An assessment of the release of inorganic cyanide from the fragrance materials benzyl cyanide, geranyl nitrile and citronellyl nitrile applied dermally to the rat

Organonitriles are widely used as components of fragrances that are incorpo rated into consumer products, many of which are for human topical use. Some organontriles are readily broken down metabolically to potentially toxic i norganic cyanide. Studies were therefore undertaken to assess whether this occurs with three representative fragrance nitriles, namely, benzyl cyanide , geranyl nitrile and citronellyl nitrile when applied dermally to the rat. The nitriles (benzyl cyanide, 150 mg/kg; geranyl and citronellyl nitriles, 400 mg/kg) were applied to the shaved backs of rats and maintained under o cclusion for 24 h. Urine samples were collected for 0-24 h, 24-48 h and 48- 72 h from the time of first application. These samples were analysed for th iocyanate, a biomarker for cyanide formation in vivo, as described previous ly (Potter, J., Smith, R.L., Api, A.M., 2000. Urinary thiocyanate levels as a biomarker for the Generation of inorganic cyanide from benzyl cyanide in the rat. Food and Chemical Toxicology 39, 141-146). In the case of benzyl cyanide, there was a marked increase in urinary thiocyanate levels attribut able to the release of cyanide in vivo. The amount of thiocyanate recovered was equivalent to 37% of the dose for males and 32% for females. For geran yl nitrile there was no significant increase in urinary thiocyanate excreti on and there was only a marginal increase in the case of citronellyl nitril e that was equivalent to 0.40% of the applied dose for males and 0.29% for females. (C) 2001 Elsevier Science Ltd. All rights reserved.