California Code of Regulations › Title 8 - Industrial Relations › Division 1 - Department of Industrial Relations › Chapter 4 - Division of Industrial Safety › Subchapter 7 - General Industry Safety Orders › Group 16 - Control of Hazardous Substances › Article 110 - Regulated Carcinogens › Appendix C - Medical Surveillance Guidelines for Benzene

Current through Register 2024 Notice Reg. No. 28, July 12, 2024
I. Route of Entry
Inhalation; skin absorption.
II. Toxicology
Benzene is primarily an inhalation hazard. Systemic
						  absorption may cause depression of the hematopoietic system, pancytopenia,
						  aplastic anemia, and leukemia. Inhalation of high concentrations can affect
						  central nervous system function. Aspiration of small amounts of liquid benzene
						  immediately causes pulmonary edema and hemorrhage of pulmonary tissue. There is
						  some absorption through the skin. Absorption may be more rapid in the case of
						  abraded skin, and benzene may be more readily absorbed if it is present in a
						  mixture or as a contaminant in solvents which are readily absorbed. The
						  defatting action of benzene may produce primary irritation due to repeated or
						  prolonged contact with the skin. High concentrations are irritating to the eyes
						  and the mucous membranes of the nose, and respiratory tract.
III. Signs and Symptoms
Direct skin contact with benzene may cause erythema.
						  Repeated or prolonged contact may result in drying, scaling dermatitis, or the
						  development of secondary skin infections. In addition, there is benzene
						  absorption through the skin. Local effects of benzene vapor or liquid on the
						  eye are slight. Only at very high concentrations is there any smarting
						  sensation in the eye. Inhalation of high concentrations of benzene may have an
						  initial stimulatory effect on the central nervous system characterized by
						  exhilaration, nervous excitation, and/or giddiness, followed by a period of
						  depression, drowsiness, or fatigue. A sensation of tightness in the chest
						  accompanied by breathlessness may occur and ultimately the victim may lose
						  consciousness. Tremors, convulsions and death may follow from respiratory
						  paralysis or circulatory collapse in a few minutes to several hours following
						  severe exposures.
The detrimental effect on the blood-forming system of
						  prolonged exposure to small quantities of benzene vapor is of extreme
						  importance. The hematopoietic system is the chief target for benzene's toxic
						  effects which are manifested by alterations in the levels of formed elements in
						  the peripheral blood. These effects have occurred at concentrations of benzene
						  which may not cause irritation of mucous membranes, or any unpleasant sensory
						  effects. Early signs and symptoms of benzene morbidity are varied, often not
						  readily noticed and non-specific. Subjective complaints of headache, dizziness,
						  and loss of appetite may precede or follow clinical signs. Rapid pulse and low
						  blood pressure , in addition to a physical appearance of anemia, may accompany
						  a subjective complaint of shortness of breath and excessive tiredness. Bleeding
						  from the nose, gums, or mucous membranes, and the development of purpuric spots
						  (small bruises) may occur as the condition progresses. Clinical evidence of
						  leukopenia, anemia, and thrombocytopenia, singly or in combination, has been
						  frequently reported among the first signs.
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.
IV. Treatment of Acute Toxic Effects
Remove from exposure immediately. Make sure you are
						  adequately protected and do not risk being overcome by vapors. Give oxygen or
						  artificial resuscitation if indicated. Flush eyes, wash skin if contaminated
						  and remove all contaminated clothing. Symptoms of intoxication may persist
						  following severe exposure. Recovery from mild exposures is usually rapid and
						  complete.
V. Surveillance and Preventive Considerations.
A. General
The principal effects of benzene exposure which form
						  the basis for this regulation 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
						  surveillance 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.
Initial examinations are to be provided at the time of
						  initial assignment, and periodic examinations annually thereafter. There are
						  special provisions for medical tests in the event of hematologic abnormalities
						  or for emergency situations.
The blood values which require referral to a
						  hematologist or internist are noted in the standard in paragraph (i)(5). The
						  standard specifies that blood abnormalities that persist must be referred
						  "unless the physician has good reason to believe such referral is unnecessary"
						  (paragraph (i)(5)). 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.
Symptoms and signs of benzene toxicity can be
						  non-specific. Only a detailed history and appropriate investigative procedures
						  will enable a physician to rule out or confirm conditions that place the
						  employee at increased risk. To assist the examining physician with regard to
						  which laboratory tests are necessary and when to refer an employee to the
						  specialist, OSHA has established the following guidelines.
B. Hematology Guidelines
A minimum battery of tests is to be performed by
						  strictly standardized methods.
1. Red cell, white cell, platelet counts, white blood
						  cell differential, hematacrit and red cell indices must be performed by an
						  accredited laboratory. 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.
Either a decline from an absolute normal or an
						  individual's base line to a subnormal value or a rise to a supranormal value,
						  are indicative of potential toxicity, particularly if all blood parameters
						  decline. The normal total white blood count is approximately
						  7,200/mm3 plus or minus 3,000. For cigarette smokers
						  the white count may be higher and the upper range may be 2,000 cells higher
						  than normal for the laboratory. In addition, infection, allergies and some
						  drugs may raise the white cell count. 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.
Certain abnormalities found through routine screening
						  are of greater significance in the benzene-exposed worker and require prompt
						  consultation with a specialist, namely:
a. Thrombocytopenia.
b. 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.
c. 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.
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.
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. 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.
2. An important diagnostic test is a careful
						  examination of the peripheral blood smear. 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). When the smear is
						  to be prepared from a specimen of venous blood which has been collected by a
						  commercial VacutainerR type tube containing neutral
						  EDTA, the smear should be made as soon as possible after the venesection. A
						  delay of up to 12 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.
3. The minimum mandatory observations to be made from
						  the smear are:
a. The differential white blood cell count.
b. Description of abnormalities in the appearance of
						  red cells.
c. Description of any abnormalities in the
						  platelets.
d. 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.
An increase in the proportion of band forms among the
						  neutrophilicgranulocytes 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.
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 the rise is
						  above 6.0 percent of the total white count.
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.
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. 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.
e. 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. 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. "Pancytopenia" coupled with the appearance of
						  immature cells (myelocytes, myeloblasts, erythroblasts, etc.), with abnormal
						  cells (pseudo Pelger-Huetanomaly, atypical nuclear heterochromatin, etc.), or
						  unexplained elevations of white blood cells must be regarded as evidence of
						  benzene overexposure unless proved otherwise. Many severely aplastic patients
						  manifested the ominous finding of 5-10 percent myeloblasts in the marrow,
						  occasional myeloblasts and myelocytes in the blood and 20-30% monocytes. 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. 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.
The findings of basophilic stippling in circulating red
						  blood cells (usually found in 1 to 5% 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.
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.
						  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.
Measurement of serum iron, determination of peroxidase
						  and of alkaline phosphatase activity in peripheral granulocytes can be
						  performed in most pathology laboratories. Peroxidase and alkaline phosphatase
						  staining are usually undertaken when the index of suspicion for leukemia is
						  high.
1. New
						  section 5218 and Appendices A-E filed
						  4-20-90; operative 5-20-90 (Register 90, No.
						  23).
Note: Authority cited: Sections
							 142.3,
							 9020,
							 9030 and
							 9040, Labor
							 Code. Reference: Sections
							 142.3,
							 9004(d),
							 9009,
							 9020,
							 9030,
							 9031 and
							 9040, Labor
							 Code.