•
Summary
Hexavalent
chromium compounds are hazardous to health, and exposure should be
well controlled to reduce the risks to workers’ health. Control
of exposure often relies on personal protective equipment to prevent
inhalation and dermal absorption. Biological monitoring has an important
role in the assessment of exposure and the adequacy of its control.
To aid the interpretation of the results of biological monitoring,
there are guidance values produced by international organisations.
Although the guidance values differ in basis and numerical value,
they have many aspects in common. All are intended for occupational
health professionals who can consider the results of biological monitoring
in context, and use them to help reduce and control exposure.
•
Introduction
Occupational
exposure to chromium compounds can occur in a wide range of industries
including the mining and processing of chromite ore, the production
and use of alloys, chromate chemicals, wood preservatives, pigments
and in welding of stainless steel (Huvinen
2004, Aw 2004). The consequences to workers’
health depend on both the nature of the chromium compounds and the
level of exposure. Metallic chromium (valence 0) is relatively inert
and shows little evidence of any toxicity. Trivalent chromium is an
essential trace element in humans required for carbohydrate metabolism
(Anderson 1995,
Davies 1997). Trivalent chromium compounds are not
mutagenic or carcinogenic (IARC
1990) but some are skin sensitisers (Kanerva
1996). In contrast, hexavalent chromium compounds
have a range of toxic effects including corrosivity, skin sensitisation
and carcinogenicity (Aitio
2001, Kanerva 1996, IARC 1990). This difference
in toxicity is reflected in occupational exposure limits with a factor
of 10 difference between trivalent chromium compounds (0.5 mg/m3)
and water soluble hexavalent chromium compounds (0.05 mg/m3)
for 8-hour time-weighted average inhalation exposures (ACGIH
2004a, HSE 2002). The toxicity of hexavalent chromium
compounds means there is a need to control occupational exposure to
levels as low as reasonably practical and ideally well below these
airborne limits. In some workplaces control of exposure may involve
the use of protective gloves to prevent skin contact and/or respiratory
protective equipment to prevent inhalation of hexavalent chromium
compounds. In these cases ambient air monitoring alone may not be
sufficient to determine if exposure is adequately controlled and biological
monitoring may help.
Biological
monitoring is the assessment of occupational exposure by all routes
(inhalation, ingestion and through the skin) by analysis of the hazardous
substance or its metabolites in biological fluids (usually urine or
blood). The roles for biological monitoring include helping occupational
health professionals assess exposure and the adequacy of exposure
controls. In addition, biological monitoring can complement a health
surveillance programme.
A
recent article for the ICDA (Aw
2004) considered the options and feasibility of
biological monitoring for chromite ore process workers. The two options
of blood or urine samples for biological monitoring were investigated
and the feedback from the participants noted that both the workforce
and the staff in the medical centre preferred collection of urine
samples to blood samples. The need for trained staff to collect blood
samples and for special collection measures (to avoid contamination
from chromium in needles) together with the hazards associated with
needles and blood samples make non-invasive urine sampling preferable
in most occupational settings.
There
are guidance values developed by various international organisations
to aid the interpretation of the results of biological monitoring.
The best known are those published by the American Conference of Governmental
Industrial Hygienists (ACGIH) (ACGIH
2004a), the Deutsche Forschungsgemeinschaft (DFG)
(DFG 2004)
and the UK Health and Safety Executive (HSE) (HSE
2002). Other countries either develop their own
biological monitoring guidance values or adopt those produced by the
ACGIH, DFG or HSE. The biological monitoring guidance values for chromium
developed by these three organisations have similarities but also
some differences of approach and these are discussed
further below.
•
Common approaches to biological monitoring guidance values
for chromium
The
aspects common to ACGIH, DFG and HSE in their approach to biological
monitoring guidance values for chromium are those based on the toxicity
of chromium and how it is absorbed and eliminated from the body. All
have a need for good quality data and all are aiming for a practical
and achievable guidance value that will help occupational hygienists
and physicians assess exposure to chromium. In addition all three
organisations document their approach (ACGIH
2004b, Bolt & Lewalter 1988, HSE 1999 & 2003).
All
three organisations have biological monitoring guidance values for
exposure to hexavalent chromium involving the determination of total
chromium in urine samples collected at the end of exposure or end
of the shift but the numerical values and rationales differ. The recommended
analytical methods all involve electrothermal atomic absorption spectrophotometry
with Zeeman background correction (Fleischer
1985) and use of an external quality assurance scheme
(Schaller et al
2001). The AGCIH also have a guidance value for
the increase in urinary chromium seen over a shift and the DFG have
a guidance value for chromium in erythrocytes after exposure to alkali
chromates (excluding welding fumes). The guidance values are all based
on a relationship to exposure and are not health-based. There is also
a common recognition that chromium is present in the urine of people
who are not occupationally exposed. This urinary chromium arises from
dietary (mainly trivalent) chromium and the concentrations are generally
well below those due to occupational exposure.
•
ACGIH Biological Exposure Index (BEI) for hexavalent chromium
(water soluble fume)
In
1998 ACGIH proposed two BEIs for exposure to hexavalent chromium (water
soluble fume), and the values of 30 µg/l in urine samples collected
at the end of exposure at the end of the week and 10 µg/l increase
during the shift were adopted in 1990. The BEIs were revised in 2002,
adopted in 2004 and are currently 25 µg/l (approximately 54
µmol/mol creatinine, in urine samples collected at the end of
exposure at the end of the workweek, and 10 µg/l (approximately
22 µmol/mol creatinine) increase during the shift. Chromium
in urine collected at the end of the shift represents the sum of long
term exposure and exposure during the working day. The increase during
the working day reflects exposure during the shift, and requires urine
samples to be collected both before and at the end of shift. The BEI
is not predictive of, and is not related to, potential health effects
such as lung cancer, clinical changes in kidney function, nor skin
or respiratory tract irritation.
The
basis for the ACGIH BEIs is the observed correlation between the measurement
of soluble hexavalent chromium in air in the breathing zone of workers
and the levels of chromium found in urine samples collected at the
end of the shift or the increase in chromium in urine during the shift.
The values of the BEIs are based on inhalation exposure for 8h at
the Threshold Limit Value (TLV) for water soluble hexavalent chromium
(0.05 mg/m3).
The
end of shift BEI was derived from a critical review of 10 peer-reviewed
studies of workplace exposure, mostly of manual metal arc welders.
The studies dated from 1977 to 1995 and involved from 5 to 136 workers
in each study. The mean total chromium in air levels in each study
ranged from 0.02 to 0.2 mg/m3, and
the end of shift urinary chromium values ranged between 10.8 and 58
µg/g creatinine (23 – 126 µmol/mol creatinine). Where
only total chromium in air data was available it was assumed that
60% of the total chromium was present as hexavalent chromium. The
correlation coef ficients for the regression equations that relate
end of shift urinary chromium levels to water soluble hexavalent chromium
ranged from 0.7 to 0.96. The mean value calculated from the regression
equations for end of shift urinary chromium corresponding to the TLV
for water soluble hexavalent chromium (0.05mg/m3) in personal breathing
zone air was 25.6 µg/l (56 µmol/mol creatinine) with a
range of 16 to 38 µg/l (approximately 35 – 83 µmol/mol).
The
BEI for the increase in chromium in urine during the shift is based
on six peer-reviewed field studies of manual metal arc welders. The
studies were six of the ten studies used for the end of shift BEI
and dated from 1977 to 1995 with a mean exposure range of 0.02 to
0.2 mg/m3. Good correlation
coefficients (range 0.7 to 0.95) were obtained for the regression
equations that related the increase urinary chromium during shift
to inhalation of water-soluble hexavalent chromium. The values calculated
from the regression equations for increased urinary chromium during
a shift corresponding to the TLV for water soluble hexavalent chromium
(0.05 mg/m3) in personal
breathing zone air ranged from 7 to 13 µg/l (approximately 15
– 28 µmol/mol creatinine) and support a BEI of 10 µg/l
(approximately 22 µmol/mol).
•
DFG EKA for alkali chromates
The
1988 DFG review of critical data for the evaluation of an EKA value
for alkali chromates, like the ACGIH BEI, also found good correlations
(r = 0.57 to 0.91) for the regression equations between urinary chromium
in end of shift urine samples and airborne exposures to hexavalent
chromium in field studies. The studies were published between 1972
and 1987 and also mostly involved welders. Four of the studies were
also used in the ACGIH review. Data from workers exposed to alkali
chromates showed a maximum concentration of 40 µg/g creatinine
in urine after 8-hour exposure to 0.1 mg/m3
hexavalent chromium. In the field studies of welders, the exposure
levels were in the range 0.038 to 0.179 mg/m3
and the urine chromium in end of shift urine samples ranged from 8.7
to 40 µg/l (approximately 10 to 87 µmol/mol creatinine).
The DFG review used a value of 50% for the proportion of hexavalent
chromium in the total chromium in welding fume and the levels predicted
by the regression equations gave urinary chromium in end of shift
samples after 8h exposure to 0.1 mg/m3
ranged from 26 to 34 µg/l (approximately 56 to 74 µmol/mol
creatinine) and were similar to those after exposure to alkali chromates.
The summary in Table 1 gives a DFG EKA value of chromium in end of
shift urine of 20 µg/l (approximately 43.5 µmol/mol creatinine)
after exposure to 0.05 mg/m3
hexavalent chromium.
•
UK Biological Monitoring Benchmark Value for hexavalent chromium
In
the UK there are currently two approaches to biological monitoring
guidance values. One is called a ‘Health Guidance Value’
and is the level of a substance or its metabolites in blood, or urine
that is not associated with any adverse health effects. Usually this
is the average value that may be found in blood or urine of workers
exposed for 8h to the current occupational exposure limit. This approach
is similar to the ACGIH BEI and DFG EKA.
The
second type of biological monitoring guidance value is called a ‘Benchmark
Value’. This type of value is proposed when there are not enough
data to set a Health Guidance Value or where a Health Guidance Value
would not be appropriate – for example for substances, like hexavalent
chromium, that can cause cancer. The benchmark value is set based
on a survey of workplaces that are considered to have good control
of exposure to the substance and it is the value found in 9 out of
10 samples in those workplaces. This type of guidance value gives
no direct guide to the risk of ill-health; rather it is a value that
is associated with good occupational hygiene practice and control
of exposure. In the UK, from 2005 the two approaches will be grouped
under one generic heading – Biological Monitoring Guidance Values
(BMGV).
The
biological monitoring benchmark value (BMV) for hexavalent chromium
was proposed in January 2003 following a survey of workplaces with
potential exposure to hexavalent chromium compounds (HSE
2003a). Following comments from industry and revision
of the guidance for the BMV, the value was adopted by HSE (HSE
2003b).
Twelve
different workplaces were selected based on a previous review of exposure
to hexavalent chromium (HSE
1999). The sites were chosen to be representative
of the range of workplaces where there may be significant numbers
of workers with potential exposure to hexavalent chromium. The workplaces
included manufacturers of chromates, pigments, timber treatment products,
metal treatment formulations and users of metal treatments (electroplating),
construction workers (cement), users of mordants in wool dyeing and
stainless steel welders.
An
occupational hygienist visited each workplace and assessed exposures
and controls. Samples of breathing-zone air and urine samples (pre-shift,
end of shift and end of week) were collected and analysed for hexavalent
chromium (air) and total chromium (urine). The observed exposures
to hexavalent chromium were low with a geometric mean of 0.0004 mg/m3
(8h TWA) or less than 1% of the UK occupational exposure limit. There
was a poor correlation between airborne exposure and urinary chromium
levels, partly due to use of respiratory protective equipment and
partly due to the low levels of exposure. Also, because of the low
levels of exposure, if pre-shift values were subtracted from post-shift
values, to give the increase during the shift, many of the results
were negative. Urine samples collected at the end of shift at the
end of the week had lower values than those collected during the week.
This was thought to be partly due to the low exposure and partly due
to a change of work pattern at the end of the week.
Data
from sixty one workers in ten of the workplaces was used for the guidance
value (two sites were rejected because their exposure controls were
poor). Ninety percent of the end of shift samples had chromium concentrations
below 10 µmol/mol creatinine (4.6 µg/g creatinine) and
this was proposed as the benchmark guidance value.
•
Background levels of chromium in urine
An
alternative approach to a guidance value for chromium in urine would
be to base the value on the upper boundary of chromium in urine due
to background or non-occupational exposure. By this definition, anything
exceeding the upper limit of background value would be most likely
to be of occupational origin. Trivalent chromium is an essential element
in the human diet and is found in the urine of people not occupationally
exposed. The background levels of chromium in urine quoted by ACGIH
(2004a)
have a median of 0.4 µg/l and a range of 0.24 to 1.8 µg/l
(approximately 0.87 µmol/mol creatinine, range 0.52 - 3.9 µmol/mol
creatinine – assuming 1g creatinine per litre of urine). The
background levels found in 241 urine samples from non-occupationally
exposed people in a recent study (Cocker
et al 2005) had a mean of 0.55 µmol/mol creatinine
(0.25 µg/l, 90% of the values were less than 1µmol/mol
creatinine (0.46 µg/l ), 95% were less than 2 µmol/mol
creatinine (0.92 µg/l ), and 99% were less than 7 µmol/mol
creatinine (3.2 µg/l ). Background levels have not been used
for chromium guidance, but the ACGIH are considering the approach
for polycyclic aromatic hydrocarbons.
•
How do the different approaches compare?
The
differ ent approaches to biological monitoring guidance values for
hexavalent chromium are summarised in Table 1 below.
Table 1. Biological monitoring guidance values
for hexavalent chromium
Organisation
(guidance value) |
Basis |
Chromium
in urine
µg/l or µg/g* |
Chromium
in urine
µmol/mol creatinine |
Collection |
ACGIH
(BEI) |
Correlation
with inhalation
exposure 0.05 mg/m3
|
25 |
54 |
End
of shift and
end of week |
ACGIH
(BEI) |
Correlation
with inhalation
exposure 0.05 mg/m3
|
10 |
22 |
Increase
during
shift (post – pre) |
DFG
(EKA) |
Correlation
with inhalation
exposure 0.05 mg/m3
|
20 |
44 |
End
of shift |
HSE
(BMV) |
Good
occupational
hygiene practice |
5 |
10 |
End
of shift |
| None |
95%
of background levels |
1 |
2 |
Random |
* assuming
1 litre of urine contains 1 g creatinine
The
ACGIH and DFG both reviewed published studies of high exposures to
hexavalent chromium (mostly in welders) and derived similar guidance
values for the average concentration of chromium in urine collected
at the end of exposure after inhalation of 0.05 mg/m3
hexavalent chromium. The ACGIH also derived a value from these high
exposures for the increase in urinary chromium during a shift, but
this approach was not found useful with the much lower exposures in
the HSE study. The hazards associated with exposure to hexavalent
chromium are such that exposures should be reduced to as low as is
reasonably practicable. The ACGIH and DFG values are therefore probably
best viewed as maximum values and most occupational hygienists would
be aiming to control exposures such that average urinary chromium
levels were 1/2 to 1 / 4 of this value thus keeping the upper end
of the distribution below the guidance value. This would mean average
urine concentrations in end of shift urine samples would be in the
range 5 - 10 µg/g creatinine (10 - 20 µmol/mol creatinine)
values closer to the 5 µg/g creatinine (10 µmol/mol creatinine)
HSE guidance value associated with good occupational hygiene practice.
The
HSE guidance value is quite close to the upper end of the distribution
of non-occupational exposures or background levels. Some of the workplaces
in the HSE study had infrequent exposures to low levels of hexavalent
chromium and the urinary values found were well below 4.6 µg/g
creatinine (10 µmol/mol creatinine). Other workplaces had more
frequent exposures to slightly higher concentrations of hexavalent
chromium compounds and although their exposure controls were good
some of the results were above the guidance value of 4.6 µg/g
creatinine (10 µmol/mol creatinine). This means that some workplaces
will have more of a challenge than others to keep biological monitoring
results below the guidance value. In addition, because of the way
the HSE benchmark value is defined, 1 sample in 10 from workers in
places with good control of exposure might be above the guidance value
due to chance, but it is unlikely that two samples from the same person
would be above the guidance value without a reason.
•
Conclusions
Biological
monitoring by analysis of chromium in the urine of workers is a useful
way to assess occupational exposure to hexavalent chromium and there
are guidance values to help interpret the results. An understanding
of the basis for deriving the reference values will help in the use
and interpretation of biological monitoring results at workplaces.
•
References
