SCREENING-LEVEL HAZARD CHARACTERIZATION
OF HIGH PRODUCTION VOLUME CHEMICALS
SPONSORED CHEMICAL
f-Butyl Alcohol (CAS No. 75-65-0)
[9th CI Name: 2-Propanol, 2-Methyl]
August 2007
Prepared by
High Production Volume Chemicals Branch
Risk Assessment Division
Office of Pollution Prevention and Toxics
Environmental Protection Agency
1200 Pennsylvania Avenue, NW
Washington, DC 20460-0001

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SCREENING-LEVEL HAZARD CHARACTERIZATION
OF HIGH PRODUCTION VOLUME CHEMICALS
The High Production Volume (HPV) Challenge Program1 is a voluntary initiative aimed at developing and making
publicly available screening-level health and environmental effects information on chemicals manufactured in or
imported into the United States in quantities greater than one million pounds per year. In the Challenge Program,
producers and importers of HPV chemicals voluntarily sponsor chemicals; sponsorship entails the identification and
initial assessment of the adequacy of existing toxicity data/information, conducting new testing if adequate data do
not exist, and making both new and existing data and information available to the public. Each complete data
submission contains data on 18 internationally agreed to "SIDS" (Screening Information Data Set1'2) endpoints that
are screening-level indicators of potential hazards (toxicity) for humans or the environment.
The Environmental Protection Agency's Office of Pollution Prevention and Toxics (OPPT) is evaluating the data
submitted in the HPV Challenge Program on approximately 1400 sponsored chemicals. OPPT is using a hazard-
based screening process to prioritize review of the submissions. The hazard-based screening process consists of two
tiers described below briefly and in more detail on the Hazard Characterization website3.
Tier 1 is a computerized sorting process whereby key elements of a submitted data set are compared to established
criteria to "bin" chemicals/categories for OPPT review. This is an automated process performed on the data as
submitted by the sponsor. It does not include evaluation of the quality or completeness of the data.
In Tier 2, a screening-level hazard characterization is developed by EPA that consists of an objective evaluation of
the quality and completeness of the data set provided in the Challenge Program submissions. The evaluation is
performed according to established EPA guidance2'4 and is based primarily on hazard data provided by sponsors.
EPA may also include additional or updated hazard information of which EPA, sponsors or other parties have
become aware. The hazard characterization may also identify data gaps that will become the basis for a subsequent
data needs assessment where deemed necessary. Under the HPV Challenge Program, chemicals that have similar
chemical structures, properties and biological activities may be grouped together and their data shared across the
resulting category. This approach often significantly reduces the need for conducting tests for all endpoints for all
category members. As part of Tier 2, evaluation of chemical category rationale and composition and data
extrapolation(s) among category members is performed in accord with established EPA2 and OECD5 guidance.
The screening-level hazard characterizations that emerge from Tier 2 are important contributors to OPPT's existing
chemicals review process. These hazard characterizations are technical documents intended to support subsequent
decisions and actions by OPPT. Accordingly, the documents are not written with the goal of informing the general
public. However, they do provide a vehicle for public access to a concise assessment of the raw technical data on
HPV chemicals and provide information previously not readily available to the public. The public, including
sponsors, may offer comments on the hazard characterization documents.
The screening-level hazard characterizations, as the name indicates, do not evaluate the potential risks of a chemical
or a chemical category, but will serve as a starting point for such reviews. In 2007, EPA received data on uses of
and exposures to high-volume TSCA existing chemicals, submitted in accordance with the requirements of the
Inventory Update Reporting (IUR) rule. For the chemicals in the HPV Challenge Program, EPA will review the
IUR data to evaluate exposure potential. The resulting exposure information will then be combined with the
screening-level hazard characterizations to develop screening-level risk characterizations4'6. The screening-level
risk characterizations will inform EPA on the need for further work on individual chemicals or categories. Efforts
are currently underway to consider how best to utilize these screening-level risk characterizations as part of a risk-
based decision-making process on HPV chemicals which applies the results of the successful U.S. High Production
Volume Challenge Program and the IUR to support judgments concerning the need, if any, for further action.
1	U.S. EPA. High Production Volume (HPV) Challenge Program; http://www.epa.gov/chemrtk/index.htm.
2	U.S. EPA. HPV Challenge Program - Information Sources; http://www.epa.gov/chemrtk/pubs/general/guidocs.htm.
3	U.S. EPA. HPV Chemicals Hazard Characterization website (http://www.epa.gov/hpvis/abouthc.html).
4	U.S. EPA. Risk Assessment Guidelines; http://cfpub.epa.gov/ncea/raf/rafguid.cfm.
5	OECD. Guidance on the Development and Use of Chemical Categories; http://www.oecd.org/dataoecd/60/47/1947509.pdf.
6	U.S. EPA. Risk Characterization Program; http://www.epa.gov/osa/spc/2riskchr.htm.
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SCREENING-LEVEL HAZARD CHARACTERIZATION
f-Butyl Alcohol (CAS No. 75-65-0)
Introduction
The sponsor, the Propylene Carbonate/t-Butyl Alcohol HPV Committee and its member companies, Lyondell
Chemical Corporation and Huntsman Corporation, submitted a Test Plan and Robust Summaries to EPA for
/-butyl alcohol (CAS No. 75-65-0; 9th CI name: 2-propanol, 2-methyl-) on April 10, 2002. EPA posted the
submission on the ChemRTK HPV Challenge website on May 2, 2002
(http://www.epa.gov/chemrtk/pubs/summaries/tbutvlal/cl3687tc.htm'). EPA comments on the original
submission were posted to the website on August 28, 2002. Public comments were also received and posted to
the website. The sponsor submitted updated/revised documents on November 24, 2004, which were posted to
the ChemRTK website on December 21, 2004.
This screening-level hazard characterization is based primarily on the review of the test plan and robust summaries
of studies submitted by the sponsor(s) under the HPV Challenge Program. In preparing the hazard characterization,
EPA considered its own comments and public comments on the original submission as well as the sponsor's
responses to comments and revisions made to the submission. A summary table of SIDS endpoint data with the
structure(s) of the sponsored chemical(s) is included in the appendix. The screening-level hazard characterization
for environmental and human health toxicity is based largely on SIDS endpoints and is described according to
established EPA or OECD effect level definitions and hazard assessment practices.
Sum m ;m-Conclusion
The lou K of/-bins I alcohol indicates llial lis potential to bioacciininlale is low / -1 > i n \ I alcohol is noi readily
biodegmdable. indicating llial il has the potential lo persist mi the ens iroiinieiii
The es ahialion of as ailable aquatic lo\icily dala lor fish. aquatic 11 in ciicbrales and aquatic plains indicates llial I lie
potential acute ha/aid of/-bills I alcohol lo aquatic organisms is low
\cnk oral and inhalation toMcily of /-biity I alcohol mi nils ;ind acute dermal toxicity in nihhils is low I 'ollow nig
repealed oral c\posiires of rats and mice lor ' months, target organs lor to\icily included the kidney. h\eraiid
miliary bladder kals were more sensitise than mice lo the repeated oral exposures I realniciii-rclaled effects ;it the
lowest cflcclis e dose in nits were reduced hods weight in males and kidney toxicity in males and females Mthoiigh
the kidney toxicity obseix ed in male rats is snggestis e of an alpha -glohnhii-niedialed effect, one of the key es ents
mi this mode of action, alpha -glohiilin accumulation has not heen demoiistrated. Therefore, a \() \I!I. lor
nephropathy in male rats s\as not established In a reprodiictise toxicity study in rats, decreases in the iinniberof
lise-born pnps per lilleraiid offspring bods sseighi occurred at a dose that s\as higher than the losses! dose that
produced clinical signs olToxicily in parental females In a des elopniental toxicity studs in rats, effects included a
decrease in fetal bods weight and an increase in the number of fetuses (but not Inters) sutli skeletal sanations
ipriniarils delased ossification) The los\est dose that produced effects on fetuses also produced impaired motor
aclis its mi the dams /-I >nts I alcohol did not show a potential lo induce gene mutation in bacterial or mammalian
cells /-Iiiiis I alcohol induced an increase mi SCI! frcqncncs in mammalian cells but did not induce chromosome
mutation in mice Due lo the negalise findings lor gene numinous in bacteria and mammalian cells and for
c h ion lost) n le mutation mi mammals in \ i\n. and the positise findings reported lor SCI!, there is onls a slight concern
lor genetic Iomciis lor /-bins I alcohol Ts\o carcinogenicity studies pros ide some es idence lor carcinogenicity of /-
bills I alcohol
I lie potential health lia/ard of /-bins I alcohol is moderate based on the results of the repeated-dose and
reprodiictis e des elopniental lo\icits
\o dala gaps were identified under the I ll'V ( hallenge I'logram
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1. Physical-Chemical Properties and Environmental Fate
A summary of physical-chemical properties and environmental fate data submitted is provided in the Appendix. For
the purpose of the screening-level hazard characterization, the review and summary of these data was limited to the
octanol-water partition coefficient and biodegradation endpoints as indictors of bioaccumulation and persistence,
respectively.
Octanol-Water Partition Coefficient
LogKow: 0.37 (measured)
Biodegradation
Biodegradation data measured according to the modified Sturm method using activated sludge inoculum indicate
that only 2.6-5.1% /-butyl alcohol degraded after 29 days.
Conclusion: The log Kow of /-butyl alcohol indicates that its potential to bioaccumulate is expected to be low. /-
Butyl alcohol is not readily biodegradable, indicating that it has the potential to persist in the environment.
2. Environmental Effects - Aquatic Toxicity
Acute Toxicity to Fish
Fathead minnows (Pimephalespromelas) were exposed to /-butyl alcohol at nominal concentrations of 0, 62.5, 125,
250, 500 or 1000 mg/L for 96 hours under flow-through conditions. Measured concentrations (average of days 0
and 4) were < 42.2, 76.0, 135, 255, 495 and 961 mg/L. Less than 50% lethality occurred at the highest
concentration tested.
96-h LCS0 > 961 mg/L
Acute Toxicity to Aquatic Invertebrates
Daphnia magna were exposed to /-butyl alcohol for 48 hours under static conditions. Neither nominal nor measured
concentrations were provided in the robust summary.
48-h ECso=5504 mg/L
Toxicity to Aquatic Plants
Green algae (Pseudokirchneriella subcapitata) were exposed to /-butyl alcohol at nominal concentrations of 0, 62.5,
125, 250, 500 or 1000 mg/L for 96 hours under static conditions. Measured concentrations were 0, 67.5, 124, 254,
494 and 976 mg/L at test initiation and 0, 49.1, 102, 194, 332 and 695 mg/L at 96 hours. Growth curves for the
controls and /-butyl alcohol treatments were similar. No decrease in cell density, area under the growth curve or
growth rate was seen after 72 or 96 hours of exposure.
96-h EC50 (growth) > 976 mg/L
Conclusion: The evaluation of available aquatic toxicity data for fish, aquatic invertebrates and aquatic plants
indicates that the potential acute hazard of /-butyl alcohol to aquatic organisms is low.
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3. Human Health Effects
Acute Oral Toxicity
(1)	Sprague Dawley rats (5/sex/group) were administered /-butyl alcohol via oral gavage at doses of 1500, 1950,
2535, 3296 and 4285 mg/kg-bw. Over a 14-day observation period, the number of deaths was 0/10, 3/10, 5/10, 5/10
and 10/10 for the 1500, 1950, 2535, 3296 and 4285 mg/kg-bw dose groups, respectively. Clinical signs of toxicity
included ataxia, piloerection, prostration, bradyapnea and hypoactivity and were observed in rats from each dose
group. Surviving animals appeared normal by 6 days after dosing.
LDS0 = 2733 (2249-3320) mg/kg-bw
(2)	Another acute oral toxicity test was conducted in rats; however, no study details were provided. ED50s were
reported for anticonvulsant activity (59 mg/kg-bw) and ataxia (530 mg/kg-bw).
LDS0 = 3500 mg/kg-bw
(3)	Rabbits administered /-butyl alcohol orally showed clinical signs of narcosis (i.e., stupor and loss of voluntary
movements; ED50 = 1408 mg/kg-bw) and toxicity at doses greater than the ED50 for narcosis including loss of
corneal reflexes, nystagmus (an involuntary movement of the eyes), dyspnea and bradycardia. No further study
details were provided.
LDS0 = 3558 mg/kg-bw
Acute Dermal Toxicity
New Zealand White rabbits (5/sex/dose) were administered neat /-butyl alcohol to abraded skin at a dose of 2000
mg/kg-bw. No deaths were observed. All animals exhibited slight to moderate erythema and Assuring of the skin
and very slight or slight desquamation. Significant weight loss was observed in 3 rabbits (2 male and 1 female) and
hemorrhage was seen in 2 rabbits (1 male and 1 female).
LDS0 > 2000 mg/kg-bw
Acute Inhalation Toxicity
Charles River CD rats (5/sex/dose) were exposed to /-butyl alcohol vapor at concentrations of 9700 or 14,100 ppm
(approximately 29.4 or 42.7 mg/L, respectively) for 4 hours and were observed for 14 days after dosing. Ataxia and
prostration were seen at both concentrations during the exposure period and dyspnea was observed in rats exposed to
the highest concentration. During the post exposure period, ataxia and dyspnea were seen in all rats exposed to the
lowest concentration. No animals died at the low concentration, while 3 of 10 animals died at the high
concentration.
LC50 > 14,100 ppm (approximately 42.7 mg/L)
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Repeated-Dose Toxicity
(1)	F344 rats (10/sex/dose) were administered /-butyl alcohol for 13 weeks via drinking water at doses of 0, 230,
490, 840, 1520 and 3610 mg/kg-bw/day in males and 0, 290, 590, 850, 1560 and 3620 mg/kg-bw/day in females.
Reduced body weight was seen in males at doses > 490 mg/kg-bw/day and mortality was reported in 10/10 males
and 6/10 females in the highest dose group. Increased kidney weight was observed in both males and females in all
/-butyl alcohol treatment groups. Increased liver weight was also reported in females at all dose levels and in males
at doses > 840 mg/kg-bw/day; however, the significance of this change in organ weight is not known because liver
histopathology findings were not provided for this study. Nephropathy with hyaline droplet accumulation was
observed in males1 at doses of > 230 mg/kg-bw/day. Nephropathy was observed (without hyaline droplet
accumulation) in females at doses > 850 mg/kg-bw/day. Transitional epithelial hyperplasia of the urinary bladder
was also observed in male rats in the highest dose group.
LOAEL (male) = 230 mg/kg-bw/day (based on nephropathy1)
LOAEL (female) = 850 mg/kg-bw/day (based on nephropathy)
NOAEL (male) = Not established
NOAEL (female) = 590 mg/kg-bw/day
(2)	B6C3F1 mice (10/sex/dose) were administered /-butyl alcohol for 13 weeks via drinking water at doses of 0,
350, 640, 1590, 3940 and 8210 mg/kg-bw/day in males and 0, 500, 820, 1660, 6430 and 11,620 mg/kg-bw/day in
females. No effects were observed in male and female mice at the three lowest doses of /-butyl alcohol. At the
highest dose, a decrease in survival was observed (6/10 males and 4/10 females). Other effects seen at the highest
dose included reduced body weight, transitional epithelial hyperplasia of the urinary bladder and increased liver and
kidney weights (females only). At 6430 mg/kg-bw/day, a female mouse died and at 3940 mg/kg-day, reduced body
weight and transitional epithelial cell hyperplasia were seen in male mice.
LOAEL (male) = 3940 mg/kg-bw/day (based on reduced body weight and bladder effects)
LOAEL (female) = 6430 mg/kg-bw/day (based on mortality)
NOAEL (male) = 1590 mg/kg-bw/day
NOAEL (female) = 1660 mg/kg-bw/day
(3)	In a 2-year drinking water study, F344 rats (60/sex/group) were administered /-butyl alcohol at doses of 0, 90,
200 or 420 mg/kg-bw/day in males and 0, 180, 330 or 650 mg/kg-bw/day in females. Decreased body weight after
week 65 was seen in low-dose males and increased kidney weight and nephropathy occurred in low-dose females.
Higher doses produced histopathological lesions in the kidney, reduced body weight and decreased survival.
LOAEL (male) = 90 mg/kg-bw/day (based on reduced bodyweight)
LOAEL (female) = 180 mg/kg-bw/day (based on increased kidney weight and nephropathy)
NOAEL = Not established
(4)	In a 2-year drinking water study, B6C3F1 mice (60/sex/group) were administered /-butyl alcohol at doses of 0,
540, 1040 and 2070 mg/kg-bw/day in males and 0,510, 1020, and 2110 mg/kg-bw/day in females. At the highest
dose, reduced body weight was observed in both males and females and reduced survival in males. Increased
thyroid follicular cell hyperplasia was seen in both males and females at the two highest doses. An increase in
thyroid follicular cell adenomas was also observed in females at the highest dose.
LOAEL (average of male and female) = 1030 mg/kg-bw/day (based on thyroid follicular cell hyperplasia)
NOAEL (average of male and female) = 525 mg/kg-bw/day
1 The presence of nephropathy in association with the hyaline droplet accumulation in male rats suggests that the
nephropathy in the males is occurring by an alpha2u-globulin-mediated mechanism, which appears to be unique to
male rats and the response is probably not relevant to humans for purposes of risk assessment. EPA's Risk
Assessment Forum has outlined the key events and the data that are necessary to demonstrate this mode of action
(Alpha2u-Globulin: Association with Chemically Induced Renal Toxicity and Neoplasia in the Rat, EP A/625/3-
91/019F). One of the key events, alpha2u-globulin accumulation, has not been demonstrated. Therefore, the
nephropathy is assumed to be relevant to human health and it is concluded that a NOAEL for nephropathy in male
rats was not established.
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Reproductive Toxicity
(1)	In a one-generation study, CRL CD rats (12/sex/group) were administered /-butyl alcohol via oral gavage at
doses of 0, 64, 160, 400 or 1000 mg/kg-bw/day for a 4 week premating period and throughout gestation and
lactation for females. Males were exposed for a total of 9 weeks and females were exposed for approximately 10-11
weeks, until gestation day 21. One male and one female pup from the F1 generation from each litter were exposed
on postnatal days 21-27; no clinical signs of toxicity were observed in these offspring. A questionable increase in
gestation length was seen in dams given 400 or 1000 mg/kg-bw/day. Exposure to 1000 mg/kg-bw/day caused a
decrease in the number of live born pups (i.e., decreased litter size) and decreased offspring body weight after
parturition and throughout lactation. Body weight gain was reduced in male rats given 1000 mg/kg-bw/day.
Clinical signs of toxicity (i.e., transient lethargy and ataxia) were observed in male and female rats at 1000 mg/kg-
bw/day and in a few females at 400 mg/kg-bw/day. In male rats, there was a dose-related increase in kidney weight
(8, 13, 15 and 30% at doses of 64, 160, 400 or 1000 mg/kg-bw/day, respectively) and a 15% increase in liver weight
at 1000 mg/kg-bw/day. Treatment with /-butyl alcohol did not produce gross or histopathological changes in male
or female parents and did not affect mating and fertility, or alter sperm motility or morphology.
LOAEL (systemic toxicity) = 400 mg/kg-bw/day (based on transient lethargy and ataxia in females)
NOAEL (systemic toxicity) = 160 mg/kg-bw/day
LOAEL (reproductive toxicity) = 1000 mg/kg-bw/day (based on decrease in live born pups/litter size, decreased
offspring body weight)
NOAEL (reproductive toxicity) = 400 mg/kg-bw/day
(2)	In the 13-week repeated-dose study with rats described previously, no effects on sperm motility or morphology
were seen in males and no effects on estrous cycle length or the percentage of time spent in the various estrous
stages were seen in females at the highest dose tested.
LOAEL (reproductive toxicity) = Not established
NOAEL (reproductive toxicity - males) = 3610 mg/kg-bw/day
NOAEL (reproductive toxicity - females) = 3620 mg/kg-bw/day
(3)	In the 13-week repeated dose study with mice described previously, no effects on sperm motility or morphology
were seen in males. In female mice, estrous cycle length was increased at the highest dose; however, the time spent
in the various estrous stages was not altered. Mortality (40%) and a significant reduction in body weights was also
observed in female mice at the highest dose tested.
LOAEL (reproductive toxicity - females) = 11,620 mg/kg-bw/day (based on increased estrous cycle length)
NOAEL (reproductive toxicity - males) = 8210 mg/kg-bw/day
NOAEL (reproductive toxicity - females) = 6430 mg/kg-bw/day
Developmental Toxicity
(1) Pregnant Sprague-Dawley rats (15-20 mated animals/group) were exposed to /-butyl alcohol via inhalation for 7
hours/day on days 1 through 19 of gestation at concentrations of 0, 2000, 3500 or 5000 ppm (approximately 0, 6.06,
10.61 or 15.16 mg/L, respectively). Decreased food consumption and maternal weight gain were observed at 5000
ppm. Dams exposed to 3500 or 5000 ppm exhibited an unsteady gait, while impaired locomotor activity was seen in
dams exposed to 2000 ppm (lowest concentration given). Fetal weight was reduced by exposure to /-butyl alcohol at
all concentrations (3.2, 2.9*, 2.8* and 2.2* g/fetus in females and 3.4, 3.1*, 3.0*, and 2.3* in males at concentrations
of 0, 2000, 3500 and 5000 ppm; *p < 0.05). The number of fetuses (but not litters) with skeletal variations
(primarily delayed ossification) was increased by exposure to 3500 or 5000 ppm /-butyl alcohol (variations in 18,
35, 53* and 76* fetuses and in 10/15, 14/17, 14/14 and 12/12 litters at concentrations of 0, 2000, 3500 and 5000
ppm, respectively; *p < 0.05).
LOAEL (maternal toxicity) = 2000 ppm (approximately 6.06 mg/L/day; based on impaired locomotor activity)
NOAEL (maternal toxicity) = Not established
LOAEL (developmental toxicity) = 2000 ppm (approximately 6.06 mg/L/day; based on decreased fetal body
weight)
NOAEL (developmental toxicity) = Not established
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(2)	Pregnant Swiss Webster mice were administered /-butyl alcohol in a liquid diet (concentrations of 0.5, 0.75 or
1%; equivalent to approximately 750, 1125 or 1500 mg/kg-bw/day, respectively) on days 6 through 20 of gestation.
Effects on offspring were monitored until postnatal day 22. Treatment at "the higher concentrations of alcohol"
apparently caused behavioral changes affecting nesting and lactation (no further details were provided). A 2-day
delay in eye opening and decreased pup weight were seen in offspring of dams receiving 1% /-butyl alcohol. A
dose-related increase in the number of stillborn pups was observed (3, 6, 14 and 20 stillborn in the 0, 0.5, 0.75 and
1% groups, respectively). Neurobehavioral effects (cliff avoidance, righting reflex, open field activity and roto-rod
performance) were reported in treated pups; however, results were not compared to controls. Maternal body weight
measured on gestation day 20 was decreased by administration of /-butyl alcohol (5 and 10% decrease at 0.75 and
1%, respectively). Average pup weights 2 days after birth were 1.78, 1.66, 1.45 and 1.10 g/pup for 0, 0.5, 0.75 and
1%, respectively (statistics not provided). Postnatal growth, measured as pup weight on postnatal day 10, was
reduced by gestational exposure to /-butyl alcohol (6.9, 6.5, 6.0 and 4.0 g/pup for 0, 0.5, 0.75 and 1%, respectively,
statistics not provided). LOAEL and NOAEL values for maternal and developmental toxicity were not provided in
the robust summary.
LOAEL (maternal toxicity) = 0.5% (approximately 750 mg/kg-bw/day; based on increased in stillborn pups)
NOAEL (maternal toxicity) = Not established
LOAEL (developmental toxicity) = 0.5% (approximately 750 mg/kg-bw/day; based on reduced pup weight)
NOAEL (developmental toxicity) = Not established
(3)	CBA/J and C57BL/6J mice (5-7 control mice/species; 9-12 treated mice/species) were administered 1550 mg/kg-
bw/day /-butyl alcohol by oral gavage (in 2 treatments) on days 6 through 18 of gestation. Controls received tap
water by gavage twice daily during the same period. /-Butyl alcohol treatment caused an increase in resorptions, but
did not cause developmental anomalies. The average number of resorptions/litter was 1.42 for CBA/J controls, 3.09
for CBA/J treated mice, 0.80 for C57BL/6J controls and 4.22 for C57BL/6J treated mice (statistics not provided).
The average number of live fetuses/litter was 8.0 for CBA/J controls, 4.75 for CBA/J treated mice, 8 for C57BL/6J
controls and 3.33 for C57BL/6J treated mice (statistics not provided). Average litter weights were 0.8 g for CBA/J
controls, 0.77 g for CBA/J treated mice, 0.94 g for C57BL/6J controls and 0.90 g for C57BL/6J treated mice
(statistics not provided). LOAEL and NOAEL values for maternal and developmental toxicity were not provided
(single-dose study) in the robust summary.
LOAEL (maternal toxicity) = 1550 mg/kg-bw/day (based on increased resorptions)
NOAEL (maternal toxicity) = Not established
LOAEL (developmental toxicity) = 1550 mg/kg-bw/day (based on decreased number of live fetuses)
NOAEL (developmental toxicity) = Not established
Genetic Toxicity - Gene Mutation
In vitro
(1)	/-Butyl alcohol was tested in several Salmonella strains (TA98, TA100, TA1535, TA1537 and TA1538) at
concentrations of 100, 500, 2500, 5000 and 10,000 |.ig/platc. with and without metabolic activation. Both positive
and negative controls were run and cytotoxicity was not evident at any of the concentrations tested. Positive control
responses were not provided in the robust summary.
/-Butyl alcohol was not mutagenic in this assay.
(2)	/-Butyl alcohol was tested in several Salmonella strains (TA98, TA100, TA1535 and TA1537) at concentrations
of 100, 333, 1000, 3333 and 10,000 |.ig/platc. with and without metabolic activation. Both positive and negative
controls were run and cytotoxicity was not evident at any of the concentrations tested. Positive control responses
were not provided in the robust summary.
/-Butyl alcohol was not mutagenic in this assay.
(3)	Salmonella strain TA102 was used and /-butyl alcohol was tested at concentrations of 100, 200, 500, 1000, 2500
and 5000 |.ig/platc. with and without metabolic activation. Both positive and negative controls were run and
cytotoxicity was not evident at any of the concentrations tested. Positive control responses were not provided in the
robust summary.
/-Butyl alcohol was not mutagenic in this assay.
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(4) In two studies, /-butyl alcohol was tested in L5178Y mouse lymphoma cells at concentrations of 1.7-32 |_iL/mL.
with and without metabolic activation. Both positive and negative controls were used in each study and cytotoxicity
was not evident at any of the concentrations tested. Positive control responses were positive in one study and
unstated in the other.
f-Butyl alcohol was not mutagenic in these assays.
Genetic Toxicity - Chromosomal Aberrations
In vitro
Sister chromatid exchange (SCE) was evaluated in Chinese hamster ovary cells following exposure to /-butyl
alcohol at concentrations of 5, 10 or 20 |_iL/mL with and without metabolic activation. A dose-related increase in
SCE frequency in the presence of metabolic activation, but not in its absence, was observed.
f-Butyl alcohol induced sister chromatid exchange in the presence of metabolic activation in this assay.
In vivo
A micronucleus assay was conducted in male B6C3F1 mice (4/dose). /-Butyl alcohol was administered via
intraperitoneal injection at doses of 0, 312.5, 625 or 1250 mg/kg-bw/day once per day for 3 days.
Cyclophosphamide (15 mg/kg-bw) was used as a positive control. Animals were sacrificed 24 hours after the last
injection and the number of micronuclei/1000 polychromatic erythrocytes was counted (2000 cells counted). The
positive control produced a statistically significant increase in micronuclei.
/-Butyl alcohol did not induce chromosomal aberrations in this assay.
Additional Information
Carcinogenicity
(1)	A 2-year drinking water study was conducted in F344 rats (60/sex/group). Doses of /-butyl alcohol were 0, 90,
200 and 420 mg/kg-bw/day in males and 0, 180, 330 and 650 mg/kg-bw/day in females. Kidney adenomas and
carcinomas were seen in male rats only.
(2)	A 2-year drinking water study was conducted in B6C3F1 mice (60/sex/group). Doses of /-butyl alcohol were 0,
540, 1040 and 2070 mg/kg-bw/day in males and 0, 510, 1020 and 2110 mg/kg-bw/day in females. Thyroid
follicular cell adenoma was seen in males (1/60, 0/59, 4/59 and 2/57 for the 0, 540, 1040 and 2070 mg/kg-bw/day
groups, respectively) and females (2/58, 3/60, 2/59 and 9/59 for the 0, 510, 1020 and 2110 mg/kg-bw/day groups,
respectively). One male mouse had thyroid follicular cell carcinoma. The study authors concluded that there was
equivocal evidence of carcinogenicity in males and some evidence of carcinogenicity in females.
Conclusion: Acute oral and inhalation toxicity of /-butyl alcohol in rats and acute dermal toxicity in rabbits is low.
Following repeated oral exposures of rats and mice for 3 months, target organs for toxicity included the kidney, liver
and urinary bladder. Rats were more sensitive than mice to the repeated oral exposures. Treatment-related effects at
the lowest effective dose in rats were reduced body weight in males and kidney toxicity in males and females.
Although the kidney toxicity observed in male rats is suggestive of an alpha2u-globulin-mediated effect, one of the
key events in this mode of action, alpha2u-globulin accumulation has not been demonstrated1. Therefore, a NOAEL
for nephropathy in male rats was not established. In a reproductive toxicity study in rats, decreases in the number of
live-born pups per litter and offspring body weight occurred at a dose that was higher than the lowest dose that
produced clinical signs of toxicity in parental females. In a developmental toxicity study in rats, effects included a
1 The presence of nephropathy in association with the hyaline droplet accumulation in male rats suggests that the
nephropathy in the males is occurring by an alpha2u-globulin-mediated mechanism, which appears to be unique to
male rats and the response is probably not relevant to humans for purposes of risk assessment. EPA's Risk
Assessment Forum has outlined the key events and the data that are necessary to demonstrate this mode of action
(Alpha2u-Globulin: Association with Chemically Induced Renal Toxicity and Neoplasia in the Rat, EP A/625/3-
91/019F). One of the key events, alpha2u-globulin accumulation, has not been demonstrated. Therefore, the
nephropathy is assumed to be relevant to human health and it is concluded that a NOAEL for nephropathy in male
rats was not established.
9

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decrease in fetal body weight and an increase in the number of fetuses (but not litters) with skeletal variations
(primarily delayed ossification). The lowest dose that produced effects on fetuses also produced impaired motor
activity in the dams. /-Butyl alcohol did not show a potential to induce gene mutation in bacterial or mammalian
cells. /-Butyl alcohol induced an increase in SCE frequency in mammalian cells but did not induce chromosome
mutation in mice. Due to the negative findings for gene mutations in bacteria and mammalian cells and for
chromosome mutation in mammals in vivo, and the positive findings reported for SCE, there is only a slight concern
for genetic toxicity for /-butyl alcohol. Two carcinogenicity studies provide some evidence for carcinogenicity of /-
butyl alcohol.
The potential health hazard of /-butyl alcohol is moderate based on the results of the repeated-dose and
reproductive/developmental toxicity.
4. Hazard Characterization
The log Kow of /-butyl alcohol indicates its potential to bioaccumulate is low. /-Butyl alcohol is not readily
biodegradable, indicating it has the potential to persist in the environment.
The evaluation of available aquatic toxicity data for fish, aquatic invertebrates and aquatic plants indicates the
potential acute hazard of /-butyl alcohol to aquatic organisms is low.
Acute oral and inhalation toxicity of /-butyl alcohol in rats and acute dermal toxicity in rabbits is low. Following
repeated oral exposures of rats and mice for 3 months, target organs for toxicity included the kidney, liver and
urinary bladder. Rats were more sensitive than mice to the repeated oral exposures. Treatment-related effects at the
lowest effective dose in rats were reduced body weight in males and kidney toxicity in males and females. Although
the kidney toxicity observed in male rats is suggestive of an alpha2u-globulin-mediated effect, one of the key events
in this mode of action, alpha2u-globulin accumulation has not been demonstrated1. Therefore, a NOAEL for
nephropathy in male rats was not established. In a reproductive toxicity study in rats, decreases in the number of
live-born pups per litter and offspring body weight occurred at a dose that was higher than the lowest dose that
produced clinical signs of toxicity in parental females. In a developmental toxicity study in rats, effects included a
decrease in fetal body weight and an increase in the number of fetuses (but not litters) with skeletal variations
(primarily delayed ossification). The lowest dose that produced effects on fetuses also produced impaired motor
activity in the dams. /-Butyl alcohol did not show a potential to induce gene mutation in bacterial or mammalian
cells. /-Butyl alcohol induced an increase in SCE frequency in mammalian cells but did not induce chromosome
mutation in mice. Due to the negative findings for gene mutations in bacteria and mammalian cells and for
chromosome mutation in mammals in vivo, and the positive findings reported for SCE, there is only a slight concern
for genetic toxicity for /-butyl alcohol. Two carcinogenicity studies provide some evidence for carcinogenicity of /-
butyl alcohol.
The potential health hazard of /-butyl alcohol is moderate based on the results of the repeated-dose and
reproductive/developmental toxicity.
5. Data Gaps
No data gaps were identified under the HPV Challenge Program.
1 The presence of nephropathy in association with the hyaline droplet accumulation in male rats suggests that the
nephropathy in the males is occurring by an alpha2u-globulin-mediated mechanism, which appears to be unique to
male rats and the response is probably not relevant to humans for purposes of risk assessment. EPA's Risk
Assessment Forum has outlined the key events and the data that are necessary to demonstrate this mode of action
(Alpha2u-Globulin: Association with Chemically Induced Renal Toxicity and Neoplasia in the Rat, EP A/625/3-
91/019F). One of the key events, alpha2u-globulin accumulation, has not been demonstrated. Therefore, the
nephropathy is assumed to be relevant to human health and it is concluded that a NOAEL for nephropathy in male
rats was not established.
10

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APPENDIX
Summary Tabic of the Screening Information Data Set
as submitted under the U.S. HPV Challenge Program
Endpoints
SPONSORED CHEMICAL
to*?-Butyl Alcohol
(75-65-0)
Structure
ch3
HO	CH3
ch3
Summary (if Physical-Chemical Properties and Environmental Fate Data
Melting Point (C)
25
Boiling Point (C)
81
Vapor Pressure
(hPa at 25C)
41.3
Log Kw
0.37
Water Solubility
(mg/L at 25C)
l.OxlO6
Direct Photodegradation
not expected, does not absorb in the region 290-800 nm
Indirect (OH ) Photodegradation
Half-life (t1/2)
9.6 d
Stability in Water (Hydrolysis) (ti/2)
does not contain functional groups that hydrolyze under
environmental conditions
Fugacity
(Level III Model)
Air(%)
Water (%)
Soil (%)
Sediment (%)
9.5
50.4
40
0.0856
Biodegradation at 28 days (%)
2.6-5.1(29 d)
Not readily biodegradable
Summary of Environmental Effects - Aquatic Toxicity Data
Fish
96-h LCS0 (mg/L)
>961
Aquatic Invertebrates
48-h ECS0 (mg/L)
5504 (4607-6577)
Aquatic Plants
72-h ECS0 (mg/L)
(growth)
(biomass)
>976
Summary of Human Health Data
Acute Oral Toxicity
LDS0 (mg/kg-bw)
2733
Acute Dermal Toxicity
LDS0 (mg/kg-bw)
>2000
Acute Inhalation Toxicity
LC50 (mg/L)
>42.7
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Summary Tabic of the Screening Information Data Set
as submitted under the U.S. HPV Challenge Program
Endpoints
SPONSORED CHEMICAL
to*?-Butyl Alcohol
(75-65-0)
Repeated-Dose Toxicity
NOAEL/LOAEL
Oral (mg/kg-bw/day)
NOAEL (male, rat) Not established; LOAEL = 490
NOAEL (female, rat) =590; LOAEL) = 850
NOAEL (male, mouse) = 1590; LOAEL = 3940
NOAEL (female, mouse) = 1660; LOAEL = 6430
Reproductive Toxicity
(mg/kg-b w/day)

NOAEL (Systemic)
LOAEL (Systemic)
NOAEL (Reproductive)
LOAEL (Reproductive)
160
400
400
1000
Developmental Toxicity
(mg/kg-b w/day)

NOAEL (Maternal)
LOAEL (Developmental)
750
750
((mg/L/day)

NOAEL (Maternal)
LOAEL (Developmental
6.06
6.06
Genetic Toxicity - Gene Mutation
In vitro
Negative
Genetic Toxicity - Gene Mutation
In vivo
-
Genetic Toxicity - Chromosomal Aberrations
In vitro
Positive
Genetic Toxicity - Chromosomal Aberrations
In vivo
Negative
Additional Information
Carcinogenicity
- indicates endpoint was not addressed for this chemical
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