Carbendazim Toxicity Study

1. Carbendazim and Reproductive Toxicity:

A sublethal dose of carbendazim administered to male rats for eight weeks caused testicular damage, reproductive toxicity, and endocrine disruption. Rats exposed to carbendazim showed impaired spermatogenesis, reduction in testicular weight, poor sperm motility, and altered hormone levels with low sperm count. Findings in male rats revealed that long-term exposure to carbendazim causes testicular damage, resulting in vacuolization of the germinal epithelium, atrophy in the testicular tubules, marked indentations in the Sertoli cells, fibrosis in the interstitial cells, changes in the mitochondria, and an altered mitochondrial structure with an expanded endoplasmic reticulum, leading to infertility in animals with poor testicular maturation. Similar findings were reported in male goats. Various studies confirm that a sublethal dose of carbendazim and its derivatives also causes abnormal sperm head development, germ cell death, and pathological changes in Leydig cells. Carbendazim alters fetal embryological health at a dose of 160 mg/kg over a period of 6 to 15 days in female rats, causing overt toxicity in the mother, resulting in fetal mental growth retardation, congenital defects, and embryonic lethality. It can lead to skeletal system changes, poor development, delayed mental growth, and disorders of the kidneys and other body organs. Carbendazim and its metabolites, such as 2-aminobenzimidazole, are readily bio-transformable and have low toxicity in mammals, with LD50 values of more than 2000 to 15000 mg/kg, depending on the animal and type of exposure. Different concentrations of carbendazim were administered subchronically to rats for eighty days before mating began. Carbendazim concentrations of 100 and 200 mg/kg were observed to lower fertility, testicular weight, sperm motility, and sperm count. Likewise, it decreases the tendency of luteinizing hormone compared to the control group and the 200 mg/kg treated group, with no effect on follicle-stimulating hormone and testosterone. Histopathological findings showed atrophy of testicular tubules, stimulation of germ cells, and a decrease in germ cells. When testicular tissue was examined, flow cytometry showed that carbendazim impaired spermatogenesis and inhibited mitotic division of the spermatogenic process.

2. Carbendazim and Hematological Alterations:

The results showed that male rats exposed to 200 mg/kg carbendazim for one month had decreased levels of hemoglobin, erythrocytes, hematocrit (Hct), plasma proteins, and liver proteins, and increased levels of leukocytes, triglycerides, liver glycogen, total lipids, creatinine, aspartate aminotransferase (AST), and alanine aminotransferase (ALT). Carbendazim (50 mg/kg) administered to male rats for nine days resulted in significant changes in the levels of AST, ALT, alkaline phosphatase (ALP), blood urea nitrogen (BUN), and creatinine, and the development of oxidative stress. Carbendazim administered at doses of 450 ppm and 16 mg/kg body weight daily for 28 days resulted in a decrease in red blood cells (RBC) and white blood cells (WBC). Findings showed that carbendazim, even at modest doses, was toxic, had an adverse effect on the liver, and altered some hematological parameters in rats.

3. Carbendazim and Histopathological Alterations in Kidney, Liver, and Gonads:

Histopathological studies in the liver and kidneys of rats treated with carbendazim for 15 weeks showed histological changes in these organs. Doses of 300 and 600 mg/kg per day caused changes in liver histology, such as Kupffer cell proliferation, portal vein congestion, infiltration with mononuclear cells, sinusoid enlargement, and hydropic degeneration. Regarding the kidneys, fibrosis was observed at the highest dose, along with other structural changes in renal tissue such as tubular degeneration, congestion, and mononuclear cell infiltration. Liver damage was studied in rats at doses of 50, 100, and 200 mg/kg for 14 days, and the results showed that carbendazim induced changes in the histopathological structure of the liver and kidneys, biochemical changes in blood chemistry, oxidative stress, and impairment of liver and kidney function. Carbendazim exposure damages the reproductive organs, affects the gonads’ hormonal secretions, alters histological structures, and disrupts cellular processes, all of which result in oxidative stress in mammals. Most studies on animal models exposed to carbendazim confirm that there are changes in the liver (hemorrhage, dilation and congestion of blood vessels, enlargement of sinusoids, disorganization of hepatic cords, and vacuole formation), in the kidneys (damage to cortical and medullary tissues, changes in normal renal corpuscles, glomeruli, and Bowman’s capsule), and in the testes (impairment of spermatogenesis, testicular weight, and testicular morphology).

4. In Vitro and In Vivo Genotoxicity by Carbendazim:

In vitro and in vivo studies confirm the genotoxicity of carbendazim. In vitro concentrations of carbendazim and benomyl of 3.2-4.3 and 3.8-4.1 μM, respectively, are shown to stimulate chromosomal aneuploidy in cultured human lymphocytes by fluorescence in situ hybridization. Carbendazim at 97% purity was administered to mice as a single oral dose of 500 or 1000 mg/kg body weight. The mice were killed after 24 and 48 hours of exposure, and a statistically significant increase in micronuclei was observed in the intestinal crypts. During cell division, α- and β-tubulin are present in vivo as heterodimers and play their roles in cell division and chromosome segregation. Carbendazim interferes with microtubule assembly and polymerization in fungal and mammalian cells, leading to the failure of normal cell division. In various microorganisms, it affects normal cell structure, metabolic and physiological processes, cell division, and enzymatic activities. Zebrafish embryos exposed to various carbendazim concentrations (LC50) of 1.1, 1.19, 1.3, 1.41, 1.53, 1.66, and 1.68 mg/L showed sub-lethality, delayed development and dysfunction, pericardial edema, a decrease in heart rate, changes in biochemical measurements for various enzymes, changes in locomotor behavior, and a decrease in body length after 96 hours of exposure. The genotoxicity of carbendazim was studied in a dose range of 125-2000 mg/kg and 250-2000 mg/kg in rats, and it was confirmed to affect cytokinesis and karyokinesis, which is a clear indication of the extrusion of nuclei in bone marrow erythrocytes, an energetic effect, polychromatophilic with pyknotic nuclei, constriction of micronucleate polychromatic (PCE) and normochromatic erythrocytes (NCE) in mouse bone marrow.

5. Environmental Toxicity of Carbendazim:

Carbendazim is a persistent fungicide with a half-life of 12 months. As a result, samples of it can be found in plant products, soil, and water. It induces changes in soil structure and affects the microbial population in the soil, and adversely affects animal health. Carbendazim not only pollutes target plants but also affects non-target plants and contaminates the soil long-term, as its residues can be found in soil for 6 months to 12 years because it is readily absorbed by soil. To check the long-term persistence of carbendazim, an instrument lysimeter investigation using 14C-labeled carbendazim was conducted on barley crops for four consecutive seasons. It was observed that the degradation of carbendazim was more in the first phase, and after four seasons, 33% of carbendazim was found in soil-bound particles and in the roots of barley. The study showed that it causes environmental toxicity and, if repeatedly applied, could lead to more contaminated soil. Applying more carbendazim as a fungicide to tobacco plants than the recommended quantity (5.2 mM) could be hazardous, dangerous, and lead to a decrease in nutrients, foliar pigments, and dry weight. It should be used within control limits to reduce risks and adverse environmental and physiological effects. Sclerotinia sclerotium of rapeseed is a fungus controlled by carbendazim. A study was conducted to assess field-based results on how carbendazim is transferred to apiculture. Pollens collected after 18 days, honey after 24 days, and royal jelly after 22 days of exposure were studied for carbendazim residues using the HPLC/ESI-MS/MS method. It was observed that carbendazim diminished over time and did not depend on the gap between sprays. However, residues of carbendazim were found to be 10 times higher in pollen compared to honey and royal jelly.