Control Centers Toxic Exposure Surveillance Research Articles

Human exposure to insecticide products containing pyrethrins and piperonyl butoxide (2001–2003)

Pyrethrum, used as an insecticide for centuries, is derived from dried and ground flowers of Chrysanthemum cinerariaefolium. Its current major use is in insecticide products to the control insects in the home and food handling establishments. We investigated human incidents reported through the American Association of Poison Control Centers (AAPCC) Toxic Exposure Surveillance System (TESS ©) associated with regulated insecticides containing pyrethrins and piperonyl butoxide (PY/PBO) from 2001 to 2003. Special attention was paid to dermal and respiratory effects. Although there are limitations associated with TESS data, we observed that ■ Despite extensive use, incidents with reports of moderate or major adverse effects were relatively rare (717 moderate and 23 major outcomes out of 17,873 calls). ■ Following label-directed use of the products, adverse dermal or respiratory reactions were very rare; (dermal – 17 moderate, 1 major; respiratory – 18 moderate, 0 major). ■ The data suggest that asthmatics and people sensitive to ragweed ( Ambrosia artisifolia) are not unusually sensitive to PY/PBO. In view of their widespread use, the data indicates that PY/PBO products can be used with a relatively low risk of adverse effects. Moreover, the data suggest that they are not likely to cause reactions in people with asthma or allergies.

The outcome of North American pediatric unintentional mushroom ingestions with various decontamination treatments: An analysis of 14 years of TESS data

The optimum empiric decontamination therapy for unintentional pediatric mushroom ingestion is not known. We sought to determine case outcomes for unintentional mushroom ingestions in children by decontamination therapies utilized. The 1992–2005 American Association of Poison Control Centers Toxic Exposure Surveillance System was queried for cases of unintentional acute mushroom ingestions in children age <6 years. Cases were excluded if outcome was unknown, if exposure was coded as unrelated to the symptoms, or if there was co-ingestion of a non-mycoid substance. The treatment subgroups analyzed were ipecac, single-dose activated charcoal, and no gastric decontamination. 82,330 cases met the inclusion criteria with 22,454 cases excluded. There were 16 cases with major effects and no deaths. There were 57,531 cases in the three treatment subgroups. There was a significantly smaller percentage of cases with moderate or major outcomes in the ipecac subgroup compared to the no decontamination subgroup. There was a significantly greater percentage of cases with moderate or major outcomes in the activated charcoal compared to the no decontamination subgroup. If decontamination therapy is being performed, and this data suggests it may not be necessary, syrup of ipecac could still be considered an effective option.

Pyrethrin and pyrethroid exposures in the United States: A longitudinal analysis of incidents reported to poison centers

Citing the Food Quality Protection Act, the US Environmental Protection Agency (EPA) decided to phase out and eliminate organophosphate insecticide use in residential environments. The phase out process spanned from 2000 to 2005, and it may have resulted in increased consumer use of insecticides containing other active ingredients. This study utilized data from the national Poison Control Center to assess possible changes in exposure incidents involving pyrethrin and pyrethroid insecticides during the phase out of organophosphates from residential uses. We extracted pyrethrin and pyrethroid insecticide exposure data from the American Association of Poison Control Centers Toxic Exposure Surveillance System (TESS) annual reports from 2000 to 2005. We examined pyrethrin and pyrethroid incidents by total exposures for each year, and we stratified exposures by age range, reason, number of cases treated in a health care facility, and medical outcome. Cases were examined as a proportion of all insecticide exposures. We calculated the annual incidence rates for exposures involving pyrethrin and pyrethroid insecticides of the population served. Pyrethrin and pyrethroid exposures increased annually in number and as a percentage of all insecticide exposure incidents. The increase in cases was observed for all age categories and exposure reasons. A statistically significant correlation was observed between advancing years (2000-2005) and the number of pyrethrin and pyrethroid incidents (p<.01). While the number of incidents treated in a health care facility increased annually during the study period, the proportion was constant (0.185 +/- 0.012) over the six year period. During the study period, the incidence rate for pyrethrin and pyrethroid exposures increased each year. 44% of all medical outcomes data was recorded, and the majority of outcomes resulted in no symptoms (37%) or minor symptoms (53%). TESS data showed a clear increase in cases involving pyrethrins and pyrethroids. The increase was temporally associated with the phase out of organophosphates from residential uses. In the future, medical toxicologists and poison control center personnel should be prepared to respond to an increasing number of pyrethrin and pyrethroid insecticide exposures.

Organophosphate Exposures in the United States: A Longitudinal Analysis of Incidents Reported to Poison Centers

The implementation of the Food Quality Protection Act of 1996 resulted in a decision by the U.S. Environmental Protection Agency to phase out and eliminate the use of organophosphate insecticides in residential environments. The phase-out and cancellation process began in the year 2000 and was complete in 2005. The purpose of this investigation was to utilize national Poison Control Center data to assess whether the risk mitigation decision had an impact on the number of incident cases involving organophosphates in the United States. Organophosphate exposure incident data were extracted from Annual Reports of the American Association of Poison Control Centers Toxic Exposure Surveillance System (TESS) for the years 1995 to 2004. The number of organophosphate exposure incidents peaked at 20,135 in 1997, and declined in each subsequent year. A statistically significant decrease was observed in the average annual number of organophosphate exposure incidents when comparing data from the time periods before (1995–1999) and after (2000–2004) the commencement of the phase-out process. The decrease in organophosphate incident cases was observed for all age categories, as well as for the circumstances surrounding the exposure (unintentional and intentional exposure incidents). TESS data showed a significant decrease in incident cases involving organophosphates in association with the phase-out from residential uses. The results of this investigation are consistent with other studies that have reported that regulatory restriction of access to pesticide formulations may have a significant impact on the number of human exposure incidents.

Fatality from Diphenhydramine Monointoxication

As an antihistamine, diphenhydramine (DPH) is well known for its use in allergy treatment. Since its introduction in 1946, it has been marketed under various trade names, the most popular being Benadryl. Three years after its introduction, the first fatality due to DPH toxicity was reported in 1949. To better understand the incidence of fatalities due to DPH monointoxication, we reviewed deaths that were reported from 2 data sources: (1) the English-language literature using PubMed, from 1946 through 2003; and (2) the Annual Report of the American Association of Poison Control Centers Toxic Exposure Surveillance System (ARAAPCCTESS), from 1983 through 2002. The results were then tabulated using age, gender, clinicopathologic findings, and toxicology results. Combined results from both data sets show the following mean (and range) for age and DPH levels: Adult, 35.6 years (18-84) and 19.53 mg/L (0.087-48.5); pediatric, 8.6 years (1.25-17) and 7.4 mg/L (1.3-13.7); infant, 31 weeks (6 weeks-11 months) and 1.53 mg/L (1.1-2.2), respectively. Most deaths were certified as accident or suicide; however, 6 infant homicides were reported. The most common symptoms for all cases were cardiac dysrhythmias, seizure activity, and/or sympathetic pupil responses. The most common autopsy finding was pulmonary congestion.

Excess Fatality From Desipramine in Children and Adolescents

To compare the case fatality rate (CFR) from desipramine ingestion in children and adolescents with that of other tricyclic antidepressants. All mentions of desipramine, amitriptyline, imipramine, nortriptyline, and doxepin in children and adolescents recorded in the American Association of Poison Control Centers Toxic Exposure Surveillance System from 1983 to 2002 were analyzed. The CFR for each drug was defined as the ratio of the number of deaths/number of mentioned exposures. There were 24 fatalities in children younger than 6 years old (desipramine, n=10; amitriptyline, n=7; doxepin, n=3; imipramine, n=3; nortriptyline, n=1) and 144 fatalities in older children and adolescents (desipramine, n=56; amitriptyline, n=30; doxepin, n=16; imipramine, n=31; nortriptyline, n=11). The CFR from desipramine was significantly higher compared with the other tricyclic antidepressants in children younger than 6 years old (chi=36, p<.001) and in older children and adolescents (chi=155, p<.001). The CFR from desipramine exceeded that of amitriptyline, doxepin, imipramine, and nortriptyline by 7- to 8-, 4-, 6- to 12-, and 7- to 10-fold, respectively. The excess CFR from desipramine in children and adolescents and the reports of sudden death in children treated with therapeutic doses call for caution in prescribing desipramine to children and adolescents.

TESS-based dose–response using pediatric clonidine exposures

The toxic and lethal doses of clonidine in children are unclear. This study was designed to determine whether data from the American Association of Poison Control Centers Toxic Exposure Surveillance System (TESS) could be utilized to determine a dose-response relationship for pediatric clonidine exposure. 3,458 single-substance clonidine exposures in children <6 years of age reported to TESS from January 2000 through December 2003 were examined. Dose ingested, age, and medical outcome were available for 1550 cases. Respiratory arrest cases (n = 8) were classified as the most severe of the medical outcome categories (Arrest, Major, Moderate, Mild, and No effect). Exposures reported as a "taste or lick" (n = 51) were included as a dose of 1/10 of the dosage form involved. Dose ranged from 0.4 to 1980 (median 13) microg/kg. Weight was imputed based on a quadratic estimate of weight for age. Dose certainty was coded as exact (26% of cases) or not exact (74%). Medical outcome (response) was examined via logistic regression using SAS JMP (release 5.1). The logistic model describing medical outcome (P < 0.0001) included Log dose/kg (P = 0.0000) and Certainty (P = 0.045). TESS data can provide the basis for a statistically sound description of dose-response for pediatric clonidine poisoning exposures.

Evaluation of toxicity of topiramate exposures reported to poison centers

Published literature on the toxicity of a topiramate overdose is limited to case reports. This retrospective study of poison center data was performed to examine the severity of topiramate overdoses. Data on single substance exposures to topiramate reported to the American Association of Poison Control Centers (AAPCC) Toxic Exposure Surveillance System (TESS) in 2000 and 2001 were retrospectively analysed. A total of 567 cases met the inclusion criteria, of which 39% occurred in adults over 19 years of age and 30.2% in children < or = 4 years old. The majority of patients (62.1%) experienced no toxicity. The most common clinical effects reported were drowsiness/lethargy (15.5%), dizziness/vertigo (4.9%), agitation (4.9%), confusion (3.9%), nausea (2.6%) and vomiting (2.5%). Symptomatic patients were older than asymptomatic patients and adults were more likely to be managed in a healthcare facility (P <0.0001). Patients who received gastrointestinal decontamination experienced less serious outcomes than those without decontamination (P <0.02). It is concluded that clinicians should expect relatively mild mental status changes in adults or children with toxicity from topiramate overdose. Serious toxic effects, such as CNS depression with respiratory depression or persistent non-anion gap metabolic acidosis, are infrequent.

2004 Annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System

2004 Annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System

Persistent Choreoathetosis in a Fatal Olanzapine Overdose: Drug Kinetics, Neuroimaging, and Neuropathology

Atypical antipsychotics are a relatively new group of medications for the management of psychosis. Currently approved medications of this category include clozapine, risperidone, quetiapine, and olanzapine. Olanzapine was first marketed in 1996 in the United States as an atypical antipsychotic medication similar to clozapine for schizophrenia. By 2002, olanzapine was widely used and in the top 20 drugs by sales (1). Olanzapine belongs to the thienobenzodiazepine drug class and is known to have a high affinity for dopamine D2, D3, and D4 receptors, all five serotonin HT2 receptor subtypes, the 5-HT6 receptor, acetylcholine muscarinic receptors, and α1-adrenergic and histamine H1 receptors (2). The drug is well absorbed from the gut and reaches maximum plasma concentration about 6 hours after an oral dose (3). In plasma, 93% of the drug is bound to serum proteins, especially albumin (3). The drug is extensively eliminated by first-pass metabolism in the liver and has a mean elimination half-life of 30 hours, with a range of 21–54 hours (3). Olanzapine is considered to have a good overall safety profile at therapeutic doses (4). Adverse effects of olanzapine that affect the nervous system include mental status deterioration and extrapyramidal signs and, rarely, delirium, mutism, confusion, aggression, and lethargy that can progress to coma. Seizures, status epilepticus, and hypersalivation occasionally develop (5, 6). Extrapyramidal signs may include dystonia, parkinsonism, akathisia, choreoathetosis, and neuroleptic malignant syndrome (7– 9). Serious systemic complications include diabetes mellitus, tachycardia and supraventricular tachycardia, arrhythmias, and cardiopulmonary arrest (10, 11). Overdoses can lead to deaths. The American Association of Poison Control Centers Toxic Exposure Surveillance System reported the number of deaths associated with olanzapine to be six in 2000 (12), 10 in 2001 (13), and 10 in 2002 (14). Before some of these deaths, concomitant agents were ingested. The majority of deaths occurred within 12 hours of overdose, and the results of autopsies, when available, were often unremarkable (15–17). We report here a patient who survived the early phase of an overdose. He then developed coma with persistent choreoathetosis and hypersalivation, and neuroimaging and autopsy findings suggested damage to the basal ganglia.

Evaluation of lamotrigine toxicity reported to poison centers.

Lamotrigine is an antiepileptic drug for the treatment of partial and generalized seizures as well as bipolar disorder. Limited published information exists describing the clinical effects of lamotrigine overdose. To examine the toxicity of exposures to lamotrigine utilizing national poison center data. Data on single-substance exposures to lamotrigine reported to the American Association of Poison Control Centers Toxic Exposure Surveillance System in 2000 and 2001 were retrospectively analyzed. There were 493 cases that met the inclusion criteria. The majority of exposures occurred within the age groups 20-59 years old (n = 198, 40.2%), followed by </=4 years old (n = 173, 35.1%). Overall, the majority of patients (52.1%) exposed to lamotrigine in overdose experienced no toxic clinical effects. The most common clinical effects reported in overdose were drowsiness/lethargy (20.9%), vomiting (11%), nausea (5.1%), ataxia (4.9%), dizziness/vertigo (4.5%), and tachycardia (4.3%). Major clinical effects included coma (n = 6), seizures (n = 8), and respiratory depression (n = 3). Medical outcome was reported as minor in 150 (30.4%), moderate in 73 (14.8%), and major in 13 (2.6%) cases. There were no deaths. These data demonstrate that the majority of patients exposed to lamotrigine in overdose experienced minor or no clinical effects. Although rare, serious effects can also occur.

Are 1 or 2 dangerous? Clozapine and olanzapine exposure in toddlers

Clozapine (Clozaril ®) and olanzapine (Zyprexa ®) are two relatively new atypical antipsychotics that are structurally and pharmacologically related. There are currently no therapeutic indications for these pharmaceuticals in infants and toddlers.Presumably, as the usage of these medications in adults increases, the frequency of unintentional pediatric ingestions will increase. In 2001 the annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System included a separate subcategory for atypical antipsychotics under the heading of sedatives/hypnotics/antipsychotics. The toxidrome resulting from these drugs is predominately central nervous system depression and anticholinergic effects. Although the desirable lack of extrapyramidal symptoms in adults results in their greatest clinical utility, several reports of toxic ingestions in small children are noteworthy for having extrapyramidal manifestations. We review here the available reported clinical experience with toxic doses of these medications that in small children may amount to as little as a single tablet. Although such doses may be lethal, supportive care and gastrointestinal decontamination in this population will generally lead to a good outcome.

2003 annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System

AAPCC's 2003 fatality verification process involved the preparation and review of abstracts on 1,390 fatalities reported to poison centers, some of which were eventually determined to be unrelated to a poison exposure.

2002 annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System.

2002 annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System.

Poison Centers’ Experience With Methylphenidate Abuse in Pre-Teens and Adolescents

To evaluate trends and toxicity of methylphenidate abuse in pre-teens and adolescents reported to poison centers. The 1993-1999 American Association of Poison Control Centers Toxic Exposure Surveillance System was queried for methylphenidate abuse cases in children aged 10 through 19 years that were followed to known outcome. Main outcome measures included number of cases annually, toxicity, management site, and coded medical outcome. Of 759 cases, 42.7% involved 10-through 14-year-olds. For the 530 (70.0%) cases involving methylphenidate only, the frequency increased sevenfold from 1993 to 1999. Of 570 patients (75.1%) managed in a health care facility, 398 were discharged from the emergency department and 172 were admitted. Symptoms occurred more commonly in exposures involving coingestants (84.3%) than in methylphenidate-only exposures (71.1%). The most common symptoms in adolescents with methylphenidate only were tachycardia (31.7%), agitation/irritability (25.7%), and hypertension (11.5%). Outcomes were no effect in 189 cases (24.9%) and mild, moderate, and severe in 318 (41.9%), 245 (32.3%), and 7 (0.9%) patients, respectively. Poison center data demonstrate increasing frequency of methylphenidate abuse. While the majority of adolescents experienced clinical effects and were managed in a health care facility, outcomes were good, especially in cases involving methylphenidate only.

Epidemiology and toxicity of pediatric guanfacine exposures.

To examine the epidemiology and toxicity of guanfacine exposures in children and adolescents reported to poison control centers. Guanfacine exposures reported to the American Association of Poison Control Centers Toxic Exposure Surveillance System from 1993 to 1999 in children and adolescents <19 years of age were analyzed. There were 870 cases that met the inclusion criteria: 478 (54.9%) were children <6 years old, 304 (34.9%) were 6-12 years old, and 88 (10.1%) were adolescents 13-18 years old. The number of cases increased eight-fold over the 7-year period, with the largest increase in children <13 years of age. Analysis showed 29.7% of exposures were managed on site (non-healthcare facility) and 68.3% were managed in a healthcare facility. There were no symptoms in 546 (62.8%) children. In 324 symptomatic children, the most common symptoms were drowsiness/lethargy (76.8%), bradycardia (30.0%), and hypotension (25.8%). The majority of cases were acute (77.5%), 182 (20.9%) were acute-on-chronic, and 14 (1.6%) were chronic. Children aged 6-12 years represented the majority of the acute-on-chronic and chronic exposures with (n = 118). Overall, there were 195 (22.4%) exposures coded as minor, 121 (13.9%) as moderate, and 8 (0.9%) as major effects. These data demonstrated a trend of increasing numbers of guanfacine exposures annually. Although the majority of children experienced minimal or no toxicity, serious toxicity can occur.

2001 Annual Report of the American Association of Poison Control Centers Toxic Exposure Surveillance System

2001 Annual Report of the American Association of Poison Control Centers Toxic Exposure Surveillance System

Methanol poisoning exposures in the United States: 1993-1998.

We investigated U.S. methanol-poisoning exposures since little recent information is available about the frequency, sources of methanol, or outcomes of individuals who consume methanol. We reviewed human methanol exposures reported to the American Association of Poison Control Centers Toxic Exposure Surveillance System 1993-1998. The mean number of cases per year was 2254. Each year 167 cases had an outcome of moderate effect, major effect, or death. One death occurred in every 183 exposures to methanol. Symptomatic cases increased abruptly from 1.8 to 2.5% for infants and children, from 14.1 to 12.3% for adolescents and adults, while the intentional exposures increased from < 1 to 21% for adolescents, and 11% for adults. Cases occurred in every decade of life but toddlers had the highest number of exposures. In 68 methanol fatalities, confusion developedfollowed by coma, hypotension, respiratory depression, and cerebral edema. Blood methanol levels were above 100mg/dL (70%), metabolic acidoses (62%), and anion gaps > 25 (100%). Methanol products were recorded, showing windshield wiper fluids to be 60.8% of exposures. Other automotive sources were 23.7%. Commercial nonautomotive products were 12.2% and pure methanol products were 2.3%. Unintentional exposures were reported in 90.3% of all cases, while 8.3% were due to intentional exposures, and 1.4% wasfor unknown or mixed reasons. Intentional exposures resulted from suspected suicides (51.2%) and from abuse and misuse (38.8%). Methanol poisonings continue to occur in the United States with toddlers at the highest risk for exposure, but adolescents and adults at the highest risk for life-threatening intoxications. Over half of product-identified cases were due to consumption of windshield wiperfluid. Efforts should be undertaken to minimize methanol exposures.

Human poisonings and rodenticides: evaluation of incidents reported to the American Association of Poison Control Centers

Author(s): Eisemann, John D.; Petersen, Brett E. | Abstract: Accidental human exposure to pesticide products is a major concern of the U.S. Environmental Protection Agency (EPA). One condition of product reregistration is the submission of product-specific incident report summaries from the American Association of Poison Control Centers (AAPCC) Toxic Exposure Surveillance System (TESS). Between 1986 and 1998, the AAPCC received a total of 22,921,827 incident reports from telephone calls and physician reports. The total number of incident reports per year more than doubled between 1986 and 1998, with 2,241,082 incidents in 1998. While the total number of incidents increased each year, the reporting per year rate remained constant at approximately 9 reports per 1,000 individuals. Rodenticide related incident reports increased from 8,705 in 1986 to 20,300 in 1998. However, the yearly reporting rate for rodenticide incidents remained constant at approximately 8 reports per 100,000 individuals. Since 1990, anticoagulants have consistently accounted for 82% to 89% of all rodenticide exposures and “long-acting” anticoagulants (i.e., 2nd generation compounds such as brodifacoum) have accounted for 83% to 91% of all anticoagulant incidents. Although there was variation between years, there were approximately 150 incident reports each year for both strychnine and zinc phosphide. “Unintentional” exposures accounted for approximately 85% of all incidents reported to the AAPCC. With the exception of strychnine, unintentional exposure to rodenticides was slightly higher, at 90%. In the case of zinc phosphide, nearly all exposures (g97%) were unintentional. The majority of exposures involved children less than 6 years old. However, adults were reported to be involved more than 50% of the strychnine incidents. Despite the high number of exposures, very few cases resulted in more than minor symptoms.

2000 Annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System

2000 Annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System