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Metal fume fever (MFF) is a work-related disease caused by the inhalation of metal particles, including zinc oxide. Chronic asthma may develop as a long-term consequence of exposure, particularly for welders and metal workers who are most at risk. In this study, we investigated the effects of ZnO fume inhalation on multiple inflammation-related cytokine- and cytokine receptor genes in mice from lung and lymph node samples, to explore the role of these in the pathogenesis of MFF. In our experiments, the animals were treated with a sub-toxic amount of ZnO fume for 4 hours a day for 3 consecutive days. Sampling occurred 3 and 12 hours post-treatment. We are the first to demonstrate that ZnO inhalation causes extremely increased levels of IL-17f gene expression at both sampling time points, in addition to increased gene expression rates of several other interleukins and cytokines, such as IL-4, IL-13, CXCL5, CSF-3, and IFN-γ. Our animal experiment provides new insights into the immunological processes of early metal fume fever development. IL-17f plays a crucial role in connecting immunological and oxidative stress events. The increased levels of IL-4 and IL-13 cytokines may explain the development of long-term allergic asthma after exposure to ZnO nanoparticles, which is well-known among welders, smelters, and metal workers.

Single and simultaneous toxic effects of glyphosate (Amega Up, 360 g L−1, 4%) and copper sulphate (0.01%) were studied in avian embryos treated either with injection directly into the air chamber or by immersion application for 30 min on day 0 of incubation. Alterations of the chicken embryos were evaluated during necropsy performed on day 19 of incubation, together with mortality, body weight and the type of developmental abnormalities. Based on the results, the injection application appeared to be more toxic than the immersion method, as it induced increased mortality and reduced the average body weight, and resulted in a higher incidence of congenital anomalies. Supposedly, a toxicodynamic interaction occurs between copper sulphate and glyphosate, which may reduce the vitality of embryos and thus decrease the number of offspring in wild birds.

Concentrations of 12 metals (As, Ba, Cd, Co, Cr, Cu, Hg, Mn, Mo, Ni, Pb and Zn) were examined in the pectoral and thigh muscle of great cormorants (Phalacrocorax carbo). The samples were collected from Central Tisza-Jászság Nature Conservation Area in Hungary. The tissue samples were analysed by inductively coupled plasma optical emission spectroscopy (ICP-OES). The aim of the study was to examine the impacts of heavy metal pollution on the water birds, determine the concentrations of the abovementioned metals in the different muscle tissues of these wetland birds, and provide the basic materials for monitoring the environmental pollution. Among the investigated elements/metals, the detected concentrations of As, Ba, Cd, Co, Cr, Mo and Ni were below the detection limit. Higher concentration of Cu, Hg, Mn and Pb was measured in the pectoral muscle compared to the thigh muscle, but only in the case of Cu and Mn were found significant differences between the tissues. In the case of the Zn concentration, the higher value was detected in the thigh muscle. There were no statistical differences between males and females in either metal concentrations.

Cd, Hg, and Pb concentrations were investigated in

The study was performed on 10 female and 10 male wild boars (Sus scrofa) after shooting during the regular hunting season to investigate the concentration of metals in the muscle and fat tissue. The concentrations of essential and non-essential elements were determined (arsenic (As), cadmium (Cd), chromium (Cr), copper (Cu), lead (Pb), manganese (Mn), mercury (Hg), and zinc (Zn)) using inductively coupled plasma optical emission spectrometry. The concentrations of As, Hg, and Cd were below the limit of detection (As, Hg: p = 0.0184). The measured concentration of Cr was 0.14 ± 0.08 mg/kg and 0.13 ± 0.06 mg/kg, and that of copper was 1.22 ± 0.14 mg/kg and 1.06 ± 0.16 mg/kg in the muscle of females and males, respectively. The same tendency was observed in the case of copper content of fat tissues (female: 0.13 ± 0.10 mg/kg; male: 0.13 ± 0.04 mg/kg; p = 0.2707). Manganese concentration of muscle was 0.45 ± 0.30 mg/kg (female) and 1.36 ± 0.96 mg/kg (male), and that of fat tissue was 0.32 ± 0.22 mg/kg (female) and 0.74 ± 0.75 mg/kg (male). The Zn was detected as 56.75 ± 7.86 mg/kg and 1.83 ± 0.76 mg/kg in the muscle and fat of females and 52.12 ± 11.51 mg/kg and 1.94 ± 0.57 mg/kg in males, respectively. Based on data, the consumption of fat and muscle tissues of the wild boars tested can be food toxicologically objectionable, mainly due to the lead content, and thus pose a risk to frequent consumers of this type of game meat.

The most important welding processes used are the Gas Metal Arc (GMA) welding, the Tungsten Inert Gas (TIG) welding, and the Manual Metal Arc (MMA) welding processes. The goal of our investigation was to monitor the distribution of iron (Fe), manganese (Mn), calcium (Ca) and magnesium (Mg) in the lung, spleen, liver, and kidney of mice after inhalation exposure of different welding methods using different steel base materials. The treatment groups were the following: MMA-mild steel, MMA-molybdenum-manganese (MoMn) alloy, TIG-mild steel, and TIG-stainless steel. The samples were taken 24- and 96 hours after the treatments.Most importantly, it was found that the Mn concentration in the lung’ samples of the MMA-mild steel and the MMA-MoMn groups was increased extremely at both sampling times and in the spleen’ samples also. In the TIG groups, the rise of the Mn concentration was only considerable in the lungs and spleens at 24h, and emerged concentration was found in the liver in 96h samples. Histopathology demonstrated emerged siderin content in the spleens of the treated animals and in siderin filled macrophages in the lungs mostly in all treated groups. Traces of high-level glycogen retention was found in the MMA groups at both sampling times. Similar glycogen retention in TIG-Ms and TIG stainless group’s liver samples and emerged number of vacuoles, especially in the hepatocytes of the TIG-stainless steel 96h group were also found.The mentioned results raise the consequence that there is a considerable difference in the kinetics of the Mn distribution between the MMA- and the TIG-fume treated groups. Hence, the result suggests that manganese has a particle-size dependent toxico-kinetics property. The anomaly of the glycogen metabolism indicates the systemic effect of the welding fumes. Also, the numerous vacuoles mentioned above show a possible liver-specific adverse effect of some components of the TIG-stainless steel welding fumes.

Plastic has been an incredibly useful and indispensable material in all aspects of human life. Without it many advances in medicine, technology or industry would not have been possible. However, its easy accessibility and low cost have led to global misuse. Basically, the production of the plastics from different chemical agents is very easy but unfortunately difficult to reuse or recycle, and it is thrown away as litter, incinerated or disposed of in landfill. Plastic once in the environment begins to degrade to very small sizes. Thus, many animals mistake them for food, so plastic enters a marine, terrestrial or freshwater food web. These microplastics although chemically inert have been shown to act as tiny "bio-sponges" for harmful chemicals found in the environment changing the nature of a plastic particle from chemically harmless to potentially toxic. It was believed that microparticles would simply pass through the gastrointestinal tract of animals and humans with no biological effect. However, studies have shown that they are sometimes taken up and distributed throughout the circulatory and lymphatic system and may be stored in the fatty tissues of different organisms. The result of the uptake of them showed potential carcinogenic effects, liver dysfunction and endocrine disruption. This review focuses on micro- and nanoplastics and their way entering marine and freshwater food webs, with particular attention to microplastic trophic transfer, their toxic side effects and influence to the human consumer in health and safety in the future.

The aim of this study was to investigate the transfer of cephalexin, penicillin-G, and ampicillin & cloxacillin from cow's milk to cheese and whey. For this purpose, raw milk was artificially contaminated to different antibiotic levels and then heat-treated to prepare fresh cheese from it. Antibiotic levels of the milk, whey and cheese were measured with LC-MS/MS. The extent of heat degradation was not sufficient to remove the antibiotic residues from milk. Antibiotic concentrations in whey and fresh cheese were in good accordance with the concentration of the same compound in milk suggesting that contamination of the milk will result in contamination of the product. The investigated antibiotics were transferred less into the cheese curd (1.6-12.5% of the original amount), than into the whey (33.2-74.1%). For penicillin-G even 100% (complete removal) was experienced.

Single and simultaneous toxic effects of glyphosate (Amega Up, 360 g/L, 4%) and copper sulphate (0.01%) were studied on avian embryos treated with injection directly into the air chamber or by immersion application for 30 minutes on day 0 of incubation. Alterations of the chicken embryos were evaluated during the necropsy performed on day 19 of incubation including the mortality, the body weight, and the type of developmental abnormalities. Based on the results, the injection application was to be more toxic than the immersion method, induced increasing of mortality and decreasing of body weight, and the incidence of the congenital anomalies was more frequent. Supposedly, an additive-type toxicodynamic interaction was occurred between the copper sulphate and glyphosate that may result in reduced vitality of the embryos and thus the number of offspring of wild-life birds.

Plastic has been an incredibly useful and indispensable material in all aspects of human life. Without it many advances in medicine, technology or industry would not have been possible. However, its easy accessibility and low cost have led to global misuse. Basically, the production of the plastics from different chemical agents is very easy but unfortunately difficult to reuse or recycle, and it is thrown away as litter, incinerated or disposed of in landfill. Plastic once in the environment begins to degrade to very small sizes. Thus, many animals mistake them for food, so plastic enters a marine, terrestrial or freshwater food web. These microplastics although chemically inert have been shown to act as tiny "bio-sponges" for harmful chemicals found in the environment changing the nature of a plastic particle from chemically harmless to potentially toxic. It was believed that microparticles would simply pass through the gastrointestinal tract of animals and humans with no biological effect. However, studies have shown that they are sometimes taken up and distributed throughout the circulatory and lymphatic system and may be stored in the fatty tissues of different organisms. The result of the uptake of them showed potential carcinogenic effects, liver dysfunction and endocrine disruption. This review focuses on micro- and nanoplastics and their way entering marine and freshwater food webs, with particular attention to microplastic trophic transfer, their toxic side effects and influence to the human consumer in health and safety in the future.

The aim of this study was to determine the individual and combined toxicity of Glialka Star herbicide (glyphosate 360 g/l) and heavy metals (copper and cadmium) on the development of chicken embryos. On the first day of incubation, chicken eggs were injected by 0.1 ml of the test materials. The applied concentration of copper and cadmium sulphate was 0.01% and that of herbicide Glialka Star was 2%. The chicken embryos were examined on day 19 by the followings: rate of embryo mortality, body mass, type of developmental anomalies by macroscopic examination. The body weight was evaluated statistically by oneway ANOVA combined with Dunnett post-test, the embryo mortality and the developmental anomalies were analysed by Fisher test. Our teratogenicity study revealed that the combined administration of heavy metals (copper, cadmium) and glyphosate (K-salt) containing herbicide formulation caused significant reduction in the body weight of embryos and a significant increase in the rate of embryonic mortality and the incidence of developmental anomalies. The joint toxic effect of heavy metals and Glialka Star is an additive effect compared to the individual toxicity of the test materials.

Eye irritation potency of pesticides (fungicides, herbicides, insecticides) was comparatively tested by HET-CAM and ICE method. Based on the results of the tests the statistical analysis of agreement between classification using individual methods was done by Goodman-Kruskal's rank correlation and determination (calculation) of Cohen's kappa coefficient. Statistical analysis of agreement between classification revealed significant correlation between results of in vivo and in HET-CAM assays (76%). There was no significant correlation between result of in vivo and in ICE methods (64%). Weakest correlation was found between the data from in vitro HET-CAM and ICE tests. The percentage of agreement between two in vitro data was 48%. They may be recommended as a part of a battery of tests to reduce experimentation on mammals and to limit or eliminate pain and injury inflicted on experimental animals. The HET-CAM test is a useful tool for studying in vivo the potential conjunctival irritation, while the ICE test can be used to study corneal irritant effects in detail.

It is undeniable that with the popularity of sushi and sashimi over the last decade the consumption of raw fish has extremely increased. Raw fish is very appreciated worldwide and has become a major component of human diet because of its fine taste and nutritional properties. Possible hazards concerning fish safety and quality are classified as biological and chemical hazards. They are contaminants that often accumulate in edible tissue of fish and transmit to humans via the food chain affecting the consumer's health. Although their concentration in fish and fishery products are found at non-alarming level of a daily basis period, they induce hazardous outcome on human health due to long and continuous consumption of raw fish. Regular sushi and sashimi eaters have to be aware of the contaminants found in the other components of their dish that often add up to acceptable residue limits found in fish. Hence, there is the urge for effective analytical methods to be developed as well as stricter regulations to be put in force between countries to monitor the safety and quality of fish for the interest of public health.

Vizsgálatunk arra irányult, hogy a növényvédelemben széles körben alkalmazott tebukonazol hatóanyagú MYSTIC 250 EC gombaölő szer és egy környezetszennyező nehézfém, az ólom-acetát egyedi és együttes méreghatását tanulmányozzuk házityúk-embriókban. A toxikológiai vizsgálat során kísérleti anyagként 0,01%-os ólom-acetát oldatot, valamint a MYSTIC 250 EC (250 g/l tebukonazol) 0,1%-os, a forgalmazó által ajánlott emulzióját alkalmaztuk. A bemerítéses kezelést a keltetés megkezdése előtt, míg a tojások feldolgozását a várható kelés előtt 2 nappal, a keltetés 19. napján végeztük el. A kórbonctani vizsgálat során lemértük az embriók testtömegét, feljegyeztük az elhalások számát, továbbá rögzítettük a makroszkópos fejlődési rendellenességeket. Statisztikai értékelésnél az élő embriók testtömegeinek összehasonlításához egytényezős varianciaanalízist (One-way ANOVA), az elhalások és a fejlődési rendellenességek számának elemzéséhez Fischer-féle egzakt tesztet alkalmaztunk. A vizsgálati anyagokkal elvégzett egyedi és együttes kezelések eredményeként a kezelt csoportokban az embriók testtömeg értékei szignifikánsan kisebbek voltak a kontroll csoporthoz viszonyítva. Az egyedi és együttes kezelések következtében jelentkező embrióletalitás - a fungiciddel egyedileg kezelt csoport kivételével - szignifikánsan emelkedett a kontroll csoporthoz képest. A fejlődési rendellenességek sporadikusan fordultak elő a kezelt csoportokban, teratogén hatás nem volt igazolható. Kísérletünkben felhasznált 0,01%-os ólom-acetát oldat és MYSTIC 250 EC fungicid 0,1%-os emulziójának egyedi méreghatása toxikus volt a tojásban fejlődő házityúk-embriókra nézve. A kísérleti anyagok együttes alkalmazása során az embriótoxikus dózisú ólom-acetát mellett a növényvédelmi gyakorlatban felhasznált MYSTIC 250 EC gombaölő szeres kezelés fokozta az embriótoxicitást, a toxikus interakció additív jellegű volt.

The toxic effects of the Taifun Forte herbicide (360 g/l glyphosate isopropylamine salt) applied alone or in combination with copper sulphate were studied on chicken embryos in the early phase of embryonic development. The test materials were injected in 0.1 ml volume into the air chamber of eggs on the first day of incubation. Subsequently, on the third day of incubation permanent preparations were made from the embryo in order to study the early developmental stage. Embryos fixed on slides and stained with osmium tetroxide solution were studied under light microscope. The embryonic mortality and the developmental anomalies was analysed statistically by Fisher test. According to the result of the statistical evaluation, the embryonic mortality was not influenced by the single treatment of copper sulphate. However, Taifun Forte and its combination with heavy metal significantly increased the early embryonic mortality. Developmental abnormalities were sporadically observed due to the single administration of copper sulphate. The incidence of it was increased due to the treatment with herbicide alone and in combination with copper sulphate. Based on the results, additive toxic interaction may occur between the copper sulphate and glyphosate that can highly reduce the viability of the embryos or can lead to extinction of wild birds in serious cases.

A novenyvedő szerek a talajban szamos abiotikus es biotikus atalakulasi folya-maton mehetnek keresztul. A talajt alkoto anyagok hatasat kulonboző adalekanya-gokkal lehet modellezni. Kutatasunk soran titan-dioxidot, agyagasvanyt, humusz-anyagokat, es benzofenont – toltesatviteli komplex kialakitasara – hasznaltunk erre a celra. A kutatas celja az volt, hogy felmerje a metabenztiazuron (MBTA) terme-szetes korulmenyek kozott lehetseges bomlasi utvonalait. A herbicid molekula es a benzofenon kozott kialakult toltesatviteli komplextől azt vartuk, hogy az energia transzfer hatekonyabba tetelevel segitse a bomlast. A kiserletunk eredmenyei igazoltak ezt a varakozast, mivel a metabenztiazuron bomlasa a benzofenon jelenleteben volt a leggyorsabb. A huminsav eredő hatasa a bomlas enyhe gatlasa volt. A titan-dioxid es a montmorillonit kis mertekben novelte a metabenztiazuron fotokemiai bomlasanak sebesseget, de a titan-dioxid eseteben ez nem tekinthető jelentős hatasnak.

In the soil, pesticides undergo various abiotic and biotic transformation reactions. The effect of soil constituents can be modelled by several additives. TiO 2 , clay minerals, humic materials and other photosensitizers have been used in several studies for this purpose. The aim of this study was to assess the possible degradation pathways of methabenzthiazuron occurring within natural circumstances by means of laboratory model experiments. The additives used for this purpose were a photosensitizer (TiO 2 ), benzophenone for studying charge transfer (sensitizing) effects, and materials naturally occurring in the soils (montmorillonite, humic acid). The charge transfer complex formed between the herbicide molecule and benzophenone was expected to promote the degradation, because it increases the efficiency of energy transfer. The results of experiments supported this expectation, since the degradation methabenzthiazuron was the fastest in the presence of benzophenone. The overall effect of humic acid was moderate inhibition. Since the humic acid–herbicide ratio occurring in soils falls to the same magnitude as utilized in these experiments; presumably, this kind of effect can take place in the soil, too. TiO 2 and montmorillonite have slightly increased the rate of degradation, however, in the case of TiO 2 this effect cannot be considered significant.

The aim of our study was to investigate the concentrations of toxic metals in the feathers of predatory birds in the Hortobagyi Madarpark (Bird Hospital Foundation). Samples were collected from different predatory birds originated from the eastern and north-eastern region of Hungary. Inductively coupled plasma optical emission spectrometry was used to determine the concentration of toxic metals. The mean values varied between bird species groups, their concentrations were between 0.29 ± 0.24 and 0.40 ± 0.30 mg/kg for arsenic (As), 0.09 ± 0.03 and 0.20 ± 0.18 mg/kg for cadmium (Cd), 1.15 ± 1.40 to 2.30 ± 1.52 mg/kg for lead (Pb) and 0.58 ± 0.31 to 2.19 ± 1.25 mg/kg for mercury (Hg), respectively. The measured values are not over the considered threshold values for these toxic metals and in accordance with similar concentrations of them recorded in similar species within Europe. No significant differences were found in their concentration between genders or age in the species. According to the detected concentrations of these metals, their levels accumulated in the feather of the investigated birds do not indicate the possibility of poisoning.

Heavy-metal content (arsenic, cadmium, lead and mercury) was investigated and evaluated in shellfish, oysters and squids. The samples were collected weekly for 20 weeks from a fishery product market in Hungary. The concentration of heavy metals was measured by Inductively Coupled Plasma Optical Emission Spectrometer (ICP-OES) analysis after sample preparation. The results were analysed statistically by one-way ANOVA method. The average concentration of arsenic (3.01 ± 1.46 mg kg

The aim of the study was to determine the individual and combined toxic effects ofthe herbicide Fozát 480 (glyphosate [isopropylamine salt] 480g/l) and cadmiumsulphate (CdSO4) on the development of chicken embryos. On the first day ofincubation, chicken eggs were injected with 0.1 ml of cadmium sulphate solution(0.1%) and/or with 0.1 ml of Fozát 480 (2.0%). The chicken embryos wereexamined on the 19th day by measuring the rate of embryo mortality and bodyweight and by identification of different types of developmental anomalies andmacroscopic malformations. The body weight data were statistically evaluated byone-way ANOVA and Dunnett tests, while the embryonic mortality and thedevelopmental anomalies were analysed by Fisher test. Our teratogenicity studyrevealed, that the combined administration of cadmium sulphate and glyphosate(isopropylamine salt) containing herbicide formulation caused a significantreduction in the body weight of embryos and increased the rate of embryonicmortality. The joint toxic effect of cadmium sulphate and Fozát 480 is an additiveeffect compared to the individual toxicity of the test materials.

The study was performed on 20 (10 males, 10 females) roe deer (Capreolus capreolus) to investigate the concentration of cadmium, lead, mercury, and arsenic in the muscle tissue. They reside in forest and meadow, about 50 km distance from industrial activities and traffic. Samples were taken from the musculus biceps femoris of each deer without external contamination after shooting during the regular hunting season on a hunting area close to Eger in Hungary. The determination of heavy metal contents was carried out by inductively coupled plasma optical emission spectrometry (ICP-OES). The statistical analysis was performed by statistical package for the social sciences (SPSS) version 11.0. The measured residue concentration of cadmium was below the limit of detection in the roe deer meat indicating no health risk for the consumers. The average lead concentration (0.48 ± 0.21 mg/kg wet weight) exceeded the regulated maximum limit, but its calculated weekly intake was below the provisional tolerable weekly intake (PTWI). The residue level of mercury is not regulated and the average mercury content of roe deer meat (0.87 ± 0.40 mg/kg wet weight) was about half of PTWI, but the consumption of meat with the highest detected concentrations results in higher PTWI than recommended. The measured concentration of arsenic (0.27 ± 0.20 mg/kg wet weight) in the roe deer meat may not pose any health risk for the human consumers according to the PTWI set by the World Health Organization.

Concentrations of different heavy metals (As, Cd, Cr, Cu, Hg, Pb, Zn) were examined in the contour feathers of long-eared owl (Asio otus), little owl (Athene noctua), tawny owl (Strix aluco), barn owl (Tyto alba), Eurasian sparrowhawk (Accipiter nisus), rook (Corvus frugilegus), hooded crow (Corvus cornix), carrion crow (Corvus corone), common buzzard (Buteo buteo) and barn swallow (Hirundo rustica). The samples were collected from the Hortobagyi Madarpark (Bird Hospital Foundation) in Hungary. The bird species were classified into six groups based on their nourishment. Feathers were analysed by inductively coupled plasma optical emission spectroscopy (ICP-OES). The aim of our study was to determine the concentration of the above-mentioned heavy metals in the six different groups and to compare them by the groups, to find a possible connection between the concentrations and the age of birds and to get some information about the heavy metal burden of the environment. The highest As concentration was measured in little owl (0.65 ± 0.56 mg/kg). The highest Cd, Cr and Pb concentration was found in the feathers of barn swallow (0.13 ± 0.06 mg/kg; 1.69 ± 0.44 mg/kg; 5.36 ± 1.46 mg/kg), while the highest Cu and Hg concentration (65.45 ± 17.66 mg/kg; 2.72 ± 1.08 mg/kg) in sparrowhawk feathers and the highest Zn concentration in owls (157.21 ± 57.3 mg/kg). Statistically significant difference has been determined between the juvenile and adult crows in the case of Cd (p = 0.011). The higher concentration was measured in adults (0.14 ± 0.04 mg/kg) than that in juveniles (0.08 ± 0.02 mg/kg). Based on our results, the examined area is not contaminated by these heavy metals on that level, which can cause any adverse effect or poisoning in birds, so this region is safe to wildlife.

The muscle, liver, kidney and fat samples of 20 roe deer of both sexes originating from a hunting area in central Hungary were investigated for the presence of heavy metals such as As, Cd, Hg and Pb, and their contents were evaluated for possible health risk to consumers. Both As and Hg were found at a level below the limit of detection (

Mercury and lead concentrations were measured in the livers of cormorant (Phalacrocorax carbo sinensis), an aquatic bird species living and nesting in the special, highly protected nature conservation area of Kis-Balaton, Hungary. The measurements of metal concentrations were performed by atomic absorption spectrometry using the cold vapour method for mercury and the electrothermal method for lead. Mercury concentrations in the livers were significantly higher in the adult population (4.479 ± 3.336 mg/kg dry matter, DM) than in the juvenile birds (2.682 ± 2.087 mg/kg DM), indicating an increase of bioaccumulation with age. A similar pattern was not observed for lead. There were no statistical differences between males and females either in mercury or in lead concentrations. The average levels of mercury (3.580 ± 2.906 mg/kg DM) and lead (0.746 ± 0.499 mg/kg DM) were statistically different in the liver. No correlation was found between the concentrations of the two heavy metals. Recently, the wild birds have been chronically exposed to subtoxic amounts of metals which have a tendency to accumulate especially in the soft tissues.

Agrochemicals and veterinary products must undergo numerous toxicological tests before registration. The use of animals in these studies is a controversial issue. The Draize eye irritation test is one of the most criticised methods because of the injuries inflicted on the test animals. Several in vitro methods have been used to investigate the toxicity of potential eye irritants with a view to replacing in vivo eye irritation testing. One of these alternative methods is the Hen’s Egg Test — Chorioallantoic Membrane (HET-CAM) test. In the present studies comparative screening was performed with a set of agrochemicals to establish parallel data on in vitro (HET-CAM) and in vivo (Draize) results. The examined materials were: Totril (ioxynil), Omite 57 E (propargit), Actellic 50 EC (pyrimiphos-methyl), Stomp 330 EC (pendimethalin), Mospilan 3 EC (acetamiprid), Alirox 80 EC (EPTC), Match 050 EC (lufenuron), Nonit (dioctyl sulphosuccinate sodium), Perenal (haloxyfop-R methyl ester), Pyrinex 48 EC (chlorpyrifos). These experiments showed good correlation between results obtained by the HET-CAM test and those of the Draize rabbit eye test in most cases. The present form of the HET-CAM test can be proposed as a pre-screening method for the determination of eye irritative potential, therefore the number of test animals can be reduced and/or experimental animals can be replaced.

The pharmacokinetics and the influence of food on the kinetic profile and bioavailability of doxycycline was studied after a single intravenous (i.v.) and oral dose of 10.0 mg/kg body weight in 7-week-old broiler chickens. Following i.v. administration the drug was rapidly distributed in the body with a distribution half-life of 0.21 ± 0.01 h. The elimination half-life of 6.78 ± 0.06 h was relatively long and resulted from both a low total body clearance of 0.139 ± 0.007 L/h·kg and a large volume of distribution of 1.36 ± 0.06 L/kg. After oral administration to fasted chickens, the absorption of doxycycline was quite fast and substantial as shown by the absorption half-life of 0.39 ± 0.03 h, the maximal plasma concentration of 4.47 ± 0.16 —g/mL and the time to reach the Cmax of 1.73 ± 0.06 h. The distribution and the final elimination of the drug were slower than after i.v. administration. The absolute bioavailability was 73.4 ± 2.5%. The presence of food in the intestinal tract reduced and extended the absorption (t1/2a = 1.23 ± 0.21 h; Cmax = 3.07 ± 0.23 µg/mL; tmax = 3.34 ± 0.21 h). The absolute bioavailability was reduced to 61.1% ± 4.4%.

Seven battery tests, employing a total of 1344 Hybro cockerels, were conducted in order to study the interaction between ionophorous anticoccidials and a new dihydroquinoline-type antioxidant known as duokvin. A significant, non-selective, toxic interaction was established, resulting in growth depression and improved anticoccidial efficacy against Eimeria tenella and E. mitis in these chickens. The duokvin itself showed no appreciable activity against the coccidia. The adverse effects of the interaction were eliminated, and the anticoccidial efficacy of the approved levels of ionophores was maintained, when the dietary levels of monovalent cation ionophorous monensin, salinomycin and narasin were reduced to approximately 12% in the presence of 120p.p.m. duokvin. No adverse effects on the growth of chickens appeared in the combination with maduramicin, yet the enhancement of anticoccidial activity allowed an approx. 50% reduction of this ionophore as well.

In two experiments, the compatibility of the anticoccidial combinations of monensin and duokvin, as well as that of maduramicin and duokvin, with some antimicrobials widely used in the broiler production was studied in cockerels. The monensin-duokvin combination was found to be fully compatible with erythromycin, sulphachlorpyrazine, and sulphaquinoxaline. With tiamulin, a slight interaction was observed, but it was far less severe than the toxic interaction between monensin and the diterpene antibiotic. The maduramicin-duokvin combination proved to be compatible with all of the chemotherapeutics tested, including tiamulin. The results of the studies indicate that the adverse interactions of monensin and maduramicin with certain antimicrobials can be considerably diminished or even abolished by using them in reduced doses in combination with the dihydroquinoline compound duokvin.