In vitro biotransformation assays using fish liver cells: Comparing rainbow trout and carp hepatocytes.

Biotransformation assays using primary hepatocytes from rainbow trout, Oncorhynchus mykiss, were validated as a reliable in vitro tool to predict in vivo bioconcentration factors (BCF) of chemicals in fish. Given the pronounced interspecies differences of chemical biotransformation, the present study aimed to compare biotransformation rate values and BCF predictions obtained with hepatocytes from the cold-water species, rainbow trout, to data obtained with hepatocytes of the warm-water species, common carp (Cyprinus carpio). In a first step, we adapted the protocol for the trout hepatocyte assay, including the cryopreservation method, to carp hepatocytes. The successful adaptation serves as proof of principle that the in vitro hepatocyte biotransformation assays can be technically transferred across fish species. In a second step, we compared the in vitro intrinsic clearance rates (CLin vitro, int) of two model xenobiotics, benzo[a]pyrene (BaP) and methoxychlor (MXC), in trout and carp hepatocytes. The in vitro data were used to predict in vivo biotransformation rate constants (kB) and BCFs, which were then compared to measured in vivo kB and BCF values. The CLin vitro, int values of BaP and MXC did not differ significantly between trout and carp hepatocytes, but the predicted BCF values were significantly higher in trout than in carp. In contrast, the measured in vivo BCF values did not differ significantly between the two species. A possible explanation of this discrepancy is that the existing in vitro-in vivo prediction models are parameterized only for trout but not for carp. Therefore, future research needs to develop species-specific extrapolation models

Hubungan Penggunaan Dan Penanganan Pestisida Pada Petani Bawang Merah Terhadap Residu Pestisida Dalam Tanah Di Lahan Pertanian Desa Wanasari Kecamatan Wanasari Kabupaten Brebes

Excessive use of pesticides causing pollution and environmental damage agriculture. Examination in Brebes on 31 samples of fruits and vegetables, found 22% of samples contain detectable residues of organophosphate and found two soil samples (10%) contained residues organochlorin. The purpose of this study was to determine the relationship of the use and handling of pesticides on their onion farmers against pesticide residues in the soil on agricultural land Wanasari Village, District Wanasari, Brebes. This study is observational method with cross sectional approach. The population in this study were all farmers in the Wanasari conducting spraying. Collecting data using the tool Banu questionnaire and examination of pesticide residues in soil using GC-MS Gas Chromatography - Mass Spectrometry. The results of this study are of 55 69.1 onion farmers use pesticides are not good. The use of pesticides covering 80% is not good in mixing pesticides, 87.3% use a smaller dose, 49.1% use pesticides that are not registered with the Ministry of Agriculture, 87.3% is not good in the way of spraying and 87.3 does well in frequency spraying. Handling pesticides in agricultural land is not good 59.1%, ie 74.5% is not good in handling pesticide containers, 90.9% is not good in storage of pesticides, 89.1% is not good in handling a spill and 87.3% did not either in place to clean pesticide containers. The research result is negative soil samples pesticide residues. The conclusion was that no pesticide residue class organochlorin

Evaluating the Environmental Fate of Short-Chain Chlorinated Paraffins (SCCPs) in the Nordic Environment Using a Dynamic Multimedia Model

Short chain chlorinated paraffins (SCCPs) raise concerns due to their potential for persistence, bioaccumulation, long-range transport and adverse effects. An understanding of their environmental fate remains limited, partly due to the complexity of the mixture. The purpose of this study was to evaluate whether a mechanistic, integrated, dynamic environmental fate and bioaccumulation multimedia model (CoZMoMAN) can reconcile what is known about environmental emissions and human exposure of SCCPs in the Nordic environment. Realistic SCCP emission scenarios, resolved by formula group, were estimated and used to predict composition and concentrations of SCCPs in the environment and the human food chain. Emissions at the upper end of the estimated range resulted in predicted total concentrations that were often within a factor of 6 of observations. Similar model performance for a complex group of organic contaminants as for the well-known polychlorinated biphenyls strengthens the confidence in the CoZMoMAN model and implies a relatively good mechanistic understanding of the environmental fate of SCCPs. However, the degree of chlorination predicted for SCCPs in sediments, fish, and humans was higher than observed and poorly established environmental half-lives and biotransformation rate constants contributed to the uncertainties in the predicted composition and ΣSCCPs concentrations. Improving prediction of SCCPs composition will also require better constrained estimates of the composition of SCCP emissions. There is, however, also large uncertainty and lack of coherence in the existing observations, and better model-measurement agreement will require improved analytical methods and more strategic sampling. More measurements of SCCPs levels and composition in samples from background regions are particularly important.acceptedVersio

Development of human biotransformation QSARs and application for PBT assessment refinement

Toxicokinetics heavily influence chemical toxicity as the result of Absorption, Distribution, Metabolism (Biotransformation) and Elimination (ADME) processes. Biotransformation (metabolism) reactions can lead to detoxification or, in some cases, bioactivation of parent compounds to more toxic chemicals. Moreover, biotransformation has been recognized as a key process determining chemical half-life in an organism and is thus a key determinant for bioaccumulation assessment for many chemicals. This study addresses the development of QSAR models for the prediction of in vivo whole body human biotransformation (metabolism) half-lives measured or empirically-derived for over 1000 chemicals, mainly represented by pharmaceuticals. Models presented in this study meet regulatory standards for fitting, validation and applicability domain. These QSARs were used, in combination with literature models for the prediction of biotransformation half-lives in fish, to refine the screening of the potential PBT behaviour of over 1300 Pharmaceuticals and Personal Care Products (PPCPs). The refinement of the PBT screening allowed, among others, for the identification of PPCPs, which were predicted as PBTs on the basis of their chemical structure, but may be easily biotransformed. These compounds are of lower concern in comparison to potential PBTs characterized by large predicted biotransformation half-lives

Development and Evaluation of a Database of Dietary Bioaccumulation Test Data for Organic Chemicals in Fish

Dietary bioaccumulation tests for fish have been conducted for about 40 years. Standardized test guidance has recently been developed. Test metrics of primary scientific and regulatory interest are the whole body depuration rate constant (<i>k</i>_T), whole body growth corrected depuration rate constant (<i>k</i>_Tg), and corresponding chemical half-lives (<i>t</i>_1/2 and <i>t</i>_1/2g), dietary chemical absorption efficiency (AE), and biomagnification factor (BMF). A database of 3032 measurement end points for 477 discrete organic chemicals including 964 half-lives, 1199 AEs and 869 BMFs from 19 species (primarily trout and carp) was developed from the literature. Biological properties (e.g., organism weight, lipid content) and exposure conditions (e.g., temperature, feeding rate, dietary lipid content, exposure duration) are documented. Test chemicals range in molar mass from 120 to 1423 g·mol^–1 with log octanol–water partition coefficients (<i>K</i>_OW) ranging from 0.8 to 14.3; 50% of the database entries are for polychlorinated biphenyls. The measured end points are derived from various protocols and sources of variability are described. The data are evaluated and categorized using proposed data quality (confidence) criteria derived from the standardized test protocol providing initial guidance for data users. Half-lives range from 0.13 to 2600 days; however, approximately 54% have an identifiable source of uncertainty. The data suggest that chemicals absorbed from the gastrointestinal tract with a log <i>K</i>_OW ≥ ∼5 and at least as high as ∼9 have biomagnification potential in fish. A mechanistic bioaccumulation model is compared to the measured data and used to illustrate the influence of growth and biotransformation rates on the BMF

Development and Evaluation of a Database of Dietary Bioaccumulation Test Data for Organic Chemicals in Fish

Dietary bioaccumulation tests for fish have been conducted for about 40 years. Standardized test guidance has recently been developed. Test metrics of primary scientific and regulatory interest are the whole body depuration rate constant (<i>k</i>_T), whole body growth corrected depuration rate constant (<i>k</i>_Tg), and corresponding chemical half-lives (<i>t</i>_1/2 and <i>t</i>_1/2g), dietary chemical absorption efficiency (AE), and biomagnification factor (BMF). A database of 3032 measurement end points for 477 discrete organic chemicals including 964 half-lives, 1199 AEs and 869 BMFs from 19 species (primarily trout and carp) was developed from the literature. Biological properties (e.g., organism weight, lipid content) and exposure conditions (e.g., temperature, feeding rate, dietary lipid content, exposure duration) are documented. Test chemicals range in molar mass from 120 to 1423 g·mol^–1 with log octanol–water partition coefficients (<i>K</i>_OW) ranging from 0.8 to 14.3; 50% of the database entries are for polychlorinated biphenyls. The measured end points are derived from various protocols and sources of variability are described. The data are evaluated and categorized using proposed data quality (confidence) criteria derived from the standardized test protocol providing initial guidance for data users. Half-lives range from 0.13 to 2600 days; however, approximately 54% have an identifiable source of uncertainty. The data suggest that chemicals absorbed from the gastrointestinal tract with a log <i>K</i>_OW ≥ ∼5 and at least as high as ∼9 have biomagnification potential in fish. A mechanistic bioaccumulation model is compared to the measured data and used to illustrate the influence of growth and biotransformation rates on the BMF

Model for Screening-Level Assessment of Near-Field Human Exposure to Neutral Organic Chemicals Released Indoors

Screening organic chemicals for hazard and risk to human health requires near-field human exposure models that can be readily parametrized with available data. The integration of a model of human exposure, uptake, and bioaccumulation into an indoor mass balance model provides a quantitative framework linking emissions in indoor environments with human intake rates (<i>iR</i>s), intake fractions (<i>iF</i>s) and steady-state concentrations in humans (<i>C</i>) through consideration of dermal permeation, inhalation, and nondietary ingestion exposure pathways. Parameterized based on representative indoor and adult human characteristics, the model is applied here to 40 chemicals of relevance in the context of human exposure assessment. Intake fractions and human concentrations (<i>C</i>_U) calculated with the model based on a unit emission rate to air for these 40 chemicals span 2 and 5 orders of magnitude, respectively. Differences in priority ranking based on either <i>iF</i> or <i>C</i>_U can be attributed to the absorption, biotransformation and elimination processes within the human body. The model is further applied to a large data set of hypothetical chemicals representative of many in-use chemicals to show how the dominant exposure pathways, <i>iF</i> and <i>C</i>_U change as a function of chemical properties and to illustrate the capacity of the model for high-throughput screening. These simulations provide hypotheses for the combination of chemical properties that may result in high exposure and internal dose. The model is further exploited to highlight the role human contaminant uptake plays in the overall fate of certain chemicals indoors and consequently human exposure