F AA-AM-72-29 

BEHAVIORAL CHANGES FROM CHRONIC EXPOSURE TO 

PESTICIDES USED IN AERIAL APPLICATION: 

EFFECTS OF PHOSDRIN ON THE PERFORMANCE OF 

MONKEYS AND PIGEONS ON VARIABLE INTERVAL 

REINFORCMENT SCHEDULES 

Mark F. Lewis, Ph.D. 

Henry W. Mertens, M.A. 

Jo Ann Steen, B.A. 

FAA Civil Aeromedical Institute 

P.O. Box 25082 

Oklahoma City, Oklahoma 73125 

August 1972 

Availability is unlimited. Document may be released 

to the National Technical Information Service, 

Springfield, Virginia 22151, for sale to the public. 

Prepared for 

DEPARTMENT OF TRANSPORTATION 

FEDERAL AVIATION ADMINISTRATION 

Office of Aviation Medicine 

Washington, D.C. 20591 
!-----------------------------------------------------------------------------------------------------------------------;---------------------------------------

: 

Federal Aviation Administration, Office of Aviation 

Medicine, Civil Aeromedical Institute, Oklahoma 

City, Oklahoma. BEHAVIORAL CHANGES FROM 

CHRONIC EXPOSURE TO PESTICIDES USED IN 

AERIAL APPLICATION: EFFECTS OF PHOSDRIN ON THE PERFORMANCE OF MONKEYS 

AND PIGEONS ON VARIABLE INTERVAL RElNFORCEMENT SCHEDULES by Mark F. Lewis, 

Henry W. Mertens, and Jo Ann Steen, August 1972, 

4 pp. Report No. FAA-AM-72-29. 

The need for study of behavioral difficulties resulting from 

exposure to pesticides is based upon reports of behavioral 

difficulties in aerial applicators following organophosphate 

poisoning and is underscored by a recent plane crash of a 

cropduster pilot in which prior exposure to several organophosphate pesticides was implicated. The present study 

examines effects on performance of pigeons and squirrel 

monkeys of Phosdrin (mevinphOs), a cholinesterase-inhibiting 

pesticide not previously studied in the laboratory. Variable 

interval schedules of reinforcement were used with both food 

and water as rewards. A dose-related decrease in response 

I. Lewis, M. F. 

II. Mertens, 

H. W. 

III. Steen, J. A. 

Descriptors 

Aerial 

Application 

Behavior 

Drug Effects 

Pesticides 

Phosdrln 

:------------------------------- ..... ________________________________________________________________________________ _ 

rate was observed with all animals. Decrements in behavior were observed at doses below which external symptoms of 

Phosdrin poisoning occurred, indicating the need for further 

investigation of the behavioral actions of pesticides. 

Federal Aviation Adminis

Medicine, Civil Aeromed

City, Oklahoma. BEHAV

CHRONIC EXPOSURE TO 

AERIAL APPLICATION

DRIN ON THE PERFOR

AND PIGEONS ON VA

lNFORCEMENT SCHEDU

Henry W. Mertens, and J

4 pp. Report No. FAA-AM

The need for study of be

exposure to pesticides is 

difficulties in aerial appl

poisoning and is undersco

cropduster pilot in which 

phosphate pesticides was 

examines effects on perf

monkeys of Phosdrin (me

pesticide not previously st

interval schedules of reinf

and water as rewards. A 

rate was observed with al

were observed at doses b

Phosdrin poisoning occurre

investigation of the behavi

----------------------------------------------------------------------------------------------------------------------------------------------------------------
,. 

-------------------------------------------------------------------------------------------------------------------------------------------------------------

Federal Aviation Administration, Office of Aviation 

Medicine, Civil Aeromedical Institute, Oklahoma 

City, Oklahoma. BEHAVIORAL CHANGES FROM 

CHRONIC EXPOSURE TO PESTICIDES USED IN 

AERIAL APPLICATION: EFFECTS OF PHOSDRIN ON THE PERFORMANCE OF MONKEYS 

AND PIGEONS ON VARIABLE INTERVAL REINFORCEMENT SCHEDULES by Mark F. Lewis, 

Henry W. Mertens, and Jo Ann Steen, August 1972, 

4 pp. Report No. FAA-AM-72-29. 

The need for study of behavioral difficulties resulting from 

exposure to pesticides is based upon reports of behavioral 

difficulties in aerial applicators following organophosphate 

poisoning and is underscored by a recent plane crash of a cropduster pilot in which prior exposure to several organophosphate pesticides was implicated. The present study 

examines effects on performance of pigeons and squirrel 

monkeys of Phosdrin ( mevinphos), a cholinesterase-inhibiting 

pesticide not previously studied in the laboratory. Variable 

interval schedules of reinforcement were used with both food 

and water as rewards. A dose-related decrease in response 

I. Lewis, M. F. 

II. Mertens, 

H. W. 

III. Steen, J. A. 

Descriptors 

Aerial 

Application 

Behavior Drug Effects 

Pesticides 

Phosdrin 

Federal Aviation Admini

Medicine, Civil Aerome

City, Oklahoma. BEHAV

CHRONIC EXPOSURE T

AERIAL APPLICATION

DRIN ON THE PERFO

AND PIGEONS ON VA

INFORCEMENT SCHED

Henry W. Mertens, and J

4 pp. Report No. FAA-AM

The need for study of b

exposure to pesticides is 

difficulties in aerial app

poisoning and is undersc

cropduster pilot in which 

phosphate pesticides wa

examines effects on per

monkeys of Phosdrin (me

pesticide not previously s

interval schedules of rein

and water as rewards. 

:------------------------------- ...... ______ ------------------------------------------------------------------------------------------------------------.... -----

rate was observed with all animals. Decrements in behavior 

were observed at doses below which external symptoms of Phosdrin poisoning occurred, indicating the need for fur.ther 

investigation of the behavioral actions of pesticides. 

rate was observed with a

were observed at doses 

Phosdrin poisoning occurr

investigation of the behav

---------------------------------------------------------------------------------------------------------------------------------------------------------------
TECHNICAL REPORT STANDARD TITLE PAGE 

1. Report No. ! . Government Access ion No . 3. Recipient" s Catalog No. 

FAA-AM-72-29 

4. Title and Subtitle BEHAVIORAL CHAN;ES FROM CHRONIC EXroSURE 5. Report Date 

TO PESTICIDES USED IN AERIAL APPLICATION: EFFECTS OF I--:---:A=-u...:;g:....u_s_t_l.,...9_7_2 __ ..,......,-----1 

PHOSDRIN ON THE PERFORMANCE OF MONKEYS AND PIGEONS ON 6. Perform ing Organization Code 

VARIABLE INTERVAL REINFORCEMENT SCHEDULES 7. Author(s) 8. Pe rforming Organization Report No. 

Mark F. Lewis, Ph.D . , Henry W. Mertens, M.A., 

and Jo Ann Steen B.A. 9 . Performing Organ i zation Name and Address 10 . Work Unit No. 

FAA Civil Aeromedical Institute 

P. 0 . Box 25082 11 . Contract or Grant No. 

Oklahoma City, Oklahoma 73125 

12. Sponsoring Agency Name ond Addres• 

Office of Aviation Medicine 

Federal Aviation Administration 

800 Independence Avenue, S.W. 

Washington, D. C. 20591 

15. Supplementary Notes 

- -------1 13. Type of Report and Period Covered 

OAM Report 

14 . Sponsoring Age"ncy Code 

This research was performed under Tasks AM-B-71-PSY-25 and AM-B-72-PSY-25. 

16. Abstract 

The need for study of behavioral difficulties resulting from exposure to 

pesticides is based upon reports of behavioral difficulties in aerial applicators 

following organophosphate poisoning and is underscored by a recent plane crash of 

a cropduster pilot in which prior exposure to several organophosphate pesticides 

was implicated. The present study examines effects on performance of pigeons and 

squirrel monkeys of Phosdrin (mevinphos), a cholinesterase-inhibiting pesticide 

not previously studied in the laboratory. Variable interval schedules of 

reinforcement were used with both food and water as rewards. A dose related 

decrease in response rate was observed with all animals. Decrements in behavior 

were observed at doses below which external symptoms of Phosdrin poisoning 

occurred, indicating the need for further investigation of the behavioral actions 

of pesticides. 

17. Key Words 

Aerial Application 

Behavior 

Drug Effects 

Pesticides 

Phosdrin 

19. Security Classif. (of th is report) 

Unc lass if ied 

Form DOT F 1700.7 IB-691 

18. Distribution Statement 

Availability is unlimited. Document may 

be released to the National Technical 

Information Service, Springfield, Virginia 

22151, for sale to the public. 

20. Security Classif. (of th is page) 21. No. of Pages 22. Price 

Unclassified 4 $3.00 
BEHAVIORAL CHANGES FROM CHRONIC EXPOSURE TO PESTICIDES 

USED IN AERIAL APPLICATION: 

EFFECTS OF PHOSDRIN ON THE PERFORMANCE OF MONKEYS 

AND PIGEONS ON VARIABLE INTERVAL REINFORCEMENT SCHEDULES 

I. Introduction. 

Although there have been several reports of 

behavioral difficulties in aerial applicators following organophosphate poisoning/ 2 experimental evaluations of the effects that cholinesterase-inhibiting pesticides have on performance 

have been so limited that one recent reviewer3 

concluded that little evidence of behavioral defi. 

cits could be found apart from obvious somatic 

symptoms. The current study examines some 

performance changes resulting from acute doses 

of Phosdrin ( mevin phos) , a cholinesteraseinhibiting organophosphate not previously 

studied in the behavioral laboratory. The need 

for rapid detection of Phosdrin poisoning is 

illustrated by a recent case study of a plane 

crash of a duster pilot following repeated exposures to Phosdrin and other organophosphate 

pesticides.4 

II. Method. 

The subjects were two adult male King pigeons, 

maintained at 80% of their free-feeding weights, 

one adult male squirrel monkey (M14) (Saimiri 

Sciurea), maintained at 75% of his free-feeding 

weight and two squirrel monkeys (M12 and 

M13), run at 24 hours of water deprivation. All 

subjects were run in operant behavior chambers 

on variable-interval (VI) schedules of reinforcement, i.e., schedules in which a response (key 

peck for the pigeons and lever press for the 

monkeys) is reinforced by presentation of food 

(water for M12 and M13) following a variable 

interval of time from the preceding reinforced 

response. The monkeys were run on a VI 1.7 

schedule in which the mean mm1mum time between reinforced responses was 1.7 minutes, 

while the pigeons were run on VI 5.9 ( 5.9 minutes mean minimum time between reinforcements). 

Experimental training, reinforcement contingencies, and data recording were controlled by a 

Linc-8 computer (Digital Equipment Corporation) with an Iconix logic interface (Siliconix 

Corporation). Variable interval schedules were 

generated by random sampling from a table containing a Fibonacci series appropriate to the VI 

schedule employed. 

All sessions lasted until a total of 60 reinforcements had been presented or until the maximum 

session time (3 hours for monkeys and 8 hours 

for pigeons) had elapsed. Reinforcement consisted of 3 seconds access to grain for the pigeons, 

75 mg banana flavored pellets for M14, and .5 

ml of water for M12 and M13. 

Graded doses of Phosdrin were injected intramuscularly every 4 or more days with control 

(saline) injections given on intervening days. 

All doses were administered immediately before 

the start of each session. Except for the data of 

M13, all experimental points represent the average of two determinations at each dose. 

III. Results. 

Figure 1 shows the average dose-effect curves 

for monkeys M12, M13, and M14. Average response rates for the first hour of the session and 

for the total session are shown. With the exception of one reversal for monkey M13 at the highest dose, response rates decreased with increasing 

doses of Phosdrin. 

Figure 2 (for pigeon B3764) and Figure 3 

(for pigeon B4373) indicate similar effects with 

pigeons: as dose increases, response rate decreases. 

1 
o M 14 

Firs! hour overage 

--- Session overage 

.10 .15 .20 .25 

L___--Phosdrin (mg/kg) ----' 

FIGURE 1. DQse response curves for the effects of 

Phosdrin on the performance of three monkeys in 

a VI 1.7 min schedule of reinforcement. 

1.30 

1.20 

1. 10 

1.00 

u 

., .90 (J) 

' .80 a: 

., .70 0 

a: .60 ., 

., 

c: .50 0 

a. 

., 

., .40 a: 

.30 

.20 

. 10 

.00 

B 3764 .__ 

~ 

Saline .10 .15 .20 

• First hour average 

o Second hour average 

o Third hour average 

• Fourth hour overage 

--- Session overoc;~e 

.25 .30 .35 

'------Phosdrin (mg/kg) ------' 

FIGURE 2. Dose response curves for the effects of 

Phosdrin on the performance of pigeon B3764 in a 

VI 5.9 min schedule of reinforcement. 

Although the dose-effect curves suggest the 

time course of drug action, cumulative response 

records demonstrate this action more clearly. 

Figure 4 for monkey M12 (food deprived) shows 

that the effect of each dose is evident at the 

beginning of each session and continues without 

indicated recovery. For monkey M14 (water 

length of suppression dose-dependent. Similar 

effects are seen in pigeon B4373 at low doses 

(Figure 6) and high doses (Figure 7). 

1.30 

1.20 

1. 10 

1.00 

u 

., .90 (J) 

' a: .80 

., .70 0 

a: .60 ., 

"' c: 

0 .50 a. 

"' ., .40 a: 

.30 

.20 

. 10 

.00 

~ 

;;:.-----

-

Saline 

8 4373 • First hour overage 

o Second hour average 

o Third hour overage 

--- Session overage 

.10 .15 .20 .25 .30 .35 

'------- Phosdrin (mg/kg) ------' 

FIGURE 3. Dose response curves for the effects of 

Phosdrin on the performance of pigeon B4373 in a 

VI 5.9 min schedule of reinforcement. 

SALI //·' 

/~ / -~ 

PHOSDRIN 0 0~ (MG / KG) ,-

.. _..--

PHOSDRIN 0 . 10 (MG / KG) ______--

~----- PHOSDRIN 0 . 15 (MG/KG) 

i 00~ R's i S.c "' 

~ 300 

• I 

0 10 zo lO 

MINUTES 

PHOSDRIN 0 .20 •(MG/KGl 

PHOSDRIN 0 .25 (MG/KG) Ml2 

FIGURE 4. Cumulative records of responding of monkey 

M12 during the second presentation of the Phosdrin 

dose series. 

The subjects were observed for external symptoms of cholinesterase-inhibition. At doses in 

excess of 0.20 mg/ kg Phosdrin, peripheral 

symptoms (tremor, salivation, and lack of coordination) were evident in the monkeys, while at 

doses below 0.15 no somatic symptoms were seen. 

2 
e ~~ M14 j_ 10 20 ~0 NINUTES 

PHOSDRIN 0 .10 (MG / KG) PHOSORIN 0 .15 (MG / KG) 

___ y ~~ 

PHOSORIN 0 .20 (MG / KG) ~ ~ 

~----

~---·H05 0R IN _ .• . _ (-MG- / K-G}------~ 

FIGURE 5. Cumulative records of responding of monkey 

M14 during the second presentation of the Phosdrin 

dose series. 

In pigeons, symptoms (rapid, excessive blinking 

and pennerection) were seen only at the highest 

dose studied ( 0.35 mg/ kg). 

IV. Discussion. 

In both pigeons and monkeys, reduction of 

response rates occurred at doses below which 

external somatic symptoms of Phosdrin poisoning occurred, although greater response suppression was accompanied by somatic symptoms at 

higher doses. Consequently, these data support 

the conclusion that performance changes can 

occur after acute doses of Phosdrin that do not 

produce peripheral parasympathomimetic signs 

of pesticide action. Because these signs or subjective symptoms are often used by aerial applicator personnel as early indicants of excessive 

FIGURE 6. Cumulative records of responding of pigeon 

B4373 during the second presentation of the low 

Phosdrin doses. 

3 

(mevinphos) may be more hazardous than pre

viously thought. Certainly, additional data are 

needed to elucidate the behavioral variables affected by cholinesterase inhibition. 

The present experiment is the first to study the 

acute behavioral effects of Phosdrin, and one of 

the few to examine the acute effects of cholinesterase inhibition on behavior under appetitive 

control. Vaillant5 observed complete suppression 

of responding in pigeons on a multiple fixedinterval fixed-ratio schedule; the duration of 

response suppression increased with dose of 

physostigmine. Behavior after resumption of 

responding was essentially normal. Doses not 

large enough to produce complete suppression 

did not produce significant effects on the behavior. 

These findings have been replicated in pigeons 

and squirrel monkeys6 and may be contrasted 

with the data of the present study in which 

complete suppression was obtained in only one 

monkey (M14) at the highest dose studied. This 

discrepancy may be a consequence of the use of 

different reinforcement schedules or of different 

drugs. However, data presented by Olds and 

Domino7 suggest a similar difference in the effects of physostigmine and arecoline on selfstimulation. Their data suggest complete response suppression with physostigmine and 

partial suppression with arecoline. 

The present report of behavioral effects of 

Phosdrin at doses below levels producing somatic 

symptoms of poisoning is in agreement with the 

FIGURE 7. Cumulative records of responding of pigeon 

B4373 during the second presentation of the high 

Phosdrin doses. 
of physostigmine which did not produce apparent 

loss of coordination did yield decrements in performance. Rosie and Bignami8 found decrements 

in avoidance behavior at doses of physostigmine 

tion. These reports strengthen the need for 

additional research information, pertinent to the 

safety of cropduster pilots, regarding the behavioral actions of pesticides. 

REFERENCES 

1. Dille, J. R., and P. W. Smith: Central Nervous 

System Effects of Chronic Exposure to Organophosphate Insecticides, AEROSPACE MEDICINE, 35:475-

478, 1964. 

2. Smith, P. W., W. B. Stavinoha, and L. C. Ryan: 

Cholinesterase Inhibition in Relation to Fitness :to 

Fly, AEROSPACE MEDICINE, 39 :754-758, 1968. 

3. Clark, G. : Organvphosphate Insecticides and Behavior, A Review, AEROSPACE MEDICINE, 42:735-

740, 1971. 

4. Wood, w'., J. Gabica, H. W. Brown, M. Watson, and 

W. W. Benson: Implications of Organophosphate 

Pesticide Poisoning in the Plane Crash of a Duster 

Pilot, AEROSPACE MEDICINE, 43:1111-1113, 1971. 

5. Vaillant, G. E. : Antagonism Between Physostigmine 

and Atropine on the Behavior of the Pigeon. ARCHlY 

4 

FUR EXPERIMENTELLE P ATHOLOGIE UND 

PHARMAKOLOGIE, 248:406-416, 1964. 

B. Vaillant, G. E.: A Comparis on of Antagonists of 

Physostigmine-Induced Suppression of Behavior, 

JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 157 :636--648, 1967. 

7. Olds, M. E., and E. F. Domino: Comparison of 

Muscarinic and Nicotinic Cholinergic Agonists on 

Self-Stimulation Behavior, JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 

166 :189-204, 1969. 

S. Rosie', N., and G. Bignami: Depression of Two-Way 

Avoidance Learning and Enhancement of Passive 

A voidance Learning by Small Doses of Physostigmine, 

NEUROPHARMACOLOGY, 9:311-316, 1970. 

25559 
---------------------------------------------------------------------------.--------------------------------------------------------------------------------

Federal Aviation Administration, Office -of Aviation 

Medicine, Civil Aeromedical Institute, 

Oklahoma 

City, Oklahoma. BEHAVIOR

AL CHA

NGES FROM 

CHRO

NIC EXPOSURE TO PESTICIDES USED IN 

AERI

AL 

APPLIC

ATIO

N : EFFECTS OF PHOSDRIN 

ON THE PERFORMA

NCE OF MONKEYS 

AND PIGEONS 

ON VARIABLE INTERVAL RE- lNFORCEMENT SCHEDULES by Mark F. Lewis, 

Henry W. Mertens, and J o Ann Steen, August 1972, 

4 pp. Report No. 

FAA- AM-72-29. 

The need for study of behavioral difficulties resulting from exposure to pesticides is based upon reports of behavioral 

difficulties in aerial applicat-ors following organophosphate 

poisoning and is underscored by a recent plane crash of a cropduster pilot in which prior exposure to several organo-

[)hosphate pesticides was implicated. 

The present study 

examines effects on performance -of pigeons and squirrel 

monkeys -of Ph-osdrin ( mevinphos), a cholinesterase-inhibiting 

pesticide not previously studied in the laboratory. Variable 

interval schedules of reinforcement were used with both food 

and water as rewards. A dose-related decrease in response 

I. Lewis, l\f. 

F. II. Mertens, 

H . W. 

III. Steen, J. A. 

Descriptors 

Aerial 

Application 

Behavi-or 

Drug Effects 

Pesticides 

Phosdrin 

Federal Aviation Adminis

Medicine, Civil Aeromed

City, Oklahoma. BEHAV

CHRO

NIC EXPOSURE TO 

AERI

AL 

APPLIC

ATIO

N 

DRIN 

ON THE PERFOR

AND PIGEO

NS ON VA

lNFORCEMENT SCHEDU

Henry W. Mertens, and Jo 

4 pp. Report No. FA

A-AM

The need for study of be

exposure to pesticides is 

difficulties in aerial appl

ooisoning and is undersco

cropduster pilot in which 

[)hosphate pesticides was 

examines effects on perf

monkeys -of Ph-osdrin ( me

oesticide not previously st

interval schedules of reinf

and water as rewards. A 

:------------------------------- ----- --------------------------------------------------------------------------------------------------------------- -------

rate was observed with all animals. Decrements in behavi-or 

were observed at doses below which external symptoms of 

Phosdrin poisoning occurred, indicating the need for further 

investigation of the behavior al actions of pesticides. 

rate was observed with al

were observed at doses b

Phosdrin poisoning occurre

investigation of the behavi

------------------------------------------------------------------------------. ---------------------------------------------------------------------------------
Federal Aviation Administration, Office of Aviation 

Medicine, Civil Aeromedical Institute, Oklahoma 

City, Oklahoma. BEHAVIORAL CHANGES FROM 

CHRONIC EXPOSURE TO PESTICIDES USED IN 

AERIAL APPLICATION : EFFECTS OF PHOSDRIN ON THE PERFORMANCE OF MONKEYS 

AND PIGEONS ON VARIABLE INTERVAL REINFORCEMENT SCHEDULES by Marl' F. Lewis, 

Henry W. Mertens, and J o Ann Steen, August 1972, 

4 pp. Report No. FAA-AM-72-29. 

The need for study of behavioral difficulties resulting from 

exposure to pesticides is based upon reports of behavioral 

difficulties in aerial applicators following organophosphate 

poisoning and is underscored by a recent plane crash of a 

cropduster pilot in which prior exposure to several organo- phosphate pesticides was implicated. The present study 

examines effects on performance of pigeons and squirrel 

monkeys of Phosdrin (mevinphOs), a cholinesterase-inhibiting 

pesticide not previously studied in the laboratory. Variable 

interval schedules of reinforcement were used with both food 

and water as rewards. A dose-related decr ease in response 

I. Lewis, M. F. 

II. Mertens, 

H. W. 

III. Steen, J . A. 

DesC?·iptors 

Aerial 

Application 

Behavior 

Drug Effects 

Pesticides 

Phosdrin 

--------------------------------------

Federal Aviation Admini

Medicine, Civil Aeromed

City, Oklahoma. BEHAV

CHRONIC EXPOSURE T

AERIAL APPLICATION

DRIN ON THE PERFO

AND PIGEONS ON VA

INFORCEMENT SCHED

Henry W. Mertens, and J 4 pp. Report No. FAA-AM

The need for study of b

exposure to pesticides is 

difficulties in aerial app

poisoning and is undersc

cropduster pilot in which 

phosphate pesticides wa

examines effects on per

monkeys of Phosdrin ( me

pesticide not previously s

interval schedules of rein

and water as rewards. 

:·------------------------------ ..... _________________ ------------------------------------------------------------------;----- --------------------------.... ·------

rate was observed with all animals. Decrements in behavior 

were observed at doses below which external symptoms of Phosdrin poisoning occurred, indicating the need for fur.ther 

investigation of the behavioral actions of pesticides. 

rate was observed with a

were observed at doses 

Phosdrin poisoning occurr

investigation of the behav

----------------------------------------------------------------------------------------------------------------------------------------------------------