Urinary thiocyanate levels as a biomarker for the generation of inorganic cyanide from benzyl cyanide in the rat.
A colorimetric procedure was developed and validated for the determination of thiocyanate in rat urine over the concentration range of 7-7000 microg/ml. It was applied to the determination of thiocyanate following its oral administration to male and female rats. The mean percentage urinary recoveries of sodium thiocyanate given by oral gavage at 10 and 100 mg/kg were 60 and 39%, respectively, for male rats and 89 and 73% for females over a period of 3 days. Most of the elimination occurred in the 0-48-h period post-dosing but significant amounts were still being excreted in the 48-72-h period. It was concluded from these results that the recoveries of urinary thiocyanate were such that this anion was suitable for use as a biomarker for the release of cyanide from organonitriles such as benzyl cyanide. Benzyl cyanide (150 mg/kg) administered orally to rats led to markedly increased urinary thiocyanate levels; for male rats this was equivalent to 54% of the dose and for females this was 65% over a period of 3 days. When adjusted for incomplete recoveries of the marker, thiocyanate, these values equated to 61 and 89%, respectively. It was concluded that this validated assay could be used to assess cyanide release from topically applied fragrance organonitriles (Potter, J., Smith, R.L., Api, A.M., 2000. An assessment of the release of inorganic cyanide from the fragrance materials, benzyl cyanide, geranyl nitrile and citronellyl nitrile applied dermally to the rat. Food and Chemical Toxicology 39, 147-151).
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 / Q000493:pharmacokinetics*; D000818:Animals; D015415:Biomarkers; D001711:Biotransformation; D003486:Cyanides / Q000378:metabolism*; D005260:Female; D007202:Indicators and Reagents; D008297:Male; D051381:Rats; D015203:Reproducibility of Results; D012996:Solutions; D013056:Spectrophotometry, Ultraviolet; D013861:Thiocyanates / Q000652:urine*
D000097:Acetonitriles; D015415:Biomarkers; D003486:Cyanides; D007202:Indicators and Reagents; D012996:Solutions; D013861:Thiocyanates; C006725:benzyl cyanide