Introduction - Uppsala Monitoring Centre

1933 Dinitrophenol (2,4-dinitrophenol) (Nox-ben-ol, Nitroment, Nitrophen, Redusols, Formula
17, Slim, Dinitrenalm, Dinitole)
Use: weight reduction (Cutting et al., 1933, Tainter et al., 1934). During the First
World War it was used in explosive manufacture and since then it has been
used as a pesticide. The ability of dinitrophenol to raise the body temperature
together with its toxicity had already been recognised in 1885 when the
compound was being used as a food colouring (Parascandola, 1977).
ADR: the first report in July 1935 was on three cases of cataract (Horner et al.,
1935) and the author later said ‘The ratio of lens changes to the total number
of patients taking dinitrophenol is small, probably less than one per cent and
perhaps nearer 0.1%. ‘(Rodin, 1936). The reaction was confirmed in August
1935 when another seventeen cases were reported (Boardman, 1935).
Cataracts in 29 female patients had an average time to onset of 11 months
(Rodin, 1936). ‘Thousands of women developed aggressive sclerosing
cataracts, sometimes requiring enucleation.’ (Temple 1996).
Granulocytopenia with thrombocytopenia and anaemia (Imerman & Imerman,
1936), severe skin rashes, jaundice, disturbance of smell and taste. The FDA
gave a warning in 1934, but before 1938 it was legal to sell it as a diet potion.
The premarketing studies lasted for less than 3 months (FDA, 1987).
SED 1952: serious warnings must be issued against the use of this drug.
ADRs include bilateral cataracts and agranulocytosis.
Withdrawn: 1938 FDA 2,4-dinitrophenol (DNP) ban as a weight loss drug. On
July 6, 1935, the AMA’s Council on Pharmacy and Chemistry reported
dinitrophenol would not be included in its quasi-official list of acceptable
remedies (Report, 1935).
Availability: advertised on the Internet to body builders
Drug Lifespan: 5 years
Delay in recognition: 1½ years, but the time to onset was about 2 to 12 months
after stopping the drug. The recognition was helped by the rapid progression
over about a month and the occurrence in a relatively young age group (45–
55 years).
Delay in regulatory action: 4 years
Comment: it is difficult to believe that it was only on sale in the USA. The FDA
was not able to ban DNP because it was rated as a diet potion and therefore
outside their jurisdiction until there was a change in the law.
1937 H1-antihistamines (Oxomemazine–Promethazine–Alimemazine–Mequitaxine)
Use: H 1 antihistamine (Phenothiazine derivatives) for coughs, allergic reactions,
motion sickness and sedation
ADR: in 1979, the possibility was raised that the use of phenothiazine
antihistamines, particularly promethazine, could be associated with sleep