Levels of polybrominated diphenyl ethers in house dust in Central Poland.

Polybrominated diphenyl ethers (PBDEs) are used as flame retardants in numerous products, from which they are emitted to the environment, including house dust. House dust is a source of human exposure to these compounds by ingestion. The aim of this article was to determine the levels of selected PBDEs in the house dust and indicate their potential sources of origin. PBDE congeners: BDE-47, BDE-99, BDE-153 and BDE-209, were analyzed in 129 samples. The geometric mean levels (and 95% CIs) of the aforementioned congeners amounted to 3.8 (3.1-4.7) ng/g, 4.5 (3.5-5.6) ng/g, 2.2 (2.1-2.4) ng/g and 345 (269-442) ng/g respectively. BDE-209 was the dominant congener in the majority of tested samples. We found a statistically significant correlation between the concentrations of BDE-47 and the computer operating time per day (rs - 0.18) and the living area (rs - 0.20). Statistically significant higher levels of BDE-99 were found in homes where the floor was not replaced during the last 2 years.

No association between body mass index and sperm DNA integrity.

STUDY QUESTION: Is overweight associated with impaired sperm DNA integrity? SUMMARY ANSWER: High body mass index (BMI) is not associated with impaired sperm DNA integrity as assessed by the DNA Fragmentation Index (DFI). WHAT IS KNOWN ALREADY: Previous studies, based on fewer subjects and including mainly subfertile men, have shown conflicting results regarding the influence of overweight and obesity on sperm DNA integrity. STUDY DESIGN, SIZE, DURATION: This cross-sectional study was based on semen samples from 1503 men from the general population. PARTICIPANTS/MATERIALS, SETTING, METHODS: We included two cohorts (cohort A and B) of military recruits (n = 275, n = 304, respectively), one group (cohort C) of fertile men and men without known fertility problems (n = 724), and one group (cohort D) of men between 19 and 40 years without known fertility problems (n = 200). In all cohorts, data were available on BMI, DFI as measured by the sperm chromatin structure assay (SCSA), standard semen characteristics, and potential confounders (age, abstinence time, smoking habits). The subjects were categorized according to BMI into four groups: underweight (<18.5 kg/m(2)), normal weight (18.5-24.9 kg/m(2)), overweight (25.0-29.9 kg/m(2)) and obese (≥30.0 kg/m(2)). Using a linear regression model, the inter-group differences in DFI were calculated. Furthermore with the normal-weight group as the reference, the odds ratios (ORs) for DFI > 20% and DFI > 30%, were calculated for the other groups. Calculations were made for the material as a whole and after exclusion of cohort C which included proven fertile men. MAIN RESULTS AND THE ROLE OF CHANCE: We found that normal-weight men had significantly higher DFI than overweight men, with a mean difference of 1.13% (95% CI: 1.05-1.22%); P = 0.001). Overweight men had a reduced risk of having DFI ≥ 20% and DFI ≥ 30%, compared with normal-weight men; adjusted odds ratio (OR) = 0.61 (95% CI: 0.42-0.88; P < 0.01) and adjusted OR = 0.48 (95% CI: 0.28-0.84; P < 0.01), respectively. When excluding cohort C, the statistical significance was lost. Regarding standard semen parameters, we found that obese men had a higher percentage of progressive motile spermatozoa than normal-weight men; mean difference 1.15% (95% CI: 1.02-1.30%, P < 0.05) but the significance was lost when excluding cohort C. All other standard semen parameters were unaffected by BMI. LIMITATIONS, REASONS FOR CAUTION: A main limitation might be the cross-sectional nature of the data. Furthermore our study included a significant proportion of men with proven fertility (75% of cohort C, n = 550), and could therefore be biased toward fertility. WIDER IMPLICATIONS OF THE FINDINGS: Our study indicates that overweight per se is not associated with a higher level of sperm DNA damage. STUDY FUNDING/COMPETING INTERESTS: This research has been given grants from the following: EU 5th and 7th framework program (Inuendo and Clear projects, [Contracts no. QLK4-CT-2001-00202 and FP7-ENV-2008-1-226217)]), the Swedish Research Council (Grants No. 2007-2590, 521-2004-6072 and 521-2002-3907); the Swedish Governmental Funding for Clinical Research, Skåne county council's research and development foundation, MAS Funds, University Hospital MAS Foundation in Malmö, Crafoordska Fund, Ove Tulefjords Fund, Foundation for Urological Research, Fundacion Federico SA, and Gunnar Nilssons Cancer Fund. The authors declare that there are no conflicts of interest.

Indices of methylation in sperm DNA from fertile men differ between distinct geographical regions.

STUDY QUESTION: Which are the main determinants, if any, of sperm DNA methylation levels? SUMMARY ANSWER: Geographical region resulted associated with the sperm methylation status assessed on genome-wide repetitive sequences. WHAT IS KNOWN ALREADY: DNA methylation level, assessed on repetitive sequences from peripheral blood lymphocyte, can vary with age, gender, alcohol consumption and white blood cell counts. STUDY DESIGN, SIZE, DURATION: A cross-sectional study. Individual data were collected from 269 young healthy men of proven fertility living in three geographical regions: Inuits from Greenland, Caucasians from Warsaw (Poland) and Kharkiv (Ukraine). Semen samples were collected between May 2002 and February 2004 and aliquots were immediately frozen. PARTICIPANTS/MATERIALS, SETTING, METHODS: We estimated sperm DNA global methylation level (DGML) in two ways. First DNA methylation in repetitive DNA sequences (LINE-1, Satα and Alu) was quantified by PCR pyrosequencing after bisulfite conversion and second by flow cytometry (FCM) using fluorescently labeled monoclonal antibodies anti-5-methylcytosine. We analyzed whether personal characteristics and habits, body mass index, semen quality parameters, sperm chromatin integrity, biomarkers of accessory gland function and the plasma concentration of reproductive hormones were associated with sperm DNA methylation levels in men. Associations were evaluated by analysis of variance and linear regression analyses. MAIN RESULTS AND THE ROLE OF CHANCE: The geographical location emerged as the main determinant when using the methylation level in repetitive sequences. FCM DGML results were not associated with those from repetitive sequence analysis. No other consistent associations between methylation markers and the assessed variables were identified across countries. LIMITATIONS, REASONS FOR CAUTION: The methods used are only surrogates of the actual sperm methylome and the methylation levels at individual specific loci were not explored. WIDER IMPLICATIONS OF THE FINDINGS: Sperm DGML is relatively independent from semen quality parameters and is a new candidate biomarker for epidemiological studies of the impact of environmental contaminants on male fertility. STUDY FUNDING/COMPETING INTERESTS: The study is part of the project CLEAR (Climate change, Environmental contaminants and Reproductive health) supported by the European Commission 7th framework program, contract no: FP7-ENV-2008-1-226217. No competing interest is declared.

Menstrual cycle characteristics in fertile women from Greenland, Poland and Ukraine exposed to perfluorinated chemicals: a cross-sectional study.

STUDY QUESTION: Does perfluorooctane sulfonate (PFOS) and perfluorooctanate (PFOA) exposure disrupt the menstrual cyclicity? SUMMARY ANSWER: The female reproductive system may be sensitive to PFOA exposure, with longer menstrual cycle length at higher exposure. WHAT IS KNOWN ALREADY: PFOS and PFOA are persistent man-made chemicals. Experimental animal studies suggest they are reproductive toxicants but epidemiological findings are inconsistent. STUDY DESIGN, SIZE, DURATION: A cross-sectional study including 1623 pregnant women from the INUENDO cohort enrolled during antenatal care visits between June 2002 and May 2004 in Greenland, Poland and Ukraine. PARTICIPANTS/MATERIALS, SETTING, METHODS: Information on menstrual cycle characteristics was obtained by questionnaires together with a blood sample from each pregnant woman. Serum concentrations of PFOS and PFOA were measured by liquid chromatography tandem mass spectrometry. Multiple imputations were performed to account for missing data. The association between PFOS/PFOA and menstrual cycle length (short cycle: ≤24 days, long cycle: ≥32 days) and irregularities (≥7 days in difference between cycles) was analyzed using logistic regression with tertiles of exposure. Estimates are given as adjusted odds ratios (ORs) with 95% confidence intervals (CIs). MAIN RESULTS AND THE ROLE OF CHANCE: Higher exposure levels of PFOA were associated with longer menstrual cycles in pooled estimates of all three countries. Compared with women in the lowest exposure tertile, the adjusted OR of long cycles was 1.8 (95% CI: 1.0; 3.3) among women in the highest tertile of PFOA exposure. No significant associations were observed between PFOS exposure and menstrual cycle characteristics. However, we observed a tendency toward more irregular cycles with higher exposure to PFOS [OR 1.7 (95% CI: 0.8; 3.5)]. The overall response rate was 45.3% with considerable variation between countries (91.3% in Greenland, 69.1% in Poland and 26.3% in Ukraine). LIMITATIONS, REASONS FOR CAUTION: Possible limitations in our study include varying participation rates across countries; a selected study group overrepresenting the most fertile part of the population; retrospective information on menstrual cycle characteristics; the determination of cut-points for all three outcome variables; and lacking information on some determinants of menstrual cycle characteristics, such as stress, physical activity, chronic diseases and gynecological disorders, thus confounding cannot be excluded. WIDER IMPLICATIONS OF THE FINDINGS: The generalizability of the study results is restricted to fertile women who manage to conceive and women who do not use oral contraceptives when getting pregnant or within 2 months before getting pregnant. To our knowledge only one previous epidemiological study has addressed the possible association between perfluorinated chemical exposure and menstrual disturbances. Though pointing toward different disturbances in cyclicity, both studies suggest that exposure to PFOA may affect the female reproductive function. This study contributes to the limited knowledge on effects of exposure to PFOA and PFOS on female reproductive function and suggests that the female reproductive system may be affected by environmental exposure to PFOA. STUDY FUNDING/COMPETING INTEREST(S): Supported by a scholarship from Aarhus University Research Foundation. The collection of questionnaire data and blood samples was part of the INUENDO project supported by The European Commission (Contract no. QLK4-CT-2001-00 202), www.inuendo.dk. The Ukrainian part of the study was possible by a grant from INTAS (project 012 2205). Determination of PFOA and PFOS in serum was part of the CLEAR study (www.inuendo.dk/clear) supported by the European Commission's 7th Framework Program (FP7-ENV-2008-1-226217). No conflict of interest declared.

Exposure to perfluorinated compounds and human semen quality in Arctic and European populations.

BACKGROUND: Perfluorinated compounds (PFCs) have been suspected to adversely affect human reproductive health. The aim of this study was to investigate the associations between PFC exposure and male semen quality. METHODS: PFCs were measured in serum from 588 partners of pregnant women from Greenland, Poland and Ukraine who provided a semen sample, using liquid chromatography tandem mass spectrometry. Perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS) and perfluorononanoic acid (PFNA) could be detected in >97% of the samples. The associations between levels of these compounds and semen volume, sperm concentration, total sperm count, motility and morphology were assessed. RESULTS: Across countries, sperm concentration, total sperm count and semen volume were not consistently associated with PFOS, PFOA, PFHxS or PFNA levels. The proportion of morphologically normal cells was 35% lower [95% confidence interval (CI): 4-66%) for the third tertile of PFOS exposure as compared with the first. A similar reduction was found in relation to increasing PFHxS levels. At the third PFOA exposure tertile, the percentage of motile spermatozoa was 19% (95% CI: 1 to 39%) higher than in the first. CONCLUSIONS: The most robust finding in the present study was the negative associations between PFOS exposure and sperm morphology suggesting adverse effects of PFOS on semen quality, possibly due to interference with the endocrine activity or sperm membrane function. It cannot be excluded that this association and the positive association between PFOA and semen motility, which was not consistent across countries, might represent a chance finding due to the multiple statistical tests being performed.

Early hepatic changes in rats induced by permethrin in comparison with DDT.

In this study permethrin [(3-phenoxyphenyl)-methyl-3-(2,2-dichloroethenyl)-2,2-dim ethylcyclopropanecarboxylate] and DDT [1,1-(2,2,2 trichloroethylidene)-bis-(4-chlorobenzene)] were compared in rats for their effects on early hepatic changes, proposed in the literature to be useful endpoints in screening for non-genotoxic hepatocarcinogenesis and/or liver tumour promotion. We compared the effects of both insecticides on the following endpoints: hepatomegaly, mitogenesis (DNA synthesis, mitotic activity, percentage of binuclear cells) and liver pathology. Male Wistar rats received permethrin (PERM) or DDT in one, three, five and 14 daily oral doses (at 24-h intervals) equivalent to 1/10 LD50. Distinct differences in early liver response between PERM and DDT were observed. DDT stimulated the early effect consisting of hepatomegaly accompanied by an increase in hepatocellular proliferation with signs of cell necrosis. Thus, it might be concluded, that the mitogenic effect of DDT was at least partly related to a regenerative liver response. Although PERM significantly affected DNA synthesis and increased binuclear hepatocytes, this compound did not increase the number of mitotic figures. These results suggest that PERM may inhibit of phase G2 in the cell cycle and consequently it may suppress the cell entering into the stage of mitosis (M-phase). In addition, the present findings provide evidence for the occurrence of abnormal mitoses in the hepatocytes of rats treated with DDT.

Studies of early hepatocellular proliferation and peroxisomal proliferation in Wistar rats treated with herbicide diclofop.

A study was performed to determine whether diclofop (2-(4-(2,4-dichlorophenoxy) phenoxy)propionic acid), introduced as a herbicide, exhibits the properties of peroxisome proliferators (PPs). Diclofop was administered orally at 7-56 mg/kg body weight per day to male Wistar rats for 2, 4, 7 or 14 consecutive days and some effects regarded as early hepatic markers of PPs were studied. The early changes in rat liver, produced by short-term treatment with diclofop consisted of mitogenesis and, time- and dose-related increase in liver weight. Hepatomegaly was typically associated with proliferation of smooth endoplasmic reticulum (SER) and peroxisomes. The parallel biochemical measurements showed that there was a dose-dependent increase in peroxisomal palmitoyl-CoA oxidation and catalase activity in treated rats. Markers of hepatocellular proliferation (S- and M-phase) indicated that mitogenesis was transient and declined despite continuation of diclofop treatment. The threshold exposure level for the palmitoyl-CoA oxidation (one of the peroxisome proliferation markers) was approximately the same (14 mg/kg body weightxper day) as for the stimulation of mitogenesis in Wistar rats. However, for hepatomegaly and catalase activity the threshold exposure level was 7 mg/kg body weightxper day. The results presented here demonstrate clearly that diclofop belongs to a class of rodent PPs.

The effect of organic chlorine compounds and their metabolites present in human milk on newborn mice.

The effect of pesticides and their metabolites (DDE, DDT, DDD, alpha, beta and gamma-HCH and PCBs) isolated from human milk on the blood and liver morphology of the mouse were studied. Mouse neonates were fed an extract of the organochlorine compounds in linseed oil for a period of 6 weeks. The lowest dose used in the experiment equalled that which a human infant can receive with its mother's milk, calculated per gram of body weight. Doses 10 and 100 times higher were also used. At the end of the experiment, tissue samples for electron microscopy and blood samples for haemotological examination were taken. Haematological examinations, in mice receiving pesticides, revealed a significant rise in the number of Heinz bodies in erythrocytes and an increased number of lymphocytes. These changes were related to the concentrations of the organic chlorine compounds that the animals were given. Electronmicroscopy demonstrated that organochlorine pesticides at doses equal to that might be received by infants caused proliferation of the smooth endoplasmic reticulum in hepatocytes without any clear damage to other subcellular structures. Doses 10 and 100 times higher resulted in more extensive proliferation of the smooth endoplasmic reticulum, reduction of the rough elements of the endoplasmic reticulum and damage to mitochondria. The latest changes were associated with an increased number of prominent Kupffer cells and the appearance of immigratory cells with traits characteristic of lymphocytes and monocytes.

Relationship between two consecutive lactations and fat level in persistent organochlorine compound concentrations in human breast milk.

An attempt was made to understand how consecutive deliveries and the following lactations have an impact on the organochlorine compound levels detected in human milk. The other goal of the study was to check for a possible dependence between fat content and the levels of the studied compounds in milk samples from the same lactations. 199 milk samples were examined for the presence of p,p'-DDT, p,p'-DDE, p,p'-DDD, alpha-, beta-, gamma-HCH and sigmaPCBs. Moreover, in 87 milk samples the fat content was additionally determined. This study has indicated that, for the mother with a shorter interval between lactations, mean concentrations of the examined compounds were higher in the milk of the first lactation than that of the second. For the other donor whose second lactation began after 2 years, the mean levels of HCB, beta-HCH, p,p'-DDD, and PCBs in her milk were higher during the first lactation. At the same time, the concentrations of p,p'-DDT and p,p'-DDE after the second delivery were slightly higher. The correlation coefficients between the two data sets (fat content in milk, concentrations of the compounds studied in milk) showed no interrelationship between them.

[Genetically modified organisms (GMO): toxicological aspects]. / Organizmy modyfikowane genetycznie (GMO)--aspekty toksykologiczne.

The genetically modified organisms (GMO) are one of the major public concerns partially due to the activity of the non-governmental organizations which believe that public opinion must be duly informed on what leaves the laboratories and enters the environment or is proposed as food. This article discusses some major toxicological and nutritional aspects of GMO designed as food for humans. The range of current use of GMOs, potential hazards for humans, safety assessment, allergenic concerns, and some aspects of the use of marker genes are discussed in regard to human safety. The need for relevant regulations is stressed.

[The influence of DDT analogues (nuarimol and fenarimol) on the frequency of occurrence of micronuclei in erythrocytes of bone marrow and spleen in mice]. / Wplyw analogów DDT (nuarimolu i fenarimolu) na czestosc wystepowania mikorojader w erytrocytach szpiku kostnego i sledziony myszy.

The clastogenic potential of the two DDT analogues: fenarimol and nuarimol was investigated, and the usefulness of the mouse spleen cells for this purpose was evaluated. Nuarimol and fenarimol were administered per o to 8-10 weeks old male mice (Swiss) according to the following protocol: nuarimol 100 and 200 mg/kg b.w. and fenarimol 50 and 100 mg/kg b.w. twice during 24 hours. Mitomycin C (2 and 4 mg/kg b.w.) and cyclophosphamide (25 and 75 mg/kg b.w.) were administered to the positive control mice. After 30, 48, 72 hours following the first administration the animals were killed and the number of micronuclei were calculated in spleen and bone marrow polychromatic and normochromatic erythrocytes. The results show that the spleen could be regarded as an appropriate tissue for the evaluation of micronuclei induction. Fenarimol and nuarimol did not cause micronuclei induction in the bone marrow and spleen erythrocytes.

[Content of mercury in human hair of Warsaw residents exposed occupationally and non-occupationally]. / Zawartosc rteci we wlosach mieszkanców Warszawy narazonych i nienarazonych zawodowo.

The concentrations of mercury in the hair of workers employed in the fluorescent tubes plant in Warsaw were determined and compared with the results obtained in our previous studies in the years 1970/1980. Total mercury in the hair was analysed by means of flameless atomic absorption spectrometry. The average mercury concentrations in the non-exposed population was at a similar level (0.17 microgram/g) as in the results obtained in 1970/80. The average concentrations of total mercury in the hair of exposed subjects were approximately 30 times lower than in the years 1970/80 and ranged from 0.38 to 1.42 micrograms/g. This substantial reduction in Hg concentration in the hair of exposed people was due to improvements in the technological process.

[Abiotic and biotic transformation of persistent organochlorine compounds in the environment]. / Abiotyczne i biotyczne przemiany persystentnych zwiazków chloroorganicznych w srodowisku.

The presence of persistent organochlorine compounds in the environment is defined as being of anthropogenic origin. They are the result of intentional production (pesticides, solvents, dielectric and hydraulic fluids, flame retardants etc.) as well as they are produced as unintentional by-products from many processes (incineration, pulp and paper production, use and production of chlorinated aromatic chemicals and PVC). Nowadays, they are recognized as one of the major classes of the contaminants in the environment because of their wide distribution and a high capacity to bioaccumulate in organisms--especially in higher levels of the trophic food chain. They have been also claimed to cause adverse effects on organisms and human. In the paper, the main classes of chlorinated hydrocarbons are presented, including pesticides, polychlorinated biphenyls and dioxins. The proposed degradative pathways--abiotic (photolysis, hydrolysis) as well as biotic (biotransformation by microorganisms and higher organisms, including human) are reviewed on the basis of current literature.

[Biological and environmental monitoring of exposure to chlorinated aromatic hydrocarbons]. / Monitoring biologiczny i srodowiskowy narazenia na chlorowane weglowodory aromatyczne.

Polychlorinated hydrocarbons due to their lipophilic properties can cumulate in animal organisms by entering of various food chains. Food, especially of animal origin, is regarded as a major source of these compounds for man. For several years the Department of Environmental Toxicology of the National Institute of Hygiene jointly with sanitary epidemiological stations perform the monitoring of organochlorine compounds in food, including infant formula and breast milk. The results of this monitoring are presented in this paper. In order to assess the environmental exposure of man to organochlorine insecticides (DDT and HCH) and other contaminants i.e. PCBs and HCB were chosen. Samples were taken in 18 voivodships in Poland. The results show that the exposure to above compounds from food of plant origin is negligible, and that the food of animal origin is the predominant source of intake of these compounds. The results of biological monitoring show that infants fed with breast milk are of greatest risk.

[An attempt of health risk assessment for environmental exposure to chlorinated aromatic hydrocarbons]. / Próba oceny ryzyka zdrowotnego w warunkach srodowiskowego narazenia na chlorowane weglowodory aromatyczne.

An attempt has been made to assess the exposure of adult humans and infants to chlorinated hydrocarbons from food. Basing on the results from monitoring performed by the sanitary epidemiological stations in Poland the average concentrations of DDT, HCH, HCB and PCBs in variety of foods items were calculated. These average values were used as a base for the estimation of daily intake of polychlorinated hydrocarbons. For this purpose the average consumption of various groups of foods, including breast milk, were taken into consideration. The Estimated Daily Intakes (EDI) of the compounds were compared with the corresponding ADI values.

[Changes in activity of G-6-pase, APase, and gamma-GTPase in liver and blood serum of rats exposed to nuarimol and NDEA]. / Zmiany aktywnosci G-6-Pazy, Apazy i gamma-GTPazy w watrobie i surowicy krwi szczurów narazonych na nuarimaol i NDEA.

The effect of simultaneous administration of N-diethylnitrosamine (NDEA) and Nuarimol on the activity of gamma-GTPase, G-6-Pase ans APase in the liver and serum of Wistar rats was investigated in the 2-weeks experiment. The two-stage hepato-cancerogenesis model was used with NDEA as initiating agent. The possible promoting potential of Nuarimol (DDT analogue) was checked in this experiment. gamma-GTPase and G-6-Pase activities were measured by biochemical and histochemical methods and AP-ase activity was measured by a biochemical method only. The occurrence of gamma-GTPase positive foci found by histochemical methods was partly confirmed by colorimetric methods. This suggest the need for further examination of this enzyme in conditions of prolonged exposure to Nuarimol.

[Residues of organochlorine insecticides in foods in the years 1986-1990]. / Pozostalosci insektycydów chloroorganicznych w zywnosci w latach 1986-1990.

During 1986-1990 4625 samples of food commodities were examined for residues of organochlorine (OC) insecticides in 10 provinces in Poland. This monitoring included analysis of total DDT (DDT+DDE+DDD), alpha, beta and gamma-HCH, HCB and Methoxychlor (DMDT) in milk and milk products, fruits, vegetables, vegetable oils and baby foods. The median values for DDT in milk and milk products varied from undetectable to 0.23 mg/kg on fat basis, and the draft national tolerance (1.0 mg/kg) was exceeded in 2-5% of samples in 1986 only. In fruits and vegetables the median concentrations of the total DDT usually were below the limit of determination. Generally, during the five years period the downward tendency in DDT complex concentration was observed, but not in case of the total HCH. The residues of OC insecticides in baby foods were generally very low due to establishing of special "low-pesticide" areas for growing raw materials for these products.

[Comparative study of the effect of synthetic pyrethroids on the induction of genetic changes in mice somatic and sex cells depending on the exposure route]. / Porównawcze badania wplywu syntetycznych pyretroidów na indukcje zmian genetycznych w komórkach somatycznych i plciowych myszy w zaleznosci od drogi narazenia.

Synthetic pyrethroid insecticides are widely used in the protection of fruits and vegetables as well as in the public hygiene due to their strong neurotoxic activity against insects. The induction of genetic changes in somatic and sex cells in male mice after different routes of exposure to permethrin and fenvalerate was studied. The male 8-10 weeks old mice were intraperitoneally exposed to 20 and 40 mg/kg bw of fenvalerate and 125 and 250 mg/kg bw of permethrin. Another groups of mice were exposed per os to fenvalerate and permethrin in the doses of 50, 100 and 200, 400 mg/kg bw respectively. For the sperm anomalies testing the exposure was repeated for five consecutive days followed by the 35 days waiting period after which the gonads were removed and spermatozoa prepared from the epididymis. The changed spermatozoa were counted in the smears after staining in the 0.5% eosin Y solution and the results compared with the number of normal cells. For the testing of the effect of pyrethroids on the micronuclei frequency in the bone marrow cells the tested substances were administered twice in 24 hours intervals and the bone marrow was sampled after 6 and 24 hours from the femur bone. The polychromatic erythrocytes and the presence of micronuclei were evaluated in the bone marrow smears. The results showed the difference in the action of the pyrethroids on the genetic material of the tested cells and the effect of the route of exposure. Permethrin induced the lesions in the sex cells regardless the route of exposure, however a substantial increase in the micronuclei frequency in the bone marrow was observed after oral exposure only. No signs of cytotoxicity accompanied the sperm anomalies and micronuclei induction. Fenvalerate induced changes in sperm cells after intraperitoneal exposure only. No increase in the micronuclei frequency in the polychromatic erythrocytes of the bone marrow was observed after per os or intraperitoneal exposure. The intraperitoneal exposure to this pyrethroid resulted in cytotoxicity in both bone marrow and sex cells.

The effect of fenarimol on marker enzymes in rat liver in two-stages model of hepatocarcinogenesis.

The two-stage model for the development of early markers of hepatocarcinogenesis was applied to assess the potential of fungicide fenarimol (alpha-(2-chlorophenyl)-alpha-(4-chlorophenyl)-5-pirimidinemethanol++ +) as a possible promoter in this process. In this experiment the rats were subjected to partial hepatectomy (to induce proliferation), followed by the single (50 mg/kg bw) dose of diethylnitrosamine (DEN) (initiator) and then, followed by the 26 weeks exposure to fenarimol administered in the olive oil suspension (250 mg/kg daily). The activities of gamma-glutamyltransferase (GGTase), glucose-6-phosphatase (G-6-Pase) and alkaline phosphatase (APase) regarded as markers of early stages of hepatocarcinogenesis were measured biochemically and histochemically in the livers of exposed rats as well as in the respective positive and negative controls. Rats exposed to 2-acetylaminofluorene (2-AAF), instead of fenarimol, served as positive controls. It was found that in the full initiation/promotion regimen both 2-AAF and fenarimol induced the increase of GGTase activity in the liver and formation of GGTase-positive hepatocytes. However the exposure to fenarimol alone also increased GGTase activity, although this response was not observed in rats exposed to 2-AAF alone. The possible mechanisms and explanation for such types of responses were discussed, and conclusion has been drawn that fenarimol did not affect the rat hepatocarcinogenesis induced by PH and DEN.

[Induction of micronuclei in erythrocytes of bone marrow and peripheral blood in laboratory mice following acute and subchronic exposure to DDT(fenarimol and nuarimol)]. / Indukcja mikrojader w erytrocytach szpiku kostnego I krwi obwodowej myszy laboratoryjnych w warunkach ostrej lub podostrej ekspozycji na analogi DDT (fenarimol i nuarimol).

The frequency of micronuclei was assessed in polychromatic erythrocytes of bone marrow and normochromatic erythrocytes in peripheral blood of mice following exposure to fenarimol (50, 100, 200 mg/kg b.w.) and nuarimol (100, 200, 400 mg/kg b.w.) for 21 days. Mitomycin C (2 mg/kg b.w.), cyclophosphamide (25 mg/kg b.w.) and colchicyne (2 mg/kg b.w.) were administered to the positive control mice for 5 days. These results obtained in this experiment were compared with the incidence of micronuclei in bone marrow and peripheral blood in mice exposed twice (two consecutive injections, 24 hours interval) to fenarimol and nuarimol and mitomycin C, cyclophosphamide and colchicine. The results show that fenarimol and nuarimol did not cause micronuclei induction in the bone marrow and peripheral blood of mice under the conditions of these experiments. However, mitomycin C, cyclophosphamide and colchicine induced of micronuclei in the investigated tissues. Moreover, the positive relationship between frequencies of micronuclei in normochromatic erythrocytes in peripheral blood and time of exposure was observed.