Residual behavior and dietary intake risk assessment of flonicamid, dinotefuran and its metabolites on peach trees.

BACKGROUND: Flonicamid and dinotefuran are widely applied to control pests and diseases in various economic crops arousing much public concerns about the potential risk to human health. In this study, the multi-determination and residual behavior of flonicamid-dinotefuran mixture on peach trees were investigated. The chronic risk of long-term dietary intake for Chinese consumers was evaluated. RESULTS: An optimized QuEChERS method combined with ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis for simultaneous determination of flonicamid, dinotefuran and its metabolites was established to analyze the residual dissipation and terminal residues in peach matrices. The results demonstrated that (i) a satisfactory linearity relationship with the detector response and the correlation coefficient R2 > 0.999, the average recoveries of these four analytes ranged from 94 to 108%, the relative standard deviation was between 1.0% and 8.8%, and the limit of the quantitation was 0.02 mg kg-1 ; (ii) the dissipation behaviors of flonicamid and dinotefuran followed with the first-order dynamic kinetics model, and the half-lives were 6.9-12.4 days and 8.1-15.1 days, respectively; (iii) the recommended preharvest interval (PHI) was 21 days, the risk quotient (RQ) values of flonicamid and dinotefuran were 16.6 and 20.7%, respectively, which were significantly less than 100%. CONCLUSION: The established analytical method met the detection requirement in terms of sensitivity, accuracy, and precision. Additionally, the results indicated that the potential dietary intake risk of the flonicamid-dinotefuran mixture on peach trees was negligible. This work can be utilized in the safe and responsible use of flonicamid-dinotefuran mixture and provide guidance for establishing its maximum residue limit (MRL) in China. © 2021 Society of Chemical Industry.

Hazard assessment using an in-silico toxicity assessment of the transformation products of boscalid, pyraclostrobin, fenbuconazole and glyphosate generated by exposure to an advanced oxidative process.

Agricultural pesticide use is ongoing and consumer concern regarding the safety of pesticide residues on produce has generated interest in techniques that can safely reduce residues post-harvest. Recently an advanced oxidative process has shown promise in substantial residue reduction on the surface of produce. Given the potential for oxidative transformation of pesticides to generate transformation products with greater toxicity than the parent residue, take for example the oxon products of the organophosphorus insecticides, it is important to consider what transformation products are generated by pesticide exposure to an oxidative process and their potential toxicity. In this study, previously published transformation products of boscalid, pyraclostrobin, fenbuconazole and glyphosate were identified after exposure to 3% hydrogen peroxide, UV-C irradiation or their combination in an advanced oxidative process on glass, their oral toxicity, carcinogenicity and developmental toxicity were identified in-silico and an initial tier hazard assessment was conducted. Of the 87 total structures that were searched for, 53 were detected by UPLC-QTOF-MS and identified by mass spectra: 15, 13, 22 and 3 structures for boscalid, pyraclostrobin, fenbuconazole and glyphosate respectively, including the parent residues. Oral toxicity of the transformation products of pyraclostrobin and glyphosate was similar to or lower than the parent residue. Several transformation products of boscalid and fenbuconazole were estimated to be significantly more orally toxic than their parent residues. While the majority of the transformation products of boscalid, pyraclostrobin and fenbuconazole were predicted to be carcinogenic there were 11 that were consistently identified to have carcinogenic potential by several assessments. 29 of the 53 molecules were predicted to be probable developmental toxicants. An initial tier hazard assessment was conducted for Cramer rules classification and mutagenicity using the threshold of toxicological concern approach and predicted rat oral LD50. Two exposure scenarios were considered, one highly protective considering each transformation product to be at the highest maximum residue limit (MRL) for the pesticide and whole produce consumption at the highest consumption rate from the USEPA Exposures Handbook, the other considering only apple consumption with the relevant MRL. As indicated by the hazard assessment, several transformation products of boscalid, pyraclostrobin and fenbuconazole should be strongly considered for further testing, either by quantifying their production or in-vivo and in-vitro toxicity tests due to their predicted toxicity and associated hazard.

Validation, residue analysis, and risk assessment of fipronil and flonicamid in cotton (Gossypium sp.) samples and soil.

Cotton crop is highly susceptible to attack by sucking pests. Being an important oilseed and feed crop, it is essential to monitor the pesticides and ensure health protection at consumer level. Therefore, a method was validated to estimate fipronil and flonicamid in various cotton samples and risk assessment was performed. Contamination of oil in the extracts from the various oil seeds and cake samples is a major problem as this oil contaminates the column and interferes with the detection of pesticides. The present manuscript for the first time describes successful analysis of the pesticides from various cotton samples including cotton oil, seed, and cake. Quick, easy, cheap, effective, rugged, and safe (QuEChERS)-based methods were validated for estimation of fipronil and flonicamid in cotton samples and in soil by LC-MS/MS. Recoveries were within the acceptable range of 70-120% with relative standard deviation ≤ 20% and HorRat values < 0.3-1.3. R2 was > 0.99. Matrix effects of 150 and 13.5% were observed for fipronil and flonicamid, respectively, in cotton leaves. Limits of quantitation (LOQs) were in the range of 0.0004 to 0.004 mg kg-1 for fipronil and flonicamid. Cotton samples collected from a field study at different locations were analyzed. Half-life ranged from 2.2 to 5.8 for fipronil and 4.6 to 7.0 days for flonicamid. A pre-harvest interval of 33 days is suggested. The risk assessment studies at maximum residue level values showed HQ < 1 at pre-harvest interval (PHI). The methods being short and easy can be extended to estimate more types of pesticides in different oilseeds. Following a PHI of 33 days, fipronil and flonicamid can be used on cotton at standard dose. As the levels of fipronil and flonicamid were below determination limit in all the soils, the environmental risk is negligible.

The Kidd (JK) Blood Group System.

The Kidd blood group system was discovered in 1951 and is composed of 2 antithetical antigens, Jka and Jkb, along with a third high-incidence antigen, Jk3. The Jk3 antigen is expressed in all individuals except those with the rare Kidd-null phenotype. Four Kidd phenotypes are therefore possible: Jk(a+b-), Jk(a-b+), Jk(a+b+), and Jk(a-b-). The glycoprotein carrying the Kidd antigens is a 43-kDa, 389-amino acid protein with 10 membrane-spanning domains which functions as a urea transporter on endothelial cells of the renal vasa recta as well as erythrocytes. The HUT11/UT-B/JK (SLC14A1) gene encoding this glycoprotein is located on chromosome 18q12-q21. The Jka and Jkb antigens are the result of a single-nucleotide polymorphism present at nucleotide 838 resulting in an aspartate or asparagine amino acid at position 280, respectively. The Kidd blood group can create several difficult transfusion situations. Besides the typical acute hemolytic transfusion reactions common to all clinically relevant blood group antigens, the Kidd antigens are notorious for causing delayed hemolytic transfusion reactions due to the strong anamnestic response exhibited by antibodies directed against Kidd antigens. The Kidd-null phenotype is extremely rare in most ethnic groups, but is clinically significant due to the ability of those with the Kidd-null phenotype to produce antibodies directed against the high-incidence Jk3 antigen. Anti-Jk3 antibodies behave in concordance with anti-Jka or anti-Jkb possessing the capability to cause both acute and delayed hemolytic reactions. Antibodies against any of the 3 Kidd antigens can also be a cause of hemolytic disease of the fetus and newborn, although this is generally mild. In this review, we will outline the makeup of the Kidd system from its historical discovery to the details of the Kidd gene and glycoprotein, and then discuss the practical aspects of Kidd antibodies and transfusion reactions with an extended focus on the Kidd-null phenotype. We will end with a brief discussion of the donor aspects related to the screening and supply management of blood from donors with the rare Jk(a-b-) phenotype.

The influence of effective microorganisms (EM) and yeast on the degradation of strobilurins and carboxamides in leafy vegetables monitored by LC-MS/MS and health risk assessment.

The aim of this study was to determine the behaviour of strobilurin and carbocyamides commonly used in chemical protection of lettuce depending on carefully selected effective microorganisms (EM) and yeast (Y). Additionally, the assessment of the chronic health risk during a 2-week experiment was performed. The statistical method for correlation of physico-chemical parameters and time of degradation for pesticides was applied. In this study, the concentration of azoxystrobin, boscalid, pyraclostrobin and iprodione using liquid chromatography-mass spectrometry (LC-MS/MS) in the matrix of lettuce plants was performed, and there was no case of concentration above maximum residues levels. Before harvest, four fungicides and their mixture with EM (1 % and 10 %) and/or yeast 5 % were applied. In our work, the mixtures of 1%EM + Y and 10%EM + Y both stimulated and inhibited the degradation of the tested active substances. Adding 10%EM to the test substances strongly inhibited the degradation of iprodione, and its concentration decreased by 30 %, and in the case of other test substances, the degradation was approximately 60 %. Moreover, the addition of yeast stimulated the distribution of pyraclostrobin and boscalid in lettuce leaves. The risk assessment for the pesticides ranged from 0.4 to 64.8 % on day 1, but after 14 days, it ranged from 0.0 to 20.9 % for children and adults, respectively. It indicated no risk of adverse effects following exposure to individual pesticides and their mixtures with EM and yeast.

Assessment of hypolipidaemic activity of three thiazolidin-4-ones in mice given high-fat diet and fructose.

Three 4-thiazolidinones, two with nicotinamide (NAT1 and NAT2) and one with 4-chlorophenoxyacetamide (PAT1) side chains were evaluated for their hypolipidaemic, hypoglycaemic activity in Swiss albino mice fed a high-fat diet along with fructose administered in drinking water. NAT1 and PAT caused reduction of elevated triglycerides, cholesterol and glucose; NAT2 was effective only against triglycerides. Nicotinamide side chain might have contributed to the lipid lowering effect of both NAT1 and NAT2, but the bulky group of the latter could have affected proper binding to the receptor sites, making it ineffective against elevated cholesterol. On the other hand, the 4-chlorophenoxyacetamide side chain of PAT might have exerted powerful hypolipidaemic activity, despite the bulky substitution at C2. As antioxidants, NAT2 and PAT1 showed superior activity, compared to NAT1. The thiazolidinone ring might be responsible for the lipid lowering effect, which is however, modified by the type of substitutions at C2 and N of the ring. Detailed study is warranted to explain the mechanism of action of these compounds as also to make more potent ones.

Final report of the safety assessment of niacinamide and niacin.

Niacinamide (aka nicotinamide) and Niacin (aka nicotinic acid) are heterocyclic aromatic compounds which function in cosmetics primarily as hair and skin conditioning agents. Niacinamide is used in around 30 cosmetic formulations including shampoos, hair tonics, skin moisturizers, and cleansing formulations. Niacin is used in a few similar product types. The concentration of use of Niacinamide varies from a low of 0.0001% in night preparations to a high of 3% in body and hand creams, lotions, powders and sprays. Niacin concentrations of use range from 0.01% in body and hand creams, lotions, powders and sprays to 0.1% in paste masks (mud packs). Both ingredients are accepted for use in cosmetics in Japan and the European Union. Both are GRAS direct food additives and nutrient and/or dietary supplements. Niacinamide may be used in clinical treatment of hypercholesteremia and Niacin in prevention of pellegra and treatment of certain psychological disorders. Both ingredients are readily absorbed from skin, blood, and the intestines and widely distribute throughout the body. Metabolites include N1-methylnicotinamide and N1-methyl-4-pyridone-3-carboxamide. Excretion is primarily through the urinary tract. While Niacinamide is more toxic than Niacin in acute toxicity studies, both are relatively non-toxic. Short-term oral, parenteral, or dermal toxicity studies did not identify significant irreversible effects. Niacinamide, evaluated in an in vitro test to predict ocular irritation, was not an acute ocular hazard. Animal testing of Niacinamide in rabbits in actual formulations produced mostly non-irritant reactions, with only some marginally irritating responses. Skin irritation tests of up to 2.5% Niacinamide in rabbits produced only marginal irritation. Skin sensitization tests of Niacinamide at 5% during induction and 20% during challenge were negative in guinea pigs. Neither cosmetic ingredient was mutagenic in Ames tests, with or without metabolic activation. Niacinamide and Niacin at 2 mg/ml were negative in a chromosome aberration test in Chinese hamster ovary cells, but did produce large structural chromosome aberrations at 3 mg/ml. Niacinamide induced sister chromatid exchanges in Chinese hamster ovary cells, but Niacin did not. Under certain circumstances, Niacinamide can cause an increase in unscheduled DNA synthesis in human lymphocytes treated with UV or a nitrosoguanidine compound. Niacinamide itself was not carcinogenic when administered (1%) in the drinking water of mice. No data on the carcinogenic effect of Niacin were available. Niacinamide can moderate the induction of tumors by established carcinogens. Niacinamide in combination with streptozotocin (a nitrosourea compound) or with heliotrine (a pyrrolizidine alkaloid), produced pancreatic islet tumors. On the other hand, Niacinamide reduced the renal adenomas produced by streptozotocin; and intestinal and bladder tumors induced by a preparation of bracken fern. Niacinamide evaluated in in vitro test systems did affect development, but Niacinamide reduced the reproductive/developmental toxicity of 2-aminonicotinamide-amino-1,3,4-thiadiazole hydrochloride and urethane. Clinical testing of Niacinamide produced no stinging sensation at concentrations up to 10%, use tests produced no irritation at concentrations up to 5%, and a 21-day cumulative irritation test at concentrations up to 5% resulted in no irritancy. Niacinamide was not a sensitizer, nor was it a photosensitizer. The CIR Expert Panel considered that Niacinamide and Niacin are sufficiently similar from a toxicologic standpoint to combine the available data and reach a conclusion on the safety of both as cosmetic ingredients. Overall, these ingredients are non-toxic at levels considerably higher than would be experienced in cosmetic products. Clinical testing confirms that these ingredients are not significant skin irritants, sensitizers or photosensitizers. While certain formulations were marginal to slight ocular irritants, other formulations were not. Niacinamide, while not carcinogenic alone, can modulate the induction of tumors by certain established carcinogens. The Panel noted that the doses in these studies are high relative to the low concentrations at which Niacinamide is used in cosmetic formulations. In neither case (tumor protection or tumor promotion) are these findings considered relevant to the use of Niacinamide at its current low concentrations of use in cosmetics. Both ingredients were considered safe as used in cosmetics.