United States
Environmental Protection
Agency
Health Effects Research
Laboratory
Research Triangle Park NC 27711
EPA-600/1-80-012
January 1980
Research and Development
Chronic Toxicity of
Lead and Cadmium
I. Changes in the
Central Nervous
System of the
Parental
Generation of Rats
After Chronic
Intoxication with
Lead and Cadmium
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RESEARCH REPORTING SERIES
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EPA-600/1-80-012
January 1380
CHRONIC TOXICITY OF LEAD AND CADMIUM
I. Changes in the Central Nervous System of the Parental Generation
of Rats After Chronic Intoxication With Lead and Cadmium
By
Zbigniew. S. Herman, Krystyna Kmieciak-Kolada, Ryszard Szkilnik,
Ryszard Brus, Kornel Ludyga, Romana Winter, Jan Jonek,
Janusz Konecki, Jan Kusz, Jakub Bodziony,
Barbara Hebrewska, Kazimierz Kaminski,
Marie Ostrowska, Janwiga Wyrebowska,
and John Laskey
Departments of Pharmacology, Biochemistry
Cytology and Histology
Central Animal Farm of Silesian Medical Academy
in Katowice
Project Officer
John Laskey
Health Effects Research Laboratory
U.S. Environmental Protection Agency
Research Triangle Park, NC 27711
HEALTH EFFECTS RESEARCH LABORATORY
OFFICE OF RESEARCH AND DEVELOPMENT
U.S. ENVIRONMENTAL PROTECTION AGENCY
-------
DISCLAIMER
This report has been reviewed by the Health Effects Research Laboratory,
U.S. Environmental Protection Agency, and approved for publication. Approval
does not signify that the contents necessarily reflect the views and policies
of the U. S. Environmental Protection Agency, nor does mention of trade names*
or commercial products constitute endorsement or recommendation for use.
-------
ABSTRACT
This paper examines the effects of chronic exposure to trace amounts of
lead and cadmium on the central nervous system of male Wistar rats. Treat-
ments consisted of two levels of lead (5 or 50 ppm), two levels of cadmium
(0.1 or 5 ppm), and two combined dosages (5 ppm lead and 0.1 ppm cadmium,
or 50 ppm lead and 5 ppm cadmium). Treatments were administered in buffered
drinking water.
The lower dosages generally produced hyperactivity, while higher
dosages produced hypoactivity. Effects of lead and cadmium on biogenic
amines varied with dose and area of the brain. Biochemical analysis of
blood and urine showed no changes in the hematocrit or hemoglobin, but the
activity of Delta-ALA dehydratase and serum phosphatase were differentially
affected. Concentrations of lead and cadmium in the liver and kidney
increased, and positive interaction effects were noted.
The results suggest that the level of biogenic amines in discrete
brain areas is a very sensitive indicator of central nervous system
toxicity to lead and/or cadmium.
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SECTION 1
INTRODUCTION
Coal is a major source of energy in the USA and Poland. During
processing, the hazardous trace elements contiguous with coal ore, such
as lead (Pb) and cadmium (Cd), may be transferred to rivers and drinking
water sources resulting in chronic human exposure. In recent years, the
Pb and Cd content in the environment and in man has increased progres-
sively (12,13,14,15,16,20). In 1971, the annual averages of Cd,concentration
in air from ten cities in Poland ranged from 0.002 to 0.05 ug/m (16).
The brain, reproductive system and other organ systems may be targets
for the potentially toxic effects of these elements (14,17,18,19).
Taking into account the possible individual and synergistic effects of
chronic exposure to Pb and/or Cd, it seemed practical to study the
functional physiology of the central nervous and reproductive systems in
rats chronically exposed to trace amounts of Pb and/or Cd in the drinking
water.
In this paper we report the influence of these elements on the
central nervous system.
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SECTION 2
MATERIALS AND METHODS
Experiments were carried out on male Wistar rats, 40 days old, from
the Central Animal Farm of the Silesian Academy of Medicine. With the ex-
ception of the control group which contained 40 animals, the animals were
divided into groups consisting of 20 rats each and received via drinking
water (buffered with 0.005 M acetate) the following treatments.
Group I (Control)
Group II - 5 ppm lead
Group III - 50 ppm lead
Group IV - 0.1 ppm cadmium
Group V - 5 ppm cadmium
Group VI - 5 ppm lead and 0.1 ppm cadmium
Group VII - 50 ppm lead and 5 ppm cadmium
Behavioral Measurements
Because of the large numbers of animals to be tested, 24 hour
locomotor activity was assessed in two waves. Wave I consisted of a
control, 5 ppm Pb, 0.1 ppm Cd and 5 ppm Pb plus 0.1 ppm Cd; and Wave II
consisted of control, 50 ppm Pb, 5 ppm Cd and 50 ppm Pb plus 5 ppm Cd.
Rats were placed for 24 hours in a photocell actometer (1) and for the
next 24 hours in a motimeter (2). They had access to standard laboratory
feed and water for 1/2 hour following 6, 12 and 24 hours in each measuring
device for the length of the experiment. Impulses elicited by locomotor
activity were noted from counters every 12 hours.
Biogem'c Amine Assays
Rats were killed by cervical dislocation at the end of experiments.
The brains were quickly removed and placed on Petri dishes filled with
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ice and dissected into the hypothalamus, medulla oblongata plus pons,
hippocampus with nucleus accumbens and striatum essentially according to
Glowinski and Iversen (3). Spectrophotofluorometric analysis of noradren-
aline (NA), 5-hydroxytryptamine (5-HT), and 5-hydroxyindoleacetic acid
(5-HIAA) levels were done according to Miller et aj. (4) and dopamine
(DA) according to Cox et aJL (5).
Biochemical Studies
Blood samples were collected by heart puncture into heparinized
syringes under light ether anesthesia. The brain was perfused through
the subclavian and carotid arteries with 60 ml of saline cooled to 4°C.
The brain was removed and immediately frozen in dry ice, weighed and
homogenized in 5 parts of 0.067 M sodium phosphate buffer, pH 7.4 in a
teflon homogenizer and placed in a beaker filled with ice. Blood levels
of hemoglobin (6) and 6-aminolevulinic acid dehydratase E.G.4.2.1.24
(ALA-D) (7) were measured. Lactate dehydrogenase E.C.I. 1.1.27 (LDH)
activity was measured spectrophotometrically, alkaline phosphatase
E.C.3.1.3.1 (Al.Ph.) activity was estimated according to Bessey et aj.
(3), brain acetycholinesterase E.C.3.1.1.7 (AChE) activity was measured
according to Ellman et a_L (9), and brain monoamine oxidase E.C.I.4.3.4.
(MAO) activity was measured according to McEven and Cohen (10) using
benzylamine as a substrate. The level of coproporphyrin in the urine
was estimated according to Haeger-Aronsen (11). Lead and cadmium concentra-
tions in 1 gram aliquots of liver, kidney and drinking water were determined
on a Pye-Unicain SP90A Series 2 atomic absorption spectrophotometer.
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SECTION 3
RESULTS
Locomotor Activity
Continuous (40 days) exposure to Pb and/or Cd (5 ppm Pb or 5 ppm Pb
plus 0.1 ppm Cd) produced hyperactivity when measured in the photocell
apparatus or in the motimeter (Table 1). The 0.1 ppm Cd exposure group,
however, was hyperactive in the photocell apparatus and hypoactive in
the motimeter. Animals exposed to higher levels of Pb and/or Cd (50 ppm
Pb, 5 ppm Cd or 50 ppm Pb and 5 ppm Cd) were hypoactive in both measuring
devices. Ratios of diurnal-nocturnal activity did not show consistent
dose-related changes.
Neurochemical Analyses
NA and DA concentrations in brain areas are'presented in Tables 2
and 3. Chronic exposure to 5 ppm Pb did not change the NA concentrations
in the brain areas examined, but a decrease in DA concentrations in the
striatum were noted. Cd at 0.1 ppm decreased the level of NA in all
brain areas except the striatum, but lowered DA level in this area.
After simultaneous exposure to Pb and Cd (5 ppm Pb and 0.1 ppm Cd) only
a decrease in the NA level in hypothalamus was observed.
Pb at 50 ppm in the water resulted in a decrease in the NA con-
centration in all areas except the limbic system (hippocampus with
nucleus accumbens) and lowered DA levels in the striatum. Cd at 5 ppm
increased NA concentration in the hypothalamus. After exposure to 50 ppm
Pb + 5 ppm Cd, there was an increase in NA concentration in the hypothalamus
and a decrease in DA concentration in the striatum.
5-HT and 5-HIAA concentrations in brain areas are presented in Tables
4 and 5. Lead at 5 ppm resulted in increased concentration of both
5-HT and 5-HIAA in the hypothalamus. Cadmium at 0.1 ppm increased 5-HT
concentrations in the brain stem and 5-HIAA concentrations in the hypo-
thalamus and the striatum. Simultaneous administration of 5 ppm Pb +
0.1 ppm Cd increased the concentrations of both 5-HT and 5-HIAA in the
brain stem, 5-HT levels in the limbic system and 5-HIAA concentrations
in the hypothalamus and striatum.
Lead at 50 ppm decreased the 5-HT and 5-HIAA concentrations in the
hypothalamus and striatum. Five ppm Cd decreased the concentration of
5-HT fn the striatum. Simultaneous exposure to 50 ppm Pb and 5 ppm Cd
decreased the concentrations of both of 5-HT and 5-HIAA in the hypothalamus
and striatum.
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TABLE 1. LOCOMOTOR ACTIVITY (COUNTS/24 HR) FOLLOWING 40 DAYS EXPOSURE
TO Pb AND/OR Cda
Control
Photocell
Apparatus
(Day 1) 322
Mot i meter
(Day 2) 349
Control
Photocell
Apparatus
(Day 1) 1172
Moti meter
(Day 2) 304
5 ppm Pb
717*d
433
50 ppm Pb
723
89**
5 ppm Pb
+
0.1 ppm Cd 0.1 ppm Cd
696* 787*
201 395
50 ppm Pb
+
5 ppm Cd 5 ppm Cd
972 476*
156* 122*
b ANOVAC
SD P Value
P
83 <.01
51 <.05
ANOVA
SD P Value
129 <.01
32 <.01
a-N = 10 for each group.
b-SD = pooled standard deviation.
c-Significance level for the analysis of variance (ANOVA).
d-Values significantly different from control values by Dunnett's multiple comparison test
(**p<.01, *p<-05).
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TABLE 2. NORADRENALINE CONCENTRATION (ug/g) IN DISCRETE BRAIN AREAS .FOLLOWING LEAD AND/OR
CADMIUM EXPOSURE8
Brain area
Hypothal amus
Pons with Medulla
Oblongata
Hippocampus with
Nucleus Accombens
Striatum
Hypothal amus
Pons with Medulla
Oblongata
Hippocapmus with
Nucleus Accombens
Striatum
Control
2.79
0.78
0.55
0.20
Control
2.71
0.76
0.77
0.20
Pb 5 ppm
2.80
0.79
0.54
0.24
Pb 50 ppm
1.62**
0.68
0.75
0.13
Cd 0.1 ppm
2.50
0.66**d
0.47
0.21
Cd 5 ppm
5.83**
0.80 ,
0.69 ,
0.19
Pb 5 ppm + Cd 0.1 ppm
2.46
0.73
0.51
0.22
Pb 50 ppm + Cd 0.1 ppm
5.83**
0.71
0.71
0.19
SD b ANOVAC P Value
P
.28 <.05
.06 <.01
.28 N.S.
.09 N.S.
SDpb ANOVAC P Value
.44 <.01
.06 <.01
.13 N.S.
.09 N.S.
a-N - 10 for each group.
b-SD = pooled standard deviation.
c-Significance level from the analysis of variance (ANOVA).
d-Values significantly different from control values by Dunnett's multiple comparison test (**p<.01).
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TABLE 3. DOPAMINE CONCENTRATION (ug/g) IN STRIATUM FOLLOWING LEAD
AND/OR CADMIUM EXPOSURE3
Control
7.13
Control
9.27
Pb 5 ppm
6.05
Pb 50 ppm
6.39*
Cd 0.1 ppm
4.79*d
Cd 5 ppm
10.68
Pb 5 ppm
+ Cd 0.1 ppm
5.85
Pb 50 ppm
+ CD 5 ppm
7.51
V
1.74
V
2.34
ANOVAC P Value
<.01
ANOVA P Value
<.01
a-N = 10 for each group.
b-SD = pooled standard deviation.
c-Significance level from the analysis of variance (ANOVA).
d-Values significantly different from control values by Dunnett's multiple
comparison test (*p<.05).
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Biochemical Analyses
No significant changes in hematocrit of hemoglobin were noted
in animals on any exposure regimen. Delta-ALA dehydratase activity in
erythrocytes was significantly decreased by exposure to 50 ppm Pb, 50
ppm Pb plus 5 ppm Cd, and 5 ppm Pb plus 0.1 ppm Cd but not by exposure to
5 ppm Pb. Neither serum AChE nor serum LDH were altered by any treatment.
Serum alkaline phosphatase activity was increased by treatment with 0.1
ppm Cd, 5 ppm Cd and 50 ppm Pb plus 5 ppm Cd.
Brain MAO activity was reduced by both Cd treatments and Pb-Cd
treatments, however, only the 5 ppm Pb treatment caused reduced activity
(Table 6). Brain AChE activity was significantly reduced by 50 ppm Pb
and 50 ppm Pb-5 ppm Cd combination (Table 6).
Twenty-four hour urinary coproporphyrin was unaffected by the low
doses of Pb and/or Cd treatment but decreased more than 50% by 50 ppm Pb
and increased more than 250% by the 50 ppm Pb-5 ppm Cd combination.
Concentration of Pb and Cd in Tissues
Cadmium and Pb concentrations in the liver and kidney are presented
in Table 7. It should be noted that the Pb treated animals when simul-
taneously treated with Cd showed increased liver and kidney Pb concentra-
tions over that resulting from Pb treatment alone. Likewise, when Cd
treated animals are simultaneously treated with Pb, liver and kidney Cd
concentrations are higher than with Cd treatment alone. No measurable
quantities of Pb or Cd were found in the drinking water.
8
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TABLE 4. 5-HYDROXYTRYPTAMINE CONCENTRATIONS (jig/g) IN DISCRETE BRAIN AREAS FOLLOWING LEAD AND/OR
CADMIUM EXPOSURE3
Brain area
Hypothalamus
Pons with Medulla
Oblongata
Hippocampus with
Nucleus Accombens
Striatum
Hypothal amus
Pons with Medulla
Oblongata
Hippocapmus with
Nucleus Accombens
Striatum
Control
2.50
1.04
0.61
1.07
Control
2.72
1.03
0.99
1.09
Pb 5 ppm
3.01**d
1.08
0.61
1.00
Pb 50 ppm
1.95
0.98
0.99
0.70**
Cd 0.1 ppm
2.59
1.25**
0.67
1.02
Cd 5 ppm
2.73
1.11
•i
1.03
0.83*
Pb 5 ppm + Cd 0.1 ppm
2.54
1.30**
0.68
1.18
Pb 50 ppm + Cd 5 ppm
2.04**
1.04
0.98
0.86
SO,, ANOVAC P Value
P
.28 <.01
.09 <.01
.32 N.S.
.32 N.S.
SO b ANOVAC P Value
.32 <.01
.13 N.S.
.09 N.S.
.19 <.01
a-N - 10 for each group.
b-SD = pooled standard deviation.
c-Significance level from the analysis of variance (ANOVA).
d-Values significantly different from control values by Dunnett's multiple comparison test (**p<.01, *p<.05).
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TABLE 5. 5-HYDROXYINDOLEACETIC ACID CONCENTRATION (ug/g) IN DISCRETE BRAIN AREAS FOLLOWING LEAD
AND/OR CADMIUM EXPOSURE3
Brain area
Hypothal amus
Pons with Medulla
Oblongata
Hippocampus with
Nucleus Accombens
Striatum
Control
2.
0.
0.
0.
27
70
99
98
Control
Hypothal amus
Pons with Medulla
Oblongata
Hippocapmus with
Nucleus Accombens
Stri atum
2.
0.
0.
0.
33
72
61
98
Pb
2.
0.
1.
0.
Pb
1.
5 ppm
88**d
73
08
94
50 ppm
75**
0.74
0.
0,
65
77
Cd
2.
0.
1.
1.
Cd
1.
0.
0.
0.
0.1 ppm
85*
64
06
12
5 ppm
87**
88
79
82
Pb 5 ppm + Cd 0.1 ppm
2.
0.
1.
1.
Pb 50 ppm
1.
0.
0.
0.
69*
83
00
37
+ Cd 5 ppm
47**
76
78
69
b
SDP
.35
.32
.25
.44
b
SDP
.28
.09
.13
,44
ANOVAC P Value
<.05
N.S.
N.S.
N.S.
ANOVAC P Value
<.01
N.S.
N.S.
N.S.
a-N - 10 for each group.
b-SD = pooled standard deviation.
c-Significance level from the analysis of variance (ANOVA).
d-Values significantly different from control values by Dunnett's multiple comparison test (**p<.01, *p<.05).
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TABLE 6. MONAMINE OXIDASE AND ACETYLCHOLINE ESTERASE (ug/min/g) CONCENTRATIONS IN WHOLE BRAIN FOLLOWING
LEAD AND/OR CADMIUM EXPOSURE3
Analysis
Monoamine Oxidase
Acetylcholine
Esterase
Control
1.49
Control
1.61
Control
10.3
Control
12.0
Pb 5 ppm
0.70
Pb 50 ppm
1.57
Pb 5 ppm
9.1
Pb 50 ppm
4.2**d
Cd 0.1 ppm
0.51
Cd 5 ppm
0.76
Cd 0.1 ppm
10.7
Cd 5 ppm
10.4
Pb 5 ppm + Cd 0.1 ppm
1.00
Pb 5 ppm + Cd 5 ppm
0.33
Pb 5 ppm + Cd 0.1 ppm
10.4
Pb 50 ppm + Cd 5 ppm
8.7*
b
SDP
1.14
— P
1.55
SDpb
2.86
2.66
ANOVA0 P Value
N.S.
ANOVA P Value
N.S.
ANOVAC P Value
N.S.
ANOVA P Value
<.01
a-N - 10 for each group.
i
b-SD = pooled standard deviation.
c-Significance level from the analysis of variance (ANOVA).
d-Values significantly different from control values by Dunnett's multiple comparison test (**p<.01, *p<.05).
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TABLE 7. LIVER AND KIDNEY LEAD OR CADMIUM CONCENTRATIONS FOLLOWING
40 DAYS EXPOSURE3
5 ppm Pb + 50 ppm Pb
5 ppm Pb 0.1 ppm Cd 50 ppm Pb +5 ppm Cd
Liver Pb . . .
Concentration, 2.3 ± 0.2 2.7 ± 0.3° 2.7 ± 0.3° 3.2 ± 0.5°
M9/9
Kidney Pb .
Concentration, 2.1 ± 0.3 2.4 ± 0.3 2.3 ± 0.2 2.7 ± 0.4
pg/g
0.1 ppm Cd 5 ppm Cd
0.1 ppm Cd +5 ppm Pb 5 ppm Cd + 50 ppm Pb
Liver Cd h
Concentration, 0.52 ± 0.10 0.59 ± 0.08 0.63 ± 0.18 0.68 ± 0.11°
Kidney Cd h K h
Concentration, 0.59 ± 0.05 0.80 ± 0.07° 0.75 ± 0.11° 0.95 ± 0.23°
a-N for each group =10.
b-Significantly different from the low dose by Dunnett's multiple
comparison test (p<0.05).
12
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SECTION 4
DISCUSSION
These results indicate that chronic exposure to 50 ppm Pb and 5 ppm
Cd for 40 days in drinking water to young rats is deleterious to CNS
function. Higher concentrations of Pb generally lowered both NA and DA
concentrations in brain areas measured. Exposure to 5 ppm Pb increased
the concentration of 5-HT in the hypothalamus, and the concomitant
treatment of the 5 ppm Pb group with 0.1 ppm Cd had the same effect in
the brain stem. Inversely it seem that treatment with 50 ppm Pb decreased
5-HT in the hypothalamus and striatum. The higher Cd exposure level
depressed the 5-HT concentration in the striatum.
These results indicate that estimation of the level of biogenic
amine levels in discrete brain areas is a very sensitive indicator of
CNS toxicity to Pb and/or Cd. Both agents have a different profile of
action on adrenergic and serotoninergic neurons in the discrete brain
areas measured in this study. No relationship between the levels of
biogenic amines and MAO activity was seen. The decrease of AChE activity
observed in animals exposed to high Pb levels may be interpreted as an
influence of this metal on cholinergic neurons. Shih and Hanin (24), in
a study with rats exposed from infancy to 4% lead acetate in chow, showed
a decrease in acetylcholine concentrations in cortex, hippocampus, midbrain
and striatum by 35, 54, 51 and 33%, respectively. This finding provides
evidence for an inhibitory effect of Pb on the central cholinergic
function jn vivo. There is some experimental evidence that biogenic
amines in the CNS act by the adenylcyclase-315'cyclic AMP system (27,28,29,30,31).
Very low concentrations of Pb or Cd inhibited adenylate cyclase activity
in homogenates and particulate fractions of rat cerebellum and cerebral
cortex. On the other hand, Pb stimulated and Cd inhibited phosphodies-
terase activity (25).
Our results indicate that both heavy metals penetrated the brain.
It was stated by others (26) that Pb penetrates the brain and is
concentrated in cortical grey matter and basal ganglia whereas Cd does
not readily penetrate the brain. All of these effects appear to be species
dependent. Biochemical examinations carried out in our experiments have
shown some typical signs of Pb and Cd intoxication. They also indicate
that LDH and /'ihE activity in serum have no value as a diagnostic factor
in Pb and Cd intoxication in rats. A dose dependent increase in serum
alakaline phosphatase activity was seen with Cd treatment. The sig-
nificance of this will be confirmed in studies currently in progress.
Our data suggest that a brief Pb and/or Cd exposure affects the subtle
functions of the CNS. The toxicological importance of these changes
requires further elucidation.
13
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Metal Toxicity. Mol. Pharmacol. 12, 390-398.
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25. Task Group of Metal Accumulation (1973). Accumulation of Toxic
Metals with Special Reference to Their Absorption, Excretion and
Biological Half-times. Environmental Physiology. Biochem., 3,
65-107.
26. Tagliamoate, A., Tagliamonte, P., Forn, J., Parez-Ornest, J.,
Krishna, G., Gessa, G. L. (1971). Stimulation of Brain Serotonin
Synthesis by Dibuhyryl-cyclin AMP in Rats. J. Nenrochem., 18,
1101-1196.
27. Bucher, M. B., Schorderet, M. (1975). Dopamine- and Aoamorphine-
sensitive Adenylate Cyclase in Homogenates of Rabbit Retina, Arch.
Pharmacol., 288, 103-107.
28. Forn, J., Krishna, G. (1971). Effect of Norepinephrine, Histamine
and Other Drugs on Cyclic 3',5'-AMP Formation in Brain Slices of
Various Animal Species. Pharmacology, 5, 193-204.
29. Nahorski, S. R., Smith, B. M. (1976). Stimulated Formation of
Cyclic AMP in Different Areas of Chick Brain. Eur. J. Pharmacol.,
40, 273-278.
30. Vetulani, J. (1977). Role of Cyclic Nucleotides in Receptor
Mechanisms. Arch. Pharmacol., 297, S45-S46.
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TECHNICAL REPORT DATA
(Please read Instructions on the reverse before completing)
1. REPORT NO.
EPA-600/1-80-012
2.
3. RECIPIENT'S ACCESSION NO.
CHRONIC TOXICITY OF LEAD AND CADMIUM I. Changes in the
Central Nervous System of the Parental Generation of
Rats After Chronic Intoxication With Lead and Cadmium.
5. REPORT DATE
January 1980
6. PERFORMING ORGANIZATION CODE
7HerTnanR, Kmieciak-Kolada, Szkilnik, Brus, Ludyga,
Winter, Jonek, Konecki, Kusz, Bodziony, Hebrowska,
l^am-incb-i He-f-yrii.ic I/a Uf\/yohr\uiclf a anH I aglf py.
8. PERFORMING ORGANIZATION REPORT NO.
9.
. PERFORMING ORGANIZATION NAME AND ADDRESS
Departments of Pharmacology, Biochemistry, Cytology
and Histology
Central Animal Farm of Silesian Medical Academy in
Katowice, Poland.
10. PROGRAM ELEMENT NO.
1AA817
11. CONTRACT/GRANT NO.
JB5-531-1
12. SPONSORING AGENCY NAME AND ADDRESS
Health Effects Research Laboratory
U.S. Environmental Protection Agency
Research Triangle Park, NC 27711
John W. Laskey - Project Officer
13. TYPE OF REPORT AND PERIOD COVERED
Interim Report
14. SPONSORING AGENCY CODE
EPA/600/11
15. SUPPLEMENTARY NOTES
16. ABSTRACT
This paper examines the effects of chronic exposure to trace amounts of lead and
cadmium on the central nervous system of male Westar rats. Treatments consisted of
two levels of lead (5 or 50 ppm), two levels of cadmium (0.1 or 5 ppm), and two combined
dosages (5 ppm lead and 0.1 ppm cadmium, or 50 ppm lead and 5 ppm cadmium). Treatments
were administered in buffered drinking water.
The lower dosages generally produced hyperactivity, while higher dosages produced
hypoactivity. Effects of lead and cadmium on biogenic amines varied with dose and area
of the brain. Biochemical analysis of blood and urine showed no changes in the hemato-
crit or hemoglobin, but the activity of Delta-ALA dehydratase and serum phosphatase
were differentially affected. Concentrations of lead and cadmium in the liver and
kidney increased, and positive interaction effects were noted.
The results suggest that the level of biogenic amines in discrete brain areas
is a very sensitive indicator of central nervous system toxicity to lead and/or
cadmium.
17.
KEY WORDS AND DOCUMENT ANALYSIS
DESCRIPTORS
b.IDENTIFIERS/OPEN ENDED TERMS C. COSATI Field/Group
Lead
Cadmiurn
Intoxication
06, T,C
18. DISTRIBUTION STATEMENT
Release to Public
19. SECURITY CLASS (This Report)
Unclassified
21. NO. OF PAGES
20
20. SECURITY.CL.ASS
Unclassified
(This page)
22. PRICE
EPA Form 2220-1 (R«v. 4-77) PREVIOUS EDITION is OBSOLETE
17
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