PB80-213887
Chlorbenzilate
Position Document 3
(U.S.) Environmental Protection Agency
Arlington, VA
11 Jul 78
J
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som-ui
REPORT DOCUMENTATION
PAGE
4. Tf.it end SubtHI.
1. REPORT NO.
EPA/SPRD 80/J35 [
Chlorobenzilate: Position Document 3
7. Authord)
J.B. Boyd
9. Performing Ortani, Mion Name and Address
Special Pesticide Review Division
Environmental Protection Agency
Crystal Mall 2
Arlington, VA
12. Sponsoring Organization Nam* and Addretl
Environmental Protection AGency
401 M St. S.VJ.
Washington, D.C. 20460
ilptont't Accession Mo.
80
*. Report Data
. Performinat Organization Rapl. No.
10. ProtKt/Tatk/wark Unit No.
1 1. Contract(C) or Grant(3) No.
(C)
(G)
13. Typa of Raport 1 Period Covered
1$. Supplementary Note*
If. Abttract (Limit: 200 words)
Risk/benefit analysis: qualitative & quantitative risks of a pesticide,
value of crop uses, availability of alternative pesticides, exposure to
man and environment. Identificiation of risk reducing regulatory options
and proposed Agency action.
17. Document Analyst* a. Descriptor*
0504,0606,0703
b. Identtfiers/Opan-ErKlea' Teum
C. COSATI Field/Uroup
If. Availability Statement
' Release Unlimited
19. Security Cl».« (Tnlm Report)
UnclassifieQle
2O. Security Clan (This Put*)
•»••» rtT O *2! C? 4 "fleO/4
21. '-to. al Pagn
138
22. Prict
(See ANSI-ZM.ll)
a
OPTIONAL FOMW 272 (4-77)
(Formerly NTIS-35)
Department of Commerce
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CHDORCBENZILATE: POSITION DOCUMENT 3
- 20/35"
J.B. BCXD
PROJECT MANAGER
SPQCZAL PESTICIOE REVIEW DIVISION
OFFICE OF PESTICIDE PBO3BM6
O.S, EN/OOWNIAL PSCC&CTIQN BGEMOf
NAT10NAI TECHWCAl
^FORMATION SWV1CE
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CHLDBDBENZIIATE
Working Group
J. Boyd, Project Manager, OPP
D. Fatten, Attorney, OGC
D. Barnes, Chemist, OTS
D. Kuroda, Physical Scientist, OBD
D. Dal ton, Entomologist, PTSED
Technical Support Team
J. Boyd, Project Manager, OPP
M. Luttner, Economist, CED, OPP
D. Severn, Chemist, CED, OPP
R. Potrepka, Pharmacologist, CED, OPP
M. McHhorter, Entomologist, CED, OPP
D. Coppage, Aquatic Biologist, CED, OPP
D, Patton, Attorney, OGC
K. Keaney, Economist, OPP
E. Siegler, Attorney, OGC
D. Reed, Chemist, RD, OPP
G. Cmara, Economist, CED, OPP
F. Kutz, Chemist, TSD, OPP
T. Dixon, Chemist, TSD, OPP
Pesticide Chemical Review Camnittee (PCRC)
W. Wells, Chairman, SPRD, OPP
E. Kuroda, Physical Scientist, OBD
J. Moore, GAG Liason, SPRD, OPP
A. Jennings, 0PM
E. Anderson, CMS
M. Menotti, OGC
J. Neyian, PTSED
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TABU: OP OONTENTS
Page
I. Introduction 1
A. Background 1
1. Chemical and Physical Properties..... 1
2. Registered Uses , 2
3. Environmental Fate 2
B. Regulatory History 4
II. Analysis and Assesanent cf Risk 8
A. Analysis of Rebuttal Submissions 8
1. Successful Rebuttal Arguments 8
a. Horn et al. (1955) 8
b. Wbodard (1966) 9
2. Unsuccessful Rebuttal Arguments 10
a. Innes et al. (1969) 10
i. Criticisms Relating to Experimental
Design and Methods 10
- Size of Test Groups 10
- Choice of Strains 11
- Assignment of Littennates to the
Same Group , 12
- Treatment of Newborns and Route
of Administration 12
- Pathogen-Free Animals 13
ii. Criticisms Relating to Pathological
Diagnoses 14
b. NCI (1977) 16
i. Nd Appraisal of Results 16
ii. Arguments Relating to Control Animals 17
iii. Variable Dose Levels 19
(iff)
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Page
c. Other Arguments Against the Innes and NCI Studies 19
d. Other Arguments 20
i. Other Cancer Tests. 20
ii. Negative Mutagenicity Testing 21
iii. Lade of Exposure Necessary to Cause Adverse
Effects 22
iv. Epideroiological Data 22
3. Adverse Testicular Effects in Rats 22
B. Exposure Analysis 25
1. Dietary Exposure , 25
2. Occupational Exposure 28
3. Cther Potential Exposure 29
C. Risk Assessment 31
Risk: Oncorienic Effects 31
Risk: Testicular Effects 34
a. Dietary Exposure...... 34
b. Occupational Exposure 34
III. Benefit Analysis 39
A. Intvoduction 39
B. Uses 39
1. Citrus Uses 39
a. Florida 40
b. Texas 41
c. California 42
d. Arizona 42
2. Non-Citrus Uses 43
(ii)
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Page
C. Alternatives to Chlorobcnzilate 44
1. Citrus Alternatives 44
a. No Miticide 44
b. Alternative Miticides: Florida and Texas 46
i. Selective Miticides 46
ii. Non-Selective Miticides 50
c. Alternative Miticides: California 51
d. Alternative Miticides: Arizona 55
2. Non-Citrus Use Alternatives 55
D. Grower Inpacts 57
1. Citrus Uses 57
a. Florida 57
b. Texas 62
c. California 63
d. Arizona... 64
2. Non-Citrus Uses 64
E. Costs to the Citrus Pulp Feed Industry 64
F. Costs to Consumers 65
1. Citrus Uses 65
2. Non-Citrus Uses 66
IV. Risk-Benefit Analysis of Alternative Courses of Action 68
A. Continue Registration of All Uses 74
B. Cancel All Uses 74
C. Continue Registration at Chlorobenzilate Use on Citrus and
Mend the Terms and Conditions of Registration; Cancel All
Other Uses 76
(iii)
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Page
1. Economic and Environmental Considerations .................. 76
2. Proposed Restrictions ...................................... 78
D. Cancel Chlorobenzilate Use on Citrus to Take Effect After
Fiv Years, and in the Interim Amend the Terns, and Con-
ditions of Registration; Cancel All Other Uses .................. 81
E. Continue Registration of Chlorobenzilate Use on Citrus;
Amend the Terms and Conditions of Registration, Require
That Exposure Data be Submitted to EPA in 18 Months;
Beevaluate the Use on Citrus After Additional Exposure
Data Becomes Available; Cancel All Other Uses ................... Sj
1, Citrus Fractionation Studies .................................. 84
2. Feeding Citrus Byproducts to Cattle Study .................... 85
". Citrus Pickers Exposure and Reentry Studies ................. ... 85
't. Aerial Application Exposure Study .......................... ... 85
5. Ground Applicator Exposure Study .............................. 86
6. Residue Monitoring of Milk From Pulp-Fad Cattle and
Residue Monitoring of By-Products of Citrus Processing ....... 86
F. Continue Registration of Chlorobenzilate Use en Citrus in
Florida, Texas, and California, Amend the Terms and Conditions
of Registration, Require that Identified Exposure Data be Sub-
mitted to EPA in 18 Months; Reevaluate the Use on Citrus After
Additional Exposure Data Becomes Available; Cancel Use on Cit-
rus in Arizona and All Other Uses ............................... 87
G. Continue Registration of Chlorobenzilate Use on Citrus, Amend
the Terms and Conditions of Registration; Prohibit the Use
of Pulp from Chlorobenzilate-Treated Citrus as Cattle Feed;
Establish Complementary Tolerances; Cancel All Other Uses ...... 87
V. Recommended Regulatory Action.... ..................................... 88
A, Introduction [[[ 88
B. Comparison of Options .......................................... 90
C. Reconnenaaticn of Option F ............. , ....................... 94
Appendix A. Summary of Other Cancer Stuc'ies
Appendix B. Other Toxicity Data
Appendix C. Risk Considerations Relating to Pesticide Substitutes for
Chlorobenzilate
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• PAGE
1. Agricultural Use of Chlorobenzilate, 1975 3
2. Survival Rates for Animals Examined Histopathologically, NCI Study 18
3. Reasonable tipper Limit of Dietary Exposure to Chlorobenzilate 27
4. Chlorobesizilate Occupational Exposure 30
5. Innes Data Used To Estimate Risk 32
6. Chlorobenzilate Potential Occupational Cancer Risk 35
7. Chlorobenzilate Potential Cancer Risk Through Dietary Exposure;
Florida Population 36
8. Chlorobenzilate Potential Cancer Risk Through Dietary Exposure;
U.S. Population (Except Florida) 37
9. Estimate of the Maximum Economic Value Lost as a Result of Uncontrolled
Mite Tr-festations in Citrus 45
10. Per-Acre Treatment Costs in Citrus with Chlorobenzilate; Alternative
Hiticides and Sealicides 48
11. Estimated Extent of Use of Chlorobenzilate and Selected Substitutes to
Replace Chlorobenzilate for Control of the Citrus Mite Complex and Scale
Insects in Florida 52
12. Estimated Extent of Use of Chlorobenzilate and Substitutes to Replace
Chlorobenzilate for Control of the Citrus Mite Complex in Texas 53
13. Estimated Extent of Use of Chlorobenzilate Compared with Amount of Oil
Treatment to Replace Chlorobenzilate for Control of the Citrus Bud Mite
on California Lemons , 54
14. Chlorobenzilat* and Alternatives for Non-Citrus Uses 56
15. Impacts Projected to Grower? Resulting from Cancellation of
Chlorobenzilate 58
16. Projected Cost of Scale Insect Control in Florida Citrus During Initial
Five Year Period Following Cancellation of Chlorotenzilate 59
17. Economic Impact of the Loss cc* Chlorobenzilate During Initial Five
year Period Following Cancellation 61
18. Regulatory Options and Maxinum Risk Incidence from ChJ.orobenzilate Use.. 69
19. Economic Impacts Resulting from Chlorobenzilate Regulavory Options 71
FIGURES
1. Metabolic Routes of Chlorobenzilate 5
(y)
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Page Intentionally Left Blank
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I. Introduction
Hie Federal Insecticide, Fungicide, and Rodenticide Act (FIFPA) and
the related regulations require the Environmental Protection Agency to re-
view the risks and benefits of the uses of registered pesticides. On May 26,
1976, the Agency initiated this review for chlorobenzilate with the issuance
of a notice of rebuttable presumption against registration and continued
registration (RPAR) of pesticide products containing chlorobenzilate (41 PR
21517, May 26, 1976). Based on information developed through the RPAR re-
view, this position document presents the Agency's analyses of the risks
and benefits of chlorobenzilate uses and recomendations regarding regula-.
tory alternatives.
y
A. Background
1. Chemical and Physical Properties
Chlorobenzilate (ethyl 4,4'-dichlorobenzilate) is a chlorinated hy-
drocarbon which is also known by its trade names: Acarfaan, Akar 338,
Rospin, Geigy 338, Benzilan, Folbex, and Kop-Mite. In pure form it is a
yellowish-brown viscous liquid with a melting point of 35° to 37°C at
0.06 mm Bg and a vapor pressure of 2.2 x 10 ran at 20°C. It is highly
soluble in most organic solvents and petroleum oils but Is insoluble in
I/ The chlorobenzilate SPAR was one of the first RPARs issued by the Agency.
At the tine it was issued, Agency RFAR procedures were still in a for-
mative stage, and a detailed position document did not accompany the
chlorobenzilate RPAR. For this reason, the Agency has included in this
position document information which under current procedures would appear
in Position Document 1 and acocnpany the RPAR.
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water. The molecular weight is 325.2 «nd its structural formula is:
2. Registered Uses
Chlorobenzilate, an acaricide, is registered for use on almonds,
apples, melons, cherries, citrus fruit, cotton, pears, walnuts, ornamen-
tals, trees, and in certain outdoor areas. It is also registered to con-
trol spiders on boats and docks. Ninety percent of the current usage
applied is on citrus crops (Table 1). there are 18 Federally-registered
chlorobenzilate products; six applications for Federal registration are
pending, and there are eight State-registered products for which notices
of application for Federal registration were filed, pursuant to 40 CFR
162.17. All pending applications are for cites already registered.
3. Environmental Fate
Little is known about the metabolism of chlorobenzilate in nan or
other organises or about its degradation in soil and water or by light.
The primary reactions which chlorobenzilate is likely to undergo after
field application may include hydrolysis, decarboxylation, conjugation,
and oxidation. Chlorobenzilate soil persistence studies found that its
half-life was 1.5 to 5 weeks, however, the degradation products were
not identified or measured (Boyd, H., 1978).
Several studies show that chlorobenzilate is not metabolized by
plants. In studies on apples (Murphy et al. 1966) and citrus fruit
(2)
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Table 1
Registered
Uses
Citrus:
Oranges, Lemons, Fl
Grapefruit
Other (Limes,
Tangerines,
elos, etc.)
All Citrus
Cotton
Fruits, Nuts, &
Miscellaneous
Crops
All Uses
V
Agricultural Use of Chi orobenzi late, 1975
Site
Fl
TX
CA
AZ
US
US
US
US
US
Active Ingredients
Used (Pounds)
805,000
101,500
7,500
6,000
920,000
75,700
995,700
39,000
81 ,000
Al 1~ c/ c/
Agricultural Farms Acreage
Uses (%)
72.1
9.1
0.7
0.5
82.4
6.8
89.2
3.5
7.3
No. % No.
8,314 80.1 523,000
2,584 50.8 43,000
315 4.1 4,000
207 6.7 3.000
11,421 43.4 573,000
N/A - 47,000
11,421+ - 620,000+
39,000
24,000
%
67.3
56.6
1.6
.2.8
47.0
45.9
50.9
0.41
1
US
1,116,000
100.0
715,000
i/ Source: Preliminary Benefit Analysis (Luttner, 1977).
b/ Percent of total U.S. chlorobenzilate used on commodity noted.
£/ Percent is of total farms and total acreage producing each commodity.
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(Gunther et al. 1955), chlorobenzilate was found only in the peel. Hassan
and Knowles (1969) found that chlorobenzilate rapidly penetrated soybean
leaves and was translocated unchjnged into the leaf stalks.
Miyazaki et al. (1970) found that chlorobenzilate was metabolized
to dichlorobenzophenone (DBF) by micro-organisms, especially yeasts. Horn
et al. (1955) found that chlorobenzilate was hydrolyzed to the free acid
(DBA) by dogs. Knowles and Ahmad (1971) found that chlorobenzilate is
metabolized by rat hepatic enzymes to at least four and perhaps as many
as seven metabolites. These results indicate that chlorobenzilate can
be metabolized by microorganisms and animals. Figure 1 illustrates these
routes and products.
B. Regulatory History
Based on a study by Innes et al. (1969), an Advisory Committee to
the Secretary of Health, Education and Welfare (the Mrak Ccranission),
recommended that human exposure to chlorobenzilate be minimized and that
use of this pesticide bt restricted to those purposes for which there are
benefits to human health which outweigh the potential hazard of carcino-
genicity (DHEW, 1969).
On May 26, 1976 [pursuant to 40 CFR 162.11(a)(3)] the Agency issued
a notice of rebuttable presumption against registration (SPAR) of pesticide
products containing chlorobenzilate (41 FR 21517, May 26, 1976) based on
studies in which tuners developed in rats (Horn et al. 1955; Wbodard, 1966)
and mice (Innes et al. 1969) which had been orally exposed to the pesticide.
After the notice of. rebuttable presumption was issued, the National Cancer
(4)
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FIGURE 1
METABOLIC BOOTES Of CHLOROBEN2ILATE
CH-
or H+
000-
-> Cl
CHLOROBENZILATE
-CO
Cl-
H
•-C
CH
4,4' -DICHLORGBENZHYDROL
PRODUCT POUND: IN VITRO
RAT HEPATIC ENZYMES
4,4'-DICHDORCBENZIUC ACID
PRCOUCT FOUND: WMM&L URINE;
YEAST
VftTER SOLUBLE CONJUGATES
(UNVERIFIED)
-OH
4,4'-DICHLORCBENZOPHCNONE
PRODUCT FOUND: IN VITRO
RAT HEPATIC ENZYMES; YEAST
P-CHLOROBEN2OIC ACID
PRODUCT FOUND: IN VITRO
RAT HEPATIC ENZYMES
(5)
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Institute (NCI} completed a chlorobenzilate carcinogenesis bloassay which
showed a statistically significant increase of tumors in mice. The Agency
provided copies of this study to registrants who requested it; these data
and EPA analyses of the data are summarized in Appendix A. Other toxidty
data are summarized in Appendix B.
Registrants and other interested parties were offered an opportunity
to review the data upon which the presumption was based and to submit in-
formation to rebut the presumption. Respondents could rebut the presump-
tion by showing that the Agency's initial determination of risk was in
error, or by showing that consideration of use patterns and exposure indi-
cates that use of the pesticide is not likely to result in any significant
chronic adverse effects [40 CFR 162.11(a)(4}]. Also, registrants and other
interested persons were offered the opportunity to submit evidence as to
whether the economic, social, and environmental benefits or the use of the
pesticide outweigh the risk of its use [162.11(a)(5))iii)]. Although the
presumption was based on three studies, the preliminary results of the
NCI carcinogenesis bloassay were available, and comments were received
on all four studies. The Agency received 35 submissions, 12 from chloro-
benzilate registrants and 23 from other interested parties.
As summarized in Section II of this position document, the Agency
has concluded that Information submitted in rebuttal to the Horn and
Woodard studies raises serious questions about the reliability of these
data for assessing the oncongenicity of chlorobenzilate, and that the re-
spondents have therefore successfully rebutted these data. The Agency has
also concluded that respondents failed to rebut data in the Innes study
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and the NCI study. As a result, the Agency has used the Innes and NCI data
to assess the risks associated with the uses of chlorobenzilate. In Sec-
tion III, the Agency has analyzed information on the benefits of chloro-
benzilate uses and the probable costs of regulatory action to cancel or
otherwise restrict uses of this pesticide. An analysis of the risks and
the social, economic, and environmental benefits which would result from
each of six different regulatory options is presented in Section IV.
Finally, Section V presents the Agency's reccnmended option and an expla-
nation of why this option achieves a sound balance between the risks and
benefits of the uses of chlorobenzilate considered in this analysis.
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II. Analysis and Assessment of Risk
y
A. Analysis of Rebuttal Submissions
Persons submitting rebuttals contended that data in the four studies
were defective in several critical respects and that exposure to chloro-
benzilate would not lead to significant adverse effects. The Agency has
reviewed the carcinogenicity data again in light of the rebuttal ooranents,
and has concluded that information and arguments submitted in rebuttal to
the Horn and Wcodard studies indicate that these data may not be reliable
for assessing chlorobenzilate's onccgenic effects. Accordingly, the Agency
accepts the rebuttal arguments against use of these data for assessing the
cancer risk of chlorobenzilate. The Agency also has concluded that argu-
ments and data submitted regarding the Innes and NCI studies did not rebut
or otherwise invalidate the presumption that chlorobenzilate is onccgenic.
1. Successful Rebuttal Arguments
a. Horn et al. (1955)
Horn et al. administered chlorobenzilate in the diet to rats fron
weaning until 104 weeks of age. Tumors were observed in some animals.
2/ The rebuttals and connents were reviewed by the Criteria and Evalua-
tion Division (CEE) of the Office of Pesticide Programs (OPP), the
EPA Cancer Assessment Group (CAG), and/or two consulting firms. These
reviewers extracted items from the rebuttal submissions which specifi-
cally and authoritatively addressed the risk data upon which the pre-
sumption against chlorobenzilate was based. The reviewers did not
analyze testimonials and other conments not supported by data or
references. The reviewers evaluated rebuttal items as they related
to the risk information and submitted their contents and conclusions
to the Agency Working Group on chlorobenzilate.
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Respondents argued, among other things, that too few animals were ex-
amined histopathologically for proper statistical analysis. For ex-
ample, although 80% of the male control animals survived, tissues were
studied from only 25% of the survivors. Agency consultants reevaluated
the use of this data to oanonstrate oncogenic effects and reported that
too few animals were examined histopathologicalJy, that tumor incidence
in the control groups was often greater than in the experimental groups,
and that examination of only representative animals and tissues may have
biased the results (Preudenthal and Leber, 1977; Savage and Hayts, 1977).
The Agency agrees that these factors indicate that the data may not be
reliable indicators of onoogenicity.
b. Moodard (1966)
The Ciba-Geigy Corporation, a chlorobenzilate registrant, had the
Woodard Research Corporation conduct a study in which rats were given
chlorobenzilate in the diet. Registrants, including Ciba-Geigy, con-
tended that the tumor incidence in the control animals was cften higher
than the treated animals, that the investigators failed to conduct ne-
cropsies of animals that died before the scheduled end of the study,
and that they failed to examine histopathologically an adequate number
of animals. For example, no more than 20% of the control and test ani-
mals from each group were histopathologically examined. Agency consul-
tants confirmed that the studies were defective in these respects and
that the data were unreliable for assessing the onoogenicity of chloro-
benzilate (Freudenthal and Leber, 1977).
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these consultants also reported that there was an increased inci-
dence of liver timers at the highest dose level which, although not sta-
tistically significant, indicated the need for further study. Since the
Znnes and NCI studies provided reliable data en chlorobenzilate-induced
liver tumors in rodents, data in this study are consistent. However, the
Agency agreed with the consultants' conclusion that these data alone do
not indicate that chlorobenzilate is an oncogen.
2. Unsuccessful Rebuttal Arguments
a. Innes et al (1969)
Innes et al. tested the tumorigenicity of 120 pesticides and in-
dustrial compounds by continous oral administration to two hybrid strains
of mice. Tuners of the liver were observed in 52.9% (9/17) of the male
mice ingesting 603 ppm chlorobenzilate compared with 10.1% (8/79) of the
control animals. Liver tumors were not observed in the females. These
data are detailed in Table 7, Subsection II,C. This section summarizes
the rebuttals of the Innes study and the Agency's response.
i. Criticisms Relating to Experimental Design
and Methods'
Size of Test Groups; Registrants argued that only 18 male and
18 female mice were fed chlorobenzilate, and that this was too f"w mice
to permit a valid statistical analysis [Alikonis, 1976a, 1976b, 1976c
I/
(23-25:30000/3)]. The Agency acknowledges that the number of animals
3/ The names and numbers in parentheses identify the source of each
rebuttal in terms of the signer, date, and EPA identification number.
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in a study does limit the sensitivity of the test, but notes that in the
Innes study an appropriate proportion of the animals were autopsied and
that both chlorobenzilate-treated groups of F hybrid male mice demonstrated
a statistically significant increase (p £ 0.02) in animals with tumors
compared to controls (Freudenthal and Leber, 1977). Toe Agency also notes
that the Mrak Report concluded that the number of animals per group in the
Innes study was sufficiently large to provide a sound basis for statistical
analysis of the results.
Some registrants noted that the Innes study was a mass screening
study which involved irany chemical canpounds snd few animals and that, in
the introduction, the authors urged against drawing conclusions from the
study without confirmatory research (Jovanovich, 1976a [1:30000/3]; Alikonis,
1976a, 1976b, 1976c [23-25:30000/3]). These considerations do not negate
the statistically significant (p < 0.001} increase of hepatctnas in chloro-
benzilate-treated male mice (Freudenthal and Leber, 1977). In computing
significance, sample size is necessarily considered. Further, the Mrak
Commission referred to the Innes study as a "fine-mesh screen designed
tr> identify as many as possible of the carcinogens submitted to it," and
concluded that it "performed this task with considerable success." More-
over, an analysis of the results of the recent NCI study confirm that
chlorobenzilate is oncogenic (Barton, 1977).
Choice of Strains: Registrants argued that the two first genera-
tion hybrid strains of mice used by Innes et al. did not have the genetic
heterogeneity of normal animals and, therefore, should not be used in can-
cer research. They noted that randomly bred animals are recommended by
(ID
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the Mrak Commission, the Food and Drug Administration Panel on Carcirogene-
sia in 1971, and the World Health Organization in 1961 [Balser, Jovanovich,
1976b (20:30000/3); Jovanovich, 1976 (31:30000/3)]. However, the Agency
has concluded that the hybrid mice used in this study wre suitable test
animals. A low incidence of tumors appeared in control groups, and the
strain was highly susceptible to induction of tumors by positive control
chemicals (HEW, 19699. While randomly bred animals are preferred by
some scientists, true random breeding is difficult to achieve in practice
and results in broad, ill-defined gene pools. Moreover, inbred strains
have been described as the best means for investigating chemical carcino-
genesis (Goldberg, 1974).
Assignment of Littermates to the Same Group; Registrants argued
that the assignment of littermates to the same experimented groups was
inappropriate [Jovanovich, 1976a (1:30000/3); Murphy, 1976a (22:30000/3)].
The Mrak Conoission reported that when the Innes data were reanalyzed
under a nore rigorous statistical procedure to take this possible bias
into account, the differences reported as statistically significant in
the original study remained significant (HEN, 1969).
Treatment of Newborns and Route of Administration! Registrants
stated that the FDA criteria for cancer testing recommend that newboms
not be included in cancer tests [Balser, Jovanovich, 1976b [20:30000/3);
Alticonis, 1976a, 1976b, 1976c (23-25:30000/3)]. Specifically, the Innes
study VJBS faulted for beginning to administer chlorobenzilate when the
mice were 7 days old. Registrants argued that the innune system in these
very young animals is incompletely developed, rendering them more sus-
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oeptible to the development oi' tumors, the registrant cited the FDA
guidelines .jhich state, This might be a satisfactory screening proce-
dure under limited conditions but cannot be reeonsmendad as a routine
test procedure" (FDA, 19/1).
Ihe Agency has rejected this argument because young and more sus-
cpetible animals are used in oncogenicity studies to optimize detection
of oncogenic activity. In addition, when a relatively small number of
animals is ussd in feeding studies, it is appropriate to increase the
sensitivity of the experiment with this technique. This approach is ex-
plained in the NCI Guidelines for Carcinogenic Bioassays in Small Rodents
(Sontag et al. 1976) which state that chronic study animals should be
weanlings, if possible, since a poorly developed immune system may sen-
sitize these animals to carcinogens and make them more susceptible. Hu-
man infants also exhibit a weak immune response.
One registrant contended that the administration of chlcrobcnzilate
to infant mice by gavage flawed the study [Jovanovich, 1976a (1:30000/3)].
Gavage is an accepted means of administering a test material to animals,
especially to young animals or when an exact oral dose is required (Wilson,
J.G., 1973; Goldberg, 1974).
Pathogen-Free Animals; With reference to the FDA guidelines (FDA,
1971), one registrant stated, "Specific pathogen-free animals should be
avoided because of possible increased susceptibility to Infection" [Balser,
Jovanovich, 1976b (20:30000/3)]. The FDA's recotmendation is intended as
an experimental design measure to safeguard against early deaths from in-
fection; reductions in the number of animals surviving a long-term study
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would result in a less valid study. Since there was a high survival rate
among the animals in the Innes study and no data indicating that there was
significant infection, the FDA precaution is no1- relevant in this case.
ii. Criticisms Relating to Pathological Diagnoses
One registrant argued that, since most of the animals in the Innes
study did not die of cancer but were sacrificed at the end of the study,
chlorobenzilate is not a potent carcinogen [Balser, Jovanovich, 1976b (20:
30000/3}]. Agency regulations which authorize the rebuttable presumption
review provide that a presumption will arise if a chemical is oncogenic,
or tumor-producing. Such tumors need not cause the death of the animals.
One registrant stated, "Many of the cancers are detected only by
microscopic er-amination" in the Innes study [Balser, Jovanovich, 1976b
(20:30000/3)1 and concluded that chlorobenzilate should not be considered
an oncogenic risk. Diagnosis of tunors by microscopic examination of his-
tological preparations is essential to a complete review of the effect of
a chemical on tissues. The risk criterion provides that a rebuttable
»
presunption shall arise it a ccnpound is oncogenic; there is no require-
ment that tumors be macroscopically detectable.
One registrant argued that chlorobenzilate should not be considered
an oncogenic risk wince tumors found in the Innes study had not generally
metastasized [Balset, Jovanovich, 1976b (20:30000/3)]. The EPA "Interim
Guidelines for Carcinogen Risk Assessment" (41 FR 21404, Hay 25, 1976)
specify that:
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Substantial evidence [that an agent is a human car-
cinogen] is provided by animal tests that demonstrate
the induction of malignant tumors in one or mare
species including benign tumors that are generally
recognized as early stages of malignancies.
Because diagnoses of cancer can be made only by expert pathologists,
several registrants have concluded that the evaluations of the Innes study
are subjective [Balser, Jovanovich, 1976b (20:30000/3); Alikonis, 1976a,
1976b, 1976c (23-25:30000/3}]. The Agency acknowledges that pathologic
diagnosis is a special skill and relies on the known ability of the pa-
thologists who reviewed the Innes study slides. The independent diagnoses
of the patholocj ists who reevaluated the slides add considerably to the
Agency's confidence in this judgment.
One registrant cited FDA's 1971 Criteria for Cancer Testing (FDA,
1971) which recommended, "It is desirable that both gross and microscopic
examinations be conducted without knowledge of the treatment of specific
animals." The registrant argued that the pathologists who reevaluated the
Innes study slides would know the treatments prior to examining the slides
[Balser, Jovanovich, 1976b (20:30000/3)]. The registrants have not submit-
ted any specific information that would cause the Agency to doubt the va-
lidity of the observations of the pathologists who reevaluated these slides.
The pathological evaluations were performed through a "blinded" evaluation
of the tissue preparations of unknown origin. This procedure precludes the
possibility of the suggested bias, regardless of whether or not the patholo-
gists knew the experimental protocol.
One registrant contended that EPA demonstrated its lack of confi-
dence in the Innes study when the Agency's Toxicology Branch, Registration
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-------
Division (RD), refused to accept data fron this study as evidence that cer-
tain other chemicals were not oncogenic [Murphy, 1976a (22:30000/3)]. The
refusal of RD to accept the fact that sane Innes study data demonstrated
that sane chemicals are not care:icgenic does not conflict with the accep-
tance of data relating to chlorobenzilate. Specifically, since chemicals
tested in this study were not administered throughout the entire lifetimes
of the animals and since a small number of animals was tested, conditions
were not optimum for tumor detection, and therefore there are bases for
questioning negative findings.
b. NCI (1977)
A summary of the final individual animal pathology data was pro-
vided by NCI on January 27, 1977 (NCI, 1977). ICI tested the oncogenicity
of chlorobenzilate in B6C3F1 mice and Osborne-Mendel rats. Neither sex
of rats showed statistically significant responses. The incidence of
hepatocellular carcinonas in male mice was 68% (32/47) at 4,000 ppm and
49% (22/45) at 6,000 ppm, compared to 24% (4/17) in 'die on'rol group.
These tumors were observed in 23% (11/49) of the female trice ingesting
3,200 pan and 26% at 6,400 (13/50), compared to 0% (0/20) in the control
group. An EPA analysis indicates that the chlorobenzilate-treated mice
snowed statistically significant increases in the number of total tumors
and heptatocellular carcinomas at p - 0.01V and p - 0.0001, respectively
(Earton, 1977a).
i. NCI Appraisal of Results
Registrants submitted a letter from the Chief of the Carcinogen
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Bioassay and Program Resources Branch, NCI, which stated that "the com-
pound appears not to be carcinogenic to mice and rats of both sexes"
[Jovanovich, 1976a (1:30000/3); Murphy, 1976a (22:30000/2)]. The letter
refers only to a preliminary inspection of unverified data as of May 13,
1976, and does not necessarily reflect the final NCI interpretation of the
data. EPA's analysis of the verified histopathology report of January 27,
1977, indicates a statistically significant (p » 0.017) increase in total
tunors for mice of both sexes fed chlorobenzilatd (Barton, 1977a). Id
has not yet completed their analysis of this final data.
ii. Arguments Relating to Control Animals
The occurrence of tumors in the control group was not the sane as
the overall incidence usually observed in untreated mice of this strain.
One registrant argued that if the incidence of tumors in the treated mice
were compared to the historical baseline incidence of tumors in this strain,
the difference in tumor occurrence would not be statistically significant
(Murphy, 1976a [22:30000/3]). tCI reports that the historical incidences
of spontaneous primary liver tunors in untreated male and female B6C3F1
mice are 15.6% and 2.5%, respectively; the comparable rates for concurrent
controls in the study were 23.5% and 0%. The Agency's Cancer Assessment
Group (CM) advised that because this difference is negligible for a sanr
ple size of 20 control animals, the historical control data does not appre-
ciably affect the significance of the chlorobenzilate findings (Albert,
1978).
Citing the World Health Organization's (VHO) recommendations, one
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registrant claimed that the control group should have contained 70 animals
[Balser, Jovanovich, 1976b (20:30000/3)]. The ocntrol group contained only
20 mice although the treatment groups contained 50 mice each. C&G evaluated
this rebuttal and the WHO guidelines, and pointed out that there should have
been 35 animals in each test group to provide optimal statistical efficiency
(Anderson, 1977). It was emphasized/ however/ that even though the test was
not as sensitive as it. could have been, a statistically significant ele-
vation in tumor incidence was found (Barton, 1977a).
One registrant argued that, since only 60% of the male mice in the
control group survived to the end of the study, meaningful statistical
evaluation of the study was not possible [Balser, Jovanovich, 1976b (20:
30000/3)]. The statistical analysis was based on the animals that survived
and were examined histopathologically. The survival rate in the controls
was better or the sane as that of the low dose group to which it was com-
pared. This comparison is shown in Table 2. As a result the significant
"p" value is not biased by better test group survival. Using the Fishers
TABLE 2. Survival Rates for Animals Examined Histopathologically (tCI, 1977)
Week of Study Control Group Low Dose Group
48 1.000 0.979
50 0.941 0.915
SI 0.941 0.872
36 0.941 0.851
63 0.941 0.830
68 0.941 0.809
69 0.941 0.787
72 0.882 0.787
73 0.824 0.787
74 0.765 0.787
77 0.765 0.766
86 0.765 0.745
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exact 2x2 test, the "p" value is less than 0.002, which indicates that
the differences in tumor incidence observed between treated and control
animals were highly significant (Anderson, 1977).
iii. Variable Dose Levels
Che registrant pointed out that dose levels varied accoring to the
age and sex of the animals [Balser, Jovanovich, 1976b (20:30000/3)]. The
dosing regimen was selected on the basis of preliminary tests to determine
maximum tolerated doses. Standard procedure for selecting dosage levels
permits variation according to sex. In addition, food intake relative to
body weight can vary with age; thus, an adjusted concentration of the chemi-
cal in the diet to accommodate for this is solid experimental procedure
(Mishra, 1977; Edwards, 1977).
c. Other Arguments Against the Innes and ICI Studies
Cne registrant argued that neither Innes nor NCI adhered to all FDA
criteria for carcinogenic it? testing (FDA, 1971), but did not note specific
inconsistencies in the NCI study (See Section II,A,2,a, for Innes inconsis-
tencies). Although the FDA criteria were developed to test methods and
to provide a sensitive screen for cancer-causing agents, deviation from
these guidelines does not alone invalidate a study. In this case, since
both the NCI and Innes studies showed statistically significant increases
in tumors in mice, the studies were clearly sensitive enough to detect on-
oogenic activity.
Another argument was that the secondary toxic effects noted in these
studies made pathological evaluation difficult [Balser, Jovanovich, 1976b
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(20:30000/3); Alikonis, 1976a, 1976b, 1976c (23-25:30000/3)]. Vhile sec-
ondary toxic effects may complicate the diagnosis of tuners, the regis-
trants have offered no evidence which casts doubt on the validity of the
patholegists' conclusions in these studies.
Several registrants contended that the Agency's presumption of
chlorobenzHate's oncogenic risk was based on false positive results from
both Innes aid NCI studies [Jovancvich, 1976c (31:30000/3)]. No data were
offered to support this argument, and based on both studies, the probability
of false positive results for the increase of tumors in chlorobenzilate-
treated mice was very slight (Barton, 19T7).
Several registrants argued that data fron the Innes and NCI studies
were unreliable because inbred strains may carry tumor-causing viruses.
These registrants maintained that the tuners found in these studies were
similar to those produced by viruses [Balser, Jovanovich, 1976b (20:30000/
3); Alikonis, 1976a, 1976b, 1976c (23-25:30000/3); Jovanovich, 1976c (31:
30000/3)]. This argument was rejected for two reasons (Mishra, 1977).
First, although the association of viruses (or C-type particles) and the
development of tumors in test animals has been demonstrated, no causal
relationship has been established. Second, even if viruses in mice were
oncogenic, the control animals used in both tests showed markedly fewer
tumors than the chlorobenzilate-tested animal.
d. Other Arguments
i. Other Cancer Tests
One registrant [Murphy, 1976a (22:30000/3)] cited a 1965 Bazelton
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-------
Laboratories' study in which chlorobenzilate was fed at levels of 0, 100,
500, and 3,000 ppm active ingredient to six beagle dogs. No evidence of
oncogenic activity was observed. However, the animals were exposed to
chlorobenzilate for only two years, which is generally too short a portion
of the dog's life span for the development and detection of tumors. It is
generally accepted that in an oncogenic bioassay, a test agent should be
administered continuously for the larger part of an animal's life span to
achieve "greatest confidence" in a negative result. This translates to a
test duration of 7-10 years for carcinogenicity tests in dogs (Page, 1977).
ii. Negative Mutagenicity Testing
Two registrants referred to the frequently observed correlation be-
tween nutagenic and oncogenic activity and cited data which suggested that
chlorobenzilate is not nutagenic and, therefore, not oncogenic [Murphy,
1976a (22:30000/3); AlDeonis, 1976d (33:30000/3)]. This argument can be
rejected for two reasons. First, mechanisms other than mutation may cause
cancer. Second, although there is a high correlation for some classes of
chemicals between carcinogenicity in nannalian test systems and nutage-
nicity in certain microbial systems, this correlation is not perfect, and
false positive and false negative indications do occur. For instance, the
reversion assay in Salmonella with metabolic activation , i.e. the Ames
test, has a high "false negative" correlation for chemical classes such
as cyclodienea, chlorinated hydrocarbons, and certain metals, foe these
classes of compounds the Ames test is often negative, although there are
positive results in mamnalian bioassays for carcinogenicity. Chloro-
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benzilate falls into the potentially "false negative" group of chemicals
(Pertel, 1977). For these reasons the negative results in the in vitro
test battery submitted in rebuttal of the carcinogenicity of chloroben-
zilate are not convincing (Pertel, 1977;1978).
iii. Lack of Exposure Necessary to Cause Adverse
Effects
Two registrants concluded that even if chlorobenzilate were carci-
nogenic, the human exposure would not be high enough to pose any risk
[Murphy, 1976a (22:30000/3); Murphy 1976b (22:30000/3)]. The exposure es-
timates in Section II,B, of this document and the risk estimate in Section
II,C, in the Agency's judgment, indicate that humans may be exposed to
amounts of chlorobenzilate which may cause sufficient adverse effects to
require the Agency to consider whether uses of chlorobenzilate offer off-
setting social, econonic, or environmental benefits.
iv. Epidemiological Data
A preliminary company report on chlorobenzilate manufacturing epi-
demiology [Murphy, 1976a (22:30000/31] was submitted to show that no un-
usual health problems had been detected among employees of a chloroben-
zilate production facility in Albania. The study was determined to be
inconclusive (Rossi, 1976), and was not further considered. No other
reliable epidemiological data is currently available.
3. Adverse Testicular Effects in Rats
The studies on which the presumption against chlorobenzila'ce was
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-------
based include data indicating that chlorobenzilate has adverse effects
en the testes of rats. The Agency did not review these data in its RPAR
notice and the registrants were not invited to comment in their rebuttals.
However, in reevaluating chlorobenzilate studies in connection with the
RPAR review, the Agency concluded that the testicular effects' data also
required consideration. Re-examination of these studies disclosed that
testicular toxicity in rats has been reported in five of the studies
examined.
Horn et al. (1955) in a two-year study using 50 and 500 ppm,
found a dose-related increase in the number of small and/or soft testes
among the survivors of the study. Conpared with 25% (4/16) of the con-
trols, at 50 ppm chlorobenzilate, 69% (9/13} of the male rats evidenced
testicular effects, and at 500 ppro chlorobenzilate, 100% (14/14) showed
i/
these effects. In a 2-year study using 40, 125 and 400 ppm, Woodard
*/
(1966) found, among the animals examined, more frequent testicular
changes at 125 ppm and 400 ppm than in the controls or at 40 ppm. At
125 ppm, 33% (2/6) of the animals evidenced change and at 400 ppm, 60%
(3/5) cccpared with 0% (0/5) in the controls and with 20% (1/5) at 40
ppm. A dietary level of 40 ppm was considered the no-effect level in
this study.
4/ The rebuttable presumption against chlorobenzilate was based in
part on orcogenicity data presented in this study, and the Agency
has concluded that respondents sucessfully rebutted these data as
Co the oncogenic presumption. However, these rebuttal arguments
do not apply for all purposes and independent analyses of the tes-
ticular effects' data is appropriate.
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A two-year study by NCI (1977), in which rats were fed 1,600 or
3,200 ppm for 78 weeks, reported an increased incidence of abnormal tes-
ticular pathology among treated males. Sixty-six percent (33/50) evi-
denced adverse effects at both the high and low doses compared with 18%
(9/49) of the controls. Testicular atrophy was the most conronly observed
effect. Further, in a 99-day subacute study using 20,100, 500, and 2,500
ppm, spenniogenetic injury and atrophy of the gonads were found in 25%
(5/20) of the rats at the highest dose level. In this study, 500 ppm was
judged to be the no-effect level (Fotrepka, 1978a). In a 3-generation study
in which F rats were fed 50 ppm and subsequent generations fed either 25
or 50 ppm, Wbodard (1966) found decreased testicular weights in F males.
Ib
At 25 ppm, mean testicular weight was reduced to 3.04 g and at 50 ppm,
significantly reduced (p » 0.05) to 2.75 g compared with 3.24 g in the
controls (Quaife, 1966).
Chlorobenzilate studies using other species are limited, and those
that are available generally do not contain conments on testicular changes.
In a review of slides from the Innes study on mice, one pathologist indicated
that there might be a treatment-related increase in testicular atrophy.
These data could only be considered suggestive because of the limited num-
ber of samples studied (Frith, 1976). Testicular effects were not re-
ported for mice in the NCI study.
Die biological significance of the adverse testicular effects has
not been established. Although the reproduction study examined did not dis-
close significant differences in fertility between treated and untreated
animals, the regular occurrence of testicular atrophy in animals exposed
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to chlorcbenzilate warrants concern. Since none of the other studies
were designed to measure reproductive capacity or testicular function,
the reproductive and physiological significance is unknown. Consistent
with its obligation to protect human health, the Agency must assume that
the data (shewing chlorobenzilate-induced injury to the tastes) indicates
that chlorobenzilate may also interfere with the endocrine or spennato-
genic function of this organ, in the absence of data establishing that no
such interference occurs.
B. Exposure Analysis
Registrants, tne U.S. Department of Agriculture, and other sources
provided data on patterns of chlorobenzilate use which the Agency has used
to identify populations which may b~- exposed to chlorobenzilate and to es-
timate the extent of exposure.
1. Dietary Exposure
The Agency's estimates of human dietary exposure are based on resi-
due data and the extent to which chlorobenzilate is used on each of the
food crops for which it is registered. A reasonable upper limit of the
dietary exposure of the general U.S. population teas calculated, based on
the average individual's consumption of oamodities, including orange
juice, produced fron crops treated with chlorobenzilate (Severn, 1978).
Because there were no detectable residues in most of the edible portions
of these foods, these sources were assumed to contain 0.1 ppra, which is
the limit of detection in the analytical method used to measure represen-
tative samples (FDA, 1971). Accordingly, the calculations presented in
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Table 3 nay be regarded as reasonable upper limit estimates. In addition,
since apples and pears are eaten whole, residues in these crops were esti-
mated at 5 ppm, the established tolerance level. Finally, although chloro-
benzilate-treated citrus is processed into other products, e.g. citrus oil,
which nay also be sources of dietary exposure, data for estimating expo-
sure from these sources were not available (See Section TV, Option E).
Florida residents may ingest additional significant amounts of
chlorobenzilate because pulp from chlorobenzilate-treated citrus fruit
is fed to dairy and beef cattle which are raised and marketed in Florida,
although a limited EPA survey of Florida milk "sarples detected no resi-
dues at the 20 ppb detection limit (TSD, 1978).
Formica, et al. (1975) reported that on days 1 thorough 42 during
which cows were fed pulp to which 20 ppm chlorobenzilate had been added,
chlorobenzilate levels in milk ranged fron 0.03 ppm to 0.04 ppm. EPA also
completed a limited survey of Florida citrus pulp-mixed feed and found that
the chlorobenzilate content averaged 0.16 ppm (TSD, 1978). Other pulp data
FDA, 1976 and proprietary data (Reed, 1978d) indicate that chlorobenzilate
can occur at 2 ppm in citrus pulp fed to cattle. Based on these data, the
Agency has estimated that chlorobenzilate may be present in milk at 1 to
3 ppb (Reed, 1978c). This level could not be detected by the current FDA
4/ The Agency's estimates of exposure and risk are based on the data,
information and assumptions cited for each estimate. In many cases,
a range of values or several reasonable assumptions, tested or un-
tested, are appropriate for the analysis. The Agency generally se-
lects values and assumptions which permit a conservative (from the
standpoint of protecting tne public health) risk estimate rather
than using average values or generalized assuiptions.
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Table 3
REASONABLE UPPER LIMIT OF DIETWOr EXPOSURE TO CHLOHOBENZILATE
U.S. Population Exposure
Ccmnodity
Citrus:
Oranges (inc.
Grapefruit
Other Citrus
Other Fruit:
Nuts:
Total U.S.
S/
Consunption
(g/dayT"
juice) 42.00
19.30
12.70
55.20
1.18
Extent
of Use by
Crop (%)
47.80
60.90
31.00
0.08
3.60
St
Assumed
Maximum
Residue (pptn)
0.1
0.1
0.1
5.0
0.1
<
Maximum
Ingestion
(ug/day)
< 2.01
< 1.18
< 0.40
< 0.21
< 0.004:
3.8 (0.002
Beef and Lamb
Milk
[Percent with
Potential ~.
Occurrence]^
143.2 10 0.04 < 0.57
184.7 100 0.0024 - 0.04 < 0.44 - < 7.39
Total Florida Additional < 1.01 - < 7.96
Grand Total Florida < 4.81 - < 11.76
(< 0.0025 - < 0.0061 ppn)
£/
Ssvern, 1978
Doane, 1976
Detection level in the nose representative sampling
Tolerance level
Feeding by-products of citrus processing (pulp and molasses) to cattle
in Florida is viewed as an indirect dietary source of chlorobenzilate.
It results in additional dietary exposure for the Florida population.
Based on limited EPA survey (Luttner and McWhorter, 1978)
127)
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monitoring method. However, because these data are inconclusive, a range
has bean expressed (Table 3) up to 40 ppb which would be the maximum theo-
retic?! occurrence (Reed/ 1978a). In addition, based on the Mattson and
Insler study (cited in Severn, 1978), the Agency estimated that chloroben-
zilate may be present at 0.04 ppm in beef (Table 3).
2. Occupational Exposure
Ground applicators and citrus pickers are exposed to chlorobenzilate
through its use on citrus crops. The USDA estimates that the current use
of chlorobenzilate in ground application on citrus is carried-out by as
few as 714 applicators for 30 to 40 days per year or by as many as 1375
applicators for 10 to 20 days per year (Severn, 1978). The worst case,
which is represented by 714 applicators for 40 days per year, is shown in
Table 4A. No data is available to indicate the actual amounts of chloro-
benzilate exposure to these applicators; however data on exposure to ground
applicators during application of other pesticides (Wolfe, et al.1967) was
used to estimate these amounts at between 120 mg and 440 mg dennally and
1 rag by inhalation during each day of application. Since similar pesticides
are known to be absorbed through the skin at a rate of only about 10%
(Feldtnann and Maibach, 1974), the daily dermal dose range was estimated to
be 12 to 40 mg; Feldian and Maibach assumed that pesticides which are in-
haled are absorbed 100%. Thus, the total daily dose for ground applicators
was estimated at 13 mg to 41 mg. Assuming up to 40 years of occupational
exposure to chlorober.zilate, the average daily dose ranged from 0.81 mg to
2.57 mg. For purposes of relating this estimated exposure to the animal
dose-response data, the average daily dose is expressed as 0.39 ppn to
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1.3 ppm dietary equivalents (Table 4).
There are approximately 25,000 to 30,000 citrus pickers who may be
occupationally exposed to chlorobenzilate, but there is too little data
available at this tune to permit a estimate of exposure and potential risk.
Since citrus pickers work in the groves after the pesticide is applied,
the Agency has assumed that their exposure is less than the applicators'
exposure. The Agency has also assumed that surface ohlorobenzilate resi-
dues on fruit and foliage surfaces may be a primary source of contact ex-
posure. If citrus pickers are exposed to the pesticide in this manner,
an exposure estimate could be based en residue data together with the 10%
dermal absorption and 40-year duration figures used in estimating appli-
cator exposure (See Section IV, Option E).
3. Other Potential Exposure
Chlorobenzilate is registered for aerial application to citrus
for the control of citrus rust mites. This manner of application could
result ir drift, depending on the speed of the wind and the size of the
5/ The applicator exposure estimate is based on amounts of chloro-
benzilate to which applicators may be exposed through the skin
and through lung absorption during pesticide application. In this
case, the values range front 0.81 to 2.57 mg/day. However, since the
risk estimates (See Section II,C) are based in part on animal test
data derived from dietary exposure, reported as ppm/day, the hu-
man exposure and the animals' exposure are not expressed in the
sane terms. Therefore, for purposes of relating the animal dose-
response data which is expressed in ppm to the human exposure
data which is calculated initially as mg/day, the latter has beer.
converted to dietary equivalents (Albert, 1978).
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Table 4
CHLORQBENZILATE
OCCUPATIONAL EXPOSURE
GROUND APPLICATORS (AGRICULTURAL-CITRUS ONLY)
SJ
Maximum Extent of Exposure (Absorbed /day)
Inhalation - 1 ing/day
Dermal - 12-40 mg/da>
Duration of Exposure
Assumption - 40 days/year for 40 years
k./
Reasonable Upper Limit of Exposure - (0.39 to 1.3 ppm)(Dietary Equivalents)
Maximum Number of Ground Applicators at This Level of Exposure - 714
a/ Adapted from Wolfe, et al. (1967) data on similar pesticides (Severn, 1978)
b/ Dally amount, time-weighted on duration of exposure (Thorsland, 1978)
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spray droplets. In this way there could be exposure to people near the
vicinity of application. However, there is no data on which to base an
estimate of the magnitude of the potential exposure in this situation.
C. Risk Assessment
1. Risk: Oncoqenic Effects
The chlorobenzilate cancer risk assessment is based on the princi-
ples and procedures outlined in the EPA cancer risk assessment guidelines
(41 PR 21402, May 25, 1976). These guidelines specify that a substance
will be considered a "presumptive cancer risk when it causes a statis-
tically significant excess incidence of benign or malignant tumors in hu-
mans or animals," that current and anticipated exposure levels are appro-
priate considerations, and that cancer risk estimates may be derived from
a variety of risk extrapolation models such as the log-prohibit and linear
non-threshold models.
In accordance with these principles, the EPA Cancer Assessment Group
(CAG) (Albert,1978), and Agency consultants (Felkner and Lcrobardini, 1978)
developed risk estimates using several different models and a range of ex-
posure estimates. CAG has concluded that "...the weight of evidence indi-
cates that chlorobenzilate is a possible human carcinogen" (Albert, 1978).
After reviewing the data sources and the preliminary risk estimates, CAG
concurred in recommendations that the final risk estimates be based on data
*/
from the Innes study using the one-hit model (Table 5) (Albert, 1978).
CAG and the consultants recommended using the Innes rather than the Nd
data because the onccgenic response per unit of dose of chlorobenzilate
6/ CAG has reviewed risk according to the NCI data (Albert, 1978b).
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Table 5
INNES DMA USED TO ESTIMME RISK
Strain
"X"
Dose (ppm)
0
603
C
603
Incidence
Hepatcraas
Hale Female
h/
3/79 (10.1%)
9/17 (52.9%)
5/90 (5.6%)
7/17 (41.2%)
0/87 (0%)
0/18 (0%)
1/82 (1.2%)
0/18 (0%)
a/ This was an eighteen-month feeding study on two hybrid strains of mice.
"Strain X" - (C57BL/6 x C3H/Arf)F,; "Strain Y" * (C57BL/6 x AKR)F,,
Innes et al., Journal of the National Cancer Institute, 42:1101-1114,
1969
b/ Used to estimate risk
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in the Innes study was 5 times greater (Albert, 1978). CAG explained
that animals in the Innes study were fed the conpound beginning at a
younger, more susceptible age. In addition, GAG concluded that the Innes
study data were more appropriate for the risk calculations because the
human response is more likely to be similar to the most sensitive animal
species and because of the possibility that people will be exposed to
chlorobenzilate as infants.
Human risk is defined mathematically as the probability that an
individual exposed to chlorobenzilate will develop a tumor due to that
exposure during his or her lifetime. To develop a risk estimate, CBG
and ftgency consultants evaluated the animal test data and the human ex-
posure data using several different models. They selected the one-hit
model as providing the most conservative estimate. This model relates
the probability of the development of tumors in hunans to the exposure
and animal test data as follows:
-(Bx)
Risk - 1-e
B >
ftere:
B
P
PC
Pt
slope coefficient of the one-hit model
(Pt-Pc)/(l-Pc)
Incidence of hepatonas in control animals
Incidence of hepatcrnas in test animals
Test animal exposure (ppm)
Potential human exposure
2/ The linear and one-hit models were both used to calculate risk po-
tential (Felkner, 1978). However, the one-hit model projected the
most risk and was therefore chosen as the more conservative basis
of projecting potential risk from the Innes data. The Log-Probit
model was considered inappropriate for estimating risk rron the
results of the Innes study (Felkner, 1978).
8/ The slope B can be derived from the general expression for the
one-hit model which is: risk - 0 +
-------
The risk estimates are summarized in Tables 6, 7, and 8.
2. Risk; Adverse Testicular Effects
The primary routes of exposure to chlorobenzilate are in the diet and
during spray application. The following estimates are based upon analyses
by the Criteria and Evaluation Division.
a. Dietary Exposure
As previously determined, the average human exposure to chlorobenzi-
late from the diet is 0.0038 rag/day for the general population and 0.0095
mg/day for the Florida population (Severn, 1978). For a 70 kg male, this
converts to daily dietary equivalents of 0.002 ppm for the general popula-
s/
tion and < 0.006 ppm for the Florida group. Because human exposure from
the diet is a lifetime possibility, it is appropriate to use a whole life
feeding model for risk calculations. Comparing the estimated exposures to
a no-observable effects level (NOEL) of 40 ppm (See Section II,A,3), indi-
cates that the margin of safety is approximately 15,000 for men exposed to
chlorobenzilate in the diet (Potrepka, 1978a).
b. Occupational Exposure
Maximum exposure to unprotected spray applicators has been estimated
to be 13 to 41 mg/day (Table 4). A direct comparison between applicator ex-
posure and a NOEL based on daily exposure over an entire life span may not
be appropriate because of the non-continuous nature of applicator exposure;
9/ See Footnote 5.
(34)
-------
Table 6
CHLOROBENZIIATE
POTENTIAL OCCUPATIONAL CANCER RISK
S/
GROUND APPLICATORS (AGRICULTURAL - CITRUS ONLY)
S/
by Maximum
Maximum Mathematical Expectation
Lifetime Probability of Numbers of Tumors
of Tumor Formation Djring a Lifetime
(Less Than) (Less Than)
One-hit Model (MCI Data)
Observed 80 to 300 in 1 million 0.1 to 0.2
One-hit Model (Innes Data)
Observed 400 to 1400 in 1 million 0.3 to 1.0
a/ There is insufficient data to allow estimates of risk to aerial ap-
plicators, non-citrus applicators or harvesters of the treated crops.
b/ Assumes that ground applicator's daily dietary exposure to chloro-
benzilate is 0.39 to 1.3 ppm. The one-hit model is a conservative
technique for projecting risk from laboratory animals to man.
c/ Since lifetime animal studies were used to make risk estimates, the
probability of cancer in humans is estimated as a lifetime proba-
bility, and should, therefore, be interpreted as an index or "mathe-
matical" expectation rather than a "clinical" expectation.
d/ In addition to normal spontaneous rate; estimate based on NCI study
male mice with hepatocellular carcinomas [32 cut of 48 (treated); 4
out of 19 (controls)] (Albert, 1978b).
e/ In addition to normal spontaneous rate; estimate based on Innes
Study "Strain X" male mice with hepatcmas [9 cut of 17 (treated);
8 out of 79 (controls)] (Albert, 1978).
f/ Estimate used.
(35)
-------
Table 7
CANCER RISK THROUGH DIETARY. EXPOSUPE
FLORIDA POPULATION (8,000,000)
t/
a/ Maximum
Maximum Mathematical Expectation
Lifetime Probability of Numbers of Tumors
of Timor Formation During a Lifetime
(Less Than) _ _ (Less Than) _
<•/
One-hit Model (NCI Data)
Observed 0.5 to 1.2 in 1 million 4 to 10
3/
One-hit Model (Innes Data)
Observed 2.7 to 6.5 in 1 million 22 to 52
a/ Assumes that dietary exposure occurs at the level of exposure expressed
as reasonable upper limit (0.0025 to 0.0061 ppra daily throughout life-
time) , and model projects conservative expression of risk.
b/ Since the animal study was conducted throughout lifetime exposure, the
chance of cancer occurrence is extrapolated as the potential of a cancer
event during a lifetime, and should, therefore, be interpreted as an in-
dex or "mathematical" expectation rather than a "clinical" expectation.
c/ In addition to normal spontaneous rate; estimate based on NCI study male
mice with hepatocellular carcinomas [32 out of 48 (treated); 4 out of 19
(controls)] (Albert, 1978b).
d/ In addition to normal spontaneous rate; estimate based on Innes study
"Strain X" male mice with hepatomas [9 cut of 17 (treated); 8 out of 79
(controls)} (Albert, 1978).
e/ Estimate used.
(36)
-------
Table 8
POTENTIAL CANCER RISK THRCUGH DIETMCf EXPOSURE
O.S. POPUIATION (EXCEPT EDORUA) (212,000,000)
s/
One-hit Model (NCI Data)
Observed
*
One-hit Model (Innes Data)
a/ Maximum
Maximum Mathematical Expectation
Lifetime Probability of Numbers of Tutors
of Tumor Formation During a Lifetime
(Less Hum) _ (Less Than) _
~
0.4 in 1 million
2.1 in 1 million
86
445
a/ Assumes that dietary exposure occurs at the level of exposure expressed
as reasonable upper limit (0.0025 to 0.0061 ppra daily throughout life-
time) , and node! projects conservative expression of risk.
b/ Since the animal study was conducted throughout lifetime exposure, the
chance of cancer occurrence is extrapolated as the potential of a cancer
event during a lifetime, and should, therefore, be interpreted as an in-
dex or "mathematical" expectation rather than a "clinical" expectation.
c/ In addition to normal spontaneous rate; estimate based on MCI study male
•ice with hepatocellular carcinomas [32 cut of 48 (treated); 4 out of 13
(controls)] (Albert, 1978b).
d/ In addition to normal spontaneous rate; estimate based on Innes study
"Strain X" male mice with hepatomas [9 out of 17 (treated); 8 out of 79
(controls)] (Albert, 1978).
e/ Estimate used.
(37)
-------
similarly, use of a NOEL from a subacute study does not consider the fact
that applicator exposure may be repetitive over most of the life span.
Assuming the analysis employed in the estimation of onoogenic risk ade-
quately adjusts for the difference between continuous and repeated ex-
posure, a dietary equivalent of 0.39 to 1.3 ppm would be derived for a
70 kg man (Albert, 1978).
Based upon a NOEL of 40 ppm, the margin of safety for unprotected
spray applicators would range from 55-169. The values given for margin
of safety were calculated based upon a comparison of approximate dose
levels (mg/kg) rather than dietary concentration (ppm) (Potrepka, 1978).
Use of either figure would result in a margin of safety within the same
order of magnitude.
If the assumption is made that the subacute model is more analo-
gous to applicator exposure, no correction would be made for the tine
span of the exposure, and the applicable NOEL would be 500 ppm. Calcu-
lations based on this assumption would yield an estimated maximum dietary
equivalent of 6.7 - 2.1 ppm. Using the subacute NOEL, 500 ppm, as a
basis, the margin of safety would range from 43 -135.
(38)
-------
10/
III. Benefit Analysis
A. Introduction
This section summarizes the benefits of the principal uses of
chlorobenzilate. The sunnary identifies the uses of the pesticide; es-
timates the quantities used; identifies and evaluates the registered al-
ternatives, their availability and their costs; and evaluates the consa-
quences of cancelling chlorobenzilate for these uses, including the pro-
jected in^acts on crop production costs and retail food prices, this
information is derived in part from rebuttal submissions.
B. Uses
For purposes of discussion, the uses of chlorobenzilate may be
grouped into two categories, citrus and non-citrus uses. Table 1 presents
the complete usage pattern for cnlorobenzilate in the United States.
- 1. Citrus Uses
The roost extensive use of chlorobenzilate is to control mites on
citrus crops, principally oranges, grapef." ;, and lanons. The major
target pests are the citrus rust mite on oranges and grapefruit and the
citrus bud mite on lemons. In 1975, chlorobenzilate use on these three
crops accounted for approximately 920,000 pounds of active ingredient;
other citrus uses (limes, tangelos, tangerines, other specialty citrus
10/ This section is based on analyses prepared by M. Luttner and
M. McWhorter, Criteria and Evaluation Division, OFF, EPA.
reference1: ire from Luttner unless otherwise noted.
(39)
-------
fruit) accounted for 76,000 pounds. In total, citrus usas accounted for
89.2% of all chlorobenzilate used in the United States.
About 50% of U.S. citrus acreage, over 620,000 acres and 11,400 farms,
is treated with chlorobenzilate. Florida citrus growers use chloroben-
zilafe most extensively. Two-thirds (523,000 acres) of the Florida acreage
used to grow oranges, grapefruit, and lemons is treated with chloroben-
zilate, accounting for 72% of the total chlorobenzilate used in the United
States. Approximately half (43,000 acres) of the Texas acreage is treated
with chlorobenzilate, which accounts for 9% of the total chlorobenzilate
used in the United States. Only 1.6% of the California citrus acreage is
treated with chlorobenzilate, which accounts for under 1% of the total
chlorobenzilate used in the United States. Another 7% of chlorobenzilate
used in the United States is applied to limes, tangerines, tangelos, and
other specialty citrus crops.
a. Florida
In Florida, chlorobenzilate plays an integral part in established cit-
rus integrated pest management programs. At present these programs are
directed at controlling the principal pests of Florida citrus, the citrus
rust mite and the citrus snow scale (Brogdon, 1976). Chlorobenzilate is
recortmended for use in these programs because it controls citrus rust
mites without harming the natural predators and parasites of the scale
insects and because it is cost-effective. Florida citrus IPM programs
have reduced previously important pests, such as puple scale and Florida
red scale, to relative insignificance through the introduction and estab-
lishment of parasites on virtually all of the Florida citrus acreage.
(40)
-------
Through the IPM program, another parasite, the Hong Kong wasp, is being
introduced to control snow scale.
b. Texas
The principal pest in Texas citrus production is the citrus rust
mite (French et al., 1978). As in Florida, chlorobenzilate is effective
in controlling the citrus rust mite while preserving beneficial insects
inportant in the control of chaff, California red, Florida red, purple,
and brown soft scales. Seventeen species of beneficial insects were re-
leased in Texas citrus production areas during the period 1952-1960 (Cocke
et al. 1978); as a result, beneficial insects have provided significant
control of purple and Florida red scale (Dean, 1955, 1975).
The citrus mealybug is also regarded as a potentially major pest
that is currently being controlled in Texas by species of lady beetles and
brown lacewing. Field experimentation indicates that the lady beetle can
effectively control citrus mealybug in orchards treated with chlorobenzilate.
Extension education programs backed by citrus IPM research at the
Texas Agricultural Experiment Station, Texas Ail University, and the USDA-
Subtropical Texas Area Citrus Insects Laboratory are helping Texas growers
to become aware of and to adopt citrus IPM control strategy. Because of
the growing acceptance of IPM, a Texas Citrus Pest Management Program that
will include insect, mite, and disease control is being developed (Cocke
et al. 1978}.
ll/ Citrus IPM in Texas is currently on a less formal basis than citrus
IPM is in Florida. However, beneficial insects established through
releases provide biological control cf scale pests. In Texas as m
Florida, the use of selective irdticides like chlorobenzilate protects
these beneficial insects, requiring less use of broad-spectrum scali-
cides than would otherwise be required.
(41)
-------
c. California
In California, chlorobenzilate is used on an "as needed" basis
(alone and in combination with oil} to control citrus bud mite on lemons
and citrus rust mite on oranges. About one eighth (approximately 5,000
12/
acres) of the lemon acreage in the southern counties is treated with
chlorobenzilate in any given year; approximately one tenth (3,300 acres)
of the orange acreage in the sane area is treated annually (USDA, 1977).
Integrated pest management programs in the southern counties are u&ed to
varying degrees for control of California red, purple, and black scales,
and brown soft scales, aphids, and mealybugs. Chlorobenzilate is used
in these programs because it is compatible with the use of the Aphytis
parasites to control California red scale, and has no adverse effect on
the natural predators of mites and other pests (Jeppson, 1959).
d. Arizona
Three major mite problems occur annually on citrus crops grown in
Arizona - citrus red rrlte, citrus flat mite and Yuna spider mite. A fourtli
species, the Texas citrus mite, is an occasional problem in local areas
(Luttner, 1977a). The citrus red mite is principally a pest specific to
lemons in Arizona, while the other mite species affect all of the citrus
crops. Chlorobenzilate is used by Arizona growers for the same reasons
it is used elsewhere, i.e., its selectivity for mites and negligible
effects upon beneficial insects. Approximately 5% (3,000 acres) of the
12/ The southern California counties in question include the following:
Imperial, Los Angeles, Orange, Riverside, San Diego, Santa Barbara,
and Ventura.
(42)
-------
Arizona acreage used to grow oranges, lemons, and grapefruit (principally
lemons) is treated with chlorobenzilate (Table 1).
2. Non-Citrus Uses
Cotton use accounts for 39,000 pounds or 5% of the total chloroben-
zilate used in the United States (1975). This ancunt was used on 39,000
acres of cotton or 0.4).% of the total U.S. cotton acreage. Non-citrus
fruits and nuts (apples, pears, cherries, aironds, and walnuts) account for
81,000 pounds or 7.3% of the total chlorober.zilate used in the United States
(1975). This amount was used on 24,000 acres of fruits and nuts or approxi-
mately 1% of the total U.S. fruit and nut acreage.
There are other registered uses of chlorobenzilate, including melons,
13/
ornamentals, boats, and docks. Little chlorobenzilate is applied for
these uses (OSDA, 1977).
13/ The registered miticide uses of chlorobenzilate other than the citrus
use, the cotton use, an? the uses on fruits and nuts are:
agricultural crops - melons (c&saba, cantaloupes, crenshaw, honeydew,
Persian);
ornamentals - (lawns and turf) - grass;
- (herbaceous plants and bulbs) - aster, carnations,
chrysanthemums, gladioli, iris, marigold, phlox,
snapdragon, zinnia;
- (woody shrubs, trees and vines) - arbovitae,
azaleas, birch, boxwood, camellia, Douglas fir,
elm, hawthorn, hemlock, holly, juniper, lilac,
locust, maple, oak, ornamental shrubs, ornamen-
tal trees, pine, poplar, rhododendron, roses,
spruce, willow yew;
domestic dwellings; - (areas other than edible-product areas) -
medical facilities & outdoor areas, boats,and docks.
schools; commercial
establishments
Source: EPA Compendium of Registered Pesticides (U.S. Environmental
Protection Agency, 1973).
(43)
-------
C. Alternatives to Chlorobenzilate
1. Citrus Alternatives
If chlorobenzilate were not available for use as a miticide, citrus
growers would face a choice of using no miticides or using miticide alter-
natives to chlorobenzilate. If growers in Florida, Texas, and Arizona de-
cided to use an alternative niticide, they would face the decision whether
to use one of the two selective alternatives or one of the non-selective
alternatives. California growers would not have the option of choosing a
selective alternative.
a. Ho Miticide
Uncontrolled, mites affect fruit size, appearance, crop yield, and
tree stock stamina (Table 9). Fruit size and appearance are important for
the fresh-fruit market because of consumer preference. Approximately 57%
of the citrus fruit grown in Texas goes to the fresh fruit market. In
W
California, 52% of the lemons and 65% of the oranges go to the fresh market.
While only 5% of the Florida citrus crop goes to the fresh fruit market,
growers cannot identify the fruit which goes to that market until the end
of the season. Since the fresh fruit market is more lucrative than the
process market, growers try to produce for this market by protecting the
appearance of their fruit.
Studies have shown (Allen, 1978) that uncontrolled mites cause re-
ductions in fruit size of 12% for oranges and 17% for grapefruit. Fruit-
size declines also occur in lemons, but these effects have not been fully
14/ State-wide average (Luttner, 1973a).
(44)
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Table 9
ESTIMATE OF THE MAXIMUM ECONOMIC VALUE LOST 1
AS A RESULT OF UNCONTROLLED MITE INFESTATIONS IN
y
State Crop
CA
FL
TX
Total
lemons
oranges
g-fruit
oranges
g-fruit
Per Year
Average
Production
(tons)
735,000
8,119,000
2,057,000
248,000
405,000
Loss Due
To Drop
(tons)
183,750
811,900
205,700
24,800
40,500
Loss Due To Total
Size Reduction Loss
(tons) (tons)
183,750
906,080 1,717,980
314,721 520,421
27,677 52,477
61,965 102,465
CITRUS
Value
($7t5n~)
116
58
57
52
51
/
Total Value
3/ of Production
Loss
$ 21,315,000
$ 99,643,000
$ 29,664,000
$129,307,000
$ 2,729,000
$ 5,226,000
$ 7,955,000
$158,577,000
I/ Luttner, (1978a)
2/ No estimate of inpact oould be derived for Arizona
3/ 3-Year average based on USDA statistics
(45)
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quantified. Also, overall yield can be reduced by mite infestations due
to fruit drop (Allen, 1978). It is estimated that such reductions in fruit
size and overall yield would reduce grower gross revenues by about $159
million per year (Table 9). Total grower gross revenues fron sales of cit-
rus crops approximate $1 billion per year. Finally, failure to control mites
reduces the life span of citrus trees, causing further economic impacts.
b. Alternative Miticides; Florida and Texas
Chlorcbenzilate is used widely because its selectivity makes it
compatible with integrated pest management programs using predators and
parasites of pests other than mites, principally scale insects. Such IPM
programs provide inexpensive control of a number of major pests. Accord-
ingly, assessment of pesticide alternatives to Chlorobenzilate must focus
on the economic consequences of replacing chlorebenzilate with a selective
miticide, compatible with these integrated pest management programs, or
with a non-selective miticide, which would disrupt those programs.
i. Selective Miticides
Only two registered selective miticides are potential chloroben-
zilate alternatives in Florida and Texas: dicofol and fenbuta tin-oxide.
IS/ Several pesticides unregistered for citrus uses may be useful as
Chlorobenzilate alternatives. Diflubenzuran (under pre-HPAR review
by the Agency) has performed adequately in pre-development testing.
Hirsutella, a naturally-occurring fungal disease of mites, has
shown effectiveness under some conditions (McWhorter, 1978). The
Agency is not evaluating unregistered potential alternatives in
this document.
16/ The Agency has conducted a preliminary risk assessment of dicofol
and fenbutatin-oxide (see Appendix C). In broad summary, dicofol
appears to be an oncogen based upon preliminary results of an NCI
study, while fenbutatin-oxide appears to cause reproductive effects
and may pose other problems.
(46)
-------
Both pesticides are included in the respective State recoimendations for
mite control (Luttner, 19T7a, 1978b). However, each poses substantial
problems as an acceptable substitute in IPM programs.
Total per-acre treatment costs with dicofol are approximately 33%
higher than total per-acre treatment costs with chlorobenzilate (Table 10).
If dicofol is used in groves infested with snow scale (approximately 75%
of Florida groves), the snow scale populations increase, causing serious
infestation and necessitating the use of scalicides (Florida Cooperative
12/
Extension Service, 1977).
Growers using dicofol in place of chlorobenzilate in groves infested
with snow scale would need to supplement dicofol applications with scalicide
applications. However, since snow scale is not a citrus pest in Texas, it
is unlikely that scale problems in Texas would be aggravated by the use of
dicofol. The per-acre cost of treatment with dicofol is approximately
$32.67, compared to $24.62 per-acre using chlorobenzilate.
Fenbutatin-oxide (marketed under the trade name Vendex) is a selec-
tive miticide which does not cause proliferation of snow scale or other
pests (Codec et al. 1978). However, feiVoutatin-oxide is expensive in com-
parison with chlorobenzilate and other alternative miticJdes. In Florida,
the per-acre cost of treatment with fenbutatin-oxide ranges from $63.31 to
IT/ The observed field sex ratio of snow scale is normally 5 males to 1
female. Applications of dicofol have increased average populations
approximately three-fold. Additionally, the sex ratio of the F.
progeny is approximately 3 females to 1 male, thus greatly expanding
the population's potential for increase (Brooks, 1973; Huffaker, 1978).
(47)
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Table 10
PER-ACRE TREATMENT POSTS IN FDORIDA CITRUS WITH CHL3ROBENZILATE;
!7
SEI£CTED ALTERNATIVE MITICIDES AND SCALICIDES
Pesticide
Mites Chlorobenzilate 4E
Dioofol 4MF
Ethion 4E
Sulfur 95%
Ethion 4F & Oil 97%
Oil 97%
Fenbutatin-Oxide 50WP
Scales Ethion 4E
Parathion 8E
Carbophenothion 4E
Oil 97%
Cost ($)
16.00/gal
17.40/gal
13.50/gal
120.00/ton
13.50/gal
$l/gal
1.00/gal
11.65/lb
13.50/gal
16.00/gal
13.50/gal
1.00/gal
y
Material
Cost/f-rre ($)
5.00
13.05
12.66
3.00
12.66 + 6.00
18.66
8.00
43.69
12.66
5.00
12.66
10.00
Total Cost/Acre
Treatment ($)
24.62
32.67
32.28
22.62
38.28
27.62-,
32.28
24.62
32.28
29.62
I/ Selected on basis of use or potential for use.
2/ Material costs as reported for Florida by the USDA Chlorobenzilate
Assessment Team.
3/ Material costs per acre based on Florida costs and application rates
specified in the Florida Citrus Spray and Dust Schedule.
4/ Total costs include application costs per acre of $19.62, which repre-
sents typical Florida costs for a dilute (1,000 gallons spray/acre)
spray treatment with tractor-pulled air-blast equipment.
5/ The total cost/acre treatment would increase to $69.87 if 6 pints of a
surfactant were added per acre.
(48)
-------
IB/
$69.87 (depending upon whether a surfactant is added); in Texas, the per-
acre cost of treatment with fenbutatin-oxide ranges from $40.01 to $46.57.
The per-acre cost of treatment with chlorobenzilate is $24.e>2 (Table 10).
Another problem associated with the use of fenbutatin-oxide in
Florida (but not Texas) is its incompatibility with oil. Fenbutatin-oxide
and oil are phytotoxic when applied together or within 30 days of one
19/
another. Oil is the treatment of choice for greasy spot, a fungal di-
20/
sease which is one of the major pest problems of Florida citrus. Mite
problems and greasy spot problems frequently occur at the sane time. If
it is passible to delay treatment of these pests for 30 days, then fen-
butatin-oxide and oil can both be used for control of greasy spot disease
and mites; however, the use of fenbutatin-oxide in the spray program would
increase grower costs, since two separate treatments would be required in
place of a single chlorobenzilate plus oil treatment. This increase would
amount to the $19.62 per-acre application cost. It is frequently not pru-
dent, however, to defer treatment of greasy spot or mites for 30 days. In
such situations, fenbutatin-oxide could only be used if seme other pesti-
cide could be substituted for oil to control greasy spot disease. If
IS/ Because fenbutatin-oxide does not act as rapidly as chlorobenzilate,
the use of fenbutatin-oxide may require the addition of a surfactant
to produce results equivalent to those obtained with chlorobenzilate.
19/ The phytotoxicity problem ocoirs primarily with immature fruit and
foliage. However, since all trees in a grove may contain both mature
and immature fruit and/or foliage at any one time, phytotoxicity is
appropriately treated as a generic problem.
20/ Other pesticides registered and recommended by the State of Florida for
control of greasy spot disease are: di Cola tan, benonyl, copper, oil.
(49)
-------
21/
benonyl were substituted for oil, the additional cost to growers would
be $8.00, the difference between the material cost of bencrryl and the ma-
terial cost of oil.
Further, while fenbutatin-oxide can substitute for chlorobenzilate on
oranges and most grapefruit varieties, it is not registered for the remain-
22/
ing chlorobenzilate citrus uses. Fenbutatin-oxide has not been used widely
in the past, and it nay not be immediately available in sufficient quantity
to be used as a substitute for chlorobenzilate. There is no reason to be-
lieve, however, that the supply of fenbutatin-oxide would not increase to
meet demand if that demand were created by cancellation of chlorobenzilate.
23/
ii. Non-Selective Miticides
Certain of the non-selective alternatives to chlorobenzilate —
ethion and ethion plus oil — can control mites as effectively as chloro-
benzilate. Another non-selective alternative, sulfur, does not provide
the level of mite control achieved with chlorobenz'late. Were these alter-
24/
natives repeatedly used in place of chlorobenzilate, the populations of
21/ Currently under RPAR review.
22/ Fenbutatin-oxide is currently registered for all citrus fruit except
tangerines, tangelos, Heed grapefruit, or Webb Red Blush grapefruit
(Luttner, 1978b).
23/ The non-selective miticides for citrus mite control are carbophe-
nothion, ethion, prcpargite, sulfur, ethion plus oil, carfoopheno-
thicc; plus oil, ethion plus sulfur, oil, dicofol plus oil. Only
these materials judged to be major chlorobenzilate alternatives
were evaluated for their impact upon beneficial insects (USDA, 1977).
24/ Non-selective miticides are currently in use; however, the level of
use is compatible with maintenance of beneficial insect populations.
(50)
-------
the predators and parasites of the scale insects and other pests would be
reduced to levels incapable of providing economic control, necessitating
the use of combinations of chemical pesticides in large volumes (Table 11
and 12}. In Florida, for example, the impact on existing IPM programs
would be severe, and it is expected that at the end of the fifth year after
cancellation of chlorobenzilate, growers using a non-selective alternative
would need to treat 100% of their acreage with one application of a miticide
and two applications of a scalicide (Table 11). The per-acre cost of such
25/
treatment would range from $72.00 to $103.00. A similar impact could be
experienced by Texas citrus growers, many of when ?re using pest management
techniques similar to those used in Florida.
The use of non-selective chlorobenzilate alternatives and widespread
scalicide treatments in Florida may have adverse effects upon fruit yield
or grade and tree vitality. Adverse fruit quality effects may also occur
in Texas (over one-half of all citrus produced in Texas is utilized in the
fresh market). However, no valid estimates on the amount of fruit that
would be damaged or unusable or the extent of tree injury are available to
evaluate this potential impact.
c. Alternative Miticides; California
There is only one chlorobenzilate alternative (oil) for control of
the citrus bud mite or the southern California lemon crop. Further, only
one chlorobenzilate alternative [wettable sulfur) is recommended by the
State of California for control of the citrus ruse mite on southern
25/ The cost range is based on the following spray regimes: sulfur,
parathicn, parathion ($72.00) and ethion plus oil, ethion, ethion
($103.00).
(51)
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Table 11
ESTIMMED EXTENT OF USE OF CHD3ROBENZILAIE ftND SEI£CTED SUBSTITUTES TO REPIACE
I/
CHLOROBENZILATE FOR CONTROL OF THE CITRUS MITE COMPLEX AND SCALE INSECTS IN FLORIDA
Miticide Use Scalicide Uses Total Use
Year 1 Year 5 Year 1 Year 5 Year 1 Year 5
Chlorobenzilate 805,000 805,000 805,000 805,000
Fenbutatin-Oxide 2,415,000 2,415,OOC — 2,415,000 2,415,000
Dicofol 418,000 418,000 418,000 418,000
Ethicn 979,000 979,000 319,000 1,594,000 1,298,000 2,573,000
Carbophenothion 319,000 1,594,000 319,000 1,594,000
^arathion 213,000 1.063,000 213,000 1,063,000
Sulfur 7,834,000 7,834,000 7,834,000 7,834,000
Oil (gals.) 1,949,000 1,949,000 850,000 4,250,000 2,799,000 6,199,000
I/ Note that all of the listed materials (except fenbutatin-oxide) would have to
be used in the quantities indicated to replace chlorobenzilate.
2/ Quantity indicates potential use level (see discussion at Section III,C,b,i).
Fenbutatin-oxide poses oil conpatibility problems (see discussion at Section
III,C,b,ii). In addition, there are problems concerning the availability of
fenbutatin-cxide in the event of cancellation of chlocobenzilate (see dis-
cussion at Section III,C,b,i). Finally, fenbutatin-oxide is not registered
for sane Texas citrus uses (see discussion at Section Til, C,b,i).
(52)
-------
Table 12
ESTIMATED EXTENT OF USE OF CHIQROBENZILATE AND SELECTED SUBSTITUTES
I/
TO REPIACE CHLOBOBENZILKTE FOR CONTROL OF THE CITRUS MITE ODMPIEX IN TEXAS
Quantity Required
Year 1 Year 5
Chlorobenzilate 102,000 102,000
Fenbutatin-Oxide 51,000 51,000
Dicofol
jofol
Ethion
Carbophenoth ion
Oil (gals.)
174,000
31,000
79,000
39,000
199,000
174,000
31,000
79,000
39,000
199,000
I/ Note that all of the listed materials (except fenbutatin-oxide) would have to
be used in the quantities indicated to replace chlorobenzilate.
2/ Quantity indicates potential use level (fee discussion at Section III,C,b,i).
There are problems concerning the availability of fenbutatin-oxide in the
event of cancellation of chlorobenzilate (see discussion at Section III,C,b,i).
Finally, fenbutatin-oxide is not registered for seme Texas citrus uses (see
discussion at Section III, C,b,i).
(53)
-------
Table 13
ESTIMATED EXl«ff OF USE OP CHLOBUBENZIIATE COMPARED WITH AMOUNT OF OIL TOEAIMEMT
TO REPLACE CHLOHDBENZIIATE FOR CONTROL OF TOE CITRUS BUD MITE ON CALIFORNIA LEMONS
Quantity Required
Year 1 Year 5
Chlorobenzilate 7,500 7,500
Oil (gals.) 493,000 2,465,000
(54)
-------
26/
California oranges (USDA, 1977). Oil and sulfur are not completely
satisfactory substitutes for chlorobenzilate since they are not as effec-
tive and their use damages fruit quality and tree vitality. However, the
use of sulfur has an adverse effect on soil chemistry requiring conpen-
sating soil treatments with line. The per-acre treatment cost of oil
and sulfur would be approximately $76.00 and $23.00, respectively, con-
pared with $61.00 for chlorobenzilate (USDA, 1977).
d. Alternative Miticides; Arizona
Although chlorobenzilate use is quite limited in Arizona citrus
groves, the adoption of non-selective alternatives on those acres where
chlorobenzilate is currently used would adversely effect the endemic para-
site and predator populations in a manner similar to that described for
Florida and Texas.
2. Non-Citrus Use Alternatives
There are numerous alternative pesticides registered to control
mites on cotton and on fruits and nuts (Table 14). Should chlorobenzilate
be cancelled as a cotton miticide, 10 of the 14 State-recaimended alter-
natives would have a lower pesticide cost per acre. Even if efficacious
control of the cotton spider mite could only be achieved with alternatives
more expensive than chlorobenzilate, the increased pesticide cost to con-
trol mites on domestic cotton would be minimal - at most approximately
$125,000 per year. Under a similar "worst case" assumption, the increased
26/ Registered alternative treatments in use in Florida and Texas have
been evaluated in California, but because of phytotoxicity problems,
conparitive ineffectiveness, or other considerations, they have not
been included for grower use.
(55)
-------
Table 14
CHIOROBENZIIArE AND ALTERNATIVES FOR NDN-CITRUS USES
Conned ity
Pesticide
Pesticide Cost/Acre ($)
Cotton
Walnuts
Apples
Chlorobenzilate
Aldicarb
Carbophenothion
Dane ton
Dicofol
Dicrotophos
Disulfoton
Ethion
Methidathion
Methyl Parathion
Monocrotophos
Parathion
Phorate
Propargite
Sulfur
Chlorobenzilate
Carbophenothion
Dicofol
Dioxathion
Ethion
Oil
Phosalone
Propargite
Chlorobenz ilate
Carbophenothion
Cyhexatin
Dicofol
Ethion
Propargite
Tetradifon
5.45
12.64
2.20
3.80
5.99
C.71
2.40
3.44
10.00
0.99
3.16
1.12
4.20
6.04
5.25
3.18
7.00
6.22
9.76
11.68
7.75
14.22
8.68
2.C4
3.50
3.00
2.92
1.46
2.17
1.77
(56)
-------
U.S. pesticide cost to control mites on fruits and nuts would also be mini-
mal - at most approximately $69,000 per year.
D. Grower Impacts
1. Citrus Uses
a. Florida
The economic impacts on growers associated with use of selected
chlorobenzilate alternatives are elaborated in Tables 11, 16, and 19.
Based upon the information previously presented, it has been determined
27/
that the non-selective chlorobenzilate alternatives would be the pre-
dominant replacement materials if chlorobenzilate were no longer available.
It was also previously explained that the use of dicofol for mite
control would not have an adverse effect upon the beneficial insects that
control purple and Florida red scale but would require additional use of
sealicides to control increased populations of snow scale.
In the short run, fenbutatin-oxide is more expensive ($63.31/acre)
than the dilorobenzilate miticide alternatives ($22.62 to $38.28 per acre).
However, in the long run, the use of chlorobenzilate alternatives and scali-
cides would lead to per-acre costs ranging from $72 to $103. Thus, in
strictly economic terms, fenbutatin-oxide would appear to be an attractive
27/ While non-selective materials would predominate, the economic assessment
of the likely consequences of chlorobenzilate cancellation performed
by the Agency (Luttner, 1977b) assumed that materials identified as
likely replacements by the USDA Assessment Team would be used in equal
distribution. In the case of Florida, on* such material was dicofol,
which is evaluated separately in this discussion front the standpoint
of its suitability as a total cnlcrobenzilate replacement. Similarly,
in the case of Texas, the analysis assumed that fenbutatin-oxide would
be utilized to sane extent.
(57)
-------
Table 15
y
lapactn Projected to Growers Resulting frca Canoellation of Chlorobenzilate
Present Value Present Value 4/ % Change 5/ % Change
of Change in of Change in Current in Current Current in Current
2/ Control Cost Affected Control Cost/ Pest Control Pest Control Production Production
Site ($000) Acres Affected Acre Cost/Acre Cost/Acre Cost/Acre Cost/Acre
PL-citrus 40,079 850,000 $47 $108 443.5 $346 +13.6
CA-lenons 3,678 41,000 $90 $220 +40.9 $1,264 +7.1
I/ Source: Luttner, 1977a. Assumes non-selective alternatives are used to
replace chlorobenzilate.
2/ Comparative data for Florida citrus is based on oranges, which comprise
approximately 75% of the Florida acreage.
3/ Cost data represents fifth-year inpacts calculated to present values
using a 7% rate of discount.
4/ Represents an average for Florida oranges and California lemons, including
pest, disease, and weed control. Based on budgets developed by Muraro and
Abbitt (Florida) and Gustafson and Rock (California).
5/ Represents averages for Florida oranges and California lemons using budgets
cited in footnote 13. Includes cultural costs and management only.
(58)
-------
Table 16
Prcjectec Cost of 5;alt Ir-sect Control ir. Fiorisa Citrj; During
Tnitia- Fivt "tar ?«iec Felixine Car'cellatior of Chlora.-»enzUate
V
Scalicioe
Scalicide +
Arolication 3/
Cost/'Xcre- Acre-Trssr^ents/Tfear
Trsaaaentt?) Year 1 Year 2 Year 3 Y=ar 4 Year 5
Cariopherothion 32.2B 85,000 17C,000 255,000 340,000 425,000
EthiOl 32.28 85,000 17C.OOC 7.55,000 340,000 425,000
Oil (97%) 29.62 85,000 170,000 255,000 340,000 425,000
Para tt ion 8E 24.62 85,000 170,000 25;,OOP 34C.OOO 425,000
Tbtils 340,000 680,000 1,020,000 1,36C,000 : .700,000
Scalicide
Carbopherath ion
Ethion
Oil (971)
Parathion BE
Ibtali
Y*ar 1
2.744
2,744
2, .518
2,093
10,399
Cost of
Year 2
5.488
5,488
5,035
4,185
20,196
Cortroi.'Tsar
fear 3
8,231
8,231
7,553
_6,278
X.293
ISOOO)
Year 4
10,975
10,975
10,071
8,371
40,392
Year 5
13,719
13,719
12.589
1C, 464
50,491
I/ The s;aiicides listed appear in tie 1*77 Florida Citr.s SiTay- and Dust
Sc.VA.le. TtK aszxiption U.at t^°se material: would be widely used for
scale control appears to be rusor^ble based on ejecting registrations,
effectiveness, ard lou cant relative to other available scalicides.
2/ Costs baaed on tte following: application rates as soecified ui the 1977
Florida Spray arei Sust Schedule; pefticide prices sufplied fcy the Assessment
T»m; ar^>lication OD«t of SIS. 62 per *cr» represents us* of dilute spray
(two 500 gallon tanks/acre ) as developed in a current production budget for
Florida (Kuraro a,-x! Aobitt, 1977 citaJ in Luttner, 1977b).
3/ Adciticnal scale control treatnents are assured to be required on 100% of
the Florida acreage Capprox. 850,000 acres) over a five year period. Q»
annual incremntal increase in acres rsguirirr truitirent is assured bo be
equal. Tra cate of increase in affected acres represents the projected rate
of spread of econor.ically darjcing scalg fooula: icus throughout the State.
Tse of scalici3es on an equal tasis represents an assjiptior. by the analyst.
Uthcugh chlorobenzilate is not used on lOCt of Florida citrus each year,
the prelected IP* inlets will irvolve all of the State's acreage. QUoro-
benzilau's use pattern lb?» of Florida acrtsce treatwl'year) indi^tas
that it is used two out of every three years on the average acre for nut*
CDTitrol, vitn the run»rous alt.err.at lues used in rotation djring the third
year. This oc=«si£nal rotation with alterratives (sane of which do not
cause serious adverse effects upon beDeficial tis«cts) pearits the oon-
tin;>ed success of the Tr"?! prcgrsn. Bowever, oontLiaous use of the al-
ternatives wxild eventually lead to development of scale control problem*
on all of the Florida acreage.
4/ Prcd'jct of scalicide + application ctst/acre-treaUrent tires acre— treatneuts
for U* respective years.
(59)
-------
alternative. However, the profitability of the Florida citrus industry is
highly variable and in many instances has been only marginally profitable
or unprofitable as measured by return on investment (Brooke, 1973). There-
fore, growers are likely to take a short-run view when selecting alternative
pesticides, even though the most economical long run alternative would be a
selective miticide.
Moreover, there are additional reasons why fenbutatin-oxide is un-
likely to be adopted as an alternative to chlorobenzilate in Florida. These
other reasons (both discussed earlier) are the oil incompatibility with
fenbutatin-oxide and the fact that fenbutatin-oxide is not registered for
some Florida citrus crops.
In Florida, using the non-selective regime to control rust mites
would also require the use of two additional dilute scalicide treatments
per year to counterbalance the reduction of currently established scale
insect parasites to levels of population incapable of providing economic
control. This phenomenon would occur on 100% of the commercial Florida
citrus acreage over a five year period.
Using the non-selective regime would increase grower treatment costs
by $2,043,000 per year or $3.17 per acre-treatment. The subsequent use of
pesticides for scale insect control in Florida would increase grower costs
by $50,491,000 in the fifth year aftei cancellation, i.e., when all of the
Florida acreage would be receiving scale control treatments (Table 17).
The costs could be expected to continue beyond the fifth year at the sane
relative level unless alternative scale control measures were developed.
(60)
-------
Table 17
Economic Inpact of the Loss of Chlorobenzilate During
Initial Five Year Period Following Cancellation .
Year After
Cancellation
Area
Cost of Mite
Control with
Alternatives
($000)
y
Economic Cost
of IPM iirpacts
(SOOO)
Present Value of
Total Economic
Impact ($000)
1
2
3
4
5
AZ
CA
FL
TX
US
AZ
CA
FL
IX
US
AZ
CA
FL
TX
US
AZ
CA
FL
TX
US
AZ
CA
FL
TX
US
0
658
2,043
274
2757?
0
1,698
2,04.3
274
4,015
0
2,739
2,043
274
37015"
0
3,780
2,043
274
"STol?
0
4,821
2,043
274
77T3F
0
—
10,099
10,099
0
20,196
20,196
0
30,293
30 ,293
0
40,392
40,392
0
50,491
50,491
0
658
12,142
274
13,074
0
1,587
20,785
256
22,628
0
2,392
28,242
239
30,873
0
3,086
34,640
224
37,950
0
3,678
40,079
209
43,9&
I/ Costs for Arizona, Florida, and Texas derived in the Preliminary
Benefit Analysis of Chlorobenzilate. Assumes that selected miticide
alternatives (Luttner, 1977a; Tables 22, 23, and 24) would be utilized
in an equal distribution on all acreage currently treated with Chlorobenzi-
late. For a detailed discussion of the methodology utilized to derive the
list of selected alternatives* (Luttrier, 1977).
2/ Assumes 2 additional scale control treatments on 100% of Florida
citrus acreage at year 5 and thereafter.
2/ Sum of cost of mite control with alternatives plus cost of IPM im-
pacts; present values calculated using a 7 percent rate of discount.
(61)
-------
28/
The present value of this change in grower costs ($38,520,000) combined
with the present value o* the increased cost of chiorobenzilate alternatives
for mite control in Florida ($1,559,000) is approximately $40,079,000 per
year after five years. Given the annual cost of the current Florida
citrus pest control program ($72.5 million), the impact ($40.08 million)
projected to occur in the fifth year following a cancellation of chioro-
benzilate would represent a 55.3% increase in the annual cost of the
state's total citrus pest control program.
The loss of chiorobenzilate would increase pest control costs to
Florida citrus growers by about $47 or 44% per acre after 5 years assuming
widespread adaption of the non-selective regime. Average per-acre pro-
duction costs for Florida citrus are projected to increase after 5 years
by 13.6% (Table 15).
b. Texas
In Texas, the use of chiorobenzilate alternatives for control of
citrus mites is projected to increase grower treatment costs by $274,000
per year or $4.72 per acre-treatment (Table 17).
Since snow scale is not a pest of major importance on Texas citrus,
diccfol can be considered a satisfactory replacement for chiorobenzilate
in existing pest management programs. If dicofol were the sole alternative
used on those acres currently treated with chiorobenzilate, Texas citrus
growers would incur additional mite control costs of approximately $432,000
per year or $7.32 per acre treatment.
"Present value" is an accounting concept used to represent future
monetary impacts at a cannon point in time.
(62)
-------
The per-acre cost of treatment with fenbutatin-oxide would in-
crease from $24.62 to $40.01 (without surfactant) or to $46.57 (with sur-
factant). If all citrus acreage currently treated with chlorobenzilate
were treated with fenbutatin-oxide, the total annual cost increase to
growers would range from $908,000 (without surfactant) to $1,295,000 (with
surfactant). Approximately 51,000 pounds of fenbatatin-oxide active in-
gredient would be required to replace the 101,500 pounds chlorobenzilate
currently used in Texas citrus (Table 12).
c. California
In California, the use of petroleum oil sprays to control citrus
bud mites on lemons would require a 3 spray on all of the infested acreage
and two sprays on two-thirds of the infested lemon acreage. This would
occur over a five-year period on all of the lemon acreage in the southern
counties. After five years, approximately 2,465,000 gallons of oil would
be required to replace the 7,500 pounds chlorobenzilate active ingredient
currently used on California lemons (Table 13).
In California the cost of controlling citrus bud mites on lemons
»
is projected to increase pest control costs to growers by an additional
$4,621,00 per year in the fifth year after cancellation (Table 17). This
cost could also be expected to remain at the sane level unless alternative
citrus bud mite control measures were developed. The present value of the
annual Inpact in the fifth year is approximately $3,678,000. Given an es-
timated cost of pest, disease, and weed control on lemons in the southern
California counties of $9,020,000 per year, cancelling ohlorobenzilate
(63)
-------
zilate would increase the cost of pest control on the affected lemon
acreage by about 40.8%.
The loss of chlorobenzilate would increase pest control costs for
California lemon growers by about $90 or 41% per acre after 5 years. Aver-
age per acre production costs would increase after 5 years by about 7.1%
(Table 15).
d. Arizona
The loss of chlorobenzilate and adoption of alternative miticides
is projected to have no net cost to Arizona citrus growers. Using alter-
natives may disrupt IPM strategies in Arizona, but the extent of such dis-
ruption has not been identified nor the resulting costs quantified.
2. Non-Citrus Uses
The cost impacts to growers for non-citrus uses of chlorobenzilate
are discussed in Section C,2.
E. Costs to the Citrus Pulp Feed Industry
Citrus pulp is a by-product of citrus processing; during the 1960's
citrus pulp became a principal feed ration ingredient for dairy cattle in
Florida. The majority (approximately 90%) of the domestic pulp feed mar-
ket consists of sales to Florida dairymen with sane sales to Florida beef
ranchers. Approximately half of the 1,000,000 tons produced annually is
exported to European markets where it is sold for use as dairy cattle feed.
The use of citrus pulp as cattle feed produces gross revenues of approxi-
mately $70 to $90 million to the processors; however, due to the large
amount of energy required to dry the pulp, net profits to tbe processors
(64)
-------
ace not significant. However, the use of citrus pulp for cattle feed has
solved a serious waste disposal problem for the citrus processors. Prior
to the development of the citrus pulp-feed industry, the processing wastes
were routinely dunped and left to rot in citrus groves. The utilization
of pulp as an animal feed ingredient has thus turned a net cost segment
of citrus processing into an outlet which provides sane (though limited)
net return to processors (Luttner, 1978g).
Since there is currently no alternative use for citrus pulp, a more
costly disposal procedure (e.g., incineration or land-filling) would pro-
bably be necessary if citrus pulp were to be disallowed as cattle feed
(Luttner, 1978g). Therefore, in order to protect the cattle feed ingre-
dient business as an outlet for the by-products of citrus processing, the
citrus processors would probably refuse to purchase chlorobenzilate-treated
fruit if a restriction is enacted which prohibits chlorobenzilate residues
in pulp. The residue restriction would result in a de_ facto cancella-
tion of chlorobenzilate, leading to the citrus IPM impacts previously
discussed.
P. Costs to Consumers
1. Citrus Uses
Consumers would be adversely affected due to higher prices end/or
fruit quality considerations only if the loss of chlorobenzilate leads to
significant reductions in yield and/or fruit grade. However, since yield
(65)
-------
and/or quality changes are not inroedlately projected to occur, there would
be little change in the quantity of citrus supplied. Also, the citrus in-
dustry is relatively stable since growers cannot elect alternative land
uses in the short run; therefore, a substantial supply response would not
be expected in response to changes in cost. Because potential yield/
quality effects are not indicated, and given the history of excess pro-
duction in the domestic citrus industry (which leads to a relatively weak
29/
market position for growers) the projected costs would be absorbed by
growers, at least in the short term, with little or no consumer impacts
anticipated.
2. Non-Citrus Uses
The analysis indicates that the potential cancellation of chloro-
benzilate for use on non-citrus crops would have insignificant effects
upon growers, marketers, and consumers of these crops. The reasons are:
1) Only small quantities of chlorobenzilate are used to
control mites on cotton and a wide variety of fruit
and nut crops.
2) Numerous chlorobenzilate alternatives are both regis-
tered and recommended for use on cotton, fruits, nuts,
and other crops.
3) Certain of the alternatives can be used at a lower pesti-
cide cost per acre.
Should the cancellation of chlorobenzilate result in the use of
higher-cost alternatives on non-citrus crops, the total estimated increase
29/ This phenomenon is reflected by citrus cold storage figures, which
relect the large stocks of citrus products carried over from one
year to the next (OSDA, 1977).
(66)
-------
in pesticide cost is $194,000 per year. Of this total, cotton accounts
for $125,000; fruits, nuts, and other crops for approximately $69,000.
If the total non-citrus production cost-increase were ccopletely passed on
to final domestic consumers under the assumption of no reduction in yields,
the consumer impact would be minimal.
(67)
-------
IV. Risk-Benefit Analysis of Alternative Courses of Action
Evaluation of the risk and benefit data suggests seven principal
regulatory options:
A. Continue Registration of All Uses.
B. Cancel All Uses.
C. Continue Registration of Chlorobenzilate Use on Citrus and Amend
th3 Terms and Conditions of Registration; Cancel All Other Uses.
D. Cancel Chlorobenzilate Use on Citrus To Take Effect After Five
Years, and in the Interim Amend the Terms and Conditions of
Registration; Cancel All Other Uses.
E. Continue Registration of Chlorobenzilate Use on Citrus, Amend
the Terms arid Conditions of Registration, Require That Identified
Exposure Data Be Submitted to EPA in 18 Months; Reevaluate the
Use on Citrus After Additional Exposure Data Becomes Available;
Cancel All Other Uses.
F. Continue Registration of Chlorobenzilate Use on Citrus in Florida,
Texas, and California, Amend the Terms and Conditions of Registra-
tion, Require that Identified Exposure Data be Submitted to EPA in
18 Months; Reevaluate the Use on Citrus After Additional Exposure
Data Becomes Available; Cancel Use on Citrus in Arizona and All
Other Uses.
G. Continue Reg.stration of Chlorobenzilate Use on Citrus, Amend
the Terms and Conditions of Registration, Prohibit the Use of
Pulp from Chlorobenzilate-Treated Citrus .is Cattle Teed; Estab-
lish Complementary Tolerances; Cancel All Other Uses.
Tables 18 and 19 summarize the risks and benefits of each option.
The specific risks and benefits pertaining to each option are described
below.
(68)
-------
OPTIUN
none A err mil
COMSUHCI8
T.bl. II
UCULATOIY OPTIONS AMU NAXIHUU NISK INCIDENCE FROM CLOIOUiiZILATE USI
or us
CITRUS CONSUMER
CITHUS PtSUClOe
APPLICATOR
FLOIIUH ClTRUg
PICKKRS
NOM C1TMI8
USE CONSUMERS
MOM-CITKUS MOM-CITniS «
PESTICIDE APPLICATION PICKEIS
A. Continue Re|iit ra-
tion of All Ui«i
1. Unc*l All U«e.
1.6 to *.»
MI nil lion
2.0
C. Cunlinui Keg lit ret ion 2.t to 6.4
of Chlorvlienitlitf ptl •illion
lUei on Cltiui and
III* TCIHI *i .a II
Munllii; ««sy..l.i»i« the Ul*
on Cilru-. AH«i A'MUlonal
Av.iUhle; C.nc.l All
Otber Dm*
l*r
2.0
per Billion
0.1
ftr •illioa
400 to UOO
per Million
4 to ?7S
per Billion
0.1 to 20
per Billion
4 to lit
ptr Billion
Mo Dill
0
No B«tl
Iteduod
Elpoiur*
0.1
pet Billion
0
0
No 0«t«
0
0
No D
-------
(Table 1J> Cent 'o)
c.
Continue K«|iatration 2.6 to *>
of Chloroben.ilete per •illion
Dee on Cicrua in
Florida, Teiae, and
California; ARMIM!
TerMa ami I:OIH! i t i one at
keg-iiic r«t ion, M««|uire
ili II. Indentifieil Eiuoiure
llel* he •unfitted to EPA
in 18 Hontha; Keevalu>ta
tlie Uae on Citrua After
AJdilinnal F.«poaure uii Citrua in Aricoita
•n.l Al I lltlier U.e«
W W
I'xktitinue Megiatrat ion of 2 per 2
CtiloiobanEilate II.« on CU- eilllicn per Hillion
ro«; Aaienil tlie Teraia and Condi-
tion! ot Neiiiatralion; Prohibit
the Uae o» |Milp !•>•«• Chloroben^
xilate-Treateil Citrua A< Cattle
feed; Initiate Action for EPA
to Kateuliali a Toteraete on Chloro-
b«n
-------
T.bl. 19
ICONOM1C IMPACTS IESULT1NC UGH CHLOROBEMZILATE KECULATOIY OPTIONS
Opt Ion
Cammotlti Icgnomic l»|>«ct
II
A. Continue ••glfttttloi at All Iliti
Citrui
Cut'on
Fruit >/Nut•
None
Non*
Nona
C
-------
Cancel Cklorobaniila la Uaa on Citrua to
Taka (ffaet After fi«e Tear, and
in tha IntariB Aaand the Taraa and
Uondltioita for ka| la t rat ion; Cancel All
Othar Uae*
(TAB1£ 19 Cbnf d)
Citrua Ho Inpict Year*
Are* IconoBic
AI
CA
?L
TX
Ub
' 0
400
1,700
200
9.300
1-S
lB)>act i
0
1.100
14.100
100
16.100
n Year Aftr Cancellation (SOOO)
0
l.«00
20.000
:oo
22.00U
0
1.100
24.600
100
17.000
0
2,500
18.500
300
31.300
Continv* lagiatratloa of Chlorobaniilate
Uae on Citrua, Aaand tha Terae and Condi-
tion* for lagiitratlon, Require That Iden-
tified tipuaura Data be aubaitted to EfA
in IS Montha; devaluate tha Uaa on Citrua
After Additional Knuoaura Data lecoaea
Available; Cancel All Othar Uiea
Continua Ragiat rat ion
of Ch1orubans11 ata
Uaa on Citrua in
Florida, Taaaa, and
California; Araand
Tarna and Cor.ditioni of
Hafiat rat ion , Hai|uir«
that I iidant 1 f i«d Cmpoawra
l>al a b« aub»ittad to EPA
in 14 Moulin, la«valua[a
tha (la* on Citrua Aftar
Additional Cipoaura Data
•acuaaa Avaliablaj Caiicrl
Uaa uii Citrua in Ariaona
and All Olliar Uaaa
Cotton.
fruica/Nuta
Citrua
Cotton
Iruita/Muta
Citrua
and thereafter -
94.4 to $ 19 . 1 Billion
for aaended uaa ..
direction —
»m.OOO/Yr
$69.000/Yr
|4.4 to $19.1 Billion
far ••enilcd u• •
d ir«ct ion 3/
PoCcncit.! for ttddl-
tion«» i.p.ct,
Jttpcndcnt on teat
reaulla
JUS.OOO/Yr
JfcV,000/Yr
?4.4 to 19.1 Billion
for a«en«t«*d uaa
direction 3/
Aricona - no econoaiic
iBpact Potential for
addtlonal iaitact*
dependent on teat
reaulta
(72)
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(TAtlLE 19 COnt'd)
C. Continue lit'>t rat Ion of Ch lorobeni i 1 a t *
Uae on Cicrue. Ae^nd the Ter«a and Cor-
dltionl of la|tit rat ion, Ftohlbit th« Ui«
of Pulp froM Chloruhenti1*ta Treated Citrue
aa C»tcl« Feed; Initiate Action tor E»A to
Katiblleh a Tolerance on Ch lorobenai I • te
Nariduu In Citrve Pulp; Cancel All Other Uaea
Cotton
fruita/Muti
Hit rue
M 2*,OOO/Vr
9 (9,000/Tr
Bcoaoaiie Inpact In Year After Cancellation ($000)
0
2,400
28,300
200
30,900
0 0
600 1.600
12,200 10,«00
300 200
13,ODD 22,600
and thereafter -'•-'
I*.* to tit.I
mi 1 I ion for
• •Mitded uee
diraction
0
1.000
36,600
200
38.000
0
3,700
40,000
200
44,000
J/
I/ All future doll«F impact* arc (Ivan in preaant valuei. The citrua can-
cullatlon laipa*-t in year 1 < $ 13 f 000,000) ia of tha aaaie na|aitude aa th<
firat y«ar i«|>a>.c if it ia delayed until the aiitli year ($9,32 2, OO'j I .
However, th« diicauntinc factuv Kaducaa praaaiit value i>f tha aint'i-yaar
Impact ralatlva to the firat-year impact.
]_/ Aaaueiaa no ea«ab 1 1 ehaiant of viable euualituta coupatlbl« -j-ft- 1PH «nj
at coat appraxinate1y equivalent to ch1orob«nziI at«'a.
j[/ Protective clothing coata for applicacora uaa aamaied to be negligible.
(Kan .Mure ill each). Kucloeed cab coata rente fro* $4.230 (cab pur-
rliaiaf t.) SH.aSO (ne« tractur with cab). Total $4.4 li $lreaeura air filtration ayatene.
4_/ Aaauaiaa luaa of ftedetuff Market will cauaa fr<'Wera to caaae uaini
chlcrobeiK i I itu | if not then laiae laipac: ai Option C.
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A. Continue Registration of All Uses
Adopting option A would indicate the Agency's conclusion that the
risks associated with each use are outweighed by the respective benefits
ana therefore, that none of the uses of chlorobenzilate cause unreasonable
adverse effects. This option would return pesticide products which con-
tain chlorobenzilate to the registration process for reregistration.
This option would not reduce the risk of cancer nor the risk of
testicular effects associated with the use of chlorobenzilate. The po-
tential lifetime risk of cancer fron all uses would remain at 2.1 in one
million for the U.S. population; at 2.7 to 6.5 in one million for the
Florida copulation; and at 400 to 1400 in one million for ground appli-
cators of chlorobenzilete (Table 18). The ground applicators' margin of
safety from testicular effects would remain in the range from 43 to 169.
There would be no adverse economic impacts associated with this
option. This option would retain the usefulness of chlorobenzilate as a
cost-effective tool for control of the mite complex, as well as the exist-
ing benefits from its use in citrus integrated pest management programs.
The choice of this option would indicate the Agency's willingness
to tolerate a level of risk greater than the levels of risk estimated for
the other options (Table 18) because there are no adverse economic effects
(Table 19) or loss of other benefits.
B. Cancel All Uses
Adopting option B would indicate the Agency's conclusion that the
risks associated with each use outweigh the respective benefits and thereby
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result in unreasonable adverse effects. This option would eliminate all uses
of chlorobenzilate.
Cancellation would eliminate all the risks associated with the use
of chlorobenzilate (Table 18) but at great cost to citrus growers. These
costs are based on the assumption that no alternative miticides as effective
as chlorobenzilate nor as compatible with citrus integrated pest management
programs would be developed and marketed at competitive oast. In the fifth
year after the cancellation of chlorobenzilate, the citrus industry's addi-
tional pest management control costs would stabilize at $44 million per
year. Florida growers would incur 90% of the increased cost generated by
using chlorobenzilate substitutes (Table 19).
In addition, the switch to alternatives may involve undesired risX
consequences. To obtain the degree of pest control currently obtained in
citrus integrated pest management programs using chlorobenzilate, increased
amounts of these substitute chemicals would be required (Table 9). At the
present time, the safety data on several of these substitutes (carbopheno-
thion, ethion, sulfur, and propargite) is incomplete.
The annual economic impacts of cancelling chlorobenzilate's non-
citrus uses are relatively small, ranging from $£9,000 on fruits and nuts
to $125,000 on cotton.
The choice of this option would indicate the Agency's unwilling-
ness to tolerate the level of risk associated with all uses, based on a
conclusion that the benefits do not outweigh those risks (Tables 18 and
19).
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C. Continue Registration of Chlorobenzilate Use on Citrus and Amend
the Terms and Conditions of Registration; Cancel AIlTfeher Uses"
Option C would indicate the Agency's conclusion that the benefits
arising fron the use of Chlorobenzilate on citrus in Florida, Texas, Cali-
fornia, and Arizona exceed the risks (reduced by amending the terms and
conditions of registration) estimated to exist from the use of chloroben-
zilate on citrus in each of these four States. Option C would indicate,
moreover, that the risks associated with the non-citrus uses of chlorcben-
zilate are not outweighed by these benefits.
1. Economic and Environmental Considerations
The economic and other inpacts of cancellation of Chlorobenzilate
for use on Florida, Texas, Arizona, and California citrus are discussed
in detail in Part III of this document.
In general, it is likely that cancellation of the uses of Chloroben-
zilate on citrus in Florida would result in extensive use of non-selective
mitic-des - principally organcphosphates - and consequent destruction of
existing IPH programs. Per—acre treatment costs would increase sharply -
from $24.62 to between $72 and $103 in the fifth year after cancellation
and thereafter. The aggregate cost impact of the expected use of non-
selective pesticides could range from $40.3 million to $66.6 million annu-
ally in the fifth year after cancellation and thereafter. In addition to
inposing a severe cost inpact, the use of non-selective organcphosphates
would involve a substantial increase in the volume of pesticides used
which could cause untiesired adverse effects, including adverse health im-
pacts. ?enbutatin-oxide, a selective raiticide compatible with IPM pro-
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grans, could be used to sane extent but fenbutatin-oxide would be unlikely
to gain acceptance because of its high cost and inappropriateness in seme
situations.
In Texas, dicofol probably would gain increased usage, since its
cost would be only 33% higher than ohlorobenzilate's and it could be used
in IPM programs. However, recent preliminary NCI data indicate that di-
30/
cofol may pose a more sertous risk of cancer than chlorobenzilate. Fen-
butatin-oxide could substitute for chlorobenzilate in many instances and
would be conpatit.e with IPM programs. Fenbutatin-oxide's per-acre treat-
ment cost increase over chlorobenzilate is lower in Texas than in Florida,
but treatment costs with fenbutatin-oxide would be twice as high as treat-
ment with chlorobenzilate. Moreoever, fenbutatin-oxide may pcse a more
30/
serious risk of reproductive effects than chlorobenzilate. In Texas,
as in Florida, growers may choose non-selective pesticides to replace
chlorobenzilate; the IPM impacts of such a choice would be similar to
those predicted for Florida. As for Florida, a conclusion that the bene-
fits of the citrus uses of chlorobenzilate in Texas exceed the risks would
*
be based upon both economic and health concerns but the health concerns
would weigh more heavily and the economic concerns less heavily than for
Florida.
In Arizona, the economic consequences of cancellation would be
insignificant.
30/ See Appendix C.
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In California, a conclusion that chlorobenzilate's citrus uses should
be continued would reflect a determination that the risks are snail when
weighed against the absence of satisfactory alternatives for the control of
the citrus bud mite and the citrus rust mite.
2. Proposed Restrictions
The data show that the populations at risk with respect to chloro-
benz ilate use are the U.S. population at large, Florida residents, pesticide
applicators, and citrus pickers. Under this option, pesticide applicator
exposure would be reduced by changes to the terms and conditions of regis-
tration. Directions for use would be modified so that citrus growers would
2i/
be allowed to select one of the following application methods:
i) Ground application with applicators using additional
protective clothing and respirators.
ii) Ground application with applicators using suitably-
equipped enclosed cabs.
iii) Aerial application
In Addition, the following registration amendment would be required
for the continued use of chlorobenzilate on citrus:
iv) Classify as a restricted use pesticide, for use by
or under the direct supervision of certified ap-
plicators.
Based on data and experience frcm other pesticides, the Agency has
concluded that the measures described below would reduce exposure to chloro-
31/ See Appendix D for specific label amendments.
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benzilate applicators and therefore would reduce a substantial portion of
the risk from chlorobenzilate use.
Protective clothing and respirators could reduce the ground appli-
cators' exposure and potential risks. The exposure estimates for ground
applicators (Severn, 1978) are based on exposure to arms, hands and face
(15.8% of the total body surface); covering the arms and hands would re-
duce the dermal exposure from between 12-40 ing/day to between 2.4-8.0 rag/
day. Therefore, to reduce the exposure the Agency would require applica-
tors to wear heavy-duty work gloves and full-length, long-sleeved, one-
piece jumpsuits made of fine weave fabric (jersey) (Griffiths, 1978). Both
would have to be laundered after each day of use. Applicators would also
be required to wear a broad-brimmed hat. Further, face-piece respirators
would effectively eliminate exposure by inhalation, estimated at 1 rog/day
without protection. Therefore, the Agency would require applicators to
wear suitable respirators which fit over the mouth and nose and have a
filtering cartridge (NIOSH approved respirators for pesticide spray ap-
plicators referred to in Appendix D).
Protective clothing and respirators would reduce citrus pesticide
ground applicators' estimated lifetime cancer risk (Table 18) by a factor
of five (Severn 1978). There would also be a greater margin of safety
(215 to 845) from testicular effects. These risk reductions would out-
weigh the minimal oast for the protective clothing and the respirators.
Use of suitably-equipped enclosed cabs by applicators would also
reduce ground applicator exposure and potential risks. The Agency would
require that these rarn be completely enclosed and employ systems for
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delivering filtered air to the operator, as described in a recent study
(Taschenberg and Bourke, 1975). In this study, the cab substantially re-
duced (99%) the amounts of pesticide spray which could cone into contact
with the applicator. Applying the results of this study to chlorobenzilate
exposure estimates would reduce exposure from between 13 and 41 rug/day to
between 0.13 and 0.41 ing/day when an enclosed cab is used. This would re-
duce the lifetime cancer risk to ground applicators from between 400 and
1400 to between 4 and 278 in one million. The margin of safety from tes-
ticular effects would be 4300 to 16,900. The costs of this approach can-
not be fully assessed. However, the capital cost of air-conditioned cabs
(which are anticipated to be somewhat less expensive than filtered air
cabs) would run between $4.4 and $19.1 million if all growers selected
this measure, depending upon the extent to which existing equipment could
be retrofitted (Luttner, 1978). While growers have indicated interest in
equipment of this type, it is probable that requiring enclosed cabs for
all ground applicators would drive citrus growers to use other chemicals,
rather than incur the capital cost of new application equipment.
Aerial application of pesticides is favored by seme large growers,
and current information indicates it would continue to be an accepted
method of application where suitable. When chlorobenzilate is applied
aerially, usually by helicopter, there is a minimum exposure to the ap-
plicator, but exposure from drift could potentially increase for people
in the vicinity of citrus groves.
Classification to use only by certified applicators would also re-
sult in reductions in applicator exposure. .The key concept behind classi-
(80)
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ficaticn to use by certified applicators is that certification can gene-
rally upgrade applicator skills and that with more skill and knowledge
applicators are more likely to use pesticides carefully and efficiently.
It would be reasonable to conclude that a general upgrading of the skills
of chlorcbenzilate applicators would, for these reasons, result in re-
duced exposures.
Cancelling the non-citrus uses of chlorobenzilate would have the
impacts discussed in Option B.
Choice of this option would indicate acceptance of the level of
risk to consumers frctn chlorobenzilate citrus use*; and would reduce the
level of ris/c (lowered by amended terns and conditions of registration)
posed to applicators. However, this risk level is based on somewhat un-
certain assumptions due to the lack of definitive data on exposure to
chlorobenzilate. While the Agency would impose additional safeguards with
regard to the level of risk posed to applicators, it has not recommended
protective measures for citrus pickers because it has no data base upon
which to evaluate risk to them.
D. Cancel Chlorobenziiate Use on Citrus to Take Effect After
Five Years and In the Interim Amend the Terms and Conditions
of Registration; Cancel All Other Uses.
Option D would indicate the Agency's unwillingness to accept the
risk levels of Option C indefinitely, but would demonstrate acceptance
of the Option C level cf risk for a five-year period in order to reduce
the initial economic irapact and encourage technological innovation.
This option would reduce by approximately 14-fold the potential
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lifetime cancer risk and risk from tes'cicular effects, since the period of
exposure would be reduced fron a lifetime to five years (Table 18). The
combined effect of the amended use directions ard the limited tine span
would reduce the risk of cancer for citrus pesticide applicators from 400
to 1400 per one million to between 0.3 and 20 per one million (Table 18).
The testicular effects margin of safety for citrus pesticide applicators
would be increased from between 43 and 169 to between 3,010 and 236,000.
This option would allow time to develop and register an alternative
to chlorobenzilate (e.g. Zaroex and Hirsutella) for use in citrus IPM pro-
grams. The five-year phase out would lessen the otherwise substantial im-
pacts fron the loss of chlorobenzilate.
Choice of this option would reflect a conclusion that die risks as-
sociated with the citrus uses are acceptable for the period of time neces-
sary to develop and register an alternative compatible with IPM programs, in
order to avoid the econonic irapacts of immediate cancellation (See Option B).
However, choice of this option also would reflect a conclusion that indefi-
nite, future use of chlorobenzilate involves risks which are unacceptable in
view of the benefits, and that indefinite continued registration of chloro-
benzilate creates unacceptable barriers to the development of alternatives.
This option would require the Agency to deal with two important areas
of uncertainty: the period of time that would be necessary to develop and
regist3r an alternative(s), and the fact that the economic and environmental
impacts of the alternatives which may be developed necessarily cannot be
assessed at this time. Both areas of uncertainty would be addressed by tte
selection of a five-year phase out for chlorobenzilate. Generally speaking,
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3 years sre necessary to carry a pesticide all the way through the develop-
ment and registration process, using the date that a compound is selected
as a candidate for development in early screening tests. Since Zardex and
Hirsutella are already well beyond this stage, a five year-period would seem
adequate to accomplish development and registration of alternatives. More-
over, seler.ion of a five-year phase out period would also reflect an Agency
decision that sufficient time would be available after the registration (or
failure to register) of an altemative(s) to permit applications for renewed
registration of chlorobenzilate to be considered and acted upon.
Finally, it should be noted that selection of this option would re-
flect an Agency decision that incentives are necessary to stimulate de-
velopment and registration of alternatives, and that the creation of in-
centives justifies the uncertainties and burdens associated with the op-
tions. Selection of this option would further reflect a decision that
the probability that an alternative would be developed and registered is
unacceptably low without the creation of incentives by the Agency.
E. Continue Registration of Chlorobenzilate Use on Citrus, Amend
the Terms and Conditions of Registration, Require That Identified
Exposure Data Be Submitted to EPA in 18 jtonths; Reevaluate the
Use on Citrus After Additional Exposure Data Becomes Available;
Cancel All Other Uses.
Option E would reflect an Agency conclusion that the risks of the
non-citrus uses of chlorobenzilate outweigh the benefits and that the
benefits of the citrus uses of chlorobenzilate outweigh vie risks, as re-
duced by modifications to the terms and conditions of registration (see
Option C). Option E would further reflect the Agency's conclusion that
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additional exposure data is necessary, and a determination to reevaluate
the citrus uses of chlorobenzilate after these data are available.
•RiLs option would eliminate all risks associated with chlorobenzi-
late's non-citrus uses. It would require the same amended use directions
as those explained in Option C for the continued use of chlorobenzilate pro-
ducts on citrus. It would also preserve the usefulness of chlorobenzilate
in integrated pest management, at least until the additional data has been
submitted to and evaluated by the Agency.
Option E would allow risks to continue at levels comparable to that
of Option C but would require new data to substitute or refute current risk/
benefit estimates or to indicate the need for a revised evaluation of risks
and benefits. Should new data indicate higher risks or lower benefits than
have been found in the present analysis, the Agency would reassess its regu-
latory decision. If the data confirms the present assessment, this option
would be equivalent to Option C. The isroediate economic inpact of this op-
tion would be ccoparable to that of Option C.
If this oprion is adopted, registrants would be required to submit
data derived from the studies described belcw; specific protocols have to
be submitted by the registrants for approval within six months.
1. Citrus Fractionation Studies
Very little information is available on chlorobenzilate residues in
citrus by-products. Limited data indicates that residues are present in
citrus pulp and suggests the potential for residues in other by-products
such as citrus oil. A fracticoation study is necessary to measure chloro-
benzilate residues in the by-products of citrus processing and, using these
(84)
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measurements, to estimate exposure fron the products which have commercial
utility. Since each residue analysis step (1 per by-product) is estimated
to cost $100 to $200, and fractionation of citrus fruit requires approximately
ten steps, the study would cost an estimated $1000 to $2000 for each citrus
fruit type.
2. Feeding Citrus By-products to Cattle Study
Existing data indicates that chlorobenzilate residues are present
in the citrus pulp used to feed cattle in Florida, and that milk and beef
from cattle that were fed chlorobenzilate-contaminated pulp may contain
chlorobenzilate residues. The proposed feeding study is needed to measure
chlorobenzilate residues in milk and meat from cows that were fed pulp frcra
citrus fruit treated with chlorobenzilate. Data from this study would be
used to estimate exposure to Florida consumers from these dietary sources.
The study would cost approximately $100,000.
3. Citrus Pickers Exposure and Re-entry Studies
The Agency has no data to determine whether chlorobenzilate residues
on fruit surfaces and tree foliage create an exposure source to citrus
pickers. Procedures which determine whether dislcdgable chlorobenzilate
residues adhere to pickers and the degradation rate of chlorobenzilate in
field conditions will permit estimates of the occupational exposure and
risk levels for pickers. These studies would cost between $100 and $200
per sample. Because sixty samples are estimated to be required, the total
study would cost between $6,000 and $12,000.
4. Aerial Application Exposure Study
The Agency lacks data on exposure levels which result from the aerial
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application of chlorobenzilate. This stud' wwould provide relevant data
concerning exposure to the drift which results from aerial application of
pesticides in order to estimate ohlorobenziiate exposure levels and eval-
uate the risk to nearby inhabitants.
The Agency estimates that the number of samples required rnay range
from 500-1000 and at $100-5200 pur sample, the study would cos. between
$50,000-$200,000.
5. Ground Applicator Exposure Study
The current exposure estimates for citrus ground applicators are
based on studies with other pesticide sprays. An exposure study of chloro-
benizilate ground applicators would allow better analysis and consequently
better assessment of their potential risk from spray applications of chloro-
benzilate. The study should cover mixing/ loading and application exposure.
The Agency estimates that 50 samples would be required at a cost of be-
tween $100 and $200 per sample; the entire study would cost $5,000-510,000.
6. Residue Monitoring of Milk from Pulp-Fed Cattle and
Residue Monitoring of By-products of Citrus Process'i.ig
Vhile a preliminary analysis of milk samples from Florida does not
indicate detectable residues of chlcrobenzilate (Kutz, 1978), an earlier
study (Formica et al., 1975) demonstrated chlorobenzilate residues in milk
from cattle that were fed pulp to which chlorobenzilate had been added.
In addition, there are studies by Mattson and Insler (cited in Severn,
1978} which indicate that chlorobenzilate residues could be expected to
occur in beef. Therefore, a need exists to establish methods for detect-
ing chlorobenzilate residues in milk and beef from cattle that have been
fed pulp from chlcrobenzilate-treated citrus fruit.
(86)
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application of chlorobenzilate. This study would provide relevant data
concerning exposure to the drift which results from aerial application of
pesticides in order to estimate chlorcbenzilate exposure levels and eval-
uate the risk to nearby inhabitants.
The Agency estimates that the number of samples required nay range
frcm 500-1000 and at $100-5200 per sample, the study would cost between
$50,000-$200,000.
5. Ground Applicator Exposure Study
The current exposure estimates for citrus ground applicators are
based on studies with other pesticide sprays. An exposure study of chloro-
benizilate ground applicators would allow better analysis and consequently
better assessment of their potential risk frcm spray applications of chloro-
benzilate. The study should cover mixing, loading and application exposure.
The Agency estimates that 50 sanples would be required at a cost of be-
tween $100 and $200 per sample; the entire study would cost $5,000-$10,000.
6. Residue Monitoring of Milk from Pulp-Fed Cattle and
Residue Monitoring of By-products of Citrus Processing
Wiile a preliminary analysis of milk samples from Florida does not
indicate detectable residues of chlorobenzilate (Kutz, 1978), an earlier
study (Formica et al., 1975) demonstrated chlorobenzilate residues in milk
from cattle that were fed pulp to which chlorobenzilate had been added.
In addition, there are studies by Mattson and Insler (ciced in Severn,
1978) which indicate that chlorobenzilate residues could be expected to
occur in beef. Therefore, a need exists to establish methods for detect-
ing chlorobenzilate residues in milk and beef frcm cattle that have been
fed pulp frcm chlorobenzilate-treated citrus fruit.
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Refinement of the analytical detection method is estimated to cost
approximately $55,000. This assumes a 10% overhead cost. The estimated
cost of monitoring the samples would be $100-200 per sample or an esti-
mated $3,000-$6,000 for the entire sample monitoring study.
F. Continue Registration of Chlorobenzilate Use on Citrus in
Florida, Texas, and California, Amend the Terms a->d Con-
ditions of Registration, Require that Identified Exposure
Data be Submitted to EPA in 18 Months; Reevaluate the Use
on Citrus After Additional Exposure Data Becomes Available;
Cancel Use on Citrus in Arizona and All Other Uses!
Option F is the same is Option E, except that Option F would -.ndi-
cate that the Agency recognizes a different risk/benefit argument for
citrus uses between regions. In Arizona, the loss of Chlorobenzilate and
adoption of alternative miticides is projected to have no economic impact.
Cancellation of citrus use in Arizona would yield a marginal reduction
in risk to consumers; however, it would eliminate the risk to Arizona
applicators.
G. Continue Registration of Chlorobenzilate Use on Citrus, Amend
the Terms and Conditions of Registration; Prohibit the Use of
Pulp from Chlorobenzilate-Treated Citrus as Cattle Feed; Estab-
lish Complementary Tolerances; Cancel All Other Uses.
Option G is the same as Option C, except that Option G would in-
dicate that the Agency is unwilling to accept the potential risk posed to
the Florida population through consumption of milk and beef from cattle
fed pulp fron chlorcbenzilate-treatcd citrus. Accordingly, this option
would prohibit the feeding of citrus pulp to cattle and would propose the
establishment of complimentary tolerances under the Federal Food, Drug,
and Cosmetic Act.
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V. Recommended Regulatory Action
OPTION F:
Continue Registration of Chlorobenzilate Use on Citrus in Florida,
Texas, and California, Amend the Terms and Conditions of Registra-
tion. Require that Identified Exposure Data be Submitted to EPA
in 18 Months; Reevaluate the Use on Citrus After Additional Expo-
Data Becones Available; Cancel Use on Citrus in Arizona and All
Other Uses.
A. Introduction
The foregoing review sumnarizes and analyzes information on the
risks and benefits of the uses of Chlorobenzilate and evaluates a series
of regulatory options. Several particularly significant factors stand
out in the analysis.
With Respect to Risks
Several studies provide a reliable basis for concluding
that Chlorobenzilate induces oncogenic effects in mice.
Under the Agency's Interim Cancer Assessment Guidelines,
these laboratory studies provide substantial evidence that
Chlorobenzilate poses a cancer risk to man. In view of
the human exposure which may result from its uses, Chloro-
benzilate poses a cancer risk to man of sufficient magni-
tude to require the Agency to determine whether these
use; offer offsetting social, economic, or environmental
berefits. The key populations at risk with respect to
di'.orobenzilate are the U.S. population at large, Florida
residents, pesticide applicators, and citrus pickers.
Chlorobenzilate causes adverse effects to the testes of
male rats, and may cause adverse effects to the testes of
applicators. Exposure levels of male pesticide applicators
are high enough, in comparison to the "no observable effect"
levels for adverse testicular effects in rats/ to warrant
a conclusion that Chlorobenzilate may pose a risk of ad-
verse effects to humans of sufficient magnitude to require
the Agency to determine whether offsetting social, envi-
ronmental or economic benefits result from the uses of the
pesticide.
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With Respect to Benefits
Chlorobenzilate is used on citrus crops in Florida, Texas,
Arizona, and California to control mites. Most use occurs
in Florida (72.1%). Significant adverse economic effects,
including production losses, would occur if mite pests are
not controlled. Chlorobenzilate is utilized in citrus in-
tegrated pest management because it is selective to mites
and does not kill natural predators and parasites used to
control citrus scale pests. Such integrated pest .oanage-
ment approaches are used extensively in Florida, and to a
lesser extent in the other citrus growing regions. There
are several other selective miticides registered for use
on citrus crops, and a number of non-selectiv> miticides
are also registered for use on these crops.
Cancellation of chlorobenzilate would significantly in-
crease pest control costs in Florida. Non-selective mi-
ticides would be the predcr.-L-.ant replacements for chloro-
benzilate, for economic and other reasons developed in
detail in Section III. This would result in abandoning
BW control of scale, because populations of beneficial
insects would b> reduced, and large volumes of chemical
pesticides would have to te used to control scale insects.
Relatively small amounts of chlorobenzilate are used in
California and only on a few citrus crops in one area.
However, cancellation of chlorobenzilate would have sig-
nificant impacts, because there are no registered alter-
natives that are regarded as suitable chlorobanzilate
replacements.
The loss of chlorobenzilate and the adoption of alterna-
tive miticides is projected to have no net cost to Arizona
citrus growers. Using alternatives may disrupt IPM strate-
gies in Arizona, but the extent of any such disruption has
not been identified, nor the resulting cost quantified.
Registered efficacious alternatives are available for each
of the other uses of chlorobenzilate; in some cases these
alternatives are less expensive and achieve comparable
levels of control.
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B. Comparison of Options
In selecting a regulatory option, the Agency must decide which of
the proposed options achieves the most appropriate balance between risks
and benefits. This decision turns in part on the key factual elements
suranarized above, and in part on the relative merits of each proposed
option.
Option A, which would continue registration of all uses, and Option
B, which would cancel all uses, represent an all-or-nothing approach to
regulation. Under Option A, the Agency would do nothing whatsoever to re-
duce the known risks of chlorobenzilate nor would it otherwise recognize
that the RPAR review confirmed the presunption of oncogenicity. By con-
trast. Option B would succeed in eliminating risk, but only with substan-
tial increased costs for substitute pesticides and possibly serious en-
vironmental and agricultural consequences as the result of disrupting
established IPM programs or using unsatisfactory subsitutes. The latter
result would be particularly unfortunate because of the Agency's avowed
interest in promoting the use of IPM as an alternative to the indis-
criminate use of pesticides.
Further, Options A and B are even less tenable in view of the range
of available moderately restrictive measures described in Options C through
G, which would reduce risk to sane extent without significant benefit im-
pacts and would avoid the harsh consequences of across-the-board cancella-
tion. These considerations indicate that Option A would be reasonable only
if the benefits clearly outweighed the risks, and if risk reductions could
not be achieved without unacceptable benefit consequences. Such ccnsidera-
(90)
-------
tions further indicate that Option B would be reasonaole only if the
risks clearly outweigh the benefits, and significant reductions in risks
cannot be achieved by measures short of cancellation, without unaccep-
table benefit impacts. The facts indicate that neither situation per-
tains, and that litese options are not reasonable regulatory measures in
this case.
The analysis of risks and benefits of the uses of chlorobenzilate
indicates that risks and benefits from citrus uses in Florida, Texas,
and California nay be. close to equilibrium; however, in each situation
significant risk reductions can be achieved, without significant inpacts
on the benefits of the use. With respect to the citrus use in Arizona
and the non-citrus uses on the other hand, the analysis suggests that risks
exceed benefits, primarily because the projected impacts of cancellation
are insignificant while the risks of the uses (particularly to applicators)
are not insignificant. Option C and the options which follow it all rep-
resent possible regulatory responses to this general assessment of the
risks and benefits of chlorobenzilate uses and the balance that should
properly be struck between them.
Option C has three distinct components, each of which is designed
to reduce the risks of cancer and adverse testicular effects associated
with the uses of chlorobenzilate without simultaneously creating the ad-
verse economic, social, or environmental impacts associated with cancel-
lation. In proposing measures to reduce risks by cancelling some uses
and restricting the conditions of use for the registrations which re-
main in effect, this option is distinguishable from Option A which would
(91)
-------
allow the currently projected risks to continue indefinitely. And by
preserving the uses of chlorobenzilate in the major IPM programs, this
option is distinguishable fron Option B which Mould eliminate IPM use
and produce substantial adverse economic and agricultural inpacts.
Options D and G are based on Option C and, like Option C, each
would preserve sane chlorobenzilate uses under restricted use conditions,
thereby reducing riskr and also avoiding substantial economic impacts.
Each also has a special feature designed to reduce risks which would not
be affected by the terms of Option C. The special feature of Option D,
cancellation in five years, would reflect a judgment that lifetime ex-
posure to the risks of chlorobenzilate is unacceptable. To ameliorate
the adverse economic impact of iranediate cancellation as described in
Option B, Option D would propose that chlorobenzilate be phased out over
a period of five years, durirg which time satisfactory alternatives may
be developed. There is, of course, no certainty that these alternatives
would be developed in this time. However, since alternatives are cur-
rently under development, cancellation would not be necessary to bring
this about.
The special features of Option G, measures to reduce exposure to
Florida residents frcm milk and beef, address the risk which the popu-
lation in this State may experience. Since these measures would elimi-
nate the market for citrus pulp, this option would reduce growers net
income and create a costly disposal problem for processors. Tc avoid
these consequences processors may not purchase chlorabenzilate-treated
fruit, and growers may not use chlorobenzilate. In effect, then, elimi-
(92)
-------
nation of this market oxxd constitute de facto cancellation.
Although Option C and, derivatively, Options D and G would achieve
risk reduction without serious adverse economic impacts, these options
would not provide measures to validate or expand the information base and
thereby make the bases for the proposed regulatory action more certain.
Although the Agency believes that it has made a sound and prudent
assessment of the available data, any analysis of this sort requires that
a number of uncertainties be dealt with by assumptions drawn from the
Agency's expedience and expertise. The Agency has strived to use conser-
vative assunptions, consistent with its responsibilities to protect public
health. However, it is possible that the Agency has underestimated po-
tential human exposure, and therefore, underestimated the risks of chloro-
benzilate use. if so, Option C (which would permit continued use of
chlorobenzilate based upon these estimates) would allow a potentially un-
acceptable risk to continue indefinitely.
Option D presents the reverse problem. If the uncertain data base
has resulted in over-estimates of probable human exposure, Option D would
propose more stringent regulatory action than would be required to reduce
actual risk, and would do so on the speculative assunption that more satis-
factory alternatives will be developed.
Options C, D, and E would allow continued use of chlorobenzilate on
all citrus with the provisions discussed above. However, there is no in-
formation in the record to indicate that substantial benefits derive from
the use of chlorobenzilate in Arizona. Acceptance of this option by the
Agency would ignore the apparent imbalance of risks and benefits in Arizona,
particularly with respect to Arizona applicators.
(93)
-------
C. Recommendaticn of Option F
Option F eliminates the risk from the citrus use in Arizona as
well as the risk from all non-citrus uses by cancellation of those uses.
This option also reduces the risk to spray applicators, the population
at greatest risk from citrus uses of chlorobenzilate, by amending the
terns and conditions of registration so that chlorobenzilate may be ap-
plied only by certified applicators and only in accord with label direc-
tions which reduce exposure.
Specifically, this option requires two amendments to the terms
and conditions of chlorobenzilate registrations for citrus use. The
first is a requirement that this pesticide be applied only by certified
pesticide applicators to ensure, to the extent possible, that pesticides
will be applied only ty persons skilled and knowledgeable in handling
pesticides. The second requirement is that chlorobenzilate be applied
only if applicators are protected by protective clothing (hat, gloves,
coverall-type suit), respirators, or by working in an enclosed air-
filtered cab. The clothing cost would be minimal. The cabs would add
a substantial cost to the application process, but if the Agency requires
cabs for other pesticides that may be harmful to applicators, this cost
would not be fully attributable to the chlorobenzilate regulatory program.
The cancellation and use restriction elements in this option are
basad on the conclusion that when used in accordance with the modified
terms and conditions of registration, the risks associated with the major
citrus ores are not unreasonable, in view of the benefits of those uses
(94)
-------
and the related probable adverse economic impacts of cancellation. In
addition, this option also reduces risks appreciably without unacceptable
benefit consequences.
Since the continuation of citrus registrations without any other
restrictions on use does not reduce the risks to consumers, a decision
to continue these uses reflects a determination that these uses do not
cause unreasonable adverse effects with respect to this group.
Option F imposes new costs to replace chlorobenzilate with al-
ternatives for non-citrus uses, and other costs in connection with new
protection for spray applicators and testing to develop additional data
for exposure estimates, but avoids substantial adverse economic effects.
Specifically, the cost of cancelling non-citrus uses is minimal ccnpared
to the cost of cancelling citrus uses. Further, since cancelling non-
citrus uses does not affect IPM programs as would cancelling citrus uses,
this option avoids disruption of these programs.
Finally, Option F is preferable to the other proposed options be-
cause it provides a regulatory mechanism to clarify and enlarge the data
base for the exposure estimates which underlie the risk assessments and
risk/benefit analyses. 1t> accomplish this objective, Option F requires
chlorobenzilate registrants to develop additional data to confirm or
evaluate the Agency's chlorobenzilate risk assessments and the related
regulatory decisions.
(95)
-------
1. Albert, Roy E. (CM), 1978. EPA memo of June 8, 1978 to J.B. Boyd
(SPRD). Comments on the chlorobenzilate risk assessment.
2. Albert, Roy E. (GAG), 1978a. EPA memo of June 23, 1978 to J.B. Boyd
(SPRD). Chlorobenzilate risk assessment issues.
3. Albert, Hoy E. (CAS), 1978b. Carcinogen Assessment Group's Surmary
and Conclusions for Assessment of Carcinogenic risk of Chlorobenzi-
late. Unpublished EPA report dated June 16, 1978.
4. Allen, Jon C., 1978 "The Effect of Citrus Rust Mite Damage on Citrus
Fruit Drop", Unpublished report of the University of Florida, IPAS,
Agricultural Research and Education Center.
5. Anderson, Elizabeth (CAG), EPA memo of May 29, 1977, to J.B. Boyd
(SPRD). CAG assessment of rebuttal points on chlorcbenzilate.
6. Barton, Anne (OTS), EPA memo of December 7, 1977, to J.B. Boyd (SPRD).
Chlorobenzilate: overall false positive rate.
7. Barton, Anne (OTS), 1977a. EPA memo of February 15, 1977 to J.B. Boyd
(SPRD). Statistical analysis of td chlorobenzilate study.
8. Boyd, Hudson (CED), 1978. Environmental Fate Prof ile: Chlorobenzilate.
Unpublished report.
9. Boyd, J.B. (SPRD). EPA memo of December 6, 1977 to Edwin L. Johnson
(DAA for Pesticide Programs). Chlorobenzilate RPAR Rebuttal Decision.
10. Boyd, J.B. (SPRD). EPA roeno of April 1, 1977 to Clayton Bushong (CED).
Determination of ecological risks associated with the use of chloroben-
zilate alternatives.
11. Boyd, J.B. (SPRD). EPA memo of April 1, 1977 to Lamar Dale (CED).
Determination of health risks associated with the use of chloroben-
zilate alternatives.
12. Boyd, J.B. (SPRD). EPA memo of March 6, 1978 to SPRD Record. Rebut-
tals and contents on the chlorobenzilate RPAR.
13. Brogdan, James E., 1976. Extension entomologist. University of Florida,
Gainesville, Florida, personal communication of August 6, 1976 to
Mark Luttner (cited in Preliminary Benefit Analysis of Chlorobenzilate).
14. Brogdan, Janes E. and Fred P. Lawrence, 1974. Insects and Mites of
Florida Citrus, University of Florida, Institute of Food and Agricul-
tural Sciences, Gainesville, Florida, (cited in Preliminary Benefit
Analysis of Chlorobenzilate).
-------
15, Brooke, Oonale L., 1573. Citrus production costs and returns in
Florida season 1971-1972 with comparisons. Cooperation Extension
Service, Institute of Food and Agricultural Sciences. University
of Florida.
16. Brooks, R.F., 1977. Integrated Control of Florida Citrus Pests,
the Citrus Industry.
17. Brooks, R.F. and J.D. Whitney, 19 . Citrus snow scale control in
Florida. Florida Agricultural Experiment Stations Journal, Series
Mo. 4890.
18. Bullock, R.C., 1977. Aerial Application to Florida Citrus (Unpolished
Report)*
19. Burnam, W.L.. EPA memo of May 4, 1978 to J.B. Boyd (SPED). Chloro-
benzilate Alternatives Review.
20. Burnam, W.L. EPA nemo of June 20, 1978 to J.B. Bcyd (SPED). Vendex
Review.
21. Bushong, Clayton (CED). EPA memo of August 8, 1977 to J.B. Boyd (SPRD).
Chlorobenzilate risk anlaysis, Fish and Wildlife.
22. Codce, J., G.C. Lyons, and A. Amader, 1978. Texas Citrus Pest
Management Proposal. Texas Agricultural Extension Service. The
Texas A & M University System.
23. California Dept. of Agriculture, 1972. Pesticide Use Report 1971,
Sacramento, California.
24. California Department of Food and Agriculture, 1974 Pesticide Use
Report 1973, Sacramento, California, (cited in Preliminary Benefit
Analysis.
25. Dale, Lamar (CED). EPA mano of May 4, 1978 to J. B. Boyd (SPRD).
Limitation of the Chlorobenzilate alternatives review.
26. Dean, H.A., 1975. "Complete biological control of Lepidosaphes beckii
on Texas citrus with Aphytis Lepidosaphes." Environ. Entrool. 4:110-114.
27. Dean, H.A., 1955. "Factors affecting biological control of scale in-
sects on Texas citrus." J. Econ. Entnol. 48:444-447.
28. Dean, H.A. and J.C. Bailey, 1964. "Certain post blccm treatments
for control of Texas citrus mites and theic effect on chaff scale
parasites." J. Rio Grande Valley Hort. Soc. 18:29-32.
29. Dean, H.A., W.G. Hart, and S.J. Ingle, 1977. "Pest management
considerations of the effects of pesticides on Texas citrus pests
and certain parasites." J. Rio Grande Valley Hort. Soc. 31:37-44.
-------
30. Doane Agricultural Service Inc., 1976. "Pesticide Use Data on Se-
lected Specialty Crops," Current Pesticide Use and User Profiles for
Selected Pesticide Intensive Crops; Report No. 4, EPA Contract 68-
01-1928, St. Louis, Missouri.
31. Edwards, Gordon S. More of August 2, 1977 to Elizabeth Anderson (CftG).
Comments on criticisms of the Innes study raised by pesticide regis-
trants and within EPA.
32. Federal Register, May 26, 1976. Notice of presumption against regis-
tration and continued registraion of pesticide products containing
chlorobenzilate. 41(103):21517-21519.
33. Federal Register, June 11, 1976. Notice of presunption against regis-
tration and continued registraion of pesticide products containing
chlorobenzilate. 41(114):23753.
34. Federal Register, July 14, 1976. Hot ice of presumption against regis-
tration and continued registraion of pesticide products containing
chlorobenzilate. 41(136):29015.
35. Federal Register, July 14, 1976. Notice of extension of period for
submission of rebuttal evidence and comnents with regard to presunp-
tion against registration and continued registration of pesticide
products containing chlorobenzilate. 41(136):29015.
36. Federal Register, May 25, 1976. Notice on "Interim Procedures and
Guidelines for Health Risk and Economic Inpact Assessments of Sus-
pected Carcinogens." 41(102):21402-21405.
37. Feldman, R. J. and H. I. Maibach, 1974. "Percutaneous Penetration
of Some Pesticides and Herbicides in Man*. Tax. Appl. Pharm.
28:126-132.
38. FeUcner, I.C., 1978. Commentary on cancer risk from exposure to
chlorobenzilate. Unpublished EPA report, dated April 23, 1978.
39. Florida Cooperative Extension Service, 1977. Florida Citrus Spray
and Oust Schedule, 1977; Circular 393-C. University of Florida,
Gainesville.
40. Food and Drug Administration (FDA), 1971. Food and Drug Adminis-
tration Advisory Ccnrcittee on protocols for safety evaluation;
Panel on carcinogenesis report on cancer testing in the safety
evaluation of food additives and pesticides. Toxicol. Appl.
Pharmacol. 20:419-438.
41. Forjnica, G., W. Blass, and D. Eberle, 1975. "Gas chronatographic
residue determination and residues of chlorobenzilate and two major
metabolites in plant materials and milk." Meded. Fac. Landbouwwet.,
Rijks Univ. Gent. 40(2, Pt.2): 1135-1148.
-------
42 French, V., P.J. Rathwell and Reed J. Reeve, 1978. Management of
Texas citrus. Citrograph. 63:77-79.
43. Freudenthal, R.I. and P. Leber, 1977. Evaluation of chlorobenzi-
late toxicology data to determine its potential health hazards to
nan or domestic animals. Battelle Columbus Laboratories, Columbus,
Ohio. (Unpublished).
44. Frith, Charles, 1976. National Center for Toxicological Research.
Analysis of Innes Slides and Animal Diagnosis. (Unpublished).
45. Golberg, L., ed., 1974. Carcinogenesis testing of chemicals. CRC
Press, Cleveland, Ohio.
46. Griffith, Jade (HEMB). EPA memo of June 20, 1978 to J.B. Boyd (SPRD).
Permeability of protective clothing.
47. Gustafson, C.D. and Robert C. Rock, 1977. Lemon Production Costs.
Cooperative Extension Service, University of California, San Diego.
48. Hufiaker, G., 1978. (Editor). Accomplishments Torward Improving
Integrated Pest Management for Citrus. Principles, Strategies,
and Tactics of Pest Population Regulation and Control in Major
Crop Ecosystems. In press, Wiley and Sons.
49. Hassan, T.K. and C.O. Knowles, 1969. "Behavior of Three (T -labeled
Benzilate Acaricides When Applied Topically to Soybean Leaves."
J. Boon. Entonal. 62(3):618-619.
50. Horn, H.J., R.B. Bruce, and O.E. Paynter, 1955. Toxicology of chloro-
benzilate. J. Agric. Food Chem. 3(9):752-756.
51. Innes, J.R.M., B.M. Ulland, M.G. Valeric, L. Petrucelli, L. Fishbein,
E.R. Hart, &.J. Pallotta, R.R. Bates, H.L. Falk, J.J. Gart, M. Klein,
I. Mitchell and J. Peters, 1969. Bioassay of pesticides and indus-
trial chemicals for tumorigenicity in mice: a preliminary note. J.
Nat'l. Cancer Inst. 42:1101-1114.
52. Jeppson, Lee R. (Entomologist), 1976. University of California,
Riverside, California, personal ocmrounication of September 12, 1976
to Mark Luttner. (cited in Preliminary Benefit Analysis).
53. Knowles, C.O. and S. Ahmad, 1971. "Comparative metabolism of chloro-
benzilate, chloropropylate and brcmo-propylate. Can. J. Physiol.
Phannaool. 49(6):590-597.
54. Luttner, Mark A., 1978a. EPA memo of April 27, 1978 to J. B. Boyd (SPRD).
Estimate of the maxim an economic value lost rs a result of uncon-
trolled mite infestations in citrus.
-------
55. Luttner, Mark A., 1978b. EPA memo of June 13, 1978 to J.B. Boyd (SPRD).
Vendex as a replacement for chlorobenzilate.
56. Luttner, Hark A., 1978c. EPA msno of June 13, 1978 to J.B.Boyd (SPRD).
Vendex.
57. Luttner, Mark A., 1978d. EPA memo of March 21, 1978 to J.B. Boyd (SPRD).
Chlorobenzilate exposure analysis.
58. Luttnar, Mark A., 1978e. EPA memo of April 14, 1978 to J.B. Boyd (SPED).
Chlorobenzilate: estimated cost of equipment modification requirement.
59. Luttner, Mark A., 1978f. EPA memo of March 28, 1978 to J.B. Boyd (SPRD).
Considerations re: restriction of chlorobenzilate use to aerial
applications only.
60. Luttner, Mark A., 1978g. SPA mono of May 2, 1978 to J.B. Boyd (SPRD).
Chlorobenzilate (Impact of prohibiting use of citrus pulp as cattle
£e«d).
61. Luttner, Mark A., 1977a. Preliminary Benefit Analysis of Chloroben-
zilate. Unpublished EPA report.
62. Luttner, Mark A., 1977b. Supplement to the Preliminary Benefit Analysis
of Chlorobenzilate. Unpublished EPA report.
63. Maxey, Robert. Pesticides Monitoring Laboratory Memo of June 6, 1978
to Han Tai. Chlorobenzilate.
64. McWhorter, Mike (CED), 1978a. EPA mare of April 5, 1978 to J. B. Boyd
(SPRD). Utilization of Dimilin and Hirstuella fungus for control of the
citrus mite complex.
65. McWhorter, Mike (CED), 1978b. EPA mono of April 14, 1978, to J. B. Boyd
(SPUD). Efficacy of Zardez.
66. Mishra, Lakshni C. (CED). EPA memo of February 3, 1977 to J.B. Boyd
(SPBD). Evaluation of the documents submitted by registrants in re-
buttal of chlorobenzilate FPAR.
67. Mishra, L.C., and P. Hebborn, 1971. Ultraoentrifugation of mouse
plasma containing Rausc^r virus. Life Sci. 10 (Part II): 1375-1380.
68. Miyazaki, S., G.M. Boush, and P. Matsumura, 1970. "Microbial Degra-
dation of Chlorobenzilate (Ethyl 4,4'-dichlorobenzylate) and chloro-
propylate (Isopropyl 4,4'-dicnlorobenzylate). J. Agric. Food Chen.
69. Murphy, R., R. Kahrs, and A. M. Mattson, 1966. Dnpublished Report,
Geigy Cwnical Corporation.
100-
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70. National Cancer Institute (NCI), 1977. Final individual an:onal pa-
thology table for chlorobenzilate. U.S. Oept. of Health, Elation,
and Welfare, Bethesda, Maryland. (Unpublished).
71. Page, N.P., 1977. Chronic Toxieity .^nd Carcinogenicity Guidelines.
J. Envtl. ?dth. and Tex.. 1:161-182'.
72. Parrish, Dale W. (HEMB-TSD). Meno of April 6, j.978 to Director, Texas
Epidemiologic Studies Program. Assessment of carcinogenesis data
(chlorobenzilate).
73. Pertel, Ruth (SPRD). Memo dated January 27, 1978 to J.B. Boyd (SPRD)
and Pat Miller (SPRD). Mut^enicity rebuttal on chlorobenzilate:
oonments.
74. Pertel, Ruth (SPRD). EPA memo of January 31, 1977 to J.B. Boyd (SPRD).
Mutagenicity rebuttal on chlorobenzilate: carments.
75. Potrepka, Robert F. (CED), 1978a. EPA meno of June 5, 1978 to J.B. Boyd
(SPRD). Testicular atrophy in rats from chlorobenzilate.
76. Potrepka, Rocert F. (CED), 1978b. EPA memo of June 9, 1978 to J.B. Boyd
(SPRD). Testicular atrophy in rats from chlorobenzilate, addendum to
June 5, 1978 memo.
77. Reed, Donald (KD), 1978a. EPA memo of March 17, 1978 to J.B. Boyd (SPRD).
Chlorobenzilate residues in milk and meat.
78. Reed, Donald (RD), 1978b. EPA memo of May 3, 19"8 to J.B. Boyd (SPRD).
Chlorobenzilate residues in milk.
79. Reed, Donald (RD), 1978c. EPA memo of June 2, 1978 to J. B. Boyd (SPRD).
EPA Chlorobenzilate residue analysis of citrus pulp.
80 Reed, Donald (RD), 1978d. EPA memo of May 16, 1978 to J.B. Boyd (SPRD).
Chlorobenzilate residues in citrus pulp; re: discussion of 5/19/78.
81. Rossi, Lois (SPRD). EPA memo c: April 4, 1978 to J. B. Boyd (SPRD).
Observed deaths among workers in Chlorobenzilate area of Ciba-Geigy
Mclntosh plant.
82. Savage, E.P., and R.O. Hayes, 1977. Chlorobenzilate. Colorado State
University, Fort Collins, Colorado. (Unpublised).
83. Severn, David J., 1978. Exposure Analysis for Chlorobenzilate. Un-
published EPA report dated March 14, 1978. CONFIDENTIAL.
84. Sontag, J.M., N.P. Page, and U. Saffiotti, 1976. Guidelines for
carcinogen bioassay in small rodents. National Cancer Institute,
Bethesda, Maryland.
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85. Sutton, Harvey J. 1977. Economics of Helicopter Application for Pest
Control at Waverley Growers Cooperative (Unpublished Report).
86 Taschenberg, E.F. and John B. Bourke, 1975. "An Air Filter-Pressuriza-
tion Unit to Protect the Tractor Operator Applying Pesticides,* BuU.
of Environmental Contamination and Toxicology 13(3):263-268.
87. Technical Services Division (TSD). "Chlorcbenzilate Analysis - citrus
pulp and feed." Unpublished EPA paper, dated May 22, 1978.
88. Three Month Feeding Study of Chlorobenzilate, 1965. Bonn, Germany.
Submitted to EPA on February 1, 1965 in support of Food Additive
Petition No.6Hl980.
89. U.S. Dept. of Agriculture (USDA), 1970. PR Notice 70-8. Loose-
leaf pub.
90. USDA Cooperative State Research Service, USDA/State Chlorobenzilate
Assessment Team. An economic and biotic evaluation of Chlorobenzilate
and its alternatives for rust mite control on citrus in Florida; Re-
camended Chlorobenzilate treatments and evaluation of alternative
treatments on citrus in California; the state of Chlorcbenzilate use
in Texas citrus 1977. 1977, Washington, D.C.
91. USDA, 1977b. Fruit Situation Economic Research Service, U.S. Dept.
of Agriculture. TFS-205.
92. USDA Economic Research Service, 1974. Farmers use of pesticides
in 1971.... Quantities. Washington, D.C.
93. U.S. Dept. of Health, Education, and Welfare (HEW), 1969. Report
of the Secretary's Commission on Pesticides and Their Relationship
to Environmental Health. Washington, D.C.
94. Wilson, 1973. Environment and Birth Defects. Academic Press, New
York.
95. Hblfe, H.R., H.F. Durham, and J.F. Armstrong, 1967. "Exposure of
Markers to Pesticides." Arch. Environ. Health. 14:622-633. (Cited
in Severn, 1978).
96. Wbodard Research Corporation, 1966. Chlorobenzilate safety eval-
uation by dietary feeding to rats for 104 weeks: final report. Geigy
Chemical Corporation, Yorkers, New York. (Unpublished). CONFIDENTIAL.
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REBUTTAL SUBMISSIONS
1. Alikonis, Robert J., June 25, 1976; Crystal Manufacturing Corpora-
tion; [19:30000/3].
2. Alikonis, Robert J., August 27, 1976; Crystal Manufacturing Corpora-
tion; [19:30000/3],
3. Alikonis, Robert J., August 24, 1976; Crystal Manufacturing Corpora-
tion; [19:30000/3],
4. Alikonis, Robert J., June 25, 1976; Tower Chemical Co.; [11:30000/3].
5. Alikonis, Robert J., August 25, 1976; Tower Chemical Co. [17:30000/3].
6. Alikonis, Robert J., August 27, 1976; Tower Chemical Co.; [23:30000/3A],
7. Alikonis, Robert J., Sept. 9, 1976; Tower Chemical Co.; [33:30000/3].
8. Alikonis, Robert J., June 25, 1976; Trans. Chemical Ind. Inc.; [10:
30000/3].
9. Alikonis, Robert J., June 25, 1976; Trans. Chemical Ind. Inc.; [18:
30000/3].
10. Alikonis, Robert J., August 27, 1976; Trans. Chemical Ind. Inc.; [25:
30000/3C].
11. Altraan, Melvin D., June 25, 2976; Shanna; [15:30000/3].
12. Baldi, A., August 11, 1976,; Aceto Agricultural Chemicals Corp.; [34:
30000/3].
13. Baldi, A., August 26, 1976; Aceto Agricultural chemicals Corp.; [28:
30000/3].
14. Balser, Richard L., Andrew P. Jovanovich, August 27, 1976; Agrico
Chemical Co. and Western United Resources, Inc.; [20:30000/38],
15. Davis, Kent J., DVM, June 7, 1976; [2:30000/3].
16. Goldberg, Melvin, June 10, 1976; Solchem Inc.; [4:30000/3].
17. Goldberg, Melvin, August 26, 1976; Solchem inc.; [29:30000/3],
18. Griffiths, J.T., June 22, 1976; Florida Citrus Mutual; [8:30000/3],
19. Hall, Graydon B. by Ross A. Pinbauch, June 2'-, 1976; County of Santa
Barbara, CA, Office of Agricultural Ccranissi er; [13:30000/3].
103-
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20. Hinkle, Maureen K., August 27, 1976; Environmental Defense Fund;
[21:30000/31.
21. Hunkapiller, Paul, June 25, 1976; Helena Chemical Co.; [9:30000/3].
22. Hunkapiller, Paul, August 27, 1976; Helena Chemical Co.; [26:30000/31.
23. Jeppson, L.R., June 1, 1977; University of California, Riverside
Dept. of Entomology; [35:30000/3].
24. Jovanovich, Andrew P., May 17, 1976; Agrico Chemical Co.; [1:30000/3].
25. Jovanovich, Andrew P., August 30, 1976; Agrico Chemical Co.; [31:30000
/3J.
.26. Jovanovich, Andrew P., October 25, 1976; Western United Resources Inc.;
[20A: 30000/3].
27. Kerdrick, Janes B. Dr., L.T. Wallace, August 24, 1976; State of Califor-
nia, Dept. of Food & Agriculture; [27:30000/31.
28. Lichty, Ralph W., June 15, 1976; Industry Committee on Citrus Additives
& Pesticides, Inc.; [5:30000/3],
29. Lichty,. Ralph W., Oct. 5, 1976; Industry Committee on Citrus Additives
& Pesticides, Inc.; [5A:30000/3].
30. Little, Kenneth K., June 23, 1976; County of San Diego; [14:30000/3].
31. McCog, Clayton W., Sept. 24, 1976; University of Florida, Institute
of Food b Agricultural Sciences; [30:30000/3].
32. McKown, Bobby F., June 18, 1976; Florida Agricultural Research Insti-
tute; [7:30000/3].
33. Murphy, R.T., June 7, 1976; Ciba-Geigy; [3:30000/3].
34. Murphy, R.T., Sept. 7, 1976; Ciba-Geigy; [32:30000/3],
35. Murphy, R.T., Nov. 4, 1976; Ciba-Geigy; [22A.-30000/3B].
36. Vice, Bob L., June 17, 1976; San Diego County Farm Bureau; (6:30000/3).
37. Weidenfeld, Edward L., June 28, 1976; Attorney foe Agriro Co.; [16:
30000/3].
104-
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APPEMJDC A
SUMMARY OF OTHER CANCER STUDIES
Preceding page Wank
106
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HonyHazelton Study, 1955*
Dose
(PP»)
0
50
500
Nur.ter
Sex
M
F
M
M
F
Initial
20
20
20
20
20
Survived
16
12
13
14
14
Ccnplete
Necropsy
4
10
5
6
6
Rats with
Tunors
2
1
2
2
5
* Horn, H.J., et al., J. flgri^. Food Chan., 3s752-756, 1955.
-------
Vtoodard Research Corporation
19S6 TVo-year Rat Study
Dose Number of Animals Animals With
(ppm) Sex Initial Survived NecropsieJ Liver Sarcomas
0 H 30 8 5 1
F 30 1.1 5
40 M 30 5 5
f 30 14 5
125 M 30 10 6 4
F 30 14 5
400 M 30 10 5
F 30 15 5
5
/\
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SUMAKY* OF RECENTLY COMPLETED NCI BIOASSAY ON FEMME OSBORNE MQCBL RATS
Dose (ppm)
0
1175
2350
Site
Mamnary Gland
Pituitary
Thyriod
Uterus Nos
Subcut Tissue/Flank
Maimary Gland
Pituitary
Adrenal
Pancreatic Islets
•Hiyriod
Manraary Gland
Pituitary
Adrenal
Uterus Nos
Thyroid
Tumors
Fibcoadencra Nos
Chranophobe Adenoma
C-oell Adenoma
Endometrial Stromal Polyp
Hemang ioearcona
Pibroadenona Nos
Chranophobe Adenana
Cortical Adenoma
Islet-cell Adenoma
Follicular-cell Adenona
Fibroadenona Nos
Chronophobe Adenana
Cortical Adenoma
Endcnetrial Stromal Polyp
Follicular-cell Carcinoma
Mnber of
Incidence Animals
15 /50
14
5
4
2
14 /4U
11
2
2
2
16 /48
U
5
4
3
* Provided by NCI, 1977
(iii)
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SUMMARY* OP RECENTLY COMPLETED NCI BIQASSAY ON MAI£ 06BORNB MENDEL RATS
Dose (ppm)
Site
Tumors
Incidence
Hunter of
Animals
Thyroid
Spleen Nos
Pituitary
Thyroid
Urinary Bladder Nos
Follicular-cell carcinoma 4
Hemangiosarcuma 4
Chranophobe Adenoma 4
Follicular-cell Adenoma 3
Papillona Nos 3
/49
1600
Pituitary
Adrenal
Multiple Organ Nos
Thyroid
Subcut Tissue/Back
Chranophobe Adenoma 7
Cortical Adenoma 6
Malig.Lynphoma Histiocyti 2
Follicular-cell Adenoma 2
Bemangiosarooma 2
/50
3200
Pituitary
Thyroid
Adrenal
Subcut Tissue/Axilla
Thyroid
Chranophobe Adenoma 4
Follicular-cell Adenoma 4
Cortical Adenoma 3
Fibruna Nos 2
Follicular-cell Carcinoma 2
/50
* Provided by NCI, 1977
s
/I
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APPENDIX B
OTHER TOXICrrc DMA
-------
BODENT SUBACOTE TCKICm
Bats
44 weeks at 40 ppm
44 weeks at 800 ppm
99-day at 2,500 ppm
500 ppm
100 ppm
20 ppm
histologic damage to
adrenals and pancrease
retanV'd growth;
incres.^d htsncpoietic
activity
atrcphic testes;
no effect
Sensitivity -
90-day rat feeding study no effect
of 2,500 dichlorobnezilate
Miscellaneous
r'bbit: eye irritation - severe primary skin irritation -
slight to moderate
hunanr.: repeated skin patch test - no priroary irritation or
sensitizati'jn
Neurotoxicity -
Not tested
-------
MCJIftSENIC lESTS
Negative in these systems:
E. ooli
S. typhimurium
Host mediated with S. typhimurium
Bacillus subtil is
Preceding page blank
114
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FISH ACUTE roxicrrc
Rainbow Trout
Sheephead Minnow
Bobwhite Quail
Mallard Dude
48-hour DC
50
48-hour 1C
50
AVIAN ACUTE TOXICITY
7-day
50
5-day DC
50
RODENT ACOTE
Rats
Mice
Rat
Rabbit
Rabbit
Oral 1C
50
Oral IX)
50
Dermal ID
50
Dermal 1C
50
Inhalation 1C
0.71 mgA
1.0 iog/1
3,375 ppn
> 8,000 ppm
50
702 ng/feg
729 mg/kg
> 4 g/hg/clay
> 10.2 g/kg
> 21? < rog/1 air
-------
CHRONIC TOXICm
Rats 2 years at 50 ppn Slight decreased size of
testes; slight growth effect
at 500 ppn Decreased size of testes;
retarded growth
Rats 52 weeks at 40 ppn No effect
at 125 ppn Testicular asymetry
at 400 ppn Testicular asymetry: markedly
reduced Henoglobin
Rats 2 years at 1,600 ppn Testicular atrophy
3,200 ppn Testicular atrophy
Dogs 2 years; 1 to 14 weeks at 5,000 ppn Moderate to severe anemia
within 14 weeks
20 to 104 weeks at 3,000 ppn Organ weight changes;
Effects on liver and spleen;
Hematcpoiesis
500 ppn to effect level
K
H
05
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APPENDIX C
RISK CONSIDERATIONS REIATIN3 TO PESTICIDE
SUBSTITUTES FOR CHLOFOBENZILA.TE
-------
APPENDIX C
RISK CONSIDERATIONS BELKTIUS TO PESTICIDE
SUBSTITUTES FOR QgflROBENZILME
I. FEMBUTftTIN-OXIDE
Preliminary inspection of Registration Division file data indi-
cates that toxic effects have been reported for test animals exposed to
fenbutatin-oxide in several different studies (Burnara, 1978). Decreased
liver, brain, spleen, and kidney weights and decreased body weight gain
was reported for animals ingesting 100, 300 and SCO ppm fenbutatin-oxide
during the first three months of a two-year chronic feeding study, and for
animals ingesting 500 and 100C ppm during a 28-day subacute study (Shell,
Proprietary). Serum alkaline phosphatase was elevated at 300 and 600 ppm,
indicating tissue injury at these doses. The no-effect level is 100 ppm
for the 3-month exposure and 250 ppm for the subacute exposure (Shell,
Proprietary). These changes are indicators of general toxicity.
In the chronic study the test is weights and the testis-to-body-
weight ratios were increased at 300 ppm and 600 ppn fenbutatin-oxide, but
these changes were not accompanied by hypertrophy or other fenbutatin-
oxide related changes. Later in the two-year study, animal growth rates
were normal and no fenbutatin-oxide related tumors or lesions were reported.
Adverse reproductive effects were reported in a three-generation
reproduction study in rats, with two litters in each generation. The
viability index was seriously reduced in the first litter of the first
generation at 300 ppm and moderately reduced in both third generation 1it-
118-
-------
ters at this dose level. At 300 ppm, the parents and pups were smaller
in size, were reported to be somewhat hyperactive and irritable at tines,
and the lactation index was reduced in the second litter. Weaning body
weights were reduced in five of the six litters produced during the study.
At 100 and 300 ppm, there was a statistically significant decrease (p •
0.05) in the testis to body weight ratio, but at 50 ppn the test and con-
trol data were ccoparable. The no-effect level for all parameters includ-
ing testis weight was 50 ppm (Shell, Proprietary, 1974).
Because fenbutatin-oxide and chlcrobenzilate are applied in the
sane manner, the chlorobenzilate exposure estimates were applied to make
the preliminary fenbutatin-oxide risk assessments. Assuming that spray
applicators may experience dermal exposure of 0.57 rag/kg and based on a
no-effect level of 100 ppm, the margin of safety for subacute exposure
I/
to an applicator would be approximately 8.7.
I/ The absorption factor for fenbutatin-oxide is unknown and probably
less than 10%. If 10% is used, the exposure would be 0.57 mg/kg.
Based on a no-effect level of 100 ppm, the margin of safety for
subacute exposure to an applicator would be: 100 ppn » 5 mg/kg,
then 5 mg/kg divided by 0.57 mgAg * approximately 8.7.
The margin of safety of 8.7 should be put in perspective. Since expo-
sure is estimated at 0.57 mg/kg/day tines 100 * 57 mg/kg, and 1 mg/kg
- 20 ppra in the rat's diet. Total dietary exposure is (57 x 20) 1140
ppm. Very few pesticides can be fed at levels of 1140 ppm and those
having a no-effect level at 1140 are very, very few in number.
The only conclusion is that any pesticide applied in a manner similar
to chlorobenzilate would have a margin of safety or safety factor of
considerably less than 100 (Burnham, 1978).
tii)
-------
17. DIOOPOL
In comparing dicofol with chlorobenzilate ths following facts are
pertinent: a) both compounds induce bepatocellular carcinomas in male
mice; b) chlorobenzilate induces the same kind of lesion in female mice
but at a lower rate, and dicofol has no carcinogenic effect on female
mice; c) neither compound induces a significant tumorigenic response in
maleor female rats; and d) the corapcunds have similar chemical structure,
implying that their mechanism of tumor induction may be tl » same. In
view of these facts, it is legitimate to compare the potency of the cam-
pounds. This is done by taking the ratio of the one-hit slope parameters
from the NCI experiments. The results are B(dicofol)/B (chlorobenzilate)
« 2.40 x 10~3/2.02 x NT4 - 11.9. Under similar test conditions, di-
oofol is about 12 times more potent than chlorobenzilate (Albert, 1978b).
III. NDM-SEI£CTIVE SUBSTl'lUIES
A. Wildlife
Ethion, sulfur, propargite, and carbophenothicn do not appear to
present significant acute toxicity risks to wildlife from use on citrus
(Boshong, 1977).
B. Aquatic Organisms
Acreages involved in citrus uses of chlorobenzilate are large
enough to be contiguous with biologically significant todies of water
(iii)
120-
-------
and the alternatives, ethion and carbophenothion, appear to present more
risk from acute effects than chlorobenzilate (fish kills likely to occur
in contiguous waters). Propargite appears to present about the sane acute
risk as chlorobenzilate while sulfur probably presents no acute risk.
C. Human Effects
Use of ethion and carbophenothion present greater risk due to acute
toxicity than chlorobenzilate as evidenced by tests of laboratory animals
and pesticide episode data (Burnam, 1978). It appears that there would he
a greater potential hazard in association with immediate injury to those
occupationally involved during or subsequent to use of these substitutes
on citrus.
(iv)
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APPENDIX D
LABEL REQUIREMENTS
-------
APPPPIX D
THE FOLLOWItC STATEMENTS MUST APPEAR ON THE IABELS
OF PESTICIDE PBODUCTS CONTAINING CHDOBOBENZILftTE
Restricted Use Pesticide
For retail sale to and use only by certified applicators or persons
under their direct supervision and only for those uses covered by
the certified applicators certification.
General Precautions
A. Take special care to avoid getting chlorobenzilate in eyes, on skin,
or on clothing.
B. Avoid breathing vapors or spray mist.
C. In case of contact with skin, wash as soon as possible with soap
and plenty of water.
D. If chlorobenzilate gets on clothing, remove contaminated clothing
and wash affected parts of body with soap and water. If the extent
of contamination is unknown, bathe entire body thoroughly. Change
to clean clothing.
E. Nash hands with soap and water each tine before eating, drinking,
or socking.
F. At the end of the work day, bathe entire body with soap and plenty
of water.
G. Wear clean clothes each day and launder before reusing.
Required Clothing and Equipment for Application
A. Fine weave cotton fabric (Jersey), one-piece junpsuit, long sleeves,
long pants.
B. Wide-briimed hat.
C. Heavy-duty fabric work gloves.
D. Any article which has become contaminated must be replaced.
(i)
123-
-------
B. Pace-piece respirator of the type approved f-r pesticide spray applica-
tion* by the National Institute for Occupational Safety and Health.
F. Instead of the above specified clothing and equipment, the applicator
can use an enclosed tractor cab which provides positive pressure and
a filtered air supply. Aerial application nay be conducted without
the aeove specified clothing and equipment.
Handling Precautions
A. Heavy-duty rubber or neqprene gloves and apron roust be worn during
loading, unloading, and equipment clean-up.
(ii)
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