United States
                   Environmental Protection
                   Agency	
Office of Health and
Environmental Assessment
Washington. DC 20460
                   Research and Development
EPA/600/S8-84/026F July 1988
4>EPA          Project Summary

                    Health Assessment
                    Document  for Beryllium
                      The  chemical and  geochemical
                   properties of beryllium resemble
                   those of aluminum, zinc, and  mag-
                   nesium. This resemblance  is pri-
                   marily due to similar ionic potentials
                   that facilitate covalent  bonding. The
                   three most  common  forms  of
                   beryllium in industrial emissions are
                   the  metal,  the oxide, and  the
                   hydroxide.
                      The  main routes  of beryllium
                   intake for  man and  animals are
                   inhalation and ingestion. While the
                   absorption of ingested beryllium is
                   probably quite small,  the chemical
                   properties of beryllium  are such that
                   inhaled beryllium  has  a  long
                   retention time in the lungs and, thus,
                   a greater potential for absorption
                   and/or physical  irritation. The tissue
                   distribution of absorbed beryllium is
                   characterized by depositions pri-
                   marily in the skeleton where the
                   biological half-time is fairly long.
                      The  lung is  the critical organ of
                   both acute  and  chronic  non-
                   carcinogenic effects. However, unlike
                   most other metals,  the lung effects
                   caused  by chronic  exposure to
                   beryllium may  be  combined  with
                   systemic  effects,  of which one
                   common factor  may be hypersen-
                   sitization. Certain beryllium  com-
                   pounds  have shown   carcinogenic
                   activity in various experimental ani-
                   mals by various routes of exposure,
                   but  not by ingestion  per se.
                   Epidemiologic  studies are inade-
                   quate to demonstrate or refute  a
                   human carcinogenlcity potential. In
                   terms of the weight of evidence for
                   carcinogenicity.  beryllium is judged
                   to be in  Group B2 signifying that the
                   animal evidence for carcinogenicity
                   is sufficient and that  beryllium and
                   its compounds are  regarded as
                   probably carcinogenic for humans.
                      This Project Summary  was
                   developed by EPA's Environmental
 Criteria  and  Assessment  Office,
 Research  Triangle  Park, NC,  to
 announce key findings of the research
 project that is fully documented in a
 separate report of the same title (see
 Project Report ordering information at
 back).

 Introduction
    The full report evaluates  the effects
 of beryllium on human health, with
 particular emphasis  on those effects that
 are of most concern to the general U.S.
 population. It is organized into chapters
 that  present in a  logical order those
 aspects of beryllium that relate directly to
 human health risk. The chapters include:
 an  executive  summary (Chapter  2);
 background  information on the chemical
 and  environmental aspects of beryllium,
 including  levels of  beryllium in media
 with  which U.S. populations  may come
 into  contact (Chapter 3);  beryllium
 metabolism, where  absorption, biotrans-
 formation,  tissue distribution, and
 excretion  of beryllium are discussed with
 reference to  the  element's toxicity
 (Chapter 4); beryllium toxicology, where
 the various acute, subacute, and chronic
 health effects of beryllium in man  and
 animals  are reviewed  (Chapter  5);
 beryllium mutagenesis,  in   which   the
 ability  of beryllium  to cause gene
 mutations, chromosomal aberrations, and
 sister-chromatid  exchanges  is
 discussed (Chapter 6); and  information
 on  beryllium  carcinogenesis,  which
 includes a discussion of selected dose-
 effect and dose-response relationships
 (Chapter 7).
    The full report  is not an  exhaustive
 review of all the beryllium literature,  but
 is focused  instead upon those data
 thought to be  most relevant to  human
 health risk  assessment. Literature  on
 beryllium  was collected and reviewed up
 to January  1986. General  information
 pertaining to the calculation of unit  risk
 values was reviewed up to April  1987. In

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view of the fact that the full document is
to provide a basis for making decisions
regarding the regulation of beryllium as a
hazardous  air  pollutant under  the
pertinent sections of the  Clean  Air Act,
particular emphasis is placed on those
health effects  associated  with exposure
to airborne beryllium. Health  effects
associated with the ingestion of beryllium
or with exposure via other  routes are also
discussed, providing a basis for  possible
use of this document for multimedia risk
assessment purposes. The background
information  provided   on  sources,
emissions, and ambient concentrations of
beryllium in various media  is presented
to provide a  general  perspective for
viewing  the health-effects evaluations
contained  in  later chapters  of  the
document.  More  detailed exposure
assessments will be prepared separately
for use in subsequent U.S. Environmental
Protection  Agency (EPA)  reports  re-
garding  regulatory  decisions  on beryl-
lium.

Results and Conclusions

Background
    The industrial  use of beryllium  has
increased  tenfold in the  last 40 years.
Despite  this  fact,  increases  in  the
environmental  concentrations of beryl-
lium have  not  been detected.  Atmos-
pheric beryllium is primarily derived from
the combustion of coal.
    Contamination  of the  environment
occurs almost  entirely by the deposition
of beryllium from  the air.  Beryllium from
the atmosphere  eventually reaches the
soil or sediments, where it is probably
retained in the  relatively insoluble form of
beryllium oxide. Since the time of the
industrial revolution, it  is likely that  no
more than 0.1  ng Be/g has been added
to the surface of the soil,  which  has a
natural beryllium concentration of 0.6
pg/g.  Distributed  evenly  throughout the
soil column, beryllium derived from the
atmosphere could  account  for not more
than  one  percent of  the total soil
beryllium. Allowing for greater mobility of
atmospheric beryllium in soil than natural
beryllium, it is possible  that 10  to  50
percent of the beryllium in plants  and
animals may be of anthropogenic origin.
    The  typical  American  adult usually
takes in 400 to 450 ng Be/day,  of which
50 to 90 percent comes  from food and
beverages. Some of this beryllium found
in  food may  be  derived  from  the
atmosphere;   however,  aside from
primary  and  secondary occupational
settings, air or dust has  little impact on
total human intake.
Beryllium Metabolism

    Inhalation and ingestion are the main
routes  of beryllium  intake for man and
animals.  Percutaneous  absorption  is
insignificant. Due to the specific chemical
properties of beryllium compounds, even
primarily  soluble  beryllium  compounds
are partly transformed to  more insoluble
forms in the lungs. This can result in long
retention time  in the lungs following
exposure to all types  of beryllium
compounds. Like other paniculate matter,
dose and particle size are critical factors
that determine  the  deposition  and
clearance of inhaled beryllium particles.
Of  the deposited  beryllium  that  is
absorbed, part  will  be rapidly excreted
and part will be  stored in bone. Beryllium
is  also transferred  to regional lymph
nodes.  Beryllium transferred from  the
lungs to the gastrointestinal  tract  is
mainly  eliminated in  the feces with only a
minor portion being absorbed.
    There are  no quantitative  data  on
absorption of beryllium from the gastro-
intestinal  tract  in humans,  but  several
animal studies  indicate  that  the
absorption of ingested beryllium is less
than one percent.  The  absorption  of
beryllium  through  intact skin  is  very
small, as  beryllium is tightly bound in the
epidermis.
    Absorbed beryllium  will  enter  the
blood,  but  there are no data  on  the
partitioning of beryllium between plasma
and  erythrocytes. In plasma, there are
limited  data to suggest that,  at  normally
occurring levels of  beryllium, the main
binding is to various plasma proteins. In
animal  experiments,  it has  been shown
that large doses of injected beryllium are
found in aggregates bound to phosphate.
The smaller the  dose, the more beryllium
will be in the diffusible form. The  data
are insufficient  to permit  an  estimate of
the levels of beryllium normally occurring
in blood or plasma.
    Absorbed beryllium is deposited in
the  skeleton,  with other  organs
containing only  very  low levels. In the
liver, beryllium seems to be preferentially
taken up by  lysosomes. There are not
enough data to  permit  any definitive
conclusions  about the distribution and
amounts of beryllium normally present in
the human body. However, total body
burden is probably less than 50 tig.
    Based on animal studies,  beryllium
appears to have a  long  biological  half-
time, caused mainly by  its retention in
bone.  The half-time in soft  tissues is
relatively short,  except in the lung.
    Beryllium  seems to be normally
excreted in  small  amounts in urine,
normal  levels  being  only  a
nanograms per liter. Animal data indicati
that some excretion occurs by way of th<
gastrointestinal tract.

Beryllium Toxicology

Subcellular and Cellular Aspects
of Beryllium Toxlcity
    It is not well known in  what form c
through which mechanism  beryllium i
bound  to  tissue. Beryllium can bind t
lymphocyte membranes,  which  ma
explain the sensitizing properties  of  th
metal.  A  number  of  reports  describ
various in  vivo and  in vitro  effects c
beryllium  compounds  on  enzymes
especially alkaline phosphatase, to whic
beryllium  can  bind.  Effects on protei
and nucleic acid metabolism  have bee
shown  in  many experimental studie;
however, the doses in these studies hav
been large and parenterally administers*
Because such administrative routes hav
less practical application to humans,  th
data from  these studies have limite
utility  in advancing an understanding i
human effects, which are mainly on  tt-
lung. Beryllium particles retained  in  th
lung are found in the macrophages,  ar
the understanding of how these and oth<
pulmonary cells  metabolize beryllium
probably of most  relevance  to the  u
derstanding of chronic beryllium diseas
    An  important  aspect  of  berylliu
toxicology  is that  beryllium can  cau:
hypersensitivity which  is  essential
cell-mediated. There  are  species  d
ferences;  humans  and guinea  pigs  c;
be sensitized to beryllium, whereas  tl
present  data indicate  that   no  sue
mechanism exists  for the rat.  There  a
also strain differences among guinea pit
indicating  that a genetic component mi
be operative. Patch tests have been usi
to detect  beryllium  hypersensitivity
humans,  but these tests are  no  long
used since they  were shown  to cause
reactivation of latent beryllium disea;
Presently, the lymphoblast transformatii
test is regarded as  the most useful test
detect hypersensitivity to beryllium.

Pulmonary and Systemic
Toxicity of Beryllium in Man an
Animals
    There are  no data  indicating  tl
moderate  beryllium  exposure by  o
administration  causes any   local
systemic  effects in humans or anim.
Respiratory effects, occasionally  co
bined  with systemic effects,  constit
the major health  concern  of  beryllii
exposure, with  hypersensitization  lik

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 laying  an  important  role  in  the
manifestation  of the systemic  effects.
Respiratory effects may occur as either a
nonspecific acute disease or as a more
specific chronic beryllium disease.
    The  most  acutely toxic  beryllium
compounds  are probably beryllium
oxides fired at low temperatures, e.g.,
500°C, and some salts, such as the
fluoride and the sulfate. The latter forms
of  beryllium are acidic, and part of the
toxic  reactions  caused by  these  com-
pounds may be due to the acidity of the
particles. Acute  effects have  generally
occurred  at concentrations above 100 pg
Be/m3. The main feature of  such effects
is  a chemical pneumonitis  which may
lead  to  pulmonary edema and  even
death. In animal experiments, concen-
trations of  more than 1 mg/m3 have
generally been needed to produce acute
effects, but effects have been reported at
lower levels of exposure. In  most cases,
the acute disease will regress,  but it may
take several  weeks or months  before
recovery is complete. If there is  no
further excessive exposure to beryllium,
it is generally  believed that acute disease
will not lead to chronic beryllium disease.
The amount  initially deposited  during
acute exposure and an individual's pre-
disposition are probably the  main factors
leading to later sequelae.
    Acute beryllium poisoning was quite
common  in the 1940's, but  since the
present standards  were established  in
1949, the number of new cases reported
has been relatively small.
    Chronic beryllium  disease occurred
as an epidemic in the  1940's, which led
to  the establishment of the "Beryllium
Case Registry" (BCR),  a file  for all cases
of  acute  and  chronic beryllium disease.
Chronic  beryllium disease  is char-
acterized by dyspnea, cough, and weight
loss.  It is  sometimes  associated with
systemic  effects in  the  form  of
granulomas in the skin  and  muscles, as
well as effects  on  calcium  metabolism.
There are  many similarities  between
chronic  beryllium  disease  and sar-
coidosis,  but in  sarcoidosis the systemic
effects are much  more prominent.  In
most cases of chronic beryllium disease,
there are  only lung   effects  without
systemic  involvement. Pathologically, the
disease is  a  granulomatous  interstitial
pneumonitis in  which  eventually there
may be fibrosis, emphysema, and also
cor pulmonale.  Deaths from chronic
beryllium disease are  often due to cor
pulmonale. A long latency time is typical;
sometimes  there may  be  more than  20
years between  last exposure  and the
diagnosis of the disease.
    It has been very difficult to establish
the levels of beryllium in air that  may
cause the disease. One reason for this
difficulty  is that exposure data have not
always been obtainable. Another factor is
that  hypersensitization  may  cause  the
occurrence of the disease in people with
relatively low exposures, whereas  in
nonsensitized people with much  higher
exposures there may be  no effects.
Diagnosis of the disease is obtained by
X-ray examinations, but  vital  capacity
may decrease before roentgenological
changes  are seen. Hypersensitization
can  be detected by  the lymphoblast
transformation test.
    There are limited  data on levels of
beryllium found in lung tissue in cases of
acute and chronic beryllium disease, and
these data do not allow for conclusions
about dose-effect relationships.
    New  cases  of  chronic  beryllium
disease are still  being reported due to
the fact  that,  in  some instances,  the
occupational standards have  been  ex-
ceeded. In industries where the average
exposure  generally  has been  below 2
ng/m3, there  have been  very  few  new
cases of chronic beryllium disease.
    There have  also been  a  large
number  of  "neighborhood"  cases  of
beryllium  disease. Neighborhood cases
are those  in which  chronic  beryllium
disease occurs in people living  in  the
vicinity of beryllium-emitting plants. The
air concentrations of beryllium in such
areas at  the  time  when the disease
occurred  have probably been around 0.1
iig/m3, but considerable exposure  via
dust transferred to homes on workclothes
likely  contributed to the  occurrence  of
the disease.  No  new  "neighborhood"
cases  of  beryllium  disease  have
occurred  since standards of 0.01  iig/m3
were set  for the ambient air and  the
practice of washing  workers'  clothes in
the plants  was  initiated.  Presently,
ambient air levels are  generally below 1
Ng/m3, although a few urban areas report
values between 1 and 6 Ng/m3.

Dermatological Effects of
Beryllium Exposure
    Contact dermatitis  and  some other
dermatological effects  of beryllium have
been  documented  in occupationally
exposed  persons, but there are no  data
indicating  that  such  reactions  have
occurred,  or may occur, in the general
population.

Teratogenic and Reproductive
Effects  of Beryllium Exposure
    Available  information  on  the
teratogenic or reproductive  effects  of
beryllium exposure  is  limited to three
animal  studies.  The  information from
these  studies  is  not  sufficient  to
determine whether beryllium compounds
have the potential to produce adverse
reproductive  or  teratogenic effects.
Further studies are needed in this area.
Mutagenic Effects of Beryllium
Exposure
    Beryllium  has been  tested  for  its
ability  to  cause  gene  mutations  in
Salmonella  typhimurium, Escherichia
co//', yeast,  cultured human lymphocytes,
and Syrian hamster embryo cells; DNA
damage in  Escherichia  co//;  and
unscheduled  DNA  synthesis  in   rat
hepatocytes.
    Beryllium sulfate and  beryllium
chloride  have  been shown  to   be
nonmutagenic  in all bacterial  and yeast
gene mutation assays. However, this may
be due to the fact that bacterial and yeast
systems generally are not  sensitive  to
metal  mutagens. In  contrast,  gene
mutation studies  in cultured mammalian
cells,  Chinese hamster V79  cells, and
Chinese hamster ovary (CHO) cells have
yielded  positive mutagenic responses of
beryllium. Similarly, chromosomal aber-
ration  and sister-chromatid  exchange
studies  in cultured human lymphocytes
and Syrian hamster embryo  cells have
also resulted in  positive  mutagenic
responses of beryllium. In DNA damage
and repair  assays,  beryllium  was
negative in pol,  rat  hepatocyte,  and
mitotic recombination  assays, but was
weakly positive in the rec assay. Based
on  available  information,   beryllium
appears to have the potential to cause
mutations.

Carcinogenic Effects of
Beryllium Exposure

Animal Studies
    Experimental  beryllium  carcino-
genesis has been induced by intravenous
or intramedullary injection of rabbits and
by inhalation exposure or by intratracheal
injection of rats and monkeys. With one
possible  exception, beryllium carcino-
genesis  has  not been induced   by
ingestion. Carcinogenic responses have
been induced  by  a variety  of forms  of
beryllium  including  beryllium sulfate,
phosphate,  oxide, and beryl ore.  The
carcinogenic  evidence in mice  (intra-
venously  injected  or  exposed via
inhalation) and guinea pigs and hamsters
(exposed via inhalation) is equivocal.
    Osteosarcomas are the predominant
types of tumors induced in rabbits. These
tumors are highly invasive, metastasize

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readily,  and  are  judged  to  be
histologically  similar  to  human osteo-
sarcomas. In rats, pulmonary adenomas
and/or  carcinomas  of  questionable
malignancy  have  been  obtained,
although pathological endpoints have not
been well documented in many cases.
    Although, individually, many of the
reported  animal   studies  have
methodological and reporting limitations
compared  to current standards  for
bioassays, collectively  the  studies
provide reasonable  evidence  for
carcinogenicity.  Responses  have been
noted in multiple species at multiple sites
and, in some cases, afford evidence of a
dose response. On this basis, using EPA
Guidelines  for  Carcinogen Risk
Assessment to  classify  the weight of
evidence for  carcinogenicity in experi-
mental  animals,  there is  "sufficient"
evidence to conclude that  beryllium is
carcinogenic in  animals. Since  positive
responses were seen for a variety of
beryllium  compounds,  all forms  of
beryllium  are   considered  to  be
carcinogenic.

Human Studies
    Epidemiologic  studies   provide
equivocal conclusions  on  the carcin-
ogenicity  of  beryllium and beryllium
compounds. Early epidemiologic studies
of beryllium-exposed workers do  not
report  positive evidence for increased
cancer incidence.  However, recent
studies  do  report a  significantly
increased risk of lung cancer in exposed
workers.  The absence of beryllium ex-
posure levels  and  a demonstrated
concern  about  possible confounding
factors within the workplace make the
reported positive  correlations  between
beryllium exposure and increased risk of
cancer  difficult to  substantiate.  This
relegates the reported statistically  sig-
nificant increases  of  lung cancer to, at
best,  an elevated incidence that is not
statistically  significant. Because of these
limitations, the  EPA  considers  the
available epidemiologic evidence to be
"inadequate"  to  support  or refute the
existence of  a carcinogenic hazard  for
humans exposed to beryllium.
    This  designation   of the  epi-
demiologic  data as "inadequate" differs
from that of the International Agency for
Research on  Cancer (IARC) which con-
cluded that  the epidemiologic  data
provide  "limited"  evidence  for  the
carcinogenicity of beryllium. In the EPA
evaluation, more recent unpublished
tabulations  and analysis of the earlier
study cohorts that correct for  errors  in
the data base and the National Institute
for  Occupational  Safety  and  Health
(NIOSH)  Life-Table program were
included. Use of this newer data provides
a basis to change the  weight-of-
evidence conclusion for the human data.

Qualitative Carcinogenicity
    Using the  EPA weight-of-evidence
criteria for  evaluating both  human  and
animal  evidence,  beryllium is most
appropriately classified  in  Group  82,
indicating that,  on the strength of animal
studies, beryllium should be considered
a probable human carcinogen.  This
category  is reserved for chemicals
having "sufficient"  evidence for carcin-
ogenicity  in   animal  studies   and
"inadequate" evidence in human  studies.
In this particular case,  the  animal
evidence demonstrates that all beryllium
species should be regarded  as probably
being carcinogenic for humans.
Human Health Risk Assessment
of Beryllium

Exposure Aspects
    In the  general  U.S.  population, the
dietary intake  of beryllium  is probably
less  than 1 ng a day, and due to its
chemical  properties,  very little is
available  in the gut for  absorption.
Approximately  half  of  the absorbed
beryllium enters the skeleton.
    For most people, the daily amount of
beryllium  inhaled  is only  a  few
nanograms. However, it is  likely  that
much of this is  retained in the lungs. The
available data indicate that the beryllium
lung burden in  the  average adult ranges
from 1 to 10 pg. Since beryllium occurs
in cigarettes, it is possible that smokers
will  inhale and retain more beryllium  than
nonsmokers. Unfortunately,  the data on
beryllium concentrations in  mainstream
smoke are, at present, uncertain.

Relevant Health Effects
    Occupational exposure to  various
beryllium compounds has been  as-
sociated  with acute respiratory  disease
and  chronic beryllium disease  (in the
form  of granulomatous interstitial pneu-
monitis). Some systemic effects  have
also been noted and a hypersensitization
component probably  plays a major role
in the manifestation of these  effects.  In
the past, chronic beryllium  disease was
found in  members  of the  general
population  living near beryllium-emitting
plants, but past exposures were relatively
high  compared to present  levels of
beryllium  in  the  ambient air.  Con-
taminated workclothes brought home for
washing  contributed to these exposures.
No  "neighborhood"  cases  of  chronf
beryllium disease have been reported i
the past several years.
    Numerous animal studies have bee
performed to determine whether or n<
beryllium  and  beryllium-containin
substances are carcinogenic. Althoug
some of these studies have limitation!
the overall evidence from animal studie
is considered  to  be "sufficient"  usin
EPA Guidelines  for Carcinogen  Ris
Assessment. The IARC has also  cor
eluded that  the  evidence from anim;
studies is "sufficient." Human studies c
beryllium carcinogenicity  have  deficiei
cies  that limit any definitive conclusic
that a true association between berylliui
exposure and cancer exists.  Neve
theless,  it is possible that a portion  of tr
excess  cancer risks  reported in  thej
studies may, in fact, be due to berylliui
exposure. Although IARC  concluded  th
beryllium and  its  compounds should t
classified as  having  "limited" humj
evidence of carcinogenicity, the EPA
Carcinogen  Assessment  Group (CAC
has  concluded that  the  direct hurm
evidence is "inadequate."
Dose-Effect and Dose-
Response Relationships of
Beryllium
    As  previously stated, beryllium  a
act  upon the  lung in two  ways,  eith
through  a  direct toxic effect  on  pi
monary tissue  or through  hype
sensitization. Even if reliable and detaili
exposure data were  available,  it  wot
still  be  difficult to establish dose-effe
and  dose-response  relationships due
this hypersensitization factor. No adver
non-cancerous effects have  been  not
in industries complying with the  2  pg/r
standard set by the Occupational Safe
and  Health  Administration (OSH/
therefore, it appears that this  level
beryllium in  air provides good protecti
with  regard to non-cancer respiratc
effects.  It is  unknown whether exposur
to the  maximum  permissible  pe
standard (25 pg/m3) can  cause  delay
effects.
    From available data,  the  Agen
assessment  document has discussed 1
estimation of carcinogenic unit  risks
inhalation exposure  to beryllium.  T
quantitative  aspect of carcinogen  r
assessment  is included here because
may  be of use  in  setting regulate
priorities and in evaluating the adequc
of technology-based controls and  otl
aspects of the  regulatory decisii
making  process.  However, the  meth<
ologic  uncertainties  associated  w
estimating cancer risks to humans at

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 svels of exposure should be recognized.
The linear extrapolation procedures used
typically  provide a  rough but plausible
estimate of the upper limit of risk-that is,
it is not likely that the true risk would be
much higher than the estimated risk, but
it could be considerably lower. In the
case  of   beryllium,  the  uncertainty
introduced by specific characteristics of
the data base may be best thought of as
affecting  the  confidence in the upper-
limit estimates. These  risk  estimates
should not be  regarded, therefore,  as
accurate  representations of true cancer
risks. The estimates presented  may,
however,  be factored  into regulatory
decisions  to the extent that the concept
of upper-limit  risks are found to  be
useful.
    Both  animal and human studies have
been used to examine the  carcinogenic
potency of beryllium. For quantitative risk
assessment purposes the  animal data
present some difficult  analytical prob-
lems because of weaknesses  in the de-
sign  and  the reporting  of  the  studies.
Despite the weaknesses  of the individual
studies, however, there is little doubt that
beryllium  induces cancer in  laboratory
animals.
    An additional difficulty in the use of
animal data for quantitative assessment
is that not only did  many of the animal
studies utilize different forms of beryllium
than those  commonly  present in the
ambient   environment,   but  the  car-
cinogenic  response varied   with the
beryllium compound used. Moreover, the
form most common in  ambient air is
beryllium  oxide and, although  all the
animal studies  were deficient in some
respects,  the ones  utilizing  beryllium
oxide were more deficient, as  a group,
than those utilizing beryllium  salts.
Nevertheless, it was felt that  the quan-
titative analysis should  focus  upon the
form of beryllium humans are most likely
to be exposed to.
    While the available  beryllium oxide
studies were individually weak, a cor-
relation of estimates from  several data
sets would be  expected  to  increase
confidence in the results. Potency factors
were thus calculated using data  from
eight beryllium oxide animal studies. The
results were  reasonably  consistent and
the geometric mean of all eight potency
factors was 2.1  x  1Q.-3/(ng/m3),  which
agreed quite well with the potency factor
derived from the human epidemiologic
data.
    The  question of beryllium  potency
by ingestion  is  debatable  due to the
equivocal  or  negative results  from  in-
gestion  studies. From a weight-of-
evidence point of view, the potential for
human  carcinogenicity  by  this  route
cannot be  dismissed  given  the know-
ledge that some beryllium  (<1%) would
be  absorbed from the  gastrointestinal
tract,  and  intravenous  injection  of
beryllium produced distant site tumors.
For  practical  purposes, however,  the
potency of beryllium via ingestion must
be  considered  as largely  unknown, al-
though an upper  bound  risk estimate is
provided.
    Even  though the  epidemiologic
studies  have been judged to  be
qualitatively  inadequate  to assess  the
potential of  carcinogenicity for humans,
these  studies can  be analyzed  to
determine the  largest plausible risk that
is consistent with the available epidemi-
ologic  data.  This  upper  bound is a  risk
estimate and can be used to evaluate the
reasonableness of estimates derived
from animal studies.  Information from  a
published  epidemiologic study and  the
industrial hygiene reviews by NIOSH and
other investigators have  been combined
to estimate a plausible upper bound for
incremental  cancer risk  associated with
exposure to  air  contaminated with
beryllium oxide. The epidemiologic data,
while being useful for  estimating  the
cancer potency  of  beryllium,  nev-
ertheless,  also has  interpretative lim-
itations because  of the  uncertainties
regarding  exposure  levels.  In  the
occupational exposure studies  upon
which  the risk analysis is based,  the
narrowest  range  for median exposure
that could be  obtained on the basis of
available information  was  100 to  1,000
iig/m3. Furthermore, an assumption was
made that the  ratio of exposure duration
to years at risk ranged from 0.25 to  1.0.
The geometric  mean  of  the potency
factors derived  using these assumptions
equals 2.4 x 1p-3/(iig/m3).
    The unit risks from  the animal data
sets are best  viewed as  a  sensitivity
analysis, as opposed to a collection of
reasonable  upper-bound  risk  values.
The sensitivity  relates to  the  beryllium
species tested, and for beryllium oxide,
perhaps to firing  temperature. Because
of the  need  to  assume exposure levels,
the  risk estimate derived  from the human
epidemiology data is, in effect, also the
result of a sensitivity analysis.
    With these noted caveats, the GAG
feels that  a  recommendation for  a
specific upper-bound estimate of risk is
warranted, even though it does  evolve
from  less  than ideal data, in  order to
provide a crude measure of the potential
for  public  health impact if, in fact,
beryllium is  a human carcinogen. Taken
together the notable comparability of the
animal and human  based  estimates
encourages  one to consider these es-
timates as  being of  some  utility. Given
the correlation  of  animal  and  human
estimates, the upper-bound incremental
lifetime cancer risk  associated  with  1
iig/m3 of  beryllium, after rounding to one
significant figure, is 2 x 10-3. This value
is based  on  the  assumption that
beryllium is present in the environment in
the oxide form. If,  however, the  form  of
beryllium present includes  more than a
small fraction of beryllium salts, then this
potency  value may  underestimate the
upper limit and consideration should be
given  to  the animal estimates based on
exposure to  beryllium sulfate. The
incremental  upper-limit risk, 2  x  10'3/
(ng/m3),  places  beryllium in the  lower
part of the third quartile of 58  suspect
carcinogens evaluated by the GAG.

Populations at Risk
    In  terms  of  exposure, persons
engaged in  handling  beryllium   in
occupational environments  obviously
have a higher potential for  risk than the
general  public.  With  regard  to the
population at large, there may be  some
risk for  people  living near beryllium-
emitting industries. However, the  risk for
such  individuals  may  not  be  from
ambient air levels of beryllium, but rather
from beryllium-contaminated dust within
the household.  There  are  no data that
allow  an  estimate of the  number  of
people that may  be at such risk,  but it is
reasonable to  assume that  it  is a very
small  group. It should  be noted  that no
new  "neighborhood" cases of beryllium
disease have been reported since the
1940s.

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  Donna Slvulka is the EPA Project Officer (see below).
  The complete report, entitled  "Health Assessment Document for Beryllium,"
        (Order No. PB 88-179 2051 AS; Cost: $25.95, subject to change) will be
        available only from:
            National Technical Information Service
            5285 Port Royal Road
            Springfield, VA 22161
            Telephone: 703-487-4650
  The EPA Project Officer can be contacted at:
            Environmental Criteria and Assessment Office
            U.S. Environmental Protection Agency
            Research Triangle Park, NC 27711
United States    /-
Environmental Protection
Agency       /
Center for Environmental Research
Information
Cincinnati OH 45268
Official Business
Penalty for Private Use $300

EPA/600/S8-84/026F
                       PS
         CHICAGO

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