TOXICOLOGICAL AND BIOCHEMICAL CONSEQUENCES OF EXPOSURE OF THE RAT TO ORGANOPHOSPHATE PESTICIDES

Abstract

Effects of sublethal dosage of the organophosphate pesticides Chlorpyrifos and Diazinon, were studied on the blood and liver of adult albino Sprague Dawley rats under short term (high dosage) and long term (low dosage) regimes. For the short term study the dosage of the two pesticides was 120 mg/kg body weight/day and 80 mg/kg body weight/day, respectively . . For the long term study the dosage was 60 mg/kg body weight/day and 40 mg/kg body weight/day, respectively. For both pesticides the maximum period of short term exposure was 7 days and for long term exposure it was 18 months. In the former regime, four groups of experimental rats each comprising 5 animals were kept in separate cages and sacrificed on 1, 2, 3 and 7 days post treatment. In the latter regime, six groups of 5 rats each were maintained similarly and sacrificed on completion of 3, 6, 9, 12, 15 and 18 months of exposure to the pesticides. Chlorpyrifos Absolute body weight did not ch ange in any of the long term Chlorpyrifos-treated groups except the 9-month group which showed noticeable deviation from the respective control rats. Weekly percent increase in body weight decreased in almost all treatment groups. Relat ive liver weight (RLW) declined significantly in both the short and the long term experiments, the decrease being only t ransient in the latter r egime. Chlorpyrifos had no effect on haemoglobin (Rb) but RBC, WBC and packed cell volume (PCV) showed significant and transient decline in the short term tests. The mean corpuscular volume (MCV) and mean corpuscular haemoglobin (MCR) showed transient increase, while mean corpuscular haemoglobin concentration (MCRC) increased persistently. In the long-term regime Rb and RBC decreased significantly with a delay. The WBC and PCV values showed the most persistent decline. The derived parameters MCV, MCH and MCHC also changed significantly but with considerable inconsistency in respect to timing and direction of change. Serum alkaline phosphatase (AP), glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT) and lactic dehydrogenase (LDH) activities decreased in a time-dependent manner in both short and long term regimes. The change in LDH and GOT was the most consistent and in AP only transient on short term exposure to Chlorpyrifos. The decrease in the activity of GPT was delayed but was also transient. In the long term regime, the earliest change (decrease) was recorded for AB the decrease being only transient. The activities of GOT and GPT showed persistent but delayed decrease. Of the metabolites, cholesterol decreased transiently in short term tests. Bilirubin first increased and then decreased only transiently. Serum proteins declined with a delay but persistently. In the long term situation also, AP, GOT and GPT activities dropped significantly, the former quite early and the latter two with much delay. The activity of LDH decreased only in the 18- month group. The serum proteins and bilirubin declined early and transiently. Serum cholesterol declined first in the 9-month group and remained so in all other groups. Chlorpyrifos had no significant effect on liver AP, GOT and LDH in the short term condition. The activity of GPT and soluble protein, level fell below control values only transiently. The content of cholesterol increased only in the 3 and 7-day groups. In the long term experiments, the activity of AP, GOT and GPT increased with much delay. Only transient changes were recorded for LDH, cholesterol and soluble proteins. Normal levels (control) were restored beyond 9 and 12-month periods. Morphometric and histological examination of the liver of Chlorpyrifostreated rats showed significant and drastic alterations in both short and long term Chlorpyrifos-treatment regimes. The histopathological alterations in the liver were similar, pronounced and dosage-dependent in both time-phased regimes. These were characterized by sinusoidal dilatation in centrilobular zone, kupffer cell hyperplasia, hypertrophy of hepatocytes in periportal areas, cytoplasmic vacuolation, granular margination, nuclear pyknosis, focal necrosis and cell loss due to changes resembling fatty degeneration. Diazinon Long term exposure to Diazinon caused transient decrease in absolute body weight and % weight gain. The RLW remained unaffected by short term exposure to Diazinon but declined significantly and belatedly in 12, 15 and 18- month treatment groups. The effect of Diazinon on these parameters was comparatively less pronounced than that of Chlorpyrifos. Of the haematological parameters, Hb, RBC and PCV showed significant declines in short term tests. The decrease for Hb was delayed and that for PCV was transient. The MCV and MCHC also responded with delay, the former increased and the latter decreased. Both WBC and MCH remained unaffected. Long term exposure to Diazinon resulted in significant decrease in Rb, RBC and PCV; the effect on the latter two parameters was considerably delayed. The WBC and MCH values also declined, the MCV increased only in the 18 month group whereas the values of MCHC fluctuated, ultimately falling below the control values in the 18-month group. Serum AP declined drastically in short term tests but following an initial increase ultimately declined in the long term regime. Serum GOT increased transiently but GPT remained unaltered following short term exposure to Diazinon. In the long term condition, both parameters decreased but with much delay. The effect of the pesticide on LDH was opposite in the two regimes, persistently dropping in short term groups but increasing in all long term tests except the 18-month group where it ultimately decreased. Serum bilirubin, cholesterol and proteins dropped below control values in both short and long term tests. Compared to Chlorpyrifos, most of the liver enzymes and metabolites were more conspicuously affected by Diazinon in both short and long term tests. The effects on AP, GOT and GPT in the two regimes were opposite. The activity of AP increased in the short term regime but decreased transiently in the long term situation. Doth GOT and GPT decreased in the former but increased in the latter regime with some delay. The activity of LDH remained unaffected on short term exposure but showed delayed increase (15, 18 months) in the long term tests. Cholesterol increased in both regimes, again with a delay. Soluble protein . content was affected by Diazinon only in the long term experiments where it decreased significantly only iri 15 and 18- month groups. The morphometric data on hepatocyte number per unit area and changes in size of nuclei and nucleoli complemented the observed histopathological modifications in the liver. Diazinon brought about histopathological alterations in the liver comparable to those noted with Chlorpyrifos. The changes were dosage-dependent, being most drastic in the longest exposure groups in the two regimes. The above results reveal definite and significant effects of both pesticides on blood and liver of the rat under the experimental conditions used. The intensity of effects of the two pesticides varied for individual blood and liver parameters. Clear differences for the two pesticides could be noted in respect to body weight and haematolog"ical parameters. Chlorpyrifos had stronger effect on body weight as compared to Diazinon whereas Diazinon caused comparatively more pronounced effect on haematology. The most consistent influence of the two pesticides was on the liver where drastic histopathological alteration occurred in a dosage-related manner.