralization in cartilage at all dose levels was present. Marked alterations of spontaneous motor and exploratory behaviours were evident even at 40 mg/kg. Histological alterations were observed in all tissues; thyroid and ovary effects were present also at 40 mg/kg. The present study indicate that the NOAEL in juvenile rats is lower than 40 mg/kg for SEM oral administration. SEM administration during juvenile period exerted pleiotropic effects and further studies are suggested to elucidate mechanisms.     

Characterisation and toxicological behaviour of Basic Methacrylate Copolymer for GRAS evaluation

Basic Methacrylate Copolymer is a fully polymerised cationic copolymer with taste-masking and moisture protection properties. It is used as a pharmaceutical excipient and has potential use as a glazing/coating agent to solid food supplements. This article describes available information on the safety of the substance.Oral administration of radiolabelled copolymer to rats showed the major route of excretion to be via the faeces. Minor absorption may occur at <0.02%. Safety studies revealed no adverse toxicity following repeated administration at up to 2000 mg/kg/day in a sub-chronic study in the rat or 750 mg/kg/day in a sub-acute study in the dog. No reproductive toxicity occurred at up to 1000 mg/kg/day in the rat. The substance shows no evidence of genotoxicity, has low acute toxicity and no irritation or sensitisation potential.As per the FDA approach an ADI of 20 mg/kg bw can be concluded. Daily exposure from use as a food additive is estimated as up to 11.7 mg/kg bw in adults and 13.3 mg/kg bw in children. In view of the high molecular weight of the substance, its lack of absorption and its low toxicity profile, the ADI is deemed adequate.     

Effect of carbaryl on some biochemical changes in rats: The ameliorative effect of bee pollen

In this study, 42 female Wistar albino rats, weighing between 200 and 250 g, were used and they were divided into six equal groups. Group 1 was allocated as the control group. Rats included in groups 2 and 3 were administered a water-solubilized extract of bee pollen at a dose of 50 mg/kg bw/day and 100 mg/kg bw/day, respectively. Group 4 received 225 mg/kg bw/day carbaryl. Groups 5 and 6 were given a water-solubilized extract of bee pollen at a dose of 50 mg/kg bw/day and 100 mg/kg bw/day, respectively, plus 225 mg/kg bw/day carbaryl. The indicated administrations were continued for 21 days for groups 1–6 by gavage. MDA levels and the activities of CAT, SOD and GSH-Px were analysed in blood and tissues (liver, kidney, brain and heart). At the same time, levels/activities of total protein, albumin, glucose, triglyceride, T-cholesterol, T-bilirubin, BUN, creatinine, uric acid, GGT, LDH, AST, ALT and ALP, magnesium, sodium, potassium and chloride were evaluated in serum samples. In conclusion, carbaryl was determined to cause negative changes in most of the oxidative stress markers and serum biochemical parameters investigated. These effects were observed to alleviate with the administration of bee pollen.     

Safety evaluation of steroidal saponin DT-13 isolated from the tuber of Liriope muscari (Decne.) Baily

Steroidal saponin DT-13 (25 (R, S)-ruscogenin-1-O-[β-d-glucopyranosyl - (1 → 2)] [β-d-xylopyranosyl-(1 → 3)]-β-d-fucopyranoside) is the main active component of the tube of Liriope muscari (Decne.) Baily and has been studied as a candidate drug for cancer metastasis. The objective of this study was to evaluate the safety of DT-13 systematically by genotoxicity and acute oral toxicity and subchronic 90-day oral gavage toxicity. Results of Ames test confirmed that DT-13 did not induce mutations in histidine auxotrophs Salmonella typhimurium (TA 97, TA 98, TA 100 and TA 102) both in the presence and absence of metabolic activation system at the doses of 0.05-500 μg/plate. Meanwhile, DT-13 did not induce clastogenicity at doses of 1250, 2500 and 5000 mg/kg in mouse micronucleus test. And the single oral dose of DT-13 at 5000 mg/kg did not produce mortality or significant changes in the general behavior and gross appearance of the internal organs of mice. In subchronic toxicity study, DT-13 was administrated to Sprague-Dawley rats via oral gavage at doses of 10, 60 and 360 mg/kg for 90 days. Necropsy, hematological and biochemical analysis, and histopathological examination did not reveal any remarkable and treatment related changes. In conclusion, DT-13 is of low toxicity at the tested doses.     

No toxicological effects on acute and repeated oral gavage doses of single-wall or multi-wall carbon nanotube in rats

Three female Crl:CD(SD) rats/group were dosed with single wall carbon nanotube (SWCNT) or multi wall carbon nanotube (MWCNT) four times by gavage at a total of 50 mg/kg bw or 200 mg/kg bw (four equally divided doses at one-hour intervals). Acute oral doses of SWCNT and MWCNT caused neither death nor toxicological effects, and thus the oral LD50 values for SWCNT and MWCNT were considered to be greater than 50 mg/kg bw and 200 mg/kg bw, in rats respectively. Five or ten Crl:CD(SD) rats/sex were dosed with SWCNT once daily by gavage at a dose of 0 (control), 0.125, 1.25 or 12.5 mg/kg bw/day for 28 days with a 14-day recovery period (0 and 12.5 mg/kg bw/day groups). Six or twelve Crl:CD(SD) rats/sex were dosed with MWCNT once daily by gavage at a dose of 0 (control), 0.5, 5.0 or 50 mg/kg bw/day for 28 days with a 14-day recovery period (0 and 50 mg/kg bw/day groups). Based on no toxicological effects, the no observed adverse effect levels (NOAELs) of repeated dose toxicity of SWCNT and MWCNT were considered to be 12.5 mg/kg bw/day and 50 mg/kg bw/day (the highest dose tested), respectively. It was suggested that SWCNT and MWCNT dosed by gavage reached the gastro-intestinal tract as agglomerates and were mostly excreted via feces.     

Safety evaluation of an açai-fortified fruit and berry functional juice beverage (MonaVie Active)

The safety of an açai (Euterpe oleracea Mart.) pulp enriched fruit and berry juice, MonaVie Active^®, fortified with the functional ingredient, glucosamine, was studied. The beverage was found not to be mutagenic, clastogenic, cytotoxic, or genotoxic, as determined by the bacterial reverse mutation assay, chromosomal aberration assay, mouse micronucleus assay, and mammalian cell gene mutation (L5178Y) assay. The single dose LD50 based on a 14-day acute oral toxicity study is greater than 20,000 mg/kg bw, the highest dose tested. In a repeat dose 90-day oral subchronic toxicity study by gavage, 220 animals were randomly assigned to a control group, an untreated group, or one of three experimental groups (10, 20 and 40 g/kg bw). No treatment-related significant changes in body weight, food and water consumption, ophthalmology, organ weights, urinanalysis, hematological and clinical chemistry, or gross pathology, were observed in surviving animals compared to the control groups. Three animals died midway through the observation period (male, 20 g/kg bw/day; male 40 g/kg bw/day; and, female, 10 g/kg bw/day). These animals died without preceding clinical symptoms, histopathological lesions, or evidence of injury to tissue or organs except for signs of suffocation/aspiration congestion, which was concluded to be due to problems with the gavage administration of the fluid test article, and not due to the test article itself. The NOEAL was determined to be 40 g/kg bw/day for male and female rats, which was the highest dose tested. Phylloquinone (vitamin K1) content averaged 21.7 μg/100 g, comparable to amounts found in iceberg lettuce. In conclusion, the results provide additional experimental evidence that MonaVie Active^® juice is non-toxic.     

Toxicity value for 3-monochloropropane-1,2-diol using a benchmark dose methodology

3-Monochloropropane-1,2-diol (α-chlorohydrin, 3-MCPD) is a well-known contaminant that has been detected in a wide range of foods, and that is principally generated in foods prepared by hydrochloric acid hydrolysis, such as acid-hydrolyzed vegetable protein (acid-HVP). 3-MCPD is nephrotoxic to animals at high doses and induced tumors in some organs in both sexes of rodents. NITR have recently reported on the carcinogenicity of 3-MCPD in SD rats that were exposed for 2 years to drinking water. We considered that the kidney was the main target organ for 3-MCPD in SD rats and that renal tubular hyperplasia was the most sensitive endpoint. Benchmark dose analysis of the dose–response data for renal tubular hyperplasia in male and female rats exposed to 3-MCPD in drinking water for 2 years was conducted. We applied this to the benchmark dose (BMD) methodology to yield a point of departure for developing tolerable daily intakes (TDIs). The calculated BMDs and lower-bound confidence limits (BMDLs) for the critical endpoint were estimated using the seven different models. Predicted doses associated with 10% extra risk were calculated. The smallest Akaike’s Information Criterion (AIC) was used in selecting the appropriate model. The model chosen by AIC for males was the logistic and for females it was the multistage. In summary, the predicted BMD₁₀ and BMDL₁₀ were 1.21 mg/kg bw/day and 0.87 mg/kg bw/day for the male rat incidence data, and values for female rats were 26.31 mg/kg bw/day and 19.47 mg/kg bw/day. In this study, the BMDL₁₀ of 0.87 mg/kg bw/day for male rats was suggested as the point of departure for deriving the human tolerable daily intake level of 3-MCPD.     

Developmental toxic potential of 1,3-dichloro-2-propanol in Sprague–Dawley rats

This study investigated the potential adverse effects of 1,3-dichloro-2-propanol (1,3-DCP) on pregnant dams and the embryo-fetal development after maternal exposure on gestational days (GD) 6 through 19 in Sprague–Dawley rats. The test chemical was administered to pregnant rats by gavage at dose levels of 0, 10, 30, and 90 mg/kg per day (n = 10 for each group). All dams underwent Caesarean sections on GD 20, and their fetuses were examined for morphological abnormalities. Maternal toxicity was noted at 90 mg/kg/day. Manifestations of toxicity included clinical signs of illness, lower body weight gain, decreased food intake, and increases in the weight of the adrenal glands and the liver. Developmental toxic effects including decreases in fetal body weight and increases in visceral and skeletal variations also occurred at the highest dose. At 30 mg/kg, only a minimal maternal toxicity, including a decrease in maternal food intake and an increase in the liver weight, was observed. No adverse maternal or developmental effects were observed at 10 mg/kg/day. These results revealed that a 14-day repeated oral dose of 1,3-DCP was minimally embryotoxic but not teratogenic at a maternal toxic dose (90 mg/kg/day), and was not embryotoxic at a minimally maternal toxic dose (30 mg/kg/day) in rats. Because the developmental toxicity of 1,3-DCP was observed only in the presence of maternal toxicity, it is concluded that the developmental findings observed in the present study are secondary effects to maternal toxicity. Under these experimental conditions, the no-observed-adverse-effect level of 1,3-DCP is considered to be 10 mg/kg/day for dams and 30 mg/kg/day for embryo-fetal development.     

Safety evaluation of water extracts of Toona sinensis Roemor leaf.

The purposes of this study were to evaluate the safety of water extracts of Toona sinensis Roemor leaf (TSL-1). The mutagenic properties of TSL-1 was investigated using the Ames test, and no mutagenicity was found toward all tester strains (Salmonella typhimurium TA98, TA100, TA102 and TA1535). In the acute oral toxicity study, a single limit dose of 5000 mgTSL-1/kg bw was given to male and female ICR mice, then observed for a 14-day period. In the subacute study, TSL-1 was administered as oral daily dose of 1000 mg/kg bw/day for 28 days. The results showed no acute lethal effect at a maximal tested dose of 5000 mg/kg bw TSL-1 in male and female mice. The subacute toxicity showed the oral administration of 1000 mg/kg bw for consecutive 28 days was safe in male mice. TSL-1 treated female mice showed decreases of food intake and kidney relative weight in acute oral toxicity test, and decreases of body weight gain, food intake and lung relative weight in subacute toxicity trial. However, no remarked toxic effects were found in the biochemical and histopathological parameters of TSL-1 treated female mice. These effects whether related to the major components or other ingredients in TSL-1 need to elucidate in the further studies.     

Safety evaluation of Lactobacillus pentosus strain b240

Lactobacillus pentosus has a long history of use in cooked and uncooked fermented foods. Viable and heat-killed nonviable preparations of L. pentosus strain b240 were evaluated for short term and subchronic toxicity and genotoxic potential. Dose levels were determined through acute oral toxicity tests with viable (LD₅₀ > 2500 mg/kg) and nonviable (LD₅₀ > 2000 mg/kg) b240. In the short term study, rats received 2500 mg/kg/day (∼1.7 × 10¹¹ cfu/kg/day) viable b240 for 28 days. In the subchronic study, rats received 500, 1000 or 2000 mg/kg/day (up to ∼3.0 × 10¹² cfu equivalents/kg/day) nonviable b240 for 91 days followed by a 28-day recovery. No mortalities occurred. No treatment-related effects were identified for general condition, body weight, food-water consumption, ophthalmology, urinalysis, hematology, blood chemistry, organ weights, histopathology and gross pathology. Although statistically significant effects were noted for several endpoints in the short term and subchronic studies, none were related to the test materials. The NOAEL for nonviable b240 was 2000 mg/kg/day, the highest dose tested. Additionally, nonviable b240 (?5000 μg/plate) was not mutagenic in Salmonella typhimurium or Escherichia coli tester strains nor did nonviable b240 orally administered to rats at levels ? 2000 mg/kg/day for two days, induce a clastogenic response.     

Safety studies conducted on a proprietary high-purity aloe vera inner leaf fillet preparation,Qmatrix®

The aloe vera plant has a long history of safe use for oral and topical applications. This publication describes safety studies conducted on a proprietary high-purity aloe vera inner leaf fillet preparation, Qmatrix®. In a 13-week study in rats, Qmatrix® was administered via gavage at 0, 500, 1000 and 2000 mg/kg body weight (bw)/day. There were no significant changes in food or water consumption, body weight, serum biochemistry or hematology at any of the doses tested. Sporadic, significant increases were observed in some of the measured urinalysis parameters; however, these variations were not treatment-related, as most were observed only in one sex, not dose-dependent and within historical control values. Organ weights were unaffected, except for a statistically significant, though not dose-dependent, increase in absolute and relative weights of the right kidney in males at 500 and 2000 mg/kg bw/day, respectively. Histopathological analysis revealed no abnormal signs. Qmatrix® was non-mutagenic in an Ames test and a chromosomal aberration test at concentrations up to 10,000 μg/plate, and in an in vivo bone marrow micronucleus test at doses up to 5000 mg/kg bw/day. Based on these results, Qmatrix® is not genotoxic in vitro or in vivo and; has an oral NOAEL greater than 2000 mg/kg bw/day following 90 days of oral exposure.     

Propolis alleviates aluminium-induced lipid peroxidation and biochemical parameters in male rats

Aluminium is present in many manufactured foods and medicines and is also added to drinking water during purification purposes. Therefore, the present experiment was undertaken to determine the effectiveness of propolis in alleviating the toxicity of aluminium chloride (AlCl₃) on biochemical parameters, antioxidant enzymes and lipid peroxidation of male Wistar Albino rats. Animals were assigned to 1 of 4 groups: control; 34 mg AlCl₃/kg bw; 50 mg propolis/kg bw; AlCl₃ (34 mg/kg bw) plus propolis (50 mg/kg bw), respectively. Rats were orally administered their respective doses daily for 70 days. The levels of thiobarbituric acid reactive substances (TBARS) was increased, and the activities of glutathione S-transferase, superoxide dismutase, catalase and glutathione peroxidase were decreased in liver, kidney and brain of rats treated with AlCl₃. While, TBARS was decreased and the antioxidant enzymes were increased in rats treated with propolis alone. Plasma transaminases, lactate dehydrogenase, glucose, urea, creatinine, bilirubin, total lipid, cholesterol, triglyceride and LDL-c were increased, while total protein, albumin and high HDL-c were decreased due to AlCl₃ administration. The presence of propolis with AlCl₃ alleviated its toxic effects in rats treated with AlCl₃. It can be concluded that propolis has beneficial influences and could be able to antagonize AlCl₃ toxicity.