scholarly journals TOXICOLOGICAL CHARACTERISTICS OF A VETERINARY ANTI-PARASITIC PREPARATION WITH A PROLONGED ACTION IN THE FORM OF A SOLUTION FOR INTERNAL ADMISSION

2021 ◽  
pp. 67-73
Author(s):  
Arisova
Keyword(s):  
Oral Solution ◽  
Female Rats ◽  
Hazardous Substances ◽  
Male Rats ◽  
Prolonged Action ◽  
Oral Toxicity ◽  
Subchronic Toxicity ◽  
Hazard Class ◽  
Cutaneous Toxicity ◽  
White Rats

This article presents the results of studies of the toxicological characteristics of a longacting veterinary medicinal product "Neoterica Protecto Syrup" based on moxidectin in the form of an oral solution. Acute oral toxicity was studied in white mice and white rats. As a result, the LD50 of the drug was 4300 mg/kg for male and female mice, 3500 mg/kg for male rats, and 5700 mg/kg for female rats, and on the basis of which it was established that the drug belongs to the 3rd hazard class (moderately hazardous substances) according to GOST 12.1.007-76. Acute cutaneous toxicity was investigated and the irritant effect of the drug on white rats was assessed, for the drug the 4th hazard class (low-hazard substances) was established according to GOST 12.1.007-76. The subchronic toxicity of doses of 1/10, 1/20 and 1/50 of the LD50 of the drug, established in an acute experiment, with daily use for 5 days was studied in white rats. As a result, it was found that doses of 350, 175 and 70 mg/kg with daily use in white outbred rats for 5 days are inoperative.

scholarly journals Toxicological Evaluation of the Complex Insectoacaricidal Preparation "Neoterika Protecto 12"

2018 ◽  
Vol 12 (3) ◽  
pp. 60-66
Author(s):  
E.N. Indyuhova ◽  
M.V. Arisov ◽  
G.B. Arisova ◽  
I.A. Stepanova
Keyword(s):  
Aqueous Suspension ◽  
Hazardous Substances ◽  
Laboratory Animals ◽  
Hazard Class ◽  
Toxicological Evaluation ◽  
Cutaneous Toxicity ◽  
Oral Supplementation ◽  
Subacute Toxicity ◽  
White Rats ◽  
Active Substances

The purpose of the research: toxicological evaluation of a medicinal product for veterinary use "Neoterica Protecto 12" on laboratory animals. Materials and methods. White outbred rats, mice and guinea pigs were used in the experiment. In the study of acute oral toxicity in mice and rats, acute cutaneous toxicity, subacute toxicity, irritant action of an aqueous suspension of a combination of active substances, allergenic properties of the collar «Neoterika Protecto 12» conventional methods were used. Results and discussion. The median lethal doses LD50 for oral supplementation to white mice (1070 mg/kg) and oral supplementation to white rats (3210 mg/kg) were diagnosed, which allowed to designate the preparation to the 3rd hazard class (moderately hazardous substances). In the study of acute cutaneous toxicity on white rats LD50 amounted to more than 10 000 mg/kg, therefore, according to the generally accepted hygienic classification, the preparation belongs to the 4th hazard class during cutaneous application. In the study of subacute toxicity of the medication on rats for 6 months after application of the aqueous suspension of the combination of active ingredients in doses of 1000, 500 and 200 mg/kg, no changes in general state and behavior were observed in animals. When an aqueous suspension of a combination of active substances of the collar was applied to the skin of rats, there were no signs of irritant effect, but a mild effect on the mucous membrane of the guinea pig's eyes was recorded. It was found that the preparation does not have allergic and sensitizing effects.

The Effect of Sodium Nitrite on Experimental Animals

1942 ◽  
Vol 6a (1) ◽  
pp. 63-73 ◽  
Author(s):  
H. L. A. Tarr ◽  
N. M. Carter
Keyword(s):  
Sodium Nitrite ◽  
Lethal Dose ◽  
Oral Route ◽  
Female Rats ◽  
Male Rats ◽  
Subcutaneous Route ◽  
Healthy Male ◽  
Experimental Animals ◽  
White Rats ◽  
Healthy Female

Incorporation of sodium nitrite in the diet of cats and white rats on the basis of an average sized man consuming 1 lb. (454 g.) of fish containing 0.2 per cent (908 mg.) of this salt daily for six days each week does not appear to affect their growth rate nor the development (weight) of their thyroid, heart, lungs, spleen, liver, kidneys or adrenals. The fecundity of white rats as judged by their ability to breed and raise normal litters is apparently not affected thereby. The lethal dose of sodium nitrite by oral route is about 1.1 to 2.0 g./kg. for healthy male rats, 0.46 to 1.2 g./kg. for healthy female rats and 0.073 g./kg. for cats (one animal). The lethal dose by subcutaneous route is about 0.19 to 0.20 g./kg. for healthy male rats and 0.057 to 0.13 g./kg. for healthy female rats.

Amended Final Report on the Safety Assessment of Polyacrylamide and Acrylamide Residues in Cosmetics1

2005 ◽  
Vol 24 (2_suppl) ◽  
pp. 21-50 ◽  
Keyword(s):  
Thyroid Gland ◽  
Female Rats ◽  
Male Rats ◽  
Oral Toxicity ◽  
Uterine Tumors ◽  
Cosmetic Formulations ◽  
Oral Tissue ◽  
Acrylamide Monomers ◽  
Follicular Tumors ◽  
Reproductive Study

Polyacrylamide is a polymer of controllable molecular weight formed by the polymerization of acrylamide monomers available in one of three forms: solid (powder or micro beads), aqueous solution, or inverse emulsions (in water droplets coated with surfactant and suspended in mineral oil). Residual acrylamide monomer is likely an impurity in most Polyacrylamide preparations, ranging from <1 ppm to 600 ppm. Higher levels of acrylamide monomers are present in the solid form compared to the other two forms. Polyacrylamide is reportedly used in 110 cosmetic formulations, at concentrations ranging from 0.05% to 2.8%. Residual levels of acrylamide in Poly acrylamide can range from < .01 % to 0.1 %, although representative levels were reported at 0.02% to 0.03%. Because of the large sizes of Polyacrylamide polymers, they do not penetrate the skin. Polyacrylamide itself is not significantly toxic. For example, an acute oral toxicity study of Polyacrylamide in rats reported that a single maximum oral dose of 4.0 g/kg body weight was tolerated. In subchronic oral toxicity studies, rats and dogs treated with Polyacrylamide at doses up to 464 mg/kg body weight showed no signs of toxicity. Several 2-year chronic oral toxicity studies in rats and dogs fed diets containing up to 5% Polyacrylamide had no significant adverse effects. Polyacrylamide was not an ocular irritant in animal tests. No compound-related lesions were noted in a three-generation reproductive study in which rats were fed 500 or 2000 ppm Polyacrylamide in their diet. Polyacrylamide was not carcinogenic in several chronic animal studies. Human cutaneous tolerance tests performed to evaluate the irritation of 5% (w/w) Polyacrylamide indicated that the compound was well tolerated. Acrylamide monomer residues do penetrate the skin. Acrylamide tested in a two-generation reproductive study at concentrations up to 5 mg/kg day x in drinking water, was associated with prenatal lethality at the highest dose, with evidence of parental toxicity. The no adverse effects level was close to the 0.5 mg/kg day x dose. Acrylamide tested in a National Toxicology Program (NTP) reproductive and neurotoxicity study at 3, 10, and 30 ppm produced no developmental or female reproductive toxicity. However, impaired fertility in males was observed, as well as minimal neurotoxic effects. Acrylamide neurotoxicity occurs in both the central and peripheral nervous systems, likely through microtubule disruption, which has been suggested as a possible mechanism for genotoxic effects of acrylamide in mammalian systems. Acrylamide was genotoxic in mammalian in vitro and in vivo assays. Acrylamide was a tumor initiator, but not an initiator/promoter, in two different mouse strains at a total dose of 300 mg/kg (6 doses over 2 weeks) resulting in increased lung adenomas and carcinomas without promotion. Acrylamide was tested in two chronic bioassays using rats. In one study, increased incidence of mammary gland tumors, glial cell tumors, thyroid gland follicular tumors, oral tissue tumors, uterine tumors and clitoral gland tumors were noted in female rats. In male rats, the number of tumors in the central nervous system (CNS), thyroid gland, and scrotum were increased with acrylamide exposure. In the second study, using higher doses and a larger number of female rats, glial cell tumors were not increased, nor was there an increase in mammary gland, oral tissue, clitoral gland, or uterine tumors. Tumors of the scrotum in male rats were confirmed, as were the thyroid gland follicular tumors in males and females. Taken together, there was a dose-dependent, but not statistically significant, increase in the number of astrocytomas. Different human lifetime cancer risk predictions have resulted, varying over three orders of magnitude from 2 × 10 3 to 1.9 × 120 6. In the European Union, acrylamide has been limited to 0.1 ppm for leave-on cosmetic products and 0.5 ppm for other cosmetic products. An Australian risk assessment suggested negligable health risks from acrylamide in cosmetics. The Cosmetic Ingredient Review (CIR) Expert Panel acknowledged that acrylamide is a demonstrated neurotoxin in humans and a carcinogen in animal tests, but that neurotoxic levels could not be attained by use of cosmetics. Although there are mechanisms of action of acrylamide that have been proposed for tumor types seen in rat studies that suggest they may be unique to the rat, the Panel was not convinced that these results could be disregarded as a species-specific finding with no relevance to human health and safety. Based on the genotoxicity and carcinogenicity data, the Panel does not believe that acrylamide is a genotoxic carcinogen in the usual manner and that several of the risk assessment approaches have overestimated the human cancer risk. The Panel did conclude, however, that it was appropriate to limit acrylamide levels to 5 ppm in cosmetic formulations.

scholarly journals Acute and sub-acute oral toxicity of aqueous whole leaf and green rind extracts of Aloe vera in Wistar rats

2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Florence Nalimu ◽  
Joseph Oloro ◽  
Emanuel L. Peter ◽  
Patrick Engeu Ogwang
Keyword(s):  
Toxicity Test ◽  
Wistar Rats ◽  
Leaf Extract ◽  
Aloe Vera ◽  
Female Rats ◽  
Male Rats ◽  
Aqueous Extracts ◽  
Acute Oral Toxicity ◽  
Oral Toxicity ◽  
Leaf Extracts

Abstract Background Several local communities in Central, Western, Eastern, and Northern regions of Uganda have been using the whole leaf extracts of Aloe vera (L.) Burm. f. (Asphodelaceae) in the treatment of various ailments. Also, several commercial companies sell A. vera as soft drinks in Uganda. However, there are inadequate reports on the toxicities of such preparations. This paper reports the acute and sub-acute oral toxicity of aqueous extracts of whole leaf and green rind of A. vera in Wistar rats. Methods Acute oral toxicity test was carried out in female Wistar rats at doses of 175, 550, 1750, and 5000 mg/kg, p.o. The animals were observed for signs of toxicity for 14 days. Similarly, a sub-acute oral toxicity test was performed in both sexes of rats at doses of 200, 400, and 800 mg/kg, p.o. daily for 28 days. All the groups of animals were monitored for behavioral, morphological, biochemical, and physiological changes, including mortality and compared with respective controls. Body weights were measured weekly while the animals’ relative organ weights, hematological, biochemical, gross, and microscopic pathology were examined on day 29. Results There was no mortality or apparent behavioral changes at the doses tested in acute and sub-acute oral toxicity tests. Thus, the Median Lethal Dose (LD50) of green rind and whole leaf aqueous extracts was above 5000 mg/kg. Gross anatomy revealed that the rats’ relative spleen weight in green rind extract at 200 mg/kg significantly decreased compared to the control group. The creatinine levels in female rats that received green rind extract and the chloride ion levels in male rats administered whole leaf extract were significantly elevated. Conversely, Mean Corpuscular Hemoglobin Concentration (MCHC) levels significantly decreased at lower doses of the green rind extract compared to the control. Histopathology of the kidney revealed the renal interstitium’s inflammation at doses of 200 and 800 mg/kg of the whole leaf extract. Conclusion The findings demonstrated that A. vera green rind and whole leaf extracts are non-toxic at relatively high doses when used for a short duration. Prolonged use of the aqueous whole leaf extract might be associated with kidney toxicity.

scholarly journals Determination of the cumulative and skin-resorptive action of the Zoodizin disinfectant

2020 ◽  
Vol 22 (97) ◽  
pp. 26-30
Author(s):  
O. L. Nechyporenko ◽  
A. V. Berezovskyy ◽  
T. І. Fotina ◽  
R. V. Petrov
Keyword(s):  
Skin Irritation ◽  
White Male ◽  
Cumulative Effect ◽  
Female Rats ◽  
Male Rats ◽  
White Female ◽  
Test Substance ◽  
High Concentration ◽  
White Rats ◽  
Single Effect

The rational organization and implementation of effective disinfection activities plays an important role in the complex of measures for the prevention of infections. The development and introduction of new disinfectants into production is an urgent issue of modern poultry farming. When developing a disinfectant, it is important to determine the cumulative effect of the drug. The purpose of the study was to determine the cumulative and skin-resorptive action of the disinfectant “Zoоdizin”. For the toxicological study of the drug used healthy white male rats and white female rats weighing 200 ± 10 g 1.5 years of age. To study the toxicity of the drug “Zoоdizin” when applied to the skin used the method of immersion of the tails of rats in a test tube with the test substance. The tail was injected 2/3 into a regular tube with a 5 % solution of the drug “Zoоdizin”. The tube was closed with a cork ring whose diameter was slightly larger than the tail diameter. For 15 days, the tubes were placed daily in a water bath at 28–30 °C for 2 hours. Control animals tails were immersed in distilled water. To establish the local action of the drug “Zoodizin” on the mucous membranes of the study drug was introduced into the conjunctival sac of the right eye of the rabbit at a dose of 50 mg, and in the left eye was buried saline in a volume of 0,05 cm3. When studying the cumulative effect of Zoоdizin, no significant changes in the biochemical parameters in the serum of rats were observed. In the study of possible irritant or damaging effect on the skin and the development of contact non-allergic dermatitis found that a single application of disinfectant “Zoоdizin” on the unaffected skin of the back of white rats in the maximum significant recommended concentration of working solutions (2 %) did not cause signs. The single effect of the drug on the intact areas of the skin did not cause skin irritation, but it can be stated that prolonged daily epicutaneous exposure of high concentration (5 %) of the solution of the drug “Zoоdizin”, which is 2.5 times higher than the maximum recommended concentration, caused a general resorption. When assessing the cumulative properties, it was taken into account that the total dose administered to rats was Zodizin 42000 mg/kg body weight and did not result in animal death. It did not allow to calculate the cumulative coefficients for the “lethal effect”. A single effect of the product on the intact areas of the skin did not cause skin irritation, but it can be stated that prolonged daily epicutaneous exposure of a high concentration (5 %) of the Zodizin solution, which is 2.5 times the maximum recommended concentration, caused a general resorption. In the future, it is planned to study the virulidal properties of the biocide “Zoоdizin”.

scholarly journals Toxicity assessment of a technical product of the triazole class

2020 ◽  
Vol 99 (11) ◽  
pp. 1276-1279
Author(s):  
Valery N. Rakitskii ◽  
Tatiana M. Epishina ◽  
Elena G. Chkhvirkiya
Keyword(s):  
Body Weight ◽  
The Body ◽  
Male Rats ◽  
Acute Oral Toxicity ◽  
Oral Toxicity ◽  
High Biological Activity ◽  
Experimental Animals ◽  
Technical Product ◽  
White Rats ◽  
Toxicological Studies

Introduction. Historically, pesticides are evaluated more strictly from a medical point of view than other chemicals. Since their features, such as deliberate introduction into the environment, the possibility of contact with them by large masses of the population, and the high biological activity determine their potential danger to humans. Purpose of research - study of the biological effect of a technical product derived from triazoles when it is repeatedly ingested orally in mammals (rats), establishment of inactive and active doses, justification of the permissible daily dose (DSD) for humans. Material and methods. In acute experiments, white rats were used, including 6 animals in the group. Tested dose: 500-4000 mg/kg of body weight. A chronic (12 months) experiment was performed on 80 male rats with a bodyweight of 180-190 g at the beginning of the study. Tested doses: 5.0; 16.0 and 55.0 mg/kg of body weight (1 control and 3 experimental animals, 20 individuals each). In the dynamics of the experiment, we observed the condition and behavior of animals, water, and food consumption, recorded the timing of death, changes in body weight, physiological, biochemical, and hematological indices. Results. Indices of the acute oral toxicity on the studied product LD50 male rats were 2250 ± 483 mg/kg body weight. The dose of 5.0 mg / kg of body weight was not found to cause significant changes in all studied indices. The doses of 16.0 and 55.0 mg/kg of body weight had a polytropic effect on the body in experimental animals. Discussion. The studied product for the acute oral toxicity refers to low-hazard compounds, the doses of 16.0 and 55.0 mg/kg of body weight has a polytropic effect on the mammalian body, causing changes in carbohydrate, lipid, and lipoprotein metabolism in the body of rats - was accepted as acting. The dose of 5.0 mg / kg of body weight, when administered in rats, there are no changes in all the studied parameters throughout the experiment, is accepted as invalid. Based on the inactive dose-5.0 mg/kg of body weight and taking into account the reserve factor of 100, we have scientifically justified DSD for a person at the level of 0.05 mg/kg. Summary. The conducted sanitary and Toxicological studies indicate the need to assess the toxicity of new technical products to the mammalian body, to increase the reliability of the developed hygiene standards in environmental objects and food products.

scholarly journals Pharmaco-toxicological Assessment of Antiparasitic Drug for Dogs and Cats "Gelmintal Mini Syrup"

2020 ◽  
Vol 14 (3) ◽  
pp. 90-98
Author(s):  
G. B. Arisova ◽  
M. V. Arisov ◽  
I. A. Stepanova ◽  
V. V. Khristenko
Keyword(s):  
Acute Toxicity ◽  
White Male ◽  
Male Rats ◽  
Subchronic Toxicity ◽  
Hazard Class ◽  
Toxicological Assessment ◽  
Antiparasitic Drug ◽  
And Behavior ◽  
Macroscopic Examination

The purpose of the research is conducting pharmaco-toxicological assessment of Gelmintal Mini Syrup based on a combination of moxidectin and toltrazuril. Materials and methods. The study was carried out on 64 white male rats and 40 white mice. Each animal species was divided into 4 equivalent groups of 6–10 animals each. When studying acute toxicity, the drug was administered in the form of a syrup (without dilution) to animals once at doses of 11 400, 22 800 and 28 500 mg/kg; when studying subchronic toxicity, the drug was administered daily for 14 days at doses of 570, 1425 and 2850 mg/kg (1/10 and 1/20 and 1/50 of the maximum possible dose administered into the stomach according to the vivisection results). When studying acute toxicity, the animals were followed up for 14 days; we recorded the general condition and behavior of the animals, changes in their body weight, the manifestation of toxic symptoms or possible death. When studying subchronic toxicity, the animals were followed up during the entire period of the drug use (14 days); on the 15th and 24th days of the experiment, we performed euthanasia, collected the blood to determine hematological and biochemical values, and carried out macroscopic examination of the organs. Results and discussion. We did not record the animals’ death at doses of 11 400, 22 800 and 28 500 mg/kg; and no signs of intoxication were noted for the entire follow-up period. LD50 of Gelmintal Mini Syrup exceeds the dose of 28500 mg/kg, i.e. the drug is classified as the 4th hazard class. The results of the studied subchronic toxicity showed that the drug was inactive at doses of 570 mg/kg, 1425 and 2850 mg/kg when administered orally for 14 days.

scholarly journals Acute and sub-acute toxicity of the aqueous extract of the stem bark of Rauwolfia vomitoria (Apocynaceae) in Wistar rats.

2020 ◽  
Vol 8 (3) ◽  
pp. 373-385
Author(s):  
Youmbie Djanche Duplex Bonheur ◽  
Dzeufiet Djomeni Paul Désiré ◽  
Kada Sanda Antoine ◽  
Fotsing David ◽  
Dimo Théophile
Keyword(s):  
Histological Examination ◽  
Aqueous Extract ◽  
White Blood Cells ◽  
Stem Bark ◽  
Female Rats ◽  
Male Rats ◽  
Control Group ◽  
Acute Oral Toxicity ◽  
Oral Toxicity ◽  
Liver And Kidney

The present study investigated the toxicological potential of the oral administration of the stem bark aqueous extract of R. vomitoria on the liver and kidney in rats. Acute oral toxicity study of the extract to a single dose of 2000 mg/kg was studied in 10 rats of both sexes. Sub –acute oral toxicity of aqueous extract of was carried out on 60 rats. We constituted 4 groups of 10 rats each (5 males and 5 females) which were orally administered 300, 600, and 900 mg/kg of aqueous extract and control group received water. 2 group satellites (SAT) of 10 rats each (5 males and 5 females) in which one group (SAT 900 mg/kg) was received orally 900 mg/kg of aqueous extract and another (SAT control) water. Serum blood was collected for biochemical and haematological parameters. The liver and kidney served for histological examination. No deaths of acute oral toxicity were recorded. In female rats, Aspartate Aminotransferase (ASAT) activity increased by 31.20 % and Alamine Aminotransferase (ALAT) increased by 37.20 %. In male rats, only ALAT activity increased significantly by 35.37 % compared to control. Haematological analysis revealed in male rats treated at the dose of 900 mg/kg an increase significant (p<0.001) level of white blood cells with 52.20 %, compared to control group. Histological examination of liver and kidney showed normal architecture. Aqueous extract has untoward effect on liver and kidney, could be considered non-toxic.

scholarly journals Acute Oral Toxicity of the Supramolecular Complex Based on Albendazole and Triclabendazole (Altric-Extra) in Laboratory Outbred Mice and Rats

2020 ◽  
Vol 14 (1) ◽  
pp. 64-69
Author(s):  
Ekaterina V. Lagereva ◽  
Vladislav E. Abramov
Keyword(s):  
Body Weight ◽  
Acute Toxicity ◽  
The Body ◽  
Male Rats ◽  
Laboratory Animals ◽  
Oral Toxicity ◽  
Hazard Class ◽  
Russian Research Institute ◽  
Starch Gel ◽  
Outbred Mice

The purpose of the research is to evaluate the acute toxicity of Altric-Extra when introduced into the stomach to mice and rats. Materials and methods. The studies were conducted in the vivarium of the All-Russian Research Institute of Fundamental and Applied Parasitology of Animals and Plants. The acute toxicity of Altric-Extra was determined on 20 white outbred male mice weighing 19.3–23.3 g, 10 animals in a group and on 30 white outbred male rats weighing 150–196 g, 6 animals in a group. Altric-Extra was administered to mice of the experimental group once into the stomach in the form of a suspension in a dose of 5,986 mg/kg at the rate of 0.2 ml/10 g of body weight. Altric-Extra rats were also administered once into the stomach in the form of a suspension at the rate of 2.0 ml/100 g body weight. As a carrier in the preparation of the suspension, 1% starch gel was used. The experimental rats of groups 1, 2, 3 and 4 were given Altric-Extra at doses of 4,580.2 mg/kg, 3,846.2; 3,088.8 and 1,577.9 mg/ kg respectively. Mice and rats of the control groups were administered once with 1% starch gel. For 14 days, the behavior and condition of the animals was monitored. The body weight of the experimental animals was measured on the 1st, 3rd, 7th, 9th and 14th days of the experiment. Results and discussion. Medium lethal doses of LD50 have been established for oral administration to laboratory animals. For mice, the LD50 was more than 5 986 mg/kg, i.e., according to the generally accepted hygienic classification, Altrick-Extra belongs to hazard class 4 (low-hazard substances). On rats, the LD50 was 3 103.1±48.5 mg/kg (2,354.6÷3,851.5 mg/kg). Therefore, Altrik-Extra belongs to hazard class 3 (substances are moderately hazardous).

scholarly journals Acute and 30-day oral toxicity studies of a novel coccidiostat – ethanamizuril

2019 ◽  
Vol 8 (5) ◽  
pp. 686-695 ◽  
Author(s):  
Wenlong Xiao ◽  
Xiaoyang Wang ◽  
Chunmei Wang ◽  
Mi Wang ◽  
Chenzhong Fei ◽  
...  
Keyword(s):  
Clinical Signs ◽  
Female Rats ◽  
Male Rats ◽  
Wall Thickening ◽  
High Dose ◽  
Alveolar Wall ◽  
Oral Toxicity ◽  
Male And Female Rats ◽  
Adverse Effect Level ◽  
Ld50 Value

Abstract Ethanamizuril is a novel triazine compound that exhibits remarkable anticoccidial activity. Owing to its pharmacological properties, this study was conducted to evaluate the acute and 30-day oral toxicity of ethanamizuril. In the acute study, ethanamizuril was administered once by oral gavage to mice and rats. The calculated LD50 values for mice and rats were 5776 and 4743 mg per kg b.w, respectively, but the LD50 value for male rats was higher than that of female rats. In the subchronic study, male and female rats were fed with diets supplemented with 0, 20, 60 or 120 mg kg−1 ethanamizuril for 30 days. Treatment related clinical signs of alopecia on the back and neck of the animals were observed in the 60 and 120 mg kg−1 dose groups from the third week of treatment. Significant differences in haematological and biochemical parameters as well as organ-to-body weight ratios were detected between the 60 and 120 mg kg−1 groups. Histopathological observations revealed that 60 and 120 mg kg−1 ethanamizuril could induce focal hepatocellular necrosis and split phase. Slight renal tubule protein casts in the kidneys and alveolar wall thickening in the lungs were also observed in the high dose groups of both genders. The dietary no-observed-adverse-effect level (NOAEL) of ethanamizuril for 30 days was 20 mg kg−1 feed.

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