Occupational Exposure To Nor-Nitrogen Mustard: Chemical and Biological Monitoring

Abstract

Nor-nitrogen mustard is an alkylating agent used in kilogram quantities in the production of various cytostatics. It has been shown to be mutagenic in vitro, and therefore must be regarded as a health hazard. We have studied the environment and blood of a small group of individuals working with nor-nitrogen mustard. New chemical methods for measuring surface contamination were used to make comparisons with ambient air levels of nor-nitrogen mustard. Surprisingly high levels of surface contamination were found even after decontamination, which has led to new decontamination routines and the establishment of wipe test limits of 0.5 microgram nor-nitrogen mustard/dm2. The wipe test has proved effective in following the day-to-day routine handling of nor-nitrogen mustard. Blood samples were taken before, during, and after production runs and analyzed for the frequency of chromosome aberrations (CAs), sister chromatid exchanges (SCEs), and somatic (HPRT) mutations. No significant differences in chromosome aberrations, SCEs, or somatic mutations were found in the peripheral blood from production workers before, during, or after handling of nor-nitrogen mustard. Nor was any difference found between the production workers and a local control group. However, the local controls' chromosome and HPRT frequencies appeared to be somewhat high, demonstrating the problems involved in these types of studies, in which the group sizes are small.

A new approach to assessing occupational exposure to antineoplastic drugs in hospital environments

“…In the case of cytotoxic ADs, monitoring surface contamination in hospital environments usually involves wipe tests as a simple way to indirectly assess dermal occupational exposure (12). However, most of the monitoring (13)(14)(15)(16)(17)(18)(19)(20) is focused on no more than five ADs among the following drugs: CP, MT, iphosfamide (IP), paclitaxel (PTX), doxorubicin (DXR), 5-fluorouracyl (5-FU), docetaxel (DTX), epirubicin (EPI), and gemcitabine (GEM). Only a few (21)(22)(23) have expanded the range from seven to ten [5-FU, PTX, CP, IP, MT, GEM, DXR, EPI, vincristine (VNC), vinblastine (VNB), docetaxel (DTX), etoposide (ETP), cytarabine (CTB), irinotecan (IRT), oxaliplatin, and vindesine].…”

Molecular methods for the detection of mutations

“…The frequency of these events in circulating blood cells of normal humans varies from very rare in the case of hemoglobin mutations (10 -8 -10 -7 ) to ~10 -4 in the TCR genes. Claims have been made for detecting significant increases in mutant frequency in patients exposed as part of their treatment regimes to relatively high doses of radiation or DNA-damaging chemotherapy drugs, and mutant frequencies have been monitored in a number of populations following accidental, workplace or environmental exposure [9][10][11][12][13][14].…”