U.S. DEPARTMENT OF COMMERCE
National Technical Information Service
PB-285 532
Assessment of the Hazards of
Polybrominated Biphenyls
(U.S.) Environmental Protection Agency, Washington, D C
Apr 78
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EPA-560/6-77-037
April 1978
ASSESSMENT OF THE HAZARDS OF POLYBROMINATED BIPHENYLS
by
Frederick J. Di Carlo
Joseph Seifter
Vincent J. DeCarlo
In House Report
Project Officer
Frederick J. Di Carlo
April 1978
ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF TOXIC SUBSTANCES
WASHINGTON, D.C. 20460
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TECHNICAL REPORT DATA
(Please nod Instructions on the reverse before completing)
1. REPORT NO.
EPA-560/6-77-037
4. TITLE AND SUBTITLE
Assessment of the Hazai-ds'pf Poiybrominated Biphenyls
6. REPORT DATE
. April 1978
6. PERFORMING ORGANIZATION CODE
7. AUTHOR(S)
Frederick J.'Di Carlo, Joseph "Seifter and
Vincent J. DeCarlo '" •'•' : •''
8. PERFORMING ORGANIZATION REPORT NO.
9. PERFORMING ORGANIZATION NAME AND ADDRESS
OTS IN-HOUSE REPORT
10. PROGRAM ELEMENT NO.
11. CONTRACT7GRANT NOT
; IN HOUSE
12. SPONSORING AGENCY NAME AND ADDRESS
.EPAj Office of Toxic Substances
Health Review Division, .
401 M Street, S;W.. '
Washington, D.C. 20460 .
13. TYPE OF REPORT AND PERIOD COVERED
14. SPONSORING AGENCY CODE
EPA/OTS - TS-792
16. SUPPLEMENTARY NOTES . .
Project Officer: Frederick J.'D'j. Carlo
16. ABSTRACT . .
During their peak use period, PEBs-'-r-epresented under 1% of the total sales of fire re-
tardant chemicals, and very probably would have escaped intensive study if the had not
been mixed.accidentally with animal.feed preparations. Instead, international attention
was drawn' to PBBs by the.state-supervised killing of.-over 35,'000 cattle-which had been
contaminated with PBBs. Interestingly, Ipw doses of PBBs exert a broad spectrum'of
toxicological,. pharmacological,-and.tidchemi'cal effects despite low actite toxicity.
These effects .and the intensive bioaccumulation of PBBs derive .from their structure and
their consequent resistance pf biotransfcarnation and high solubility in fat. In rodents,
PBBs are teratogenic, iomunosuppressive, 'and potentially carcinogenic. .In bovine, ro-
dent; and avian.species,.PBBs reduce feed intake and induce mixed, function oxidases of
liver•microsdmes. The latter effect may be responsible for steriod level changes which
underline hormonal.toxicities observed in cows, mink, rats, and chickens. The effects
of PBBs on humans are controversial, but data'suggestive df immunologies!, skin, and
liver disorders continue to accumulate.' Concern about the clinical effects of PBB's
is heightened by the knowledge that these.cpmpounds .readily enter the fetus by crossing
the placental barrier "and can be transferred to .newborn children after -extensive passage
into breast milk. -.''.'. ' "• . „
17.
KEY WORDS AND DOCUMENT ANALYSIS
DESCRIPTORS
b.lOENTIFIERS/OPEN ENDED TERMS
c. COSATI Fjeld/Croup
polybrominated. biphenyls
PBB's ' . : ,
hexabromob ipheny1
octabromobiphenyl ' ..-.,.
decabromobiphenyl •
fire retardants . /
industrial sites
air ;
soil •
water, sediment
landfill ••'''.
human exposure .
FDA guidelines
health effects
metabolism
bioaccumulation
18. DISTRIBUTION STATEMENT
RELEASED UNLIMITED
INSECURITY CLASS (ThitReport)
UNCLASSIFIED
21.
20. SECURITY CLASS (This page)
UNCLASSIFIED
22. PRICE
EPA Form 2220-1 (R«». 4-77) PREVIOUS EDITION is oasoLiPre
cn
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(i)-
This document is available through
the National Technical Information
Service (NTIS), 5285 Port Royal Rd,
Springfield VA 22161. Telephone:
(703) 557-4650.
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(ii)
This report has been reviewed by the
Office of Toxic Substances, EPA, and
approved for publication. Approval
does not signify that the contents
necessarily reflect Environmental Pro-
tection Agency views and policies; nor
does mention of trade names or commer-
cial products constitute endorsement
or recommendation for use.
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Assessment
Polybrominafed Biphenyls
by Frederick J. Di Carlo,* Joseph
and Vincent J. DeCarSo*
During their peak use period, PBBs represented under 1% of the total sales of Tire retardant chemicals,
and very probably would have escaped intensive study if they had not been mixed accidentally with animal
feed preparations. Instead, international attention was drawn to PBBs by the state-supervised killing of
over 35,000 cattle which had been contaminated with PBBs. Interestingly, low doses of PBBs exert a
broad spectrum of lexicological, pharmacological, and biochemical effects despite low acute toxicity.
These effects and the intensive bioaccumulation of PBBs derive from their structure and their consequent
resistance of biotransformation and high solubility in fat. In rodents, PBBs are teratogenic, Immunosup-
pressive, and potentially carcinogenic. In bovine, rodent, and avian species, PBBs reduce feed intake and
induce mixed function oxidases of liver microsomes. The latter effev« may be responsible for steroid level
changes which underline hormonal toxicities observed in cows, mink, rats, and chickens. The effects of
PBBs on humans are controversial, but data suggestive of immunological, skin, and liver disorders
continue to accumulate. Concern about the clinical effects of PBBs is heightened by the knowledge that
these compounds readily enter the fetus by crossing the placenta! barrier and can be transferred to
newborn children after extensive passage into breast milk.
Introduction
Fire safety legislation during the last decade
greatly stimulated the discovery, production, and
application of fire retardant chemicals (/). By 1975,
production of these compounds reached approxi-
mately1350 x 106 Ib. At present, more than 60% of
the total production is used to fireproof carpets and
rugs. The balance is impregnated into clothing,
home furnishings and a wide variety of construc-
tion, electrical and electronic products. PBBs were
introduced in 1970, and their manufacture increased
100-fold by 1974 (2). Even in 1974, however, the
sale of PBBs constituted less than 1% of the total
market for fire retardants, because their application
was limited predominantly to incorporation into
thermoplastics used to construct housings for busi-
ness machines and electrical units.
In 1973, the accidental addition of 500-1000 Ib of
PBBs, as FireMaster BP-6, instead of magnesium
oxide to animal feed in Michigan resulted in wide-
* Office of Toxic Substances. U. S. Environmental Protection
Agency, Washington, D £• 20460.
spread contamination of farm animals requiring the
destruction of approximately 29,800 cattle, 5,920
hogs, 1,470 sheep, and 1.5 million chickens (3). Also
removed from the commercial market were at least
865 tons of animal feed, 17,790 Ib of cheese, 2630 Ib
of butter, 34,000 Ib of dry milk products, and nearly
5 million eggs. This mixing error has been alleged to
have caused a great number of health problems in
people who consumed the milk and food contam-
inated with PBBs (4-15). As a result of this incident,
the production of FireMaster BP-6 by Michigan
Chemical Corp. was stopped in 1974.
The Environmental Protection Agency has con-
tinued to work wjth the State of Michigan and other
Federal Agencies in an effort to bring the PBB prob-
lem in Michigan under control. In addition, in early
1977, when information was received on the pro-
duction of PBBs in New Jersey, an immediate in-
vestigation was initiated to determine the level and
scope of contamination around the identified man-
ufacturing facilities. This study is currently under-
way; environmental .and human contamination have
been found near plants of the Hexcel Corp. in
Sayreville, N.J. and White Chemical Co. in Bay-
onne, N. J. As a consequence of the Michigan inci-
dent and the effects of PBBs on animals, the EPA is
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(2)
investigating the need for possible regulatory ac-
tion.
Production of PBBs
Chemistry
The term polybrominated biphenyls (PBBs) re-
fers to a group of chemicals which are formed by
substituting bromine for hydrogen in biphenyl. Al-
though theory allows the formation of 209 bromi-
nated biphenyls, only about 40 have been syn-
thesized in pure form even on a laboratory scale
(16).
Commercial PBB products are mixtures. These
mixtures contain compounds which differ with re-
gard to both the extent and positions of bromina-
tion. For example, 18 different components were
detected in coirimercial FireMaster BP-6 (17), al-
though this preparation was commonly identified as
"hexabromobiphenyP' by the manufacturer. The
quantity of hexabromobiphenyls in BP-6 varied;
contents of > 60% (18), 63% (19, 20), about 75%
(2/), and 90% (22) have been reported. It is clear
that the major hexabromobiphenyl in BP-6 is the
2,2',4,4',5,5' isomer (17, 20, 23). In addition to
hexabromobiphenyls, BP-6 contains isomeric tetra-
bromobiphenyls, pentabromobiphenyls, heptabro-
mobiphenyls, arid an octabromobiphenyl (17,19,20).
The major heptabromobiphenyl contains bromine at
positions 2,2',3,4,4',5, and 5' (21). FireMaster FF-1
(BP-6 mixed with 2% calcium silicate) was found to
be contaminated with trace quantities of hexa-
bromonaphthalene, pentabromonaphthalene, and
tetrabromonaphthalene (18, 20), and with at least 23
other compounds (20). Commercial octa-
bromobiphenyl (OBB) contained at least four com-
pounds; a heptabromobiphenyl, isomeric octa-
bromobiphenyls, and a nonabromobiphenyl (24). As-
says of two samples of OBB showed their chemical
composition to be 1.8% heptabromobiphenyl,
45.2% octabromobiphenyl, 47.4% nonabromo-
biphenyl, and 5.-7% decabromobiphenyl (25); and
1.0% heptabromobiphenyl, 33.0% octabromo-
biphenyl, 60.0% nonabromobiphenyl, and 6.0%
decabromobiphenyl (26). It is noteworthy that the
major component of commercial OBB was nona-
bromobiphenyl, not octabromobiphenyl. Commer-
cial decabromobiphenyl (DBB) was found to consist
of 96.8% decabromobiphenyl, 2.9% nonabromo-
biphenyl, and 0.3% octabromobiphenyl (27).
BP-6 is a solid which softens at 72°C and decom-
poses above 300°C. It is extremely soluble in non-
polar solvents sucjh as toluene and benzene, but dis-
solves only slightly in water. Its solubility in water
has been estimated as 11 ppb (79) and 610 ppb (28).
Upon irradiation with ultraviolet light,
2,2',4,4',5,5'-hexabromobiphenyl in methanol was
degraded rapidly to less brominated PBBs and to
small quantities of methoxybiphenyls containing I
to 5 bromine atoms (29). Exposing a methanolic
solution of BP-6 to ultraviolet irradiation for 45 min
converted 70% of the material to pentabromo-
biphenyl and tetrabromobiphenyl (30). OBB dis-
solved in xylene was also readily photodegraded by
reductive denomination (25). Further investigation
of the photochemical reactivity of PBBs containing
2 to 8 bromine atoms disclosed that denomination
proceeds most readily in positions ortho to. the
biphenyl linkage (31).
OBB is a solid which melts at 200-250°C and de-
composes at 435°C. The solubility of OBB in water
was reported as 20-30 ppb (25). OBB dissolves
readily in organic solvents, but is considerably less
soluble than BP-6 (25). Commercial deca-
bromobiphenyl is a solid which melts at 380-386°C
(32).
Assay
The original identification of PBBs in animal feed
by Dr. George F. Fries was performed by gas chro-
matography (3), and this type of instrumentation
has been used in assay methods which were de-
.veloped subsequently (32-35). The increasingly
stringent FDA guidelines for PBBs in foods and
animal feeds have been based upon the sensitivity
of these methods, not upon toxicological findings
(3). Electron-capture detectors were employed be-
cause they are highly sensitive to halogenated com-
pounds. These detectors have disadvantages, how-
ever. One problem is that they are so easily con-
taminated that their sensitivity becomes variable,
and reproducible data can be obtained only by run-
ning standards frequently and by intervening with
thorough bakeouts. Two noteworthy efforts were
made to minimize sample contamination. One in-
volves gel-permeation chromatOgraphy as a cleanup
procedure for the assay of PBBs in extracts of fat
from butter, milk and cheese (33). The other method
involves cleanup by elution from Florisil columns
and was used to determine PBBs in animal feeds
(34). These procedures can measure PBBs at levels
as low as 7 ppb in dairy products and 3 ppb in dry
animal feeds. Another problem with electron-
capture detectors is that they are difficult to use
routinely in conjuction with temperature pro-
gramming because they require very good temper-
ature isolation between the column and detector
and rigorous control of the purity of the carrier gas
to preclude the collection of impurities at the head
of the column whence they elute and produce poor
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(3)
baselines. These problems were circumvented in
the most sophisticated PBB assay methodology de-
veloped to date (35). The method involves gas
chromatography/mass spectrometry/computer
analysis. A wide variety of environmental soil and
water samples were assayed for PBBs by using the
mass spectrometer in the multiple ion detection
mode to attain high sensitivity. This assay system,
unlike the others, allowed temperature program-
ming which facilitated the resolution of biphenyls
substituted with one to 10 atoms of bromine.
Manufacture
The bromination of biphenyls to PBBs was cov-
ered in four patents granted between 1966 and 1974
(36-39). Two of the processes involve bromination
in the presence of large quantities of chlorine (36,
39). The third employs an aluminum halide catalyst
(37) and the fourth involves using bromine dissolved
in chlorosulfonic acid and iodine, aluminum, and
iodide-iron mixtures as catalysts (38).
The commercial production of PBBs began in
1970. As shown in Table 1, approximately 13.3 mil-
lion Ib of PBBs were produced in the U.S. from
1970 through 1976 (40). About 11.8 million Ib of this
total was hexabromobiphenyl; the remaining 1.5
million Ib consisted of octabromobiphenyl and
decabromobiphenyl. Michigan Chemical Corp. (St.
Louis, Mich.) produced BP-6, and White Chemical
Co. (Bayonne, N. J.) and Hexcel Corp. (Sayreville,
N. J.) manufactured octabromobiphenyl and deca-
bromobiphenyl. The Michigan Chemical Corp. pro-
duced no BP-6 in 1975, but the other two companies
continued their production of the more highly
brominated biphenyls into 1977. No production fig-
ures for 1977 are available, but 1976 production was
estimated to consist of 30,000 Ib of octa-
bromobiphenyl . and 775,000 Ib of decabromobi-
phenyl (40).
Import/Export
At present, no PBBs are being imported in com-
mercial quantities. On the other hand, the export of
PBBs from the U. S. to Europe has increased during
the past several years and totalled 805,000 Ib in 1976
(40). No information is available on the extent of
PBB import in the form of finished plastic products.
Industrial Users
More than 130 companies in the U. S. used PBBs
prior to 1976 (41). In 1974, the major user of BP-6
was the Borg-Warner Corp, producing flame fetar-
dant resins of acrylonitrile, butadiene, arid styrehe
for business machine and electrical housings. At
that time, BP-6 was also used in coatings and lac-
quers and in polyurethane foam for automobile up-
holstery (40). All of these uses were discontinued in
late 1974 as a result of knowledge of the Michigan
incident. No current users have been identified in
the United States.
Pollution from Manufacture and
Industrial Users of PBBs
Losses of PBBs to the environment at sites of its
manufacture (40) can total 51,000 Ib/million Ib of
product through: emission to the air from the vents
of the hydrogen bromide recovery system, losses in
the waste waters resulting from the quenching and
washing of the PBBs as they are recovered from the
reaction mass, and solid losses to landfills resulting
from drying, handling of the product, shipping and
transportation.
Michigan Chemical Corp. discontinued BP-6
production in 1974, and White Chemical Co. and
Hexcel Corp. discontinued their OBB and DBB
production in early 1977. The following process
losses reflect environmental losses that occurred at
those plants when PBBs were being produced.
Air
In 1977, the maximum air losses as particulate
matter at production sites were estimated to total
1125 Ib of PBBs/million Ib manufactured (40).
In May 1974, air emissions at the Michigan
Table 1. Commercial production of polybrominated biphenyls in the U. S., 1970-1976.
Estimated production, ib
Product
1970
1971
1972
1973
1974
1975
1976
1970-1976
Hexabromobiphenyl0
Octabromobiphenyl and
decabromobiphenyl'
Total P$Bs
20,900
31
51
,000
,900
185,000
31,000
216,000
2,221
32
2,253
,000
,000
,000
3,889,000
359,000
4,248,000
4,882
106
4,988
,000
,000
,000
0
170,000
170,000
0
805,000
805,000
11,800,000
1.544,000
13,344,000
° Manufactured by Michigan Chemical Corp.
* Manufactured by White Chemical Co. and Hexcel Corp. Manufacture was continued in 1977, but production figures are unavail-
able.
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Chemical Corp. showed BP-6 levels of 2-3 x
10~* mg/1. at vents. From these data, the total emis-
sion of BP-6 to the air from the vents of the hy-
drogen bromide recovery system was estimated as
0.07 Ib/million Ib produced (79, 40).
Since PBBs were precipitated from the solvent
used during bromination, the reaction mixtures be-
came slurries' from which the products were recov-
ered by centrifugation. Paniculate PBB was lost to
the atmosphere during this centrifugation, but no
data are available for the Michigan production site.
After collection by centrifugation, PBBs were
dried and pulverized to a fine powder. Dust from
this operation was removed by a bag type filter.
During May and October 1974, atmospheric levels
of BP-6 in the Michigan Chemical Corporation bag-
ger area were 0.016-0.032 mg/1. of air during the
bagging operation and 0.003 mg/1. of air after bag-
ging was completed (41). Lower levels were de-
tected in other areas of the plant.
Ambient PBBs were not detected in air samples
collected downwind from the Hexcel Corp. plant
'(42). However, a New Jersey permit application by
this company indicates that some paniculate PBBs
were lost to the atmosphere during centrifugation
and that this loss was less than 0.05% of the product
(43).
PBBs were detected at the same concentration (6
x 10"" mg/1.) in air samples collected downwind
and crosswind from the White Chemical Co. plant
(42).
Water and Sediment
The losses of PBBs to sewers at manufacturing
sites were estimated in 1977 to be only 0.0046 Ib/
million Ib of product (40).
In manufacturing PBBs, water was added to the
reaction mixture when the desired extent of bro-
mination was achieved. Samples of the Michigan
Chemical Corp. effluent discharges were found to
contain the highest PBB levels (98-503 ppm) in 1972
(44). The company outfalls assayed in 1974 and
early 1975 were found to have PBB concentrations
as high as 104 ppb. and the total quantity of PBBs
then being discharged to the Pine River was esti-
mated as 0.25 Ib daily (44). Unfiltered Pine River
water collected in mid-1974 showed PBB levels of
3.2 ppb and 0.01 ppb in specimens collected 75 yd
and 8 miles, respectively, downstream from the
plant. The losses of BP-6 to the sanitary sewer sys-
tem were estimated as 0.0046 Ib/million Ib of prod-
uct (40).
PBBs reached higher concentrations in stream
sediments. Assays conducted from July 1974 to
April 1975 showed PBB levels up to 77 ppm in near-
shore sediments, and declines in sediment content
to 16.2 ppm one-half mile downstream and to O.I
ppm 24 miles downstream (44).
Unfiltered water from an industrial storm sewer
at the Hexcel Corp. plant contained 92 ppb, mainly
as decabromobiphenyl (42). Hexabromo-,
octabromo-, and nonabromobiphenyls were also
measurable. A swamp containing runoff water from
the plant showed the presence of 135 ppb, again
predominantly as decabromobiphenyl. Reeds in the
swamp contained 25-62 ppm of PBBs, and a turtle
captured nearby contained 20 ppb of hexa-
bromobiphenyl.
Liquid effluents from the White Chemical Co.
plant were piped to the head of a dead end canal
called the Platte Kill, This canal, which acts as a
treatment area, empties into the Kill Van Kull
River. Unfiltered water from the head of the Platte
Kill contained up to 31 ppb of PBBs, while water at
the mouth of the canal contained 7 ppb (42). Sedi-
ment at the head of the Platte Kill contained up to
290 ppm while sediments in the Kill Van Kull con-
tained 20 ppb or less. Interestingly, monobromo-
through decabromobiphenyls were found in sedi-
ment at the head of the Platte Kill whereas only
hexabromo- and heptabromobiphenyls were found
in the Kill Van Kull sediment. Fish taken from the
Kill Van Kull contained up to 160 ppb of PBBs.
Landfill
A recent estimate of PBB losses as solid waste to
landfill was 50,000 Ib/million Ib of product (40).
The Michigan Chemical Corp. reported that their
solid waste was approximately 59f of the BP-6 pro-
duced and that about half of this waste (269.000 Ib)
had been deposited in the Gratiot County landfill in
St. Louis, Michigan during 1971-1973 (41). An in-
vestigation of this landfill was initiated in February
1977 (45). Groundwater samples were found to
contain very low PBB levels (0.1-0.2 pph), bui the
concentrations in drainage ditch and catch basin
specimens were far greater (0.35-1.2 ppm) (4f>).
Soil
Soil samples from the bagging and loading areas
of the Michigan Chemical Corp. contained PBBs at
concentrations of 3500 and 2500 ppm. respectively
(44).
PBBs in soil near the Hexcel Corp. plant ranged
from 40 ppb to 3.1 ppm (42). Most of the material
was decabromobiphenyl, but lower hrominated
forms down to hexabromobiphenyl were also pres-
ent.
Soil near the White Chemical Co. plant ranged
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from 750 and 2800 ppb in PBBs (42). Again, al-
though the decabromo compound was most plenti-
ful, there were significant levels of the less bromi-
nated biphenyls down to hexabromobiphenyl.
Human Exposure
Air
Workers involved in {he synthesis of PBBs or the
manufacture of PBB-containing plastics and plastic
products can be exposed to PBBs present in air as
vapor or dust.
While PBBs are effective fire retardants in ther-
moplastics, they can pose a health hazard because
flameless combustion of the consumer products
(e.g., in a garbage dump or an office fire) causes
volatilization of intact PBBs (47).
Water
, There are no data on the direct exposure of hu-
mans to PBB-containing water.
Soil
The useful life of most products containing PBBs
has been estimated as 5-10 years, at which time
they are discarded or buried in a sanitary landfill (2,
19). Adsorption studies show that PBBs are bound
tightly by clay minerals (45) and various soils (28).
Thus, PBBs may remain in soil for many years be-
cause they are als.0 nonvolatile and resistant to
bacterial degradation (17).
Nonaccidental Entrance into Food Chain
Grass and carrots grown in PBB-containing soil
absorbed very little of the contaminant (17),
suggesting no hazard from this source. However,
the recalcitrance of PBBs to leaching and bacterial
degradation indicates that the compounds will be
present indefinitely in soils where they can be in-
gested by farm animals which are used for food.
Accidental Entrance into Food Chain
Through the misuse of PBBs in Michigan, several
farms received feeds containing very high levels of
the flame retardant. The maximum PBB concentra-
tions ingested by farm animals ranged from 4,000 to
13,500 ppm (9). Secondary contamination of animal
feed and medicinals occurred through the use of
contaminated equipment and facilities. In 1974,68%
of 1770 feed samples collected in Michigan con-
tained PBB residues; 60% in the range of trace to
0.99 ppm, and 8% over 1 ppm (48). Resampling in
1975 revealed that 6% of 1208 feed samples were
contaminated and that fewer than 0.16% contained
more than 1 ppm of PBBs. In 1976, only 0.3% of 663
samples analyzed were contaminated; no samples
contained more than 0.1 ppm (48). In 1974 and 1975,
low level feed contamination with PBBs was de-
tected in Indiana and Illinois (49). Contributing to
the introduction of PBBs into farm animals was the
distribution of contaminated aureomycin by the
Farm Bureau; levels of PBBs in their antibiotics
were as high as 70 ppm (50).
PBB-containing meats, milk, butter, eggs and
cheese entered the human food chain before the
cause of the Michigan problem was identified. The
magnitude of the surveys for PBBs in food is evi-
dent from the report that 29,170 products had been
assayed as of April I, 1977 (5/). In 1974, 14 of 16
milk samples, 4 of 34 butter samples and II of 23
cheese samples collected in Michigan were found to.
exceed FDA guidelines for PBBs (49). Another sur-
vey showed that 24.9% of 272 finished product
samples collected from May to October 1974 were
contaminated with PBBs and that 15.8% contained
more than 0.3 ppm (52). PBBs were detected even
in beef in Iowa, duck in Wisconsin, chicken in
Alabama, Mississippi, New York and Texas, and
turkey in Indiana: the levels were extremely low
(52).
PBB food levels in Michigan decreased in 1975
(49). None of J8 milk samples, 3 of 14 butter sam-
ples, and none of 13 cheese samples exceeded FDA
guidelines (which had been lowered from I ppm to
0.3 ppm on a fat basis) (53). Also in 1975, 245 of
2040 meat samples were contaminated with PBBs;
24 contained more than 0.3 ppm (49). None of the
meat specimens collected in 1976 exceeded FDA
guidelines; 96% of 1430 samples were contam-
inated, but only I sample contained more than 0.6
ppm of PBBs (49). A market basket survey of meat
in 1976 revealed detectable PBBs in only I of 102
samples in Michigan (54). Outside of Michigan,
PBBs were found in 9 of 597 food samples during
1975'and 1976(52).
A recent study (55) has confirmed the early im-
pression that PBB levels in dairy products tend to
be proportional to their fat content. Additionally, it
was found that the spray-drying process apparently
exposed and volatilized PBBs from whole and skim
milk to reduce PBB levels in the dried products.
On nonquarantined farms, 99% of 74 adults and
97% of 30 children had PBB blood values below
0.019 ppm while, on quarantined farms, only 56% of
82 adults and 29% of 28 children showed levels
below 0.019 ppm (6, 13). There were 6 adults and 7
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(6)
children with levels between 0.5 and 2.26 ppni.
Levels in fat were consistently higher than those in
plasma. The mean concentration in adipose tissue
was reported as J 965 ±356 ppb in quarantined farm-
ers and 516±92 ppb in nonquarantined farmers (5).
Breast milk is rich in fat, and serves as a route of
eliminating PBBs. PBB levels are much higher in
mijk than in blood serum (13). The Michigan De-
partment of Public Health conducted studies in 1976
to learn the percentage of women who were passing
PBBs into breast milk. Random sampling of 53
women in the lower peninsula showed that 96% of
their milk samples contained PBBs; 63% were
below 0.1 ppm, 32% were between 0.1 and 1 ppm,
and 1 sample was above 1 ppm. Similar sampling of
42 women in the upper peninsula disclosed PBBs in
43% of the specimens; 98% were below 0.1 ppm and
1 sample was between 0.1 and 0.5 ppm (7).
In 1976, PBBs. were still present in 26 of 28 culti-
vated fields which had been highly contaminated
two years earlier. Additionally, soils where con-
taminated milk had been dumped contained PBBs at
levels up to 1 ppm. Stockpiles of decomposing ma-
nure contained about 1.5 ppm, and manured garden
soils contained up to 0.035 ppm of PBBs (56).
PBBs have been identified in the fat of deer, rab-
bits, coyote', ravens, and ducks (44, 45, 57). They
were also found in herring gull eggs at six different
Michigan locations on the Great Lakes (45) and in
fish taken from the Pine River (44).
FDA Guidelines for PBB Levels in Food and
Animal Feed
In May 1974, the FDA set guidelines of 1.0 ppm
of PBB in the fat of milk, meat and poultry, 0.1 ppm
in whole eggs and 0.3 ppm in animal feeds. In
November 1974,-the FDA reduced the guidelines to
0.3 ppm in the fat of milk, meat and poultry, and
0.05 ppm in whole eggs and animal feeds. In July
1977, the Michigan state legislature voted to lower
their guidelines for PBBs in cattle to 0.02 ppm, an
action which may require the destruction of 34,000
cows (55).
Health Effects
Structural Considerations
The physical'and chemical characteristics of
PBBs favor long periods of residence in living or-
ganisms. Their high solubility in fat results in stor-
age, in andipose tissues; their chemical stability
minimizes change to more water-soluble, more
readily excretable molecules; their polarity favors
nonspecific adsorption to tissue macromolecules
and plasma proteins; their molecular weight favors
enterohepatic recirculation; and their polybromina-
tion blocks sites where biphenyl would be
metabolized by hydroxylation.
Various studies have shown that PBBs concen-
trate in adipose tissue; they would also be expected
to be collected in Kupffer cells of the liver, and.
perhaps by macrophages. While PBB levels in th?
body would decline slowly under normal condi-
tions, physiological changes, such as loss of weight,
parturition and lactation, would mobilize PBBs
from tissue reservoirs with their release into the
systemic circulation.
Disposition in Man and Lower Animals
A wide variety of animal species have been found
to absorb PBBs. These species include man, cow,
pig, dog, mink, guinea pig, rat, mouse, Japanese
quail, gull, chicken, and fish. The most definitive
quantitative study showed that rats absorbed at
least 90% of I4C-labeled 2,2!,4,4',5,5'-hexa-
bromobiphenyl administered by gavage in doses up
to 30 mg/kg even when the material was adminis-
tered on four consecutive days (59). BP-6 blood
levels of 2 /ig/ml were observed in children and
adults on quarantined farms (6). Much higher
plasma concentrations (24-41 pig/ml) were reached
in cows given a single 3-gram dose of encapsulated
BP-6 (60).
Information on OBB absorption is less clear. A
study in rats showed that 62% of a single oral dose
of I4C- OBB was eliminated in the feces during the
first day (25). This finding may indicate that the
compound was not completely absorbed.
No information is available on the extent of ab-
sorption of DBB.
Studies with radiolabeled PBBs were' performed
in rats. The levels of radioactivity in adipose tissue,
skin, muscle and liver were measured for 6 weeks
after intravenous administration of HC-2,2',4,-
4',5,5'-hexabromobiphenyl (59). After 1 day, mus-
cle contained more than 40% of the isotope and the
liver contained more than 10%. These concentra-
tions fell sharply, and at 7 days muscle retained only
5% and the liver less than 2% of the administered
radioactivity. Most of this radioactivity was redis-
tributed to the fat, which contained about 25% of
the label on day 1 and 60% on day 7. During the
subsequent 5 weeks, muscle and liver slowly lost
radioactivity while adipose tissue became enriched.
The quantity of 14C in skin was within the range of
15-20% of the dose over the entire 6-week period.
Similar patterns were observed after the oral ad-
ministration of radiolabeled 2,2',4,4',5,5'-
hexabromobiphenyl, indicating that the initial tissue
-------
distribution and subsequent redistribution of this
compound are independent of the route of adminis-
tration (59). Another study showed the presence of
much higher levels of "C in fat, adrenal gland, heart
and skin than in liver, pancreas and spleen 16 days
after administering a single oral dose of "C- OBB
(25). When nonradioactive OBB was fed daily to
rats, the bromine concentration in the adipose tis-
sue and liver increased steadily, with no plateau
during the entire' 6 months of the study (25). The
accumulation of bromine in the fat, liver and muscle
of rats was shown to be related to the concentration
of OBB m the diet (61,, 62), Bromine from OBB did
not accumulate in rat kidney, skeletal muscle or
testis (25). There are no data on the tissue distribu-
tion of DBB.
A study in laying chickens showed the presence
of 12% of the BP-6 does in muscle, 10% in adipose
tissue, and 2% in liver (63).
A study in Holstein dairy calves indicated that
PBB levels in muscle, fat, liver, and kidney in-
creased with the dose (64). PBB accumulation in
these tissues was especially evident when the dose
was increased from 10 mg/kg to 100 mg/kg. A study
in lactating cows showed that PBBs entered the
bone marrow in a dose-related manner (65). PBBs
have also been found in the adrenal, brain, heart,
kidney, fiver, mammary gland, muscle, spleen, and
thyroid of cows (60, 64-67) and sheep (66), in the
bile, lung, lymph nodes, ovary, rumen wall, spinal
cord, spleen, synovial fluid, testis, thymus, tongue,
and uterus of cattle (60) and in chicken muscle and
liver (63).
Humans store PBBs in fat, where concentrations
up to 370 (13) and 15,000 (/5) times higher than the
blood levels have been reported. A study of 16 men
and women, indicated that fat levels of PBB de-
creased 39% in 6 months (7).
PBBs are capable of passing through the placenta!
barrier into the developing fetuses of cows (68) and
rats (61, 69).
The excretion of "C-2,2',4,4',5,5'-hexa-
bromotyphenyl by rats was extremely slow (59).
After the intravenous administration of a single
dose, only 6.6% of the label was excreted in feces
over a period of 6 weeks and the total urinary
excretion was less than 0.1%. Mathematical ex-
trapolation of the excretion data "indicates that
only 9.5% of the total PBB dose would ever be ex-
creted in the feces" (59).
OBB was eliminated much faster by rats (25).
After a single oral dose of "C- OBB, 65% of the
isotope appeared in the feces in 1 day and a total of
73% was excreted in feces in 16 days. The extensive
elimination in 24 hr may reflect incomplete absorp-
tion.
A pig excreted only 1% of a single intraperitoneal
dose of BP-6 in urine and feces in 7 days (70).
Approximately 58% of the dose fed to laying
chickens was deposited in eggs; 11% was found in
excreta (65). Gulls also transfer PBB to their eggs
(45). Cows excrete far more PBB in feces than in
urine (60); approximately 50% of a single PBB dose
was excreted in feces in 7 days and 24% of the dose
was excreted with the milk over a period of 95 days.
It is well known that PBBs pass into human milk
(5, 7, 13), but there are no data on the urinary and
fecal excretion of these compounds. Further, there
is no information on excretion via the skin; this
route may be important for PBBs because lipids (71)
and halogenated hydrocarbons (72) are excreted by
glands in the skin, primarily by sebaceous glands
associated with hair follicles.
HaBlT-Lif® sund BiofflcciflinnnuiSaltBOirii
The biological or elimination half-life of a sub-
stance is determined from a semilogarithmic plot of
the concentration of the substance in blood plasma
(on a logarithmic scale) against time (on a linear
scale). The plot describes a straight line, and the
time required for this concentration at any point on
the line to decrease by one-half is the biological
half-life. In many cases, plotting tissue levels gives
lines with the same slope as the lines obtained from
plasma levels. In order to obtain reliable half-life
values, studies are performed over periods of four
to six half-lives.
Obviously, the repeated exposure of a living or-
ganism to a substance with a long half-life results in
bioaccumulation.
The most striking study on this topic dealt with
14C-2,2',4,4',5,5'-hexabromobiphenyl in the rat, and
concluded that "extrapolation of the rate of excre-
tion to infinity indicates that less than 10% of the
total dose would ever be excreted" (59). Data ob-
tained in a study of UC- OBB in rats was interpreted
to indicate biphasic fecal excretion; the half-life of
the first phase was considered to have been less
than 24 hr, while the half-life of the second phase
was clearly greater than 16 days (25). However, one
may question the existence of the short half-life
phase in the absence of data establishing the com-
plete absorption of OBB by the oral route. This
point can be clarified by investigating the excretion
of >4C- OBB after intravenous administration. Fur-
ther, this report on OBB is difficult to reconcile with
the observation that bromine levels in the fat of rats
dosed with OBB did not decrease during a period of
18 weeks after cessation of dosing (61, 62).
PBB excretion in cow milk was observed to be
biphasic (32). The half-life for the first phase has
-------
(8)
been estimated as 10.5 days (66) and that for the
second phase as 58 days (67). Data from another
study indicated that cow milk would decrease from
200-400 ppm of BP-6 in fat to 0.3 ppm in 120 weeks
(73).
Eggs laid by hens after cessation of BP-6 feeding
showed decreasing levels of PBBs. From the data,
the half-life of PBB elimination by this route was
calculated to be 17 days (63). A more specific report
on this type of PBB elimination placed the half-life
of hexabromobiphenyl at 28 days and the half-life of
heptabromobiphenyl at 20 days (74).
The half-life of PBBs in man has been estimated
to be in the order of 10-11 months (75), although
there are data showing no significant decrease in
plasma levels for 5 months (13)
The long biological half-life of PBBs in avian, ro-
dent, bovine, and primate species indicates that
PBB bioconcentration occurred upon repeated in-
gest ion. It has been amply demonstrated that BP-6
accumulates quickly in fish and that the bioconcen-
tration factor can exceed 10,000 (2, 24, 44, 75).
However, the bioaccumulation of OBB occurred
measurably in rats (23, 60), but not in fish (25). It is
clear that humans experienced the bioconcentration
of BP-6 due to storage in fat where concentrations
were more than 4000 times the serum levels (5).
Biotransformation
PBBs are capable of biotransformations which
would yield large numbers of isomeric products. In
general, these biotransformations will proceed
slowly, but the stereochemistry varies so widely
among PBBs that some reactions will proceed much
faster than others. The major expected end prod-
ucts would be sulfates, glucuronides, and mercap-
turic acids. The higher molecular weight metabo-
lites would be excreted slowly due to their entrance
into the enterohepatic circulation whereas the lower
molecular weight metabolites would be excreted
quickly by the kidney.
Definitive work on the biotransformation of PBBs
has yet to be done. One publication states that ap-
proximately 1% of the BP-6 administered to a pig
w'as excreted as a monohydroxypentabromo-
biphenyl (70). However, it is not clear whether this
metabolite was formed from hexabromobiphenyl
,(by reductive debromination followed by hy-
droxylation) or directly from pentabromobiphenyl
(by hydroxylation). Similarly, there is a single re-
port which suggests the formation of monohy-
droxydibromobiphenyl in fish (75). Another paper
implies that fish may debrominate the more highly
brominated components of PBB mixtures (24). No
unconjugated PBBs could be detected in the urine
of cows given single 3-gram doses of BP-6 (60), and
no metabolites of any kind were found in the feces
of rats dosed intravenously and orally with radioac-
tive 2,2',4,4',5,5'-hexabromobiphenyl (59).
Biochemical Pharmacology
PBBs induce oxidative microsomal enzymes in
the liver of dogs (76), Japanese quail (77), adult rats
(27, 69, 78-84), and neonatal rats (69, 83) and in the
kidney and mammary gland of maternal rats (69,
84). PBBs also induce enzymes in liver cytosol and
mitochondria; this was reflected by the elevation of
serum levels of glutamic-oxalacetic transaminase
(SOOT) in rats (27) and cows (55), and lactic dehy-
drogenase in cows (55). Additionally, these com-
pounds appear to enhance the catabolism of
thyroxine and male sex hormones in cockerels, and
of estrogens in hens (63) and Japanese quail (21). It
also appears that PBBs may change the estrogen-
progesterone balance in cows (55, 56), mink (57),
and mice (55).
Test compounds administered to rodents dosed
with BP-6 were cleared more rapidly from plasma
and excreted more rapidly in bile (59-97). BP-6 de-
creased the toxicity of ouabain in rats by accelerat-
ing the rate of ouabain removal from the blood and
liver (97). This stimulation of hepatic transport was
classified as "a significant drug interaction."
Effects on Animals
Acute Effects. The acute oral LDSO of BP-6 has
been reported to be approximately 21.5 g/kg for rats
(92, 93). Although this dose is very high, it is
noteworthy that indications of systemic toxicity
(such as emaciation) occurred after the oral admin-
istration of 10 g/kg (92). The acute oral toxicity of
OBB is greater than 2 g/kg for rats and greater than
12.5 g/kg for Japanese quail (67). The oral LDSO of
decabromobiphenyl (DBB) is higher than 20 g/kg in
the rat (94).
BP-6 was more toxic than OBB or DBB when
applied to the skin of rabbits. The approximate le-
thal doses were stated to be 5 g/kg for BP-6 (95),
greater than 10 g/kg for OBB (95) and greater than 8
g/kg for DBB (94). Another study placed the acute
dermal toxicity of BP-6 in the range of 2.15-10.0
g/kg (93).
Rats did not die as the result of inhaling BP-6 dust
at a concentration of 71.1 mg/1. of air for 1 hr, but
became emaciated after four such exposures (94).
Rats were unaffected by exposure to OBB dust at a
level of 0.96 mg/1. for 4 hr (26) and by the inhalation
of DBB at a level of 200 mg/1. for 1 hr (94).
OBB caused transient irritation of conjunctiva!
-------
membranes, but not of the cornea, iris, or lens, of
the rabbit eye (27, 94, 95). BP-6 (94) and DBB (94)
were stated to have no irritative effects on these eye
tissues. However, fats exposed to 5 mg of DBB
dust/1, air for 6 hr on 5 consecutive days showed mild
dyspnea and eye irritation (27).
Inspecting the toxicological data shows that
PBBs act slowly. In the acute oral toxicity study of
BP-6, the first rat to die on the second highest dose
(10 g/kg) did so 13 days after dosing (92). In the
same study, the first rat to die on the highest dose
(21.5 g/kg) did so 6 days after dosing and the second
rat died on day 9. Deaths were also delayed in the
acute dermal toxicity study of BP-6 in rabbits; four
of the 15 animals died 5, 7, 8, and 14 days after
dosing (92). There was a similar finding with DBB;
the rabbit which died in the dermal toxicity test did
so on day 14 (94). One report classified this delayed
mortality as "semichronic toxicity" (96). This term
was used to describe the observation that 500 ppm
of BP-6 in the diet of Japanese quail caused deaths
in 3 weeks whereas no birds died after receiving a
much larger quantity (1 g) as a single oral dose. A
similar finding was the death of 37% of chicks fed a
diet containing 400 ppm of BP-6 for 15 days (97).
The administration of single doses of BP-6 to
pregnant rats caused fetal resorption and two
teratogenic malformations (cleft palate and dia-
phragmatic hernia) (98). At high doses, the pregnant
rodents ate less and their fetuses weighed less than
normal. Another important toxic effect from single
doses of BP-6 was the formation of liver nodules
indicative of potential carcinogenicity in rats (99).
Administering a single dose of OBB to male rats
enlarged the liver and produced changes in its ul-
trastructure (100). A single dose of BP-6 induced
mixed function oxidases (MFOs) for prolonged
periods in Japanese quail .(77).
Chronic Effects. The chronic administration of
PBBs has been observed to produce a wide variety
of biological effects in many animal species.
Perhaps the most significant adverse .effects were
the expression of teratogenicity (cleft palate and
exencephaly) in mice (101, 102), the suppression of
humoral immunity in guinea pigs (97), and the sup-
pression of cell-mediated immune mechanisms in
mice and rats (103, 104).
PBBs adversely affect reproduction by different
species, These compounds decrease the comb
weight of cockerels (63. 97), and decrease the fertil-
ity of mink (57), hens (63), and Japanese quail (63).
They induce fetal resorption in mice (88, 105) and
ruts (98), and abortion in cows (85. 86). Addition-
ally. PBBs reduce the survival rate of newborn
calves (88), mink (57), mice (88), and chicks (63),
and reduce the hatchability of avian eggs (63, 106).
Other effects of PBBs which have been noted in
different species include: reduced feed consumption
by cows (55,86,55, 707), rats (75,108) and chickens
(63,109); liver enlargement in cows (56), dogs (76),
rats (62, 64, 69, 78, 81, 84, 88, 91, 110), guinea pigs
(97), mice (90, 91, 102), chicks (63, 97), and
Japanese quail (21, 63, 96); increased liver micro-
somal enzyme activity in dogs (76), rats (69, 75, 79,
52, 59,707,110), mice (55,101), and Japanese quail
(27); and reduced hematocrit values in chickens (63)
and rats (25). PBBs have also been observed to pro-
duce thyroid and testis weight increases in cock-
erels (63), and kidney weight increases in rats (25).
It is interesting that hyperkeratosis was observed on
the eyelids of cows dosed orally with BP-6 (56) and
on the interior surface of the ears of rabbits after
application of the so-called "polar" fraction (99).
The term "polar" was used in a relative sense; no
components of the fraction have been identified.
BP-6 acted synergistically with colchicine to in-
crease the rate of mitosis in rat bone marrow; no
chromosomal aberrations were observed (777).
Other noteworthy effects of BP-6 in rats are re-
duced adipose tissue weight, elevated plasma
cholesterol levels, increased liver lipid and de-
creased liver RNA (707).
Abnormalities in the synthesis of heme result in
the formation of large quantities of porphyrin. This
disorder, called porphyria, was produced in
Japanese quail fed BP-6 (96, 7/2, 113). The ac-
cumulation of porphyrins was on a macroscopic
scale in the bile, liver, kidney, intestine, and bone of
the birds (96). The accumulation in the liver was
attributed to damage to the mitochondria (7/2).
Minimum Effective Doses. Table 2 shows the
lowest doses of PBBs found to have adverse effects
in animals. When possible, these doses are ex-
pressed as ppm of either commercial hexa-
bromobiphenyl (BP-6) or commercial octa-
bromobiphenyl (OBB) in the diet.
Effifecite om Hturaainis
It is clear that hundreds of thousands (1/6) if not
millions (117, 118) of people have ingested food
products containing PBBs. It is also clear that man,
being at the top of the food chain, has bioconceh-
trated the very slowly excreted PBBs. The effects
of PBBs on human health, however, have been
clouded by controversy. Following is an effort to
re-evaluate the information from a scientific
standpoint aided by recent findings.
The expression, short-term effects, connotes a
cause and effect relationship which is measurable
within minutes, hours, or days. Review of the avail-
able information indicates that there is no informa-
-------
(10)
Table 2. Minimum effective doses of PBBs In diet (or by gavage as noted).
BP-6° (Ref.)
OBB" (Ref.)
Cows
Reduced feed intake
Decreased body weight
Liver enlargement
Abortions
Reduced progeny survival
Altered heart, respiratory function
Severe debilitation, death
Kidney, liver, skin pathology
Dogs
Liver enlargement
Induced MFOs
Mink
Reduced litter size
Reduced progeny survival
Nursing rats
Induced MFOs
Rats
Reduced feed intake
Thyroid enlargement
Liver enlargement
Liver histopathology .
Induced MFOs
Kidney enlargement
Reduced fetal weight
Cleft palate in fetus
Reduced hematocrit
Liver nodules
Immunosuppression
Guinea pigs
Liver enlargement
Mice
Liver enlargement
Induced MFOs
Reduced progeny survival
Reduced fetal weight
Cleft palate in fetus
Exencephaly in fetus
Immunosuppression
Nursing mice
Liver enlargement
Induced MFOs
Hens
Reduced feed consumption
Reduced egg production
Reduced egg hatchability
Reduced progeny survival
Reduced progeny growth
Chicks
Reduced weight gain
Reduced body weight
Liver enlargement <
Thyroid enlargement
Decreased comb weight
Increased testis weight
Decreased spleen weight ^
Reduced hematocrit
Reduced hemoglobin
Increased hydropericardium
5,000 ppm (85. 88)
5,000 ppm (85. 88. 114)
5,000 ppm (115)
5,000 ppm (850
10 ppm (88)
5,000 ppm (88, 114)
5,000 ppm (88. 114)
5,000 ppm (88. 115)
1 mg/kg (76 )r
1 mg/kg (76Y
1 ppm (87)
1 ppm (87)
1 ppm (88)
500 ppm (78)
100 ppm (25)
5 ppm (78) 100 ppm (25. 61)
100 ppm (61, 62)
5 ppm (78. 80. 81)
1.000 ppm (25)
100 ppm (102)
200 mg/kg W
10,000 ppm (25)
i g/kg (wr
30 mg/kg (103)
500 ppm (97)
50 ppm (84. W)
50 ppm (84)
200 ppm (105)
50 ppm (102)
50; 1.000 ppm (101. 102)
[00 ppm (101. 102)
30 mg/kg (103)
50 ppm (VI )
1 ppm (88)
125 ppm (63)
20 ppm (10V)
10 ppm 1/06)
30 ppm (63)
45 ppm (63)
10 ppm (106)
75 ppm (6J)
50 ppm (63)
100 ppm (63)
50 ppm (63):
200 ppm (63)
100 ppm (63)
75ppm(6J)
75 ppm (63)
75 ppm (63)
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(11)
Table 2 (Continued)
BP-6° (Ref.)
OBB" (Ref.)
Japanese quail
Reduced feed consumption
Reduced egg production
Reduced egg hatchability
Induced MFCs
SCOppma/)
ICOppm(2/)
100ppm(2/)
20ppm(2/)
• Commercial hexabromobiphenyl
* Commercial octabromobiphenyl.
/ Administered by gavage.
tion on the effects of PBBs in man within this time
frame.
The first effects of PBBs were observed in cattle
in September 1973 (116) as a result of feeding Farm
Bureau pellets purchased during July and fed to the
animals in August 1973 (119). Another version of
the timetable states that sick cows were noticed
after one week of feeding the contaminated pellets
(119). In any case, it is evident that the Michigan
Department of Public Health began its study of
pe'ople exposed to PBBs during the summer of 1974
(119) and presented their report on March 19, 1975.
Thus, their findings reflect the health of people who
ingested PBBs for periods up to 20 months, and
cannot be considered to have been short term.
The 189 adults investigated by the Michigan De-
partment of Public Health presented the following
list of complaints: numbness, balance problems,
nausea, stomach pain, appetite change, weight
change, liver trouble, hepatitis, fainting, loss of
power, blurred vision, light sensitivity, thyroid
trouble, headache, fatigue, irritability, anxiety, de-
pression, pink eye, rash, sores, acne, skin color
change, and hair/fingernail change.
After conducting physical examination and lab-
oratory tests, the department concluded: ".
there has been no consistent pattern of illness or
symptoms which occurred excessively in exposed
persons."
The preceding conclusion was challenged, and
one well-qualified medical research director (116)
wrote a critique stating that the study was "poorly
planned, does not conform to the standards of
adequate scientific medical and epidemiological
evaluation, was incomplete, probably biased and
does not support the conclusions reached and pub-
lished by the lay press. The study has not been pub-
lished in the scientific literature, and it probably
would not be accepted for publication in a bona-fide
scientific journal with a competent and unbiased
editorial review board,"
A study was made of lymphocytes from 75 New
York City residents, 46 Wisconsin dairy farmers
and 45 Michigan residents (720). With one excep-
tion, the lymphocytes i of all of the New York and
Wisconsin subjects showed normal T and B cell
counts and immunological activities. Of the Michi-
gan people, 27 had similarly normal lymphocytes.
Lymphocytes from the other 18 Michigan subjects
were low in T cells. Further, their T cells contained
a high proportion of null (immunologically incom-
petent) cells. The total number of effective T cells in
these 18 people was only 5-10% of normal.
A dermatological study was made of 1029 people
from Grand Rapids, Michigan and a control group
of 221 people from Wisconsin (121). The incidence
of halogenacne (21/1029) and of unexplained hair
loss (23/1029) in the Michigan group were highly
significant because none of the Wisconsin group
showed these conditions.
In November 1976, a group of 343 children (ages
0-16) from rural Michigan were studied for possible
PBB effects (722). In March 1977, 72 children (ages
0-16) from Wisconsin dairy farms were investigated
similarly. Rather arbitrarily, the children were di-
vided into three groups; namely, Michigan
symptomatic (120), Michigan asymptomatic (223)
and Wisconsin asymptomatic (71) groups. The
Michigan asymptomatic group differed significantly
from the Wisconsin asymptomatic group by greater
prevalence of tiredness, decreased appetite and
diarrhea. It was concluded that: "There exists a
reasonable basis to suspect that ingested PBBs do
have acute adverse effects on the health of chil-
dren" and that "symptoms of ill health can be in-
distinguishably produced by acute, high-level in-
gestion and by chronic, low-level ingestion of
PBBs."
In five liver function tests, at least five times as
many Michigan as Wisconsin residents showed ab-
normalities (123). The incidence of abnormalities in
the Michigan group (who had been exposed to
PBBs) was 5-1 \% in the various tests. Abnormal
liver function tests had been reported earlier by a
private physician treating patients exposed to PBBs
(124).
Among the hazardous effects of PBBs on animals
are teratogenicity, immunosuppression, and poten-
tial carcinogenicity in rodents. Other distinctly un-
toward effects are hypothyroidism in rats and chick-
ens, testosterone destruction in cockerels, inanition
in bovine, rodent, and avian species, and porphyria,
reduced egg production, reduced egg hatchability,
-------
(12)
and reduced progeny survival in birds. The enlarged
livers and high levels of liver enzymes induced by
PBBs in bovine, canine, rodent and avian species
appear to be relevant to man, but this matter has not
been pursued in the clinic.
It is not surprising that the information gained
from PBB studies fails to answer a host of important
questions and therefore precludes extrapolation of
findings in lower species to expectations in man.
There are two underlying reasons for this situation.
First, commercial PBBs are mixtures of many com-
pounds and these compounds have seldom been
studied individually. Thus, it is impossible to draw
structure/activity relationships. Indeed, specific
toxic effects cannot be assigned to specific
molecules. This disadvantage is worsened by the
fact that similar chemical compounds may act addi-
tively, antagonistically or synergistically. Second,
the metabolism of PBBs remains almost totally un-
known. This means that the various components of
PBBs may be converted to metabolites which are
also capable of additive, antagonistic or synergistic
activities in different experimental and clinical set-
tings.
The resistance of at least some PBBs to enzymic
attack, coupled with their long biological half-life,
assures, the bioconcentration of these compounds
by man. This process of accumulation is now con-
tinuing and may produce some manifestation of
toxicity at any time, possibly in Michigan residents
of some specific genetic description.
The authors are grateful for the competent assistance of Mr.
William A. Coniglio, Mr. Thomas Kopp, Ms. Cindy McMillin,
Dr. George Parris, and Mr. Michael J. Weaver.
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e °n Oversi«hi and Investigations of the
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, Investi8ati«8 Committee on Poly-
i975 contamination crisis in Michi-
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