title: Routes and modes of administration of resorcinol and their relationship to potential manifestations of thyroid gland toxicity in animals and man.
abstract: Medical case reports published in the 20th century over the course of several decades show that resorcinol caused reversible adverse effects on the human thyroid gland (TG) manifested as hypothyroidism. Affected patients had ulcerating leg varicosities and underwent prolonged treatment with ointments containing high concentrations of resorcinol. In animal studies resorcinol failed to induce TG toxicity, unless pharmacokinetic/toxicokinetic (PK/TK) conditions were manipulated (e.g., injection of resorcinol in oil or application in a slow release formulation). A recently completed two-generation reproductive toxicity study in rats did not detect any adverse effects on either reproductive or TG end points (Welsch, Nemec, and Lawrence, 2008, Int. J. Toxicol. 37, this issue). Resorcinol intake via drinking water up to the palatability limit had resulted in average daily intakes (mg/kg) of 233 in F0 and F1 males and 304 (premating/gestation) or 660 (lactation) in females. Free resorcinol in blood plasma was barely detectable in a few parental animals, indicating rapid metabolism. This short review communication offers a perspective on compromised human skin barrier function as a likely cause of drastic increases in resorcinol absorption. In conjunction with multiple daily applications over many months to hyperemic, inflamed, and lesioned human skin much higher absorption was likely responsible for the reported human TG toxicity.
authors.affiliation: Orbitox, International Toxicology Consultants, Santa Fe, New Mexico 87508, USA. welsch@orbitox.com
authors.forename: Frank
authors.initials: F
authors.lastname: Welsch
mesh_terms: D000818:Animals; D001682:Biological Availability; D006801:Humans; D012118:Resorcinols / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity*; D012869:Skin Absorption / Q000502:physiology; D013959:Thyroid Diseases / Q000139:chemically induced*
chemical_list: D012118:Resorcinols; C031389:resorcinol