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PubMed1997

Agricultural and horticultural chemical poisonings: mortality and morbidity in the United States.

STUDY OBJECTIVE: To provide a comprehensive analysis of morbidity and mortality from poisoning by agricultural and horticultural chemicals in the United States. METHODS: Descriptive analysis of national mortality data, National Hospital Discharge Survey data, and American Association of Poison Control Centers national data for 1985 through 1990. RESULTS: There were 341 fatalities from agricultural and horticultural chemicals over the 6-year period, of which 64% were suicides, 28% were unintentional, and 8% were of undetermined intent. There were 25,418 hospitalizations; 78% were reported to be unintentional. Both deaths and hospitalizations occurred more frequently in males, and rates were higher in nonwhites than in whites. There were 338,170 poison exposures reported to poison centers for fungicides, herbicides, pesticides/insecticides, and rodenticides. Life-threatening manifestations or long-term sequelae occurred in 782 cases, and 97 deaths were reported. Pesticides and insecticides accounted for 72% of the poison center cases and 63% of the fatalities. Although they accounted for only 8% of poison exposures, herbicide deaths were disproportionately high (25%). CONCLUSION: Poisonings with agricultural and horticultural chemicals are an important public health problem. Prevention efforts need to incorporate the fact that many serious cases, such as paraquat poisonings, are suicidal in nature.

Accidents, Home↗
PubMed2000

Sensitivity of the SRBC PFC assay versus ELISA for detection of immunosuppression by TCDD and TCDD-like congeners.

The splenic antibody plaque forming cell (PFC) assay is a widely used assay in immunotoxicity testing. A recent revision of the Federal Insecticide, Fungicide and Rodenticide (FIFRA) Immunotoxicity test guidelines by the EPA recommended that either the PFC assay or the sheep red blood cell (SRBC) specific serum IgM enzyme-linked immunosorbent assay (ELISA) be used to assess the primary humoral response to SRBCs. The PFC assay quantifies the number of plasma cells in the spleen producing SRBC-specific antibody, while the ELISA measures SRBC-specific IgM antibody in the serum. Because these two assays measure different endpoints, there is a need for comparison of their sensitivity and reliability. The purpose of this project was to determine if these two assays are equally sensitive to suppression of the SRBC response in B6C3F1 female mice. Female B6C3F1 mice were given a single oral exposure to different doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or four TCDD-like congeners. One week later, two sets of mice were immunized with SRBC. The first set was evaluated for the PFC response and the second for the ELISA response, on day 4 or 5 post-immunization, respectively. The four TCDD-like congeners tested were: 1,2,3,7,8-pentachlorodibenzo-p-dioxin (PeCDD), 1,2,3,4,7-pentachlorodibenzofuran (4PeCDF), 3,3',4,4',5-pentachlorobiphenyl (PCB126) and 2,3',4,4',5-pentachlrorbiphenyl (PCB118). The results were used to generate dose-response curves for the determination of the ED(50) for TCDD and each TCDD-like congener. For all chemicals tested, measuring the level of SRBC-specific IgM antibody by ELISA was more sensitive than the PFC assay to detect immunosuppression, as indicated by lower ED(50) values. These results indicate that the SRBC-specific IgM ELISA is a more sensitive assay for detecting the T-cell mediated immunotoxicity of dioxin-like chemicals in this rodent model.

Animals↗
PubMed2000

Biological Monitoring of Pesticide Exposure: a review. Introduction.

Pesticides are used worldwide in agriculture, industry, public health and for domestic applications: as a consequence, a great part of the population may be exposed to these compounds. In spite of this extensive use, knowledge on the health risks associated with prolonged exposure is rather poor, and major uncertainties still exist. Epidemiological observations in man have so far produced little conclusive information, mainly because of weaknesses in exposure assessment. Therefore, information on the type and levels of exposure is fundamental in order to better understand and characterize risk to human health. Exposure assessment can be carried out via measurement of environmental concentrations, as well as via determination of the chemical or its metabolites in body tissues (biological monitoring). Besides indices of internal dose, biological monitoring also includes measurements of early effects attributable to interaction between the chemical agent and the human body. Biological monitoring has the advantage, over environmental monitoring, of determining the dose actually absorbed via any possible route: differences in absorption can be taken into account. whether they are due to biological variability or to use of protective equipment. When, in some cases, a combination of occupational and non-occupational exposure occurs, this also can be taken into consideration by biological monitoring. Few reference documents have been published on biological monitoring of pesticides. For this reason, the Office of Occupational Health of the World Health Organization gave ICPS a mandate to prepare a monograph specifically addressed to reviewing methods for biological monitoring of pesticide exposure. This review is based on more than 300 studies published over the period 1980-1999. For the most representative chemical classes, the available biological exposure indices are reported. Both indices of internal dose and. when available, of early effects are discussed. The reported tests were used to monitor exposure of pesticide applicators in agriculture and public health, manufacturing and formulating workers. subjects poisoned after accidental exposure or attempted suicide, volunteers involved in pharmacokinetic studies, as well as sub-groups of the general population exposed to environmentally persistent pesticides. Single chapters deal with organophosphorus insecticides, carbamate pesticides, dithiocarbamates, phenoxyacids, quaternary ammonium compounds. coumarin rodenticides, synthetic pyrethroids, organochlorine pesticides, chlorotriazines, and pentachlorophenol.

Animals↗
PubMed1982

[Myoclonus of toxic origin].

EEG, EMG and clinical correlates of myoclonus due to poisoning are reviewed. The authors propose a classification into two groups. I. Sporadic diffuse asynchronous asymmetrical myoclonic jerks, responding to treatment. These states are encountered essentially in acute intoxication by vegetal poisons (strychnine), rodenticide (chloralose) and various medications (isoniazide, tricyclic antidepressant agent, lithium). These transitory manifestations are functional and prognosis is favourable. II. Subintrant generalized synchronous symmetrical myoclonus, uncontrolled by therapeutics. These myoclonus states observed over weeks or months are frequently consecutive to organic injuries due to direct toxicity (methylbromide) or after anoxia (toxic cardiac arrest). EEG and EMG correlations are very inconstant in both groups. EEG abnormalities are a sign of cortical and/or subcortical dysfunction. Normal EEG suggests a disease of the lower central nervous structure (brain stem, medulla). Chronic bismuth and dialysis encephalopathies are also related. Withdrawal syndrome with myoclonus jerks after sudden cessation of barbiturate or benzodiazepine long-term treatment is mentioned.

Aluminum↗
PubMed1987

Central nervous system intoxications other than lead.

Other than lead, organophosphates and carbamates are probably the most important classes of toxicants affecting the central nervous system in food animals. Chlorinated hydrocarbons continue to present problems from time to time, as do certain poisonous plants. Less frequently encountered substances such as nitrofurans, certain rodenticides, herbicides, and other miscellaneous poisons are also discussed.

Animals↗
PubMed2000

Phosphine-induced oxidative damage in rats: attenuation by melatonin.

Phosphine (PH(3)), from hydrolysis of aluminum, magnesium and zinc phosphide, is an insecticide and rodenticide. Earlier observations on PH(3)-poisoned insects, mammals and a mammalian cell line led to the proposed involvement of oxidative damage in the toxic mechanism. This investigation focused on PH(3)-induced oxidative damage in rats and antioxidants as candidate protective agents. Male Wistar rats were treated ip with PH(3) at 2 mg/kg. Thirty min later the brain, liver, and lung were analyzed for glutathione (GSH) levels and lipid peroxidation (as malondialdehyde and 4-hydroxyalkenals) and brain and lung for 8-hydroxydeoxyguanosine (8-OH-dGuo) in DNA. PH(3) caused a significant decrease in GSH concentration and elevation in lipid peroxidation in brain (36-42%), lung (32-38%) and liver (19-25%) and significant increase of 8-OH-dGuo in DNA of brain (70%) and liver (39%). Antioxidants administered ip 30 min before PH(3) were melatonin, vitamin C, and beta-carotene at 10, 30, and 6 mg/kg, respectively. The PH(3)-induced changes were significantly or completely blocked by melatonin while vitamin C and beta-carotene were less effective or inactive. These findings establish that PH(3) induces and melatonin protects against oxidative damage in the brain, lung and liver of rats and suggest the involvement of reactive oxygen species in the genotoxicity of PH(3).

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1996

Impact of the Delaney Clause in the EPA.

The U.S. Environmental Protection Agency serves as the lead agency of the Federal government for the regulation of pesticide use in the United States. Regulatory responsibilities are mandated in the Federal Insecticide Fungicide and Rodenticide Act (FIFRA) and several sections of the Federal Food Drug and Cosmetic Act (FFDCA). In order for a pesticide to be used in the U.S., it must either be granted a full registration under Section 3, or offered special consideration under Section 18 or 24 of FIFRA. Tolerances (maximum allowable residue limits) for pesticides to be used on agricultural commodities meant for human consumption or animal feed are established under Sections 408 and/or 409 of FFDCA. This presentation will describe the underlying conflict between Section 409 of FFDCA and both Section 408 and FIFRA, the recommendations made by the National Academy of Sciences in its 1987 publication Regulating Pesticides in Food--The Delaney Paradox, EPA's attempts to implement these recommendations, the true impact of "Delaney" on the ability of EPA to grant tolerances on raw or processed foods for chemicals determined to meet the "induce cancer" criterion and the status of legislation designed to "fix" Delaney.

Carcinogens↗
PubMed1992

Drug-induced diabetes.

The only drugs which commonly cause diabetes during therapeutic use are the anti-hypertensive vasodilator diazoxide, and corticosteroids in high doses such as those used to palliate intracranial tumours. Thiazide diuretics have in the past been used in higher doses than necessary to treat hypertension, and the lower doses now used probably carry only a slight risk of inducing diabetes. The risk from beta-blockers is also quite small, but there is some evidence that thiazides combined with beta-blockers may be more likely to cause diabetes than either drug alone. The combination is probably best avoided in patients with a family history of non-insulin-dependent diabetes. The effect of the low-oestrogen combined oral contraceptive pill seems to be slight, and it presents a risk only to women who have had gestational diabetes. Bodybuilders who take enormous doses of anabolic-androgens can develop impaired glucose tolerance. Several drugs, including theophylline, aspirin, isoniazid and nalidixic acid can cause transient hyperglycaemia in overdosage, but only streptozotocin, alloxan and the rodenticide Vacor are likely to cause permanent diabetes.

Diabetes Mellitus↗
PubMed2002

Headspace solid-phase microextraction with 1-pyrenyldiazomethane on-fibre derivatisation for analysis of fluoroacetic acid in biological samples.

A new and in part automated headspace solid-phase microextraction method for quantitative determination of the highly toxic rodenticide fluoroacetic acid (FAA) in serum and other biological samples has been developed. FAA and deuterated acetic acid (internal standard) were extracted from acidified samples by a StableFlex divinylbenzene-Carboxen on polydimethylsiloxane fibre. The acids were derivatised on the fibre in-situ with 1-pyrenyldiazomethane and detected using gas chromatography-mass spectrometry with electron impact ionisation and selected ion monitoring. The calibration curve for FAA in serum was linear over the range from 0.02 to 5 microg/ml, with limits of detection and quantification of 0.02 and 0.07 microg/ml, respectively. The method was also tested with spiked whole blood, urine, stomach contents and kidney samples. It was sufficiently reliable, reproducible and sensitive for use in routine forensic toxicology applications.

Calibration↗
PubMed1982

Mechanism of coumarin action: sensitivity of vitamin K metabolizing enzymes of normal and warfarin-resistant rat liver.

The in vitro effects of two coumarin anticoagulants, warfarin and difenacoum, on rat liver microsomal vitamin K dependent carboxylase, vitamin K epoxidase, vitamin K epoxide reductase, and cytosolic vitamin K reductase (DT-diaphorase) from the livers of normal and a warfarin-resistant strain of rats have been determined. Millimolar concentrations of both coumarins are required to inhibit the carboxylase and epoxidase activities in both strains of rats. Sensitivity of DT-diaphorase to coumarin inhibition differs when a soluble or liposomal-associated substrate is used, but the diaphorases isolated from both strains of rats have comparable sensitivity. The anticoagulant difenacoum is an effective rodenticide in the warfarin-resistant strain of rats, and the only enzyme studied from warfarin-resistant rat liver that demonstrated a significant differential inhibition by the two coumarins used was the vitamin K epoxide reductase. This enzyme also showed the greatest sensitivity to coumarin inhibition among the enzymes studied. These results support the hypothesis that the physiologically important site of action of coumarin anticoagulants is the vitamin K epoxide reductase.

4-Hydroxycoumarins↗
PubMedDate not supplied

Additional alkaloids of Pachygone ovata.

Pachygone ovata (Menispermaceae), indigenous to the sandy seashores of southern India, is a woody climber whose fruits have been used as a rodenticide and fish poison. Chromatography of the extract of the roots resulted in the reisolation of the alkaloids liriodenine, coclaurine, trilobine (1), and magnoflorine and the isolation of stepholidine, coreximine, isoboldine, norjuziphine, and nortrilobine (2). Nortrilobine (2) is a new dibenzo-p-dioxin bisbenzylisoquinoline alkaloid whose structure was established by a consideration of spectral data and conversion to isotrilobine (3).

Alkaloids↗
PubMed1999

[Derailed oral anticoagulation with very high INR values and poor response to oral vitamin K--cholestasis as a possible cause].

A 76-year-old man under long term oral anticoagulant treatment showed unclottable prothrombin time (PT) without overt bleeding. After oral administration of vitamin K1, PT remained severely prolonged and the patient was hospitalized. INR was 8.0 and responded to parenteral vitamin K. Cholestasis resulting in poor intestinal vitamin K resorption was assumed to have caused "overanticoagulation". Quick test is a global clotting test for the extrinsic and common pathways of the coagulation system. Increased PT, i.e. decreased Quick percentage, may be due to different conditions and should--if unexplained--be further analyzed by assaying factors II, V, VII, X and fibrinogen. Preanalytical problems, plasma dilution with clotting factor-free volume replacement, decreased vitamin K-dependent clotting factors (oral anticoagulation, intoxication with certain rodenticides, vitamin K deficiency), impaired liver synthetic capacity, disseminated intravascular coagulation, or massive heparin contamination may cause prolonged PT. Newborns physiologically have longer PT and should receive vitamin K prophylaxis.

Administration, Oral↗
PubMed2001

Childhood poisoning: access and prevention.

OBJECTIVES: To investigate the circumstances and means of access to six poisoning agents by children under 5 years of age and to make recommendations for countermeasures and strategies for implementation. METHODOLOGY: A case series study of access to six poisoning agents was conducted. Cases were identified prospectively through a poisons information centre and hospital emergency departments. Interviews were conducted with 523 parents and caregivers using a structured questionnaire. RESULTS: The majority of children (94.1%) accessed the agent in their own home or another home and, in 38% of cases (excluding mistakes in administration), the parent or caregiver was present in the immediate area at the time of the incident. In cases in which the child was alone in the room, caregivers were frequently involved in household duties (51%), with only 10% undertaking leisure activities and 8% on the telephone. The span of unsupervised time reported was 5 min or less in 79.5% of these cases. The means of access was generally during periods of use of the agent (75.3%), including just purchased, rather than when agents were in their usual storage place. CONCLUSIONS: There is little scope for improved supervision as a major intervention. Design and regulatory changes such as local safe storage for bench tops and while travelling, improved labelling and packaging, improved child-resistant packaging and its more general application are required. These and agent-specific interventions, including child-resistant bait stations for rodenticides and well covers for vaporizers, are more likely to prevent poisoning. The recent identification of childhood poisoning prevention as a national priority may lead to coordinated action to implement these and other preventive measures.

Australia↗
PubMed2001

Childhood poisoning in Queensland: an analysis of presentation and admission rates.

OBJECTIVE: To determine the presentation rates for paediatric poisoning by ingestion and the determinants of hospital admission. METHODOLOGY: Cross-sectional survey using an injury surveillance database from emergency departments in South Brisbane, Mackay and Mt Isa, Queensland, from January 1998 to December 1999. There were 1516 children aged 0-14 years who presented following ingestional poisoning. RESULTS: The presentation rates for poisoning were 690, 40 and 67 per 100000 population aged 0-4, 5-9 and 10-14 years, respectively. The admission rates to hospital for poisoning were 144, 14 and 22 per 100000 population aged 0-4, 5-9 and 10-14 years, respectively. Although presentation rates for poisoning were higher in the rural centres the admission rates were disproportionately high for the 0-4 years age group. The agents most frequently ingested were paracetamol, Dimetapp, rodenticides and essential oils. CONCLUSION: There is a need to design and implement interventions aimed at reducing poison exposures and unnecessary hospital admissions in the 0-4 years age group.

Adolescent↗
PubMed1994

The potential of murine cytomegalovirus as a viral vector for immunocontraception.

Wild populations of house mice (Mus domesticus) regularly undergo population eruptions in the cereal growing regions of S.E. Australia, causing significant damage to crops. Rodenticides are costly and are of limited usefulness, and the need for a biological control agent is widely recognized. The options for the use of an infectious agent to control mouse populations are considered. The three main types are: infectious agents which establish lethal infection; those which directly interfere with fertility; and recombinant virus vectors encoding fertility-associated proteins such as zona pellucida or sperm antigens in order to induce immunocontraceptive responses in infected mice. Ectromelia, a murine pox virus, has the potential for reducing mouse populations by lethal infection but it is not present in wild mice in Australia. The disadvantages of using ectromelia are that it would pose a significant threat to colonies of laboratory mice, there appears to be substantial innate resistance in Australian wild mice and it may not be entirely mouse-specific, thus placing native rodents at risk. A number of factors influencing the selection of a virus as a vector for immunocontraception are discussed. The mouse-specific murine cytomegalovirus (MCMV) fits most of these criteria. Infection with MCMV is already widespread in Australia with 80-90% of Mus domesticus tested being seropositive. It is a large DNA virus which establishes persistent, non-lethal infection, it is a suitable vector for the insertion of foreign genes and has a number of properties, including the capacity for superinfection, that should assist the recombinant virus to persist in wild mouse populations and induce an immunocontraceptive effect.

Animals↗
PubMedDate not supplied

Household pesticide usage in the United States.

A total of 10,000 U.S. households in 25 standard metropolitan statistical areas and 25 counties were included in the United States. More than 8,200 households granted an interview. Nine of every ten households in the United States used some types of pesticide in their house, garden, or yard. Households in the southeastern United States used the most pesticides. Although more than 500 different pesticide formulations were used by the sampled households, 15 pesticides accounted for 65.5% of all pesticides reported in this study. Thirteen of these 15 pesticides were insecticides, one was a herbicide, and one was a rodenticide.

Data Collection↗
PubMed1989

Brodifacoum poisoning in a dog.

A case of brodifacoum poisoning is described in a six-year-old male Kelpie cross working dog. The clinical features were severe exercise intolerance, haemorrhage from the oral and nasal cavities, dyspnoea and pale mucous membranes. Diagnosis was confirmed by demonstrating an abnormally long whole blood clotting time. The dog was treated successfully by administering 1 litre of whole blood intravenously, intramuscular vitamin K1 and a three week course of oral vitamin K3. Experience at the Massey University Small Animal Clinic and Hospital has indicated that poisoning of dogs with the newer long acting anticoagulant rodenticides is becoming more common.

Journal Article↗
PubMed1988

Production of antibodies and development of an immunoassay for the anticoagulant, diphacinone.

Diphacinone, a commonly used anticoagulant rodenticide, was coupled to protein via an (O-carboxymethyl) oxime bridge. Immunization in rabbits produced antibodies with good ability to recognize the hapten as demonstrated by indirect EIA and affinity column adsorption. A competitive EIA was developed which clearly measured 10 micrograms/L diphacinone concentrations showing the sensitivity of the assay. Cross-reactivity study with chlorophacinone showed that the antisera possessed a high degree of diphacinone specificity.

Animals↗