Safety and Toxicology

The acute oral LD50 (dose sufficient to kill one-half of the population of tested subjects) of caffeine is more than 200 mg kg-1 in rats, 230 mg kg-1 in hamsters and guinea pigs, 246mgkg-1 in rabbits, and 127mgkg-1 in mice. The sensitivity of rats to the lethal effects of caffeine increases with age, and higher toxicity is observed in male than in female rats.

Vomiting, abdominal pain, photophobia, palpitations, muscle twitching, convulsions, miosis, and unconsciousness were described in several reports of nonfatal caffeine poisonings in children who ingested 80mgkg-1 caffeine. In several fatal accidental caffeine poisonings, cold chills, stomach cramps, tetanic spasms, and cyanosis were reported. The likely lethal dose in adult humans has been estimated to be approximately 10 g, which corresponds roughly to 150-200 mg kg-1. With daily doses of 110mgkg-1 given via intragastric cannula to female rats over 100 days, hypertrophy of organs such as the salivary gland, liver, heart, and kidneys was reported. Caffeine also induced thymic and testicular atrophy. Developmental and reproductive toxicity was associated with high, single daily doses of caffeine. The no-effect level for teratogenicity is 40 mg kg-1 caffeine per day in the rat, although delayed sternebral ossification can be observed at lower doses. This effect has been shown to be reversed in the postnatal period. Available epi-demiological evidence suggests that maternal caffeine consumption does not cause morphological malformation in the fetus. Caffeine intake has been linked with reduced fetal size in some studies, particularly when intake was more than 600 mg per day, whereas others have not shown an impact on growth. High daily levels given as divided doses in rats were less toxic than when given as a single dose, in which case reduced fetal body weight was the only effect observed.

Caffeine at high concentration levels has mutagenic effects in bacteria and fungi and causes chromosomal damage in vitro. However, there is consensus that caffeine is not mutagenic in higher animals.

An epidemiological study showed no chromosomal aberrations in lymphocytes of normal, caffeine-exposed people, and other studies reported an increased frequency of micronucleated blood cells and the absence of mutagenic compounds in urine. In long-term studies, caffeine was shown to have no carcinogenic potential in rodents. Caffeine has not been classified as carcinogenic in animals or humans by the International Agency for Research on Cancer.

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