Toxicology of Industrial Compounds

23
Antioxidants and Light Stabilisers : Toxic Effects
of 3,5-Di-alkyl-4hydroxyphenyl Propionic Acid
Derivatives in the Rat and their Relevance for
Human Safety Evaluation
HELMUT THOMAS, PETER DOLLENMEIER, ELKE
PERSOHN, HANSJÖRG WEIDELI and FELIX WAECHTER
Ciba-Geigy Limited, Basle
Introduction
Antioxidants and light stabilisers are important additives for a wide range
of plastic materials used for industrial as well as for medicinal and food
packaging purposes. Technical efficiency requires that these compounds are
mobile within the polymer network. This implies that humans may be
exposed to such compounds not only during the manufacturing process but
also in the course of the decay of polymers, by direct contact with
substances that have migrated to the surface of plastic materials or by
ingestion of diffusion-contaminated food. It is of considerable interest,
therefore, to be aware of the toxicological properties of these compounds
and the relevance of these properties for the safety assessment in humans.
Sterically hindered phenolic antioxidants
Phenolic antioxidants have been widely used as food preservatives and
their almost classical representatives, 2,6-di-tert-butyl-4-methyl phenol
(BHT) and 2-tert-butyl-4-methoxyphenol (BHA) have been characterised in
extenso with respect to their biochemical and toxicological properties
(Søndergaard and Olsen, 1982; Conning and Phillips, 1986; Ito et al.,
1986a; Williams et al., 1990a,b; Verhagen et al., 1991). Being nongenotoxic,
these compounds were found upon oral administration to
rodents to cause slightly increased liver weight, to induce mainly epoxide
hydrolase and phase II drug metabolising enzymes and to exert some anticarcinogenic
effect (Benson et al., 1979; Choe et al., 1984; Gregus and
Klaassen, 1988; Prochaska and Talalay, 1988; Perchellet and Perchellet,
1989; Rodrigues et al., 1991). Pulmonary toxicity and carcinogenicity
particularly of BHT in the mouse and formation of forestomach carcinoma
and papilloma in the rat and Syrian hamster, respectively, have been
reported and are considered to be largely species-specific effects (Abraham
et al., 1986; Anon, 1986; Ito et al., 1986a, b; Verhagen et al., 1989).
Industrial phenolic antioxidants as used in the polymer technology, by