<p><strong>Lethal doses</strong></p><p>Acute oral LD50 values have been reported as over 1.0 g/kg in humans, cats, and dogs, 0.92 g/kg - 1.48 g/kg in albino rats, 1.19 g/kg in guinea pigs, 1.1 g/kg in mice, and 1.8 g/kg in rabbit models <sup class="text-reference-group"><a class="reference-popover-link" data-content="Official drug label" href="#label-reference">Label</a></sup>.</p><p><strong>Acute toxicity</strong></p><p>Salicylate toxicity is a problem that may develop with both acute and chronic salicylate exposure <sup class="text-reference-group"><a class="reference-popover-link" data-content="Authors unspecified: Guidance document: management priorities in salicylate toxicity. J Med Toxicol. 2015 Mar;11(1):149-52. doi: 10.1007/s13181-013-0362-3. (PubMed ID 25715929)" href="#reference-A35408">7</a></sup>.
Multiple organ systems may be affected by salicylate toxicity, including the central nervous system, the pulmonary system, and the gastrointestinal system. Severe bleeding may occur. In the majority of cases, patients suffering from salicylate toxicity are volume-depleted at the time of presentation for medical attention. Fluid resuscitation should occur immediately and volume status should be monitored closely. Disruptions in acid-base balance are frequent in ASA toxicity <sup class="text-reference-group"><a class="reference-popover-link" data-content="Authors unspecified: Guidance document: management priorities in salicylate toxicity. J Med Toxicol. 2015 Mar;11(1):149-52. doi: 10.1007/s13181-013-0362-3. (PubMed ID 25715929)" href="#reference-A35408">7</a></sup>. </p><p>The acute toxicity of acetylsalicylic in animals has been widely studied. The signs of poisoning in rats from lethal doses are mild to severe gastroenteritis, hepatitis, nephritis, pulmonary edema, encephalopathy, shock and some toxic effects on other organs and tissues. Mortality has been observed following convulsions or cardiovascular shock. An important differentiating property between various animal species is the ability to vomit toxic doses. Humans, cats and dogs have this ability, but rodents or rabbits do not <sup class="text-reference-group"><a class="reference-popover-link" data-content="Official drug label" href="#label-reference">Label</a></sup>. </p><p><strong>Chronic toxicity and carcinogenesis</strong></p><p>Chronic ASA toxicity is frequently accompanied by atypical clinical presentations that may be similar to diabetic ketoacidosis, delirium, cerebrovascular accident (CVA), myocardial infarction (MI) or cardiac failure. Plasma salicylate concentrations should be measured if salicylate intoxication is suspected, even if there no documentation available to suggest ASA was ingested. In older age, nephrotoxicity from salicylates increases, and the risk of upper gastrointestinal hemorrhage is increased, with higher rates of mortality <sup class="text-reference-group"><a class="reference-popover-link" data-content="Durnas C, Cusack BJ: Salicylate intoxication in the elderly. Recognition and recommendations on how to prevent it. Drugs Aging. 1992 Jan-Feb;2(1):20-34. (PubMed ID 1554971)" href="#reference-A32954">8</a></sup>. It is also important to note that ASA toxicity may occur even with close to normal serum concentrations. Prevention of chronic ASA includes the administration of smallest possible doses, avoidance of concurrent use of salicylate drugs, and therapeutic drug monitoring. Renal function should be regularly monitored and screening for gastrointestinal bleeding should be done at regular intervals <sup class="text-reference-group"><a class="reference-popover-link" data-content="Durnas C, Cusack BJ: Salicylate intoxication in the elderly. Recognition and recommendations on how to prevent it. Drugs Aging. 1992 Jan-Feb;2(1):20-34. (PubMed ID 1554971)" href="#reference-A32954">8</a></sup>. </p><p>Chronic toxicity studies were performed in rodents. ASA was administered at doses measured to be 2 to 20 times the maximum tolerated clinical dose to mice for up to one year. Negative dose-related effects were seen. These include decreased mean survival time, decreased number of births and progeny reaching an appropriate age for weaning. No evidence of carcinogenesis was found in 1-year studies <sup class="text-reference-group"><a class="reference-popover-link" data-content="Official drug label" href="#label-reference">Label</a></sup>. At daily doses of 0.24 g/kg/day given for 100 days to albino rats, ASA led to signs to excessive thirst, aciduria, diuresis, drowsiness, hyperreflexia, piloerection, changes in respiration, tachycardia, followed by soft stools, epistaxis, sialorrhea, dacryorrhea and mortality during hypothermic coma in the second study month <sup class="text-reference-group"><a class="reference-popover-link" data-content="Official drug label" href="#label-reference">Label</a></sup>.</p><p><strong>Use in pregnancy and lactation</strong></p><p>While teratogenic effects were observed in animals nearly lethal doses, no evidence suggests that this drug is teratogenic in humans <sup class="text-reference-group"><a class="reference-popover-link" data-content="Official drug label" href="#label-reference">Label</a></sup>. It is advisable, however, to avoid ASA use the first and second trimester of pregnancy, unless it is clearly required. If acetylsalicylic acid containing drugs are ingested by a patient attempting to conceive, or during the first and second trimester of pregnancy, the lowest possible dose at the shortest possible duration should be taken <sup class="text-reference-group"><a class="reference-popover-link" data-content="Official drug label" href="#label-reference">Label</a></sup>. This drug is contraindicated in the 3rd trimester of pregnancy <sup class="text-reference-group"><a class="reference-popover-link" data-content="Official drug label" href="#label-reference">Label</a></sup>. </p>