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PubMed1995

In vitro and in vivo generation of reactive oxygen species, DNA damage and lactate dehydrogenase leakage by selected pesticides.

Reactive oxygen species may be involved in the toxicity of various pesticides and we have, therefore, examined the in vivo effects of structurally dissimilar polyhalogenated cyclic hydrocarbons (PCH), such as endrin and chlordane, chlorinated acetamide herbicides (CAH), such as alachlor, and organophosphate pesticides (OPS), such as chlorpyrifos and fenthion, on the production of hepatic and brain lipid peroxidation and DNA-single strand breaks (SSB), two indices of oxidative stress and oxidative tissue damage. The selected pesticides were administered p.o. to female Sprague-Dawley rats in two 0.25 LD50 doses at 0 h and 21 h and killed at 24 h. In a parallel set of experiments, we have determined the in vitro effects of these pesticides on the DNA-SSB and enhanced lactate dehydrogenase leakage (LDH) from neuroactive PC-12 cells in culture. In vitro production of reactive oxygen species by these pesticides was also assessed by determining the enhanced chemiluminescence responses of hepatic and brain homogenates. Following treatment of rats with endrin, chlordane, alachlor, chlorpyrifos and fenthion, increases of 2.8-, 3.0-, 4.2-, 4.3- and 4.8-fold were observed in hepatic lipid peroxidation, respectively, while at these same doses, increases in lipid peroxidation of 2.4-, 2.1-, 3.6-, 4.6- and 5.3-fold, respectively, were observed in brain homogenates. Increases of 4.4-, 3.9-, 1.6-, 3.0- and 3.5-fold were observed in hepatic DNA-SSB following treatment of the rats with endrin, chlordane, alachlor, chlorpyrifos and fenthion, respectively, while at these same doses, increases of 1.9-, 1.7-, 2.2-, 1.4-, 1.4-fold, respectively, were observed in brain nuclear DNA-SSB. Following in vitro incubation of hepatic and brain tissues with 1 nmol/ml of each of the five pesticides, maximum increases in chemiluminescence occurred within 4-7 min of incubation and persisted for over 10 min. Increases of 3.0-, 2.7-, 3.6-, 4.9- and 4.4-fold were observed in chemiluminescence following in vitro incubation of the liver homogenates with endrin, chlordane, alachlor, chlorpyrifos and fenthion, respectively, while increases of 1.7-, 1.8-, 2.0-, 3.4- and 3.7-fold, respectively, were observed in the brain homogenates. Increases of 2.2-, 2.3-, 2.9-, 2.9- and 3.4-fold were observed in the chemiluminescence responses in the liver homogenates of the animals treated with endrin, chlordane, alachlor, chlorpyrifos and fenthion, respectively, while increases of 1.8-, 2.0-, 3.2-, 2.9- and 2.4-fold, respectively, were observed in the brain homogenates. Cultured neuroactive PC-12 cells were incubated with the pesticides and the release of the enzyme lactate dehydrogenase (LDH) into the media as an indicator of cellular damage and cytotoxicity was examined. Maximal release of LDH from cultured PC-12 cells was observed at 100 nM concentrations of the pesticides. Increases of 2.3-, 2.5-, 2.8-, 3.1 and 3.4-fold were observed in LDH leakage following incubation of the PC-12 cells with endrin, chlordane, alachlor, chlorpyrifos and fenthion, respectively. Following incubation of the cultured PC-12 cells with 100 nM concentrations of these same pesticides, increases in DNA-SSB of 2.5-, 2.2-, 2.1-, 2.4- and 2.5-fold, respectively, were observed. The results clearly demonstrate that these different classes of pesticides induce production of reactive oxygen species and oxidative tissue damage which may contribute to the toxic manifestations of these xenobiotics. Reactive oxygen species may serve as common mediators of programmed cell death (apoptosis) in response to many toxicants and pathological conditions.

Acetamides↗
PubMedDate not supplied

Differences between organophosphorus insecticides in human self-poisoning: a prospective cohort study.

BACKGROUND: Although more than 100 organophosphorus insecticides exist, organophosphorus poisoning is usually regarded as a single entity, distinguished only by the compound's lethal dose in animals. We aimed to determine whether the three most common organophosphorus insecticides used for self-poisoning in Sri Lanka differ in the clinical features and severity of poisoning they cause. METHODS: We prospectively studied 802 patients with chlorpyrifos, dimethoate, or fenthion self-poisoning admitted to three hospitals. Blood cholinesterase activity and insecticide concentration were measured to determine the compound and the patients' response to insecticide and therapy. We recorded clinical outcomes for each patient. FINDINGS: Compared with chlorpyrifos (35 of 439, 8.0%), the proportion dying was significantly higher with dimethoate (61 of 264, 23.1%, odds ratio [OR] 3.5, 95% CI 2.2-5.4) or fenthion (16 of 99, 16.2%, OR 2.2, 1.2-4.2), as was the proportion requiring endotracheal intubation (66 of 439 for chlorpyrifos, 15.0%; 93 of 264 for dimethoate, 35.2%, OR 3.1, 2.1-4.4; 31 of 99 for fenthion, 31.3%, 2.6, 1.6-4.2). Dimethoate-poisoned patients died sooner than those ingesting other pesticides and often from hypotensive shock. Fenthion poisoning initially caused few symptoms but many patients subsequently required intubation. Acetylcholinesterase inhibited by fenthion or dimethoate responded poorly to pralidoxime treatment compared with chlorpyrifos-inhibited acetylcholinesterase. INTERPRETATION: Organophosphorus insecticide poisoning is not a single entity, with substantial variability in clinical course, response to oximes, and outcome. Animal toxicity does not predict human toxicity since, although chlorpyrifos is generally the most toxic in rats, it is least toxic in people. Each organophosphorus insecticide should be considered as an individual poison and, consequently, patients might benefit from management protocols developed for particular organophosphorus insecticides.

Acetylcholinesterase↗
PubMed1998

Possible mechanisms for sensitivity to organophosphorus and carbamate insecticides in eastern screech-owls and American kestrels.

Effects of a single dietary exposure to fenthion and carbofuran on the survival, feeding behavior and brain ChE activity of eastern screech-owls, Otus asio and American kestrels, Falco sparverius, were evaluated. Birds were exposed to fenthion (23.6-189.0 ppm) or carbofuran (31.7-253.6 ppm) via meatballs. Carbofuran-exposed owls ate either < or = 10% or > or = 80% of the meatball whereas all kestrels ate < or = 10% of the meatball before exhibiting acute signs of toxicity. Fenthion-exposed owls and kestrels displayed a wide spectrum of meatball consumption (< 10-100%). Significant brain ChE inhibition was observed in dead and surviving kestrels exposed to fenthion and carbofuran and dead owls exposed to fenthion (P < 0.0001). Brain ChE activity of owls exposed to carbofuran that survived was not different from that of controls (P = 0.25). Data suggest: (1) slow feeding on a carbamate-contaminated item may provide limited protection from the toxicity of the chemical at certain rates of exposure; (2) the degree of ChE inhibition at neuromuscular junctions may be critical in determining the sensitivity of a species to a carbamate insecticide; (3) sensitivity may be a function of the ChE affinity for the carbamate inhibitor; and (4) the importance of neuromuscular junction ChE depression in determining the sensitivity of an animal may be species-specific.

Animals↗
PubMed1994

Tomato mutants altered in bacterial disease resistance provide evidence for a new locus controlling pathogen recognition.

We have employed a genetic approach to study the resistance of tomato to the phytopathogenic bacterium Pseudomonas syringae pv tomato. Resistance to P. s. tomato depends upon expression of the Pto locus in tomato, which encodes a protein with similarity to serine/threonine protein kinases and recognizes pathogen strains expressing the avirulence gene avrPto. Eleven tomato mutants were isolated with altered resistance to P. s. tomato strains expressing avrPto. We identified mutations both in the Pto resistance locus and in a new locus designated Prf (for Pseudomonas resistance and fenthion sensitivity). The genetic approach allowed us to dissect the roles of these loci in signal transduction in response to pathogen attack. Lines carrying mutations in the Pto locus vary 200-fold in the degree to which they are susceptible to P. s. tomato strains expressing avrPto. The pto mutants retain sensitivity to the organophosphate insecticide fenthion; this trait segregates with Pto in genetic crosses. This result suggested that contrary to previous hypotheses, the Pto locus controls pathogen recognition but not fenthion sensitivity. Interestingly, mutations in the prf locus result in both complete susceptibility to P. s. tomato and insensitivity to fenthion, suggesting that Prf plays a role in tomato signaling in response to both pathogen elicitors and fenthion. Because pto and prf mutations do not alter recognition of Xanthomonas campestris strains expressing avrBsP, an avirulence gene recognized by all tested tomato cultivars, Prf does not play a general role in disease resistance but possibly functions specifically in resistance against P. s. tomato. Genetic analysis of F2 populations from crosses of pto and prf homozygotes indicated that the Pto and Prf loci are tightly linked.

Crosses, Genetic↗
PubMed2004

Development of biodegradable aluminium carboxymethylcellulose matrices for mosquito larvicides.

The use of ecofriendly biodegradable controlled-release formulations of mosquito larvicides could reduce the frequency of application and losses due to degradation of the insecticide compared with conventional formulations. Among the 20 matrices developed by entrapping the organophosphorus mosquito larvicide, fenthion, in carboxymethylcellulose ionotropically cross-linked with aluminium ions which were studied for release profiles, two matrices, CRF3b and CRF5b, were found to be stable for 16 and 14 weeks under simulated field conditions. The average concentration of fenthion released per week ranged from 0.06 to 3.5 mg litre(-1) for CRF3b and 0.09 to 2.72 mg litre(-1) for CRF5b. Of these two formulations, CRF3b was the more stable, maintaining the concentration of the active ingredient at the level required to effect mosquito control. The cumulative release of fenthion per pellet was 80% from CRF3b and 72% from CRF5b. Based on the study with fenthion, two similar matrices for triflumuron, a benzoylphenylurea insect growth regulator, STAR3b and STAR5b were developed. These matrices were stable up to 16 weeks with the average concentration of triflumuron released per week ranging from 0.05 to 3.44 mg litre(-1) for STAR3b and 0.07 to 2.71 mg litre(-1) for STARSb. The cumulative release of triflumuron per pellet was 75% from STAR3b and 76% from STAR5b. From the results of this study under simulated conditions, it is estimated that the application of four pellets of either fenthion or triflumuron per square metre of the breeding surface may play a useful role in controlling Culex quinquefasciatus Say in larval habitats for about 4 months.

Aluminum↗
PubMed1988

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.

Acetylcholinesterase↗