JPRS ID: 10144 USSR REPORT LIFE SCIENCES BIOMEDICAL AND BEHAVIORAL SCIENCES

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• Sequence Number: 59
• Content Type: REPORTS

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JPRS L/ 10144
30 November 1981
USSR Re ort
p
LIFE SCIENCES
BIOMEDICAL AND ~EHAVIORAL SCIENCES
(FC~UO 1 ~ /81)
Fg~$ FOREIGN BROADCAST INFORMATION SERVICE
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NOTE
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COPYR7GHT LAWS AND REGULATIONS GOVERNING OWNERSHIP OF
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- JPRS L�/10144
30 November 1981
USS R REPORT
LIFE $CIENCES
BIOMEDICAL AND BEHAVIORAL SCIENCES
(FOUO 16/81)
CONTENTS
B I OTECHNOLO(~Y
Electrocardiographic Instruments: Basic Technical Specifications--
GoST 19687-74 1
MEDICINE
Initial Evaluation of Cytogenetic Activity and Potential
Mutagenic Hazaxd of 22 Pesticides 22
PHYSIOLOGY
List of Materials of 8th All-Union Conference on Electrophysiology
of Central Nervous S`ystem 32
HUMAN FACTORS
Influence of Some Factors of Spaceflight on Human Vestibulax
Analyzer (According to Data From Soviet and Foreign Press) 73
Modeling Pilot Control Activity 82
PSYCHOLOGY
Correlative Parameter of Electroencephalogram in Presence of
~notional Stress 88
_ a- [III - USSR - 21a S&T FOUO]
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BIOTECHNOLOGY
~
UDC 612.172.4---72(083.7~)
ELECTROCARDIOGRAPHIC INSTRUMENTS: BASIC TECHNICAL SPECIFICATIONS--GOST 19687-74
Moscow ELEKTROKARDIOGRAFY: OBSHCHIYE TEKHNICHESKIYE USLOVZYA (GOST 19687-74)
- in Russian 1974 (signed to press 10 Jun 74) pp 1-18
[All-Uni4n State Standard, Group R24, L. A. Burmistrov, editor]
[Text] Decree of the State Committee for Standards of USSR Council of Ministers,
9 April 1974~ No 8~7, period of validity set: from 1 Jar~uary 1975 to 1 Jan~ary
1978
~ Nonobservance of the atandard will be prosecuted by law.
The instant standard affects electrocardiographs (hereinafter EKG's) designed for
diaEnostics in therapeutic and prophylactic medical institutions.
1. Technical Requirements
1.1 With respect to accuracy of signal form reproduction and recording of
amplitudes and time intervals~ EKG's of three elasses--1, 2 and 3--must be
manufactured.
1.2 With respect to the number of chennels~ the following types of EKG's must be
~ manufactured;
single-channe~; .
two-channel;
four-channel;
six-channel.
. In technically valid cases it is acceptable to manufaeture three-channel EKG's.
1.3 With respect to the type of recording element and sort of recording medium~
the following kinds of EKG's must be manufactured:
pen EKG's recording with ink on paper;
pen EKG's recording on thermosensitive paper;
- pen EKG's recording on paper and using a recorder chart;
pen EKG's recording on an eleetrosensitive chart;
. jet EKG's recording on paper;
beam-type EKG's recowding on photographic paper or film with subsequent
development;
beam-type EKG's recording on paper with immediate development;
beam-type EKG's recording on semiconductive paper;
- 1
.
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beam-type EKG's recording on paper.
1.~~ With respect to the type of power pack, EKG's must be manufactured:
with a feed line;
_ with an autonomous power supply;
with a composite power supply;
Note: At the purchaser's request, the EKG's must be fed from an alternating
- current supply-line at a frequency of 50 and 60 Hz.
1.5 The standard labeling of the EKG's is governed by GOST 17562-72
- 1.6 The basic parameters of the EKG's must correspond to those presented in table
1.
1.7 The potential lead points and the electrocardiographic leads of the EKG's
must have the labels presented in appendix 1.
_ 1.8 The EKG must provide electrocardiogram recording at the leads the labelings
of which are indicated in appendix 1.
~ 1.9 The external edges of the eleetrocnnductive part of the electrode for leading
potentials from the thorax which interface with the skin, must form a circle of no
more than 20 mm in diameter.
1.10 The EKG's must provide recording of processes in an orthogonal system of
coordir.ates.
1.11 The input circuits of the EKG's must be asserobled in such a manner that
connecting the source of constant voltage between the wires of the lead cable in
the polarity indicated in table 2~ produces a positive (upwards) deviation of the
recording line.
1.12 The labeling of the lead cable is presented in fig 1.
1.13. The technical documentation approved by the estat~lished procedure for EKG's
of the specific types~ shall also contain the following additional requirements:
for electrical safety;
for resistance to climatic and mechanical influenees;
_ for the time to establish operating conditions;
for the input and output parameters for connecting aecessories or gages;
for the power line parameters;
for labeling and commutating leads;
for the parameters of the battery volume indicator;
for the accuracy o~' limb potential neutralization when the midpoints of
- single-band leads are obtained;
for the calibrator;
for electrical power used;
for overall dimensions;
_ for mass.
2
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Table 1.
Hopue~ JA~ K7~G~0! TpVNOCTII
~z~ Hox~~eHOSaxiu napa~iclpoe
1 2 I A
~3/ ~.,IIH3i1230H H3~12p2HNA H8- '
npA;~er+u~ U, MB 0� 03-5 I 0� 03,;,c~,
(4) I 2� ~F+ana3oH N3~12PCHHA HH� '
repea ~os epeMe?+H t, c I' 0.0~-2.00
/ 3. Ilor ewHOCrb H3Ne eNNa 0 1 0�15 0.2
`5) HanpA~+:eH~~A ~U, MB P I�(~
U+O,OGU~I�f ~U ~ 0,1 U) +~EU -F 0,15U~
~
- ~ 4. ]lorpew?rocTe H3MCP2HHA + ~=~-~0 O~t ~ a
_ Ht+Tepeanos epeMeHN flc, c I -C t, ~ ) t( ~+O,1T1
~ 7~ 5. 4yecre~i- *u~nNWa ~nHaA 5
TE'.1hHOCTb t~1CIlHAA
IdMjIdB
MBK~NMS.91.IIdA ~
6. CNOPOCTb AHHMftHHA HOCN- ~7~ ~ ~J
TenA 3anxcx u, ~~M/c )0; 25; 50; 50 50
100; 2.50 100
~9~ 7.3Q~�exrHeHas wHpeHa aa� I 100 I 40 -
n?+c~~ KaHana E, MM, ?+e MeHee
~ 10~ 8. Tlpene.nd cMeu~eHNA Hyne- �40 +1~
eoH AHHHH or cpeAHero nono� .
~EHHA IL, MTd
(ii) 9. Ba~6poc Ha nepexoaxo~ 5 10
xapaKrepxrrHKe b, xe 6onee 1
(12) ~O. }~03~~HLiH2HT OTHOCN� ~ � ~0-~
TCJIbHOF1 N2CNM~12TPI1~1 xax, NC I
- 6onee �
~ ~3~ 1 I. 3KeF~saneHTHOe conporee� 15' I 100
neHHe ci+x�+aatidx noMex R.io~, ~ ~
On+, He 6onee
( j,y~) I2. K03~~NUHCNT B3aHM0� ~
BIIIIAHNA Me~n,qy xaHanaMx
, �b, He 6onee
~15~ 13. Mahcs~n~an~Haa HecHH� 0.4
xpoHHOCrb per?+cTpau?+N ~+e~Ay
KaHanaMN, MM, He 6o.~ee
_ ~ 16~ 14. TonulHea nNyyH sanH- I
CN, MM Q �3-~
~ 17~ 15. Cxopocrb ttpeN~a Hyne� ~ 30 50
BOf1 nNHHN, I1pHBEACHH2A I(0
- B%OAY Vpp, MKB~C, ee 6onee
(',8) ~E. ~~p082Hb BH)'TpEHHNX IllY- ~ ~
MOB, i1PHBfACHHWFf KO BXO-
11' U~. MNB, He 6onee
r'j(~l I~. ~NCTEp23NC 32I111CH MM, I ~ I ~~2
~ ~ He Gonee
~ 20~ I8. BpeM~ ycnoKOeH~fA, c, He I 3
6onee '
3
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(1) Hop~id ta� CA~tGO! TOVMOtYX
(2,J H~M4tN0liM11Y nspa~ieTpos
~ Z ~
~2i~ 19. Cxoporrs sanNCx u~, b/c. I ~p 1. .
- xe ~~eHee _
~22~ 20. HepaexoMepeocrb awnnx- �5 t~p t15
'ryAxo�vacrorHO~ xapaKrepxcrH-
xN a, ~yb~
~23~ 21. Bepzx~A rpaxNyHaA yao- IOr 800 1to 1000 Or 70 ,qo 100 Or 60 Ao 70
Tora I'u ~ �
~ 2~~ 22. 3aean eepwyHw nepexoA- ~
NOFI J(8p2K7CpNCiH~y 32 SptMA
2,2 c a, xe bonee
Key:
1. Norms for classes of accuracy
2. Parameters
3. Range of voltage measurement~ U, in mV
4. Range of time interval measurement~ U~ in mV
5. Accuracy of voltage measurement~ o~, in mV
6. Accuracy of time interval measurements,p t, in seconds
~ 7. Sensitivity, in mm/mV
Minimum
Average
Maximum
8. Rate of movement of recording medium, h~ in mm/s
9. Effective recording width of channel, E, in mm, no less than
10. Range of bias of zero line from median position, h, in mm
11. Rejection on transient response:b, in percent, no greater than
12. Coefficient of relative asymmetry, Kra, no greater than
13. Equivalent resistance to inphase interference, Re~i~ , no greater
than
14. Coefficient of interferenee between channels, W, in percent, ~
no greater *han
15. Maximum asynchronicity of recording between channels, in mm~ no greater
than
16. Thickness of recording line~mm
17. Drift rate of zero line attributed to input~ v~~ ~uV/s~ no more than
18. Level of internal noise attributed to input, Un,JaV, no more than
19. Recording hysteresis~ mm~ no greater than
20. Damping time~ s, no greater than
21. Recording rate, v3~ m/s~ no less than
22. Irregularity of amplit~~e-frequency characteristic, a, in percent
23. Upper edge frequency, f~ in Hz
24. Drop in peak of transient response in 2.2 s~ o, in percent, no greater
than
~
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Notes:
1. EKG's intended for operation in sutomatic systems for analysis and processing
vf electrocardiograms, may have an effective recording width of 30 mm.
2. In place of the coefficient of relative asymmetry and equivalent resistance to
inphase interference, it is permissible to use as the standard the re~ection
coefficient (Kr), the value of which must be no less than 60 dB for EKG's of all
classes.
3. Single-channel EKG's may have a rate of recording medium movement equal to 25
and 50 mm/s.
4. EKG's of the first class of accuracy with ~et-on-paper recording may have a
rate of recording medium movement equal to 5. 10, 25, 50 and 100 mm/s.
5. EKG's of the first class of accuracy must offer the possibility of limiting
the upper edge frequency to 65-75 Hz and to ?50-300 Hz.
6. The dispersion of the rated values of resistances forming a unipolar lead must
not exceed 2 percent for EKG's of the first class, 3 percent for the second class
and 4 percent for the third class.
Table 2.
Polarity of Voltage Lead Marking
in Wires of Lead
Cable I II III aVR aVL aVF v,- v~
Minus R R L LF FR RL RLF
Plus L F F R L F C 1- C 6
5
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C+3e 4
~ 30 ' I.t~cr. ~ )
~ o;~~ ~too�r~n fc~~~a (5)
c n c2~ ~6 ~ c6~ .
~ ~ C5 .
~ ~
- C
~ ~
~ .
~ s
'SOOri ~ CP ~ '
1000...,~000 ~'so . 6) -
. Nl~rprr. 7)
- y ( 8)
Figure 1.
. ~y `
- 1. Connector for connecting cable 4. Feliox
to EKG or site of cable 16ad 5. Green
to EKG 6. white
2. Common cord 7. Bla.ck
3. Device for connecting frire to 8. Red
electrode
Note: The number of wires in the lea.d cable for connection to the thoracic
electrodes must be equa.l to the number of thora.cic electrodes employed
simulta,neously or consecutively according to the commuta.tion of the EKG
leads. If the EKG is designed for use of one thorac~.c electrode only,
the wire for connecting to this electxode must be tmxiced with the letter
S.
6
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1.14 The probability of reliable operation of the EKG's for 500 hours of
- relatively uninterrupted operation with confidence of ?�=0.8 shall be no less than
0.8.
2. Inspection Rules
2.1 In order to test the compliance of the EKG's With the requirements of the
instan~ standard, the manufacturing enterprise must conduet state, acc~ptance,
periodical and standard tests.
2.2 State testing of EKG's is governed by GOST 8.001--72.
- 2.3 Each EKG is sub~ected to acceptance testing for compliance with the
requirements of pars 1-22, table 1; 1.12; 1.14 (except for testing for resistance
to climatic and mechnical influences).
2.4 EKG's from among those which passed acceptance testing are sub~ected to
periodical testing. Periodical testing is conducted onee annually on three EKG's
for compliance with all requirements of the instant standard except for par.
1.1u, and once every three years on eight EKG's for compliance to par 1.14. If
during periodical testing the noncompliance of an EKG with at least one of the
requirements of the instant standard is established, the test results are
considered unsatisfactory, and repeat testing of a doubled number of test
specimens for the complete program must be performed. The results of repeat
testing are conclusive.
2.5 When the model, design, materials or industrial manufacturing process is
changed, standard testing of EKG's is performed on three EKG's for compliance with
all requirements of the instant standard, except for compliance with par. 1.14,
and on eight EKG's for compliance with the requirements of par. 1.14. If during
standard testing for compliance with all requirement~ of the instant standard
except for par 1.14~ the EKG's d~ not meet at least one of the requirements,
repeat tests are conducted on a doubled number for the complete program.
3. Methods of Testing
3.1 The basic parameters of the EKG's are tested using a source of a signal of
subsonic and low frequencies having an output signal in the form of a sinusoid and
a sequence of orthogonal pulses and separate serrate pulses. Measuremznt on the
recording is performed using rulers with a scale division of 0.5 mm. Measurement
_ of dimensions af les4 than 15 mm is performed using rulers with a scale division
of no less than 0.1 mm. No allowance is made for the width of the recording line
(fig 2).
3.2 The test signal to the input of the EKG channel is fed through the lead cable
at any of the electrocardiographic leads which may be commutated to a given
channel. As this takes place, the value of the mean level of constant voltage of
any polarity between each of the pairs of aetive electrodes and the neutral
electrode must be no less than 100 mV~ and between the active electrodes--not less
than 50 mV.
7
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~
Q
N
Figure 2.
_
~ 2~
(1) ~i~
1~
~ 2~ ~
~
Figure 3.
Key i
1. hi
2. h~
8
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3.3 The basic parameters of the EKG's are tested after test voltages with a line
frequency-inphase value of 2T0.2 V eff,and an antiphase value of 2+0.2 mVeff are
first fed simultaneously to the inputs of the channels for three s.
3.4 The measurement and error ranges of the EKG's (par. 1-4, table 1) are tested
- under the influence of extreme values of influential factors indicated in the
technical documentation.
3.5 The complianee of the EKG's with the~requirements of pars 1.2; 1.~; 1.5;
1.7-1.10; 1.12; 4.1-4.6 is tested by external inspection ar~d a measuring
instrument Which offers the required accuracy.
3.6 The accuracy of electrocardiogram recording ( par. 1.8), as well as of the
input circuits wiring (par. 1.11), is tested at average sensitivity at the
electrocardiographic leads listed in appendix 1 by recording an orthogonal pulse
with an ~mplitude of 1+0.1 mV. The depiction of the impulse must be positive for
each of the leads on all channels to which this lead may be commutated.
3.7 Error in voltage measurement (par 3, table 1) is determined by connecting to
the EKG input the maximum values of the equivalents of electrode full resistance
to the electrical equivalent of the sub~ect presented in appendix 2 and recording
serrate nr orthogonal test pulses of positive and negative polarity in accordance
with table 2, at nominal sensitivity values (gar 5, table 1) and at any location
of the zero line, h(par 8, table 1), within the range of the effective recording
Width of the channel, E. (par 7~ table 1) based on the correlation:
- f UE~ 2+~h~ ahere h~ 0;
�UE ~ 2 �~h~ where h>0.
Pulse Amplitude Pulse Width
mV s
5.00 0.015
4.00 0.015
2.00 0.010
1.00 0.100
0.40 0.150
0.20 0.200
0.10 0.100
0.03 0.100
Error in determing the amplitude of the test pulse must not exceed one-third of
the acceptable error in voltage measurement for the accuracy class of the EKG's
being tested. Error in determining pulse width must not exceed percent. The
build-up time of the orthogonal test ~ulse must be no greater than 0.1 ms.
9
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The period of the orthogonal pulse sequence must be no less than 1 s.
Wh~n the requirements of par. 3, table 1 are met, the requirements of pp 1; 5;
7-9~ table 1 are considered to have been met.
- Amplitudes hi and h~ are measured on the recordin~ (fig 3).
Error in voltage measurement (par 3, table 1) is determined in mV according to the
formula:
- U = U - hi .
Error in voltage measurement is determined in three ways: by the lapse of time to
establish operating conditions; 2 hours after turning on the power; 4 hours after
turning on the power.
Rejection on the transient response (par 9~ table 1) is determined according to
the formula:
, h
a = v ~ 100 percent
hi
Note. Up to 1977~ the method of testing by serrate pulses is optional.
3.8 Error in measurement of time intervals (par table 1) is determined at all
the values of the rate of movement of the recording medium~ v, stipulated in par
6, table 1, by recording a sinusoidal or orthogonal-shaped periodie signal with a~
period of T='v s fed to the input of the EKG's for 5 s. Error in determining
period duration must not exceed one-third of the aceeptable error of ineasurement
of time intervals depending on the accuracy class of the EKG's being tssted.
When the requirements of par 4, table 1 are met~ the requirements of pars 2 and 6,
table 1 are cansidered to have been met.
The time intervals t in the range specified in par 2, table 1 are determined by
the number of periods n of the test signal
: - n T.
- The time intervals on the recording, t I(fig 4), which correspond to the time
intervals t, are determined by measurement of the length 1, in mm, of any segment
of the recording containing n periods of the test signal with allowance for the
relation 0.5 ~1~50, and by computing
~t
ta = .
v
10
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~ l
i �
I
II " ~ ~ ~ ~ ~ ~A ~ rl !Rt I~! i~
~'I I III ` i~ I ~~i , II~;{~~
Figure 4.
_ ~
~
- r ~
Figure 5.
11
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~ ~i~ ~ ~2~
~
I ?
F'igure 6.
~Y=
1. A
2. Af .
~M ~ .
~ ~
� 910
Figure 7.
12
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Error in measurement of t:~me intervals pt is determined according to the formula:
A:=~-ta.
- 3.9 The coefficient of relative asymmetry (par 10, table 1) is determined at all
possible combinations of the equivalents of electrode full resistance in
accordance with appendix 2 by recording a sequence of inphase orthogonal test
pulses fed to the input of the EKG's at any sensitivity. The width of the pulses
- in the seque~ce is 0.2+0.02 s. The on-off ti~e is 2. The amplitude of the pulses
must be within the linearity range of the amplitude characteristic of the EKG's
for the inphase signal. '
The amplitude of impulses, A, is measured in mm on the recording, with allowance
for rejection.
The coefficient of relative asymmetry is determined according to the formula:
_ K _ A
ra U�~~
3.10 Equivalent resistance to inphase interference (par 11, table 1) is
determined at maximum unbalances of the input circuits by recording a sinusoidal
signal at a frequency of 50�2 Hz with voltage of U p(appendix 2).
The double amplitude of the sinusoid A is measured on the recording.
Equivalent resistance to inphase interference is determined according to the.
formula:
A-l0~
Re~ i~ = 2l~ 2~ Urp
where A is the double amplitude of the sinusoid measured on the recording, in mm;
; is the sensitivity of the EKG's, in mm/mV;
UP is the voltage fed to iche input of the EKG's in conformance with appendix
2' ~ eff'
3.11 The coefficient of interference between channels (par 12, table 1) is
determined by recording a sequence of orthogonal test pulses fed to the input of
one of the channels of the EKG while the inputs of the other ehannels are elosed.
The width of the pulses in the sequence is 0.2+0.02. The on-off time ia 2. The
sensitivity of the channel on which the test signal is fed must be minimum, and
the intensity of the input signal, such as to ensure recording~ the double
amplitude of which is equal to the effective recording width of the channel. The
sensitivity of channels with closed inputs must be maximum, and the
amplitude-frequency characteristie must not be restricted at the top.
13
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The test signal is fed in turn to all channels of the EKG.
PUlse amplitude~ A, is measured in mm on a recording of the channels with cloaed
inputs with allowance made for re~ection.
The coefficient of interfzrence between eha~nnels is determined according to the
formula:
W = E ' 100 percent.
3.12 The maximum asynchronism of r~cording between channels (par 13, table 1) is
determined by recording a discontinuity in constant voltage fed to all inputs
simultaneously. The build-up time of the test voltage must be no greater than 0.4
ms.
- The maximum deviation along the time axis for two channels between inphase points
in the process is measured on the recording.
The requirement of par 13~ table 1 must be met at any position of the zero line of
the channel.
3.13 The thickness of the recording line (~ar 14, table 1) is determir~ed by
recording the zero line with the channel input closed and ~t minimum sensitivity.
` 3.14 The drift rate of the zero line (par 15, table 1) and the level of internal
_ noise (par 16, table 1) attributed to an input are determined at the maximum
sensitivity of the EKG by recording the zero line for 5 s. The maximum values of
equivalents of the electrode impedances of the electrie equivalent of the subject
are connected to the input of the EKG (appendix 2).
The size of the monotonic vertical displacement of the zere line caused by
amplifier drift~ hdr, and the width of th~ noise track, hn (defined as exceeding
the width of the zero line without making allowance for individual re~eetions) are
measured in mm on the recording.
The drift rate of the zero line attributed to an input is determined according to
the formula:
v~ = i o3 ' ~ar
. . ~E
where t is the time in which the drift of the zero line is measured~ in seconds.
The level of internal noise attributed to an input is determined using the
formula:
Un = 103 � hn
~
. 14
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3�15 Recording hysteresis (par 17. table 1) is determined at maximum sensitivity
_ by recording orthogonal pulses of first positive~ and then negative~ polarity at a
rate of movement of' the recording medium equal to 50 mm/sec at any position df' the
zero line. The input to which th~ test pulses are fed and a diagram of their
feeding must be indi~cated in the technical documentation for EKG's of the specific
type.
The height of the fronts of test pulses on the recording, h, must be no less than
10 mm~ the duration of pulse decay~ no less than 20.us. The interval between
pulses must be from 0.2 to 0.4 seconds.
Values h and o h are measured on the recording (fig 5).
3.16 The damping time (par 18. table 1) is determined at all values of
sensitivity of tl~e EKG specified in par 5, table 1 by feeding to its input a
discontinuity in constant voltage kith an amplitude of 50�5 m1f. No later than 3
seconds after feeding the voltage, the "damping" knob must be pressed. The zero
line must be set in the initial stable position which preceded the feeding of the
discontinuity in cons*ant voltage with error not exceeding 2 mm for a duration of
not more than 3 seconds, including the time the knob is pressed.
The damping time, which corresponds to the length of time the knob is pressed
during which the zero line is set in the initial position, is measured on the
recording by the length of zero line segments. Damping time is determined by test
voltage of both polarities.
3.17 Recording speed (par 19~ table 1) is determined by recording a sinusoidal
signal with double amplitude h and frequency f.
The maximum recording speed v Z.~ is determined according to the formula:
vZ = n . f . It.
� The value of h must be no less than 10 mm. At the selected value of the maximum
recording speed, there will be a corresponding maximum frequency f, in Hz, at
which segmer.ts of the sinusoid are still di~tinguishable to the naked eye at
points of transition across the origin.
For EKG's recording with pen on thermosensitive paper, the requirements of par 19~
table 1 must be met within 5 seconds after the recurding system is turned on.
3.18 Irregularity of the amplitude-frequeney eharacteristics (par 20~ table 1)
and the upper edge frequency (par 21~ table 1) are determined at the maximum value
of sensitivity of the EKG's by recording a sinusoidal signal in the frequency
range of 20 to 2f Hz and a sequence of orthogonal pulses fed to the input. The
width of the pulses in the sequence is 0.2�0.02 seconds. The on-off time is 2.
The amplitude of the orthogonal pulses and double amplitude of the sinusoid must
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be equal to 1 mV. Error in determining amplitude must not exceed +2 pereent.
The amplitude of the orthogonal pulses A and double amplitude of the sinusoid Af
are measured on the recording (fig 6).
3.19 Irregularity of the amplitude-irequency characteristic in the frequency
range lower than f is determined according to the formula:
a= ~~AA �100~,
At frequencies higher than f the amplitude-frequency characteristic must fall
monotonically.
The upper edge frequency of f is determined by the highest frequency for which the
va~ue a~remaina negative and has the maximum acceptable value.
3.20 The probability of trouble-free operation (par 1.14) is tested at one level
of reliability by the method of simultaneous sampling with the acceptable number ~
of failures equal to zero in complianee with GOST 13216-67. Test conditions are
governed by GOST 13216-67. After every100 hours of operation the EKG's are tested
_ for compliance with the requirements of table 1 using the methods of pars
3.7-3.19. An EKG is considered to have passed reliability testing if not one
failure occurred during the test period.
~
During reliability tes~ing, each contaet of the commutating unit must close no
- less than 30 times in 8 hours of uninterrupted operation.
3.21 The rejection coefficient (see note to table 1) is tested at all positions
of the lead switch at a sensitivity of 10 rom/mV. The terminals of the lead cables
- connected to the active electrodes are connected through resistors of 5 k,R +10
percent to a common point. When sinusoidal voltage at 100 mV (from peak to peak)
is fed between this point and the ground at any ~'requency within the range of 0.05
to 100 Hz~ the amplitude of the signal on the recording (from peak to peak) must
not exceed 1 mm.
3.22 The drop in the peak of the transient a~esponse (par 22, tabZe 1) is
determined at the maximum sensitivity of the EKG's and a rate of recording medium
movement equal to 50 mm/s~ by recording a discontinuity in constant voltage fed to
the input at first positive~ then negative~ polarity. The duration of feeding of
the voltage must be no shorter than 5 seconds.
Plotting is done on the recording (fig 7), and linear dimensions hi and hZ are
measured. The transient response of each channel must be a monotonic, inverted
curvature to the side of the zero line and must not intersect it.
The drop in the peak Q,is determined accarding to the formula:
_ a _ ~ '
_ h ' 100 percent.
i
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4. Marking, Packaging, Shipping and Storage
_ 4.1 Attached to each EKG must be a metal plate made in compliance with GOST
12969-67 and containing:
the trade mark of the manufacturing enterprise;
standard marking of the EKG;
the year of output;
the serial nu:nber of the EKG according to the numbering system of the
manufacturing enterprise;
the inscription "Made in the USSR" (for equipment intended for export).
4.2 The metal parts of the structure of the EKG's must be subjected to corrosion
proofing in accordance with GOST 13168-69.
4.3 Packaging of the EKG's is governed by GOST 9181-59. Marking of the shipping
crate is governed by GOST 14192-71.
4.4 The t~chnical description, certificate and shipping invoice, enclosed in a
polymer or polyethylene film. are placed in the shipping crate in accordance with
~ GOST 10354-73.
4.5 Shipment of the EKG's is governed by class S, and storage, by class L of GOST
15150-69.
5. Manufacturer's Guarantees
_ 5.1. The manufacturing enterprise must guarantee the compliance of the EKG's with
the requirements of the instant standard when the consumer observes the storage,
shipping and operating conditions set by the present standard.
5.2 The guarantee period of the EKG's is no less than 18 months from the day of
their placement in operation, and of EKG's intended for export~ from the time they
cross the national border of the USSR.
AppendiM 1
� Labeling of EKG Leads
1. The potential lead points must have the following labels:
R--right hand;
L--left hand;
F--left foot;
N--right foot;
C1--to the right of the sternum at the fourth interspace;
C2--to the left of the sternum at the fourth interspace;
- C--at the fifth rib. geometrical roidpoint between C.~ and C4;
C~--at the fifth interspace on l~ft midclavicular line;
CS--between C4 and C6 along left anterior axillary line;
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C6--along left midaxillary line at level C.
2. The electrocardiographic leads must have the following labels:
I--lead from L to R;
II- lead from F to R;
III-lead from F to L.
- aVR--lead from R to midpoint LF, formed when the potential lead points from G and
F are connected at equal resistance,
aVL--lead from L to midpoint FR, formed when the potential lead points from F and
R are connected at equal resistance;
aVF--lead from F to the midpoint RL, formed when the potential lead points from R
and L are connected at equal resistance;
V1-V 6--lead from C1 -C6 to midpoint RLF, formed when the potential lead points from
RL and F are connected at equal resistance.
- Appendix 2
Electrical Equivalent of the Subject
The electrical equivalent of the sub~ect (EES) is used in determining error in
measurement of amplitude, the coefficient of relative asymmetry, equivalent
resistance of inphase interference, the drift rate of the zero line and the
internal noise level.
A diagram of the connection of the EKG to the test signal source to determine the
above enumerated parameters is presented in the illustration.
The equivalents of electrode full resistance consist of condensers and resistors
connect~d in parallel. The values of capacitanee and active resistance directed
to 1 cm of surfacP of the electrode interfacing with the unin,jured skin of the
person being examined are given in the table presented below.
The values of the capacitances and active resistances for the~full resistances
" presented in the chart are determined aecording to the formulas: .
R'
. R _ e
e S ;
- e
Ce = Ce' � 8e,
where Se ia the electroconductivz area of the electrode, interfacing with the
subject's skin.
Deviation of the values of resistances and capacitances from the reference values
_ must not exceed the limits of ~ percent of the nominal values.
In determining error in measurement of amplitude and the coefficient of relative
asymmetry, the electrical equivalent of the subject, is eonnected by switch B1 to
the test signal source at inputs R, L~ F~ N~ Ct=C~, to which a signal is fed in a
pattern and polarity corresponding to table Z o the instant standard. In
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R' C'
eq, eq~
Site of Electrode Z~' Ohm�cm2 cm~
Forearms and shins Min. 3~~05 0.0166
Max. 10 0.01
Thorax Min. 105 0.0233
1~a~c. 2.7�105 o.oi66
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determining equivalent resistance of inphase interference, inputs R, L~ F, N~
C are switched off from the test signal source, and the test signal is fed to
inpu~ V. The drift rate of the zero line and level of internal noise lead to the
input are determined in the absence of the test signal in the position of switch
B1 which switches off inputs R~ L, F, N~ C1-C6.
Switches B2-B10 serve to connect the maximum or minimum values of equivalents of
_ electrode full resistances.
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~ 3 N~ Z9n ~ 7~ 90~ 2
N d~~ ly 3X!'
~ / ~
~ I ~ MUM.
~
R ~ Na~'~�'-~ R
_ I ~ � z�~ 6~
Muy 83 ~
~ MoK
~ Z9x (
NUN B4 I f '
f I I MQX � Z
_ . ~
- ~ nun. B5 .
C1 I C1
~ M0~ ~ z, s
NflN 86 C~
C2 MCA' .
' I MUK Z~ 8~
C3 ~ B~ C3
MOK .
I ~ z~r(s~l -
Muy
C4 ~ ~ ~ C4
MaR . Z .
~ n8
~ MuN. 89 C5
C5 ~ Na?r . Z
I s~( 8
"yN 8~~ C6
C6 I
MQ
z,~, (
~ yn 1M ~
-------1 .
Figure.
Key:
1. Electrical equivalent of subject 7. Ze~ = equivalent of e~ectrode full
2. EKG undergoing testing resistance at neutral electxodes;
3. Test signal source Z = Z
4. Bl ~ test signal s?rltc:h e0 eq max
5. B2-B10 = switches for electrode 8. Z = equivalents of electrod,e
. full resistances et full .resistances at thoracic
6. Z = equivalents caf electxode electxodes
eq full resista,nces at 9. Minlmum
potential electxodes 10. Maximum
COPYRIGHTc Izdatel'stvo standaxtov, 1974
9380
CSOs 8144/1607
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_ MEDICINE
UDC 575.591
INITIAL EVALUATION OF CYTOGENETIC ACTIVITY AND POTENTIAL MUTAGENIC HAZARD OF 22
PESTICIDES
Kiev TSIT~T.OGIYA I GENETIKA in Russian Vol 14, No 6, Nov-Dec 80 (manuscript.received
3 Jul 79) Pp 1~1-1t7
/Article by M. A. Pilinskaya, A. I. Kurinnyy, T. S. L'vova and I. V. German, All-Union
Scientific Research Institute of Hygiene and Toxicology of Pesticides, Polymers and
Plastics of the UkSSR Ministry of Iiealth, Kiev/
/Text/ Introduction. The development of scientifically substantiated measures
aimed at preventing the pollution of the environment with mutagens is one of the
immediate tasks of environmental protection in the genetic aspect.
Such a task requires a mass check for mutagenicity of widespread chemical compounds,
as well as ttiose planned for an extensive use, including pesticides, for the pur-
pose of detecting and identifying genetically active substances and distributing
them according to the degree of potential mutagenic hazard.
T.he authors were guided by the indicated ob~ective during the performance of this
investigation devoted to an initial evaluation of the potential mutagenic hazard
of 22 pesticides--representatives of nine classes of chemical compounds--on the
basis of the results of their cytogenetic st'.udy on mice in accordance with the
principle proposed earlier /1/, modif ied in the courae of performance of this in-
vestigatio:~ and briefly set forth in a refined form in the presented report.
Material and methods. The substances for the inveatigation were selected on the
basis of a list of pesticides recommended for application in agriculture by the
State Commission oz Chemical Agents for the Control of Peata and Diseases of Plants
and Weeds. The list of the studied preparatians is presented in table 1.
The initial check of pesticides for mutagenicity was made by the method of ineta-
phasa analysis of bone marrow cells of white nonline mice, which meet most of the
requirements placed upon an object used for mass investigations (relatively low
material expenditures, simplicity, availability, good reproducibility of resu?ts
and a~~ifficient rate of chromosome analysis). The cytogenetic activity of sub-
stances was studied on 2- to 3-month old male mice. Chromosame preparations were
made by Ford's standard method in our modification. Pesticides were studied with
a single intragastri~ administration (in the form of a auspension on milk or wa-
ter emulsion) and bone marrow fixation 20 hours after the effect. Some substances
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were studied after a daily fivefold administratiou. The amount of the maximum dose
of preparations depended on the degree of their toxicity and in each specific case
was N1/2-1/5 LD50. When a mutagenic effect was detected, the study of pesticidzs
continued up to the ineffective dose. A total of 33,100 metaphases were investi-
- gated, including 2,000 in control animals. The difference between the frequency
of aberrant cells in experimental and control groups of mice was eva.luated by stand-
ard statistical methods /2/. ,
_ Table 1. List of Investigated Pesticides
Investit~ated substance Chemical name Function
Organochlorine Pesticides
Kelthane 1,1-di-(4-chlorophenyl)-2,2,2-trichloroethanol Acaricide
Chlorocholine chloride (S-ethyl chloride)trimethyl ammonium chloride Retardant
- Euparen N, N-dimethyl-~I-phenyl-N-fluorodichlorometh- Fungicide
ylthiosulfamide
_ Dith3ocarbamic Acid Derivatives
Cuprocin A mixture of jointly obtained zinc and copper Fungicide
salts of ethylenebisdithiocarbamic acid in a
ratio of 9:1
Polymarcin A complex of zinc and m3nganese salts of eth- Fungicide
ylenebisdithiocarbamic acid with ethylene-
thiuramdisulf ide in a ratio of 2:1:2
Benzimidazole Derivatives
~ BNC Methyl-N-(2-benzimidazolyl)-carbamate Fungicide
Uzgen Methyl ether-N-(1-butylcarbamoylbenzi- Fungicide
midazolyl-2) of carbamic acid
Alkyl Ethers of Aryl Carbamic Acid
Betanal 3-methoxy-carbonyl-aminophenyl-N-(3-methyl- Herbicide
phenyl) carbamate
Pirimor 5,6-dimethylamino-4-pyrimidinyl-dimethyl Aphicide,
. carbamate insecti-
cide
Thiocarbamic Acid Derivatives
Alipur A mixture of N-cyclooctyl-N,N-dimethyl urea Herbicide
- and BIPC
Vernam S,N,N-tripropyl-thiocarbamate Herbicide
Sutan S-ethyl-N,N-diisobutyl-thiocarbamate Herbicide
Carboxylic Acid Derivatives
2M-4X 2-methyl-4-chlorophenoxyacetic acid Herbicide
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Pref ix 2,6-d~chlorothiobenzamide Herbicide
_ Propanid 3,4-dichloranilide of propionic acid Herbicide
Ramrod N-isopropyl-N-phenyl-chloracetamide Herbicide
Pyridine Derivatives
Reglone l,l-ethylene-2,2-dipyridylium-dibromide Arboricide,
herb ic ide
~ Phenol Derivatives ~
Acrex 0-isopropyl-0-(2,4-dinitro-6-isobutyl- Acaricide,
phenyl) carbonate fungicide
Karathane 2,4-dinitro-6-(2-octyl)-phenyl crotonate Fungicide
Organophosphoric Pesticides
Anthio 0,0-dimethyl-S-(N-methyl-N-iormyl-carbamoyl- Insecti-
methyl)-dithiophosphate cide
Bromophos 0,0-dimethyl-0-(4-bromo-2,5-dichlorophenyl) Insecti-
- ~ thiophosphate cide
Khostathion 0,0-diethyl-0-(1-phenyl-1,2,4-triazolyl-3) Insecti-
thiophosphate cide
Results of investigations and their discussion. The evaluation of the potential
genetic hazard of pesticides can be based on the principle of determination of the
mutagenic potential of substances according to the following three parameters,
which we suggested earlier: degree of manifestation of the effect, ]:evel of effec-
tive doses and universality of the mutagenic effect /1/. The results of the study
of the cyrogenetic effect of pesticides on mammals can serve as the basis for their
initial evaluation according to the f irst two indicated criteria.
The degree of manifestation of the effect is an indicator reflecting the relation-
ship bEtween the induced and control levels of mutations, which is established ac-
cording to the excess of the induced effect over the control level multiple to it
and in case of a significant difference is quantitatively equal to this multiplic-
- ity. In accordance with this the degree of manifeatation of the effect can have
the following values: 0--when differences with control are insignificant; 1--when
the control level is exceeded signif icantly; 2--when the twofold control level is
exceeded significantly; n--when the n-fold control level is exceeded signif icantly.
If the bone marrow of animals as the object of investigation is designated with the
letter symbol the numerical index in it will correspond to the degree of man-
ifestation of the effect (Ba...Bn).
- The level of effective dose, which, according to the scheme presented in table 2,
is determined according to the minimum effective dose with due regard for the deg-
ree of its toxicity is the second indicator of the cytogenetic activity of pesti-
cides. The degree of toxicity is evaluated with reapect to LD50 and is designated
_ as "A" with a dose smaller than or equal to 1/5 LD50 and as "ct" with a dose exceed-
ing 1/5 LD50�
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Table 2. Scheme of Determination of the Level of Effective Dose
.
Y~IOBCHb i~Qn�NNNHO(I J{031t O~09qsqlNNC ypOBHA 5Q1~1GKTHAfiOA ,AWW C y4lTOM CC
! ~ \ ~ ~ ~ '1'OKCp4HOCT=
\ !
~3~ ,,,ry,u. ~4~ ~+n~ (5)
(16 ) 5MK -I- -1- ~ - Ltrcr. n~ [b~ 61 ~15~
(17) Y~rex (6exow~) -f- $ -I- ~ -I-' - ~r. no [b~6-9j~15~
- (18) Brraxan 0 - 0 0 0 ~ 0 L(at. no [5] ~15~
(19) n+P~P 0 - 0 0 0 0 0 (10J
(Zp~ Anxnyp - 0 0' 0 0 0 0. L(pr. no (6] (15)
(Zl) BepHaM - 0 0 0 0 0 0 To xsa ~22~
2M-4X - 0 0 0 0 s
~ 2, ~ n~NK~ - o 0 0 0 0 0 ~
' ( 2 4~ IlponaeHA f 0 0 0 0 0 ~
~ 2 5~ PaupoA 0 0 - 0 0 0 0 s
~26~ Pernox t 0 0 0 0 - s
~ 2 ~1 AxpeKC = 0 0 0 0 0 ~ 1 l~
Z 3S I(8P8T8H 0 0 0 0 0 0 (3]
~ 29~ Ax~o 0 0 - o 0 0 0 [12~
Remark. "0"--the substance was not studied; "+"--positive effect; "--"--negative
effect; "�"--contradictory data; "+"--colchicine-Iike effect.
' Key:
1. Investigated substance 12. Kelthane
2. Mutagenicity on various ob~ects 13. Chlorocholine chloride
3. Microorganisms 14. Euparen
4. Fungi 15. Quoted from
5. Plants 16. BMC
6. Insects 17. Uzgen (benomyl)
7. Animal and human cells 18. Betanal
8. Laboratory animals 19. Pirimor
9. Cytogenetics 20. Alipur
10. Dominant lethals 21. Vernam
11. Literature 22. The eame
- /Key continued on following page/
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23. Prefix 27. Acrex
24. Propanid 28. Ra.rathane
25~ Ramrod 29. Anthio
26. Reglone
Itcan be seen from the results of the study of the cytogenetic effect of pestici-
des on bone marrow cells of mice (table 5) that nine substances- betanal, pirimor,
(alkyl ethers of aryl carbamic acid); alipur, vernam, sutan (thiocarbamic acid de-
rivatives); prefix, propanid, ramrod (carboxqlic acid derivatives) and acrex (phe-
nol derivative)--induced a significant increase in the frequencp of aberrant meta-
phases as com~ared with control.
As can be seen from the data presented in table 6, these pesticides differ in the
_ degree of potential mutagenic hazard.
Ramrod should be considered the most hazardous (group I). Its maximum cytogenetic
effect (4.5Y) exceeded the threefold control level significantly and the minimum
effec~ive dose (10 mg/kg, 1/30 LD50) pertained to the fourth level of effective
doses.
Pirimor. can be included in group II. It induced a cytogenetic effect in a wide
range of doses, including in relatively low (both in terms of weight and taxicity)
quantities. The minimum effective dose of pirimor was 2 mg/kg (,~1/50 LD50). The
maxi~um effect (3.1%) exceeded the twofold cantrol level sigaif icantly.
~ Betanal and acrex also induced a signif icant excess over the twofold cantrol level.
However, their minimum effeceive doses corresponded to the third level of effec-
tive doses, which gave reason to include these pesticides in group III. It should
be noted that betanal induced genome mutations, significantly increasing the fre-
quency of polypl~id metaphases in the bone marrow of mice.
Propanid was included in group IV. It induced a significant excess over.the cbn-
trol level only in the dose of 100 mg/kg, amounting to 1/5 LD5 (it is the mini-
mum effective dose and corresponds to the third level of effec~ive doses).
Alipur, vernam,. sutan and prefix induced a cytogenetic effect of the first degree
of manifestation only in high doses (500-1,000 mg/kg), which in all.cases exceeded
- 1/5 LD This gave reason to assume the nonspecific nature of this effect and to
include~the indicated pesticides in so-called "doubtful mutagens" (group V).
A total of 13 pesticides did not have a mutagenic effect on bane marrow cells of
mice and on the basis of the results of the cytogenetic study were included in
group VI as the least hazardous compounds.
It should be noted that the conclusion on the degree of potential genetic hazard
of the investigated pesticides drawn an the basis of their cytogenetic investiga-
tion is tentative and to some extent relative, which is due to the difficulty of
presently introducing a parameter making it possible to evaluate the universality
of the mutagenic effect. Theref ore, at this stage of investigations the practical
recommendations with regard to the studied compounds can be only of a temporary
comvromising nati~re with a tendency toward underestimatine pesticides as compo-
nents of rhe mutagenic background of the environment.
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~ Tahle 5. Fx~equency of Chromosome Aberrations in Bone Marrow Cells Under the Effect
of the Investigated Pesticidies
_ - .
- - ~3~ r/,l Sl 4ecno a6eppeuNi~- -
- S }.fccle~ji~~+~+oe eeu~ecr- ~(o~, Konxvecrno ~~cTdra weta� ~ xa opxy Mera~asy ~6 ~
~ eo ~r/Kr b~~tapp�xxdx ~aa c a6eppa- p
Mera~a~ w+sma, npou� ecero yccneAo- I a6ep-
pex~ �
~ eyro
KCJIbT&H (lO) lOO 6OO 1~00~0,40 1Z O~OIO 2,00 ~O~OS
b0 600 1,50�0,49 12 0~020 1,33 ~0,05
~Z1~ XaopxonxaxnopaA 100 600 1~,OOy-0,40 6 Q,O10 1,00 ~0,05
50 600 1,17-!-0,44 7 0,011 1,00 ~0,05 ,
50X5 600 0,67-!-0,33 4 0,006 I,00 ~0,05
9ynapea (1 2) 500 600 1,33~-0,47 8 0,013 1,00 >0,05
, 100 600 1,17~-0,44 ? O,OII 1,00 >0,05
~ Kynpauae (13) 1000 600 0,50=0,29 b 0,008 1,67 ~0,05 ~
' ' 500 600 1,001-0,41 6 0,010 1,00 ~U,05
f IionHn+apq~1H (14 1~ 600 1,50=0,50 9 0,015 I,00 )0,05
~ 100 fi0p 1,17~0,44 7 0,012 1,00 )0,05
~ BMK (15) 5~ 800 0,75-~0,30 6 0,075 1,00 ~0,05
1~ 800 1,50-~0,43 12 0,015 1,00 ]0,05
. Ysrex (16) l~ 600 1,17�0.44 7 0,012 l,pp >O,pS
5~ 600 0,83-!-0,37 b 0,008 1,00 >O,pS
500X5 600 1,33=0,47 8 O,Ol3 1,00 >0,05
Beraxan (1 7) l000 600 3,00=0,69 26 0,043 1,44 ~0,001
1~ 600 2,67-~0,66 1$ 0,030 1;12 C0,001
Ilxpxt~op (18) 50 1000 2,70-!-0,51 28 0,028 1,03 C0,001
. 1~ 1000 3,10-~0,55 34 0,034 1,10 C0,001
2 1000 2,40�0,48 ZT 0,027 1,15 C0,001
j ~.2 600 1,17=0,44 7 0,011 1,00 ]0,05
_ ~ Anenyp (19) ~ 600 2,33=0,61 15 0,02b 1,07 ~0,05
I 100 600 1,OOt0,40 6 0,010 1,00 >0,05
~ ~ 300 0,33=0,31 1 0~003 1,00 >0,05
~ Bepeau (20) ~ 600 3,00=0,69 18 0,030 1,00 0~05
; cy,a� (21) ~ooo soo 2,si=o,si i4 0,02o i,oo ~o,os
> 600 1,33~0,46 8 0,013 ~~pp )p~~
i 2M-4X 1~ 600 1,33~0,46 $ O,Ol3 l,pp >0,05
~ ~ 600 0,33~0,22 6 0,010 3~pp >O,Ob
~ IIpe~Hxc (22) 100~b gpp ~~83_p~b,} 11 O,OlB 1,00 0~~
~ nponanHll (23) 1 0 600 2,17~O,b9 14 0~020 1.p7 G0~05
~ ~WO 0,?b~0~43 3 0,007 l,pp >0~05
PaMpoA ( 24 100 600 4, b0=p, 84 27 0, 040 pg ~0, 001
~ ~ 600 3,17~0,71 20 0,030 i~p5 ~0.001
r 10 600 2,67_0,66 16 O,d27 l,pp ~G0~001
~ ~ 600 I~17=0,43 8 0,010 l~~p >0,05
Pernox (25) b0 600 1,00~0,40 6 0,010 ~~pp >0,05
~ AKpexc ~26~ 100 fi00 3,00-~0,69 18 0,030 1,00 C0,001
600 I,bO�0,49 16 0,030 1,80 >0.05
26 600 1,83=0,b4 I1 0,011 ~~pp C0,05
Kaparex (27) 2b 600 1,17~0;43 7 0,011 ~,pp >0,05
12,b fipQ 1,17~0,43 7 0,011 ~~pp ~0~~
5 600 0,67~0,34 5 0,008 1;20 ~O,Ob
AxTxo (28) 100 600 1,00�0,40 6 0,010 ~ pp
j 1~ 300 1,00�0,57 3 0,010 ~,00 ~0,05
~ spo~+~ ( 29 ) 5~ 600 1,16-!-0, 43 ? 0, O11 ~ pp ~0, 05
500Xb 600 1,00-!-0,40 6 0,010 ~~pp ~0,05
XocrarHOx ~gp~ 10 600 1,50~-0,49 9 0,015 1,00 >0,05
- 1 300 1,00=0,b7 3 0,010 1,00 >0,05
KOHTppJp~ ( 31) 2000 0, 70~ O, l y 17 0, 007 1, 00 -
28 /Key on following page/
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Key :
1. Investigated substance 16. Uzgea
2. Dose, mg/kg 17. Betanal
3. Number of investigated metaphases 18. Pirimor
- 4. Frequency of inetaphases with aber- 19. Alipur
rations, percent 20. Vernam
5. Number of aberrations 21. Sutan
6. Per metaphase 22. Prefix
7. Total 23. Propanid
8. Investigated 24. Ramrod
9. Aberrant 25. Reglone
10. Kelthane 26. Acrex
11. Chlorocholine chloride 27. Karathane
12. Euparen 28. Anthio
13. Cupracin 29. Bromophos _
14. Polymarcin 30. ~ostathion
15. BMC 31. Control
Table 6. Evaluation of the Degree of Potential Mutagenic Hazard of the Investigated
Pesticides
- - _ _ _ _ _ _ -
. r ~ea ~T Mama....~
~aa., (4)~ .5~~
i~ct~te A~P'"'"N" nores-
Ayewx ~raoR ryn.
ee~ec~rso x~p+~'nprctr~ rna~ o~e-
pax~r~~t: r~ ~ 04eau rr/a' Anj,~ O~t~a ~ oocr~
4wa. apon. .
(10) ~~R 4�~='0,~ Ss l0 1/30 A+ A.6= I
(11) .~PxKOp 3,14=0. b5 E~ 2 I/60 A~ A~B~ II ~
(lz)~ Beranan 3,00~0,69 6~ 100 1/2b A~ A~S~ III
(13) AtcpeKC 3,00�0,69 6~ 2b 's�ai ~I R j suo taoo
. x ~
~;,o ~ so~ .
, ms
: i r'! ry^~ % rl ~ 1i n r ~ns '
. ~=-..y:#:..;~~~'~'~,~~i~iti,~ 7t~ t~ ~ ~r~r~~
-c,oo -tcvo ~+,~x~ ~ f ~11 x~ iu~, ~un,~ : '-~ow , jo~ suo~ ~J
j~ 1
' ,
' i .'1 '1 , + � 2 ~ , r� 1 r mS t`< j,Q .
s t ~ i: i. ~ (1 ~ R'1. '1 r( ms
..~..T,.,.;t,,,~. : i41:
.'~`i"'""~,'X:�.. a ; ~ �,.,c.,~,
- -UPO ..SOJJ ~SpP ' ~ : ~ , lOCO :5~0 ' �~j. ,~s~':~~~ t (~I'`' ms became restless, aggressive, presented more
i 1 ~I.'. ti,': frequent motor reactions manifested by
--.f.~--,= , .
' u,oo_ ~c:~~+ lo,~ ~oo I
u o o t w i t c h i n g a n d e v e n c o n
v u l s i
v e seizures,
r' attempts to break away; some of them chewed
~ through the wires; there were instances of
_ ':,o , ms aggression against the experimenter. Some
n 7~ h animals urinated and defecated. After the
~ ~ ~i ' ' ~ . .,.~;:,...c' experiments, th~re was heightened motor
.~;,o~oi:~~~'o~~,oo` ~`iD01i activity in tfie rabbits' behavior� as soon
as the cage door was opened to give them
water or food, the rabbits lunged and
~ ms tipped the clish. This excited state was
? "..y~l-rr�!r~
` often associated with distinctive "~rowling."
< 1` n00 c:. ~ ` Ifi00 .100J
Some of these symptoms were associated in
some animals with passive defense reactions
Figure 7. of the "anxiety" [alarm] and "fear" type,
19t1~ experiment; stable persistence of while others were overtly in the nature
cross correlations. Conventional of aggressive "rage."
designations are the same as in
Flgure 4. After numerous stimuli, the changes in
various directions referable to the
hypothalamus- cortex and hypothalamus-ret~cular formation became very stable:
no appreciable change to the end of the experiment in response to the stimuli or
in the intervals between them, i.e., for 6-8 h(Figure 9). At this time, the
coefficient of variation for the curves of distribution of maximums of cross-
correlation functions was significantly lower than at the start of the experiment,
which was indicative of stabilization of cross correlations. In the next
113
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experiments (startinb wtth the second), such correlations were demonstrated in
background EEG acttvity even prior to delivery of electrodermal stimuli, which was
indicative of already formed pretriggering integration of the nociceptive emc,tional
r~action. In view of the fact that stressor features in tension rhythm analogous
to electrodermal stimuli were recorded also during the entire interval between
stimuli and persisted in subsequent experiments, we can mention a rather important
point: continuity of emotional tension in time during irregular delivery of stimuli,
which is i.ndicative of the animal's constant readiness for nociceptive stimuli
(Figure 9).
~ ~ ~~a-~ ,~~-,~!.1~~~.~; .,a, r~ r~ .r ~c r~: ~r n r i--s,,
S;"IC .~~w" v.v,~:.vM'.H.~r
TC w'rw~'^w~,�~'rwv~J4W~�y/~,wyKwr?.rM�av~,4n,MVrMW+~AN~'~'~1w.wN~~"'V/+M^P~,I~
OC ~-.~w�~M ~,~.+.wr,w.~w.,w.~.~.rw
KT~ ~ ~~wr,~
At~t ~ n~+a+'~w+~r~"vn+w'Iw~+~w'A~r~'hw,+w'~'~w+~'^+'~?'r~'~'w~M~h+'~M~+^~^~rrJ~~Y~kv~Mw~'
T hr~wNw~~+~"~'+WAt~n'e~v~t~h~yti4~r~k~rr,wvw,wu~~ti*Y,U^'~+'A~"'~'''?~^h"~~"f~'~h1`ti!!'~ti'~r�,wN f
HTp ~'~~~`~~~~~~~IY~1^~~II~iil~~n'A~~f'dA'"~i~~I~~i~}i~~~rtjY~~~~i~~'~~~~~I~Y~'nn~'~~il~~'~11i~~I1~Y':~If~l'
~
~ ~~1~1~''~+r'~~''w~~4~~~t~~~~'h~~P~~~~~'~~~~fl~r~~~hk
R ~~Rf~~4i~~+~i
~'~NIJ~~~~~ �''~N~~kn~~�~,~,in~u~~~Na11111~Illll~~pq~~'~1~~~~~lf d~+"i~l ~~I~~~puquu"f~~~~~
~ lin,~ill~~uii~ll I ~~llll ll+ud~l uli .I ~ ~ ~ ~ ~~I~II~~i~i~ilil~d,i /
i~~~'~i'~~~~III'^~ ~u~~,,,~~,,.,~~
' EKG p~Wlll~ lP~~ � ~IV~jy~'. ;~~~iG~~~7i~d1G;,!�~~..;,~,., ,:I~� ,:~~:c;~;i{i:
~ .
~ ~ ~i
EMG ~M~`n'~'~~`~
'
Figure 8. EEG, respiration (R), EKG and EMG following numerous deliveries
or irre~ularly timed electrodermal stimuli [same key as Figure 2]
Delivery of numerous irregularly timed stimuli [68, 76, 1 47] caused a decline of
cortical energy level and attenuation of its functional relations to the hypo-
thalamic emotiagenic zone, the excitability of which significantly increased
(Figure 10).
According to the conceptions of I. P. Pavlov, a decline of cortical functi4n and
its functional relation to the "subcortex" could be indicative of development of
"protective inhibition" in the higher parts of the brain when exposed to "excessive
stimuli."
Analysis of changes in parameters of tension rhythm of the cerebral cortex, as
related to the hypothalamus, revealed certain differences. Thus, EEG changes
111~
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occurring between the posterior hypothalamus and sensorimotor projection region,
where the most refined analysis of i~ociceptive stimuli is made, were the most
significant.
. _
Ccr lst experiment 21st experiment
'�0 r HT'
~ RF
a o,c - z ,
~f SMC
o
z "r' TP
_ ~
t(~ ms? ~
eu ~ MC
, HTp
b ,s
az
16
o - I FjTP
~c RF
t~ ms,j
0, relat.uni ~s _ _ _ _ m,1tl
so
+o �
c ~o HTp
to v ~
_
,u = SMC
n, relat.units
3co~ _ R
G
d
.oo
ioo
.
~
BG + a w to ~o ~o fo co ~o eo ~x� uo to ~o co eo ~oo ~~o wo
Number of nociceptive stiunuli
Figure 9. Graphic illustration of averaged hypothalamo-cortical (SMC-
- HTp [sensorimotor cortex--posterior hypothalamus] and hypotha-
_ lamo-reticular (HTp-RF) cross correlations in first group of rabbits:
1} interval between stimuli D) dispersion of tension rhythm
2) during delivery of~electrodermal stimuli n) heart rate (EKG) and
BG) background respiratory excurs~ons of
mXt) mathematical expectation ~ the chest (R)
This means that, in stress situations, the anterio~ parts of the brain were trie
most sensitive, vulnerable, and this could, first of all, disrupt processes of
afferent synthesis and affect making an adequate decision. Expressly these
neocortical elements are essentially the acceptors of deep emotiogenic stimuli
and participate in organization of complex forms of emotionally colored goal-
oriented behavioral reactions.
The question arises as to whether the above-described changes in parameters of ten-
sion rhythm are limited solely to emotiogenic subcortical structures of nociceptive
11S
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motivation and their projections in the cortex, or they also extend to interaction of
ttie posterior hypothalamus with other subcortical structures of the brain also in-
volved in forming negative emotional reactions. What distinctions are observed
here?
.
Background Emotional tension
SMC
1
_ ~
P ' . ` _r V ~
~
R~t(TJCCY'�0~6J R~,t(il CCr'0,99
VS ~ SMC-HTp VS �-67ms
SMC-HTp :o ~ + ~,o '
i ~ 9 ~ J ' raoo
w~~ 7�0~ 7oI 000 mg':1)-rooo -JOO oCu
Ccr � ~~d Ccr. ~0,99 .
HTp-RF ~ VS' ~TS ms HTp-RF VS � o
ta ''0
~ I ,1
y/-~~ 7 ` ?000
2~~~ :Spp V~ I~. !JO l000 mglt) H'0 D~0 -1 . y~
DSMC - 5-10 DSMC - 1-2�5
= DHTp = 10-15 DHTp = 24-30
D~, = 11-15 RF
_ Figure 10. Schematic illustration of hypothalamo-cortical (1) and hypothalamo-
reticular (2) changes in different directions
Key:
Ccr) coefficient of cross correlation [?--"Kkr" in source] D) dispersion
VS) expansion unknown
See Figure 2 for other ahbreviations.
To answer this question, we submitted tension rhythm of the posterior hypothalamus
in relation to slow EEG waves of the ventromedial hypothalamus, amygdala and
thalamus during formation of nociceptive stress to statistical processing.
Analysis of cross-correlograms (Figure 4) revealed that the slow waves of the
subcortical structures ~tudied were~es~entially synphasic before delivery of
electrodermal stimuli in relation to the posterior hypothalamus. The functional
relations determined from the maximum of cross-correlation functions of slow waves
of the posterior hypothalamus in relation to slow waves of subcortical structures
were on the average in the range of 0.6-0.7; they were highest in relation to the
medial thalamic nucleus and lowest to the ventromedial hypothalamic nucleus. The
_ first deliveries of electrodermal stimuli to the posterior leg of the rabbit induced
slight (16-25 ms) phase shifts in tension rhythm, mainly of the posterior and ventro-
medial hypothalamic nuclei and an increase in maximum of their cross-correlation
functions. These ctianges were less markPd than the cortico-hypothalamic parameters.
1.16
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After repeated electrodermal stimulation, the phase shifts betw~en these structures
increased to 67 ms and functional relations to 0.74 (Figure 5).
There3fter, the phase shifts reached an ave~age of 75 ms and became stabilized to
the end of the experiment, but the maximums of cross-correlation functions dropped
- to 0.3-0.35 (Figure 6). As for the amygdala, the phase shifts of electric poten-
tials did not change in relation to slow waves of the posterior hypothalamus. Of
course, there were analogous findings in the intervals between atimuli. However,
in this time, the other parameter of tension rhythm--maximum of cross-correlation
functions between these structures--increased (0.76).
After SO-70 stimuli, the phase shifts of slow waves between the amygdala and pos-
terior tiypathalamus began to increase to 68-70 ms, and they were associated with
- decline of functional relations to 0.37-0.4.
Subsequent delivery of numerous irregular electrodermal stimuli elicited an in-
crease in phase shifts between slow waves of the medial center of the thalamus and
posterior hypothalamus. Concurrently, the maximum of cross-correlation functions
between them dropped to 0.4-0.43. These relations between the posterior hypo-
- thalamus and analyzed subcortical structures became stabilized and persisted to
the end of the experiment (Figures 6, 7).
It should be noted that dispersion of tension rhythm increased in all of these sub-
cortical structures, but less than in the posterior hypothalamus and reticular
formation.
In analyzing the physiological mechanisms of pretriggering integration, it should
be noted that, as in the case of electrodermal stimuli, there were analogous
changes over the entire interval between stimuli. This was indicative of the
_ continuous nature of formed emotional tension with irregular stimuli.
Under these conditions, synphasic correlations and a high level of functional
relations of EEG tension rhythm between the ppsterior hypothalamus and reticular
- formation were found to be the most stable (Figures 6, 7).
- Thus, in the course of formation of nociceptive stress there were changes in
correlations between pacemaker structures of nociceptive motivation and projection
regions of the cortex, as well as various subcortical structures of the brain's
limbic system.
The process advanced against the attenuated background of interaction of projec-
tion zones of the cerebral cortex with the posterior hypothalamus. There was an
increase in phase discrepancies and decrease in functional relations of the ventro-
medial hypothalamus, amygdala and medial thalamic center with the posterior hypo-
thalamus. Disruption of relations b etween subcortical structures intensified
the state of tension. Indeed, we know from the literature that not only the
cerebral cortex, buC various subcortical structures of the limbic system can have
a restraining effect on emotiogenic centers of the posterior hypothalamus and
reticular formation.
We know [39J that reciprocal relations between electrical activity of anterior
and posterior parts of the hypothalamus xre disrupted under the influence of noci-

; ceptive stimuli. These changes alter hypothalamo-cortical correlations and cause
formation of negative emotional states.
117
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~ ~ : ms ~ms
~ /y~ , :
i ~ , 'f' . ~ ~ ' ~ A t ~ .i .
. t
f j � x t~, t a * r~~
c i ~ t ~ ~ ~ ~ ~ ~ ,ti~ ~ 3 u ;
_ ~co -i~ ; ' ' i ' f 1 ~ ~
_ < ~
- ~ ~sa ~cc '
c s e ...~~.s..yr~rn y+~+~+-~ .
_ ~ ' l, . . "
~ 6 ~ ; ~ ~ ~'fi~Y'.U t .
1' ~ ~ ~ s . 2 t ._..r �
, . ~y~ . ~ e . . .
: ~ 2 a IIjs+ ~ q;.,. , ~ ~r.~ L i II1S
' ~ � ~ . :r are ~.f ~ :
. . � ~.i.z t ~ ` # .
z I~ ' "T ~ ~ ~ ~
e ~ ~ ~.Y ~ < i
~h ~~'~~a.s.~ t ~ _ ~ ~ ( : . i~r~ i
,
~ ~ ~
T ~ ; j ~ '4~~, ~ ~ ~ '.~D F___~ ~
~ 'Y :f3"2 F~ ~ t T 1~ ~
i~ p,3~t S!'~~> t, e~'!~''~ ' j ' xs' e # :
:
: ` ?~'^b'-^..- ~..:...-}y..,. -r.f .
S, - ~Ee~~,~a t.ds7.~' ~ L x . ~ 7~t . . ~
�c .r ~ ~ Z . e r ( ~ r S
E . i .-r 4K. _....:._.Gj.:
~ ms ~ ~ , , ;
' ms
~ ~ : f . j ~ ~ 1
~ + ~ r t~~ , ' t ~ V'
a ~ ' ' :
~t e
~ t ~ � i~.i->Y 2 f 1~ ~ e~,
1 f a r U' ~ ~ ~ry~
E ` K