Acute oral safety study of sodium caseinate glycosylated via maillard reaction with galactose in rats.

In order to potentially use sodium caseinate (SC) glycated with galactose (Gal) in the food industry as a new functional ingredient with proved technological and biological properties, an evaluation of oral acute toxicity has been carried out. An acute safety study with SC-Gal glycoconjugates in the Wistar rat with a single oral gavage dose of 2,000 mg/kg of body weight was conducted. The SC-Gal glycoconjugates were well tolerated; no adverse effects or mortality was observed during the 2-week observation period. No abnormal signs, behavioral changes, body weight changes, or alterations in food and water consumption occurred. After this period, no changes in hematological and serum chemistry parameters, organ weights, or gross pathology or histopathology were detected. It was concluded that SC-Gal glycoconjugates obtained via the Maillard reaction were well tolerated in rats at an acute oral dose of 2,000 mg/kg of body weight. The SC-Gal glycoconjugates have a low order of acute toxicity, and the oral 50 % lethal dose for male and female rats is in excess of 2,000 mg/kg of body weight.

Acute and repeated dose (28 days) oral safety studies of ALIBIRD in rats.

ALIBIRD, a test substance composed of oligosaccharides derived from lactulose, a hydrolysate of a whey protein concentrate, and a supercritical extract of rosemary (1:0.5:0.05), was prepared in the laboratory and evaluated for its safety as a multifunctional food additive. In oral toxicity studies (acute and 28 days repeated dose) using Wistar rats, ALIBIRD was administered in a single oral gavage dose of 2,000 mg/kg of body weight and resulted in no adverse events or mortality; a daily dose of 2,000 mg/kg of body weight for 28 days by gavage also resulted in no adverse effects or mortality. No abnormal clinical signs, behavioral changes, body weight changes, or changes in food and water consumption occurred in either study. There were no changes in hematological and serum chemistry values, organ weights, or gross or histological characteristics. Based on test results, it is concluded that ALIBIRD is well tolerated in rats at an acute and subchronic (28 days) dose of 2,000 mg/kg of body weight.

Plasma disposition and tissue depletion of difloxacin and its metabolite sarafloxacin in the food producing animals, chickens for fattening.

Chickens were used to investigate plasma disposition of difloxacin after single intravenous (IV) and oral dose (10 mg/kg body weight (BW)) and to study residue depletion of difloxacin and its major metabolite sarafloxacin after multiple oral doses (10 mg difloxacin/kg BW, daily for 5 days). Plasma and tissue samples were analyzed using a HPLC method. After IV and oral administration, plasma drug concentration-time curves were best described by a two-compartment open model. Mean (± SD) elimination half-lives (t(½)ß) of difloxacin were 9.53±1.00 and 12.23±1.81 h after IV and oral administration. Maximum plasma concentration was 2.34±0.50 µg/ml and interval from oral administration until maximal concentration was 1.34±0.03 h. Oral bioavailability was found to be 68.89±15.21%. Difloxacin was converted to sarafloxacin. After multiple oral dose (10mg difloxacin/kg BW, daily for 5 days), mean kidney, liver, muscle and skin + fat tissue concentrations of difloxacin and sarafloxacin ranging between 604.8±132.5 and 368.1±52.5 µg/kg and 136.4±18.3 and 10.4±1.2 µg/kg, respectively, were measured 1 day after administration of the final dose of difloxacin. A withdrawal time of 5 days was necessary to ensure that the residues of difloxacin were less than the maximal residue limits (MRL) or tolerance established by the European Union.

Acute oral safety study of dairy fat rich in trans-10 C18:1 versus vaccenic plus conjugated linoleic acid in rats.

The acute oral toxicity of a trans-10 C18:1-rich milk fat (T10, 20% of total FA), and a trans-11 C18:1+cis-9 trans-11 C18:2-rich milk fat (T11-CLA, 14% and 4.8% of total FA, respectively) was studied in rats receiving a single oral dose of 2000 mg/kg body weight (BW). T10 and T11-CLA milk fats were well tolerated; no adverse effects or mortality were observed during the 2-week observation period. Two weeks following a single oral dose of 2000 mg/kg BW of T10 and T11-CLA milk fats there were no changes in haematological and serum chemistry parameters (excepting plasma lipid) organ weights, gross pathology or histopathology. In rats treated with T10 milk fat a significant increase of triglycerides was observed. In contrast, in rats treated with T11-CLA milk fat significantly decreased triglycerides were detected. It was concluded that dairy fats rich in T10 and T11-CLA have a low order of acute toxicity, the oral lethal dose (DL50) for male and female rats are in excess of 2000 mg/kg BW. Our results suggest that the T10 milk fat treatment tended to increase triglycerides concentrations, whereas the T11-CLA milk fat treatment tended to reduce it.

Acute oral safety study of rosemary extracts in rats.

Increasing interest in rosemary plants is due to their antioxidant and health-enhancing properties. The aim of this study was to evaluate the potential acute toxicity of two supercritical fluid extracts of rosemary. An acute safety study of rosemary extracts was conducted in Wistar rats at a single oral gavage dosage of 2,000 mg/kg of body weight. Rosemary extracts were well tolerated; no adverse effects or mortality were observed during the 2-week observation period. No abnormal signs, behavioral changes, body weight changes, or change in food and water consumption occurred. Two weeks after a single oral rosemary extract dose of 2,000 mg/kg of body weight, there were no changes in hematological and serum chemistry values, organ weights, or gross or histological characteristics. Rosemary extracts appear to have low acute toxicity, and the oral lethal doses (LD50) for male and female rats are greater than 2,000 mg/kg of body weight.

5-HT loss in rat brain by type II pyrethroid insecticides.

STUDY OBJECTIVE: Type II pyrethroids are a group of insecticides largely used in agriculture and public health. The nervous system is the main target for pyrethroids in insects and mammals. One notable form of toxicity associated with over exposure has been a facial cutaneous paraesthesia and irritation-related respiration symptoms including behavioural excitation mainly observed in workers spraying pyrethroids or in occupational settings. In acutely exposed rats, type II pyrethroids produce a severe syndrome characterized by salivation and choreoathetosis. Because many of the acute functional effects of type II pyrethoids can be associated with the neurotoxic effect on 5-hydroxytryptamine (5-HT) neurones, the objective of the present study was to examine whether deltamethrin, cyfluthrin and lambda-cyhalothrin administration results in changes of 5-HT content in rat brain. Characterizing this target will help us to better understand the toxicological effects of type II pyrethroids. DESIGN: Rats were injected with either corn oil or pyrethroids (deltamethrin, 20 mg/kg per day, i.p., for 6 days; cyfluthrin, 14 mg/kg per day, i.p., for 6 days; lambda-cyhalothrin, 8 mg/kg per day, i.p., for 6 days). The frontal cortex, hippocampus, midbrain and striatum were removed at 24 hours post treatment and were analysed for content of 5-HT and 5-HIAA using a HPLC method with electrochemical detection. RESULTS: A serotonin depleting effect was produced by these type II pyrethroids. The concentration of 5-HT and its metabolite 5-HIAA decreased in the brain regions from pyrethroid treated animals. Pyrethroids accelerated the turnover of 5-HT in midbrain and striatum areas. It is concluded that pyrethroids affect serotonin neurotransmission.

Pharmacokinetic characteristics and tissue residues for marbofloxacin and its metabolite N-desmethyl-marbofloxacin in broiler chickens.

OBJECTIVES: To determine pharmacokinetic characteristics of marbofloxacin after a single IV and oral administration and tissue residues after serial daily oral administration in chickens. ANIMALS: 40 healthy broiler chickens. PROCEDURE: Two groups of chickens (groups A and B; 8 chickens/group) were administered a single IV and oral administration of marbofloxacin (2 mg/kg). Chickens of group C (n = 24) were given serial daily doses of marbofloxacin (2 mg/kg, PO, q 24 h for 3 days). Plasma (groups A and B) and tissue concentrations (group C) of marbofloxacin and its major metabolite N-desmethyl-marbofloxacin were determined by use of high-performance liquid chromatography. Residues of marbofloxacin and N-desmethylmarbofloxacin were measured in target tissues. RESULTS: Elimination half-life and mean residence time of marbofloxacin in plasma were 5.26 and 4.36 hours after IV administration and 8.69 and 8.55 hours after oral administration, respectively. Maximal plasma concentration was 1.05 microg/ml, and interval from oral administration until maximum concentration was 1.48 hours. Oral bioavailability of marbofloxacin was 56.82%. High concentrations of marbofloxacin and N-desmethyl-marbofloxacin were found in the kidneys, liver, muscles, and skin plus fat 24 hours after the final dose of marbofloxacin; however, marbofloxacin and N-desmethyl-marbofloxacin were detected in only hepatic (27.6 and 98.7 microg/kg, respectively) and renal (39.7 and 69.1 microg/kg, respectively) tissues 72 hours after termination of marbofloxacin treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Analysis of pharmacokinetic data obtained in this study reveals that a minimal therapeutic dose of 2 mg/kg, PO, every 24 hours should be appropriate for control of most infections in chickens.