I. Basis for Medical Screening and Surveillance Requirements

A. Route of Entry Inhalation

B. Toxicology

 Inhalation of BD has been linked to an increased risk of cancer,
damage to the reproductive organs, and fetotoxicity. Butadiene can be
converted via oxidation to epoxybutene and diepoxybutane, two
genotoxic metabolites that may play a role in the expression of BD's
toxic effects.
 BD has been tested for carcinogenicity in mice and rats. Both
species responded to BD exposure by developing cancer at multiple
primary organ sites. Early deaths in mice were caused by malignant
lymphomas, primarily lymphocytic type, originating in the thymus.
 Mice exposed to BD have developed ovarian or testicular atrophy.
Sperm head morphology tests also revealed abnormal sperm in mice
exposed to BD; lethal mutations were found in a dominant lethal test.
In light of these results in animals, the possibility that BD may
adversely affect the reproductive systems of male and female workers
must be considered.
 Additionally, anemia has been observed in animals exposed to
butadiene. In some cases, this anemia appeared to be a primary
response to exposure; in other cases, it may have been secondary to a
neoplastic response.

C. Epidemiology

 Epidemiologic evidence demonstrates that BD exposure poses an
increased risk of leukemia. Mild alterations of hematologic
parameters have also been observed in synthetic rubber workers
exposed to BD.

II. Potential Adverse Health Effects

A. Acute

 Skin contact with liquid BD causes characteristic burns or
frostbite. BD is gaseous form can irritate the eyes, nasal passages,
throat, and lungs. Blurred vision, coughing, and drowsiness may also
occur. Effects are mild at 2,000 ppm and pronounced at 8,000 ppm for
exposures occurring over the full workshift.
 At very high concentrations in air, BD is an anesthetic, causing
narcosis, respiratory paralysis, unconsciousness, and death. Such
concentrations are unlikely, however, except in an extreme emergency
because BD poses an explosion hazard at these levels.

B. Chronic

 The principal adverse health effects of concern are BD-induced
lymphoma, leukemia and potential reproductive toxicity. Anemia and
other changes in the peripheral blood cells may be indicators of
excessive exposure to BD.

C. Reproductive

 Workers may be concerned about the possibility that their BD
exposure may be affecting their ability to procreate a healthy child.
For workers with high exposures to BD, especially those who have
experienced difficulties in conceiving, miscarriages, or stillbirths,
appropriate medical and laboratory evaluation of fertility may be
necessary to determine if BD is having any adverse effect on the
reproductive system or on the health of the fetus.

III. Medical Screening Components At-A-Glance

A. Health Questionnaire

 The most important goal of the health questionnaire is to elicit
information from the worker regarding potential signs or symptoms
generally related to leukemia or other blood abnormalities.
Therefore, physicians or other licensed health care professionals
should be aware of the presenting symptoms and signs of
lymphohematopoietic disorders and cancers, as well as the procedures
necessary to confirm or exclude such diagnoses. Additionally, the
health questionnaire will assist with the identification of workers
at greatest risk of developing leukemia or adverse reproductive
effects from their exposures to BD.
 Workers with a history of reproductive difficulties or a personal
or family history of immune deficiency syndromes, blood dyscrasias,
lymphoma, or leukemia, and those who are or have been exposed to
medicinal drugs or chemicals known to affect the hematopoietic or
lymphatic systems may be at higher risk from their exposure to BD.
After the initial administration, the health questionnaire must be
updated annually.

B. Complete Blood Count (CBC)

 The medical screening and surveillance program requires an annual
CBC, with differential and platelet count, to be provided for each
employee with BD exposure. This test is to be performed on a blood
sample obtained by phlebotomy of the venous system or, if technically
feasible, from a fingerstick sample of capillary blood. The sample is
to be analyzed by an accredited laboratory.
 Abnormalities in a CBC may be due to a number of different
etiologies. The concern for workers exposed to BD includes, but is
not limited to, timely identification of lymphohematopoietic cancers,
such as leukemia and non-Hodgkin's lymphoma. Abnormalities of
portions of the CBC are identified by comparing an individual's
results to those of an established range of normal values for males
and females. A substantial change in any individual employee's CBC
may also be viewed as "abnormal" for that individual even if all
measurements fall within the population-based range of normal values.
It is suggested that a flowsheet for laboratory values be included in
each employee's medical record so that comparisons and trends in
annual CBCs can be easily made.
 A determination of the clinical significance of an abnormal CBC
shall be the responsibility of the examining physician, other
licensed health care professional, or medical specialist to whom the
employee is referred. Ideally, an abnormal CBC should be compared to
previous CBC measurements for the same employee, when available.
Clinical common sense may dictate that a CBC value that is very
slightly outside the normal range does not warrant medical concern. A
CBC abnormality may also be the result of a temporary physical
stressor, such as a transient viral illness, blood donation, or
menorrhagia, or laboratory error. In these cases, the CBC should be
repeated in a timely fashion, i.e., within 6 weeks, to verify that
return to the normal range has occurred. A clinically significant
abnormal CBC should result in removal of the employee from further
exposure to BD. Transfer of the employee to other work duties in a
BD-free environment would be the preferred recommendation.

C. Physical Examination

 The medical screening and surveillance program requires an initial
physical examination for workers exposed to BD; this examination is
repeated once every three years. The initial physical examination
should assess each worker's baseline general health and rule out
clinical signs of medical conditions that may be caused by or
aggravated by occupational BD exposure. The physical examination
should be directed at identification of signs of lymphohematopoietic
disorders, including lymph node enlargement, splenomegaly, and
hepatomegaly.
 Repeated physical examinations should update objective clinical
findings that could be indicative of interim development of a
lymphohematopoietic disorder, such as lymphoma, leukemia, or other
blood abnormality. Physical examinations may also be provided on an
as needed basis in order to follow up on a positive answer on the
health questionnaire, or in response to an abnormal CBC. Physical
examination of workers who will no longer be working in jobs with BD
exposure are intended to rule out lymphohematopoietic disorders.
 The need for physical examinations for workers concerned about
adverse reproductive effects from their exposure to BD should be
identified by the physician or other licensed health care
professional and provided accordingly. For these workers, such
consultations and examinations may relate to developmental toxicity
and reproductive capacity.
 Physical examination of workers acutely exposed to significant
levels of BD should be especially directed at the respiratory system,
eyes, sinuses, skin, nervous system, and any region associated with
particular complaints. If the worker has received a severe acute
exposure, hospitalization may be required to assure proper medical
management. Since this type of exposure may place workers at greater
risk of blood abnormalities, a CBC must be obtained within 48 hours
and repeated at one, two, and three months.

[61 FR 56746, Nov. 4, 1996]