A total of 33 pesticides have been banned from Chinese medicinal materials and decoction pieces(plants) according to Chinese Pharmacopoeia(2020 edition). According to the chemical structures, they are mainly divided into seven categories: organophosphorus compounds, organochlorines, carbamates, amidines, sulfonylureas, phenylpyrazoles, and ethers. These banned pesticides exhibit neurotoxicity, reproductive toxicity, immune system toxicity, teratogenicity, carcinogenesis, and mutagenesis, seriously damaging human and animal health. They affect not only the quality and safety of traditional Chinese medicines and resulting products, but also their competitiveness in the international market. Due to the numerous varieties of traditional Chinese medicines and their complex substrates, it is necessary to establish a universal and highly sensitive method for pesticide residue detection. This review systematically summarized the residual status, toxicity, and analytical methods of banned pesticides in traditional Chinese medicines, and forecasted the prospects of different analytical techniques, so as to provide reference for further safety and risk assessment of banned pesticide residues in traditional Chinese medicines, thus ensuring the safe production of traditional Chinese medicines.
China ; Drugs, Chinese Herbal/toxicity* ; Humans ; Medicine, Chinese Traditional ; Organophosphorus Compounds ; Pesticide Residues/toxicity* ; Pesticides/analysis*

Objective: Bioinformatics methods were used to mine differentially expressed genes (DEGs) and enriched signal pathways induced by chronic pesticide exposure, and explore its potential pathogenic mechanisms and key genes. Methods: In July 2021, high-throughput gene expression profile data related to pesticide toxicity was downloaded from Gene Expression Omnibus (GEO) database to obtain DEGs. The samples were from American male farm workers who had been exposed to pesticides for a long time and other industry workers. The functional enrichment analysis of GO, KEGG and Geme Set Enrichment Analysis (GSEA) were performed by R package clusterProfiler. STRING, Cytoscape and other tools were applied to construct and visualize the protein interaction network. With the help of MCODE and Cytohubba plugins, gene function modules were obtained, and hub gene was screened out. Results: 189 DEGs were screened from GSE30335 dataset, including 101 up-regulated genes and 88 down-regulated genes. The results of GO, KEGG and GSEA were mainly enriched in biological functions such as regulation of neuron projection development, regulation of locomotion, ribosomal protein synthesis, and pathways related to complex nervous system diseases such as Parkinson's disease. And the comprehensive screening showed that KLF1 was the hub gene of pesticide exposure, with a fold change of 0.456 (t=-3.82, P=0.021) . Conclusion: Long term exposure to pesticides results in the differential expression of multiple genes in the exposed population, which may be involved in the pathological changes of nervous system by down regulating KLF1 and related biological pathways.
Computational Biology/methods* ; Gene Expression Profiling/methods* ; Gene Regulatory Networks ; Genetic Association Studies ; Humans ; Male ; Pesticides/toxicity*

We designed and fabricated a novel high throughput brain-on-chip with three dimensional structure with the aim to simulate the in vivo three-dimensional growth environment for brain tissues. The chip consists of a porous filter and 3D brain cell particles, and is loaded into a conventional 96-well plate for use. The filter and the particle molds were fabricated by using computer modeling, 3D printing of positive mold and agarose-PDMS double reversal mold. The 3D cell particles were made by pouring and solidifying a suspension of mouse embryonic brain cells with sodium alginate into a cell particle mold, and then cutting the resulting hydrogel into pieces. The loaded brain-on-chip was used to determine the neurotoxicity of pesticides. The cell particles were exposed to 0, 10, 30, 50, 100 and 200 µmol/L of chlorpyrifos or imidacloprid, separated conveniently from the medium by removing the porous filter after cultivation. Subsequently, cell proliferation, acetylcholinesterase activity and lactate dehydrogenase release were determined for toxicity evaluation. The embryonic brain cells were able to grow and proliferate normally in the hydrogel particles loaded into the filter in a 96-well plate. Pesticide neurotoxicity test showed that both chlorpyrifos and imidacloprid presented dose-dependent inhibition on cell growth and proliferation. Moreover, the pesticides showed inhibition on acetylcholinesterase activity and increase release of lactate dehydrogenase. However, the effect of imidacloprid was significantly weaker than that of chlorpyrifos. In conclusion, a novel brain-on-chip was developed in this study, which can be used to efficiently assess the drug neurotoxicity, pharmacodynamics, and disease mechanism by combining with a microtiterplate reader.
Animals ; Brain ; Chlorpyrifos/toxicity* ; Culture Media ; Mice ; Oligonucleotide Array Sequence Analysis ; Pesticides/toxicity*

BACKGROUND/AIMS: Most pesticide formulations contain both chief and additive ingredients. But, the additives may not have been tested as thoroughly as the chief ingredients. The surfactant, nonyl phenoxypolyethoxylethanol (NP40), is an additive frequently present in pesticide formulations. We investigated the effects of NP40 and other constituents of a validamycin pesticide formulation on cell viability and on the expression of genes involved in cell damage pathways. METHODS: The effects of validamycin pesticide ingredients on cell viability and of NP40 on the mRNA expression of 80 genes involved in nine key cellular pathways were examined in the human neuroblastoma SK-N-SH cell line. RESULTS: The chemicals present in the validamycin pesticide formulation were cytotoxic to SK-N-SH cells and NP40 showed the greatest cytotoxicity. A range of gene expression changes were identified, with both up- and down-regulation of genes within the same pathway. However, all genes tested in the necrosis signaling pathway were down-regulated and all genes tested in the cell cycle checkpoint/arrest pathway were up-regulated. The median fold-change in gene expression was significantly higher in the cell cycle checkpoint/arrest pathway than in the hypoxia pathway category (p = 0.0064). The 70 kDa heat shock protein 4 gene, within the heat shock protein/unfolded protein response category, showed the highest individual increase in expression (26.1-fold). CONCLUSIONS: NP40 appeared to be particularly harmful, inducing gene expression changes that indicated genotoxicity, activation of the cell death (necrosis signaling) pathway, and induction of the 70 kDa heat shock protein 4 gene.
Aged ; Cell Cycle Checkpoints/drug effects/genetics ; Cell Line, Tumor ; Cell Survival/drug effects ; Dose-Response Relationship, Drug ; Female ; Gene Expression Regulation/drug effects ; Genes, cdc ; HSP110 Heat-Shock Proteins/genetics/metabolism ; Humans ; Inositol/*analogs & derivatives/chemistry/poisoning ; Necrosis ; Neurons/*drug effects/metabolism/pathology ; Nonoxynol/chemistry/*toxicity ; Pesticides/chemistry/*poisoning ; RNA, Messenger/metabolism ; Signal Transduction/drug effects ; Surface-Active Agents/chemistry/*toxicity

To determine the correlation between the working environment and the health status of employees in solar greenhouse, 1171 employees were surveyed. The results show the 'Greenhouse diseases' are affected by many factors. Among general uncomforts, the morbidity of the bone and joint damage is the highest and closely related to labor time and age. Planting summer squash and wax gourd more easily cause skin pruritus. Asthma-related cough, eye disease, and skin pruritus are significantly correlated with the cultivation of wax gourd. The application of inorganic fertilizer and fertigation dramatically induce the bone and joint damage. The smell of covering film greatly influence skin pruritus. Personal protection is badly scanty and normative occupational health and safety need to be completed.
Adult ; Asthma ; chemically induced ; Cough ; chemically induced ; Crops, Agricultural ; Educational Status ; Environment, Controlled ; Eye Diseases ; chemically induced ; Fertilizers ; toxicity ; Humans ; Middle Aged ; Nose Diseases ; chemically induced ; Occupational Exposure ; Pesticides ; toxicity ; Pruritus ; chemically induced ; Risk Factors ; Stomach Diseases ; chemically induced ; Workplace

The development of the kidneys and other organs of the urinary tract follows the natural rule of gene-environment-lifestyle interaction. Both intrinsic and extrinsic factors may be associated with the etiology of various kinds of urinary malformations, but the environmental factor is an extrinsic factor. Related literatures were reviewed in this paper, which focuses on the association of congenital urinary malformations with possible environmental factors. It is concluded that urinary malformation is associated with low birth weight, maternal disease, placental insufficiency, maternal drug exposure, and maternal exposure to environmental pesticides. Living environment and socioeconomic factors may also influence the incidence of urinary malformation.
Female ; Fetus ; drug effects ; Gene-Environment Interaction ; Humans ; Infant, Low Birth Weight ; Pesticides ; toxicity ; Placental Insufficiency ; Pregnancy ; Socioeconomic Factors ; Urinary Tract ; abnormalities

Epidemiological studies have suggested an association between pesticide exposure and Parkinson's disease. In this study, we examined the neurotoxicity of an organochlorine pesticide, heptachlor, in vitro and in vivo. In cultured SH-SY5Y cells, heptachlor induced mitochondria-mediated apoptosis. When injected into mice intraperitoneally on a subchronic schedule, heptachlor induced selective loss of dopaminergic neurons in the substantia nigra pars compacta. In addition, the heptachlor injection induced gliosis of microglia and astrocytes selectively in the ventral midbrain area. When the general locomotor activities were monitored by open field test, the heptachlor injection did not induce any gross motor dysfunction. However, the compound induced Parkinsonism-like movement deficits when assessed by a gait and a pole test. These results suggest that heptachlor can induce Parkinson's disease-related neurotoxicities in vivo.
Animals ; *Apoptosis ; Astrocytes/drug effects/pathology ; Cell Line, Tumor ; Cells, Cultured ; Dopaminergic Neurons/*drug effects/pathology ; Gait ; Heptachlor/*toxicity ; Humans ; *Locomotion ; Mice ; Neurotoxicity Syndromes/etiology/physiopathology ; Parkinsonian Disorders/chemically induced ; Pesticides/*toxicity ; Substantia Nigra/*drug effects/pathology/physiopathology

OBJECTIVETo analyze the results of the first-stage toxicological evaluation of 1 502 pesticide samples.

METHODSThe classification of the 1 502 pesticide samples was analyzed, and the experimental results of the samples in different years were compared.

RESULTSMost of the 1 502 pesticide samples were insecticides, accounting for 52.5% of all, followed by bactericides and herbicides. In the 5 years, the proportion of biogenic insecticides showed a significant rising trend (χ² = 11.426, P < 0.05). The proportion of single pesticides was 65.8%; mixed pesticides accounted for 32.7%; original pesticides accounted for only 1.5%. From 2008 to 2012, most pesticides had low toxicity, regardless of the exposure route (via the mouth, skin, or respiratory tract). Acute oral and dermal toxicity tests showed that pesticides with moderate toxicity declined year by year (oral exposure χ² = 18.036, P < 0.01; dermal exposure χ² = 40.482, P < 0.01). There was a small proportion of pesticides with high toxicity. We did not detect any pesticide with extreme toxicity. Acute skin irritation and eye irritation test showed an upward trend in proportion of non-irritating pesticides (χ² = 77.110, P < 0.01; χ² = 12.693, P < 0.05), while the proportion of medium-irritation pesticides decreased significantly (χ² = 18.941, P < 0.01; χ² = 13.129, P < 0.05). Sensitization test showed that all samples were weak sensitizers.

CONCLUSIONThe major type of investigated pesticides was insecticide. Most samples were single pesticides, and there was a certain proportion of mixed pesticides. Novel pesticides such as bio-pesticides are the development tendency. The tested pesticides were mainly low-toxicity pesticides, with a certain proportion of medium- and high-toxicity pesticides. Personal protection should be strengthened during production and use of pesticides.

Animals ; Pesticides ; classification ; toxicity ; Toxicity Tests, Acute

OBJECTIVETo establish the threshold of toxicological concern(TTC) approach and to apply it in the risk assessment of metabolites, degradation and reaction products of pirimicarb.

METHODSTTC decision tree approach based on Cramer classification was established and Lazar software was used to predict the genotoxicity of the seven transformation products of pirimicarb, namely, R34836, R34885, R35140, R31805, R34865, R16210 and R16192. Dietary exposure in general population as well as in six age population groups was estimated by using data from the Chinese National Nutrition and Health Survey and pirimicarb residue data from national chemical surveillance data in 2011. TTC decision tree approach was used for risk assessment and the exposure was compared with the corresponding TTC values.

RESULTSOf the seven transformations of pirimicarb active substance, namely, R34836, R34885, R35140, R31805, R34865, R16210 and R16192, the maximum dietary exposure of mean and large portion(P 97.5) were all belong to 2-6 age group. The mean exposures of the seven transformation products for 2-6 age group,were 0.0290, 0.0207, 0.0015, 0.0320, 0.0005, 0.6918 and 0.1274 µg/kg,respectively, and the corresponding P 97.5 exposures were 0.0817,0.0581,0.0042,0.0900,0.0014, 1.9459 and 0.3585 µg/kg. Besides, the mean and P 97.5 exposure of R16210 for 2-6 age group was the largest,which were 0.6918 and 1.9459 µg/kg, accounting for 46.12% and 129.73% of the TTC threshold,respectively.

CONCLUSIONTTC decision tree approach is a useful tool for prior screening and primary risk assessment of the transformation products of pesticide active substance.

Carbamates ; toxicity ; Food Contamination ; Humans ; Maximum Allowable Concentration ; Pesticide Residues ; toxicity ; Pesticides ; toxicity ; Pyrimidines ; toxicity ; Risk Assessment

Animals ; Humans ; Neurotoxins ; toxicity ; Pesticides ; toxicity ; Pyrethrins ; toxicity ; Toxicology