Scientific Paper 2.

BIOLOGICAL MONITORING AND EARLY DETECTION

TO WORKERS EXPOSED TO 5-FLUOROURACIL

Agustiany
1806363760

Lecturers:
DR. Dr. Astrid Sulistomo, MPH, Sp.Ok
Dr. Suryo Wibowo, MKK, Sp.Ok

OCCUPATIONAL MEDICINE SPECIALIST EDUCATION PROGRAM

FACULTY OF MEDICINE UNIVERSITAS INDONESIA
JAKARTA
MAY 2019
 CHAPTER 1
INTRODUCTION

1.1. Background
Cancer incidence has been increasing for years leading to an increased use of chemotherapy
by antineoplastic drugs, usually highly toxic compounds. In France, more than 49 400
healthcare professionals (HCP) are occupationally exposed to these drugs and could be
contaminated through systemic absorption of the drugs handled. Most professional
exposures occur through dermal and oral exposure due to poor hygienic precautions.
Respiratory contamination may also occur.1

Occupational exposure to antineoplastic drugs can occur in hospital pharmacies and in

hospitals where ANDs are prepared or administered to patients, mainly through inhalation
and skin contact. The health risks related to handling antineoplastic drugs have therefore
become a major concern for occupational medicine in hospitals. Several guidelines for the
safe handling of antineoplastic have been developed by professional associations and health
agencies.2

However, to evaluate the occupational health risks associated with handling these drugs,
reliable quantitative data on exposure levels are needed. Biological monitoring can be used
advantageously to assess personal exposure as it takes into account all the exposure routes.
Since it is unrealistic to measure all antineoplastic drugs, the most frequently used
compounds, including cyclophosphamide, ifosfamide, methotrexate and 5-fluorouracil (5-
FU), have generally been used as occupational exposure markers.2

One of the antineoplastic drugs most frequently handled by HCP is 5-fluorouracil (5-FU). It is
prescribed in the treatment of breast, digestive and ovarian cancers. An analytical method
has been developed for 5-FU urine11 assay but due to the very short half-life of 5-FU
(approximately 8 to 20 minutes),12 this biomarker is not efficient enough for biological
monitoring of 5-FU exposures.1

1.2. Problem Statement

Epidemiological studies showed increased risk of fetal malformations, spontaneous
abortions, reduced fertility and even cancers such as leukemia in healthcare professionals.
Antineoplastic drugs have thus been listed as hazardous drugs for handling in healthcare
settings due to their potential risk of carcinogenic and/or mutagenic effect and/or
reproductive toxicity.1

Nurses and pharmacy employees are exposed at the workplace to a wide spectrum of these
agents in sub-therapeutic concentrations, with unknown biological consequence.3 Recently,
the National Institute for Occupational Safety and Health (NIOSH) published an ‘Alert’
document addressed to workers handling hazardous drugs (including cancer
chemotherapeutics).4

A study conducted by Delia Cavallo et al. proved that exposure to 5-FU in oncology nurses and
pharmacists had a chromosomal aberrations frequency that was significantly higher than in
controls (p < 0.01 for each group). They found an increase of about 2.5-fold for total structural
aberrations (4–6- fold without gaps) and, in particular, an increase of up to 5.0-fold for breaks
in exposed groups as compared with control subjects.5

Due to the risks associated with 5-FU, it is important to evaluate and monitor occupational
exposures through biomonitoring. Workers that exposed to 5-FU are pharmacists and nurses
who prepare this medicine for cancer patients.

1.3. Objective
The aim of this scientific paper is:
1) To increase knowledge about 5-FU for all occupational health doctor.
2) To find out about health effects caused by 5-FU exposure.
3) To determine the biological monitoring and early detection of workers exposed to
5-FU, based on research studies.

1.4. Methods
Search Strategy
Literature searching were conducted to determine the biological monitoring of workers
exposed to 5-FU through an electronic database review: Pubmed, Scopus and Cochrane. The
keywords used were “5 Flurouracil AND biological monitoring AND workers”. The inclusion
criteria of this searching were clinical trial, review, systematic review, and full text. The
exclusion criteria was inaccessible article. The searching was done in April, 21th 2019 at 19.50
PM. The result of this searching is shown as bellow table (Table 1)
Table 1. Searching strategy using database from PubMed, Google Scholar and Cochrane
Database Search strategy Hit Selection

PubMed ("fluorouracil"[MeSH Terms] OR 23

"fluorouracil"[All Fields] OR "5 fluorouracil"[All
Fields]) AND ("environmental monitoring"[MeSH
Terms] OR ("environmental"[All Fields] AND
"monitoring"[All Fields]) OR "environmental
monitoring"[All Fields] OR ("biological"[All Fields]
AND "monitoring"[All Fields]) OR "biological
monitoring"[All Fields]) AND ("occupational
groups"[MeSH Terms] OR ("occupational"[All
Fields] AND "groups"[All Fields]) OR
"occupational groups"[All Fields] OR
"workers"[All Fields])
Scopus TITLE-ABS-KEY ( 5-fluorouracil AND "biological 20
monitoring" )

Figure 1. Flow chart search strategy

 CHAPTER 2
LITERATURE REVIEW

2.1.

REFERENCE
1. Alice D, Benoit A, Beatrice M, Karine T, Marine R, Mohamed SC, Catherine VE, Mathieu M,
Antoine V and Mireille CR. Biomonitoring of occupational exposure to 5-fluorouracil by
assaying α-fluoro-β-alanine in urine with a highly sensitive UHPLC-MS/MS method.
Analyst, 2018, DOI: 10.1039/C8AN00479J.
2. S Ndaw, F Denis, P Marsan, A d’Almeida, A Robert. Biological monitoring of occupational
exposure to 5-fluorouracil: Urinary fluoro-alanine assay by high performance liquid
chromatography tandem mass spectrometry in health care personnel. Journal of
Chromatography B, 878 (2010) 2630–2634.
3. IARC, Some Antiviral and Antineoplastic Drugs, and Other Pharmaceutical Agents, vol. 76,
1999.
4. NIOSH, Alert Document Preventing Occupational Exposure to Antineoplastic and other
Hazardous Drugs in Health Care Settings, US Department of Health and Human Service,
Public Occupational Safety and Health DHHS, 2004, NIOSH Publication No. 2004-165.
5. Delia C, Cinzia LU, Barbara P, Arianna DF, Margherita G, Federico MR, Alessandro M, Sergio
L. Evaluation of genotoxic effects induced by exposure to antineoplastic drugs in
lymphocytes and exfoliated buccal cells of oncology nurses and pharmacy employees.
Mutation Research 587 (2005) 45–51.
6.