Retrospective identification of ricin in animal tissues following administration by pulmonary and oral routes.
A previously characterised amplified ELISA for ricin (sensitivity limit approximately 200 pgmL(-1)) has been employed to quantify ricin following a novel recovery method from selected tissues. Tissue samples from rats dosed by pulmonary instillation or orally with ricin were homogenised and treated with an elution buffer to extract ricin. This is the first time that ex vivo recovery of ricin post exposure following pulmonary or oral challenge has been achieved using clinically acceptable sampling methods, with promise in terms of diagnosis for the timely implementation of therapy. The toxin was detected and quantified using the ELISA in conjunction with pure ricin standards. Extracts from tissues sampled, including lung, blood, liver and spleen tested positive for ricin with maximum yield in lung associated fractions for pulmonary dosing and liver tissue for oral administration. This indicates the potential of lavage and blood sampling for timely diagnosis of ricin poisoning by pulmonary and oral routes, respectively. Time course analysis at 24 and 48 h also indicated the progression of ricin from surfaces of the lung into the lung tissue. Inter-subject variation was observed in the case of oral dosing, with data for ricin-treated and vehicle control tissues not statistically different in all samples. In addition the oral toxicity of the crude ricin administered was found to be higher than expected in the rat, based upon published information and an unpublished in house murine study.
Cook
David Leslie
DL
Immunotoxicology Group, Biology, Biomedical Sciences, Dstl, Porton Down, Salisbury, Wiltshire SP4 0JQ, UK.
David
Jonathan
J
Griffiths
Gareth David
GD
D000284:Administration, Oral; D000818:Animals; D002619:Chemical Warfare Agents / Q000032:analysis* / Q000493:pharmacokinetics / Q000506:poisoning; D004591:Electrophoresis, Polyacrylamide Gel; D019570:Inhalation Exposure; D007928:Lethal Dose 50; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D009928:Organ Specificity; D011041:Poisoning / Q000097:blood / Q000175:diagnosis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012276:Ricin / Q000032:analysis* / Q000097:blood / Q000493:pharmacokinetics / Q000506:poisoning; D012680:Sensitivity and Specificity; D013154:Spleen / Q000378:metabolism; D013997:Time Factors; D014018:Tissue Distribution
D002619:Chemical Warfare Agents; D012276:Ricin