FACTS ABOUT NICOTINE TOXICITY

Irena BRÈIÆ KARAÈONJI
Institute for Medical Research and Occupational Health, Zagreb, Croatia
Received in July 2005



TOXICITY DATA AND TOXICITY EVALUATION
General toxicity
Acute toxicity



In experimental animals, the dose of nicotine
which is lethal to 50 % of the animals (LD50) varies
widely, depending on the route of administration
and the species used. The intravenous (i.v.) LD50
dose of nicotine in mice is 7.1 mg kg-1 body weight
(22). By direct i.v. administration the LD50 to rats was
determined to 1 mg kg-1 (23). The intraperitoneal (i.p.)
LD50 values for nicotine in mice and rats have been
found to be 5.9 mg kg-1 and 14.6 mg kg-1, respectively
(22). The oral LD50 dose for nicotine in rats is 50 mg
kg-1 to 60 mg kg-1 (24). The wide variation in sensitivity
to the toxic effects of nicotine in rodents appears to
be genetically determined (25). Dermal acute toxicity



(LD50) in rabbits is 140 mg kg-1 (26). In interpreting

animal toxicity data it is important to recognise that the
route of administration is an important determinant of
toxicity. Rapid i.v. injections result in the highest blood
and brain concentrations and produce toxicity at the
lowest doses. In contrast, oral or i.p. administration
require higher doses to produce toxicity. This is due
in part to pre-systemic (“first pass”) metabolism of
nicotine whereby, after absorption into the portal
venous circulation, nicotine is metabolised by the liver
before it reaches the systemic venous circulation.


Probable oral lethal dose in humans is less than
5 mg kg-1 or a taste (less than 7 drops) for a 70 kg
person (27). It may be assumed that ingestion of 40
mg to 60 mg of nicotine is lethal to humans (27).
No inhalation toxicity data are available on which to
base an immediately dangerous to life or health
concentration (IDLH) for nicotine. Therefore, the
revised IDLH for nicotine is 5 mg m-3 based on acute
oral toxicity data in humans and animals (28).
A number of poisonings and deaths from ingestion
of nicotine, primarily involving nicotine-containing
pesticides, have been reported in humans (6). Nicotine
poisoning produces nausea, vomiting, abdominal
pain, diarrhoea, headaches, sweating, and pallor. More
severe poisoning results in dizziness, weakness, and
confusion, progressing to convulsions, hypotension,
and coma. Death is usually due to paralysis of
respiratory muscles and/or central respiratory failure.


Dermal exposure to nicotine can also lead to poisoning.
Such exposures have been reported after spilling or
applying nicotine-containing insecticides on the skin
or clothes and as a consequence of occupational
contact with tobacco leaves (6, 8). Acute intoxication
may occur in children following ingestion of tobacco
materials. Four children, each of whom ingested two
cigarettes, developed salivation, vomiting, diarrhoea,
tachypnoea, tachycardia, and hypertension within 30
min, followed by depressed respiration and cardiac
arrhythmia within 40 min and convulsions within 60
min (29). All recovered and suffered no complication.
Although ingestions of tobacco are common, deaths
due to ingestion of tobacco are extremely rare, due
to early vomiting and first pass metabolism of the
nicotine that is absorbed.



Long-term toxicity


As attested to in the U.S. Surgeon General’s reports
since 1964, smoking causes coronary and peripheral
vascular disease, cancer, chronic obstructive lung

disease, peptic ulcer disease, and reproductive
disturbances, including prematurity (30). Nicotine
may contribute to tobacco-related disease, but direct
causation has not been determined because nicotine
is taken up simultaneously with a multitude of other
potentially harmful substances that occur in tobacco
smoke and smokeless tobacco. However, particularly
now that nicotine may be prescribed in the form of
gum or other delivery systems, the potential health
consequences of chronic nicotine exposure deserve
careful consideration.







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