Introduction - Uppsala Monitoring Centre

dose for six months, mice also developed genetic damage (November 1996
as NTP’s Technical Report Series, No. 465 (TR-465): Toxicology and
Carcinogenesis Studies of Phenolphthalein (CAS No. 77-09-8); HO Drug
Information vol.11, 4, 1997). Phenolphthalein is possibly carcinogenic in
humans (IARC vol 76, 2000).
Because it undergoes enterohepatic circulation, it is eliminated slowly and it
has been associated with adverse effects, notably skin reactions, potassium
loss and atonia (WHO, 2003).
SED 1952: erythema exudativum multiforme, pemphigus, erythrodermia,
contact dermatitis, fixed eruption, acute nephrosis with anuria, polyneuritis and
haemorrhagic diathesis.
Withdrawn: in Norway and Yemen in 1979, UK in 1980, Bangladesh in 1982
and Greece in 1985 probably because of skin reactions, potassium loss and
atonia. USA, Canada, France, Morocco and the European Community in
1997, in Oman and Japan in 1998, Saudi Arabia in 1999, Brazil in 2002, also
in Poland, South Africa, New Zealand, Singapore, and Bahrain, because of
potential genotoxicity and carcinogenicity (rats and mice). In the USA, the
FDA reclassified the drug from category 1 (safe and effective) to category III
(more safety information needed) in response to the animal data and then
later withdrew it (Cobert & Biron, 2002). HAI: banned in the EC + 12 countries
and restricted in one.
Availability: remains in wide usage often in over-the-counter preparations, e.g.
Thailand (HAI, 2008).
Drug Lifespan: 77 years
Delay in recognition: skin reactions > 50 years; carcinogenicity 95 years
Delay in regulatory action: skin reactions > 27 years; carcinogenicity None.
Time span of withdrawals: 23 years
Comment: prior to the discovery of animal carcinogenicity in 1997 there was one
spate of withdrawals and then a second spate afterwards.
1908 Cincophen–Cinchophene (Atophan, Cinchphan, Navarrard)
A uricosuric drug, was introduced, but it had been discovered in 1887.
Use: gout and as an analgesic
ADR: Seifert says that the urine can be dark yellow, reddish or brown with a
peculiar smell and also cystitis with dysuria and haematuria (Seifert,1915).
Severe hepatitis with subacute hepatic necrosis was first reported in 1923,
(Worster-Drought, 1923) and by 1931 thirty four deaths had been reported
(Parsons and Kimball, 1931). In 1941 the Council on Pharmacy and
Chemistry of the American Medical Association concluded that the case
against cincophen was not proved and that an urgent need existed for
controlled clinical studies. Twenty-five years later, such studies had still not