UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON D.C., 20460 

MEMORANDUM 

Date: May 28, 2014 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

SUBJECT: Dichlorvos (DDVP): Re-examination of the Toxicity Study, Endpoint and Point of 

Departure Selected for Short- and Intermediate-term Risk Assessments 

PC Code: 084001 

Decision No.: 491158 

Petition No.: N/ A 

Risk Assessment Type: N/ A 

TXR No.: 0056973 

MRID No.: N/A 

DP Barcode: 420277 

Registration No.: 

Regulatory Action: 

Case No.: NA 

CAS No.: 62-73-7 

40 CFR: NA 

FROM: 

Health 

Ray Kent, 

Effects 

Senior 

Division 

Scientist 

(7509P) 

a 1' t~ 

THROUGH: 

Health 

Jess Rowland, 

Effects 

Deputy 

Division 

Director 

(7509P) 

~~ 

TO: Garland Waleko, Risk Manager Reviewer 

Risk Management and Implementation Branch 2 

Pesticide Re-Evaluation Division (7508P) 

I. Introduction 

EPA has agreed to re-examine the Reference Doses (RIDs) and Population-Adjusted Doses 

(PADs) for DDVP in the 1996 DDVP RED to the extent that the RIDs/PADs relied upon a human 

study, Gledhill, A. J. (1997) Dichlorvos: A Single-Blind, Placebo Controlled, Randomised Study to 

Investigate the Effects of Multiple Oral Dosing on Erythrocyte Cholinesterase Inhibition in Healthy 

Male Volunteers (MRID 44248801) ("Gledhill study"). EPA agreed to revise these RIDs/PADs if 

it determines that revision is appropriate and to rescind any existing RID/PAD for which there are 

no longer existing pesticide uses. EPA further agreed issue a memorandum explaining the results 

of its re-examination ofthe DDVP RID/PADs by May 31,2014. This agreement was memorialized 

in a Settlement Agreement between EPA and NRDC in connection with NRDC'sjudicial challenge 

to EPA's denial ofNRDC's petition to revoke DDVP tolerances [Settlement Agreement, NRDC v. 

EPA, No. 12-3671-ag (2013)]. 

1 
2 

 EPA specifically agreed to re-examine the following risk assessment scenarios that relied 

upon the Gledhill study: short-term incidental oral exposure; short-term, intermediate-term, and 

long-term dermal exposures; and short-term and intermediate-term inhalation exposure. EPA 

defines a Level of Concern for non-dietary scenarios such as these by using an approach referred to 

as the target Margin of Exposure (MOE), whereas EPA defines the Level of Concern for dietary 

exposure using RfDs and PADs. As EPA has explained previously, “the RfD/PAD and MOE 

approaches are fundamentally equivalent.” 73 FR 42683, 42688 (July 23, 2008). Both approaches 

choose a Point of Departure (PoD) from a relevant toxicity study and take into account appropriate 

uncertainty/safety factors in calculating the Level of Concern. Most importantly, “[f]or a given risk 

and given exposure to a pesticide, if exposure were found to be acceptable under an RfD/PAD 

analysis it would also pass under the MOE approach, and vice-versa.” Id. For the risk assessment 

scenarios named above, EPA in the DDVP RED assessed the risk posed by the scenarios using the 

target MOE approach, just as it does generally with other non-dietary risks. 

To be consistent with general Agency practice and EPA’s prior assessment of DDVP risk, 

HED has re-examined the above risk assessment scenarios using the Level of Concern approach 

referred to as the target MOE. Just as was done in the DDVP RED, HED has identified a PoD and 

target MOE for each risk assessment scenario. 

This memorandum contains HED’s recommendations as to the appropriate study for the risk 

assessment scenarios mentioned above and the associated PoDs and target MOEs for the affected 

scenarios.1

 As discussed below, HED has concluded that the Gledhill study is not appropriate for 

regulatory use, and thus HED has concentrated in this memorandum on what alternative study or 

studies should be relied upon for endpoint and PoD selection and how selection of an alternative 

study or studies affect the target MOE. On a separate track, HED is undertaking a comprehensive 

review of the organophosphate (OP) pesticides, including dichlorvos, as part of Registration 

Review. For the OPs during Registration Review, acetylcholinesterase inhibition will be reevaluated in the toxicology database in multiple species, durations, lifestages, and routes. The 

temporal pattern of acetylcholinesterase inhibition from single dosing and repeated dosing studies 

in laboratory animals will also be evaluated. Typically, OPs exhibit a phenomenon known as 

steady state acetylcholinesterase inhibition, which is characterized as acetylcholinesterase inhibition 

coming into equilibrium with the synthesis of new, uninhibited enzyme after repeated dosing with 

the same concentration of the OP. Thus, the degree of acetylcholinesterase inhibition at a given 

dose remains consistent across duration. In general, OPs reach steady state within 2- 3 weeks but 

this varies among OPs. This comprehensive re-evaluation may result in revisions to the selection of 

endpoints of concern, PoDs, and Levels of Concern (RfD/PADs and target MOEs), for OPs 

generally as well as DDVP specifically. 

 

1

 If NRDC wishes to know what a “RfD/PAD” would be for these risk assessment scenarios, such a number can be 

calculated by dividing the PoD for the scenario by the target MOE. 
3 

II. Decision on Use of the Gledhill study. 

HED conducted a refined statistical reanalysis of the underlying data in the Gledhill study 

(D420275). Based on this analysis, HED recommends that EPA no longer rely on the Gledhill study 

for risk assessment, and to instead use another study or studies to provide points of departure for the 

aforementioned risk assessment scenarios. This new statistical analysis is briefly summarized in the 

following paragraphs]. 

A total of 9 male subjects were enrolled in the Gledhill study. At the beginning of the study each 

subject had blood drawn every few days over a 2-week period to establish a baseline of red blood 

cell acetylcholinesterase (RBC cholinesterase) activity. Following the pre-dosing period, on day 0 

of the dosing phase of the study, 6 of the 9 subjects were selected to receive 0.1 mg/kg of DDVP 

via capsule on a daily basis for 3 weeks. The remaining 3 subjects served as controls and were 

given a placebo. The study is “single-blind” in that none of the subjects knew whether he was 

receiving DDVP or a placebo. The baseline for comparison of RBC cholinesterase activity during 

the 3-week dosing period was the mean of the pretreatment and 0-day baseline RBC cholinesterase 

measurements. Using the pooled predose measurements as a reference point, there was a clear 

indication that dosing of the male subjects with DDVP resulted in up to 16% inhibition of RBC 

cholinesterase activity (See Figure 1). 

Figure 1. Apparent Effect of DDVP Administration on RBC Acetylcholinesterase in Male 

Volunteers 
4 

There is a key assumption in the original analysis – that the pre-dosing measurements of 

RBC cholinesterase activity are independent of each other and randomly distributed. HED did not 

make such an assumption in the follow-up analysis. Instead each subject was followed throughout 

the study commencing with the first pre-dosing measurement of cholinesterase activity to the 

termination of dosing. When the individual pre-treatment measurements of RBC cholinesterase 

activity are taken into account rather than averaged, the distribution of RBC cholinesterase in the 

pre-dosing period was not random, but declined over the two-week duration of pre-dosing in those 

subjects who were later selected to receive DDVP. As shown in Figure 2, the slope of RBC 

cholinesterase activity in the placebo group is essentially flat over the entire study while the slope 

of the RBC cholinesterase activity for the treatment group declines over the study, including the 

pre-treatment period. Moreover, the statistical analysis showed that the slopes of the two groups 

were significantly different from one another in the pre-treatment period (p-value < 0.001). No 

explanation was provided in the Gledhill study either for the differences in cholinesterase activity in 

the two groups or why this difference was not taken into account. Once the pretreatment 

differences in cholinesterase activity in the two groups is incorporated into the statistical analysis 

that analysis shows that there is no statistically significant effect of dosing with 0.1 mg/kg DDVP 

on either the slope or intercept of the treated group mean response. 

Figure 2. Lack of Effect of DDVP Administration on RBC Acetylcholinesterase in 

Male Volunteers 
5 

Based on this statistical analysis there are at least two reasons for rejecting reliance on the 

Gledhill study. First, the unexplainable non-random responses in the treated subjects (i.e., the 

decline in RBC cholinesterase activity that began pre-dosing), create a fundamental uncertainty as 

to whether the study examined essentially equivalent groups of subjects (other than due to DDVP 

treatment), and thus render the data unreliable. Second, even putting this flaw to one side, the study 

included insufficient dose levels to show what the analysis now purports to indicate – that 0.1 

mg/kg/day is a no observed adverse effect level (NOAEL) for DDVP. Generally, to show a 

NOAEL, a study would need multiple dose levels so that the study could both detect the NOAEL as 

well as a dose that does cause adverse effects. In the absence of a dose that causes adverse effects, 

it is uncertain that the study was capable of ascertaining adverse effects, if they were present. The 

Gledhill study is not usable for regulatory purposes. 

III. Risk Assessment Scenarios under Consideration/Rescission of Unnecessary PoDs 

 As noted, EPA is re-examining its prior choice of the target MOE and associated PoD for 

the following risk assessment scenarios that all used the Gledhill study for risk assessment: shortterm incidental oral exposure; short-term, intermediate-term, and long-term dermal exposure; and 

short-term and intermediate-term inhalation exposure. HED has determined that there are no longer 

any registered uses that result in long-term dermal exposure. Prior pet-collar uses that do result in 

such exposure have been canceled. 72 FR 35235 (June 27, 2007). Accordingly, HED recommends 

that the target MOE and PoD for long-term dermal exposure is no longer required. HED’s reexamination addresses all of the other named scenarios. 

IV. Selection of Alternative Study and Point of Departure to Assess Relevant Risk 

Assessment Scenarios 

 Because the Gledhill study will not be used for risk assessment, an alternative study (or 

studies) must be identified for assessing risks associated with exposures over short (up to 1 month) 

and intermediate (up to 6 months) time frames. HED reviewed the DDVP toxicology data base and 

selected the following studies most relevant to these time frames: 1) the 13-week subchronic 

toxicity study in rats (MRID 41004701); 2) the 90-day subchronic neurotoxicity study in rats 

(MRID 42958101): 3) the repeated dose component of the comparative cholinesterase assay in 

young and adult rats (MRID 46153304); and the 1-year chronic toxicity study in dogs (MRID 

41593101). Each of the studies will be briefly discussed. 

 

1. Subchronic Toxicity Study in Rats: In an acceptable 13-week subchronic study (Kleeman, 

1998, MRID 41004701), Crl:CDR(SD)BR rats, 10/sex/group, were gavaged with 0, 0.1, 1.5 or 15 

mg DDVP/kg/day, 5 days/week, for 13-weeks. Effects noted during the 13-week dosing period 

included instances of salivation and/or urine stains in some high-dose males and females at 

approximately 30 to 60 minutes post-dosing; and generalized retinal atrophy at terminal sacrifice 

was noted in 2/10 high-dose and 1/10 low-dose females (but no control females. Increased 

liver/body weight ratio seen in high dose males was not accompanied by any body weight or 

enzyme changes. 

 
6 

 Plasma and RBC cholinesterase activity were reduced in mid and high dose animals, and 

RBC cholinesterase activity was reduced in 0.1 mg/kg/day females at 14 weeks; however, the 

reduction was less than ten percent below control and such a small change in RBC cholinesterase 

activity is not considered an adverse effect. The reduction of brain cholinesterase activity in high 

dose male and female rats at study termination was biologically significant. No other changes were 

seen in the test animals which could be attributed to administration of the test compound. 

 The data presented support a NOAEL of 0.1 mg/kg/day and a LOAEL of 1.5 mg/kg/day 

based on cholinesterase inhibition (plasma and RBC in males and RBC in females at week 7 and 

RBC only in males and females at week 14). For brain cholinesterase inhibition, the NOAEL is 1.5 

mg/kg/day based on decreased brain cholinesterase activity in both sexes at the high dose only. 

Subsequent to the initial review, the dose-response data were analyzed by benchmark dose analysis. 

Whenever possible and appropriate EPA prefers to use Benchmark Dose (BMD) analysis for 

determining PoDs, because such an analysis utilizes the whole dose-response curve and provides a 

more quantitative alternative to the first step in dose-response assessment than the NOAEL/LOAEL 

process. The results of the BMD analysis are summarized in the following table (Table 1): 

Table 1. BMD Analysis of the 13-Week Subchronic Study in Rats 

DDVP inhibitory concentration (mg/kg/day) 

Test group 

RBC Brain 

BMD10 BMDL10 BMD10 BMDL10

49day - (Male) 0.57 0.41 -- -- 

49day - (Female) 0.65 0.45 -- -- 

98day - (Male) 0.60 0.49 1.81 0.43 

98day - (Female) 0.65 0.54 2.35 1.83 

2. Subchronic Neurotoxicity Study in Rats. In a subchronic oral neurotoxicity study (Lamb, 

1993, MRID 42958101), DDVP was administered in deionized water to 15 Sprague-Dawley 

rats/sex/group at gavage doses of 0, 0.1, 7.5, or 15.0 mg/kg/day for 90 days. Within each dose 

group, 10 rats/sex were allocated for brain cholinesterase determination and 5 rats/sex were 

allocated for neuropathology evaluation. Additionally, blood samples were collected for 

cholinesterase measurements pre-study and on study weeks 3, 7, and 13. Five rats/sex/dose from the 

cholinesterase group and 5/sex/dose from the neuropathology group were evaluated with the 

Functional Observational Battery (FOB) and motor activity tests pretest and on study weeks 3, 7, 

and 12. Body weight and food consumption were measured weekly. 

There was no treatment-related mortality. Mean body weight in high-dose females was 

consistently lower than the control (11-21%) throughout the study. No body weight effects were 

observed in any other animals, and there was no treatment-related effect on food consumption. 

Tremors, salivation, exophthalmos, lacrimation, and clear material on the forelimbs were observed 

in high-dose males and females approximately 15 minutes post-dosing. Rales, chromodacryorrhea, 

and red/yellow/orange material around the nose and mouth were also seen in high-dose rats. 

Tremors were observed in three mid-dose males and nine mid-dose females. Generally, the clinical 
7 

signs occurred during the third week of treatment in the mid-dose animals and as early as the first 

week of dosing and throughout the study in the high-dose rats. Cholinesterase activity was 

decreased in mid- and high-dose male and female rats as follows: plasma 30-58%; erythrocyte 8-

35%; brainstem and brain cortex 10-16%. There were no treatment-related effects in the FOB or 

motor activity tests. No treatment-related neurohistopathological lesions and no apparent changes in 

brain weight or size were observed. The NOAEL is 0.1 mg/kg/day and the LOAEL is 7.5 

mg/kg/day based on decreased cholinesterase activity and clinical cholinergic signs. 

EPA used benchmark dose analysis where feasible to refine points of departure from the 

subchronic neurotoxicity study. Many useful analyses of brain substructures were performed, but 

analyses of RBC and plasma cholinesterase were not useful primarily because of poor fit of the 

BMD models to the data. 

3. Comparative Cholinesterase Assay in rats. In a series of special comparative cholinesterase 

inhibition (ChEI) assay, DDVP was administered by gavage to groups of either Sprague-Dawley or 

Wistar rats. In the repeated dosing phase of the studies, seven daily doses of 0, 0.1, 7.5, or 15 

mg/kg/day were given to groups of 5 rats/sex beginning on either post-natal day 12 (pre-weaning) 

or 42 (young adult). Animals were sacrificed one hour after the last dose. RBC and brain ChE 

activities were measured in all animals. Plasma enzyme activity was not measured (Moxon, 2003, 

MRID 46153304), 

 In pre-weaning rats, tremors were observed in 5/5 males and 5/5 females at 15 mg/kg/day 

on 3-5 days of the dosing interval. In young adult rats at 15 mg/kg/day, tremors were observed in 

3/5 males and 5/5 females on one to four days of the dosing interval. In addition, tremors were seen 

in one young adult male after the last dose of 7.5 mg/kg/day. No clinical signs of toxicity were 

observed in the remaining groups. 

Dose-related inhibition of RBC and brain ChE activities was apparent in both adult and 

pre-weaning rats. Biologically significant inhibition of RBC enzyme activity (>50%) occurred at 

doses of 7.5 and 15 mg/kg/day in both sexes of adults and pre-weaning and at 0.1 mg/kg/day for 

adult animals (11-17%). Brain enzyme activity was statistically and biologically inhibited in 

both sexes at doses of 7.5 and 15 mg/kg/day for adults (>50%) and at all doses for pups (>20%). 

The dose-response data for cholinesterase inhibition were subsequently analyzed by 

benchmark dose modeling. The following table (Table 2) briefly summarizes the results of the 

analysis: 
8 

Table 2. BMD Analysis of Repeated Dose Comparative Cholinesterase Data 

DDVP inhibitory concentration (mg/kg/day) 

Test group 

RBC Brain 

BMD10 BMDL10 BMD10 BMDL10

Pre-weaning (M) 1.66 1.41 1.50 1.40 

Pre-weaning (F) 1.47 0.83 1.46 0.76 

Young adults (M 1.63 1.31 2.02 1.80 

Young adults (F) 1.55 1.26 1.55 1.26 

4. One-year Chronic Toxicity Study in Dogs. Generally chronic studies are used in selecting 

a PoD for chronic exposures and for evaluating potential carcinogenic effects. However, for 

DDVP, the chronic dog study is relevant to shorter than chronic exposure periods because 

plasma and RBC cholinesterase activity measurements were recorded at 5 intermediate time 

points during the study, and, for the mid- and high-dose groups, statistically significant 

cholinesterase inhibition was seen within a few weeks of the onset of the study. 

In the chronic feeding study (Markiewicz, 1990, MRID 41593101), groups of beagle 

dogs were administered DDVP by capsule for 52 weeks at dose levels of 0, 0.1, 1.0 and 3.0 

mg/kg/day. The 0.1 mg/kg/day dose was lowered to 0.05 mg/kg/day on day 22 due to the 

inhibition of plasma cholinesterase noted after 12 days (plasma cholinesterase was decreased in 

males (21.1%) and females (25.7%) at week 2 in the 0.1 mg/kg/day group). At time points after 

week 2, plasma cholinesterase activity was only significantly reduced in the mid- and high-dose 

groups. With one exception, RBC cholinesterase activity was not decreased at any point in the 

study at the low dose (either the initial 0.1 mg/kg/day dose or the 0.05 mg/kg/day dose). The one 

exception occurred at week 6. At that time point, reported RBC cholinesterase activity was 

reduced in males (23.6%) and females (50.1%). HED’s initial review of the study suggested that 

this reported RBC cholinesterase activity might be an effect on RBC cholinesterase of the higher 

dose of 0.1 mg/kg/day that had been administered earlier. RBC cholinesterase activity was 

significantly decreased in the mid- and high-dose groups starting at week 2. Brain cholinesterase 

activity was significantly reduced in males in the mid-dose group and in both sexes in the high 

dose group. However, the brain cholinesterase measurement was only made at the end of the 

study and thus has limited relevance for evaluating the effects of short- or intermediate-term 

exposure. The NOAEL was 0.05 mg/kg/day and the LOAEL was 1.0 mg/kg/day based on 

plasma, RBC and brain cholinesterase inhibition in males and females. 

Further analysis of the RBC cholinesterase inhibition at 6 weeks in the 0.05 mg/kg/day 

dose group indicates that it is unlikely to be due to “an effect on RBC cholinesterase of the 

higher dose of 0.1 mg/kg/day” for several reasons. First, all dose groups exhibited a higher than 

expected increase in RBC inhibition at 6 weeks. Second, the increase in RBC cholinesterase 

inhibition did not occur until approximately 20 days after the low dose was decreased. Finally, 

the 6-week “bump-up” in RBC cholinesterase inhibition was not seem with plasma 
9 

cholinesterase activity measurements. Plasma cholinesterase did not show significant inhibition 

once the dose was reduced at day 22. The most likely cause of the 6-week RBC inhibition 

increase is a mistake in analysis of all of the RBC 6-week samples. Therefore, data from the 6-

week measurement was not used for endpoint selection. 

Brain and RBC cholinesterase data were analyzed by benchmark dose methods, and the results 

are summarized in Table 3. 

Table 3. BMD Analysis of the 1-Year Oral Subchronic Study in Dogs 

DDVP inhibitory concentration (mg/kg/day) 

Test group 

RBC Brain 

BMD10 BMDL10 BMD10 BMDL10

13wk - (Male) 0.14 0.13 -- -- 

13wk - (Female) 0.13 0.09 -- -- 

53wk - (Male) 0.11 0.09 0.54 0.41 

53wk - (Female) 0.21 0.18 0.84 0.58 

V. Selection of the Appropriate Study. 

HED determined that the chronic toxicity study in dogs is the appropriate study for selecting an 

endpoint and PoD for short- and intermediate-term risk assessments. Compared to the other 

considered studies, both the NOAEL for RBC cholinesterase inhibition and the BMDL10 for that 

effect were lowest in the chronic dog study. Further, RBC cholinesterase inhibition was 

observed within a few weeks of the start of dosing and generally remained at the same level 

throughout the study. Thus, the study is relevant to short- and intermediate-term exposure. 

RBC, not brain, cholinesterase inhibition is recommended as the endpoint of concern because the 

benchmark dose analysis shows that RBC cholinesterase is more sensitive than brain 

cholinesterase to the inhibitory effects of DDVP (Table 3). Although HED has previously 

indicated (77 FR 54402, 54418; September 5, 2012), that the subchronic rat study would be the 

proper study for selecting an endpoint and PoD for short- and intermediate-risk assessment of 

dichlorvos in the absence of the Gledhill study, that determination was made prior to full 

consideration of the relevance of the chronic dog study and a BMD analysis of that study. 

Reliance on oral studies to assess risk from exposure under the dermal and inhalation routes is an 

issue being comprehensively examined as part of Registration Review for OPs, including 

dichlorvos. 

VI. Selection of Point of Departure 

The RBC BMDL10 values at study week 13 are 0.09 mg/kg/day in females and 0.13 

mg/kg/day in males. Since there is no indication in the study data of a sex difference in 

sensitivity to RBC cholinesterase inhibition, HED has selected 0.1 mg/kg/day, an average of 

these values, as the PoD for risk assessment. 
10 

This PoD is lower than any other for repeated dose studies analyzed by benchmark dose 

methods, but all such studies had PoDs close to the recommended one. The PoD should be used 

to assess short-term incidental oral risk; short-term and intermediate-term dermal risk; and shortterm and intermediate-term inhalation risk. As explained earlier, HED has determined that there 

are no longer any registered uses that result in long-term dermal exposure and thus no PoD for 

long-term dermal risk assessment is required. 

VII. Uncertainty/Safety Factors 

In the 1996 RED, a 3X FQPA Safety Factor was retained due to a lack of a NOAEL in the 

human study (Gledhill, 1997) that was used for assessing risk via short-term incidental oral; short-, 

intermediate-, and long-term dermal; short- and intermediate-term inhalation of vapors; and shortand intermediate-term inhalation exposure scenarios. 

In this re-examination, the FQPA Safety Factor is not required (i.e., 1X) since an animal 

study with a NOAEL has replaced the human study with a LOAEL and also due to the 

completeness of the DDVP toxicity database, the lack of residual uncertainties for pre- and/or 

postnatal toxicity, and the fact that the DDVP food, drinking water, and residential assessments 

are not expected to underestimate exposure. For more details on the DDVP FQPA Safety Factor, 

refer to the Human Health Risk Assessment, dated June 22, 2006, and to the comprehensive 

analysis of the need for a FQPA safety factor for dichlorvos in response to the petition seeking 

revocation of dichlorvos tolerances. See 72 FR 68662, 68694-68695 (December 5, 2007); 73 FR 

42683, 42696 (July 23, 2008); 77 FR 54402, 54412-54419 (September 5, 2012). 

 Therefore, the Agency’s Level of Concern in a target Margin of Exposure of 100 which 

include the conventional 100 uncertainty factors. The default interspecies factor of 10x for 

uncertainties related to the extrapolation of toxicokinetic and toxicodynamic properties of a 

chemical in a test species to an average human is appropriate; as well as the default intraspecies 

factor of 10x for uncertainties related to the variation in susceptibility in the human population to 

the toxicity of individual chemicals should be applied to the selected PoD to derive a level of 

concern 

VIII. Conclusion 

HED recommends a PoD of 0.1 mg/kg/day with a Level of Concern of 100 for short-term 

incidental oral exposure; short-term and intermediate-term dermal exposure; and short-term and 

intermediate-term inhalation exposure. Further, as explained earlier, HED has determined that 

there are no longer any registered uses that result in long-term dermal exposure and thus the 

designated PoD and target MOE for long-term dermal exposure should be rescinded. 

As mentioned above, organophosphates, including dichlorvos, are presently undergoing a 

comprehensive reevaluation as part of Registration Review. Conclusions in this memorandum 

may change based on that comprehensive reevaluation. 
11 

IX. Bibliography 

Kleeman, J. (1988) 13-Week Gavage Toxicity Study with DDVP in Rats: Final Report: Project 

ID: HLA 6274-102. Unpublished study pre- pared by Hazleton Laboratories America, Inc. 294 p. 

MRID 41004701. 

Lamb, I. (1993) A Subchronic (13 Week) Neurotoxicity Study of Dichlorvos in Rats: Final 

Report: Lab Project Number: WIL-188004. Unpublished study prepared by WIL Research Labs, 

Inc. 1199 p. MRID 42958101. 

Markiewicz, V. (1990) A 52-Week Chronic Toxicity Study on DDVP in Dogs: Lab Project 

Number: 2534/102. Unpublished study prepared by Hazleton Laboratories America, Inc. 431 p. 

MRID 41593101 

Moxon, M.E. (2003) Dichlorvos: Repeat dose cholinesterase inhibition study in pre-weaning and 

young adult rats. Central Toxicology Laboratory, Cheshire, UK SK104TJ. Laboratory report 

number CTL/KR1490/Regulatory/Report; Study No. KR1490, 24-OCT-2002. MRID 46153304. 

Unpublished. 

Nguyen, (2014). Statistical Report: Dichlorvos - A Single Blind, Placebo Controlled, 

Randomized Study to Investigate the Effects of Multiple Oral Dosing on Erythrocyte 

Cholinesterase Inhibition in Healthy Male Volunteers. Memorandum dated May 28, 2014, 

(D420275)