Combination of fluoride and endosulfan induced teratogenicity and developmental toxicity in Swiss albino mice exposed during organogenesis

Abstract

The present investigation was conducted to evaluate the teratogenic and developmental toxicity of fluoride and endosulfan alone and in combination in pregnant Swiss albino mice exposed during the organogenetic period (5–14 days) of gestation. Fluoride (25.1 mg/kg body weight in water) and endosulfan (1.8 mg/kg bw by oral intubation) when administered alone and in combination (fluoride 25.1 mg/kg bw + endosulfan 1.8 mg/kg bw) to pregnant mice caused significant teratogenic effects in developing fetuses. There was no maternal mortality but significant decreases in maternal weight gain and numbers of live fetuses and significant increases in numbers of fetal resorption were recorded in the treated groups. The fetal body weight and litter size also decreased significantly in all treated groups. No external malformations were observed in any of the fetuses. The percent of visceral and skeletal anomalies increased in the fetuses of all treated groups. The fetal malformations observed were internal hydrocephaly, microphthalmia, anophthalmia, pulmonary edema, subcutaneous edema, reduced ossification of skull bones, widened cranial sutures, rib anomalies (short, wavy, partially ossified, or absent ribs), and reduced ossification of phalanges. The occurrence of visceral and skeletal malformations was more severe in the combination group, suggesting additive interaction of fluoride and endosulfan in inducing developmental toxicity in Swiss albino mice.

Fluoride and endosulfan together potentiate cytogenetic effects in Swiss albino mice bone marrow cells

“…There were no maternal deaths with fluoride (25.1 mg kg −1 bw) and endosulfan (1.8 mg kg −1 bw) given individually or in combination. A significant reduction in bw of animals treated with fluoride (25.1 mg kg −1 bw) and endosulfan (1.8 mg kg −1 bw) alone was observed, which is similar to the results of earlier reports (Collins et al, 2001; Gupta et al, 1978; Hiyasat et al, 2000; Sharma et al, 2019). Similar to our previous study (Sharma et al, 2019), maximum decrease was observed when doses of both fluoride and endosulfan were given together, indicating an additive effect.…”

“…A significant reduction in bw of animals treated with fluoride (25.1 mg kg −1 bw) and endosulfan (1.8 mg kg −1 bw) alone was observed, which is similar to the results of earlier reports (Collins et al, 2001; Gupta et al, 1978; Hiyasat et al, 2000; Sharma et al, 2019). Similar to our previous study (Sharma et al, 2019), maximum decrease was observed when doses of both fluoride and endosulfan were given together, indicating an additive effect. The reduction in bw might be attributed to the toxicity caused by fluoride and endosulfan treatment as supported by increased degradation of lipids and proteins or probably due to the effect of these compounds on the gastrointestinal tract, resulting in decreased appetite (Goel et al, 2005; Mansour and Mossa, 2011; Venkatesanwarlu et al, 1997).…”

“…Humans and animals are commonly exposed to more than one chemical concurrently from various sources such as air, water, and food (Bolognesi and Morasso, 2000). Previously, much emphasis was on evaluating the toxic effects of a single chemical, but these days increased attention is being paid to the interaction of xenobiotics with one another (DeRosa et al, 2004; Sharma et al, 2019; Wade et al, 2002). The ubiquitous presence of pesticides along with other naturally contaminants like fluoride, arsenic, and other dissolved salts merits special attention as this has increased the possibility of exposure to humans and animals resulting in its various toxic effects (Aktar et al, 2009; Rao and Mamatha, 2004; Yanez et al, 2002).…”

“…Because of its persistent nature, it bioaccumulates in the food chain. Its residues and metabolites have been found in water, food, milk, tissues, and human blood samples affecting the central nervous, reproductive, and immune systems (Cerrillo et al, 2005; Jayashree and Vasudevan, 2007; Joshi et al, 2001; Nag and Raikwar, 2007; Naqvi and Vaishnavi, 1993; Rand et al, 2010; Sharma et al, 2019). Studies have reported that endosulfan is mutagenic and causes cancer and immunosuppression (Kumar et al, 2011; Lu et al, 2000; Singh et al, 2011; Sutherland et al, 2004; Usha and Reddy, 1986; Yaduvanshi et al, 2012).…”

“…Similarly, the presence of fluoride in ground water has caused health problem in several regions of the world including India (Bhattacharya and Samal, 2018; Ghosh et al, 2013; Gupta et al, 2006). Prolonged exposure of fluoride through drinking water induces various harmful effects like skeletal changes, neurological damage, and reproductive, developmental, and teratological effects (Ortiz-Pérez et al, 2003; Ozsvath et al, 2009; Sharma et al, 2019). Various reports regarding the genotoxicity of fluoride during in vitro and in vivo studies in humans and rodents have given inconclusive results (Ha et al, 2004; He and Chen, 2006; Liu et al, 2007; Manivannan et al, 2013; Podder et al, 2008, 2011; Ribeiro et al, 2004; Tripathi et al, 2009).…”