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At least 19 recordsLinked to original sources
PubMedDate not supplied

Acute and subacute toxicology and safety evaluation of hexahydro-1,3,5-triethyl-S-triazine.

Acute and subacute toxicology and safety evaluation was determined for hexahydro-1,3,5-triethyl-s-triazine (Vancide-TH), a bacteriostatic and fungiastatic agent proposed for industrial use by R. T. Vanderbilt and Co., Inc. Single dose oral toxicity, subacute 14 day dermal toxicity and eye irritation studies were conducted on either the rat or the rabbit. The data obtained indicate that Vancide-TH should be classified as a "toxic, corrosive and an eye-irritating" substance as defined under the "Regulations" of the Federal Hazardous Substances Act. Since the acute dermal LD50 closely approximated the acute oral LD50 in rats, this route might constitute the most serious hazard involved with V-TH and special precautions should be exercised when handling or using this substance. Because of the severe eye-irritating action, precautions should be taken to protect the eyes when handling or using the compound; the ocular damage produced may be irreversible. The "in use" concentrations (1,000 to 10,000 ppm) produced a much lesser toxocity in animals and could be without hazard if precautions are taken.

Animals↗
PubMed2026

Comprehensive In Vitro, Genomic, Microbiota, and Subacute Toxicological Safety Characterization of Lactiplantibacillus plantarum ATA-LPC98052.

BACKGROUND: Lactiplantibacillus plantarum is a widely studied probiotic species; however, probiotic characteristics and safety profiles are strain-specific, requiring independent evaluation. This study characterized Lactiplantibacillus plantarum ATA-LPC98052 as a candidate probiotic raw material. METHODS: ATA-LPC98052 was evaluated for hemolysis, acid/bile tolerance, Caco-2 adhesion, cytotoxicity, and storage stability. Subacute oral safety was assessed in Wistar rats by gavage for 28 days at 1.2 × 1011 CFU/kg/day; the study design incorporated selected principles of OECD Test Guideline 407. Clinical, hematological, biochemical, organ-weight, and macroscopic endpoints were evaluated. Fecal microbiota was analyzed by 16S rRNA sequencing; WGS was used for taxonomic confirmation and genomic safety screening. RESULTS: ATA-LPC98052 was γ-hemolytic and maintained 60% viability at pH 1.5 and 96% at pH 5.0, while viability ranged from 74% to 82% across 0.1-0.5% bile salt concentrations. Caco-2 cell viability was 99%, adhesion exceeded 90%, and the lyophilized preparation remained stable for 15 months, maintaining 9.6 log10 CFU/g. Repeated oral administration caused no mortality or consistent treatment-related toxicological pattern. Longitudinal microbiota analysis showed no significant treatment × time effects on alpha diversity or Bray-Curtis community structure, and no genus-level MaAsLin2 association was FDR-significant. WGS confirmed L. plantarum identity and no contamination; ResFinder detected no acquired antimicrobial resistance determinants meeting specified thresholds, whereas CARD/RGI identified low-identity qacJ and vanY homologs requiring cautious interpretation. CONCLUSION: ATA-LPC98052 demonstrated favorable in vitro probiotic characteristics, technological stability, gut microbiota-modulating potential, and a favorable subacute safety profile under the tested conditions; however, microbiota findings were exploratory, and phenotypic MIC testing remains warranted.

Animals↗
PubMed1979

Acute and subacute (30-day) toxicological investigations of 4-(p-chlorophenylthio) butanol (W-2719) in mice, rats and dogs.

The acute and subacute toxicity of 4-(p-chlorophenylthio) butanol (W-2719), on anti-allergy agent, was investigated in mice, rats and dogs. Acute LD50 values in the mouse (1145.0 mg/kg p.o.) and rat (greater than 1400.0 mg/kg p.o.) and maximum tolerated dose in the dog (420.0 mg/kg p.o.) were very high, indicative of a high degree of safety following a single oral dose. The subacute toxicity studies were conducted by repeated daily oral administration of the compound for 30 days. In the rat, W-2719 did not produce any significant toxicity up to a dose level of 100.0 mg/kg/day, when administered as a drug-diet admixture. A higher dose, i.e., 200.0 mg/kg/day, produced marked reductions in body weight gain, food consumption, RBC and WBC (females especially), and other hematological parameters. In the purebred beagle dog, W-2719 did not produce any significant toxicity up to a dose level of 100.0 mg/kg/day, the highest dose level tested in this species.

Animals↗
PubMed1977

[Comparative toxicity of triacetin and diethylene glycol diacetate].

The approximative lethal dose of triacetin and diethylene glycole acetate is determined after the method of Deihmann and Leblanc. Experiments are conducted on white rats to establish the acute and subacute oral, dermal and inhalatory toxicity of the two substances. Changes in weight, liver and kidneys weight coefficient, hematopoiesis and hepatic function (biochemical and pathomorphological), as well as the stimulating effect on mucosa and skin are studied. The results of the study show a weak stimulating action on mucosa and skin, and insignificant cumulation. Emphasis is laid on the functional character of changes in the values of some enzymes -- alkaline phosphatase, cytochrome oxidase, cholinesterase -- and of the pathomorphologically established parenchymatous dystrophy. Presumably, it is a matter of changes more strongly manifested in imported triacetin. The conclusion is reached that imported triacetin may be substituted for lokally produced diethylene glycoldiacetate which proves to be with a lower acute and subacute toxicity.

Animals↗
PubMed1977

[Toxicologic study on the antihypertensive agent urapidil].

The acute toxicity of 6-(3-[4-(o-methoxyphenyl)-1-piperazinyl-propylamino)-1,3-dimethyluracil (urapidil, Ebrantil) was tested in rats and mice using oral and intravenous routes. The tolerance upon repeated oral administration was tested in subacute and chronic toxicity studies lasting 3 weeks, 3, 6 and 12 months in the rat, as well as studies lasting 4 weeks and 6 months in the dog. The effect of urapidil on the reproduction in mice, rats and rabbits was also investigated. Sedation is seen in mice and rats after a single administration of urapidil, at lethal doses, tremor and convulsions appear. The same symptoms were seen in experiments with repeated oral administration in the rat (stomach tube) or in the dog (tablets) as the criterium of tolerance. In feeding studies in the rat, the decreased body weight gain was the criterium of toxicity. The no-effect dose in the rat is 42 times the therapeutic dose in man. The no-effect dose in the dog lies between 8 and 21 times the average therapeutic dose. An inhibition of the estrus cycle in the rat proved to be species-specific. In reproductin studies, significant toxic effects were seen besides functional disturbances specific to the rat. Urapidil was not teratogenic. The development and reproductive capacity of the F1-generation was not affected.

Administration, Oral↗
PubMed1977

Toxicological investigation of 2,3-dihydro-9H-isoxazolo[3,2-b]quinazolin-9-one (W-2429). Acute and subacute toxicity in mice, rats and dogs.

The acute and subactue toxicity of 2,3-dihydro-9H-isoxazolo[3,2-b]quinazolin-9-one (W-2429), a non-narcotic analgesic agent, was investigated in mice, rats and dogs. The subacute toxicity study was conducted by repeated oral administration of the compound for 30 days. Treatment with W-2429 was well tolerated by rats as well as dogs. In the dog, the only signs of toxicity observed were decreased appetite and salivation at 100 mg/kg/day. No other significant evidence of physical, chemical, gross or histopathologic change was observed.

Animals↗
PubMed1979

Toxicological and teratological studies of 2-chloro-11-(2-dimethylaminoethoxy)-dibenzo[b,f]thiepine (zotepine), a new neuroleptic drug.

Toxicological and teratological studies of 2-chloro-11-(2-dimethylaminoethoxy)dibenzo[b,f]thiepine (zotepine) were performed in mice, rats, rabbits and dogs. There was no essential difference among mice, rats, rabbits and dogs in the acute toxicity of i.v. given zotepine. The rather small variation between intravenous and oral acute toxicity suggests the good absorption of zotepine from the gastrointestinal tract. In the subacute and chronic toxicity studies in rats, significant changes attributed to the drug were impairment of growth, alveolar proliferation in the mammary gland, decrease in uterine weight and increased number of diestrous rats. These changes were dose-dependent in the animals given 16 mg/kg or higher. Incidence of tumor in the treated groups in the 12-month study was almost the same as that in the control. In the subacute and chronic toxicity studies in dogs, abnormal quietness and abnormal gait occurred. Enlarged breasts and galactorrhea also occurred in females given 16 and 64 mg/kg in the 6-month study. Apart from these changes, one dog given 64 mg/kg had reversible hepatic dysfunction. In the teratological studies, zotepine had no adverse effects on pregnant animals and their fetuses in rats and rabbits, or reproductive performance of the F1 rats.

Animals↗
PubMed1977

Toxicologic and teratologic studies of oxibendazole in ruminants and laboratory animals.

Acute toxicity of oxibendazole was assessed with single oral doses given to mice (4 to 32 g/kg of body weight), sheep (230 to 600 mg/kg), and cattle (600 mg/kg); there were no ill effects. Subacute toxicity did not occur with multiple doses given 5 days to cattle (30 to 75 mg/kg/day) and to sheep (10 to 50 mg/kg/day). Chronic effects did not occur with daily doses of 3 to 30 mg/kg given 98 days to rats and dogs. Teratogenicity of the compound was studied in mice, rats, and sheep medicated at a dose level of 30 mg of oxibendazole/kg and in cattle given 75 mg/kg on selected dates during pregnancy. Microscopically, rodent fetuses seemed normal, and on gross physical examination, lambs and calves were free of malformations and ossification variations.

Abnormalities, Drug-Induced↗
PubMed1979

An evaluation of the toxicity of cefaclor in laboratory animals.

The toxicity of cefaclor, a new orally-administered cephalosporin, was evaluated in laboratory animals given single or multiple doses of the antibiotic. The acute toxicity data for cefaclor in mice, rats, dogs and monkeys were comparable to that previously reported for cephalexin. Rats were maintained on dietary mixtures of cefaclor which provided average daily doses of approximately 230 to 950 mg/kg for 28 days in subacute toxicity tests, and 160 to 675 mg/kg for 1 year in chronic toxicity tests. Treatment-related effects in the above studies were limited to soft stool excretion and caecal dilatation in the subacute test. Effects in dogs given daily oral doses of 50 to 200 mg/kg for 30 days were limited to a transient moderate fall in haemoglobin concentration in the two males at the highest dose. Soft stool excretion and occasional episodes of emesis were observed in dogs given cefaclor for 1 year at oral doses of 100 to 400 mg/kg/day. A reversible thrombocytopenia occurred in one animal at the highest dose. Analysis of various tissue fluids taken 2 hours after the last dose revealed that the concentration of cefaclor in the synovial fluid was approximatley one-half of that in serum. The results of these studies indicate that cefaclor has a low toxic potential in the species tested.

Animals↗
PubMed1976

[Toxicological studies on ipratropiumbromide (author's transl)].

The acute, subacute and chronic toxicity of (8r)-3alpha-hydroxy-8-isopropyl-1alphaH,5alphaH-tropaniumbromide (ipratropiumbromide, Sch 1000, Atrovent) was studied on mice, rats, dogs and monkeys following oral, s.c., i.v. administration and inhalation. With toxic doses all typical symptoms of atropine or atropine derivatives were present, like mydriasis, dryness of the mucosa and meteorism with coprostasis. It was not possible to determine the LC50 of the substance due to its low toxicity.

Administration, Oral↗
PubMedDate not supplied

Antimicrobial and toxicological studies on an antiseptic based on hexachlorophene and destructive distillate of castor oil.

Bactericidal, bacteriostatic, fungistatic and toxicological evaluaton of an emulsion containing 0.25% hexachlorophene (W/V), 9.5% terpineol (V/V), 1.5% oil of terpentine (V/V), 13% ethanol (V/V), 6% castor oil distillate 1201275 degrees C (V/V) and 6% sodium salt of the residue (W/V) in aqueous medium was performed. The bactericidal concentration for Salmonella typhi was found to be 1:400 which increased to 1:350 in the presence of 5% horse serum. The bacteriostatic concentration of the emulsion varied from organism to organism. A 4% solution of the emulsione was found to be most effective against Microsporum vanbreuseghemii showing an inhibition zone of 7.2 cm and was least effective on Aspergillus niger. 1 to 8% solution of the emulsion given orally or instilled into conjunctival sacs of albino mice indicated lethal and insignificant toxic manifestations respectively but a dose equivalent to 50 mg/Kg given subcutaneously was found to produce a subacute lethal effect in guinea pigs.

Animals↗
PubMed1978

Drug residues in animal tissues and their regulatory significance--the Canadian point of view.

Today it is almost impossible to produce food of animal origin which is free from traces of drugs or chemicals. In Canada the problem of drug residues is controlled by a method of assessment of human safety which involves many factors. The toxicity of the drug in laboratory animals or, if possible, in man, is established and a no-effect dose is then estimated. These studies require oral administration of the drug and include acute, subacute, and teratogenicity studies. Depending on these results, chronic reproductive or carcinogenicity studies may be required before a no-effect dose can be estimated. Residue studies must encompass data on metabolism, pharmacokinetics, and depletion studies in edible tissues and for products such as milk and eggs. For veterinary drug residues, we must consider the target food animal with its particular metabolism, tissue disposition, and excretion patterns. The analytical method for residue detection must be acceptable and its sensitivity limits suitable for the drug and its major metabolites.

Animals↗
PubMed1975

Short-term oral and dermal toxicity of MCPA and MCPP.

The herbicieds 2-methyl-4-chlorophenoxy acetic acid (MCPA) and 2-(2-methyl-4-chlorophenoxy) propionic acid (MCPP or mecoprop) were tested for 90 days in rats. The compounds were added to the diet at levels of 0, 50, 400, and 3200 ppm. Growth, food intake, mortality, haematology, blood and liver chemistry, organ weights and histopathology were used as criteria. The main effects of both compounds were growth retardation and elevated relative kidney weights at levels of 400 ppm and more. The 50 ppm dose level can be considered as a no-toxic-effect level in the 90-day study. In subacute dermal studies in rabbits during 3 weeks the dosages were 0, 0.5, 1.0 and 2 g MCPA or MCPP per kg body weight. Therafter followed a recovery period of 2 weeks. Growth, mortality, skin reaction, haematology, organ weights (MCPP) and histopathology were recorded and determined. Both compounds caused slight to moderate erythema at all dose levels, whereas elasticity of the skin was decreased. In both experiments the skin returned to normal during the recovery period. Weight loss was observed at all dose levels. In the MCPA experiment high mortality and histopathological changes in the liver, kidneys, spleen and thymus were recorded at the two highest dose levels. The cause of this could have been either the treatment with MCPA or a dysbacteria infection which developed during the experiment. Oral and intraperitoneal acute toxicity of MCPP for the rat were found to be 1210 and 402 mg/kg, respectively. After a single oral or dermal application of MCPA to the rabbit, the compound was excreted unchanged in the urine.

Administration, Oral↗