HBM4EU occupational biomonitoring study on hexavalent chromium and other harmful chemicals

HBM4EU (Human Biomonitoring for Europe, www.hbm4eu.eu/about-hbm4eu) is a
European study, which aims to harmonise and use human biomonitoring to
understand people*s exposure to chemicals in the environment, via their
occupation or use of consumer products and the related health risks, in order
to improve chemical risk management. It is funded by the European Commission
and national governments and includes experts from 28 countries and European
Union agencies and will run from 2017 to 2021.

HBM4EU includes both the use of biomonitoring in the characterisation of the
exposure and risks to the general population and to workers. Occupational
exposure to specific chemicals may in many instances be several times higher
than the exposure of the general populations from the environment from the use
of consumer products. Human biomonitoring gives important information on the
combined exposure via all routes of exposure; via inhalation, oral, dermal
contact and via hands-to-mouth. It usually complements environmental
measurements and can inform us on the effectivity of preventive and protective
measures (including personal protective equipment).

Within the HBM4EU project, several priority chemicals were identified
(https://www.hbm4eu.eu/thesubstances/), which may be of concern for the
European population. Several of those are also relevant at European workplaces,
such as hexavalent chromium, Cr(VI). According to IARC (IARC 2012), Cr(VI)
compounds are carcinogenic to humans (Group I). They are known to cause lung
cancer in humans. The European Commission has recently proposed to add Cr(VI)
to the Carcinogens and Mutagens Directive (CMD, 2004/37/EC) and has proposed a
binding limit value for exposure to hexavalent chromium (EC, 2017). In
addition, the use of hexavalent chromium compounds in various applications,
including in the surface treatment of metals, is authorized under EU REACH
regulation (EC1907/2006). Based on this, the need to collect new data on human
exposure in the European countries has been emphasised.

A principal biomarker used for the biomonitoring of Cr(VI) exposure at the
workplace is urinary (total) chromium (Cr). The main .limitation of this
biomarker is that it is not specific for Cr(VI) since it measures exposure to
both trivalent and Cr(VI). Especially in welding, exposure to both trivalent
and Cr(VI) occurs, which makes it challenging to interpret urinary Cr levels.
Also in surface treatment activities, part of the Cr(VI) present in air may be
reduced to trivalent form. Therefore, it is important to develop more specific
biomarkers for Cr(VI). In addition, it is important to test how well these more
specific biomarkers correlate with the routine *gold standard* urinary (total)
Cr method. The new, more specific markers include Cr in red blood cells and
Cr(VI) in exhaled breath condensates (EBCs). Cr in red blood cells reflects the
exposure specifically to Cr(VI) since only Cr(VI) is able to pass though the
red blood cell membrane, with the levels of Cr in plasma reflecting the
exposure to trivalent Cr (Goldoni et al., 2010). Cr(VI) in EBC samples is an
important new biomarker since it can give specific information on the Cr(VI)
levels in the main target tissue i.e. in lungs (Leese et al., 2017). It is also
a less invasive biomarker than blood. Cr(VI) and Cr(III) can be analyzed
separately from the EBC samples.

The correlations between air Cr(VI), wipe samples, EBC, blood and urinary Cr
levels allows further study of the fate and transformation of Cr(VI) to
trivalent form when entered to the body. Additionally, the establishment of a
relationship between exposure biomarkers and effect biomarkers in biological
samples of Cr(VI)-exposed workers in EU is expected to provide meaningful data
for a comprehensive risk assessment.

In the HMB4EU, hexavalent chromium occupational exposure study exposed workers
and controls from companies performing chrome plating, surface treatment with
chromates or stainless steel welding will be recruited from nine countries,
namely: Austria Belgium, Finland, France, Germany, Italy, Poland, Portugal, The
Netherlands and United Kingdom. In order to achieve comparable data in a
harmonised way, the enclosed Standard Operating Procedures (SOPs) are intended
to be used. Every participating country is obliged to, as far as is reasonable
possible, follow these procedures. The SOPs for the selection of participants
and recruitment, information to the participants, informed consent (annex 1),
completion of questionnaires (annex 2) and instructions for blood, EBC, urine,
air and wipe sampling (annexes 3-7) provided separately. The general objective
of the HMB4EU hexavalent chromium occupational study is to contribute to
building a sound and valid scientific basis to propose biological limit values
for occupational Cr(VI) exposure. In addition, the study will provide reference
values for the general population (from data collected from controls) and study
the impact of the recent regulatory measures to the exposure at European
workplaces.

To contribute to building a sound scientific basis for the regulatory EU
institution to set-up occupational exposure limits and related biological limit
values, as well as reference values for the general population and to study the
impact of the recent regulatory measures to the exposure at European
workplaces.

Cross sectional survey in 10 Eureopean countries

The burden for the participants consists of :
- the effort of collection of urine samples (two times)
- undergoing blood collection by vena puncture (one time)
- breathing in an apparatus for collection of end-exhaled condensate (two times)
- participating in taking of hand wipes (five times)
- carrying air sampling equipment during work hours (5 times)
- participating in an interview related to collect contextual information such
as information on lifestyle and work-related determinants of exposure to
chromium and other metals
- participating in a short daily interview regarding the tasks performed during
the shift.