Subchronic Oral Toxicity Evaluation of Lanthanum： A 90-day, Repeated Dose Study in Rats

Objective The present study was undertaken to evaluate the subchronic toxicity of lanthanum and to determine the no observed adverse effect level（NOAEL）,which is a critical factor in the establishment of an acceptable dietary intake（ADI）.Methods In accordance with the Organization for Economic Co-operation and Development（OECD） testing guidelines,lanthanum nitrate was administered once daily by gavage to Sprague-Dawley（SD） rats at dose levels of 0,1.5,6.0,24.0,and 144.0 mg/kg body weight（BW） per day for 90 days,followed by a recovery period of 4 weeks in the 144.0 mg/kg BW per day and normal control groups.Outcome parameters were mortality,clinical symptoms,body and organ weights,serum chemistry,and food consumption,as well as ophthalmic,urinary,hematologic,and histopathologic indicators.The benchmark dose（BMD） approach was applied to estimate a point of departure for the hazard risk assessment of lanthanum.Results Significant decreases were found in the 144.0 mg/kg BW group in the growth index,including body weight,organ weights,and food consumption.This study suggests that the NOAEL of lanthanum nitrate is 24.0 mg/kg BW per day.Importantly,the 95% lower confidence value of the benchmark dose（BMDL） was estimated as 9.4 mg/kg BW per day in females and 19.3 mg/kg BW per day in males.Conclusion The present subchronic oral exposure toxicity study may provide scientific data for the risk assessment of lanthanum and other rare earth elements（REEs）.

Subchronic Oral Toxicity Evaluation of Sodium Dehydroacetate: A 90-day Repeated Dose Study in Rats

Objective The present study was undertaken to evaluate the subchronic oral toxicity of sodium dehydroacetate(DHA-Na)and to determine the point of departure(POD),which is a critical factor in the establishment of an acceptable dietary intake.Methods DHA-Na was administered once daily by gavage to Sprague–Dawley rats at dose levels of 0.0,31.0,62.0,and 124.0 mg/kg BW per day for 90 days,followed by a recovery period of 4 weeks in the control and 124.0 mg/kg BW per day groups.The outcome parameters were mortality,clinical observations,body weights,food consumption,hematology and clinical biochemistry,endocrine hormone levels,and ophthalmic,urinary,and histopathologic indicators.The benchmark dose(BMD)approach was applied to estimate the POD.Results Significant decreases were found in the 62.0 and 124.0 mg/kg BW groups in terms of the body weight and food utilization rate,whereas a significant increase was found in the thyroid stimulating hormone levels of the 124.0 mg/kg BW group.Importantly,the 95%lower confidence limit on the BMD of 51.7 mg/kg BW was modeled for a reduction in body weight.Conclusion The repeated-dose study indicated the slight systemic toxicity of DHA-Na at certain levels(62.0 and 124.0 mg/kg BW)after a 90-day oral exposure.

Pharmacokinetics of metadoxine for injection after repeated doses in healthy volunteers

Alcohol-induced liver disease is one of the main .epidemic problems nowadays. Metadoxine is apyridoxine-pyrrolidone carboxylate with significant scavenging property. Metadoxine is able to accelerate the elimination of alcohol from the blood and tissues, help restore the functional structure of the liver and relieve neuro-psychological disorders associated with alcohol intoxication.The purpose of the study was to assay the pharmacokinetics of domestic metadoxine after repeated doses.

Safety Evaluation of the Dichloromethane Extract of Hysterionica pinifolia: A Potential Raw Material for the Development of Biopesticides

At the moment, there is a growing concern about the negative effects on human health and the environment due to the widespread and indiscriminate use of conventional insecticides. Since plants have been used throughout history to control microorganisms and insects, the safety is an aspect that must also be evaluated to guarantee that its use does not affect human health and the environment. The aim of the present study was to evaluate the safety of the dichloromethane extract of Hysterionica pinifolia, species with insecticidal activity, to be employed as a raw material for the development of biopesticides. The acute and subacute toxicity and the dermal and ocular irritation were evaluated. In these studies, the dichloromethane extract of H. pinifolia showed no ocular and a slight dermal irritation. Oral acute toxicity was greater than 2000 mg/Kg and less than 5000 mg/Kg (slightly hazardous) and no signs of toxicity were observed at repeated doses of 100 mg/kg body weight. These promising results showed that Hysterionica pinifolia could be considered as a potential raw material for the development of an insecticide from natural sources, safe for human health and the environment.

Toxicity of Danshen Injection in Beagle's Dogs by Repeated iv Injection

Objective To re-evaluate the potential toxicity of Danshen Injection(DI) in Beagle's dogs by repeated iv injection.Methods DI was iv given to the dogs at the doses of 0,1.6,5.4,and 16.0 g/(kg·d)(4 per sex per group) for 13weeks.During the test period,the clinical signs,mortality,body weights,food consumption,rectal temperature,ophthalmoscopy,electrocardiography,urinalysis,hematology,serum biochemistry,organ weights,gross findings,and histopathology were examined.Results Dogs iv given with DI at the doses of 0,1.6,5.4,and 16.0 g/(kg·d) for13 weeks had no drug-related changes in mortality,body weight,food consumption,temperature,electrocardiography,ophthalmoscopy,urinalysis parameters,and organ weights.The hematological parameter data showed a significant decrease in red blood cells and hemoglobin concentration in the high-dose group and a significant increase in activated partial thromboplastin time suggesting an effect on haemopoiesis.For biochemical parameters,a significant decrease in glucose and a significant increase in total bilirubin were observed in the high-dose group,and the latter was considered to be toxicologically insignificant as lack of histopathological correlate.However,the histopathological examinations of the injection site showed that DI could cause dose-dependent focal inflammation.Conclusion That the iv injection with DI into dogs at 16 g/(kg·d) for 13 weeks could cause the decreases in red blood cell parameters and glucose,as well as the lesions of the injection site.The no observed adverse effect level is5.4 g/(kg·d),which suggests that safe clinical dosing be possible.