Hypomethylation of the c-myc promoter region induced by phenobarbital in rat liver

Background: The changes in DNA methylation are considered as one of the early events in hepatocarcinogenesis. Objective: We evaluated the ability of phenobarbital (PB) ­ the most widely used anticonvulsant worldwide and classical rodent liver carcinogen ­ to cause the promoter region of the c-myc protooncogene hypomethylation as well as changes of mRNA level of this gene. Moreover, the expression of Dnmt1 protein in rat treated with this compound was analyzed. Material and Methods: Male Wistar rats received PB in daily oral doses of 92.8 mg kg-1 b.w. day-1 (at 24-h intervals; for one, three and fourteen days). Methylation of the c-myc promoter region was measured by PCR-based methylationsensitive restriction enzyme analysis (MSRA). Levels of mRNA for c-myc and protein Dnmt1 were assayed using Real-Time PCR and Western Blot, respectively. Results: The study showed that phenobarbital stimulated persistent changes in DNA methylation, i.e. loss of methylation in the promoter region of the c-myc gene and up-regulated its mRNA level. In addition, a significant increase in protein level of Dnmt1 in the c-myc over-expressing liver cells was observed. Conclusion: The oppose relationship between Dnmt1 activity and methylation status of c-myc gene was demonstrated. The c-myc over-expression by demethylation might represent an important, early events in the mechanism of action (MOA) of phenobarbital.

Validation of the analytical method for the simultaneous determination of selected polybrominated diphenyl ethers, polychlorinated biphenyls and organochlorine pesticides in human blood serum by gas chromatography with microelectron capture detector.

BACKGROUND: Polybrominated diphenyl ethers (PBDEs) as other persistent organic pollutants like polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) pose a significant hazard to human health, mainly due to interference with the endocrine system and carcinogenetic effects. Humans are exposed to these substances mainly through a food of animal origin. These pollutants are globally detected in human matrices which requires to dispose reliable and simple analytical method that would enable further studies to assess the exposure of specific human populations to these compounds. OBJECTIVE: The purpose of this study was to modify and validate of the analytical procedure for the simultaneous determination of selected PBDEs, PCBs and OCPs in human blood serum samples. MATERIAL AND METHODS: The analytical measurement was performed by GC-µECD following preparation of serum samples (denaturation, multiple extraction, lipid removal). Identity of the compounds was confirmed by GC-MS. RESULTS: The method was characterised by the appropriate linearity, good repeatability (CV below 20%). The recoveries ranged from 52.9 to 125.0% depending on compound and level of fortification. The limit of quantification was set at 0.03 ng mL(-1) of serum. CONCLUSIONS: The modified analytical method proved to be suitable for the simultaneous determination of selected PBDEs, PCBs and OCPs in human blood serum by GC-µECD with good precision.

Phthalates, perfluoroalkyl acids, metals and organochlorines and reproductive function: a multipollutant assessment in Greenlandic, Polish and Ukrainian men.

OBJECTIVES: Numerous environmental contaminants have been linked to adverse reproductive health outcomes. However, the complex correlation structure of exposures and multiple testing issues limit the interpretation of existing evidence. Our objective was to identify, from a large set of contaminant exposures, exposure profiles associated with biomarkers of male reproductive function. METHODS: In this cross-sectional study (n=602), male partners of pregnant women were enrolled between 2002 and 2004 during antenatal care visits in Greenland, Poland and Ukraine. Fifteen contaminants were detected in more than 70% of blood samples, including metabolites of di(2-ethylhexyl) and diisononyl phthalates (DEHP, DiNP), perfluoroalkyl acids, metals and organochlorines. Twenty-two reproductive biomarkers were assessed, including serum levels of reproductive hormones, markers of semen quality, sperm chromatin integrity, epididymal and accessory sex gland function, and Y:X chromosome ratio. We evaluated multipollutant models with sparse partial least squares (sPLS) regression, a simultaneous dimension reduction and variable selection approach which accommodates joint modelling of correlated exposures. RESULTS: Of the over 300 exposure-outcome associations tested in sPLS models, we detected 10 associations encompassing 8 outcomes. Several associations were notably consistent in direction across the three study populations: positive associations between mercury and inhibin B, and between cadmium and testosterone; and inverse associations between DiNP metabolites and testosterone, between polychlorinated biphenyl-153 and progressive sperm motility, and between a DEHP metabolite and neutral α-glucosidase, a marker of epididymal function. CONCLUSIONS: This global assessment of a mixture of environmental contaminants provides further indications that some organochlorines and phthalates adversely affect some parameters of male reproductive health.

Risk assessment for pesticides' MRL non-compliances in Poland in the years 2011-2015.

BACKGROUND: Human exposure to trace levels of pesticide residues present in food of plant origin is inevitable as long as pesticides continue to be applied in agriculture. Since Maximum Residue Levels (MRL) are not toxicological endpoint values, their violation is not by default equivalent to health risk for consumers. However, its essential to provide a health- based risk assessment for each case of MRL non-compliance reported during monitoring and official control of foodstuffs. OBJECTIVE: To assess the potential short-term risk associated with consumption of food products of plant origin containing pesticide residues above MRL values based on notifications forwarded by the National Contact Point for RASFF in Poland during 2011-2015. MATERIAL AND METHODS: 115 notifications including 127 analytical results non-compliant with respective MRL values were forwarded to provide risk assessment. An internationally accepted deterministic approach based on conservative model assumptions for short-term exposure assessment was applied. The risk was characterized by comparing an estimated dietary intake with respective acute reference dose (ARfD). RESULTS: Black currant, tea, lettuce, Chinese cabbage and carrot were among the most frequently notified products in years 2011-2015. Among pesticides exceeding respective MRL values, over 90% belonged to fungicides and insecticides/acaricides such as acetamiprid, chlorpyrifos, dimethoate, imidacloprid, dithiocarbamates and procymidone. For 15 and 6 results noncompliant with respective MRL value, a predicted short-term intake exceeded ARfD for children and adults, respectively. CONCLUSIONS: Residue levels that could potentially pose a health threat are found incidentally. The science-based and transparent risk assessment process with regard to the data, methods and assumptions that are applied is essential to risk management authorities. KEY WORDS: risk assessment, pesticide residues, MRL, dietary intake, RASFF, food safety.

Endocrine disruptors in food contact materials; is there a health threat?

Food Contact Materials (FCMs) are a major source of endocrine disrupting chemical substances (EDCs), thus forming an important part of human exposure to these compounds, to which this article is addressed. The potential impact of such exposures on endocrine function, and thereby health outcomes, requires scientifically valid evidence so that appropriate risk management decisions can be taken to diminish human exposure, particularly in vulnerable population groups like infants and small children. Relevant aspects of exposure assessment are discussed based on testing migration of EDCs from FCMs, together with the different approaches so used. The specific migration testing determines whether limits for defined substances are met. However not all EDCs present in the leachate may be found by these means. In fact, the chances of detecting EDCs in the food simulant (leachate) are improved when it is subjected the relevant biological testing, thus helping to provide improved protection against these chemical substances. Nevertheless, official controls and risk management decisions do not necessarily take such testing into account, as the relevant legislation is based on specific migration limits that may be easily quantified and addressed in the risk management process. Elucidating the link between observed endocrine activity and any toxic effects so arising, is complicated by the complexity of endocrine interrelationships coupled with relatively limited sensitivity of toxicological tests. Any risk assessment implies a rather high uncertainty and should include also any cumulative effects. This review discusses the effects of the EDCs like bisphenol A, phthalates and benzophenone found in FCMs. In addition, the approaches from the USA and EU for systematically evaluating man-made EDCs in the environment are also considered, including appropriate prioritisation criteria.

Effect of chlorpyrifos on the profile of subpopulations immunocompetent cells B, T and NK in in vivo model.

BACKGROUND: Current studies have indicated many environmental factors, such as pesticides, that cause immune system disorders through inducing changes in humoral and cellular responses thereby increasing the risk of contracting infectious diseases and cancer. The literature suggests that low exposures to certain organophosphorus pesticides stimulate the immune system, whilst high exposures result in decreased function. Precise mechanisms for the fall in immunocompetence are often unclear, however it can be predicted that the intimate interaction between the nervous and immune systems can potentially lead to toxicity. OBJECTIVES: To determine the effects of organophosphorus pesticide, chlorpyrifos that is often used in Poland, on selected immunological responses, such as immune-competent cell proportions formed experimentally in-vivo by cells of Wistar rats during subchronic exposures after 45 and 90 days. MATERIALS AND METHODS: The test was carried out on ten male and ten female Wistar rats in each of three test groups, who received 3 chlorpyrifos doses for 90 days intragastrically, according to OECD guidelines (No. 401). Two control groups were given olive oil. After completion, the animals were deeply anaesthetised by a mixture of ketamine (Vetaketam) and xylazine (Vetaxym). Immuno-competent cells were profiled by a commercial monoclonal antibody method. In order to measure the dynamics of any changes, the aforementioned immunological responses were investigated after 45 days using the same procedures for obtaining the relevant biological test material. RESULTS: Test animals exposed to chlorpyrifos had altered number of white bood cells which were either increased or decreased relative to controls after 45 and 90 days for all exposure levels used. CONCLUSIONS: The study demonstrated changes in white-blood cell (lymphocyte) response profiles, reflecting an immunomodulation although such changes were equivocal, where both suppression and stimulation were observed. KEY WORDS: immunomodulation, immune system, lymphocyte, organophosphorus pesticides, chlorpyrifos.

Development and validation of a method for determination of selected polybrominated diphenyl ether congeners in household dust.

BACKGROUND: Polybrominated diphenyl ethers (PBDEs) belong to group of so-called persistent organic pollutants (POPs). These compounds occur in nearly all elements of the environment, including household dust which constitutes one of a major route for human exposure. Their main adverse effects on human health are associated mainly with endocrine disruption--they interfere with thyroid function exhibit anti-androgenic action. OBJECTIVES: To develop and validate analytical method for determination of BDE-47, BDE-99, BDE-153, and BDE-209 congeners in household dust. MATERIAL AND METHODS: Household dust was sampled in residences from Warsaw and the surrounding areas. An automated Soxhlet extraction of samples was then performed and PBDE congeners were subsequently measured in cleaned-up extracts by GC-microECD. The identity of quantified compounds was confirmed by GC/MS. RESULTS: Household dust samples were fortified at levels of 2.88, and 28.8 ng g(-1) for BDE-47, BDE-999, and BDE-153, and for BDE-209 at levels of 101.2, and 540 ng g(-1). Recoveries ranged between 72 - 106%. The relative standard deviations (RSD) were less than 16% for all PBDE congeners analysed. The relative error determined on the basis of multiple analyses of certified reference material ranged from 1.07 - 20.41%. The method's relative expanded uncertainty varied between 16 - 21%. CONCLUSION: The presented method was successfully validated and can be used to measure concentrations of BDE-47, BDE-99, BDE-153 and BDE-209 congeners in household dust.

Computer modelling as a tool for the exposure assessment of operators using faulty agricultural pesticide spraying equipment.

BACKGROUND: Faulty but still operating agricultural pesticide sprayers may pose an unacceptable health risk for operators. The computerized models designed to calculate exposure and risk for pesticide sprayers used as an aid in the evaluation and further authorisation of plant protection products may be applied also to assess a health risk for operators when faulty sprayers are used. OBJECTIVE: To evaluate the impact of different exposure scenarios on the health risk for the operators using faulty agricultural spraying equipment by means of computer modelling. MATERIAL AND METHODS: The exposure modelling was performed for 15 pesticides (5 insecticides, 7 fungicides and 3 herbicides). The critical parameter, i.e. toxicological end-point, on which the risk assessment was based was the no observable adverse effect level (NOAEL). This enabled risk to be estimated under various exposure conditions such as pesticide concentration in the plant protection product and type of the sprayed crop as well as the number of treatments. Computer modelling was based on the UK POEM model including determination of the acceptable operator exposure level (AOEL). Thus the degree of operator exposure could be defined during pesticide treatment whether or not personal protection equipment had been employed by individuals. Data used for computer modelling was obtained from simulated, pesticide substitute treatments using variously damaged knapsack sprayers. These substitute preparations consisted of markers that allowed computer simulations to be made, analogous to real-life exposure situations, in a dose dependent fashion. Exposures were estimated according to operator dosimetry exposure under 'field' conditions for low level, medium and high target field crops. RESULTS: The exposure modelling in the high target field crops demonstrated exceedance of the AOEL in all simulated treatment cases (100%) using damaged sprayers irrespective of the type of damage or if individual protective measures had been adopted or not. For low level and medium field crops exceedances ranged between 40 - 80% cases. CONCLUSIONS: The computer modelling may be considered as an practical tool for the hazard assessment when the faulty agricultural sprayers are used. It also may be applied for programming the quality checks and maintenance systems of this equipment.

[Indoor dust as a pathway of human exposure to polybrominated diphenyl ethers (PBDEs)]. / Kurz zródlem narazenia czlowieka na polibromowane difenyloetery (PBDE).

The brominated diphenyl ethers (PBDEs) belong to a class of synthetic, additive brominated flame retardants (BFRs). PBDEs are used to reduce the flammability of commercial and household products such as textiles, various plastic polymers, furnishing foam, and electronic equipment. People spend a large percentage of their life-time indoors at home, in offices and cars, etc, providing many opportunities for lengthy exposure to PBDEs from residential settings and commercial products in an indoor environment. In recent time, the foodstuffs, mainly food of animal origin, have been indicated as the main pathway of human exposure to PBDEs. However, many studies have shown that the indoor environment, mainly indoor dust, can be also a significant source of exposure to PBDEs, especially for younger children (toddlers) because of their behavioral patterns, eg. putting fingers, toys, and other items in their mouth. Numerous studies show that the median intakes of PBDEs via dust for adult range from 1.41 to 277 ng x day(-1) is lower than that via food which range from 135 to 333 ng x day-', while the median intake of these compounds via indoor dust for children range from 101 to 404 ng x day(-1) is much higher than via food: 77-190 ng x day(-1). The congener pattern observed in the indoor dust is different to that found in food. The indoor dust is dominated by the congener BDE-209 vs. food where the most dominated congeners are BDE-47 and BDE-99. Human exposure to PBDEs and other brominated flame retardants (BFRs) is widely widespread throughout the world and it depends on a country range of usage, production and legislation concerning these chemicals as well as a citizen's behavior. Generally, human exposure has been found higher in North America than in Europe and Asia. Within European countries the significant highest concentrations in dust have been found in the United Kingdom. It should be noted that many uncertainty factors such as personal habits, dietary preferences, and time spent in various rooms, cars and outdoors could affect the exposure assessment. In some cases the occupational exposure is the most important source of PBDEs for adults, for example air crews, car sale employees and disposal/recycling of electronic waste workers.

Risk assessment for infants exposed to furan from ready-to-eat thermally processed food products in Poland.

BACKGROUND: Thermal processes and long storage of food lead to reactions between reducing sugars and amino acids, or with ascorbic acid, carbohydrates or polyunsaturated fatty acids. As a result of these reactions, new compounds are created. One of these compounds having an adverse effect on human health is furan. OBJECTIVE: The aim of this paper was to estimate the infants exposure to furan found in thermally processed jarred food products, as well as characterizing the risk by comparing the exposure to the reference dose (RfD) and calculating margins of exposure. MATERIALS AND METHODS: The material consisted of 301 samples of thermally processed food for infants taken from the Polish market in years 2008 - 2010. The samples included vegetable-meat, vegetables and fruit jarred meals for infants and young children in which the furan levels were analyzed by GC/MS technique. The exposure to furan has been assessed for the 3, 4, 6, 9,12 months old infants using different consumption scenarios. RESULTS: The levels of furan ranged from <1 microg/kg (LOQ) to 166.9 microg/kg. The average furan concentration in all samples was 40.2 microg/kg. The estimated exposures, calculated with different nutrition scenarios, were in the range from 0.03 to 3.56 microg/kg bw/day and exceeded in some cases RfD set at level of 1 microg/kg bw/day. Margins of exposure (MOE) achieved values even below 300 for scenarios assuming higher consumption of vegetable and vegetable-meat products. CONCLUSIONS: The magnitude of exposure to furan present in ready-to-eat meals among Polish infants is similar to data reported previously in other European countries but slightly higher than indicated in the recent EFSA report. As for some cases the estimated intake exceeds the RfD, and MOE) values are much lower than 10000 indicating a potential health concern, it is necessary to continue monitoring of furan in jarred food and estimate of its intake by infants.

[Dioxins and food safety]. / Dioksyny a bezpieczenstwo zywnosci.

Among numerous potential chemical food contaminants, polychlorinated dibenzo-p-dioxins, dibenzofurans and dioxin-like polychlorinated biphenyls, collectively referred as dioxins, are commonly considered as bearing substantial risk for human health due to their toxicological properties, persistency and ability to bioaccumulate in food chains. The results of epidemiological studies suggest that environmental exposure to these compounds may affect multiple physiological processes in humans, mainly by the mechanism of endocrine disruption. Adverse health effects linked to the long-term exposure to dioxins include the increase of cancer risk, reproductive and developmental impairment as well as effects on immune functions. Exposure through food (mainly of animal origin) is the major source of dioxin exposure for humans, estimated to account for about 95% of the total intake for non-occupationally exposed persons. Recent studies showed that a consistent part of the European population has an intake exceeding internationally agreed "safe" doses as the Tolerable Daily or Weekly Intake (TDI, TWI). It is worthy to note that percentage of persons with estimated dioxin intake above tolerable limits is much higher among children than in adults. Since the "Belgian dioxin crisis" that occurred in 1999, the estimation of human exposure to these compounds and related consumer risk assessment has been recognized in the European Union as one of the priority activities in the field of food safety. Among activities undertaken by the European Commission during implementation of the Community Strategy for dioxins, furans and polychlorinated biphenyls the maximum and action levels have been established with random monitoring by Member States. The legislation on the requirements for sampling and methods of analysis used in the official control laboratories has been set up as well. Member States are obliged to measure background levels of dioxins and dioxin-like PCBs in defined food categories for the EU monitoring program on a yearly basis and to forward the results to the European Commission (since 2008 to the European Food Safety Authority). The monitoring results, covering samples collected from 1999 to 2008, evaluated and reported recently by EFSA, became the basis for updating maximum levels of dioxins and dl-PCBs as set up in Commission Regulation (EC) 1881/2006. The legislation will also be changed by replacing the current toxicity equivalency factors (TEFs) system from 1998 (WHO,1998-TEFs) by a new TEFs proposed by the WHO in 2005 (WHO 2005-TEFs). It is expected that new limits for dioxins and dl-PCBs in food will come into force not later than in the beginning of 2012.

[Ubiquitous perfluorinated compounds]. / Wszechobecne zwiazki perfluorowane.

Perfluorinated compounds are derivatives of hydrocarbons, in which all or most of hydrogen atoms are substitiuted by fluorine atoms. These compounds are commonly used in many branches of industry. Perfluorinated compounds are in the limelight because of numerous reports concerning their toxicity and negative effects on human health as well as contradictory information about their cancerogenic effect. The above compounds are used in production of many commonly used products including such brand names as Gore-Tex, Teflon, Stainmaster. The most common ways of penetrating these compounds into a human organism are: via food, inhalation and skin contact. Perfluorooctanesulfonate (PFOS) has been added to the list of persistent organic pollutants (POPs).

[Application of the quechers method coupled with gas chromatography with electron capture detection (GC-ECD) in analysis of pesticide residues in food]. / Zastosowanie metody QuEChERS w polaczeniu z chromatografia gazowa z detektorem wychwytu elektronów (GC-ECD) w analizie pozostalosci pestycydów w zywnosci.

In 2003 Anastassiades and Lehotay described the "quick, easy, cheap, effective, rugged and safe" (QuEChERS) method for the multi-class, multiresidue analysis of pesticides in fruit and vegetables. The QuEChERS method allows to obtain high quality results with a minimum number of steps and a low solvent and glassware consumption. The QuEChERS method based on liquid-liquid partitioning with acetonitrile followed by a cleanup step with dispersive-SPE (Solid Phase Extraction). The aim of this study was to check the usefulness of the QuEChERS method coupled with gas chromatography with electron capture detection (GC-ECD) in analysis of pesticide residues in food. Ready-to-use QuEChERS reagents kits and own-weighed reagents have been applied. In recovery experiment for 15 selected pesticides, three matrices belonging to different groups--carrots (high carotenoids content), raspberry (highly acidic matrix) and tomatoes (high water content)--have been used, according to the SANC0/10684/2009 guideline and PN-EN 15662:2008 requirements. Fourteen compounds showed a recovery in the range of 70-120% and only one compound (trifluralin in raspberry) presented a recovery lower than 70% at the 0.5 mg/kg fortification level. The repeatability was satisfying with a RSD lower than 20% apart from trifluralin in raspberry (27.16%).

Fetal loss and maternal serum levels of 2,2',4,4',5,5'-hexachlorbiphenyl (CB-153) and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE) exposure: a cohort study in Greenland and two European populations.

BACKGROUND: In the present study, the aim is to examine the risk of fetal loss related to environmental 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) or 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE) exposure. METHODS: We related LC/MS/MS measurements of CB-153 and p,p'-DDE in serum samples to interview-data on previous fetal loss in populations of pregnant women from Poland, Ukraine and Greenland. RESULTS: In total, 1710 women were interviewed, and 678 of these had at least one previous pregnancy. The risk of ever experiencing a fetal loss increased at higher levels of CB-153 and p,p'-DDE exposure, with an adjusted odds ratio (OR) of 2.4; confidence interval (CI) (1.1-5.5) for CB-153>200 ng/g lipid compared to 0-25 ng CB-153/g lipid and OR of 2.5 CI (0.9-6.6) for p,p'-DDE>1500 ng/g lipid compared to 0-250 ng DDE/g lipid. However, no clear dose response associations were observed. The results further suggest that high level of organochlorine serum concentrations may be related to repeated loss. CONCLUSIONS: The risk of fetal loss may increase at higher levels of CB-153 and p,p'-DDE exposure, although lack of dose response and inconsistencies between countries did not allow for firm conclusions.

Association of maternal serum concentrations of 2,2', 4,4'5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE) levels with birth weight, gestational age and preterm births in Inuit and European populations.

BACKGROUND: Epidemiological studies on the association between maternal exposure to persistent organic pollutants (POPs) and fetal growth alteration report inconsistent findings which weights in favor of additional studies. METHODS: Blood samples were collected from interviewed pregnant women in Greenland (572), Kharkiv (611) and Warsaw (258) and were analyzed for CB-153 and p,p'-DDE by gas chromatography-mass spectrometry. Data on birth weight, gestational age and preterm birth were obtained for 1322 singleton live births. We examined the association between natural log-transformed serum POPs concentration and birth weight and gestational age using multiple linear regression and the association with prematurity using logistic regression controlling for potential confounding factors. RESULTS: The median serum concentrations of CB-153 and p,p'-DDE were for Inuit mothers 105.6 and 298.9, for Kharkiv mothers 27.0 and 645.4 and for Warsaw mothers 10.7 and 365.2 ng/g lipids, respectively. Increase in CB-153 concentration by one unit on the log scale in Inuit mothers serum was associated with significant decrease in infant birth weight of -59 g and gestational age by -0.2 week. Decreases observed in the cohorts in Kharkiv (-10 g and -0.1 week) and in Warsaw (-49 g and -0.2 week) were not statistically significant. Increase in p,p'-DDE concentration by one unit on the log scale was associated with a statistically significant decrease in infant birth weight of -39.4 g and -104.3 g and shortening of gestational age of -0.2 week and -0.6 week in the Inuit and Warsaw cohorts, respectively. In the Kharkiv cohort decrease in birth weight (-30.5 g) was not significant, however a shortening of gestational age of -0.2 week per increase in p,p'-DDE concentration by one unit on the log scale was of the borderline significance. There was no significant association between CB-153 and p,p'-DDE concentrations and risk of preterm birth however, in all cohorts the odds ratio was above 1. CONCLUSIONS: In utero exposure to POPs may reduce birth weight and gestational age of newborns however, new insights as to why results vary across studies were not apparent.

[Toxicological evaluation of crop protection chemicals in the EU registration process]. / Ocena toksykologiczna srodków ochrony roslin w procesie rejestracyjnym UE.

Authorisation of crop protection chemicals prior to placing into the market is being regulated with standardized regulations in the European Community territory. The Member States are obliged to introduce all provisions constituting the base for the evaluation of protection chemicals and determining their safety for man and environment. The rules governing toxicological evaluation of plant protection products and their active substances have been discussed and the practical relevance of the harmonized provisions for the safety assessment of pesticides in the EU were also presented. Introducing the assessment of risk resulting from treatments with chemical crop protection chemicals in the registration process widens the safety margin for users of plant protection products as well as fixes new safety standards at agrochemical works.

[Organohalogen compounds--new and old hazards for people]. / Zwiazki halogenorganiczne --stare i nowe zagrozenia]

The organohalogen compounds (OCs, PCBs, PBDEs) are persistent organic pollutants (POPs) that have a widespread distribution in the environment. Their chemico-physical stability and lipophylic properties are responsible for their accumulation in the human body. The general human population is exposed to PCBs and OCs through foodstuffs, mainly food of animal origin. However the main source of the human exposure to PBDEs are also food and inhalation of dust or respirable phase of the indoor air The POPs from this group are present on different levels in human tissues (fat tissue, liver; placenta), and even in human blood and breast milk. The organohalogen compounds may cause endocrine disrupting (ED) effects as they have been shown to interact as antagonists or agonists with androgen, progesterone, and estrogen receptors. Most of them shows antiandrogenic, estrogenic and antiestrogenic activity.

[The role and tasks of the National Reference Laboratory in the scope of pesticide residues in food]. / Rola i zadania krajowego laboratorium referencyjnego w zakresie pozostalossci pestycydów w zywnosci.

The Member States are obliged to establish the specific programmes and the control systems ensuring that food products placed on the market are safe for the consumer In Poland, the official food control laboratories of the State Sanitary Inspection carry out the analysis of food contaminants, including pesticide residues. Those laboratories closely cooperate with the National Reference Laboratories (NRLs). They are also receiving necessary technical assistance from NRLs.

[The effects of di-n-butyl phthalate on the somatic cells of laboratory mice]. / Wplyw ftalanu di-n-butylu (DBP) na komórki somatyczne myszy laboratoryjnych.

Phthalates are widely used as a plasticizers in manufacture of synthetic materials and as solvents in sanitary products, cosmetics and pharmaceutical products. Dibutylphthalate (DBP) is used as a plasticizers and as a textile lubricating agent and as solvent in printing ink. The study aimed the evaluation of the magnitude of DNA damage in liver and bone marrow cells and estimation of dibutyl phthalate (DBP) concentration in peripheral blood following prolonged exposure to DBP. Experiments were conducted an the Pzh:Sfis male mice. Animals were exposed 8 weeks, 3 days per week per os to DBP suspension in oil in doses of 500 mg/kg bw (1/16 LD50) and 2000 mg/kg bw (1/4 LD50). Following groups of mice were sacrificed 4 and 8 weeks after the start of exposure and 4 weeks after the end of exposure. Decreased body weight of mice and statistically significant decreased liver and relative liver weights were observed following 8-weeks exposure to 2000 mg/kg bw DBP. In the same time higher however not statistically significant level of DNA damage measured by Comet assay in liver cells were noted. DBP did not induce enhanced frequency of DNA damage in bone marrow cells. Following 8-weeks exposure to the dose of 2000 mg/kg bw DBP the increased level of DBP in peripheral blood was observed. Enhanced levels of DBP were still noted 4 weeks after the termination of exposure. Results confirmed that DBP acts as a weak mutagen for DNA of somatic cells. However, following prolonged exposure this compound seems to undergo slower metabolism and was reaching temporarily higher levels in peripheral blood.

[Analysis of scientific background of establishing definitions for Maximum Residue Levels (MRLs)]. / Analiza podstaw naukowych ustalania definicji Najwyzszych Dopuszczalnych Poziomów Pozostalosci pestycydow (NDP).

For each pesticide used in food or feed productions, the legislative authorities have to establish the residue definitions, that mean compounds which need to be taken into account in risk assessment in process of authorization of plant protection products as well as in establishing and enforcing Maximum Residue Levels (MRLs). The residue definition for a given pesticide can be different depending on the aim for which they are used. Inclusion of a compound in such definition results in consequence in its later analysis in different matrices during monitoring and official control. Inclusion of compounds in the definition depends on a number of factors, and the decisions on whether they should be included have to be made for every case separately. The definition should include toxicologically important compounds, and those which contribute into the residue in 10 or more percent of TRR, or those that have been detected in livestock and plants as metabolites different than those found in rats.