August, 1987
DRAFT
Health Advisory
Office of Drinking Water
U.S Environmental Protection Agency
I. INTRODUCTION
The Health Advisory (HA) Program, sponsored by the Office of Drinking
Water (ODW), provides information on the health effects, analytical method-
ology and treatment technology that would be useful in dealing with the
contamination of drinking water. Health Advisories describe nonregulatory
concentrations of drinking water contaminants at which adverse health effects
would not be anticipated to occur over specific exposure durations. Health
Advisories contain a margin of safety to protect sensitive members of the
population.
Health Advisories serve as informal technical guidance to assist Federal,
State and local officials responsible for protecting public health when
emergency spills or contamination situations occur. They are not to be
construed as legally enforceable Federal standards. The HAs are subject to
change as new information becomes available.
Health Advisories are developed for one-day, ten-day, longer-term
(approximately 7 years, or 10% of an individual's lifetime) and lifetime
exposures based on data describing noncarcinogenic end points of toxicity.
Health Advisories do not quantitatively incorporate any potential carcinogenic
risk from such exposure. For those substances that are known or probable
human carcinogens, according to the Agency classification scheme (Group A or
B), Lifetime HAs are not recommended. The chemical concentration values for
Group A or B carcinogens are correlated with carcinogenic risk estimates by
employing a cancer potency (unit risk) value together with assumptions for
lifetime exposure and the consumption of drinking water. The cancer unit
risk is usually derived from the linear multistage model with 95% upper
confidence limits. This provides a low-dose estimate of cancer risk to
humans that is considered unlikely to pose a carcinogenic risk in excess
of the stated values. Excess cancer risk estimates may also be calculated
using the One-hit, Weibull, Logit or Probit models. There is no current
understanding of the biological mechanisms involved in cancer to suggest that
any one of these models is able to predict risk more accurately than another.
tacause each model is based on differing assumptions, the estimates that are
derived can differ by several orders of magnitude.
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II. GENERAL INFORMATION AND PROPERTIES
CAS No. 25057-89-0
Structural Formula
3-( 1 -Methylethyl)-1H-2,1,3-benzothiadiazin-4(3H)-one,2,2-dioxide
Synonyms
0 Basagran; Bendioxide; Bentazone (Worthing, 1983).
Uses
0 Selective postemergent herbicide used to control broadleaf weeds in
soybeans, rice, corn, peanuts, dry beans, dry peas, snap beans for
seed, green lima beans and mint (Meister, 1986).
Properties (Worthing, 1983)
Chemical Formula GI g^l2N2°3S
Molecular Weight 240.3
Physical State Colorless crystalline powder
Boiling Point —
Melting Point 137 to 139°C
Density —
Vapor Pressure ~
Water Solubility 500 mg/L
Log Octanol/water Partition
Coefficient
Taste Threshold --
Odor Threshold —
Conversion Factor ~
Occurrence
0 Bentazon was not found in sampling performed at two water supply
stations in the STORET database (STORET, 1987). No information
on the occurrence of bentazon was found in the available literature.
Environmental Fate . ' -
0 Bentazon, at 1 ppm,. was stable to hydrolysis for up to 122 days in
unbuffered water (initial pH 5, 7, and 9) at 22°C (Drescher, 1972c).
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The bentazon degradate, 2-amino-N-isopropyl benzamide (AIBA) at
1 ppm, was stable to hydrolysis in unbuffered, distilled water at pH 5,
7, and 9, during 28 days' incubation in the dark at 22°C (Orescher,
1973b).
14c-Bentazon at 2 to 10 ppm, degraded with a half-life of less than
2 to 14 weeks in a sandy clay loam, loam, and three loamy sand soils
(Drescher and Otto, 1973a; Drescher and Otto, 1973b). The soils were
incubated at 14 to 72% of field capacity and 23°C. The bentazon
degradation rate was not affected by soil moisture content but was
decreased by lowering the temperatures to 8 to 10°C. At pH 6.4, the
degradation rate in a loamy sand soil was 2.5 times longer than at
pH 4.6 and 5.5. The bentazon degradate, AIBA, was identified at less
than 0.1 ppm. AIBA degraded in loamy sand soil with a half-life of
1 to 10 days (43% of field capacity). 14c-Bentazon at 1.7 ppm did
not degrade appreciably in a loamy sand soil during 8 weeks of incubation;
AIBA was detected at a maximum concentration of 0.008 ppm.
Bentazon did not adsorb to Drummer silty clay loam, adjusted to pH 5
and 7, and 11 other soils tested at pH 5 (Abernathy and Wax,
1973). In the same study, using soil TLC, (14c)bentazon was very
mobile in 12 soils, ranging in texture from sand to silty clay loam,
with an Rf value of 1.0.
Bentazon was very mobile in a variety of soils, ranging in texture
from loamy sand to silty clay loam and muck, based on soil column
tests (Drescher and Otto, 1972; Abernathy and Wax, 1973; Drescher,
1973a; Drescher, 1972a). Approximately 73. to 103% of the bentazon
applied to the columns was recovered in the leachate.
AIBA (100 ug applied to loamy sand soil) was very mobile (Drescher,
1972b). After leaching a 12-inch soil column with 500 ml (10 inches)
of distilled water, 86.3% of the applied material was found in the
leachate.
Bentazon has the potential to contaminate surface waters as a result
of its mobility in runoff water and application to rice fields
(Devine, 1972; Wuerzer, 1972).
In the field, bentazon at 0.75 to 10 Ib ai/A dissipated with a half-
life of less than or equal to 1 month in the upper 6 inches of soil,
ranging in texture from sand to clay (Daniels et al., 1976; Devine
and Hanes, 1973; Stoner and Hanes, 1974b; Stoner and Hanes, 1974a;
BASF Wyandotte Corporation, 1974; Devine and Tietjens, 1973; Devine
et al., 1973). In the majority of soils (6 of 9), bentazon had a
half-life of less than 7 days. AIBA was detected at less than or
equal to 0.09 ppm. Collectively, the available data indicated that
geographic region (NC, TX, MS, AL, MN, or ID) and crops treated
(peanuts, soybeans, corn or fallow soil) had little or no effect on
the dissipation rate of bentazon in soil.
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III. PHARMACOKINETICS
Absorption
0 Male and female rats (200 to 250 g) given 0.8 mg Hc-bentazon in 1 mL
of 50% ethanol by stomach tube excreted 91% of the administered dose
in the urine within 24 hours. This suggests that bentazon is almost
completely absorbed when ingested (Chasseaud et al., 1972).
Distribution
0 Whole-body autoradiography of rats indicated high levels of radio-
activity in the stomach, liver, heart and kidneys after 1 hour of
dosing with 14c-bentazon. Radioactivity was not observed in the brain
or spinal cord (Chasseaud et al., 1972).
Metabolism
e Bentazon is poorly metabolized. Two unidentified metabolites
were detected (Chasseaud et al., 1972).
Excretion
Rats given radiolabeled bentazon excreted 91% of the administered dose
in the urine as parent compound. Feces contained 0.9% of the administered
dose (Chasseaud et al., 1972).
IV. HEALTH EFFECTS
Humans
No information on the health effects of bentazon in humans was found
in the available literature.
Animals
Short-term Exposure
0 The oral LD5Q of bentazon in the rat was reported to be 2,063 mg/kg
(Meister, 1986).
0 LD50 values for bentazon in the rat, dog, cat and rabbit are reported
to be 1,100, 900, 500 and 750 mg/kg, respectively (RTECS, 1985).
0 Acute, subchronic and chronic oncogenicity studies on bentazon have
been invalidated because of data gaps and deficiencies. However, the
RfD Workgroup (U.S. EPA 1986a) calculated a Reference Dose (RfD) for
bentazon from a 13-week study in dogs. This study is described in
detail in Section V. Quantification of Toxicological Effects. Note
that the calculated RfD value has a low confidence level.
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Dermal/Ocular Effects
0 No valid information on the dermal/ocular effects of bentazon was
found in the available literature.
Long-term Exposure
0 As indicated under Short-term Exposure, long-term studies, including
reproductive effects and carcinogenicity studies, have been invalidated.
Reproductive Effects
0 No valid information on the reproductive effects of bentazon was
found in the available literature.
Developmental Effects
0 No valid information on the developmental effects of bentazon was
found in the available literature.
Mutagenicity
0 No valid information on the mutagenic effects of bentazon was found
in the available literature.
Carcinogenicity
0 No valid information on the carcinogenic effects of bentazon was
found in the available literature.
V. QUANTIFICATION OF TOXICOLOGICAL EFFECTS
Health Advisories (HAs) are generally determined for one-day, ten-day,
longer-term (approximately 7 years) and lifetime exposures if adequate data
are available that identify a sensitive noncarcinogenic end point of toxicity.
The HAs for noncarcinogenic toxicants are derived using the following formula:
where:
HA = (NOAEL or LOAEL) x (BW) = mg/L ( ug/L)
(UF) x ( L/day)
NOAEL or LOAEL = No- or Lowest-Observed-Adverse-Effect-Level
in mg/kg bw/day.
BW = assumed body weight of a child (10 kg) or
an adult (70 kg).
UF = uncertainty factor (10, 100 or 1,000), in
accordance with NAS/ODW guidelines.
L/day = assumed daily water consumption of a child
(1 L/day) or an adult (2 L/day).
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One-day Health Advisory
No data were found in the available literature that were suitable for
determination of One-day HA values. It is, therefore, recommended that the
Longer-term HA value for a 10-kg child (0.25 mg/L, calculated below) be used
at this time as a conservative estimate of the One-day HA.
Ten-day Health Advisory
No data were found in the available literature that were suitable for
determination of Ten-day HA values. It is, therefore, recommended that the
Longer-term HA value for a 10-kg child (0.25 mg/L, calculated below) be used
at this time as a conservative estimate of the Ten-day HA.
Longer-term Health Advisory
A 13-week study in beagle dogs has been selected for the calculation of
a Longer-term HA (Leuschner et al., 1970). Beagle dogs (three dogs/sex/dose)
were gven 0 (control), 100, 300, 1,000 and 3,000 ppm (0, 2.5, 7.5, 25 and
75 mg/kg/day; Lehman, 1959) of bentazon for 13 weeks. At a dose level of
3,000 ppm, overt signs of toxicity, including weight loss and ill health, were
observed; 1/3 males and 2/3 females died. At 3,000 ppm, all males showed signs
of prostatitis. Similar signs were observed in one male each at the 300- and
1,000-ppm levels. This study suggests a NOAEL of 100 ppm (2.5 mg/kg/day).
Utilizing this NOAEL, a Longer-term HA for a 10-kg child is calculated
as follows:
Longer-term HA = (2.5 mg/kg/day) (10 kg) = 0.25 mg/L (250 ug/L)
(100) (1 .L/day)
where:
2.5 mg/kg/day = NOAEL, based on absence of prostatic effects in dogs.
10 kg = assumed body weight of a child.
100 = uncertainty factor, chosen in accordance with NAS/ODW
guidelines for use with a NOAEL from an animal study.
1 L/day = assumed daily water consumption of a child.
The Longer-term HA for the 70-kg adult is calculated as follows:
Longer-term HA = (2.5 mg/kg/day) (70 kg) . 0.875 /L (875 /L)
(100) (2 L/day)
where:
2.5 mg/kg/day = NOAEL, based on absence of prostatic effects in dogs.
70 kg = assumed body weight of an adult.
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1 00 * uncertainty factor, chosen in accordance with NAS/ODW
guidelines for use with a NOAEL from an animal studyo
2 L/day - assumed daily water consumption of an adult.
Lifetime Health Advisory
The Lifetime HA represents that portion of an individual's total exposure
that is attributed to drinking water and is considered protective of noncar-
cinogenic adverse health effects over a lifetime exposure. The Lifetime HA
is derived in a three-step process. Step 1 determines the Reference Dose
(RfD), formerly called the Acceptable Daily Intake (ADI). The RfD is an esti-
mate of a daily exposure to the human population that is likely to be without
appreciable risk of deleterious effects over a lifetime, and is derived from
the NOAEL (or LOAEL), identified from a chronic (or subchronic) study, divided
by an uncertainty factor(s). From the RfD, a Drinking Water Equivalent Level
(DWEL) can be determined (Step 2). A DWEL is a medium-specific (i.e., drinking
water) lifetime exposure level, assuming 100% exposure from that medium, at
which adverse, noncarcinogenic health effects would not be expected to occur.
The DWEL is derived from the multiplication of the RfD by the assumed body
weight of an adult and divided by the assumed daily water consumption of an
adult. The Lifetime HA is determined in Step 3 by factoring in other sources
of exposure, the relative source contribution (RSC). The RSC from drinking
water is based on actual exposure data or,. if data are not available, a
value of 20% is assumed for synthetic organic chemicals and a value of 10%
is assumed for inorganic chemicals. If the contaminant is classified as a
Group A or B carcinogen, according to the Agency's classification scheme of
carcinogenic potential (U.S. EPA, 1986b), then caution should be exercised in
assessing the risks associated with lifetime exposure to this chemical.
Lifetime studies were not available to calculate a Lifetime HA. However,
with the addition of another safety factor of 10 for studies of less-than-
lifetime duration, the Lifetime HA may be calculated from the 13-week feeding
study in dogs (Leuschner et al., 1970).
Using the NOAEL of 2.5 mg/kg/day, the Lifetime HA for bentazon is
calculated as follows:
Step 1: Determination of a the Reference Dose (RfD)
RfD = (2.5 mg/kg/day) = 0.0025 mg/kg/day
(1,000)
where:
2.5 mg/kg/day = NOAEL, based on the absence of prostatic effects in
dogs.
1,000 = uncertainty factor, chosen in accordance with NAS/ODW
guidelines for use with a NOAEL from an animal study
of less-than-lifetime duration.
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Step 2: Determination of the Drinking Water Equivalent Level (DWEL)
DWEL - (0.0025 mg/kg/day) (70 kg) „ Oo0875 mg/L (87.5 ug/L)
(2 L/day)
where:
0.0025 mg/kg/day * RfD.
70 kg • assumed body weight of an adult.
2 L/day « assumed daily water consumption of an adult.
Step 3: Determination of the Lifetime Health Advisory
Lifetime HA = (0.0875 mg/L) (20%) = 0.0175 mg/L (17.5 ug/L)
where:
0.0875 mg/L = DWEL.
20% = assumed relative source contribution from water.
Evaluation of Carcinogenic Potential
0 No valid data are available to make a determination of the carcino-
genic potential of bentazon.
0 Applying the criteria described in EPA's guidelines for assessment
of carcinogenic risk (U.S. EPA, 1986b), bentazon may be classified
in Group D: not Classified. This category is for agents with inadequate
animal evidence of carcinogenicity.
VI. OTHER CRITERIA, GUIDANCE AND STANDARDS
0 In response to a bentazon-tolerance review petition, EPA's Office of
Pesticide Programs has concluded that "a tolerance cannot be supported
at this time."
VII. ANALYTICAL METHODS
* Analysis of bentazon is by a gas chromatographic (GC) method applicable
to the determination of bentazon in water samples (U.S. EPA, 1985).
In this method, an aliquot of sample is acidified and extracted with
ethyl acetate. The extract is dried, concentrated to 1 to 2 mL, and
methylated with diazomethane. The methylated extracts are analyzed
by gas chromatography with flame photometric detection. The method
detection limit for bentazon has not been determined.
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VIII. TREATMENT TECHNOLOGIES
0 There is no information available regarding treatment technologies
used to remove bentazon from contaminated water*
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IX. REFERENCES
Abernathy, J. R. and L. M. Wax. 1973. Bentazon mobility and adsorption in
twelve Illinois soils. Weed Science. 21(3):224-226.
BASF Wyandotte Corporation. 1974. Analytical residue reports (soil and
water): bentazon. Unpublished study.
Chasseaud, L. F., D.R. Hawkins, B.C. Cameron, B.J. Fry and V.H. Saggers. 1972.
The metabolic fate of bentazon. Xenobiotica. 2(3): 269-276.
Daniels, J., J. Gricher and T. Boswell. 1976. Determination of bentazon
(BAS 351-H) residues in sand soil samples from Yoakum, Texas: Report
No. IRDC-3; BWC Project No. I-2-G-73. Unpublished study prepared by
International Research and Development Corporation, submitted by BASF
Wyandotte Corporation, Wyandotte, MI.
Devine, J. M. 1972. Determination of BAS 351-H (3-isopropyl-lH-2,l,3-benzo-
thiadiazin-4(3H)-one-2,2-dioxide) residues in soil and runoff water.
Report No. 133.
Devine, J. M. and R. E. Hanes. 1973. Determination of residues of BAS
351-H(3-isopropyl-lH-2,l,3-benzothiadiazin-4(3H)-one-2,2-dioxide) and
its benzamide metabolite, AIBA (2-amino-N-isopropyl benzamide), in
Sharkey silty clay soil from Greenville, Mississippi: Field Experiment
No. 72-99. Unpublished study prepared by State University of New
York—Oswego, Lake Ontario Environmental Laboratory and United States
Testing Company, Inc., submitted by BASF Wyandotte Corporation,
Parsippany, NJ.
Devine, J. M. and F. Tietjens. 1973. Determination of BAS 351-H (3-isopropyl-
lH-2,l,3-benzothiadiazin-4(3H)-one-2,2-dioxide) residues in Commerce
silt loam soil from Greenville, Mississippi: Field Experiment No. 72-76.
Unpublished study prepared by State Univeristy of New York—Oswego, Lake
Ontario Environmental Laboratory and United States Testing Company,
Inc., submitted by BASF Wyandotte Corporation, Parsippany, NJ.
Devine, J. M., C. Carter, L. W. Hendrick et al. 1973. Determination of
residues of BAS 351-H (3-isopropyl-lH-2,l,3-benzothiadiazin-4(3H)-one-
2,2-dioxide) and its benzamide metabolite, AIBA (2-amino-N-isoopropyl
benzamide), in Webster Glencoe silty clay loam soil from Prior Lake,
Minnesota: Field Experiment No. III-B-6-72. Unpublished study prepared
by State University of New York—Oswego, Lake Ontario Environmental
Laboratory and others, submitted by BASF Wyandotte Corporation,
Parsippany, NJ.
Drescher, N. 1972a. A comparison between the leaching of bentazon and 2,4-D
through a soil in a model experiment: Laboratory Report No.. 679.
Drescher, N. 1972b. Leaching of 2-amino-N-isopropyl benzamide (AIBA) from
the soil. Laboratory Report No. 682.
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Bentazon August, 1987
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Drescher, N. 1972c. The effect of pH on the rate of hydrolysis of bentazon
(BAS 351-H) in water: Laboratory Report No. 1107. Translation;
unpublished study prepared by Badische Anilin- and Soda-Fabrik, AG,
submitted by BASF Wyandotte Corporation, Parsippany, NJ.
Drescher, N. 1973a. Leaching of bentazon in a muck soil. Laboratory Report
No. 1138.
Drescher, N. 1973b. The influence of pH on the hydrolysis of the bentazon
metabolite AIBA (2-amino-N-isopropyl benzamide) in water. Laboratory
Report No. 1136.
Drescher, N. and S. Otto. 1972. Penetration and leaching of bentazon in
soil: Laboratory Report No. 1099. Translation; unpublished study
prepared by BASF, AG, submitted by BASF Wyandotte Corporation,
Parsippany, NJ.
Drescher, N. and S. Otto. 1973a. Degradation of bentazon (BAS 351-H) in
soil. Report No. 1140.
Drescher, N., and S. Otto. 1973b. Degradation of bentazon (BAS 351-H) in
soil. Report No. 1149.
Lehman, A.J. 1959. Appraisal of the safety of chemicals in foods, drugs and
cosmetics. Assoc. Food Drug Off. U.S.
Leuschner, F., A. Leuschner, W. Schwerdtfeger and H. Otto. 1970. 13-Week
toxicity study of 3-isopropyl-1H-2,1,3-benzothiadiazin-4(3H)-one-2,2-
dioxide to beagles when administered with the food. Unpublished report
prepared by Laboratory of Pharmacology and Toxicology, W. Germany.
September 28.
Meister, R., ed. 1986. Farm chemicals handbook. Willoughby, OH: Meister
Publishing Co.
RTECS. 1985. Registry of Toxic Effects of Chemical Substances. National
Institute for Occupational Safety and Health. National Library of
Medicine Online File.
Stoner, J.H., and R.E. Hanes. 1974a. Determination of residues of bentazon
and AIBA (2-amino-N-isopropyl benzamide) in Commerce silt loam soil from
Greenville, MS: Field Experiment No. 73-41. Unpublished study prepared
in cooperation with Stoner Laboratories, Inc., and United States Testing
Company, inc., submitted by BASF Wyandotte Corporation, Parsippany, NJ.
Stoner, J. H., and R. E. Hanes. 1974b. Determination of residues of bentazon
(BAS 351-H) and AIBA i'n Commerce silt loam soil from Greenville, MS:
Field Experiment No. 73-43. Unpublished study prepared in cooperation
with Stoner Laboratories, Inc. and United States Testing Company, Inc.,
submitted by BASF Wyandotte Corporation, Parsippany, NJ.
STORET. 1987.
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Bentazon August, 1987
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U.S. EPA. 1985. U.S. Environmental Protection Agency. U.S. EPA Method 107
- Revision A, Bentazon. Fed. Reg. 50:40701. October 4, 1985.
U.S. EPA. 1986a. U.S. Environmental Protection Agency. RfD Work Group.
Worksheet dated April 7.
U.S. EPA. 1986b. U.S. Environmental Protection Agency. Guidelines for
carcinogen risk assessment. Fed. Reg. 51 (1 85):33992-34003.
September 24.
Worthing, C.R., ed. 1983. Die pesticide manual. Great Britain: The Lavenham
Press, Ltd., p. 39.
Wuerzer, B. 1972. Bentazon model box runoff study: Runoff Report 73-6.
Unpublished study prepared in cooperation with United States Testing
Company, submitted by BASF Wyandotte Corporation, Parsippany, NJ.
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