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 incorporated into consumer products, many of which are for human topical use. Some organontriles are readily broken down metabolically to potentially toxic inorganic 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 occlusion 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 thiocyanate, a biomarker for cyanide formation in vivo, as described previously (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 attributable 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 geranyl nitrile there was no significant increase in urinary thiocyanate excretion and there was only a marginal increase in the case of citronellyl nitrile that was equivalent to 0.40% of the applied dose for males and 0.29% for females.
Quintiles Toxicology/Pathology Services, Quintiles England Ltd, Bromyard Road, HR8 1LH, Ledbury, UK.
J
J
Potter
R L
RL
Smith
A M
AM
Api
D000097:Acetonitriles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000287:Administration, Topical; D000818:Animals; D003486:Cyanides / Q000378:metabolism* / Q000652:urine; D004224:Diterpenes / Q000493:pharmacokinetics*; D005260:Female; D008297:Male; D039821:Monoterpenes; D009570:Nitriles / Q000493:pharmacokinetics*; D010476:Perfume / Q000737:chemistry*; D051381:Rats; D011919:Rats, Inbred Strains; D012727:Sex Characteristics; D013729:Terpenes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013861:Thiocyanates / Q000652:urine
D000097:Acetonitriles; D003486:Cyanides; D004224:Diterpenes; D039821:Monoterpenes; D009570:Nitriles; D010476:Perfume; D013729:Terpenes; D013861:Thiocyanates; C006725:benzyl cyanide; C022300:citronellyl nitrile; C031760:thiocyanate