Assessment of the genotoxicity of tert-butyl alcohol in an in vivo thyroid comet assay.

Chronic exposure to high (20,000 ppm) concentrations of tert-butyl alcohol (TBA) in drinking water, equivalent to ~2100 mg/kg bodyweight per day, is associated with slight increases in the incidence of thyroid follicular cell adenomas and carcinomas in mice, with no other indications of carcinogenicity. In a recent toxicological review of TBA, the U.S. EPA determined that the genotoxic potential of TBA was inconclusive, largely based on non-standard studies such as in vitro comet assays. As such, the potential role of genotoxicity in the mode of action of thyroid tumors and therefore human relevance was considered uncertain. To address the potential role of genotoxicity in TBA-associated thyroid tumor formation, CD-1 mice were exposed up to a maximum tolerated dose of 1500 mg/kg-day via oral gavage for two consecutive days and DNA damage was assessed with the comet assay in the thyroid. Blood TBA levels were analyzed by headspace GC-MS to confirm systemic tissue exposure. At study termination, no significant increases (DNA breakage) or decreases (DNA crosslinks) in %DNA tail were observed in TBA exposed mice. In contrast, oral gavage of the positive control ethyl methanesulfonate significantly increased %DNA tail in the thyroid. These findings are consistent with most genotoxicity studies on TBA and provide mechanistic support for non-linear, threshold toxicity criteria for TBA. While the mode of action for the thyroid tumors remains unclear, linear low dose extrapolation methods for TBA appear more a matter of policy than science.

Electrochemical degradation of diclofenac generates unexpected thyroidogenic transformation products: Implications for environmental risk assessment.

Diclofenac (DCF) is an environmentally persistent, nonsteroidal anti-inflammatory drug (NSAID) with thyroid disrupting properties. Electrochemical advanced oxidation processes (eAOPs) can efficiently remove NSAIDs from wastewater. However, eAOPs can generate transformation products (TPs) with unknown chemical and biological characteristics. In this study, DCF was electrochemically degraded using a boron-doped diamond anode. Ultra-high performance liquid chromatography coupled with high-resolution mass spectrometry was used to analyze the TPs of DCF and elucidate its potential degradation pathways. The biological impact of DCF and its TPs was evaluated using the Xenopus Eleutheroembryo Thyroid Assay, employing a transgenic amphibian model to assess thyroid axis activity. As DCF degradation progressed, in vivo thyroid activity transitioned from anti-thyroid in non-treated samples to pro-thyroid in intermediately treated samples, implying the emergence of thyroid-active TPs with distinct modes of action compared to DCF. Molecular docking analysis revealed that certain TPs bind to the thyroid receptor, potentially triggering thyroid hormone-like responses. Moreover, acute toxicity occurred in intermediately degraded samples, indicating the generation of TPs exhibiting higher toxicity than DCF. Both acute toxicity and thyroid effects were mitigated with a prolonged degradation time. This study highlights the importance of integrating in vivo bioassays in the environmental risk assessment of novel degradation processes.

Effects of Subacute Exposure of Dibutyl Phthalate on the Homeostatic Model Assessment, Thyroid Function, and Redox Status in Rats.

Dibutyl phthalate is an endocrine disruptor used in a wide range of industrial and agriculture applications. The present study focuses on elucidating the effect of subacute exposure (4-weeks) of DBP on insulin and its sensitivity indexes, oxidative status, thyroid function, energy metabolites, serum biochemistry, and anthropometry in rats. A total of 64 rats were divided into 4 treatment groups as mg DBP/Kg body weight per day: (a) 0 mg/Kg (control), (b) 10 mg/Kg (DBP-10), (c) 50 mg/Kg (DBP-50), and (d) 100 mg/Kg (DBP-100). The rats in each treatment (n = 16) were further divided into male (n = 8) and female (n = 8) rats for studying treatment and gender interactions. Intraperitoneal glucose tolerance test (IPGTT) was performed on the 21st day. Anthropometry, nutritional determinants, fasting plasma glucose, fasting plasma insulin, homeostatic model assessment (HOMA), thyroid hormones, energy metabolites, and oxidative status were studied during the experimental period. Two-way ANOVA was used to analyze the data (p < 0.05). Tukey's posthoc test was used for pair-wise comparisons. DBP increased body weight gain and feed efficiency in an inverted nonmonotonic U-shaped fashion. Hyperglycemia and increased blood glucose area under the curve were observed in DBP-100 at 120 minutes in IPGTT. The HOMA also showed a linear monotonic contrast. Thyroxin decreased significantly in the DBP-100 rats, whereas malondialdehyde, nonesterified fatty acids, and beta hydroxyl butyrate were increased with the DBP treatments. In conclusion, DBP could be attributed to the development of hyperglycemia and insulin resistance in rats. Further investigations into the lipid peroxidation pathways can improve our understanding of the mechanisms involved in metabolic disruption.

Individual and community level factors associated with use of iodized salt in sub-Saharan Africa: A multilevel analysis of demographic health surveys.

INTRODUCTION: Iodine deficiency disorder a common problem in sub-Saharan Africa (SSA). It affects not only the health of the affected individual but also the economic development of the country. However, to the best of our knowledge, there is a scarcity in literature about the associated factors of iodized salt utilization in sub-Saharan Africa. Therefore, this study aimed to identify both individual and community level determinants of iodized salt utilization in sub-Saharan Africa. METHODS: This study used the appended datasets of the most recent demographic and health survey from 31 sub-Saharan countries. A total weighted sample of 391,463 households was included in the study. Both bivariable and multivariable multilevel logistic regression were done to determine the associated factors of iodized salt utilization in SSA. P value ≤ 0.05 was used to declare statistically significant variables. RESULTS: Those households with primary (AOR = 1.53, 95% CI = 1.50-1.57), secondary (AOR = 1.81, 95% CI = 1.76-1.86) and higher education level (AOR = 2.28, 95% CI = 2.17-2.40) had higher odds of iodized salt utilization. Households with middle (AOR = 1.05, 95% CI = 1.02-1.08), richer (AOR = 1.13, 95% CI = 1.09-1.17) and richest wealth index (AOR = 1.23, 95% CI = 1.18-1.28) also had an increased chance of using iodized salt. Households from high community media exposure (AOR = 2.07, 95% CI = 1.71-2.51), high community education level (AOR = 3.78, 95% CI = 3.14-4.56), and low community poverty level (AOR = 1.29, CI = 1.07-1.56) had higher odds of using salt containing iodine. CONCLUSION: Both individual and community level factors were found to be associated with use of salt containing iodine in sub-Saharan Africa. Education level, media exposure, community poverty level, wealth index, community education, and community media exposure were found to be associated with use of salt containing iodine in SSA. Therefore, to improve the use of iodized salt in the region, there is a need to increase access to media sources and develop the socioeconomic status of the community.

Predictive Value of a Thyroid-Absorbed Dose with a Shorter Effective Half-Life on Efficacy in Graves Disease Patients Receiving Iodine-131 Therapy.

BACKGROUND Although radioiodine therapy (RIT) efficacy is thoroughly validated for Graves disease (GD), there is a lack of research on the predictive factors of RIT, especially the optimal thyroid-absorbed dose (TD) with a shorter effective half-life (Teff ≤5 days). The goal of this study was to explore the predictive value of TD in GD patients receiving RIT with a shorter Teff. MATERIAL AND METHODS We studied 208 GD patients receiving RIT with a shorter Teff. Plotting the receiver-operating characteristic (ROC) curve verified the accuracy of TD for predicting RIT efficacy in GD patients. In addition, we conducted univariate and multivariate analyses to investigate the influence of 14 factors, including thyroid weight, TD, 24-h radioiodine uptake rate (RAIU), the highest RAIU, thyrotrophin receptor antibody level, thyroglobulin antibody level, thyroid peroxidase antibody level, and others, on curative effects of RIT. RESULTS Of the 208 study participants, complete remission and the total effectiveness rates were 68.3% and 92.3%, respectively. The threshold value of TD to predict RIT efficacy was 70.2 Gy, based on ROC analysis. Univariate analysis showed that 24-h RAIU, Teff, total iodine dose, iodine dose per gram of thyroid tissue, TD, and thyrotropin receptor antibody level were significantly associated with RIT efficacy. Multivariate analysis indicated that 24-h RAIU, total iodine dose, iodine dose per gram of thyroid tissue, and TD were significant independent predictors of RIT efficacy. CONCLUSIONS Predicting RIT efficacy from TD with a shorter Teff was feasible in GD patients, and TD above 70.2 Gy had an especially high predictive accuracy.

Effect of growth hormone therapy on thyroid function in isolated growth hormone deficient and short small for gestational age children: a two-year study, including on assessment of the usefulness of the thyrotropin-releasing hormone (TRH) stimulation test.

Background The relationship between growth hormone (GH)-replacement therapy and the thyroid axis in GH-deficient (GHD) children remains controversial. Furthermore, there have been few reports regarding non-GHD children. We aimed to determine the effect of GH therapy on thyroid function in GHD and non-GHD children and to assess whether thyrotropin-releasing hormone (TRH) stimulation test is helpful for the identification of central hypothyroidism before GH therapy. Methods We retrospectively analyzed data from patients that started GH therapy between 2005 and 2015. The free thyroxine (FT4) and thyroid-stimulating hormone (TSH) concentrations were measured before and during 24 months of GH therapy. The participants were 149 children appropriate for gestational age with GHD (IGHD: isolated GHD) (group 1), 29 small for gestational age (SGA) children with GHD (group 2), and 25 short SGA children (group 3). Results In groups 1 and 2, but not in group 3, serum FT4 concentration transiently decreased. Two IGHD participants exhibited central hypothyroidism during GH therapy, and required levothyroxine (LT4) replacement. They showed either delayed and/or prolonged responses to TRH stimulation tests before start of GH therapy. Conclusions GH therapy had little pharmacological effect on thyroid function, similar changes in serum FT4 concentrations were not observed in participants with SGA but not GHD cases who were administered GH at a pharmacological dose. However, two IGHD participants showed central hypothyroidism and needed LT4 replacement therapy during GH therapy. TRH stimulation test before GH therapy could identify such patients and provoke careful follow-up evaluation of serum FT4 and TSH concentrations.

Thyroid function assessment before and after diagnosis of schizophrenia: A community-based study.

Alterations in thyroid hormone levels may affect brain and mental disorders. Conversely, schizophrenia and its antipsychotic treatments can affect thyroid hormone levels. However, data on thyroid hormone levels during the course of schizophrenia disorder are scant. The aim of the study was to assess the rate of thyroid hormone disorders in outpatients before and after diagnosis of schizophrenia. A retrospective matched-control design was used. The cohort included 1252 patients suffering from ICD-10 schizophrenia, and 3756 control subjects matched for gender, age, socioeconomic status, and origin. All were identified from the database of a large health management organization. The pertinent clinical data were collected from the electronic medical records. There was no significant between-group difference in the distribution of thyroid-stimulating hormone levels. Before diagnosis, both groups had a similar rate of hypothyroidism. After diagnosis of schizophrenia and initiation of antipsychotic treatment, the rate of hypothyroidism was significantly higher in the patient group. It remained significantly higher after exclusion of patients receiving lithium. The increased rate of hypothyroidism in patients with schizophrenia after, but not before, the diagnosis of schizophrenia suggests that antipsychotic medications may affect thyroid hormone levels. Screening for thyroid disorders is warranted in patients with schizophrenia under antipsychotic treatment.

Uncertainty quantification of bioassay functions for the internal dosimetry of radioiodine.

Bioassay functions, which are provided by the International Commission on Radiological Protection, are used to estimate the intake activity of radionuclides; however, they include considerable uncertainties in terms of the internal dosimetry for a particular individual. During a practical internal dose assessment, the uncertainty in the bioassay function is generally not introduced because of the difficulty in quantification. Therefore, to clarify the existence of uncertainty in the bioassay function and provide dosimetrists with an insight into this uncertainty, this study attempted to quantify the uncertainty in the thyroid retention function used for radioiodine exposure. The uncertainty was quantified using a probabilistic estimation of the thyroid retention function through the propagation of the distribution of biokinetic parameters by the Monte Carlo simulation technique. The uncertainties in the thyroid retention function, expressed in terms of the scattering factor, were in the ranges of 1.55-1.60 and 1.40-1.50 for within 24 h and after 24 h, respectively. In addition, the thyroid retention function within 24 h was compared with actual measurement data to confirm the uncertainty due to the use of first-order kinetics in the biokinetic model calculation. Significantly higher thyroid uptakes (by a factor of 1.9) were observed in the actual measurements. This study indicates that consideration of the uncertainty in the thyroid retention function can avoid a significant over- and under-estimation of the internal dose, particularly when a high dose is predicted.

The impact of nandrolone decanoate abuse on experimental animal model: Hormonal and biochemical assessment.

Nandrolone decanoate (ND) is one of the most commonly abused anabolic androgenic steroids compounds in the world owing to its ability to improve physical performance but its abuse is associated with several adverse effects. The current study was performed to evaluate the effect of recommended and overdose of nandrolone decanoate (ND) for short and long term on the alterations of biochemical markers related to kidney, liver, adrenal, thyroid gland functions and oxidant and antioxidant activities. Sixty male rats were randomly assigned into two major groups. The first was treated with ND for 6 weeks and the second was treated with same drug for 12 weeks. Each of these groups was further subdivided into three sub groups: 1-Control (untreated rats), 2- Rats intraperitoneally injected with ND 3 mg/kg weekly, 3- Rats intraperitoneally injected with ND 15 mg/kg weekly. Administration of high ND dose for either short or long term significantly elevated kidney function biomarkers, liver enzymes both in serum, cytosol and mitochondria, insignificantly increased thyroid function, significantly increased adrenal function while, decreased ACTH. Moreover, oxidative stress biomarkers were significantly upregulated associated with depression in antioxidants activities. Administration of high ND dose for either short or long term as well as the repeated use of recommended ND dose for long term proved to have harmful effects manifested in impairing the functions of kidneys, liver, thyroid and adrenal glands as well as oxidant antioxidant balance.

A critical evaluation of thyroid hormone measurements in OECD test guideline studies: Is there any added value?

Recently several OECD test guidelines were updated to include thyroid hormone measurements for assessing endocrine disruptor potency, which led to an imperative need to align interpretation of these results by the different stakeholders. We therefore evaluated 124 repro screening studies, which showed in 38% of the studies a statistical significant finding for T4 in at least one treatment group, probably due to disturbances of normal homeostasis causing high variation. Consequently, for a thorough evaluation it is extremely important to take the historical control range into account. In conclusion, the current testing approach is not providing specific information needed to assess endocrine disruption, as too often a statistical significant finding is noted and as down-stream adverse effects are not evaluated. Therefore, major modifications are urgently needed. Instead of extending the in vivo experiments, it should be investigated if in vitro assessments will provide more relevant information on human endocrine disruptor potential.

Assessment of the effects of repeated doses of potassium iodide intake during pregnancy on male and female rat offspring using metabolomics and lipidomics.

Preparedness for nuclear accident responsiveness includes interventions to protect pregnancies against prolonged exposure to radioactive iodine. The aim of this study was to investigate a new design consisting of repeated administration of potassium iodide (KI, 1 mg/kg) for 8 days in late pregnancy gestational day 9-16 (GD9-GD16) in rats. The later-life effects of this early-life iodine thyroid blocking (ITB) strategy were assessed in offspring two months afterbirth. Functional behavioral tests including forced swimming test (FST) and rotarod test (RRT) in rats of both genders showed lower FST performance in KI-treated females and lower RRT performance in KI-treated male pups. This performance decline was associated with metabolic disruptions in cortex involving amino acid metabolism, tyrosine metabolism, as well as docosahexaenoic acid (DHA) lipids and signaling lipids in males and females. Beyond these behavior-associated metabolic changes, a portion of the captured metabolome (17-25%) and lipidome (3.7-7.35%) remained sensitive to in utero KI prophylactic treatment in both cortex and plasma of post-weaning rats, with some gender-related variance. Only part of these disruptions was attributed to lower levels of TSH and T4 (males only). The KI-induced metabolic shifts involved a broad spectrum of functions encompassing metabolic and cell homeostasis and cell signaling functions. Irrespective Regardless of gender and tissues, the predominant effects of KI affected neurotransmitters, amino acid metabolism, and omega-3 DHA metabolism. Taken together, data demonstrated that repeated daily KI administration at 1 mg/kg/day for 8 days during late pregnancy failed to protect the mother-fetus against nuclear accident radiation. Abbreviations: CV-ANOVA: Cross-validation analysis of variance; DHA: Docosahexaenoic acid; FST: Forced swimming test; FT3: plasma free triiodothyronine; FT4: plasma free thyroxine; GD: Gestational day; ITB: Iodine thyroid blocking; KI: potassium iodide; LC/MS: Liquid chromatography coupled with mass spectrometry; MTBE: Methyl tert-butyl ether; m/z: mass-to-charge ratio; PLS-DA: Partial least squares-discriminant analysis; PRIODAC: Repeated stable iodide prophylaxis in accidental radioactive releases; RRT: Rotarod test; TSH: Thyroid-stimulating hormone; VIP: Variable importance in projection.

PRACTICAL METHODS FOR INTERNAL DOSE ASSESSMENT FOR RADIOIODINE INTAKE AFTER THYROID BLOCKING: CLASSIFICATION OF DEGREE OF BLOCKAGE AND DETERMINATION OF INSENSITIVE MEASUREMENT POINT.

Iodine thyroid blocking (ITB) suppresses the uptake of iodine to the thyroid and reduces internal doses after radioiodine intake; however, its disturbance of thyroid biokinetics causes considerable uncertainty in the use of dosimetric data intended for assessment of unblocked normal thyroid. To more accurately assess internal dose after ITB, practical dosimetry methods were proposed that consider the ITB effect in a dosimetric manner. A method using the ratio of urine excretion to thyroid retention activity was proposed to retrospectively determine individual-specific ITB levels; bioassay functions and dose coefficients corresponding to ITB levels were calculated separately using the latest biokinetic model and fundamental data. Moreover, insensitive measurement points of time, which led to similar results regardless of ITB level, were determined based on the dose per unit content. Proposed insensitive points for inhalation of vapour forms and particulate forms, respectively, were 1.5 days and 2 days after exposure.

Is normalized hindlimb length measurement in assessment of thyroid disruption in the amphibian metamorphosis assay relevant?

The amphibian metamorphosis assay represents an OECD Level 3 and EDSP Tier 1 ecotoxicity test assessing thyroid activity of chemicals in African clawed frog (Xenopus laevis). To evaluate the effectiveness of snout-vent length (SVL) normalization of hindlimb length (HLL), correlation between the HLL and SVL or body weight was evaluated in the control groups of 10 individual studies from three laboratories. Two studies required separate analysis of the Nieuwkoop-Faber (NF) stage ≤60 and >60 animals creating a total of 12 data sets. On study day 7, significant positive correlation between HLL and SVL or body weight was observed in eight and seven of the 10 data sets, respectively (r = 0.608-0.843 and 0.583-0.876). On study day 21, significant positive correlation between HLL and SVL or body weight was found in three and four of the 12 data sets, respectively (r = 0.452, 0.480 and 0.553 and r = 0.621, 0.546, 0.564 and 0.378). Significant positive correlation between HLL and SVL was found in three of five studies, including ≤NF stage 60 data (r = 0.564, 0.546 and 0.621). In one of eight studies, including >NF stage 60 data, the positive correlation between HLL and body weight was determined (r = 0.378). Negative or no correlation between HLL and SVL or body weight was found in the other late stage data sets. Therefore, use of SVL-normalized HLL to assess thyroid-mediated effects in X. laevis tadpoles is not warranted. HL stage relative to body stage should be considered.

In ovo exposure to brominated flame retardants Part II: Assessment of effects of TBBPA-BDBPE and BTBPE on hatching success, morphometric and physiological endpoints in American kestrels.

Tetrabromobisphenol A bis(2,3-dibromopropyl ether) (TBBPA-BDBPE) and 1,2-bis(2,4,6-tribromophenoxy)ethane (BTPBE) are both brominated flame retardants (BFRs) that have been detected in birds; however, their potential biological effects are largely unknown. We assessed the effects of embryonic exposure to TBBPA-BDBPE and BTBPE in a model avian predator, the American kestrel (Falco sparverius). Fertile eggs from a captive population of kestrels were injected on embryonic day 5 (ED5) with a vehicle control or one of three doses within the range of concentrations that have been detected in biota (nominal concentrations of 0, 10, 50 or 100 ng/g egg; measured concentrations 0, 3.0, 13.7 or 33.5 ng TBBPA-BDBPE/g egg and 0, 5.3, 26.8 or 58.1 ng BTBPE/g egg). Eggs were artificially incubated until hatching (ED28), at which point blood and tissues were collected to measure morphological and physiological endpoints, including organ somatic indices, circulating and glandular thyroid hormone concentrations, thyroid gland histology, hepatic deiodinase activity, and markers of oxidative stress. Neither compound had any effects on embryo survival through 90% of the incubation period or on hatching success, body mass, organ size, or oxidative stress of hatchlings. There was evidence of sex-specific effects in the thyroid system responses to the BTBPE exposures, with type 2 deiodinase (D2) activity decreasing at higher doses in female, but not in male hatchlings, suggesting that females may be more sensitive to BTBPE. However, there were no effects of TBBPA-BDBPE on the thyroid system in kestrels. For the BTPBE study, a subset of high-dose eggs was collected throughout the incubation period to measure changes in BTBPE concentrations. There was no decrease in BTBPE over the incubation period, suggesting that BTBPE is slowly metabolized by kestrel embryos throughout their ∼28-d development. These two compounds, therefore, do not appear to be particularly toxic to embryos of the American kestrel.

Effects of citrate ester plasticizers and bis (2-ethylhexyl) phthalate in the OECD 28-day repeated-dose toxicity test (OECD TG 407).

Citrate esters are considered functional alternatives to phthalate plasticizers, but their toxicity remains poorly understood. The toxicity of citrate esters, including triethyl 2-acetylcitrate (ATEC) and trihexyl O-acetylcitrate (ATHC), were examined together with that of bis (2-ethylhexyl) phthalate (DEHP) using the Organization for Economic Co-operation and Development Test Guideline 407 (OECD TG407). Following 28-day oral administration, no significant differences in body weight or the weight of the brain, pituitary, heart, epididymis, seminal vesicles, or coagulating gland were found between the vehicle control and DEHP, ATEC or ATHC groups. In the 400 mg/kg day DEHP group, liver, adrenal, thymus, spleen, kidney, testis, and prostate weights were significantly increased. In the 400 mg/kg day ATHC group, kidney, adrenal, thymus, testis and prostate weights were significantly increased. In the 400 mg/kg day ATEC group, kidney, adrenal and testis weights were significantly increased. Hepatocyte size was significantly increased in the 400 mg/kg day DEHP group, suggestive of hepatotoxicity, but was not increased in the ATEC or ATHC groups. There were no significant differences in white blood cell, red blood cell or platelet counts, hemoglobin concentrations, hematocrit, mean corpuscular volume, fasting glucose, insulin, or testosterone concentrations between the vehicle control and DEHP, ATEC and ATHC groups. In the ATHC 400 mg/kg day group, T3 was decreased while T4 was increased, suggestive of disruption of thyroid function. The results of the OECD TG407 subacute repeated dosing toxicity test indicate ATEC is less toxic compared to ATHC or DEHP and could be recommended as an alternative to phthalate plasticizers.

Characterization of the modes of action and dose-response relationship for thiocyanate on the thyroid hormone levels in rats using a computational approach.

Current practices for evaluating the cumulative risk of thyroid-active chemical mixtures (perchlorate, thiocyanate, nitrate) focus on the inhibition of thyroidal iodide uptake via the sodium iodide symporter (NIS) as the mode of action for potency equivalence calculations. However, unlike perchlorate, thiocyanate presents additional modes of action within the thyroid that could contribute to the overall thyroid perturbation. We tested the hypothesis of whether assuming a single mode of action of thyroidal iodide uptake inhibition is sufficient for describing the observed dose-response relationship for thiocyanate and its effects on serum thyroxine levels. An interaction model was developed by linking a biologically based dose-response model for iodide and thyroid hormones to a thiocyanate physiologically based pharmacokinetic model. Each model, adapted from the literature, was restructured and recalibrated in a Bayesian framework for the current mode of actions study. For a chronic exposure scenario, NIS inhibition alone was found not to be sufficient to describe the dose-response relationship for thiocyanate. Inclusion of additional modes of action involving iodide flux across the thyroid membrane and inhibition of iodide organification via thyroid peroxidase showed only moderate improvements in capturing the dose-response at environmental thiocyanate doses of exposure and failed to capture trends at very high doses. Our findings emphasize the need for more mechanistic data for chronic exposure scenarios to characterize better the overall dose-response relationship for thiocyanate. Risk assessment approaches for thyroid-active chemical mixtures that rely on NIS inhibition as the single mode of action may over-predict the contribution of thiocyanate to thyroid disruption.

Probabilistic cumulative dietary risk assessment of pesticide residues in foods for the German population based on food monitoring data from 2009 to 2014.

Cumulative dietary risks for the German population owing to pesticide residues in foods were assessed using food monitoring and consumption data. Based on grouping principles for cumulative assessment groups (CAG) as defined by the European Food Safety Authority, probabilistic modelling gave cumulative long- and short-term dietary exposures relevant to the nervous and thyroid system. Compound specific toxicological reference values were considered to assess the total margins of exposure (MoEs) for each CAG, allowing an assessment of the cumulative dietary consumer risk. For the German population, no public health concerns were identified for 6 of 11 CAGs. For three CAGs high uncertainties remained, since MoEs were less than the usually required threshold of 100 for the upper confidence interval of the modelling uncertainty. For two CAGs relevant to the nervous and thyroid system, possible health risks cannot be excluded with the selected approach. Most potent risk drivers were chlorpyrifos and the group of dithiocarbamates (expressed as propineb). For regulatory decisions on possible cumulative dietary health risks the limitations of the published approaches and the absence of harmonized data sources for robust refinements have to be considered. Future research to reduce this high uncertainty is considered necessary in this area.

Hygienic assessment of the effects of pesticides application on adult population morbidity with thyroid gland diseases.

OBJECTIVE: Introduction: It is proved that some groups of fungicides and herbicides are capable of affecting the thyroid gland, provoking its growth, leading to a compensatory change in the activity of the hormones synthesis. Therefore, the presence of their residual amounts in plant may affect the level of thyroid gland pathology. The aim of the work was to analyze the influence of pesticide application on the Ukrainian adult population morbidity with thyroid diseases in the period from 2001 to 2014. PATIENTS AND METHODS: Materials and methods: The methods of empirical and theoretical research of scientific information, namely analysis, synthesis, induction, deduction and systematization, epidemiological, cartographic and statistical methods were used. RESULTS: Results: The maximum level of thyroid pathology was found in the northern, western and northwestern regions, where the diffuse goiter dominates in the morbidity and prevalence of thyroid diseases; minimal - in the southern, eastern and south-eastern regions. It was established that the highest volumes of application of chemical plant protection products in the period 2001-2013 took place in the southern and central regions of Ukraine, namely in Poltava, Vinnitsa, Kharkiv, Dnipropetrovsk, Khmelnytsky, Odesa and Mykolaiv regions. Sufficiently high levels of pesticide application were in the Kyiv, Kherson regions, Crimea, Zaporizhia, Kirovograd and Cherkasy regions. CONCLUSION: Conclusions: The probability of the active chemical plant protection products usage effect on the level of prevalence and incidence of thyroid cancer, various types of goiter, hypothyroidism, thyrotoxicosis and thyroiditis in the central and southern regions was determined. Are regions with well-developed agricultural production.