Enhancement of parathion toxicity to quail by heat and cold exposure

Effects of ambient temperature on the acute oral toxicity of parathion were investigated in Japanese quail (Coturnix japonica) maintained at thermoneutral temperature (26°C) or exposed to elevated (37°C) or reduced (4°C) temperatures commonly encountered by free-ranging wild birds. Based upon estimates of the median lethal dosage, there was up to a twofold enhancement of parathion toxicity in birds chronically exposed to heat or cold. Twenty-four hours after administration of a low dosage (4 mg/kg body wt, po), there was markedly greater cholinesterase inhibition in surviving heat-exposed quail compared with those reared at 26°C (e.g., brain acetylcholinesterase depression of 42% versus 12%). There were no differences in hepatic activities of parathion oxidase, paraoxonase, or paraoxon deethylase which could account for greater toxicity to chronically heat-exposed birds. In contrast, 4 mg parathion/kg wt elicited less plasma cholinesterase inhibition in cold-exposed quail compared to thermoneutral controls (e.g., <10% versus 48% depression after 24 hr). Increased liver weight and a doubling of paraoxonase activity may have been associated with greater tolerance to sublethal doses of parathion in chronically cold-exposed quail. These findings, together with limited field observations, indicate that the hazard associated with anticholinesterase exposure of wild birds is substantially influenced by environmental temperature.     

Hormonal responses and tolerance to cold of female quail following parathion ingestion

Thirty-week-old female bobwhite quail (Colinus virgininus), maintained at 26 ± 1°C, were provided diets containing 0,25, or 100 ppm parathion ad libitum. After 10 days, birds were exposed to mild cold (6 ± 1°C) for 4, 8, 12, 24, or 48 hr. Brain acetylcholinesterase activity was inhibited in a dose-dependent manner in birds receiving 25 and 100 ppm parathion. Body weight, egg production, and plasma luteinizing hormone and progesterone concentrations were reduced in birds receiving 100 ppm parathion compared with other groups. Cold exposure did not alter plasma corticosterone levels in the 0- and 25-ppm parathion groups, but a two- to fivefold elevation of plasma corticosterone was observed in birds fed 100 ppm parathion. These findings indicate that (i) short-term ingestion of parathion can impair reproduction possibly by altering gonadotropin or steroid secretion, and (ii) tolerance to cold may be reduced following ingestion of this organophosphate.     

The toxicological significance of paraoxon deethylation

The in vivo formation of deethylation and hydrolytic products of paraoxon degradation after parathion or paraoxon administration was nearly equal in control male rats, and the relative abundance of metabolites was not appreciably altered by pretreatment of rats with enzymeinducing agents. However, pretreatment with inducers dramatically increased the oxidative paraoxon O-deethylase of male rat liver while having little effect on hydrolytic enzymes. Prior to induction, the hepatic O-deethylase activity was greatly inferior to the various hydrolytic enzymes, but nearly equal levels of both enzyme systems were found after induction. These results indicate that a large portion of the hepatic hydrolases detected in vitro is not active in vivo. It also appears that the majority of the induced hepatic deethylase was not involved in vivo at the dosage levels employed. The in vivo metabolism of monoethyl paraoxon was also demonstrated. The predominant metabolite of ethyl-[1-¹⁴C]monoethyl paraoxon is ¹⁴CO₂, while phenyl-[1-¹⁴C]monoethyl paraoxon yielded 4-nitro[1-¹⁴C]phenol. Paraoxon deethylation was also shown to be an important detoxication mechanism in female rats and male mice and must be considered in interpreting the toxicological properties of parathion and paraoxon.     

Degradation of parathion applied to peach leaves.

Parathion was applied to peach trees in three different formulations 70 days before harvest. Leaf samples were taken periodically through the 70-day period and gas-liquid chromatographic analyses were conducted for dislodgable and penetrated residues. Analyses were also conducted for paraoxon and the s-ethyl isomer of parathion. Punched samples were compared to whole-leaf samples; generally residue levels for both types corresponded closely. A new experimental formulation, encapsulated parathion, produced highest levels of total parathion throughout the 70-day study, but even this formulation resulted in low total residue levels around 1 ppm at time of harvest. Degradation of the s-ethyl isomer of parathion was generally very rapid in all formulations studied. Dislodgable residues of paraoxon may be significant in some formulations and should be included in parathion degradation studies. Much of the parathion found on peach leaves throughout the growing season was dislodgable residue, but this depended considerably on the formulation used.     

Significance of phosphorylation in organophosphate-mediated β-glucuronidase release from the rat liver

The elevation of rat blood β-glucuronidase caused in vivo by O,O-dialkyl O-phenyl phosphates and phosphorothioates correlated well with the electron-withdrawing tendency (σ^?) of leaving group substituents indicating the importance of a phosphorylation mechanism in the enzyme release. Hydrophobic bonding of these compounds may facilitate the phosphorylation since hydrophobicity (π) of substituents also correlated with the enzyme release. SKF 525-A decreased the elevation of β-glucuronidase by parathion through the suppression of paraoxon production. Pretreatment of rats with phenobarbital or DDE resulted in lower and delayed enzyme release caused by parathion.     

植物次生物质对棉铃虫谷胱甘肽S-转移酶和乙酰胆碱酯酶的影响

分别用含０．０１％的芸香甙,槲皮素２－十三烷酮的人工饲料连续饲养棉铃虫Ｈｅｌｉ－ｃｏｖｅｒｐａａｒｍｉｇｅｒａＨｕｂｎｅｒ１～７代,测定不同处理的棉铃虫种各谷胱甘肽Ｓ－转移酶（ＧＳＴ）和乙酰胆碱酯酶（ＡＣｈＥ）的活性变化以及幼虫对杀虫剂的反应,以单独人工饲料养的各种作对照,芸香甙Ｆ１代对甲基硫磷的耐药性提高３倍,槲皮素Ｆ１,Ｆ２代和２－十三烷酮Ｆ１代对甲基对硫磷的耐药性有所提高,对灭多威和溴氰菊酯     

Organophosphate degradation by insecticide-resistant and susceptible populations of mosquitofish (Gambusia affinis)

Phosphorothionate and phosphate degradation was investigated as a factor which could influence the tolerance of organochlorine compound-resistant and susceptible mosquitofish (Gambusia affinis) to parathion and methyl parathion. The greater toxicity of methyl parathion than parathion can be attributed in part to a higher rate of degradation of methyl paraoxon than paraoxon (7-fold), but not to any difference in phosphorothionate dearylation. Resistant fish possess higher levels of microsomal mixed-function oxidases which can degrade methyl parathion (1.3-fold); these higher levels could contribute to the increased methyl parathion tolerance by this population over the susceptible population. Environmentally induced tolerance to parathion in the resistant population may be the result of increased levels of parathion degradation by induced mixed-function oxidases which can dearylate parathion. The increased tolerance of either insecticide by the resistant population is not caused by degradation of the phosphates by phosphotriesterases.     

Recovery of cholinesterase activity in five avian species exposed to dicrotophos,and organophosphorus pesticide

The responses of brain and plasma cholinesterase (ChE) activities were examined in mallard ducks, bobwhite quail, barn owls, starlings, and common grackles given oral doses of dicrotophos, an organophosphorus insecticide. Up to an eightfold difference in response of brain ChE activity to dicrotophos was found among these species. Brain ChE activity recovered to within 2 SD of normal within 26 days after being depressed 55 to 64%. Recovery of brain ChE activity was similar among species and followed the model Y = a + b (log₁₀X).     

Organophosphorus poisoning: A comparative study of the toxicity of chlorfenvinphos [2-chloro-1- (2′, 4′, -dichlorophenyl) vinyl diethyl phosphate] to the pigeon,the pheasant and the Japanese Quail

The acute oral toxicity of chlorfenvinphos [2-chloro-1-(2′, 4′-dichlorophenyl)vinyl diethyl phosphate] was measured in pigeon (Columba livia), pheasant (Phasianus colchicus), and quail (Coturnix coturnix japonica) and the compound was shown to be particularly toxic to pigeons. Additionally, all three species were fed chlorfenvinphos at 100 ppm in their diet for two or four weeks and esterase measurements were made by conventional and electrophoretic methods on extracts of liver, kidney and brain. The conventionally measured esterase inhibition correlated well with the acute oral toxicity figures. A more detailed study of the histochemically stained electrophoregams showed some discrepancies compared with conventional methods but offered a possible explanation of the inter-species toxicity difference in that it revealed differential inhibition of some brain iso-esterases in pigeon but not in pheasant or quail.     

Determination of residues of promecarb and its metabolite, 3-methyl-5-isopropylphenol,in cattle

A procedure is described for the colorimetric determination of promecarb as 3-methyl-5-isopropylphenol in tissues using 2,6-dichlorpbenzoquinone-4-chlorimine as the chromogen. Cattle were exposed to either 1, 3, 5 or 8 spray applications of a 0·2% promecarb emulsion at 3-day intervals or were fed promecarb at 2 ppm or 20 ppm daily in the diet for 20 days. All animals were slaughtered 30 h after final exposure. Of the animals in the spraying trial, residues in omental fat ranged from 0·9 ppm to 1·5 ppm promecarb and 0·4 ppm to 1·9 ppm 3-methyl-5-isopropylphenol. Residues in perirenal fat ranged from 0·8 ppm to 1·9 ppm promecarb and 0·9 ppm to 1·6 ppm 3-methyl-5-isopropylphenol. Residues in diaphragm muscle did not exceed 0·06 ppm. In the feeding trial, the maximum residues induced were 2·2 ppm promecarb and 1·4 ppm 3-methyl-5-isopropylphenol in omental fat of an animal fed for 20 days on a diet containing 20 ppm promecarb.     

Neurotoxic effects of subacute exposure of dichlorvos and methyl parathion at sublethal dosages in rats

The present study was designed to understand the effects of sublethal dosages of dichlorvos (DIC) and methyl parathion (MP) on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in various tissues of rats exposed to 5 and 10 ppm of DIC and MP in drinking water ad libitum for 28 days continuously. According to the results, AChE activity was significantly decreased in all the tissues of rats treated with both dosages of DIC and MP except for in the lungs treated with both dosages of DIC. With regard to the BChE, MP caused a significant decrease in the liver, heart and lungs with 5 ppm dosage whereas it did not change the BChE activity in the other tissues with two dosages. Also, DIC caused a significant decrease in BChE activity in the heart tissue treated with both dosages and in the brain of rats treated with 5 ppm. The observations presented led us to conclude that the administrations of MP and DIC at sublethal concentrations inhibited AChE and BChE activities in the rats. These results suggest that inhibition of AChE may be a better biomarker for the assessment of neurotoxic effects in the living.     

Action of pesticides on earthworms. Part III: Inhibition and reactivation of cholinesterases in Eisenia foetida (Savigny) after treatment with cholinesterase-inhibiting insecticides

The degree of inhibition and the rate of recovery of total cholinesterase level were investigated after in-vivo treatment of the earthworm Eisenia foetida (Savigny) with aldicarb, carbaryl, carbofuran, oxamyl, and the O-analogues of bromophos (bromo-phosoxon), parathion (paraoxon), parathion-methyl (paraoxon-methyl), and trichloronate (trichloronatoxon). The results can be explained by the presence of two cholinesterases (E1 and E2), which were demonstrated by in-vitro inhibition studies. E1 was the most sensitive to all the inhibitors tested. The in-vivo reactivation rate after inhibition with paraoxon was very high for E1 and very low for E2. Therefore, pretreatment with paraoxon probably increased the toxicity of carbaryl. It was concluded that the toxicity towards E. foetida can be explained in terms of cholinesterase inhibition, provided that the action on the two cholinesterases and the worms' tolerance for a transient but almost total cholinesterase depression are taken into account. Data are given showing that two other species of earthworms also contain different types of cholinesterases with respect to reactions with inhibitors.     

Action of pesticides on earthworms. Part II: Elimination of parathion by the earthworm Eisenia foetida (Savigny)

The earthworm, Eisenia foetida, eliminated parathion and carbofuran at first order rates when continually rinsed in water after treatment with the pesticides. This experiment was also carried out on Lumbricus rubellus for comparison. Carbofuran which is more soluble in water, was eliminated quicker than parathion. The later rate of elimination was very similar for the two species, but immediately after injection the rate was much higher in E. foetida. The metabolism of 1-ethyl¹⁴C labelled parathion and paraoxon (diethyl 4-nitrophenyl phosphate) was studied in E. foetida. The worm was able to convert parathion to paraoxon by a rather slow process although this metabolite could not be detected in the worms due to its rapid transformation to diethyl hydrogen phosphate. Indirectly, paraoxon can be postulated as a parathion metabolite because of a progressive depression of cholinesterase level observed after treatment with parathion. Small amounts of diethyl hydrogen phosphate were detected as a metabolite of parathion; this is also an indication of paraoxon formation. During the 30 h following injection of parathion, only 4.4% of the applied dose was recovered as water-soluble metabolites (2.8% in the worms and 1.6% in the sand surrounding them), while 52% was recovered as unmetabolised parathion. Because of inefficient injection, only 70-59% of the dose thought to be injected was recovered. Therefore the part of the actual applied dose that remained unmetabolised was probably even greater (88%). Five days after injection of parathion, 15 and 9.3 % of the recovered radioactivity in the surrounding sand and in the worm extracts, respectively, was identified as O,O-diethyl O-hydrogen phosphorothioate, 3.7 and 7.0% as diethyl hydrogen phosphate, 8.8 and 3.3% as O-ethyl O-4-nitrophenyl O-hydrogen phosphorothioate (desethylparathion) and/or O-4-aminophenyl O,O-diethyl phosphorothioate, while 70.3 and 80.4% was unmetabolised parathion. Paraoxon was very quickly hydrolysed to diethyl hydrogen phosphate in vivo and in vitro. The in-vitro hydrolysis was associated with a microsomal fraction and was not inhibited by ethylenediaminetetra-acetic acid or 4-(chloromercuri)benzoic acid, and incompletely by aldicarb. Cholinesterase and arylesterase were therefore excluded as enzymes responsible for the activity.     

Effectiveness of cyfluthrin dust treatment for control and protection of shelled maize against infestation by the larger grain borer,Prostephanus truncatus (Horn) (Coleoptera: Bostrichidae) in Tanzania

Abstract

Knockdown, mortality and residual activity of pyrethrins and cyfluthrin were studied on the larger grain borer (LGB), Prostephanus truncatus (Horn). Pyrethrum marc with 0.4% pyrethrins and cyfluthrin dust (0.1% a.i.) when applied on filter paper at 0.72 mg/cm² gave 98.6% and 100% knockdown (KD) respectively after 6 h. Cyfluthrin dust had a faster KD effect with 100% KD compared to 93.1% for pyrethrum marc, ½1/2>h after treatment. After 24 h there was no recovery from KD in both treatments. After 72 h, 23.2% of the LGB had recovered from KD while mortality was 76.8% in the pyrethrum marc treatment. After the same period, cyfluthrin resulted in 100% mortality. Mortality of P. truncatus exposed to different dosages of cyfluthrin dust in shelled maize was less than 100% at dosages lower than 1 part per million (ppm) but was 100% at 1 ppm and higher dosages 3 days after treatment. Progeny emergence was suppressed at all dosage levels above 0.25 ppm compared to a mean progeny of 68.8 in the check after 45 days. Cyfluthrin dust was more residually toxic at 0.5 ppm and higher dosages, with mortality of >90% at 5 months after treatment. This suggests that cyfluthrin dust at 0.1% a.i. mixed with shelled maize at 1 ppm will give protection and control of LGB infestation.     

Survival Dynamics of Aphanomyces cochlioides Oospores Exposed to Heat Stress

ABSTRACT To determine how exposure to heat effects their survival, oospores of Aphanomyces cochlioides isolate C22 were exposed in water to 35, 40, 45, or 50 degrees C for prescribed times and then examined for viability. The Weibull model was modified to represent the effects of temperature on survival of oospores. The final fitted model gave lethal doses for 50% of the oospores of 251, 49.8, 9.8, and 1.9 h at 35, 40, 45, and 50 degrees C, respectively. To determine if alternating high and low temperatures resulted in (i) recovery from heat damage during low temperature periods, (ii) increased susceptibility to heat damage, or (iii) if effects of heat damage were cumulative, oospores were examined after each of four 24-h cycles at 45 degrees C for 4 h and 21 degrees C for 20 h. Survival of oospores exposed to alternating high and low temperatures fit the cumulative effects model. Significant variability in heat tolerance among five isolates was observed (P< 0.001) but model parameters successfully accommodated this variability (R(2) = 0.96, P < 0.001). This research shows that under wet conditions, there are predictable patterns to mortality for A. cochlioides oospores exposed to continuous or fluctuating high temperatures.     

Factors affecting the sequential acquisition by Danish houseflies (musca domestica L.) of resistance to organophosphorus insecticides

The prolonged use of dimethoate, introduced into Denmark to control houseflies (Musca domestica L.) that had become resistant to parathion and diazinon, resulted ultimately in dimethoate resistance. Selection with dimethoate led to the disappearance of the hydrolytic phosphatase, a major mechanism of resistance to parathion and diazinon, and its replacement by the acetylcholinesterase AChER with somewhat decreased sensitivity to inhibition by organophosphorus (OP) insecticides. The hydrolytic phosphatase probably disappeared because low substrate turn-over made it ineffective against dimethoxon (O, O-dimethyl S-methylcarbamoylmethyl phosphorothioate, also known as omethoate). which accumulates at higher concentrations than paraoxon (diethyl4-nitrophenyl phosphate) in the haemolymph. Dimethoate selected AChER preferentially because it improved the chances of houseflies surviving against the relatively poor AChE inhibitor dimethoxon, whereas its relatively small insensitivity to OP insecticides, unimportant against good inhibitors such as paraoxon, prevented its selection by parathion.     

Toxicity in the brain of organophosphate insecticides: Comparison of the toxicities of metabolites with parent compounds using an intracerebral injection method

The toxicity in the brain of several parathion, fenthion, and fensulfothion insecticides and their toxic metabolites was determined by a technique of directly injecting the compounds into the region of the third ventricle of conscious mice, an area rich in cholinesterase activity. The results were compared on a body weight basis to the toxicity of these compounds when given by ip and oral routes. The results show that there is a direct relationship between the relative inhibition of cholinesterase activity in the brain by the organophosphates (e.g., methyl paraoxon, Sumioxon, and some members of the fenthion series) and the toxicity of these compounds in the brain. Methyl paraoxon and Sumioxon were found to be very toxic in the brain, Sumioxon being three to four times less toxic than methyl paraoxon. This is of the same order of effect of these compounds in inhibiting cholinesterases. It is concluded that any selective effects of Sumithion compared with methyl parathion must be due to the greater rate of metabolism of Sumithion to less toxic metabolites as well as to the lower toxicity of the oxon metabolite and not due to the relative rates of penetration of the toxic oxygen metabolites as previously suggested [J. Miyamoto, Agr. Biol. Chem.28, 422 (1964)]. A gas-liquid chromatographic method was employed to assess the distribution in the brain following intracerebral injection of the parathion-type compounds. The results suggest that there may be intracerebral metabolism of thionophosphates in vivo.     

Perfusion analysis of periportal and centrilobular metabolism of paraoxon in the rat liver

Paraoxon infused into the rat liver during perfusion in situ with Waymouth's medium underwent chromatographic translobular migration with an apparent hepatic transit time of 3 min. Intralobular heterogeneity of paraoxon metabolism was examined by analyzing metabolites produced under conditions minimizing the chromatographic translobular migration of paraoxon. Periportal and centrilobular activities were estimated following forward and retrograde infusion of paraoxon, respectively. Centrilobular hepatocytes exhibited nearly twice the metabolic rate of the periportal cells. Pretreatment of the rat with DDE resulted in about a threefold increase in the ratio of oxidative deethylation to hydrolytic dearylation in the centrilobular region. The differentials observed by these analyses were less pronounced than expected from enzyme analyses in vitro, possibly reflecting secondary metabolism or intracellular heterogeneity of metabolic activities.     

Metabolism of [14C]parathion and [14C]paraoxon in isolated,perfused rat livers

Perfusion of ¹⁴C-(ring)-parathion or ¹⁴C-(ring)-paraoxon with blood through isolated, intact rat livers resulted in the rapid degradation of these insecticides. Degradation was negligible in the absence of rat liver (controls), thus demonstrating the capacity of the liver per se to effectively degrade these compounds. Of the total radiocarbon recovered after liver perfusion with [¹⁴C]parathion, 33 % could be attributed to unchanged [¹⁴C]parathion (similarly distributed between the liver and the blood) while 67.9 % was degraded to water soluble compounds and 2.5% was converted to organic soluble paraoxon and traces of p-nitrophenol. Nearly all of the [¹⁴C]paraoxon, however, was degraded by the intact rat liver, resulting in water soluble products that amounted to 98.5% of the total radiocarbon recovered. Unexplained losses of radiocarbon with the perfusion apparatus used were lower in the presence of rat liver which degraded the insecticides to more water soluble compounds. The water soluble degradation products produced from [¹⁴C]parathion and [¹⁴C]paraoxon were non-toxic to mosquito larvae (Aedes aegypti L.). These ring-labelled products were found to be conjugated p-nito-phenol. Nearly all of the water soluble radiocarbon was located in the perfused blood, while only small amounts (1.8 to 3.0% of recovered) were excreted via the bile or were associated with the liver tissue (1.3 to 1.8 % of recovered).     

Methyl parathion induced nephrotoxicity in male rats and protective role of vitamins C and E

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.