CDAL TAR, CR£LSOTE, AND GOAL TAR NELTFAL OIL
POSITION DOCUMENT 1
Coal Tar and Coal Tar Products Working Group
Heman Gibb, Project Manager
U.S. Environmental Protection Agency
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50272-101
REPORT DOCUMENTATION I >• report no.
PAGE ~ ! EPA/SPRD-80/82
4. Trtle and Subtitle
Coal Tar, Creosote, and Coal Tar Neutral Oil: Position
Document 1
3. Recipient's Accession No
PB 80 2138? o
7. Author(s)
9. Performing Organization Name and Address
Special Pesticide Review Division
Environmental Protection Agency
Crystal Mall #2
Arlington, VA
5. Report Date
10/18/78
8. Performing Organiuton R«ct. No
12. Sponsoring Organization Name and Address
Environmental Protection Agency
401 M. St. S.W.
Washington, D.C. 20460
15. Supplementary Notts
10. Project/Task/Work Unit No.
11. Contract(C) or Grant(G) No.
tc>
(Gt
13. Type of Report & Period Covered
16. Abstract (Limit: 2O0 words)
Preliminary Risk Assessment: Examination of possible unreasonable
risks associated with uses of pesticide and a gathering of all available
information to determine whether or
exist. Initiates literature search and evaluates risk data,
information on exposnre to forecast extent of risk.
not this or any other risk does
Limited
17. Document Analysis a. Descriptors
0504,0703,0606
b ldentJfiers/Open.E»ded Terms
c. COSATI Field/Group
18. Availability Statement
Unlimited
19. Security Class (This Report)
U n classified
20. Security Class (This Pa(«)
llnr.1 a q<;i fi prl
21. No. of Pages
116
22. Price
(See ANSI-Z39.18) Sn Instructions on Reverse OPTIONAL FORM 272 (4-77)
(Formerly NTlS-35)
Department of Commerce
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UM.LL CP Xi.TEI.-2S
Peres
I. Background 1
A. Cher.ical and Physical Characteristics 1
B. recisterec Uses, Frcciuction, and Supply 3
1. Uses 3
2. Production and Supply .. 3
C. Fate in the Physical Environment c
1. Vapcr Loss rrcc: Land Use/
2. Less in a Marine Envircr-.ient 7
3. Less in a Freshwater I;-.vircn.-.er.t i/
L. Fate in the Eioiocical Environment. 9
1. i :icrcbiai Eeyratiation 9
2. Eioaccunulation ' " 1Q
3. Effect or. Freshwater Cr^anisrs 11
E. Secjulatory History 11
II. Surrary of Scientific Evidence Relating to Rebuttable Presur.-ption.. 12
A. Oncogenicity 12
1. Sur.-Jiary Table cf Coal Tar, Creosote, and Coal Tar Iteutral
Oil Studies 13
2. Coal Tar 19
a. Case Reports of Skin Cancer of '.workers 19
b. Anir-al Studies 21
3. Creosote. 52
a. Case I-eccrts cf Skir. Cancer in Workers 52
t. Ar.ir.ajl Studies zj
4. Coal Tar I.eutral Oil C-
//
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FayfcS
5. Conclusion 73
a. Cocl Tar 73
b. Creosote 7
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I. Lackcround
A. Chemical and Physical Characteristics
Coal tar is produced by the carbaiization, also called cckirx;, of
ccal. Creosote and neutral oils are products cf coal tar. Although
creosote and neutral oil may be distilled frcr.; sources other than coal,
the terms "creosote" and neutral oil" in this docunent will refer to
distillates of coal tar. Coal tar is described in the Condensed Chemi-
cal Dictionary (iiawley, 1977) as:
A black, viscous liquid (or sei.u-sclid), naphthalene-
like odor; sharp burning taste; obtained by the ces-
tructive distillation of bituminous coal, as in coke
evens; 1 ton cf ccal yields o.B callers of coal-tar.
Oxibustible. Specific cravity l.lb-1.23 {GC/tC F).
Soluble in ether, benzene, carbon disulfide, chloro-
form; partially soluble in alcohol, acetone, ;x-thar.cl,
and benzene; only slightly soluble in water.
Although it lias ether uses, the ten., creosote usually refers tc
that coal tar distillate which is used for wood preservation, befini-
1/
tiens of creosote vary, however.
1/ As a wood preservative, creosote is defined by the Arerican Wood
Preservers' Association (1S76) as:
A distillate derived fra.; ccel tar. As used in the
wood preserving industry, creosote denotes a distil-
late of coal tar produced by the high temperature
carbonization of bitur.inccs coal. Creosote consists
principally cf liquid and solid arenatic hydrocarbons
and contains son*; tar acids and tar bases; it is
heavier than water and has a continuous boiling
rancje be^innir/j at about 2CC°C.
(continued on pace 2)
(1)
-------
Coal tar neutral oils are generally defined as a mixture of naph-
thalene, fluorene, anthracene, and other neutral hydrocarbons (Smale,
1977). Neutral hydrocarbons are those coal tar hydrocarbons other than
coal tar acids (such as phenols, cresols, and cresylic acids), and coal
tar bases (such as pyridines, quinolines, and acridines).
Hie actual constituents of coal tar, creosote, and the neutral oils
are highly variable. They depend on the source of the coal used to pro-
duce the tar, the design and attendant operating conditions (temperature,
asking time, gas collection systems) of the coke ovens, and in the case of
the coal tar distillates the design and operating parameters of the still
(e.g. the feed rate, temperature, and the blending of various tar distil-
late fractions) (Leach and Weinert, 1976).
Over three hundred compounds have been positively identified in
coal tar. It is estimated that as many as ten thousand compounds may
1/ (continued fran page 1)
The Condensed Chemical Dictionary (Havley, 1977) defines cresosote as:
A yellowish to dark brown, oily liquid; clear at 38°C
or higher; naphthalenic odor; frequently contains sub-
stantial amounts of naphthalene and anthracene; distill-
ing range 200-400 C; flash point 165 F (closed cup);
soluble in alcohol, benzene, and toluene; immiscible
with water. Combustible.
Von Rumker et al. (1975) defined creosote as a distillate of coal
tar distilling in the temperature range 271-362 C, heavy creosote as dis-
tilling in the range of 235-395°C, and light creosote as distilling in
the range of 238-291°C. Ross (1948) identified creosote oil asQa distil-
late of coal tar distilling in the temperature range of 230-270 C.
(2)
-------
exist, though many are present only in trace amounts (NIOSH, 1977). Be-
cause the conposition of coal tar and coal tar products is kncwn to vary,
they are usually assayed and specified by their physical characteristics
(including water content, specific gravity impurities, and fractional dis-
tillation curve). Using these physical characteristics, specifications
for creosote used to pressure-treat wood have been established by the
American Wood Preservers' Association, the American Society for Testing
and Materials, and the United States General Services Administration (Ap-
pendix A). The American Wood Preservers' Association has also established
specifications for creosote-coal tar solutions (Appendix B). About 98%
of the creosote used for wood preservation in the United States is applied
by pressure-treating methods (American Wood Preserver's Institute, 1977).
Pressure-treating forces creosote to penetrate deeply into the wood.
B. Registered Uses, Production, and Supply
1. Uses
The largest pesticiaal coal tar and creosote use is as a wood pre-
servative. Coal tar is also used as an insect repellent, an acaricide,
and a crow repellent. Creosote's other pesticidal uses are as an herbicide
an insecticide, an acaricide, an arachnicide, a fungicide, a tree dressing,
a disinfectant, and a horse repellent. Coal tar neutral oil is registered
as a disinfectant, a larvicide, an insecticide, a wood preservative, an
arachnicide, an acaricide, and a fungicide. Specific uses and sites are
given in Table 1.
2. Production and Sucply
Von Rumker et al. (1975) reported that in 1972, 1,150 million
(3)
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l
USEii k:
mi'LL- fc:. gcal i;:,, CvLci:cii, ccsi r,:-; li:
(C^.j.irKS, 11.77)
Product
Coal lar
uSc
Preservative
Ir.sect F.e-uellent
Acaricicfe
Crc.; I.£v.ell=r.t
Cite
i.ocu
iiur.i&n 'Ju-iiti (Lxce:.t l-'crei jb&u)
L'Ojs
LctC CwlTii
.recECte
Preservative
Lisecticice
(ECre.A.Cl".":;
<-.caricicc
(:.iites)
Araci-nicice
(tic/.s)
I.er-ioice
rUj<--'lClc:e
Tree Cressire
iicrs-te i-CL-eiie-ilt
Lisir.£ectar.t
..crses t-x"iu ».u-cb
Poultry
l-cultr/ i.CLSeS
i-dene reset;, r.i'.....-..=v£, Fvr.cea
Lawns; Flcver
r.zzovi:t L^uipr.
Ccal ..eutral oil rreseLVdwive
r-xac!-.r.ici-^
(tic.\:=)
.ca.
Hex incuses; Lcxj
..-r^e iit^Llts; Lc>,.= .
(--)
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TABLE 1
(continued)
USES AND SITES FOR QQftL TAR, CREOSOTE, AND OPAL TAR NEUTRAL OIL
Product
Coal Neutral Oil
Use
Larvicide
(mosquito)
Insecticide
(srewworm)
Larvicide
(gypsyraoth)
Acaricide
(mites)
Larvicide
(fly)
Insecticide
(lice)
Insecticide
(fleas)
Disinfectant
Site
Marshy Land; Stagnant Pools and Srall
Streams;. Sewers; Drains; Small Non-
fish Bearing Lakes and Ponds; Temporary
Rain Pools; Rain Barrels; Clogged
Gutters; Intermittently Flooded Areas;
Tree Holes; Eaves; Canals and Ditches.
Horses and Mules.
Gypsy Moth Nests."
Fungicide
(ringworm)
Horses.
Garbage Trucks.
Horses; Dogs; Hog Houses; Sheep Barns;
Dog Kennels; Horse Stables.
Hog Houses; Sheep Barns; Dog Kennels;
Horse Stables; Dogs.
Soluble Cutting Oils for Machinery; Hog
Houses; Sheep Barns; Dog Kennels; Horse
Stables; Yards and Pens; Poultry Feeders;
Waterers and Incubators; Boots; Aaimal
Equipment and Utensils; Cellars; Sinks;
Bed Pans; Washrocnsj Garbage Cans and
Pools; Hcraes; Factories; Offices; Schools;
Public Buildings; Water Closets; Urinals;
Spittocns; Sickroan Walls; Kitchens; Bath-
roans; Lavatories; Woodwork and Floors;
Wash Basins; Toilet Bowls and Seats; Live-
stock Trucks; Cotton Mills; Farrowing
BquiFnent; Poultry and Meat Dressing
Plants; Ships; Planes; Railroad Cars;
Busses; Sick-rocn Thermometers; Dishes;
Trays and Sputum Cups; Diaper Cans.
Horses
(5)
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pounds of creosote were used in the United States, of which 990 million
pounds were domestically produced and 160 million pounds vrere imported.
Of its total use, wood preservation accounted for 972 million pounds and
fuel burning for about 178 million pounds. Puller et al. (1977) reported
that 96,266^000 gallons of creosote, approximately 843 million pounds,
and 23,625,000 gallons of coal tar, approximately 238 million pounds,
were used for wood preservation in 1975. Pesticide production data re-
ported to the Environmental Protection Agency under Section 7 of FIFRA
indicated that 34,847,384 pounds of coal tar, 366,839,110 pounds of creo-
sote, and 2,019,951 pounds of coal tar neutral oil were formulated or
blended for pesticid&l use in 1975.
¦ C. Fate in the Physical Environment
Little information is available in the literature regarding the
environmental fate of coal tar and coal tar products used for purposes
other than as wood preservatives. Ihe following studies indicate that
coal tar and creosote migrate to seme extent frcm the treated wood into
the surrounding environment. However, the impact of this migration is
not known.
Leach and We inert (1976) reviewed the literature cn the loss of
creosote frcm impregnated wood and found that the loss was aependertt on
many variables; among these are the kind of coal used to produce the ooal
tar, the kind of coke even (temperature, coking time, and gas collection
system) frcm which the coal tar is made, the distillation facilities and
operating parameters (feed rate, tsnperature, and blend of various tar
distillate fractions), the treatment and handling fcy the wood preservers
(6)
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(seasoning ana incising of the wood; tenperature, pressure, and time of
treatment? and the after-treatment cooling period) and the situations un-
der which the wood is used (surface of wood exposed, orientation of the
creosoted wood with reference to the wood grain, and the exposure envi-
rorment).
1. Vapor Loss
Stasse (1964) found that the creosote vapor loss was greater fran
seasoned poles than fran green poles. Vapor loss is also related to the
temperature distillate fractions of the creosote; the higher the tempera-
ture of the distillate fractions, the lcwer the vapor loss. Over a three-
year period, low residue (residue, in this study, was defined as the por-
tion of creosote distillate over 355°C) creosote was found to have a va-
por loss of 27.5% and 15.2%, fran the outer 2 inches of seasoned and green
poles, respectively; high residue creosote was found to have a 10.3% and
4.4% vapor loss, respectively.
2. Loss in a Marine Environment
Bramhall and Cocper (1972} found that the creosote concentration
in the treated zone of pilings of a 40-year-old wharf averaged 15 pounds
per cubic foot (74% of the current minimum) in the outer 1.5 inches.
Whether the substandard retention was due to the original treatment or"
to leaching could not be determined. Sweeney et al. (1958) found that
creosote was lost fran treated panels when wet due to the swelling of the
wood fibers. Panels 5x1 1/2 x 1/8 inches were pressure-treated with
creosote and exposed to flawing seawater at 25°C. Based en distilla-
tion analyses, approximately 30% of the creosote was lost in the first
(7)
-------
month of exposure. By the twelfth month, approximately 40% of the creo-
sote was lost. Ihe rapid initial loss was attributed to the initial hy-
dration of the wood fibers resulting in mechanical loss. It would be
difficult to determine the loss of creosote fran marine pilings based on
the loss fran small panels. This work, however, does indicate that coal
tar-creosote may be lost fran marine pilings by mechanical means, if not
by true leaching.
Miller (1977) found that the ability of Douglas fir marine piles
to retain.creosote in cool estuarine waters was directly related to the
density of the wood. Of the three piles studied, one had a detectable
less of about 0.31 pounds of creosote per linear foot of immersed pile
during the first year, 0.05 pounds/year the second year, 0.06 pounds/year
the third year, 0.22 pounds/year the fourth year, and an average of 0.15
pounds/year each year for the last 4 years of the 8-year study. Thus,
in the first year a pile with 30 feet of its length in water would lose
about 9.3 pounds of creosote, a daily loss of about 11.6 grans. Ihe
speed of the water flowing past the pilings was about 2 feet per second
during flood tide and about 0.8 feet per second during ebb tide? upstream
tide volume between the mean lowest and the mean highest daily tides was
900 million cubic feet of water. Miller concluded that because of the^vel-
ocity and the volume of the water flowing past the pilings, the creosote
lost fran the pilings was greatly diluted. Hochman (1967) found that about
20% of the creosote initially impregnated into wood is expelled in the
marine environment during the first year as a result of wood hydration.
Stasse (1967) found a creosote displacement loss of 21.7% fran voad panels
(8)
-------
ever a b.s-year pence m ocean water.
3. Loss in the Frcs'nvater Envirorrer.t
?:elso and Dehr (1977) found that the greatest loss of cremate frcr
round Southern Pine roles in fresh water occurred ir. the outer 0.5 inch
zone where 45.1% of the creosote v,2s depleted in 13 ronth.s. Overall losses
for the 13-ronth period were 12.5%.
c* Fate in the Siclocical Environment
1. Microbial Degradation
Eean-F.ayrcnci anc Earths C1975) isolated six strains cf bacteria
fra:i oil polluted estuarire water; all six ere.-; on rap ir.thalene, 2-r*;thyl-
naphthalene, ana 2-e thylnachthalene. Fhenanthrene and anthracene \.ert=
netabclized t^ three cf the six strains. IVo of the six strains r.etaLo-
lized 1,5—JL~ethy 1 naphthale ne anc one strain metabolized 1-::ethy inarr.ti;a-
ler.e. riaphthalene, 2-methylnaphthaler.e, 2-ethylnaphthalene, l-retiiyln&pb-
thalene, and 1,5-cir.ethylnafhthalene have all been identified in creosote
(National Research Council, 1?~5) (Lcrenz arc Gjcvih, 1572).
Drisko anc 0'lie ill (19bc) found that the mixture cf microorganisms
present on crecsotec pilings in the Port Huenene, California harbor i.ad
the ability to retabclize creosote, causimj loss of creosote frcr: the pil-
inns. 1\.o of the arcratic hydrocarbons present ir. creosote - naphthalene
art] phenanthrene - were metabolized to a significant extent. Pseudor.cr.as
creosctensis, which was isolated frcr, the mixture cf :.;icrocruanisr.'.s, uti-
lized a nurcer of neutral creosote constituents as a source of energy;
conversely, acioic arc basic creosote constituents inhibited its gro-.th.
Ue^ner (1977) found that creosote in a scil to sand mixture (1:2)
{*}
-------
vas deconposed by soil microorganisns. Fertilized soil plots were watered
weekly for 22 weeks with the equivalent of one inch of rain per week.
Analyses shewed that the leachates degraded rapidly when creosote concen-
trations in the soil were 0.1% or lower. Higher concentrations of creo-
sote can be degraded in the soil bat at a much lower rate (Hepner, 1977).
Davies and Evans (1964) studied the roetabolisn of naphthalene by
a Pseudcmonas species. Hie ultimate metabolic products were salicylalde-
hyde and acetaldehyde.
2. B ioaccumula tion
Dunn and Stich (1975) showed that mussels taken frcm crecsoted pil-
ings contained significantly more benzo[ajpyrene (B[a]P), a known carcino-
gen (IAEC, 1976), than those growing on other surfaces. B[a]P has been
identified as a constituent of creosote oil (Lijinsky et al., 1963). Mis-
sels taken frcm the creosoted wood shewed mean B[a]P levels of 49 + 5.8
ug/kg, while mussels taken frcm the same body of water but remote fron the
pilings shewed mean contamination levels of 2.1 +_ 0.3 ug/kg. Samples of
creosote-treated wood pilings (outer 4 mm) showed 3[a]P levels averaging
570 ppn. Bun-layer chranatograms of piling extracts and of mussels grac-
ing on these pilings shewed "similar fluorescent barri patterns" and may
indicate that the creosote migrated frcm the pilings into the mussels.
Dunn and Stich (1976) also measured the B[a]P content of mussels
attached to and near a partially crecsoted wharf. Creosoted pilings
served as a bumper system around a concrete wharf, and a barricade of
creosoted timbers was placed at one end of the wharf. Mussels taken frcm
rocks underneath and near the wharf were contaminated with creosote, rang-
(10)
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iny fra.: 54 tc 7U ucj/kcj wt tissue -weight; while those crc\.inc directly
on the creosoted barricade v.e.re ccntoranateo with 2x5 u%/~rsJt art; those
on roclx 1 r.etcr frari the barricade with 172 u.j/kg. The auti^rs suc-
c,ested that the levels cf il[a]P in r.ussels in this area are uuch hi^r.er
than tlx.se Generally found near crecsotee structures anc ray reflect t;.<
aye cf the treated ti.n
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infecting potato bins and other equipment used in potato production.
February 1, 1969 - USEft. canceled the registrations of creosote and
coal tar neutral oil-coal tar acid combination products used on beef cat-
tle, goats, poultry, sheep, and swine.
February 26, 1970 - USDA canceled the registrations of products
containing coal tar neutral oil-coal tar acid combinations used on dairy
bams and the registration of products containing creosote used cn animal
sleeping quarters, barns, hog pens, and sheep folds.
March 12, 1971 - EPA canceled the registrations of coal tar neutral
oil-coal tar acid combination products used on poultry houses.
II • Sunroary of Scientific Evidence Relating to Rebuttable Presumption
A. Oncogenicity
40 CFR Section 162.11(a) (3) (ii) (A) provides that "a rebuttable
presumption shall arise if a pesticide's ingredient(s), metabolite(s),
or degradation product(s)... induces oncogenic effects in experimental
mammalian species or in man as a result of oral, inhalation, or dermal
exposure..."
This discussion concerns only reports of the oncogenicity of coal
tar, creosote, and coal tar neutral oil. Reports on the oncogenicity of
soot, pitch, and petroleum, which have many constituents in camion with
coal tar, creosote, and coal tar neutral oil will not be discussed here.
In determining that the oncogenicity criterion was exceeded,
the Working Group considered case reports of wsrxers who were occupa-
tionally exposed to coal tar or creosote and who developed tumors, and
reports of animal experiments in which mice, rats, or rabbits developed
(12)
-------
tumors fran either dermal or inhalation exposure to coal tar, creosote, or
coal tar products. In addition, the Working Group considered conclusions
by the Carcinogen Assessment Group (CAG) (CftG, 1977; CAG, 1978; McGaughy,
1978) that coal tar, creosote, and coal tar neutral oil are oncogenic.
Also, the Working Group is aware that a number of polycylic and
heterocyclic arcraatic hydrocarbons present in coal tar creosote and coal
tar have been well established as carcinogens [International Agency for
Research on Cancer (IARC), 1973; Freudenthal and Jones, 1976; Ccnrnittee
on Biologic Effects of Atmospheric Pollutants, 1972). Specifically, IAPC
(1973) reported that the following constituents of coal tar or creosote
were carcinogenic to animals by one or more routes of administration:
benz[a]anthracene, benzo[b}fluoranthene, ben2o[j]fluoranthene, benzo[a]-
pyrene, benzole]pyrene, chrysense, dibenzo[a,h]anthrancene, dibenzo[a,h]-
pyrene, diben2ota,i]pyrene, indenoll,2,3~cd]pyrene, benzlc]acrid ine, di-
benz[a,h]acridine, and dibenzla,jjacridine.
Hiere way be differences in the chemical composition of the coal
tars and coal tar derivatives in pesticide products subject to this pre-
smption and the coal tar substances discussed in this section. If a
registrant seeks to rebut the presumption on the ground that identified
oncogens are not constituents of a particular pesticide product, the
registrant should include relevant data on pesticide composition in-the
rebuttal submission.
1. Summary Table of Coal Tar, Creosote, and Coal Tar Neutral
Oil Studies
Because of the numerous studies and reports on the oncogenicity
of coal tar, creosote, and coal tar neutral oil, a summary table has
been prepared and precedes the discussions of the studies (Table 2}.
(13)
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-V'-LLi: 2
tzr/j-Fu cr cu± t;:-., chosen:, Cc;--L i/i- cil
--L Li u.
llur-cn Ccsc I'.e.-Ort£
iU^Stai'iCCr
¦occu-acicr.
arc 11i-€
cf L::_csec.
Z.\\e of Turcr
Authors
fear
cf Lxccsure
Individual
]• esvcr.se
wi ,cT -i-cU-l j
1L-35
C'_al _ar ui
r is: .«r:..tp. - i.et
ic.et:.al catcir'.a..as ci
i:<.--.air needle
left i.tr;;cri
ti.e lever ii:-
i:c1j :;€t"crr.
iir.S
:,aurc
1&S1
^anc.iir;<.j uf
Tar c.isciii=ry
v_i.-.riCter wl , iiCi." — Cu,
Coal 1=.r ritcr.
••"OiT/v'E ITS
Ci.es:., -i:
Jvcsr.-aniti.
1>53
Let Ceal Tar
Tar L-arrtsl filler
sVirocGiiuiir e^..«.er i:.
¦Vancrs
scar uf cur vs.". ±r. ti.i:\a-
tc-us lu-us ir.fectie:.
—
X* ii".
;n
ir.-ai ifjoict
nal Lxi.osur^
w:ul-s tance
Authors
"•ear
nCC+"&**
Strain
I'.eS-CT.Se
»a'c j i"./C
IL15
CCclI l.c.L"
r>ci.i.itS (itlfair.
i-ir.iilu as cf the- car
U ICtil/Ut'iVC
Lncefined)
(site of e^-iicacicr.)
Tsuitswi
lS'iu
i. ituv. incus
; J.ce - UnoHs;:
PaL iij.j .as, c^rcii.j
coal tar
ai-sj ceil sarcu-a
r*enn».ay
l'J25
Ccal tar i.ro^
Mice (£trai:i
c];in turgors {i.iji.er r-t=
CUCtS cf 4SC Cf
Liide-firCw)
cf carcinogenesis a:
L* C, £[ 1,^31/
C
:.i^i:&r tr;...jcr=tarvs)
ci~t ilia tier:
terj.eraturd.
-------
TABLE 2
{continued)
.GOAL TAR
Animal Studies
Dermal Exposure
(continued)
Authors
Year
Substance
Tested
Animal &
Strain
Type of Tumor
Resoar.se
Watson &
Mellanby
Bonser &
March
Gorski
Hue per
& Payne
Horton
Deelman
Shabad
et al.
1930 Dermal Applica-
tion of coal tar
following dermal
application of
fats, oils, or
tannic acid
Coal tar dermal
application com-
bined with addi-
tion of butter
to diet
1932 Scottish blast
furnace tar;
English crude tar
1959 Coal tar
1960 Coal tar
1961 Coal tars, coal
tar mixture,
benzo[a]pyrene
mixture
Coal tar dis-
tillates
1962 Coal Tar
1971 Coal tar
ointments
Mice (Strain
Undefined)
Increased tumor produc-
tion
Mice (Strain
Undefined)
Mice (Strain
Undefined)
Mice
(Bn Strain)
Mice - Black
(C57 Strain)
Mice
(C3M Strain)
Mice
{C3M Strain)
Mice (Strain
Undefined)
Mice (C57 CHA
Hybrid Strain)
Higher incidence of lung
nodules
Papillomas and squamous
cell carcincnas of the
skin
Skin tumors (scree
ralignant)
Skin carcincrias
Skin tumors in 7£% of
each group of animals
Skin tumors
Skin carcincnas and
papillomas
Skin tumors
(15)
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TABLE 2
(continued)
COAL TAR
Animal Studies
Inhalation Exoosure
Authors
Year
Substance
Tested
Animal &
Strain
lype of Tumor
Response
Horton
1961
Herton
et al.
Tye &
Stemmer
1963
1967
Kinkead;
McConnell
& Specht;
MacEwen &
Vemot
1972-
1974
MacEwen &
Vemot;
MacEwen
et al.
1976
Coal tar fumes
preceeded by in-
halation of for-
maldehyde; coal
tar fumes
Coal tar aerosol;
Coal tar aerosol
& gaseous formal-
dehyde
Coal tar; coal
tar & phenolic
& non-phenolic
fractions of
coal tar; non-
phenolic frac-
tions of coal tar
Aerosolized
coal tar -
light oil &
solid fraction
removed
Aerosolized
Coal tar
Mice (C3M
Strain)
Mice (C3H
Strain)
Mice (C3H/HeJ
Strain)
Mice {ICR-CFl)
Mice (JAX-CAFl)
Weanling rats
(Sprague-Dawiey)
Yearling rats
(Sprague-Dawiey)
Hamsters
(Syrian golden)
Rabbits (New
Zealand white)
Mice (ICR-CFl)
Mice (JAX-CAFl)
Rats (Sprague-
Dawiey)
Rabbits (New
Zealand albino)
Monkeys (Hacaca
Mullata)
Both groups developed
proliferative alveolar
neoplasia; one mouse
(group unspecified) de-
veloped a squamous cell
carcincma
Both groups aevelcpea
squamous cell tumors of
lung and lung adencnas
Adenanas & carcinomas of
the lung
Mice developed skin tu-
mors due to aerosolized
material deposited en
skin; Tumor response was
not reported for rabbits,
hamsters, or rats
Mice - Alveolargenic car-
cincna and skin tumors;
Rats - Squamous cell car-
cinomas; No tumor response
was reported for rabbits
or monkeys.
(16)
-------
17--LLL 2
(ccr-.tinut-J)
hu:.«J5 Ccssc* Reverts
Authors
Year
iu^stjr.cc
hr.~ lyr.e
of Lx~..oiure
^cu-atior.
of _ic.oseu
Ir.aivic:udl(t)
or T'-.wr
1 ts- cr.sc
. .eCktrPZiij
lo J Li
i-or.j.
CJ: Itilt:— L^..~
cc^csits iri liv'tr,
.-v^.r.OyS ii-- . .¦=—I" w
nent"'
llyi7
.-.anulir.^ ci
>*.rsCSCtc
37 :.-i=r. cf various
cccj:-c tiers
Cuci'.ecui
1- 5o
raintir.^ CI
Creosote
Shicyerc v.orl'.er
Pxii.^ai ituc:i'=£
C^. t i-.f.fc'JUi;
tw. cri cf t_:e r"£.c-_-
!^ei~.3± r.x. csure
nuti.crs
Veer
tcii iCir
lestfeG
r~X j, 1.. ^LL 6
Strain
1v" i or lu.' -or
Kesr.cr.sfc
tall -
£l,=ar
I'j-tU
Crecsctt u
Urnzolc;] 1:yr<=i"'=
:.ice (str-i:: ;.)
.-.cct-Iirc-ti--. turcr
^ ^ r> —
W* W4 4
* .(XX'J ,CUS«
IloC
Crocsctv i.i^
;.ice
Lnceiinec ttrair.;
ilia is & c^rci.'ic^s
.1
•» Ol •
" ( ,
-i cr=c-jct=
Cli
. .ICte ~~ [iisj
i-i:.ill<-.^ii - c£.rcir.j.i-i
-------
TABLE 2
(continued)
CREOSOTE
Animal Studies
Dermal Exposure
(continued)
Authors
Year
Substance
Tested
Animal &
Strain
Type of Tumor
Response
Poel & 1957 Blended creosote
Kammer oils;
Mice (C57L
Strain)
Light creosote oil Mice (C57L
Strain)
Papillomas & carcinomas
metastatic growths in
lungs & lymph nodes
Papillaris
Boutwell 1958 Creosote
& Bosch (Carbasota)
Roe 1958 Creosote oil
et al. (Carbasota)
Mice (Albino
randan bred)
Mice (Strain
Undefined)
Papillomas & carcincmas
Skin & lung tumors
COAL TAR NEUTRAL OIL
Animal Studies
Dermal Excosure
Authors
Year
Substance
Tested
Animal &
Strain
iype of Turror
Response
Cabot 1940
et al.
Berenblum 1947
& Schoental
Horton
1961
Benzene solution
of neutral oil
& benzo[alpyrene
5 Coal tar neu-
tral oil frac-
tions
Coal tar neutral
oils (maleic anhy-
dride extracts)
Mice - albino
"market" mice
Mice (Strain
Undefined)
Rabbits (Strain
Undefined)
Mice (Strain
Undefined)
Inhibitory effect of tu-
mor response as canparea
to tumor response with
benzola]pyrene (effect
credited to skin damage)
All fractions but two
were oncogenic
All fractions but one
were oncogenic
Produced tumors in 34.1
and 32.1 veeks
(18)
-------
2. Coal Tar
a. Case Reports of Skin Cancer of Workers
Numerous reports of workers who developed cancer subsequent to coal
tar exposure have been reported in the literature. The following is a
sunnary of three of these case studies.
(1) Shainbaugh
Shambaugh (1935) described his investigations of the incidence of
cancer anong fishermen and net loft workers who used and repaired tarred
nets. Coal tar was used on nets to prevent them frcm rotting, and tar was
often inadvertently smeared cn the arms and face through use of the nets.
Sharebaugh's interest was prcrnpted by the case of a patient who had sought
medical help because of a growth on his neck. The growth was subsequently
found to be an epidermal carcinaaa involving the lymph nodes and invading
the sufcn\axillary gland. Closer examination of the patient additionally
revealed a snail, puckered scar cn the lip, which the patient described
as a "fisherman's sore." The patient had been a fishenran for 6 years,
and while mending his nets he had held the tar-smeared needle between his
lips at the spot where the growth developed. He had smoked a pipe but
normally held it on the opposite side of his mouth. This case led Sharcbaugh
to interview fishermen in Boston, Gloucester, New Bedford, and Prcvince-
tcwn, Mass. Using records of cases of cancer of the lip treated at Collis
P. Huntington Manorial Hospital in Boston in 1932 and 1933, four fisher-
men with lip cancer were identified. Each had used tarred nets and at
least one held the repair needle in the mouth on the side where the can-
cer developed. Tobacco was not used by this fisherman, but the other
(19)
-------
three sacked pipes. Two of the three cancers developed on the opposite
side of the mouth fran where the pipe was held.
Among net loft workers, three cancer cases were reported. All
held the repair needle in the raouth, and at least one of these workers
did not use tobacco. Two had died of lip cancer, while one was treated
successfully with radium.
Ihe exposure to tar through net repair needles in the eight cases
ranged frcn 5—60 years. All were epidermoid carcinomas of the lower lip.
(2) Mauro
Workers in a tar distillery were examined by Mauro (1951). Of a
crew of 32, 20 had significant exposure to tar (14 day laborers, 4 dis-
tillers, and 2 stokers). All except the two stokers had sane type of
skin disorder; foer of these were cancers. A 61-year-old distiller de-
veloped cancer of the scrotum after a 30-year exposure. Treatment with
surgery and radiation was unsuccessful, and the patient died. A 50-year-
old distiller, employed for 25 years, developed cancer of the scrotum
and forearm. He was also treated with surgery and radiation, but the
outcome was not stated. A 64-year-old day laborer developed cancer of
the cheek after a 30-year exposure and was cured with radiation. A 53-
year*-old day laborer developed lip cancer after 22 years of exposure. ~
He was treated successfully with radiation. Ihe author stated that the
workers were exposed to both tar and pitch, and that the two substances
produce essentially identical cancers.
(3) Rosnanith
Rosmanith (1953) described the case of a worker who developed
(20)
-------
skin cancer in tl.-e scar cf a cured ervther-atcus lupus i:\iecticr.. ire
patient hfeLi oe«n employed for 10 vfears fiili.%. i^rreis wit:: tar; U.iie
oenciry, over ti:e oper-ir.^ of tne carrel, hot tar valors i£o cu .e ir. cu;v-
tact vitin his face. he protective Ltui" was used ouier thcJ: sieves, 'h~.e
co;x;iticr. Lecsn c"t the rcct of tl.e ncsc- as several srall solic yr~..t:a
which cjrew anu expanded. H.e tuner v.as identifiec as a spir.oceiluitr
cancer, radiation treatment was unsuccessful.
t. Aniral Stuoies - llerr.-^l ana Inhalation Zx'.csure
11 ;e icllc^-.ir.'u 15 aur.^l stuuies ere presentee chronologically.
Ir. ueneral, they she., that turors were [.rcc^cec rclicwi.*.j dei:..ai aa-
ir_.alac.icr. exposure tc coal tar. The "..crhing (Jrcup r.ctes that ir.t-.-
pretaticr, of sci .e cf tr.e early studies is li:..it=d ^ t:,e bi.ser.ee cf
control data, i.e.,ever, later stucies which incluue £;xrc:.i.-iate c_;-.ti".;l
croups generally ccr.firr. ari_ reinforce tr.e ocservatio;;s in th^ early
studies.
(1; lara-iwa bikj Ichi-'.c'iws
"ia:.-aci'.,£ and Ichi>:a-,.a (ii-15) pairte-h tar en th* inr.cr an; uutu-r
surface ana ir. open '..cunus of rahoits' =a_s. ^evtr.cy-cr.e to li'iL ucy s
folicf..l:vj painting, pauiila.:«s were observed in 71~ [12 cf 17) of Lcirs
cf ears that i:ad beer, ^ir.tec a: tie inner surface. rc._ illav.at were
seen after c4 cays in ITi (1 of C) of rauuits' ears pai:.t=^ ct. the outer
surface, ii^hty-ei-jht (percent (7 of i) of the oars painted on the inner
surface rao iapillci.;as in race its survivi.-^, lorcjer than b'J cays. Or.!;,
ciife ;.a,.iller..a '..as four.c in rahr.its v.!.ere tnt pair.tiix, hao Leer, acne on
the cuter surface cr ir. a cut v.cu:;c.. Ihe authors unserved cr.e uruCc->,
' ' iU)
-------
papillcna {site unspecified) that had the appearance of a carcinoma, but
were unable to exar.ine the tunor histologically. The authors felt that
the inner surface of the ear was wore susceptible to the develcp.ient of
papillavas than the outer surface of the ear because there were fewer hair
follicles. The author did not report using any controls.
{2) Tsutsui Study
Tsutsui (191B) studied the turor response frcn bituminous coal tar
applied to the skin of "strong" English nice. The tar was applied every
third or fourth cay. A total of 259 mice in seven groups were used; ho.r-
ever, only 67 mice survived for ICO days. Turors were examined histolo-
gically and photographed.
Papillaris developed in 4C% (32/67) of the mice that survived ICO
cays. Later sere of the papillcnas developed into carcinomas, which in-
vaded adjacent tissue, and were found in 24% (16/67) of the nice. A spirt-
ale cell sarccna was found in one rouse, and lung metastases, confirmed
on histological examination, v^re present in two nice. The author die not
report using any controls.
(3) Kennawav
o o o
A study of coal tar products of 450 C, 560 C, and 1,250 C distil-
lation temperatures showed a higher rate of carcinogenesis at the higher
temperature fractions (Kennaway, 1925). The tars were applied to the inter-
scapular region of 100 mice twice a week. After 230 days, 50% (10/20) had
o
skin tumors in the 1>250 C-tar group, 34% (1C/2S) had skin tumors in the
o o
560 C-tar group, and 4% (2/49) had skin tuners in the 450 C-tar group. Most
o o
turrors were nalignant in the 1,250 C and 560 C croups. IJearly half the ani-
(22)
-------
o c
r.als in tlie 560 C and 1,250 C c.rours h.aa died by day 173, and rcre died as
the experiment continued. Ihe author die net report using any controls.
(4) l.'atson and I-;ellanbv
k study reported by ii'atsor. and X-ellanDy (1930) tested the carci-
nogenic effect cr. i.'.ice (undefined strain) cf the combination of fats in
the diet with dernal application of coal tar, of trie ccnbination of the
derral application of various fats, oils, or tannic acic; prior to the
cer7r.al applicator cf ccal tar, and cf the ccrhinaticr. cf precreatr.ert
cf skin with petroleur etlier to remove sore of the fatty substances with
skin application cf coal' tar. Four groups of 7u ::ice were. rfer.ally pre-
treated twice each week with fats (extracted fro-, either ncrral reuse
tissue cr frcr. reuse tissue cf rice who had died frcr tar-induced turners),
olive oil, or tannic acid (first applied in the experiment as a lu% so-
lution arc later in tie experiment as a saturated scluti'-r.). Coal tar
was applied to the skin 30 ir.inutes later. Control croups cf the sarc-
size were treated only with coal tar. Ihe re were no controls in v.i.icr.
healthy anirals were used for comparison. The anirals were treated for
120 cays arid were cbserved for a subsequent 240-day period except in the
case of the olive oil group which was observed for 2C ccys subsequent tc
yu cays of application, rots were added tc the diet by the addition of
butter to the fooc;. The r.ice were fee a diet cf one cart powdered bread
and one pert Sussex ground cats r.^de into a roist paste with water. This
diet was fed daily and was supplemented cnce weekly vith cod liver oil and
rarr.ite. Butter was acnec ir. amounts varying fra:. 12.5-25^ cf tix diet cf
ti-.e test r.ice. A control croup ccnsistec. of rdce tc which no cutter wai.
(23)
-------
added to the diet but to which coal tar was derrnaliy applied. There \/ere
no controls in which healthy animals were used for ccnparison. This ex-
periment was done twice; once with 70 nice in both the test group and the
controls and once with 90 nice in the test group and the controls.
Sixty male nice were treated with petroleur. ether to rencve at
least sane of the fatty substances in the skin. The petroleum ether
i (B.P. 60-80°C> was applied by neans of a cottors-vool plug 3C minutes
prior to the dermal tar application. This treatment was performed twice
weekly for 120 days, and the nice were observed fcr an additional 33C
days. A control group consisted cf 60 nale nice v.hich were treated der-
nally with coal tar twice weekly for 120 days and then observed for 33C
days. There were no controls in" which healthy animals were used for
comparison. An analysis cf results of all the experiments is found ir.
Table 3.
The application of tannic acid solution to the skin of ra.ce prior
to coal tar application did not affect incidence relative to the inci-
dence produced by ccal tar alone. The fat extracts or the olive oil,
however, increased tumor incidence above the incidence produced by coal
tar alone. Fat extracts fro:, nomal nice and frcr. rice which had ciec
frcxi tar turors increased tunor incidence to alrost the sane extent.—
Olive oil applied to the skin of nice prior to coal tar application re-
sulted in a 72% lung tunor incidence anong the skin tunor-bearing nice
ccrparec to 57% for controls (those treated with coal tar alone). The
nice treated with fats or oils prior to tar treatment often developed
turors at several locations, which was not true of those treated with
(24)
-------
TALLE 3
EFFECTS OF VARIOUS FATS AND OILS APPLIED DERHALLY CP. It; TrIE
DIET ON 1U-!OR IriDUCTICfti BY COAL TAR (Katsor. and Hellanbv, 193C)
Preccnditionino
No, Tumors/
No. anirals
Percent of
Timor-Bearing Aninals
Developing Lunc Tuners
I. Skin Treatments
Experiment 1
Tannic Acid
Mouse Extract
(Tumor-Bearing)
Mouse Extract
(Norrral)
Tar Only
Experiment 2
Olive Oil
Tar Only
II. Dietary Treatments
Experiment 1
Butter-fed
No Butter
Experiment 2
Butter-fed
to Butter
III. Washing with Petroleur. Ether
Petroleuri Ether
(Wash)
Tar Only
19/70 (27%}
35/70 (50%)
41/70 (59%)
18/70 (26%)
29/70 (41%)
21/70 (30%)
39/70 (56%)
20/70 (29%)
31/90 (34%)
37/90 (41%)
19/60 (32%)
37/60 (62%)
47
63
59
50
72
57
60
37
55
41
47
61
(25)
-------
tar alone. The addition of butter to the diet of two groups of mice led
to a higher incidence of lung nodules in nice with tumors (6U% vs. 37%
and 55% vs. 41% in the two experiments)/ as canpared to nice treated with
tar with no dietary change. Butter-fed mice developed a greasy appearing
coat. Mice washed with petroleum ether to remove sar
-------
tuners were grossly identifier.' Thirty-one of the total 57 tuircrs i-.hich
heO deveicpec were confirr.ee histologically. results appear in Table 4.
In nice treated with the three Scottish scrples, the first tuners
appeared at trie loth v.-eel:. The Scottish 1, II, and III tar samples pro-
duced a tirror incidence cf 7/GD (12%), 10/6C (17%), and H/bi (13<) respec-
tively. The turors were ralignant in three nice. The first turner ap-
peared at the 21st v.-eek -when an English crude tar was use*:. Eight rice
(13%) treated witi; the English crude tar arc 24 i/.ice (4(A) treated": v;ith
an ether extract cf the English crjde tar eevelqed turners. '..ir.e turors
in nice given the ether extract were .,x=licnant. .st 3u <.veks there v.ere
25 survivors in tl:e latter group cf nice, and over S Js f.c.6 turcrs.
The tunors were papillaris cr scuar.cus cell carcir.cr.as cf the ski;..
The carcinomas invaded the r.uscle. Cne i.«lignant tuner, seen after 47
weeks of application of ether extract of English tar, consisted cf a rass
of "noncnuclear round cells" invading the adjacent r.-.uscle ant; fat sro re-
tastasizing to the lyxT.h nodes.
In this study, blast-furnace tar obtained fra: a variety cf sources
induced benign and raligr.ant turcrs cf the skin in race. The carcinogenic
properties %/ere enhanced by extraction witi: ether.
(o) Corski — .
Gorski (1059) investigated the carcinogenic prefer ties cf tv.-c ccal
tars (one produced frcr. coal fror, the "Sobrek" rlne and one produced frcr.
ccal fra.. the "1-cwa huta" nine), a soft pitch, a hard pitch, arc: an arr-
trxacene fraction. Thirty Dr. r.icc- abcct 2.4 ircntl.s old and cf approxi-
mately equal sex distribution -..ere in each test group. Th.e autl.crs c.i*-
(27)
-------
TAllLi: 1
iiodkmci: of skin wk)r;; in hick 'i'inwii:d wrni wast iijuiaci: tahs
Carcinogen Asr.essnH.-nt Group (CACi), 197U
Number of A[j[jcarance of
Tumors per l-'irst Tumor liali
-------
not report using a control group. The mice were described as having a
"low threshold for spontaneous growths." One drop of the test solution
was applied to the skin near the backbone of the mice twice a veek for
5 months, for a total of 44 applications per mouse. No data vere pro-
vided on controls.
The test solutions were prepared by dissolving the materials in
benzene (a 1:1 ratio). Pitch, being insoluble in benzene, was extracted
using Soxhiet's apparatus, which provided a 1:5 solution in benzene.
Skin changes observed included peeling, swelling, and wart-like
growths of differing shapes and sizes. Skin effects appeared earliest
and with greatest intensity in the soft pitch group. Tumor results are
reported in Table 5.
After 8 weeks, sere nice had died in each group. Skin tuner ob-
servations were made at 4 ncnths. Tar from the "Bobrek" irdce produced
an average of 0.6 tumors per mouse in 22 irj.ee; 6 had malignant tumors."
Eight of 26 surviving mice in the Nowa Huta nine tar grcup had malignan-
cies, and there were, on the average, 0.2 tumors per animal. Twenty-one
mice survived in the hard pitch group, with an average of one turner per
mouse; eight had rnalianant tumors. In the soft pitch group, 28 nice sur-
vived, with an average of 2.9 tumors each; 14 mice had malignant tuners.
Of those to which an anthracene fraction was applied, 24 mice survived
with an average of 0.3 tunors each; 4 nice had malignancies.
Mice with skin changes in all groups vere debilitated anc died
by the end of the severrmonth experiment. Vvhite hard growths ranging
in size frcn that of a pinhead to that of a peppercorn were found by
(29)
-------
¦nroi< i-KoNTi'ior: n; f.ici: i>i;uiai.i,y iixi-oiii.i) '.o u\:h mrr/. n
(A:|< t liiicut Kiytlit. Wool.:; («iflur 'I nxaitlis) llinloltxjicvilly
IV il >r«1 'i'iir
:mi
'I'I
4.4.
0.(,
(>/22
{21\)
l.fA.,1 llUtil 'J l1 l
'3D
!!(>
0. 2
i'/2()
(Jlv)
I It ird l'itt:li
30
2)
1.0
\\p.\
< 1S1?)
Soft I'i tell
:jo
2l'>
J .<>
\*,/2h
('jtlV.)
AnLlinicxiie l'iu|. .ilivu alU-i v.cel-:!..
(HJ)
-------
dissection of the skin tumors, particularly in the later stages of the
experiments. Cther changes included enlarged lymph nodes, growths in
the lungs, flaccidity of the liver, pale hard growths on the kidneys, and
degeneration of the liver and kidneys. Metastases to the lymph nodes
were confimed in mice frcn the soft and hard pitch groups.
The author concluded that all the products tested were carcino-
genic, that soft pitch was the roost carcinogenic, anthracene fraction
the least carcinogenic, and the two tars and the hard pitch were in an
"intermediate" group.
(7) Kueper and Payne
Hueper arse Payne (I960) found that skin tunors were produced in
mice following the application of coal tar. Coal tar, four petroleum
road asphalts (Venezuelan, Kississippian, Oklahcnan, and Californian),
one petroleum roofing tar, and paraffin oil were applied to the napes
of the necks of groups of 50 black C57 nice (25 of each sex) for two
years. An untreated control group consisted of 2C0 nice. So that the
materials could be applied as droplets, the coal tar and roofirsc as-
phalt were heated to make then liquid, anc the road asphalts were di-
luted with a sufficient anount of acetone. The paraffin oil was painted
on the skin. Postmortem examinations were performed on all nice, and
histological examinations were made of all tissues which exhibited
gross abnormalities. The results are found in Table 6.
Carcinomas of .the skin were found in 22 of 50 (44%) and papillo-
mas in one of 50 (2%) mice receiving dermal applications of coal tar,
whereas control rice did not develop tumors of the skin.
(31)
-------
TABLE b
SKIN HJMORS IN MICK GIV111 DERMAL APPLICATIONS 01' COAL TAKf PLTROLLUM
ROOFING TAR, PARRAt'IN 01Ly OR PLTR01.LUM ROAD ASPHALTS
Carcinogen Assessment Croup (CAP), 1D7U
Skin
Carcinomas
Skin
Papillomas
Treatment
Total
Control
0/200
(0%)
0/200
(0%)
0/200
(0%)
Coal Tar
22/50
(44%)
1/50
(2%)
23/50
(46%)
Petroleum Roofing Tar
1/50
(2*)
0/50
(0*)
1/50
(2*)
Paraffin Oil
1/50
(2S)
1/50
(2*)
2/50
(4%)
Petroleum Road Asphalt
Venezuelan
0/50
(0%)
0/50
(0%)
0/50
(0%)
Mississippian
1/50
(2%)
1/50
(2%)
2/50
(4%)
Oklatranan
0/50
(0%)
1/50
(2*)
1/50
(2%)
Californian
1/50
(2%)
0/50
(0%)
1/50
(2%)
(32)
-------
Hueper and Payne also administered scne of the substances via in-
halation and intramuscular injection. Coal tar did not produce lung tu-
mors in rats or guinea pigs inhaling such fumes for periods up to two
years but did produce muscle sarcomas following intramuscular injection.
Hie results of the intramuscular study are not discussed here because
intramuscular injection is not a route of exposure induced in the cri-
teria of 40 CFR 162.11(a)(3)(ii) (A).
(S) Horton
In several experiments Kcrton (1961) tested a number of crude coal
tars, coal tar distillates, and fractions of coal tar for skin tumor re-
sponse in C3M nice. In the first part of the study, five ooal tars (four
fraii the coking of bituminous coal and one frcm the coking of lignite
coal), a mixture of one of the bituminous coal tars in 50% benzene, and a
benzol a) pyrene mixture were tested. The authors did not report using a
control group. No data were provided on the number of mice tested nor on
the length of time the animals were treated; however, the time-to-tunor
for each group was reported. Ihe incidence of tuners was reported to be
greater than 75% (only a percentage was reported) for each test group.
Horton developed a numerical index designed to grade the various tars
and tar fractions for relative carcinogenic potency. This index was re-
ferred to as the potency for a minimum concentration of material (PNC).
A high PMC value is meant to indicate a greater carcinogenic potency.
For tars D-l and D-613 for which multiple doses were applied, a oose
response was evident. Ihe mean time-to-turor (in weeks), the schedule
of application, and the FMC values for each of the tars, the tar solu-
(33)
-------
TAELE 1
InZAK Ti:£-CC-TUI-.CR AMD F.'.C VALUES FOB PGUP. UTUyjICUS
TARS, 01 iL LIoklTE TAR, ATX Cl.E SCLLTICr; CF DIHiZG la] FYRhlJL
(Adapted frar. Rcrtor,, 1961)
Treatment
Schedule of
Application
(r/week - rxj)
!fian Tirr.e-to-
Tur.or (weer-s)
f::c
C-l - titminous tar
1-4 - bitun.incus tar
L-5 - bituminous tar
D-5A - 5C-b dilution
by weiijiit of
L-5 tar
D-S - biturrir.ous tar
L-12 - lignite tar
D-613 - benzo[a]pyrene
in 85% be ta-
re thy lnapthaler.e
and 15% benzene
solution
2-10
2-SC
3-1CC
2-1U
2-1C
2-10
3-5C
3-50
2-15
2-5C
15.6*
12.6*
7.0*
23.6
25.1
21.9
17.1
33. C*
30.6*
0.27*
C.37*
C .£3*
C.13
U • it
0.13
0.11
0.16
0.0£*
0.1L*
* The nsultiple coses fcr Tars D-l anc L-613 de.cnstrated a r.^an tirx—
tc-tui.or and a Pf-iC dose responses.
(3%)
-------
tion, and the benzo[a]pyrene solution are reported in Table 7.
Two tars frcn the previous group (D-l and l>8) were chosen to test
the effect of skin washing with a detergent in water 5 or 60 zrinutes after
tar application, liars D-l ar*3 D-S had the highest (0.8) and lowest (0.1)
benzene-insoluble content, respectively. Washing delayed turaor develop-
ment, but the final tumor incidence was not significantly changed. The
delay was greater in the animals washed 5 nanutes after dermal application.
Horton also determined the relationship between the amount of benzo
la]pyrene in distillates of ccal tar and the carcinogenic potency of those
distillates. Tar D-l, a distillate oil of i>l (the first 9-13.5% of the
distillation), a proportionate reblend of nine distillate fractions of D-l,
and two distillate fractions (a carbolic oil arc a light creosote oil) of
a coal tar (D-9).not previously used in the experiments were tested for
B[a]P content and carcinogenic potency (PMC) to the skin of nice. With
the exception of Tar D-l, all test materials were'applied to rice (strain
unspecified) in 10 ng coses. Tar D-l was applied in 20 ng doses. The
number of applications was described as "repeated," but neither the fre-
quency nor the duration was specified. The PMC values and benzola]pyrene
content of the test substances are reported in Table 8.
Comparison of the benzol a} pyrene content with the carcinogenic po-
tencies of various fractions showed that no tumors were produced by these
fractions in which no benzoIa]pyrene could be detected, while the carcino-
genic potency of the test materials that contained benzo [a] pyrene was cor-
related with their content by weight of this carcinogen. Despite this ob-
servation, the authors did caution that tliese results co net inply that
benzo[a]pyrene is the only carcinogen in these substances.
(35)
-------
TAHLI' 0
MC VALUFS AND ULNZOtuI I'Yld'NI- QKllM' FOR '1VX) OUAL TA1&, SLVKKAL
IJISTIU-ATi'JS OF 'IIIOSL; COAL '1'Altfj, AND A I'KJPOiyi'lONATL: l&lll.LND OF
nil; DISTILIATI2J FlOl CJNli OF 'lilt; TA1
-------
(9) Deelr.an
Deeinan (1962) studied the effect of tin;e between tar applications
on tunor development. He found that papillomas developed after 18 appli-
cations regardless of the interval between applications (2 to 7 days). The
nurijer of carci.ncr.as was snail after IB applications. In tire, after the
end of the applications, however, rrany of the papilla.ias becar.e carcmcras.
Vihen tar was applied to different size skin areas or fields, it
was found that rice with the largest field (2C x 25 nr.) had an average of
one carcinoma and seven papillaris each. Eight race, with a tarred field
of 2.5 x 25 rxr. (The ccal-tarred area for the eight r.ice ccr\bir.ed is equal
to the largest field tested or 20 x 25 nxr. field for cr.e rouse.) had a to-
tal of 34 papillomas and three carcinoses airong ther.:. It was found that
among the tar fields tested (20 x 25 :z.\, lu x 25 m ana 2.5 x 25 rxi), the
smaller the tar field, the larger the nurroer of turrors per unit area.
This may be a result of the greater toxicity to the ar.irals with the larger
tar fields; the author observed that raortality, weight less, and kidney
damage increased as the size of the tar field increased. I.o untreated
controls were used in the study.
(10) Shabac et al.
Shabad et al. (1971) applied three coal tar ointr.ents [Lcracorten
tar ointner.t (USA), CIEA ccal tar ointment (Switzerland), anc coal tar
ointnent (USSR)] to C57 CBA hybrid ir.ice two or three tires each week for
10 or 12 ironths to test for tumor production. Hie authors did not report
using any control groups. All of the nice ciec within 16 months or were
sacrificed because of their poor condition. Eighteen of IS (94.7%), 20
(37)
-------
of 21 (55.2%), and 16 of 17 (94.1%) of the anirals in USSR, CIBA, arc
Loracorten ointment groups, respectively, developed tumors. .The benzo
la]pyrene content of the three ointments was 225, 5,020, and 5,190 ug/g,
respectively. Shabad also tested the effect of two birchwood tar oint-
ments, Vishnevsky and Tashkent, on groups of 20 and 24 C57CEA mice, tone
of the mice in the groups develpec tumors after 18 months. The benzo [a]
pyrene contents of the Vishnevsky and Tashkent tars '*ere 0.0013 and 0.044
ug/g, respectively.
(11) Horton
Horton (1961) studied the lung turor response in C3H nice after
exposure to coal tar fumes. One group of mice inhaled focraicehyde-
contaminated air intemittently for an unspecified amount of time, while
a second group was kept in clean air. The former group developed scuareus
metaplasia as a result of their exposure to formaldehyde. Both creeps
were then exposed to coal tar fumes (0.33 rag/liter) for one hour/cay, three
days/week for 13 to 33 weeks. A majority of the race (numbers were not re-
ported) in betli groups developed proliferative alveolar neoplasia, and one
(the group was not reported) develcped a squamous cell carcincra. The two
groups of mice showed no difference in neoplasia incidence. A third group
of mice, exposed intermittently to formaldehyde alone for 64 weeks, shewed
no alveolar proliferation or carcinana aevelcpment.
(12) Horton et al.
Horton et al. (1963) examined C3H nice (a strain that was reported
to have a low historical incidence of spontaneous pulmonary adenomas) for
lung tumors following inhalation exposure to coal tar aerosol, gaseous for-
(36)
-------
maldehyde, or gaseous formaldehyde followed by coal tar aerosol. In the
first pert of the experiment, groups of 60, 60, and 42 mice were exposed
to concentrations of 0.5, 0.10, or 0.20 mg/'liter, respectively, of gaseous
formaldehyde for three 1-hour periods per week. The control group consis-
ted of 59 untreated nice. After 35 weeks, none of the animals that were
sectioned of those that died {118 of 221) during the 35-week period had
developed lung tumors. The surviving animals were used to conduct fur-
ther experiments with coal tar anc formaldehyde. The surviving 33 nice
frcn the control group in'the first part of the experiment and the surviv-
ing 26 mice frcm the croup in the first part of the experiment that had
been exposed to 0.10 mg/1 of gaseous formaldehyde were exposed to C.30
ng/l of coal tar aerosol for three 2-hour periods per week for up to 36
weeks. The surviving 36 mice frcn the group that had been exposed to
0.05 mg/1 of formaldehyde in the first part of the experiment were ex-
posed to 0.15 ng/1 of formaldehyde for three 1-hour periods each week for
1/
up to 35 weeks. There was also an untreated control group which was ob-
served for 82 weeks.
The test animals v*ere exposed to the test substances until death;
the first death occurred 1 to 11 weeks after exposure and the longest
time until death v.as 36 \«eeks. Serial sections of the trachea, large-
bronchi, and lung frcn the exposed animals and frar. the lungs of 30
unexposed mice were examined (Table 9).
1/ The initial size of the untreated group was not reported. At the
~ termination of the experiment at S2 weeks, the group consisted of
30 mice.
(39)
-------
TAbLE 9
'lUMUUS OF nil: LUUG IN MICE INHALING POIWALUUIYUE AND/OH ARIOSO!, Ol'- COAL TAR
Carcinogen Assessment Croup (CAG), 197(1
Treatment Squamous Cell Tumors Adonanas Total
(-) 0/30 (0%) 0/30 (0%) 0/30 (0*)
Coal Tar 6/33 (1B%) 1/33 (3%) 7/33 (21%)
Fotwaldiihyde 1/26 (4%) 1/26 (4%) 2/26 (B%)
and Coal Tar
[•'ounaldeliyde 0/36 (D't) 0/36 (0'i) 0/36 (0%)
(40)
-------
Five iv.ice inhaling ccal tar aercsol and one rouse inhaling foe'.ai-
de hyde followed by coal tar develqed squamous cell turners in the periph-
ery of the lung, involving 1/3 to 1/2 cf the lol:-e. In two :.;ice frcr the
fcrr.er group, several loLes were involved. A sixth r.iousc in the fcrt.x-r
group that died after 20 weeks cf ex^sure hac an invasive squarous cell
carcina"^, which was described as "unquestionably a srua;.cus cell carci-
ncra whereas these occurring in the other five aninals prcbcbly repre-
sented an earlier stage of development at the tir.*s cf death." Cr.e reuse
in each 5 roup had acencma of the lung. Tuners of tl'.e lung w-ere not ob-
served in nice breathing forraldehyce only or in untreated -ccncrcia.
There were other changes produced ir. the tracheobronchial epithe-
lium as the result of the inhalation cf coal tsr. Ihe rest striking v;ass
a necrotizing tracheobronchitis in the rrajorits of r-ice; the incidence was
net reported. In addition, scuar-ous cell netaplasia extended into tl.e
sraller brcr.cni. hyperplasia cf the bronchial epitheliur. occurred fre-
quently, scretir.es with papillary infoicing, Ih.e epitheliur. cf untreated
nice was norral shoving neither netaplasia nor hyperplasia.
Epithelial chances in mice inhaling forraicehyde involved rcstly
the trachea; extension into the re.jcr bronchi was ir.freouent and did not
occur at ail in the seller bronchi. In general, the inhalation of £
-------
(13) Tve and Starrer
Tve and Sterner (lrJ67) separated tvo different ccal tars into
phenolic (P-tar) and nonphenolic (; -tar) fractions and exposed r.ace -~y
inhalation to various blends of the coal tar fractions and to one of ti.e
original tars, The sar-fe coal tar (T-l) (Specific yravity 1.17, 4.5%
tar acid, C.7% ber.zo[a]p^Tene and 67^ Diels-Aciler ccrrounds) that was usee
in tiie experiments by iiorton, Tve, an.: Sterner (1SG3) and a second, scr>_—
uhat different tar (T-2) (Specific gravity 1.24, 1.4% tar acid, 1.1% Len-
zolalpyrene, and 2% Diels-filder ccrpcuncs), \vere the t..c tars 2rcr \hich
the phenolic (r-tar} and nenpher.ciic (h'-tar) fracticns v.ere separatee,.
Fifty rrale C3ll/haJ nice, tixee tc five rcnths cic, vere in each
test grcup. Ibe tests groups consisted of untreated, Tar-1, h-Tar-i, l>
Tar-1 plus r-Tar-1, --Tar-1 plus F—Tar-2, and I .-Tar-2 :.lus ?-Tar-1. -"ice
were exposed for two hours every three veehs. During the first eight
weeks, the 'exposure was at a concentration of C.2G r^l, tut this \.?.s re-
duced to C.12 ng/l because so nary nice died.
Three nice fra:. each, group were killer, after four weeks, and five
-ice were hilled after 31 v.ee---£. Sur-'ivinr. nice vere killed at the end
of 55 weeks, "ortality frcr. exposure \.as high in all groups of treated,
race, /it the end of the experiment, there v.ere 31/50 (£2%), li/5o i22%),
11/50 (22%), 1C/5C (2C%), 21/50 (42%), arxi 21/5G (42%) nice alive in the
control, Tar-1, h-Tnr-l, h-Tar-1 plus F-Tcr-1, !<-Tar-l plus r—Tar-2, and
I .-Tar-2 plus P-Tar-1 r.rccrs, respectively. Turcr res;x^nse is recorded
ir. TaLlc- 1'".
The r.cs t rrcr.iner.t lesions vere ir.trahrcnchial arenex'c.s and adt—
(*»2)
-------
TAliLK 10
V
itonno: of lutx:; 'iumurs in met: inii'ai.hkj ai:hxjoi,s of cuai. taks
Carcinotjen Assessment Group (CAG), l'J7U
2/ Adenuaas t»
Treatment Metaplasia Adenomas Adenocarcinomas Carcinomas
(-)
0/32
( 0%)
0/32
(0%)
0/32
(0%)
0/32
(0%)
Tar-1
VI3
(30V.)
12/13
(
-------
nocarcincmas, occurring anywhere in the bronchial tree. Multiple tumors
were frequently seen. Hie intrabranchial adenanas were papillary. There
also were alveloar adenanas which were peripheral. Turrors of the lung
were diagnosed as adenocarcinomas only if there was invasion or if metas-
tases were cbserved.
Adenanas and carcinanas of the lung were cbserved in 60% to 100% of
the mice inhaling aerosols of coal tars, whereas tumors were not seen ir.
any of the control nice. Incidences of squamous metaplasia varied fraii
10% to 38% in treated mice and were absent in control nice. "Alveolar
epithelization" was also cbserved, but less often than squamous metaplasia.
Areas of squamous and alveolar metaplasia were not considered as tumors,
even when they occupied relatively large spaces.
(14) Kinkead, McConnell and Specht, and MacEwen
and Vernot
MacEwen and Veroot (1972-1974), Kinkead (1973), and McConnell and
Specht (1973) reported on a study in which mice, rats, hamsters, and rab-
bits were exposed to a coal tar aerosol fran which the light oil and solid
fraction was removed. Gross skin pathology for the nice was reported; any
other tumor response in the mice and in the other animals was not repor-
1/
ted.
Groups of 64 female yearling and 64 weanling (32 of each sex)
Sprague-Dawley rats, 50 male JAX-CAFl mice, and 50 male ICR-CFl mice were
1/ Per contractual agreement, Sasnore performed internal and skin
histopathology for the study and reported his results (Sasmore,
1976), but because information in the Sasraore report is in-
canplete, no conclusions can be made about the report.
(44)
-------
tsxi-cttwj continuously fur OL ways (enceyt fur 15 ;.j.nutuc a iay tc «licv for
aniri.1 r-ainten^ncc) tc concentrations of o.2, 2.1', unu iJ.L* : -jv. cL ccii
tor aerosol. Lic.ht^-tv.o ferule ye-riir/- ::yrc.^ue-Lav..ley rate, '-2 dinj
SyriCjue-L'uwliy rats (73 ior.&le ai*! 'j ;:^lt), 75 uiiit.- j^.-CrJTl .'dec, 75 :.i.lu
IC':—Ci'l ~ice, iCl i iJ.e cjclcer. L;irian hw.iturs, inc 14 1 ev Z^cAe-ia. w.it«
rabbits v/ere exycstC continuously, =£ aucve, for ti.c s^ne ^-riuu
3
tc a concentration of 20 . -::e centre! an u..sis: consist"-, cf -1 fc-
r.iLLi " 1 E/yi'c.yue-'I .<£/.•<¦ Isy '..eanlir.-j race, w«_ .a.ie L_.rc<.jCe"~i.c.. —
i'-j rats , ' I; i.«ale 1 _¦ i.i-le XV..."uE — *
-------
TABLE 11
TOMOR RESPONSE IN MALE ICR-CFl AND JAX-CAFl MICE FOLLOWING EXPOSURE
COAL TAR AEROSOL (Adapted fran McConrtell and Specht, 1973)
3 y y
Dose (mg/m ) ICR-CFl JAX-CAF1
2/
2/
20.0
10/36
(28%)
10/27
(37%)
3/
3/
10.0
3/8
(38%)
0/12
(0%)
3/
3/
2.0
2/25
(8%)
0/47
(0%)
3/
3/
0.2
0/2
(0%)
0/47
(0%)
2/
2/
0.0
0/62
(0%)
0/74
(0%)
1/ The numerator is the number of animals with timors at 415 days post
exposure. The denominator is the number of animals that vrere alive
at 93 days post exposure.
2/ This dose group began with 75 animals.
3/ This dose group began with 50 animals.
TABLE 12
LATSOT PERIOD OF FIRST TUMOR INDUCTION IN CIV-I EXPOSED ICR-CFl MICE
(McConnell and Specht/ 1973)
3
Dose (mg/m ) Time of Tumor Appearance (Days)
20 <93
10 128
2 142
(46)
-------
(15) ;-ciC^-or. VLrr.ct, 'zc~\ _r. et
. «ci.ven ere Vcixet (.1-75 li>7b) jjK.; : &i. (IL-Ti.) rc-
en r..o stu^i^s cf ri.e t'_ i."i: i.->=£\o:.j=e cf icc, lv-.u., r^~iti, u...
:-orufcys fciio;*incj e.vcsure to coil tur «orcu.l. Is; ti.& first stu.* , ...
Ltrl.xiXvi i]" L"C.-JUS-i.?A•• j.v<2£lTxir>j L'itS/ Oi- ^.r^V-JOe-i-£V>.i.£y '..tc:!_i.i; .-_• i_w-1 J
i.«iss are -tC' fts-tzles), 75 r.ice, 75 IC.;—Cirl ..isle- i.icc, cry
lit l.Clt
*^r rXuiii l.cj.st-^rs v.t ire Cwizoir
c^_.i iioL i .mutes £ ciw^ to cu-Ic., Lw/L c-T.j_ -u-1 int^r.^fiCc) wn- wOiiCtr."--"
3
— «* X . *" f • • W f >W A W • N*1 '» / I » W * V*b-> ^ (• ->» r ^-^C • t"J i UXt M • *'¦«* . •
i.e ^ercsci ir. i.is szucv \ r.c:
a ca.'.^siteo : i;:tcre cdlecTi-f ira . r.uitiyl*: cc;.i:v
covins ercur.u t:;-.r i-ric.ttr i-itt=~er^.: ere::, '_:.e col-.ir.^
cvtri -=ie ci i^veral ^ifferer.r ty.es -i^ u3cu c'.if-
iertr.t coed sources tor t..eii: stortiiv ; iit_-riils.
Ti:e ccke ever, effluents "*ti:e cclloct'^c'. ir. c.ir ccij.ec-
ticr. vlavices •_£ir.<._ a c.iilec vater i"iy to coreer-ie
t:.e i.iy.^r Lciii;%, Ciszillat- frecticiis. After ~ez-
tiiry. ire i-«r.£ration of tr.« ii-..i:i».. L'i^s.cz, t/.e varices
ccal tea: sc^:..: lt;3 '. ere- Ller.^'rv. to-jL-crei: ;.it:. c; LiA ~y
voiui« tu cur.t cf ti:fe :-1". (i.^nzis:.-«; tciuer«; ;ryiisr.i;5
frtcticr. cf the i.rticlc sizt uctt;r.-.i:v.ticr: in •Li:t ^::v-oi:u:-r c\.c: -.c.^ :er-
forr:ec, ^ri" it \ as fcui.ij tl:it a ;..i;-;i: .u:.. cf -7^ cf ciii ..r^. i^tw ¦.¦.•«i:-c i
re&^ir«i;ife rtnut or rivs ;-acrcn£ or I«ss i:~. viiJiX-tOiT. Cr.iy il-d.:: clj cr
rtes;cn£.u for t;.e : .ice '..as re.crtc-c. 13). Vu or ivs-crs'i vt-s r.c t
re;, or too icr t.:o i:«i: itc-rs ci: r«.ts.
x!\ S'rCL.r..^ SUuL-^* /— I'-ji-c.—~ C.r.v. i.LL I :"lvV V -
c-1; tlUi CI" £Li-C^_ 11^*^) | L-v - .. IC- • ^
tc.r.t ;.ri>. , •... :xi.i s:v. -=•..• Cri-. 5-trc.i:.
V
-------
TABLE 13
SKIN 1UM0K KESl-ONSK IN ICK-CFl ANIJ JAX-CAl'l MICE IXJLLUWINC; EXl-USUKE
IP COAL TAR ALKOSQL (MacLVcn arid Vernot, 197G) ,
y
Cumulative Num>x?r o£ Tumors
3 Week of 2/ ICH-CFl JAX-CAFl
Dose (inci/m ) Observation Exposed Control loosed Control
10
100
44/75
(59%)
3/75
(4%)
10/75
(24%)
1/75
(1%)
2
103
14/75
-------
ling rats, 18 New Zealand albino rabbits, and 5 male and 9 female f-lacaca
3
jiiulatta rronkeys were exposed to 10 mg/m of coal tar aerosol for 6 hours
each day, five days per week for 18 months. The coal tar used to generate
the aerosols in this study was the sanse as that of the first study. Aero-
sol particle size was determined monthly in the exposure chambers. A nini-
mun of 99% of the total droplets in both chambers vere 5 microns or less
in diameter and were thus within a resoirable sire range for rodents.
3
Exposure to the coal tar at 10 rrg/n significantly reduced the body
weight of rabbits and rats ccqpared with the controls, whereas monkeys
showed no significant change in body weight. Sixteen of 18 rabbits and
six control mice died during the test period. These deaths were attributed
to a chronic respiratory infection which caused debilitation and dehydra-
tion. At the conclusion of the exposure period, the test monkeys and the
surviving test rabbits along with the unexposed controls were delivered to
the KICSH Laboratories in Cincinnati, Ohio, for lcng-term post-exposure
observation, but the results were not reported in MacEven et al. (1976).
Discussion with MacEwen indicated that while the monkeys are still under
observation, the number of surviving rabbits (2 of 18) was too few for
statistical comparison, and those animals were sacrificed (Gibb, 1978a).
Ko turor response was found in the sacrificed rabbits (Gibb, 1978b). ~
Alveolargenic carcincnas vere produced in 26 of 61 (43%) ICR-CFl
mice and in 27 of 50 (54%) JAX-CAFl mice. The number of tumors in the
IC3-CF1 and the JAX-CAFl control mice were 3 of 68 (4%) and 8 of 48 (17%),
respectively. The exposed and control groups did not differ in the inci-
dence cf other types of tumors including squamous cell carcincnas, lympno-
(49)
-------
s^rccr^s, subcutaneous sarcu..as, ulveoiarvcr.ic acenQ..as, L-tonc^io^enic car
citicras, reticulum. cell sarcomas, Lev-an-icsarca.Uss, and fte.'.o:.oietic tui.crs
Shin tuners were i-rujuc&d in b ct (?•*) cf ti^e ICI.-Cxi ;..ic* anu
2 cf 5U (-.'¦<) of the J<*.-CAF1 ;:.ice as ca.;;arud to 3 of 75 (3\.) ai:o i or St
(2%) in the ICK-CFl and J/'-X-O"!"! controls, res^ctivtiy. U;
-------
V
tabm: 14
GOAL TAX 'lUHORlCiaJIJSIS IN RATS
(NiicL'uen, 1976)
H ol-
Controls Kx[->osed
Males Females Moles Females
V
lJumlx?r examined Histologically 30 37 3U 30
Nuinljer of Rats with Tumors:
Squamous Cell Careinana, Lung 0 0 3U 31
Sguaceous Cell Carcincita 0 1 0 0
Intraabdominal Carcinana 0 1 0 0
Mamuary Fibruadenana 0 1 0 3
Mammary Adenocarcinoma 0 1 0 0
Other Tuiiiors 0 1 0 2
Overall Tumor Incidence (%) 0 13 100 H2
1/ The original nunAjer of rats ptr group was 40. However, localise of
autolysis and/or cannihalization, a few animals were unsuited for
histo|>atlio logical exciminations.
»
(51)
-------
.'.any araratic hydrccarLcns sucn as tkufcc icu:u in cciil tar aire ?,.t.
tc fluoresce. .Hioe (skir. and hair) tissue cin..5.1ss taker. during tr.e o:ixisvi'-j
tAjrioo fro:. the ICi'.-CFl i.iice in tlx seccrv- exyerii e:it 'were extracteo v.itl: to-
luene aix. anal yz to icr fluorescent content, insults are i'cunc. in Taoi-c 15.
iiiOe fluorescence curing ex^sure cc-rrtlatec vith tl» turcr response.
3. Creosote
Keycrts ci workers wise cevtlqieti cancer suL£sc;uent tc creosotc-
e::^'sure Lave doen reycrtc-d in ti.e literature. The fclla-;i:x, is a
c:ircr.clex*ica- Library or these reverts.
a. Case Hetcrts of Ski;. Cancer in Workers
(1) : .ackenzie
'ackenziv (lo^C) reported the case or a r.ar. e*.ylc;,ed fcr years
diyyin-i;, railway lies in licuiu creosote in an air-tioht cha^i.er. Ti.e
V/crker stated that ciily his cr..s and henot ca..e into contact v.itI. ti.-
cri-yirx. pianks. In several yiaces cn his fcr^arr.a, tnere \.ere n£h_.'.
elevations of a >.arty character about ti.e s::= of sylit :<=as." L~ the
ri-.ji.t half of the yatient1 s scroti:. i.ere several yav.iilu.atcus ^..ellin^s
fra.. the size of a yea to that of a ni_t, rather sort Out covered '..it:, u
i.eny crust and sore tc the touch. 1'i.e yatient had yicked several off,
leaving a Lleeoinc; surges. Ai.e author su^-eotcd that the to; crs ..'--re
likely to occore <=_. itholioi.;c.tcus.
(2) c' r.onovan
C'Loncvar. (1SLC) lists three cas=s of s,.ir. cancer of r.er. ccc.:/a-
tic:.allj exacted to creosote; too- of ti.t . ,s_:: crecsctec uocd, a;x: one
yickled v;co*. in cieusotc. -d'Lcncvar. details.-- t/.c case of one .'.an •>.!.•.•
(5L)
-------
TABLE 15
2
SUMMARY OF HIDE FLUORESCENCE (uq/cm ) OF ICR-CFl MICE DURING
AND AFTER EXPOSURE TO GOAL TAR AEROSOL
ICR-CFl Mouse
Days of Exposure 30 Days Skin TUmors at
Dose (mg/m )
1
7
30
60
90
Post-Exposure
100 Weeks
10.0
26.9
34.9
19.2
•
23.8
21.6
0
44/75 (59%)
2.0
2.4
9.3
7.6
4.4
9.9
0
14/75 (19%)
0.2
0.4
1.6
4.9
1.0
3.8
0
1/75 (1%)
(53)
-------
had been creosoting timber for 40 years. Karts had appeared on his hands,
legs, and behind his ears seven years prior to reporting his case. The
warts had fallen off and left scars behind then. Eighteen Tenths before
the case was reported, a wart on the patient's scrotum had fallen off,
leaving a grail sore which never healed and steadily enlarged. Three
months before admission to the hospital, the glands of the left groin en-
larged; the patient steadily lost weight and grew weaker. Cn admission
to the hospital, the case was considered inoperable.
(3) Cookson
Cookson (1924) reported an a worker employed for 33 years to carry
crecsoted wood. At least 15 years before the case was reported, a snail
swelling appeared an the back of the worker's right hand, ^fce swelling
would occasionally break open and then heal again. About 7 years later,
the swelling increased substantially in size until the growth had to be
renoved. A portion was examined histologically prior to being excised
and proved to be a squamous epithelicna. Following the patient's death
several years later, an autopsy was performed, and small secondary epi-
thelicna tous deposits were found in the liver, both lungs, and in both
kidneys. There were also two secondary deposits in the heart walls.
One in the left ventricular wall involving its whole thickness was the
size of a walnut and was beginning to break dewn in the interior. The
other was the size of a pea at the right border of the right ventricle.
(4) Henrv
Henry (1947) reviewed 753 cases of cutaneous epithelicrata re-
ported to the British Medical Inspector of Factories free. 1320 to 1945
(54)
-------
and found 37 cases attributable to creosote exposure. Of these cases 14
occurred among workers treating timber, 9 among people handling creosote
in storage, and 10 among people using creosote as a releasing agent for
brick molds. One case of epithelioma was reported among workers using
creosote for the manufacture of furnace crucibles, and one case among
workers manufacturing creosote disinfectants. Hie author also reports
two cases of cutaneous cancer not reported to the British Medical In-
spector of Factories: a railway platelayer handling creosoted ties and
an assistant chemist testing creosote for 16 months in a tar distillery
laboratory.
(3) Lenson
Lenson (1956) described a shipyard worker who had worked with creo-
sote for three years. Malignant cutaneous tumors of the face appeared 5
years after working with the creosote. The worker had been a painter for
41 years and had mixed his own paints, using lead and oils. Turpentine
and white gasoline had been used as paint removers,
b. Animal Studies
The following 6 animal studies are presented chronologically. In
general they show that tumors were produced following dermal exposure to
creosote. As with coal tar, the Working Group notes that the interpreta-
tion of seme of the early studies is limited by the absence of ccntroL
data. However, later studies which include appropriate control groups
generally confirm and reinforce the observations in the early studies.
(1) Sail and Shear
Sail and Shear (lS4u) reported an several experrnents which tested
(55)
-------
the potential of the basic fractions of creosote to accelerate tumor pro-
duction by known carcinogens. Percale Strain A mice obtained frar. the
Roscoe B. Jackson Meirorial Laboratory in Bar Harbor, Maine, were used in
all the experiments which included administration by skin painting and
subcutaneous injection. In the skin painting experiments a mixture of 1%
basic creosote and either 0.02% or 0.05% benzo[a]pyrene was applied three
times per week to the treated anirals. Concentrations of benzo[a]pyrene,
at 0.02% and 0.05% were used alone for two control groups; another con-
trol group was painted with 1% basic creosote alone. There were no con-
trol groups in which healthy anirals *
-------
papillomas and 9 carcinaiias) were reported. This was the highest number
of tumors in the 10 treatment groups tested. There was no control group.
(3) Lijinskv et al.
A study by Lijinsky et al. (1956) evaluated creosote and its basic
fracton as possible tumor-prcnoting agents. The experixnent failed tc dem-
onstrate that creosote acts as a strong prareter when administered to nice
receiving a single painting of 7,12-dinethylbenzla]anthrancene (niEA), but
) it did demonstrate that creosote is independently carcinogenic.
o
The creosote used was a "#1 oil, dry point 240 C, collected as a
distillation fraction frcm a V.'ilton still." The basic fraction was pre-
pared by the procedure of Cabot et al. (194U). Treatments were given
twice weekly for 70 weeks to four groups of 30 female Swiss mice, k sirr
. gle drop of the treatment solution was applied with a glass dropper to
the intrascapular region of the skin, which was kept free of hair by clip-
ping with scissors. A control group (Group 1) consisting of 5u mice was
treated with the initiating agent, 7,12-airethylbenz[a]anthrancene (DtiEA)
given as a 1% solution in mineral oil. Group 2 was painted with undiluted
creosote. The three retraining groups received a single initial painting
of 1% EISA in mineral oil; one week later they were treated with undiluted
creosote (Group 3), 10% creosote in acetone (Group 4), or a 2% basic frac-
tion of creosote solution in acetone (Group 5). There were no control
groups in which healthy aniirals were used for caparison.
The tumor incidence in the five groups is shown in Table 16. The
survival rate of the control animals given U'Eh alone was not given; what-
ever their nurber, none of then were reported tc have developed tuners.
(57)
-------
TAULU 16
SKIN TUMUK INCIDENCE IN MICE THEATEI) Willi amOSOTE
Carcinogen Assessment Group (CAG), 11)77
Initial IV/ice Weekly Incidence oE YJ Nos. of Nos7~o£
Group Painting Painting TumotMlearing Mice Papillotnas Carcinomas
Average Latent
Period (weeks)
1% LMMA None
0/50 (0%)
None
1* LflliA
1% LMI1A
1% IM»A
Creosote:
undiluted
Creosote:
undiluted
Creosote
10% in Acetone
Creosote: 2%
Basic Fraction
1J/26 (50%)
17/23 (71%)
11/2'J (311%)
0/12 (0%)
16
26
50
39
43
1/ In group 1 there were 50 animals initially. In groups 2, 3, and 4 the denominator-
is the nunJjer oC survivors at time o£ appearance oC first tuinor. In yroup 5 there
there were 12 survivors at 56 weeks.
(5U)
-------
In contrast, there was a high tumor rate for animals pre-treated with EMBA
and then treated repetitively with either undiluted or 10% creosote. Seme
enhancement of the action of a single initiating dose of D-1BA was noted
when given with undiluted creosote (50% vs. 74%), although the difference
was not significant. Dilution of the creosote to 10% in acetone diminished
the tunor producing action of cr-iBA plus creosote, while the basic fraction
did not prove to be oncogenic.
In a canpanion study (Lijinsky et al., 1956) the creosote was chen*-
ically analyzed for benzola]pyrene, but less than 100 mg of benzo[a]pyrene
was found per liter of creosote, an arount the authors consider too snail
to account for the carcinogenic activity of creosote, They suggested tiiat
sere of the carcinogenic activity may result frcn the presence of benzla}
anthracene which was found in a relatively large quantity (2.75 cr/liter).
The results of this study showed that undiluted creosote alor.e pro-
duced a carcinogenic effect which was slightly augmented by the initial
EMBA. treatment, vihen the creosote was diluted to 10% the prcroting ac-
tion was scnewhat diminished in relation to the undiluted creosote. The
basic fraction of creosote at a 2% strength was inactive. The authors
reported that the carcinogenic potential of the undiluted creosote was
comparable to results founo with EMEA, a potent carcinogen, in a similar
test conducted at the sane laboratory.
(4) Poel and Karer
Poel and Karsner (1957) tested two "creosote oils" for carcinogenic
potential on rale and female mice. In the introduction to their report,
Poel and llsnrez described the difference between the definitions of coal
(59)
-------
tar fractions as they are classically defined and coal tar fractions as
they are industrially used:
The crude industrial fractions distilled fro:, high-
temperature coal tars are designated light oil/ middle
oil or napthalene crude cut/ heavy creosote oil/ an-
thracene oil and pitch {Table 17). k clear cut separa-
tion of tar into these distinctive fractions is usually
not practiced on an industrial scale. In fact, such
terns as creosote/ heavy oil, and anthracene oil have
been used synonymously, while certain industries to
this day designate sere pitches as "tars". licet of the
Clarke ted oil products are blends or smears, containing
both creosote and anthracene oils plus varying amounts
of the residual fractions fran the middle-oil cut - the
fraction shown in Table 17 to have a boiling range of
2C0 to 250 C.
The two "creosote oils" used in the study were described by Peel
and Kar.iner as follows:
Both are fractions frcrt a high— teirperature horizontal
by-product-coke-oven tar. One is a crystal-free oil,
carketed as a blend of creosote, anthracene oils, and
the oil drained fran the naphtlialene recovery opera-
tion. This blend of oils has been described as non-
toxic to hurrans and is used principally for the pre-
servation of wood.... The second sanple, considered
a light creosote oil industrially [Table 17} is the
residual oil drained frcn the naphthalene recovery
operation.
The blended sample was tested in toluene at two dilution levels,
20% and 80%; the light creosote oil was tested at a 50% dilution in to-
luene. As a positive control, benzola]pyrene was tested in toluene at
two dilution levels, 0.05% and 0.25%. Toluene was tested as a negative
control.
The test anirrals were C57L rice, ferules, 10 to 12 weeks old and
rales 8 to 11 weeks old. The test solution was applied three tires per
week on the shaved Lack of each rouse for its lifespan or until persis-
(60)
-------
'i/'i.u: 17
ckui i; upai. i/,i- distiuv/iL;;; (ix>i:i. mid i>aiit:i:u. r.n/7)
/>[! roxmule LVuctiun
llis-.til liilion Ifccwurtcl
Iinitiiit.vial Cut lUirKie ((C) I'ran 'I'.ir (%)
ri"iricij>nl Cuii|X>nc}ntr.
of Fuictiuti
I.i-jhl oil
Hirldle oil
Cl' 300
f>2
I'ib.li Oil, Ciiilioii
(t>l)
»
-------
tent papillomas developed at the application site. Hesults of the test
are found in Table 18.
These results show a significant increase in tumor incidence after
topical treatment with both concentrations of blended creosote as com-
pared to the incidence produced by the toluene control. All mice exposed
to both dilutions of the blended creosote oil developed papillomas, and
7 of the 8 in each dilution group developed carcincnas. toonc the creo-
sote-treated animals that developed carcincnas, 5 of 14 had metastatic
growths in the lungs and/or the regional lyraph nodes. The 50% solution
of light creosote oil in toluene produced tumors in all 11 rale C57L-rdce
tested, after exposure ranging frar, 22 to 41 weeks. It was not reported
whether the tumors were malignant or not. The presence of benzo[a]pyrene
was tested for in light creosote oil and in the anthracene fraction of the
blended creosote oil (where it roost likely would be found). Detectable
levels were not observed, and the authors concluded that the tumor res-
ponse seen was due, at least in part, to other agents.
In surmary, dermal application of light and blended creosote oils
frcn high-temperature-coke-oven-tars induced significant increases in
skin tunors on mice. Most of the tumors frar. the blended oil were car-
cinomas.
(5) Boutwell and Bosch
In a study which evaluated the tumor initiating and prcncting ac-
tivity of several chemicals, including creosote, and the carcinogenic po-
tential of creosote without the use of initiating or prcnoting agents,
Boutwell and Ecsch (195S) found that creosote was carcinogenic when ap-
(62)
-------
TABLE 16
TU>DR IKPUCTICN IK C57L MICE TREATED VTIHi BLEI.DED 1/
CREOSOTE, LIGHT CREOSOTE, BLN2Q [a] PYPJE^E, K.'L TOLL'S £
Cone, in
Test Material Toluene(%)
to. Mice
with Tuners
No. Mice with
EDiaerral Cancer
to. Mice with
Metastasis
5/
Creosote Blend 80
fcreosote Blend 20
Light Creosote 50
Benzol a] pyrene 0.25
E-enzc [a] pyrene 0.05
Toluene Control 0.0
8/8 (100%)
8/8 (100%)'
i
11/11 (100%)"
8/8 (100%)'
8/9 (89%)
0/10 (0%)
2/
r
2/
)
£/
>
2/
7/8 (88%)
7/8 (88%)"
3/8 (100%:
7/9 (78%)
0/10 (0%)
y
i
3/
2/
3
2
2
1
0
1/ Ferale C57L mice were used in all croups except light creosote which
used irvales.
-5
2/ Significantly higher than controls (d - 2.3 x 10 ).
—4
3/ Significantly higher than controls (p = 2.5 x 10 ).
—6
4/ Significantly higher than controls (p = 2.8 x 10 ).
5/ The light creosote oil was . administered as one crop of 50% (in toluene]
creosote oil along with one drop of toluene.
(63)
-------
plied to mouse skin, and that it had the ability to initiate tumor forma-
tion when applied for a limited period prior to treatment with croton oil.
The mice used in the test were 8-week old, randcr—bred ferale aloino nice.
The creosote was tested at full strength as obtained from Barrett
Chemical Company. The trade name of the oil is Carbasota. It is described
as "fractions distilled frcn a high temperature coke-oven-tar in the boil-
ing range of 200 to over 400°C." Croton oil and EHBA used in the study
were dissolved in re-distilled benzene. Solutions were protected fran ex-
posure to light and evaporation.
The solutions were applied as a 25 ul drcp to the shaved skin of
the back. Mice were inspected for tunors weekly and papillcnas larger
than 1 m in diameter were counted. Hie gross identification of both
benign and malignant tuners was confirmed periodically by microscopic
examination.
There were 30 female mice in each group. The group applications
were as follows: (Group 1} one drcp (25 ul) of urailuted creosote twic^-
weekly with no initial treatment; (Group 2) one application of 75 ug CHBA
followed (one week later) with 25 ul of benzene twice-weekly; (Graip 3)
single applications of EHBA as in Group 2, followed after one week with
twice-weekly applications of 25 ul undiluted creosote; (Group 4) same
initial treatment as in Groups 2 and 3 but followed with twice-weekly
applications of 25 ul of a 0.5% croton oil in benzene solution; (Group
5) croton oil alone with no pre-treatment; (Group 6) undiluted creosote
twice-weekly for four weeks only with no secondary treatment; (Group 7)
undiluted creosote twice-weekly for four weeks followed with croton oil
(64)
-------
as in Groups 4 and 5. There were no controls in which healthy anijnals
were used for conparison. The length of observation of each group was
determined by the carcinogenic response (Table 19).
Papillcras and carcinomas developed in all groups given creosote
except Group 6, where the duration of treatment nay not have been long
enough. Comparison of the results frcn Groups 6 and 7 show that creosote
can act as an initiating agent prior to the application of crotcn oil.
Pre-treatsient with EMBA slightly reduces the induction tire of turgors
produced by repeated continuous creosote administration.
(6) Roe et al.
Roe et al. (1958) found that anirals receiving cetral applica-
tions of creosote developed turors of the skin and the lungs. The study
consisted of two experiments. Two to three-ncnth old nice were obtained
fran a coxiercial breeder for the first experiinent. Prior to treating
with creosote, the authors observed a total of 7S8 lung adenccas. on the
lobe surface of the lungs of 138 race (an average of 5.8 adenonas per
mouse) at 6-8 months of age. Since the cu.iercial breeder had used creo-
soted wooden boxes to house the aniisals, it was determined that the lung
adenaras were the result of housing the anir-als in these boxes. Scne of
these irdce were alleged to breed in steel cages in the laboratory. The
resulting progeny were found to have an average of only 0.5 adenonas per
animal. Two groups of tits fourth generation of the original nice were
used in the first experirent. One group was bred in stainless steel cages
and 24 of the resulting progeny (Group 1) v«re kept as untreated controls
for eight months. Twenty-five progeny (Group 2) were treated twice-weekly
(65)
-------
TAIJLi: 19
SCIIliUUIJS OK TKEATMHWTS AND 1UMOR INCIDtaCC IN MICE LXKJSLD ID DMBA AND Q(LOtK/fE
Secondary Period of Induction Time Incidence 1/
Initial Treatment Treatment and Carcincmas of Carcincrias
Group Treatment (2x/wk) Observation (wks) (wks) (%J
y
1
None
Creosote
2H
26
82
2
75 uy DMIVA
benzene
56
3
75 uq 1/lllA
Creosote
2 U
23
y
82
4
75 u
-------
on the backs with one drop (25 ul) of creosote oil (Carbasota) from the
age of three weeks until six months and were observed for two months lon-
ger. The Carbasota was produced by the Barrett Chemical Ccrnpany and was
described as "a material in the boiling range of 20U°C to ever 40U°C
distilled fran a high temperature coke-overr-tar." Progeny frun the second
group of the fourth generation mice were bred in wooden cages which were
"thoroughly impregnated with creosote oil." They produced 29 young (Group
3). Group 3 mice were kept in the cages for the duration of the experiment
and were treated for five r-onths with one drop (25 ul) of creosote oil (Car-
basota) applied twice-weekly after which they were kept for three months
without treatment. After eight months Group 1 had an average of less than
0.5 adencnas per mouse. Group 2 had almost six per irouse and Group 3 al-
most 11 per mouse (Table 20, Experiment 1). Groups 2 and 3 together totaled
53 mice. Of this number, 5 bore skin tumors but no lung tumors; nine had
lung tuners but no skin tumors; and 39 bore both skin and lung tumors.
The incidence of skin and lung tumors in the controls was not given; there-
fore, a statistical analysis of the control versus the experimental groups
is not possible. However, the total number of lung acencmas in Groups
2 and 3 was greatly increased over those of the controls (Group 1).
In the second experiment, randa?-bred albino'mice were obtained
fran a supplier who used only metal cages for breeding. The control
group (Group 1) of 50 animals consisted of toco groups frcn a related
study (Boutwell and Bcsch, 1958), in which one group was treated initi-
ally with 75 ug of I2EA followed by a twice-weekly application of 25 ul
of a 0.5% solution (w/v) of crcton oil in benzene? and the other group
(67)
-------
TABLE 20
THE EFFECTS OF CREOSOTE TREAJMECT ON TOE INCIDEEO: OF LUNG
ADENQ'''iAS (Carcinogen Assessment Group, 1977}
Experiment GrouD Treatment
No. of Mice
Adenaaas
on Lung
Surfaces
Adentxias
per Mouse
1 None {control)
2 One drop of creosote
2 times/week for 23
weeks
3 One crop of creosote
2 tires/week for 19
weeks in creosotea
Cages
19
24
29
9
139
315
0.5
5.8
10.8
2 1 Initial treatment with 50 15 0.3
75 ug of DMEA followed
by one drop of croton oil
or benzene 2 times/week
for approximately 55
weeeks (control)
2 One drcp of creosote 2 23 37 1.6
times/week for 4 weeks.
(68)
-------
was treated initially with 75 ug of EMEk followed by a twice-weehly appli-
cation of 25 ul of benzene. l-:in tuixsrs were reported for any of the nice in Experiment 2.
4. Coal Tar "eutral Oil
No huran studies were found on coal tar neutral oil. Che following
three aniral studies on coal tar neutral oil are presented chronologically.
(1) Cabot et al.
Cabot et al. (1940) painted albino "market" nice with benzene so-
lutions of various creosote oil fractions together with fcenso[a]pyrene.
The fractions of creosote were prepared frcn a creosote oil obtained frcrn
a vertical-retort coal tar; 9C% of the crecsote oil distilled between
o o
160 C and 300 C (Fraction 1). The basic constituents were first rercved
frcn creosote with aqueous hydrochloric acid (Fraction II); the phenols
were removed with acueous sodiun hydroxide (Fraction III). T3^e rerfin-
ing neutral iraterial (Fraction IV) was stean distilled, producing "neu-
tral distillate" or neutral oil (Fraction V), and leaving the "neutral
residue " (Fraction VI). The six fractions were dissolved in benzene con-
taining either 0.2% ,cr 0.05% benzc[a]pyrene. Tliese solutions were painted
on groups of 20 nice three tires weekly for 2C weeks. Thereafter, the
(6S)
-------
solutions containing 0.2% benzole]pyrene were applied twice-weekly for six
additional weeks. With the solutions containing 0.05% benzo [ a) pyrene, the
the painting was continued three times per week for an additional 18 weeks.
When a papilloma appeared/ painting was continued until the skin growth
attained an average diameter of about 4 millimeters. Control groups were
painted with benzene solutions containing either 0.2% or 0.05% benzo [a]
pyrene. No untreated controls were used.
Skin tumors occurred sooner and with greater incidence in animals
tested with the high benzpvrene concentration than with the low concen-
tration treatments. Four of the fractions had lc*er rates of tumor for-
mation than the rates produced by benzola]pyrene alone. These four frac-
tions were the parent creosote mixture, the phenolic fraction, the concen-
trated neutral distillate, and the neutral residue. The authors attributed
the inhibitory effect of all but the phenolic fraction to skin da*fl2ge, but
suggested further experiments on the inhibition mechanism of phenolic
fractions. Of the two promoting fractions, only the basic fraction had an
enhancing effect at both ben2o[a]pyrene concentrations.
(2) Berenblum and Schoental
Berenblum and Schoental (1947) extracted a horizontal-retort gas
1/
tar with light petroleum, then removed basic and acidic constituents, by
shaking with dilute HCl followed by dilute NaQH. !Ihe remaining neutral
1/ Although gas tar is made fran coal, it is somewhat different from bi-
tuminous ccking operation coal tar which is used for pesticide produc-
tion in the United States. 3he Working Group, however, decided that
the physical and chemical characteristics of the two are similar enough
to make the results of this study relevant..
(70)
-------
fraction was chrcnatographed and five coal tar neutral oil fractions
were separated:
I. All bands up to and including anthracene
II. After anthracene, before benzotalpyrene
III. Benzola]pyrene bands
IV. Fluorescence bands 351, 412, arri 430 rau.
V. Fluorescence bands at 385 rcu, and residue
Ihe fractions were tested dermally on groups of 10 mice and 5 rab-
bits, for periods of 17-26 weeks, and were applied cnce a week on nice
and twice a week on rabbits. I-
-------
arc bases had been removed were subjected to repeated contact with r.a-
leic anhydride in benzene solution at bO°C to extract the neutral an-
thracene-type or hydrocarbons (the neutral oils). Zhe adaucts formed
with rcaleic anhydride were mixed with powdered soda-line, and the neu-
tral oil was regenerated by short path distillation at a dull red heat
at atmospheric pressure. The retraining residue after extraction of the
tar acids, the tar bases, and the neutral oil hydrocarbons was called
the residual tar. Che tar acids and the tar bases were dissolved in ben-
zene at a concentration equivalent to their concentrations ir. the origi-
nal coal tar. The maleic anhydride fraction (the neutral oil) was tested
in a 1% solution of benzene. Ihe residual crude tars were tested at 1C0%
concentration; in addition, one of the crude tars was tested at a 5U% con-
centration in benzene.
Tterrmg coses of the two coal tars ana the diluted coal tar were
deroally applied twice-weekly to mouse skin (the number and strain of
mice tested was not stated), and 10-mg coses of the fractions and re-
sidual tars were applied three times per week, tto untreated controls
were used. Ihe time of the tuoor appearance was noted, and the relative
carcinogenic potency of the different test substances was calculated on
the basis of differences in time-to-tunvor. This index was referred tc
as the potency for a minimum concentration of material (PMC). A high
PMC value means a greater carcinogenic potency. Skin tumors appeared
most quickly frcn the residual and crude tars: 24.8 and 23.6 weeks and
18.4 and 13.4 weeks fran their respective residual tars, to tuners were
reported fran the acidic fractions of either tar. The basic fractions
(72)
-------
of the two tars produced tumors in 48.6 and 40.6 weeks, respectively, and
the coal tar neutral oils (rcaleic anhydride extracts) fran the two tars
produced tumors in 34.1 and 32.1 weeks. The PMC values indicated that
the residual and crude tars were roost carcinogenic, with calculated values
of 0.14 and 0.22 for the residual tars and 0.13 and 0.14 for the crude
tars. PMC values for the coal tar neutral oils were 0.05 and 0.06; the
PMC values for the basic fractions were 0.03 and 0.04. Since no tumors
were produced by the acidic fractions, PMC values were not calculated.
5. Conclusion
a. Coal Tar
Shanbaugh (1935), Mauro (1951), and Bosmanith (1953) reported on
fishermen and net loft workers, tar distillery workers, and a tar worker,
respectively, who had been occupationally exposed to coal tar and who had
developed skin cancer. In animal studies, dermal application of coal tar
produced skin tumors with mice [Horton (1961), Shabad et al. (1971),
Watson and Mellanby (1930), Tsuitsui (1918), Hueper and Payne (1960),
Deelman (1962), Bonser and Manch (1932), Gorski (1959), and Kennaway
(1925)], and rabbits [Yarcagiwa and Ichikawa (1915)]. Inhalation exposure
to coal tarr produced lung tumors in mice [Horton (1961), MacEwen et al.
(1976), Horton et al. (1963), and Tye and Steramer (1967)], and rats [MacEwen
et al. (1976)]. Exposure of mice to coal tar aerosol also produced skin
tumors (McConnel and Specht, 1973; and MacEwen et al. 1976).
Horton (1961) found a dose response for skin tumors in mice follow-
ing dermal application of coal tar. McConnell and Specht (1973) and
(73)
-------
Ilaci^wen ard Vernct (1576) found a dose response for skin turrors in ICK-CFl
rice following inhalation exposure to coal tar aerosol, hcrton (1561)
and KcConnell and Specnt (1973) also found tliat the tinie-to-turcr •was dose-
related.
The Working Group concludes tliat coal tar produced tumors in three
species of animals: rice, rats, and rabbits; that tuner response and tir.e-
to-tunor in the Horton (1561), McConnell and Specht (1973), and liacLven
and Vernct (1976) studies were, dose-related; and that workers-occupation-
ally exposed to coal tar developed tutors. The working Group thus con-
cludes that coal tar is an oncogen and that it exceeds the criteria of 4C
CFR 162.11(a)(3)(ii)(A). Accordingly, the Agency is issuing a rebuttable
presunption acainst all pesticides containing coal tar.
b. Creosote
Kenry (1947), Lenson (1S56), C'Lcncvan (1S2C), Cockscn (1524), and
Mackenzie (18S>£) described various kinds cf workers who were occupaticn-
ally exposed to creosote and developed skin turors. Derr^l applicaticr.
of creosote produced skin turrors in nice (Woodhouse (1950), Poel and
Kamer (1257), Lijinsky et al. (1S56), Ecutwell and Bosch (1S5&), anc
Roe et al. (1558)]. Roe et al. (1958) also found that cecr-al application
of creosote to nice produced lung tuners. Eoutweil and Bosch (lS5o)_
found that creosote had the ability' to initiate tur.cr foration when ap-
plied for a limited period prior to treatr-ent with croton oil. Sail and
Shear (1940) found that the nur.be r cf skin turors was increased by der-
mal treats,£nt with creosote and benzc[a)pyrene over the number cf turors
produced by benzc [ a] pyrene cr creosote alone. I^.e Working Group ccr.-
(74)
-------
eludes that creosote produces tur.ors in nice; that creosote, when applied
aenrally, is a tumor-initiating agent v^hen followed by cenral treatment
with croton oil (Boutwell and Bosch, 1958); that creosote accelerates the
tunor production caused by benzola]pyrene (Sail and Shear, 1940); and
that workers occupetionally exposed to creosote developed turrors. The
Working Group concludes that creosote is an oncogen and exceeds the cri-
teria of 40 CFR 162.11 (a)(3){ii)(A). Accordingly, the Agency is issuing
a rebuttable presunption against all pesticides containing coal tar.
c. . Coal Tar Neutral Cil
Korton (1961) found that derral application of coal tar neutral
oil to mice produced skin tumors. Eerenblum and Schcentiial (1547) found
that several chraratographic fractions of coal tar neutral cil produced
skin tumors when demally applied to -dee. Cabot et al. (1S4D) found
that fixtures of coal tar neutral cil with benzo[a]pyrene decreased the
number of tuners produced by benzo[a]pyrene alone, but suggested that
this inhibiting effect was due to skin oarage. The 'Working Group con-
cludes that coal tar neutral oil produces tuners in r.ice, and that as an
oncogen, it exceeds the criteria of 40 CFR 162.11(a)(3)(ii)(A). Accord-
ingly, the Agency is issuing a rebuttable presurpticn against all pesti-
cides containing coal tar neutral oil.
B. Hutagenicity
40 CFR 162.11(a)(3)(ii)(A) pruvides that "a rebuttable presumption
shall arise if a pesticide's ingredient(s), metabolite (s), or degradation
procuct(s)... induces mutagenic effects, as detenr-ined by raoititest evi-
dence."
(75)
-------
In determining that this criteria was exceeded, the Working Group
considered reports by Simmon and Poole (1978) and Mitchell and Tajiri
(1978) who examined a creosote mixture of American Wood Preservers' Asso-
ciation (AWPA) specification P-l and a coal tar-creosote mixture of *WPA
specification P-2, Class C. The £WPA specifications for P-l and P-2,
Class C, are found in Appendices A and B. P-l creosote is used for founda-
tion piles, fresh-water piles, telephone poles, utility poles, fence posts,
and other land and fresh-water uses. Class C P-2 coal tar-creosote is
used primarily for railroad ties (Gibb, 1978c). In vitro microbiological
assays with four strains of Salmonella typhimuriura, TA 1535, TA 1537, TA
98, and TA 100, and Escherichia coli WP2 (Simmon and Poole, 1978) and in
vitro mammalian cell bioassays with L5178Y mouse lymphoma cells (Mitchell
and Tajiri, 1978) were conducted an both of the coal tar-crecsote mixtures.
1. Siitraon and Poole
Simmon and Poole (1978) conducted in vitro microbiological mutagenic
assays on P-l and P-2 using Salmonella typhimurium and Escherichia coli
strains. Ihese microbiological assays were "conducted both with and without
metabolic activation. Metabolic activation was provided by use of an Aro-
chlor 1254-stimulated rat liver hcmogenate. Metabolic activation provides
metabolic steps that the bacteria either are incapable of conducting jor
do not carry out under the assay conditions.
Hie Salmonella strains used were all histidine auxotraphs. Uiey
included: Strains TA 1537 and TA98 which are sensitive to frameshift mu-
tations, TA 1535 which is sensitive to base-pair substitutions, and TA 100
which is sensitive to base-pair substitutions and sane frameshift mutations.
The E. coli WP2 strain is a tryptophan auxotrcch and is sensitive to base-
(76)
-------
pair substitutions. The results of the mutagen tests on Fl and Y2 are
found in Table 21.
Except at the higher doses which were toxic, creosote PI and coal
tar-crecsote P2, Class C, when netabolically activated, cenonstrated a
mutagenic dose-response and a doubling ever the background level in the
bacterial assay with Salironella tynhirmriur. strains TA 1537, TA 98, and
TA IOC. typhiruriun strain TA 1535 and coli strain V.T2 did not
demonstrate a positive mutagenic response with iretabolic activation.
None of the strains demonstrated a positive response without activation.
The fact that a mutagenic dose-response was fcund in the TA 1537, TA DC,
and TA 100 S^_ typhirturiun strains indicates that the mutagenic node of
action of the creosote and the creosote-coal tar mixture is by frareshift
station.
2. Kitchell and Tajiri
Mitchell and Tajiri (1S7S) tested creosote of Pw.TA specification
PI and a coal tar-crecsote mixture of ?J-;PA specification P2, Class C, for
mutagenic activity on an in vitro naroalian mutagenesis assay using L517CY
mouse lyrphcna cells heterozygous at the thymidine kinase {TK) locus. The
purpose of the test was to determine the effects of•the Pi and P2 nixture
on the forward nutation frequency of the TK locus, TK+// —» TK ^ , t&la-
tive to the background level. Similar to the nicrcbial assay described
above, the rouse lyrphcma study was conducted both with and without meta-
bolic activation using an Arochlor 1254 stinulatec rat liver licrccenate
nixture.
The nouse lyrphcna cells were crwn ir. suspension culture. The
{77)
-------
TABLE 21
IN VITRO ASSAYS SAL'-EKELLA TYPHIMURIUM AND ESCHERICHIA COLI
(Sij.Ticn and Poole, 197B)
Arount of
Sarr.ple Average dumber of Revertants Per Plate
Metabolic Added Per S. typhinuriur. E. coli
Sanole Activation Plate (ua) TA1535 TA1537 TAS& TAlOO WP2
Neqative Control
Positive Control
9-Aninoacrid ine
2-Anthrariine
Creosote PI
-
25
8
27
136
47
+
17
8
41
154
44
ICO
671
+
2.5
17 S
1017
1211
+
10
542*
_
5*
26
6
17
142
39
-
10
32
6
2tf
132
39
-
50
37
5
25
123
42
—
100
34
7
IB
137
34
-
250*
25
4
16
75
39
-
500
m
a
4
16
•m
A
37
-
1000*
m
A
1-0
26
—
5000*
m
X
T
+
5*
12
11
52
212
45
+
10
20
14
60
215
49
+
50
19
22
119
304
48
+
100
17
30
125
330
40
+
250*
26
52
149
441
47
+
500
12
50
172
156
58
+
1000*
T
31
214
T
44
+
5000*
A
m
-i.
T
* Indicates the results of just one experiment. All other data are the average of
two assays conducted on separate days.
T = Itoxic
(7b)
-------
TABLE 21
(continued)
IN VITRO ASSAYS SAI/PNELLA TYPHIHURIUH AND ESCHERICHIA COLI
(Siixon and Poole, 1978)
Anount of
Sample
Metabolic Added Per
Sarole Activation Plate (ug)
Coal tar-Crecsote - 5*
P2, Class C 10
50
100
250
500
1000
5000
+ 5*
+ 10
+ 50
+ 100
+ 250
+ 500
+ 1000
+ 5000
Average Number of Revertants Per Plate
S. typhimuriun
E. coli
TA1535
TA1537
TA98
TA10G
WP2
31
4
31
106
37
22
6
23
128
35
28
3
23
119
45
28
7
17
122
40
21
6
15
70
43
21
3
15
55
40
11
4
14
T
27
T
T
T
T
10
11
43
185
55
16
23
62
186
61
19
26
95
293
62
20
37
147
347
49
16
41
183
65
72
15
58
163
196
59
8
40
145
m
4
49
T
T
171
A
T
* Indicates the results of just one experiment. All other data are the average of
two assays conducted on separate days.
T = Toxic
(79)
-------
Pi cm: f2 fixtures were dissolve*: in cirethylsulfoxice (Li" LO) ark. v-ere
added to the cell cultures in varying test concentrations. h solvent
control usinc- 1% WLC- anc a positive control usinc; either airethylr.itro-
sa-nine (C"i:) (in the presence of r.etabolic activation) or ethyl rxthane-
sulfonate (ES) (in the absence of r:etaLclic activation) were also tested
The cells were plated (duplicates of each exposure concentration, the scl
vent control, and the positive control v.-ere run) on a selective rediu'.
containing trifluorothyr.icir.e. Ihe stated ceils ere., on the nediis-; tht
cells which haC not n:utated cid net ere.:.
Mutation frequency v.=s calculated as the ratio of the number cf ~u
tant cells to surviving cells at each concentration of test ch.uv.ical. 1"
nean r.utation frequency of the negative control samples wan subtracted
fror. tiie nutation frequency cf esc!" treated sar.ple tc oive inducec muta-
tion frequencies. A relative total growth was determined for the control
ar.d for each test concentration. Ihe relative total ^rc-th is ar. expres-
sion of cell grartl. in relation to the negative control and is expressed
as a percentage (Tables 22 through 25).
Creosote Fl at£ coal tar-creosote ?2 had similar hut not identical
effects on the forwato nutation frequency at ti'.e 7h locus of L517'
-------
TABLE 22
MDUSK LYMPhGi 1A FCK^ATlj MTT/^Tia: ASSAY OF CTJOSOli: PI Hi HIE ABSC.CE OF
IInLoCED .'iCIAEGLIC ACTIVTCia, (Mitchell and Tajiri, 1578)
Calculitec Induced
Relative Total Kutaticn 6 Iiutation 6
Gravth (%) Frequency (x 1C ) Frequency (x 10 )
Concentration
(cercent v;v)
Solvent Ccntrol
(1% DJISO)
Positive Ccntrol
(500 uc/rrJ. EMS)
o.sec x 10~2
0.6S6 x 10
-2
0.4S0 x 10
-2
-2
0.336 x 10
0.235 x 1C~2
0.165 x 10"2
C.115 x lu"2
0.081 x 10
-2
10b.4
90.2
37.2
52.1
0.16
0.03
38.6
40.3
71.4
55.3
78.3
76. S
68.2
6b.3
79.6
13S.9
54.1
85.1
71.9
40
66
573
663
2So
4?">
57
S2
60
55
79
77
47
71
75
54
62
68
56
520
610
233
417
4
2S
26
lb
22
1
15
3
(SI)
-------
TABLE 23
NCUSE LYTiFHGiA FUM.ARC MUTATION ASsAY OF C-JjOSCTE Pi IK THE PKLSLZICE CF
1/
INDUCED METADCLIC ACTIVATIC:. (Mitchell and Tajiri, 1S7L)
Calculated Induced
Concentration Relative Total r-iutation 6 nutation 6
(percent vtv) Growth (%) Frequency (x 10 ) Frecnencv (x 10 )
Solvent Control
S7.4
1C1
—
(1% a-SO)
102.6
54
—
Positive Control
€.3
445
347
(100 uo/rJ ET!N'}
10.8
2b 2
184
.-3
3.00 x 10
0.8
459
3C1
1.0
398
301
2.40 x 10-3
3.9
318
221
4.4
305
207
1.92 x 10"3
S.9
213
115
12.9
222
124
1.54 x 10~3
23.0
167
7C
21.3
185
67
1.23 x 1C"3
36.7
180
82
43.3
140
42
0.9S x 10"3
42.S
169
71
43.1
174
76
o.7y x lo~3
62.7
151
53
74.5
141
43
C.63 x 10~3
84.3
120
23
77.9
126
3u
1/ Arochlor 1254-
induced rat liver S-E>,
batch IR-11.
(S2)
-------
TAELE 24
MOUSE LYMPHOMA FCFSARD MUTATION ASSAY OF CPAL TRft-CRECSUXE P2 IK '1HL ABSENCE OF
INDUCED METABOLIC ACTIVATION (Mitchell and Tajiri, 1978)
Calculated Induced
Relative Total Mutation 6 fiutatior. 6
Growth (%) Frecruency (x 10 ) Frequency (x 1G )
Concentration
(oercent v:v)
Solvent Control
(1% EKSC)
10S.4
90.2
40
66
Positive Control
(500 ug/rnl CIS)
0.980 x 10"2
37.2
52.1
0.C2
0.01
573
663
233
233
417
227
0.6S6 x 10
0.480 x 10
-2
41.6
32.9
57.7
63.2
143
175
37
79
90
123
34
26
C .336 x 10
0.235 x 10
-2
75.9
70.7
85.5
to
53
12
5
0.165 x 10
-2
0.115 x 10
—9
0.081 x 10
-2
60.3
65.7
67.5
55.4
66. e
93
59
61
74
52
40
6
B
21
0
(33)
-------
TABLE 25
MOUSE LYMPH&yiA POPvARD MUTATION ASSAY OF CCAL TAR-CKKCSCTiZ P2 IN PRESENCE Or
_ ^
INDUCED METABOLIC ACTIVATIUi: (Mitchell ar,c Tajiri, 1976)
Calculated Induced
Concentration Relative Total station 6 rotation 6
(piercer.t v:v) Growth (%) Frecuencv. (x 10 ) Precuency (x 10 )
)
Solvent Control
97.4
101
—
(1% Ct'£C)
102.6
94
—
Positive Control
6.3
445
347
(100 ug/nl aiJ)
10.8
282
1B4
-3
3.CO x 10
2.8
3b 6
2£9
1.9
370
273
2.40 .x 10"3
7.0
269
172
5.8
338
24u
1.92 x 10"3
14.4
2C4
10 b
16.1
236
139
1.54 x 10"3
35.C
134
37
36.7
190
92
1.23 x 10~3
35.0
140
43
36.3
147
49
0.53 x 1U-3
50.7
177
80
56.9
152
55
0.79 x 1C"J
58.9
153
56
77.8
117
20
0.63 x 10"3
73.7
123
26
75.9
121
23
1/ Arochlor. 1254-
•induced rat liver S-5,
batch IK-11.
(84)
-------
growth was below 1%. For coal tar-creosote P2 without i.etabolic activa-
-2 -2
tion, tv.o concentrations, C.£j6 x 10 % and 0.636 x 1C yielded a uuta-
tion frequency significantly above the spontaneous frequency. Again, the
-2
relative total gra*th value at 0.98 x 10 % was below 1% survival. At
0.686 x 1C % the relative total growth value was approximately 35%.
3. Conclusion
Sijrjron and Poole (197E) found that following raetabolic activation
by Arochlor 1254-sti.T.ulated rat liver hcrsogenate both the creosote ?1 anc
the coal tar-creosote P2, Class C, produced a mutagenic ocse-respc:ise and
a doubling above background rotation irate with Salmonella f.-i-hi-nuriuir,
strains Th 1537, 1A 98, and 1A 100. Hitchell and Tajiri (197o) found that,
following inetacolic activation by Arochlor 1254-stir.uIatec rat liver hcxc-
genate, creosote Pi and coal tar-crecsote F2, Class C, increased the nur..-
ber of forward rrutaticns at the thymidine kinase locus of 1517by reuse
lynphcna cells in a dose-related ranner. The Working Group concluded that
Pi and P2, Class C, caused mutations in Salrcnella typl.ii.;uriui-; strains
TA 1537, TA S>8, and TA ICC, and in L5178Y reuse lyi^-hcnia cells. 7ne V.'ork-
ing Group, therefore, concluded that PI and ?2 are mutagenic in a r^ulti-
test syster. and exceed the criteria of 40 CFH 162.11(a)(3)(ii)(A). Accord-
ingly, the Agency is issuing a rebuttable presumption gainst creosote
and coal tar-creosote fixtures.
C. Exposure
Although 4C CFR 162.11(c) (3) (ii) {A) dpes not require that exposure
be demonstrated in order tc presume against a pesticide on the basis of
oncogenicity or on the basis of nutagenicity in a nultitest systen, a
(S5)
-------
uiscussicn cf exposure tc coal tar, creosote, anc coal tar neutriJ. oil
is induced for ccrrer.t Ly interested yerscns. Working Creu^ ce:>-
si-'jerec three areas of exposure tc these substances - industrial
treatment, fcod residue, and user exposure.
1. Industrial wood Treatment
a. General
The .rest ir.yortant r.incr r.stiKX- of application is therr.al treat-
ment in which wccc is ii-rsrsec; in cj-t-n trouuhs fillec wit:; iiCt creosote
followed :.y introduction cf relatively cold creosote. Th= '..crhir.ij Cro_-.
is net £v;are or any intonation cr. =kwC-sur-_ to creosote ircx. ther:.-.&l
treatment. Ihe application cf ever ei oil ccai tar-creosote fix-
tures for v;cod yres=rvu;:ien is Ly pressure tre=-er.t (.-w.ericar. hood rr=~
servers1 Institute, lb").
Ihe pressure treatment system is a close- system, and tie re is
r.e need for direct worker contact with the lic.uiu creosote cr coal t-r
i-rior to its i,v.ore<;naticn intc the wood. '.he ".aterial arrives uj tr_ch
or rail and is ur.'i-eu ir.to a ucldinc tanh where it is vasiwhec. If the
.".oterial is a crecsote/ccal tar solution cf ..articular tr^e o-x-ciii-
cations, the solution is r"re;'.ixed at the production facility so td.at
r.e .v.ixing cr manual transfer operations ax. t mtii l w* c-1 t* % in eat. 4 *t
i-lant. Tr.e treatrer.t itself involves ;;r*jssurization in airtight cham-
bers. Ik; ^rkers are lii:ely to be ex^escu fra.. ti:e treatment cv lingers
ourirs^ the actual treatment process, ncr ere weavers other tJ-ar. treating
roar, Ci.eraters r-_-.,uirec. to or iri u.e Lj.ec.iate vicinity ef u-.e chi^ero
at tnis tir;e. -he treatment eyerater is res-enciolc for the r.eteri:.v
ar.c introduction of ccaj. ter/crecsoto into tho cylinders. yhis funo-
i-ii
-------
tion is performed in a control house near ti:e charters. In older facili-
ties leakage of coal tar and creosote frcn old pipes art; fittings ray re-
sult in relatively high inhalation exposure to the treatment operators.
Treatment time varies but ranges frcn about six to seven hours for eacn
change of material, following treatment, a vacuum is generally applied
to withdraw excess preservative. After the excess is withdrawn, the
chaT.ber door is cracked cpen by a doorman. While still under vacuum,
prior to withdrawal of the trar. cars holding the treated wood, the door
remains cracked open for approximately 15 rrinutes. The greatest cppor-
tunity for inhalation exposure appears to occur during the mechanical
withdrawal of the trar. cars frar\ the pressure charter. The \-ooc-laden
tram cars are linked to an engine and withdrawn to a storage area where
the wood refrains until shiprent to the buyer.
Coal tar and creosote crippage occurs along the rail tracks lead-
ing frail tiie chamber. This arippage is collected Li ditches alongside
the tracks ana is pumped to a collecting pond along with creosote that
has dripped frcn the pressure char.bers at the tire the charge was removed.
Dike systems are employed around wood treatment plants to prevent runoff
of creosote frcrr. the plant area. In at least one case, hcwever, creosote
was found to migrate from a treatment plant into the ground water supply
of a neighboring community. Hie plant has since been shut down (Mittelman,
1973).
¦ Non-rcutine operations such as cleaning of the treatment chamber
nay occur several times yearly. Worriers in such operations are provided
with suitable respirators and protective clothing.
(B?)
-------
b. Inhalation Exposure
On February 24-25, 1976, representatives of the National Institute
of Occupational Safety and Health; (IIIOSK) Ili.S. Cepartrent of Health,
Education, and l.elfare (USDK30 , 1977J and of Koppers Ca.ipany (Snith,
1977) performed two separate air monitoring surveys at a Kcppers Carpany
wood preservation plant in Little Rock, Arkansas. Air sarples were col-
lected using lapel sailing pumps and analyzed for polycylic particulate
organic matter (PPCri) by the NICSH yravir.^etric method (MGSK, 1977). The
V
results of the two studies are presented in Table 26 and Table 27.
Koppers Ccrcpar.y also per ferried an air monitoring survey in July,
1977 {Webb, 1977) at the sar.e Little Rock, Arkansas plant ssvplec cy Koppers
1/ The lapel air sampling pur.ps collected the PPG: cn a silver r.-erijrane-
glass fiber filter which was held in place by a cellulose pad. reliev-
ing collection of the air sar^ple, i.ICSh (USELi:;, 1977) cesorbeo the fil-
ter and the cellulose pad with cychlohexane. Ey contrast, Koppers
(Williams, 1577) (Table 27) desorbec the filters, but not the cellulose
pads, with benzene. The cyclchexane solution, or the benzene solution
in the case of the Koppers' analyses, was placed in a teflcn cup and
the benzene or the cyclohexane wag evaporated by placing the cup in a
vacuicn oven for three hours at 40 C. T^e weight of the refining ".ar-
terial was the cyclohexane or benzene soluble material. The concentra-
tion of ng/r. was determined by dividing the weight of the cyclc-
hexane or benzene soluble n^terial by the volure of air sanplec. The
results of the NICSH analysis vrere generally higher than those of
Koppers'. KICSH, however, as stated above, desorbec the cellulose pad
as well as the filter with cyclohexane, while Koppers aesolved oaly the
filter. Analysis of two blank cellulose pads for PPCH by I.'ICL'K produced
results of 115 and 120 ug/filter. tto adjustrrent in the UICSH report was
race for the blank cellulose pads. To adjust for the blank sarples,
117.5 ug/filter (the average of 115 and 12C ug/filter) was subtracted
frar. the ug/filter reported for the KICSH test samples by an EFA chei.'ist
for the purpose of presenting the table of results in this document.
I .here no results are reported for the "ug/filter" in Table 2S, the ug/
filter of the blank saj.pl e was higher than tiie test sarnie.
(SS)
-------
TABLE 26
RESULTS OF 1576 NIGSh MONITOKING STUDY AT KOPPD^S
OCMPAKY l^GD TREATT-ILi'^T PLANT IN LITTLC KOCK, AKlAt^AS
(U.S. Department of Health, Education, and Welfare/ 1977)
2/ 3/
Concentration Code cf
1/ Air Volure3 In^ Worker
Description (Date) ug/filter Sampled (n ) Air (mq/n J or Site
Treating Operator (2/24)
32.5
C.49
C.C7
S-l-o
Doorman (2/24)
-
0.53
-
U-i-7
Treating Operator (2/25)
62.5
C. 49
0.13
S-nll
Doorman (2/25)
-
.0.51
-
S:-12
Loccrctive Operator (2/24)
12.5
0.49
0.03
s-'-e
Loccnotive Operator (2/25)
52.5
0.56
0.09
S-I-15
Loccnotive Switchman (2/24)
-
0.73
-
S'-rj
Loccnotive Switchman (2/24)
-
0.57
-
S-:-lC
Loccnotive Switchman (2/25)
137.5
0.50
0.28
S-'!—13
Locomotive Switchman (2/25)
1/
Treating Area
42.5
52.5
0.50
0.44
C.08
0.12
sr-:-l4
SM-16
.mm
1/ This is the total anount measured on the filters minus the a."
-------
TABLi: 27
1
-------
TABLE 28
RESULTS CF 1977 KCPPERS OCMPAIIY M3I»TITORP.vG
STUDY AT LITTLE KQCK, ARKANSAS (Webb, 1977)"
1/
Description
Doornan
Doorman
Treating Operator
Treating Operator
Switchman
Switchman
Switchnan
Locomotive Operator
Loccmotive Operator
Boring Operation
Area Clean Up
Concentration In Air (nq/ir,
0.02
3/
0.07
0.05
0,01
0.03
0.02
< 0.C1
0.05
0.01
0.04
0.02
3)
2/
1/ The weather corvfitions curing the study were the following:
tercperature, 72-83 F; relative hurrddity, 74-91%; barometric pressure,
30.00 inches Hg; and winds Iran the north at 5 r^ph.
2/ This is the concentration in the air of benzene soluble raterial. —
3/ This doorman's exposure ray have been higher because of his recovering
a trair. inside the cylinder following a bred: of the tran\ tc*; cable.
(91)
-------
Ca.^-any arc I.ICSI. in July 1S>76 arc usiiv. the i.ICoL gravimetric ttoiinirue
usfed in the first Lookers' stu-i. ite results of the Iv77 study are re-'
^porteu in Table 2fc.
Ihe 197G arc 1S77 Xor.ijers' studies four.il a range of < C.Gl tc
3
0.10 ~cj/r. benzene soluble raterial concentration in the air arcunc the
Little Pock wood treatment plant. The 1976 i.'ICSii stuuy four/. a rar.-e
3
cf u.03 tc 0.2b rc/zi cyclchexane soluble material in the air arcur.c the
Little ~cck plant. i.o correlation appears to be evident between the typx=
cf \.ork nerforrr«d (e.g. treating operator, loccr.ct.ive Svitci-jrau;, ccoc.ar.,
etc.) arc the amount cf air exposure.
H.ere are several limitations to the rethoc of collection sr.[lc£'eb
iI.'ICSH. stated, the nethoc cf analysis useu is a Gravimetric ::csthoc
and measures only the beri2ene or cyclchexane soluble fraction cf pi'lycy-
clic articulate organic ratter in air sarrles. Ihus, var-cu :-hase pcly-
nuclear arcn-etic (F:) hyorocarbcns v.culc gc uncollected. r-Jsc, the
c ravine trie r.ethoc useu has net been fully evaluate--, fcr r;recisiu.n cr
accuracy nor has the solvent syste~ oeen properly assessed fcr ^trac-
tion efficiency. Another limitation tc this r.etiico cf analysis is its
r.onspecificity, i.e., the organic rate rial weighed ray incluc-e innocuous
as ;
-------
2. Residues in Food
Creosote, coal tar, and coal tar neutral oil are not applied to
food crops. Scrae evidence exists, however, that creosote or creosote-
coal tar mixtures nay leach out of marine pilings and contaminate rarine
life in the near vicinity and that this marine life may be eaten by
hunans or move through tte food chain.
Dunn and Stich (1975, 1976a, 1976b) monitored mussel benzola]-
pyrene contamination, and Zitko (1975) monitored various aquatic fauna
for pyrene equivalents. Ujnn and Stich (1975) found that mussels taken
frcm a relatively pollution-free location contained higher tenzola}-
pyrene-levels (45 + 5.8 ppb) when near crecsoted pilings than when dis-
tant frar. the pilings (2.1 + C.3 ppb). Analyses for the BlajP was per-
performed by thin layer chromatography (TLC) and fluorescent emission
spectra. Vib.ile 1I£ techniques have, for the rest part, been superseded
by high pressure liquid chrcratography (hPLC) and gas chromatography
(GC) methods offering greater separation frcn potential interferences
and greater sensitivity, the data generated is valid and deserves greater
investigation. Although it was not conclusively demonstrated that creo-
sote was the source of the 5[a]P contamination, it is not unlikely that
creosote constituents may migrate frcm wood over tine if only by purely
mechanical means such as abrasion or swelling of the wood. The extent
of this migration is unknown, but the data provided by Dunn and Stich
(1975) must be considered in tlve absence of better-developed data.
Ihe Working Group concluded that the extent of potential dietary
exposure due to shellfish is unknown, but is likely to be small. A
(93)
-------
total of 3.73 g/day of fresh, frozen, and earned shellfish was censured per
capita in the United States in 1974 (USLA, 1974). If it is assumed that
shellfish taken frcn sites near crecsoted pilings certain approximately 50
ppo B(a]P (i.e. 50 ug/kg) (Dunn and Stich, 1975), then the naxinura daily
intake of EfajP would be 50 ug/kg x 3.73 g = 0.19 ug/person/day Bla]P.
This exposure would result only if all shellfish contained tlie ii[a]P con-
tent detected by Dunn and Stich, an assumption without supporting data,
and also assuring the data of Dunn anc Stich is representative of all
shellfish near creosotea pilings.
3. User Exposure
a. Use of Treated Wood
Schwartz (1942) reported that workers exposed tc creosoted floors
develcped erythematous, papular, and vesicular eruptions on their ankles
cne to two weeks After beginning work. The Pesticide Episode Reporting
System (PEKS) (1576) reported a nuirher of incidents in which vorkers
handling creosote-treated wood suffered adverse effects frcn exposure to
the creosote (Appendix C).
The Working Group concluded that exposure frcrc the handling of
treated wood by workers such as railroad workers, utility pole vork^ts,
and workers installing pilings deserved greater attention, When this
work is cone in the summer, workers would probably incur the greatest
potential exposure because of the inconvenience and discaofort of wear-
ing protective clothing during this tine of year.
(94)
-------
b. Manual Application of Coal Tar, Creosote, and Coal
Tar Keutral Oil for V.:ooc Preservation
Birdwoca (1938) reported on the permanent danage to vision of
two gardeners who had gotten creosote in their eyes while treating
fences. Jonas (1943) reported tliat 1-iavy construction workers devel-
oped skin and eye irritation as a result of exposure to creosote while
applying the creosote curing construction. The Pesticide Episode Re-
porting System (1976) reported a nunber cf incidents in which workers
applying creosote suffered adverse effects frcr. exposure (Appendix D).
The Working Group concluded that applicators who ranually apply
creosote are exposed, but no information is available to quantify this
exposure.
c. Application of Creosote as an Herbicide
The Pesticide Episode Reporting Svsten reported two cases of burns
to applicators applying creosote as an herbicide (Appendix E).
The Working Group concluded that exposure to creosote does result
fran its application as an herbicide. The Working Group, however, is net
aware of any information that is available to quantify this exposure.
d. Other Uses
Coal tar neutral oil and creosote are active ingredients of twe in-
secticides used on horse and mule wounds (2 registrations). Coal tar neu-
tral oil and creosote are both active ingredients of disinfectants for
water closets, outhouses, garbage cans, anircal areas, institutional preni-
ses, and sickroan areas (approximately 57 registrations). Coal tar and
coal tar neutral oil are active ingredients in pesticide dips and sham-
poos for dogs (approximately 7 registrations). Creosote is ar. active
(55)
-------
ingredient cf a pesticide registered fcr r.ite end tic): control in poultry
houses. Coal tar neutral oil is an active ingredient cf e pesticide
registered for use on hoc, housc-s, si-eep Ums, cot kennels, and horse sta-
bles (6 registrations).
Creosote is an active ingreoient in registrations fcr horse repel-
lent (1 registration), a tree and shrub dressing (3 registrations), and
an herbicide (2 registrations). Coal tar is an active ingredient in a
era™- repellent for seed ccrn (1 registration) and a huran insect repel-
lent (1 registration). Coal tar neutral oil is an active ingredient of
approximately 16 rcscuito larvicide registrations and 2 gypsy rroth lar-
vicide registrations.
Vo infcn.aticn is available regarding the potential e::posure cur-
ing application for the above uses. 1he uses involving cc*J. tar arc its
derivatives ir. animal dips, washes or shannccs and the use of coal tar as
a hunar. insect repellent appear rest likely to result in direct: huran
contact.
CSIIES AIAT?££ ITFL'CTS '
A, General
Ihe inforratior. in this section relates to other adverse effects
of creosote. The i.crkinc Group has concluded that ti'.e presently avail-
able information does not require issuance cf a rebuttable presur.'i. ticn
against registration cr. these effects. Che /-cency does solicit ir.forv.c-
tion on these problems, however, and requests t'r.at studies be- conductor:
v.T.ere necessary.
(Ori \
\ ~ i
-------
B. Skin and Eve Irritation
The Working Group reviewed several reports indicating that creo-
sote is a potent skin and eye irritant.
BinJwood (193b) reported on two gardeners who got creosote into
their eyes while creosoting fences. The two patients both ccnplained
of blurred vision and upon examination were found to have iraculae upon
the cornea and keratitis of the cornea. Birdwood reported that for both
patients the iirpainrient of vision would be permanent..
As indicated previously, the Pesticide Episode Reporting Syster.
(1976) reported 33 cases of eye Garage, burns, cr dermatitis resulting
frcxi creosote exposure either frcn treated wood cr by application curing
the period August 1568 to April 1976 (Appendices C,D, and E).
rjcHillan (1976) reported on the accident history of 50 of the ap-
proximately 175 pressure-treating plants in the United States and Canada
which use creosote to treat wood. About 3,000 employees cut of approxi-
mately 7,000 employed in the industry were surveyed. Of these surveyed,
230 were reported to be directly exposed to creosote and fifteen hundred
employees were reported to be either directly or indirectly exposed. Tne
report was vague on the period of tire which the survey covered. One em-
ployer reported for a 6-year period (1969-1575), one erx:lcyer reported for
a 10-year period (1961-1971), and 5 employers' reports were terr.ee "his-
torical." The tine period covered for the other 43 plants was not re-
ported. Also vague in ti*e report was the nun be r of treatment plants which
documented cr did not document the accident history. Of those which were
dccuirentec, 98 cases of chemical conjunctivitis and 19 cases of eye irri-
(57)
-------
tation were reported. At least one treatment plant reported that eye
irritation was "occasional." Sixty cases of skin burns and tiro aller-
gic reactions were reported. At least one plant reported that skin
burns vjere "infrequent."
Pfitzer et al. (1965) found that the instillation of 0.1 rdlli-
liter of creosote into the eyes of rabbits caused the conjunctiva to be-
came slightly erythematous. Examination of the exposed eyes 24 hours
following exposure showed that slight redness of the conjunctiva per-
sisted in two of the eyes tested and the regaining four exposed eyes
were essentially free of irritation. All of the exposed eyes were free
of any apparent effects after seven days. Pfitzer et al. (1965) also re-
ported that the contact of creosote with the intact and abraded areas cf
the skin of the bellies cf rabbits fer a maximum period of 24 hours pro-
duced nocerate erythensa and noderate to severe edesra. The skin reac-
tions regained relatively unchanged 72 hours following exposure. After
14 days, the exposed areas revealed severe epidermal flaking.
Schwartz (1942) reported that workers exposed to creosote treated
floors developed erythematous, papular, and vesicular eruptions on their
uncovered ankles one to two weeks after beginning work.
Jonas (1943) treated 450 Havy construction workers (1/6 cf the-
workers at a Kavy carp) for creosote burns, lie found that fair-skinned,
light-hairec workers were particularly affected by creosote bums and
that the nurber of burns increased on sunny days. Seventy percent of the
burns were r.ila, while 30% were nore severe and characterized by intense
burning, itching, ana considerable subsequent piyr.entaticn followed by
(98)
-------
desquamation. Fifteen percent of the 450 patients hac inflamation cf the
conjunctiva, with mild cases being characterized by hyperennia of the nu-
cus r-enbranes and more severe forms by photophobia and a large anount of
serous secretion. Three percent hac injuries to the cornea varying frcr,
snail abrasions to nultiple larye ones. One-third of these cases developed
pemanent corneal scars leaving hazy vision. These injuries were caused
by flying chips of creosoted wood.
C. Toxicity to Livestock
The Working Group reviewed several reports indicating that creoscte
ray have been responsible for toxic effects and death in scrre livestock.
1. Hanion
Hanlcn (1536) reported the loss of four steers and two ccws frcr.
a lot of 94 head of cattle frcr. what appeared to ce creosote poisoning.
The cattle were believed to have licked electric light poles which had
recently been creosotec. Symptoms in affected animals consisted of ex-
tremely rapid respiration and evidence of burning ever the mucosa of the
mouth, tongue and lips, which were white and hardened. The pupils were
contracted, the skin was cold, and the anirads were in a ccnatcse con-
dition. Feces were black in color and t]ie affected animals were 2ppar*-
ently in agony. In the early stages they were reported to have evinced
great thirst. A steer in extrer.is was killed, and an autopsy carried
out ijirediately. Intense inflairraticn and congestion was evident in
the whole gastrointestinal tract.
2. Lander
Lander (1926) (cited in Hanlcn, 193& and harrison, 1S>59) reported
(95)
-------
the death of stock that had access to freshly treated railway ties. Be
stated that water nay dissolve sufficient cresuls.frcn creosote-treated
sleeper ties to cause livestock poisoning.
3. Wanntorp
V.'anntorp (1953) (cited in Harrison, 195S) described several cases
in which calves and ccws died or had to be slaughtered after licking creo-
soted wood or poles. He mentions also the possibility that losses of
poultry following the treatment .of fowl houses with carboiineur. (a high
boiling point tar oil) niay have been cue to poisoning by tar derivatives.
4. Luke
Luke (1954) reported the death of four pigs, the suspected cause of
which was the ingestion of coal tar pitch frcr. the floor of their pen. The
floor was made of old railway ties leveled off with pitch. Prior tc death,
the appetite of the pigs was very poor and coughing was widespread. Fcst-
irorten examination of the pigs found narked enlargement of the liver and
several other liver anomalies in all four cases. Also, the abccninal cavi-
ties contained varying quantities of bloodstained fluid, and there was an
excess of straw colored fluid in the pleural cavities. A pyogenic pneuinc-
nia was found in two carcasses, and in one of these there was a well-narked
pericarditis. She lungs were normal in two cases and in one of these a
marked cystic condition of the kidneys was found. C. pvonenes was isolated
frcn the pneuinonic lungs but cultures frcn liver, spleen, and heart blood
were unifourly negative. Frcr. their findings, the authors cor.clixiec that
pneumonia was not the principal cause of death, but that the death resulted
frcn the liver canace. To test this hypothesis, the pitch was fed tc t.-;c
(100)
-------
groups of healthy pigs. Croup A was carprised cf three healthy pigs, each
about 60 pounds in weight, and Group E of tvx> pigs, each about 40 pounds
in weight. The pi9s in Group B were not thriving quite as well as tiose
in Group A. A quantity of pitch was ground up and a snail quantity aduec
daily to the food for both groups. Over a period of 2C days, Group A re-
ceived a quantity of two pounds of pitch. Ifce pigs in Group h received
four ounces of pitch over a period of 12 days. In both groups the addi-
tion cf the pitch affected appetite and the pigs tended to be constipated.
At the end cf feeding for both groups, the pigs were killed anc exar.ir.ee.
In all three cases fra.i Group A tr
-------
the only danger to stock would be through their access to tlie raw preserv-
ing fluid either near stacks of freshly impregnated tir.iber or on freshly
treated fam trnber and nearby contaminated vegetation.
6. Olafson and Leutritz
Olafson and Leutritz (1956) applied crescte tc the skin of calves ever
the jaw area to preclude licking off the material. About three days after
application, the skin developed slight swelling and becarre harder than nor-
j-el. Gray creases appeared. Frcrr. 7 to 10 cays later, a cry crusty thicken-
ing of the skin had occurred. Healing took place slowly and recovery was
not ccnplete in four weeks.
Olafson and Leutritz (1958) also studied calf response following oral
administration of creosote. Thev retorted that a 1,0CG-pound ccw would
have to ingest over 75 cc of creosote before appreciable ham would re-
sult, although the exact basis for this determination was not stated.
D. Fetotoxicitv
The Working Group identified one livestock study, tlie results of
which ray pose a question as to the fetotoxicity of creosote.
Schipper (1961) found a creosote-related fetetoxic effect with prey-
nant sows; the platforms of the cages in which the sows were housed had had
three brush applications of a carrerciai creosote wood preservative.*" 71;e
sows were confined in the cages 2 and 10 days before giving birth. Twenty-
four of the forty-one pigs delivered by the four sews were dead at birth.
Of the renaininc offsprings, six pigs died on day 1, four pigs on day 2,
and one pic on day 3. The surviving pigs had rough skin, were dehydrated,
and had severe diarrhea; weight gains were hindered until they were 5 and
(IC2)
-------
o weeks old. A control group was not included in the study, and the au-
thor did not report the route nor the a*nour.t of exposure.
)
(103)
-------
Appendix A
SPECIFICATIONS FOR COaLtaK CREOSOTE (NEW MATERIAL) (Fuller j 1977)
SPECIFICATION NUMBER
Pl-SS*11
Pi 8-65®
D39M701
TT-C445bUl
Class 1
Class 2
Class 3
"Water (*> by volume)
> U
> 1-5
Umax
?X BIX
Umax
SX max
Matter insoluble in benzene by weight)
> 0.5
> 0.5
tlimax
Umax
LSmax
1 £ max
Specific gravity at 88° C compared to
water at 1W°C
Original creosote
< 1j050
< U080
1.05 mis
1.050 mis
1jD50 mis
1.080 Blin
235-315*C fraction
< 1j027
< 1J030
0.027 mis
1JJ27 mm
1.027 mia
14)30 mis
SlMS5eC fraction
< L095
< 1J05
1.095 mic
L09Smic
1.095 mio
1410 min
Residue above S55eC
—
< 1.160
—
_
—
1.1 GO mia
Distillation
To 210°C
> 2.0
> to
2.0 max
2.0 max
SXmax
2.0 max
To23S°C
>12.0
>12X
12-0 B>LX
12J) max
1ZS) max
12X1 max
To 270®C
<20.0>40J)
2Ci)>40.0
20.0-40.0
20-40
20-40
20-40
To315®C
<45.th>45.0
45-0->65.0
45.O65.0
45-65
40-65
4545
To 35S°C
<65.Ch>82.0
65.O75.0
<5.0-82.0
75-82
6S42
€5-75
Btmw
Land, fresh
Marine
Land. Ireth
Poles
General
Marine
water
water
land.iresh
•water
(II For Und sod fresh water use. A WPA Sid.
(2) For marine (touuJ waiert uses. A WPA Sid.
C) For land and fresh water use. ASTM Sid.
<4)GSA standards (or ereosote in use
104^
-------
\
AWPA SPECIFICATIONS OF CREOSO'fi&COAL TAR SOLUTIONS (NEW MATERIAL)
(Fuller, 1977)
AWPAP2-68
REFERENCE <
Composition
Creosote
Coal Tit
•Water 1% by volume)
Benzene, insol. ("to by weight)
Coke residue by weight)
Specific Gravity (36,15-5)
Whole oil
235-3l5°C friction
S15-S55°C fraction
Residue
Estill* tion
To2l0eC
To235°C
To 270°C
ToS15°C
To S5S°C
Residue
O' Far bsc is treatment of msrise pDe» ud tiaberv
6c*ra:IUnJoMiU?721
T12-6B(1)
RADEA
3
C
D
8.0
> 8.0
> 8.0
> 8.0
£J0
> 2X
> 8X1
> 8.5
> 4.0
1M.0
> S.0
> 7j0
> S.0
>11.0
4.0-7JO
1jD6-1.11
1J07-1.12
1 JOS-US
1.09-1J4
1.09D
1j025
1j025
1.025
1.025
1.030
1D85
1J5&5
IjOSS
1.0&5
1.105
—
—
1185
5
S
5
t
£.0
25
25
25
25
15X1
_
—
—
20-35
86
84
S2
SO
85-50
60
66
£2
46
S5-70
105 ^
-------
APPEIiDIX C
y
REPORT- OF EPISODES OF EXPQSURL TO CREOSOTE FTOM HvEATED LUMECR
(Adapted frgr. PO
-------
appendix c
(continued)
REPORT CF EPISODES CF EXPOSURE TO CREOSOTE FROM TREATED LU'SLR
(Aca^tec £rcr: PERS, 1976)
1/
Date of
Ecisoce
State
2/
Causative Agent
Verification
3/
Rerarjcs
9/20/73
1/75
CA
CA
Probable
Yes
Laborer developed contact derrratitis cn
his buttocks while working with treated
lurber.
Laborer working witii treated wooc en-
veloped dermatitis on hands and ar.rs.
1/ Kecorcs checked frcn 1967 through April, 1976.
2/ Verification indicates whether the pesticide associated with tije episode
was established as the causative agent which resulted in death, illness,
etc. "Yes" indicates that substantial evidence exists linking the pesti-
cide to the episode's effects; "Probable" indicates circunstantial evi-
dence exists linking tlie pesticide to the episode's effects.
3/ In all cases 1 human received nedical attention.
107 <
-------
y
kltcis- ct u-1-.CDLb a cipcsurx r.c crzcscii; r:c:: ai-?lic^.txu-
(nusytcC. UrCj'.. i-^7u)
£/
Date cr" Causative ;*,ent 3/
E;;isac-e State Verification
2/23/12 G\
FrcbeLle
A carpenter develcr-eo six-scute ccnjuncti-
vitis after vyettir.y creosote- ir. i.is eye
at ucrk.
b//2
O.
rrooaLie
/-. caryer.ter sustained corns cr t:.e tact,
all 6 ctliCi i.ciTiJS V'tid: ire? Gc*-Vc ijiLC CC':;lcC'
v.iw# CL'tsJcC-Cc s».riv»
10/2/71;
I**rccaole
r\ construction '..orkfcr ^eveIoy--o a rasr.
cn all extremities U.iie '..crkin- wit.;
cr^cscww•
i/23/7
construction -..'crker oevel'jyeo c.er.ical
uurns of ccth forfearrr.s v.i.iic carryi.'v
creosote-treatec wocc.
4/26/73 C-\
A laborer at a lurier yarxi sustnii.ec
first ceyree curr;s on Loth an.is 1-:
rcvir/. dTxrCSOtc rrcr.i c c£*vi»
6/0/73
a.
Provable
A laborer ueveictec ery tl.e..a cr the race,
neck a;i. fcr=arr..s ;,i.en i.-e ir.uovertenly
tuoceo creosote on ti.er/..
fc/ii/73 C\
Prooafcle
t-. carpenter splas.-£u creosote into cot.;
eyes and ceveioyeG che..icai heratccct^Lno
tivitis.
6/1E/73 Ck
A carpenter skilled creosote cn ar:.£ ant1
face an;"; deveiq.ee s~yerficial irritation
of er:..5 art" lace.
G/27/73
j-i'ci-.aL2fc
A etu.er.t -jot creosote or. forar:r.B
ixintir... ;>ctts ar.o ievelc.ed ci.e~.iced -
108 <
-------
APPENDIX D
(continued)
1/
REPC-nI' OF EPISODES CF EXPOSURE To CREOSOTE FRGr". APPLICATION
(Adacted tror. PLRS, 1976)
2/
Date of Causative Agent 3/
Et>isode State Verification Remarks
7/24/73 CA
7/26/73 CA
7/31/73 CA
Prenable
Probable
Pr doable
A laborer developed first degree burns of
the anrs, face and hands after painting
pests with creosote.
A carpenter sustained first decree bums
or. his face, fcrearr.s and lever abccren
v.hen he splashed the rnaterial or. hirself
during an application operation.
A laborer for a construction ccr.pany sus-
tained a chemical burn when the Tutorial
•was scraved cn his arr.'is and face.
9/24/73 CA
8/24/74
4/25/75
5/25/75
;u
CA
CA
Probable
Yes
N/A
Probable
A laborer got creosote in his face anc
eyes thereby sustaining a chemical burn.
A wcran was injured when the car. frcr.
which she was pouring creosote onto the
foundation of her ha;.e, slipped frcn her
hand, splashing the chsnical or. her legs
and into her eyes.
A ran was applying creosote.to a rarp when
he accidentally splashed it on his face.
Ihe effect of the accident was not reported.
An erplcyee was treating a wooden kiock.
Material splashed onto hir:., resulting' in
contact dernatitis.
1/ Records checked free 1967 through April, 197G.
2/ Verification indicates whether tlie pesticide associated with the episoce
was established as the causative agent which resulted in death, illness,
etc. "Yes" indicates that substantial evidence exists linking tl« pesti-
cide to the episode's effects; "Probable" indicates circumstantial evi-
dence exists linking tl« pesticiue to the episode's effects.
3/ In all cases 1 hurcan received recical attention.
109^
-------
APPEKLIX £
sEPCKT EPISODES OF LUFKS SUFFERED FRC.S THE APPLICATION'
1/
OF CREOSOTE AS AK HERBICIDE (Adapted frcn PEPS, 1976)
1/
Date of Causative Agent 3/
Eoiscce State Verificatior. Rerarks
4/21/73 CA
Probable
A pest control operator sustained clerical
burns of the face while snravinc weeds.
o/14/73 CA
Probable
A lurLer ccr.perry worker was spraying weecs.
Y.'ind blew the herbicide into his face and
the worker sustained first cegree terns.
1/ P&ccrds checked frcr.i 1S67 through April, 1976.
2/ Verification indicates whether the i.-esticide associated with ths e::isoue
was established as the causative agent which resulted ir. death:, illness,
etc. "Yes" indicates that substantial evidence exists linking the pesti-
cide to the episode's effects; "Probable" indicates circumstantial evi-
dence exists linking the pesticide to the episode's effects.
3/ In all cases 1 huran received medical attention.
11CK
-------
REFERL1.CES
1. ArericanTTood Preservers' Association (1976). ft.PA Bock of Stan-
dards , Washington, D.C.
2. American Wood Preservers' Institute, Environmental Programs Task
Group Subcommittee Ko. 5 (1577). "Creosote and Creosote Solutions-
Vtood Preservatives." Mernorandun for the Office of Pesticide Pro-
grams, Environmental Protection agency.
3. Berenblun, I. and P.. Schoental (1547). "Carcinogenic Constituents
of Coal-Tar." British Journal of Cancer 1:157-163.
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