Prolonged cholinergic crisis and compartment syndrome following subcutaneous injection of an organophosphate compound for suicide attempt.

A case of poisoning with highly lipid soluble organophosphate compound, fenthion is reported in which cholinergic crisis recurred upto 25 days following a suicide attempt. Subcutaneous injection of fenthion in the antecubital fossa by the patient produced massive swelling, cellulitis and compartment syndrome of the left arm. Emergency fasciotomy helped in restoration of circulation and saved the limb from being amputated.

Antiandrogenic activity and metabolism of the organophosphorus pesticide fenthion and related compounds.

We investigated the endocrine-disrupting actions of the organophosphorus pesticide fenthion and related compounds and the influence of metabolic transformation on the activities of these compounds. Fenthion acted as an antagonist of the androgenic activity of dihydrotestosterone (10(-7)M) in the concentration range of 10(-6)-10(-4)M in an androgen-responsive element-luciferase reporter-responsive assay using NIH3T3 cells. The antiandrogenic activity of fenthion was similar in magnitude to that of flutamide. Fenthion also tested positive in the Hershberger assay using castrated male rats. Marked estrogenic and antiestrogenic activities of fenthion and related compounds were not observed in MCF-7 cells. When fenthion was incubated with rat liver microsomes in the presence of NADPH, the antiandrogenic activity markedly decreased, and fenthion sulfoxide was detected as a major metabolite. The oxidase activity toward fenthion was exhibited by cytochrome P450 and flavin-containing monooxygenase. Fenthion sulfoxide was negative in the screening test for antiandrogens, as was fenthion sulfone. However, when fenthion sulfoxide was incubated with liver cytosol in the presence of 2-hydroxypyrimidine, an electron donor of aldehyde oxidase, the extract of the incubation mixture exhibited antiandrogenic activity. In this case, fenthion was detected as a major metabolite of the sulfoxide. Metabolic interconversion between fenthion and fenthion sulfoxide in the body seems to maintain the antiandrogenic activity.

Comportamiento de las enximas colinesterasa y alanin transaminasa en ratones B6D2F1 expuestos a fention / Enzimes cholinesterase and alanín transaminase Activities in mice B6D2F1 exposed to Fenthion

Las actividades enzimáticas de la colinesterasa y la Alanin Transaminasa, así como las pruebas histológicas de higado, fueron monitoreadas a las 0, 8, 16, 24 y 48 horas de administración de 80 mg/Kg. de Fention a ratones de la línea B6D2F1 via oral. En los resultados obtenidos se observó una inhibición significativa de la enzima colinesterasa y un aumento de la actividad Alanin Transaminasa en los grupos de ratones tratados con el insecticida, no encontrándose una correlación significativa entre los comportamientos de ambas enzimas. Los estudios histopatológicos de las muestras de hígados de los ratones tratados con Fentión corroboraron la presencia de daños celulares en este órgano(AB)

Comportamiento de las enximas colinesterasa y alanin transaminasa en ratones B6D2F1 expuestos a fention / Enzimes cholinesterase and alanín transaminase Activities in mice B6D2F1 exposed to Fenthion

Las actividades enzimáticas de la colinesterasa y la Alanin Transaminasa, así como las pruebas histológicas de higado, fueron monitoreadas a las 0, 8, 16, 24 y 48 horas de administración de 80 mg/Kg. de Fention a ratones de la línea B6D2F1 via oral. En los resultados obtenidos se observó una inhibición significativa de la enzima colinesterasa y un aumento de la actividad Alanin Transaminasa en los grupos de ratones tratados con el insecticida, no encontrándose una correlación significativa entre los comportamientos de ambas enzimas. Los estudios histopatológicos de las muestras de hígados de los ratones tratados con Fentión corroboraron la presencia de daños celulares en este órgano(AB)

A study of cognitive functions and event related potentials following organophosphate exposure.

To study the cognitive changes following chronic occupational exposure to organophosphate (OP) pesticides, a clinical and neurophysiological study was performed on 31 workers engaged in spraying fenthion, an OP pesticide. The mean age of the workers was 32.1 years (range 19-55) and mean duration of exposure 10.5 years (range 1-14). The workers reported mild transient symptoms after spraying. There was no clinical evidence suggestive of excessive cholinergic activity. Clinical psychometry revealed significant changes in Benton visual retention test, memory quotient, and Alexander's Passalong Test. Serum AChE level was 27% less in the exposed group compared to the controls. P3 of event related potentials were elicited in 28 subjects, P3 latency though was prolonged in one subject only but the group difference was significant. The amplitude of P3 however did not show significant difference. The results suggest subtle subclinical effect of chronic fenthion exposure on the cognitive functions and event related potentials.

Research note: ability of fenthion to increase gizzard erosion in broiler chicks.

Fenthion, an irreversible cholinesterase inhibitor, was used to study the role of the cholinergic system on the development of gizzard erosion. Fenthion increases the gizzard erosion score in a dose-dependent manner and this effect became significant at levels higher than .1 ppm (p less than .05). An inverse relationship between plasma cholinesterase activity and pesticide concentration was also observed at doses higher than 1 ppm (P less than .05). These results show the necessity to evaluate organophosphate pesticide levels during the selection of fish meals in poultry.

A study of nerve conduction velocity, late responses and neuromuscular synapse functions in organophosphate workers in India.

To study the effect of occupational organophosphate exposure on neuromuscular function, 24 workers exposed to fenthion [0,0-dimethyl-0(4-methyl mercapto-3 methyl phenyl)phosphorothioate], whose mean age was 31.7 years (range 22-50) and mean duration of exposure to fenthion 8.5 years (range 1-19) were subjected to detailed clinical and neurophysiological evaluation after spraying. The neurophysiological tests included motor and sensory nerve conduction velocity; F response, H reflex and electromyographic neuromuscular synapse testing. Fenthion exposure was monitored by serum acetyl cholinesterase (AchE) levels. The observations were repeated after withdrawing the workers from fenthion exposure for 3 weeks to study the reversibility of the observed changes. There was no clinical evidence of peripheral neuropathy or muscle weakness. However, peroneal motor conduction velocity (p less than 0.05) terminal motor latency of median (p less than 0.1), and peroneal nerve (p less than 0.05); F minimal latency and H reflex latency (p less than 0.01) were significantly affected. Twenty-nine per cent of workers had repetitive muscle activity. Serum AchE levels also showed significant changes (p less than 0.01). The clinical significance of these subtle neurophysiological changes requires further investigation and follow-up.

Effects of aerial thermal fog applications of fenthion on caged pink shrimp, mysids and sheepshead minnows.

Mosquito control applications of fenthion by aerial thermal fog equipment were studied at 2 sites in Collier County, FL, for sprays that occurred on June 20 and 23, 1984. Acute, lethal effects of fenthion deposited in these estuarine habitats were assessed for caged pink shrimp (Penaeus duorarum), mysids (Mysidopsis bahia) and sheepshead minnows (Cyprinodon variegatus). At Site 1, along a bay with substantial dilution and tidal mixing, fenthion concentrations of 1.5 and 0.29 micrograms/liter were measured in samples taken immediately after both sprays. Concentrations decreased to less than or equal to 0.020 microgram/liter 12 h postspray and no mortality was observed for caged pink shrimp and mysids. Site 2 was along a residential canal system that offered limited dilution and mixing. Maximum concentrations were 2.6 and 0.51 micrograms/liter and measurable concentrations (greater than 0.038 microgram/liter) of fenthion persisted at this site for 4 days. Fenthion concentrations in surface waters were toxic to caged pink shrimp and mysids after both sprays. No mortality occurred among caged sheepshead minnows at either site.

Some observations on the macula of pesticide workers.

To study the retinal changes in occupationally exposed pesticide workers, 79 subjects exposed to an organophosphate, fenthion, and 18 exposed to an organochlorine pesticide DDT [1,1,1-trichloro-2,2-bis(p-chlorophenyl) ethane], were subjected to a detailed study, including history taking, physical examination and ophthalmic evaluation. Fluorescein angiography was performed in selected cases. Serum cholinesterase level in 22 workers and serum DDT residue in 17 workers of the respective groups were also estimated. Fifteen workers (19%), who were exposed to fenthion had macular changes (P less than 0.01). The macular lesions were characterized by perifoveal irregularity of pigmentation and areas of hypopigmentation of 1/8-1/3 disc diameter. Mean age of the subjects having macular involvement was 30.6 years and mean duration of exposure 7.9 years. The symptoms reported by them were diminution of vision (8), dislike for bright light, flash of light, black dots in front of the eyes (2 each) and visual blurring (1). Paracentral scotoma and constriction of peripheral field were present in three workers each. Fluorescein angiography suggested pigment epithelium defect. Other causes of macular involvement in these workers were excluded; a possible role of pesticides in the genesis of these macular changes is suggested.

Asthma due to insecticide sensitivity.

Two patients are reported in whom asthma was precipitated by exposure to synthetic organophosphorous insecticides. Investigation showed no evidence of systemic poisoning or cholinesterase inhibition and indicated that the asthmatic reactions may have been due to a sensitivity response. The mechanism of this response is unknown but it was inhibited by corticosteroids in one patient. A history of insecticide exposure was obtained from the affected patients only after careful questioning and indicates the need for awareness that sensitivity to insecticides may precipitate asthma and that little exposure is necessary to elicit a response.

Clinical and biochemical changes in chronically exposed organophosphate workers.

Health effects of occupational organophosphate exposure were investigated by subjecting 22 workers chronically exposed to an organophosphate pesticide, fenthion (O,O-dimethyl-O-(4-methylmercapto-3-methylphenyl)-phosphorothioate) to clinical evaluation, estimation of serum cholinesterase, serum alkaline phosphatase (SAP), serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT). The mean age of the workers was 31 years and the mean duration of fenthion exposure 8.2 years. Headache (59%), giddiness (50%), ocular symptoms (27%) and paresthesia (18%) were the commonest symptoms. Serum acetylcholinesterase and butyrylcholinesterase levels were significantly lower than in controls. After withdrawing the workers from organophosphate exposure for 3 weeks, the follow-up study revealed absence of transient symptoms. There was no change in their neurological status, and serum acetylcholinesterase and butyrylcholinesterase levels were raised significantly, whereas the other serum enzymes showed no significant change. For monitoring of occupational organophosphate exposure, the importance of both clinical and biochemical parameters is emphasised.

Correction of organophosphate-induced neuromuscular blockade by diphenhydramine.

Dogs exposed to topical organophosphate (fenthion) developed decreased plasma and muscle cholinesterase activities. After 2 doses were applied (1 week between doses), plasma concentrations declined 80% and muscle cholinesterase activity was reduced by 56%. Decremental responses to repetitive nerve stimulation developed after fenthion administration. Diphenhydramine, but not placebo, corrected the electrical abnormalities caused by organophosphate application, but without altering plasma or muscle cholinesterase activity. Control dogs housed in the same kennel demonstrated a slight decrease (18%) of plasma cholinesterase, which indicates that there may be potential cross contamination. Diphenydramine may be effective in treating organophosphate-induced neuromuscular weakness which is refractory to other forms of therapy.

Retinal degeneration in rats exposed to an organophosphate pesticide (fenthion).

Pigmented (Long-Evans) and albino (Wistar) rats were chronically exposed to an organophosphate pesticide (fenthion). Fenthion (50 mg/kg) was administered subcutaneously twice a week for 1 year; the total dosage for each animal ranged from 1.6 to 1.8 g. Concurrent with the fenthion administration, the amplitude of the scotopic electroetinogram (ERG) gradually declined, disappearing by the 12th month in all treated pigmented rats. For the albino experimental rats, however, the ERG amplitude disappeared as early as the 6th month in 7 out of 15 treated animals. Funduscopically, degeneration of the retina was observed in all rats when ERG responses had disappeared. Histopathological studies confirmed degeneration of the sensory retina and marked abnormalities in the pigment epithelium cells. Treated pigmented rats also had reduced a rhodopsin concentration in the retina by the 3rd month even though the photoreceptors were structurally normal. Interestingly, the plasma vitamin A levels remained normal and liver stores of vitamin A actually increased during the course of the study. Levels of butylcholinesterase in plasma and liver, on the other hand, were extremely reduced after 3 months of fenthion treatment. In general, the biochemical and functional (ERG) changes appeared before any structural damage could be detected in the retina.

Gill lesions in Cichlid fishes after intoxication with the insecticide Fenthion.

The toxic effects of Fenthion on the gills of Cichlid fishes were investigated. In Herotilapia multispinosa hyperplasia and separation of the respiratory epithelium, lamellar telangiectasis and thrombosis occurred. The lamellar epithelium of surviving fish regenerated in all cases. In Tilapia leucosticta no telangiectasis was found, but all the secondary lamellae were fused due to the severe hyperplasia of the gill epithelium.