ABSTRACT
Pesticide formulation includes solvents (methanol and xylene) and antifreeze (ethylene glycol) whose metabolites are anions such as formic acid, hippuric acid, and oxalate. However, the effect of the anion gap on clinical outcome in acute pesticide intoxication requires clarification. In this prospective study, we compared the anion gap and other parameters between surviving versus deceased patients with acute pesticide intoxication. The following parameters were assessed in 1,058 patients with acute pesticide intoxication: blood chemistry (blood urea nitrogen, creatinine, glucose, lactic acid, liver enzymes, albumin, globulin, and urate), urinalysis (ketone bodies), arterial blood gas analysis, electrolytes (Na(+), K(+), Cl(-) HCO3 (-), Ca(++)), pesticide field of use, class, and ingestion amount, clinical outcome (death rate, length of hospital stay, length of intensive care unit stay, and seriousness of toxic symptoms), and the calculated anion gap. Among the 481 patients with a high anion gap, 52.2% had a blood pH in the physiologic range, 35.8% had metabolic acidosis, and 12.1% had acidemia. Age, anion gap, pesticide field of use, pesticide class, seriousness of symptoms (all P < 0.001), and time lag after ingestion (P = 0.048) were significant risk factors for death in univariate analyses. Among these, age, anion gap, and pesticide class were significant risk factors for death in a multiple logistic regression analysis (P < 0.001). In conclusions, high anion gap is a significant risk factor for death, regardless of the accompanying acid-base balance status in patients with acute pesticide intoxication.
Subject(s)
Anions/chemistry , Biomarkers/chemistry , Pesticides/poisoning , Acid-Base Equilibrium , Acidosis/etiology , Adolescent , Adult , Aged , Aged, 80 and over , Anions/metabolism , Biomarkers/metabolism , Blood Gas Analysis , Chemically-Induced Disorders/mortality , Chemically-Induced Disorders/pathology , Electrolytes/analysis , Female , Humans , Intensive Care Units , Logistic Models , Male , Middle Aged , Odds Ratio , Prospective Studies , Risk Factors , Survival Analysis , Urinalysis , Young AdultABSTRACT
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.
Subject(s)
Inositol/analogs & derivatives , Neurons/drug effects , Nonoxynol/toxicity , Pesticides/poisoning , Surface-Active Agents/toxicity , Aged , Cell Cycle Checkpoints/drug effects , Cell Cycle Checkpoints/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 , HSP110 Heat-Shock Proteins/metabolism , Humans , Inositol/chemistry , Inositol/poisoning , Necrosis , Neurons/metabolism , Neurons/pathology , Nonoxynol/chemistry , Pesticides/chemistry , RNA, Messenger/metabolism , Signal Transduction/drug effects , Surface-Active Agents/chemistryABSTRACT
To determine the change in pesticides used during suicide attempts after the 2012 paraquat (PQ) ban, we evaluated the annual number of suicide attempts by pesticide ingestion between 2011 and 2014. We extracted demographic, clinical outcome, and pesticide class data from the medical records of 1,331 patients that attempted suicide by pesticide ingestion. Pesticides were sorted into 5 groups: herbicides, insecticides, fungicides, other pesticides, and combined pesticides. Each group was subdivided into various classes based on publications by the respective Resistance Action Committees. The chi-square test for trends was used to compare the annual incidence of categorical variables. The total number of suicide attempts decreased each year, from 399 in 2011 to 245 in 2014. Simultaneously, PQ ingestion decreased from 253 patients in 2011 to 60 in 2014. The proportion of PQ to pesticides also decreased from 63.4% in 2011 to 24.5% in 2014. Furthermore, the rate of decrease in the proportion of PQ to all herbicide categories increased by calendar year. In conclusion, there is a significant trend in increased annual number of suicides and proportion of suicides using glyphosates and glufosinates versus total herbicides. However, the number of suicide attempts using glyphosate and glufosinate is lower than that using PQ. The ratio of persons completing suicide to those attempting suicide after pesticide ingestion has decreased every year after the PQ ban.
