Introduction - Uppsala Monitoring Centre

SED 1952: habituation causes symptoms of insomnia and delirium tremens
(Fühner, 1948). Neoplastic lesions found in mice in 1986 (Rijhsinghani et al.,
1986). The IARC 178 (1995) evaluated the carcinogenicity data for chloral
hydrate and it was concluded that there was inadequate evidence in humans
and limited evidence in experimental animals for the carcinogenicity of chloral
hydrate. A two-year study in which male mice were treated with chloral
hydrate in drinking water showed increases in hepatocellular adenomas
among all treated groups (George et al., 2000). In 2003 the Reproductive and
Cancer Hazard Assessment Section Office of Environmental Health Hazard
Assessment of the California Environmental Protection Agency said that ‘there
is evidence indicating the carcinogenic potential of this chemical, including the
carcinogenicity findings in the animal bioassays, extensive observations of
genetic toxicity, and chemical structural analogies with known carcinogens.’
The first report of its abuse was in 1880 (Anon, 1880). A cohort study in the
USA did not find persuasive evidence to support a causal relationship
between chloral hydrate exposure in humans and the development of cancer
(Haselkorn et al., 2006).
Withdrawn/Restricted: it was withdrawn in France and the USA in 2001
because it was mutagenic and carcinogenic in animals, but a single dose was
permitted in the USA for children under 5 years of age. Chloral hydrate is
restricted because of the IARC ruling ‘not classifiable’ as to its carcinogenicity
to humans (Group 3). In France it is restricted to hospital usage and only by
prescription.
Availability: Martindale: available in Canada, USA, Belgium, France, Germany,
Italy, Netherlands, Switzerland, Austria, Spain, Australia, Rumania, Hungary
and the UK (BNF, 1999) allowed for short term treatment only in 2009.
Drug Lifespan: 132 years
Delay in recognition: probably less than 12 years.
Delay in regulatory action: 15 years
Time span of withdrawals: zero
Comment: the delay may have been due to the doubts expressed as to its
carcinogenicity and its application to humans. Bearing in mind that it was
widely known as a drug of abuse in 1896 and that it continued to be on the
market for a further 105 years indicates that its removal was for the threat of
carcinogenicity and not because of abuse.
1875 Bismuth (insoluble salts, less than 1% absorbed in the gastrointestinal tract)
178 IARC = International Agency for Research on Cancer (World Health Organisation) Monographs on the
Evaluation of Carcinogenic Risks to Humans. Overall Evaluations of Carcinogenicity: http- monographs.iarc.fr-
ENG-Monographs-suppl17-suppl17.url Accessed 1 st November 2008