Triketone toxicity: a report on two cases of sulcotrione poisoning.

INTRODUCTION: Sulcotrione is a herbicidal agent belonging to the family of triketones. Sulcotrione herbicides are used for weed control in maize and flax crops. To date, no cases of human poisoning had been reported in the literature linked to different herbicidal agents in the triketone family. We report here on two cases of the voluntary ingestion of this substance in the form of the branded product Mikado(TM), which were recorded by the Angers Poison Centre. CASE REPORT: Both cases of voluntary ingestion constituted attempted suicide, and involved two men aged 30 and 37 years. Their symptoms linked to sulcotrione were limited to vomiting, despite elevated plasma concentrations of sulcotrione. In one case, hypertyrosinemia has been demonstrated. The outcome was favourable in both patients and at follow up, no ocular disorders were observed. In the second case, hypotension and transient renal failure could be linked to the concomitant ingestion of chlorophenoxy herbicides. DISCUSSION: In animal toxicity studies, sulcotrione inhibit 4-hydro-phenylpyruvate dioxygenase leading to hypertyrosinemia and corneal opacities. In both cases, no ocular disorders were observed despite hypertyrosinemia in one case. These case reports were consistent with the animal toxicology findings concerning triketones, and particularly their relative safety in mammals following acute poisoning. However it seems prudent to monitor plasma tyrosine concentrations and to screen prospectively for corneal deposits if further acute intoxication events occur.

Intentional self-poisoning with the chlorophenoxy herbicide 4-chloro-2-methylphenoxyacetic acid (MCPA).

STUDY OBJECTIVE: Data on poisoning with MCPA (4-chloro-2-methyl-phenoxyacetic acid) are limited to 6 case reports. Our objective is to describe outcomes from intentional self-poisoning with MCPA in a prospective case series of 181 patients presenting to hospitals in Sri Lanka. METHODS: Patient information was collected by on-site study physicians as part of an ongoing prospective cohort study of poisoned patients. Medical history, clinical details, and blood samples were obtained prospectively. RESULTS: Overall clinical toxicity was minimal in 85% of patients, including mild gastrointestinal symptoms in 44% of patients. More severe clinical signs of chlorophenoxy poisoning reported previously, such as rhabdomyolysis, renal dysfunction, and coma, also occurred but were uncommon. Eight patients died (4.4%). Most deaths occurred suddenly from cardiorespiratory arrest within 48 hours of poisoning; the pathophysiological mechanism of death was not apparent. The correlation between admission plasma MCPA concentration and clinical markers of severity of toxicity (physical signs, symptoms, and increased creatine kinase level) was poor. CONCLUSION: Intentional self-poisoning with MCPA generally causes mild toxicity, but cardiorespiratory arrest and death may occur. All patients should receive routine resuscitation and supportive care. It seems reasonable to correct acidosis and maintain an adequate urine output, but there is insufficient evidence to support other specific interventions. Our data do not support a clinical role for measurement of plasma MCPA in the acute management of poisoning, and insufficient data were available to fully examine the utility of measured electrolytes and creatine kinase levels.

Body mass index and bromoxynil exposure in a sample of rural residents during spring herbicide application.

Bromoxynil (3,5-dibromo-4-hydroxybenzonitrile), a phenolic herbicide, is widely used in production of cereals and other crops. Little is known, however, about bromoxynil exposure in humans. Results of previous research suggest a longer residence time in the body for bromoxynil compared to phenoxy herbicides [e.g., (2,4-dichlorophenoxy)acetic acid (2,4-D), 4-chloro-2-methylphenoxyacetic acid (MCPA)] and that bromoxynil would tend to partition into fatty tissue more so than 2,4-D. In previous research, body mass index (BMI) was found to be an independent predictor of plasma concentrations of 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE), the persistent lipophilic metabolite of the chlorinated pesticide bis(4-chlorophenyl)-1,1,1-trichloroethane (DDT). As part of the Prairie Ecosystem Study, gas chromatography/mass spectrometry analysis was used to measure concentrations of bromoxynil and seven other herbicides (2,4-D, dicamba, fenoxaprop, MCPA, ethalfluralin, triallate, and trifluralin) in plasma from residents (104 men, 88 women, 24 youths age 12-17 yr) of a cereal-producing region in Saskatchewan, Canada, during spring herbicide application, 1996. Multiple logistic regression analysis was used to explore whether BMI predicted detection of bromoxynil in plasma from the adults. The prevalence of detection (detection limits: 2-50 microg/L) was markedly higher for bromoxynil (men, 44.2%; women, 14.8%; youths, 20.8%) compared to each of the other herbicides including 2,4-D (men, 16.5%; women, 3.4%; youths, 12.5%) and MCPA (men, 6.8%; women, 1.1%; youths, 4.2%), although bromoxynil is commonly formulated or tank mixed with these herbicides. In the multiple logistic regression analysis, the variables BMI, exposure group [bromoxynil applicators, non-applicator family members of bromoxynil applicators, all others (reference group)], and days elapsed since the last use of bromoxynil were found to be independent predictors of detection of bromoxynil, while age, gender, and farm residency were not statistically significant. With adjustment for exposure group [bromoxynil applicators: odds ratio (OR = 24.30, 95% confidence interval (CI) = 9.59-61.58; nonapplicator family members of bromoxynil applicators: OR = 3.53, 95% CI = 1.19-10.44; all others (reference group)], the OR for detection of bromoxynil was 2.35 (95% CI = 0.87-6.33) for participants in the middle (25.53-29.00 kg/m2) tertile (men: OR = 2.85, 95% CI = 0.75-10.82; women: OR = 1.63, 95% CI = 0.36-7.40) of BMI and 4.01 (95% CI = 1.46-11.03) for participants in the highest (> 29.00 kg/m2) tertile (men: OR = 4.67, 95% CI = 1.17-18.58; women: OR = 2.20, 95% CI = 0.44-10.99) with participants in the lowest (< 25.53 kg/m2) tertile as the reference group. Similar ORs were observed for BMI with adjustment for days elapsed since the last use of bromoxynil. In conclusion, further research is needed to investigate whether adiposity is an important modifying factor for persistence of bromoxynil in the body.

Myocardial perfusion imaging versus biochemical markers in acute coronary syndromes.

The assessment and appropriate clinical management of patients with acute chest pain and non-diagnostic electrocardiograms remain a continuing clinical problem. Accordingly, there is considerable interest in evaluating new strategies to improve early diagnostic accuracy in patients with possible acute myocardial ischaemia. Cardiac troponins (T and I) and acute rest myocardial perfusion imaging have similar sensitivities for detecting acute myocardial infarction. Whereas cardiac markers require 6-12 h to become positive, acute rest myocardial perfusion imaging immediately reflects the status of regional myocardial blood flow at the time of radiopharmaceutical injection. The measurement of cardiac troponins is particularly useful in the diagnosis and estimation of the degree of myocardial injury in those patients with a high likelihood of coronary artery disease and myocardial necrosis and for prognostication of adverse cardiac events in those patients with unstable angina. In contrast, the most appropriate use of acute rest myocardial perfusion imaging is in the setting of patients with acute ischaemic symptoms, non-diagnostic electrocardiogram and a low likelihood of myocardial necrosis, in which early imaging will assist in effective triage decisions.

Simultaneous determination of 2,4-D and MCPA in canine plasma and urine by HPLC with fluorescence detection using 9-anthryldiazomethane (ADAM).

A method for the simultaneous determination of 2,4-dichlorophenoxyacetic acid (2,4-D) and 2-methyl-4-chlorophenoxyacetic acid (MCPA) in canine plasma and urine has been developed. This method used derivatization of extracted samples with 9-anthrylmethane (ADAM) for analysis by reversed-phase high-performance liquid chromatography with fluorescence detection. Precision and accuracy were within the accepted limits of 15% and 85-115%, respectively, for both analytes in plasma and urine. Calibration curves for 2,4-D and MCPA in plasma were linear (r2 > 0.99) between 0.50 and 5.0 mg/L and 5.0 and 100 mg/L. Calibration curves for 2,4-D and MCPA in urine were linear (r2 > 0.99) between 5.0 and 70.0 mg 2,4-D/L and 10.0 and 70.0 mg MCPA/L. The lower limit of detection was 62.5 ng/mL for both 2,4-D and MCPA.

Massive ingestion of the herbicide 2-methyl-4-chlorophenoxyacetic acid (MCPA).

OBJECTIVE: To report the course of a massive ingestion of the herbicide 2-methyl-4-chlorophenoxyacetic acid or MCPA (4-chloro-2-methyl phenoxy acetic acid) and to correlate plasma 2-methyl-4-chlorophenoxyacetic acid levels with symptoms of intoxication and treatment. CASE REPORT: After intentional ingestion of the herbicide, 2-methyl-4-chlorophenoxyacetic acid, a young man suffered burning in his mouth, spasmodic pain in the extremities and a severe hypotensive crisis. Plasma 2-methyl-4-chlorophenoxyacetic acid concentration was 546 mg/L two hours after ingestion. Therapy by forced diuresis was ineffective until the urine was alkalinized (Day 4). This resulted in a rapid decline of the plasma 2-methyl-4-chlorophenoxyacetic acid level to 6 mg/L and recovery of the patient.

Renal handling of 2-methyl-4-chlorophenoxyacetic acid (MCPA) in rats.

Following i.p. administration of various doses of 2-methyl-4-chlorophenoxyacetic acid (MCPA), ca. 50% is excreted during a 5-h diuresis experiment. After i.p. administration of MCPA, virtually no distribution occurs (Vrel = 18% of the body weight). Renal excretion of MCPA can be accelerated by inhibition of its renal tubular reabsorption. The distinct inhibition of renal excretion of MCPA by simultaneous administration of probenecid or p-aminohippurate (PAH) indicates the active tubular transport of MCPA; this transport process can be stimulated by treatment of rats with triiodothyronine. Active tubular transport of MCPA was confirmed by measurement of MCPA accumulation in renal cortical slices, both under aerobic and anaerobic conditions. Accumulation of MCPA under anaerobic conditions indicates an additional passive uptake and binding of MCPA in kidney tissue in accordance with the high degree of binding to plasma albumin (85%).

Studies on phenoxy acid herbicides. II. Oral and dermal uptake and elimination in urine of MCPA in humans.

Five healthy volunteers were given 15 micrograms MCPA per kg body weight. The highest concentration in plasma, 0.15 micrograms/ml, was found after 1 h. In urine the excretion during the first 6 h was 0.46 microgram/min and 40% of given dose was excreted during the first 24 h. About 1 g of MCPA emulsion was applied on the skin of the thigh and was washed away after 2 h. Plasma level slowly increased with maximum, 0.12 micrograms/ml, after 24 h. In urine a slow excretion continued for up to 5 days later with maximum 24-48 h after application. In agricultural field exposure urinary MCPA should be estimated immediately after stop of exposure as well as 24 h after exposure. Levels under 0.5 micrograms/ml of MCPA in urine might be used as a practical biological level for good work practice. In spot samples the concentration of urine must be considered.

EC-GLC determination of the herbicidal monohalogenated phenoxyalkyl acid mecoprop in tissues, urine and plasma after derivatization with pentafluorobenzylbromide.

An EC-GLC method for the determination of the systemic herbicide methylchlorophenoxypropionic acid (meco prop), a monohalogenated phenoxyalkyl acid, in 0.5 gram of rabbit tissues and in one ml human urine and plasma, is presented. Monohalogenated chlorophenoxyalkyl acids can reach a high sensitivity for electron-capture detection as pentafluorbenzylester derivatives; so their minimum detectable amount is about 5 pg. A test-tube micro-extraction method for MCPP fromurine, plasma and homogenized tissues with benzene, after acidification with 2 N HC1, the derivatization the residue, and the column clean-up over silicagel, are described in detail. Results of recovery studies with variation-coefficient determination are given by analysis of spiked tissues liver and brain, urine and plasma using p-chlorophenoxy-isobutyric acid (CPIB) as the internal standard. With this method other chlorophynoxyalkyl acid herbicides also can be determined in biological post-mortem material