Cancer risk assessment for health care workers occupationally exposed to cyclophosphamide.
In the present study a cancer risk assessment of occupational exposure to cyclophosphamide (CP), a genotoxic carcinogenic antineoplastic agent, was carried out following two approaches based on (1) data from an animal study and (2) data on primary and secondary tumors in CP-treated patients. Data on the urinary excretion of CP in health care workers were used to estimate the uptake of CP, which ranged from 3.6 to 18 micrograms/day. Based on data from an animal study, cancer risks were calculated for a health care worker with a body weight of 70 kg and a working period of 40 years, 200 days a year (linear extrapolation). The life-time risks (70 years) of urinary bladder cancer in men and leukemias in men and women were found to be nearly the same and ranged from 95 to 600 per million. Based on the patient studies, cancer risks were calculated by multiplication of the 10-year cumulative incidence per gram of CP in patients by the estimated mean total uptake in health care workers over 10 years, 200 days a year. The risk of leukemias in women over 10 years ranged from 17 to 100 per million using the secondary tumor data (linear extrapolation). Comparable results were obtained for the risk of urinary bladder tumors and leukemias in men and women when primary tumor data were used. Thus, on an annual basis, cancer risks obtained from both the animal and the patient study were nearly the same and ranged from about 1.4 to 10 per million. In The Netherlands it is proposed that, for workers, a cancer risk per compound of one extra cancer case per million a year should be striven for ("target risk") and that no risk higher than 100 per million a year ("prohibitory risk") should be tolerated. From the animal and the patient study it appears that the target risk is exceeded but that the risk is still below the prohibitory risk.
Sessink
P J
PJ
Department of Toxicology, Faculty of Medical Sciences, University of Nijmegen, The Netherlands.
Kroese
E D
ED
van Kranen
H J
HJ
Bos
R P
RP
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D002986:Clinical Trials as Topic; D003520:Cyclophosphamide / Q000009:adverse effects* / Q000378:metabolism / Q000652:urine; D005260:Female; D006282:Health Personnel; D006801:Humans; D007938:Leukemia / Q000139:chemically induced; D007942:Leukemia, Experimental / Q000139:chemically induced; D008297:Male; D009369:Neoplasms / Q000139:chemically induced*; D009374:Neoplasms, Experimental / Q000139:chemically induced*; D009784:Occupational Diseases / Q000139:chemically induced*; D016273:Occupational Exposure; D010051:Ovarian Neoplasms / Q000188:drug therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012307:Risk Factors; D012878:Skin Neoplasms / Q000139:chemically induced; D013997:Time Factors; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced
D003520:Cyclophosphamide