Metabonomics evaluation of urine from rats administered with phorate under long-term and low-level exposure by ultra-performance liquid chromatography-mass spectrometry.

The purpose of this study was to investigate the toxic effect of long-term and low-level exposure to phorate using a metabonomics approach based on ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Male Wistar rats were given phorate daily in drinking water at low doses of 0.05, 0.15 or 0.45 mg kg⁻¹ body weight (BW) for 24 weeks consecutively. Rats in the control group were given an equivalent volume of drinking water. Compared with the control group, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TBIL), urea nitrogen (BUN) and creatinine (CR) were increased in the middle- and high-dose groups whereas albumin (ALB) and cholinesterase (CHE) were decreased. Urine metabonomics profiles were analyzed by UPLC-MS. Compared with the control group, 12 metabolites were significantly changed in phorate-treated groups. In the negative mode, metabolite intensities of uric acid, suberic acid and citric acid were significantly decreased in the middle- and high-dose groups, whereas indoxyl sulfic acid (indican) and cholic acid were increased. In the positive mode, uric acid, creatinine, kynurenic acid and xanthurenic acid were significantly decreased in the middle- and high-dose groups, but 7-methylguanine (N7G) was increased. In both negative and positive modes, diethylthiophosphate (DETP) was significantly increased, which was considered as a biomarker of exposure to phorate. In conclusion, long-term and low-level exposure to phorate can cause disturbances in energy-related metabolism, liver and kidney function, the antioxidant system, and DNA damage. Moreover, more information can be provided on the evaluation of toxicity of phorate using metabonomics combined with clinical chemistry.

Biochemical and histopathological changes in serum creatinine and kidney induced by inhalation of Thimet (Phorate) in male Swiss albino mouse, Mus musculus.

This work was conducted to investigate the biochemical and histopathological changes in serum creatinine level and kidney of male Swiss albino mouse, Mus musculus, exposed to the recommended field dose of Thimet (20 kg ha(-1)). The animals were exposed to this dose in a whole-body inhalation chamber for 12 weeks and the biochemical and histopathological changes were studied in the 2nd, 4th, 6th, 8th, 10th, and 12th weeks of exposure. Creatinine level of serum was measured by the Jaffe method, and histopathological lesions were studied by the hematoxylin-eosin staining method. A significant rise in creatinine level was observed from the 4th week of exposure until the end of the experiment. This rise suggests impairment of the glomerular function and tubular damage in the kidneys. These changes were confirmed by histopathological studies in the tubules. Kidney lesions were present throughout the experimental period. These consisted of mild to severe multifocal cloudy and hydropic degeneration with necrosis in the tubules, though the glomerular damage was not seen by light microscopy. After a 30-day recovery period, the histopathological and biochemical changes were absent and normal patterns were restored.

Pharmacological studies on the molluscicidal activity of phorate on Pila globosa (Gastropoda).

Amongst heart, rectum and radula protractor muscles of Pila globosa, the heart showed a negative inotropic and negative chronotropic response while the rectum and radula protractor showed a positive tonotropic response to exogenously applied acetycholine (ACh). The anti-cholinesterase pesticide phorate substantially increased the response to ACh; at high doses it could also evoke cholinomimetic response from the heart. The anti-cholinesterase property of phorate gradually increased with an increase in its contact period to the tissue. The extent of alteration in ACh response caused by prior treatment with low and high doses of phorate were very similar, indicating that the efficacy of phorate is by and large time-dependent rather than dose-dependent. The effect of phorate remained irreversible even after prolonged washing. The mode of action of phorate has been discussed in the light of the above findings.