Table 8
Medical Guidelines For Evaluating Employees Exposed to
Benzene
| Part 1: Becoming familiar with medical requirements
in this chapter |
| In addition to requiring employers to train employees and
protect them from exposure to benzene, this chapter (the
Benzene rule) requires employers to monitor their
employees' health with assistance from licensed health
care professionals (LHCPs). |
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For employees who will use respirators, the LHCP
will also need to provide the employer with a written
medical opinion clearing the employee for
workplace respirator use. |
| These guidelines were designed to support an informed
partnership between the LHCP and the employer when
monitoring the health of employees exposed to benzene. |
| The employer initiates this partnership by providing the
LHCP with a copy of the chapter and other supporting
information about the employee and job conditions. The
LHCP can then become familiar with the medical
monitoring requirements found in WAC 296-849-12030
through 296-849-12080, which address: |
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Frequency and content for routine (initial and
periodic) medical examinations and consultations; |
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Emergency and other unplanned medical follow-up; |
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Medical opinions; |
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Employee medical removal; |
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Medical records retention and content. |
| Part 2: Benzene toxicology |
| Benzene is primarily an inhalation hazard. Systematic
absorption may cause depression of the hematopoietic
system, pancytopenia, aplastic anemia, and leukemia.
Clinical evidence of leukopenia, anemia, and
thrombocytopenia, singly or in combination, has been
frequently reported among the first signs. |
| Health information about benzene, WAC 296-848-50010, provides basic information about the
health effects and symptoms associated with benzene
exposure. |
| Reference: |
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Other sources for toxicology information include: |
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ToxFAQs and the Toxicological Profile for
Benzene. This free document is available from
the Agency for Toxic Substances and Disease
Registry (ATSDR) and can be obtained by: |
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Visiting
http://www.atsdr.cdc.gov/toxprofiles |
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OR |
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Calling 1-888-422-8737 |
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A variety of technical resources on benzene
from the National Institutes for Occupational
Safety and Health (NIOSH) by visiting
http://www.cdc.niosh/topics/chemicals.html |
| Part 3: Treatment of acute toxic effects |
| When providing assistance to someone contaminated
with benzene, make sure you are adequately protected
and do not risk being overcome by benzene vapor. |
| Remove the patient from exposure immediately. |
| Give oxygen or artificial resuscitation, if indicated. |
| Flush eyes, wash skin if contaminated and remove all
contaminated clothing. |
| Recovery from mild exposures is usually rapid and
complete. Symptoms of intoxication may persist
following severe exposures. |
| Part 4: Preventive considerations |
| The principal effects of benzene exposure which form the
basis for the requirements in this chapter are pathological
changes in the hematopoietic system, reflected by
changes in the peripheral blood and manifesting clinically
as pancytopenia, aplastic anemia, and leukemia. |
| Consequently, the medical monitoring program is
designed to observe, on a regular basis, blood indices for
early signs of these effects, and although early signs of
leukemia are not usually available, emerging diagnostic
technology and innovative regimes make consistent
surveillance for leukemia, as well as other hematopoietic
effects, essential. |
| Symptoms and signs of benzene toxicity can be
nonspecific. Only a detailed history and appropriate
investigative procedure will enable a physician to rule out
or confirm conditions that place the employee at
increased risk. |
| Bone marrow may appear normal, aplastic, or
hyperplastic, and may not, in all situations, correlate with
peripheral blood forming tissues. Because of variations
in the susceptibility to benzene morbidity, there is no
"typical" blood picture. |
| The onset of effects of prolonged benzene exposure may
be delayed for many months or years after the actual
exposure has ceased and identification or correlation with
benzene exposure must be sought out in the occupational
history. |
| There are special provisions for medical tests in the event
of hematologic abnormalities or for emergency situations. |
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This chapter specifies that blood abnormalities
that persist must be referred "unless the
physician has good reason to believe such
referral is unnecessary." Examples of
conditions that could make a referral
unnecessary despite abnormal blood limits are
iron or folate deficiency, menorrhagia, or blood
loss due to some unrelated medical
abnormality. |
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Blood values that require referral to a
hematologist or internist are noted under Part 5:
Hematology guidelines. |
| Part 5: Hematology guidelines |
| The following guidelines are established to assist the
examining LHCP with regard to which laboratory tests are
necessary and when to refer an employee to the
specialist. A minimum battery of tests is to be performed
using strictly standardized methods. |
| Basic tests |
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The following must be determined by an accredited
laboratory: |
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Red and white cell counts; |
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Platelet counts; |
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White blood cell differential; |
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Hematocrit; |
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Red cell indices. |
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The normal ranges for the red cell and white cell
counts are influenced by altitude, race, and sex, and
therefore should be determined by the accredited
laboratory in the specific area where the tests are
performed. |
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Either a decline from an absolute normal or an
individual's baseline to a subnormal value or a rise
to a supra-normal value, are indicative of potential
toxicity, particularly if all blood parameters decline. |
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The normal total white blood count is
approximately 7,200/mm3 plus or minus 3,000; |
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For cigarette smokers the white count may be
higher and the upper range may be 2,000 cells
higher than normal for the laboratory; |
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In addition, infection, allergies and some drugs
may raise the white cell count; |
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The normal platelet count is approximately
250,000 with a range of 140,000 to 400,000.
Counts outside this range should be regarded
as possible evidence of benzene toxicity. |
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Certain abnormalities found through routine
screening are of greater significance in the
benzene-exposed worker and require prompt
consultation with a specialist, namely: |
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Thrombocytopenia; |
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A trend of decreasing white cell, red cell, or
platelet indices in an individual over time is
more worrisome than an isolated abnormal
finding at one test time. The importance of
trend highlights the need to compare an
individual's test results to baseline and/or
previous periodic tests; |
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A constellation or pattern of abnormalities in
the different blood indices is of more
significance than a single abnormality. A low
white count not associated with any
abnormalities in other cell indices may be a
normal statistical variation, whereas if the low
white count is accompanied by decreases in
the platelet and/or red cell indices, such a
pattern is more likely to be associated with
benzene toxicity and merits thorough
investigation; |
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Anemia, leukopenia, macrocytosis or an
abnormal differential white blood cell
count should alert the physician to
further investigate and/or refer the
patient if repeat tests confirm the
abnormalities. If routine screening
detects an abnormality, follow-up tests
which may be helpful in establishing the
etiology of the abnormality are the
peripheral blood smear and the
reticulocyte count; |
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The extreme range of normal for
reticulocytes is 0.4 to 2.5 percent of the
red cells, the usual range being 0.5 to 1.2
percent of the red cells, but the typical
value is in the range of 0.8 to 1.0 percent; |
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A decline in reticulocytes to levels of
less than 0.4 percent is to be regarded as
possible evidence (unless another
specific cause is found) of benzene
toxicity requiring accelerated
surveillance. An increase in reticulocyte
levels to about 2.5 percent may also be
consistent with (but is not as
characteristic of) benzene toxicity. |
| Additional tests |
| 1. Peripheral blood smears: |
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Collecting the sample: As with reticulocyte count,
the smear should be with fresh uncoagulated blood
obtained from a needle tip following venipuncture
or from a drop of earlobe blood (capillary blood). If
necessary, the smear may, under certain limited
conditions, be made from a blood sample
anticoagulated with EDTA (but never with oxalate
or heparin). |
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Prepping the smear: When the smear is to be
prepared from a specimen of venous blood which
has been collected by a commercial Vacutainer type
tube containing neutral EDTA, the smear should be
made as soon as possible after the venesection. A
delay of up to twelve hours is permissible between
the drawing of the blood specimen into EDTA and
the preparation of the smear if the blood is stored at
refrigerator (not freezing) temperature. |
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Minimum mandatory observations: |
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The differential white blood cell count; |
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Description of abnormalities in the appearance
of red cells; |
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Description of any abnormalities in the
platelets; |
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A careful search must be made throughout of
every blood smear for immature white cells
such as band forms (in more than normal
proportion, i.e., over 10 percent of the total
differential count), any number of
metamyelocytes, myelocytes, or myeloblasts.
Any nucleate or multinucleated red blood cells
should be reported. Large "giant" platelets or
fragments of megakaryocytes must be
recognized; |
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An increase in the proportion of band
forms among the neutrophilic
granulocytes is an abnormality deserving
special mention, for it may represent a
change which should be considered as
an early warning of benzene toxicity in
the absence of other causative factors
(most commonly infection). Likewise, the
appearance of metamyelocytes, in the
absence of another probable cause, is to
be considered a possible indication of
benzene-induced toxicity; |
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An upward trend in the number of
basophils, which normally do not exceed
about 2.0 percent of the total white cells,
is to be regarded as possible evidence of
benzene toxicity. A rise in the eosinophil
count is less specific but also may be
suspicious of toxicity if it rises above 6.0
percent of the total white count; |
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The normal range of monocytes is from
2.0 to 8.0 percent of the total white count
with an average of about 5.0 percent.
About 20 percent of individuals reported
to have mild but persisting abnormalities
caused by exposure to benzene show a
persistent monocytosis. The findings of
a monocyte count which persists at more
than 10 to 12 percent of the normal white
cell count (when the total count is
normal) or persistence of an absolute
monocyte count in excess of 800/mm3
should be regarded as a possible sign of
benzene-induced toxicity; |
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A less frequent but more serious
indication of benzene toxicity is the
finding in the peripheral blood of the
so-called "pseudo" (or acquired)
Pelger-Huet anomaly. In this anomaly
many, or sometimes the majority, of the
neutrophilic granulocytes possess two
round nuclear segments - less often one
or three round segments - rather than
three normally elongated segments.
When this anomaly is not hereditary, it is
often but not invariably predictive of
subsequent leukemia. However, only
about two percent of patients who
ultimately develop acute myelogenous
leukemia show the acquired Pelger-Huet
anomaly. Other tests that can be
administered to investigate blood
abnormalities are discussed below;
however, such procedures should be
undertaken by the hematologist. |
| 2. Sucrose water test and Ham test: |
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An uncommon sign, which cannot be detected from
the smear, but can be elicited by a "sucrose water
test" of peripheral blood, is transient paroxysmal
nocturnal hemoglobinuria (PNH), which may first
occur insidiously during a period of established
aplastic anemia, and may be followed within one to
a few years by the appearance of rapidly fatal acute
myelogenous leukemia. Clinical detection of PNH,
which occurs in only one or two percent of those
destined to have acute myelogenous leukemia, may
be difficult; if the "sucrose water test" is positive,
the somewhat more definitive Ham test, also known
as the acid-serum hemolysis test, may provide
confirmation. |
| Important clinical findings |
| 1. Individuals documented to have developed acute
myelogenous leukemia years after initial exposure to
benzene may have progressed through a preliminary
phase of hematologic abnormality. In some instances
pancytopenia (i.e., a lowering in the counts of all
circulating blood cells of bone marrow origin, but not to
the extent implied by the term "aplastic anemia")
preceded leukemia for many years. |
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Depression of a single blood cell type or platelets
may represent a harbinger of aplasia or leukemia.
The finding of two or more cytopenias, or
pancytopenia in a benzene-exposed individual,
must be regarded as highly suspicious of more
advanced although still reversible, toxicity. |
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"Pancytopenia" coupled with the appearance of
immature cells (myelocytes, myeloblasts,
erythroblasts, etc.), with abnormal cells (pseudo
Pelger-Huet anomaly, atypical nuclear
heterochromatin, etc.), or unexplained elevations of
white blood cells must be regarded as evidence of
benzene overexposure unless proved otherwise. |
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Many severely aplastic patients manifested the
ominous findings of: |
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5 to 10 % myeloblasts in the marrow; |
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Occasional myeloblasts and myelocytes in the
blood; |
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20 to 30 monocytes. |
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It is evident that isolated cytopenias,
pancytopenias, and even aplastic anemias induced
by benzene may be reversible and complete
recovery has been reported on cessation of
exposure. However, since any of these
abnormalities is serious, the employee must
immediately be removed from any possible exposure
to benzene vapor. |
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Certain tests may substantiate the employee's
prospects for progression or regression. One
such test would be an examination of the bone
marrow, but the decision to perform a bone
marrow aspiration or needle biopsy is made by
the hematologist. |
| 2. The findings of basophilic stippling in circulating red
blood cells (usually found in one to five percent of red
cells following marrow injury), and detection in the bone
marrow of what are termed "ringed sideroblasts" must be
taken seriously, as they have been noted in recent years
to be premonitory signs of subsequent leukemia. |
| 3. Recently peroxidase-staining of circulating or marrow
neutrophil granulocytes, employing benzidine
dihydrochloride, have revealed the disappearance of, or
diminution in, peroxidase in a sizable proportion of the
granulocytes, and this has been reported as an early sign
of leukemia. However, relatively few patients have been
studied to date. Granulocyte granules are normally
strongly peroxidase positive. A steady decline in
leukocyte alkaline phosphatase has also been reported as
suggestive of early acute leukemia. |
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Peroxidase and alkaline phosphatase staining
are usually undertaken when the index of
suspicion for leukemia is high. |
| 4. Exposure to benzene may cause an early rise in serum
iron, often but not always associated with a fall in the
reticulocyte count. Thus, serial measurements of serum
iron levels may provide a means of determining whether
or not there is a trend representing sustained
suppression of erythropoiesis. |
| 5. Measurement of serum iron, determination of
peroxidase and of alkaline phosphatase activity in
peripheral granulocytes can be performed in most
pathology laboratories. |