Adrenalectomy and the adaptive liver response in mirex-treated rats

Mirex, an organochlorine compound, was administered as a single oral dose (100 mg/kg body wt) to both intact and adrenalectomized juvenile male Sprague-Dawley rats. Both mirex-treated intact and adrenalectomized animals (dosed 24 hr postsurgery) exhibited significant increases in liver weight to body weight ratios compared to controls. However, the liver weight to body weight ratios in mirex-treated intact animals were significantly greater than those observed in mirextreated adrenalectomized animals. Significant increases were observed in liver weight to body weight ratios in adrenalectomized animals treated with mirex 4 days after surgery. However, the 96-hr mortality in mirex-treated adrenalectomized animals increased from 20% (mirex dose given 1 day postadrenalectomy) to 56% (mirex dose given 4 days postadrenalectomy). Mirex treatment of intact and adrenalectomized animals had no significant effect upon either serum or hepatic activities of glutamic oxalacetic transminase, glutamic pyruvic transaminase, sorbitol dehydrogenase, or protein concentrations. Bromsulfophthalein clearance also was not affected by mirex treatment in adrenalectomized animals. Serum glucose concentrations were significantly decreased in both intact and adrenalectomized animals by mirex treatment. Daily corticosterone supplements to adrenalectomized animals restored liver hypertrophy and serum glucose concentrations to levels observed in mirex-treated intact animals. These results suggest that mirex-induced liver enlargement may be mediated by corticosterone.     

Glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) enzyme activities in different tissues of Sarotherodon mossambicus (Peters) exposed to a carbamate pesticide,carbaryl

The activity levels of glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) enzymes were estimated in liver, muscle and brain tissues of the fish, Sarotherodon mossambicus (Peters), which had been exposed to sub-lethal (3 mg litre⁻¹) and lethal (25 mg litre⁻¹) concentrations of the carbamate insecticide carbaryl. Based on the results obtained, the changes in GOT and GPT levels in liver, muscle and brain following different periods of sub-lethal and lethal carbaryl exposures suggested that S mossambicus showed adaptive elevation in the activity levels of the two aminotransferase enzymes in the tissues, thereby probably aiding gluconeogenesis through transamination of glucogenic amino acids to meet the energy demand under carbaryl toxicity. © 1999 Society of Chemical Industry     

Mirex residues in wildlife and soils, Hawaiian pineapple-growing areas--1972-74.

A monitoring program was conducted in the pineapple-growing areas of Hawaii from 1972 to 1974 to survey mirex residues in sediments, soils, and aquatic and terrestrial wildlife. Residues in pineapple field soils ranged from 3 to 18 ppb 9 months after mirex had been applied. No residues were found in the sediments. Only 8 fish of 110 aquatic animals sampled contained mirex; these levels were low and ranged from 3 to 7 ppb. Mirex residues in birds ranged from undetectable to 10 ppm; residues in rodents were quite variable, but in terms of the geometric mean, the amounts in the Polynesian rat decreased with time from 1,270 to 56 ppb. Similarly, values for the roof rat ranged from 666 to 17 ppb. The geometric mean for residues in mongooses decreased from 2,200 ppb immediately after application to 238 ppb 39 weeks later. Aerial application of mirex to the pineapple fields did not contaminate the marine environment of Hawaii and no evidence of mirex residue buildup in the aquatic food chain was apparent. Mirex accumulation in terrestrial biota was temporary; there was no definitive indication of permanent accumulation in the wildlife of the areas studied.     

Organochlorine pesticide and polychlorinated biphenyl residues in selected fauna from a New Jersey salt marsh--1967 vs. 1973.

More than a half million pounds of DDT were applied to control mosquitoes in salt marsh estuaries of Cape May County, New Jersey, from 1946 to 1966. The use of DDT was discontinued in the County after 1966. In 1967, mean concentrations of DDT and metabolites ranged from 0.63 to 9.05 ppm in aquatic fauna, but by 1973 mean residue levels had decreased 84 to 99 percent among nine species. DDE was still present at reduced levels in nearly all samples in 1973, but other DDT isomers had mostly disappeared. Dieldrin was detected only in clapper rails, and residue levels decreased during the period. Mean concentrations of PCB's increased in the clapper rail, remained the same in the fiddler crab and mud snail, and decreased in the sheepshead minnow, mummichog, striped killifish, and salt marsh snail. Small amounts of mirex, toxaphene, cis-chlordane (and/or trans-nonachlor), oxychlordane, and HCB were detected in a few specimens.     

DDE increases the toxicity of parathion to coturnix quail

Adult male Japanese quail (Coturnix coturnix) were exposed to DDE or chlordane in the diet and subsequently dosed with parathion or paraoxon. Pretreatment with 5 or 50 ppm DDE in the diet for 12 weeks resulted in increased cholinesterase (ChE) activity in plasma, but not in the brain. Dietary concentrations of 5 and 50 ppm DDE caused increased susceptibility of quail that were challenged with parathion or paraoxon. The increased mortality resulting from DDE pretreatment was reflected in brain ChE inhibition. The synergistic action of DDE was apparent after 3 days of exposure to 50 ppm DDE and 1 week of exposure to 5 ppm DDE. Birds exposed for 3 weeks to 5 or 50 ppm DDE retained their DDE-potentiated sensitivity to parathion after 2 weeks on clean diet. Chlordane pretreatment resulted in decreased susceptibility (antagonism) to parathion, but not to paraoxon dosage. Implications of differing responses in ChE and mortality among controls, DDE-, and chlordane-pretreated birds after parathion or paraoxon dosage are discussed.     

Effect of endosulfan in female rats growing on low- and high-protein cereal diet

Endosulfan (α,β-1,2,3,4,7,7-hexachlorobicyclo(2,2,1)-heptene-(2)-bis-hydroxymethylene(5,6)sulfite) fed daily 0.5 and 100 ppm in the diet proved significantly toxic to female rats (initial weight 40–50 g) growing on a low-protein (5%) diet as compared to those growing on a high-protein (24%) diet. The toxic symptoms which developed exclusively in low-protein-fed rats included growth retardation, low blood counts, low RNA and protein levels in liver, and high glutathione levels in liver and blood. However, no changes in the activities of liver RNase, blood glucose-6-phosphate dehydrogenase, and glutathione reductase were observed. Liver glucose-6-phosphatase activity increased significantly. Endosulfan induced an increased accumulation of perirenal adipose in rats raised both on low- and high-protein diets. Endosulfan elicited cumulative toxic manifestations as evident from the relative degree of toxicity caused by 0.5 ppm and 18 weeks feeding. α-Endosulfan, β-endosulfan, and endosulfan sulfate were recovered from adipose tissue, the recovery being higher in adipose tissue of rats raised on a low-protein diet.     

Biochemical and physiological investigations into the delayed toxicity produced by O,O,S-trimethyl phosphorothioate in rats

Oral administration of O,O,S-trimethyl phosphorothioate (OOS), an impurity in several technical organophosphorus insecticides, causes delayed toxicity in rats with death occurring up to 28 days after the treatment. The oral LD₅₀ was determined to be 60 mg/kg. The effect of a single nonlethal dose of OOS (20 mg/kg) on in vivo protein synthesis in different organs was determined by measurement of the incorporation of [¹⁴C]leucine at 6 hr to 28 days after treatment. As early as 6 hr after OOS treatment the incorporation of [¹⁴C]leucine into the liver, lung, thymus, kidney, and spleen was elevated and remained elevated for up to 7 days. With the exception of the lung, organ weights were significantly decreased during the same time period. On Day 28 after treatment, the amount of [¹⁴C]leucine incorporation had decreased to the control level in all of the organs studied. Treatment with OOS at 20 mg/kg caused a significant increase in hematocrit on Days 3,5, and 7, and as early as 6 hr after treatment at 60 mg/kg. The clinical biochemistry of plasma indicated that there was no significant change from control values in the glutamic pyruvic transaminase, glutamic oxalic transaminase, lactate dehydrogenase, or alkaline phosphatase activities with the 20 mg/kg dose. The analysis of the intermediary metabolites indicated that the redox state of cytosol was more reduced on Day 5, whereas that of mitochondria was not affected by OOS. Data obtained at selected times after oral administration of a 60 mg/kg dose of OOS and that obtained from animals starved for 3 days are also discussed.     

Effects of sodium fluoride on hepatic toxicity in adult mice and their suckling pups

In this investigation, we have evaluated the effect of sodium fluoride (NaF) on hepatic function in pregnant and lactating mice and their suckling pups. Experiments were carried out on female Wistar mice given 500 ppm sodium fluoride (226 ppm fluoride ion) in their drinking water from the 15th day of pregnancy until day 14 after delivery. All mice were sacrificed on day 14 after parturition. Our results showed a significant decrease in serum levels of total protein and albumin, a marked hypoglycaemia and a significant decline in serum cholesterol and triglyceride levels in fluoride-treated mice and their pups. Whereas globulin and biluribin levels in serum were not significantly changed by NaF treatment. On the other hand, serum transaminase activities (aspartate transaminase; alanine transaminase), which well known as markers of liver function, were elevated indicating hepatic cells’ damage after treatment with fluoride. Lipid peroxidation increased in NaF-treated mice and pups, as revealed by high liver malondialdehyde levels, while serum total antioxidant status showed a significant decline. These biochemical modifications in NaF-treated mice also correspond histologically with extensive ballooning, hepatocellular necrosis and infiltration of mononuclear cells. These effects were not observed in controls.     

Mirex residues in bobwhite quail after aerial application of bait for fire ant control, South Carolina--1975-76

Mirex, the organochlorine compound used for control of the imported fire ant (Solenopsis invicta Buren), was applied aerially under supervision of the South Carolina Plant Pest Regulatory Service in October 1975 to a game management area in Hampton County, S.C. Influenced by recent reports indicating that low levels of mirex were toxic to certain nontarget organisms in laboratory studies, authors initiated a program for monitoring mirex residues in bobwhite quail (Colinus virginianus). Pretreatment residues were recorded on a dry-weight basis in bobwhite quail breast and adipose tissue; conversion factors for determining wet-weight concentrations are approximately as follows: fat, 0.77; and breast, 0.29. Residues ranged from 0.000-0.178 ppm and 0.247-2.763 ppm, respectively. Mirex residues in quail adipose tissue showed up to five-fold increase within the first month after treatment and declined thereafter. A residue peak was noticed the spring following mirex treatment, corresponding with insect emergence. Mirex residues in quail collected in summer 1976 following a fall bait application showed slightly higher residue levels than had birds taken in summer 1975; however, little, if any, human food chain contamination would result in the consumption of birds with residue levels found in this study.     

Effects of sodium fluoride on hepatic toxicity in adult mice and their suckling pups

In this investigation, we have evaluated the effect of sodium fluoride (NaF) on hepatic function in pregnant and lactating mice and their suckling pups. Experiments were carried out on female Wistar mice given 500 ppm sodium fluoride (226 ppm fluoride ion) in their drinking water from the 15th day of pregnancy until day 14 after delivery. All mice were sacrificed on day 14 after parturition. Our results showed a significant decrease in serum levels of total protein and albumin, a marked hypoglycaemia and a significant decline in serum cholesterol and triglyceride levels in fluoride-treated mice and their pups. Whereas globulin and biluribin levels in serum were not significantly changed by NaF treatment. On the other hand, serum transaminase activities (aspartate transaminase; alanine transaminase), which well known as markers of liver function, were elevated indicating hepatic cells’ damage after treatment with fluoride. Lipid peroxidation increased in NaF-treated mice and pups, as revealed by high liver malondialdehyde levels, while serum total antioxidant status showed a significant decline. These biochemical modifications in NaF-treated mice also correspond histologically with extensive ballooning, hepatocellular necrosis and infiltration of mononuclear cells. These effects were not observed in controls.     

The relationship between mirex-induced liver enlargement and the adrenal glands

A single oral dose of mirex given to male rats produced a doubling in liver mass (liver weight/body weight) within 3 days. The response was both dose and time related. There was an accompanying increase in adrenal gland weight (adrenal weight/body weight). In adrenalectomized animals given a single oral dose of mirex, the increase in liver weight/body weight response was drastically reduced. Adrenalectomized animals given corticosterone supplements showed a similar liver weight increase when given mirex as did intact mirex dosed animals. These results suggest a relationship between mirex-induced liver enlargement and adrenal gland secretions.     

Persistence and degradation of chlorfenvinphos,diazinon, fonofos and phorate in soils and their uptake by carrots

Analytical methods are described for the determination of residues of chlorfenvinphos, diazinon, fonofos and phorate in soils and carrots. The insecticides, applied in June 1969 at 2 kg (a.i.)/ha, persisted longer in peaty loam than in sandy loam. After 7 months, the sandy loam contained 1% of the applied diazinon and 20–30% of the applied chlorfenvinphos, fonofos and phorate, the latter as its sulphone; the corresponding figures for the peaty loam were 10, 40–50, 40–50 and 30–40% respectively. None of the residues showed any substantial change from October to January. Although high initial concentrations (up to 50 ppm) of the residues in carrots were diluted by plant growth, it is shown that concentrations >1 ppm could be present in marketable crops 12–14 weeks after application at recommended rates. Carrots harvested 26 weeks after sowing contained <0.2 ppm of all insecticides. In contrast, during the first 15 weeks of crop growth the weights of residues in the carrots increased and remained approximately proportional to the square root of the carrot mean weight. Rates of uptake declined as carrot growth declined and subsequently the amounts of chlorfenvinphos, diazinon and fonofos residues in the carrots changed very little, while phorate sulphone steadily declined.     

Concentration related responses of chlorpyriphos in antioxidant, anaerobic and protein synthesizing machinery of the freshwater fish, Heteropneustes fossilis

Impacts of chlorpyriphos (2, 4, 6 ppm) on the profiles of antioxidant (catalase) and anaerobic (lactate dehydrogenase) enzymes and other macromolecular contents (DNA, RNA, protein) of various tissues of the freshwater fish, Heteropneustes fossilis were studied. Chlorpyriphos significantly decreased the specific activity of catalase (CAT) and lactate dehydrogenase (LDH) in the brain, liver, gill and skeletal muscle of the fish. The reduction in specific activity might be due to the binding of chlorpyriphos or its metabolites with the enzyme molecules or affecting the synthesis and/or degradation of the enzymes. Like enzymes, the DNA, RNA and protein contents decreased in the brain, liver, gill and skeletal muscle of the fish as a function of increase in chlorpyriphos concentrations (2-6 ppm). The chlorpyriphos-induced reduction in these biochemical constituents might be because of alteration in their turnover (synthesis/degradation) in different tissues. The maximum effects on CAT, LDH, DNA, RNA and protein were obtained in response to 6 ppm chlorpyriphos. The present findings suggest chlorpyriphos concentration related impairment in antioxidative, anaerobic and protein synthesizing capacity of the fish. Therefore, the use of higher concentrations of chlorpyriphos should be avoided to protect the health of economically important freshwater food fish.     

Dose-dependent sub-chronic toxicity of diethyl phthalate in female Swiss mice

The experiment was conducted to study the after effects of administering DEP at different doses to female Swiss mice for a period of 90 days. Group I mice were fed on normal diet and water ad libitum. Group II mice were maintained on normal diet mixed with corn oil at 8.25 mg/kg of the diet/day as oil control. Group III, IV and V mice were given diethyl phthalate dissolved in corn oil mixed with the diet at 10, 25 and 50 mg/kg of the diet/day, which is approximately equal to 1.25, 3.125 and 6.25 mg/kg body weight/day. A significant dose dependent increase was observed in serum acid phosphatase (ACP) whereas, serum and liver triglycerides levels showed a significant increase only in the high-dose treated group. Significant dose-dependent increase in serum aspartate and alanine aminotransferase (AST and ALT) and liver glycogen was observed. Serum lactate dehydrogenase (LDH) was significantly increased only in 25 and 50 ppm DEP-treated mice. Liver cholesterol was significantly increased in all the treated groups. Liver histology by light microscopy showed intracellular vacuolations in all the treated groups which was much more evident in the 25 and 50 ppm DEP-treated mice while hepatocellular degeneration and hypertrophy of the hepatocytes was evident in 50 ppm DEP-treated mice. Proliferation of mitochondria and peroxisomes was evident in the electron micrographs of the 10 ppm DEP-treated mice while 25 and 50 ppm DEP-treated mice showed increase in lipid droplets and severe mitochondrial proliferation.     

Mirex residues in nontarget organisms after application of 10-5 bait for fire ant control, northeast Florida--1972-74

The 10-5 bait formulation of mirex insecticide was applied to a 20,000-acre area of northeast Florida. For 24 months after application, samples of a wide variety of fauna were collected and analyzed for mirex content. Insects accumulated mirex to the greatest extent in the first 6 months after application; most residues had decreased greatly by 12 months. Other invertebrates showed low mirex levels during the first 9 months after application and none after 12 months. Fish possessed low levels of insecticides for 9 months; amphibians showed mirex residues for 12 months after application. In general, reptiles had low levels throughout the 24-month period and mammals had higher levels, particularly in fat tissues. Birds consistently had low to moderate mirex levels. After a single application of 10-5 mirex bait, only relatively low levels of insecticide were detected in exposed fauna. After 24-months, mirex was found infrequently and at low levels.     

A study on low dose cypermethrin induced histopathology, lipid peroxidation and marker enzyme changes in male rat

The short term effect of low dose synthetic pyrethroid and insecticide α-cypermethrin was investigated in selected tissues of male albino Wistar strain rats. Cellular antioxidant activities, specific enzyme markers and tissue histopathology were studied using this compound at 5, 10, 25 and 50 mM at given time points during independent experiments. α-Cypermethrin was administered intradermally. Selective tissue responses were determined 6 h post administration employing control and experimental animals using established methods. Different doses of α-cypermethrin increased the malondialdehyde (MDA) content in the brain, heart, liver, kidney and testis of the male rats. Alanine transaminase (ALT), alkaline phosphatase (ALP) and gamma glutamyl transferase (GGT) enzyme activity levels were altered in these tissues and in the serum. Cytotoxic effects produced by α-cypermethrin were reflected in histopathology sections of the treated tissues. α-Cypermethrin decreased the cellular antioxidant activity, altered marker enzyme activity and effected histopathological changes in the treated animal tissues.     

Comparative tissue distribution of mirex and chlordecone in fetal and neonatal rats

The transport of mirex and chlordecone (Kepone) across the placenta during late gestation and through the milk during lactation was investigated in the rat. In the placental transport study, doses of 5 mg/kg were administered on Day 15, 18, or 20 of gestation and animals were killed 4, 24, or 48 hr after treatment. Both compounds crossed the placenta and were present in the fetus at all examination times. Maternal tissue levels exceeded fetal tissue levels by a factor of 4 to 5. Slightly higher levels of chlordecone as compared to mirex were found in maternal and fetal tissues. No effects of gestational age at time of treatment or of position of the fetus in the uterus were seen. In the lactation study, doses of 1 or 10 mg/kg/day were administered on Days 2–5 postpartum and pups were killed at intervals up to 12 days after treatment. The secretion of milk appeared to be a major route of elimination for both pesticides for nursing females, and the greater amount of mirex excreted via the milk as compared with chlordecone is in agreement with differences in their reported octanol-water partition coefficients. Initially, mirex entered the milk more rapidly than chlordecone. After cessation of treatment, mirex milk levels fell quickly, but chlordecone levels remained fairly constant. In the pups, mirex tissue levels paralleled milk levels; chlordecone levels, however, continued to increase in the tissues throughout the observation period.     

Fate of endosulfan in rats and toxicological considerations of apolar metabolites

[¹⁴C]Endosulfan, α or β isomers separately, was administered to rats as a single oral dose and as a dietary supplement for 14 days. No appreciable differences were observed in the fate of the two isomers. Five days after the single dose, 75% of the dose had been voided in the feces and 13% in the urine. Of the total radiocarbon consumed in the diet after 14 days, 56% had been eliminated in the feces and 8% in the urine. Bile collection studies showed that up to 47% of a single oral dose was eliminated from the liver via this route; enterohepatic circulation was not apparent. Maximum [¹⁴C]endosulfan equivalents in body tissue occurred in the kidney and liver, 3 and 1 ppm, respectively, after 14 days of feeding 5 ppm of endosulfan. Apolar metabolites in the excreta and/or tissues were a minor portion of the total residues and consisted of the sulfate, diol, α-hydroxy ether, lactone, and ether derivatives of endosulfan. The sulfate was slightly more toxic to mice than endosulfan, while the other products were less toxic. Neither endosulfan nor its metabolites were active in the Salmonella mutagenicity test. Endosulfan in the diet of rats for 28 days at 50 ppm did not induce liver oxidase enzymes, alter liver or kidney weights, or influence the rate of weight gain of the animals.     

Subacute chlorpyrifos-induced oxidative stress in rat erythrocytes and the protective effects of catechin and quercetin

This study examined the effects of chlorpyrifos in the rat erythrocyte antioxidant system and evaluated the ameliorating effects of catechin and quercetin on the oxidative damage induced by chlorpyrifos. Sexually mature male Wistar rats were given chlorpyrifos (5.4 mg/kg, 1/25 of the oral LD₅₀), catechin (20 mg/kg), quercetin (20 mg/kg), catechin plus chlorpyrifos, and quercetin plus chlorpyrifos daily via gavage for four weeks. No statistical differences were found in the catechin-only and quercetin-only groups compared with the control group. By the end of the fourth week, chlorpyrifos alone increased the levels of malondialdehyde (MDA) and decreased superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities compared with the control group in rat erythrocytes. In the catechin-plus-chlorpyrifos and quercetin-plus-chlorpyrifos groups, there were statistically significantly decreased MDA levels and increased SOD, CAT, and GPx activities compared with the chlorpyrifos-only group. Thus, it appears that catechin and quercetin ameliorate chlorpyrifos-induced oxidative stress in rat erythrocytes in vivo.     

Mercury concentrations in fish, North Atlantic offshore waters--1971.

Mercury concentrations were determined in muscle and liver of 41 species of fish and a limited number of plankton, sediment, and invertebrate samples collected from North Atlantic offshore waters in 1971. The average mercury concentration in fish muscle was 0.154 ppm with a standard deviation of 0.124. Invertebrate samples had mercury concentrations which were generally less than 0.1 ppm. In a single lobster sample, however, 0.31 ppm mercury was found in the tail muscle and there was 0.60 ppm in the liver. Mercury levels in all 9 plankton and 10 sediment samples taken were less than 0.05 ppm.