No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Subacute oral toxicity of azimsulfuron and penoxsulam herbicides on male albino rats
Abstract
The present study was conducted to determine the effect of subacute oral toxicity of azimsulfuron (Gulliver 50% WG) and penoxsulam (Granite24% SC) herbicides on adult male albino rats at 2000 mg/kg body weight for 30 consecutive days followed by 30 days as a recovery period. Rats were sacrificed after 10, 20, 30 and 60 days from treatment. Body weight gain, organs weight, haematological and biochemical parameters and sperm dynamics were determined. General speaking, the body weight gains and relative testes weight of all treated rats significantly decreased comparing the control treatments, but it was almost the same in all treatments at the end of recovery period. In addition, varied increasing values were recorded with the relative weights of liver, kidneys, lungs, spleen, brain and heart, white blood cell counts (WBCs), plasma aspartate amino transferase (AST) and alanine amino transferase (ALT), alkaline phosphatase, creatinine and urea concentrations. On the other hand, red blood cell counts (RBCs), haemoglobin concentration (Hb), total protein content, sperm counts and sperm motilities were decreased in treated rats compared to those of control. Generally, candidate herbicides, particularly azimsulfuron, showed harmful toxic effects to treated rats during the experimentation periods.
ResearchGate has not been able to resolve any citations for this publication.
Cypermethrin (CY), a type II pyrethroid has become a major class of insecticides used to control of ectoparasites that infecting caged layer hens. Although many studies have been done on toxicity of CY on mammals and fishes, little has been evaluated on chicks, especially hens. Thus, this study was carried out on forty-five, 70 weeks old laying hens to evaluate the safety of cypermethrin emulsifiable concentrate 15% (CY-EC) and cypermethrin dust (CY-D). Birds received CY-EC or CY-D applied as a spray and dust, respectively, at the rate of 3-fold higher doses than recommended by the manufacturer and hematological and serum biochemical parameters were evaluated. Results obtained to hematological and biochemical findings showed that CY-EC significantly (p<0.05) increased the levels of hemoglobin, MCV and MCHC while WBC reduced in the treated birds. Similarly, significantly increase in MCHC values was marked in CY-D treated birds; additionally, WBC and basophils values became significantly reduced (p<0.05). There were no statistical differences in the serum chemistry values between layer hens groups before or after CY-EC treatment. However, layer hens CY-D-treated presented decrease of total protein and GGT when compared with the control while glucose showed significantly high values. It can be concluded that CY-EC and CY-D affecting some hematological and biochemical parameters when applied on 3-fold higher doses than recommended by the manufacturer.
Rhamdia quelen (jundiá) e Leporinus obtusidens (piava) foram expostos a formulação comercial Roundup(r), um herbicida a base de glifosato nas concentrações de 0,2 e 0,4 mg/L por 96h. Os efeitos do herbicida foram analisados na atividade da alanina aminotransferase (ALT), aspartato aminotransferase (AST) e glicose no plasma, glicose e proteína na camada de muco, hidrólise de nucleotídeos no cérebro e a proteína carbonil no fígado. Os parâmetros foram escolhidos devido à falta de informação com relação a análises integradas, considerando parâmetros oxidativo, danos no fígado, efeitos na composição da camada do muco e atividade da trifosfato difosfoidrolase (NTPDase). Níveis de glicose plasmática foram reduzidos em ambas às espécies, enquanto a atividade das transaminases (ALT e AST) aumentou após exposição ao herbicida. A exposição ao herbicida aumentou a proteína e níveis de glicose na camada de muco em ambas as espécies. Houve uma redução em ambas atividades de NTPDase e ecto-5'-nucleotidase no cérebro de piava, e um aumentou a atividade destas enzimas em jundiás em ambas as concentrações testadas. As espécies mostraram um aumento na proteína carbonil no fígado após exposição a ambas as concentrações de glifosato. Nossos resultados demonstraram que a exposição ao Roundup(r) causou danos no fígado, como evidenciado pelo aumento das transaminases plasmáticas e proteína carbonil no fígado em ambas as espécies de peixes estudadas. A composição do muco alterou e uma hipoglicemia foi detectada após a exposição ao Roundup(r) em ambas espécies. A hidrólise de nucleotídeos em cérebro mostrou diferente resposta para cada espécie estudada. Esses parâmetros indicam alguns importantes e indicadores potenciais da contaminação do glifosato no ecossistema aquático.
The present study evaluates the effects of short term (15 days) exposure of low dose (300 μg kg(-1)) of atrazine (2-chloro-4-ethylamino-6-isopropylamino-1,3,5-triazine) on antioxidant status and markers of liver and kidney damage in normal (nondiabetic) and diabetic male Wistar rats. Rats were divided into four groups: Group I as normal control, Group II as atrazine treated, Group III as diabetic control, and Group IV as atrazine treated diabetic rats. Atrazine administration resulted in increased MDA concentration as well as increased activities of SOD, CAT, and GPx in both liver and kidney of atrazine treated and atrazine treated diabetic rats. However, GSH level was decreased in both liver and kidney of atrazine treated and atrazine treated diabetic rats. Atrazine administration led to significant increase in liver damage biomarkers such as AST, ALT, and ALP as well as kidney damage biomarkers such as creatinine and urea in both normal and diabetic rats, but this increase was more pronounced in diabetic rats when compared to normal rats. In conclusion, the results of the present study demonstrate that short term exposure of atrazine at a dose of 300 μg kg(-1) could potentially induce oxidative damage in liver and kidney of both normal and diabetic rats.
The present study describes the reproductive effects of technical and formulated forms of tribenuron-methyl on mail albino rats. Tribenuron-methyl was orally administered in single and repetitive doses. For single dose treatments of technical and formulated forms, testosterone concentration (ng mL-1) was insignificantly affected (P ≤ 0.05). While, in repetitive doses, such effects were more pronounced, also after treatment with 25 and 50 mg kg-1 formulated and 50 and 100 mg kg-1 technical tribenuron-methyl were significant at (P < 0.05), respectively. Also treatment with 100 mg kg-1 formulated tribenuron-methyl caused highly significantly increase in serum testosterone concentration (ng mL-1) as compared with control group. The body and testis weight of animals groups were not affected with single dose, but in repetitive doses significantly decreased specially with formulated compound. There was no histopathological alteration in testis, except in male rat treated with 100 mg, repetitive dose of formulated tribenuron-methyl which caused degeneration in most seminiferous tubules and the lumenae of epididymis were mostly free from spermatozoa.
Three acetolactate synthase (ALS) inhibiting herbicides are currently being evaluated for the control of hydrilla (Hydrilla verticillata L.f. Royle) and other submersed aquatic weeds. The impacts of long-term aqueous exposures of these herbicides on non-target native emergent plant species are unknown. Therefore, trials were conducted to determine the effect of aqueous applications of the ALS-inhibitors penoxsulam [2-(2,2-difluoroethoxy)-N-(5,8-dimethoxy [1,2,4]triazolo[1,5-c] pyrimidin-2-yl)-6-(trifluoromethyl) benzenesulfonamide], imazamox [2-[4,5-dihydro-4-methyl-4-(1-methylethyl)-5-oxo-1H-imidazol-2-yl]-5-(methoxymethyl)-3-pyridinecarboxylic ac-id], and bispyribac sodium [2,6-bis(4,6-dimethoxypyrimidin-2-yloxy)benzoic acid] on established soft-stem bulrush (Scir-pus validus Vahl.), Egyptian panicgrass (Paspalidium gemina-tum (Forssk.) Stapf), maidencane (Panicum hemitomon Schult.), pickerelweed (Pontederia cordata L.) and sagittaria (Sagittaria lancifolia L.). Plants were exposed to initial aque-ous concentrations of each herbicide at 25, 75, 150 and 300 µg/L for 66 d. At harvest, shoot and root biomass of untreat-ed controls by species increased from 100 to >1500%. While both grass species increased in biomass following exposure to ALS-inhibitors at rates up to 300 µg/L, the shoot biomass of panicgrass was inhibited by bispyribac and penoxsulam at concentrations of 75 µg/L and higher when compared to un-treated controls. Maidencane was generally more tolerant than panicgrass to all three herbicides. Bulrush shoot growth was inhibited at all concentrations, with differential respons-es to the 3 herbicides. Pickerelweed shoot growth was re-duced below pre-treatment weights at 25 µg/L and higher following treatment with penoxsulam and bispyribac. Sagit-taria was more sensitive to penoxsulam at rates of 25 and 75ug/L compared to imazamox and bispyribac. There was in-hibition of root growth for all species, but whether inhibition resulted from direct toxicity to roots or as an indirect result of shoot inhibition was not determined. The spectrum of her-bicidal activity for all three herbicides was similar (in order of increasing tolerance: pickerelweed<sagittaria<bulrush<pan-icgrass<maidencane). Use patterns for control of submersed plants need to be established in order to determine the likeli-hood of impacting non-target emergent plants.
The present study was undertaken to evaluate the toxicity and effects of a commercial formulation of the herbicide atrazine (Rasayanzine) on lipid peroxidation and antioxidant enzyme system in the freshwater air breathing fish Channa punctatus. The 12, 24, 48, 72 and 96 h LC(50) of atrazine, calculated by probit analysis, were determined to be 77.091, 64.053, 49.100, 44.412 and 42.381 mg·L(-1), respectively, in a semi static system with significant difference (p < 0.05) in LC(10-90) values obtained for different times of exposure. In addition to concentration and time dependent decrease in mortality rate, stress signs in the form of behavioral changes were also observed in response to the test chemical. In fish exposed for 15 days to different sublethal concentrations of the herbicide (1/4 LC(50) = ∼10.600 mg·L(-1), 1/8 LC(50) = ∼5.300 mg·L(-1) and 1/10 LC(50) = ∼4.238 mg·L(-1)) induction of oxidative stress in the liver was evidence by increased lipid peroxidation levels. The antioxidants superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GR) responded positively in a concentration dependent pattern, thus, suggesting the use of these antioxidants as potential biomarkers of toxicity associated with contaminations exposure in freshwater fishes.
Cypermethrin is considered as one of the endocrine disruptors. Isoflavones play an important role in various physiological processes in the body. It has both estrogenic and antioxidant effects. The objective of this study was to evaluate the protective role of isoflavones (2 mg/kg B.W) on semen quality and plasma testosterone levels of male New Zealand White rabbits given sublethal dose (24 mg/kg BW every other day for 12 weeks) of cypermethrin. Results showed that treatment with cypermethrin caused a significant decreases (P < 0.05) in ejaculate volume, sperm concentration, total sperm output, sperm motility (%), total motile sperm per ejaculate (TMS), packed sperm volume (PSV), semen initial fructose and plasma testosterone. In addition, live body weight (LBW), dry matter intake (DMI) and relative weights of testes and epididymis were decreased. On the other hand, treatment with cypermethrin increased (P < 0.05) the numbers of abnormal and dead sperms, and initial hydrogen ion concentration (pH). Results indicated that the presence of isoflavones together with cypermethrin was capable to minimize its harmful effects. Treatment with isoflavones alone had positive effects on some semen characteristics in spite of it is considered as estrogen-like compound. Since it causes significant increases in libido (by decreasing the reaction time), PSV, sperm motility and TMS, while abnormal and dead sperm were reduced compared to control animals. Meanwhile, isoflavones had no negative effect on ejaculate volume, total sperm output, sperm concentration, initial fructose concentration, pH and plasma testosterone levels. Results demonstrated the beneficial influences of isoflavones in reducing the negative effects of cypermethrin on reproductive characteristics of mature male rabbits. Interestingly, data showed that isoflavones alone caused an improvement in some semen quality and had no negative effects on male fertility, and did not have negative effects on male fertility.
Studies using high dose testosterone (T) administration in normal men as a male contraceptive have resulted in azoospermia rates of only 50-70%. Previous studies of T and progestogen combinations have shown comparable rates of azoospermia, but have been uncontrolled or used T in doses less than that associated with maximal suppression of sperm production. We conducted a randomized, placebo-controlled, single blind trial comparing 6 months of T enanthate administration (100 mg, im, weekly) with the same dose of T enanthate in conjunction with the progestogen levonorgestrel (LNG; 500 micrograms, orally, daily) in 36 normal men, aged 20-42 yr (n = 18 in each group). The primary end points were induction of azoospermia or severe oligospermia (< 3 million sperm/mL). The combination of T plus LNG was much more effective in suppressing sperm production than T alone. Sixty-seven percent of the T plus LNG group (12 of 18) and 33% of the T alone group (6 of 18) achieved azoospermia by 6 months (P = 0.06). Severe ol...
In present study herbicides 2,4-D dissolved in olive oil was administered orally to male rats at dose level 50, 100 and 150 mg/kg b.wt./day for 30 and 45 days. Its reproductive toxicity was evaluated on the basis of fertility, hormonal analysis and biochemical parameters. There was a significant decrease in the weight of testes and sex accessories, and reduction in sperm counts both in epididymis and testes in treated animals. Histology of testes showed degenerative changes in seminiferous tubules. The fertility test showed 30%, 60%, 80% and 50% 80% and 100% negative results for the respective dose levels and days. Testicular glycogen and sialic acid were reduced whereas testicular protein and cholesterol were increased. In addition, a significant decrease in serum testosterone, FSH and LH level was also observed. Present study indicated that 2,4-D showed toxic effects on male reproductive functions.
Butachlor, a chloroacetanilide herbicides, widely used in agriculture by farmers was evaluated to determine its effects on testes of rats. Oral administration of butachlor at dose level of 200 mg/kg b.wt./day for 30 day leads to alterations in the testes. Haematological studies showed decrease in erythrocyte count, haematocrit and haemoglobin levels while an increase was noticed in leukocytes count, blood urea and blood sugar. The weight of testes and accessory sex organs decreased significantly. Butachlor administration brought about marked reduction in sperm counts. A significant reduction in glycogen and sialic acid and an increase in protein and cholesterol content of testes were noticed. Histological examination revealed shrunken seminiferous tubules exhibiting loosened epithelium and reduced number of spermatozoa. Fertility test showed 90% negative fertility in treated rats. In addition, acid phosphatase enzyme activity increased significantly whereas alkaline phosphatase enzyme activity showed sharp decline. It also suppressed testosterone, FSH and LH levels significantly. In conclusion, butachlor has deleterious effects on male reproduction.
The purpose of this study was to investigate the effect of dimethoate (DM), an organophosphorus insecticide, on oxidative stress in kidneys of adult rats and their suckling pups. Female Wistar rats were given daily DM in drinking water 0.2 g/L equivalent to 40 mg/kg bw from day zero until day 10 after delivery. A significant increase was found in relative kidney weights of treated adult rats and their offspring. DM administration affected strongly specific markers of kidney function such as the 24-h urine volume which was higher than in the controls. In test group we have found higher plasma levels and lower urinary levels of creatinine, a specific indicator of glomerular function, and urea than in the controls. Significant increase in creatinine clearance was also found in treated mothers and their suckling pups. These results indicated that DM exposure provoked low glomerular filtration rate in treated group. Interestingly, these biochemical modifications were accompanied by a marked enhancement of lipid peroxidation in kidney indicating significant induction of oxidative damage and alterations of enzymatic antioxidant defences in test group. Impairment of renal function corresponds histologically. In fact, histological changes, seen in the kidney of mothers and their pups treated with DM are characterized by a narrowed Bowman’s space, degenerative of tubular epithelial cells and widened tubular lumen. Moreover in mothers, extensive vascular congestion was observed.We concluded that the effect of DM treatment in lactation period of mothers was fairly reflected in the offspring in all parameters analysed.
Methyl parathion is an organophosphate insecticide that has been used in agriculture and domestic for several years. Vitamin C (200 mg/kg bw per day) + vitamin E (200 mg/kg bw per day), methyl parathion (0.28 mg/kg bw per day) and vitamin C (200 mg/kg bw per day) + vitamin E (200 mg/kg bw per day) + methyl parathion (0.28 mg/kg bw per day) combination were given to rats orally via gavage for 7 weeks. Body and kidney weights, malondialdehyde (MDA) levels and histopathological changes were investigated at the end of 4th and 7th weeks comparatively with control group. When methyl parathion-treated group and vitamins C and E + methyl parathion-treated group were compared to control group body and kidney weights decreased significantly at the end of 4th and 7th weeks. MDA levels increased in kidney tissues of the methyl parathion- and vitamins C and E + methyl parathion-treated groups compared to control group. MDA levels decreased significantly in vitamins C and E + methyl parathion treated group compared with methyl parathion treated group at the end of 4th and 7th weeks. In our light microscopic investigations, after 4 weeks of methyl parathion exposure, glomerular atrophy and vascular dilatation, and after 7 weeks, necrosis and edema were observed in the kidney tissues. After 4 weeks of vitamins C and E + methyl parathion exposure, mononuclear cell infiltrations, and after 7 weeks, calcification were detected in the kidney tissues.
2,4-Dichlorophenoxyacetic acid (2,4-D) is largely used as a selective herbicide in Tunisia. The purpose of this study was to investigate the effects of 2,4-D on the kidneys of adult rats and their suckling pups. Female Wistar rats were divided into two groups: the controls and the treated rats that received 600 mg/L of 2,4-D in their drinking water from the 14th day of pregnancy until day 14 after delivery. Exposure to 2,4-D induced nephrotoxicity as evidenced by an increase in thiobarbituric acid reactive substances and protein carbonyl levels and a decrease in antioxidant enzyme activities such as catalase, superoxide dismutase, glutathione peroxidase in the kidneys of suckling pups and their mothers. In addition, a significant decline in kidney glutathione, non-protein thiol and vitamin C levels was also observed. Histological changes, seen in the kidney of mothers and their pups treated with 2,4-D are characterized by a narrowed Bowman's space, tubular epithelial cells degeneration, widened tubular lumen and vascular congestion.
Glyphosate is the active ingredient and polyoxyethyleneamine, the major component, is the surfactant present in the herbicide Roundup formulation. The objective of this study was to analyze potential cytotoxicity of the Roundup and its fundamental substance (glyphosate). Albino male rats were intraperitoneally treated with sub-lethal concentration of Roundup (269.9mg/kg) or glyphosate (134.95mg/kg) each 2 days, during 2 weeks. Hepatotoxicity was monitored by quantitative analysis of the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) activities, total protein, albumin, triglyceride and cholesterol. Creatinine and urea were used as the biochemical markers of kidney damages. The second aim of this study to investigate how glyphosate alone or included in herbicide Roundup affected hepatic reduced glutathione (GSH) and lipid peroxidation (LPO) levels of animals as an index of antioxidant status and oxidative stress, respectively, as well as the serum nitric oxide (NO) and alpha tumour necrosis factor (TNF-α) were measured. Treatment of animals with Roundup induced the leakage of hepatic intracellular enzymes, ALT, AST and ALP suggesting irreversible damage in hepatocytes starting from the first week. It was found that the effects were different on the enzymes in Roundup and glyphosate-treated groups. Significant time-dependent depletion of GSH levels and induction of oxidative stress in liver by the elevated levels of LPO, further confirmed the potential of Roundup to induce oxidative stress in hepatic tissue. However, glyphosate caused significant increases in NO levels more than Roundup after 2 weeks of treatment. Both treatments increased the level of TNF-α by the same manner. The results suggest that excessive antioxidant disruptor and oxidative stress is induced with Roundup than glyphosate.
"Désormone Lourd" is a 2,4-Dichlorophenoxyacetic based herbicide that includes 600 g/L 2,4-D. In this study we analyzed the toxic effects of 2,4-D on rat liver. Animals were daily treated with 15, 75 and 150 mg/kg, via oral gavage during 4 weeks. Hepatotoxicity was monitored by quantitative analysis of the serum enzymes markers of hepatotoxicity. Oxidative stress markers, catalase and glutathione reductase (CAT and GR), were analyzed in liver. We also investigated liver tissues histopathologically. Our results revealed that, when rats of 2,4-D treated groups were compared with the control group, the body weight decreased and the liver weight increased significantly at the end of the 4th week. The microscopic evaluation showed that 2,4-D induced hepatic cord disruption, focal necrosis, vessel dilation and pycnotic nucleus. Histological effects were found in all treated groups and their severity was dose dependent. Through sub-acute treatment, starting from the low to the high doses of 2,4-D, it was observed that there were effects on the activity of the serum enzyme markers, on TSP, Alb and the glycemia levels. We also observed a significant reduction in the hepatic antioxidant enzyme activities. To conclude, we can suggest that 2,4-D induces hepatoxicity and cellular alterations in rat.
The pesticides are one of the most potentially harmful chemicals liberated in the environment in an unplanned manner Malathion is widely used as a potent pesticide in many countries and has been shown to produce some adverse health effects. A study was conducted to asses the effects of malathion on the male reproductive system of wistar rats. The pesticide was administered to rats orally at dose levels of 50, 150 and 250 mg/kg/body wt/day for 60 days. In comparison to the control rats, there was a significant reduction in the weight of testes, epididymis, seminal vesicle and ventral prostate. Testicular and epididymal sperm density were decreased in the animals treated with malathion. Pre and post fertility test showed 80% negative results after treatment Biochemical profile of the testis revealed a significant decline in the contents of sialic acid and glycogen. Whereas a significant increase in the protein content of testis and testicular cholesterol was observed. The activity of testicular enzyme acid phosphatase increased significantly while decreased alkaline phosphatase activity was found. Malathion also suppressed the level of testosterone significantly Results of the present study clearly suggest that malathion induce toxic effects on the male reproductive system of rats.
A histochemical technique for demonstrating leucocyte alkaline phosphatase activity (LAP), based on direct precipitation of lead phosphate at pH 9.5, is described. The effect of fixative, temperature and stability of the medium on the activity of the enzyme and stability of the colour reaction was thoroughly studied. Peripheral blood smears obtained from both normal humans and pathological cases were studied and the results were compared with these obtained by the azo-dye method.
Fertile male hamsters were injected daily with 66 mg α chlorohydrin/kg to determine the onset and duration decreased and None of the males became infertile within the first 2 days bt marked loss of fertilizing ability of spermatozoa had occurred by 24 hr from the second injection. Infertility occurred in all 5 males after the fourth dose. The fertilizing ability of the spermatozoa was not impaired when the equivalent of 4 daily doses was given as a single dose, thus indicating that sequential daily treatment was necessary for the induction of infertility. The prompt recovery of fertilizing ability of spermatozoa in males which had ligated ductuli efferentes and were given 4 daily doses of α chlorohydrin (66 mg/kg) shows that transport of epididymal spermatozoa and their acquisition of fertilizing ability are not influenced by the drug.
Male hamsters of known fertility were injected subcutaneously with α chlorohydrin to determine the minimal antifertility dose and to elucidate its site of action. Fertility tests at 4 day intervals showed that α chlorohydrin (66 mg/kg) induced infertility within 4 days and fertilization did not occur after artificial insemination with spermatozoa from the cauda epididymidis of such animals. Comparable daily treatment produced the same antifertility effect subsequent to bilateral ligation of the corpus epididymidis and also in castrated animals given daily treatment (100 μg/day) with either testosterone, 5α dihydrotestosterone or 3α androstanediol. The infertility was not related to deficiency of androgen, as judged by the concentration of fructose in the seminal vesicles, or to impaired ejaculation.
The male partners of 68 couples exhibiting 5.1 +/- 0.3 (SEM) years of unexplained infertility were assessed using the conventional criteria of semen quality, the movement characteristics of the spermatozoa and the outcome of the zona-free hamster egg penetration test. After a follow-up period of 2.3 +/- 0.06 (SEM) years, 25 (37%) of these patients were found to have initiated a pregnancy, thereby permitting an analysis of those aspects of semen quality which most accurately predicted their subsequent fertility. A multivariate discriminant analysis revealed that the conventional semen profile, per se, was not of significant value in discriminating the incidence of pregnancy. However, significant discrimination (P = 0.0173) was obtained when the postcapacitation movement characteristics of the spermatozoa were incorporated into the analysis. The accuracy of this prognosis was further increased if either the duration of infertility or the outcome of the zona-free hamster egg penetration test was taken into consideration. Overall classifications of fertility were then 76.3% and 76.5% accurate, respectively. These results suggest that in vitro assessments of human sperm function are of significant value in evaluating male fertility.
The aim of this study was to evaluate the agreement between the glomerular filtration rate (GFR) and an estimate of creatinine clearance (CCr), calculated from the values of body cell mass (BCM) and of plasma creatinine (PCr), thus avoiding urine collection. The value of BCM was obtained from the measurement of total body impedance in 80 renal patients. The relationship between 24-hour urinary creatinine excretion and BCM was evaluated in 30 of these patients. Body cell mass CCr (ml/min) was then calculated in each of the remaining 50 patients. For comparison, 24-hour CCr was measured in the same patients. The correlation coefficient of BCM CCr with GFR was 0.961, while that of 24-hour CCr with GFR was 0.869. Also, the agreement with GFR was better for BCM CCr than for 24-hour CCr. In conclusion, creatinine clearance predicted from body cell mass and plasma creatinine is a better indicator of renal function than measured 24-hour creatinine clearance.
Prior studies had suggested that triptolide, a diterpene triepoxide isolated from a Chinese medicinal plant, might be an attractive candidate as a post-testicular male contraceptive agent. Despite the promise that triptolide would not affect testis function, nagging concerns remained that a delayed onset of testicular effect might exist. The objectives of this study were to assess the effects of relatively longer treatment duration of triptolide on fertility, spermatogenesis, and epididymal sperm pathophysiology; and to evaluate the reversibility of these effects after the cessation of treatment. Adult male Sprague-Dawley rats were fed daily with either 30% gum acacia as a vehicle control (n = 12) or 100 microg/kg body weight (BW) of triptolide for 82 days (n = 12) followed by a recovery period of up to 14 weeks (n = 6). At the end of the treatment period, all rats treated with triptolide were sterile. Cauda epididymal sperm content decreased by 84.8% and sperm motility was reduced to zero. In addition, virtually all cauda epididymal sperm in the triptolide-treated group exhibited severe structural abnormalities. The most striking changes observed were head-tail separation, premature chromatin decondensation of sperm nuclei, a complete absence of the plasma membrane of the entire middle and principle pieces, disorganization of the mitochondrial sheath, and aggregation of many sperm tails. Longer treatment duration of triptolide also affected spermatogenesis, with marked variability in the response of individual animals. The degree of damage ranged from apparently normal-looking seminiferous tubules to flattened seminiferous epithelium lined by a single layer of cells consisting of Sertoli cells and a few spermatogonia. Affected tubules exhibited intraepithelial vacuoles of varying sizes, multinucleated giant cells, germ cell exfoliation, and tubular atrophy. Recovery occurred as early as 6 weeks after cessation of treatment. By 14 weeks, 4 out of 6 triptolide-treated males were fertile and the females that were impregnated by 3 out of 4 triptolide-treated male rats produced apparently normal litters. These results suggest that triptolide has 2 phenotypic effects on mature and maturing germ cells. The first action appears earlier and manifests mainly in epididymal sperm. The second action presumably is directly on germ cells in testis and causes a variable impairment of spermatogenesis that may not be completely reversible. It is unclear if the earlier effect is a delayed manifestation of subtle testicular injury or post-testicular action.
Pregnant CD-1 mice were administered a commercial 2,4-dichlorophenoxyacetic acid (2,4-D) formulation on days 6-16 days of gestation, in drinking water at concentrations ranging from 0 to 1.0% of the formulated product, equivalent to approximately 0-650 mg/kg per day expressed as the amine derivative. The effect of 2,4-D on immune function was evaluated in offspring 7 weeks after birth. The dams tolerated repeated 2,4-D exposure in drinking water without difficulty. The offspring exhibited decreased body weight with minor reductions in the kidney weights in the 0.1 and 1.0% 2,4-D treatment groups. A generalized suppression of lymphocyte stimulation by concanavalin A (Con A) was observed at high dose of commercial 2,4-D formulation (1.0%). Cytometric studies of the lymphocyte subpopulations demonstrated an increased relative count of B cells and reduced T cytotoxic or suppressor cells in the 1.0% formulation. The humoral immune response, antibody production against sheep red blood cells and peritoneal macrophage phagocytic function, were not altered by 2,4-D. Since the immune alterations in the offspring were observed many weeks after exposure, it appears as though 2,4-D exposure during gestation causes permanent changes in cell types associated with immune function. Since 2,4-D is not considered a persistent chemical, it is unlikely that 2,4-D residues are contributing significantly to the observed immune alterations. The immune alterations were observed only in the higher treatment groups. Therefore, the impact on human and animal health from an immune perspective, which would be encountered following normal application in the environment, would be minimal.
The male antifertility effect of a water-chloroform extract (GTW) from the root xylem of Tripterygium wilfordii has attracted worldwide interest. In the present study, by using whole-cell recording, the effects of GTW and two isolated monomers from GTW, demethylzeylasteral and L-epicatechin, on the T-type Ca(2+) channels in mouse spermatogenic cells were investigated. The results showed that each of them concentration-dependently and partially reversibly inhibited T-type Ca(2+) current in the cells. The IC(50) of GTW and demethylzeylasteral were approximate, while L-epicatechin inhibited the channels at a much higher concentration. The voltage dependence of the inhibitory effect and the changes in activation and inactivation time constants after application of these compounds were also examined. These data suggest that the inhibition of T-type Ca(2+) currents could be responsible for the antifertility activity of these compounds.
Deltamethrin is a synthetic pyrethroid insecticide used worldwide in agriculture, home pest control, protection of foodstuff and disease vector control. The objective of this study was to investigate the propensity of deltamethrin to induce oxidative stress and changes in biochemical parameters and enzyme activities in male rats following a short-term (30 days) oral exposure and its possible attenuation by Vitamin E (Vit. E). Rats were assigned to 1 of 4 treatment groups: 0mg Vit. E and 0mg deltamethrin/kg body weight (BW) (control); 100mg Vit. E/kg BW; 1.28mg deltamethrin/kg BW; 100mg Vit. E plus 1.28mg deltamethrin/kg BW. Results obtained showed that deltamethrin significantly (P<0.05) induced thiobarbituric acid-reactive substances (TBARS; the marker of lipid peroxidation) in plasma. The activities of glutathione S-transferase (GST) and superoxide dismutase (SOD) were significantly decreased due to deltamethrin administration. On the other hand, treatment with Vitamin E alone increased the activities of GST and SOD, and decreased the levels of TBARS. Also, Vitamin E alleviated the harmful effect of deltamethrin in the combination group. Enzymatic activities of aminotransferases (AST and ALT), phosphatases (AcP and AlP) and lactate dehydrogenase (LDH) in plasma were significantly increased, while acetylcholinesterase (AChE) was inhibited. Deltamethrin significantly (P<0.05) increased the levels of plasma total lipid (TL), cholesterol, triglyceride (TG), low density lipoprotein (LDL) and very low density lipoprotein (VLDL), while the level of high density lipoprotein (HDL) decreased. Vitamin E alone decreased the levels of lipids and lipoproteins, and alleviated the harmful effects of deltamethrin. Concentrations of glucose, urea, creatinine and total bilirubin were increased. While, plasma total protein (TP), albumin (A) and globulin (G) were significantly (P<0.05) decreased. The present study revealed that the presence of Vitamin E could diminish the adverse effects of deltamethrin on most of biochemical parameters, lipid peroxidation and enzyme activities in rats.
This study investigates the effects of subchronic exposure to organophosphate insecticide Malathion (Fyfanon 50 EC 500 g/l) of commercial grade. It was administered intragastrically by stomach tube in the amount of 1 ml of corn oil containing 100 mg/kg body weight (BW) daily for 32 days. At the end of the experiment, acetylcholinesterase activity (AChE), haematocrit value, haemoglobin content, and blood glucose concentration were estimated. The liver and the skeletal muscle were removed to determine hepatic and muscular glycogen, hepatic proteins and lipids contents. No sign of toxicity was observed until the end of experiment. No significant change in the haematocrit value was observed, in spite of the significant increase in haemoglobin content, which can be considered as an adaptive situation in order to guarantee a good oxygenation in response to pulmonary damage induced following subchronic exposure to organophosphorus compound. Malathion intoxication decreased significantly hepatic proteins and lipid contents that could be associated to liver gluconeogenesis. This result was coupled with a significant decrease in muscular glycogen rate, which indicates a stimulated glycogenolysis in favour of glucose release into the blood until reaching hyperglycaemia. Several studies indicate that hyperglycaemia is temporary, which is probably due to a stimulated glycogenesis that increases hepatic glycogen deposition and return of glucose to control levels, as demonstrated in our study. One possible explanation for these results could be the turnover of glucose by a succession between its release via glycogenolysis and gluconeogenesis, which involves abnormal hyperglycaemia, and its storage via glycogenesis in subchronic exposure to malation.
Juvenile rats are more susceptible than adults to the acute toxicity of organophosphorus insecticides like chlorpyrifos (CPF). Age- and dose-dependent differences in metabolism may be responsible. Of importance are CYP450 activation and detoxification of CPF to chlorpyrifos-oxon (CPF-oxon) and trichloropyridinol (TCP), as well as B-esterase (B-est) and PON-1 (A-esterase) detoxification of CPF-oxon to TCP. In the current study, a physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) model incorporating age-dependent changes in CYP450, PON-1, and tissue B-est levels for rats was developed. In this model, age was used as a dependent function to estimate body weight which was then used to allometrically scale both metabolism and tissue cholinesterase (ChE) levels. In addition, age-dependent changes in brain, liver, and fat volumes and brain blood flow were obtained from the literature and used in the simulations. Model simulations suggest that preweanling rats are particularly sensitive to CPF toxicity, with levels of CPF-oxon in blood and brain disproportionately increasing, relative to the response in adult rats. This age-dependent nonlinear increase in CPF-oxon concentration may potentially result from both the depletion of nontarget B-est and a lower PON-1 metabolic capacity in younger animals. The PBPK/PD model behaves consistently with the general understanding of CPF toxicity, pharmacokinetics, and tissue ChE inhibition in neonatal and adult rats. Hence, this model represents an important starting point for developing a computational model to assess the neurotoxic potential of environmentally relevant organophosphate exposures in infants and children.
The present study was undertaken to determine the effect of simulated microgravity on the testis of the rats and to evaluate the possibility of spermatogenesis failure in space environment. Fifty-four adult male albino rats were used in this study. They were divided equally into intact control, stress control and experimental groups. The rats of the intact control group (Group Ia) were kept without intervention. The rats of both the stress control and experimental groups were subjected to inguinal canal ligation and tail-suspension. In the stress control group (Group Ib) the hindlimbs were not elevated above the floor of the housing units whereas in the experimental groups the hindlimbs were elevated for one week (Group II) and six weeks (Group III), respectively. In a third experimental group (Group IV) the rats were hindlimb-suspended for six weeks followed by another six weeks without suspension to allow recovery. Prior to sacrifice, the animals were weighed and anesthetized, and the testes were excised and weighed. Testicular specimens were processed for histological, histochemical and morphometric studies. The results of the present study revealed that only after six weeks of hindlimb-suspension, the rats showed a significant decline in testicular weight compared with the control groups. Histologically, few abnormalities were observed in some seminiferous tubules in one-week hindlimb-suspended group. Spermatogenesis was significantly reduced by six-week of hindlimb-suspension marked by atrophy of the testes and loss of all germ cells, except a few spermatogonia. Spermatogenesis was partially restored in the recovery group. In all groups the appearance of Sertoli cells remained the same. Proliferation of Leydig cells was observed in the experimental groups. It is concluded that spermatogenesis is severely inhibited by six weeks of hindlimb-suspension and that it is partially restored following six weeks of recovery. This study provides further insights regarding the serious effects of long-term exposure to microgravity on the testes of mammals, including human beings.
Bhawalpur is a major cotton-growing area in Pakistan. Cotton picking in Pakistan is carried out by females and as a result of the intensive use of pesticides during the growing season these females are exposed to pesticide residues in the picking season. In the present study, peripheral blood was obtained from 69 cotton pickers and 69 unexposed females and used to assess the effect of pesticide exposure on genetic damage as well as on hepatic enzymes and serum cholinesterase. The subjects were of similar average age in workers and control groups (37.55 +/- 12.75 vs. 37.52 +/- 13.47, P > 0.05). Average exposure time of the picker females was 10.26 +/- 6.14 years. Subjects from the exposed group did not use any protective measures during their work activities. Levels of serum cholinesterase were lower, and levels of alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase were higher in the exposed workers as compared with the control group (P < 0.001). The exposed group exhibited significantly increased frequencies of binucleated cells with micronuclei (12.72 +/- 3.48 vs. 4.35 +/- 2.44, P < 0.001) and total number of micronuclei in binucleated lymphocytes (16.51 +/- 4.27 vs. 5.86 +/- 3.09, P < 0.001) in comparison with subjects of the control group. The binucleated cells with micronuclei frequency also seemed to increase with age in both the groups, however, the magnitude of increase was greater in exposed group than the control. Results from the present study indicate that occupational exposure to pesticide mixtures results in cytogenetic damage in exposed females.
Organophosphates are among the most widely used synthetic insect pesticides. The widespread use of organophosphates has stimulated research into the possible existence of effects related with their reproductive toxic activity. Present study was therefore, undertaken to assess the effects of chlorpyrifos on testes, the main organ of male reproduction. Chlorpyrifos at the dose levels of 7.5, 12.5 and 17.5 mg/kg b. wt./day was administered orally to male rats of Wistar strain for 30 days to evaluate the toxic alterations in testicular histology, biochemistry, sperm dynamics and testosterone levels. The body weight of animals did not show any significant change, however, a significant reduction was observed in testes. Chlorpyrifos also brought about marked reduction in epididymal and testicular sperm counts in exposed males and a decrease in serum testosterone concentration. Histopathological examination of testes showed mild to severe degenerative changes in seminiferous tubules at various dose levels. Fertility test showed 85% negative results. A significant reduction in the sialic acid content of testes and testicular glycogen was noticed, whereas the protein and cholesterol content was raised at significant levels. All these toxic effects are moderate at low doses and become severe at higher dose levels. From the results of the present study it is concluded that chlorpyrifos induces severe testicular damage and results in reduction in sperm count and thus affect fertility. Small changes in sperm counts are known to have adverse affects on human fertility. Therefore, application of such insecticide should be limited to a designed programme.
12-month chronic dietary toxicity study in Beagle dogs
- B Altmann
Altmann, B., 2000. 12-month chronic dietary toxicity study in Beagle dogs. Toxicology, Novartis
Crop Protection AG, Stein, Switzerland, Basel Report No. 971012, Novartis No. 1219-98, 2
August 2000.
Evaluation of the new active azimsulfuron in the product Gulliver herbicide. Australian Pesticides & Veterinary Medicines Authority
APVMA, 2006. Evaluation of the new active azimsulfuron in the product Gulliver herbicide.
Australian Pesticides & Veterinary Medicines Authority. Public Release Summary.
A subchronic (3-month) toxicity study of DPX-66037-24 in the dog via dietary administration
- J E Atkinson
Atkinson, J.E., 1991. A subchronic (3-month) toxicity study of DPX-66037-24 in the dog via dietary
administration. Bio/dynamics, Inc., East Millstone, NJ, Project No. 91-3653, 12/20/91.
28-day exploratory toxicity study in male rats (gavage)
- M Bachmann
Bachmann, M., 1996. 28-day exploratory toxicity study in male rats (gavage). Short/Long-term
Toxicology, Novartis Crop Protection AG, 4332 Stein, Switzerland; Study ID: 961089;
9/2/96.
A subchronic (3 months) oral toxicity study with TH-913 in the rat via dietary admixture
- D S Barrett
Barrett, D.S., 1990. A subchronic (3 months) oral toxicity study with TH-913 in the rat via dietary
admixture. Bio/dynamics, Inc., East Millstone, NJ, Laboratory Project Identification: 87-3244, 10/18/1990.
Florasulam: assessment of immunotoxic potential using the sheep red blood cell assay after 28-day dietary exposure to female F344/DuCrl rats
- D R Boverhof
Boverhof, D.R., 2011. Florasulam: assessment of immunotoxic potential using the sheep red blood
cell assay after 28-day dietary exposure to female F344/DuCrl rats. Toxicology & Environ.
Res. and Consulting, The Dow Chemical Company, Midland, MI., Study ID: 101078, 28
November 2011.
Effect of acute exposure of glyphosate herbicide, on wistar rats with reference to haematology and biochemical analysis. The bioscan an Intl
- U S Deshmukh
- F Iram
- M S Joshi
Deshmukh, U.S., F. Iram and M.S. Joshi, 2013. Effect of acute exposure of glyphosate herbicide, on
wistar rats with reference to haematology and biochemical analysis. The bioscan an Intl.
Quart. J. of Life Sci., Vol. 8 (2): 381-383.
Gulliver herbicide. Safety Data Sheet (SDS), Version 2.3, Doc. no. 130000000625
- Du Pont
Du Pont, 2015. Gulliver herbicide. Safety Data Sheet (SDS), Version 2.3, Doc. no. 130000000625.
Du Pont (Australia) Pty. Ltd.
Peer review of the pesticide risk assessment of the active substance penoxsulam
EFSA, 2009. Peer review of the pesticide risk assessment of the active substance penoxsulam.
European Food Safety Authority, EFSA Scientific Report, 343, 1-90.
Penoxsulam: report of the cancer assessment review committee PC code: 119031. Office of Prevention, Pesticides and Toxic Substances
EPA, 2004. Penoxsulam: report of the cancer assessment review committee PC code: 119031. Office
of Prevention, Pesticides and Toxic Substances, March 24, 2004.
Methods of clinical surveillance: Effects on liver and other organs
- H J Fallon
Fallon, H.J., 1987. Methods of clinical surveillance: Effects on liver and other organs. 1909-1912.
A rapid and precise method for the determination of urea
- J K Fawcett
- J E Soctt
Fawcett, J.K. and J.E. Soctt, 1960. A rapid and precise method for the determination of urea. J Clin
Path 1960; 113: 156.
3-month oral toxicity study in rats (administration in the food). Toxicology, Novartis Crop Protection AG
- R Gerspach
Gerspach, R., 1998. 3-month oral toxicity study in rats (administration in the food). Toxicology,
Novartis Crop Protection AG, 4332 Stein, Switzerland; Study ID: 971009; 1/20/98.
24-months carcinogenicity and chronic toxicity study in rats
- R Gerspach
Gerspach, R., 2000. 24-months carcinogenicity and chronic toxicity study in rats. Toxicology,
Novartis Crop Protection AG, Stein, Switzerland, Basel Study No. 971014, Novartis No. 828-97, 26 September 2000.
Pesticides and Health Risks
- R C Gilden
- K Huffling
- B Sattler
Gilden, R. C., K. Huffling and B. Sattler, 2010. Pesticides and Health Risks. Journal of Obstetric,
Gynecologic and Neonatal Nursing (JOGNN), 39: 103-110. DOI: 10.1111/j.1552-6909.2009.01092.x http://jognn.awhonn.org.