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occurred 1n mice exposed to >620 ppm for 13 weeks (Physiologic Research
Laboratories, 1980a). Reduced rate of body weight gain was noted In female
mice at >310 ppm. Impaired male fertility 1n mice occurred in a 3-week
gavage study at 2 mg/day (70.2 mg/kg/day) but not at 1.5 mg/day (52.6
mg/kg/day) (Herschberger et a!., 1969). Toxlclty studies not Included in
Table 9-10 include developmental toxicity studies using parentenal adminis-
tration on embryo culture.
CSs for mortality in mice, elevated relative liver weight In rats,
testlcular degeneration in rats and Impaired fertility in male mice are
presented in Table 9-11. The CS for testicular effects in rats was based on
the study by Physiologic Research Laboratories (1980a) rather than the data
by Nelson and Steinberger (1953) because the former study was longer and
more completely reported. CSs range from 16.4-25.6. The CS of 25.6
associated with Impaired male fertility Is chosen to represent the systemic
toxicity of nitrofurazone (Table 9-12).
Data regarding other nltrofurans that are the subject of this report
were insufficient for derivation of RQs based on systemic toxicity.
9.2. BASED ON CARCINOGENICITY
Data were not located regarding the carcinogenicity of the nltrofurans
to humans by oral or inhalation exposure; however, several oral exposure
studies 1n animals were available.
The carcinogenicity data for furazolldone were available only from
secondary sources. U.S. DHEW (1976a,b) reported the incidences of mammary
tumors in female Sprague-Dawley and Carworth Farms rats fed diets containing
1000 ppm furazolldone for 45 weeks and observed for a total of 53 or 52
weeks (see Table 6-2). U.S. DHEW (1976a) also reported that furazolldone
Induced tumors 1n Sprague-Dawley and Fischer rats fed diets containing 1000
0060d 9-16 07/06/87
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0060d
9-17
06/05/87
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TABLE 9-12
NHrofurazone
Minimum Effective Dose (MED) and Reportable Quantity (RQ)
Route: oral
Dose*: 36.4 mg/day
Effect: Impaired fertility
Reference: Hershberger et al., 1969
RVd: 3.2
RVe: 8
Composite Score: 26
RQ: 100
*Equ1valent human dose
0060d 9-18 06/05/87
-------
ppm for 18 or 20 months, In Sprague-Dawley rats at 15 mg/kg/day from the
diet for 2 years and In Swiss MBR/ICR mice at 150 or 300 ppm in the diet for
18 months. Because tumor incidence data were not reported, these data are
not useful for quantitative risk assessment. These data constitute suffi-
cient evidence for the carclnogeniclty of furazolldone, which was assigned
an EPA classification of 82.
Carcinogenic potencies for furazolldone were estimated based on the
induction of mammary tumors in female Sprague-Dawley and female Carworth
Farms rats In the 52- to 53-week studies reported by U.S. DHEW (1976a,b)
{Appendices B-l, B-2). The larger human q,*, 3.8 {mg/kg/day)"1, for
oral exposure, was based on the data in Carworth Farms rats. These data are
also appropriate for derivation of a Potency Factor (F) for furazolldone
(Table 9-13). An F factor for furazolldone of 22 (mg/kg/day)"1 places the
chemical in Potency Group 2, which, combined with an EPA classification of
82, results in a Hazard Ranking of MEDIUM, corresponding to an RQ of 10.
Furium is carcinogenic in rats, mice, hamsters and dogs. In two similar
studies in female Sprague-Dawley rats, furlum at 1990 ppm in the diet
Induced a highly significant Incidence of mammary and salivary tumors
(Erturk et al., 1970a) (see Table 6-3) and mammary tumors (Cohen et al.,
1975) (see Table 6-4). Several experiments establish furlum as a potent
leukemogen in mice fed the compound In the diet (Cohen et al., 1970,
1973a,b; Cohen and Bryan, 1978) and as an Inducer of urinary bladder tumors
in guinea pigs exposed through the diet (Croft and Bryan, 1973). Mammary
tumors and tumors of the gall bladder developed In dogs treated orally with
furium (Erturk et al., 1970b). These data constitute sufficient evidence
for the carclnogeniclty of furlum, which was ass'igned an EPA classification
of B2.
0060d 9-19 07/06/87
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TABLE 9-13
Derivation of Potency Factor (F) for Furazolldone
Reference:
Exposure route:
Species:
Strain:
Sex:
Vehicle or physical state:
Body weight:
Duration of treatment:
Duration of study:
Lifespan of animal:
Target organ:
Tumor type:
Experimental dose/exposure (ppm):
Transformed dose (mg/kg/day):
Tumor incidence:
Unadjusted 1/ED10:
Adjusted 1/ED-|0 (F factor):
U.S. DHEW, 1976a,b
oral
rat
Carworth Farms
Female
' diet
0.350 kg*
45 weeks
52 weeks
104 weeks
mammary gland
total mammary tumors
0 1000
0 43.3
0/15 15/17
0.47 (mg/kg/day)"1
21.9 (mg/kg/day)'1
*Reference body weight for rats (U.S. EPA, 1980)
0060d
9-20
07/06/87
-------
Estimations of q,*s for furlum were based on the Incidence of total
mammary tumors in female Sprague-Dawley rats (Erturk et al., 1970a,
(Appendix B-3), the induction of leukemia in female Swiss mice (Cohen et
al., 1970, Appendix B-4; Cohen et al., 1973a, Appendix B-5; Cohen and Bryan,
1978, Appendix B-6), and the Induction of tumors of the urinary bladder "In
male Syrian golden hamsters (Croft and Bryan, 1973, Appendix B-7). The
largest human q,*, chosen to represent the carcinogenic potency of furlum,
was based on Induction of leukemia In mice In the study by Cohen et al.
(1970) (Appendix B-4). These data are suitable for derivation of an F
factor (Table 9-14). The F factor for furium of 347 (mg/kg/day)""1 places
the chemical in Potency Group 2, which, when combined with an EPA
classification of B2, results in a Hazard Ranking of MEDIUM and corresponds
to an RQ of 10.
Morris et al. (1969) Investigated the cardnogenicity of 5-nitro-2-
furancarboxaldehyde dlacetate in experiments where the material was fed at
2000 ppm 1n the diet to female rats for 36 or 44.5 weeks. Mammary tumors
developed 1n rats after 44.5 weeks, but the Incidence 1n treated rats was no
higher than in controls. These data were judged to be Inadequate evidence
for carcinogenlcity and 5-nitro-2-furancarboxaldehyde dlacetate was placed
1n EPA Group D. Data are insufficient for derivation of a Potency Factor
(F) and no hazard ranking based on cardnogenicity is possible.
NHrofurantoln was negative for cardnogenicity in two dietary studies
In which 3000 ppm was fed to female Holtzman rats for periods of 36 or 44.5
weeks (Morris et al., 1969), and 1n a 75-week feeding period 1n female
Sprague-Oawley rats (Cohen et al., 1973c). Nitrofurantoin was also negative
in a 24-month dietary experiment in male and female mice (Ito et al., 1983).
An Increased incidence of mammary tumors, however, was reported In an
experiment with small numbers of germ-Tree rats fed dietary nitrofurantoln
0060d 9-21 07/06/87
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TABLE 9-14
Derivation of Potency Factor (F) for FuMum
Reference:
Exposure route:
Species:
Strain:
Sex:
Vehicle or physical state:
Body weight:
Duration of treatment:
Duration of study:
Hfespan of animal:
Target organ:
Tumor type:
Experimental dose/exposure (ppm):
Transformed dose (mg/kg/day):
Tumor Incidence:
Unadjusted 1/ED10:
Adjusted 1/ED10 (F factor):
Cohen et al., 1970
oral
mice
Swiss
Female
diet
0.03 kg
14 weeks
28 weeks
104 weeks
lymphatic organs
leukemia
0 100 250
0 6.5 16.3
0/15 7/10 8/12
0.51 (mg/kg/day)'1
347 (mg/kg/day)'1
500
32.5
9/13
1000
65.0
8/9
0060d
9-22
07/06/87
-------
for 2 years (Wang et a!., 1984). In view of the other negative rat studies,
the small numbers used by Wang et al. (1984), the unnatural condition of the
germ-free rat and the fact that the results of an NTP dietary study In rats
and mice are pending, the data base was considered to be Inadequate evidence
of cardnogenlclty for animals and nltrofurantoin was classified 1n EPA
Group D. Data are Insufficient for derivation of a Potency Factor (F) and
no hazard ranking based on cardnogenlclty 1s possible.
Nltrofurazone 1s clearly oncogenlc In female rats. A borderline
response 1n mammary tumors was reported by GMswold et al. (1968) who
administered 10 gavage doses to female rats over a 30-day period. A marked
Increase In the Incidence of mammary tumors was noted In female rats fed
nltrofurazone 1n the diet for 36 or 44.5 weeks (Morris et al., 1969) or for
46 weeks (Erturk et al., 1970c). U.S. DHEW (1976b) also reported a highly
significant Increase 1n the Incidence of mammary tumors 1n rats fed nltro-
furazone In the diet for 45 weeks. These data were considered sufficient
evidence for the cardnogenlcHy of nltrofurazone, which was assigned an EPA
classification of B2.
Carcinogenic potencies for nltrofurazone were estimated from the data
from three studies In which the Incidence of mammary tumors 1n female rats
was markedly Increased (Erturk et al., 1970c; U.S. DHEW, 1976b). The
largest human q,*, 1.5 (mg/kg/day)"1, for oral exposure was based on the
Incidence of mammary tumors In female Sprague-Dawley rats reported by Erturk
et al. (1970c) (see Table 6-12, Appendix B-8). These data are also suitable
for derivation of a Potency Factor (F) {Table 9-15). An F factor of 10
(mg/kg/day)"1 places nltrofurazone In Potency Group 2, which, with an EPA
classification of B2, results In a cancer hazard ranking of MEDIUM and a
cancer-based RQ of 10.
0060d 9-23 07/10/87
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TABLE 9-15
Derivation of Potency Factor (F) for NHrofurazone
Reference:
Exposure route:
Species:
Strain:
Sex:
Vehicle or physical state:
Body weight:
Duration of treatment:
Duration of study:
Llfespan of animal:
Target organ:
Tumor type:
Experimental dose/exposure (ppm):
Transformed dose (nig/kg/day):
Tumor Incidence:
Unadjusted 1/EDig:
Adjusted 1/ED10 (F factor):
Erturk et al., 1970c
oral
rat
Sprague-Dawley
Female
diet
0.350 kg
46 weeks
66 weeks
104 weeks
mammary gland
all tumors
0 1000
0 29.7
2/29 22/29
0.43 (mg/kg/day)"1
9.87 (mg/kg/day)'1
0060d
9-24
07/06/87
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In the only cancer experiment with nitrovin, Erturk et al. (1980, 1983)
fed a diet containing 1000 ppm to female Sprague-Dawley rats for 46 weeks
with negative results. The data were judged inadequate to evaluate the
carcinogenicity of nitrovin in antmals and nitrovin was assigned to EPA
Group D. No hazard ranking based on carcinogenicity is possible.
Cancer-based RQs were not derived for the other nitrofurans that are a
subject of this report.
0060d 9-25 06/05/87
-------
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APPENDIX A
LITERATURE SEARCHED
This HEED Is based on data Identified by computerized literature
searches of the following:
TSCATS
CASR online (U.S. EPA Chemical Activities Status Report)
TOXLINE
TOXBACK 76
TOXBACK 65
RTECS
OHM TADS
STORET
SRC Environmental Fate Data Bases
SANSS
AQUIRE
TSCAPP
NTIS
Federal Register
These searches were conducted 1n February, 1987. In addition, hand searches
were made of Chemical Abstracts (Collective Indices 5-9), and the following
secondary sources should be reviewed:
«•
ACGIH (American Conference of Governmental Industrial Hyg1en1sts).
1986. Documentation of the Threshold Limit Values and Biological
Exposure Indices, 5th ed. Cincinnati, OH.
ACGIH (American Conference of Governmental Industrial Hyg1en1sts).
1986-1987. TLVs: Threshold Limit Values for Chemical Substances In
the Work Environment adopted by ACGIH with Intended Changes for
1986-1987. Cincinnati, OH. Ill p.
Clayton, G.D. and F.E. Clayton, Ed. 1981. Patty's Industrial
Hygiene and Toxicology, 3rd rev. ed., Vol. 2A. John WHey and
Sons, NY. 2878 p.
Clayton, G.D. and F.E. Clayton, Ed. 1981. Patty's Industrial
Hygiene and Toxicology, 3rd rev. ed., Vol. 2B. John WHey and
Sons, NY. p. 2879-3816.
Clayton, G.D. and F.E. Clayton, Ed. 1982. Patty's Industrial
Hygiene and Toxicology, 3rd rev. ed., Vol. 2C. John Wiley and
Sons, NY. p. 3817-5112.
A-l
-------
Grayson, M. and D. Eckroth, Ed. 1978-1984. Kirk-Othmer Encyclo-
pedia of Chemical Technology, 3rd ed. John Wiley and Sons, NY. 23
Volumes.
Hamilton, A. and H.L. Hardy. 1974. Industrial Toxicology, 3rd ed.
Publishing Sciences Group, Inc., Littleton, HA. 575 p.
IARC (International Agency for Research on Cancer). IARC Mono-
graphs on the Evaluation of Carcinogenic Risk of Chemicals to
Humans. WHO, IARC, Lyons, France.
Jaber, H.M., W.R. Mabey, A.T. L1eu, T.W. Chou and H.L. Johnson.
1984. Data acquisition for environmental transport and fate
screening for compounds of Interest to the Office of Solid Waste.
SRI International, Menlo Park, CA. EPA 600/6-84-010. NTIS
PB84-243906.
NTP (National Toxicology Program). 1986. Toxicology Research and
Testing Program. Chemicals on Standard Protocol. Management
Status.
Ouellette, R.P. and J.A. King. 1977. Chemical Week Pesticide
Register. McGraw-Hill Book Co., NY.
Sax, I.N. 1984. Dangerous Properties of Industrial Materials, 6th
ed. Van Nostrand Relnhold Co., NY.
SRI (Stanford Research Institute). 1986. Directory of Chemical
Producers. Menlo Park, CA.
U.S. EPA. 1986. Report on Status Report In the Special Review
Program, Registration Standards Program and the Data Call In
Programs. Registration Standards and the Data Call In Programs.
Office of Pesticide Programs, Washington, DC.
U.S. EPA. 1985. CSB Existing Chemical Assessment Tracking System.
Name and CAS Number Ordered Indexes. Office of Toxic Substances,
Washington, DC.
USITC (U.S. International Trade Commission). 1985. Synthetic
Organic Chemicals. U.S. Production and Sales, 1984, USITC Publ.
1422, Washington, DC.
Verschueren, K. 1983. Handbook of Environmental Data on Organic
Chemicals, 2nd ed. Van Nostrand Relnhold Co., NY.
Wlndholz, M., Ed. 1983. The Merck Index, 10th ed. Merck and Co.,
Inc., Rahway, NJ.
Worthing, C.R. and S.B. Walker, Ed. 1983. The Pesticide Manual.
British Crop Protection Council. 695 p.
A-2
-------
In addition, approximately 30 compendia of aquatic toxldty data were
reviewed, Including the following:
Battelle's Columbus Laboratories. 1971. Water Quality Criteria
Data Book. Volume 3. Effects of Chemicals on Aquatic Life.
Selected Data from the Literature through 1968. Prepared for the
U.S. EPA under Contract No. 68-01-0007. Washington, DC.
Johnson, W.W. and M.T. Flnley. 1980. Handbook of Acute Toxldty
of Chemicals to Fish and Aquatic Invertebrates. Summaries of
Toxlclty Tests Conducted at Columbia National Fisheries Research
Laboratory. 1965-1978. U.S. Dept. Interior, Fish and Wildlife
Serv. Res. Publ. 137, Washington, DC.
McKee, J.E. and H.W. Wolf. 1963. Water Quality Criteria, 2nd ed.
Prepared for the Resources Agency of California, State Water
Quality Control Board. Publ. No. 3-A.
Plmental, D. 1971. Ecological Effects of Pesticides on Non-Target
Species. Prepared for the U.S. EPA, Washington, DC. PB-269605.
Schneider, B.A. 1979. Toxicology Handbook. Mammalian and Aquatic
Data. Book 1: Toxicology Data. Office of Pesticide Programs, U.S.
EPA, Washington, DC. EPA 540/9-79-003. NTIS PB 80-196876.
A-3
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APPENDIX 81
Cancer Data Sheet for Derivation of q-|* for Furazolldone
1n Sprague-Dawley Rats
Compound: furazolldone
Reference: U.S. DHEW, 1976a,b
Specles/strain/sex: rat/Sprague-Dawley/female
Body weight = 0.350 kga
Length of exposure (le) = 45 weeks
Length of experiment (Le) = 53 weeks
Llfespan of animal (L) = 104 weeks
Tumor site and type: total mammary tumors
Route/vehicle: oral/diet
Experimental Doses Transformed Dose " Incidence
Exposure (ppm) (mg/kg/day) No. Responding/No. Tested
0 0 0/33
1000 . 42.5b 14/32
Unadjusted q-|* = 2.05xlO"2 (mg/kg/day)"
Human q-|* = 9.1-xlO"1 (mg/kg/day)"ld
Reference body weight for rats (U.S. EPA, 1980)
Estimated by assuming a food factor for rats of 0.05 (U.S. EPA, 1980) and
multiplying the dietary concentration In ppm by 45/53 to expand to contin-
uous exposure throughout the experimental period.
cCompuU'd using Global 82, the multistage model of Howe and Crump (1982).
^Calculated by multiplying the unadjusted q-j* by the cube root of the
ratio of reference human to animal body weight (70 kg/0.350 kg)1/3 and a
factor (104 weeks/53 weeks)3 to correct for the experimental duration
which was less than the natural Hfespan of the rat.
B-l
-------
APPENDIX B2
Cancer Data Sheet for Derivation of q-j* for Furazolldone
In Carworth Farm Rats
Compound: furazolldone
Reference: U.S. DHEW, 1976a,b
Specles/straln/sex: rat/Carworth Farms/F
Body weight = 0.350 kga
Length of exposure (le) = 45 weeks
Length of experiment (Le) = 52 weeks
Llfespan of animal (L) = 104 weeks
Tumor site and type: total mammary tumors
Route/vehicle: oral/diet
Experimental Doses Transformed Dose Incidence
Exposure (ppm) (mg/kg/day) No. Responding/No. Tested
0 0 0/15
•
1000 43.3b 15/17
Unadjusted q-|* = 8.2xlO~* (mg/kg/day)~lC
Human q-|* = 3.8 (mg/kg/day)"ld
Reference body weight for rats (U.S. EPA, 1980)
bEst1mated by assuming a food factor for rats of 0.05 (U.S. EPA, 1980) and
multiplying the dietary concentration In ppm by 45/52 to expand to contin-
uous exposure throughout the experimental period.
cComputed using Global 82, the multistage model of Howe and Crump (1982).
Calculated by multiplying the unadjusted q-|* by the cube root of the
ratio of reference human to animal body weight (70 kg/0.350 kg)1/3 and by
a factor (104 weeks/52 weeks)3 to correct for the experimental duration
which was less than the natural Hfespan of the rat.
B-2
-------
Cancer Data Sheet for Derivation of q-|* for Furlum
1n Sprague-Dawley Rats
Compound: furl urn
Reference: Erturk et al., 1970a
Spec1es/strain/sex: rat/Sprague-Dawley/F
Body weight = 0.225 kga
Length of exposure (le) = 46 weeks
Length of experiment (Le) = 66 weeks
Llfespan of animal (L) = 104 weeks
Tumor site and type: total mammary tumors
Route/vehicle: oral/diet
Experimental Doses Transformed Dose Incidence
Exposure (ppm) (mg/kg/day) No. Responding/No. Tested
0 0 0/28
1990 82.3b 6/56
Unadjusted q-|* = 2.5xlO"3 (mg/kg/day)"lC
Human q-|* = 6.7xlO~2 (mg/kg/day)~ld
Estimated from growth curve
blnvest1gators reported cumulative dose of 8.55 g/rat.
cComputed using Global 82, the multistage model of Howe and Crump (1982).
^Calculated by multiplying the unadjusted q-j* by the cube root of the
ratio of reference human to animal body weight (70 kg/0.225 kg)^/3 an(j by
a factor (104 weeks/66 weeks)3 to correct for the experimental duration
which was less than the natural Ufespan of the rat.
B-3
-------
APPENDIX B4
Cancer Data Sheet for Derivation of q-|* for Furlum
in Swiss Mice (1)
Compound: furl urn
Reference: Cohen et al., 1970
Specles/straln/sex: mlce/Swiss/F
Body weight = 0.030 kga
Length of exposure (le) = 14 weeks
Length of experiment (Le) = 28 weeks
Llfespan of animal (L) = 104 weeks
Tumor site and type: leukemia
Route/vehicle: oral/diet
Experimental Doses Transformed Dose Incidence
Exposure (ppm) (mg/kg/day) No. Responding/No. Tested
0
100
250
500
1000
Unadjusted q-j* =
Human q-|* = 50.4
0
6.5
16.3
32.5
65.0
7.4xlO~2 (mg/kg/day)~lC
(mg/kg/day)~ld
0/15
7/10
8/12
9/13
8/9
Reference body weight for mice (U.S. EPA, 1980)
bEstimated by assuming a food factor for mice of 0.13 (U.S. EPA, 1980) and
applying a factor of 14/28 to expand to continuous exposure throughout the
experimental period.
cComputed using Global 82, the multistage model of Howe and Crump (1982).
^Calculated by multiplying the unadjusted q-j* by the cube root of the
ratio of reference human to animal body weight (70 kg/0.030 kg)l/3 and by
a factor (104 weeks/28 weeks)3 to correct for the experimental duration
which was less than the natural Hfespan of the mouse.
B-4
-------
APPENDIX B5
Cancer Data Sheet for Derivation of q-j* for FuMum
1n Swiss Mice (2)
Compound: furl urn
Reference: Cohen et al., 1973a
Specles/straln/sex: m1ce/Sw1ss/F
Body weight = 0.030 kga
Length of exposure (le) = 14 weeks
Length of experiment (Le) = 30 weeks
Llfespan of animal (L) = 104 weeks
Tumor site and type: leukemia
Route/vehicle: oral/diet
Experimental Doses Transformed Dose
Exposure (ppm) (mg/kg/day)
0
500
1000
Unadjusted q-|* =
Human q-|* = 22.0
0
46. 0B
93. 7C
4.0xlO~2 (mg/kg/dayrid
(mg/kg/day)"^
Incidence
No. Responding/No. Tested
1/28
18/25
26/27
Reference body weight for mice (U.S. EPA, 1980)
blnvest1gators estimated a cumulative dosage of 0.29 g/mouse.
Clnvest1gators estimated a cumulative dosage Of 0.59 g/rnouse.
dComputed using Global 82, the multistage model of Howe and Crump (1982).
"^Calculated by multiplying the unadjusted q-j* by the cube root of the
ratio of reference human to animal body weight (70 kg/0.030 kg)1/3 and by
a factor (104 weeks/30 weeks)3 to correct for the experimental duration
which was less than the natural Ufespan of the mouse.
B-5
-------
APPENDIX B6
Cancer Data Sheet for Derivation of q-j* for Furium
in Swiss Mice (3)
Compound: furium
Reference: Cohen and Bryan, 1978
Species/strain/sex: mice/Sw1ss/F
Body weight = 0.030 kga
Length of exposure (le) = 14 weeks
Length of experiment (Le) = 30 weeks
Lifespan of animal (L) = 104 weeks
Tumor site and type: leukemia
Route/vehicle: oral/diet
Experimental Doses
Exposure (ppm)
Transformed Dose
(mg/kg/day)
Unadjusted q^ = 3.1xlO~2 (mg/kg/day)'
Human qi* = 16.9 (mg/kg/day)~lf
Incidence
No. Responding/No. Tested
0
250
500
1000
0
23. 8b
54. Oc
109. 5d
0/27
8/22
17/22
23/25
Reference body weight for mice (U.S. EPA, 1980)
DInvestigators estimated a cumulative dosage of 0.15 g/mouse.
clnvestigators estimated a cumulative dosage Of 0.34 g/mouse.
Investigators estimated a cumulative dosage of 0.69 g/mouse.
Computed using Global 82, the multistage model of Howe and Crump (1982).
^Calculated by multiplying the unadjusted q-j* by the cube root of the
ratio of reference human to animal body weight (70 kg/0.030 kg)1/3 and by
a factor (104 weeks/30 weeks)3 to correct for the experimental duration
which was less than the natural Hfespan of the mouse.
B-6
-------
APPENDIX 87
Cancer Data Sheet for Derivation of q-j* for Furlum
1n Syrian Golden Hamsters
Compound: furl urn
Reference: Croft and Bryan, 1973
Specles/straln/sex: hamster/Syrian golden/M
Body weight = 0.175 kg (controls)3
0.140 kg (treated)3
Length of exposure (le) = 48 weeks
Length of experiment (Le) = 70 weeks
Llfespan of animal (L) = 125 weeksb
Tumor site and type: urinary bladder, all tumors
Route/vehicle: oral/diet
Experimental Doses Transformed Dose Incidence
Exposure (ppm) (mg/kg/day) No. Responding/No. Tested
0
1000
0
46. 5C
0/24
16/24
Unadjusted q-|* = 3.6xlO~2 (mg/kg/day)~ld
Human q-|* = 1.6 (mg/kg/day) ie
aEst1mated from graphic data provided by Investigators.
bReference llfespan for hamsters (U.S. EPA, 1985).
Clnvest1gators estimated cumulative dosage at 12.6 mmol (3191 mg)/hamster.
dComputed using Global 82, the multistage model of Howe and Crump (1982).
^Calculated by multiplying the unadjusted q-|* by the cube root of the
ratio of reference human to animal body weight (70 kg/0.140 kg)1/3 and by
a factor (125 weeks/70 weeks)3 to correct for the experimental duration
which was less than the natural llfespan of the hamster.
B-7
-------
APPENDIX B8
Cancer Data Sheet for Derivation of q-j* of NHrofurazone
in Sprague-Dawley Rats (1)
Compound: nltrofurazone
Reference: Erturk et al., 1970c
Species/strain/sex: rat/Sprague-Daw!ey/F
Body weight = 0.350 kga
Length of exposure (1e) = 46 weeks
Length of experiment (Le) = 66 weeks
Llfespan of animal (L) = 104 weeks
Tumor site and type: total mammary tumors
Route/vehicle: oral/diet
Experimental Doses
Exposure (ppm)
Transformed Dose
(mg/kg/day)
Incidence
No. Responding/No. Tested
0
1000
0
29.7b
Unadjusted q-|* = 6.7xlO~2 (mg/kg/day)~
Human q-|* = 1.5 (mg/kg/day)~ld
1C
2/29
22/29
Reference body weight for rats (U.S. EPA, 1980).
blnvest1gators estimated cumulative dosage of 4800 mg/rat.
cComputed using Global 82, the multistage model of Howe and Crump (1982).
^Calculated by multiplying the unadjusted q-|* by the cube root of the
ratio of reference human to animal body weight (70 kg/0.350 kg)1/3 and by
a factor (104 weeks/66 weeks)3 to correct for the experimental duration
which was less than the natural Hfespan of the rat.
B-8
-------
APPENDIX B9
Cancer Data Sheet for Derivation of q-j* of NHrofurazone
In Sprague-Dawley Rats (2)
Compound: nltrofurazone
Reference: U.S. DHEW, 1976b
Spec1es/strain/sex: rat/Sprague-Daw!ey/F
Body weight = 0.350 kga
Length of exposure (le) = 45 weeks
Length of experiment (Le) = 53 weeks
Llfespan of animal (L) = 104 weeks
Tumor site and type: total mammary tumors
Route/vehicle: oral/diet
Experimental Doses
Exposure (ppm)
Transformed Dose
(mg/kg/day)
Incidence
No. Responding/No. Tested
0
500
1000
0
23.8b
46.7C
Unadjusted q-j* = 2xlO~2 (mg/kg/day)"ld
Human q-j* = S.SxlO'1 (mg/kg/day)~*e
0/33
12/33
13/30
Reference body weight for rats (U.S. EPA, 1980).
Investigators estimated dosage rate at 28 mg/kg/day during exposure
period.
Clnvest1gators estimated dosage rate at 55 mg/kg/day drulng exposure
period.
Computed using Global 82, the multistage model of Howe and Crump (1982).
Calculated by multiplying the unadjusted q-|* by the cube root of the
ratio of reference human to animal body weight (70 kg/0.350 kg)1/3 and by
a factor (104 weeks/53 weeks)3 to correct for the experimental duration
which was less than the natural Hfespan of the rat.
B-9
-------
APPENDIX BIO
Cancer Data Sheet for Derivation of q-|* for NHrofurazone
1n Carworth Farms Rats
Compound: nltrofurazone
Reference: U.S. DHEW, 1976b
Specles/straln/sex: rat/Carworth Farms/f
Body weight = 0.350 kga
Length of exposure (le) = 45 weeks
Length of experiment (Le) = 52 weeks
Llfespan of animal (L) = 104 weeks
Tumor site and type: total mammary tumors
Route/vehicle: oral/diet
Experimental Doses
Exposure (ppm)
Transformed Dose
(mg/kg/day)
Incidence
No. Responding/No. Tested
0
1000
0
.43.3b
Unadjusted qi* = 3.2xlO~2 (mg/kg/day)~lC
Human q-|* = 1.5 (mg/kg/day)~ld
0/15
11/19
Reference body weight for rate (U.S. EPA, 1980).
^Investigators estimated dosage rate at 50 mg/kg/day during exposure
period.
cComputed using Global 82, the multistage model of Howe and Crump (1982).
^Calculated by multiplying the unadjusted q-|* by the cube root of the
ratio of reference human to animal body weight (70 kg/0.350 kg)l/3 and by
a factor (104 weeks/52 weeks)3 to correct for the experimental duration
which was less than the natural Hfespan of the rat.
B-10