Pyrethroid insecticides have been broadly used as pest control in agriculture and residential spaces, exerting high effectiveness of insecticidal property and relatively low toxicity to humans. Several animal studies suggested that exposure to pyrethroids may induce hematological abnormalities, thereby altering the number of blood cells and resulting in blood disorders. However, no epidemiologic study has reported on the effect of pyrethroid insecticide exposure on hematological changes, except for occupational exposure. This study aimed to investigate the effect of urinary 3-phenoxybenzoic acid (3-PBA) concentrations on hematological parameters in a representative South Korean adult population. We analyzed data from 6296 adults enrolled in the Korean National Environmental Health Survey (2012–2014). We employed multiple linear regression analysis to evaluate the association of urinary 3-PBA levels with eight hematological profiles: white blood cells (WBCs), red blood cells (RBCs), hemoglobin, hematocrit, platelets, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC). The urinary 3-PBA levels were negatively associated with WBC, RBC, and hemoglobin levels and positively associated with MCV levels. The direction and magnitude of the association between the 3-PBA and hematological parameters varied according to sex and age. The adverse effects of 3-PBA on hematological parameters were distinctive among males aged 60 years and older. In this age group, 3-PBA levels were negatively associated with the WBC, RBC, hemoglobin, hematocrit, and MCHC levels among males. This study is the first to verify that urinary 3-PBA concentrations at the levels found in a Korean population are associated with blood parameters. This finding merits further investigation to understand the impact of 3-PBA on human blood function and public health.
|Journal||International Journal of Hygiene and Environmental Health|
|Publication status||Published - 2022 Jun|
Bibliographical noteFunding Information:
Once pyrethroids enter the body, they are rapidly detoxified by carboxylesterase-mediated hydrolysis, produce several metabolites (e.g., 3-PBA, trans-DCCA, cis/trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (cis/trans-DCCA), 4-fluoro-3-phenoxybenzoic acid (4-F-3PBA), and cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropanecarboxylic acid (DBCA)), and are eliminated in the urine (Barr et al., 2010). Therefore, these metabolites are widely used as biomarkers for exposure to pyrethroids. Pyrethroids and their metabolite 3-PBA penetrate various organs, including blood, causing adverse effects on humans. Although the biological mechanisms by which pyrethroids affect blood function have yet to be fully clarified, multiple pathways may be involved. For example, cell destruction, decreased or delayed mitosis in hematopoietic progenitor cultures, production of immature granulocytes and RBCs due to the destruction of the cells of myeloid lineage, marrow cellular apoptosis, fewer leukocytes by a diminished function of the immune system, and oxidative stress induced by the pyrethroid chemicals are considered major mechanisms (Arif et al., 2020; Chatterjee et al., 2013; Mandarapu and Prakhya, 2015; Wang et al., 2016). Mandarapu and Prakhya (2015) demonstrated that bone marrow is one of the most sensitive tissues against pyrethroids, and that several pyrethroid metabolites destroy hematopoietic progenitor cells in the bone marrow, inhibit blood cell production, and finally cause degenerative diseases such as aplastic anemia. Several studies have suggested that pyrethroids destroy erythropoietin, inhibiting red blood cell and heme production, which decreases the number of RBCs, hemoglobin, and hematocrit in the blood (Khan et al., 2012; Manna et al., 2004). Other studies have reported that pyrethrin-induced oxidative stress leads to immune toxicity, resulting in leukopenia (ATSDR, 2003; Khan et al., 2012). Therefore, this study's observations that urinary 3-PBA decreased the WBC, RBC, hemoglobin, and hematocrit levels were supported by plausible biological explanations.Different associations according to sex were found between the urinary 3-PBA levels and hematological parameters in this study. Our results showed that the urinary 3-PBA levels were negatively associated with RBC, hemoglobin, hematocrit, and MCHC among males; however, no significant association was found among females, and lower WBC and elevated MCV levels were observed only in females as well. Few epidemiological studies have observed sex-specific associations between 3-PBA and hematological parameters, making it difficult to compare the results of this study which are supported only by the results of studies on males (Hassanin et al., 2018; Shearer et al., 2019). Shearer et al. (2019) observed lower RBC counts and higher granulocytes in samples of male farmers exposed to permethrin, indicating an association with multiple myeloma development. Although clear mechanisms for the sex-dependent association are not yet available, the following mechanisms may partially explain such differences. First, 3-PBA directly interacts with the receptor of sex hormones (estrogen and androgen) and adversely affects blood function. Generally, androgen in men acts on the bone marrow to produce erythropoietin, generating red blood cells and hemoglobin or promoting erythropoietin production in the kidneys, whereas estrogen in women inhibits this action (Murphy, 2014). 3-phenoxybenzyl alcohol (3-PBA1c), which is degraded into 3-PBA, is known to induce an anti-androgenic activity (Tyler et al., 2000). Thus, it could be inferred that 3-PBA inhibits blood cell production by disturbing the action of sex hormones in men. In addition, the endocrine-disrupting effects of pyrethroids may indirectly affect hematological parameters. 3-PBA interferes with the reproductive function related to the hypothalamic-pituitary-gonadal axis or transforms the metabolism and transport of sex steroid hormones (Ye and Liu, 2019). Also a neurotoxicant, pyrethroids target voltage-gated sodium channels and calcium channels and disrupt sex steroid hormone gene expression (Ye and Liu, 2019). This implies that abnormal sex hormone-related properties induced by pyrethroids or 3-PBA may impact the hematopoietic system. Finally, gender differences in the metabolism and excretion of 3-PBA can be explained. An in vivo study reported that the excretion rate of 3-PBA1c and 3-peoxybenzaldehyde in female mice was much faster than that in male mice (Ueyama et al., 2010). However, further studies are needed to verify these mechanisms due to insufficient evidence on the different vulnerabilities by sex.This study was supported by the Pyeongtaek University Environmental Health Center through the researcher training program, funded by the Korea Ministry of Environment, and the Korean National Environmental Health Survey data provided by the Korea Ministry of Environment.
This study was supported by the Pyeongtaek University Environmental Health Center through the researcher training program, funded by the Korea Ministry of Environment , and the Korean National Environmental Health Survey data provided by the Korea Ministry of Environment .
© 2022 Elsevier GmbH
- 3-phenoxybenzoic acid (3-PBA)
- Hematological parameters
- Korean National Environmental Health Survey (KoNEHS)
ASJC Scopus subject areas
- Public Health, Environmental and Occupational Health