Introduction - Uppsala Monitoring Centre

second Hyderabad Chloroform Committee was appointed and they reported
that chloroform did not affect the heart to any critical extent (Brunton, 1890).
The results were hampered by the absence of the use of electrocardiograms
that had only been discovered in 1887 and by the difficulties of extrapolating
from animals to man, since all the committee’s investigations were in animals.
In 1911 the ECG evidence for ventricular fibrillation was established (Levy,
1911). Some members of the medical profession (physicians, nurses and
pharmacists) became addicted to chloroform (Lewin, 1893).
SED 1952: no mention of sudden death during anaesthesia or of carcinogenicity.
In 1976 the National Cancer Institute of the USA, found malignant kidney
tumours in rats and hepatocellular carcinoma in mice as a part of the programme
of carcinogenicity in pharmaceuticals and concluded that the overall evaluation
was that it was carcinogenic and possibly carcinogenic in humans.
Withdrawn: in the USA, Greece, Turkey, Japan, Panama in 1976; Brazil and
Saudi Arabia in 1977; Italy, Canada, Norway, Philippines in 1978; UK in 1979;
New Zealand in 1980; Denmark, Ethiopia and Zimbabwe in 1981; Germany
and Bangladesh in 1982; Belgium and Dominica in 1983; Nigeria in 1985;
Ireland in 1989; Oman as an excipient.
Drug Lifespan: 145 years
Delay in recognition: 11 years
Delay in regulatory action: nil
Time span of withdrawals: 16 years
Comment: anaesthetists gradually adopted safer anaesthetics and only its use
as a solvent, preservative or flavouring continued until its carcinogenicity was
shown.
1869 Chloral Hydrate (CCl 3 CHO)
Synthesised in 1832 by Justus von Liebig, but only marketed in 1869 (Welldorm,
Noctec, Somnos). It was also known as ‘Mickey Finn’ or ‘Knock Out Drops’.
Use: hypnotic and sedative
ADR: 1881 ‘Its habitual use as particularly noted in England and America, even
in ‘chloral drinkers’ causes no habituation to the effects of the drug, and gives
rise to no deleterious consequences so long as the standard doses are not
exceeded.’ (Lewin, 1881). A 1896 Dictionary of Domestic Medicine states:
‘Unfortunately the properties of chloral render it liable to great abuse and
many persons have seriously injured their health by frequent and large doses;
in some instances death has resulted from one overdose, inadvertently or
intentionally taken.’ (Thomson et al., 1896). ‘The tendency to habituation to
chloral exists as for all the other narcotics. In many of the subjects, the
habituation and the progression in dosage hasn’t taken place as quickly as
with morphine.’ (Lewin, 1928).