and ingestion, in both adults and young children. Minor, moderate, and serious adverse effects involved adults and young children. Minor effects correlated with e-cigarette liquid poisoning were tachycardia, tremor, chest pain and hypertension. More serious effects were bradycardia, hypotension, nausea, respiratory paralysis, atrial fibrillation and dyspnea. The exact correlation is not fully known between these effects and e-cigarettes. 58% of e-cigarette calls to US poison control centers were related to children 5 years old or less. E-cigarette calls had a greater chance to report an adverse effect and a greater chance to report a moderate or major adverse effect than traditional cigarette calls. Most of the e-cigarette calls were a minor effect. From September 1, 2010 to December 31, 2014, there were at least 5,970 e-cigarette calls to US poison control centers. During the same period, the ten most frequent adverse effects to e-cigarettes and e-liquid reported to US poison control centers were vomiting (40.4%), eye irritation or pain (20.3%), nausea (16.8%), red eye or conjunctivitis (10.5%), dizziness (7.5%), tachycardia (7.1%), drowsiness (7.1%), agitation (6.3%), headache (4.8%), and cough (4.5%). E-cigarette exposure cases in the US National Poison Data System increased greatly between 2010 and 2014, peaking at 3,742 in 2014, fell in 2015 though 2017, and then between 2017 and 2018 e-cigarette exposure cases increased from 2,320 to 2,901. The majority of cases (65%) were in children under age five and 15% were in ages 5–24. Approximately 0.1% of cases developed life-threatening symptoms. Toxicology The of nicotine is 50 mg/kg for rats and 3 mg/kg for mice. 0.5–1.0 mg/kg can be a lethal dosage for adult humans, and 0.1 mg/kg for children. However the widely used human LD50 estimate of 0.5–1.0 mg/kg was questioned in a 2013 review, in light of several documented cases of humans surviving much higher doses; the 2013 review suggests that the lower limit causing fatal outcomes is 500–1000 mg of ingested nicotine, corresponding to 6.5–13 mg/kg orally. An accidental ingestion of only 6 mg may be lethal to children. It is unlikely that a person would overdose on nicotine through smoking alone. The US Food and Drug Administration (FDA) stated in 2013: "There are no significant safety concerns associated with using more than one [over the counter] OTC [nicotine replacement therapy] NRT at the same time, or using an OTC NRT at the same time as another nicotine-containing product—including a cigarette." Ingestion of nicotine