Neurotoxicity of individual metals is well investigated but that of metal mixture (MM), an environmental reality, in the developing brain is relatively obscure. We investigated the combinatorial effect of arsenic (As), cadmium (Cd), and lead (Pb) on rat brain development, spanning in utero to postnatal development. MM was administered by gavage to pregnant and lactating rats, and to postweaning pups till 2 months. The pups exhibited behavioral disturbances characterized by hyperlocomotion, increased grip strength, and learning-memory deficit. Disruption of the blood-brain barrier (BBB) was associated with dose-dependent increase in deposition of the metals in developing brain. Astrocytes were affected by MM treatment as evident from their reduced density, area, perimeter, compactness, and number of processes, and increased apoptosis in cerebral cortex and cerebellum. The metals induced synergistic reduction in glial fibrillary acidic protein (GFAP) expression during brain development; however, postweaning withdrawal of MM partially restored the levels of GFAP in adults. To characterize the toxic mechanism, we treated rat primary astrocytes with MM at concentrations ranging from lethal concentration (LC)(10) to LC(75) of the metals. We observed synergistic downregulation in viability and increase in apoptosis of the astrocytes, which were induced by proximal activation of extra cellular signal-regulated kinase (ERK) signaling and downstream activation of Jun N-terminal kinase (JNK) pathway. Furthermore, rise in intracellular calcium ion ([Ca(2+)](i)) and reactive oxygen species generation promoted apoptosis in the astrocytes. Taken together, these observations are the first to show that mixture of As, Cd, and Pb has the capacity to induce synergistic toxicity in astrocytes that may compromise the BBB and may cause behavioral dysfunction in developing rats.

Phthalic acid esters (PAEs) are well-known ubiquitous environmental pollutants and used as plasticizers for the manufacturing of plastic products. During this exploratory study, an attempt has been made to determine the concentration and distribution of five prominent PAEs, viz. di-methyl phthalate (DMP), di-ethyl phthalate (DEP), di-butyl phthalate (DBP), di-(2-ethylhexyl) phthalate (DEHP), and di-octyl phthalate (DOP) in the sediment samples of Gomti River collected from 30 different locations. Identification and quantification of PAEs were performed by high-performance liquid chromatography. The mean concentration values of DMP, DEP, DBP, DEHP, and DOP were found as 10.54, 4.57, 10.41, 31.61, and 5.16 microg/kg, respectively. Limit of detection and limit of quantification for each PAE were also calculated and found in the ranges of 0.09-0.55 and 0.28-1.67 microg/kg. DEHP was the most frequently detected PAE (present in 93.3% samples); however, DOP was found only in 36.7% samples.

-Rats exposed to liquid mosquito repellent (LMR) containing allethrin (3.6% w/w) 8-hrs/ day for a period of ninety days did not produce any signs of toxicity or death. Significant increases in relative weight of liver and adrenal in males, brain and thyroid in females were observed. No significant changes were noticed in clinical enzyme profile, gonadal enzymes and histopathology of vital organs except mild changes in the activities of liver and serum alkaline phosphates (ALP), testicular glucose-6-phosphate dehydrogenase (G-6PDH) and epididymal sorbitol dehydrogenase (SDH). Rats exposed to LMR for one generation had not produced changes in their reproductive indices such as fertility index, gestation index, live pups/ dam and sex ratio. There was no change in the preweanling evaluation of pups such as survival and growth index on post-natal days (PND) 0, 4, 7,14 and 21. No significant pathomorphological changes were observed in liver, brain, kidney and gonads of PND 21 pups. Absences of any major adverse effects in the adult as well as weanling rats suggest the safe use of allethrin-based LMR.