Poisonings in animals: the 1993-1994 report of the American Association of Poison Control Centers.

More than 82% of the 140,614 animal poison exposures reported in 1993 and 1994 occurred in dogs and almost 14% occurred in cats. Almost all reported were acute exposures to a single product. Tables of detailed data are provided.

Suspected bentonite toxicosis in a cat from ingestion of clay cat litter.

A 2 1/2-y-old spayed female cat was presented for lethargy and weakness. The cat was hypokalemic (3.1 m Eq K/L) and severely anemic (60% PVC, 1.3 g hemoglobin/dL). The cat was known to ingest bentonite-containing cat litter. It recovered with treatment of i.v. fluids, electrolytes and whole blood transfusion and was discharged. Two months later the cat was presented again with signs similar to those seen previously. This occurred 1 mo after the owner resumed the use of bentonite-containing cat litter. The signs were remarkably similar to those reported in humans from the chronic ingestion of bentonite clays. Bentonite toxicosis is suggested by the coexistence of hypokalemia hypochromic anemia in cats presented with lethargy and muscle weakness.

Evidence that the NH2-terminus of substance P modulates N-methyl-D-aspartate-induced activity by an action involving sigma receptors.

Behaviors induced in mice by intrathecal injections of either N-methyl-D-aspartate (NMDA) or kainic acid are modulated by NH2-terminal fragments of substance P, such as substance P-(1-7). The action of substance P-(1-7) on kainic acid depends on sigma receptor activity. The present study was designed to test the hypothesis that sigma receptor activity is also necessary for modulation of NMDA by substance P-(1-7). Intrathecal injection of mice with NMDA results in a brief burst of biting and scratching behaviors which decrease in intensity when NMDA is injected repeatedly at 2 min intervals. Pretreatment with 1,3-di-O-tolylguanidine (DTG), a ligand at both sigma 1 and sigma 2 sites, converted NMDA-induced desensitization to sensitization, thereby enhancing tonic NMDA receptor activity. Although haloperidol (30 min) alone was without effect, the potentiation of NMDA-induced activity by DTG was abolished by haloperidol but unaffected by an equimolar dose of either spiperone or thiothixine, two dopamine receptor antagonists. When mice received substance P-(1-7), NMDA-induced behaviors were initially inhibited but then potentiated. Pretreatment with haloperidol prevented both inhibitory and potentiative effects of substance P-(1-7) whereas thiothixine did not, suggesting inhibitory as well as potentiative modulation of NMDA by sigma receptor activity. Endogenous sigma 1 receptor activity may enhance NMDA receptor activity as a treatment regimen that down-regulates sigma 1 binding also inhibited responses to NMDA. In contrast, pretreatment with haloperidol just 5 min prior to challenge, which blocks both sigma 1 and sigma 2 receptor activity, increased responses to NMDA suggesting an inhibitory effect of sigma 2 receptor activity. In summary, modulation of NMDA by substance P-(1-7) appears to depend on activity at sigma sites as substance P-(1-7) mimicked the potentiative effects of DTG, while haloperidol inhibited the effects of both DTG and substance P-(1-7).

The NH2-terminus of substance P modulates NMDA-induced activity in the mouse spinal cord.

Excitatory amino acids (EAAs) and substance P are believed to transmit nociceptive information in the spinal cord. As substance P NH2-terminal fragments can modulate non-NMDA EAA-mediated activity, we examined the effects of substance P fragments to ascertain whether the COOH- or NH2-terminus of substance P modulates the actions of NMDA in the spinal cord. NMDA activity was measured by the intensity of behaviors produced by NMDA (0.2 nmol) administered intrathecally in the mouse. The NMDA response was attenuated after pretreatment with either substance P (22.5 pmol, 30 min) or the NH2-terminal fragment of substance P, SP-(1-7). Pretreatment with the COOH-terminal fragment SP-(5-11) (22.5 pmol, 30 min), a neurokinin ligand, had no effect on NMDA-induced behaviors, suggesting that the inhibitory effect of substance P is caused by the NH2-terminus. Pretreatment with D-Pro2,D-Phe7 substance P-(1-7), a SP-(1-7) antagonist, potentiated NMDA activity, suggesting a tonic inhibitory effect of the substance P NH2-terminus. Desensitization to NMDA typically develops when NMDA is injected at 2 min intervals. While pretreatment with SP-(1-7) inhibited NMDA, coadministration of SP-(1-7) (22.5 pmol), with the first of four injections of NMDA, first inhibited but then potentiated responses to each challenge with NMDA. Coadministration of the same dose of SP-(1-7) with the fourth injection of NMDA immediately potentiated the response to NMDA.(ABSTRACT TRUNCATED AT 250 WORDS)

Melaleuca oil poisoning.

A 23-month-old boy became confused and was unable to walk thirty minutes after ingesting less than 10 mL of T36-C7, a commercial product containing 100% melaleuca oil. The child was referred to a nearby hospital. His condition improved and he was asymptomatic within 5 hours of ingestion. He was discharged to home the following day. Melaleuca oil, extracted from the Melaleuca alternifolia, contains 50-60% terpenes and related alcohols. Clinical experience with products containing melaleuca oil is limited. This case report suggests that ingestion of a modest amount of a concentrated form of this oil may produce signs of toxicity.

Adenosine receptors are not involved in theophylline-induced seizures.

One of the most dangerous aspects of theophylline toxicity is seizures. A review of the literature suggests that current anticonvulsant therapy remains far from optimal. As it is known that some of the pharmacologic effects of theophylline occur via antagonism of the adenosine A1 receptor, we tested the hypothesis that agonists acting at the adenosine A1 receptor can inhibit seizures caused by toxic doses of theophylline in mice. Dose-response curves were constructed for the ability of theophylline to produce tonic seizures in animals pre-treated with vehicle or several adenosine A1 receptor agonists. The LD50 (95% CI) for each dose-response curve was calculated. The results of these experiments showed that pretreatment with the direct-acting adenosine A1 agonists carbamazepine and cyclohexyladenosine and the indirect-acting agonist dipyridamole each failed to inhibit the ability of theophylline to cause tonic seizures (p > 0.05). Failure of these drugs to protect against theophylline-induced seizures suggests these seizures are produced by other mechanisms. Based on our results, adenosine A1 agonists, such as carbamazepine, appear to offer no therapeutic benefit in the treatment of theophylline-induced seizures.

Nitroethane poisoning from an artificial fingernail remover.

Confusion between acetone fingernail polish removers and artificial fingernail products containing acetonitrile and N,N-dimethyl-p-toluidine has resulted in pediatric morbidity and mortality. In the present case, a 20-month-old boy drank less than one ounce of Remove Artificial Nail Remover containing 100% nitroethane. In the emergency department he displayed cyanosis and 39% methemoglobinemia. Following intravenous methylene blue, the child's methemoglobin level dropped to 5.7% and he recovered uneventfully. Toxicity from nitroethane has not previously been reported in humans. Poison centers and emergency department personnel should be alert to another nail product which may be easily confused with acetone-containing nail polish removers.

A report of acute ethanol poisoning in a child: mouthwash versus cologne, perfume and after-shave.

The ingestion of ethanol-containing products, such as cologne, perfume and after-shave, in children under six years of age is common, but serious poisoning is rarely reported. Thus, it has been recently suggested that children ingesting up to 3.5 ounces of these products may be safely observed at home as long as they remain asymptomatic. While it may be assumed that products with a significantly lower alcohol content represent a much smaller poisoning hazard, mouthwashes are a relatively frequent cause of serious poisoning in children. In the following case report, 75 milliliters of mouthwash caused hypoglycemia, coma and manifestations of tonic seizure activity. Because of the palatable nature of mouthwash, wine and liquor, it appears that children are more apt to drink large quantities, consuming dangerous amounts of ethanol. The apparent safety of cologne, perfume, and after-shave may be due to a lack of palatability as well as the irritant nature of high concentrations of ethanol. This case suggests that consumer items such as mouthwash should be packaged in child-resistant containers.

Antinociceptive effects of intrathecal taurine and calcium in the mouse.

Taurine (Tau), calcium (Ca+2) and opiates each produce antinociception when injected i.t. in mice. This study was initiated to determine whether there is a common mechanism underlying their antinociceptive effects. Using the abdominal stretch assay, the antinociceptive effects of both Tau (12 nmol) and Ca+2 (72 nmol) were antagonized by i.t. TAG (4.4 nmol), a Tau antagonist, but not by i.p. injection of the opiate antagonist naloxone (5 mg/kg). The antinociceptive effects of Tau and Ca+2 correlated with their ability to inhibit the intensity of caudally-directed biting and scratching behaviors produced by i.t. NMDA or kainic acid. The inhibitory effects of both Tau and Ca+2 on the biting and scratching behaviors behaviors induced by substance P or excitatory amino acids were reversed by TAG, suggesting a common mediation by Tau. These data indicate that the antinociceptive effects of both Tau and Ca+2 appear to be mediated, at least in part, by Tau but not by the release of endogenous opioid compounds. In addition, inhibition of chemical irritant-induced nociception may be produced by a simple blockade of excitatory amino acid activity.

A poison information service for small animals offered by a regional poison center.

Since 1985 the Hennepin Regional Poison Center has provided the same quality service to veterinarians and pet owners that parents of small children, physicians and other health care providers have enjoyed for many years. To facilitate this service, the poison center has expanded its data base to include information on small animal poisonings and has periodically mailed newsletters state-wide to veterinarians. In addition, the poison center began to routinely assist per owners in the home treatment of minor ingestions in dogs, and enlisted the aid of a veterinary toxicologist who is on-call for consultation. Prior to 1985, animal-related exposures totaled 1,092 cases, which comprised 3.9% of the center's total annual cell volume. As a result of the above efforts, calls from veterinarians and pet owners increased to approximately 2,000 cases annually for the period 1986-88 (average 6.3%). Recently, the poison center received the financial support of the Minnesota State Veterinary Association for the printing of telephone stickers promoting a line exclusively for pet calls (337-PETS). This Pet Poison Information Service appears well received, resulting in an additional 58% increase in pet-related calls. During 1990 this center consulted on over 3,500 exposures in companion animals. Based on our experience, veterinarians and pet owners appear to have been relatively neglected by poison centers. Poison centers may play an important role in the treatment of poisonings in pets.

Absorption of iron after experimental overdose of chewable vitamins.

Even though ingestion of chewable iron preparations is much more common, treatment recommendations for iron overdose are usually based on experience with nonchewable preparations. To determine the optimal time to measure serum iron concentrations, five volunteers were given chewable iron in 5 mg/kg and 10 mg/kg doses and their serum iron concentrations monitored. Peak levels occurred at 4.2 and 4.5 hours, respectively, after ingestion, and levels drawn at 3 hours were within 90% of the peak. Nausea and headache were experienced by all volunteers, and serum iron exceeded baseline total iron binding capacity in two subjects at the 10 mg/kg dose. In minor iron overdose resulting from the ingestion of chewable vitamins, serum iron concentrations measured between 3 and 7 hours (95% confidence level of peak concentrations) may be adequate in assessing the peak serum iron concentration.

Seizures induced by fluoroacetic acid and fluorocitric acid may involve chelation of divalent cations in the spinal cord.

Fluoroacetic and fluorocitric acid toxicity is often characterized by seizures, however the mechanism of this activity is unknown. Intrathecal (i.t.) injection of fluorocitrate in mice resulted in seizures after an average latency of 15 s, while intracerebroventricular (i.c.v.) injection produced seizures after 36.5 min, and required higher doses to achieve this effect. This indicates the probable site of fluoroacetate and fluorocitrate neurotoxicity is the spinal cord. To mimic citrate accumulation, characteristic of fluoroacetate and fluorocitrate poisoning, citric acid was injected i.t. and also found to produce seizures. The structurally unrelated compounds EDTA, EGTA, glutamic acid and lactic acid also produced seizures identical to fluorocitrate. The ability of these compounds to chelate Ca2+ correlates well with their ability to cause seizures when administered i.t. and coadministration of calcium greatly attenuated the neurotoxicity of these compounds as well as fluoroacetate and fluorocitrate. In contrast, Ca2+ was unable to inhibit seizures elicited by strychnine, suggesting calcium's ability to inhibit chelators of divalent cations is not due to a general anticonvulsant effect. These results suggest that changes in Ca2+ concentration in the spinal cord may be responsible for some forms of seizure activity.

Toxicity of nightshade berries (Solanum dulcamara) in mice.

Ripened nightshade berries (Solanum dulcamara) are among the most commonly reported plant ingestions in Minnesota. Because of the lack of adequate information regarding the toxic qualities of S. dulcamara berries, the ingestion of even small quantities by children is usually treated conservatively with syrup of ipecac. The toxicity of S. dulcamara berries was studied by gavaging mice with a preparation of lyophilized berries, ripened and unripened, collected at various times of the year. Mice receiving unripened fruit from early in the season had gastrointestinal tissue changes consistent with solanine toxicity. Animals dosed with unripened fruit from the latter part of the year showed behavioral signs suggestive of solanine toxicity, however gastrointestinal lesions were not observed. In no case did the ripened fruit produce behavioral or histologic toxicity. Aggressive treatment of children ingesting limited amounts of ripened S. dulcamara berries appears to be unnecessary.

Selective inhibition of excitatory amino acids by divalent cations. A novel means for distinguishing N-methyl-D-aspartic acid-, kainate- and quisqualate-mediated actions in the mouse spinal cord.

Biting and scratching behaviors produced by intrathecal injection of excitatory amino acid (EAA) agonists were examined to determine whether the biting and scratching behavioral effects produced by these compounds are altered selectively in vivo by coadministration with divalent cations. N-methyl-D-aspartate (NMDA)-induced behavior was inhibited by both magnesium and calcium but not by zinc. Kainic acid (KA)-induced behavioral activity was also inhibited by coadministration with calcium but not by magnesium or zinc. In contrast to both NMDA and KA, calcium, magnesium and zinc failed to alter the intensity of quisqualic acid (Quis)-induced biting and scratching behaviors. Based on this selective inhibition of the three EAA subtypes by divalent cations, we examined the behavioral responses produced by Glu and Asp in combination with calcium or magnesium to identify the receptor population involved in these motor effects. Calcium antagonized the biting and scratching behavior produced by i.t. injected Glu in contrast with Asp which was inhibited significantly by magnesium. Our results support the concept that Glu and Asp produce biting and scratching behaviors by an interaction with distinct receptor populations in the spinal cord. To date, there are no selective antagonists at the KA or Quis receptors. Thus, a systematic examination of the selective inhibition of EAA activity by divalent cations in addition to currently available pharmacologic antagonists may prove to be a useful approach to the identification of NMDA, KA and Quis receptor interactions.