June 27th 2018
Phenytoin

The Health Council of the Netherlands reviewed the drug phenytoin. Phenytoin is a synthetic anticonvulsant, which can be used in the treatment of most types of seizure disorders and status epilepticus. Occasionally, phenytoin is used as an antiarrhythmic drug. Man can be occupationally exposed to phenytoin in the pharmaceutical industry, in pharmacies or in hospitals. This occupational exposure may lead to adverse health effects. This report is part of a series, in which the Health Council evaluates the effects of substances on reproduction, at the request of the Minister of Social Affairs and Employment.

Executive summary

At the request of the Minister of Social Affairs and Employment, the Health Council of the Netherlands evaluated the effects of phenytoin on reproduction. This advisory report has been drafted by the Subcommittee on the Classification of Reproduction Toxic Substances of the Dutch Expert Committee on Occupational Safety (DECOS) of the Health Council, hereafter called the Committee. The Health Council has a permanent task in assessing the hazard of substances to which man can be occupationally exposed. More information about this task can be found at www.gezondheidsraad.nl.

Use of phenytoin

Phenytoin is a synthetic anticonvulsant, which can be used in the treatment of most types of seizure disorders and status epilepticus. Occasionally, phenytoin is used as an antiarrhythmic drug. Workers can be occupationally exposed to phenytoin in the pharmaceutical industry, in pharmacies or in hospitals.

Classification according to strength of evidence for toxic effect

For assessing the effects on reproduction, the Committee evaluates the effects on male and female fertility and on the development of the offspring. Moreover, the Committee considers the effects of a substance on lactation and on the offspring via lactation.
If there are data indicating hazardous properties, the Committee recommends classification in a category based on the strength of the evidence. Based on that proposal, the Minister of Social Affairs and Employment can decide whether to classify the substance as toxic to reproduction. The classification is performed according to EU-regulation (EC) 1272/2008.

Recommendations to the State Secretary

Based on the available scientific data, the Committee recommends to classify phenytoin only for effects on offspring development. There are insufficient data for classification with regard to effects on paternal and maternal fertility and effects on or via lactation.

The Committee’s classification proposal for phenytoin:

  • For fertility, the Committee recommends not classifying phenytoin due to a lack of appropriate data.
  • For developmental toxicity, the Committee recommends to classify phenytoin in category 1B (presumed human reproductive toxicant) and to label it H360D (may damage the unborn child).
  • For effects on or via lactation, the Committee recommends not labelling phenytoin due to a lack of appropriate data.