EPA-560/1-76-005
CHEMICALS WHICH HAVE BEEN
TESTED FOR
NEUROTOXIC EFFECTS
MAY 1976
FINAL REPORT
ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF TOXIC SUBSTANCES
WASHINGTON, D.C.
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EPA-560/1-76-005
CHEMICALS WHICH HAVE BEEN TESTED
FOR NEUROTOXIC EFFECTS
Final Report
May 1976
Contract 68-01-3255, Task 4
Office of Toxic Substances
Invironmental Protection Agency
Washington, D.C. 20460
Frank Letkiewicz
Project Officer
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NOTICE
This report has been reviewed by the
Office of Toxic Substances, EPA, and
approved for publication. Approval does
not signify that the contents necessarily
reflect the views and policies of the
Environmental Protection Agency, nor does
mention of trade names or commercial pro-
ducts constitute indorsement or recommen-
dation for use.
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PREFACE
This document presents information obtained from the literature on
substances that have been tested for neurotoxic effects. Damage to the
central and/or peripheral nervous systems is an important category of
hazards from chemicals that enter the human environment. A variety of
chemicals are known to be neurotoxic and there are many reported incidents
of chemically induced neurotoxicity in humans. However, this category of
hazards has received far less attention than other hazards such as cancer
and birth defects.
Recognizing this, the office of Toxic Substances (OTS) initiated a
task to collect reports of chemicals tested for neurotoxic activity
published in the scientific literature. One intention of this task was to
develop a data base which could be utilized by the Office of Toxic Substances
in developing techniques for correlating reported effects (in this case neuro-
toxic effects) of substances with their chemical and/or physical properties.
At the same time, it was recognized that the data base developed would be
the first such compilation of information, and, as such, could find use
an.ong other persons or organizations concerned with adverse health effects
induced by chemicals. Therefore, it was decided that the collected data
should be made available through publication. It should be noted that
reports of tests for neurotoxic effects yielding both positive and negative
findings were extracted for this document.
For the purpose of this task, neurotoxic effects are defined as
structural or functional damage to the nervous system, such as, histological
changes in nerve tissue, grossly observable dysfunction (e.g., paralysis),
ir.strumentally detectable dysfunction (e.g. electroencephalographic changes),
and performance dysfunction (e.g., using the rotating rod test for balance).
Qualitative effects such as hallucinations or mental depression were also
included in the case of reports on humans. Teratological findings affecting
the offspring of pregnant females exposed to chemical substances were included.
Biochemical disturbances in the nervous systems produced by chemical
substances were generally not included; some exceptions are: inhibition of
the enzyme cholinesterase and other esterases present in the nervous system,
GABA levels, and serotonin levels.
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Problems of terminology were met in the literature at every stage of
the task. Technical terms were found to be used in different senses, often
imprecisely, so that the degree and often the type of dysfunction was dif-
ficult to infer from many of the reports. In such cases it was impossible
to modify the terms to conform to a meaningful, consistent nomenclature.
Thus, the descriptive medical terms used in the extracts are generally the
authors' own.
This problem was most apparent in the literature search. Most of the
secondary sources are not indexed by general terms for neurotoxicity.
It was necessary, therefore, to perform much of the literature searching
by scanning primary publications directly. Practical constraints resulted
in the ability to scan only select journals, and many of those only for
select years of publication. However, the selection of journals and other
sources searched provided for a reasonably thorough coverage of the subject.
The sources employed in the literature search are listed in the appendix.
ii
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Table of Contents
Page
Preface i
Introduction . . iv
Extracts
Index 1231
Appendix 1330
iii
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Introduction
The text of this document consists of a series of brief extracts of
studies in which chemicals were tested for neurotoxic effects. A separate
extract was prepared for each chemical reported in each article. The
extracts, which are arranged in alphabetical order by subject chemical,
are a structured arrangement of data as presented in the original articles.
Each review contains, if it was available, the following information:
Compound; the subject chemical of the study. The chemical nomenclature
used is that established by the Chemical Abstracts Service for
their 8th Collective Index.
Reference; a complete bibliographic citation, consisting of author(s),
journal, volume, issue, pages and year of publication.
Observed neurotoxic effects; reported dysfunctions and structural changes
of the nervous system effected by exposure to the subject compounds.
Animals; species, variety, age, sex, and weight of the test animals.
Preparation and Dose or History of Patient; preliminary treatment of test
animals, quantity of compound administered, and duration of exposure.
Route and Site; method and location of administration of the compound.
Control Information; preparation and treatment of control animals.
Duration of experiment; period of time during which the test animals
were observed.
Exam. Type; general technical procedures employed in the study.
iv
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The following is a list of the abbreviations used in the extracts.
atm - atmosphere
av - average
CD,.. - the dose which was calculated
'' to cause convulsions in 50%
of the animals
cmpd - compound
CN!> - central nervous system
d •• day
ED,.. - the dose which was calculated
' to be effective for 50% of the
animals for the test employed
F -• female
g -• gram
GAM - gamma-aminobutyric acid
grp - group
in;i - injection
I.]'. - intraperitoneal
I.Tub. - intubation
IU - international unit
I.V. - intravenous
kg - kilogram
LDrn - the dose which was calculated
to be lethal to 50% of the
animals
M -• male; mole
MA(! - Maximum acceptable concentration
mcCi - microcurie
meg - microgram
mEq - milliequivalent
mg - milligram
min - minute
ml - milliliter
mM - millimole
mo - month
ns - not stated
PNS - peripheral nervous system
P.O. - per os
ppm - parts per million
sacr. - sacrificed
S.C. - subcutaneous
sec - second
soln - solution
TLV - threshold limit value
trtd - treated
untrtd - untreated
wk - week
w/v - weight/volume
yr - year
An index has been prepared to facilitate the use of this document. To
loc:ate a compound in the text, one should first look it up in the index.
The. index will identify the page(s) of the text dealing with the compound.
It will also identify the class of chemical, selected neurotoxic effects
induced by the chemical, and reported human exposure to the chemical. The
ind.ex can also be used to identify the chemicals in a given class, chemicals
which induce selected neurotoxic effects, and chemicals for which incidents or
studies involving humans have been reported.
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COMPOUND: Acetaldehyde
000075070
REFERENCE: Schneider, F.H.
Biochem. Pharm. 23:223-229, 1974.
OBSERVED NEUROTOXIC EFFECTS:
Total catecholamines expressed as micromoles of
epinephrine. Rate of release Increased with time of
exposure to acetaldehyde; concentration-
response curve shifted to left with acetaldehyde
but not with carbachol. When cone, of acetaldehyde
was lowered below 2 x 10" M, delay of peak
response increased. Withdrawal of acetaldehyde
returned catecholamine levels to normal.
COMPOUND: Acetaldehyde, chloro-, (2,4-dinitrophenyl) hydrazone
005135808
REFERENCE: Ambrose, A.M., Borzelleca, J.F., Larson, P.S., Smith, R.B., Jr.,
and Hennigar, G.R.
Tox. Appl. Pharm. 8:472-481, 1966.
OBSERVED NEUROTOXIC EFFECTS: Subacute: 1500 and higher levels, hindlimb rigidity.
Chronic: 1000 ppm, at 15th mo. episodic hindlimb
ataxia, later convulsions, no lesions
reported at autopsy.
ANIMALS: Bovine adrenals.in vitro.
ANIMALS: Dogs, purebred beagle, 2 M and 2 F, age 6 mo.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Adrenals 10-20 g perfused with Tyrode soln at
37° containing acetaldehyde at 1.5 x 10 to 2.5
x 10 M. Perfusate was analyzed for total catecholamines.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0, 100, 400, 1000 ppm in diet for 2 yr (chronic toxicity);
Subacute studies 0-3000 ppm.
ROUTE AND SITE: Perfusion was retrograde via adrenal vein, at 10 ml/min.
CONTROL INFORMATION: Some adrenals were perfused with carbachol.
ROUTE AND SITE: oral
CONTROL INFORMATION: Zero treatment
DURATION OF EXPERIMENT: About 2 hr.
EXAM. TYPE: Biochemical
DURATION OF EXPERIMENT: 2 yr
EXAM. TYPE: Behavior, biochemistry (clinical), autopsy
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COMPOUND: Acetamide, 2-fluoro-N-methyl-N-l-napthyl
005903139
REFERENCE: Hashimoto, Y., Noguchi, T., Mori, T. and Kltagawa, H.
Tox. Appl. Pharm. 13:174-188, 1968.
COMPOUND: Acetanilide, 2'-(2-bromo-3-thienyl)thio-
REFERENCE:
Grol, C.J. and Rollema, H.
J. Med. Chem. 18:857-861, 1975.
OBSERVED NEUROTOXIC EFFECTS:Toxic or lethal doses produced EEC's with no evidence
of convusive pattern, but a flat wave pattern before death
indicated severe brain impairment. Toxicity, judged small,
was attributed to the metabolite, monofluoroacetic
acid.
OBSERVED NEUROTOXIC EFFECTS: This compound gave positive results in a
neurotoxicity screening test in which the
criteria were ptos'is, sedation and catalepsy.
ANIMALS: Eats, albino, M, 150 g Rabbits
10 Mice, M, 20 g Cats
10 Guinea-pigs, albino, M, 350 g Dogs
In vitro • Monkeys
PREPARATION AND DOSE
or HISTORY OF PATIENT: Manyschedules and dosages, acute and chronic; some animals
prepared surgically.
ANIMALS:
Rats and mice, no details
PREPARATION AND DOSE
or HISTORY OF PATIENT: 40 mg/kg.
ROUTE AND SITE: Various
CONTROL INFORMATION: Various
ROUTE AND SITE: I.P.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Many: EEC relevant here.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior screening tests
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COMPOUND: Acetanllide, 4'-(4-(3-dimethyl amino)propyl)-l-piperazinyl)-
COMPOUNO: Acetanilide, 2'-(3-thienyl)thio-
REFERENCE: Benitz, K.F. and Kramer, A.W.
Fd. Cosmet. Toxicol. 6: 125-133, 1968.
REFERENCE:
Grol, C.J. and Rollema, H.
J. Med. Chem. 18:857-861, 1975.
OBSERVED NEUROTOXIC EFFECTS: Hydrocephalus, oedema, hyperaemla and lesions of the
brain. Vacuolization of the choroid plexus.
OBSERVED NEUROTOXIC EFFECTS: This compound gave positive results in a
neurotoxiclty screening test in which the
criteria were ptosis, sedation and catalepsy.
ANIMALS: Rats (CFN and Sherman), Mongolian Gerbils, Swiss Albino Mice,
African Green Monkeys and Miniature Pigs (Pitman-Moore strain)
ANIMALS:
Rats and mice, no details
PREPARATION AND DOSE
or HISTORY OF PATIENT: 60-488 mg/kg/d
PREPARATION AND DOSE
or HISTORY OF PATIENT: 40 mg/kg.
ROUTE AND SITE: Oral, gavage
CONTROL INFORMATION: ns
ROUTE AND SITE: I.P.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: Serial Sacr. 2 d to 50 wk
EXAM. TYPE: Histology
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior screening tests
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COMPOUND: Acethydrazide
001068571
REFERENCE: Jenney, E.H. and Pfeiffer, C.C.
J. Pharm. Exp. Ther. 122: 110-123, 1958.
OBSERVED NEUROTOXIC EFFECTS: Convulsions
COMPOUND:
Acetic acid, bis(p-chlorophenyl)- (DDA, a metabolite of DDT)
REFERENCE: Bleiberg, M.J., Cefaratti, M., Klinman, N. and Kornblith, P.
Tox. Appl. Pharm. 4:292-312, 1962.
OBSERVED NEUROTOXIC EFFECTS:
Blocked patellar reflex at doses over 2 mg/rabbit;
in vitro block on choline acetylase, probably at
the acetate activating .step, in brain, and blocked
in vitro peristalsis of gut preparations.
Interpreted in terms of mode of action of toxicity
of DDT.
ANIMALS: Mice, Harlan, 19-21 g
PREPARATION AND DOSE
or HISTORY OF PATIENT: 2.1 mM/kgm
ROUTE AND SITE: I.P.
CONTROL INFORMATION: ns
ANIMALS: (1) Rabbits, white, 2.5-3.5 kg, surgically prepared.
(2) Rabbit small intestine in vitro.
(3) Guinea-pig ileum in vitro.
(4) Rabbit brains, powdered and acetone-dried.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Sodium salt of DDA used.
(1) In vivo single or successive doses 0.4-2.3 mg/rabbit,
(2&3) 10"^ to 10"-* M in medium, various schedules and
combinations.
(4) AChE inhibition by 10 mcgM DDA in vitro.
ROUTE AND SITE: In vivo: intra-arterial, lumbar.
CONTROL INFORMATION: Yes
DURATION OF EXPERIMENT: Acute
EXAM. TYPE: Clinical
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Biochemistry, electrophysiology
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COMPOUND: Acetic acid, cyano-, hydrazide
REFERENCE: Jenney, E.H. and Pfeiffer, C.C.
J. Phann. Exp. Ther. 122: 110-123, 1958.
OBSERVED NEUROTOXIC EFFECTS: Convulsions
COMPOUND: Acetic acid, (2,3-dichloro-4-(2-methylenebutryl) phenoxy)-
000058548
REFERENCE: Schneider, W.J. and Becker, E.L.
Arch. Inter. Med. 117:715-717, 1966.
OBSERVED NEUROTOXIC EFFECTS: Acute deafness.
ANIMALS: Mice, Harlan, 19-21 g
ANIMALS: 5 Humans: 4 F, 1M, age 20-76
PREPARATION AND DOSE
or HISTORY OF PATIENT: 1.8 mM/kgm
PREPARATION AND DOSE
or HISTORY OF PATIENT:
150-700 mg.
ROUTE AND SITE: i.p.
CONTROL INFORMATION: ns
ROUTE AND SITE: I.V. and oral
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: Acute
EXAM. TYPE: Clinical
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Clinical, behavior, urinalysis
10
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COMPOUND: Acetic acid, 2,4-dichlorophenoxy-
COMPOUND:
Acetic acid, 2,4-dichlorophenoxy-
REFERENCE: Desi, I. and Sos.J.
Acta Med. Acad. Sci. Hung. 18: 429-433, 1962.
REFERENCE: Desi, I., Sos, J. and Nikolits, I.
Acta Physiol. Acad. Sci. Hung. 22: 73-80, 1962.
OBSERVED NEUROTOXIC EFFECTS: Acute studies: reversible EEC inhibition. Chronic:
gradual slowing of EEC and shortening of desynchron-
ization times; disordered conditioned reflexes
OBSERVED NEUROTOXIC EFFECTS:
EEC: Lower frequency and greater amplitude at
24 hr; after 5 d, big, slow, toxic waves predominated.
Little or no desynchronization response to reticular
formation stimuli. The authors concluded that DCPA
acted first on the cortex; the thyroid and cardiac
disturbances being attributed to secondary subcor-
tical lesions.
ANIMALS: 24 rats, white, M, 240-250 g
4 cats
2 dogs
PREPARATION AND DOSE
or HISTORY OF PATIENT: 200 mg/kg/d (rat I.P. LD5Q reported as 640 mg/kg)
ANIMALS: 15 cats, 2.5-3.5 kg, 11 treated, all surgically prepared
PREPARATION AND DOSE
or HISTORY OF PATIENT: 100 mg/kg/d 11 d
ROUTE AND SITE: I.P.
CONTROL INFORMATION: Untreated
ROUTE AND SITE: ns
CONTROL INFORMATION: 4 cats
DURATION OF EXPERIMENT: Up to 6 d
EXAM. TYPE: Behavior, electrophysiology
DURATION OF EXPERIMENT: 15 d
EXAM. TYPE: EEC
11
12
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COMPOUND: Acetic acid, (2,4-dichlorophenoxy)-
OOOOQA7S7
REFERENCE: Goldstein, N.P., Jones, P.H. and Brown, J.R.
J. Am. Med. Assn. 171:1306-1309, 1959.
OBSERVED NEUROTOXIC EFFECTS:
Peripheral neuropathy. Delayed and prolonged
polyneuritis, especially of lower limbs, slow
nerve conduction, incomplete recovery.
ANIMALS: 3 Humans
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Exposure during horticulture.
ROUTE AND SITE: Skin absorption
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: 3 yr.
EXAM.. TYPE: Clinical, electophysiology
13
COMPOUND: Acetic acid, (2,4-dichlorophenoxy)-, compound with dimethylamine (1:1)
002008391
REFERENCE: Berkley, M.C. and Magee, K.R.
Arch. Int. Med. 111:351-352, 1963.
OBSERVED NEUROTOXIC EFFECTS: Peripheral neuropathy, mainly sensory, gradual
imporvement after "several weeks".
ANIMALS:' 1 Human, M, age 39
PREPARATION AND DOSE
or HISTORY OF PATIENT: Exposure to agricultural spray
ROUTE AND SITE: skin contact, probable inhalation
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: Follow-up for 9 mo.
EXAM. TYPE: Physical; clinical laboratory; electromyography
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COMPOUND: Acetic acid, (ethylene-dinitrilo) tetra-
000060004
REFERENCE:
Swenerton, H. and Hurley, L.S.
Science 173:62-63, 1971.
COMPOUND: Acetic acid, fluoro-, sodium salt
000062748
REFERENCE:
Corsi, A. and Granata, A.L.
Biochem. Pharmacol. 16:1083-1089, 1967.
OBSERVED NEUROTOXIC EFFECTS: Hydrocephalus, anencephalus, hydranencephalus,
exencephalus, prevented by 1000 ppm of zinc in diet
but not by 100 ppm. Author suggests the congenital
anomalies caused, may be due to zinc deficiency.
OBSERVED NEUROTOXIC EFFECTS: No effect on respiration of brain mitochondria
with any substrate. No effect on oxidation of glucose. Citrate found
higher in brain homogenates from trtd rats, but this could not be reproduced
in vitro.
ANIMALS: Rats,.S-D, F, 210 g.
ANIMALS:
Rats, Uistar
PREPARATION AND DOSE
or HISTORY OF PATIENT:
(1) 2% or 3% in diet throughout.
(2) 3% in diet from d 6 to 21, or d 6-14 of
pregnancy, followed by control diet until
term.
(3) 3% in diet, plus 1000 ppm of zinc from d 6-21.
ROUTE AND SITE: Oral
CONTROL INFORMATION: Rats fed control diet, without compound.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 20 mg/kg one dose, rats killed after 1 hr, brain mitochondria
incubated in vitro with various substrates, slices and homogenates of brain
cortex incubated with/without glucose.
ROUTE AND SITE: i.p., incubation In vitro.
CONTROL INFORMATION: Laboratory controls
DURATION OF EXPERIMENT: Pregnancy
EXAM. TYPE: Teratology
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry
15
16
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COMPOUND: Acetic acid, imlnodi
000142734
REFERENCE: Curtis, D.R. and Watkins, J.C.
J. Neurochem. 6:117-141, 1960.
OBSERVED NEUROTOXIC EFFECTS:
Treatment caused excitation or depression of
neuronal activity. Excitatory ranking: glutamic,
S-aminoglutaric, aspartic, cysteic, cysteine-
sulfinic acids, 8-hydroxyglutamic, N-methylaspartic,
N-formiminoaspartic acids.
Depressant ranking: B-alanine, GABA, taurine,
N-methyl-B-alanine, 6-amino-B-hydroxybutyric,
glycine, a-alanine, 6-aminovaleric, B-aminoisobutyric
acids.
Structure-activity relationships established.
ANIMALS: Cats, surgically prepared to exposed motoneurones, Renshaw cells or
dorsal horn interneurones in lumbar cord.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Qualitative doses.
COMPOUND: Acetic acid, lead (2+) salt
000301042
REFERENCE: Brown, S., Dragann, N. and Vogel, K.H.
Arch. Env. Hlth. 22:370-372, 1971.
OBSERVED NEUROTOXIC EFFECTS: No significant effects on learning or memory
of rats as tested in water-filled T-maze.
ANIMALS: Rats, S-D, M, aged 8 d to 5 wk.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 100 mg/kg/d, 3-4 in. most cases.
ROUTE AND SITE: Topical, iontophoresis
CONTROL INFORMATION: Laboratory
ROUTE AND SITE: I.P.
CONTROL INFORMATION: Rats sodium acetate treated.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry, electrophysiology
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior
17
18
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COMPOUND: Acetic acid, lead (2+) salt
000301042
REFERENCE: Carson, T.L., Van Gelder, G.A. Karas, G.C. and Buck, W.B.
Env. Hlth. Persp. 7:233-237, 1974.
OBSERVED NEUROTOXIC EFFECTS:
Poor performance of auditory discrimination task
by adults, no change in reinforcement behavioral
task. Lambs, no change in closed-field maze task,
slow learning of nonspatial two-choice visual
discrimination tasks at 10-15 mo. of age after
prenatal exposure.
ANIMALS;. . Sheeps, 3 grps. of 5 adults and 5 grps of 4 lambs.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Adults: 100 mg/kg/d for 9 wk, 120 and 230 mg/sheep/d
for 27 wk.
Lambs: Exposed prenatally, 16 or 34 mcl/100 ml of blood,
postnatal 2-16 mg/kg/d in diet.
ROUTE AND SITE: Oral, transplacental
CONTROL INFORMATION: Untreated controls
DURATION OF EXPERIMENT: Up to 15 mo.
EXAM. TYPE: Behavior
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COMPOUND: Acetic acid, lead (2+) salt
000301042
REFERENCE: Goiter, M. and Michaelson, I.A.
Science 187:359-360, 1975.
OBSERVED NEUROTOXIC EFFECTS: More active than controls; more norepinephrine,
no change of dopamine in brains (opposite findings to previous report,
see under Lead carbonate, Sauerhoff and Michaelson.
ANIMALS: Rats, S-D, F, pregnant 16 d
PREPARATION AND DOSE
or HISTORY OF PATIENT: (B) Neonates 1 mg of Pb in 0.1 ml for 15 d, then 40 ppm
Pb in diet.
(C) Dams 5% Pb-acetate in diet till neonates 16 d old, then 40 ppm Pb
in diet; neonates 40 ppm in diet from d 16, weaning.
ROUTE AND SITE: oral
CONTROL INFORMATION: (A) Dams untrtd; neonates 0.1 ml of 2% Na-acetate d 1-15,
then weaned onto normal diet.
DURATION OF EXPERIMENT: Serial sacr to 81 d of age of neonates.
EXAM. TYPE: Behavior, biochemistry
20
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COMPOUND:
REFERENCE:
Acetic acid, lead (2+) salt
000301042
Michaelson, I.A. and Sauerhoff, M.W.
Env. Hlth. Persp. 7:201-225, 1974.
COMPOUND: Acetic acid, lead (2+) salt
000301042
REFERENCE: Michaelson, I.A. and Sauerhoff, M.W.
Toxicol. Appl. Pharin. 28:88-96, 1974.
OBSERVED NEUROTOXIC EFFECTS:
30% less food eaten by lactating dams, offspring
had 85% more lead than controls in cerebellum and
cerebral cortex with 10-20% less DNA in cerebellum at
3 wk of age, paraplegia and cerebellar damage after
eating lead diet. After 25 ppm lead in diet
encephalopathy less severe: hyperactivity,
tremors, stereotype behavior, 15-20% decrease of .
dopamine but no change in 5-HT, GABA or NE, no
"debilitating histopathology."
OBSERVED NEUROTOXIC EFFECTS: Histological lesions in the cerebellum and
paraplegia. Hyperactivity, aggressiveness
and tremors.
ANIMALS:
Rats, Forton, newborn with dams.
ANIMALS: Rats, S-D pregnant and offspring.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
4.5 or 5% in diet fed to dams and, at weaning, to litters.
Diet gave 2.73% Pb, and produced milk containing 25 ppm
Pb. Some diets adjusted to contain 25 ppm Pb.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 5% in diet to mothers immediately after birth, when
offspring were 16 d old, mother's diet was changed to
25 ppm lead to compare to that in maternal milk.
ROUTE AND SITE: Oral
CONTROL INFORMATION:
Diets without lead, pair-feeding controls
ROUTE AND SITE: Oral
CONTROL INFORMATION: Control sucklings, no treatment to mothers
DURATION OF EXPERIMENT: 30 d
EXAM. TYPE: Behavior, biochemistry
DURATION OF EXPERIMENT: Sucklings sacr at 25 d age.
EXAM. TYPE: Histology
21
22
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COMPOUND: Acetic acid, lead (2+) salt
000301042
REFERENCE: Schlaepfer, W.W.
J. Neuropath. Exp. Neurol. 28(3): 401-418, 1969.
OBSERVED NEUROTOXIC EFFECTS: Segmental demyelination and remyelination in peripheral
nervous system and spinal nerve roots. Wallerian degen-
eration present in distal peripheral nervous system and
in posterior nerve roots.
PNS: 6/14 axonal or Wallerian degeneration and
9/14 segmental demyelination and remyelination.
Spinal cord: Wallerian and segmental change.
COMPOUND: Acetic acid, lead (2+) salt
000301042
REFERENCE: Silbergeld, E.K. and Goldberg, A.M.
Life Sci. 13:1275-1283, 1973.
OBSERVED NEUROTOXIC EFFECTS: Induced hyperactivity (not dose-related), peripheral
ataxia ar.d splayed gait. 10 mg/ml for 90 days
produced convulsions and death.
ANIMALS: 18 Rats, S-D, 200-250 gm.
ANIMALS: Mice, age 12 hr
PREPARATION AND DOSE
or HISTORY OF PATIENT: 1% soln., avg. 60 cc/rat/d.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 2, 5, or 10 mg/ml in drinking water
ROUTE AND SITE: Oral
CONTROL INFORMATION: 3 Rats untreated.
ROUTE AND SITE: Oral
CONTROL INFORMATION: Age and dose matched with sodium acetate
DURATION OF EXPERIMENT: Serial sacr 3-18 mo.
EXAM. TYPE: Ultrastructural, histochemistry
DURATION OF EXPERIMENT: 90 d
EXAM. TYPE: Behavior
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24
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COMPOUND: Acetic acid, mercaptophenyl-, ethyl ester, S-ester with 0,0-dimethyl
phosphorodithioate
REFERENCE: Sherman, M., Ross, E. and Chang, M.T.Y.
Tox. Appl. Pharm. 6:147-153, 1964.
OBSERVED NEUROTOXIC EFFECTS: (D Convulsions followed in many by death within
18 hr. Survivors were lethargic for 6-19 hrs.
post treatment. (2) 50% cholinesterase inhibition
by dose <50 ppm.
COMPOUND: Acetic acid, thallium (1) salt
000563688
REFERENCE: Spencer, P.S., Peterson, t.K., Madrid, R. and Raiiie, C.3.
J. Cell Biol. 58: 79-95, 1973.
OBSERVED NEUROTOXIC EFFECTS: Mitochondria in axons of peripheral nerve fibers were
enlarged after 2 hours, then mitochondria swelled to
become axonal vacuoles, which coalesced, and the
outer membranes had affinity for thallium which is
electron-dense. Swelling made myelin retract from
nodes of Ranvier, but there was no degeneration, and
conduction was not lost. There were similar changes,
but less severe, in dorsal root ganglia and central
fibers, but not in other cell types.
ANIMALS: Cockerels, White Leghorn, single-comb, 10-50/grp, 12 d old
ANIMALS: In vitro cross-sections of fetal mouse spinal cord with dorsal root
ganglia, 14 d in utero
PREPARATION'AND DOSE
or HISTORY OF PATIENT: (i) Acute: LD (56.6 mg/kg) in gelatin capsule.
(2) Subacute: 50-800 ppm in feed.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 10 meg/ml
2 x 10~5M
ROUTE AND SITE: Oral
CONTROL INFORMATION: Untreated diet.
ROUTE AND SITE: in vitro
CONTROL INFORMATION: Laboratory
DURATION OF EXPERIMENT: 1 wk
EXAM. TYPE: Mortality, behavior, blood ChE
DURATION OF EXPERIMENT: Cultures grown for 12 wk, exposed to thallium for up to 4 d
EXAM. TYPE: Histology
25
26
-------
COMPOUND: Acetic acid, p-tolyl-, 3-alpha-tropanyl ester
REFERENCE: Friess, S.L. and Anderson, J.B.
Tox. Appl. Pharm. 22: 208-212, 1972.
COMPOUND: Acetic acid, zinc salt
000557346
REFERENCE: Prakash, N.J., Fontana, J. and Henkin, R.I.
Life Sci. 12(1):249-259, 1973.
OBSERVED NEUROTOXIC EFFECTS:
With the above compound or its quaternary methiodide
separately, there was reversibility of induced blockade
on washing depending on the extent of N-substitution,
quaternary methiodide being more reversible than the
tertiary ester. But 1 mM of tropine-£-tolylacetate
added to 5mM of its quaternary methiodide halved the
reversibility of quaternary methiodide blockade. More
than 1 mM of tropine-2.-t°lylacetate had no more effect.
OBSERVED NEUROTOXIC EFFECTS: At concentrations over 0.1 mM, Zn"1"1" completely
inhibited (Na+ + K+) ATPase. Inhibition involved
blockage of norepinephrine and choline uptake.
ANIMALS: In vitro excitable nodes of Ranvier in single fibers of frog sciatic
nerve.
ANIMALS:
Rat brain synaptosomes in vitro
PREPARATION AND DOSE
or HISTORY OF PATIENT: 5mM for separate incubations with tropine-p_-tolylacetate and
its quaternary methiodide; tropine-£-tolylacetate:the quater-
nary methiodide ratios in mixed incubations 1:5, 2:5, and
3:5 in mM.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Zn acetate added to medium in various expts.
ROUTE AND SITE: in vitro
CONTROL INFORMATION: Laboratory
ROUTE AND SITE: in vitro
CONTROL INFORMATION: Lab
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Incubation, removal, washing, observing by electrophysiology
DURATION OF EXPERIMENT: Minutes
EXAM. TYPE: Biochemistry
27
28
-------
COMPOUND: Acetone
000067641
REFERENCE:
Ross, D.S.
Ann. Occup. Hyg. 16:73-75, 1973.
OBSERVED NEUROTOXIC EFFECTS: Urine level at least 4.6-7.15 mg% after exposure,
0.39-1.29 mg% 7 d later. Dizziness, unconsciousness,
with recovery.
COMPOUND: Acetone, allophanylhydrazone
REFERENCE: Jenney, E.H. and Pfeiffer, C.C.
J. Pharm. Exp. Ther. 122: 110-123, 1958.
OBSERVED NEUROTOXIC EFFECTS: Convulsions
ANIMALS: 7 Human cases of industrial exposure
ANIMALS: Mice, Harlan, 19-21 g
PREPARATION AND DOSE
or HISTORY OF PATIENT: 900-12,000 ppm 2 min - 4 hr (acute exposure).
PREPARATION AND DOSE
or HISTORY OF PATIENT: 2.5 mM/kgm
ROUTE AND SITE: inhalation
CONTROL INFORMATION: None
ROUTE AND SITE: i.p.
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: 7 d ttmt afterwards
EXAM. TYPE:Clinical, urinalysis
DURATION OF EXPERIMENT: Acute
EXAM. TYPE: Clinical
29
30
-------
COMPOUND: Acetone semicarbazone
000110203
REFERENCE: Jenney, E.H. and Pfeiffer, C.C.
J. Pharm. Exp. Ther. 122: 110-123, 1958.
OBSERVED NEUROTOXIC EFFECTS: Convulsions
ANIMALS: Mice, Harlan, 19-21 g
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.78 mM/kgm
ROUTE AND SITE: i.v.
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: Acute
EXAM. TYPE: Clinical
31
COMPOUND: Acetone, thiocarbohydrazone
REFERENCE: Jenney, E.H. and Pfeiffer, C.C.
J. Pharm. Exp. Ther. 122: 110-123, 1958.
OBSERVED NEUROTOXIC EFFECTS: Convulsions
ANIMALS: Mice, Harlan, 19-21 g
PREPARATION AND DOSE
or HISTORY Of PATIENT: 0.27mM/kgm
ROUTE AND SITE: I.P.
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: Acute
EXAM. TYPE: Clinical
32
-------
COMPGUiiD:
Acetone, thiocarbohydrazonodi-
REFERENCE: Jenney, E.H. r,nd Ffeiffer, C.C.
J. Pharra. Exp. Thor. 122: 110-123, 1958.
OBSERVED KEUROTOXIC EFFECTS: Convulsions
ANIMALS: Mice, Harlan, 19-21 g
PREPARATION AND DOSE
or HISTORY Of PATIENT: 0.55
ROUTE AND SITE: I.P.
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: Acute
EXAM. TYPE: Cllulr.al
33
COMPOUND: Acetone thiosemicarbazone
001752303
REFERENCE: Jenney, E.H. and Pfeiffer, C.C.
J. Pharm. Exp. Ther. 122: 110-123, 1958.
OBSERVED NEUROTOXIC EFFECTS: Convulsions
ANIMALS: Mice, Harlan, 19-21 g
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.18 mM/kgm
ROUTE AND SITE: I.P.
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: Acute
EXAM. TYPE: Clinical
-------
COMPOUND: Acetophenone, 2-chloro
000532274
REFERENCE: Rutledge, C.O. and Dietrich, R.A.
Biochem. Pharmacol. 20:193-201, 1971.
OBSERVED NEUROTOXIC EFFECTS: Inhibited norepinephrine catabolism. Inhibited
formation of phenolic acids and enhanced that of
phenolic glycols. In vitro aldehyde dehydrogenase
was inhibited (prevented with glutathione, reversed
with sulfhydryl reagents).
COMPOUND:
Acetophenone, thiocarbohydrazone
REFERENCE: Jenney, E.H. and Pfeiffer, C.C.
J. Phartn. Exp. Ther. 122: 110-123, 1958.
OBSERVED NEUROTOXIC EFFECTS: Convulsions
ANIMALS:. Rabbits, adult M, 2.0-2.5 kg.
ANIMALS: Mice, Harlan, 19-21 g
PREPARATION AND DOSE
or HISTORY OF PATIENT: In vivo pretreatment: 300 mg/kg in 100% EtOH (1.33 g/kg) .
In vitro incubation of brain cortex xlices (150 mg)
with and without 2-chloroacetophenone.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 1.2 tnM/kgm
ROUTE AND SITE: I.P.; addition to medium.
CONTROL INFORMATION: Pretreatment: ethanol only. In vitro: HC1.
ROUTE AND SITE: i.p.
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: In vitro: 30-40 min.
EXAM. TYPE: Biochemical
DURATION OF EXPERIMENT: Acute
EXAM. TYPE: Clinical
35
36
-------
COMPOUND: Acrylamlde
000079061
REFERENCE: Auld, R.B. and Bedwell, S.F.
Can. Med. Assn. J. 96:652-654, 1967.
COMPOUND:
Acrylamide
000079061
REFERENCE:
Barnes, J.M.
Erie. J. Indust. Med. 27:147-149, 1970.
OBSERVED NEUROTOXIC EFFECTS:
Contact dermatitis with polyneuropathy of extremities
attributed to sympathetic overactivity. Complete
recovery in 3 mo. "Believed" to have resulted
from acrylamide, and claimed as the first human
case-report.
OBSERVED NEUROTOXIC EFFECTS:
(1) Most rats died within a few days. The
rest had signs of gross general weakness.
(2) Within four weeks, signs of disability
appeared; marked by eight weeks.
ANIMALS: Human: 1 case-report, M aged 21 yr.
ANIMALS: Rats> Porton( albino
PREPARATION AND DOSE
or HISTORY OF PATIENT: Industrial exposure to 10% aqueous solution 35 hr/wk,
signs after 2 wk, hospitalized after 3 mo.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
(1) Two doses, 100 mg/kg
(2) 400 ppm
ROUTE AND SITE: Skin contact, especially face and forearms
CONTROL INFORMATION: None
ROUTE AND SITE: Oral
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: Observations total 6.5 mo.
EXAM. TYPE: Clinical, hospital laboratory
DURATION OF EXPERIMENT: 10 wk
EXAM. TYPE: Behavior, physiology
37
38
-------
COMPOUND: Acrylamide
000079061
REFERENCE: Edwards, P.M.
Br. J. Ind. Med. 32:31-38, 1975.
COMPOUND: Acrylamide
000079061
REFERENCE:
Fullerton, P.M. and Barnes, J.M.
Br. J. Indust. Med. 23:210-221, 1966.
OBSERVED NEUROTOXIC EFFECTS:
(1) Rats: Ataxia, waddling gait, hindlitnb weakness.
(2) Hens: Slight ataxia; degeneration of sciatic
and peroneal nerve fibers and medullary
and cervical spinocerebellar tracts.
(3,4) Frogs, goldfish: sublethel effects varying
with dosage-.
OBSERVED NEUROTOXIC EFFECTS:
Ataxia and limb weaknesses at single or repeated
doses of 25-100 mg/kg (gavage) or 100-400 ppm
(diet). Severe cases 20%.slower nerve conduction.
Degeneration of myelin and axis cylinders in
long fibers of peripheral nervous system. On
stopping treatment, clinical recovery, normalized
conduction, and some histological regeneration.
ANIMALS: (i) Rats, Porton, M, 200 g
(2) Hens, Star Cross, adult, 3 leg
(3) Frogs, R. Temporaria, M
(4) Goldfish
PREPARATION AND DOSE
or HISTORY OF PATIENT: Dose varied with species
ANIMALS: Rats, Porton, M and F, various ages.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
ROUTE AND SITE: (1) Oral, I.P.
(2) Oral
CONTROL INFORMATION: „ u. ,
Vehicles only
(1) 100 mg/kg, one dose, or two doses on successive days.
(2) 50 mg/kg/d, 12 doses in 15 d.
(3) 25 mg/kg/d, 5 d/wk.
(4) 10 mg/kg/d for 55 or 116 doses.
(5) 100 mg/kg twice/wk, once/wk, once/10 d, once/14 d.
(6) Diets with 0-400 ppm (greatest intake 30 mg/kg/d).
(3) Dorsal sac injection or via exposure
(4) Through natural habitat
ROUTE AND SITE: Gavage or oral (diet).
CONTROL INFORMATION: only in (6), diet alone.
DURATION OF EXPERIMENT: Up to 13 wk
EXAM., TYPE: Behavior, histology
DURATION OF EXPERIMENT: up to 52 wk.
EXAM. TYPE: Behavior, electrophysiology, histology
39
40
-------
COMPOUND: Acrylamide
000079061
REFERENCE: Fullerton, P.M.
J. Neurol. Neurosurg. Psychiat. 32:186-192, 1969.
COMPOUND: Acrylamide
000079061
REFERENCE: Hashimoto, K. and Ando, K.
Biochera. Pharm 22:1057-1066, 1973.
OBSERVED NEUROTOXIC EFFECTS: Sural nerve biopsies from the lateral malleolus
(ankle), showed degeneration and regeneration
thought to have begun before onset of symptoms.
Sensory nerve action potentials were weak or absent;
motor conduction was slow.
OBSERVED NEUROTOXIC EFFECTS: Hindlimb weakness at 2 wk, paralysis at 4 wk,
clinical recovery 5-6 wk after ttmt ended. In-
corporation of labeled lysine and methionine into
proteins of sciatic nerve and spinal cord altered
by compound.
ANIMALS: Human: 3 cases, M (already reported by Garland & Patterson 1967).
ANIMALS: Rats, SD, M, 8 wk old. Groups of 3, 5, or 15.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
ROUTE AND SITE: ns.
CONTROL INFORMATION:
(1) Exposure for 1 mo, symptoms then progressive for
2 mo.
(2) Exposure for 6 wk, then severely disabled after 6 wk.
(3) Exposure for 18 mo, then symptoms progressive for
2 mo and recovery incomplete 10 wk later.
None
PREPARATION AND DOSE
or HISTORY OF PATIENT: 500 ppm in "Oriental M" powder diet for 4 wk, followed
by 4 wk control diet.
ROUTE AND SITE: Oral
CONTROL INFORMATION: Groups fed powder diet only.
DURATION OF EXPERIMENT: Up to 2-1/2 yr
EXAM. TYPE: Electrophysiology, histology
DURATION OF EXPERIMENT: Up to 6 wk after ttmt, sacr
EXAM. TYPE: Behavior; radioautography; biochemistry.
41
-------
COMPOUND: Acrylamide
000079061
REFERENCE: Igisu, H., Goto, I., Kawamura, Y., Kato, M., Izumi, K. and
Kuroiwa, Y.
J. Neurol. Neurosurg, Psychiat. 38:581-584, 1975.
OBSERVED NEUROTOXIC EFFECTS: Signs appeared 3 wk after act of contamination,
subacute mental confusion and/or truncal ataxia;
good recovery within 4 mo.
ANIMALS: Human: 1 family of 5 (F 65, M 42, F 40, M 13, F 10)
PREPARATION AND DOSE
or HISTORY OF PATIENT: Well-water found to contain 400 ppm, from roadworks
performed 1 mo. before sampling; exposure max 4 wk.
ROUTE AND SITE: oral, skin contact
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: l mo., plus follow-up 4 mo.
EXAM. TYPE: Clinical, electrophysiology
43
COMPOUND: Acrylamide
000079061
REFERENCE: Kaplan, M.L., Murphy, S.D. and Gilles, F.H.
Tox. Appl. Pharm. 24:564-579, 1973.
OBSERVED NEUROTOXIC EFFECTS:
Cumulative total to produce neurologic deficit
was 360 mg/kg in controls, to 600 mg/kg in Pheno-
barbital-premedicated. The latter and young rats
had severe peripheral nerve damage; unpretreated
adults did not. Rotarod appratus used to measure
neurologic deficit.
ANIMALS: Rats, Holtzman, M, 200-300 g or 5 wk old.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Daily aq soln, various compounds given to modify
the "neurologic deficit." Complex schedules. Some
rats adrenalectomized.
ROUTE AND SITE: I.p., in vitro
CONTROL INFORMATION:
DURATION OF EXPERIMENT:
EXAM. TYPE: Behavior, histology, in-vitro.
44
-------
COMPOUND: Acrylamide
000079061
REFERENCE:
Kuperman, A.S.
J. Pharm. Exp. Ther. 123:180-192, 1958.
OBSERVED NEUROTOXIC EFFECTS:
Lethal doses produced convulsions; sublethal
doses produced ataxia and tremors like cerebellar
asynergia. No other biological effects, no
histological alterations. Primary site of non-
convulsive action was subcortical, diffuse; author
infers the mesencephalic tegmentum as the primary
site of intoxication.
COMPOUND: Acrylamide
000079061
REFERENCE: Leswing, R.J. and Ribelin, W.E.
Arch. Env. Hlth. 18: 22-29, 1969
OBSERVED NEUROTOXIC EFFECTS: Paralysis, especially hindlimbs, at higher dosage
in monkeys. Conduction in sciatic nerves 28% slower in cats, 22% in monkeys,
20% in ulnar nerve of monkeys, with longer latencies. Degeneration of myelin
and axons in affected nerves. When treatment stopped, signs improved.
ANIMALS: Cats, intact and surgically prepared: spinal cord transection,
decerebellation, decortication, or decerebration.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Nonconvulsive doses of 1-50 mg/kg/d. Convulsive single
doses of 75-1000 mg/kg. Many schedules used, acrylamide
99.2% pure in water.
ANIMALS: (1) 11 cats, unselected young adults
(2) 4 Cebus albifrons monkeys
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) Cats: 20 mg/kg/d
(2) Monkeys: 20 mg/kg/d for 8 wk, then 30 mg/kg/d
ROUTE AND SITE: z.v. Or I.P.
CONTROL INFORMATION: None
ROUTE AND SITE: oral
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: Different schedules.
EXAM. TYPE: Behavior, EEC, histology.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior, electrophysiology, histology
45
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COMPOUND: Acrylamlde
000079061
REFERENCE: McCollister, D.D., Oyen, F. and Rowe, V.K.
Tox. Appl. Pharm. 6:172-181, 1964.
COMPOUND: Acrylamide
000079061
REFERENCE: Morgan-Hughes, J.A., Sinclair, S. and Durston, J.H.J.
Brain 97:235-250, 1974.
OBSERVED NEUROTOXIC EFFECTS:
Weakness and ataxia, starting in hindlimbs. Re-
covery of survivors prolonged according to dose(s);
"no nerve tissue pathology has been found in the
affected animals, not even in those severely
intoxicated to the point of death."
OBSERVED NEUROTOXIC EFFECTS:
Peripheral neuropathy, flacid weakness of the
hindlimbs, retarded nerve growth. Axonal degeneration
Crush injury healed in 8 wk in controls, healing
delayed or inhibited in those treated. Less
regeneration and when regeneration occured it was less
than usual.
Monkeys, F (no other details)
ANIMALS: Rats, Dow-Wistar, M and F, about 60 d old
Guinea-pigs, M
Rabbits, M and F
Cats (no details)
PREPARATION AND DOSE
or HISTORY OF PATIENT: Various schedules
ANIMALS:
20 Rats, Wistar, 300-440 g.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 200 ppm (12 rats) or 300 ppm (2 rats) in diet. Right
sciatic crush injury 7-22 wk after start of experiment.
ROUTE AND SITE: Gavage (one dose); skin contact; eye contact; I.P.; I.V.; diet
(oral)
CONTROL INFORMATION: Zero dosage
ROUTE AND SITE: Oral
CONTROL INFORMATION:
14 matched rats, untreated.
DURATION OF EXPERIMENT: Up to 1 yr (diet, cats and monkeys)
EXAM. TYPE: Clinical, pathology
DURATION OF EXPERIMENT: Up to 30 wk after sciatic crush
EXAM. TYPE: Electrophysiology, histology, clinical
47
48
-------
COMPOUND: Acrylamide
000079061
REFERENCE: Prineas, J.
J. Neuropath. Exp. Neurol 28(4):598-621, 1969.
COMPOUND: Acrylamide
000079061
REFERENCE: Schaumberg, H.H., Wlsniewski, H.M.,and Spencer, P.S.
J. Neuropathol. Exp. Neurol 33:260-284, 1974.
OBSERVED NEUROTOXIC EFFECTS:
Left tibial nerve and right anterior horn
cells of cord showed "dying-back changes"
of axons. Subcellular changes differed from
those due to TOCP. Behavior "was very similar
to that seen in TOCP intoxication," progressive
weakness of limbs starting with hind limbs.
OBSERVED NEUROTOXIC EFFECTS: Unsteady gait, head tremor and distal muscle
weakness. Loss of peripheral myelinated fibers,
unmyelinated were preserved. Degeneration of Pacinian
corpuscles, muscle spindles, and some neuromuscular
junctions, consistent with dying back.
ANIMALS: 6 Cats, M and F, 2.5-4.0 kg.
ANIMALS: 12. Cats, 3 aged 1 yr or more, 9 aged less.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
(1) 5 cats: 10 mg/kg/d in 2 ml water.
(2) 1 cat: 150 mg/kg in 2 doses, 21 hr apart.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
(1) 10 mg/kg/d.
(2) 10 mg/kg alternating with 20-40 mg/kg.
(3) 3 mg/kg/d in drinking water.
ROUTE AND SITE: s.C.
CONTROL INFORMATION: 4 Cats from another study.
ROUTE AND SITE: (1) I.P. (2) I.P. (3) Oral
CONTROL INFORMATION: 6 control cats.
DURATION OF EXPERIMENT: Serial sacr up to 49 d
EXAM. TYPE: Behavior, histology
DURATION OF EXPERIMENT: 7-294 d, irregular schedules.
EXAM. TYPE: Behavior, histology (biopsy and autopsy)
49
50
-------
COMPOUND: Acrylamide
000079061
REFERENCE: Suzuki, K. and Pfaff, L.D.
Acta Neuropath 24:197-213, 1973.
OBSERVED NEUROTOXIC EFFECTS: Weakness of limb muscles, recovered after 1-2 mo.,
some adults had hindlimb paralyzed. Axonal
degeneration, demyelination in sciatic nerve,
regeneration observed.
COMPOUND: Acrylamide, N,N-diethyl-
REFERENCE: Edwards, P.M.
Br. J. Ind. Med. 32:31-38, 1975.
OBSERVED NEUROTOXIC EFFECTS:
(1) Rats: Ataxia,"waddling gait, hindlimb weakness.
(2) Hens: Slight ataxia; degeneration of sciatic
and peroneal. nerve fibers and medullary
and cervical spinocerebellar tracts.
(3,4) Frogs, goldfish: sublethel effects varying
with dosage..
ANIMALS: Rats, Osborn-Mendel, 30 suckling-5 to 8 g, 28 adults 150-300 g.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
50 mg/kg in saline, 3/wk to 18 doses, 2 adults had
26 doses.
ANIMALS: (i) Rats, Porton, M, 200 g
(2) Hens, Star Cross, adult, 3 leg
(3)- Frogs, R. Temporaria, M
(4) Goldfish
PREPARATION AND DOSE
or HISTORY OF PATIENT: Dose varied with species
ROUTE AND SITE: I.P.
CONTROL INFORMATION: 12 rats saline only
DURATION OF EXPERIMENT: Up to about 4 mo.
EXAM. TYPE: Histology of sciatic nerve
ROUTE AND SITE: (1) Oral, I.P.
(2) Oral
CONTROL INFORMATION: .. , . , ,
Vehicles only
DURATION OF EXPERIMENT: Up to 13 wk
EXAM/TYPE: Behavior, histology
(3) Dorsal sac injection or via exposure
(4) Through natural habitat
51
52
-------
COMPOUND: Acrylamide, N-hydroxymethyl-
COMPOUND: Acrylamide, N-hydroxymethyl-
REFERENCE: Barnes, J.M.
Brit. J. Industr. Med. 27:147-149, 1970.
REFERENCE: Edwards, P.M.
Br. J. Ind. Med. 32:31-38, 1975.
OBSERVED NEUROTOXIC EFFECTS: "Fine tremors and were generally affected." No
gross signs of weakness.
OBSERVED NEUROTOXIC EFFECTS:
(1) Rats: Ataxia, waddling gait, hindlimb weakness.
(2) Hens: Slight ataxia; degeneration of sciatic
and peroneal nerve fibers and medullary
and cervical spinocerebellar tracts.
(3,4) Frogs, goldfish: sublethel effects varying
with dosage.
ANIMALS: 6 .young Adult rats, Po.rton Strain, M
PREPARATION AND DOSE
or HISTORY OF PATIENT:
7 doses of 100 mg/kg in 12 d.
2 doses of 200 mg/kg on day 23 and 24.
ANIMALS: (i) Rats, Porton, M, 200 g
(2) Hens, Star Cross, adult, 3 leg
(3) Frogs, R. Temporaria, M
(4) Goldfish
PREPARATION AND DOSE
or HISTORY OF PATIENT: Dose varied with species
ROUTE AND SITE: Oral
CONTROL INFORMATION: ns.
ROUTE AND SITE: (1) Oral, I.P.
(2) Oral
CONTROL INFORMATION: „ . . , ,
Vehicles only
(3) Dorsal sac injection or via exposure
(4) Through natural habitat
DURATION OF EXPERIMENT: 37 d.
EXAM. TYPE: Behavior, physiology
DURATION OF EXPERIMENT: Up to 13 wk
EXAM. TYPE: Behavior, histology
53
54
-------
COMPOUND:
Acrylamide, N-methyl
COMPOUND: Acrylamide, N-methyl
REFERENCE: Barnes, J.M.
Brit. J. Industr. Med. 27:147-149, 1970.
REFERENCE: Edwards, P.M.
Br. J. Ind. Med. 32:31-38, 1975.
OBSERVED NEUROTOXIC EFFECTS:
2 of the 3 had definite weakness like mild
acrylamide poisoning. One rat died after
second series of doses.
OBSERVED NEUROTOXIC EFFECTS:
(1) Rats: Ataxia, waddling gait, hindlimb weakness
(2) Hens: Slight ataxia; degeneration of sciatic
and peroneal. nerve fibers and medullary
and cervical spinocerebellar tracts.
(3,4) Frogs, goldfish: sublethel effects varying
with dosage.
ANIMALS: (1) 6 Rats, Porton, Albino, M
(2) 4 Rats, Porton, Albino, M
(3) 3 Rats, Porton, Albino, M
PREPARATION AND DOSE
or HISTORY OF PATIENT:
(1) 400 ppm for 10 wks followed by 3 wks at 800 ppm.
(2) 7 doses of 100 mg/kg for 2 wks.
(3) 10 doses of 50 mg/kg, then 11 doses of 100 mg/kg for 3 wks.
ANIMALS: (i) Rats, Porton, M, 200 g
(2) Hens, Star Cross, adult, 3 leg
(3) Frogs, R. Temporaria, M
(4) Goldfish
PREPARATION AND DOSE
or HISTORY OF PATIENT: Dose varied with species
ROUTE AND SITE: (1) diet (2) — (3) oral dose
CONTROL INFORMATION: 2 animals, not described.
ROUTE AND SITE: (1) Oral, I.P.
(2) Oral
CONTROL INFORMATION: ...... ,
Vehicles only
(3) Dorsal sac injection or via exposure
(4) Through natural habitat
DURATION OF EXPERIMENT: Approximately 18 wks
EXAM. TYPE: Behavior, physiology
DURATION OF EXPERIMENT: Up to 13 wk
EXAM.. TYPE: Behavior, histology
55
56
-------
COMPOUND: Acrylamide monomer
REFERENCE: Garland, T.O. and Patterson, M.W.H.
Br. Med. J. iv:134-138, 1967.
COMPOUND:
Acrylic acid, 2-cyano-, methyl ester
000137053
REFERENCE: Dutton, J. and Yates, P.O
J. Neurosurg. 24: 876-882, 1966.
OBSERVED NEUROTOXIC EFFECTS: Limb numbness and paresthesias, weakness,
sweating and peeling, ataxia, lethargy, tremors,
slurred speech, wt loss, bladder dysfunction;
authors infer peripheral neuropathy and midbrain
disturbance. Recovery 2-12 mo., not always complete.
OBSERVED NEUROTOXIC EFFECTS:
The dura matter in the brain of 13 cats was incised
and then closed with a fascial graft and coated with
the compound. 9 reacted and later healed, with no
underlying damage and no damage to controls. Vertical
incisions in the brain of 5 cats showed the death of
neurons and glial response. Saphenous nerves were
coated (30 cats) with 8 showing perineural inflammation
and some damage to neurolemmaand axons. All specimens
showed inflammatory or granulomatous response, and
fibrin proliferated between glue and tissues.
ANIMALS: Human: 6 cases, M, aged 19-59
ANIMALS:
Cats, M & F, 2-2.5 kg, surgically prepared
PREPARATION AND DOSE
or HISTORY OF PATIENT: Exposure to process of polymerization in manufacturing of
flocculators.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Experimental brain incisions (unilateral) were coated with
compound.
ROUTE AND SITE: skin of hands and inhalation of dust.
CONTROL INFORMATION: None
ROUTE AND SITE: Topical
CONTROL INFORMATION: Saline contralaterally
DURATION OF EXPERIMENT: Exposure of 4 wk to over 1 yr.
EXAM. TYPE: clinical
DURATION OF EXPERIMENT: 3 d to 8 wk
EXAM. TYPE: Autopsy, histology
57
58
-------
COMPOUND: Acrylic acid, 2-cyano-, methyl ester
000137053
REFERENCE: Kline, D.G. and Hayes, G.J.
J. Neurosurg. 20: 647-654, 1963.
COMPOUND: Actinomycin D
000050760
REFERENCE: Torvik, A., and Heding, A.
Acta Neuropath. 9: 146-157, 1967.
OBSERVED NEUROTOXIC EFFECTS:
The compound caused inflammation in all cases, tubular
and axonal damage in most, and necrosis of neurons (no
damage in any controls). In monkeys, inflammation,
necrosis, demyelination and loss of axons were observed.
The authors commented that the compound was not well
tolerated by nerve tissues.
OBSERVED NEUROTOXIC EFFECTS: Animals treated i.p. had no histologic brain
changes. After intracerebral treatment changes in all neurons from the
anterior part of the brain to sacral segments of spinal cord. Control
animals: changes at injection site only. Neurons nucleoli disintegrated
rapidly. Retrograde reactions due to sectioning are blocked by Actinomycin D
when injection given at time of operation.
ANIMALS: Dogs, mongrel, M & F, 30-45 Ibs, 2 grps of 10, surgically prepared.
Monkeys, no details
ANIMALS: 75 mice, albino, 60-75 d old, 20-25 g.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Dogs: Part-isolated peroneal nerves of both hindlegs, one
coated with compound, the other with saline.
Bilateral trephination, 5 drops of compound applied
to cortex; same of saline to other side.
Monkeys: Optic-chiasm implants.
ROUTE AND SITE: Topical
CONTROL INFORMATION: Saline
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) 3 mice: 1.5 meg in 0.07 ml water, every 3hr for 48hr,
Vllth (facial) nerve sectioned.
(2) 14 mice: 1.5 meg in 0.03 ml water or 0.9% saline,
every 3-4 hr for 2-48 hr.
(3) 14 mice: as above, first inj given at time of operation
to facial nerve.
ROUTE AND SITE: !-p- (4) 12 mice: as above, except doses begun 48hr after operat
and Intracerebral.
CONTROL INFORMATION: control groups: vehicle alone, operation only, vehicle and
operation.
DURATION OF EXPERIMENT: Serial 2-12 wk
EXAM. TYPE: Autopsy, histology
DURATION OF EXPERIMENT: Serial sacr to 4d
EXAM. TYPE: Histology
59
60
-------
COMPOUND: Adenosine, 3'-(alpha-amino-p-methoxy hydrocennamamido)-3'-deoxy-N,N-
dimethyl (Puromycin)
000053792
REFERENCE: Moss, E.E., Moss, D.R. and Fahrney, D.
Pharm. Biochem. Behav. 2: 271-275, 1974 6
COMPOUND: Adenosine, 3'-(alpha-amlno-p-methoxy hydrocennamamido)-3'-deoxy-N,N-
dimethyl ("vrc—*=ir.)
000053792
REFERENCE: Zech, R. and Domagk, G.F.
Brain Res. 86:339-342, 1975.
OBSERVED NEUROTOXIC EFFECTS: Puromycin gave 50% inhibition of the cholinesterase
at O.SraM with SOtnM substrate. The authors inferred
that puromycin binds at two enzyme sites, one of
which is allosteric.
OBSERVED NEUROTOXIC EFFECTS:
Puromycin inhibited the activity of the enzyme,
noncompetitively and reversibly.
ANIMALS: In vitro rat brain cholinesterase preparation.
ANIMALS: In vitro human brain acetylcholinesterase
PREPARATION AND DOSE
or HISTORY OF PATIENT: Various
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Chemical enzyme inhibition system
ROUTE AND SITE: in vitro
CONTROL INFORMATION: ns
ROUTE AND SITE: In vitro
CONTROL INFORMATION: Lab
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Biochemistry
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry
61
62
-------
COMPOUND: Alanlne, 3-(3,4-dihydroxyphenyl)-, L-
000059927
REFERENCE: Narotzky, R., Griffith, D., Stahl, S., Bondareff, W. and Zeller, E.A.
Exp. Neurol. 38:218-230, 1973.
COMPOUND:
Alanine, 3-mercapto-, hydrogen sulfate (ester)
REFERENCE: Olney, J.W., Misra, C.H., De Gubareff, T.
J. Neuropath. Exp. Neurol 34(2):167-177, 1975.
OBSERVED NEUROTOXIC EFFECTS: Increased spontaneous motor activity and pain
responses with decrease of norepinephrine, inter-
preted with respect to psychiatric side-effects of
parkinsonism therapy.
OBSERVED NEUROTOXIC EFFECTS:
Induction of glutamate type of neuropathology in
rat central nervous system.
(1) Lesions in retina and arcuate nucleus of
hypothalamus.
(2) Neuron-necrotizing lesion in brain, acute
neuronal degeneration.
ANIMAIS: Rats, S-D, M, 1.5-2 yr old, 3-4 per group
ANIMALS:
(1) 18 Rats, Wistar albino, 5 days old
(2) Rats, Holtzman, adult
PREPARATION AND DOSE
or HISTORY OF PATIENT:
12.5-62.5 mg/kg, or 250-1000 rag/kg
PREPARATION AND DOSE
or HISTORY OF PATIENT:
(1) 1 injection at one of 3 doses (0.04, 0.4 and 4.0
m moles/kg) aqueous, pH 7.0 + 0.1.
(2) 2 mcl of 77 mM soln, total dose 0.15 me moles.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: Vehicle only; untrtd.
DURATION OF EXPERIMENT: 1-20 hr.
EXAM. TYPE: Behavior, biochemistry, histology
ROUTE AND SITE: (i) s.C. (2) Intracerebral
CONTROL INFORMATION:
DURATION OF EXPERIMENT:
EXAM. TYPE: Histology.
(1) 6 litter-mate injected subcut. with NaCl, 4 m moles/kg.
(2) 3 rats: 2 mcl inj 154 mM NaCl, 3 rats: cannulated no
other treatment.
Sacr after 3 hrs following injections.
63
-------
COMPOUND:
Alanine, N-methyl-3-sulfo-, L- (N-methyl-L-cysteic acid)
COMPOUND: Alanine, phenyl-, L-
REFERENCE:Curtis, D.R. and Watkins, J.C.
J. Physiol. 166:1-14, 1963.
REFERENCE: Adelman, L.S., Mann, J.D., Caley, D.W. and Bass, N.H.
J. Neuropath. Exp. Neurol. 33(2):380-393, 1974.
OBSERVED NEUROTOXIC EFFECTS: N-methyl-D-aspartic and D-homocysteic acids were
stronger excitants of depolarization than all
others. With some compounds the action was
prolonged for many seconds after the stimulus
was terminated, notably N-n_-propyl-D-aspartic
acid. There were no differences among types of
neurons tested; structure-activity relationship
was observed.
OBSERVED NEUROTOXIC EFFECTS: Neuropathic lesions in the cerebellum. Axonal
swelling.
ANIMALS: Cats prepared for electrophoretlc application of chemicals to single
central nervous system neurons.
ANIMALS: 12 Rats, CDR, 14-16 days gestation
108 Weanling rats.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Dilutions 0.1-0.5 M of 31 compounds mainly of aspartic,
glutamic and cysteic acids listed in order of
potency of results.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
0.9 mg/kg/d.
ROUTE AND SITE: Electrophoretic application, various sites in central nervous
system.
CONTROL INFORMATION: „
None
ROUTE AND SITE: s.C.
CONTROL INFORMATION: 18, dose and age matched.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Electrophyslological
DURATION OF EXPERIMENT: Serial sacr. 8, 13, 15, 20, 30, and 50
EXAM. TYPE: Microscopy, neuropathology
65
66
-------
COMPOUND: Alanine, phenyl-, L-
COMPOUND:
Alanine, 3-sulflno-
REFERENCE: Shah, S.N., Peterson, N.A. and McKean, C.M.
J. Neurochem. 19:479-485, 1972.
OBSERVED NEUROTOXIC EFFECTS: Reduced cholesterol, glycollpids, and myelin
in brains; DNA and protein unchanged, myelin
composition unchanged. Authors inferred cholesterol
reduction as the mechanism.
REFERENCE: Curtis, D.R. and Watkins, J.C.
J. Neurochem. 6:117-141, 1960.
OBSERVED NEUROTOXIC EFFECTS:
Treatment caused excitation or depression of
neuronal activity. Excitatory ranking: glutamic,
B-aminoglutaric, aspartic, cysteic, sulfino-
alanfnes, B-hydroxyglutamic, N-methylaspartic,
N-formiminoaspartic acids.
Depressant ranking: 6-alanine, GABA, taurine,
N-methyl-B-alanine, 6-amino-B-hydroxybutyric,
glycine, a-alanine, 6-aminovaleric, B-aminoisobutyric
acids.
Structure-activity relationships established.
ANIMALS: Rats, S-D, aged 5 d
ANIMALS: Cats, surgically prepared to exposed motoneurones, Renshaw cells or
dorsal horn interneurones in lumbar cord.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 3 mg/g/d in 3 doses for 5, 10, 15 d.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Qualitative doses.
ROUTE AND SITE: I.M.
CONTROL INFORMATION: Controls: saline only
ROUTE AND SITE: Topical, ionophoresis
CONTROL INFORMATION: Laboratory
DURATION OF EXPERIMENT: Serial sacr to 30 d
EXAM. TYPE: Biochemistry
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry, electrophysiology
67
68
-------
COMPOUND: Alanine, 3-sulfino-
COMPOUND: Alanine, 3-sulfo-, D-
u~ r\ T
--- 1 ni ---
Exp. Brain Res. 14:61-76, 1971.
OBSERVED NEUROTOXIC EFFECTS: The compound was equipotent to monosodium
glutamate in necrosing neurons in the retina
and brain. This compound is a powerful neuro-
excitant and the neurotoxic properties may be
governed by similar mechanisms.
REFERENCE:Curtis, D.R. and Watkins, J.C.
J. Physiol. 166:1-14, 1963.
OBSERVED NEUROTOXIC EFFECTS:
N-methyl-D-aspartic and D-homocysteic acids were
stronger excitants of depolarization than all
others. With some compounds the action was
prolonged for many seconds after the stimulus
was terminated, notably N-n_-propyl-D-aspartic
acid. There were no differences among types of
neurons tested; structure-activity relationship
was observed.
ANIMALS: Mice, Swiss-webster age 10 d, total 250
PREPARATION AND DOSE
or HISTORY OF PATIENT: Initially 12 mmoles/kg, then range established for
each compound.
ANIMALS: Cats prepared for electrophoretic application of chemicals to single
central nervous system neurons.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Dilutions 0.1-0.5 M of 31 compounds mainly of aspartic,
glutamic and cysteic acids listed in order of
potency of results.
ROUTE AND SITE:
S.C.
CONTROL INFORMATION: Compounds compared with monosodium L-glutamate (MSG)
potency for selectively necrosing neurons in retina
and brain (hypothalamus)
DURATION OF EXPERIMENT: 5 hr or serial intervals including 5 hr.
EXAM. TYPE: Histology
ROUTE AND SITE: Electrophoretic application, various sites in central nervous
system.
CONTROL INFORMATION: „ ' '
None
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Electrophysiological
69
70
-------
COMPOUND:
Alanine, 3-sulfo-, L-
COMPOUND: Alanine, 3-sulfo-, L-
REFERENCE: Curtis, D.R. and Watkins, J.C.
J. Neurochem. 6:117-141, 1960.
REFERENCE:Curtis, D.R. and Watkins, J.C.
J. Physiol. 166:1-14, 1963.
OBSERVED NEUROTOXIC EFFECTS:
Treatment caused excitation or depression of.
neuronal activity. Excitatory ranking: glutamic,
6-aminoglutaric, aspartic, cysteic, cysteine-
sulfinic acids, B-hydroxyglutamic, N-methylaspartic,
N-formiminoaspartic acids.
Depressant ranking: B-alanine, GABA, taurine,
N-methyl-8-alanine, S-amino-B-hydroxybutyric,
glycine, a-alanine, S-aminovaleric, B-aminoisobutyric
acids.
Structure-activity relationships established.
OBSERVED NEUROTOXIC EFFECTS:
N-methyl-D-aspartic and D-homocysteic acids were
stronger excitants of depolarization than all
others. With some compounds the action was
prolonged for many seconds after the stimulus
was terminated, notably N-ii-propyl-D-aspartic
acid. There were no differences among types of
neurons tested; structure-activity relationship
was observed.
ANIMALS: Cats, surgically prepared to exposed motoneurones, Renshaw cells or
dorsal horn interneurones in lumbar cord.
ANIMALS: Cats prepared for electrophoretic application of chemicals to single
central nervous system neurons.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Qualitative doses.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Dilutions 0.1-0.5 M of 31 compounds mainly of aspartic,
glutamic and cysteic acids listed in order of
potency of results.
ROUTE AND SITE: Topical, ionophoresis
CONTROL INFORMATION: Laboratory
ROUTE AND SITE:
CONTROL INFORMATION:
Electrophoretic application, various sites in central nervous
system.
None
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry, electrophysiology
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Electrophysiological
71
72
-------
COMPOUND: Alanine, 3-sulfo-, L-
COMPOUND:
Alanine, 3-(2-thienyl)-
Dcccorwrc.
Exp. Brain Res. 14:61-76, 1971.
OBSERVED NEUROTOXIC EFFECTS: The compound was equlpotent to monosodium glutamate
in necrosing neurons in the retina and brain.
This compound is a powerful neuroexcitant
and the neurotoxic properties may be governed by
similar mechanisms.
REFERENCE:
Capobianco, J.O. and Beck, S.L.
Teratology 4:295-302, 1971.
OBSERVED NEUROTOXIC EFFECTS:
Prenatal treatment during "period of accelerated
neural growth and differentiation" resulted in
decreased brain weight and increased body wt
compared to controls. Treated offspring had
more sound-induced seizures than untreated controls,
but not more than solvent-treated. Sound-
stressed mice had lower brain catecholamine levels.
ANIMALS: Mice, Swiss-webster age 10 d, total 250
PREPARATION AND DOSE
or HISTORY OF PATIENT: Initially 12 mmoles/kg, then range established for
each compound.
ANIMALS:
Mice, 12th-13th generations of 4-way outcross of C3H/HeH,
CBA/Gr, A/Gr, and C57BL/Gr strains, pregnant females. Tot
480 animals.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
40, 60 or 70 mg in 1 ml saline, 0.1 N HC1 and 0.1
N NaOH (18:1:1) per d, on d 10-12 of gestation.
ROUTE AND SITE:
S.C.
CONTROL INFORMATION: Compounds compared with monosodium L-glutamate (MSG)
potency for selectively necrosing neurons in retina
and brain (hypothalamus)
DURATION OF EXPERIMENT: 5 hr or serial intervals including 5 hr.
EXAM. TYPE: Histology
ROUTE AND SITE: i.p.
CONTROL INFORMATION:
Groups of solvent ttd and unttd animals.
DURATION OF EXPERIMENT: Sacr 23 d postnatal
EXAM. TYPE: Sound-stress, and biochemistry
73
74
-------
COMPOUND: Alanine. 2.4,5-trihvrtroxyphenyl-
REFERENCE: Richardson, J.S., Cowan,N., Hartman, R. and Jacobowitz, D.M.
Res. Comm. Chem. Path. Pharm.. 8(l):29-44, 1974.
OBSERVED NEUROTOXIC EFFECTS: Lowered norepinephrine 25-50%; in combination
with 5,6-dihydroxytryptamine (I) lowered norepinephrine and serotonin;
no effect on dopamine. Alone or in combination with I, lowered food
and water intakes. Alone, but not in combination with I, lowered
spontaneous locomotion. Increased emotionality scores; I attenuated
the increase. Other complex effects reported, and the causes speculated
to be selective destruction of noradrenergic and/or serotonergic nerve
terminals.
ANIMALS: Rats, S-D, M, 180-200 g, 5-12/group
PREPARATION AND DOSE
or HISTORY OF PATIENT:
90 meg/rat
ROUTE AND SITE: Intraventricular
CONTROL INFORMATION: Vehicle
DURATION OF EXPERIMENT: 14 d
EXAM. TYPE: Behavior
75
COMPOUND: Alanine, 2,4,5-trihydroxyphenyl-
REFERENCE: Sachs, C. and Jonsson, G.
J. Neurochem. 19:1561-1575, 1972.
OBSERVED NEUROTOXIC EFFECTS: Doses (1) lethal, (2) MTD. Degeneration of central
and peripheral norepinephrine neurons, mediated by
decarboxylation of 6-OH-DOPA to 6-OH-Da. Neither
5-HT neurons nor dopamine neurons were affected.
ANIMALS: Mice, N.M.R.I., M, 25-30 g
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) 250 or 400 mg/kg, one dose.
(2) 100 mg/kg, 1-6 doses at intervals.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: Controls untreated.
DURATION OF EXPERIMENT: Up to 42 d
EXAM. TYPE: Biochemistry, fluorescence histochemistry
76
-------
COMPOUND: Alanine, 2,4,5-trihydroxyphenyl-, hydrobromide
COMPOUND: Alkyl mercury
REFERENCE: Bonagura, V., Cassebaum, L., Dangman, K., Freund, J., Cabbat, F., Dembiec,
D., Helkkila, R. and Cohrn, G.
Res. Comm. Chem. Path. Pharm. 4: 163-171, 1972,
OBSERVED NEUROTOXIC EFFECTS: Treatment caused diminished uptake of norepinephrine,
resulting from destruction of adrenergic nerve terminals.
Accumulation of the compound at site needed for these
effects. Desipramine, 25 mg/kg, protected under conditions
of this experiment.
REFERENCE:
Charlton, K.M.
Can. J. Comp. Med. 38(1):75-81, 1974.
OBSERVED NEUROTOXIC EFFECTS:
Weakness of gait, blindness in affected pigs,
aimless walking, reflexes minimally altered,
death. Peripheral nervous system: Wallerian
degeneration of sensory fibers, neuronal degeneral
of dorsal root ganglia. Central nervous system:
degeneration of neurons and glia.
ANIMALS: Mice, Swiss-Webster, M, 25g
ANIMALS: 20 Pigs, Yorkshire, 7 M and 13 F, aged approx. 10 wk.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 100 mg/kg
PREPARATION AND DOSE
or HISTORY OF PATIENT:
0.24-5.76 mg/kg/d of mercury for 11-199 d.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: Saline
ROUTE AND SITE: ns.
CONTROL INFORMATION: 4 of above kept as controls, untreated
DURATION OF EXPERIMENT: 72 hr
EXAM. TYPE: Biochemistry of heart slices
DURATION OF EXPERIMENT: Killed on d 13-205.
EXAM. TYPE: Behavior, histology
77
78
-------
COMPOUND:
Allophanic acid, hydrazide
COMPOUND:
Aloes
REFERENCE: Jenney, E.H. and Pfeiffer, C.C.
J. Pharm. Exp. Ther. 122: 110-123, 1958.
REFERENCE:
Steer, H.W. and Colin-Jones, D.G.
J. Path. 115:199-205, 1975.
OBSERVED NEUROTOXIC EFFECTS: Convulsions
OBSERVED NEUROTOXIC EFFECTS: More lysosomal activity and lysosotnes in Schwann
cells and neurons of submucosal plexus of colonic
mucosa.
ANIMALS: Mice, Harlan, 19-21 g
ANIMALS: Human: 7 aged 24-80 with melanosia coli who took purgatives;
1 who had taken purgatives for only 1 m.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 2.5 mM/kgm
PREPARATION AND DOSE
or HISTORY OF PATIENT: Rectal biopsy before and 3-7 m after stopping medication
ROUTE AND SITE: I.P.
CONTROL INFORMATION: ns
ROUTE AND SITE: Oral
CONTROL INFORMATION:
7 aged 27-70 with other gut disorders who had taken no
purgatives for 3 m.
DURATION OF EXPERIMENT: Acute
EXAM. TYPE: Clinical
DURATION OF EXPERIMENT: About 7 m.
EXAM. TYPE: Histology, histochemistry
79
80
-------
COMPOUND: Aluminum hydroxide
COMPOUND: Ammonium, (O-b-romobenzyl)ethyldimethyl-, p-toluenesulfonate
000061756
Acta Neuropath. 11:311-329, 1968.
Quinton, R.M.
Br. J. Pharmac. 21:51-66, 1963.
OBSERVED NEUROTOXIC EFFECTS: No effect in nonmyelinated white-matter of
juveniles; severe demyelination and gliosis of white-matter in adults,
with added effects on grey-matter.
OBSERVED NEUROTOXIC EFFECTS: The compound enhanced the effect of Yohimbine
and lowered its lethal dosage.
ANIMALS: 10 cats, various ages, in 3 grps.
ANIMALS:
Mice, TT, M, 18-25 g.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.03-0.12 ml, one dose.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
ED5Q >40 mg/kg
ED__ = dose producing a 50% mortality of mice injected
S.C. with yohimbine hydrochloride (20 mg/kg).
ROUTE AND SITE: intracerebral
CONTROL INFORMATION: None
ROUTE AND SITE: S.C., Oral
CONTROL INFORMATION: Various
DURATION OF EXPERIMENT: Serial sacr: 7 d, 40 d, 3 mo.
EXAM. TYPE: Histology.
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Behavior, electrophysiology, biochemistry
81
82
-------
COMPOUND: Ammonium, (3-carboxypropyl) trimethyl-, carboxylate
COMPOUND:
Ammonium, dibutyl(2-hydroxyethyl)methyl-
REFERENCE: Curtis, D.R. and Watkins, J.C.
J. Neurochem. 6:117-141, 1960.
OBSERVED NEUROTOXIC EFFECTS:
ANIMALS:
Treatment caused excitation or depression of
neuronal activity. Excitatory ranking: glutamic,
B-aminoglutaric, aspartic, cysteic, cysteine-
sulfinic acids, 6-hydroxyglutamic, N-methylaspartic,
N-formiminoaspartic acids.
Depressant ranking: 6-alanine, GABA, taurine,
N-methyl-B-alanine, 6-amino-B-hydroxybutyric,
glycine, a-alanine, 6-aminovaleric, B-amlnoisobutyric
acids.
Structure-activity relationships established.
Cats, surgically prepared to expose- motoneurones, Renshaw cells or
dorsal horn interneurones in lumbar cord.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Qualitative doses.
REFERENCE: Hartung, R. and^Cornish, H.H.
Tox. Appl. Pharm. 12:486-494, 1968.
OBSERVED NEUROTOXIC EFFECTS:
This compound was tested with a group of other amino-
ethanols and choline analogs, all of which inhibited
cholinesterase in vitro. In vitro inhibition
increases as the number of carbon atoms attached
on the nitrogenous head of the 2-amino-ethanol moledule.
In the in vivo tests the oral LDj-'s were uniformly
higher than the i.p. LD . values. When given i.p.,
compound reduced brain cnolinesterase.
ANIMALS: Rats, S-D, M
PREPARATION AND DOSE
or HISTORY OF PATIENT: In vitro: 10 4 to 10"1.
In vivo:
and lower doses.
ROUTE AND SITE: Topical, ionophoresis
CONTROL INFORMATION: Laboratory
ROUTE AND SITE: Oral, i.p., in vitro
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry, electrophysiology
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry
83
84
-------
COMPOUND:
Ammonium, diethyl(2-hydroxyethyl)methyl-
COMPOUND: Ammonium, (2-hydroxyethyl)triethyl-
REFERENCE:
Hartung, R. and Cornish, H.H.
Tox. Appl. Pharm. 12:486-494, 1968.
OBSERVED NEUROTOXIC EFFECTS:
This compound was tested with a group of other
aminoethanols and choline analogs, all of which
inhibited cholinesterase in vitro. In vitro
inhibition increases as the number of carbon atoms
attached on the nitrogenous head of the 2-amino-
ethanol molecule. In the in vivo tests the oral
LD were uniformly higher than the i.p. LD values.
REFERENCE: Bhatnagar, S.P., Lam, A. and McColl, J.D.
Blochem. Pharm. 14: 421-434, 1965.
OBSERVED NEUROTOXIC EFFECTS: Muscular weakness, respiratory paralysis, failure
of transmission at cholinergic synapses; inhibition
of acetylcholine synthesis.
ANIMALS: Rats, S-D, M
PREPARATION AND DOSE
or HISTORY OF PATIENT: In vitro: 10~4 to 10.
In vivo: LD anc^ l°wer doses.
ANIMALS: Mice, CFW, F, 15-20 g and mouse brain tissues in vitro
Cats, M & F, 2-3 kg, surgically prepared
In vitro reaction mixtures
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Various doses
ROUTE AND SITE: Oral, i.p., in vitro
CONTROL INFORMATION: ns.
ROUTE AND SITE: Various routes
CONTROL INFORMATION: Various controls
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry
DURATION OF EXPERIMENT: various
EXAM. TYPE: Chemistry, electrophysiology
85
86
-------
COMPOUND: Ammonium, (2-hydroxyethyl) triethyl-, p-toluenesulfonate, 3,4,5-
trimethoxybenzoate
COMPOUND: Ammonium, (m-hydroxyphenyl)trimethyl-, bromide, dimethylcarbamate
000114807
REFERENCE: Bhatnagar, S.P., Lam, A. and McColl, J.D.
Biochem. Pharm. 14: 421-434, 1965
REFERENCE: Tang, A.H. and Schroeder, L.A.
Tox. Appl. Pharm. 12:44-47, 1968.
OBSERVED NEUROTOXIC EFFECTS:
Muscular weakness, respiratory paralysis, failure
of transmission at cholinergic synapses; inhibition
of acetylcholine synthesis.
OBSERVED NEUROTOXIC EFFECTS: Produced variable results, ranging from reversal to
enhancement of neuromuscular blockade.
ANIMALS: Mice, CFW, F, 15-20 g and mouse brain tissues in vitro
Cats, M & F, 2-3 kg, surgically prepared
In vitro reaction mixtures
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Various doses
ANIMALS:
4 Rabbits
PREPARATION AND DOSE
or HISTORY OF PATIENT: 25-100 meg/kg administered at peak of the neuromuscular
blockade from lincomycin (50 mg/kg).
ROUTE AND SITE: Various routes
CONTROL INFORMATION: Various controls
ROUTE AND SITE: I.V.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Chemistry, electrophysiology
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Electrophysiology
87
88
-------
COMPOUND: Ammonium ion (+1)
COMPOUND: Andros t-5-en-3-beta-ol, 17-beta-((3-(dlmethylamino)propyl)methylamino)-
REFERENCE: Lux, H.D., Loracher, C. and Neher, E.
Exp. Brain Res. 11: 431-447, 1970.
REFERENCE: Suzuki, K., Zagoren, J.C., Chen, S.M. and Suzuki, K.
Acta Neuropath. 29:141-156, 1974.
OBSERVED NEUROTOXIC EFFECTS:
Treatment caused reversible reductions of IPSP-
equilibrium potential which were more sensitive to
extracellular and systemic ammonium than to intra-
cellular ammonium. The authors suggest that slow
release from inside the cells explains the long
duration effects after intracellular applications.
The effective extracellular doses corresponded to
intracerebral concentrations of compound reported
for preconvulsive states of epilepsies induced
metabolically.
ANIMALS:
45 Cats, adult, 1.5-2.5 kg, surgically prepared
OBSERVED NEUROTOXIC EFFECTS:
ANIMALS:
Scattered intracytoplasmic osmiophilic inclusions
in central nervous system (far fewer than with
Triparanol, q.v.) at higher dose-level only.
No degeneration of oligodendroglia. Massive
accumulations of desmosterol and less of A->»'«'''-
cholestatriene-36-ol. Authors argue that as a
A -reductase inhibitor causes massive accumulations
of 7-dehydrocholesterol (provitamin D3), as
A7' and A5' ' sterols produce Triparanol-like
lesions, and as diazacholesterol produces few
such lesions, the lesions may be due to a double
bond at the 7-position.
Rats, Wistar, M and F, newborn
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Compound applied by iontophoresis to exposed neurons, both
intra- and extra-cellularly
PREPARATION AND DOSE
or HISTORY OF PATIENT:
30 or 60 mg/kg/d in saline, from d 5 of age.
ROUTE AND SITE: See above
CONTROL INFORMATION: Laboratory
ROUTE AND SITE: I.P.
CONTROL INFORMATION: Saline only
DURATION OF EXPERIMENT: Various to 120 min
EXAM. TYPE: Electrophysiology
DURATION OF EXPERIMENT: Serial, 15-32 d
EXAM. TYPE: Histology, biochemistry
89
90
-------
COMPOUND: Androst-5-en-17-one, 3-beta-hydroxy-, succinate, sodtum salt
REFERENCE:
Heuser, G., Ling, G.M. and Buchwald, N.A.
Arch. Neurol 13:195-203, 1965.
OBSERVED NEUROTOXIC EFFECTS:
Doses of 40-70 mg/kg produced sedation and slow
wave activity. Doses of 100-150 mg/kg (high)
resulted in repeated tonic seizures and intermittent
falling spells.
COMPOUND: Aniline, 4,4'-sulfonyldi-
000080080
REFERENCE:
duVivier, A. and Fowler, T.
Proc. Royal Soc. Med. 67:439-440, 1974.
OBSERVED NEUROTOXIC EFFECTS: Wasting of hand muscles and of some feet muscles.
Sensorimotor neuropathy with denervation of small hand muscles with pro-
longed distal latency. Axonal degeneration and denervation atrophy. 4 mo.
after withdrawal of dapsone, no recovery.
ANIMALS:
Monkeys, Squirrel, surgically prepared
ANIMALS: 1 Human, M, age 57 yr.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Varying doses approx 5-200 mg/kg.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 200-300 mg/d for 18 yr for dermatitis herpetiformis.
Complained of tingling of hands and feet and weakness of hands, starting
1 yr. before.
ROUTE AND SITE:
I.V. or I.P.
CONTROL INFORMATION:
Sham inj as well as saline and sodium bicarbonate soln
were used as controls. Control injections did not
produce sedative or convulsion effects.
DURATION OF EXPERIMENT: Up to approx 30 min/test
EXAM. TYPE: Electrophysiology, behavior
ROUTE AND SITE: oral
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: 18 yr. drug treatment, follow-up 4 mo.
EXAM. TYPE: Clinical, electromyography, nerve and muscle biopsy.
91
92
-------
COMPOUND: o-Anisamide, 4-amino-5-chloro-N-(2-diethylamino)ethyl)-
REFERENCE: DeSilva, K.L., Muller, P.J. and Pearce, J.
Practitioner 211: 316-320, 1973.
COMPOUND: Anthraquinone, dihydroxy-
001322607
REFERENCE: Steer, H.W. and Colin-Jones, D.G.
J. Path. 115: 199-205, 1975
OBSERVED NEUROTOXIC EFFECTS: Extrapyramidal signs, spasms especially of face, tongue
and jaws, torticollis, opisthotonus, trismus; onset in
2-60 hrs. commonest in young. No dose relationship,
recovery after withdrawal. One case had added dienceph-
alic features. Authors comment that etiology still
unknown, and suggest idiosyncracy to class of drugs
(phenothiazines).
OBSERVED NEUROTOXIC EFFECTS: More lysosomal activity and lysosomes in Schwann
cells and neurons of submucosal plexus of colonic
mucosa.
ANIMALS: Human: 10 cases, M & F, 14-30, selected from 20 cases treated at a
hospital serving 500,000 population, over 2 yrs
ANIMALS: Human: 7 aged 24-80 with melanosis coli who took purgatives;
1 who had taken purgatives for only 1 m.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 4 cases: 10 mg t.d.s., P.O.
Adverse drug reaction.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Rectal biopsy before and 3-7 m after stopping medication
ROUTE AND SITE: t.d.s., P.O. (see above)
CONTROL INFORMATION: None
ROUTE AND SITE: Oral
CONTROL INFORMATION: 7 aged 27-70 with other gut disorders who had taken no
purgatives for 3 m
DURATION OF EXPERIMENT: 12-48 hrs.
EXAM. TYPE: Clinical
DURATION OF EXPERIMENT: About 7 m.
EXAM. TYPE: Histology, histochemistry
93
94
-------
COMPOUND:
Arsenic
007440382
REFERENCE: Chhuttani, P.N., Chawla, L.A. and Sharma, T.D.
Neurology 17:269-274, 1967.
OBSERVED NEUROTOXIC EFFECTS: Mainly sensory polyneuropathy, degeneration
correlating in severity with clinical data, no specific pattern.
ANIMALS: Human: 34 M, 6 F aged 20-65 yr (av. 34.2) seen over 12 yr. in a
series of 708 neuropathies (these were the cases due to As).
PREPARATION AND DOSE
or HISTORY OF PATIENT: Unknown amts. Sources: prescription 27, homicide 5,
culinary 3, accident 3, injection 2.
ROUTE AND SITE: 30 Oral, 2 parenteral
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: 12yr
EXAM. TYPE: Behavior, biochemistry, histology
95
COMPOUND: Arsenic
007440382
REFERENCE: Hassin, G.B.
J. Nerv. Ment. Dis. 72:628-636, 1930.
OBSERVED NEUROTOXIC EFFECTS: Paralysis or polyneuritis of sudden onset
deposits of arsenic seen as bands in nails, high arsenic content in hair.
ANIMALS: 6 Human case-reports
PREPARATION AND DOSE
or HISTORY OF PATIENT: Source, type and amount of arsenic intake not discovered.
ROUTE AND SITE: N.S.
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: weeks to years
EXAM. TYPE: clinical and laboratory
96
-------
COMPOUND:
Aspartic acid
COMPOUND: Aspartic acid, D-
REFERENCE: Olney, J.W. and Ho., 0.
Nature 227:609-610, 1970.
OBSERVED NEUROTOXIC EFFECTS:
Necrosis of hypothalamic neurons in mice given
glutamate, compound or cysteine, dose-related;
zero damage from other compounds
ANIMALS:
75 Mice, Swiss Webster, age 10 d.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
One of 10 amino acids and various other compounds, 2.5 or 10%
in water, 0.25-2 g/kg.
REFERENCE: Curtis, D.R. and Watkins, J.C.
J. Neurochem. 6:117-141, 1960.
OBSERVED NEUROTOXIC EFFECTS:
ANIMALS:
Treatment caused excitation or depression of
neuronal activity. Excitatory ranking: glutamic,
6-aminoglutaric, aspartic, cysteic, cysteine-
sulfinic acids, B-hydroxyglutamic, N-methylaspartic,
N-formiminoaspartic acids.
Depressant ranking: 6-alanine, GABA, taurine,
N-methyl-B-alanine, 6-amino-S-hydroxybutyric,
glycine, a-alanine, 6-aminovaleric, S-aminoisobutyric
acids.
Structure-activity relationships established.
Cats, surgically prepared to expose motoneurones, Renshaw cells or
dorsal horn interneurones in lumbar cord.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Qualitative doses.
ROUTE AND SITE: Gavage
CONTROL INFORMATION: Intubated, no treatment, 10 mice
ROUTE AND SITE: Topical, ionophoresis
CONTROL INFORMATION: Laboratory
DURATION OF EXPERIMENT: 5 hr.
EXAM. TYPE: Histology
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry, electrophysiology
97
98
-------
COMPOUND: Aspartlc acid, D-
COMPOUND: Aspartlc acid, D-
REFERENCE.'Curtis, D.R. and Watkins, J.C.
J. Physiol. 166:1-14, 1963.
OBSERVED NEUROTOXIC EFFECTS:
N-methyl-D-aspartic and D-homocysteic acids were
stronger excitants of depolarization than all
others. With some compounds the action was
prolonged for many seconds after the stimulus
was terminated, notably N-nj-propyl-D-aspartic
acid. There were no differences among types of
neurons tested; structure-activity relationship
was observed.
REFERENCE:
Olney, J.W., Ho, O.L. and Rhee, V.
Exp. Brain Res. 14:61-76, 1971.
OBSERVED NEUROTOXIC EFFECTS: The compound was equipotent to monosodium
glutamate in necrosing neurons in the retina
and brain. This compound is a powerful neuro-
excitant and the neurotoxic properties may be
governed by similar mechanisms.
ANIMALS: Cats prepared for electrophoretic application of chemicals to single
central nervous system neurons.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Dilutions 0.1-0.5 M of 31 compounds mainly of aspartic,
glutamic and cysteic acids listed in order of
potency of results.
ANIMALS: Mice, Swiss-webster age 10 d, total 250
PREPARATION AND DOSE
or HISTORY OF PATIENT: Initially 12 mmoles/kg, then range established for
each compound.
ROUTE AND SITE:
CONTROL INFORMATION:
Electrophoretic application, various sites in central nervous
system.
None
ROUTE AND SITE:
B.C.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Electrophysiological
CONTROL INFORMATION: Compounds compared with monosodium L-glutamate (MSG)
potency for selectively necrosing neurons in retina
and brain (hypothalamus)
DURATION OF EXPERIMENT: 5 hr or serial intervals including 5 hr.
EXAM. TYPE: Histology
99
100
-------
COMPOUND: Aspartic acid, DL-
COMPOUND: Aspartic acid, L-
REFERENCE: Curtis, D.R. and Watkins, J.C.
J. Neurochem. 6:117-141, 1960.
REFERENCE: Curtis, D.R. and Watkins, J.C.
J. Neurochem. 6:117-141, 1960.
OBSERVED NEUROTOXIC EFFECTS:
Treatment caused excitation or depression of
neuronal activity. Excitatory ranking: glutamic,
8-aminoglutaric, aspartic, cysteic, cysteine-
sulfinic acids, 8-hydroxyglutamic, N-methylaspartic,
N-formiminoaspartic acids.
Depressant ranking: B-alanine, GABA, taurine,
N-methyl-B-alanine, 6-amino-B-hydroxybutyric,
glycine, a-alanine, 6-aminovaleric, B-aminoisobutyric
acids.
Structure-activity relationships established.
OBSERVED NEUROTOXIC EFFECTS:
Treatment caused excitation or depression of
neuronal activity. Excitatory ranking: glutamic,
g-aminoglutaric, aspartic, cysteic, cysteine-
sulflnic acids, B-hydroxyglutamic, N-methylaspartic,
N-formiminoaspartic acids.
Depressant ranking: B-alanine, GABA, taurine,
N-methyl-B-alanine, 6-amino-B-hydroxybutyric,
glycine, a-alanine, 6-aminovaleric, B-aminoisobutyric
acids.
Structure-activity relationships established.
ANIMALS:
Cats, surgically prepared to expose motoneurones, Renshaw cells or
dorsal horn interneurones in lumbar cord.
ANIMALS:
Cats, surgically prepared to expose motoneurones, Renshaw cells or
dorsal horn interneurones in lumbar cord.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Qualitative doses.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Qualitative doses.
ROUTE AND SITE: Topical, ionophoresis
CONTROL INFORMATION: Laboratory
ROUTE AND SITE: Topical, ionophoresis
CONTROL INFORMATION: Laboratory
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry, electrophysiology
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry, electrophysiology
101
102
-------
COMPOUND: Aspartic acid, L-
COMPOUND: Aspartic acid, L-
REFERENCE:Curtis, D.R. and Watkins, J.C.
J. Physiol. 166:1-14, 1963.
OBSERVED NEUROTOXIC EFFECTS:
N-methyl-D-aspartic and D-homocysteic acids were
stronger excitants of depolarization than all
others. With some compounds the action was
prolonged for many seconds after the stimulus
was terminated, notably N-ti-propyl-D-aspartic
acid. There were no differences among types of
neurons tested; structure-activity relationship
was observed.
REFERENCE:
Olney, J.W., Ho, O.L. and Rhee, V.
Exp. Brain Res. 14:61-76, 1971.
OBSERVED NEUROTOXIC EFFECTS:
The compound was equipotent to monosodium
glutamate in necrosing neurons in the retina
and brain. This compound is a powerful neuroexcitant
and the neurotoxic properties may be governed
by similar mechanisms.
ANIMALS: Cats prepared for electrophoretic application of chemicals to single
central nervous system neurons.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Dilutions 0.1-0.5 M of 31 compounds mainly of aspartic,
glutamic and cysteic acids listed in order of
potency of results.
ANIMALS: Mice, Swlss-webster age 10 d, total 250
PREPARATION AND DOSE
or HISTORY OF PATIENT: Initially 12 mmoles/kg, then range established for
each compound.
ROUTE AND SITE: Electrophoretic application, various sites in central nervous
system.
CONTROL INFORMATION: „ ' '
None
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Electrophysiological
ROUTE AND SITE:
S.C.
CONTROL INFORMATION: Compounds compared with monosodium L-glutamate (MSG)
potency for selectively necrosing neurons in retina
and brain (hypothalamus)
DURATION OF EXPERIMENT: 5 hr or serial intervals including 5 hr.
EXAM. TYPE: Histology
103
104
-------
COMPOUND:
Aspartic acid, N-acetyl-, L-
COMPOUND: Aspartic acid, N-acetyl-, L-
REFERENCE: Curtis, D.R. and Watkins, J.C.
J. Neurochem. 6:117-141, 1960.
REFERENCE:
OBSERVED NEUROTOXIC EFFECTS:
ANIMALS:
Treatment caused excitation or depression of
neuronal activity. Excitatory ranking: glutamic,
8-aminoglutaric, aspartic, cysteic, cysteine-
sulfinic acids, B-hydroxyglutamic, N-methylaspartic,
N-formiminoaspartic acids.
Depressant ranking: 6-alanine, GABA, taurine,
N-methyl-B-alanine, S-amino-B-hydroxybutyric,
glycine, a-alanine, 6-aminovaleric, B-aminoisobutyric
acids.
Structure-activity relationships established.
Cats, surgically prepared to expose motoneurones, Renshaw cells or
dorsal horn interneurones in lumbar cord.
PREPARATION AND DOSE-
or HISTORY OF PATIENT: Qualitative doses.
Olney, J.W., Ho, O.L. and Rhee, V.
Exp. Brain Res. 14:61-76, 1971.
OBSERVED NEUROTOXIC EFFECTS: No cytotoxicity was observed.
ANIMALS: Mice, Swiss-webster age 10 d, total 250
PREPARATION AND DOSE
or HISTORY OF PATIENT: Initially 12 mmoles/kg, then range established for
each compound.
ROUTE AND SITE: Topical, ionophoresis
CONTROL INFORMATION: Laboratory
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry, electrophysiology
ROUTE AND SITE:
S.C.
CONTROL INFORMATION: Compounds compared with monosodium L-glutamate (MSG)
potency for selectively necrosing neurons in retina
and brain (hypothalamus)
DURATION OF EXPERIMENT: 5 hr or serial intervals including 5 hr.
EXAM. TYPE: Histology
105
106
-------
COMPOUND: Aspartic acid, N-carbamoyl-, DL-
COMPOUND: Aspartic acid, N,N-dimethyl-, D-
REFERENCE: Curtis, D.R. and Watkins, J.C.
J. Neurochem. 6:117-141, 1960.
REFERENCE:Curtis, D.R. and Watkins, J.C.
J. Physiol. 166:1-14, 1963.
OBSERVED NEUROTOXIC EFFECTS:
Treatment caused excitation or depression of
neuronal activity. Excitatory ranking: glutamic,
6-aminoglutaric, aspartic, cysteic, cysteine-
sulfinic acids, 8-hydroxyglutamic, N-methylaspartic,
N-formiminoaspartic acids.
Depressant ranking: g-alanine, GABA, taurine,
N-methyl-B-alanine, 6-amino-8-hydroxybutyric,
glycine, a-alanine, 6-aminovaleric, £-aminolsobutyric
acids.
Structure-activity relationships established.
OBSERVED NEUROTOXIC EFFECTS:
N-methyl-D-aspartic and D-homocysteic acids were
stronger excitants of depolarization than all
others. With some compounds the action was
prolonged for many seconds after the stimulus
was terminated, notably N-n-propyl-D-aspartic
acid. There were no differences among types of
neurons tested; structure-activity relationship
was observed.
ANIMALS'. Cats, surgically prepared to exposed motoneurones, Renshaw cells or
dorsal horn interneurones in lumbar cord.
ANIMALS: Cats prepared for electrophoretic application of chemicals to single
central nervous system neurons.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Qualitative doses.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Dilutions 0.1-0.5 M of 31 compounds mainly of aspartic,
glutamic and cysteic acids listed in order of
potency of results.
ROUTE AND SITE: Topical, ionophoresis
CONTROL INFORMATION: Laboratory
ROUTE AND SITE: Electrophoretic application, various sites in central nervous
system.
CONTROL INFORMATION: „
None
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry, electrophysiology
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Electrophysiological
107
108
-------
COMPOUND: Aspartic acid, N.N-dimethyl-, DL-
COMPOUND:
Aspartic acid, N,N-dimethyl-, DL-
REFERENCE: Curtis, D.R. and Watkins, J.C.
J. Neurochem. 6:117-141, 1960.
REFERENCE:Curtis, D.R. and Watkins, J.C.
J. Physiol. 166:1-14, 1963.
OBSERVED NEUROTOXIC EFFECTS:
Treatment caused excitation or depression of
neuronal activity. Excitatory ranking: glutamic,
6-aminoglutaric, aspartic, cysteic, cysteine-
sulfinic acids, B-hydroxyglutamic, N-methylaspartic,
N-formiminoaspartic acids.
Depressant ranking: g-alanine, GABA, taurine,
N-methyl-B-alanine, 6-amino-B-hydroxybutyric,
glycine, a-alanine, 6-aminovaleric, B-aminoisobutyric
acids.
Structure-activity relationships established.
OBSERVED NEUROTOXIC EFFECTS:
N-methyl-D-aspartic and D-homocysteic acids were
stronger excitants of depolarization than all
others. With some compounds the action was
prolonged for many seconds after the stimulus
was terminated, notably N-n-propyl-D-aspartic
acid. There were no differences among types of
neurons tested; structure-activity relationship
was observed.
ANIMALS:
Cats, surgically prepared to exposed motoneurones, Renshaw cells or
dorsal horn interneurones in lumbar cord.
ANIMALS: Cats prepared for electrophoretic application of chemicals to single
central nervous system neurons.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Qualitative doses.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Dilutions 0.1-0.5 M of 31 compounds mainly of aspartic,
glutamic and cysteic acids listed in order of
potency of results.
ROUTE AND SITE: Topical, ionophoresis
CONTROL INFORMATION: Laboratory
ROUTE AND SITE:
CONTROL INFORMATION:
Electrophoretic application, various sites in central nervous
system.
None
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry, electrophysiology
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Electrophysiological
109
110
-------
COMPOUND: . Aspartlc acid, N-ethyl, D-
COMPOUND: Aspartic acid, N-ethyl-, DL-
REFERENCE:Curtis, D.R. and Watkins, J.C.
J. Physiol. 166:1-14, 1963.
REFERENCE:Curtis, D.R. and Watkins, J.C.
J. Physiol. 166:1-14, 1963.
OBSERVED NEUROTOXIC EFFECTS:
N-methyl-D-aspartic and D-homocysteic acids were
stronger excitants of depolarization than all
others. With some compounds the action was
prolonged for many seconds after the stimulus
was terminated, notably N-ii-propyl-D-aspartic
acid. There were no differences among types of
neurons tested; structure-activity relationship
was observed.
OBSERVED NEUROTOXIC EFFECTS:
N-methyl-D-aspartic and D-homocysteic acids were
stronger excitants of depolarization than all
others. With some compounds the action was
prolonged for many seconds after the stimulus
was terminated, notably N-ii-propyl-D-aspartic
acid. There were no differences among types of
neurons tested; structure-activity relationship
was observed.
ANIMALS: Cats prepared for electrophoretic application of chemicals to single
central nervous system neurons.
ANIMALS: Cats prepared for electrophoretic application of chemicals to single
central nervous system neurons.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Dilutions 0.1-0.5 M of 31 compounds mainly of aspartic,
glutamic and cysteic acids listed in order of
potency of results.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Dilutions 0.1-0.5 M of 31 compounds mainly of aspartic,
glutamic and cysteic acids listed in order of
potency of results.
ROUTE AND SITE:
CONTROL INFORMATION:
Electrophoretic application, various sites in central nervous
system.
None
ROUTE AND SITE:
CONTROL INFORMATION:
Electrophoretic application, various sites in central nervous
system.
None
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Electrophysiological
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Electrophysiological
111
112
-------
COMPOUND: Aspartic acid, N-ethyl, L-
COMPOUND-
Aspartic acid, N-formimino-, L-
REFERENCE:Curtis, D.R. and Watkins, J.C.
J. Physiol. 166:1-14, 1963.
REFERENCE: Curtis, D.R. and Watkins, J.C.
J. Neurochem. 6:117-141, 1960.
OBSERVED NEUROTOXIC EFFECTS:
N-methyl-D-aspartic and D-homocysteic acids were
stronger excitants of depolarization than all
others. With some compounds the action was
prolonged for many seconds after the stimulus
was terminated, notably N-ii-propyl-D-aspartic
acid. There were no differences among types of
neurons tested; structure-activity relationship
was observed.
OBSERVED NEUROTOXIC EFFECTS:
Treatment caused excitation or depression of
neuronal activity. Excitatory ranking: glutamic,
6-aminoglutaric, aspartic, cysteic, cysteine-
sulfihic acids, B-hydroxyglutamic, N-methylaspartic,
N-formiminoaspartic acids.
Depressant ranking: 6-alanine, GABA, taurine,
N-methyl-B-alanine, 6-amino-B-hydroxybutyric,
glycine, a-alanine, 6-aminovaleric, B-aminoisobutyric
acids.
Structure-activity relationships established.
ANIMALS: Cats prepared for electrophoretic application of chemicals to single
central nervous system neurons.
ANIMALS:
Cats, surgically prepared to exposed motoneurones, Renshaw cells or
dorsal horn interneurones in lumbar cord.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Dilutions 0.1-0.5 M of 31 compounds mainly of aspartic,
glutamic and cysteic acids listed in order of
potency of results.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Qualitative doses.
ROUTE AND SITE:
CONTROL INFORMATION:
Electrophoretic application, various sites in central nervous
system.
None
ROUTE AND SITE: Topical, ionophoresis
CONTROL INFORMATION: Laboratory
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Electrophysiological
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry, electrophysiology
113
114
-------
COMPOUND: Aspartic acid, N-iminomethyl-, D-
COMPOUND' Aspartic acid, N-iminomethyl-, L-
REFERENCE:Curtis, D.R. and Watklns, J.C.
J. Physiol. 166:1-14, 1963.
REFERENCE:Curtls, D.R. and Watkins, J.C.
J. Physiol. 166:1-14, 1963.
OBSERVED NEUROTOXIC EFFECTS:
N-methyl-D-aspartic and D-homocysteic acids were
stronger excitants of depolarization than all
others. With some compounds the action was
prolonged for many seconds after the stimulus
was terminated, notably N-nj-propyl-D-aspartic
acid. There were no differences among types of
neurons tested; structure-activity relationship
was observed.
OBSERVED NEUROTOXIC EFFECTS: N-methyl-D-aspartic and D-homocysteic acids were
stronger excitants of depolarization than all
others. With some compounds the action was
prolonged for many seconds after the stimulus
was terminated, notably N-n^propyl-D-aspartic
acid. There were no differences among types of
neurons tested; structure-activity relationship
was observed.
ANIMALS: Cats prepared for electrophoretic application of chemicals to single
central nervous system neurons.
ANIMALS: Cats prepared for electrophoretic application of chemicals to single
central nervous system neurons.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Dilutions 0.1-0.5 M of 31 compounds mainly of aspartic,
glutamic and cysteic acids listed in order of
potency of results.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Dilutions 0.1-0.5 M of 31 compounds mainly of aspartic,
glutamic and cysteic acids listed in order of
potency of results.
ROUTE AND SITE: Electrophoretic application, various sites in central nervous
system.
CONTROL INFORMATION: „
None
ROUTE AND SITE: Electrophoretic application, various sites In central nervous
system.
CONTROL INFORMATION:
None
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Electrophysiological
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Electrophysiological
115
116
-------
COMPOUND:
Aspartic acid, N-methyl-, D-
COMPOUND: Aspartic acid, N-methyl, DL-
REFERENCE:Curtis, D.R. and Watkins, J.C.
J. Phyaiol. 166:1-14, 1963.
REFERENCE: Curtis, D.R. and Watkins, J.C.
J. Neurochem. 6:117-141, 1960.
OBSERVED NEUROTOXIC EFFECTS:. Aspartic acid, N-methyl-, Dr and.D-homocysteic acid wer
stronger excitants of depolarization than all
others. With some compounds the action was
prolonged for many seconds after the stimulus
was terminated, notably N-n-propyl-D-aspartic
acid. There were no differences among types of
neurons tested; structure-activity relationship
was observed.
OBSERVED NEUROTOXIC EFFECTS:
Treatment caused excitation or depression of
neuronal activity. Excitatory ranking: glutamic,
6-aminoglutaric, aspartic, cysteic, cysteine-
sulfinic acids, 6-hydroxyglutamic, N-methylaspartic,
N-fonniminoaspartic acids.
Depressant ranking: S-alanine, GABA, taurine,
N-methyl-B-alanine, 6-amino-B-hydroxybutyric,
glycine, a-alanine, 6-aminovaleric, B-aminoisobutyric
acids.
Structure-activity relationships established.
ANIMALS: Cats prepared for electrophoretic application of chemicals to single
central nervous system neurons.
ANIMALS:
Cats, surgically prepared to expose- motoneurones, Renshaw cells or
dorsal horn interneurones in lumbar cord.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Dilutions 0.1-0.5 M of 31 compounds mainly of aspartic,
glutamic and cysteic acids listed in order of
potency of results.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Qualitative doses.
ROUTE AND SITE:
CONTROL INFORMATION:
Electrophoretic application, various sites in central nervous
system.
None
ROUTE AND SITE: Topical, ionophoresis
CONTROL INFORMATION: Laboratory
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Electrophysiological
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry, electrophysiology
117
118
-------
COMPOUND" Aspartic acid, N-methyl-, DL-
COMPOUND:
Aspartic acid, alpha-methyl-, DL-
REFERENCE:Curtis, D.R. and Watkins, J.C.
J. Physiol. 166:1-14, 1963.
OBSERVED NEUROTOXIC EFFECTS:
N-methyl-D-aspartic and D-homocysteic acids were
stronger excitants of depolarization than all
others. With some compounds the action was
prolonged for many seconds after the stimulus
was terminated, notably N-ir-propyl-D-aspartic
acid. There were no differences among types of
neurons tested; structure-activity relationship
was observed.
REFERENCE:
Olney, J.W., Ho, O.L. and Rhee, V.
Exp. Brain Res. 14:61-76, 1971.
OBSERVED NEUROTOXIC EFFECTS: The compound was toxic to non-neurol components
(glia, etc.), but not to neurons.
ANIMALS: Cats prepared for electrophoretic application of chemicals to single
central nervous system neurons.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Dilutions 0.1-0.5 M of 31 compounds mainly of aspartic,
glutamic and cysteic acids listed in order of
potency of results.
ANIMALS: Mice, Swiss-webster age 10 d, total 250
PREPARATION AND DOSE
or HISTORY OF PATIENT: Initially 12 mmoles/kg, then range established for
each compound.
ROUTE AND SITE: Electrophoretic application, various sites in central nervous
system.
CONTROL INFORMATION:
None
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Electrophysiological
ROUTE AND SITE:
S.C.
CONTROL INFORMATION: Compounds compared with monosodium L-glutamate (MSG)
potency for selectively necrosing neurons in retina
and brain (hypothalamus)
DURATION OF EXPERIMENT: 5 hr or serial intervals including 5 hr.
EXAM. TYPE: Histology
119
120
-------
COMPOUND:
Aspartic acid, N-methyl-, DL-
REFERENCE:
Olney, J.W., Ho, O.L. and Rhee, V.
Exp. Brain Res. 14:61-76, 1971.
OBSERVED NEUROTOXIC EFFECTS: The compound was more potent than monosodlum
glutamate in necrosing neurons in the retina
and brain. This compound is a powerful neuro-
excitant and the neurotoxic properties may be
governed by similar mechanisms.
ANIMALS: Mice, Swiss-webster age 10 d, total 250
PREPARATION AND DOSE
or HISTORY OF PATIENT: Initially 12 mmoles/kg, then range established for
each compound.
ROUTE AND SITE:
S.C.
CONTROL INFORMATION: Compounds compared with monosodium L-glutamate (MSG)
potency for selectively necrosing neurons in retina
and brain (hypothalamus)
DURATION OF EXPERIMENT: 5 hr or serial intervals including 5 hr.
EXAM. TYPE: Histology
121
COMPOUND:
Aspartic acid, N-methyl-, DL-
REFERENCE: Olney, J.W., Ho, O.L. and Rhee, V.
Exp. Brain Res. 14:61-76, 1971.
OBSERVED NEUROTOXIC EFFECTS: The compound was more potent than monosodium
glutamate in necrosing neurons in the retina
and brain. This compound is a powerful neuro-
excitant and the neurotoxic properties may be
governed by similar mechanisms.
ANIMALS: Mice, Swiss-webster age 10 d, total 250
PREPARATION AND DOSE
or HISTORY OF PATIENT: Initially 12 mmoles/kg, then range established for
each compound.
ROUTE AND SITE:
S.C.
CONTROL INFORMATION: Compounds compared with monosodium L-glutamate (MSG)
potency for selectively necrosing neurons in retina
and brain (hypothalamus)
DURATION OF EXPERIMENT: 5 hr or serial intervals including 5 hr.
EXAM. TYPE: Histology
122
-------
COMPOUND: Aspartic acid, N-methyl-, L-
COMPOUND: Aspartic acid, N-propyl-, D-
REFERENCE:Curtis, D.R. and Watkins, J.C.
J. Physiol. 166:1-14, 1963.
REFERENCE:Curtis, D.R. and Watkins, J.C.
J. Physiol. 166:1-14, 1963.
OBSERVED NEUROTOXIC EFFECTS:
N-methyl-D-aspartlc and D-homocysteic acids were
stronger excitants of depolarization than all
others. With some compounds the action was
prolonged for many seconds after the stimulus
was terminated, notably N-n-propyl-D-aspartic
acid. There were no differences among types of
neurons tested; structure-activity relationship
was observed.
OBSERVED NEUROTOXIC EFFECTS:
N-methyl-D-aspartic and D-homocysteic acids were
stronger excitants of depolarization than all
others. With some compounds the action was
prolonged for many seconds after the stimulus
was terminated, notably N-nj-propyl-D-aspartic
acid. There were no differences among types of
neurons tested; structure—activity relationship
was observed.
ANIMALS: Cats prepared for electrophoretic application of chemicals to single
central nervous system neurons.
ANIMALS: Cats prepared for electrophoretic application of chemicals to single
central nervous system neurons.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Dilutions 0.1-0.5 M of 31 compounds mainly of aspartic,
glutamic and cysteic acids listed in order of
potency of results.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Dilutions 0.1-0.5 M of 31 compounds mainly of aspartic,
glutamic and cysteic acids listed in order of
potency of results.
ROUTE AND SITE:
CONTROL INFORMATION:
Electrophoretic application, various sites in central nervous
system.
None
ROUTE AND SITE: Electrophoretic application, various sites in central nervous
system.
CONTROL INFORMATION: ' '
None
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Electrophysiological
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Electrophysiological
123
124
-------
COMPOUND: Aspartic acid, N-propyl-, L-
COMPOUND:
Atropine
REFERENCE:Curtis, D.R. and Watkins, J.C.
J. Physiol. 166:1-14, 1963.
OBSERVED NEUROTOXIC EFFECTS:
N-methyl-D-aspartic and D-homocysteic acids were
stronger excitants of depolarization than all
others. With some compounds the action was
prolonged for many seconds after the stimulus
was terminated, notably N-ii-propyl-D-aspartic
acid. There were no differences among types of
neurons tested; structure-activity relationship
was observed.
REFERENCE: pfeiffer, C.C., Murphree, H.B., Jenney, E.H., Robertson, M.G.,
Randall, A.H. and Bryan, L.
Neurology 9: 249-250, 1959.
OBSERVED NEUROTOXIC EFFECTS: The authors concluded that synthetic atropines are more
j active hallucinogens than atropine or scopolamine, pro-
ducing effects lasting 24-48 hr. Synthetic antltremor
drugs had fewer peripheral nervous system side-effects,
but central nervous system side-effects (hallucinations)
may have been exaggerated.
ANIMALS: Cats prepared for electrophoretic application of chemicals to single
central nervous system neurons.
ANIMALS: Human: prison volunteers, drug-sophisticated, no other details
PREPARATION AND DOSE
or HISTORY OF PATIENT: Dilutions 0.1-0.5 M of 31 compounds mainly of aspartic,
glutamic and cysteic acids listed in order of
potency of results.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 2 mg/man
ROUTE AND SITE: Electrophoretic application, various sites in central nervous
system.
None
CONTROL INFORMATION:
ROUTE AND SITE: Oral
CONTROL INFORMATION: LSD-25: 0, 25, 50, 100 meg/man
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Electrophysiological
DURATION OF EXPERIMENT: Up to 3 d
EXAM. TYPE: Opinion of volunteers
125
126
-------
COMPOUND: Atropinium, 8-methyl-, nitrate
000052880
REFERENCE: Qulnton, R.M.
Br. J. Pharmac. 21:51-66, 1963.
OBSERVED NEUROTOXIC EFFECTS: The compound enhanced the effect of Yohimbine
and lowered its lethal dosage.
COMPOUND: Atropinium, 8-methyl-, nitrate
000052880
REFERENCE: Spooner, C.E. and Winters, W.D.
Int. J. Neuropharmacol. 5: 217-236, 1966
OBSERVED NEUROTOXIC EFFECTS: Compound produced locomotor ataxia and arousal EEGs.
ANIMALS:
Mice, TT, M, 18-25 g.
ANIMALS: 200 Cockerels, White Leghorn, ages 5-14 d, 45-100 g
PREPARATION AND DOSE
or HISTORY OF PATIENT:
ED5Q 15 mg/kg
= dose producing a 50% mortality of mice injected
"50
S.C. with yohimbine hydrochloride (20 mg/kg).
PREPARATION AND DOSE
or HISTORY OF PATIENT: 2 mg/kg
ROUTE AND SITE: S.C., Oral
CONTROL INFORMATION: Various
ROUTE AND SITE: S.C. near axillary vein; I.P. for doses over 0.05 ml
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Behavior, electrophysiology, biochemistry
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Behavior, EEC
127
128
-------
COMPOUND: Atroplne SO^ (2:1)
000055481
REFERENCE: Quinton, R.M.
Br. J. Pharmac. 21:51-66, 1963.
COMPOUND: Atropine S04 (2:1)
000055481
REFERENCE: Spooner, C.E. and Winters, W.D.
Int. J. Nr.uropharmacol. 5: 217-236, 1966
OBSERVED NEUROTOXIC EFFECTS: The compound enhanced the effect of Yohimblne
and lowered its lethal dosage.
OBSERVED NEUROTOXIC EFFECTS: Compound produced locomotor ataxia and arousal EEGs.
ANIMALS:
Mice, TT, M, 18-25 g.
ANIMALS: 200 Cockerels, White Leghorn, ages 5-14 d, 45-100 g
PREPARATION AND DOSE
or HISTORY OF PATIENT:
ED5Q 40 mg/kg
ED,- = dose producing a 50% mortality of mice injected
S.C. with yohimbine hydrochloride (20 mg/kg).
PREPARATION AND DOSE
or HISTORY OF PATIENT: 2-10 mg/kg
ROUTE AND SITE: S.C., Oral
CONTROL INFORMATION: Various
ROUTE AND SITE: S.C. near axillary vein; I.P.'for doses over 0.05 ml
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Behavior, electrophysiology, biochemistry
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Behavior, EEC
129
130
-------
COMPOUND: Barbituric acid, 5-allyl-5-(l-Methylbutyl)-
000076733
REFERENCE:Melville, K., Jordon, G., Douglas, D.
Toxicology and Applied Pharmacology 9:363-375, 1966.
OBSERVED NEUROTOXIC EFFECTS: Ataxia or "no spontaneous movement" as compared to
intense central nervous system depression by
synergistic action with alcohol.
COMPOUND: Barbituric acid, 5-allyl-l-methyl-5-(l-methyl-2-pentynyl)-,
sodium salt
000309364
REFERENCE: Spooner, C.E. and Winters, W.D.
Int. J. Neurophannacol. 5: 217-236, 1966
OBSERVED NEUROTOXIC EFFECTS: Compound produced depression and associated slow-
wave EEGs.
ANIMALS: Mongrel dogs, 7.0-12.0 kg, M and F.
ANIMALS: 200 Cockerels, White Leghorn, ages 5-14 d, 45-100 g
PREPARATION AND DOSE
Or HISTORY OF PATIENT: 25 mg/kg in total volume of 60 ml water
PREPARATION AND DOSE
or HISTORY OF PATIENT: 10-30 mg/kg
ROUTE AND SITE: Stomach tube
CONTROL INFORMATION: ns.
ROUTE AND SITE: s.C. near axillary vein; I.P. for doses over 0.05 ml
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: More than 1 wk.
EXAM. TYPE Behavior
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Behavior, EEC
131
132
-------
COMPOUND: Barbituric acid, 5,5-Diethyl-, sodium salt
000144025
REFERENCE: Essig, C.F. and Flanary, H.G.
Exp. Neurol. 3: 149-159, 1961f
COMPOUND: Barbituric acid, 5-ethyl-5-(l-methylbutyl)-, sodium salt (Nembutal)
REFERENCE: Becker, R.F., Flannagan, E. and King, J.E.
Neurology 8: 776-782, 1958.
OBSERVED NEUROTOXIC EFFECTS: Withdrawal caused major and minor seizures with bi-
laterally symmetrical inter-seizure EEC abnormalities.
The cerebral cortex appeared to be involved, but only
as secondary brainstern involvement.
OBSERVED NEUROTOXIC EFFECTS: Nembutal sedation of mother followed by Cesarian
delivery resulted in severe neural damage. Of spontan-
eous deliveries after treatment with Nembutal on day
22, 42, or 63 of gestation, birth mortality was high;
surviving young showed only mild signs of brain
damage. Heavy anesthetization of newborn caused
severe neuropathy.
ANIMALS: Cats, surgically prepared, 6
ANIMALS: Guinea-pigs, pregnant
PREPARATION AND DOSE
or HISTORY OF PATIENT: Increasing doses, 95-335 mg/kg/d up to 267 d; then abrupt
withdrawal
PREPARATION AND DOSE
or HISTORY OF PATIENT: 30 or 38 mg/kg before spontaneous delivery
ROUTE AND SITE: Oral (capsules)
CONTROL INFORMATION: 3 cats prepared but untreated
ROUTE AND SITE: I.P.
CONTROL INFORMATION: Saline; Cesarian section.
DURATION OF EXPERIMENT: 106-267 d
EXAM. TYPE: Electrophysiological, behavioral
DURATION OF EXPERIMENT: term (average 66.5 d)
EXAM. TYPE: Teratology
133
134
-------
COMPOUND: Barbituric acid, 5-ethyl-5-(l-methylbutyl)-, sodium salt
000057330
REFERENCE: Spooner, C.E. and Winters, W.D.
Int. J. Neuropharmacol. 5: 217-236, 1966.
OBSERVED NEUROTOXIC EFFECTS: Compound produced depression and associated slow-wave
EEGs.
COMPOUND: Barbituric acid, 5-ethyl-5-(l-methylbutyl)-2-thio-, sodium salt
000071738
REFERENCE: Spooner, C.E. and Winters, W.D.
Int. J. Neuropharmacol. 5: 217-236, 1966
OBSERVED NEUROTOXIC EFFECTS: Compound produced depression and associated slow-
wave EEGs.
ANIMALS: 200 Cockerels, White Leghorn, ages 5-14 d, 45-100 g
ANIMALS: 200 Cockerels, White Leghorn, ages 5-14 d, 45-100 g
PREPARATION AND DOSE
or HISTORY OF PATIENT: 2-100 mg/kg
PREPARATION AND DOSE
or HISTORY OF PATIENT: io-30 mg/kg
ROUTE AND SITE: s.C. near axillary vein; I.P. for doses over 0.05 ml
CONTROL INFORMATION: ns
ROUTE AND SITE: S.C. near axillary vein; I.P. for doses over 0.05 ml
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Behavior, EEC
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Behavior, EEC
135
136
-------
COMPOUND: Barbituric acid, 5-ethyl-5-phenyl-
000050066
REFERENCE: Schain, R.J. and Watanabe, K.
Exp. Neurol. 47:509-515, 1975.
OBSERVED NEUROTOXIC EFFECTS: Body and brain growth retarded, not due only
to impaired nutrition. In cerebellum, accumulation of cholesterol
was retarded more than of DNA, RNA or protein, interpreted by authors
as interference with myelination.
COMPOUND: Benzamide, p-amino-n-(2-(dlethylamino)ethyl))-
REFERENCE:
Drachman, D.A. and Skom, J.H.
Arch. Weurol. 13:316-320, 1965.
OBSERVED NEUROTOXIC EFFECTS: Muscle weakness attributed to acetylcholine
inhibition, recovered after withdrawal of compound
on two occasions.
ANIMALS: Rats, Wistar, newborn M pups
ANIMALS:
1 Human, M aged 78 yr.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 30-60 mg/kg/d, from d 3-d 21, vehicle ns.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Myasthenia gravis with myocardial infarction on many
drugs in hospital; single doses of 500 and 250 mg of
compound, then 6 hourly doses of 250 mg for 14 doses.
ROUTE AND SITE: s.C.
CONTROL INFORMATION: Littermate controls, vehicle only
ROUTE AND SITE: Oral
CONTROL INFORMATION:
None
DURATION OF EXPERIMENT: Sacr at 21 d age
EXAM. TYPE: Biochemical
DURATION OF EXPERIMENT: About 1 mo.
EXAM. TYPE: Clinical
137
138
-------
COMPOUND: Benzenearsonic acid, 4-hydroxy-3-nitro-
000121197
COMPOUND: Benzilic acid, l-methyl-3-piperidyl ester, hydrochloride
REFERENCE: Wise, D.R., Hartley, W.J. and Fowler, N.G.
Res. Vet. Sci. 16: 336-340, 1974.
OBSERVED NEUROTOXIC EFFECTS:
REFERENCE: Pfeiffer, C.C., Murphree, H.B., Jenney, E.H., Robertson, M.G.,
Randall, A.H. and Bryan, L.
Neurology 9: 249-250, 1959.
Those fed over SOppm exhibited ataxic and leg weakness. nDCcm.rn urnon-rAvr,- rr-rr^-rc-
No damage was found in the central nervous system, but OBbtRVED NEUROTOXIC EFFECTS: The authors concluded that synthetic atropines are more
distal peripheral nervous system degeneration (wallerian) active hallucinogens than atropine or scopolamine, pro-
of myelin and axons was observed. ducing effects lasting 24-48 hr. Synthetic antitremor
drugs had fewer peripheral nervous system side-effects,
but central nervous system side-effects (hallucinations)
may have been exaggerated.
ANIMALS: 75 Turkey hens, 1 d old, in 5 groups of 15
ANIMALS: Human: prison volunteers, drug-sophisticated, no other details
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0-547 PPm in diet
PREPARATION AND DOSE
or HISTORY OF PATIENT: 6 mg/man (experimental)
9 mg/man (hallucinogens)
ROUTE AND SITE: oral
CONTROL INFORMATION: untreated
ROUTE AND SITE: Oral
CONTROL INFORMATION: LSD-25: 0, 25, 50, 100 meg/man
DURATION OF EXPERIMENT: 35 d
EXAM. TYPE: Behavior, histology
DURATION OF EXPERIMENT: Up to 3 d
EXAM. TYPE: Opinion of volunteers
139
140
-------
COMPOUND: 2-Benzimidazolinone, l-(l-(3-(p-fluorobenzoyl)propyl)-l,2,3,6-
tetrahydro-4-pyridyl)-
REFERENCE: DeSilva, K.L., Muller, P.J. and Pearce, J.
Practitioner 211: 316-320, 1973.
COMPOUND: 3H-l,4-Benzodiazepine, 7-chloro-2-(methylamlno)-5-phenyl-, 4-oxide
REFERENCE:
UUUU30Z3J
Pearlman, C. and Becker, M.
Psychopharmacologia A2:63-66, 1975.
OBSERVED NEUROTOXIC EFFECTS:
Extrapyramidal signs, spasms especially of face, tongue
and jaws, torticollis, opisthotonus, trismus; onset in
2-60 hrs. commonest in young. No dose relationship,
recovery after withdrawal. One case had added dienceph-
alic features. Authors comment that etiology still
unknown, and suggest idiosyncracy to class of drugs
(phenothiazines).
OBSERVED NEUROTOXIC EFFECTS:
Cooperative behavior training and performance pre-
vented when compound administered a few minutes
after feeding session, no effects if given 3 hr
afterwards. Authors concluded mechanism was pre-
vention of REM sleep during this time.
ANIMALS: Human: 10 cases, M & F, 14-30, selected from 20 cases treated at a
hospital serving 500,000 population, over 2 yrs
ANIMALS: Rats: Long-Evans, F, 3 mo. age.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
1 case: 10 mg. I.V.
Adverse drug reaction.
PREPARATION AND DOSE
Or HISTORY OF PATIENT: 4 mg/kg on alternate days a few minutes after session
or after 3 hrs. of rest.
ROUTE AND SITE: I.V. (see above)
CONTROL INFORMATION: None
ROUTE AND SITE: I.P.
CONTROL INFORMATION: 6 Controls undistrubed sleep, 6 had saline inj. followed
by normal sleep.
DURATION OF EXPERIMENT: 3 hrs.
EXAM. TYPE: Clinical
DURATION OF EXPERIMENT: Approx. 10 d
EXAM. TYPE: Behavior
141
142
-------
COMPOUND: 3H-l,4-Benzodiazepine, 7-chloro-2-(methylamino)-5-phenyl-, 4-oxide
000058253
REFERENCE: Zbtnden, G., Bagdon, R.E., Keith, E.F., Phillips, R.D., and Randall, L.O.
Toxicol. Appl. Pharmacol. 3: 619-637, 1961.
COMPOUND: 2H-l,4-Benzodiazepin-2-one,7_chloro-l,3-dihydro-l-methyl-5-phenyl-
006613850
REFERENCE: Greenblatt, D.J. and Kock-Weser, J.
Am. J. Med. Sci. 266: 261-266, 1973.
OBSERVED NEUROTOXIC EFFECTS: (D Ingestion caused sedation, often ataxia and dysarthria,
and in rare instances sleep and coma
„ (2 and 3) Symptoms similar to (1)
OBSERVED NEUROTOXIC EFFECTS: Apnea and coma, hypotension and coma, confusion and
obtundation were observed in patients with contributory
complications or other drug therapy.
ANIMALS: (D Human, 6 M and 16 F, 15 to 59 yr (attempted suicides)
(2) Rats, CFN
(3) Dogs
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) 200 to 2250 mg/kg
(2) 20, 40, or 80 mg/kg/day for 52 wk
(3) 5 to 80 mg/kg/day for 6 mo
ANIMALS: Human: 6 patients ages 40-91, 3.5% of 173 subjects given compound I.V.,
who were 1.2% of 2,623 patients receiving compound, who were 18.3% of
14,344 patients studied in a drug surveillance program.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Doses 5-30 mg/patient, one dose
ROUTE AND SITE: Oral
CONTROL INFORMATION: ns
ROUTE AND SITE: I.v.
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: 52 wk
EXAM. TYPE: Clinical
DURATION OF EXPERIMENT: Up to 19 d
EXAM. TYPE: Clinical
143
144
-------
COMPOUND: Benzole acid
000065850
REFERENCE: Krels, H., Frese, K., and Wilmes, G.
Fd. Cosmet. Toxicol., 5: 505-511, 1967.
COMPOUND: Benzole acid, p-amino-, 2-(diethylamino)ethyl ester (Procalne)
O00059':61
REFERENCE: Hirst, G.D.S. and Wood, D.R.
Br. J. Pharmac. 41: 94-104, 1971.
OBSERVED NEUROTOXIC EFFECTS:
Retarded growth, irritation, ataxia,tonic-clonic
convulsions. Necrosis of parenchymal cells of
stratum granulosum of fascia dentata and cortex
of lobus plriformis. Feeding of 1.1% failed to
induce any neurotoxic signs or pathological changes
in the brain.
OBSERVED NEUROTOXIC EFFECTS: Procaine caused paralysis resembling that produced
by tubocurarine. At low stimulation rates, it produced
no depression of transmitter release but at high rates,
a distinctive prejunctional failure was observed.
ANIMALS: Rats, Weanling, M.
ANIMALS: Phrenic nerve-diaphragm preparations from rats, Wistar, M, 150-250 g
PREPARATION AND DOSE
or HISTORY OF PATIENT:
(1) 3% dietary level for 5 d.
(2) 1.1% in diet for 35 d.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.025-0.1 mM
ROUTE AND SITE: Oral
CONTROL INFORMATION: ns.
ROUTE AND SITE: m vitro
CONTROL INFORMATION: Laboratory
DURATION OF EXPERIMENT: 5 d
EXAM. TYPE: Pathology, behavior
DURATION OF EXPERIMENT: various
EXAM. TYPE: Electrophysiology
145
146
-------
COMPOUND:
Benzole acid, hydrazide
00613945
REFERENCE: Jenney, E.H. and Pfeiffer, C.C.
J. Pharm. Exp. Ther. 122: 110-123, 1958.
OBSERVED NEUROTOXIC EFFECTS: Convulsions
ANIMALS: Mice, Harlan, 19-21 g
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.9 mM/kgm
ROUTE AND SITE: i.p.
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: Acute
EXAM. TYPE: Clinical
147
COMPOUND: Benzoxazole, 2-amino-5-chloro-
000061803
REFERENCE: Fujii, K., Jaffe, H. and Epstein, S.S.
Tox. Appl. Pharm. 13:431-438, 1968.
OBSERVED NEUROTOXIC EFFECTS: Temporary paralysis
ANIMALS: Mice, ICR Swiss Albino, A/J, and BALB/c
PREPARATION AND DOSE
or HISTORY OF PATIENT: 80 mg/kg as part of a larger study.
ROUTE AND SITE: i.p.
CONTROL INFORMATION: Various
DURATION OF EXPERIMENT: 5 hr.
EXAM. TYPE: clinical
148
-------
COMPOUND: Benzyl alcohol, 3,4-dichloro-alpha-((isopropylamino)methyl)-,
hydrochloride
REFERENCE: Quinton, R.M.
Br. J. Pharmac. 21:51-66, 1963.
COMPOUND: Benzyl alcohol, m-hydroxy-alpha-(methylamino)methyl)-, hydrochloride, (-)-
REFERENCE: Ceilings, H.
Arch. Neurol. 3:656-660, 1960.
OBSERVED NEUROTOXIC EFFECTS: The compound enhanced the effect of Yohimbine
and lowered its lethal dosage.
OBSERVED NEUROTOXIC EFFECTS: Polyneuropathy, severe disintegration of myelin in
peripheral nerves and nerve roots.
ANIMALS:
Mice, TT, M, 18-25 g.
ANIMALS:
Human: 4 case reports; 1 case in addendum.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
ED5Q >50 mg/kg
ED,. = dose producing a 50% mortality of mice injected
S.C. with yohimbine hydrochloride (20 mg/kg).
ROUTE AND SITE: S.C., Oral
CONTROL INFORMATION: Various
PREPARATION AND DOSE
or HISTORY OF PATIENT:
ROUTE AND SITE: Oral
CONTROL INFORMATION:
Furacin 0.5 g three times daily for 2 d, then four times
daily for a total of 30.5 g; furadantin 100 mg
four times daily for a total 24 g in 59 d; furandantin 100
mg four times daily for total of 18 g in 45 d (intermittent
therapy). Addendum: furaltadone 250 mg four times daily
for a total of 52 g in 26 d. (Furacin = Nitrofurazone;
furadantin = nitrofurantoin)
None
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Behavior, electrophysiology, biochemistry
DURATION OF EXPERIMENT: Months of follow-up
EXAM. TYPE: Behavior, autopsy
149
150
-------
COMPOUND: Benzylamine, N-(2-chloroethyl)-N-(l-methyl-2-phenoxyethyl)-
000059961
REFERENCE: Quinton, R.M.
Br. J. Pharmac. 21:51-66, 1963.
OBSERVED NEUROTOXIC EFFECTS: The compound enhanced the effect of Yohimbine
and lowered its lethal dosage.
COMPOUND: Benzylamine, N-methyl-N-2-propynyl-, hydrochloride
000306070
REFERENCE: Quinton, R.M.
Br. J. Pharmac. 21:51-66, 1963.
OBSERVED NEUROTOXIC EFFECTS: The compound enhanced the effect of Yohimbine
and lowered its lethal dosage.
ANIMALS:
Mice, TT, M, 18-25 g.
ANIMALS:
Mice, TT, M, 18-25 g.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
ED5Q 33 mg/kg
EDen = dose producing a 50% mortality of mice injected
"50
S.C. with yohimbine hydrochloride (20 mg/kg).
PREPARATION AND DOSE
or HISTORY OF PATIENT:
ED5Q 80 mg/kg
ED_n = dose producing a 50% mortality of mice injected
S.C. with yohimbine hydrochloride (20 mg/kg).
ROUTE AND SITE: s.c., Oral
CONTROL INFORMATION: Various
ROUTE AND SITE: S.C., Oral
CONTROL INFORMATION: Various
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Behavior, electrophysiology, biochemistry
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Behavior, electrophysiology, biochemistry
151
152
-------
COMPOUND: Bicuculline
nnn/.os/.o/.
REFERENCE: Davidoff, R.A.
Science 175: 331-333, 1972,
OBSERVED NEUROTOXIC EFFECTS: The compound blocked the normal actions of GABA (gamma-
aminobutyric acid).
COMPOUND: Bicuculline
000485494
REFERENCE: Hill, E.G., Simmonds, M.A. and Straughan, D.W.
Br. J. Pharmac. 45: 176P-177P, 1972 (Abstract of proceedings).
OBSERVED NEUROTOXIC EFFECTS: The convulsive threshold was reached in 20 min;
abnormal electrographs were seen before GABA antagon-
ism, and were related with seizures. GABA was
ineffective in preventing convulsions.
ANIMALS: Frog spinal cord preparation, in vitro
ANIMALS: Cats, surgically prepared
PREPARATION AND DOSE
or HISTORY OF PATIENT: 5 to 20 meg/ml
PREPARATION AND DOSE
or HISTORY OF PATIENT: 20 mcg/min/kg
ROUTE AND SITE: in vitro
CONTROL INFORMATION: ns
ROUTE AND SITE: i.v. infusion
CONTROL INFORMATION: Leptazol (6 mg) used as control
DURATION OF EXPERIMENT: 10 hr
EXAM. TYPE: Electrophysiology
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Biochemistry, behavior
153
154
-------
COMPOUND: Bicuculline (Biculline)
REFERENCE:
Johnston, G.A.R. and Mitchell, J.F.
J. Neurochem. 18:2441-2446, 1971.
OBSERVED NEUROTOXIC EFFECTS:
COMPOUND: Biphenyl (Diphenyl)
000092524
REFERENCE: Hakkinen, I., Siltanen, E., Hernberg, S., Seppalainen, A.M.
Karli, P. and Vikkula, E.
Arch. Env. Hlth. 26: 70-74, 1973.
All four compounds influenced the release of GABA,
but not its uptake. Biculline, at 10~5 M (not
more or less) potentiated evoked release of GABA
but not the resting release. Metrazol inhibited
the electrically resting release but not the
electrically evoked release. Strychnine and
picrotoxin inhibited the electrically evoked
release of GABA.
OBSERVED NEUROTOXIC EFFECTS:
There was evidence of central and peripheral nervous
system damage. The damage to the peripheral nervous
system was judged to be demyelination, while that of
central nervous system appeared in an uncertain site
affecting memory and temper as well as sensorimotor
functions. The damage was progressive, with minor
function recoveries, for observed 6-7 month follow-u
after stopping exposure and the authors state that
prognosis must await longer follow-ups.
ANIMALS: In vitro slices of rat cerebral cortex
ANIMALS:
Human: 32 M, IF
PREPARATION AND DOSE
or HISTORY OF PATIENT:
ROUTE AND SITE: in vitro
CONTROL INFORMATION: Lab
Preincubated with compounds for 15 min, then with labeled
GABA for 10 min.
PREPARATION AND DOSE
or HISTORY OF PATIENT
ROUTE AND SITE:
History of exposure for various times to diphenyl in fruit
paper manufacture. Case-reports of 1 fatal, 9 nonfatal ca
exposed 5-15 yr to 4-128 mg/m (measured in 1959) or 0.6-1
mg/m (measured in 1970). TLV of 1 mg/m was set in 1968,
manufacturers claimed no dangers in paper-making in 1965.
process involved 800-840 hr/yr exposure to 128 (1959) or 6
(1970) mg/ni
Inhalation and skin contact
CONTROL INFORMATION: None, and few data found in literature
DURATION OF EXPERIMENT: 25 min
EXAM. TYPE: Biochemistry
DURATION OF EXPERIMENT: 5-15 yr with 6-7 mo follow-ups
EXAM. TYPE: History (ethanol and tri- and tetrachlorethylene solvents were
eliminated), electromyography, EEC
155
156
-------
COMPOUND: Biphenyl (Diphenyl)
000092524
REFERENCE: Seppalainen, A.M. and Hakkinen, I.
J. Neurol. Neurosurg, Psychiat. 38:248-252, 1975.
COMPOUND: Biphenyl, chloro-
REFERENCE: Mural, Y. and Kuroiwa, Y.
Neurology 21:1173-1176, 1971.
OBSERVED NEUROTOXIC EFFECTS: Abnormal EEC in 10, no recovery in 7 after 2 yr.
Abnormal electromyographs in 9, fibrillation in 7. Reduced nerve conductions.
These signs also persisted. Thus both central nervous system and peripheral
nervous system were affected.
OBSERVED NEUROTOXIC EFFECTS: Sensory neuropathy (symptoms and reduced
conduction velocity) found in about one-half of the cases. Only one case
of reduced motor conduction.
ANIMALS: Human: 23 M and 1 F selected from a larger group with industrial
exposure.
ANIMALS:
21 Humans, ages 7-60 yr.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Chronic, long term, to concentrations well over the
TLV of 1 mg/m-'. Exposure ceased at start of study (after 1 fatality).
PREPARATION AND DOSE
or HISTORY OF PATIENT: 21 consecutive cases seen at a hospital, in a mass outbreak
of tetrachlorobiphenyl poisoning (total about 350 cases). Contaminated rice
oil used for cooking.
ROUTE AND SITE: Inhalation, skin contact, perhaps oral too.
CONTROL INFORMATION: ns.
ROUTE AND SITE: Oral
CONTROL INFORMATION: Normal subjects were measured.
DURATION OF EXPERIMENT: 2 yr.
EXAM. TYPE: Clinical, electrophysiology
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Clinical, electrophysiological
157
158
-------
COMPOUND: Bis(p-aminophenoxy) alkane series
COMPOUND: Biuret, diamino-
REFERENCE: Udall, V.
Proc. Roy. Soc. Med. 65: 197-199, 1972.
OBSERVED NEUROTOXIC EFFECTS: Retinal damage to pigmented epithelium, no pupil
reflexes, perception deficits.
REFERENCE: Jenney, E.H. and Pfeiffer, C.C.
J. Pharm. Exp. Ther. 122: 110-123, 1958.
OBSERVED NEUROTOXIC EFFECTS: Convulsions
ANIMALS: Cats and Rabbits
ANIMALS: Mice, Harlan, 19-21 g
PREPARATION AND DOSE
or HISTORY OF PATIENT: ns
PREPARATION AND DOSE
or HISTORY OF PATIENT: 3.0 mM/kgm
ROUTE AND SITE: oral
CONTROL INFORMATION: ns
ROUTE AND SITE: i.p.
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Fundoscopy and histology
DURATION OF EXPERIMENT: Acute
EXAM. TYPE: Clinical
159
160
-------
COMPOUND:
REFERENCE:
Boric acid
ni r\r\/. one o
Pfeiffer, C.C., Hallman, L.F. and Bersh, I.
J. Am. Med. Assn. 128:266-274, 1945.
COMPOUND: Boric acid
010043353
REFERENCE: Watson, E.H.
J. Am. Med. Assn. 129:332-333, 1945.
OBSERVED NEUROTOXIC EFFECTS:
Acute: antemortem rigidity of legs. The largest amount of
boric acid was found in the brain: whole brain
214 mg/100 cc, cortex 231, corpus callosum
142 mg/100 cc. There was an increase of microglia,
and a shrinkage of cord neurons. Cortex lesions
"were distributed through grey-matter in some, and
concentrated around blood vessels in others.
There was an accumulation in the brain after
repeated doses.
OBSERVED NEUROTOXIC EFFECTS: Fatai in 3 wk. convulsions and coma, blindness,
deafness. At autopsy "irreparable damage to the
central nervous system" but brain not reported
as examined.
ANIMALS:
Dogs
ANIMALS: Human: M, age 4 1/2 mo., fatal case.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Acute: 1.5-2 g/kg.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Eczema, treated with whole-body applications of compound,
total estimated 60-100 g.
ROUTE AND SITE: Acute: S.C.
CONTROL INFORMATION: ns.
ROUTE AND SITE: Topical
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior, biochemistry, histology
DURATION OF EXPERIMENT: 3 wk.
EXAM. TYPE: Clinical
161
162
-------
COMPOUND: Boric acid, tri-o-tolyl ester
COMPOUND: Botulinum toxin type A
REFERENCE: Hine, C.H., Dunlap, M.K., Rice, E.G., Coursey, M.M., Gross, R.M.
and Anderson, H.H.
J. Pharm. Exp. Ther. 116:227, 1956.
OBSERVED NEUROTOXIC EFFECTS: (1) All had paralysis. (2) All died.
REFERENCE: Duchen, L.W.
Proc. Roy. Soc. Med. 65: 196-197, 1972.
OBSERVED NEUROTOXIC EFFECTS:
The leg muscles were paralysed in 24 hours and
recovered after 1 week. Progress and abnormalities
in axonal regenerating sprouts were observed
sequentially in time. The author concluded that
the toxin binds either to the presynaptic axolemma
or to a component of the motor nerve terminal
axoplasm to block neuromuscular transmission; only
new axonal tissue can transmit. Also concluded that
the compound can induce the observed regeneration.
ANIMALS:
22 Chickens, White Leghorn, M, 0.75-1.3 kg
ANIMALS: Mice, no details
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) 0.5 gm/kg
(2) 1.0 gm/kg
PREPARATION AND DOSE
or HISTORY OF PATIENT: "Sublethal" doses
ROUTE AND SITE: (1) S.C., (2) Oral
CONTROL INFORMATION: One group of 5 per experimental group.
ROUTE AND SITE: LM., one hindleg
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: 14-36 d after treatment.
EXAM. TYPE: Behavior, histology
DURATION OF EXPERIMENT: Probably 6-7 d
EXAM. TYPE: Histology
163
164
-------
COMPOUND: Botulinum toxin type A
COMPOUND:
Botulinum toxin type A
REFERENCE: Holman, M.E. and Spitzer, N.C.
Br. J. Pharmac. 47: 431-433, 1973.
REFERENCE:
Simpson, L.L. and Rapport, M.M.
J. Neurochem. 18:1341-1343, 1971.
OBSERVED NEUROTOXIC EFFECTS: The toxin depressed or abolished transmission from
postganglionic nerves to smooth-muscle, less rapidly
than in rat diaphragm reported elsewhere.
OBSERVED NEUROTOXIC EFFECTS:
(1) Trisialoganglioside G± produced the solution
with the least residual toxicity. (2) Survival
time was prolonged in ratio to the amount of
G^; asialo-G^-ganglioside was ineffective in vitro
and in vivo as were sialic acid, glucose, galactose,
galactosamine, or ceramide. (3) Potency for
paralysing synaptic transmission was similarly
diminished. Authors' conclusion: first
demonstration of direct interaction of a compound
with a natural constituent of nerve tissue.
ANIMALS: Isolated vas deferens preparations from mice and guinea-pigs
PREPARATION AND DOSE
or HISTORY OF PATIENT: Concentrations of compound ns
ANIMALS: (1) In vitro incubation of toxin with test substances
(2) Residual toxicity tested in mice in vivo.
(3) Residual toxicity measured in vitro in rat phrenic nerve-diaphragm
preparations.
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) Brain gangliosides singly or mixed 0.1-100 meg
incubation with compound type A at 103 or 10^ MLD/ml.
(2) 10 4 MLD incubation, 0.1 ml of solution.
(3) as for (2).
ROUTE AND SITE: Incubations in vitro
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: Up to 6 hr
EXAM. TYPE: Electrophysiology
ROUTE AND SITE: (1) In vitro (2) I.V. (3) Added to incubation mix in vitro.
CONTROL INFORMATION:
(1) Without ganglioside.
(2) Without ganglioside, 103 MLD.
(3) Similar.
DURATION OF EXPERIMENT: (1) ns. (2) Over 300 min. (3) ns.
EXAM. TYPE: (1) Chemistry (2) Survival time (3) Physiology
165
166
-------
COMPOUND: Brisacodyl
REFERENCE: Steer, H.W. and Colin-Jones, D.G.
J. Path. 115:199-205, 1975.
COMPOUND: a-Bungarotoxin
11032794
REFERENCE: Katz, B. and Miledl, R.
Br. J. Pharmac. 49: 138-139, 1973.
OBSERVED NEUROTOXIC EFFECTS: More lysosomal activity and lysosomes in Schwann
cells and neurons of submucosal plexus of colonic
OBSERVED NEUROTOXIC EFFECTS: The toxin inhibited acetylcholine sensitivity
irreversibly but not the amplitude nor time-
course of "elementary" potential changes.
ANIMALS:
Human: 7 aged 24-80 with melanosis coli who took purgatives;
1 who had taken purgatives for only 1 m.
ANIMALS: in vitro endplates of frog muscle fibers
PREPARATION AND DOSE
or HISTORY OF PATIENT: Rectal biopsy before and 3-7 m after stopping medication
PREPARATION AND DOSE
or HISTORY OF PATIENT: lontophoretic application
ROUTE AND SITE:
CONTROL INFORMATION:
7 aged 27-70 with other gut disorders who had taken no
purgatives for 3 m.
ROUTE AND SITE: m vitro
CONTROL INFORMATION: Laboratory
DURATION OF EXPERIMENT: About 7 m.
EXAM. TYPE: Histology, histochemistry
DURATION OF EXPERIMENT: About 30 min
EXAM. TYPE: Electrophysiology
167
168
-------
COMPOUND:
1,3-Butanediamine, N,N,N',N'-tetramethyl-
000097647
REFERENCE: Goldberg, M.E. and Johnson, H.E.
Tox. Appl. Pharm. 4:522-545, 1962.
COMPOUND: 1,4-Butanediol
0001110634
REFERENCE: Zabik, J.E., Van Dam, D.P. and Maickel, R.P.
Res. Conm. Chem. Path. Pharm. 8(1):83-90, 1974.
OBSERVED NEUROTOXIC EFFECTS: This compound selectively blocked autonomic ganglia, and
produced ocular disturbances.
OBSERVED NEUROTOXIC EFFECTS:
Loss of righting reflex, assumed to show toxicity.
This reflex was reduced, dose-dependent, from
50 mg/kg on up, with complete loss at 300 and 400
mg/kg. No increase in triglycerides (metabolic).
ANIMALS: Rats, CFE, M, 5-6 wk old, 90-120 g, 5 rats/grp or 6/grp (inhalation)
Rabbits, NZ white, 2.5-3.5 kg, M, 4 rabbits/grp, and isolated ileum.
Mice, white, F, 20^28 g.
41 mongrel dogs (8.5-12.5 kg) M and F. 10 cats, F, 2.2-3.8 kg.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Various schedules
ANIMALS: Rats, S-D, M, 300-350 g
PREPARATION AND DOSE
or HISTORY OF PATIENT:
50-1600 mg/kg/d, 1-14 doses. 1600 mg/kg was LD,QO»
1328 mg/kg was U>50, «° deaths below 1000 mg/kg.
ROUTE AND SITE: Topical, shaved skin (rabbits); inhalation (rats, mice);
intra-arterial (carotid) (dogs, cats) and I.V. femoral (dogs, cats)
CONTROL INFORMATION: Varied.
ROUTE AND SITE: i.p.
CONTROL INFORMATION: Mentioned, not described
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Physiology, biochemistry
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior, metabolism
169
170
-------
COMPOUND: 2-Butanol,4-(dlmethylamino)-3-methyl-l,2-diphenyl-, propionate (ester),
hydrochloride (-•-)-
001639607
REFERENCE: Chapman, J.E. and Walaszek, E.J.
Tox. Appl. Pharm. 4:752-758, 1962.
OBSERVED NEUROTOXIC EFFECTS: The LD of this compound, when given i.p., was
68-105 mg/kg. Convulsions produced and shown
to be of cerebral origin.
COMPOUND: 2-Butanol, 4-(dimethylamino)-3-methyl-l,2-diphenyl-, propionate (ester).
hydrochloride (+)-
001639607
REFERENCE: Young, D.J.
Arch. Int. Med. 129:62-66, 1972.
OBSERVED NEUROTOXIC EFFECTS: Tissue levels reached 130 mg/kg in brain where
measured. Convulsions and respiratory arrest.
Blood levels miniscule. Death resulted from anoxia
and complications. Central nervous system stimulation
hypothesized by author.
ANIMALS: Rats, Holtzman, F, 200 g
ANIMALS: Human: 10 cases, 9 suicides and 1 survival (3M, 7 F)
PREPARATION AND DOSE
or HISTORY OF PATIENT: 10-160 mg/kg with/without nalorphine; Some rats were
prepared surgically-spinal cord sectioned.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Doses of 1-2 g where known.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: Antagonist or no controls.
ROUTE AND SITE: Oral None
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: Observed until death or recovery.
EXAM. TYPE: Behavior, mortality.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Pathology (gross), behavior
171
172
-------
COMPOUND: Butyl alcohol
onnrmifii
REFERENCE: Roach, M.K., Davis, D.L. Pennlngton, W. and Nordyke, E.
Life Sci. 12(1):433-441, 1973.
OBSERVED NEUROTOXIC EFFECTS:
Butanol inhibited active transport of probable
neurotransmitters of the central nervous system
by synaptosomes. Authors conclude that alcohol
interacts with membrane lipids of synaptosome.
COMPOUND: Butyric acid, 4-amino
000056122
REFERENCE: Olney, J.W. , Ho, O.L. and Rhee, V..
Exp. Brain Res. 14:61-76, 1971.
OBSERVED NEUROTOXIC EFFECTS: N° cytotoxicity was observed.
ANIMALS: Rats, S-D, M, 200-250 g, brains removed and homogenates incubated in vitro.
ANIMALS: Mice, Swiss-webster age 10 d, total 250
PREPARATION AND DOSE
or HISTORY OF PATIENT: Butanol added as 25% soln, at start of preincubation period.
Butanol cone 5-30 mg/ml. Incubated in vitro with labeled
norepinephrine, GABA and glutamate.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Initially 12 mmoles/kg, then range established for
each compound.
ROUTE AND SITE: in vitro
CONTROL INFORMATION: Control: incubation in medium with no alcohol.
DURATION OF EXPERIMENT: Laboratory procedure
EXAM. TYPE: Biochemistry
ROUTE AND SITE:
S.C.
CONTROL INFORMATION: Compounds compared with monosodium L-glutamate (MSG)
potency for selectively necrosing neurons in retina
and brain (hypothalamus)
DURATION OF EXPERIMENT: 5 hr or serial intervals including 5 hr.
EXAM. TYPE: Histology
173
174
-------
COMPOUND: Butyric acid, 2-amino-4-hydroxy-, phosphonate, (ester)
COMPOUND: Butyric acid, 2-amino-A-sulfino-, DL-
REFERENCE: Olney, J.W., Ho, O.L. and Rhee, V.
Exp. Brain Res. 14:61-76, 1971.
OBSERVED NEUROTOXIC EFFECTS: The compound was toxic to non-neurol components
(glia, etc.), but not to neurons.
REFERENCE:Curtis, D.R. and Watkins, J.C.
J. Physiol. 166:1-14, 1963.
OBSERVED NEUROTOXIC EFFECTS: N-methyl-D-aspartic and D-homocysteic acids were
stronger excitants of depolarization than all
others. With some compounds the action was
prolonged for many seconds after the stimulus
was terminated, notably N-n_-propyl-D-aspartic
acid. There were no differences among types of
neurons tested; structure-activity relationship
was observed.
ANIMALS: Mice, Swiss-webster age 10 d, total 250
PREPARATION AND DOSE
or HISTORY OF PATIENT: Initially 12 mmoles/kg, then range established for
each compound.
ANIMALS: Cats prepared for electrophoretic application of chemicals to single
central nervous system neurons.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Dilutions 0.1-0.5 M of 31 compounds mainly of aspartic,
glutamic and cysteic acids listed in order of
potency of results.
ROUTE AND SITE:
S.C.
CONTROL INFORMATION: Compounds compared with monosodium L-glutamate (MSG)
potency for selectively necrosing neurons in retina
and brain (hypothalamus)
DURATION OF EXPERIMENT: 5 hr or serial intervals .including 5 hr.
EXAM. TYPE: Histology
ROUTE AND SITE: Electrophoretic application, various sites in central nervous
system.
CONTROL INFORMATION:
None
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Electrophysiological
175
176
-------
COMPOUND: Butyric acid, 2-hydrazino-2-methyl-
COMPOUND: Butyric acid, 2-(methylamino)-4-sulfo-, DL-
REFERENCE: Jenney, E.H. and Pfeiffer, C.C.
J. Pharm. Exp. Ther. 122: 110-123, 1958.
OBSERVED NEUROTOXIC EFFECTS: Convulsions
REFERENCE:Curtis, D.R. and Watkins, J.C.
J. Physiol. 166:1-14, 1963.
OBSERVED NEUROTOXIC EFFECTS: N-methyl-D-aspartic and D-homocysteic acids were
stronger excitants of depolarization than all
others. With some compounds the action was
prolonged for many seconds after the stimulus
was terminated, notably N-n-propyl-D-aspartic
acid. There were no differences among types of
neurons tested; structure-activity relationship
was observed.
ANIMALS: Mice, Harlan, 19-21 g
PREPARATION AND DOSE
or HISTORY OF PATIENT: 1.52 mM/kgm
ANIMALS: Cats prepared for electrophoretic application of chemicals to single
central nervous system neurons.
PREPARATION AND DOSE
Or HISTORY OF PATIENT: Dilutions 0.1-0.5 M of 31 compounds mainly of aspartic,
glutamic and cysteic acids listed in order of
potency of results.
ROUTE AND SITE: I.p.
CONTROL INFORMATION: ns
ROUTE AND SITE: Electrophoretic application, various sites in central nervous
system.
CONTROL INFORMATION:
None
DURATION OF EXPERIMENT: Acute
EXAM. TYPE: Clinical
DURATION OF EXPERIMENT: ns. '
EXAM. TYPE: Electrophysiological
177
178
-------
COMPOUND: Cadmium chloride
010108642
REFERENCE: Gabbiani, G., Bale, D. and Deziel, C.
Exp. Neurol. 18:154-160, 1967..
OBSERVED NEUROTOXIC EFFECTS: Hemorrhagic damage, especially to granular layer
of cerebellum, also cerebrum, but only in young rats
and rabbits.
COMPOUND: Cadium chloride
010108642
REFERENCE: Gabbiani, G., Gregory, A. and Baic, D.
J. Neuropath. Exp. Neurol. 26(3):498-506, 1967.
OBSERVED NEUROTOXIC EFFECTS: Acute hemorrhagic lesions of Gasserian and
sensory spinal ganglia in all species. Nuclear pyknosis, PAS - and
H-positive masses in nerve fibers. Pretreatment with zinc acetate or
glutathione protected the animals.
ANIMALS: Rats, aged 1-30 d, 5 groups of 10 (S-D)
Rabbits, 43, aged 1-30 d
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Rats: 10 mg/kg
Rabbits: 20 mg/kg
ANIMALS: Guinea-pigs, golden hamsters, and mice in grps of 10; 260 rats:
S-D, 205 g, in grps of 15. 3 grps of rats also had surgical transection
of the spinal cord, right sciatic and femoral nerves.
PREPARATION AND DOSE
Or HISTORY OF PATIENT: 10 mg/kg in water (1 ml/inj); rats given 2 mg/rat in 1 ml
of water.
ROUTE AND SITE: S.C.
CONTROL INFORMATION: 2 rats/1 rabbit per group untreated.
ROUTE AND SITE: S.C., interscapular region
CONTROL INFORMATION: 20 rats untreated
DURATION OF EXPERIMENT: 30 d mentioned, real duration ns.
EXAM. TYPE: Histology
DURATION OF EXPERIMENT: 1-96 hr
EXAM. TYPE: Behavior, histology
179
180
-------
COMPOUND: Cadmium chloride
REFERENCE: Tischner, K.H. and Schroder, J.M.
J. Neurol. Sci. 16:383-399, 1972.
OBSERVED NEUROTOXIC EFFECTS: Glycogen deposits in periphery of neuronal
perikarya, dose-related. Other ultrastructural changes including mitochondria
and unmyelinated axons (degeneration). Authors conclude that cadmium ions
are direct pathogens for nerve tissues.
COMPOUND: Caffeine
REFERENCE: Scott, C.C., Anderson, R.C. and Chen, K.K.
J. Pharm. Exp. Ther. 86: 113-119, 1946.
OBSERVED NEUROTOXIC EFFECTS: Produced tetanic convulsions.
ANIMALS: Dorsal root ganglia from 19-21 d Wistar rat embryos in culture.
ANIMALS: Mice
PREPARATION AND DOSE ,
or HISTORY OF PATIENT: 4 x 10 M in medium, replenished every 3 d, exposures
1 d to 3 wk.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
84.4 mg/kg (median convulsive dose)
ROUTE AND SITE: In vitro
CONTROL INFORMATION: ns.
ROUTE AND SITE: I.V., tail vein
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: Cultures maintained up to 2 mo.
EXAM. TYPE: Histology, chemistry
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Clinical
181
182
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COMPOUND:
Calcium chloride
010043524
REFERENCE: Tang, A.H. and Schroeder, L.A.
Tox. Appl. Pharm. 12:44-47, 1968.
COMPOUND:
Carbamic acid, diethylthio-, sodium salt
REFERENCE: Edington, N. and Howell, J. McC.
Nature 210:1060-1062, 1966.
OBSERVED NEUROTOXIC EFFECTS: The compound did not antagonize the effects of
lincomycin.
OBSERVED NEUROTOXIC EFFECTS:
Copper level in the CNS was increased by compound,
not by saline. Cord white matter had Wallerian
degeneration throughout, loss of structure in
some grey-matter neurons. Corpus striatum
not damaged. Some sciatic nerves also contained
Wallerian degeneration.
ANIMALS: 3 rabbits
ANIMALS: 18 Rabbits, Dutch and NZ
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.1-50 mg/kg during the neuromuscular blockade produced by
lincomycin.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Dose ns., but after 5 mo. it was 10 ml/kg/d, in 15
rabbits for a further 2.5 mo.
ROUTE AND SITE: i.v.
CONTROL INFORMATION: ns.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: 3 given saline, 5 ml/kg/d.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Electrophysiology
DURATION OF EXPERIMENT: Approx 7.5 mo.
EXAM. TYPE: Histology, biochemistry
183
184
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COMPOUND:
Carbamic acid, diethyldithio-, sodium salt
COMPOUND: Carbamic acid, diethylthio-, sodium salt
REFERENCE: Edington, N. and Howell, J. McC.
Acta Neuropath. 12:339-347, 1969.
REFERENCE: Howell, J. McC. and Edington, N.
J. Neuropath. Exp. Neurol. 27:464-472, 1968.
OBSERVED NEUROTOXIC EFFECTS: Degeneration: at 6 wk in accessory cuneate
nucleus and Clarke's column, at 18 wk in spinocerebellar tracts of cerebellum
and in medulla, at 24 wk in peripheral white-matter of cord. Peripheral
Nervous System effects "minimal."
OBSERVED NEUROTOXIC EFFECTS: Wallerian nerve fiber degeneration in -cerebellum,
medulla, cord, and peripheral nerves.
ANIMALS: 25 Rabbits, (Dutch x NZ), M and F, 2.6-3.3 kg in 5 grps of 5.
ANIMALS: 13 Hens, Thornber's 404 strain, age 6 mo.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 330 mg/kg/d, 6 d/wk, in buffer to all 5 grps.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 330 mg/kg/d, 5 d/wk, as 10% solution in phosphate buffer
pH 7.2-7.4 (7 hens).
ROUTE AND SITE: I.P.
CONTROL INFORMATION: None
ROUTE AND SITE: Deposited in crop
CONTROL INFORMATION: 4 hens given saline in buffer
DURATION OF EXPERIMENT: Serial sacr 6-30 wk.
EXAM. TYPE: Histology
DURATION OF EXPERIMENT: 19 wk
EXAM. TYPE: Histology
185
186
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COMPOUND: Carbamic acid, diethylthio-, sodium salt
COMPOUND:
Carbamic acid, diethylthio-, sodium salt
REFERENCE: Howell, J. McC., Ishmael, J., Ewbank, R. and Blakemore, W.F.
Acta Neuropath. 15:197-207, 1970.
REFERENCE: Rasul, A.R. and Howell, J.McC.
Acta Neuropath. 24:68-75, 1973.
OBSERVED NEUROTOXIC EFFECTS: No signs of incoordination. All lambs had
peritonitis. Microscopic lesions in medulla and spinal cord: swollen
axons but no nerve fiber degeneration. High copper levels found in spinal
cord.
OBSERVED NEUROTOXIC EFFECTS: Degeneration of the long tracts of the spinal
cord: fragmented axons and ballooned myelin sheaths. Lesions could be
traced into cerebellum. Lesions were first seen after 18 wk in chicks and
4 wk in adults. Ataxia was observed after 25 wk in chicks and 5 wk in adults.
Degeneration characterized as a "dying back process" and an "organophosphorous
pattern."
ANIMALS: Sheep, 20 Clun Forest purebreds or crosses, 5 aged 2 d, 11 aged 1 mo.
ANIMALS: Cockerels, Thornber's 909, aged 1 wk or 6 mo.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 165 or 330 mg/kg in phosphate buffer pH 7.0, daily 5 d/wk.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 330 mg/kg/d, 6 d/wk, in phosphate buffer
ROUTE AND SITE: i.P.
CONTROL INFORMATION: 2 aged 2 d, vehicle only
ROUTE AND SITE: Oral
CONTROL INFORMATION: Untreated birds
DURATION OF EXPERIMENT: one survivor arid the controls sacr at 16 wk.
EXAM. TYPE: Histology, behavior, biochemistry.
DURATION OF EXPERIMENT: Serial to 35 wk
EXAM. TYPE: Behavior, histology
187
188
-------
COMPOUND: Carbamic acid, diethyldithio-, sodium salt
UUUJL4B103
REFERENCE: Rasul, A.R. and Howell, J. McC.
Acta Neuropath. 24:161-173, 1973.
COMPOUND: Carbamic acid, ethyl ester
REFERENCE: Fern., V.H.
Arch. Path. 81: 174-177, 1966.
OBSERVED NEUROTOXIC EFFECTS: No effects on neuromuscular endplates, peripheral
nerves, or "teased" nerve fibers. Treatment
for 9 wk, fewer large-diameter fibers. In central
nervous system: Wallerian degeneration and
eosinophilic bodies seen after 4 wk of treatment;
long spinal tracts involved, initial lesions
inferred in thoracic cord. •
OBSERVED NEUROTOXIC EFFECTS: Exencephaly and failure of neural tube to close after
administration of compound, more so after I.V. treatment.
ANIMALS:
20 Rabbits, Dutch, M, 12 wk, 1.88-2.48 kg.
ANIMALS: Golden hamsters, F, pregnant, 100-125 g
PREPARATION AND DOSE
or HISTORY OF PATIENT: 330 mg/kg/d, 5-d/wk as 10% soln in NaPO
buffer pH 7.2-7.4
PREPARATION AND DOSE
Or HISTORY OF PATIENT: 25-150 rag/hamster on d 9, 10 or 11
ROUTE AND SITE: Oral
CONTROL INFORMATION: 10 rabbits NaPO buffer only.
ROUTE AND SITE: t.V. lingual vein or I.P.
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: Serial sacr 4,6,9 wk.
EXAM. TYPE: Histology
DURATION OF EXPERIMENT: 24-72 hr. after treatment.
EXAM. TYPE: Teratological
189
190
-------
COMPOUND:
Carbamic acid, dimethyl-6-methyl-2-propyl-4-pyrimidnyl ester
002532492
REFERENCE: Sherman, M., Herrick, R.B., Ross, E. and Chang, M.T.Y.
Toxicol. Appl. Pharm. 11: 49-67, 1967.
OBSERVED NEUROTOXIC EFFECTS: Ataxia, paralysis, convulsions.
COMPOUND: Carbamic acid, methyl-, benzo(b)thien-4-yl-ester
0010793310
.-EFERENCE: Galnes, T.B.
Tox. Appl. Pharm. 14: 515-534, 1969.
OBSERVED NEUROTOXIC EFFECTS: 400 mg/kg produced leg weakness
ANIMALS: Cockerels, Single Comb White Leghorn, 10-12 d old
ANIMALS: Chickens, White Leghorn, F
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) Acute: LD - 60.0 mg/kg
2: 50-8C-
(2) Subacute: 50-800 ppm in diet, 20 chicks/grp, for 2 wk
PREPARATION AND DOSE
or HISTORY OF PATIENT: 15 mg/kg atropine sulfate orally 15 min prior to compound;
graded doses compound in peanut oil
ROUTE AND SITE: Oral
CONTROL INFORMATION: Untreated control grps
ROUTE AND SITE: S.C., under right wing
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: 1-3 wk
EXAM. TYPE: Behavior, mortality
DURATION OF EXPERIMENT: 1 yr
EXAM. TYPE: Clinical
191
192
-------
COMPOUND: Carbamic Acid, methyl-, benzo(b)thien-4-yl-ester
001079330
REFERENCE: Sherman, M., Herrick, R.B., Ross, E. and Chang, M.T.Y.
Toxicol. Appl. Pharm. 11: 49-67, 1967.
OBSERVED NEUROTOXIC EFFECTS: Ataxia, paralysis, convulsions.
Carbamic acid, methyl-, S-sec-butyl-2-chlorophenyl ester
COMPOUND:
REFERENCE: Sherman, M., Herrick, R.B., Ross, E. and Chang, M.T.Y.
Toxicol. Appl. Pharm. 11: 49-67, 1967.
OBSERVED NEUROTOXIC EFFECTS: Ataxia, paralysis, convulsions.
ANIMALS: Cockerels, Single Comb White Leghorn, 10-12 d old
ANIMALS: Cockerels, Single Comb White Leghorn, 10-12 d old
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) Acute: LD5Q 85.4 mg/kg
(2) Subacute: 50-800 ppm in diet, 20 chicks/grp, for 2 wk
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) Acute: LD 19.4 mg/kg
(2) Subacute: 50-800 ppm in diet, 20 chicks/grp, for 2 wk
ROUTE AND SITE: Oral
CONTROL INFORMATION: Untreated control grps
ROUTE AND SITE: Oral
CONTROL INFORMATION: Untreated control grps
DURATION OF EXPERIMENT: 1-3 wk
EXAM. TYPE: Behavior, mortality
DURATION OF EXPERIMENT: 1-3 wk
EXAM. TYPE: Behavior, mortality
193
194
-------
COMPOUND:
Carbamic acid, methyl-m-sec-butylphenyl ester
REFERENCE: Sherman, M., Herrick, R.B., Ross, E. and Chang, M.T.Y.
Toxicol. Appl. Pharm. 11: 49-67, 1967.
OBSERVED NEUROTOXIC EFFECTS: Ataxia, paralysis, convulsions.
COMPOUND: Carbamic acid, methyl-, m-cumenyl ester
000064006
REFERENCE: Sherman, M., Herrick, R.B., Ross, E. and Chang, M.T.Y.
Toxicol. Appl. Pharm. 11: 49-67, 1967.
OBSERVED NEUROTOXIC EFFECTS: Ataxia, paralysis, convulsions.
ANIMALS: Cockerels, Single Comb White Leghorn, 10-12 d old
ANIMALS: Cockerels, Single Comb White Leghorn, 10-12 d old
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) Acute: LD5Q 13.6 mg/kg
(2) Subacute: 50-800 ppm in diet, 20 chicks/grp, for 1 wk
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) Acute: LI>50 12.0 mg/kg
(2) Subacute: 50-800 ppm in diet, 20 chicks/grp, for 2 wk
ROUTE AND SITE: Oral
CONTROL INFORMATION: Untreated control grps
ROUTE AND SITE: Oral
CONTROL INFORMATION: Untreated control grps
DURATION OF EXPERIMENT: 1-3 wk
EXAM. TYPE: Behavior, mortality
DURATION OF EXPERIMENT: 1-3 wk
EXAM. TYPE: Behavior, mortality
195
196
-------
COMPOUND: Carbamic acid, methyl-,2,3-dlhydro-2,2-dimethyl-7-benzofuranyl ester
001563662
REFERENCE: Sherman, M., Herrick, R.B., Ross, E. and Chang, M.T.Y.
Toxicol. Appl. Pharm. 11: 49-67, 1967.
OBSERVED NEUROTOXIC EFFECTS: Ataxia, paralysis, convulsions.
ANIMALS: Cockerels, Single Comb White Leghorn, 10-12 d old
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) Acute: LD,,. 6.3 mg/kg
(2) Subacute: 50-800 ppm in diet, 20 chicks/grp, for 2 wk
ROUTE AND SITE: Oral
CONTROL INFORMATION: Untreated control grps
DURATION OF EXPERIMENT: 1-3 wk
EXAM. TYPE: Behavior, mortality
197
COMPOUND- Carbamlc acld' methyl-,4-dimethyl-amino-3,5-xylyl ester
000315184
REFERENCE:Tucker, R.K. and Crabtree, D.G.
J. Econ. Entomol. 62:1307-1310, 1969.
OBSERVED NEUROTOXIC EFFECTS:
Varying with the species the following symptoms
were observed: Tachypnea, ataxia, tremors,
salivation, lachrimation, plloerection, clonic
or tonic convulsions, opisthotonus, phonation,
anorexia, nystagmus. Death tended to follow
respiratory paralysis. Birds were generally
more susceptible than mammals; cumulative
effects were not marked; teratology was not
demonstrated; the authors concluded that practical
exposures would be far below toxic levels.
ANIMALS: Rats (S-D), Rabbits (NZ White), Lesser sandhill cranes, Canada geese,
Mourning doves, Mallard ducks, Coturnix quails, Ring-necked pheasants,
House finches, Chukar partridges, Domestic pigeons, Sharp-tailed
grouse, Domestic goats, Mule deer, House sparrows, Bullfrogs.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Acute oral U),Q varied from 1 mg/kg in cranes to
800 mg/kg in bullfrogs. Subacute feeding tests
at various doses. Acute dermal toxicity tests
in rabbits, 2 g/kg.
ROUTE AND SITE: oral; dermal
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: Subacute, 30 d.
EXAM. TYPE Behavior, mortality
198
-------
COMPOUND:
Carbamic acid, methyl-, m-(l-methylbutyl)phenyl ester
REFERENCE: Sherman, M., Herrick, R.B., Ross, E. and Chang, M.T.Y.
Toxicol. Appl. Pharm. 11: 49-67, 1967.
COMPOUND: Carbamic acid, methyl-, 1-naphthyl ester
000063252
REFERENCE: Gaines, T.B.
Tox. Appl. Pharm. 14: 515-534, 1969.
OBSERVED NEUROTOXIC EFFECTS: Ataxia, paralysis, convulsions.
OBSERVED NEUROTOXIC EFFECTS: 800 mg/kg produced leg weakness
ANIMALS: Cockerels, Single Comb White Leghorn, 10-12 d old
ANIMALS: Chickens, White Leghorn, F
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) Acute: LD Q 44.3 mg/kg
(2) Subacute: 50-800 ppm in diet, 20 chicks/grp, .for 2 wk
PREPARATION AND DOSE
or HISTORY OF PATIENT: 15 mg/kg atropine sulfate orally 15 min prior to compound
graded doses compound in peanut oil
ROUTE AND SITE: Oral
CONTROL INFORMATION: Untreated control grps
ROUTE AND SITE: S.C., under right wing
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: 1-3 wk
EXAM. TYPE: Behavior, mortality
DURATION OF EXPERIMENT: 1 yr
EXAM. TYPE: Clinical
199
200
-------
COMPOUND: Carbamic acid, methyl-, 1-naphthyl ester
REFERENCE: Smalley, H.E., O'Hara, P.J., Bridges, C.H. and Radeleff, R.D.
Tox. Appl. Pharm. 14:409-419, 1969.
OBSERVED NEUROTOXIC EFFECTS: Myasthenia, incoordination, ataxia, tremor,
clonic contractions, paraplegia. Compound
inhibits cholinesterase. Central nervous
system lesions: edema of tnyelinated tracts of
cerebellum, brain stem, and upper cord, with vascular
degeneration.
Carbamic acid, methyl-, 3,4-5-trimethylphenyl ester
REFERENCE: Gaines, T.B.
Tox. Appl. Pharm. 14: 515-534, 1969,
OBSERVED NEUROTOXIC EFFECTS: 400 mg/kg produced leg weakness
ANIMALS: Pigs, Yorkshire, litter of 4 M and 4 F, in 2 groups.
ANIMALS: Chickens, White Leghorn, F
PREPARATION AND DOSE
or HISTORY OF PATIENT: 150 and 300 mg/kg/d in diet.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 15 mg/kg atropine sulfate orally 15 min prior to compound;
graded doses compound in peanut oil
ROUTE AND SITE: Oral, incidental inhalation
CONTROL INFORMATION: 2 pigs of litter
ROUTE AND SITE: S.C., under right wing
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: Up to 85 d
EXAM. TYPE: Clinical, histology
DURATION OF EXPERIMENT: 1 yr
EXAM. TYPE: Clinical
201
202
-------
COMPOUND:
Carbonic add, methyl-,3,4-5-trioethylphenyl ester
002686999
Sbenam, M., Herrick, R.B., Ross, E. and Chang, M.T.Y.
l. Fharo. 11: 49-67, 1967.
Ataxia, paralysis, convulsions.
COMPOUND: Carbohydrazlde
000497187
REFERENCE: Jenney, E.H. and Pfelffer, C.C.
J, Pharm. Ezp. Ther. 122: 110-123, 1958.
OBSERVED NEUROTOXIC tfFtCTS: Convulsions
AJHIWLS: Cockerels, Single Comb White Leghorn, 10-12 d old
ANIMALS: Mice. Bar Ian, 19-21 g
PREPARATION MID MSE
or HISTORY OF PATIENT: (1) Acute: LD^ 50.3 ng/kg
(2) Snbacute: 50-800 ppm in diet, 20 chicks/grp, for 2 wk
PREPARATION AND DOSE
or HISTORY Of PATIENT: 1.3 nM/kgm
pROMTE Mm SITE: Oral
' IJtFOJMftTIOSI: Untreated control grps
ROUTE AND SITE: i.v.
CONTROL INFORMATION: ns
I OF EXPERINENT: 1-3 sk
EXAM. TYPE: Behavior, mortality
DURATION OF EXPERIMENT: Acute
EXAM. TYPE: Clinical
203
204
-------
COMPOUND:
Carbohydrazide, thio-
002231574
REFERENCE: Jenney, E.H. and Pfelffer, C.C.
J. Fhann. Exp. Ther. 122: 110-123, 1958.
OBSERVED NEUROTOXIC EFFECTS: Convulsions
COMPOUND: Carbon dioxide
REFERENCE: Walker, J.L., Jr. and Brown, A.M.
Science 167:1502-1504, 1970.
OBSERVED NEUROTOXIC EFFECTS:
Some neurons were depolarized, others hyperpolarized,
others unaffected. Mechanism: acidosis that
increased membrane chloride conductance of responsive
cells.
ANIMALS: Mice, Harlan, 19-21 g
ANIMALS: Aplysia californica surgically prepared.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.04 mM/kgm
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Abdominal ganglion exposed to 5% CO
ROUTE AND SITE: i.p.
CONTROL INFORMATION: ns
ROUTE AND SITE: Laboratory methods described.
CONTROL INFORMATION: Described
DURATION OF EXPERIMENT: Acute
EXAM. TYPE: Clinical
DURATION OF EXPERIMENT: About.1 min.
EXAM. TYPE: Electrophysiology
205
206
-------
COMPOUND: Carbon disulfide
000075150
REFERENCE: Alpers, B.J. and Lewy, F.H.
Arch. Neurol. Psychiat. 44:725-739, 1940.
COMPOUND: Carbon disulfide
000075150
REFERENCE: Ferraro, A., Jervis, G.A., & Flicker, D.J.
Arch. Pathol. 32: 723-738, 1941.
OBSERVED NEUROTOXIC EFFECTS: Apathy, hostility. Damage to cortex, basal
ganglia, cerebellum; moderate involvement of cord; little involvement of brainstem
and peripheral nervous system.
OBSERVED NEUROTOXIC EFFECTS: Cerebrovascular proliferation with diffuse nerve
cell changes (from chrolatolysis to severe degeneration) scattered through
brain and cerebellum. Salivation, dyspnea, restlessness, rarely vomiting,
progressing to tremors, apathy, and occasionally coma.
ANIMALS: 9 Dogs
ANIMALS: 5 cats.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Exposure 8 hr/d, 5 d/wk, for 2-6 wk. Concentration ns.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 8-10 mg/liter of air, 0.5-2.5 hr/d, total exposures 19-65
ROUTE AND SITE: Inhalation
CONTROL INFORMATION: None
ROUTE AND SITE: Inhalation
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: Serial sacr 2-6 wk.
EXAM. TYPE: Behavior, Histology
DURATION OF EXPERIMENT: Serial sacr to 92 d
EXAM. TYPE: Behavior, histology
207
208
-------
COMPOUND:
Carbon disulfide
REFERENCE: Juntunen, J., Haltia, M. arid Linnoila, I.
Acta Neuropath. 29:361-366, 1974.
COMPOUND: Carbon disulfide
000075150
REFERENCE: Lewey, F.H.
Ann. Int. Med. 15: 869-883, 1941.
OBSERVED NEUROTOXIC EFFECTS: Slight weakness, progressing to severe in hindlimbs.
Only intramuscular nerves examined: axonal degeneration. Intense
nonspecific cholinesterase activity correlated with degeneration. Authors
suggest that non-specific cholinesterase activity could be used as an
indicator of early axonal degeneration in progressive polyneuropathy.
OBSERVED NEUROTOXIC EFFECTS:
Any part of the central or peripheral nervous system
can be affected. In general, the first signs were
psychic with peripheral neuropathy, progressing to
cranial nerve involvement, eye muscle control, pyra-
midal and extra-pyramidal signs. Parkinsonism and
a thalamic syndrome were seen. The author concluded
that some neuropathy was secondary to induced thiamine
deficiency.
ANIMALS: 21 Eats, S-D, age 3 mo.
ANIMALS: Human: 120 viscose rayon workers
PREPARATION AND DOSE
or HISTORY OF PATIENT: 750 ppm in air, 6 hr/d for 5 d/wk or (later) 3/d/wk.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Long-term chronic exposures
ROUTE AND SITE: Inhalation
CONTROL INFORMATION: 5 rats untreated
ROUTE AND SITE: Inhalation
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: 5 wk to 5 mo.
EXAM. TYPE: Behavior, histology, histochemistry
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Clinical, biochemistry, statistics
209
210
-------
COMPOUND: Carbon disulfide
000075150
REFERENCE: Lukas, E., Kotas, P. and Obrusnik, I.
Br. J. Indust. Med. 31: 288-291, 1974.
OBSERVED NEUROTOXIC EFFECTS: Slow conduction measured In lumbar plexus-tibial nerves.
Copper levels increased, while zinc did not.
COMPOUND: Carbon disulfide
000075150
REFERENCE: Richter, R.
J. Neuropath. Exp. Neurol. 4:324-353, 1945.
OBSERVED NEUROTOXIC EFFECTS: Grey-metter necrosis especially in globus pallidus
and substantia nigra, thought to have developed acutely after long cumulative
exposures; other changes such as gliosis in nonnecrotic parts of Central
Nervous System thought to have developed gradually.
ANIMALS: Rats, SPF, M, 300 g, 18/gp, 2 gps trtd.
ANIMALS: 4 Rhesus monkeys (M. mulatta), healthy, young.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 2.4 or 3.6 mg/liter of air, 6 hr/d, 5 d/wk.
PREPARATION AND DOSE
Or HISTORY OF PATIENT: Exposure to vapor, concentration not measured, for about
6 hr/d, 5 d/wk, for 1-2 yr.
ROUTE AND SITE: Inhalation
CONTROL INFORMATION: Same numbers of rats.
ROUTE AND SITE: inhalation
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: Sacrifice when neuropathy obvious (13 or 37 wk).
EXAM. TYPE: Electrophysiology, biochemistry.
DURATION OF EXPERIMENT: 1-2 yr.
EXAM. TYPE: Behavior, histology
211
212
-------
COMPOUND: Carbon disulfide
000075150
REFERENCE: Tarkowski, S. and Cramer, J.E.
J. Neurochem. 19:2631-2640, 1972.
OBSERVED NEUROTOXIC EFFECTS:
Ataxia, tremors, some convulsions; brain glutamine
rose, glutamate and GABA fell, interpreted as due
to increased removal of ammonia and interference
with pyridoxal-PO,-dependent enzymes.
COMPOUND:
Carbonic acid, dithio-, cyclic S,S-(6-methyl-2,3-quinoxalinediyl) ester
REFERENCE: Sherman, M., Herrick, R.B., Ross, E. and Chang, M.T.Y.
Toxicol. Appl. Pharm. 11: 49-67, 1967.
OBSERVED NEUROTOXIC EFFECTS: Ataxia, paralysis, convulsions.
ANIMALS:
Rats, Forton, M, 8-10 wk, 180-200 g.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 2.5 mg/liter of air for 15 hr.
ANIMALS: Cockerels, Single Comb White Leghorn, 10-12 d old
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) Acute: LD5Q 979.6 mg/kg
(2) Subacute: 50-800 ppm in diet, 20 chicks/grp, for 2 wk
ROUTE AND SITE: Inhalation
CONTROL INFORMATION: Same, no compound
DURATION OF EXPERIMENT: 15 hr.
EXAM. TYPE: Behavior, biochemistry
ROUTE AND SITE: Oral
CONTROL INFORMATION: Untreated control grps
DURATION OF EXPERIMENT: 1-3 wk
EXAM. TYPE: Behavior, mortality
213
214
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COMPOUND:
Carbon monoxide
000630080
COMPOUND:
REFERENCE: Bogusz, M., Cholewa, L. Pach, J. and Mlodkowska, K.
Arch. Toxicol. 33:141-149, 1975.
Carbon monoxide
000630080
REFERENCE: Einhorn, I.N.
Env. Hlth. Persp. 11:163-189, 1975.
OBSERVED NEUROTOXIC EFFECTS:
Lactate, pyruvate, aspartate aminotransferase,
LDH, all increased; muscle twitching to convulsions.
A triple-normal lactate was considered reason for
hospitalization, and triple-normal Asp-At signified
complications.
OBSERVED NEUROTOXIC EFFECTS:
Level 3 (motor collapse) : no changes observable
in central or peripheral nervous system by light
microscopy in 10 rats exposed 30 d, but on
electron microscope changes seen in Ranvier nodes
in peripheral nervous system. Demyelination apparent
at level 4, especially of large fibers in central
nervous systems white-matter.
ANIMALS: 47 patients: 28 F, 19 M, ages 14-88 yr.
ANIMALS:
Rats
PREPARATION AND DOSE
or HISTORY OF PATIENT: Exposure to coal-stove gas or lighting gas for 1-16
hr, hospitalized 1-5 hr after onset of symptoms.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Levels 2-5 of toxicity produced by various exposures.
ROUTE AND SITE: Inhalation
CONTROL INFORMATION: None
ROUTE AND SITE: Inhalation
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Clinical, biochemistry
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Electrophysiology, histology, behavior
215
216
-------
COMPOUND: Carbon monoxide
000630080
REFERENCE: Shillito, F.H., Drinker, C.K. and Shaughnessy, T.J.
J. Am. Med. Assn. 106: 669-674, 1936.
OBSERVED NEUROTOXIC EFFECTS:
43 cases had sequelae sufficient for admission to mental
institutions; confusion psychosis, disorientation,
amnesia, parkinsonism, increased deep reflexes, skin
anesthesia and peripheral neuropathy. All such cases
had unconsciousness during acute phase, none had low-
level chronic exposures. Of the 43, 23 recovered com-
pletely, 9 had permanent nerve or mental damage, and
11 died.
COMPOUND: Carbon monoxide
000630080
REFERENCE: Snyder, R.D.
Neurology 20:177-180, 1970.
OBSERVED NEUROTOXIC EFFECTS: Symmetrical peripheral neuropathy not due only
to hypoxia, additional to Central Nervous system involvement, suspected of
"toxic or ischemic basis."
ANIMALS: Human: 43 cases abstracted from 10-yr records of 21,143 cases in
New York metropolitan area
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Various exposures
ANIMALS: Human: family of 4 (M 25 yr, F 29 yr, M 5 yr, F 3 yr).
PREPARATION AND DOSE
or HISTORY OF PATIENT: Exposure to malfunctioning gas heaters in closed house, for
approx. 2 d.
ROUTE AND SITE: Inhalation
CONTROL INFORMATION: None
ROUTE AND SITE: Inhalation
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: Various
EXAM. TYPE: clinical
DURATION OF EXPERIMENT: About 2 d
EXAM. TYPE: Autopsy (F, 29), electrophysiology, blood chemistry, behavior
217
218
-------
COMPOUND: Carbon tetrachloride
000056235
REFERENCE: Cohen, M.M.
Neurology 7: 238-244, 1957.
OBSERVED NEUROTOXIC EFFECTS: The compound caused patchy pontine necrosis and demyelin-
ation and Purkinje cell damage; other effects were con-
sidered secondary to vascular, hepatic or renal damage.
COMPOUND: Carbon tetrachloride
000056235
REFERENCE: Hasson, J. and Leech. R.W.
Arch. Path. 84:286-289, 1967.
OBSERVED NEUROTOXIC EFFECTS: Globus pallidus was examined; Alzheimer glia cell
changes were not found, but astrocytic nuclear
size was increased significantly in cirrhotic
vs. control rats.
ANIMALS: Human: 2 fatal cases, M, 24 and 40
ANIMALS: Rats, S-D, M, 150 g, 2 groups of 18
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) A suicide; history of alcohol, drugs and liver damage.
(2) Accidental inhalation; history of alcohol
PREPARATION AND DOSE
or HISTORY OF PATIENT: i ml/kg twice/wk for 5 wk (10 doses), 1 group, to produce
liver cirrhosis.
ROUTE AND SITE: (1) Oral (2) Inhalation
CONTROL INFORMATION: None
ROUTE AND SITE: Gavage
CONTROL INFORMATION: 1 group untrtd
DURATION OF EXPERIMENT: (1) Survived 13 d; (2) survived less than 24 hr
EXAM. TYPE: Histology (autopsy)
DURATION OF EXPERIMENT: Sacrifice 1 d after 10th dose.
EXAM. TYPE: Histology
219
220
-------
COMPOUND: Carbon tetrachloride
000056235
REFERENCE: Knoct. P..T. and Curzcn, G.
Biochem. Pharmacol. 24:963-966, 1975.
COMPOUND: Carbon tetrachloride
000056235
REFERENCE: Luse, S.A.. and Wood, W.G.
Arch. Neurol. 17:304-312, 1967.
OBSERVED NEUROTOXIC EFFECTS: Brain tryptophan, tyrosine, 5-HIAA and (less)
5-HT increased; related decrease of food intake.
Brain changes not seen with restricted intake alone.
Interpreted with reference to appetite control and
liver failure.
OBSERVED NEUROTOXIC EFFECTS:
Mental stupor, confusion, convulsion. Edema
and spongiform lesions through pons, cerebellum,
cerebrum. No demyelination by electronmicroscopy,
though appearance of it by photomicroscopy.
Edema was extracellular.
ANIMALS: Rats, S-D, M, 140-150 g.
ANIMALS:
Human: one case, M, 32
PREPARATION AND DOSE
or HISTORY OF PATIENT: 10% in arachis oil, 13 ml/kg when mean wt was 200 g,
one dose.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Used a CC14 extinguisher for a fire in a closed room.
Died 7 d later, without reporting this.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: Arachis oil vehicle only; restricted diet 48 hr.
ROUTE AND SITE: inhalation
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: 48 hr.
EXAM. TYPE: Biochemical
DURATION OF EXPERIMENT: 7 d
EXAM. TYPE: Behavior, clinical, histology
221
222
-------
COMPOUND:
Cardiotoxin
COMPOUND:
Gascara
REFERENCE:
Chang, C.C., Chuang, S-T., Lee, C.Y. , Wei, J.W.
Br. J. Pharmac. 44:752-764, 1972.
REFERENCE:
Steer, H.W. and Colin-Jones, D.G.
J. Path. 115:199-205, 1975.
OBSERVED NEUROTOXIC EFFECTS:
Affected axonal conduction, but less potent
than crude cobra venom. Blocking action
accelerated by addition of PhA, the minimum
effective concentration being 100 meg/ml. 3 meg/ml
completely depolarized superficial muscle fibers
within 60 min, this dose being three times more
potent than crude venom. CaCl2 antogonized nerve
blocking and depolarizing effect.
OBSERVED NEUROTOXIC EFFECTS: More lysosomal activity and lysosomes in Schwann
cells and neurons of submucosal plexus of colonic
mucosa.
ANIMALS:
Phrenic nerve-diaphragm preparation from Long-Evans rats.
ANIMALS: Human: 7 aged 24-80 with melanosls coli who took purgatives;
1 who had taken purgatives for only 1 m.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Various doses in vitro.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Rectal biopsy before and 3-7 m after stopping medication
ROUTE AND SITE: in vitro
CONTROL INFORMATION: Laboratory
ROUTE AND SITE: Oral
CONTROL INFORMATION:
7 aged 27-70 with other gut disorders who had taken no
purgatives for 3 m.
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Electrophysiology, chemistry
DURATION OF EXPERIMENT: About 7 m.
EXAM. TYPE: Histology, histochemistry
223
224
-------
COMPOUND:
beta-Chloroethylamine, ethyl-n-propyl-, hydrochloride
REFERENCE: Goldin. A.. Now. H.A.. ^Mins, B.H.,
J. Phann. Exp. Ther. 94:249-261, 1958.
OBSERVED NEUROTOXIC EFFECTS:
Waltzing syndrome was produced by dialkyl and hetero-
cyclic B-chloroethylamines but not when (a) OH
or bromine replaced the S chlorine, (b) a 6-phenyl
group replaced one of the 8 hydrogens in the
chlorinated chain, or (c) phenyl groups were introduced
into the dialkyl carbons. No effect from primary/
.secondary B-chloroethylamines, related quaternary
compounds, or bis-, tris-, or tetrakis-B-chloro-
ethylamines. Piperidine and morpholine analogs and
arsacetin produced waltzing. Cerebellar and
axial lesions found consistent with behavior.
ANIMALS:
Mice, CF1, M, 2-3m, 18-25 g; also CF1 F and C3H M.
COMPOUND: Choralose, alpha
015879933
REFERENCE: Spooner, C.E. and Winters, W.D.
Int. J. Neuropharmacol. 5: 217-236, 1966
OBSERVED NEUROTOXIC EFFECTS: Compound produced depression and associated slow-
i wave EEGs.
ANIMALS: 200 Cockerels, White Leghorn, ages 5-14 d, 45-100 g
PREPARATION AND DOSE
or HISTORY OF PATIENT:
1-625 mg/kg in saline or (insolubles) 10% acacia,
various schedules.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 20-50 mg/kg
ROUTE AND SITE: I.P.
CONTROL INFORMATION: Vehicle alone
ROUTE AND SITE: s.C. near axillary vein; I.P. for doses over 0.05 ml
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: At least 10 d after treatment.
EXAM. TYPE: Behavior, histology.
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Behavior, EEC
225
226
-------
COMPOUND: Citric acid, fluoro-
COMPOUND: Citric acid, fluoro-
REFERENCE: Koenig, H.
Science 164:310-312, 1969.
OBSERVED NEUROTOXIC EFFECTS: Convulsions. Cord neurons expelled lysosomes,
mitochondria, other cytoplasmic structures into their axons. Axons and
mitochondria swelled.
REFERENCE: Patel, A. and Koenig, H.
J. Neurochem. 18: 621-628, 1971.
OBSERVED NEUROTOXIC EFFECTS:
Fluorocitrate blocks citrate (isocitrate) hydrolyase
(EC A.2.1.3); before and during convulsions, rat brair
and cat spinal cord alanine rose, and free aspartate,
glutamate and glutamine fell; GABA rose, then fell;
citrate rose markedly; glycogen fell; ammonia and ATP
remained constant; incorporation of glucose and lysint
into nerve proteins fell sharply. The authors proposi
that convulsions follow complexing of excess citrate
with Mg and consequent chemical reactions.
ANIMALS: Cats
PREPARATION AND DOSE
or HISTORY OF PATIENT: 3-50 meg of active isomer in 0.003-0.05 ml water, one
dose.
ANIMALS: Rats, S-D, F, 180-200 g
Cats, adult, 2-3 kg
PREPARATION AND DOSE
or HISTORY OF PATIENT:
1.5 meg/rat
10 meg/cat
ROUTE AND SITE: Inj. into lumbar subarachnoid space
CONTROL INFORMATION: None
ROUTE AND SITE: Rats, intracerebral; cats, into lumbar subarachnoid space
CONTROL INFORMATION: Compound omitted from treatment
DURATION OF EXPERIMENT: Serial sacr up to 24 hr, av 1-6 hr.
EXAM. TYPE: Behavior, histology
DURATION OF EXPERIMENT: Rats 20 min, cats 30 min
EXAM. TYPE: Biochemistry
227
228
-------
COMPOUND: Cobalt ion (+2)
REFERENCE: Nichols, R.A. and Nakajima, Y.
Brain Res. 86: 493-498, 1975
OBSERVED NEUROTOXIC EFFECTS: Cobalt inhibited the generation of the IPSP (sic) of
the stretch receptor neuron and had some depolarizing
action on the soma.
COMPOUND: Cobalt ion (+2)
REFERENCE: Prakash, N.J., Fontana, J. and Henkin, R.I.
Life Sci. 12(1):249-259, 1973.
OBSERVED NEUROTOXIC EFFECTS: Inhibited (Na+ + K+) ATPase, although never more
than 20%, even at 0.2 mM. Inhibition involved
blockage of norepinephrine and choline uptake.
ANIMALS: In vitro: slow adapting stretch receptors from 8th thoracic segment
of lobster (I!, americanus) and crayfish (Oronectes), or from
the 2nd-3rd abdominal segment of crayfish.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Co at 0-5 mM
ANIMALS:
Rat brain synaptosomes in vitro
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Co chloride added to medium in various expts.
ROUTE AND SITE: In vitro
CONTROL INFORMATION: Zero treatment
ROUTE AND SITE: in vitro
CONTROL INFORMATION: Lab
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Biochemistry, electrophyslology
DURATION OF EXPERIMENT: Minutes
EXAM. TYPE: Biochemistry
229
230
-------
COMPOUND: Cobra toxin
COMPOUND:
Colchicine
000064868
REFERENCE: Chang, C.C., Chuang, S-T., Lee, C.Y., Wei, J.W.
Br. J. Pharmac. 44:752-764, 1972.
OBSERVED NEUROTOXIC EFFECTS: Ineffective on axonal conduction and on membrane
potentials.
REFERENCE: Daniels, M.P.
J. Cell Biol. 58: 463-470, 1973.
OBSERVED NEUROTOXIC EFFECTS: Reversible inhibition of neurite elongation and
reversible neurite retraction was seen within 6 hr.
Assembly of the microtubules was interrupted and
disassembly started. Neurite outgrowth involves
assembly.
ANIMALS:
Phrenic nerve-diaphragm preparation from Long-Evans rats.
ANIMALS: In vitro cultures of chick dorsal-root ganglia
PREPARATION AND DOSE
or HISTORY OF PATIENT: Various doses in vitro.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.05 meg/ml
ROUTE AND SITE: in vltro
CONTROL INFORMATION: Laboratory
ROUTE AND SITE: In medium
CONTROL INFORMATION: Laboratory
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Electrophysiology, chemistry
DURATION OF EXPERIMENT: Up to 62 hr
EXAM. TYPE: Biochemistry, histology
231
232
-------
COMPOUND: Colchicine
000064868
REFERENCE: Wisnlewski, H. and Terry, R.D.
Lab. Invest. 17:577-587, 1967.
COMPOUND:
Copper (II) chloride
rtrtl tf./.C to
REFERENCE: Borchard, U. and Schneider, K.U.
Arch. Toxicol. 33:17-30, 1974.
OBSERVED NEUROTOXIC EFFECTS: After 2 mg died in 2 hr in status epilepticus;
others mild paresis by 6 hr quadriparesis by 1 d, died or were killed
within 6 d. Large neurons of brainstem and cord altered structurally,
and axons distended.
OBSERVED NEUROTOXIC EFFECTSJAmplitude of b-wave of ERG decreased reversibly at Cu
6 x 10"^ m/liter and irreversibly above that, during 30 min
of testing. Complexing agents suggested that intoxication
might be caused by blocking of enzymes containing
sulfhydryl groups.
ANIMALS: 15 rabbits, M and F, 3-4 kg.
ANIMALS: Frog retina in vitro
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.01-2.0 mg in 0.1 ml H20 (one dose)
PREPARATION AND DOSE
-6
or HISTORY OF PATIENT: 3-60 x 10 m/liter of medium
ROUTE AND SITE: Injection into cisterna magna
CONTROL INFORMATION: None
ROUTE AND SITE: Incubation
CONTROL INFORMATION: Laboratory
DURATION OF EXPERIMENT: Serial to 6 d
EXAM. TYPE: Behavior, histology
DURATION OF EXPERIMENT:About 1 hr.
EXAM. TYPE: Electrophysiology (ERG)
233
234
-------
COMPOUND:
Copper Ion (+2)
REFERENCE:
Prakash, N.J., Fontana, J. and Henkin, R.I.
Life Sci. 12(1):249-259, 1973.
OBSERVED NEUROTOXIC EFFECTS: At concentrations over 0.01 mM, Cu
completely inhibited (Na+ + K+) ATPase.
Inhibition involved blockage of norepinephrine
and choline uptake.
ANIMALS:
Rat brain synaptosomes in vitro
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Cu chloride added to medium in various expts.
ROUTE AND SITE: in vitro
CONTROL INFORMATION: Lab
DURATION OF EXPERIMENT: Minutes
EXAM. TYPE: Biochemistry
235
COMPOUND: Copper II sulphate
007758987
REFERENCE: Howell, J. McC., Blakemore, W.F., Gopinath, C., Hall, G.A. and
Parker, J.H.
Acta Neuropath. 29:9-24, 1974.
OBSERVED NEUROTOXIC EFFECTS: Central Nervous System examined: astrocytic
changes, vacuoles in white-matter, swollen astrocytes accumulated glycogen,
mitrochondria and endoplasmic reticulum. Authors conclude brain changes in
chronic copper poisoning may arise as result of altered glial transport mechanisms.
ANIMALS: Sheep: 39 (Clun Forest x Sussex) and 3 Welsh halfbred, 6-12 mo. old.
PREPARATION AND DOSE
Or HISTORY OF PATIENT: Av. 7 ppm copper in feed. 29 sheep given 0.5% aqueous
soln of copper sulphate daily: 22 at rate of 20 mg/kg, 7 at rate of 30 mg/kg.
ROUTE AND SITE: oral
CONTROL INFORMATION: 13 sheep untreated
DURATION OF EXPERIMENT: Serial sacr to 37 wk. 9 sacr before, 11 sacr during
and 9 died after hemolysis.
EXAM. TYPE: Blood chemistry, histology.
236
-------
COMPOUND:
Copper(II) sulfate pentahydrate (1:1:5)
\J I I JO77O
REFERENCE: Morgan, K.T.
Res. Vet. Sci. 15: 88-95, 1973.
COMPOUND: Cortlsol
ouuuso^av
REFERENCE:
Heuser, G., Ling, G.M. and Buchwald, N.A.
Arch. Neurol. 13:195-203, 1965.
OBSERVED NEUROTOXIC EFFECTS:
The treatment caused a spongy transformation of
the white matter. Vacuoles were seen in the myelin
and lamellae split, but neurones and glia were not
involved and there was no extracellular edema.
OBSERVED NEUROTOXIC EFFECTS:
Compound produced neither sedation nor seizures
in these monkeys.
ANIMALS:
Lambs, 6 mo total 8
ANIMALS:
Monkeys, Squirrel, surgically prepared
PREPARATION AND DOSE PREPARATION AND DOSE
or HISTORY OF PATIENT: Diet had 5 ppm of copper; 5 lambs drenched with 1 g compound/d or HISTORY OF PATIENT: Varying doses, exact amts not given, however comparable
5 d/wk 11 wk to doses of 5-200 mg/kg of other steroid sodium succinate
salts.
ROUTE AND SITE: Oral
CONTROL INFORMATION: 3 untreated
DURATION OF EXPERIMENT: 11 wk
EXAM. TYPE: Histology
ROUTE AND SITE:
I.V. or I.P.
CONTROL INFORMATION: Sham inj as well as saline and sodium bicarbonate soln
were used as controls. Control inj did not produce
sedative or convulsion effects.
DURATION OF EXPERIMENT: Up to approx. 30 min/test
EXAM. TYPE: Electrophysiology, behavior
237
238
-------
COMPOUND:
Cortisol, 21-acetate
COMPOUND:
Cottonseed oil
REFERENCE:
Cotterrell, M., Balazs, R. and Johnson, A.L.
J. Neurochem. 19:2151-2167, 1972.
REFERENCE: Boyd, E.M. and Boulanger, M.A.
Tox. Appl. Pharm. 14:432-438, 1969.
OBSERVED NEUROTOXIC EFFECTS:
By 35 d body wt reduced by 50%, brain wt by 30%
of norms; 20% fewer cells in cerebrum, 30% in
cerebellum; cell size not affected as judged by DNA;
cell destruction not affected. Thus growth retardation
in terms of new cell divisions was inferred.
OBSERVED NEUROTOXIC EFFECTS: The clinical signs included: listlessness, epistaxis,
ataxia, and anorexia. Autopsy showed congestion of
the brain associated with generalized capillary-
venous congestion.
ANIMALS: Rats, Porton, M, newborn
ANIMALS: (1) 20 Rats: Wlstar, young, M.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.125-0.4 mg/rat/d, various periods; most rats got 0.2
mg/d for 4 d.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 5-110 rag/kg for 4 d, cumulative amounts of 200-440 ml/kg.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: Saline treated controls
ROUTE AND SITE: i.e.
CONTROL INFORMATION: 66 control rats
DURATION OF EXPERIMENT: Serial sacr to 35 d.
EXAM. TYPE: Biochemistry.
DURATION OF EXPERIMENT: 5 d.
EXAM. TYPE: Behavior, autopsy, histopathological
239
240
-------
COMPOUND: Coumarin, 3-chloro-7-hydroxy-4-methyl-, bis(2-chloroethyl) phosphate
(Haloxon)
REFERENCE: Malone, J.C.
Res. Vet. Sci. 5: 17-31, 1964.
OBSERVED NEUROTOXIC EFFECTS:
At high doses, haloxon produced hindleg ataxia in
sheep and in poultry. Histological examination
revealed axonal degeneration. There was no apparent
relationship of the effects with cholinesterase.
COMPOUND:
Coumarin,3-Chloro-7-hydroxy-4-methyl,0-ester with 0,0-diethyl phosphorothioate
000056724
REFERENCE: Gaines, T.B.
Tox. Appl. Pharm. 14: 515-534, 1969.
OBSERVED NEUROTOXIC EFFECTS: 100 mg/kg produced leg weakness
Mice, M, 20-25 g
ANIMALS: Rats, S-D, F, 110-150 g
Guinea-pigs, F, 400-600 g
Rats, S-D, weanling, M & F
Cats, adult, no details
PREPARATION AND DOSE
or HISTORY OF PATIENT: c
Many formulations and doses, from
Dogs, adult, no details
Monkeys, adult, no details
Hens, 18 mo, 16 groups of 10
Sheep, lambs 1-8 mo, ewes & wethers 1 )
ewes over 4 yr, rams 1-5 yr
.-
down.
ANIMALS: Chickens, White Leghorn, F
PREPARATION AND DOSE
or HISTORY OF PATIENT: 15 mg/kg atropine sulfate orally 15 min prior to compound;
graded doses compound in peanut oil
ROUTE AND SITE: Oral, in diet; I.P.; dermal.
CONTROL INFORMATION: Various
ROUTE AND SITE: S.C., under right wing
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Behavior, biochemistry, histology
DURATION OF EXPERIMENT: 1 yr
EXAM. TYPE: Clinical
241
242
-------
COMPOUND: Coumarin, 7-hydroxy-4-methyl-, bis(2-chloropropyl)phosphate
REFERENCE: Aldridge, W.N. and Barnes, J.M.
Biochemical Pharm. 15:541-548, 1966.
COMPOUND: 0-Cresol, 4,6-dinitro- (DNOC)
000534521
REFERENCE: Burkatskaya, E.N.
Hygiene and Sanitation 30: 197-201, 1965. (Russ.) (Translated)
OBSERVED NEUROTOXIC EFFECTS: Weakened limbs. Histological changes in the
spinal cord and sciatic nerves. Inhibition of
CNS esterase.
OBSERVED NEUROTOXIC EFFECTS: Cats (2 of 4) exhibited twitching, tremor, dyspnea
and ataxia, with a blood DNOC level of 6-15 mg%;
DNOC gradually disappeared from the blood in 6-8
days.
Humans (indoors): changes in central and autonomic
nervous systems (sic); (outdoors): only slight changes
ANIMALS:
Hens, grps of 2-4, RIR x Light Sussex, 2-3
ANIMALS:
Cats.
Humans (exposed industrially)
PREPARATION AND DOSE
or HISTORY OF PATIENT: Mostly 1 dose, amount varied by compound
PREPARATION AND DOSE
or HISTORY OF PATIENT: Cats: 4 exposed to dust containing 0.036-0.06 mg/liter
Humans: exposed to av. 0.9mcg/liter in breathing zone
indoors; 0.7 in agriculture
ROUTE AND SITE: oral, s.c., or i.p.
CONTROL INFORMATION: ns.
ROUTE AND SITE: Inhalation
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: u-21 d
EXAM. TYPE: Biochemistry, histology
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Clinical
243
244
-------
COMPOUND:
Crotonic acid,3-hydroxy-,alpha-methylbenzylester, dimethyl phosphate, (E)-
007700176
COMPOUND: Cyanic acid
REFERENCE: Gaines, T.B.
Tox. Appl. Pharm. 14: 515-534, 1969.
OBSERVED NEUROTOXJC EFFECTS: 200 mg/kg produced leg weakness
REFERENCE: Papayannopoulou, T., Stamatoyannopoulos, G,, Giblett, E.R. and
Anderson, J.
Life Sci. 12(2):127-133, 1973.
OBSERVED NEUROTOXIC EFFECTS:
In vitro electrophoretic changes in 25 enzymes.
In vivo changes in 10 of these enzymes in 5 tissues
including brain homogenates, dose-related; in
LDjO survivors no changes detected. Changes
reversible. Interpreted by authors to show tissue
protein carbamylation independent of effects on
blood.
ANIMALS: Chickens, White Leghorn, F
PREPARATION AND. DOSE
Or HISTORY OF PATIENT: 15 mg/kg atropine sulfate orally 15 min prior to compound;
graded doses compound in peanut oil
ROUTE AND SITE: S.C., under right wing
CONTROL INFORMATION: ns
ANIMALS: In vitro tissues from "animals";
C3H mice, aged 12-14 wk, 4 groups total 42 mice.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
80 mg/kg, 12 doses in 3 wk; 100 mg/kg, 5 doses in 1 wk;
22 mg/kg, 17 doses in 3 wk; 250 mg/kg, one dose of the
sodium salt (equal to LD50), survivors used.
In vitro: 0.05 M cyanate added to medium incubating
blood.
ROUTE AND SITE: i.p. Or I.V.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: 1 yr
EXAM. TYPE: Clinical
DURATION OF EXPERIMENT:
EXAM. TYPE: Biochemical
20-24 hr after last injection.
245
246
-------
COMPOUND: Cyanide
000057125
REFERENCE:
Bass, N.H.
Neurology 18:167-177, 1968.
COMPOUND: Cyanide
000057125
REFERENCE: Hirano, A., Leving, S. and Zimmerman, H.M.
J. Neuropath. Exp. Neurol. 27(2) :234-245, 1968.
OBSERVED NEUROTOXIC EFFECTS: Myelin lesions in somatosensory cortex and
subcortical white-matter. At 5 hr after 1 dose white-matter DNA lower by
29%, residue protein up by 28%, cortex gangliosides down by 27%. At
30 d chronic-treated rats had no cortical lesions but white-matter demyelination
with 28% gain in residue protein, and losses of DNA (37%) and cerebrosides
.(65%).
OBSERVED NEUROTOXIC EFFECTS: Corpus callosum and callosal radiation (the only
tissues reported on) had distortions of remyelination
shown at 4 mo. after intoxication. Observations,
not fully reported, imply that demyelination had
occurred on intoxication.
ANIMALS:- (1) 30 Rats, COBS, M, adult 300 g.
(2) 10 Rats, COBS, M, adult 300 g.
ANIMALS:
Rats, young albino.
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) Chronic: 8 mg/kg/d stepped up during 25 d in survivor
(2) Acute: 2 mg/rat/10 min for 3 doses.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Deep intoxication for 30, min (ref. Leving, S.
and Stypulkowski, W. Arch. Path. 67:306 (1959)).
ROUTE AND SITE: S.C., abdominal wall
CONTROL INFORMATION: 10 rats untreated
ROUTE AND SITE: Inhalation
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: 30 d
EXAM. TYPE: Chemistry, Histology
DURATION OF EXPERIMENT: 1 wk to 6 mo. after intoxication, serial sacr.
EXAM. TYPE: Electronmicroscopy
247
248
-------
COMPOUND: Cyanide
000057125
REFERENCE: Van Houten, W.H. and Friede, R.L.
Exp. Neurology 4:402-412, 1961.
COMPOUND: 1,3,5-Cycloheptatriene
000544252
REFERENCE: Brown, V.K.H., Kerrigan, L.W. and Stevenson, D.E.
Ann. Occup. Hyg. 10:123-126, 1967.
OBSERVED NEUROTOXIC EFFECTS:
Increase of oxidative enzymatic activity in white
matter; increase of enzyme activity in neuroglia
cell perikarya-astrocytes. Edema, anoxia.
OBSERVED NEUROTOXIC EFFECTS: Clonic convulsions preceded death. (LD50 dosages).
ANIMALS:
45 Rats, Albino, 200-300 mg.
ANIMALS: Rats, Hooded Lister, 4 M and 4 F/group, 150-250 g Mice, CF No. 1,
4 M and 4 F, 21-25 g.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Inhalation of air bubbled through 10% soln of potassium
cyanide in a 1 gallon jar until animal became unconscious
and remained so for 20 mins. Few given additional
exposures at 24 hr intervals.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Rats: Oral 57 mg/kg percutaneous 442-884 rag/kg
Mice: Oral 171 mg/kg
ROUTE AND SITE: Inhalation
CONTROL INFORMATION: ns.
ROUTE AND SITE: Gavage, topical (dorso-lumbar skin)
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: Animals killed 24 hrs or more after last exposure
EXAM. TYPE: Histochemical.
DURATION OF EXPERIMENT: Death in 24 hr, usually in'minutes
EXAM. TYPE: Behavior, histopathological
249
250
-------
COMPOUND: Cyclohexane, 1,2,3,4,5,6-hexachloro-, gamma-isomer
000058899
REFERENCE: Czegledl-Janko, G. and Avar, P.
Br. J. Indust. Med. 27: 283-286, 1970.
OBSERVED NEUROTOXIC EFFECTS: EEC and clinical findings increased with blood
concentration over 0.02 ppm.
COMPOUND: Cyclohexane, 1,2,3,4,5,6-hexachloro-, gamma isomer (Lindane)
000058899
REFERENCE: St. Omer, V.
J. Neurochem. 18: 365-374, 1971,
OBSERVED NEUROTOXIC EFFECTS:
Convulsions, starting in some cases during injection.
Intensity and other signs were directly related to
Increases of brain ammonia. Toxicity ranking:
lindane > dieldrin > heptachlor > DDT. Brain gluta-
mlne increases resulting from conversion of ammonia
to glutamine were related to the toxicity ranking,
suggesting that the 4 compounds produced convulsions by
one mechanism involving interference with the production
and/or utilization of ammonia.
ANIMALS: -37 men, working in a fertilizer factory.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Final product'contained 1.5% lindane; no other toxic agent,
but 22 subjects had previous exposure to aldrin, 3 acute
histories (convulsions), another 3 EEC disorders. Lindane
not measured, exposure lasted 0.5-2 yr. Blood levels
0.002-0.340 ppm.
ROUTE AND SITE: Inhalation, skin contact
CONTROL INFORMATION: Blood levels in 20 of general population 0.003-0.017 ppm.
ANIMALS: Rats, adult F, Wistar, 250-300 g, surgically prepared.
Cockerels, White Leghorn or Barred Plymouth Rock, 12 wk, 1.4-1.6 kg,
surgically prepared.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Rats: mg/kg — lindane 11.5, DDT 50, dieldrin 6, heptachlor 13
Cockerels: mg/kg — lindane 6.3, DDT 30, dieldrin 6, heptachlo
The compounds stated to be structurally unrelated.
ROUTE AND SITE: Intra-arteriai (carotid) at 1 ml/min
CONTROL INFORMATION: Vehicle only
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Blood lindane, EEC, clinical.
DURATION OF EXPERIMENT: Up to 60 min, in controls 7 d
EXAM. TYPE: Behavior, biochemistry
251
252
-------
COMPOUND: 5H-Cyclooct(b)indole, 5-(3-(dimethylamino)propyl)-6,7,8,9,10,ll-
hexahydro-
UU5560725
REFERENCE: Lullmann-Rauch, R.
Acta Neuropath. (Berl.) 29: 237-249, 1974.
OBSERVED NEUROTOXIC EFFECTS: Significant ultrastructural alterations of nerve
cells, both in spinal cord and in cerebellar cortex.
COMPOUND: Cyclopentanecarboxylic acid, 1-amino
000052528
REFERENCE: Ross, R.B., Noll, C.I., Ross, W.C.J., Nadkarni, M.V., Morrison,
B.H., Jr., and Bond, H.W.
J. Med. Pharm. Chem. 3:1-23, 1961.
OBSERVED NEUROTOXIC EFFECTS: Dogs: Slight derayelination of cerebellum.
Mice: Slight demyelination of central nervous system.
Nerve effects not mentioned for other species.
ANIMALS: Rats, Wistar, M, young adult
ANIMALS: Dogs, rats, mice, cats, monkeys, humans
PREPARATION AND DOSE
or HISTORY OF PATIENT: 125 mg/kg bw, 5d/wk in water, 0.5 ml/100 g bw, for 5 wk.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Dogs: 31.6 mg/kg/d for 30 d (lower doses no effect;
LD,Q one dose was 300 mg/kg).
Mice: 200-1259 mg/kg.
ROUTE AND SITE: I. Tub.
CONTROL INFORMATION: Force-fed pure water.
ROUTE AND SITE: Dogs: Oral (capsule) Mice: Gavage
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: 5 wk
EXAM. TYPE: Histology
DURATION OF EXPERIMENT:
EXAM. TYPE: clinical, autopsy
253
254
-------
COMPOUND: Cyclopentane carboxylic acid, 1-phenyl-, 2-(diethylamino)ethyl ester,
hydrochloride
000125859
REFERENCE: pfeiffer, C.C., Murphree, H.B., Jenney, E.H., Robertson, M.G.,
Randall, A.H. and Bryan, L.
Neurology 9: 249-250, 1959.
OBSERVED NEUROTOXIC EFFECTS: The authors concluded that synthetic atropines are more
active hallucinogens than atropine or scopolamine, pro-
ducing effects lasting 24-48 hr. Synthetic antitremor
drugs had fewer peripheral nervous system side-effects,
but.central nervous system side-effects (hallucinations)
may have been exaggerated.
COMPOUND: Cyclopropylamine, 2-phenyl-, sulfate trans- (+,-)-, (2:1)
REFERENCE: Quinton, R.M.
Br. J. Pharmac. 21:51-66, 1963.
OBSERVED NEUROTOXIC EFFECTS: The compound enhanced the effect of Yohimbine
and lowered its lethal dosage.
ANIMALS: Human: prison volunteers, drug-sophisticated, no other details
ANIMALS:
Mice, TT, M, 18-25 g.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 25 mg/man
PREPARATION AND DOSE
or HISTORY OF PATIENT:
»5o 4 mg/kg
ED50 " dose producing a 50% mortality of mice injected
S.C. with yohimbine hydrochloride (20 mg/kg).
ROUTE AND SITE: Oral
CONTROL INFORMATION: LSD-25: 0, 25, 50, 100 meg/man
ROUTE AND SITE: S.C., Oral
CONTROL INFORMATION: Various
DURATION OF EXPERIMENT: Up to 3 d
EXAM. TYPE: Opinion of volunteers
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Behavior, electrophysiology, biochemistry
255
256
-------
COMPOUND:
Cysteine, L-
COMPOUND:
Cysteine, L-
REFERENCE: Olney, J.W. and Ho., 0.
Nature 227:609-610, 1970.
REFERENCE: Olney, J.W., Ho, O.L. and Rhee, V.
Exp. Brain Res. 14:61-76, 1971.
OBSERVED NEUROTOXIC EFFECTS: Necrosis of hypothalamic neurons in mice given
glutamate, aspartate, or cysteine, dose-related;
zero damage from other compounds
OBSERVED NEUROTOXIC EFFECTS: The compound was equipotent to monosodium
glutamate in necrosing neurons in the retina
and brain. This compound is a powerful neuro-
excitant and the neurotoxic properties may be
governed by similar mechanisms.
ANIMALS: 75 Mice, Swiss Webster, age 10 d.
ANIMALS: Mice, Swiss-webster age 10 d, total 250
PREPARATION AND DOSE
or HISTORY OF PATIENT:
One of 10 amino acids and various other compounds, 2.5 or 10%
in water, 0.25-2 g/kg.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Initially 12 mmoles/kg, then range established for
each compound.
ROUTE AND SITE: Gavage
CONTROL INFORMATION: Intubated, no treatment, 10 mice
DURATION OF EXPERIMENT: 5 hr.
EXAM. TYPE: Histology
ROUTE AND SITE: s.C.
CONTROL INFORMATION: Compounds compared with monosodium L-glutamate (MSG)
potency for selectively necrosing neurons in retina
and brain (hypothalamus)
DURATION OF EXPERIMENT: s.hr or serial intervals including 5 hr.
EXAM. TYPE: Histology
257
258
-------
COMPOUND: Cysteine, N-acetyl-, L-
000616911
REFERENCE: Olney, J.W., Ho, 0.1. and Rhee, V.
Exp. Brain Res. 14:61-76, 1971.
OBSERVED NEUROTOXIC EFFECTS: No cytotoxicity was observed.
COMPOUND:
Decaborane
017702419
REFERENCE: Feinsilver, L., Lawson, L.H., Yevich, P.P. and Jacobson, K.H.
U.S. Army CWL Report CWLR 2367, 1960.
OBSERVED NEUROTOXIC EFFECTS: LC5Q under conditions were:
Rats - 46ppm; mice - 12ppm. Signs included ataxia,
depression, prostration, tremors, clonic convulsions,
interpreted as "marked effects upon" the central
nervous system.
ANIMALS: Mice, Swiss-webster age 10 d, total 250
PREPARATION AND DOSE
or HISTORY OF PATIENT: Initially 12 mmoles/kg, then range established for
each compound.
ANIMALS: Rats, ages 8-10 wk, M
Mice, 8-10 wk, F
Dogs, beagle, M.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Exposed to vapors of compounds in LC5Q study, 2-4 hr
ROUTE AND SITE: s.C.
CONTROL INFORMATION: Compounds compared with monosodium L-glutamate (MSG)
potency for selectively necrosing neurons in retina
and brain (hypothalamus)
DURATION OF EXPERIMENT: 5 hr or serial intervals including 5 hr.
EXAM. TYPE: Histology
ROUTE AND SITE: Inhalation
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: Observation to 7 d after exposure
EXAM. TYPE: Behavior, pathology
259
260
-------
COMPOUND: Decaborane, ethyl
COMPOUND:
1,4-Diazabicyclo(2.2.2.)octane
REFERENCE: Feinsilver, L., Lawson, L.H., Yevich, P.P. and Jacobson, K.H.
U.S. Army CWL Report CWLR 2367, 1960.
REFERENCE: Goldberg, M.E. and Johnson, H.E.
Tox. Appl. Pharm. 4:522-545, 1962.
OBSERVED NEUROTOXIC EFFECTS: LC5Q under conditions were:
Rats - 23ppm; mice - 6ppm; dogs - approximately •
6ppm. Signs included ataxia, depression, prostration,
tremors, clonic convulsions, interpreted as "marked
effects upon" the central nervous system.
OBSERVED NEUROTOXIC EFFECTS: Treatment apparently stimulated sympathetic ganglia.
ANIMALS: Rats, ages 8-10 wk, M
Mice, 8-10 wk, F
Dogs, beagle, M.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Exposed to vapors of compounds in LC5Q study, 2-4 hr
ANIMALS: Rats, CFE, M, 5-6 wk old, 90-120 g, 5 rats/grp or 6/grp (inhalation)
Rabbits, NZ white, 2.5-3.5 kg, M, 4 rabbits/grp, and isolated ileum.
Mice, white, F, 20-28 g.
41 mongrel dogs (8.5-12.5 kg) M and F. 10 cats, F, 2.2-3.8 g.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Various schedules
ROUTE AND SITE: Inhalation
CONTROL INFORMATION: None
ROUTE AND SITE: Topical, shaved skin (rabbits); inhalation (rats, mice);
intra-arterial (carotid) (dogs, cats) and I.V. femoral (dogs, cats)
CONTROL INFORMATION: Varied
DURATION OF EXPERIMENT: Observation to 7 d after exposure
EXAM. TYPE: Behavior, pathology
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Physiology, biochemistry
261
262
-------
COMPOUND: 5H-Dibenz(b,f)azepine, 3-chloro-5-(3-(dimethylamlnopropyl)-10,
11-dihydro-
Lullmann-Rauch, R.
REFERENCE: Acts Neuropath. (Berl.) 29: 237-249, 1974.
OBSERVED NEUROTOXIC EFFECTS: Very mild changes in the fine structure of neuronal
lysosomes, in cord and cerebellar cortex.
COMPOUND: 5H-Dibenz(b,f) azepine, 5-(3-(dimethylamino)propyl)-10,ll-dlhydro-
000050497
REFERENCE: Pearlman, C. and Becker, M.
Psychopharmacologia 42:63-66, 1975.
OBSERVED NEUROTOXIC EFFECTS:
Cooperative behavior training and performance
prevented when compound administered a few minutes
after feeding session, no effects if given 3
hr afterwards. Authors concluded mechanism was
prevention of REM sleep during this time.
ANIMALS: Rats, Wistar, M, young adult
ANIMALS: Rats, Long-Evans, F, 3 mo. age.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 150 mg/kg bw, 5d/wk, in water 0.5 ml/100 g bw for 4 wk.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 5 mg/kg on alternate days a few minutes after session or
after 3 hrs of rest.
ROUTE AND SITE: I. Tub.
CONTROL INFORMATION: Controls force-fed pure water
ROUTE AND SITE: !•?•
CONTROL INFORMATION: 6 controls: undisturbed sleep, 6 had saline inj followed
by normal sleep.
DURATION OF EXPERIMENT: 4 wk.
EXAM. TYPE: Histology
DURATION OF EXPERIMENT: Approx. 10 d
EXAM. TYPE: Behavior
263
264
-------
COMPOUND: : 5H-Dibenz(b,f) azeplne, 5-(3-(dimethylamino)propyl)-10,ll-
-------
COMPOUND: 5H-Dibenzo(a,d) cycloheptene-delta (Sup 5), gamma-propylamine, 10,11-
dihydro-M.N-dimethyl-
000050486
Lullmann-Rauch, R.
REFERENCE: Acta Neuropath. (Berl.)29: 237-249, 1974
OBSERVED NEUROTOXIC EFFECTS: Administration for lOwk did not induce alterations
in the nerve cells of spinal cord and cerebellar cortex cells examined.
COMPOUND: 5H-Dibenzo(a,d) cycloheptene-delta (sup5), gamma-propylamine, 10,11-dihydi
N,N-dimethyl-, hydrochloride
000549188
REFERENCE: Quinton, R.M.
Br. J. Pharmac. 21:51-66, 1963.
OBSERVED NEUROTOXIC EFFECTS: The compound enhanced the effect of Yohimbine
and lowered its lethal dosage.
ANIMALS: Rats, Wistar, M, young adult.
ANIMALS:
Mice, TT, M, 18-25 g.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 150 mg/kg bw, 5d/wk in water, 0.5 ml/100 g bw, for 8 wk.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
ED,
'50
mg/kg
ED,.- = dose producing a 50% mortality of mice injected
"50
S.C. with yohimbine hydrochloride (20 mg/kg).
ROUTE AND SITE: I. Tub.
CONTROL INFORMATION: Controls force-fed pure water.
ROUTE AND SITE: S.C., Oral
CONTROL INFORMATION: Various
DURATION OF EXPERIMENT: 8 wk.
EXAM. TYPE: Histology
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Behavior, electrophysiology, biochemistry
267
268
-------
COMPOUND: 5H-Dibenzo(a,d)cyclohepten-5-one, 10,ll-dihydro-,o-(2-(dimethyl
amino)e thy1)oxime
COMPOUND:
Dibenzo-p-dioxin,2,3,7,8-tetrachloro
001746016
REFERENCE: Lullmann-Rauch, R.
Acta Neuropath. 29: 237-249, 1974.
REFERENCE:
Oliver, R.M.
Br. J. Indust, Med. 32:49-53, 1975.
OBSERVED NEUROTOXIC EFFECTS: Administration for 10 wk did not induce alterations
in the nerve cells of spinal cord and cerebellar cortex cells examined.
OBSERVED NEUROTOXIC EFFECTS: Personality disorders, emotional instability,
loss of hearing, sense of smell or taste.
Headaches and blurred vision. Neuropathy recovered
over approx. 6 mo.
ANIMALS: Rats, Wistar, M, young adult.
ANIMALS:
3 Humans: M, age 45, 33, 35 yr.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 150 mg/kg bw, 5d/wk, in water 0.5 ml/100g bw for 8 wk
PREPARATION AND.DOSE
or HISTORY OF PATIENT: Scientists in the same lab, extent of exposure unknown.
ROUTE AND SITE: i. Tub.
CONTROL INFORMATION: Controls force fed pure water
ROUTE AND SITE: Unknown
CONTROL INFORMATION: 3 other scientists in same lab with no known exposure to
dioxin.
DURATION OF EXPERIMENT: 8 wk
EXAM. TYPE: Histology
DURATION OF EXPERIMENT: 3 yr.
EXAM. TYPE: Clinical,"biochemical
269
270
-------
COMPOUND: 6H-Dibenzo(b,d)pyran-l-01,3-(l'2'-dimethylheptyl)-7,8,9,10-tetrahydro-
f-, 1,3-tr imethyl- (Dimethylheptylpyran)
REFERENCE: Karler, R., Cely, W. and Turkanis, S.A.
Res. Comm. Chem. Path. Pharm. 7(2):353-358, 1974.
OBSERVED NEUROTOXIC EFFECTS:
Bar-walk test gave decreasing order of toxicity
as dimethylheptylpyran, A'-tetrahydrocannabinol,
cannabidiol; anticonvulsant and "toxic" actions
concluded to be separable.
ANIMALS: Mice, ICR, 4-5 wk old
PREPARATION AND DOSE
or HISTORY OF PATIENT:
3-20 mg/kg
ROUTE AND SITE: i.p.
CONTROL INFORMATION:
Own controls
DURATION OF EXPERIMENT:
EXAM. TYPE: Behavior
271
COMPOUND: 6H-Dibenzo(b,d)pyran-l-ol, 6a,7,10,10a-tetrahydro-7-alpha, 11-
d ihydroxy-6,6,9-trimethyl-3-pentyl-
REFERENCE: Christensen, H.D., Freudenthal, R.I., Gidley, J.T., Rosenfeld, R.,
Boegli, G., Testino, L., Brine, D.R., Pitt, C.G. and Wall, M.E.
Science 172: 165-167, 1971.
OBSERVED NEUROTOXIC EFFECTS: The biological activity of the above compound, and
other cannabinoids was compared to that of A9-Tetrahydrocannabinol. Similar
neurological and behavioral responses were found for all, provided that high
concentrations were given. The potency of the compounds varied depending on
structure and route of administration. Behavioral pattern was character-
ized by irritability, decrease in activity, reduced sensorimotor responses.
This compound was approx. seven times more potent by intracerebral admin.
than by I.V.
ANIMALS: Mice
PREPARATION AND DOSE
or HISTORY OF PATIENT: Amount ns., table included comparing relative potency of
A9THC to compound tested.
ROUTE AND SITE: I.V. or Intracerebral
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior
272
-------
COMPOUND- 6H-Dibenzo(b,d)pyran-l-ol, 6a,7,10,10a-tetrahydro-7-beta,ll-dihydroxy-
e, fi q_fviifi-?-^er-tvl-
REFERENCE: Christensen, H.D., Freudenthal, R.I., Gldley, J.T., Rosenfeld, R.,
Boegli, G., Testino, L., Brine, D.R., Pitt, C.G. and Wall, M.E.
Science 172: 165-167, 1971.
OBSERVED NEUROTOXIC EFFECTS: The biological activity of the above compound, and
other cannabinoids was compared to that of A9-Tetrahydrocannabinol. Similar
neurological and behavioral responses were found for all, provided that high
concentrations were given. The potency of the compounds varied depending on
structure and route of administration. Behavioral pattern was character-
ized by irritability, decrease in activity, reduced sensorimotor responses.
This compound was approx. seven times more potent by intracerebral admin.
than by I.V.
COMPOUND: 6H-Dibenzo(b,d)pyran-1-ol, 6a, 7,8,lOa-tetrahydro-8,11-dihydroxy-
6,6,9-trimethvl-3-oentyl-
REFERENCE: Christensen, H.D., Freudenthal, R.I., Gidley, J.T., Rosenfeld, R.,
Boegli, G., Testino, L., Brine, D.R., Pitt, C.G. and Wall, M.E.
Science 172: 165-167, 1971.
OBSERVED NEUROTOXIC EFFECTS: The biological activity of the above compound, and
other cannabinoids was compared to that of A9-Tetrahydrocannabinol. Similar
neurological and behavioral responses were found for all, provided that high
concentrations were given. The potency of the compounds varied depending on
structure and route of administration. Behavioral pattern was character-
ized by irritability, decrease in activity, reduced sensorimotor responses.
This compound was significantly more potent by intracerebral admin, than by I.V.
ANIMALS: Mice
ANIMALS: Mice
PREPARATION AND DOSE
or HISTORY OF PATIENT: Amount ns., table included comparing relative potency of
A9THC to compound tested.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Amount ns., table included comparing relative potency of
A9THC to compound tested.
ROUTE AND SITE: i.V. or Intracerebral
CONTROL INFORMATION: ns.
ROUTE AND SITE: i.V. or Intracerebral
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior
273
274
-------
COMPOUND: 6H-Dibenzo(b,d)pyran-l-ol, 6a, 7,10,10a-tetrahydro-ll-hydroxy-
6,6,9-trimethyl-3-pentyl-
REFERENCE: Christensen, H.D., Freudenthal, R.I., Gidley, J.T., Rosenfeld, R.,
Boegli, G., Testino, L., Brine, D.R., Pitt, C.G. and Wall, M.E.
Science 172: 165-167, 1971.
OBSERVED NEUROTOXIC EFFECTS: The biological activity of the above compound, and
other cannabinoids was compared to that of A -Tetrahydrocannabinol. Similar
neurological and behavioral responses were found for all, provided that high
concentrations were given. The potency of the compounds varied depending on
structure and route of administration. Behavioral pattern was character-
ized by irritability, decrease in activity, reduced sensorimotor responses.
This compound was approx. seven times more potent by intracerebral admin.
than by I.V.
COMPOUND: 6H-Dibenzo(b,d)pyran-1-ol, 6a,7,10,10a-tetrahydro-6,6,9-
trimethyl-3-pentyl-
REFERENCE: Christensen, H.D., Freudenthal, R.I., Gidley, J.T., Rosenfeld, R.,
Boegli, G., Testino, L., Brine, D.R., Pitt, C.G. and Wall, M.E.
Science 172: 165-167, 1971.
OBSERVED NEUROTOXIC EFFECTS: The biological activity of the above compound, and
other cannabinoids was compared to that of A^-Tetrahydrocannabinol. Similar
neurological and behavioral responses were found for all, provided that high
concentrations were given. The potency of the compounds varied depending on
structure and route of administration. Behavioral pattern was character-
ized by irritability, decrease in activity, reduced sensorimotor responses.
Immobility was more pronounced with the A° THC compounds. Equipotent by
either method of admin, faster onset of activity after intracerebral.
Activity after I.V. may be due to conversion to 11-hydroxy metabolite.
ANIMALS: Mice
ANIMALS: Mice
PREPARATION AND DOSE
or HISTORY OF PATIENT: Amount ns., table included comparing relative potency of
A9THC to compound tested.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Amount ns., table included comparing relative potency of
A9THC to compound tested.
ROUTE AND SITE: i.v. Or Intracerebral
CONTROL INFORMATION: ns.
ROUTE AND SITE: i.v. or Intracerebral
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior
275
276
-------
COMPOUND:
6H-Dibenzo(b,d)pyran-l-ol, 6a,7,10,lOa-tetrahydro-6,6,9-trimethy1-3-
pentyl-
REFERENCE: McCaughran, J.A., Jr., Corcoran, M.E. and Wada, J.A.
Pharm. Biochem. Behav. 2: 227-233, 1974.
COMPOUND: 6H-Dibenzo(b,d)pyran-l-ol, 6a,7,8,10a-tetrahydro-6,6,9-trimethyl-3-
•-"- r' -" trans1-
1972083
REFERENCE: Carlini, E.A., Karniol, I.G., Renault, P.F. and Schuster, C.R.
Br. J. Pharmac. 50: 299-309, 1974.
OBSERVED NEUROTOXIC EFFECTS: The rats exhibited flaccid muscles, ataxla, catalepsy,
hyperreactivity, and loss of righting. These symptoms
were dose-related from 0 (1 mg/kg) to 100% (9 mg/kg).
A TD5_ of 4.3 mg/kg was determined. Protection against
metrazol induced seizures was provided by far higher
doses.
OBSERVED NEUROTOXIC EFFECTS: ^ compound dlsrupted time production tasks,
Increased pulse rate and provoked psychic
reactions in humans. The different animals
responded similarly.
ANIMALS: Rats, hooded, M, 300-480 g, total over 200 in groups of 4
PREPARATION AND DOSE
or HISTORY OF PATIENT: 1-9 mg/kg, one dose (toxicity)
15-200 mg/kg (protection against induced seizures)
ANIMAIS- Rabbits, .albino, adult M, 2.5-3.5 kg
Mice, albino, M, 3 mo, 25-30 g
Rats, no details
Human: 11 physicians and 22 medical students, all M, 18-42 yr, 51-80 kg
PREPARATION AND DOSE
or HISTORY OF PATIENT: Rabbits: continuous infusions
Rats: 0-40 mg/kg
Mice: 0-80 mg/kg
Humans: 1-20 mg/man
ROUTE AND SITE: I.P.
CONTROL INFORMATION: ns
ROUTE AND SITE: Rabbits: I.V.; rats: ns; mice: I.P.; humans: inhalation.
CONTROL INFORMATION: Zero treatment, placebo
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Behavior
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Behavior
277
278
-------
COMPOUND: 6H-Dibenzo(b,d)pyran-l-ol, 6a,7,8,10a-tetrahydro-6,6,9-
trimethyl-3-pentyl-,(6 afl^trans)-
1972083
REFERENCE: Christensen, H.D., Freudenthal, R.I., Gldley, J.T., Rosenfeld, R.,
Boegli, G., Testlno, L., Brine, D.R., Pitt, C.G. and Wall, M.E.
Science 172: 165-167, 1971.
OBSERVED NEUROTOXIC EFFECTS: The biological activity of the above compound, was
compared to other cannabinoids. Similar neurological and behavioral responses
were found for all provided that high concentrations were given. Behavioral
pattern was characterized by irritability, decrease in spontaneous activity,
reduced sensorimotor responses. The potency of the compounds varied depending
. on structure and route of administration. Measurable behavioral alterations
after intracerebral 0.05 mg. Compound is approximately equipotent by
either method of administration, however, faster onset of activity after
intracerebral.
COMPOUND: 6H-Dibenzo(b,d) pyran-1-ol, 6a,7,8,10a-tetrahydro-6,6,9-trimethyl-3-
pentyl-, (6 aR-trans)-
1972083
REFERENCE: Fried, P.A. and Husband, C.A.
Life Sci. 12(1):289-295, 1973.
OBSERVED NEUROTOXIC EFFECTS: Visual cliff test. No differences in depth
perception in treated vs control groups. Acute group took significantly
longer than other groups to perform the tests.
ANIMALS:
Mice. Also in vitro study of metabolism.
ANIMALS: 43 Rats, hooded, M, Aged 2 mo, 6 grps of 7-8 rats
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.05 mg, 0.2 mg or 0:.| mg.
Relative potency of A THC to related compounds given in table.
In vitro: 1.0 mg labeled/g tissue for 1 hr in 0.1M potassium
phosphate buffer.
ROUTE AND SITE: 1.7., or Intracerebral
CONTROL INFORMATION: ns.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Chronic: 0.5 or 4 mg/kg in propylene glycol, 1/2 d
for 44 d prior to testing.
Acute: 0.5 or 4 mg/kg once, preceded by 21 inj 0.5
cc propylene glycol 1/2 d.
ROUTE AND SITE: i.p.
CONTROL INFORMATION: 1 group vehicle only, 1 group sham inj.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior, biochemistry
DURATION OF EXPERIMENT: 44 d plus testing time.
EXAM. TYPE: Behavior
279
280
-------
COMPOUND: 6H-Dibenzo(b,d) pyran-1-ol, 6a,7,8,10a-tetrahydro-6,6,9-trimethyl-3-
pentyl-, (6 aR-trans)-
1972083
REFERENCE: Fujimori, M., Trusty, D.M. and Himwich, H.E.
Life Sci. 12(1):553-563, 1973.
COMPOUND- 6H-Dibenzo(b, d)p-yran-l-ol, 6a, 7,8,10a-tetrahydro-6,6,9-trimethyl-
3-pentyl-, (6aR-trans)-
REFERENCE: Hockman, C.H., Perrin, R.G. and Kalant, H.
Science 172:968-970, 1971.
OBSERVED NEUROTOXIC EFFECTS: Simultaneous EEC changes, hypotension, slow
EKG, all dose-dependent. Authors suggest mechanism
of action may be different from that of other
psychotomimetrics.
OBSERVED NEUROTOXIC EFFECTS: Doses at all levels produced disruption of both
behavior and electroencephalogram.
ANIMALS: 46 Rabbits, white, 3.1-3.7 kg, tracheotomized, 10-12/grp
ANIMALS: 6 Cats, surgically prepared
PREPARATION AND DOSE
or HISTORY OF PATIENT: 4 different doses: 0.1, 0.5, 1.0 and 2.0 mg/kg as
1 mg/ml in soln of 10% propylene glycol.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.5, 1 and 4 mg/kg to each cat in successive trials,
4-7 d intervals.
ROUTE AND SITE: I.V. rate 1 ml/min.
CONTROL INFORMATION: Control measurements taken prior to testing of compound.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: Self-controls
DURATION OF EXPERIMENT: Serial sacr 0-90 min after dose.
EXAM. TYPE: Electrophysiological
DURATION OF EXPERIMENT: 60-min sessions
EXAM. TYPE: Electrophysiology, behavior
281
282
-------
COMPOUND' 6H-Dibenzo(b,d) pyran-1-ol, 6a,7,8,10a-tetrahydro-6,6,9-trimethyl-3-
pentyl-, (6 aR-trans)-
1972083
REFERENCE: Karler, R., Cely, W. and Turkanis, S.A.
Res. Comm. Chem. Path. Pharm. 7(2):353-358, 1974.
COMPOUND: 6H-Dibenzo(b,d) pyran-1-ol, 6a,7,8,10a-tetrahydro-6,6,9-trimethyl-3-
pentyl-, (6 aR-trans)-
1972083
REFERENCE: McCaughran, J.A., Jr., Corcoran, M.E. and Wada, J.A.
Pharm. Biochem. Behav. 2: 227-233, 1974,
OBSERVED NEUROTOXIC EFFECTS:
Bar-walk test gave decreasing order of toxicity
as dimethylheptylpyran, the above compound,
cannabidiol; anticonvulsant and "toxic" actions
concluded to be separable.
OBSERVED NEUROTOXIC EFFECTS: The rats exhibited flaccid muscles, ataxia, catalepsy,
hyperreactivity, and loss of righting. These symptoms
were dose-related from 0 (1 mg/kg) to 100% (9 mg/kg).
A TD5_ of 3.4 mg/kg was determined. Protection against
metrazol induced seizures was provided by far higher
doses.
ANIMALS: Mice, ICR, 4-5 wk old
ANIMALS: Rats, hooded, M, 300-480 g, total over 200 in groups of 4
PREPARATION AND DOSE
or HISTORY OF PATIENT:
40-130 mg/kg
PREPARATION AND DOSE
or HISTORY OF PATIENT: 1-9 mg/kg, one dose (toxicity)
15-200 mg/kg (protection against induced seizures)
ROUTE AND SITE: i.p.
CONTROL INFORMATION:
Own controls
ROUTE AND SITE: I.P.
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT:
EXAM. TYPE: Behavior
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Behavior
283
284
-------
COMPOUND. Dibenzylamine, N-(2-chloroethyl)-
UUUU313UJ
REFERENCE: Quinton, R.M.
Br. J. Pharmac. 21:51-66, 1963.
COMPOUND: Diethylamine, 2,2'-dichloro-N-methyl-
nnnnci-750
REFERENCE: McDonald, T.P. and Asano, M.
Am. J. Path. 38:695-702, 1964.
OBSERVED NEUROTOXIC EFFECTS: The compound enhanced the effect of Yohimbine
and lowered its lethal dosage.
OBSERVED NEUROTOXIC EFFECTS:
Severe, dose-related, neuronal shrinkage with later
focal necrosis, peak on d 6-8. Most affected:
neocortex, pyriform cortex, hippocampus,
cerebellum, medulla oblongata. Signs: inactivity,
incoordination, irritability, convulsions,
lacrimation.
ANIMALS:
Mice, TT, M, 18-25 g.
ANIMALS: Mice, RF, F aged 10 wk, 21-26 g, total 189 used in an acute toxicity
study.
PREPARATION AND uoSE
or HISTORY OF PATIENT:
50 mg/kg
dose producing a 50% mortality of mice injected
S.C. with yohimbine hydrochloride (20 mg/kg).
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.05-0.4 mg/mouse in 0.9% NaCl at pH 4.2-4.6.
ROUTE AND SITE: S.C., Oral
CONTROL INFORMATION: Various
ROUTE AND SITE: i.v., dorsal caudal vein
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Behavior, electrophysiology, biochemistry
DURATION OF EXPERIMENT: Serial sacr 1-28 d
EXAM. TYPE: Histology, behavior
285
286
-------
COMPOUND: 6,7-Dihydrodipyrido[l,2-a:2',l'-c] pyrazidllnium dibromide
COMPOUND: 1,4:5,8-Dimethanonaphthalene, acetoxy-1,2,3,4,10,10-hexachloro-
l,4,4a,5,8,8a-hexahydro-, exo-
REFERENCE: Clark, D.G. and Hurst, E.W.
Brit. J. Industr. Med. 27: 51-55, 1970.
OBSERVED NEUROTOXIC EFFECTS: Large doses (4 or 5 times LD5Q) produced signs indicative
of an action on the central nervous system: lethargy,
labored respiration, muscular twitching, generalized
convulsions.
REFERENCE: Ryan, W.H. and Shankland, D.L.
Life Sci. 10(1):193-200, 1971.
OBSERVED NEUROTOXIC EFFECTS:
Instability and block of activity of giant fibers;
no direct action on axonal membrane. Exo-acetoxy
analog of aldrin was nontoxic.
ANIMALS: Rats, Alderly Park (albino), 180-200 g
ANIMALS: Cockroach (Perlo^angta americana), surgically prepared
Housefiles, NAIDM strain
PREPARATION AND DOSE
or HISTORY OF PATIENT: Compound given as dichloride or dibromide, 99% pure, LD,
10-11 mg/kg
50'
PREPARATION AND DOSE
or HISTORY OF PATIENT: DDT 10 M, other compounds (aldrin, dieldrin, endrin,
heptachlor) 2 x 10~6 to 5 x 10 M (cockroaches). Up to
300 mcg/g (houseflies).
ROUTE AND SITE: S.c.
CONTROL INFORMATION: ns
ROUTE AND SITE: Irrigation of exposed nerves (cockroaches), topical (houseflies)
CONTROL INFORMATION: Three types (described)
DURATION OF EXPERIMENT: 13 d
EXAM. TYPE: Clinical
DURATION OF EXPERIMENT: Several hours
EXAM., TYPE: Electrophysiology
287
288
-------
COMPOUND: 1,4:5,8- Dimethanonapthalene, 1,2,3,4,10,10-hexachloro-6,7-epoxy-
1,4, Aa, 5, fi, 7.8, 8a-octahydro-, endo, endo-
000072208
REFERENCE: Ryan, W.H. and Shankland, D.L.
Life Sci. 10(1):193-200, 1971.
COMPOUND: 1,4:5,8-Dimethanonapthalene, 1,2,3,4,10,10-hexachloro-6,7,epoxy-1,4,4a,
5,6,7,8,8a-octahydro, endo, exo- (Dieldrin)
000060571
REFERENCE: Ryan, W.H. and Shankland, D.L.
Life Sci. 10(1):193-200, 1971.
OBSERVED NEUROTOXIC EFFECTS:
Instability and block of activity of giant fibers;
no direct action on axonal membrane. Exo-acetoxy
analog of aldrin was nontoxic. DDT with other
compounds produced effects not seen with any compound
alone.
OBSERVED NEUROTOXIC EFFECTS:
Instability and block of activity of giant fibers;
no direct action on axonal membrane. Exo-acetoxy
analog of aldrin was nontoxic. DDT with other
compounds produced effects not seen with any compound
alone.
ANIMALS: Cockroach (Perjplaneta americana). surgically prepared
Housefiles, NAIDM strain
ANIMALS:
Cockroach (Pe_riplaneta ag
Housefiles, NAIDM strain
icana), surgically prepared
PREPARATION AND DOSE
,,-4
or HISTORY OF PATIENT: DDT 10 M, other compounds (aldrin, dieldrin, endrin,
heptachlor) 2 x 10~6 to 5 x 10 M (cockroaches). Up to
300 mcg/g (houseflies).
PREPARATION AND DOSE
or HISTORY OF PATIENT: DDT 10 M, other compounds (aldrin, dieldrin, endrin,
heptachlor) 2 x 10"^ to 5 x 10 M (cockroaches). Up to
300 mcg/g (houseflies).
ROUTE AND SITE: Irrigation of exposed nerves (cockroaches), topical (houseflies)
CONTROL INFORMATION: Three types (described)
ROUTE AND SITE: Irrigation of exposed nerves (cockroaches), topical (houseflies)
CONTROL INFORMATION: Three types (described)
DURATION OF EXPERIMENT: Several hours
EXAM.. TYPE: Electrophysiology
DURATION OF EXPERIMENT: Several hours
EXAM..TYPE: Electrophysiology
289
290
-------
COMPOUND: l,4:5,8-Dimethanonapthalene, l,2,3,4,10,10-hexachloro-6,7,epoxy-l,4,4a,
5,6,7,8,8a-octahydro, endo, exo- (Dieldrin)
000060571
REFERENCE: St. Omer, V.
J. Neurochem. 18: 365-374, 1971.
COMPOUND: 1,4:5,8-Dlmethanonapthalene, 1,2,3,4,10,10-hexachloro-6,7,epoxy-1,4,4a,
5,e,7,?,«a-octahydro, endo, exo- (Dieldrin)
000060571
REFERENCE: Schaffer, C.H. and Sun, Y.P.
J. Econ. Entomol. 60: 1580-1583, 1967.
OBSERVED NEUROTOXIC EFFECTS:
Convulsions, starting in some cases during injection.
Intensity and other signs were directly related to
increases of brain ammonia. Toxicity ranking:
lindane > dieldrin > heptachlor > DDT. Brain gluta-
mine increases resulting from conversion of ammonia
to glutamine were related to the toxicity ranking,
suggesting that the 4 compounds produced convulsions by
one mechanism involving interference with the production
and/or utilization of ammonia.
OBSERVED NEUROTOXIC EFFECTS:
No evidence found that binding within the fly central
nervous system is a factor in resistance; no metabolism
of dieldrin in central nervous system tissues was detected
in resistant or susceptible flies. The authors concluded
that resistance might be due to insensltivity at the
receptor site.
ANIMALS: Rats, adult F, Wistar, 250-300 g, surgically prepared.
Cockerels, White Leghorn or Barred Plymouth Rock, 12 wk, 1.4-1.6 kg,
surgically prepared.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Rats: rag/kg — lindane 11.5, DDT 50, dieldrin 6, heptachlor 13.
Cockerels: mg/kg — lindane 6.3, DDT 30, dieldrin 6, heptachlor 6.3.
The compounds stated to be structurally unrelated.
ANIMALS: Houseflies (Musca domestica)
PREPARATION AND DOSE
or HISTORY OF PATIENT:
In most cases, 0.02 meg/fly; 25 meg/fly to resistant flies
ROUTE AND SITE: Intra-arterial (carotid) at 1 ml/min
CONTROL INFORMATION: Vehicle only
ROUTE AND SITE: Injection or infusion
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: Up to 60 min, in controls 7 d
EXAM. TYPE: Behavior, biochemistry
DURATION OF EXPERIMENT: Up to 24 hr
EXAM. TYPE: Biochemistry, behavior
291
292
-------
COMPOUND: 1,4:5,8-Dimethanonapthalene, 1,2,3,4,10,10-hexachloro-l,4,4a,5,8,8a-hexa-
nydro-, enao, enao-
000309002
REFERENCE: Avar, P., Czegledi-Janko, G.
Brit. J. Industr. Med. 27:279-282, 1970.
COMPOUND: 1,4:5,8-Dimethanonapthalene, 1,2,3,4,10,10-hexachloro-l,4 ,4a,5,8,8a-hexa-
000309002
REFERENCE: Ryan, W.H. and Shnnkland, D.L.
Life Sr.i. 10(1) : 193-200,
OBSERVED NEUROTOXIC EFFECTS: Three had epileptiform fits.
OBSERVED NEUROTOXIC EFFECTS:
Instability and block of activity of giant fibers;
no direct action on axonal membrane. Exo-acetoxy
analog of aldrin was nontoxic. DDT with other
compounds produced effects not seen with any compound
alone.
ANIMALS: 15, humans from plant manufacturing aldrin and lindane, M.
ANIMALS:
Cockroach (Peri£lan.eta americana) , surgically prepared
Housefiles, NAIDK strain
PREPARATION AND DOSE
or HISTORY OF PATIENT:
.02, .039, .014, .006 ppm HEOD in whole blood.
PREPARATION AND DOSE
or HISTORY OF PATIENT: DDT 10~* M, other compounds (aldrin, dieldrin, endrin,
Iieptachlor) 2 x 10~6 to
300 mcg/g (houseflies).
M, other .
Iieptachlor) 2 x 10~° to 5 x 10 M (cockroaches). Up to
ROUTE AND SITE: ns.
CONTROL INFORMATION: 12 Humans
ROUTE AND SITE: Irrigation of exposed nerves (cockroaches), topical (houseflies)
CONTROL INFORMATION: Three types (described)
DURATION OF EXPERIMENTS yrs.
EXAM. TYPE: EEC, biochemistry, neurology
DURATION OF EXPERIMENT: Several hours
EXAM..TYPE: niectrophysiology
293
294
-------
COMPOUND: 4-Dimethylamino-3,5 xylyl methylcarbamate, 22.3% emulsifiable concentrate
REFERENCE: Shennan, M., Herrick, R.B., Ross, E. and Chang, M.T.Y.
Toxicol. Appl. Pharm. U: 49-67, 1967.
OBSERVED NEUROTOXIC EFFECTS: Ataxia, paralysis, convulsions.
COMPOUND: Distannoxane, hexabutyl-
000056359
REFERENCE: Robinson, I.M.
Fd. Cosmet. Toxicol. 7: 45-52, 1969
OBSERVED NEUROTOXIC EFFECTS: Treatment lowered brain epinephrine, norepinephrine.
and serotonin for 48 hours.
ANIMALS: Cockerels, Single Comb White Leghorn, 10-12 d old
ANIMALS: Rats, Osborne-Mendel, F, 190-220 g, 18/group
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) Acute: LD,.. 4.4 mg/kg
(2) Subacute: 50-800 ppm in diet, 20 chicks/grp, for 3 wk
PREPARATION AND DOSE
or HISTORY OF PATIENT: 10 mg/kg in corn oil
ROUTE AND SITE: Oral
CONTROL INFORMATION: Untreated control grps
ROUTE AND SITE: i.P.
CONTROL INFORMATION: Equivalent corn oil
DURATION OF EXPERIMENT: 1-3 wk
EXAM. TYPE: Behavior, mortality
DURATION OF EXPERIMENT: Serial to 48 hr
EXAM. TYPE: Behavior, biochemistry
295
296
-------
COMPOUND: Disulfide, bis (diethylthiocarbamoyl)
uuuuy////a
REFERENCE: Gardner-Thorpe, C. and Benjamin, S.
J. Neurol. Neurosurg, Paychiat. 34:253-259, 1971.
OBSERVED
NEUROTOXIC EFFECTS: Peripheral neuropathy and optic neuritis.
COMPOUND: Ephedrine HC1
REFERENCE: Quinton, R.M.
Br. J. Pharmac. 21:51-66, 1963.
OBSERVED NEUROTOXIC EFFECTS: The compound enhanced the effect of Yohimbine
and lowered its lethal dosage.
ANIMALS: Human: 7 case-reports
ANIMALS:
Mice, TT, M, 18-25 g.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 250-1500 mg/d for alcoholism, long term.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
ED
5Q
4 rag/kg
ED,,. = dose producing a 50% mortality of mice injected
S.C. with yohimbine hydrochloride (20 mg/kg) .
ROUTE AND SITE: Oral
CONTROL INFORMATION: None
ROUTE AND SITE: S.C., Oral
CONTROL INFORMATION: Various
DURATION OF EXPERIMENT: Follow-up to 2 yr after discontinuing drug
EXAM. TYPE: Clinical chemistry, behavior, nerve-conduction tests
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Behavior, electrophysiology, biochemistry
297
29.8
-------
COMPOUND: Ergoline-8-beta-carboxamide, 2-bromo-9,10-didehydro-N,N-diethyl-6-methyl
000050373
REFERENCE: Brown, I.R. and Liew, C.C.
Science 188:1122-1123, 1975.
OBSERVED NEUROTOXIC EFFECTS: LSD stimulated acetylation of specific histones
in cerebral hemispheres and midbrain 30 min
after injection.
COMPOUND: Ergoline-8-beta-carboxamide, 2-bromo-9,10-didehydro-N,N-diethyl-6-metl
000050373
REFERENCE: Diaz, J-L. and Huttunen, M.O.
Science 174:62-63, 1971.
OBSERVED NEUROTOXIC EFFECTS: Chronic oral intake raised synthesis and turnover
of 5-HT by 25-30%, and levels of 5-HT (13%) and
tryptophan (18%). No "grossly" evident behavioral
changes in treated rats.
ANIMALS: Rabbits, young NZ White, M, 1 kg
ANIMALS: Rats, S-D, M, 150-160 g
PREPARATION AND DOSE
or HISTORY OF PATIENT: 10 and 100 meg/kg in 0.1 ml saline.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 20 mcg/kg/d in 1.0 ml water for 1 mo. The dose was
increased daily according to weight gain.
ROUTE AND SITE: l.v., ear vein
CONTROL INFORMATION: Vehicle only
ROUTE AND SITE: Gavage
CONTROL INFORMATION: Controls treated water only.
DURATION OF EXPERIMENT: 15 and 30 min
EXAM. TYPE: Biochemistry
DURATION OF EXPERIMENT: 1 mo.
EXAM. TYPE: Biochemistry
299
300
-------
COMPOUND: Ergoline-8-beta-carboxamide, 2-bromo-9,10-diehydro-N,N-diethyl-6-methyl
000050373
REFERENCE: Farrow, J.T. and Van Vunakis, H.
Blochem. Pharmacol. 22:1103-1113, 1973.
OBSERVED NEUROTOXIC EFFECTS:
Synaptosomes of cortical grey-matter contained low
concentrations of high- and medium- affinity
binding-sites for LSD. Synaptic membranes had
2.2 times more high-affinity sites/mg protein
but only 1.8 times more medium-affinity sites than
synaptosomes. These sites are not found elsewhere
in the brain. Binding inhibited by chlorpromazine
or any of 10 other hallucinogens; enhanced by cAMP
or prostaglandin E .
COMPOUND: Ergoline-8-beta-carboxamide, 2-bromo-9,10-didehydro-N,N-diethyl-6-methyl
000050373
REFERENCE: Idanpaan-Heikkila, J.E. and Schoolar, J.C.
Science 164:1295-1297, 1969.
OBSERVED NEUROTOXIC EFFECTS: Brain uptake higher than blood concentration.
Part of dose (2.5% early in pregnancy, 0.5% late)
passed into the fetuses in 5 min, over 70%
being unmetabolized LSD. For 30 min LSD in
cortex higher than in white-matter. Related
behavior started at 3-4 min and lasted 40-60 min.
ANIMALS:
Rat cerebral cortex fractions in vitro.
ANIMALS: Mice, Yale Swiss, 4 M and 6 F pregnant
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Myelin, synaptosomes, mitochondria obtained by centrimga-
tion and verifeid by electronmicroscopy. Binding of
3H-LSD studied.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 19.8 and 9.9 mcg/g of labeled compound.
ROUTE AND SITE: In vitro
CONTROL INFORMATION: Laboratory controls
ROUTE AND SITE: I.V., tailvein
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Biochemical
DURATION OF EXPERIMENT: Serial sacr 5 min to 24 hr.
EXAM. TYPE: Autoradiography
301
302
-------
COMPOUND: Ergollne-8-beta-carboxamlde, 2-bromo-9,10-didehydro-N,N-diethyl-6-methyl
000050373
REFERENCE:
Peters, D.A.
Biochem. Pharmacol. 23:231-237, 1974.
OBSERVED NEUROTOXIC EFFECTS:
Brainstem: norepinephine and tyrosine hydroxylase
lower after 20 mcg/kg/d for 14 d, more so after 100
mcg/kg/d. Mixed results with serotonin and
5-hydroxyindoleacetic acid.
COMPOUND: Ergoline-8-beta-carboxamide, 2-bromo-9,10-didehydro-N,N-diethyl-6-methyl
000050373
REFERENCE: Quinton, R.M.
Br. J. Pharmac. 21:51-66, 1963.
OBSERVED NEUROTOXIC EFFECTS: The compound enhanced the effect of Yohimbine
and lowered its lethal dosage.
ANIMALS:
Eats, S-D, M, 160-180 g
ANIMALS:
Mice, TT, M, 18-25 g.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
ROUTE AND SITE: i.p.
CONTROL INFORMATION:
500 meg/kg in saline 2 ml/kg. One dose, or 5 x 100
meg/kg half-hourly for 5 doses (acute). 500 mcg/kg/d
(chronic). Sacrifice 24 hr after last dose. Chronic
rats also given lower daily amounts (from 20 meg) ns.
under Methods.
Saline only, all studies.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
ED5Q >10 mg/kg
ED,_ = dose producing a 50% mortality of mice injected
S.C. with yohimbine hydrochloride (20 mg/kg).
ROUTE AND SITE: S.C., Oral
CONTROL INFORMATION: Various
DURATION OF EXPERIMENT:
EXAM. TYPE: Biochemical
14 d (chronic)
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Behavior, electrophysiology, biochemistry
303
304
-------
COMPOUND: Ergoline-8-beta-carboxamide, 2-bromo-9,10-didehydro-N,N-diethyl-6-methyl
000050373
REFERENCE: Spooner, C.E. and Winters, W.D.
Int. J. Neuropharmacol. 5: 217-236, 1966
COMPOUND' Ergollne-8-beta-Carboxylic acid, 9,10-didehydro-6-methyl-,morpholide
REFERENCE: Gogerty, J.H. and Dille, J.M.
J. Pharm. Exp. Ther. 120: 340-348, 1957.
OBSERVED NEUROTOXIC EFFECTS: Compound produced excitement, abnormal postures,
arousal EEGs, then depression.
OBSERVED NEUROTOXIC EFFECTS: The compound induced behavior changes like those from
LSD, the equivalent dose being one-third more than LSD
and the duration of effects half as long.
ANIMALS: 200 Cockerels, White Leghorn, ages 5-14 d, 45-100 g
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.025-0.1 mg/kg
ANIMALS: Mice, albino, 25 g
Cats
Rabbits
Rats, F
Human: 2 volunteers
PREPARATION AND DOSE
or HISTORY OF PATIENT: Various schedules and doses
ROUTE AND SITE: s.C. near axillary vein; I.P. for doses over 0.05 ml
CONTROL INFORMATION: ns
ROUTE AND SITE: i.v. (mice, cats, rabbits); S.C. (rats); oral (humans)
CONTROL INFORMATION: Various
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Behavior, EEC
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Behavior, clinical
305
306
-------
COMPOUND: Ergotamine, dihydro-, monomethanesulfonate
001381028
REFERENCE: Quinton, R.M.
Br. J. Pharmac. 21:51-66, 1963.
OBSERVED NEUROTOXIC EFFECTS: The compound enhanced the effect of Yohimbine
and lowered its lethal dosage.
COMPOUND: D-Erythro-D-galacto-octo pyranoside, methyl 6,8-dideoxy-6-(l-methyl-4-
propyl-2-pvrrolidine carbox.amido)-l-thio-
REFERENCE: Tang, A.H. and Schroeder, L.A.
Tox. Appl. Pharm. 12:44-47, 1968.
OBSERVED NEUROTOXIC EFFECTS: (1 and 2) Depressed neuromuscular transmission at
doses of 25 and 50 mg/kg. (3) Immediate ataxia,
higher doses were lethal.
ANIMALS:.
Mice, TT, M, 18-25 g.
ANIMALS: (1 and 2) 6 Rabbits
(3) 3 Chickens
PREPARATION AND DOSE
or HISTORY OF PATIENT:
ED
...
>20 mg/kg
dose producing a 50% mortality of mice injected
S.C. with yohimbine hydrochloride (20 mg/kg).
PREPARATION AND DOSE
or HISTORY OF PATIENT: (D 25 mg/kg followed by 50 mg/kg, in saline.
(2) 50 mg/kg during each of four stimulation frequencies
in a latin-square design.
(3) 200 mg/kg or 300-500 mg/kg.
ROUTE AND SITE: S.C., Oral
CONTROL INFORMATION: Various
ROUTE AND SITE: I.V.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Behavior, electrophysiology, biochemistry
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Electrophysiology, behavior
307
308
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Ethanamine
COMPOUND:
REFERENCE: Curtis, 0.R. and Watkins, J.C.
J. Neurochem. 6:117-141, 1960.
COMPOUND: Ethane, 2-bromo-2-chloro-l,l,l-trifluoro-
REFERENCE: Chang, L.W., Dudley, A.W., Jr., Lee, Y.K. and Katz, J.
Exp. Neurol. 45: 209-219, 1974.
OBSERVED NEUROTOXIC EFFECTS:
ANIMALS:
Treatment caused excitation or depression of
neuronal activity. Excitatory ranking: glutamic,
(3-aminoglutaric, aspartic, cysteic, cysteine-
sulfinic acids, B-hydroxyglutamic, N-methylaspartic,
N-formiminoaspartic acids.
Depressant ranking: 6-alanine, GABA, taurine,
N-methyl-B-alanine, (5-amino-B-hydroxybutyric,
glycine, a-alanine, 6-aminovaleric, 6-aminoisobutyric
acids.
Structure-activity relationships established.
Cats, surgically prepared to exposed motoneurones, Renshaw cells or
dorsal horn interneurones in lumbar cord.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Qualitative doses.
OBSERVED NEUROTOXIC EFFECTS: Superior parasagittal cerebral cortex showed
collapses of neuronal rough endoplasmic reticulum, dilated.Golgi complex,
and some vacuoles in cytoplasm. After higher dose, effects more severe:
loss of mitochondrial membranes, coagulative necrosis of cortical neurons,
and edematous glial cells.
ANIMALS: Rats, young M and F
PREPARATION AND DOSE
or HISTORY OF PATIENT:
(1) 5 rats: 10 ppm 8 hr/d, 5d/wk for 8 wk.
(2) 5 rats: 500 ppm 8 hr/d, 5d/wk for 4 wk.
ROUTE AND SITE: Topical, ionophoresis
CONTROL INFORMATION: Laboratory
ROUTE AND SITE: Inhaiation
CONTROL INFORMATION: 6 control rats
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry, electrophysiology
DURATION OF EXPERIMENT: (i) 8 wk, (2) 4 wk
EXAM. TYPE: Histology
309
310
-------
COMPOUND: Ethann, 2-bromo-2-chloro-l,l,1-trifluoro-
REFERENCE: Chang, L.W., Dudley, A.W., Jr., Katz, J. and Martin, A.H.
Teratology 9:A-15, 1974. (Abstract)
OBSERVED NEUROTOXIC EFFECTS:
No gross fetal anomalies. Brain ultrastructure
of newborn focal weakness/disruption of cortical
neurons, vacuolation, myelin anomalies, abnormal
synapses.
COMPOUND: Ethane, l,l'-oxybis-
000060297
REFERENCE: Denst, J.
Neurology 3: 239-249, 1959.
OBSERVED NEUROTOXIC EFFECTS:
Coma from 8 hours to 35 days. Cerebral lesions charac-
terized by: anemic infarction, loss of Purkinje cells,
and severe gliosis of the molecular layer of the cere-
bellum; neuronal degeneration and focal necrosis of corte:
degeneration of basal nuclei; necrosis of cerebral white
matter with giant-cell granulomas. This damage was not
attributed to anoxemia or circulatory stagnation.
ANIMALS: Rats, S-D, pregnant F
ANIMALS: Human: 3 cases (M, 8; M, 72; F, 33)
PREPARATION AND DOSE
or HISTORY OF PATIENT: 10 ppm, 40 hr/wk thru pregnancy.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Anesthesia by open-drip or closed system
ROUTE AND SITE: Inhalation
CONTROL INFORMATION: ns.
ROUTE AND SITE: Inhalation
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: Gestation
EXAM. TYPE: Histology
DURATION OF EXPERIMENT: Up to 35 d
EXAM. TYPE: Clinical; autopsy
311
312
-------
COMPOUND: Ethane, l,l'-oxybis-(ether)
000060297
REFERENCE: Owens, G.
Neurology 8: 827-831, 1958.
COMPOUND: Ethane, l,l,l-trichloro-2,2-bis (p-chlorophenyl)- (DDT)
000050293
REFERENCE: Dale, W.E., Gaines, T.B. and Hayes, W.J., Jr.
Tox. Appl. Pharm. 4: 89-106, 1962,
OBSERVED NEUROTOXIC EFFECTS: Convulsions were recorded by EEC in dogs subjected
to hyperthermia and ether anesthesia, probably due
to fat embolisms. Prior heparinization protected
the animals.
OBSERVED NEUROTOXIC EFFECTS: Signs correlated with increases of DDT concentration
in brain induced by starvation; this concentration was
not parallel with concentrations of metabolites DDE
(plasma metabolite) and DDA (urinary metabolite).
Tremors developed during the 12th week.
ANIMALS: Dogs, 2 groups of 10
ANIMALS: Rats, Sherman, 22-28 d old weanlings, M & F
PREPARATION AND DOSE
or HISTORY OF PATIENT: Closed gas system, dose ns
PREPARATION AND DOSE
or HISTORY OF PATIENT: 200 ppm DDT in diet
ROUTE AND SITE: Inhalation
CONTROL INFORMATION: ns
ROUTE AND SITE: Oral
CONTROL INFORMATION: Untreated rats
DURATION OF EXPERIMENT: Up to 2 wk
EXAM. TYPE: Clinical, biochemistry, histology
DURATION OF EXPERIMENT: Up to 140 d
EXAM. TYPE: Behavior, biochemistry
313
314
-------
COMPOUND: Ethane, l,l,l-trichloro-2,2-bis (p-chlorophenyl)-
000050293
REFERENCE: Dvorchik, B.H. and Maren, T.H.
Comp. Gen. Pharm. 5: 37-49, 1974.
COMPOUND: Ethane, l,l,l-trichloro-2,2-bls (p-chlorophenyl)-
000050293
REFERENCE: Eaton, J.L. and Sternburg, J.G.
J. Econ. Entomol. 60: 1699-1703, 1967.
(DDT)
OBSERVED NEUROTOXIC EFFECTS:
The compound was taken up by all tissues and stored
mainly in the liver and muscle with no significant
storage in red cells nor excretion. Metabolism was
slow (after 17 d 95% of liver store was intact).
The brain level at autopsy after receiving the LD
suggested that the brain was more sensitive to the
compound than that of mammals.
OBSERVED NEUROTOXIC EFFECTS:
The frequency of DDT-induced trains in the abdominal
central nervous system was not directly related to the
DDT content of the central nervous system. More trains
appeared after topical application than after injection,
although less DDT was found in the abdominal central
nervous system. Injection into the 6th abdominal ganglion
produced dose-related trains indicating that high afferent
(sensory) activity was needed. Therefore, the synaptic
block following DDT was secondary to some more direct
action of DDT or a metabolite.
ANIMALS: Dogfish, M, 1-3 kg (Squalus acanthias)
ANIMALS: American cockroach (Periplaneta americana), adult M.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 1-20 mg/kg, or 60 meg/kg of labeled compound
PREPARATION AND DOSE
or HISTORY OF PATIENT:
(a) 120 meg/cockroach
(b) 1 meg/cockroach
ROUTE AND SITE: I.V.
CONTROL INFORMATION: Sham injections
ROUTE AND SITE: (a) Topical, on both cerci; (b) Injected into the 6th abdominal ganglion
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: 1 hr to 15 d (serial), or longer (1 mo)
EXAM. TYPE: Biochemistry
DURATION OF EXPERIMENT: Probably 24 hr
EXAM. TYPE: Electrophysiology, biochemistry
315
316
-------
COMPOUND: Ethane, l,l,l-trichloro-2,2-bis (p-chlorophenyl)- (DDT)
000050293
REFERENCE:
Peters, D.A.V., Hrdina, P.D., Singhal, R.L. and Ling, G.M.
J. Neurochem. 19:1131-1136, 1972.
COMPOUND: Ethane, l,l,l-trichloro-2,2-bis (p-chlorophenyl)-
(DDT)
REFERENCE: Ryan, W.H. and Shankland, D.L.
Life Set. 10(1):193-200, 1971.
OBSERVED NEUROTOXIC EFFECTS
ANIMALS:
A single dose raised the brainstem 5-hydroxy-
indoleacetic acid but not 5-hydroxytryptamine.
Pretreatment with Pargyline allowed 5-hydroxy-
tryptamine to increase. Administration of
DL-£-chlorophenylalanine with DDT blocked the
rise of 5-hydroxyindoleacetic acid and neuropathy
signs (pyrexia, tremors, convulsions) from DDT.
DL-6-fluorotryptophan (serotonin inhibitor)
blocked the rise of 5-hydroxyindoleacetic acid
and pyrexia but not tremors and convulsions.
The authors infer that 5-hydroxytryptamine turnover
is connected with pyrexia.
Rats, Wistar, M, 190-220 g, at least 4/grp.
OBSERVED NEUROTOXIC EFFECTS:
Instability and block of activity of giant fibers;
no direct action on axonal membrane. Exo-acetoxy
analog of aldrin was nontoxic. DDT with other
compounds produced effects not seen with any compound
alone.
ANIMALS: Cockroach (PerjLplanepa flrogi-l|c,aina') - surgically prepared
Housefiles, NAIDM strain
PREPARATION AND DOSE
or HISTORY OF PATIENT:
600 mg/kg in corn oil with/without other compounds.
PREPARATION AND DOSE
or HISTORY OF PATIENT: DDT 10 M, other compounds (aldrin, dieldrin, endrin,
heptachlor) 2 x 10~6 to 5 x 10 M (cockroaches). Up to
300 mcg/g (houseflies).
ROUTE AND SITE: Oral; other compounds given I.P.
CONTROL INFORMATION: One group, vehicle
ROUTE AND SITE: Irrigation of exposed nerves (cockroaches), topical (houseflies)
CONTROL INFORMATION: Three types (described)
DURATION OF EXPERIMENT: Serial to 5 hr.
EXAM. TYPE: Biochemistry
DURATION OF EXPERIMENT: Several hours
EXAM. TYPE: Electrophysiology
317
318
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COMPOUND: Ethane, l,l,l-trichloro-2,2-bis (p-chlorophenyl)- (DDT)
000050293
REFERENCE: St. Omer, V.
J. Neurochem. 18: 365-374, 1971,
OBSERVED NEUROTOXIC EFFECTS:
Convulsions, starting in some cases during injection.
Intensity and other signs were directly related to
increases of brain ammonia. Toxlcity ranking:
lindane > dieldrin > heptachlor > DDT. Brain gluta-
mine increases resulting from conversion of ammonia
to glutamine were related to the toxicity ranking,
suggesting that the 4 compounds produced convulsions by
one mechanism involving interference with the production
and/or utilization of ammonia.
COMPOUND: Ethane, l,l,l-trichloro-2,2-bis (p-chlorophenyl)- (DDT)
000050293
REFERENCE: Shankland, D.L.
Tox. Appl. Pharm. 6:197-213, 1964.
OBSERVED NEUROTOXIC EFFECTS:
Symptoms in hindlimbs if spinal reflexes
functioned, then excised tibial nerves responded
to electrostimulation. Without reflexes, neither
symptoms arose, nor did excised'nerves respond.
Course of DDT-tremors similar to that in the American
cockroach.
ANIMALS: Rats, adult F, Wistar, 250-300 g, surgically prepared.
Cockerels, White Leghorn or Barred Plymouth Rock, 12 wk, 1.4-1.6 kg,
surgically prepared.
ANIMALS:
Rats, Purdue-Wistar (sic), M and F, 150-400 g
PREPARATION AND DOSE PREPARATION AND DOSE
or HISTORY OF PATIENT: Rats: mg/kg ~ lindane 11.5, DDT 50, dieldrin 6, heptachlor 13. or HISTORY OF PATIENT:
Cockerels: mg/kg — lindane 6.3, DDT 30, dieldrin 6, heptachlor 6.3.
The compounds stated to be structurally unrelated.
50-300 mg/kg in oil, 100 mg/ml
ROUTE AND SITE: Intra-arterial (carotid) at 1 ml/min
CONTROL INFORMATION: Vehicle only
ROUTE AND SITE: Gavage or instillation into throat
CONTROL INFORMATION: Untrtd rats
DURATION OF EXPERIMENT: Up to 60 min, in controls 7 d
EXAM. TYPE: Behavior, biochemistry
DURATION OF EXPERIMENT: ns., apparently up to about 1 wk
EXAM. TYPE: Electrophysiology, behavior
319
320
-------
COMPOUND: Ethane, l,l,l-trichloro-2,2-bis (p-chlorophenyl)-
000050293
. Wooiey, D.t. and Barren, B.A.
Tox. Appl. Pharm. 12: 440-454, 1968.
COMPOUND: Ethane, l,l,l-trlchloro-2,2-bis (p-chlorophenyl)-
000050293
REFERENCE:
Woolley, D.E. and Runnells, A.L.
Tox. Appi. Pharm. 11:389-395, 1967.
OBSERVED NEUROTOXIC EFFECTS: Hyperexcitability and tremors. Mild clonic
convulsions occurred only rarely, but seen in
rats which died. Spontaneous electric activity
changed before onset of tremors (10 areas measured),
most in cerebellum.
OBSERVED NEUROTOXIC EFFECTS:
High peak concentration of compound in central
nervous system grey-matter by 6-12 hr, slower
uptake and lower concentration in myelinated
tissues, e.g. brainstem and cord. Hyperirritability
and tremor more intense at 6-12 hr than at 24 hr,
corresponding with peak concentrations in neocortex
and cerebellum. Fine tremor thought related to
brain peak, coarse tremor to cord peak.
ANIMALS: 22 Rats, S-D, F, 200-250 g, surgically prepared.
ANIMALS: RatS) s-D, F, 200-250 g, total 24.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 50 and 100 mg/kg.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 100 mg/kg after 24-hr fast.
ROUTE AND SITE: oral
CONTROL INFORMATION: ns.
ROUTE AND SITE: Gavage
CONTROL INFORMATION: 4 rats untrtd
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Electrophysiology
DURATION OF EXPERIMENT: 6, 12, 24 hr
EXAM. TYPE: Biochemistry
321
322
-------
COMPOUND: Ethanol, 2-butylamino
000111751
REFERENCE: Hartung, R. and Cornish, H.H.
Tox. Appl. Pharm. 12:486-494, 1968,
OBSERVED NEUROTOXIC EFFECTS:
COMPOUND: Ethanol, 2-(p-chlorophenyl)-l-(p-(2-(diethylamino)ethoxy)phenyl)-
1-p-tolyl-
000078411
REFERENCE: Suzuki, K., Zagoren, J.C., Chen, S.M. and Suzuki, K.
Acta Neuropath. 29:141-156, 1974.
This compound was tested with a group of other
aminoethanols and choline analogs, all of which
inhibited cholinesterase in vitro. In vitro
inhibition increases as the number of carbon atoms
attached on the nitrogenous head of the 2-amino-
ethanol molecule. In the in vivo tests the oral
OBSERVED NEUROTOXIC EFFECTS:
LD 's were uniformly higher than the i.p.
values .
Intracytoplasmic osmiophilic inclusions throughout
central nervous system in all treated rats, dose-
related, followed by degeneration especially of
oligodendroglia, and demyelination. Large
accumulations of A7>2^-cholestadiene-36-ol and
(less) of desmosterol. Authors state that the former
produces identical lesions and attribute them (see
also under 20, 25-diazacholesterol) to the presence
of a double bond at the 7-position.
ANIMALS: Rats, S-D, M
ANIMALS: Rats, Wistar, M and F, newborn
PREPARATION AND DOSE
or HISTORY OF PATIENT: In vitro: 10 to 10 .
In vivo: LD and lower doses.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
250 mg/kg/d in olive oil, from d 5 of age.
ROUTE AND SITE: Oral, i.p., in vitro
CONTROL INFORMATION: ns.
ROUTE AND SITE: oral or I.P.
CONTROL INFORMATION: Olive oil only, or (biochemistry) untreated
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry
DURATION OF EXPERIMENT: Serial, 3-9 d
EXAM. TYPE: Histology, biochemistry
323
324
-------
COMPOUND: Ethanol, 2-(dibutylamino)-
000102818
REFERENCE: Hartung, R. and Cornish, H.H.
Tox. Appl. Pharm. 12:486-494, 1968.
COMPOUND: Ethanol, 2-(diethylamino)-
REFERENCE: Hartung, R. and.: Cornish, H.H.
Tox. Appl. Pharm. 12:486-494, 1968.
3BSERVED NEUROTOXIC EFFECTS:
This compound was tested with a group of other
aminoethanols, all of which inhibited cholinesterase
in vitro. In vitro inhibition increases as the
number of carbon atoms attached on the nitrogenous
head of the 2-aminoethanol molecule. In the in vivo!
tests the oral LD,. 's were uniformly higher than the
i.p. LDqn values. When given i.p., compound reduced
brain
cholinesterase.
OBSERVED NEUROTOXIC EFFECTS:
This compound was tested with a group of other amino-
ethanols, all of which inhibited cholinesterase in
vitro. In vitro inhibition increases as the number
of carbon atoms attached on the nitrogenous head of
the 2-aminoethanol molecule. In the in vivo tests I
the oral LD 's were uniformly higher than the i.p.
LD5Q values.
ANIMALS: Rats, S-D, M
ANIMALS: Rats, S-D, M
PREPARATION AND DOSE
or HISTORY OF PATIENT: In vitro: 10 to 10 .
In vivo:
and lower doses.
PREPARATION AND DOSE
or HISTORY OF PATIENT: In vitro: 10~^ to 10 i.
In vivo: LD5g and l°wer doses.
ROUTE AND SITE: Oral, i.p., in vitro
CONTROL INFORMATION: ns.
ROUTE AND SITE: Oral, i.p., in vitro
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry
325
326
-------
COMPOUND: Ethanol, 2-dimethylamino-
000108010
REFERENCE: Hartung, R. and Cornish, H.H.
Tox. Appl. Pharm. 12:486-494, 1968.
COMPOUND: Ethanol, 2-(ethylamino)-
000110736
REFERENCE: Hartung, R. and Cornish, H.H.
Tox. Appl. Pharm. 12:486-494, 1968.
OBSERVED NEUROTOXIC EFFECTS:
This compound was tested with a group of other .
aminoethanols, all of which inhibited cholinesterase
in vitro. In vitro inhibition increases as the
number of carbon atoms attached on the nitrogenous
head of the 2-aminoethanol molecule. In the in vivo
tests the oral ID 's were uniformly higher than the
i.p. l^rn values. When given i.p., compound reduced
brain cRolinesterase.
OBSERVED NEUROTOXIC EFFECTS:
This compound was tested with a group of other
aminoethanols, all of which inhibited cholinesterase
in vitro. In vitro inhibition increases as the
number of carbon atoms attached on the nitrogenous
head of the 2-aminoethanol molecule. In the in vivo'
tests the oral ID 's were uniformly higher than
the I.P. U>5Q values. When given i.p., compound
reduced brain cholinesterase.
ANIMALS: Rats, S-D, M
ANIMALS: Rats, S-D, M
PREPARATION AND DOSE . .
or HISTORY OF PATIENT: In vitro: 10 * to 10 i.
In vivo: ^cn an<^ l°wer doses.
PREPARATION AND DOSE
or HISTORY OF PATIENT: In vitro: 10 to 10 .
In vivo:
and lower doses.
ROUTE AND SITE: Oral, i.p., in vitro
CONTROL INFORMATION: ns.
ROUTE AND SITE: Oral, i.p., in vitro
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry
327
328
-------
COMPOUND: Ethanol, 2-methoxy-
REFERENCE: Goldberg, M.E., Haun, C. and Smyth, H.F.
Tox. Appl. Pharm. 4:148-164, 1962.
OBSERVED NEUROTOXIC EFFECTS: Specific Inhibition of conditioned avoidance -
escape behavior without motor imbalance. Given
i.p., barbiturate hypnosis was potentiated, same if
inhaled; pretreatment with LSD antagonized this effect.
COMPOUND: Ethanol, 2-methoxy-
000109864
REFERENCE: Greenburg, L., Mayers, M.R., Goldwater, L.J. Burke, W.J. and
Moskowitz, S.
J. Ind. Hyg. Toxicol. 20:134-147, 1938.
OBSERVED NEUROTOXIC EFFECTS: Abnormal reflexes, tremor, mental retardation,
lethargy; abnormal blood picutre. Compound only
the probable cause of the neuropathy.
ANIMALS: Rats: DW or CFE, F, 130 g
Mice: White, F, 22 g
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) 0.5-2 mg/kg
(2) 125-32,000 ppm in air
ANIMALS: Humans 19 M 16-26 yr (av. 20)
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Industrial exposure 25-76 ppm, occasionally more;
other compounds in mix EtOH, MeOH, ethylacetate,
petroleum naptha. Exposures of 1-3 mo.
ROUTE AND SITE: (1) I.P. (2) Inhalation
CONTROL INFORMATION: Untreated groups
ROUTE AND SITE: Inhalation
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: Various schedules
EXAM. TYPE: Behavior
DURATION OF EXPERIMENT: 1 yr of follow-up
EXAM. TYPE: Hematology, Behavior
329
330
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COMPOUND: Ethanol, 2-(methylamino)-
00019831
REFERENCE: Hartung, R. and Cornish, H.H.
Tox. Appl. Pharm. 12:486-494, 1968.
OBSERVED NEUROTOXIC EFFECTS:
This compound was tested with a group of other amino-
ethanols, all of which inhibited cholinesterase
in vitro. In vitro inhibition increases as the
number of carbon atoms attached on the nitrogenous
head of the compounds molecule. In the in !
vivo tests the oral LD 's were uniformly higher
than the i.p. LD.-Q values.
COMPOUND: Ether, chloromethyl methyl
000107302
REFERENCE: Laskin, S., Drew, R.T., Cappiello, V., Kuschner, M. and Nelson, N.
Arch. Env. Hlth. 30:70-72, 1975.
OBSERVED NEUROTOXIC EFFECTS: One rat developed esthioneuroepithelioma of olfactory
epithelium after exposure; one rat developed undif-
ferentiated pituitary tumor considered "coincidental."
ANIMALS: Rats, S-D, M
ANIMALS: 74 Rats, 90 hamsters
PREPARATION AND DOSE
or HISTORY OF PATIENT: In vitro: 10"4 to 10 .
In vivo: ^D an<* lower doses.
PREPARATION AND DOSE
or HISTORY OF PATIENT: i ppln, 6 hr/d, 5 d/wk, 565 exposures in 852 d.
ROUTE AND SITE: Oral, i.p., in vitro
CONTROL INFORMATION: ns.
ROUTE AND SITE: inhalation
CONTROL INFORMATION: 74 Rats, 88 hamsters
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry
DURATION OF EXPERIMENT: 128 wk after 1st exposure
EXAM. TYPE: Carcinogenesis bioassay
331
332
-------
COMPOUND: "-thy! alcohol
000064175
REFERENCE: Ahtee, L. and Svartstrom-Fraser, M.
Acta Pharmacol. Toxicol. 36:289-298, 1975.
COMPOUND: Ethyl alcohol
000064175
REFERENCE: Bauer-Moffett, C. and Altaian, J.
Exp. Neurol. 48:378-382, 1975.
OBSERVED NEUROTOXIC EFFECTS: Rigidity, convulsions. Rapid disappearance
and low levels of noradrenaline in brain.
OBSERVED NEUROTOXIC EFFECTS: Histology on 2 rats/litter. Dry and wet wt of
cerebellum reduced by 26%, of rest of brain by about 14%. Reduction of
Purkinje cells averaged 27.4%. Bodyweights, livers, lungs all found normal;
thiamine 10 mcg/d did not relieve damage.
ANIMALS: Rats, M, S-D, 250-300 g.
ANIMALS: Rats, Purdue-Wistar, cross-fostered, 8/litter.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 8-11 g/kg/d, 7-10 d, then withdrawal.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 3.5-4.0% in air, inhaled for 2 x 90 min/d for 3-20 d.
Cardiac blood after 2nd exposure averaged 268 mg EtOH/ 100 ml; all
rats remained conscious. Experiment started at day 3 of age.
ROUTE AND SITE: Gavage
CONTROL INFORMATION: Untreated controls
ROUTE AND SITE: Inhalation
CONTROL INFORMATION: Air only
DURATION OF EXPERIMENT: Maximum lid
EXAM. TYPE: Behavior, biochemistry
DURATION OF EXPERIMENT:
EXAM. TYPE: Histology
20 d
333
334
-------
COMPOUND: Ethyl alcohol
000064175
REFERENCE: Blum, K., Wallace, J.E. and Geller, I.
Science 176:292-294, 1972.
COMPOUND: Ethyl alcohol
000064175
REFERENCE: Davis, V.E. and Walsh, M.J.
Science 167:1005-1007, 1970.
OBSERVED NEUROTOXIC EFFECTS: Glycine or serine enhanced ethanol-induced sleeptime;
authors inferred interaction in the central nervous
system.
OBSERVED NEUROTOXIC EFFECTS: Ethanol indirectly augmented formation of tetrahydro-
papaveroline, a morphine-like compound.
ANIMALS: Mice
ANIMALS: Rat brainstem homogenates in vitro.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 10 mmoles/100 g and/or 0.45-0.9 mmole/100 g of glycine.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Incubation mixture with dopamine and added EtOH 100
mM, or acetaldehyde 0.5-2 mM.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: Saline
ROUTE AND SITE: In vitro
CONTROL INFORMATION: Laboratory
DURATION OF EXPERIMENT: Up to 140 min.
EXAM. TYPE: Behavior, biochemistry
DURATION OF EXPERIMENT: 30 min
EXAM. TYPE: Biochemistry
335
336
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COMPOUND: Ethyl alcohol
000064175
REFERENCE: Decker, J.B., Wells, C.E. and McDowell, F.
Neurology 9: 361-366, 1959.
COMPOUND: Ethyl alcohol
nnnn £. /.tic
REFERENCE: Goldberg, M.E., Haun, C. and Smyth, H.F.
Tox. Appi. Pharm. 4:148-164, 1962.
OBSERVED NEUROTOXIC EFFECTS: Leg function of the patients suggested cerebellar dys-
function, which responded to diet and supplements. The
authors concluded that ethanol rather than diet deficits
had been the cause.
OBSERVED NEUROTOXIC EFFECTS: Treatment did not produce inhibition of conditioned
avoidance—escape behavior without motor imbalance
separately from ataxia.
ANIMALS: Human: 10 patients aged 33-68, all M
ANIMALS:
Rats: DW or CFE, F, 130
Mice: White, F, 22 g
PREPARATION AND DOSE
or HISTORY OF PATIENT: History of prolonged alcoholism with poor diet
PREPARATION AND DOSE
or HISTORY OF PATIENT: 2,000-32,000 ppm in air.
ROUTE AND SITE: Oral
CONTROL INFORMATION: None
ROUTE AND SITE: Inhalation
CONTROL INFORMATION: Untreated groups
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Clinical
DURATION OF EXPERIMENT: Various schedules.
EXAM. TYPE: Behavior
337
338
-------
COMPOUND: Ethyl alcohol
000064175
REFERENCE: Israel, M.A. and Kuriyama, K.
Life Sci. lOf2):591-599, 1971.
COMPOUND: Ethyl alcohol
000064175
REFERENCE:
Jarlstedt, J. and Hamberger, A.
J. Neurochem. 19:2299-2306, 1972.
OBSERVED NEUROTOXIC EFFECTS:
Mitochondrial ATPase rose after acute and chronic
ethanol. The increase was mainly Mg -dependent,
ouabain-insensitive, and not DNP-activated. No
effect on ATPase in synaptosomes or microsomes.
OBSERVED NEUROTOXIC EFFECTS: Ethanol diminshed incorporation of leucine into
glial but not neuronal proteins.
ANIMALS: Mice, Siss albino, M, 25-28 g.
ANIMALS:
Eats, S-D, M, 100-110 g.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Acute: 4 g/kg as 20% w/v in saline.
Chronic: 6% w/v cf diet.
PREPARATION AND DOSE
or HISTORY OF PATIENT. 1. 3.2 g/kg, preceded by 15 hr fast.
2. 0.1-5% in medium to brain cortex slices.
ROUTE AND SITE: Acute: I.P. Chronic: Oral
CONTROL INFORMATION: Sucrose instead of compound.
ROUTE AND SITE: I.P.; in vitro
CONTROL INFORMATION: Saline treated controls
DURATION OF EXPERIMENT: 2 wk.
EXAM. TYPE: Biochemistry
DURATION OF EXPERIMENT: 3 hr.
EXAM. TYPE: Biochemistry
339
340
-------
COMPOUND: Ethyl alcohol
000064175
REFERENCE: Kurlyama, K. and Israel, M.A.
Biochem. Pharmacol. 22:2919-2922, 1973.
COMPOUND: Ethyl alcohol
000064175
REFERENCE: Kuriyama, K., Sze, P.Y. and Rauscher, G.E.
Life Sci. 10(2):181-189, 1971.
OBSERVED NEUROTOXIC EFFECTS: Adenyl cyclase activity in homogenates of cerebral
cortex declined after 10 min incubation of controls but not of ethanol
groups; no change of phosphodiesterase activity. No effect of in vitro.
additions of ethanol; nevertheless cAMP content increased significantly,
all groups.
OBSERVED NEUROTOXIC EFFECTS: Protein synthesis by brain ribosomes was inhibited
acutely (3 hr) and increased chronically (7-14 d)
in vivo. Not related to blood ethanol levels, or to
observed central nervous system depression.
ANIMALS: Mouse, Swiss albino, F, 25-30 g.
ANIMALS: Mice, Swiss ablino, M, 25-28 g.
PRF.PARATION AND DOSE
or HISTORY OF PATIENT: 6% in liquid diet, av. intake 7-9 ml/d, dose of ethanol
16-21 g/kg. Acute study: 4 g/kg.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Acute: 4 g/kg as 20% w/v in saline, 1 dose.
Chronic: liquid died 6% ethanol.
ROUTE AND SITE: Oral. Acute study: I.P.
CONTROL INFORMATION: Control group treated isocaloric sucrose diet.
ROUTE AND SITE: Acute: I.P. Chronic: Oral
CONTROL INFORMATION: Control group sucrose treated.
DURATION OF EXPERIMENT: 3 wk.
EXAM. TYPE: Biochemical
DURATION OF EXPERIMENT: Serial sacr to 14 d
EXAM. TYPE: Biochemistry
341
342
-------
COMPOUND: Ethyl alcohol
000064175
REF£RENCE:Melvllle, K., Jordon, G., Douglas, D.
Toxicology and Applied Pharmacology 9:363-375, 1966.
COMPOUND: Ethyl alcohol
000064175
REFERENCE: Novak, D.J. and Victor, M.
Arch. Neuirol. 30: 273-284, 1974.
OBSERVED NEUROTOXIC EFFECTS: Ataxia with depression; maximal effects occurred
during 1st hr. Synergistic action with glutethimide
increased central nervous system depression and
produced surgical anesthesia.
OBSERVED NEUROTOXIC EFFECTS: Non-inflammatory degeneration of myelinated nerve
fibers affecting peripheral nerves (legs more than arms). Denervation atrophy.
Primary degeneration of the vagus nerves, lesions acute and extended throughout
all portions of the nerve.
ANIMALS: Mongrel dogs, 7.0-12.0 kg, M and F.
ANIMALS: 4 human alcoholics.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
50% soln of EtOH in water. Dose of 1 ml/kg hourly,
3 or 5 times.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Alcoholic neuropathy with hoarseness and weakness of
the voice, dysphagia, and derangements of the autonomic
nervous functions.
ROUTE AND SITE: Stomach tube
CONTROL INFORMATION: ns.
ROUTE AND SITE: Oral.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: More than 1 wk.
EXAM. TYPE Behavior
DURATION OF EXPERIMENT: "Many years"
EXAM. TYPE: Histology
343
344
-------
COMPOUND: Ethyl alcohol
000064175
REFERENCE: Roach, M.K., Davis, D.L., Pennlngton, W. and Nordyke, E.
Life Sci. 12(1):433-441, 1973.
COMPOUND: Ethyl alcohol
000064175
REFERENCE: Skillicorn, S.A.
Neurology 5:524-534, 1955.
OBSERVED NEUROTOXIC EFFECTS:
Ethanol inhibited active active transport of probable
neurotransmitters of the central nervous system by
synaptosomes. Authors conclude that alcohol interacts
with membrane lipids of synaptosome.
OBSERVED NEUROTOXIC EFFECTS: Ataxia of legs; no nystagmus; pneumoencephalograms
suggested diffuse degenerative disease of the
cerebrum as well as cerebellar atrophy of a
presenile type.
ANIMALS:
Rats, S-D, M, 200-250 g, brains removed and homogenates incubated in
vitro.
ANIMALS:
Human: 6 cases, 39-55 at onset
PREPARATION AND DOSE
or HISTORY OF PATIENT: Ethanol added as 25% soln, at start of preincubation period.
Ethanol cone 5-30 mg/ml. Incubated in vitro with labeled
norepinephrine, GABA and glutamate.
PREPARATION AND DOSE
Or HISTORY OF PATIENT: History of prolonged chronic alcoholism and gait
disorder lasting 1-15 yr
ROUTE AND SITE: In vitro
CONTROL INFORMATION: Control: incubation in medium with no alcohol.
ROUTE AND SITE: Oral
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: Laboratory procedure.
EXAM. TYPE: Biochemistry.
DURATION OF EXPERIMENT: 6 mo
EXAM. TYPE: Clinical, neurological
345
346
-------
COMPOUND: Ethyl alcohol
000064175
COMPOUND: Ethyl alcohol
000064175
REFERENCE:
Sutton, I. and Simmonds, M.A.
Biochem. Pharmacol. 22:1685-1692, 1973.
REFERENCE:
Tytell, M. and Myers, R.D.
Biochem. Pharmacol. 22:361-372, 1973.
OBSERVED NEUROTOXIC EFFECTS: Endogenous y-aminobutyric acid (GABA) no change
after acute ethanol but increased 48% after chronic treatment. Exogenous
GABA disappeared at same rate throughout, The enzyme GAD increased after
acute ethanol treatment, and the enzyme GABA-T increased after chronic ethanol.
OBSERVED NEUROTOXIC EFFECTS:
Acute (see below) rats converted more 5-hydroxy-
tryptamine to 5-hydroxyindoleacetic acid than
chronic or controls in caudate nucleus; chronics
no different from controls; no differences in
production of 5-hydroxytrytophol. In this, "some
parts" of central nervous system differ from
peripheral nervous system, according to the authors.
ANIMALS: Rats, Wistar, M., 160-200 g (acute), 130 g (chronic)
ANIMALS: Rats, adult Royal Victoria hooded (sex ns.), 3 per group (acute,
chronic, control)
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) Acute: 4g/kg as 20% soln in saline, preceded
by 24 hr fast and followed 30 min by admin, of labeled GABA.
(2) Chronic: 14% in water as only drink for 3 wk, followed by 24 hr
fast and admin labeled GABA.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
All rats prepared surgically for brain perfusion, 3 sites,
with labeled serotonin.
Acute: 6 g/kg EtOH in 20% v/v solution intragastric
Chronic: Sole drink 8% v/v EtOH plus 2% malt extract.
Control: Water ad lib, no treatment.
ROUTE AND SITE:
Acute: I.P., Chronic: Oral
CONTROL INFORMATION- Acute: saline treated only, Chronic: water treated only.
All: GABA or no GABA.
ROUTE AND SITE: Oral or intragastric
CONTROL INFORMATION: 3 Rats, as stated above.
DURATION OF EXPERIMENT: 3 wk.
EXAM. TYPE: Biochemical
DURATION OF EXPERIMENT:
EXAM. TYPE: Biochemical
130-147 d
347
348
-------
COMPOUND: Ethyl alcohol
REFERENCE:
Veloso, D., Passoneau, J.V. and Veech, R.L.
J. Neurochem. 19:2679-2686, 1972.
OBSERVED NEUROTOXIC EFFECTS: (1) Rats lost their righting reflex within 6-7
min. after injection, general anesthesia within 8 min. Rises of brain glucose,
G6P and citrate, no change in arterial pCO-.
(2) General anesthesia, rises of glucose, G6P, glycogen, arterial pCO.,
falls of lactate, pyruvate, a-oxoglutarate, malate, glutamate, aspartate.
Interpreted as effects on nerve cell membrane, contrasted with liver where
ADH is "primary target."
COMPOUND: Ethyl alcohol
000064175
REFERENCE: Walsh, J.C. and McLeod, J.G.
J. Neurol. Sci. 10:457-469, 1970.
OBSERVED NEUROTOXIC EFFECTS: Slow sensory and motor conduction; sural nerves
(myelinated fibers) axonal or Wallerian degeneration and regeneration.
ANIMALS: Rats, S-D, M, 390-400 g
ANIMALS: 11 Humans with alcoholic peripheral neuropathy, ages 41-73 yr
(av 58 yr).
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Rats starved for 72 hr prior to treatment.
1. Acute: 3.5 ml of 7M ethanol in 0.15M NaCl.
2. Chronic: 3 ml at 13 and 5 hr and 1 ml at 3 and 1 hr.
prior to brain removal. 7 M ethanol in 0.15
m NaCl.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: Controls treated with 0.15M NaCl.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Studied within 3 wk of admission to hospital.
ROUTE AND SITE:
CONTROL INFORMATION: 20 control subjects aged 38-73 yr (av 54).
DURATION OF EXPERIMENT: Acute: 8 min; Chronic: 13 hr.
EXAM. TYPE: Behavior, biochemistry
DURATION OF EXPERIMENT:
EXAM. TYPE: Electrophysiology, histology (biopsy)
349
350
-------
COMPOUND: Ethylamine, 2-chloro-N,N-dimethyl-, hydrochloride
COMPOUND: Ethylamine, 2-chloro-N,N-dipropyl-
REFERENCE: Goldin, A., Now, H.A., Landing, B.H., Shapiro, D.M. and Goldberg, B.
J. Pharm. Exp. Ther. 94:249-261, 1958.
REFERENCE: Goldin, A., Now, H.A., Landing, B.H., Shapiro, D.M. and Goldberg, B.
J. Pharm. Exp. Ther. 94:249-261, 1958.
OBSERVED NEUROTOXIC EFFECTS:
Waltzing syndrome was produced by dialkyl and hetero-
cyclic B-chloroethylamines but not when (a) OH
or bromine replaced the $ chlorine, (b) a B-phenyl
group replaced one of the B hydrogens in the
chlorinated chain, or (c) phenyl groups were introduced
into the dialkyl carbons. No effect from primary/
secondary B-chloroethylamines, related quaternary
compounds, or bis-, tris-, or tetrakis-B-chloro-
ethylamines. Piperidine and morpholine analogs and
arsacetin produced waltzing. Cerebellar and
axial lesions found consistent with behavior.
OBSERVED NEUROTOXIC EFFECTS:
Waltzing syndrome was produced by dialkyl and hetero-
cyclic B-chloroethylamines but not when (a) OH
or bromine replaced the B chlorine, (b) a B-phenyl
group replaced one of the B hydrogens in the
chlorinated chain, or (c) phenyl groups were introduce
into the dialkyl carbons. No effect from primary/
secondary B-chloroethylamines, related quaternary
compounds, or bis-, tris-, or tetrakis-B-chloro-
ethylamines. Piperidine and morpholine analogs and
arsacetin produced waltzing. Cerebellar and
axial lesions found consistent with behavior.
ANIMALS:
Mice, CF1, M, 2-3m, 18-25 g; also CF1 F and C3H M.
ANIMALS:
Mice, CF1, M, 2-3m, 18-25 g; also CF1 F and C3H M.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
1-625 mg/kg in saline or (insolubles) 10% acacia,
various schedules.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
1-625 mg/kg in saline or (insolubles) 10% acacia,
various schedules.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: Vehicle alone
ROUTE AND SITE: I.P.
CONTROL INFORMATION: Vehicle alone
DURATION OF EXPERIMENT: At least 10 d after treatment.
EXAM. TYPE: Behavior, histology.
DURATION OF EXPERIMENT: At least 10 d after treatment.
EXAM. TYPE: Behavior, histology.
351
352
-------
COMPOUND: Ethylamine, 2-chloro-N-ethyl-N-methyl-, hydrochloride
COMPOUND:
Ethylamine, N-chloro-methyl-N-propyl-2-, hydrochloride
REFERENCE: Goldin, A., Now, H.A., Landing, B.H., Shapiro, D.M. and Goldberg, B.
J. Pharm. Exp. Ther. 94:249-261, 1958.
OBSERVED NEUROTOXIC EFFECTS:
Waltzing syndrome was produced by dialkyl and hetero-
cyclic B-chloroethylamines but not when (a) OH
or bromine replaced the 8 chlorine, (b) a B-phenyl
group replaced one of the B hydrogens in the
chlorinated chain, or (c) phenyl groups were introduced
into the dialkyl carbons. No effect from primary/
secondary B-chloroethylamines, related quaternary
compounds, or bis-, tris-, or tetrakis-8-chloro-
ethylamines. Piperidine and morpholine analogs and
arsacetin produced waltzing. Cerebellar and
axial lesions found consistent with behavior.
REFERENCE: Goldin, A., Now, H.A., Landing, B.H., Shapiro, D.M. and Goldberg, B.
J. Pharm. Exp. Ther. 94:249-261, 1958.
OBSERVED NEUROTOXIC EFFECTS:
Waltzing syndrome was produced by dialkyl and hetero-
cyclic B-chloroethylamines but not when (a) OH
or bromine replaced the B chlorine, (b) a B-phenyl
group replaced one of the B hydrogens in the
chlorinated chain, or (c) phenyl groups were introduced
into the dialkyl carbons. No effect from primary/
secondary B-chloroethylamines, related quaternary
compounds, or bis-, tris-, or tetrakis-B-chloro-
ethylamines. Piperidine and morpholine analogs and
arsacetin produced waltzing. Cerebellar and
axial lesions found consistent with behavior.
ANIMALS:
Mice, CF1, M, 2-3m, 18-25 g; also CF1 F and C3H M.
ANIMALS:
Mice, CF1, M, 2-3m, 18-25 g; also CF1 F and C3H M.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
1-625 mg/kg in saline or (insolubles) 10% acacia,
various schedules.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
1-625 mg/kg in saline or (insolubles) 10% acacia,
various schedules.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: Vehicle alone
ROUTE AND SITE: I.P.
CONTROL INFORMATION: Vehicle alone
DURATION OF EXPERIMENT: At least 10 d after treatment.
EXAM. TYPE: Behavior, histology.
DURATION OF EXPERIMENT: At least 10 d after treatment.
EXAM. TYPE: Behavior, histology.
353
354
-------
COMPOUND: Ethylamine, N,N-dimethyl-2-(o-methyl-alpha-pheriylbenzyl-oxy)-
REFERENCE: pfeiffer, C.C., Murphree, H.B., Jenney, E.H., Robertson, M.G.,
Randall, A.H. and Bryan, L.
Neurology 9: 249-250, 1959.
OBSERVED NEUROTOXIC EFFECTS: The authors concluded that synthetic atroplnes are more
i active hallucinogens than atropine or scopolamine, pro-
ducing effects lasting 24-48 hr. Synthetic antitremor
drugs had fewer peripheral nervous system side-effects,
but central nervous system side-effects (hallucinations)
may have been exaggerated.
COMPOUND: Ethylamine, N,N-dimethyl-2-((o-methyl-alpha-phenylbenzyl) oxy)-, hydro-
chloride
000341695
REFERENCE: Gill, D.G. and Sowerby, H.A.
Practitioner 214: 542-544, 1975.
OBSERVED NEUROTOXIC EFFECTS: Epileptiform seizures, status epilepticus. Plasma
compound level was 12.3 and 5.1 meg/ml. Both cases
recovered. The authors reviewed fatal cases with
lower plasma levels.
ANIMALS: Human: prison volunteers, drug-sophisticated, no other details
ANIMALS: Human: 2 cases, F, 23 mo 12 kg; F, 52 mo 17.1 kg.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 100 rag/man
PREPARATION AND DOSE
or HISTORY OF PATIENT: In both cases, compound was prescribed for iatrogenic
illness and was swallowed accidentally by children"
300 mg, unknown amount.
ROUTE AND SITE: Oral
CONTROL INFORMATION: LSD-25: 0, 25, 50, 100 meg/man
ROUTE AND SITE: Oral
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: Up to 3 d
EXAM. TYPE: Opinion of volunteers
DURATION OF EXPERIMENT: 3 d, 4 d
EXAM. TYPE: Clinical, biochemistry
155
356
-------
COMPOUND: Ethylamine, 2-(diphenylmethoxy)-N,N-dimethyl-
000058731
REFERENCE: pfeiffer, C.C., Murphree, H.B., Jenney, E.H., Robertson, M.G.,
Randall, A.H. and Bryan, L.
Neurology 9: 249-250, 1959.
OBSERVED NEUROTOXIC EFFECTS: The authors concluded that synthetic atroplnes are more
active hallucinogens than atropine or scopolamine, pro-
ducing effects lasting 24-48 hr. Synthetic antltremor
drugs had fewer peripheral nervous system side-effects,
but central nervous system side-effects (hallucinations)
may have been exaggerated.
COMPOUND: Ethylene, tetrachloro-
000127184
REFERENCE: Haerer, A.F. and Udelman, H.D.
Am. J. Psychiat. 121: 78-79, 1964.
OBSERVED NEUROTOXIC EFFECTS: The subject developed amnesia within 2 hours, suffering
confusion, irritation, hallucinations, distorted color-
vision, and speech difficulty. All symptoms cleared
within 3 hours of the dose with no sequelae.
ANIMALS: Human: prison volunteers, drug-sophisticated, no other details
ANIMALS: Human: one isolated case, M, 21
PREPARATION AND DOSE
or HISTORY OF PATIENT: 100 mg/man
PREPARATION AND DOSE
or HISTORY OF PATIENT: 5 ml, one dose, prescribed as anthelmintic; history
noncontributory.
ROUTE AND SITE: Oral
CONTROL INFORMATION: iSD-25: 0, 25, 50, 100 meg/man
ROUTE AND SITE: Oral
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: Up to 3 d
EXAM. TYPE: Opinion of volunteers
DURATION OF EXPERIMENT: 3 hr with follow-up
EXAM. TYPE: Clinical
357
358
-------
COMPOUND: Ethylene, trichloro-
000070916
REFERENCE: Buxton, P.H. and Hayward, M.
J. Neurol. Neurosurg, Psychiat. 30:511-518, 1967.
COMPOUND: Ethylene, trichloro-
000079016
REFERENCE: Feldman, R.G., Mayer, R.M. and Taub, A.
Neurology 20:599-606, 1970.
OBSERVED NEUROTOXIC EFFECTS: Exposure-related: after 10 min, headache and
nausea for 48 hr; after 30 min, vomiting and numbness for 15 d; after 2.5 hr,
dizziness progressing to facial diplegia by d 9, residual visual and trigeminal
motor signs present after 2.5 yr, 4 hr, facial diplegia by d 6, tracheostomy
needed by d 12, continual vomiting and emaciation, died after 51 d. Damage
most severe in brainstem and Vth-nerves; changes in cerebral and cerebellar
cortexes attributed to secondary hypoxemia. Peripheral nervous system and
cord, where examined, showed little damage.
OBSERVED NEUROTOXIC EFFECTS: Peripheral neuropathy, trigeminal sensory loss,
authors infer demyelination.
ANIMALS: Human: 4 case-reports including 1 autopsy.
ANIMALS:
Human: one case
PREPARATION AND DOSE
or HISTORY OF PATIENT: Industrial accident, exposure for 10 min. to 4 hr. while
cleaning tanks without respirators.
PREPARATION AND DOSE
Or HISTORY OF PATIENT: Industrial exposure to vapor for 5 min and indirect
exposure via closed-circuit gasmask for 1.5 hr.
ROUTE AND SITE: Inhalation
CONTROL INFORMATION: Other operators wearing fresh-air respirators had no
effects.
ROUTE AND SITE: Inhalation
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: 51 d, 2 1/2 yr.
EXAM. TYPE: History, clinical observation, autopsy
DURATION OF EXPERIMENT: Follow-up period, more than one month.
EXAM. TYPE: Behavior, electrophysiology, clinical tests
360
-------
COMPOUND: Ethyl (beta-hydroxy ethyl)trimethylaramonium hydroxide
COMPOUND: Ethyl (m-hydroxyphenyl) dimethylammonivnn chloride
REFERENCE: Hartung, R. and Cornish, H.H.
Tox. Appl. Pharm. 12:486-494, 1968.
OBSERVED NEUROTOXIC EFFECTS:
This compound was tested with a group of other
aminoethanols and choline analogs, all of which
inhibited cholinesterase in vitro. In vitro
inhibition increases as the number of carbon atoms
attached on the nitrogenous head of the 2-amino- i
ethanol molecule. In the in vivo tests the oral
LD 's were uniformly higher than the i.p. U>CQ values.
REFERENCE: Tang, A.H. and Schroeder, L.A.
Tox. Appl. Pharm. 12:44-47, 1968.
OBSERVED NEUROTOXIC EFFECTS: Produced consistent partial antagonism, the effects
of lincomycin were never completely reversed by
edrophonium.
ANIMALS: Rats, S-D, M
ANIMALS: 4 Rabbits
PREPARATION AND DOSE
or HISTORY OF PATIENT: In vitro: 10 to 10 .
In vivo: LD and lower doses.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 10-100 meg/kg administered at peak of the neuromuscular
blockade from lincomycin (50 mg/kg).
ROUTE AND SITE: Oral, i.p., in vitro
CONTROL INFORMATION: ns.
ROUTE AND SITE: l.V.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Electrophysiology
361
362
-------
COMPOUND: Follc acid
000059303
REFERENCE: Baxter, M.G., Miller, A.A. and Webster, R.A.
Br. J. Pharmac. 49: 350P-351P, 1973 (abstract of proceedings).
OBSERVED NEUROTOXIC EFFECTS:
Convulsive doses (ED,-,,) reported by three routes and
compared with those or six other compounds (leptazol,
picrotoxin, strychnine, bicuculline, glutamate,
ouabain). Folic acid produces a flexor-extensor
convulsion pattern.
COMPOUND: Folic acid, sodium salt
REFERENCE: Hill, R.G. and Miller, A.A.
Br. J. Pharmac. 50: 425-427, 1974.
OBSERVED NEUROTOXIC EFFECTS: The compound reduced presynaptic inhibition produced
by peripheral stimulation, and is a known convulsant.
The authors infer that both folic acid and picrotoxin
act by the same mechanism.
ANIMALS: Mice, no details
ANIMALS: 6 piebald Lister rats, adult, surgically prepared
PREPARATION AND DOSE
or HISTORY OF PATIENT: 17-1024 meg/mouse
PREPARATION AND DOSE
or HISTORY OF PATIENT: Concentrations: 0.1-1% w/v (1 to 10 mM)
ROUTE AND SITE: I.V. and intracerebroventricular; also oral.
CONTROL INFORMATION: ns
ROUTE AND SITE: Cannulated onto the surface of the cuneate nucleus
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Behavior
DURATION OF EXPERIMENT: About 2 hr per test
EXAM. TYPE: Electrophysiology
363
364
-------
COMPOUND: Formaldehyde
000050000
REFERENCE: Kulle, T.J. and Cooper, G.P.
Arch. Env. Hlth. 30:237-243, 1975.
OBSERVED NEUROTOXIC EFFECTS:
Examined effects of prolonged exposure. Formaldehyde
decreased response to amyl alcohol directly according
to concentration; perfusion with air for 1 hr. partly
restored response.
COMPOUND: Formanilide, 2'-(3-bromo-2-thienyl)thio-
REFERENCE:
Grol, C.J. and Rollema, H.
J. Med. Chem. 18:857-861, 1975.
OBSERVED NEUROTOXIC EFFECTS: This compound gave positive results in a
neurotoxicity screening test in which the
criteria were ptosls, sedation and catalepsy.
ANIMALS:
Rats, S-D, M, 250-400 g, surgically prepared for testing of nasopalatine
nerve twigs.
ANIMALS:
Rats and mice, no details
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.5, 1.0, 1.5, or 2.0 ppm for continuously for 1 hr.
Repeated tests in many animals, for total exposure
of 4 hr.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 40 mg/kg.
ROUTE AND SITE: Gas drawn through nasal cavities by vacuum pump.
CONTROL INFORMATION: Pre-exposure control responsiveness determined by test series
of amyl alcohol (0.3, 0.7, 1.0, 3.3, 6.7, 10.0 pph) and then
repeated after exposure to test compound. Air controls also run.
DURATION OF EXPERIMENT: Several hr.
EXAM. TYPE: Electrophysiology.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior screening tests
365
366
-------
COMPOUND: Formanilide, 2'-(3-bromo-4-thienyl)thio-
REFERENCE:
Grol, C.J. and Rollema, H.
J. Med. Chem. 18:857-861, 1975.
OBSERVED NEUROTOXIC EFFECTS: This compound gave positive results in a
neurotoxicity screening test in which the
criteria were ptosis, sedation and catalepsy.
ANIMALS:
Rats and mice, no details
PREPARATION AND DOSE
or HISTORY OF PATIENT: 40 mg/kg.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior screening tests
COMPOUND:
Formanilide, 2'(2-bromo-3-thienyl)thio-5'-chloro-
REFERENCE:
Grol, C.J. and Rollema, H.
J. Med. Chem. 18:857-861, 1975.
OBSERVED NEUROTOXIC EFFECTS: This compound gave positive results in a
neurotoxicity screening test in which the
criteria were ptosis, sedation and catalepsy.
ANIMALS:
Rats and mice, no details
PREPARATION AND DOSE
or HISTORY OF PATIENT: 40 mg/kg.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior screening tests
368
-------
COMPOUND: Foraanllide, 2'-(3-bromo-2-thienyl)thio-5'-chloro
REFERENCE:
C-rol, C.J. and Rollema, H.
J. Med. Chem. 18:857-861, 1975.
OBSERVED NEUROTOXIC EFFECTS: This compound gave positive results in a
neurotoxicity screening test in which the
criteria were ptosis, sedation and catalepsy.
ANIMALS:
Rats and mice, no details
PREPARATION AND DOSE
or HISTORY OF PATIENT: 40 mg/kg.
ROUTE AND SITE: i.P.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior screening tests
369
COMPOUND: Formanilide, 2'-(3-bromo-4-thienyl)thio-5'-chloro
REFERENCE:
Grol, C.J. and Rollema, H.
J. Med. Chem. 18:857-861, 1975.
OBSERVED NEUROTOXIC EFFECTS: This compound gave positive results in a
neurotoxicity screening test in which the
criteria were ptosis, sedation and catalepsy.
ANIMALS: Rats and mice, no details
PREPARATION AND DOSE
or HISTORY OF PATIENT: 40 mg/kg.
ROUTE AND SITE: i.P.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior screening tests
370
-------
COMPOUND: Formanilide, 2'-(2-bromo-3-thienyl)thio-5'-(trifluoromethyl)-
REFERENCE:
Grol, C.J. and Rollema, H.
J. Med. Chem. 18:857-861, 1975.
OBSERVED NEUROTOXIC EFFECTS: This compound gave positive results in a
neurotoxicity screening test in which the
criteria were ptosis, sedation and catalepsy.
ANIMALS:
Rats and mice, no details
PREPARATION AND DOSE
or HISTORY OF PATIENT: 40 mg/kg.
ROUTE AND SITE: i.P.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior screening tests
COMPOUND:
Formanilide, 5'-chloro-2'-(3-thienyl)thio-
REFERENCE:
Grol, C.J. and Rollema, H.
J. Med. Chem. 18:857-861, 1975.
OBSERVED NEUROTOXIC EFFECTS: This compound gave positive results in a
neurotoxicity screening test in which the
criteria were ptosis, sedation and catalepsy.
ANIMALS:
Rats and mice, no details
PREPARATION AND DOSE
or HISTORY OF PATIENT: 40 mg/kg.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior screening tests
372
-------
COMPOUND:
Formanilide, 2'-(3-thienyl)thio-5'-(trifluoromethyl)-
COMPOUND: Furoyl hydrazide
REFERENCE:
Grol, C.J. and Rollema, H.
J. Med. Chem. 18:857-861, 1975.
OBSERVED NEUROTOXIC EFFECTS: This compound gave positive results in a
neurotoxicity screening test in which the
criteria were ptosis, sedation and catalepsy.
REFERENCE: Jenney, E.H. and Pfeiffer, C.C.
J.-Phann. Exp. Ther. 122: 110-123, 1958.
OBSERVED NEUROTOXIC EFFECTS: Convulsions
ANIMALS:
Rats and mice, no details
ANIMALS: Mice, Harlan, 19-21 g
PREPARATION AND DOSE
or HISTORY OF PATIENT: 40 mg/kg.
PREPARATION AND DOSE
or HISTORY OF PATIENT: o.48 nM/kgm
ROUTE AND SITE: I.P.
CONTROL INFORMATION: ns.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior screening tests
DURATION OF EXPERIMENT: Acute
EXAM. TYPE: Clinical
373
374
-------
COMPOUND: Galactose
COMPOUND: D-Galactose
REFERENCE: Malone, J.I., Wells, H.J. and Segal, S.
Science 174:952-954, 1971.
REFERENCE: Blosser, J.C. and Wells, W.W.
J. Neurochem. 19:1539-1547, 1972.
OBSERVED NEUROTOXIC EFFECTS: Severe hyperosmolar dehydration which, according
to authors, could account for toxic changes in
brain chemistry.
OBSERVED NEUROTOXIC EFFECTS:
Neurotoxicity was produced, and neural lysosomes
were studied. Fragility higher than controls.
Enzyme studies indicated a role of galactitol
as well as of galactose.
ANIMALS: Chicks, Rhode Island Red, day-old
ANIMALS: Cockerels, Leghorn, day-old
PREPARATION AND DOSE
or HISTORY OF PATIENT: 10% w/v in drinking water for 2 d.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
40% (w/w) in diet.
ROUTE AND SITE: Oral
CONTROL INFORMATION: Controls water alone
ROUTE AND SITE: Oral
CONTROL INFORMATION:
DURATION OF EXPERIMENT: 2 d
EXAM. TYPE: Biochemistry
DURATION OF EXPERIMENT: Up to 64 hr.
EXAM. TYPE: Biochemistry
375
376
-------
COMPOUND: D-Galactose
REFERENCE:
Granett, S.E., Kozak, L.P., Mclntyre, J.P. abd Wells, W.W.
J. Heurochera. 19:1659-1670, 1972.
OBSERVED NEUROTOXIC EFFECTS:
Levels of ATP, G6P (down by 9 hr), FDP, 3PG,
a-GP, lactate (not down till 18 hr), and glucose
and glycogen (later stages; G1P, citrate and
cAMP not altered) suggested that compound
interfered with brain uptake of glucose.
ANIMALS: Chicks, White Leghorn, M, 1-2 d old
PREPARATION AND DOSE
or HISTORY OF PATIENT: 40% D-galactose w/w in place of glucose in diet.
ROUTE AND SITE: Oral
CONTROL INFORMATION: Glucose treated controls
DURATION OF EXPERIMENT: Up to 50 hr.
EXAM. TYPE: Biochemistry
377
COMPOUND:
Galactosiduronic acid, methyl-, methyl ester, polymer of sulfated
sodium salt
REFERENCE: Joseph, A.D.
Br. J. Pharmacol. 17: 533-538, 1961.
OBSERVED NEUROTOXIC EFFECTS: 5-10 tog of mepesulfate produced tremor, salivation,
tachypnea, loud calling, seizures, blind charging,
and then somnolence within minutes. Complete re-
covery in 24 hours. 2.5 mg produced few or no such
effects.
ANIMALS: Cats, no details, surgically prepared
PREPARATION AND DOSE
or HISTORY OF PATIENT: 5-10 mg
2.5 mg
ROUTE AND SITE: Cannulated into left lateral ventricle of brain
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: Weeks
EXAM. TYPE: Behavior
378
-------
COMPOUND: Gallium Fluoride
REFERENCE: Melgs, J.W.
J. Occup. Med. 14: 225-226, 1972.
OBSERVED NEUROTOXIC EFFECTS: Pain, motor weakness of extensor muscles (localized),
blood negative for lead and mercury, recovery after 3 mo,
neurology attributed to gallium.
COMPOUND: Gasoline
MX8006619
REFERENCE: saito, K.
Brit. J. Indust. Med. 30:352-358, 1973.
OBSERVED NEUROTOXIC EFFECTS:
Evidence of tension and excitement after 6-7 d in rats
given lead; after 1-3 d EEC showed decreased 6,6
and a waves for both types of gasoline; cortex
showed marked a and 6 activity after 6-7 d
in lead rats. Lead content and cortical re-
cordings correlated.
ANIMALS: 1 Human, F. 43, research chemist.
ANIMALS: 19 rats, Wistar, M, 330-453 g, aged 7 mo., surgically prepared
PREPARATION AND DOSE
or HISTORY OF PATIENT: Lab exposure to fumes from crystals +
PREPARATION AND DOSE
or HISTORY OF PATIENT:
10 ml/kg; from leaded gasoline rats received 16.5 mg/kg
of tetraethyl lead (LD, 13.2-18 mg/kg); one dose.
ROUTE AND SITE: Skin contact, hands and arms (despite use of fume hood), inhalation.
CONTROL INFORMATION: None
ROUTE AND SITE: I.P.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: 3 mo.
EXAM. TYPE: Clinical, blood chemistry
DURATION OF EXPERIMENT: Follow-up for 10 d
EXAM. TYPE: Electrophysiology (EEC)
379
380
-------
COMPOUND: beta-D-Glucopyranoside, (methyl-ONN-azoxy)methyl)-
REFERENCE: Hirano, A., Dembitzer, H.M. , and Jones, M.
J. Neuropath. Exp. Neurol. 31(1): 113-125, 1972,
OBSERVED NEUROTOXIC EFFECTS:
Severe ataxia. Granule cells absent, but postsynaptic
Purkinje cell dendritic spines present, surrounded by
astrocytic cytoplasm, resembling post-synaptic endings.
Membranous thickening apposed dense material in inter-
cellular cleft. Possible development of Purkinje cell
dendritic spines, independent of presynaptic ending.
COMPOUND: beta-D-Glucopyranoside,(methyl-ONN-azoxy)methyl)-
014901087
REFERENCE: Jones, M.
Am. J. Path. 62:69, 1971. (Abstract)
OBSERVED NEUROTOXIC EFFECTS:
Ataxia, abnormal gait, diminished cerebellum
with diminutive granule cells, disarrangement
of layers. Clinical signs did not persist in
less severe cases. No lesions in cord.
ANIMALS: Mice, Swiss albino, newborn
ANIMALS:
Mice, Swiss albino
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.5 mg/g
PREPARATION AND DOSE
or HISTORY OF PATIENT: ns.
ROUTE AND SITE: S.C.
CONTROL INFORMATION: Saline only
ROUTE AND SITE: ns.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: 25 d
EXAM. TYPE: Electron microscopy
DURATION OF EXPERIMENT: ns. but at least 90 d
EXAM. TYPE: Clinical, histology
381
382
-------
COMPOUND: beta-D-Glucopyranoside,(methyl-ONN-azoxy )methyl)-
014901087
REFERENCE:
Hirono, I. and Shlbuya, C.
Nature 216:1311-1312, 1967.
OBSERVED NEUROTOXIC EFFECTS: Ataxia, posterior paralysis, many deaths; nerve
histology (incomplete at time of writing) negative.
In acute study (2) death occurred without
neurological signs.
ANIMALS: (1) 60 newborn mice from 11 C57BL/6 F mice.
(2) 58 mice, C57BL/6, aged 2 mo.
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) 0.5 mg/g one dose, in saline.
(2) 0.3/0.5/1 mg/g, one dose in saline.
ROUTE AND SITE: (1) S.C., dorsal (2) Gavage
CONTROL INFORMATION: (1) 21 newborn to 3 dams, saline only (2) ns.
DURATION OF EXPERIMENT:, Over 8 mo. follow-up of 34 survivors.
EXAM. TYPE: Behavior, histology
383
COMPOUND: beta-D-Glucopyranoside, (methyl-ONN-azoxy)methyl)-
014901087
REFERENCE: Hirono, I., Shibuya, C. and Hayashi, K.
Proc. Soc. Exp. Biol. Med. 131:593-599, 1969.
OBSERVED NEUROTOXIC EFFECTS: Ataxia, disturbed gait; necrosis of granular
layer of cerebellum in newborn, persisting as developmental defect in mature
animals. These in mice and hamsters; rats not affected.
ANIMALS: 18 Golden hamsters, F, their 150 newborn, and 23 mature hamsters
29 rats, Moriyamaso, F, their 276 newborn
3 similar rats, their 21 newborn
72 C57BL/6 mice, F, their 415 newborn; 10 dd mice, their 64 newborn.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Mice: 0.5 or 1 mg/g one dose at various times.
Hamsters: 0.15-0.6 mg/g one dose at various times.
Rats: 0.5 mg/g or 250 mg/kg, various times.
ROUTE AND SITE: Oral or S.C.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: Serial sacr up to 72 hr, some animals to maturity.
EXAM. TYPE: Behavior, histology
384
-------
COMPOUND: Glue vapors
COMPOUND: Glutaconic acid, 3-hydroxy-, dimethyl ester, dimethyl phosphate
REFERENCE: Shirabe, T., Tsuda, T., Terao, A. and Araki, S.
J. Neurol. Sci. 21: 101-113, 1974.
OBSERVED NEUROTOXIC EFFECTS: Polyneuropathy after 2.5-3 yr exposure, mainly
motor with limb weakness and muscle-wasting, progressing after exposure
ceased. Sural nerve extensive axonal degeneration, no regeneration 3 mo.
after exposure ceased. Neurogenic atrophy of skeletal muscle. Deep
sensation stimuli retarded, superficial sensation stimuli less affected.
REFERENCE: Sherman, M., Herrick, R.B., Ross, E. and Chang, M.T.Y.
Toxicol. Appl. Pharm. 11: 49-67, 1967.
OBSERVED NEUROTOXIC EFFECTS: Ataxia, paralysis, convulsions.
ANIMALS: Human: M, 20: M, 19, both painters.
ANIMALS: Cockerels, Single Comb White Leghorn, 10-12 d old
PREPARATION AND DOSE
or HISTORY OF PATIENT: Glue-sniffing for 3 and 2 yr respectively.
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) Acute: LD 9.45 mg/kg
(2) Subacute: 50-800 ppm in diet, 20 chicks/grp, for 2 wk
ROUTE AND SITE: Inhalation
CONTROL INFORMATION: None
ROUTE AND SITE: Oral
CONTROL INFORMATION: Untreated control grps
DURATION OF EXPERIMENT: Follow-up 3 mo.
EXAM. TYPE: Histology (biopsy), clinical
DURATION OF EXPERIMENT: 1-3 wk
EXAM. TYPE: Behavior, mortality
385
386
-------
COMPOUND: Glutamic acid
COMPOUND: Glutamic acid
REFERENCE: Van Harreveld, A. and Fifkova, E.
Exp. Mel. Path. 15:61-81, 1971.
REFERENCE: Zarzecki, P., Blum, P.S., Cordingley, G.E. and Somjen, G.G.
Brain Reo. 89:187-191, 1975.
OBSERVED NEUROTOXIC EFFECTS:
Compound damage to cortex distinguished from
method-artifacts, dose-related. Edema, destruction
and removal of "dark" nerve cells.
OBSERVED NEUROTOXIC EFFECTS:
Excitation of cells by compound was never
enhanced by proline in the cortex, was occasionally
potentiated in the cord, no effect in the cuneate
nucleus. Authors conclude that proline may block
compound as a synaptic transmitter but not as an
excitant.
ANIMALS: Rats, surgically prepared
ANIMALS: Cats, surgically prepared.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Qualitative dosage
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Proline 0.5-2 M at pH 7.5-9.0.
ROUTE AND SITE: Electrophoretic injection
CONTROL INFORMATION: Microelectrodes filled with Ringer's soln were used
controls.
ROUTE AND SITE: Microinontophoresis, to neurons in 3 central nervous system areas;
cortex, cord, and cuneate nucleus.
CONTROL INFORMATION:
Laboratory controls.
DURATION OF EXPERIMENT: 1 hr to 15 d.
EXAM. TYPE: Histology
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemical
287
388
-------
COMPOUND: Glutamic acid, D-
COMPOUND:
Glutamic acid, D-
REFERENCE: Curtis, D.R. and Watkins, J.C.
J. Neurochem. 6:117-141, 1960.
REFERENCE:Curtis, D.R. and Watkins, J.C.
J. Physiol. 166:1-14, 1963.
OBSERVED NEUROTOXIC EFFECTS:
Treatment caused excitation or depression of
neuronal activity. Excitatory ranking: glutamic,
B-aminoglutaric, aspartic, cysteic, cysteine-
sulfinic acids, B-hydroxyglutamic, N-methylaspartic,
N-formiminoaspartic acids.
Depressant ranking: 6-alanine, GABA, taurine,
N-methyl-B-alanine, 6-amino-8-hydroxybutyric,
glycine, o-alanine, 6-aminovaleric, B-aminoisobutyric
acids.
Structure-activity relationships established.
OBSERVED NEUROTOXIC EFFECTS:
N-methyl-D-aspartic and D-homocystelc acids were
stronger excitants of depolarization than all
others. With some compounds the action was
prolonged for many seconds after the stimulus
was terminated, notably N-nj-propyl-D-aspartic
acid. There were no differences among types of
neurons tested; structure-activity relationship
was observed.
ANIMALS:
Cats, surgically prepared to expose* motoneurones, Renshaw cells or
dorsal horn interneurones in lumbar cord.
ANIMALS: Cats prepared for electrophoretic application of chemicals to single
central nervous system neurons.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Qualitative doses.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Dilutions 0.1-0.5 M of 31 compounds mainly of aspartic,
glutamic and cysteic acids listed in order of
potency of results.
ROUTE AND SITE: Topical, ionophoresis
CONTROL INFORMATION: Laboratory
ROUTE AND SITE: Electrophoretic application, various sites in central nervous
system.
CONTROL INFORMATION:
None
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry, electrophysiology
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Electrophysiological
3S9
390
-------
COMPOUND: Glutamic acid, D-
COMPOUND: Glutamic acid, DL-
REFEREHCE:
Olnoy, J.W., Ho, O.L. and Rhee, V.
Exp. Brain Res. 14:61-76, 1971.
REFERENCE: Curtis, D.R. and Watkins, J.C.
J. Neurochem. 6:117-141, 1960.
OBSERVED NEUROTOXIC EFFECTS: The compound was equipotent to monosodium
glutaraate in necrosing neurons in the retina
and brain. This compound is a powerful neuro-
excltant and the neurotoxic properties may be
governed by similar mechanisms.
OBSERVED NEUROTOXIC EFFECTS:
ANIMALS: Mice, Swiss-webster age 10 d, total 250
ANIMALS:
Treatment caused excitation or depression of
neuronal activity. Excitatory ranking: glutamic,
B-aminoglutaric, aspartic, cysteic, cysteine-
sulfinic acids, B-hydroxyglutamic, N-methylaspartic,
N-fonaiminoaspartic acids.
Depressant ranking: 6-alanine, GABA, taurine,
N-methyl-f5-alanine, 6-amino-B-hydroxybutyric,
glycine, a-alanine, 6-aminovaleric, 6-aminoisobutyric
acids.
Structure-activity relationships established.
Cats, surgically prepared to expose motoneurones, Renshaw cells or
dorsal horn interneurones in lumbar cord.
PREPARATION AMD DOSE
or HISTORY OF PATIENT: Initially 12 mmoles/kg, then range established for
each compound.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Qualitative doses.
ROUTE AND SITE:
S.C.
CONTROL INFORMATION: Compounds compared with monosodium L-glutamate (MSG)
potency for selectively necrosing neurons in retina
and brain (hypothalamus)
DURATION OF EXPERIMENT: 5 hr or serlai intervals including 5 hr.
EXAM. TYPE: Histology
ROUTE AND SITE: Topical, ionophoresis
CONTROL INFORMATION: Laboratory
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry, eleetrophysiology
391
392
-------
COMPOUND:
Glutamic acid, L-
COMPOUND: Glutamic acid, L-
REFERENCE:
Curtis, D.R. and Watkins, J.C.
J. Neurochem. 6:117-141, 1960.
REFERENCE:Curtls, D.R. and Watkins, J.C.
J. Physiol. 166:1-14, 1963.
OBSERVED NEUROTOXIC EFFECTS:
Treatment caused excitation or depression of
neuronal activity. Excitatory ranking: glutamic,
g-aminoglutaric, aspartic, cysteic, cysteine-
sulfinic acids, B-hydroxyglutamic, N-methylaspartic,
N-formiminoaspartic acids.
Depressant ranking: S-alanine, GABA, taurine,
N-methyl-B-alanine, 5-amino-B-hydroxybutyric,
glycine, a-alanine, 6-aminovaleric, B-amino-
isobutyric acids.
Structure-activity relationships established.
OBSERVED NEUROTOXIC EFFECTS:
N-methyl-D-aspartic and D-homocysteic acids were
stronger excitants of depolarization than all
others. With some compounds the action was
prolonged for many seconds after the stimulus
was terminated, notably N-ii-propyl-D-aspartic
acid. There were no differences among types of
neurons tested; structure-activity relationship
was observed.
ANIMALS:
Cats, surgically prepared to exposed motoneurones, Renshaw
cells or dorsal horn interneurones in lumbar cord.
ANIMALS: Cats prepared for electrophoretic application of chemicals to single
central nervous system neurons.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Qualitative doses.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Dilutions 0.1-0.5 M of 31 compounds mainly of aspartic,
glutamic and cysteic acids listed in order of
potency of results.
ROUTE AND SITE: Topical, ionophoresis
CONTROL INFORMATION: Laboratory
ROUTE AND SITE: Electrophoretic application, various sites in central nervous
system.
CONTROL INFORMATION:
None
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry, electrophysiology
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Electrophysiological
393
394
-------
COMPOUND: Glutamic acid, L-
COMPOUND: Glutamic acid, N-acetyl
REFERENCE:
Olney, J.W., Ho, O.L. and Rhee, V.
Exp. Brain Res. 14:61-76, 1971.
OBSERVED NEUROTOXIC EFFECTS:
The compound was equipotent to monosodium
glutamate in necrosing neurons in the retina
and brain. This compound is a powerful neuro-
excitant and the neurotoxic properties may be
governed by similar mechanisms.
REFERENCE: Curtis, D.R. and Watkins, J.C.
J. Neurochem. 6:117-141, 1960.
OBSERVED NEUROTOXIC EFFECTS:
Treatment caused excitation or depression of
neuronal activity. Excitatory ranking: glutamic,
B-aminoglutaric, aspartic, cysteic, cysteine-
sulfinic acids, 8-hydroxyglutamic, N-methylaspartic,
N-formiminoaspartic acids.
Depressant ranking: 6-alanine, GABA, taurine,
N-methyl-6-alanine, 6-amino-B-hydroxybutyric,
glycine, a-alanine, 6-aminovaleric, B-aminoisobutyric
acids.
Structure-activity relationships established.
ANIMALS: Mice, Swiss-webster age 10 d, total 250
ANIMALS:
Cats, surgically prepared to expose motoneurones, Renshaw cells or
dorsal horn interneurones in lumbar cord.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Initially 12 mmoles/kg, then range established for
each compound.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Qualitative doses.
ROUTE AND SITE: s.C.
CONTROL INFORMATION: Compounds compared with monosodium L-glutamate (MSG)
potency for selectively necrosing neurons in retina
and brain (hypothalamus)
DURATION OF EXPERIMENT: 5 hr or serial intervals including 5 hr.
EXAM. TYPE: Histology
ROUTE AND SITE: Topical, ionophoresis
CONTROL INFORMATION: Laboratory
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry, electrophysiology
395
396
-------
COMPOUND: Glutamic acid, N-acetyl, L~
COMPOUND: Glutamic acid, 3-amino-
REFERENCE:
Olney, J.W., Ho, O.L. and Rhee, V.
Exp. Brain Res. 14:61-76, 1971.
OBSERVED NEUROTOX1C EFFECTS: No cytotoxicity was observed.
ANIMALS: Mice, Swiss-webster age 10 d, total 250
PREPARATION AND DOSE
or HISTORY OF PATIENT: Initially 12 mmoles/kg, then range established for
each compound.
REFERENCE: Curtis, D.R. and Watkins, J.C.
J. Neurochem. 6:117-141, 1960.
OBSERVED NEUROTOXIC EFFECTS:
ANIMALS:
Treatment caused excitation or depression of
neuronal activity. Excitatory ranking: glutamic,
B-aminoglutaric, aspartic, cysteic, cysteine-
sulfinic acids, 6-hydroxyglutamic, N-methylaspartic,
N-formiminoaspartic acids.
Depressant ranking: B-alanine, GABA, taurine,
N-methyl-B-alanine, 6-amino-B-hydroxybutyric,
glycine, a-alanine, 6-aminovaleric, 6-aminoisobutyric
acids.
Structure-activity relationships established.
Cats, surgically prepared to expose motoneurones, Renshaw cells or
dorsal horn interneurones in lumbar cord.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Qualitative doses.
ROUTE AND SITE:
S.C.
CONTROL INFORMATION: Compounds compared with monosodium L-glutamate (MSG)
potency for selectively necrosing neurons in retina
and brain (hypothalainus)
DURATION OF EXPERIMENT: 5 hr or serial intervals including 5 hr.
EXAM. TYPE: Histology
ROUTE AND SITE: Topical, ionophoresis
CONTROL INFORMATION: Laboratory
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry, electrophysiology
397
398
-------
COMPOUND:
Glutamic acid, N-carbamoyl-, L-
REFERENCE: Curtis, D.R. and Watkins, J.C.
J. Neurochem. 6:117-141, 1960.
OBSERVED NEUROTOXIC EFFECTS:
Treatment caused excitation or depression of
neuronal activity. Excitatory ranking: glutamic,
S-aminoglutaric, aspartic, cysteic, cysteine-
sulfinic acids, B-hydroxyglutamic, N-methylaspartic,
N-formiminoaspartic acids.
Depressant ranking: g-alanine, GABA, taurine,
N-methyl-g-alanine, 6-amino-8-hydroxybutyric,
glycine, a-alanine, 6-aminovaleric, B-aminoispbutyric
acids.
Structure-activity relationships established.
COMPOUND: Glutamic acid, N-(p-(((2,4-diamino-6-pteridnyl)methyl)methylamino)
t>enzoyl)-,L-
000059052
REFERENCE:
Greenhouse, A.H., Neubuerger, K.T. and Bowerman, D.L.
Arch. Seurol. 11:618-625, 1964.
OBSERVED NEUROTOXIC EFFECTS: Aphasia, right hemiparesis, convulsions;
inflammatory lesions in left cerebral hemisphere
attributed to direct toxic action of compound.
ANIMALS:
Cats, surgically prepared to exposed motoneurones, Renshaw cells or
dorsal horn interneurones in lumbar cord.
ANIMALS:
1 Human, F aged 36 yr.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Qualitative doses.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Active lymphosarcoma; 30 mg given, further doses not
quantified.
ROUTE AND SITE: Topical, ionophoresis
CONTROL INFORMATION: Laboratory
ROUTE AND SITE: Intra-arterial, carotid
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry, electrophysiology
DURATION OF EXPERIMENT: About 3 wk.
EXAM. TYPE: Behavior, histology (autopsy)
399
400
-------
COMPOUND: Glutamic acid, N-(p-(((2,4-diamino-6- pteridny])methyl)methylamino)
benzoyl),-L-
000059052
REFERENCE: Smith, B.
J. Neurol. Neurosurg. Psychiat. 38:810-815, 1975.
COMPOUND: Glutamic acid, N.N-dimethyl-, L-
REFERENCE: Curtis, D.R. and Watkins, J.C.
J. Neurochem. 6:117-141, 1960.
OBSERVED NEUROTOXIC EFFECTS: Destruction of oligodendrites and severe
astrocytosis leading to death from therapy.
ANIMALS: Human autopsy material: 10 brains from treated leukemics.
OBSERVED NEUROTOXIC EFFECTS:
ANIMALS:
Treatment caused excitation or depression of
neuronal activity. Excitatory ranking: glutamic,
6-aminoglutaric, aspartic, cysteic, cysteine-
sulfinic acids, 6-hydroxyglutamic, N-tnethylaspartic,
N-formiminoaspartic acids.
Depressant ranking: 6-alanine, GABA, taurine,
N-methyl-B-alanlne, 6-amino-B-hydroxybutyric,
glycine, a-alanine, 6-aminovaleric, B-aminoisobutyric
acids.
Structure-activity relationships established.
Cats, surgically prepared to exposed motoneurones, Renshaw cells or
dorsal horn interneurones in lumbar cord.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 10, 12, or 12.5 mg/wk in addition to other drugs and
radiotherapy.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Qualitative doses.
ROUTE AND SITE: Intrathecal
CONTROL INFORMATION: Human autopsy material from 10 untreated leukemics.
ROUTE AND SITE: Topical, ionophoresis
CONTROL INFORMATION: Laboratory
DURATION OF EXPERIMENT: Therapy.
EXAM. TYPE: Histology
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry, electrophysiology
401
402
-------
COMPOUND: Glutamlc acid, hydrazide, L-
COMPOUND: Glutamlc acid, beta-hydroxy
REFERENCE: Curtis, D.R. and Watkins, J.C.
J. Neurochem. 6:117-141, 1960.
REFERENCE: Curtis, D.R. and Watkins, J.C.
J. Neurochem. 6:117-141, 1960.
OBSERVED NEUROTOXIC EFFECTS:
Treatment caused excitation or depression of
neuronal activity. Excitatory ranking: glutamic,
8-aminoglutaric, aspartic, cysteic, cysteine-
sulfinic acids, B-hydroxyglutamic, N-methylaspartic,
N-formiminoaspartic acids.
Depressant ranking: 6-alanine, GABA, taurine,
N-methyl-8-alanine, 6-amino-B-hydroxybutyric,
glycine, a-alanine, 6-aminovaleric, B-aminoisobutyric
acids.
Structure-activity relationships established.
OBSERVED NEUROTOXIC EFFECTS:
Treatment caused excitation or depression of
neuronal activity. Excitatory ranking: glutamic,
B-aminoglutaric, aspartic, cysteic, cysteine-
sulfinic acids, 8-hydroxyglutamic, N-methylaspartic,
N-formiminoaspartic acids.
Depressant ranking: B-alanine, GABA, taurine,
N-methyl-B-alanine, 6-amino-B-hydroxybutyric,
glycine, a-alanine, 6-aminovaleric, B-aminoisobutyric
acids.
Structure-activity relationships established.
ANIMALS:
Cats, surgically prepared to expose motoneurones, Renshaw cells or
dorsal horn interneurones in lumbar cord.
ANIMALS:
Cats, surgically prepared to expose motoneurones, Renshaw cells or
dorsal horn interneurones in lumbar cord.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Qualitative doses.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Qualitative doses.
ROUTE AND SITE: Topical, ionophoresis
CONTROL INFORMATION: Laboratory
ROUTE AND SITE: Topical, ionophoresis
CONTROL INFORMATION: Laboratory
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry, electrophysiology
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry, electrophysiology
404
-------
COMPOUND: Glutamic acid, N-methyl-, D-
COMPOUND:
Glutamic acid, alpha-methyl-, DL-
REFERENCE:Curtis, D.R. and Watkins, J.C.
J. Physiol. 166:1-14, 1963.
REFERENCE: Curtis, D.R. and Watkins, J.C.
J. Neuror.hem. 6:117-141, 1960.
OBSERVED NEUROTOXIC EFFECTS:
N-methyl-D-aspartic and D-homocysteic acids were
stronger excitants of depolarization than all
others. With some compounds the action was
prolonged for many seconds after the stimulus
was terminated, notably N-ri-propyl-D-aspartic
acid. There were no differences among types of
neurons tested; structure-activity relationship
was observed.
OBSERVED NEUROTOXIC EFFECTS:
Treatment caused excitation or depression of
neuronal activity. Excitatory ranking: glutamic,
B-aminoglutaric, aspartic, cysteic, cysteine-
sulfinic acids, 6-hydroxyglutamic, N-methylaspartic,
N-formiminoaspartic acids.
Depressant ranking: B-alanine, GABA, taurine,
N-methyl-6-alanine, 6-amino-S-hydroxybutyric,
glycine, a-alanine, 6-aminovaleric, B-aminoisobutyric
acids.
Structure-activity relationships established.
ANIMALS: Cats prepared for electrophoretic application of chemicals to single
central nervous system neurons.
ANIMALS:
Cats, surgically prepared to exposed motoneurones, Renshaw cells or
dorsal horn interneurones in lumbar cord.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Dilutions 0.1-0.5 M of 31 compounds mainly of aspartic,
glutamic and cysteic acids listed In order of
potency of results.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Qualitative doses.
ROUTE AND SITE: Electrophoretic application, various sites in central nervous
system.
CONTROL INFORMATION:
None
ROUTE AND SITE: Topical, ionophoresis
CONTROL INFORMATION: Laboratory
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Electrophysiological
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry, electrophysiology
4C5
406
-------
COMPOUND: Glutamic acid, alpha-methyl-, DL-
COMPOUND:
Glutamic acid, N-methyl-, DL-
REFERENCE: Olney, J.W., Ho, O.L. and Rhee, V.
Exp. Brain Res. 14:61-76, 1971.
REFERENCE: Curtis, D.R. and Watkins, J.C.
J. Neurochem. 6:117-141, 1960.
OBSERVED NEUROTOXIC EFFECTS: The compound was toxic to non-neurol components
(glia, etc.), but not to neurons.
OBSERVED NEUROTOXIC EFFECTS:
ANIMALS: Mice, Swiss-webster age 10 d, total 250
PREPARATION AND DOSE
or HISTORY OF PATIENT: Initially 12 mmoles/kg, then range established for
each compound.
ANIMALS:
Treatment caused excitation or depression of
neuronal activity. Excitatory ranking: glutamic,
6-aminoglutaric, aspartic, cysteic, cysteine-
sulfinic acids, B-hydroxyglutamic, N-methylaspartic,
N-formiminoaspartic acids.
Depressant ranking: 6-alanine, GABA, taurine,
N-methyl-6-alanine, 6-amino-B-hydroxybutyric,
glycine, a-alanine, 6-aminovaleric, B-aminoisobutyric
acids.
Structure-activity relationships established.
Cats, surgically prepared to exposed motoneurones, Renshaw cells or
dorsal horn interneurones in lumbar cord.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Qualitative doses.
ROUTE AND SITE: s.C.
CONTROL INFORMATION: Compounds compared with monosodium L-glutamate (MSG)
potency for selectively necrosing neurons in retina
and brain (hypothalamus)
DURATION OF EXPERIMENT: 5 hr or serial intervals including 5 hr.
EXAM. TYPE: Histology
ROUTE AND SITE: Topical, ionophoresis
CONTROL INFORMATION: Laboratory
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry, electrophysiology
407
408
-------
COMPOUND* Glutamic acid, N-methyl-, DL-
COMPOUND: Glutamic acid, N-methyl-, DL-
REFERENCE:Curtis, D.R. and Watkins, J.C.
J. Physiol. 166:1-14, 1963.
OBSERVED NEUROTOXIC EFFECTS: N-methyl^D-aspartic and D-homocysteic acids were
stronger excitants of depolarization than all
others. With some compounds the action was
prolonged for many seconds after the stimulus
was terminated, notably N-n_-propyl-D-aspartic
acid. There were no differences among types of
neurons tested; structure-activity relationship
was observed.
REFERENCE: Olney, J.W., Ho, O.L. and Rhee, V.
Exp. Brain Res. 14:61-76, 1971.
OBSERVED NEUROTOXIC EFFECTS:
The compound was more potent than monosodium
glutamate in necrosing neurons in the retina
and brain. This compound .is a powerful neuro-
excitant and the neurotoxic properties may be
governed by similar mechanisms.
ANIMALS: Cats prepared for electrophoretic application of chemicals to single
central nervous system neurons.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Dilutions 0.1-0.5 M of 31 compounds mainly of aspartic,
glutamic and cysteic acids listed in order of
potency of results.
ANIMALS: Mice, Swiss-webster age 10 d, total 250
PREPARATION AND DOSE
or HISTORY OF PATIENT: Initially 12 mmoles/kg, then range established for
each compound.
ROUTE AND SITE: Electrophoretic application, various sites in central nervous
system.
CONTROL INFORMATION:
None
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Electrophysiological
ROUTE AND SITE:
S.C.
CONTROL INFORMATION: Compounds compared with monosodium L-glutamate (MSG)
potency for selectively necrosing neurons in retina
and brain (hypothalamus)
DURATION OF EXPERIMENT: 5 hr or serial intervals including 5 hr.
EXAM. TYPE: Histology
409
410
-------
COMPOUND:
Glutamic acid, alpha-methyl ester, L-
COMPOUND:
Glutamic acid, gamma-methyl ester, L-
REFERENCE: Curtis, D.R. and Watkins, J.C.
J. Neurochem. 6:117-141, 1960.
REFERENCE: Curtis, D.R. and Watkins, J.C.
J. Neurochem. 6:117-141, 1960.
OBSERVED NEUROTOXIC EFFECTS:
Treatment caused excitation or depression of
neuronal activity. Excitatory ranking: glutamic,
6-aminoglutaric, aspartic, cysteic, cysteine-
sulfinic acids, 6-hydroxyglutamic, N-methylaspartic,
N-formiminoaspartic acids.
Depressant ranking: B-alanine, GABA, taurine,
N-methyl-S-alanine, 6-amlno-8-hydroxybutyric,
glycine, a-alanine', 6-aminovaleric, B-aminoisobutyric
acids.
Structure-activity relationships established.
OBSERVED NEUROTOXIC EFFECTS:
Treatment caused excitation or depression of
neuronal activity. Excitatory ranking: glutamic,
B-aminoglutaric, aspartic, cysteic, cysteine-
sulfinic acids, B-hydroxyglutamic, N-methylaspartic,
N-formiminoaspartic acids.
Depressant ranking: B-alanine, GABA, taurine,
N-methyl-B-alanine, 6-amino-B-hydroxybutyric,
glycine, a-alanine, 6-aminovaleric, B-aminoisobutyric
acids.
Structure-activity relationships established.
ANIMALS:
Cats, surgically prepared to expose motoneurones, Renshaw cells or
dorsal horn interneurones in lumbar cord.
ANIMALS:
Cats, surgically prepared to expose motoneurones, Renshaw cells or
dorsal horn interneurones in lumbar cord.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Qualitative doses.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Qualitative doses.
ROUTE AND SITE: • Topical, ionophoresis
CONTROL INFORMATION: Laboratory
ROUTE AND SITE: Topical, ionophoresis
CONTROL INFORMATION: Laboratory
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry, electrophysiology
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry, electrophysiology
411
412
-------
COMPOUND: Glutamic acid, monosodlum salt, L-(+)_
000142472
REFERENCE: Knaape, H.H. and Wlechert, P. (In Ger.)
J. Neurochem. 17: 1171-1175, 1970.
OBSERVED NEUROTOXIC EFFECTS: EEC seizures followed injection into the hippocampus;
other sites are ranked in order of decreasing
sensitivity to compound, the ventricle being insen-
sitive at doses used. The authors discuss the metab-
olism of compound as producing releasing factors for
EEC seizures.
COMPOUND: Glutamic acid, monosodium salt, L-(+)-
000142472
REFERENCE: Lemkey-Johnston, N. and Reynolds, W.A.
J. Neuropath. Exp, Neurol. 33(l):74-97, 1974.
OBSERVED NEUROTOXIC EFFECTS: Tremors, and damage to dentate-hippocampal
gyrl surfaces. Involvement of retina and in the
arcuate nucleus. Lesions in the tectum, habenular
nuclei, subfornical organ, dorsolateral surface of
the thalamus,cerebral cortex, area postrema, cuneatus
and the nuclei gracilis. Death.
ANIMALS: 45 cats, 2.5-5 kg, surgically prepared
ANIMALS: 3 strains of Mice, Swiss-Albino - 7-10 days, and 1 mouse - A/Jax
ICR hybrid.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 50-250 microliter in 10-15 sec
PREPARATION AND DOSE
or HISTORY OF PATIENT: 1, 2, or 4 mg/gm in 20% soln.
ROUTE AND SITE: Stereotactlc injection into various cerebral regions
CONTROL INFORMATION: ns
ROUTE AND SITE: I.P. and S.C.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: Each up to about 30 min
EXAM. TYPE: Behavior, EEC
DURATION OF EXPERIMENT: Serial Sacr. 10 min to 48 hr.
EXAM. TYPE: Histology, Ultrastructural.
413
414
-------
COMPOUND: Glutamlc acid, monosodium salt, L-(+)-
000142472
REFERENCE:
Lemkey-Johnston, N., Butler, V. and Reynolds, W.A.
Expl. Neurol. 48:292-309, 1975.
COMPOUND: Glutamic acid, monosodium salt, L-(+)-
000142472
REFERENCE: Olney, J.W.
J. Neuropath. Exp. Neurol. 28: 455-474, 1969.
OBSERVED NEUROTOXIC EFFECTS:
Glutamic acid HC1 at 2 mg/g produced lesions in
arcuate nucleus (10 of 11 mice), also preoptic
nucleus, tectum and pretectal area, subconmissural
and subfornical organs and cerebellum (neuronal
damage like that from MSG). Higher equivalency
NaCl damaged mainly caudate-putamen, cerebellum,
cortex, and habenula, related apparently to vascular
changes. Sucrose produced vascular changes but
no brain lesions.
OBSERVED NEUROTOXIC EFFECTS:
A single injection caused degeneration of the inner
retinal cells of mice aged 9-10 days. There was
evidence of edema of dendrites and cell bodies, mito-
chondria and several patterns of degeneration leading
to necrosis.
ANIMALS:
Mice, ICR or A/JAX-ICR hybrids, aged 4-12 d.
ANIMALS: Over 200 mice, Swiss albino
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Glutamic acid HC1 2 and 4 mg/g as 20% solution; NaCl
equimolar for Na to 1-10 mg/g MSG (0.31-3.12 mg/g);
sucrose 14.6-36.5 mg/g as 80% solution, also equimolar
to 4-10 mg/g MSG. Purpose: to test the components of
MSG separately.
ROUTE AND SITE: Gavage
CONTROL INFORMATION: None other than sucrose..
PREPARATION AND DOSE
or HISTORY OF PATIENT: 4 g/kg and other schedules
ROUTE AND SITE: s.C.
CONTROL INFORMATION: Various
DURATION OF EXPERIMENT^.
EXAM. TYPE: Histology, but timings and preparations are not described, though
they reportedly influence the findings.
DURATION OF EXPERIMENT: 30 min to 48 hr
EXAM. TYPE: Histology
415
416
-------
COMPOUND: Glutamic acid, monosodlum salt, L-(+)-
000142472
REFERENCE: oiney, J.W.
Science 164:719-721, 1969.
OBSERVED NEUROTOXIC EFFECTS: (1) Selective destruction of: proptic and arcuate
nuclei, some neurons in median eminence, subcommissural and subfornical
organs, medial habenular nuclei, dentate gyrus. (2 and 3) Brain lesions
found, not described. Chronic dosage: mainly non-neural studies, but stunting
found in adenohypophysis.
COMPOUND: Glutamic acid, monosodium salt, L-(+)-
000142472
REFERENCE: Olney, J.W. and Ho., 0.
Nature 227:609-610, 1970.
OBSERVED NEUROTOXIC EFFECTS: Necrosis of hypothalamic neurons in mice given
glutamate, aspartate, or cysteine, dose-related;
zero damage from other compounds
ANIMALS: (i) Mice, Swiss albino, 10 litters aged 2-9 d
(2) Adult mice
(3) Neonatal C57BL/6 mice and albino rats
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) 0.5-4 mg/g, one dose; 20 dosed daily, for d 1-10
of age.
(2) 5-7 mg/g.
(3) ns.
ANIMALS: 75 Mice, Swiss Webster, age 10 d.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
One of 10 amino acids and various other compounds, 2.5 or 10%
in water, 0.25-2 g/kg.
ROUTE AND SITE: S.C.
CONTROL INFORMATION: (1) 18 mice untreated.
ROUTE AND SITE: Gavage
CONTROL INFORMATION: Intubated, no treatment, 10 mice
DURATION OF EXPERIMENT: 1.9 mo.
EXAM. TYPE: Histology
DURATION OF EXPERIMENT: 5 hr.
EXAM. TYPE: Histology
417
418
-------
COMPOUND' Glutamic acid, monosodium salt, L-(+)-
000142472
REFERENCE: Olney, J.W.
J. Neuropath. Exp. Neurol. 30(1):75-90, 1971.
OBSERVED NEUROTOXIC EFFECTS: Hypothalamic lesions. Involvement of glial and
ependymal cells. Arcuate (infundibular) nucleus
and inner retinal neurons were destroyed. An
identical pattern of neuronal necrosis can be
induced by certain other amino acids, which have
neuroexcitatory properties.
ANIMALS:. 27 Mice, Webster Swiss, albino, 10 d post natal.
PREPARATION AND DOSE
or HISTORY OF PATIENT: IS m mole/kg in 10% aq soln.
ROUTE AND SITE: S.C.
CONTROL INFORMATION: 3 mice untreated, 3 mice: 18 m mole/kg sodium chloride.
DURATION OF EXPERIMENT: Sacr. 15 min to 8 d.
EXAM. TYPE: Histology, ultrastructure.
419
COMPOUND: Glutamic acid, monosodium salt, L-(+)-
000142472
REFERENCE: Olney, J.W., Sharpe, L.G., and Feigin, R.D.
J. Neuropath. Exp. Neurol. 31(3): 464-488, 1972.
OBSERVED NEUROTOXIC EFFECTS: Cyanosis, vomiting, convulsions, neuron-necrotized
hypothalamus, and brain lesions. Arcuate nucleus, medial habenular nucleus
neurons, subfornical organ, cingulate cortex midline, anterior hippocamus
(denate gyrus) and superior colliculus destroyed.
ANIMALS: 9 Rhesus Monkeys, (Macaca Mulatta), Infants.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 1-4 g/kg admin, as 20cc/kg of skim milk water soln.
ROUTE AND SITE: Oral and S.C.
CONTROL INFORMATION: 3 monkeys treated with NaCl
DURATION OF EXPERIMENT: Serial sacr 3-5 hrs.
EXAM. TYPE: Ultrastructural, histology, cytopathology
420
-------
COMPOUND" Glutamic acid, monosodium salt, L-(+)-
000142472
REFERENCE: Olney, J.W., Ho, O.L., Rhee, V. and DeGubareff, T.
New Eng. J. Med. 289:1374-1375, 1973.
OBSERVED NEUROTOXIC EFFECTS: Brain lesions at junction of median eminence and
arcuate-periventricular nucleus.
COMPOUND: Glutamic acid, monosodium salt, L-(+)-
REFERENCE:
Perez, V.J. and Olney, J.W.
J. Neurochem. 19:1777-1782, 1972.
OBSERVED NEUROTOXIC EFFECTS:
Arcuate nucleus, ventromedial hypothalamus
and lateral thalamus were examined:
control MSG level 25 mmol/kg dry weight, rose to 111
mmol in arcuat nucleus, 42 in ventromedial hypothalamus
and lateral thalamus, at 3 hr, back to normal in
12-15 hr, blood (normal <1 mM) rose to 40 mM in 15
min, back to normal in 1-3 hr.
ANIMALS: Guinea-pigs, age 3 d
ANIMALS: 124 Mice, 18 litters, M and F, Swiss-Webster, aged 4 d
PREPARATION AND DOSE
or HISTORY OF PATIENT: 1 mg/g
PREPARATION AND DOSE
or HISTORY OF PATIENT: 2 mg/g
ROUTE AND SITE: s.C.
CONTROL INFORMATION: Guinea-pigs sodium chloride treated.
ROUTE AND SITE: s.C.
CONTROL INFORMATION: Untreated mice, also zero time treated.
DURATION OF EXPERIMENT: 5 hr
EXAM. TYPE: Histology
DURATION OF EXPERIMENT: 7.5 min to 18 hr, serial sacr.
EXAM. TYPE: Biochemistry
421
422
-------
COMPOUND: Glutamic acid, monosodium salt, L-(+)-
000142472
REFERENCE: Reynolds, W.A., Lemkey-Johnston, N., Filer, L.J., Jr. and Pitkin, R.M.
Science 172: 1342-1345, 1971.
COMPOUND: Glutamic acid, monosodium salt, L-(+)-
000142472
REFERENCE: Snapir, N., Robinzon, B. and Perek, M.
Poulr.ry Sci. 50:1511-1514, 1971.
OBSERVED NEUROTOXIC EFFECTS: No morphological differences between treated and
control hypothalami, but some tissue fixed inadequately
resembled brain lesions.
OBSERVED NEUROTOXIC EFFECTS: Compound induced brain damage in the hypothalamus
region surrounding the ventromedial area, leaving the hypothalamus itself
unaffected.
ANIMALS: 16 Monkeys (M. mulatta and M. irus), infants
ANIMALS: 84 Chicks, New Hampshire x White Leghorn, M, aged 5 d, in 6 grps.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 1, 2, 4 g/kg, 50% soln in water.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 1 and 4 mg/g bw, one dose or daily
ROUTE AND SHE: Nasogastric tube
CONTROL INFORMATION: 5 additional monkeys, water only.
ROUTE AND SITE: S.C., back of neck
CONTROL INFORMATION: 2 grps saline
DURATION OF EXPERIMENT: 6 hr
EXAM. TYPE: Histology
DURATION OF EXPERIMENT: 40 d after first dose
EXAM. TYPE: Histology
424
-------
COMPOUND: Glutamic acid, sodium salt
COMPOUND: Glutamine, L-
REFERENCE: Fifkova, E., Van Harreveld, A.
Exp. Neurology 28:286-298, 1970.
OBSERVED NEUROTOXIC EFFECTS:
(1) Transient arrest of electrogram of corpus
striatum
(2) No noticeable effect on EEC.
Depolarizes neurons when app. electrophoretically
may arrest all activity.
REFERENCE: Curtis, D.R. and Watkins, J.C.
J. Neurochem. 6:117-141, 1960.
OBSERVED NEUROTOXIC EFFECTS:
Treatment caused excitation or depression of
neuronal activity. Excitatory ranking: glutamic,
g-aminoglutaric, aspartic, cysteic, cysteine-
sulfinic acids, 6-hydroxyglutamic, N-methylaspartic,
N-formiminoaspartic acids.
Depressant ranking: B-alanine, GABA, taurine,
N-methyl-B-alanine, 6-amino-8-hydroxybutyric,
glycine, ct-alanine, 6-aminovaleric, B-aminoisobutyric
acids.
Structure-activity relationships established.
ANIMALS: (1) Chicks, Leghorn, 16 d incubation to hatching time.
(2) Chicks, 5 d after hatching.
ANIMALS:
Cats, surgically prepared to expose motoneurones, Renshaw cells or
dorsal horn interneurones in lumbar cord.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
100 mM soln. of 1 sodium-glutamate, pH 7.2.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Qualitative doses.
ROUTE AND SITE: I.V. at rate 1.2 ml/min for 1-5-2 min.
CONTROL INFORMATION: ns.
ROUTE AND SITE: Topical, ionophoresis
CONTROL INFORMATION: Laboratory
DURATION OF EXPERIMENT:16 d incubation-5 d old chicks.
EXAM. TYPE: Neurological.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry, electrophysiology
425
426
-------
COMPOUND: Glutamine, L-
COMPOUND: Glutamine, N,N-dimethyl-, L-
REFERENCE: Olney, J.V?. , Ho, O.L. and Rhee, V.
Exp. Erain Res. 14:61-76, 1971.
OBSERVED NEUROTOXIC EFFECTS: Go cytotoxicity was observed.
ANIMALS: Mice, Swiss-webster age 10 d, total 250
PREPARATION AND DOSE
or HISTORY OF PATIENT: Initially 12 mmoles/kg, then range established for
each compound.
REFERENCE: Curtis, D.R. and Watkins, J.C.
J. Neurochem. 6:117-141, 1960.
OBSERVED NEUROTOXIC EFFECTS:
ANIMALS:
Treatment caused excitation or depression of
neuronal activity. Excitatory ranking: glutamic,
B-aminoglutaric, aspartic, cysteic, cysteine-
sulfinic acids, 6-hydroxyglutamic, N-methylaspartic,
N-forroiminoaspartlc acids.
Depressant ranking: 6-alanine, GABA, taurine,
N-methyl-B-alanine, 6-amino-B-hydroxybutyric,
glycine, a-alanine, 6-aminovaleric, B-aminoisobutyric
acids.
Structure-activity relationships established.
Cats, surgically prepared to expose . motoneurones, Renshaw cells or
dorsal horn interneurones in lumbar cord.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Qualitative doses.
ROUTE AND SITE:
S.C.
CONTROL INFORMATION: Compounds compared with monosodium L-glutamstn (MSG)
potency for selectively necrosing neurons in retina
and brain (hypothalamus)
DURATION OF EXPERIMENT: 5 hr or serial intervals including 5 hr.
EXAM. TYPE: Histology
ROUTE AND SITE: Topical, ionophoresis
CONTROL INFORMATION: Laboratory
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry, electrophysiology
427
428
-------
COMPOUND: • Glutamine, N-methyl-, L-
REFERENCE: Curtis, D.R. and Watkins, J.C.
J. Neurochem. 6:117-141, 1960.
COMPOUND: Glutaramide, 3-(2-(3,5-dimethyl-2-oxocvclohexyl)-?.-hyHroxy=ethyl)-
000066819
REFERENCE: Segal, D.S., Squire, L.R. and Barondes, S.H.
Science 172:82-83, 1971.
OBSERVED NEUROTOXIC EFFECTS:
ANIMALS:
Treatment caused excitation or depression of
neuronal activity. Excitatory ranking: glutamic,
6-aminoglutaric, aspartic, cysteic, cysteine-
sulfinic acids, B-hydroxyglutamic, N-methylaspartic,
N-formiminoaspartic acids.
Depressant ranking: 6-alanine, GABA, taurine,
N-methyl-B-alanine, 6-amino-B-hydroxybutyric,
glycine, a-alanine, 6-aminovaleric, B-aminoisobutyric
acids.
Structure-activity relationships established.
Cats, surgically prepared to expose" motoneurones, Renshaw cells or
dorsal horn interneurones in lumbar cord.
OBSERVED NEUROTOXIC EFFECTS:
PREPARATION AND DOSE
or HISTORY OF PATIENT: Qualitative doses.
ANIMALS: Mice
PREPARATION AND DOSE
or HISTORY OF PATIENT:
The compound inhibits protein synthesis (trans-
lation) and long term memory, and produces initial
hyperactivity. The effect of amphetamine on
memory in the compound treated mice is not correlated
with a measurable increase in activity. Studies
using other compounds lead the authors to conclude
that the block on memory was separate from the hyper-
activity and was due to inhibition of protein synthesis.
(1) 120 mg/kg
(2) 200 meg
(3) Amt ns. follwoed 3 hr 45 min by amphetamine, 1 mg/kg,
or saline.
ROUTE AND SITE: Topical, ionophoresis
CONTROL INFORMATION: Laboratory
ROUTE AND SITE: s.C. or Intracerebral
CONTROL INFORMATION: Controls saline treated.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry, electrophysiology
DURATION OF EXPERIMENT: 3 hr
EXAM. TYPE: Behavior
429
430
-------
COMPOUND: Glutaramide, 3-(2-(3,5-dimethyl-2-oxocyclohexyl)-2-hydroxymethyl)
000066819
REFERENCE: Zech, R. and Domagk, G.F.
Brain Res. 86:339-342, 1975.
COMPOUND: Glutaric acid
REFERENCE: Curtis, D.R. and Watkins, J.C.
J. Neurochem. 6:117-141, 1960.
OBSERVED NEUROTOXIC EFFECTS: The compound inhibited the activity of the
enzyme, noncompetitively and reversibly.
OBSERVED NEUROTOXIC EFFECTS:
Treatment caused excitation or depression of
neuronal activity. Excitatory ranking: glutamic,
B-aminoglutaric, aspartic, cysteic, cysteine-
sulfinic acids, B-hydroxyglutamic, N-methylaspartic,
N-fonniminoaspartic acids.
Depressant ranking: B-alanine, GABA, taurine,
N-methyl-8-alanine, 6-amino-g-hydroxybutyric,
glycine, a-alanine, 6-aminovaleric, B-aminoisobutyric
acids.
Structure-activity relationships established.
ANIMALS: In.vitro human brain acetylcholinesterase
ANIMALS:
Cats, surgically prepared to expose motoneurones, Renshaw cells or
dorsal horn interneurones in lumbar cord.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Chemical enzyme inhibition system
PREPARATION AND DOSE
or HISTORY OF PATIENT: Qualitative doses.
ROUTE AND SITE: In vitro
CONTROL INFORMATION: Lab
ROUTE AND SITE: Topical, ionophoresis
CONTROL INFORMATION: Laboratory
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry, electrophysiology
431
432
-------
COMPOUND:
Glutaric acid, 2-oxo-
COMPOUND: Glutarimide, 3-(2-(3,5-dimethyl-2-oxocyclohexyl)-2-hvdroxyethy1)
REFERENCE: Olney, J.W., Ho, O.L. and Rhee, V.
Exp. Brain Res. 14:61-76, 1971.
REFERENCE: Segal, D.S., Squire, L.R. and Barondes, S.H.
Science 172:62-83, 1971.
OBSERVED NEUROTOXIC EFFECTS: No cytotoxicity was observed.
OBSERVED NEUROTOXIC EFFECTS: Depression in activity from 1-4 hr after injection.
Depression did not differ significantly from that
produced by cycloheximide. No amnesic effect.
Compound does not markedly inhibit cerebral protein
synthesis. Authors conclude depression activity
is unrealted to either amnesic action or to inhibition
of cerebral protein synthesis.
ANIMALS: Mice, Swiss-webster age 10 d, total 250
ANIMALS: Mice
PREPARATION AND DOSE
or HISTORY OF PATIENT: Initially 12 mmoles/kg, then range established for
each compound.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 200 meg
ROUTE AND SITE: s.C.
CONTROL INFORMATION: Compounds compared with monosodium L-glutarcate (MSG)
potency for selectively necrosing neurons in retina
and brain (hypothalamus)
DURATION OF EXPERIMENT: 5 hr or serial intervals including 5 hr.
EXAM. TYPE: Histology
ROUTE AND SITE: Intracerebrally
CONTROL INFORMATION: Controls saline treated
DURATION OF EXPERIMENT: At least 4 d.
EXAM. TYPE: Behavior, light discrimination tests.
433
434
-------
COMPOUND:
Glutarimlde, 3-ethyl-3-methyl-
REFERENCE: Cohen, B., Rey-Bellet, J. and Bergman, P.S.
Neurology 10: 1024-1030, 1960.
COMPOUND: Gluterimide, 2-ethyl-2-phenyl-
000077214
REFERENCE: Ambre, J.J. and Fischer, L.J.
Res. Comm. Chem. Path. Pharm. 4: 307-326, 1972*
OBSERVED NEUROTOXIC EFFECTS: Grand mal seizures were induced 33 times in 26 patients,
psychomotor seizures in 2. The authors concluded that
the compound was safe for EEC activation.
OBSERVED NEUROTOXIC EFFECTS: Treatment with compound resulted in a coma lasting
about 36 hours. The intensity of the coma appeared to
correlate to the plasma level of an unidentified major
metabolite.
ANIMALS: 63 patients with definite brain disease
PREPARATION AND DOSE
or HISTORY OF PATIENT: 10-915 mg, no other details
ANIMALS: Humans: 6 patients
Dogs: 4 healthy mongrels, 20 kg
Rats: M, S-D, 400 g
PREPARATION AND DOSE
or HISTORY OF PATIENT: Humans: intoxicated by overdoses (1 case of 10 g reported)
Dogs: 400 mg/kg
Rats: 400 mg/kg
ROUTE AND SITE: ns
CONTROL INFORMATION: ns
ROUTE AND SITE: Oral (humans); gavage (dogs, rats)
CONTROL INFORMATION: Humans, 3 healthy M, 70-84 kg, 1 g/subject orally
DURATION OF EXPERIMENT: ns
EXAM. TYPE: clinical, EEC
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Behavior, biochemistry
435
436
-------
COMPOUND: Glur.erimide. 2-ethyl-2-phenyl-
000077214
REFERENCE: Haas, D.C. and Maraslgan, A.
J. Neurol. Neurosurg. Psychiat. 31: 561-564, 1968.
COMPQJJND: Gluterimlde, 2-ethyl-2-phenyl-
000077214
REFERENCE:Melville, K., Jordon, G., Douglas, D.
Toxicology and Applied Pharmacology 9:363-375, 1966.
OBSERVED NEUROTOXIC EFFECTS: Cerebellar ataxla, organic mental changes, peripheral
neuropathy
OBSERVED NEUROTOXIC EFFECTS: Ataxia, complete surgical anesthesia in 3-6 hrs.
Synergistic action with alcohol increased and
hastened central nervous system depression and
with increased dose produced surgical anesthesia.
ANIMALS: Human: 3 F, 41-45
ANIMALS: Mongrel dogs, 7.0-12.0 kg, M and F.
PREPARATION AND DOSE
or HISTORY OF PATIENT: History of alcohol treated, replaced or supplemented with
compound 1-4 g/d
PREPARATION AND DOSE
or HISTORY OF PATIENT: 100-300 mg/kg in total volumes of 50-8 ml water.
ROUTE AND SITE: Oral
CONTROL INFORMATION: None
ROUTE AND SITE: Stomach tube
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: 2 mo to 8 yr (according to histories)
EXAM. TYPE: Clinical, electrophysiology
DURATION OF EXPERIMENT: More than 1 wk.
EXAM. TYPE Behavior
437
438
-------
COMPOUND: Glycine, N-sllyl-
COMPOUND: Glycine, N-allyl-
REFERENCE: Horton, R.W. and Meldrum, S.S.
Br. J. Pharmac. 49: 52-63, 1973-
REFERENCE: Meldrum, B.S., Horton, R.W. and Brierley, J.B.
Brain 97:407-418, 1974.
OBSERVED NEUROTOXIC EFFECTS:
Seizures, photic stimulation, EEC changes, inhibition
of brain glutamate carboxylase were caused by 3-mer-
captopropionic acid more strongly than by allylglycine
or 4-deoxypryidoxine HC1. Thus the authors concluded
that seizures were due to depletion of glycine and j-
aminobutyric acid (GABA).
OBSERVED NEUROTOXIC EFFECTS: Tonic-clonic seizures in varying degrees. Eventual
brain damage in some. Selective changes in
hippocampus and neocortex, later neuronal loss
and gliosis; authors inferred medial temporal sclerosis.
ANIMALS: Mice, CFW or BALB/C, M, 20-30 g
10 Baboons (Papio papio), adolescent, from Senegal, 3-6 kg
ANIMALS: 13 Baboons: 9 _P_. papio and 4 P. cynocephalus, 3.4-6.6 kg, surgically
prepared.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Mice: ED5Q and latency 1.0 mmol/kg, 160 min.
Baboons: ED.- and latency 4 mmol/kg, 100 min.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 350-630 mg/kg in saline
ROUTE AND SITE: Mice I.P., Baboons I.V.
CONTROL INFORMATION: Timed studies
ROUTE AND SITE: I.V.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Mice: behavior, biochemistry; baboons: polygraph.
DURATION OF EXPERIMENT: 42 d
EXAM. TYPE: EEC, histology, pathology
439
440
-------
COMPOUND: Glycine, N-(gamma-glutamyl)-, L-
COMPOUND: Glycolic acid, hydrazide
REFERENCE: Curtis, D.R. and Watkins, J.C.
J. Neurochem. 6:117-141, 1960.
OBSERVED NEUROTOXIC EFFECTS:
ANIMALS:
Treatment caused excitation or depression of
neuronal activity. Excitatory ranking: glutamic,
B-aminoglutaric, aspartic, cysteic, cysteine-
sulfinic acids, 6-hydroxyglutamic, N-methylaspartic,
N-formiminoaspartic acids.
Depressant ranking: B-alanine, GABA, taurine,
N-methyl-8-alanine, 6-amino-B-hydroxybutyric,
glycine, a-alanine, 6-aminovaleric, B-aminoisobutyric
acids.
Structure-activity relationships established.
Cats, surgically prepared to expose motoneurones, Renshaw cells or
dorsal horn interneurones in lumbar cord.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Qualitative doses.
REFERENCE: Jenney, E.H. and Pfeiffer, C.C.
J. Pharm. Exp. Ther. 122: 110-123, 1958.
OBSERVED NEUROTOXIC EFFECTS: Convulsions
ANIMALS: Mice, Harlan, 19-21 g
PREPARATION AND DOSE
or HISTORY OF PATIENT: 8.9 mM/kgm
ROUTE AND SITE: Topical, ionophoresis
CONTROL INFORMATION: Laboratory
ROUTE AND SITE: I.P.
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry, electrophysiology
DURATION OF EXPERIMENT: Acute
EXAM. TYPE: Clinical
441
442
-------
COMPOUND:
REFERENCE: Walsh, J.C.
Neurology 20:455-458, 1970.
COMPOUND: Guanidine, (2-(hexahydro-l(2H)azocinyl)ethyl)-, sulphate (2:1)
000060026
REFERENCE: Quinton, R.M.
Br. J. Phannac. 21:51-66, 1963.
OBSERVED NEUROTOXIC EFFECTS: Acute peripheral neuropathy, mainly sensory
impairment, severe axonal degeneration in sural nerve.
OBSERVED NEUROTOXIC EFFECTS: The compound enhanced the effect of Yohimbine
and lowered its lethal dosage.
ANIMALS: Human: one case, F, 63 yr.
ANIMALS:
Mice, TT, M, 18-25 g.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 3 doses in 2 wk of sodium aurothiomalate (44.5-46% Au)
total 85 mg Au, for osteoarthritis.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
ED5Q >50 mg/kg
ED._ = dose producing a 50% mortality of mice injected
S.C. with yohimbine hydrochloride (20 mg/kg).
ROUTE AND SITE: Inj.
CONTROL INFORMATION: None
ROUTE AND SITE: S.C., Oral
CONTROL INFORMATION: Various
DURATION OF EXPERIMENT: 2 wk with follow-up, period ns.
EXAM. TYPE: Behavior, electrophysiology, histology (biopsy)
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Behavior, electrophysiology, biochemistry
443
444
-------
COMPOUND: Harrisite
COMPOUND: HEF-2 (mix of alkylpentaborane derivatives)
REFERENCE: Satran, R.
Neurology 11: 928-932, 1961
REFERENCE: Feinsilver, L., Lawson, L.H., Berntson, L.G., Yevich, P.P. and Groff, W.A.
U.S. Arm-/ report CRDLR 3035, 1960.
OBSERVED NEUROTOXIC EFFECTS: Grand mal seizures, EEC paroxysmal bursts of moderate
voltage spikes followed by high voltage waves, residual
on overbreathing throughout test period. Inferred from
review of literature to result from major component.
OBSERVED NEUROTOXIC EFFECTS:
Acute: ataxia, tremors, convulsions, hyperactivity
on recovery; no lesions found in brain (dogs).
Subacute: similar but less severe, guinea-pigs
least severe; no lesions found (but dogs had increase
of CSF). Concluded: Compound highly neurotoxic to
central nervous system, speculatively inhibiting
vital enzymes (but no ultrastructure was studied).
ANIMALS: Human: 3 cases, M, ages 22-32
PREPARATION AND DOSE
or HISTORY OF PATIENT: Chewed for 30 sec to 10 min
ROUTE AND SITE: Oral
CONTROL INFORMATION: None
ANIMALS: Acute: dogs, beagle, M and F.
Subacute: rats, M, ages 8-10 wk; mice, F, 8-10 wk; dogs, beagle, M;
guinea-pigs (no details) .
Odor detection: 15 volunteers, human
PREPARATION AND DOSE
or HISTORY OF PATIENT: Acute: 6 or 9.5 ppm for 4 hr (dogs, grps of 3).
Subacute: 1.9 ppm 6 hr/d, 5 d/wk, 30 d (25 rats);
same for 22 d (3 dogs); same for 31 d
(10 guinea-pigs).
Odor detection: 0.41-26.1 ppm, time ns, median threshold 6.4 ppm.
ROUTE AND SITE: Inhalation
CONTROL INFORMATION: Subacute: equal numbers untreated
DURATION OF EXPERIMENT: Up to 5 mo
EXAM. TYPE: EEC, clinical
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry, behavior, histology
445
446
-------
COMPOUND: ct-Hemolysin from Staphylococcus aureus
REFERENCE: Edelwejn, Z., Jeljaszewicz, J., Szmlgielski, S. and Zak, C.
Tox. Appl. Phann. 13:133-145, 1968.
OBSERVED NEUROTOXIC EFFECTS:"Collapse of the brain bioelectric activity" (EEC
tracings), partly prevented by antagonist. Compound
interpreted to disturb repolarization of stimulated
neurons.
COMPOUND: (-)-Heptadeca-trans-8,10,12-Trlene-4,6-Diyne-l,14-Diol
000505759
REFERENCE: Starreveld, E. and Hope, C.E.
Neurology 25:730-734, 1975.
OBSERVED NEUROTOXIC EFFECTS: Muscarinic effects, convulsions, "diffusely
abnormal" EEC, hypoxia, metabolic acidosis.
ANIMALS: 20 Rabbits, Polish lowland, M, 3 kg, surgically prepared
ANIMALS: Human: 1 case-report, M, age 54.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 10 meg/kg of purified compound with/without an antagonist
Cp_-chlorophenoxyacetic acid-dimethylaminoethyl chlorohydrate,
centrophenoxine) on various schedules.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Ate 2 bites of root, thinking plant to be type of parsnip.
ROUTE AND SITE: i.v.
CONTROL INFORMATION: Recordings before test
ROUTE AND SITE: oral
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: About 6 d.
EXAM. TYPE: EEC-
DURATION OF EXPERIMENT: n d
EXAM. TYPE: Clinical, EEC, hospital laboratory
448
-------
COMPOUND: Hepcanedioic acid, 4-amino-
COMPOUND: Heptanedioic acid, 2-amino-, DL-
REFERENCE: Curtis, D.R. and Watkins, J.C.
J. Neurochem. 6:117-141, 1960.
REFERENCE: Curtis, D.R. and Watkins, J.C.
J. Neurochem. 6:117-141, 1960.
OBSERVED NEUROTOXIC EFFECTS:
Treatment caused excitation or depression of
neuronal activity. Excitatory ranking: glutamic,
6-aminoglutaric, aspartic, cystelc, cysteine-
sulfinic acids, 8-hydroxyglutamic, N-methylaspartic,
N-formiminoaspartic acids.
Depressant ranking: S-alanine, GABA, taurine,
N-methyl-B-alanine, S-amino-B-hydroxybutyric,
glycine, a-alanine, 6-aminovaleric, S-aminoisobutyric
acids.
Structure-activity relationships established.
OBSERVED NEUROTOXIC EFFECTS:
Treatment caused excitation or depression of
neuronal activity. Excitatory ranking: glutamic,
6-aminoglutaric, aspartic, cysteic, cysteine-
sulfinic acids, 8-hydroxyglutamic, N-methylaspartic,
N-formiminoaspartic acids.
Depressant ranking: 6-alanine, GABA, taurine,
N-methyl-B-alanine, 6-amino-B-hydroxybutyric,
glycine, a-alanine, 6-aminovaleric, B-aminoisobutyric
acids.
Structure-activity relationships established.
ANIMALS:
Cats, surgically prepared to expose motoneurones, Renshaw cells or
dorsal horn interneurones in lumbar cord.
ANIMALS:
Cats, surgically prepared to expose motoneurones, Renshaw cells or
dorsal horn interneurones in lumbar cord.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Qualitative doses.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Qualitative doses.
ROUTE AND SITE: Topical, ionophoresis
CONTROL INFORMATION: Laboratory
ROUTE AND SITE: Topical, ionophoresis
CONTROL INFORMATION: Laboratory
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry, electrophysiology
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry, electrophysiology
450
-------
COMPOUND: Heptanedioic acid, 2-amino-, DL-
COMPOUND: Heptanedioic acid, 2,5-diamino-, L-
P.EFERENCE: Olney, J.W. , Ko, O.L. ,-nd Rhee, V.
Exp. Brain Res. 14:61-76, 1971.
OBSERVED NEUROTOXIC EFFECTS: Ko cytotoxicity was observed.
ANIMALS: Mice, Swiss-webster age 10 d, total 250
PREPARATION AND DOSE
or HISTORY OF PATIENT: Initially 12 mmoles/kg, then range established for
each compound.
REFERENCE: Curtis, D.R. and Watkins, J.C.
J. Neurochem. 6:117-141, 1960.
OBSERVED NEUROTOXIC EFFECTS:
ANIMALS:
Treatment caused excitation or depression of
neuronal activity. Excitatory ranking: glutamic,
B-aminoglutaric, aspartic, cysteic, cysteine-
sulfinic acids, 6-hydroxyglutamic, N-methylaspartic,
N-fortniminoaspartic acids.
Depressant ranking: 6-alanine, GABA, taurine,
N-methyl-B-alanine, 6-amino-6-hydroxybutyric,
glycine, a-alanine, 6-aminovaleric, B-aminoisobutyric
acids.
Structure-activity relationships established.
Cats, surgically prepared to exposed inotoneurones, Renshaw cells or
dorsal horn interneurones in lumbar cord.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Qualitative doses.
ROUTE AND SITE:
S.C.
CONTROL INFORMATION: Compounds compared with monosodium L-glutamate (MSG)
potency for selectively necrosing neurons in retina
and brain (hypcthalamus)
DURATION OF EXPERIMENT: 5 hr or serial intervals including 5 hr.
EXAM. TYPE: Histology
ROUTE AND SITE: Topical, ionophoresis
CONTROL INFORMATION: Laboratory
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry, electrophysiology
452
-------
COMPOUND:
Hexane
000110543
REFERENCE: Herskowitz, A., Ishl, N. and Schaumberg, H.
New Eng. J. Med. 285:82-85, 1971.
OBSERVED NEUROTOXIC EFFECTS: Weakness and sensory loss after 2-4 mo., dose-
related, peripheral nervous system demyelination and axonal degeneration,
denervation of muscles, slow clinical recovery. Authors recommend that
current safety limit of 500 ppm be reduced to 100 ppm as in Japan.
ANIMALS: Human: 3 cases, F, age 27-47.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Exposure to 650-1300 ppm in air, industrially.
COMPOUND: Hexanedioic acid, 2-amino-, DL-
REFERENCE: Curtis, D.R. and Watkins, J.C.
J. Neurochem. 6:117-141, 1960.
OBSERVED NEUROTOXIC EFFECTS:
ANIMALS:
Treatment caused excitation or depression of
neuronal activity. Excitatory ranking: glutamic,
B-aminoglutaric, aspartic, cysteic, cysteine-
sulfinic acids, B-hydroxyglutamic, N-methylaspartic,
N-formiminoaspartic acids.
Depressant ranking: 6-alanine, GABA, taurine,
N-methyl-B-alanine, 6-amino-B-hydroxybutyric,
glycine, a-alanine, 6-aminovaleric, 8-aminoisobutyric
acids.
Structure-activity relationships established.
Cats, surgically prepared to expose motoneurones, Renshaw cells or
dorsal horn interneurones in lumbar cord.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Qualitative doses.
ROUTE AND SITE: Inhalation, cutaneous, oral
CONTROL INFORMATION: None
ROUTE AND SITE: Topical, ionophoresis
CONTROL INFORMATION: Laboratory
DURATION OF EXPERIMENT: Over 6 mo.
EXAM. TYPE: Clinical, electrophysiology, histology (biopsy), biochemistry
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry, electrophysiology
453
454
-------
COMPOUND: Hexanedioic acid, 2-amino-, DL-
COMPOUND: Hexanedioic acid, 2-amino-, DL-
REFERENCE:Curtis, D.R. and Watkins, J.C.
J. Physiol. 166:1-14, 1963.
OBSERVED NEUROTOXIC EFFECTS: N-methyl-D-aspartic and D-homocysteic acids were
stronger excitants of depolarization than all
others. With some compounds the action was
prolonged for many seconds after the stimulus
was terminated, notably N-n-propyl-D-aspartic
acid. There were no differences among types of
neurons tested; structure-activity relationship
was observed.
REFERENCE: Olney, J.W., Ho, O.L. and Rhee, V.
Exp. Brain Res. 14:61-76, 1971.
OBSERVED NEUROTOXIC EFFECTS: The compound was toxic to non-neurol components
(glia, etc.), but not to neurons.
ANIMALS: Cats prepared for electrophoretic application of chemicals to single
central nervous system neurons.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Dilutions 0.1-0.5 M of 31 compounds mainly of aspartic,
glutamic and cysteic acids listed in order of
potency of results.
ANIMALS: Mice, Swlss-webster age 10 d, total 250
PREPARATION AND DOSE
Or HISTORY OF PATIENT: Initially 12 nmoles/kg, then range established for
each compound.
ROUTE AND SITE: Electrophoretic application, various sites in central nervous
system.
CONTROL INFORMATION:
None
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Electrophysiological
ROUTE AND SITE: s.C.
CONTROL INFORMATION: Compounds compared with monosodium L-glutamate (MSG)
potency for selectively necrosing neurons in retina
and brain (hypothalamus)
DURATION OF EXPERIMENT: 5 hr or serial intervals including 5 hr.
EXAM. TYPE: Histology
455
456
-------
COMPOUND: 2,5-Sexanedione
COMPOUND: 2,5-Hexanedione
REFERENCE: Raleigh, R.L., Spencer, P.S. and Schaumburg, H.H.
J. Occup. Med. 17:286, 1975. (Letter to Editor)
OBSERVED NEUROTOXIC EFFECTS: Peripheral neuropathy observed in both groups.
REFERENCE: Spencer, P.S. and Schaumburg, H.H.
J. Neurol. Neurosurg. Psychiat. 38:771-775, 1975.
OBSERVED NEUROTOXIC EFFECTS: Peripheral neuropathy with dying-back peripheral an.
central nervous system degeneration; giant axonal swelling and massed
neurofilaments.
ANIMALS: Rats
ANIMALS: 6 rats, S-D, 400 g
PREPARATION AND DOSE
or HISTORY OF PATIENT:
(1) Av. dose 340 mg/kg/d, 5d/wk for 19 wk.
(2) Av. 25 mi of 0.5% soln, 520 mg/kg/d for 2 mo.
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) 0.1 ml/rat/d, 5 d/wk for 13 wk or
(2) 0.2 or 0.4 ml/rat/d for 6-10 wk,
Mean total was equivalent to 340 mg/kg/d.
ROUTE AND SITE: (1) E.G. (2) Oral
CONTROL INFORMATION: ns,
ROUTE AND SITE: S.C.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: (1) 19 wk (2) 2 mo.
EXAM. TYPE: ns.
DURATION OF EXPERIMENT: Up to 13 wk
EXAM. TYPE: Behavior, histology
45 /
458
-------
COMPOUND: 2-Hexanone
000591786
REFERENCE: Allen, N., Mendell, J.R., Billmaier, D.J., Fontaine, R.E. and O'Neill, J.
Arch. Neurol 32:209-218, 1975.
OBSERVED NEUROTOXIC EFFECTS: Peripheral neuropathy: distal, motor, and
sensory disorder with minimal reflex loss. Muscle weakness and sensory
loss most common in hands and feet. No evidence of autonomic dysfunction
observed.
COMPOUND:
2-Hexanone
000591786
REFERENCE: Billmaier, D., Yee, H.T., Allen, N., Craft, B., Williams, N.,
Epstein, S. and Fontaine, R.
J. Occup. Med. 16:665-671, 1974.
OBSERVED NEUROTOXIC EFFECTS:
All workers screened for nerve conduction and
electromyography, 192 referred for study, 68 with
definite peripheral neuropathy, 28 more suspected,
6 severe. Sural nerve biopsies normal. Part-
recovery in 6 mo. or more, severe cases.
ANIMALS:
86 cases in 1,157 employees screened at a factory in Ohio.
ANIMALS:
Human: 1157 workers at a coated fabrics plant.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Workers in plant producting plastic-coated and color-
printed fabrics. Methyl n-butyl Ketone was implicated as causative agent on the
basis of correlation with exposure, with incidence and severity of disease,
and temporal course of out break. Exposure to 36 ppm in air for over
42 hr/wk. Synergistic effect with methyl ethyl ketone or other chemicals
possible.
ROUTE AND SITE: inhalation, skin contact
CONTROL INFORMATION: Investigative (questions and answers), retrospective
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Of approx 275 chemicals MBK was suspected (timing of use and
of cases) but methyl ethyl ketone and phthalate esters
were not ruled out. Cases centered on print-shop, were
related to work-load and to eating at work.
ROUTE AND SITE: Inhalation, skin contact, ingestion considered.
CONTROL INFORMATION: Sought but not rigorously established.
DURATION OF EXPERIMENT: Approx. 1 yr.
EXAM. TYPE: clinical and electrodiagnostic
DURATION OF EXPERIMENT: Ongoing
EXAM. TYPE: Electrophysiology, behavior, biopsy, clinical, laboratory.
459
460
-------
COMPOUND: 2-Hexanone
000591786
REFERENCE: Duckett, S., Williams, N. and Francis, S.
New Eng. J. Med. 290:1264, 1974.
OBSERVED NEUROTOXIC EFFECTS: Sciatic nerves axonal edema, degeneration associated
with secondary myelin breakdown.
COMPOUND:
2-Hexanone
000591786
REFERENCE: McDonough, J.R.
New Eng. J. Med. 290:695, 1974. (Letter to Editor)
OBSERVED NEUROTOXIC EFFECTS: Peripheral neuropathy
ANIMALS: (1) 9 rats, (2) 8 rats
ANIMALS:
6 rats
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) 200 ppm in air, 8 hr/d, 5 d/wk, for 6 wk.
(2) same plus methyl-ethyl ketone 2000 ppm.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
1300 ppm in air, 6 hr/d, 5 d/wk, 4 mo. (TLV is 100 ppm
410 mg/m ).
ROUTE AND SITE: Inhalation
CONTROL INFORMATION: ns.
ROUTE AND SITE: Inhalation
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: 6 wk
EXAM. TYPE: Histology
DURATION OF EXPERIMENT: 4 ">o-
EXAM. TYPE: ns.
461
462
-------
COMPOUND: 2-Hexanone
000591786
REFERENCE: Mendell, J.R.,
New Eng. J. Med 290: 1263-1264, 1974.
OBSERVED NEUROTOXIC EFFECTS:
182 employees with abnormal electrophyslology, 79
with clinical polyneuropathy, peripheral, related
epidemiologically to exposure. Chickens had signs
of nerve damage after 35 d at 200 ppm, cats at
33 d and rats at 60 d of 400-600 ppm. Limb weakness,
slow conduction, swollen axons, demyellnation. Rat
and human exposures were seen as "remarkably close"
in duration.
COMPOUND:
REFERENCE:
2-Hexanone
000591786
Mendell, J.R., Salda, K., Ganansia, M.F., Jackson, D.B.,
Weiss, H., Gardner, R.W., Chrisman, C., Allen, N.,
Couri, D., O'Neill, J.
Science 185:787-789, 1974.
OBSERVED NEUROTOXIC EFFECTS: Hindlimb then forelimb weakness in animals, increased
water intake, slow nerve conduction in cats, with disturbed
patterns, demyelination and axonal degeneration in
animals.
ANIMALS: 1. Human: 1161 industrial employees
2. Rats, cats, chickens
PREPARATION AND DOSE
or HISTORY OF PATIENT: 1. Exposure, 8-12 hr/d 22-24 d/mo for 9 mo. total 1584-2592
hr.
2. 200-600 ppm 24 hr/d, 7 d/wk, 60 d for .total 1440
hr exposures.
ANIMALS: 5 chickens, domestic
4 Rats, S-D
4 Cats, domestic
PREPARATION AND DOSE
or HISTORY OF PATIENT: All groups exposed 24 hr/d for 2 mo., total 1440 hr.
Chickens: 200 ppm in air, reduced to 100 ppm.
Rats: 600 ppm reduced to 400 ppm.
Cats: 600 ppm reduced to 400 ppm.
ROUTE AND SITE: Inhalation
CONTROL INFORMATION: ns
ROUTE AND SITE: Inhalatlon
CONTROL INFORMATION: Pair-fed matched controls
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Electrophysiology, behavior, histology
DURATION OF EXPERIMENT: 2 mo., on going
EXAM. TYPE: Behavior, electorphysiology, histology.
463
464
-------
COMPOUND: 2-Hexanone
000591786
REFERENCE: Raleigh, R.L., Spencer, P.S. and Schaumburg, H.H.
J. Occup. Med. 17:286, 1975 (Letter to Editor)
OBSERVED NEUROTOXIC EFFECTS: (1) No evidence of clinical neuropathy. Minimal
" histologic changes in nerve fibers in cats treated
with 330 ppm for 4.5 months, not seen in 100 ppm
group. Histological exam of rats incomplete to
date. (2) Clinical neuropathy seen. (3) Clinical
neuropathy was not produced.
COMPOUND: HiCal-2
REFERENCE: Feinsilver, L., Lawson, L.H., Yevich, P.P. and Jacobson, K.H.
D.S. Army CWL Report CWLR 2367, 1960.
OBSERVED NEUROTOXIC EFFECTS: LC«.n under conditions were:
50 3 3
Rats-103 mg/m ; mice-96 mg/m . Signs included •
ataxia, depression, prostration, tremors, clonic
convulsions, interpreted as "marked effect upon"
the central nervous system.
ANIMALS: (1) Cats, rats (2) Cats and dogs (3) Guinea pigs
PREPARATION AND DOSE
or HISTORY OF PATIENT: (D 330 ppm and 100 ppm for 6 hr/d, 5d/wk for 5 mo.
(2) 150 rag/kg, 2/d, 5d/wk for 2 mo(cat) 2-4 mo dogs.
(3) Amt ns., repeated applications over period of 8 mo.
ANIMALS: Rats, ages 8-10 wk, M
Mice, 8-10 wk, F
Dogs, beagle, M.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Exposed to vapors of compounds in LC5Q study, 2-4 hr
ROUTE AND SITE: (1) Inhalation (2) S.C. (3) Top. Sk.
CONTROL INFORMATION: ns.
ROUTE AND SITE: Inhalation
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Clinical, histological
DURATION OF EXPERIMENT: Observation to 7 d after exposure
EXAM. TYPE: Behavior, pathology
465
466
-------
COMPOUND:
Holothurin A
COMPOUND: D-Homocysteic acid
REFERENCE: Thron, C.D., Durant, R.C. and Friess, S.L.
Tox. Appl. Pharm. 6:182-196, 1964.
REFERENCE:Curtis, D.R. and Watkins, J.C.
J. Physiol. 166:1-14, 1963.
OBSERVED NEUROTOXIC EFFECTS:
Lower concentrations produced tissue responses that
were "largely irreversible," loss of excitability,
and blocks of nerve conduction. Interaction
of this animal saponin with chemoreceptors in nerve
and neuromuscular tissues is discussed.
OBSERVED NEUROTOXIC EFFECTS:
N-methyl-D-aspartic and D-homocysteic acids were
stronger excitants of depolarization than all
others. With some compounds the action was
prolonged for many seconds after the stimulus
was terminated, notably N-n-propyl-D-aspartic
acid. There were no differences among types of
neurons tested; structure-activity relationship
was observed.
ANIMALS:
In vitro nodes of Ranvier from desheather sciatic nerves of frog
(R. pipiens), and rat phrenic nerve-diaphragm preparations
ANIMALS: Cats prepared for electrophoretic application of chemicals to single
central nervous system neurons.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 5.54 x 10~10 to 10~4 M in medium, applied for brief periods.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Dilutions 0.1-0.5 M of 31 compounds mainly of aspartic,
glutamic and cysteic acids listed in order of
potency of results.
ROUTE AND SITE: In vitro
CONTROL INFORMATION: Zero application.
ROUTE AND SITE: Electrophoretic application, various sites in central nervous
system.
CONTROL INFORMATION:
None
DURATION OF EXPERIMENT: Up to about x hr.
EXAM. TYPE:
Electrophysiology
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Electrophysiological
467
468
-------
COMPOUND: DL-Homocystelc acid
COMPOUND:
DL-Homocysteic acid
REFERENCE:Curtis, D.R. and Watkins, J.C.
J. Physiol. 166:1-14, 1963.
OBSERVED NEUROTOXIC EFFECTS:
N-methyl-D-aspartic and D-homocysteic acids were
stronger excitants of depolarization than all
others. With some compounds the action was
prolonged for many seconds after the stimulus
was terminated, notably N-ii-propyl-D-aspartic
acid. There were no differences among types of
neurons tested; structure-activity relationship
was observed.
REFtRENCE:
Olney, J.W., Ho, O.L. and Rhee, V.
Exp. Brain Res. 14:61-76, 1971.
OBSERVED NEUROTOXIC EFFECTS:
The compound was more potent than monosodium
glutamate in necrosing neurons in the retina
and brain. This compound is a powerful neuro-
excitant and the neurotoxic properties may be
governed by similar mechanisms.
ANIMALS: Cats prepared for electrophoretic application of chemicals to single
central nervous system neurons.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Dilutions 0.1-0.5 M of 31 compounds mainly of aspartic
glutamic and cysteic acids listed in order of
potency of results.
ANIMALS: Mice, Swiss-webster age 10 d, total 250
PREPARATION AND DOSE
or HISTORY OF PATIENT: Initially 12 mmoles/kg, then range established for
each compound.
ROUTE AND SITE:
CONTROL INFORMATION:
Electrophoretic application, various sites in central nervous
system.
None
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Electrophysiological
ROUTE AND SITE: s.C.
CONTROL INFORMATION: Compounds compared with moncsodium L-glutamate (MSG)
potency for selectively necrosing neurons in retina
and brain (hypothalamus)
DURATION OF EXPERIMENT: 5 hr or serial intervals including 5 hr.
EXAM. TYPE: Histology
469
470
-------
COMPOUND: L-Homocysteic acid
REFERENCE:Curtis, D.R. and Watkins, J.C.
J. Physiol. 166:1-14, 1963.
OBSERVED NEUROTOXIC EFFECTS: N-methyl-D-aspartic and D-homocysteic acids were
stronger excitants of depolarization than all
others. With some compounds the action was
prolonged for many seconds after the stimulus
was terminated, notably N-n_-propyl-D-aspartlc
acid. There were no differences among types of
neurons tested; structure-activity relationship
was observed.
ANIMALS: Cats prepared for electrophoretic application of chemicals to single
central nervous system neurons.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Dilutions 0.1-0.5 M of 31 compounds mainly of aspartic,
glutamic and cysteic acids listed in order of
potency of results.
ROUTE AND SITE: Electrophoretic application, various sites in central nervous
system.
CONTROL INFORMATION:
None
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Electrophysiological
471
COMPOUND: Hydantoin, 5,5-diphenyl- (Phenytoin)
000057410
REFERENCE: Ahmad, S., Laidlaw, J., Houghton, G.W. and Richens, A.
J. Neurol. Neurosurg, Psychiat. 38:225-231, 1975.
OBSERVED NEUROTOXIC EFFECTS: Intoxication confirmed by serum phenytoin levels.
Choreoathetoid movements typical. In 3 cases intoxication resulted from
drug interactions.
ANIMALS: Human: 4 cases (m 19, F 34, F 28, F 61) epileptics
PREPARATION AND DOSE
or HISTORY OF PATIENT: Usual dose 300 g/d long term
ROUTE AND SITE: Oral
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: Years
EXAM. TYPE: Clinical, EEC, blood chemistry
472
-------
COMPOUND: Hydanm-tn. 5,5-diphenyl-
000057410
REFERENCE: Dam, M.
Acta Neurol. Scand. 42:491-494, 1966.
H..J ._..-.*-
OBSERVED NEUROTOXIC EFFECTS:
Severe ataxia, uncertain gait, difficulty in turning,
falling. Attacks recalled brain stem attacks with
tonic convulsions in legs in one pig. One showed
nystagmus. Cerebellum had altered Purkinje cells
swollen in 1 pig, shrunken and swollen in other.
Loss of ganglion cells with empty synapses.
REFERENCE: del Cerro, M.P. and Snider, R.S.
Neurology 17:452-466, 1967.
OBSERVED NEUROTOXIC EFFECTS: Severely ataxic at time of sacrafice. infrastructure
study. Lamellar concentric bodies typical of lipoidoses throughout cerebellar
cortex but most affecting Purkinje cells. Some myelinated axons were altered.
ANIMALS: 3 Pigs, 20 kg, litter-mates
ANIMALS: 30 Rats, Wistar, adult M, 200 g.
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) 10 mg/kg followed by increasing doses for 3 mo.
(2) As above, except starting with 20 mg/kg.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 10 mg/d, 5 d/wk for 1 wk, then 20 mg/d, then 30 mg/d,
then 40 mg/d for 5 d/wk till death or sacrifice. Elsewhere authors state
drug discontinued after 10 wk in animals kept for 6 mo.
ROUTE AND SITE: oral
CONTROL INFORMATION: i pig untreated
ROUTE AND SITE: I.M.
CONTROL INFORMATION: 2 Control groups: solvent only and no treatment.
DURATION OF EXPERIMENT: Approx. 3 mo.
EXAM. TYPE: Histological and chemical
DURATION OF EXPERIMENT: Serial sacr to 6 mo.
EXAM. TYPE: Histology
473
474
-------
COMPOUND: Hydantoin, 5,5-diphenyl
COMPOUND: Hydantoin, 5,5-diphenyl
REFERENCE: Hofmann, W.W.
Neurology 8:210-214, 1958.
REFERENCE: Kooiker, J.C. and Sumi, S.M.
Neurology 1:68-71, 1974.
OBSERVED NEUROTOXIC EFFECTS: Cerebellum: Purkinje cells "virtually disappeared,"
attributed by author partly to the drug. But cause of seizures was not
found.
OBSERVED NEUROTOXIC EFFECTS: Choreoathetold symptoms that disappeared with falling
serum levels of drug and did not recur when patients took the prescribed
intake (300 mg/d) and no more.
ANIMALS: Human: 1 F, 28 yr, with multiple seizures of sudden onset.
ANIMALS: Humans: 2 case-reports of adverse drug reaction
PREPARATION AND DOSE
or HISTORY OF PATIENT: 250 mg/4 hr for 4 d, then taper off, but seizures
recurred, and 250 mg/4-6 hr reinstituted, Patient died after 16 d.
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) prescribed 300 mg/d, sometimes took more; serum level
was 40 meg/ml.
(2) prescribed 300 mg/d; serum level was 64-68 meg/ml.
ROUTE AND SITE: I.V. 1 dose, then I.M.
CONTROL INFORMATION: None
ROUTE AND SITE: Oral
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: 16 d
EXAM. TYPE: Autopsy
DURATION OF EXPERIMENT: Follow-up reported: (1) 21 mo; (2) 12 d
EXAM. TYPE: Clinical, laboratory, EEC
475
476
-------
COMPOUND: Hydantoln, 5,5-diphenyl
COMPOUND:
REFERENCE:
Kutt, H., Winters, W., Kokenge, R. and McDowell, F.
Arch. Neurol. 11:642-648, 1964.
REFERENCE: Kutt, H., Wolk, M., Scherman, R. and McDowell, F.
Neurology 14: 542-548, 1964.
OBSERVED NEUROTOXIC EFFECTS:
Diphenylhydantoin blood levels (thus ability to
metabolize) related to side-effects: nystagmus at
20, ataxia at 30 mental changes at 40 meg/ml of blood.
Extent of mental changes varied widely, with lethargy
and inability to concentrate were the most frequent
manifes tations.
OBSERVED NEUROTOXIC EFFECTS: Nystagmus, ataxia and other signs correlated with
accumulations of unmetabolized compound owing to low
activity of liver production of metabolite, which appeared
to the authors to be a genetically determined deficiency.
ANIMALS:
Human, 32 patients
ANIMALS:
Human: 2 of 4 siblings and a mother of a healthy family
PREPARATION AND DOSE
or HISTORY OF PATIENT: 4-10 mg/kg/d.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Usual dosage of about 4 mg/kg and smaller dosages.
Experimentation with an important parahydroxylated
metabolite, 5-phenyl-5'-parahydroxyphenylhydantoin, normally
resulting from enzymatic reaction in liver.
ROUTE AND SITE: Oral
CONTROL INFORMATION: None
ROUTE AND SITE: Oral
CONTROL INFORMATION: Described
DURATION OF EXPERIMENT: Long-term, not described
EXAM. TYPE: Clinical
DURATION OF EXPERIMENT: About 5 wk
EXAM. TYPE: Metabolic, genetic, clinical
477
478
-------
COMPOUND: Hydantoin, 5,5-diphenyl
COMPOUND' Hydantoin, 5,5-diphenyl
REFERENCE:
Lovelace, R.E. and Horwitz, S.J.
Arch. Neurol. 18:69-77, 1968.
REFERENCE: Morrell, F., Bradley, W. and Ptashne, M.
Neurology 8: 140-144, 1958.
OBSERVED NEUROTOXIC EFFECTS:
Peripheral neuropathy in 26, absent deep tendon
reflexes in legs (both knee and ankle in 19),
related slow nerve conduction. More frequent in those
treated>10 yr, but amount of dose no guide. Slow
conduction considered an early-warning of neuropathy
from compound.
OBSERVED NEUROTOXIC EFFECTS: The compound raised the threshold for response to electrical
stimulus, decreased the spike amplitude in A fibers, abolish-
ed "nerve repetition" and reversed the effects of oxalate.
ANIMALS: Humans: 50 selected epileptics age-range 12-50 yr.
ANIMALS: 48 Rabbits, 2-3.5 kg, prepared surgically.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 200-600 mg for 5-26 yr.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Peripheral nerve preparation in situ, doses ns.
ROUTE AND SITE: Oral
CONTROL INFORMATION: None
ROUTE AND SITE: i.V. or I.P.
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Clinical, electrophysiology
DURATION OF EXPERIMENT: ns.but in one test 90 rain.
EXAM. TYPE: Electrophysiology
479
480
-------
COMPOUND: Hydantoin, 5,5-diphenyl
REFERENCE: Norris, F.H., Colella, J. and McFarlin, D.
Neurology 14: 869-876, 1964,
OBSERVED NEUROTOXIC EFFECTS: Of human cases, 2 took massive doses, and 1 had BIZ
deficiency; neuromuscular transmission was disordered.
Competitive neuromuscular blockade appeared to result
from either end-plate depolarization or anticholin-
esterase activity.
ANIMALS: (1) Human: 3 cases
(2) Rats: 150-360 g, sciatic nerve and anterior tibial and peroneus
longus preparations
PREPARATION AND DOSE
or HISTORY OF PATIENT: (D Up to 26 mg/kg
(2) 10 mg/kg
ROUTE AND SITE: Oral
CONTROL INFORMATION: Various
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Electromyography, clinical chemistry
481
COMPOUND: Hydantoin, 5,5-diphenyl
REFERENCE: Riehl, J-L. and Mclntyre, H.B.
Neurology 18:1107-1112, 1968.
OBSERVED NEUROTOXIC EFFECTS: EEC: slowing and/or increased amplitude only
in zone(s) of abnormalities, not in unaffected
zones nor in control subjects.
ANIMALS: Humans: 5F, 3 M, ages 18-60 yr.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Epileptics with abnormal EEC and no history of drug use.
50 mg/2 min to total 250 mg.
ROUTE AND SITE: i.v.
CONTROL INFORMATION: Added: 3 volunteers, M 25, F 48, 55, not epileptics yr.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: EEC
482
-------
COMPOUND: Hydantoln, 5,5-diphenyl
COMPOUND: Hydantoin, 5,5-diphenyl
REFERENCE: Roseman, E.
Neurology 11: 912-920, 1961
OBSERVED NEUROTOXIC EFFECTS: Toxlcity manifested by Dilantin "drunkenness"
accompanied by EEC changes illustrated in detail, from
slow alpha to marked delta activity. Author suggests
these as index for managing dosage of Dilantin in
difficult cases.
REFERENCE: Selhorst, J.B., Kaufman, B. and Horwitz, S.J.
Arch. Neurol. 27:453-455, 1972.
OBSERVED NEUROTOXIC EFFECTS: Peripheral neuropathy, cerebellar damage. Not
reversed after discontinuation of drug for up to 4 yr.
ANIMALS: Human: 4 cases, 2-24 yr old
ANIMALS: 2 Humans, F aged 16, M aged 11 with epilepsy.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.1 g (infants) to 0.4-0.6 g (adults) per d, judged by
results to be maximal effective dosage (not minimal).
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Histories of 300-1000 mg/d for 28 mo. and 9.5 yr.
ROUTE AND SITE: Oral
CONTROL INFORMATION: None
ROUTE AND SITE: Oral
CONTROL INFORMATION: No controls
DURATION OF EXPERIMENT: Up to about 3 mo
EXAM. TYPE: Clinical, EEC
DURATION OF EXPERIMENT: 28 mo; 9.5 yr (histories)
EXAM. TYPE: Electrophysiologlcal, radiological
483
484
-------
COMPOUND: Hydantoin, 5,5-diphenyl
COMPOUND: Hydantoin, 5,5-diphenyl
REFERENCE: Theil, G.B., Richter, R.W., Powell, M.R. and Doolan, P.D.
Neurology 11: 138-142, 1961.
REFERENCE: Wstepne, D.
Neur. Neurochir. Pol. 8: 427-431, 1974.
OBSERVED NEUROTOXIC EFFECTS: Prolonged restless coma with cycles of responsiveness.
Hemodialysis after 138 hr thought to have prevented
worse damage. Residual frontal-lobe damage suspected
after 1 yr. Male infant born during treatment appeared
normal at birth and after 1 yr.
OBSERVED NEUROTOXIC EFFECTS: Disseminated changes in neurons, and demyelination
of white matter of cerebral hemispheres. EEC showed
modified spindles in frontal leads, interpreted as
nonpathological. Chronic dose produced blood level
of 10-20 meg/ml.
ANIMALS: Human: one F, age 18, pregnant 8
ANIMALS: 8 cats
PREPARATION AND DOSE
or HISTORY OF PATIENT: 21.5 g one dose (attempted suicide)
History of grand-mal, schizophrenia
PREPARATION AND DOSE
or HISTORY OF PATIENT: 15-20 mg/kg for "several months to 1 year"
2 cats: 10-15 mg/kg I.V. one dose
ROUTE AND SITE: oral
CONTROL INFORMATION: None
ROUTE AND SITE: Oral, I.V.
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: 1 yr
EXAM. TYPE: Behavior, EEC, clinical
DURATION OF EXPERIMENT: Up to 1 yr
EXAM. TYPE: EEC and evoked potentials, histology
485
486
-------
COMPOUND: Hydantoin, 5,5-diphenyl
REFERENCE: Yanaglhara, T. and Hamberger, A.
Exp. Neurol. 32:152-162, 1971.
OBSERVED NEUROTOXIC EFFECTS: Amino acid incorporation into proteins of cerebral
cortex: in neurons inhibited quickly with recovery,
in neuroglia prolonged inhibition; perikarya
(mainly nuclei) responded sensitively and neuro-
suppressively.
COMPOUND: Hydantoin, 5,5-diphenyl-monosodium salt (Dilantin)
000630933
REFERENCE: Kokenge, R., Kutt, H., McDowell, F.
Neurology 15:823-829, 1965.
OBSERVED NEUROTOXIC EFFECTS:
(1) Nystagmus ataxia, stuporous, disoriented.
(2) High blood 6. tissue levels of Dilatin which can
damage neural tissues, loss of Purkinje
cells & occurrence of edema of Bergmann's
glial layer.
ANIMALS: Rats, S-D, F, 150-170 g.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 80-300 mg/kg/d, various schedules.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: None
ANIMALS: (1) Human, 18 yrs, 66 kg.
(2) 36 rats, Albino, 200 gm
(3) Cats
PREPARATION AND DOSE
or HISTORY OF PATIENT:
(1) 300 mg Dilantin, 90 mg phenobarbital, 500 mg
primidone, 20 mg Librium daily. Dilantin may have
been increased to 900-1000 mg and phenobarbital 300 mg.
(2) 10, 20, 30, 50, 75, 100, 150 mg/kg daily for 15-30 d.
ROUTE AND SITE: (i) oral (2) I.M.
CONTROL INFORMATION: (3) Cats
DURATION OF EXPERIMENT: Up to 12 d
EXAM. TYPE: Biochemistry
DURATION OF EXPERIMENT: (i) 15 yr (2) 15 d
EXAM. TYPE: Neurological
487
488
-------
COMPOUND: Hydantoin, l-((5-nitrofurfurylidene)amino)-
000067209
REFERENCE: Asbury, A.K.
Lancet 1:334-335, 1963.
(Nitrofurantoin)
COMPOUND: Hydantoin, l-((5-nitrofurfurylidene)amino)-
000067209
REFERENCE: Behar, A., Rachmilewltz, E., Rahamimoff, R. and Denman, M.
Arch. JJeurol. 13:160-163, 1965.
OBSERVED NEUROTOXIC EFFECTS: Polyneuropathy reported after nitrofurantoln
In presence of renal impairment claimed to be
secondary to renal impairment, as here, where
no nitrofurantoin was given.
OBSERVED NEUROTOXIC EFFECTS: Sciatic and brachial nerves showed axonal dystrophy
in all treated rats, sciatic showed increased chronaxis
and decreased conduction.velocity; all related to
amount and duration of treatment.
ANIMALS: Human: 4 cases, M, details ns.
ANIMALS: 83 Rats, Sabra, M and F
PREPARATION AND DOSE
or HISTORY OF PATIENT:
No treatment with compound.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 20, 50, 100 mg/kg/d in divided doses (2/d) for 2, 4, 6, 8 d.
ROUTE AND SITE: Nil
CONTROL INFORMATION: This group
ROUTE AND SITE: oral
CONTROL INFORMATION: 20 Rats
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Autopsy (pathology)
DURATION OF EXPERIMENT: Serial sacr to 8 d.
EXAM. TYPE: Blood chemistry, electrophysiology, histology
489
490
-------
COMPOUND: Hydantoin, l-((5-nitrofurfurylidene)amino)-
000067209
REFERENCE: Ellis, F.G., Lond, M.S.
Lancet 11:1136-1138, 1962.
COMPOUND: Hydantoin, l-((5-nitrofurfurylidene)amino)-
000067209
REFERENCE: Honet, J.C.
Arch. Phys. Med. Rehab. 48: 209-212, 1967.
OBSERVED NEUROTOXIC EFFECTS: Peripheral (limb) polyneuritis progressive till
'death or cessation of compound; part-recovery
over long time. No histology performed.
OBSERVED NEUROTOXIC EFFECTS: Peripheral neuropathy with denervatlon of limb
extremities.
ANIMALS: 6 Humans, M, 53-79 years with renal impairment.
ANIMALS: Human: one F, 43, 32.2 kg
PREPARATION AND DOSE
or HISTORY OF PATIENT:
300-400 mg/d for 4 wk to 7 mo.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 800 mg/d for 1 wk and then 400 mg/d for 3 wk
ROUTE AND SITE: Oral
CONTROL INFORMATION: None
ROUTE AND SITE: Oral
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Clinical
DURATION OF EXPERIMENT: Hospital stay 9 d
EXAM. TYPE: Clinical, electromyography
491
492
-------
Hydantoin. l-((5-nltrofurfurylldene)aTn1nn)-
000067209
REFERENCE: Llndholm, T.
Neurology 17:1017-1020, 1967.
OBSERVED NEUROTOXIC EFFECTS: Electromyographical signs of peripheral muscle
denervation in 23 (62%) treated, 2 (18%) controls; only 5 treated subjects
had behavioral (clinical) signs.
COMPOUND: Hydantoin, l-((5-nitrofurfurylidene)amino)-
000067209
REFERENCE: Loughridge, L.W.
Lancet 11:1133-1135, 1962.
OBSERVED NEUROTOXIC EFFECTS:
Blood level 5.1-6.5 meg/ml vs. normal 1.8
in similarly treated patients. Peripheral
neuropathy (limbs) diagnosed during life;
Median nerves swollen, atrophic, with Wallerian
degeneration.
ANIMALS: Human: 43 F, 5 M with urinary infections but not uremia. Treated
group: 33 F, 4 M (ages 12-70 yr, av. 43).
ANIMALS: 1 Human: M, 54, with renal failure
PREPARATION AND DOSE
or HISTORY OF PATIENT: 50-300 (av. 115) mg/d, total 0.7-77.1 (av. 15.8) g.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 100 mg, 3/d for 6 wk.
ROUTE AND SITE: Oral
CONTROL INFORMATION: 10 F, 1M (ages 20-64 yr, av. 46) untreated.
ROUTE AND SITE: oral
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Electrophysiology, behavior
DURATION OF EXPERIMENT: Approx. 7 wk.
EXAM. TYPE: Clinical, blood-chemistry, histology (autopsy)
493
494
-------
COMPOUND: Hydantoin, l-((5-nitrofurfurylidene)amino)-
000067209
REFERENCE: Morris, J.S.
J. Neurol. Neurosurg. Psychiat. 29: 224-228, 1966,
OBSERVED NEUROTOXIC EFFECTS: Signs of peripheral neuropathy (paralysis, muscle-
wasting) that were only partly reversible after
discontinuing medication.
COMPOUND: Hydantoin, l-(5-nitrofurfurylidene)amino)-
000067209
REFERENCE: Rubensteln, C.J.
J. Am. Med. Assn 187:647-649, 1964.
OBSERVED NEUROTOXIC EFFECTS: Peripheral neuropathy, mainly of lower limbs, expecially
in presence of renal impairment; recovery if
muscle weakness not severe. Wallerian degeneration
in myelin sheaths.
ANIMALS: Human: 4 cases aged 36-75, M and F
ANIMALS:
5 Humans, M, F
PREPARATION AND DOSE
or HISTORY OF PATIENT: Total doses: 8-1000 g over time
PREPARATION AND DOSE
or HISTORY OF PATIENT: 300-600 mg/d for 10 d to several yr.
ROUTE AND SITE: Oral
CONTROL INFORMATION: None
ROUTE AND SITE: Oral
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: About 2-6 mo
EXAM. TYPE: Clinical
DURATION OF EXPERIMENT: 10 d to several yr.
EXAM. TYPE: Clinical, histology
495
496
-------
rnunnimn. Kydantoin. l-((5-nitrofurfurylidene')amino)-
000067209
L'OHPOUNU: Kyuaufcoiu, i-((5-nicrofurfuryIidene;aminoj-
000067209
REFERENCE: Toole, J.F. and Parrish, M.L.
Neurology 23:554-559, 1973.
REFERENCE: Toole, J.F., Gergen, J.A., Hayes, D.M., and Felts, J.H.
Arch. Neurol. 18:680-687, 1968.
OBSERVED NEUROTOXIC EFFECTS: Symptoms began usually within 45 d, progressed in
pattern of ascending sensorimotor polyneuropathy. Degree of recovery related
to symptoms severity but not to dose, nor to continuance of drug despite
symptoms. Recovery took days to 7 mo., deaths were not drug-related. 20%
of lumbar punctures showed high protein. Demyelination, axonal chromatolysis,
but no inflammation.
OBSERVED NEUROTOXIC EFFECTS: Changes in sensory and motor nerve conduction
velocities; no related changes in blood or urine.
ANIMALS: Humans
ANIMALS: Human healthy volunteers, 7 M, 7F, ages 22-58 yr.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.0-100+ g during 7-196 d. 137 patients in world literature,
reports assembled and analyzed.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 100 mg with meals and at bedtime for 14 d
ROUTE AND SITE: Oral (I.V. in one, instilled into bladder in two, into pleura
in one).
CONTROL INFORMATION: None
ROUTE AND SITE: Oral
CONTROL INFORMATION: Placebo, double-blind
DURATION OF EXPERIMENT: Up to 196 d
EXAM. TYPE: Behavior, laboratory, histology
DURATION OF EXPERIMENT: 6 wk
EXAM. TYPE: Physical; bloods and urine
497
498
-------
COMPOUND: Hydrazine, 1,1-dlmethyl-
000057147
REFERENCE: Cornish, H.H. and Earth, M.L.
Tox. Appl. Pharm. 6:568-575, 1964.
OBSERVED NEUROTOXIC EFFECTS: Tremors followed by tonlc-clonic convulsions;
increased urinary amino acid excretion, no change
of brain sulfhydryl levels, no observed tissue
pathology.
COMPOUND: Hydrazine, 1,1-dimethyl-
000057147
REFERENCE: Rinehart, W.E., Donati, E. and Greene, E.A.
U.S. Army CCRDC Report CRDLR 3047, 1961.
OBSERVED NEUROTOXIC EFFECTS:
Compound used in guided-missile systems, known
central nervous system stimulant; aim of study
was to learn MAC for prolonged exposure. Toxic
effects seen included tremors, convulsions, death.
Mild signs seen in dogs exposed to 5 ppm 26 wk.
No lesions in central nervous system reported.
Conclusion: MAC for man should be "well below 5 ppm"
and 0.5 ppm was suggested.
ANIMALS: Rats, S-D, M, 225-275 g.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 60-120 mg/kg; 100 mg/kg was LD 80 mg/kg was dose most
used.
ANIMALS: (1) 60 Mice, CS1, F, 20-30 g
(2) 50 Rats, Wistar CRDL, M, 200 g
(3) 6 Dogs, beagle, M, 11.4 kg
PREPARATION AND DOSE
or HISTORY OF PATIENT: 5-140 ppm of air (12.2-342 mg/ni ) for 6-26 wk
(1&2) 140 ppm 6 wk and 75 ppm 7 wk
(3) 25 ppm 13 wk and 5 ppm 26 wk.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: Mentioned, not described.
ROUTE AND SITE: Inhalation
CONTROL INFORMATION: Untrtd animals in all experiments
DURATION OF EXPERIMENT: Up to 10 d
EXAM. TYPE: Behavior, biochemistry, histology
DURATION OF EXPERIMENT: At least 9 mo.
EXAM. TYPE: Behavior, pathology-histology
499
500
-------
COMPOUND: Hydrazine, hydrochlorlde
uydrazine, (aipha-methyiphenethyi;-, hydrochioride
REFERENCE: Jenney, E.H. and Pfeiffer, C.C.
J. Pharm. Exp. Ther. 122: 110-123, 1958.
OBSERVED NEUROTOXIC EFFECTS: Convulsions
REFERENCE: Quinton, R.M.
Br. J. Pharmac. 21:51-66, 1963.
OBSERVED NEUROTOXIC EFFECTS: The compound enhanced the effect of Yohimbine
and lowered its lethal dosage.
ANIMALS: Mice, Harlan, 19-21 g
ANIMALS:
Mice, IT, M, 18-25 g.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 2.5 mM/kgm
PREPARATION AND DOSE
or HISTORY OF PATIENT:
ED5Q 20 mg/kg
ED,n = dose producing a 50% mortality of mice injected
S S.C. with yohimbine hydrochioride (20 mg/kg).
ROUTE AND SITE: i.p.
CONTROL INFORMATION: ns
ROUTE AND SITE: S.C., Oral
CONTROL INFORMATION: Various
DURATION OF EXPERIMENT: Acute
EXAM. TYPE: Clinical
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Behavior, electrophysiology, biochemistry
501
502
-------
COMPOUND: Hydrazine, phenethyl-, hydrochloride
REFERENCE: Quinton, R.M.
Br. J. Pharmac. 21:51-66, 1963.
OBSERVED NEUROTOXIC EFFECTS: The compound enhanced the effect of Yohimbine
and lowered its lethal dosage.
ANIMALS: Mice, XT, M, 18-25 g.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
ED5Q 20 mg/kg
ED
'50
dose producing a 50% mortality of nice injected
S.C. with yohimbine hydrochloride (20 mg/kg).
ROUTE AND SITE: S.C., Oral
CONTROL INFORMATION: Various
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Behavior, electrophysiology, biochemistry
503
COMPOUND: Hydrazoic acid
007782798
REFERENCE: Graham, J.D.P., Rogan, J.M. and Robertson, D.G.
J. Indust. Hyg. Toxicol. 30(2):98-102, 1948.
OBSERVED NEUROTOXIC EFFECTS: Respiratory stimulation followed by depression;
generalized convulsion with or without recovery.
Central nervous system not examined.
ANIMALS: Mice, Rats, Guinea-pigs, Rabbits (no details)
PREPARATION AND DOSE
or HISTORY OF PATIENT: Lethal and sublethal doses mentioned, no details.
ROUTE AND SITE: Inj., inhalation.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior, body-counts
504
-------
COMPOUND: Hydrocyanic acid
000074908
REFERENCE: Ibrahim, M.Z.M. and Levine, S.
J. Neurol. Neurosurg. Psychiat. 30: 545-555, 1967,
COMPOUND: Hydrocyanic acid
000074908
REFERENCE: Levine, S. and Stypulkowski, W.
Neurology 9: 407-411, 1959.
OBSERVED NEUROTOXIC EFFECTS: As a result of studies of fixation-artifacts, differ-
ences among artifacts were found when rats had been
intoxicated with cyanide. Authors concluded that
oligodendroglial proliferation in central nervous
system was closely related in time to earliest detectable
photomicroscopic changes in myelin produced by the
compound.
OBSERVED NEUROTOXIC EFFECTS: The distribution of hydrogen cyanide lesions could be
reproduced by ligation alone. The authors concluded
that ischemia was the mechanism of cyanide encephalopathy.
ANIMALS: 27 rats, Lewis, young adult, M & F
ANIMALS: Rats, Wistar, F, 160 or 225 g
PREPARATION AND DOSE
or HISTORY OF PATIENT: Exposure to compound for 20-30 min, sacrificed by overdose
of same
PREPARATION AND DOSE
or HISTORY OF PATIENT: Exposure for 25-35 min in inhalation jars; half of each
group given unilateral ligation of common carotid.
ROUTE AND SITE: Inhalation
CONTROL INFORMATION: 7 other rats, untrtd, killed by other methods
ROUTE AND SITE: Inhalation
CONTROL INFORMATION: Ligation or no
DURATION OF EXPERIMENT: Serial to 80 d
EXAM. TYPE: Histology, histochemistry
DURATION OF EXPERIMENT: About 4 d after exposure
EXAM. TYPE: Histology
505
506
-------
COMPOUND: Hydrogen selenide
007783075
REFERENCE: Buchan, R.F.
Occup. Med. 3:439-456, 1947.
COMPOUND: Hydrogen sulfide
007783064
REFERENCE: Adelson, L. and Sunshine, I.
Arch. Path. 81:375-380, 1966.
OBSERVED NEUROTOXIC EFFECTS: Nausea, vomiting, dysgeusia, dizziness, lethargy;
gradual recovery over 6 mo. after removal of
selenium source.
OBSERVED NEUROTOXIC EFFECTS: Rapid and complete central nervous system paralysis,
fatal.
ANIMALS: Human: 5 case who complained, selected from 25 exposed industrially
ANIMALS: Human: 3 M, ages 21-32
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Exposure not measurable (below 0.2 ppm) because methods
admitted to be insensitive. Urine av 6.16 meg/100
ml (range 0-13.1). Source (ink) contained 52 mg/liter
as selenious acid. Odor identified by investigators.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Industrial exposure to high concentrations of gas, probably over
0.1-0.2%.
ROUTE AND SITE: Inhalation, perhpas other routes too.
CONTROL INFORMATION: Yes, but later found to have been exposed.
ROUTE AND SITE: Inhalation
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: About 1 mo.
EXAM. TYPE: Urinalysis, clinical
DURATION OF EXPERIMENT: Minutes
EXAM. TYPE: Autopsy
507
508
-------
COMPOUND: Imldazole
000288324
REFERENCE: Nishie, K. , Walss, A.C. and Keyl, A.C.
Tox. Appl. Pharm. 41:301-307, 1969.
COMPOUND: Imldazole, 1-methyl-
000616477
REFERENCE:
Nishie, K., Waiss, A.C., and Keyl, A.C.
Tox. Appl. Pharm. 41:301-307, 1969.
OBSERVED NEUROTOXIC EFFECTS: Convulsions, varying degrees of tremor, opisthotonus
and tonic extensor seizures. Authors note higher
pH correspond to lower CD - values.
OBSERVED NEUROTOXIC EFFECTS: Convulsions, varying degrees of tremor, opisthotonus
and tonic extensor seizures. Authors note higher
pH correspond to lower CD - values.
ANIMALS:
Mice, albino, M, 20-25 g.
ANIMALS: Mice, albino, M, 20-25 g.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Data reported:
CD -- 560 mg/kg I.p., 1880 mg/kg P.O.
LD- 610 rag/kg I.P., 1880 mg/kg P.O.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Data reported:
CD - 380 mg/kg I.P., 1400 mg/kg P.O.
LD " - 380 mg/kg I.P., 1400 mg/kg P.O.
ROUTE AND SITE: I.P. and P.O.
CONTROL INFORMATION: Saline or other parameter
ROUTE AND SITE: I.P., P.O.
CONTROL INFORMATION: Saline or other parameter
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Behavior, electrophysiology
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Behavior, electrophysiology.
509
510
-------
COMPOUND: Imidazole, 2-methyl-
000693981
REFERENCE: Nishie, K., Waiss, A.C. and Keyl, A.C.
Tox. Appl. Pharm. 41:301-307, 1969.
COMPOUND: Imidazole, 4-methyl-
000822366
REFERENCE: Nishie, K., Waiss, A.C., and Keyl, A.C.
Tox. Appl. Pharm. 41:301-307, 1969.
OBSERVED NEUROTOXIC EFFECTS: Convulsions, varying degrees of tremor, opisthotonus
and tonic extensor seizures. Authors note higher
pH correspond to lower CD,- values.
OBSERVED NEUROTOXIC EFFECTS:
(1) Produced convulsions, tremors, opisthotonus
and tonic extensor seizure. Authors report that
high pH values correspond to lower CD,.^ values.
(2) Tremors at dosages of 100 rag/kg to opisthotonus,
terminal tonic extensor seizures at dosages of
150 mg/kg. (3) Produced convulsions.
ANIMALS:
Mice, albino, M, 20-25 g
PREPARATION AND DOSE
or HISTORY OF PATIENT: Data reported:
CD - 500 mg/kg I.P., 1300 mg/kg P.O.
IK" - 480 mg/kg I.P., 1400 mg/kg P.O.
ANIMALS: (1) Mice, albino, M, 20-25 g.
(2) Chicks, 10 day old
(3) Rabbits, 2.3-3 kg, surgically prepared.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Data reported:
(1) LD50 - 165 mg/kg I.P., 370 mg/kg P.O.
CD5Q - 155 mg/kg I.P., 360 mg/kg P.O.
(2) LD50 - 210 mg/kg I.P., 174 mg/kg P.O.
(3) 50 - 180 mg/kg I.P. for anticonvulsant testing
ROUTE AND SITE: l.p. and P.O.
CONTROL INFORMATION: Saline or other parameter.
ROUTE AND SITE: (1) I.P., P.O. (2) I.P., P.O. (3) I.P.
CONTROL INFORMATION: Saline or other parameter
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Behavior, electrophysiology.
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Behavior, electrophysiology
511
512
-------
COMPOUND: 2-Imidazoline-2-bentyl-hydrochloride
REFERENCE: Quinton, R.M.
Br. J. Pharmac. 21:51-66, 1963.
OBSERVED NEUROTOXIC EFFECTS: The compound enhanced the effect of Yohlmbine
and lowered its lethal dosage.
COMPOUND: 1H -Indazole, l-benzyl-3(3-(dimethylamino)propoxy)-
000642728
REFERENCE: Silvestrini, B., Barcellona, P.S., Gabau, A. and Catanese, B.
Tox. Appl. Pharm. 10:148-159, 1967.
OBSERVED NEUROTOXIC EFFECTS:
Therapeutic effects of muscle relaxation and sedation
at 0.7-1 mg/kg in man. Ataxia and convulsions
in mice, rats, rabbits,.cats near LDso levels (33
mg/kg I.V. to >1000 mg/kg orally); dogs vomited
at lower dosages.
ANIMALS:
Mice, TT, M, 18-25 g.
ANIMALS:
(1) Mice and Rats
(2) Mice, rats, rabbits, cats, dogs
PREPARATION AND DOSE
or HISTORY OF PATIENT:
ED
'5Q 27 mg/kg
D,- •» dose producing a 50% mortality of mice injected
S.C. with yohimbine hydrochloride (20 mg/kg).
ROUTE AND SITE: S.C., Oral
CONTROL INFORMATION: Various
PRFPARATTflN AND
or HlS OF PAENT:
(1) A<=«te: Mouse LD5Q - 33 mg/kg for I.V., 110 mg/kg for
"" ™ ^ f°* *£•' «£ 5" mg/kf f°r °^ Rat
100 mg/kg for I. P., 1050 mg/kg for oral.
(2) General effects (convulsions, incoordination) :
Mouse: 100 mg/kg I. P., 400 mg/kg oral.
Cat: 25-50 mg/kg I. P. Rat: 50 mg/kg I. P., 400-800 mg/kg oral.
Dog: 50 mg/kg oral. Rabbit: 5 mg/kg I.V.
ROUTE AND SITE: Diet, oral dosage, gavage, I. P., I.V.
CONTROL INFORMATION: Various
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Behavior, electrophysiology, biochemistry
DURATION OF EXPERIMENT: Varied
EXAM. TYPE: Clinical, pathological, immunological, reproductive.
513
514
-------
COMPOUND: Indole, 3-(2-aminobutyl)-, monoacetate
000118683
REFERENCE: Gray, J.E., McWade, D.H., Johnston, R.L., Larson, E.J. and Freyburger, W.A.
Tox. Appl. Pharm. 4:547-560, 1962.
OBSERVED NEUROTOXIC EFFECTS:
Stimulated central nervous system of dogs when
dose is greater than 100 mg/kg. LD5Q value in
mice following intraperitoneal administration is
72 mg/kg and 49 mg/kg orally in rats.
ANIMALS: Rats, S-D and Wistar, M and F.
Mice
Dogs, beagle
Rabbits
PREPARATION AND DOSE
or HISTORY OF PATIENT: Acute, subacute and reproductive studies various levels
and schedules.
COMPOUND: Indole, 3-(2-aminoethyl)-5,6-dihydroxy-
REFERENCE: Baumgarten, H.G., Evetts, K.D., Holman, R.B., Iversen, L.L.,
Vogt, M. and Wilson, G. and Vogt and Wilson, ibid. 19:1599-1600, 1972.
J. Neurochem. 19:1587-1597, 1972.
OBSERVED NEUROTOXIC EFFECTS:
Serotonin (5-HT) depleted for several d but normal
after 2 mo. Most effect near injection site and
in cord; some permanent atrophy of septum and
caudate. No loss of noreplnephrine, dopamine,
or tyrosine hydroxylase activity. 5,6-HT inhibited
uptake of 5-HT by brain slices more than of catecholamines
Severely toxic doses caused losses of tyrosine
hydroxylase and catecholamines.
The second paper gives normal levels of 5-HT and
5-hydroxyindoleacetic acid.
ANIMALS: (1) Rats, Wistar, M and F, 200 g
(2) Rats, Wistar, F, 180-250 g
PREPARATION AND DOSE
or HISTORY OF PATIENT:
50 meg by one of two methods
ROUTE AND SITE: Oral, gavage, I.P., I.M.
CONTROL INFORMATION: Various
ROUTE AND SITE: Injected into lateral ventricle
CONTROL INFORMATION: Vehicle given
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Biochemistry, physiology
DURATION OF EXPERIMENT: 68 d
EXAM. TYPE: Biochemistry
515
516
-------
COMPOUND: Indole, 3-(2-aminoethyl)-5,6-dihydroxy-
COMPOUND: Indole, 3-(2-aminoethyl)-5,6-dihydroxy-
REFERENCE: Baumgarten, H.G., Lachenmayer, L., Bjorklund, A., Nobin, A., and
Rosengren, E.
Life Sci. 12(1): 357-364, 1973.
OBSERVED NEUROTOXIC EFFECTS: SHT in brain and cord depleted for 2 wk, brain
5HT gradually recovered by 2-4 mo., some overshoots in septum hypothamalmus;
no recovery within 6 mo in cord. Cited literature to interpret regeneration
of serotonin axon lesions by treatment (authors).
REFERENCE' Richardson, J.S., Cowan,N., Hartman, R. and Jacobowitz, D.M.
Res. Comm. Chem. Path. Pharm. 8(l):29-44, 1974.
OBSERVED NEUROTOXIC EFFECTS:
Lowered serotonin; in combination with 6-hydroxydopa
lowered norepinephrine and serotonin; no effect
on dopamine. Other complex effects reported, and
the causes speculated to be selective destruction
of noradrenergic and/or serotonergic nerve
terminals.
ANIMALS: Rats, Wistar AF HAN, M, 180-200 g
ANIMALS: Rats, S-D, M, 180-220 g, 5-12/group
PREPARATION AND DOSE
or HISTORY OF PATIENT: 75 meg/rat of free base (creatinine sulfate -H20
complex) one dose.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
50 meg/rat
ROUTE AND SITE: Inj, lateral ventricle
CONTROL INFORMATION: Age-matched controls
ROUTE AND SITE: Intraventricular
CONTROL INFORMATION: Vehicle
DURATION OF EXPERIMENT: Serial sacr 10 d to 6 mo after injection.
EXAM. TYPE: Biochemical
DURATION OF EXPERIMENT: 14 d
EXAM. TYPE: Behavior
517
518
-------
COMPOUND:
Ir.dole, 3-(2-aminoethyl)-5,7-dihydroxy-
COMPOUND:
Indole, 3-(2-aminoethyl)-5-methoxy-
REFERENCE: Baumgarten, H.G., Victor, S.J. and Lovenberg, W.
J. Neurochem. 21:251-253, 1973.
OBSERVED NEUROTOXIC EFFECTS:
Progressive depletion of tryptophan hydroxylase
in brain and cord. Degeneration of serotonergic
neurons. Less potent than 5,6-DDT, but damage
apparently greater and more specific. Animals
sedated for a few hr but then became
hyperactive and pugnacious.
REFERENCE: Rivier, L. and Lindgren, J-E.
Econ. Bot. 26: 101-129, 1972.
OBSERVED NEUROTOXIC EFFECTS: Hallucinatory (visual)
ANIMALS: Rats, Wistar, M, 150-200 g.
ANIMALS:
Humans: anecdotal and personal experiences
PREPARATION AND DOSE
or HISTORY OF PATIENT: 150 meg/rat of free base equivalent in saline and
ascorbic acid.
ROUTE AND SITE: Intraventricular
CONTROL INFORMATION: Vehicle only
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Identification and quantisation analyses, still not complete
as reported, indicate that 200 ml of drink (normal dose)
includes 30 mg hannine, 10 mg TH-harmine and 25 mg DMT
(relative amounts in separate ingredients found to be
different), taken up to 10 times/mo or more.
ROUTE AND SITE: oral
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: 2 and 12 d
EXAM. TYPE: Behavior, biochemistry
DURATION OF EXPERIMENT: Expedition, duration ns
EXAM. TYPE: Behavior, analytical chemistry
519
520
-------
COMPOUND:
Indole, 3-(2-aminoethyl)-6-methoxy-
COMPOUND:
Indole, 3-(2-aminopropyl)-, acetate
REFERENCE: Rivier, L. and Lindgren, J-E.
Econ. Bot. 26: 101-129, 1972.
REFERENCE: Gray, J.E., McWade, D.H., Johnston, R.L., Larson, E.J. and Freyburger, W.A.
Tox. Appl. Pharm. 4:547-560, 1962.
OBSERVED NEUROTOXIC EFFECTS: Hallucinatory (visual)
OBSERVED NEUROTOXIC EFFECTS:
Stimulated central nervous system of dogs when dose
is greater than 100 mg/kg. Signs of intoxication
subsided after second day. U>50 value in mice is
38 mg/kg I.P. and 22 mg/kg orally in rats.
ANIMALS:
Humans: anecdotal and personal experiences
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Identification and quantitation analyses, still not complete
as reported, indicate that 200 ml of drink (normal dose)
includes 30 mg harmine, 10 mg TH-harmine and 25 mg DMT
(relative amounts in separate ingredients found to be
different), taken up to 10 times/mo or more.
ROUTE AND SITE: oral
CONTROL INFORMATION: None
ANIMALS: Bats, S-D and Wistar, M and F.
Mice
Dogs, beagle
Rabbits
PREPARATION AND DOSE
or HISTORY OF PATIENT: Acute, subacute and reproductive studies various levels
and schedules.
ROUTE AND SITE: Oral, gavage, I.P., I.M.
CONTROL INFORMATION: Various
DURATION OF EXPERIMENT: Expedition, duration ns
EXAM. TYPE: Behavior, analytical chemistry
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Biochemistry, physiology
521
522
-------
COMPOUND:
Indole, 3-(2-(dibutylamino)ethyl)-
REFERENCE: Szara, S.
Biochem. Pharm. 8: 32, 1961.
COMPOUND: Indole, 3-(2-(diethylamino) ethyl)-
000061518
REFERENCE: Szara, S.
Biochem. Pharm. 8: 32, 1961.
OBSERVED NEUROTOXIC EFFECTS:
Treatment caused disturbances of the autonomlc, emotional
perceptual and thinking systems, dependent on the 6-
hydroxylation rate in liver; dealkylation, for instance,
produced inactive metabolites. Thus diethyl, dimethyl,
and dlpropyl homologs were active, while dibutyl was
barely active, and dihexyl was inactive.
OBSERVED NEUROTOXIC EFFECTS:
Treatment caused disturbances of the autonotnic, emotional,
perceptual and thinking systems, dependent on the 6-
hydroxylation rate in liver; dealkylation, for instance,
produced inactive metabolites. Thus diethyl, dimethyl,
and dipropyl homologs were active, while dibutyl was
barely active, and dihexyl was inactive.
ANIMALS: Human
ANIMALS: Human
PREPARATION AND DC'E
or HISTORY OF PATIENT: 1 mg/kg
PREPARATION AND DOSE
or HISTORY OF PATIENT: 1 mg/kg
ROUTE AND SITE: ns
CONTROL INFORMATION: ns
ROUTE AND SITE: ns
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: ns
EXAM. TYPE: ns
DURATION OF EXPERIMENT: ns
EXAM. TYPE: ns
523
524
-------
COMPOUND: Indole, 3-(2-dihexylaminoethyl)-
REFERENCE: Szara, S.
Biochem. Pharm. 8: 32, 1961.
COMPOUND: Indole, 3-(2-dimethylaminoethyl)-
000061507
REFERENCE: Gallagher, C.H., Koch, J.H. and Hoffman, H.
Int. J. Neuropharmacol. 6: 223-228, 1967.
OBSERVED NEUROTOXIC EFFECTS:
Treatment caused disturbances of the autonomic, emotional,
perceptual and thinking systems, dependent on the 6-
hydroxylation rate in liver; dealkylation, for instance,
produced inactive metabolites. Thus diethyl, dimethyl,
and dipropyl homologs were active, while dibutyl was
barely active, and dihexyl was inactive.
OBSERVED NEUROTOXIC EFFECTS:
Convulsions, spasms. The authors showed that the
convulsions originated in the brain and that the
spasms originated in the spinal cord.
ANIMALS: Human
ANIMALS: Sheep, surgically prepared
PREPARATION AND DOSE
or HISTORY OF PATIENT: 1 mg/kg
ROUTE AND SITE: ns
CONTROL INFORMATION: ns
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Dimethyl tryptamine (1) and 5-methoxydimethyltryptamine (2)
were administered as HC1 derivatives; 5-hydroxydimethyltrypt-
amine (3) as a bioxalate derivative. 0.05-0.1 mg/kg of each,
mixed, or 0.05-0.1 mg/kg of"^(2), or 0.25-0.5 mg/kg of (3)
were equivalent doses. One sheep that was poisoned while
grazing was obtained.
ROUTE AND SITE: I.V., jugular; oral.
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: ns
EXAM. TYPE: ns
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Electrophysiology, pharmacology
525
526
-------
COMPOUND: Indole, 3-(2-dimethylaminoethyl)-
000061507
REFERENCE: Rivier, L. and Lindgren, J-E.
Econ. Bot. 26: 101-129, 1972.
OBSERVED NEUROTOXIC EFFECTS: Hallucinatory (visual)
COMPOUND: Indole, 3-(2-dimethylaminoethyl)-
000061507
REFERENCE: Szara, S.
Biochem. Pharm. 8: 32, 1961.
OBSERVED NEUROTOXIC EFFECTS:
Treatment caused disturbances of the autonomic, emotional,
perceptual and thinking systems, dependent on the 6-
hydroxylation rate in liver; dealkylation, for instance,
produced inactive metabolites. Thus diethyl, dimethyl,
and dipropyl homologs were active, while dibutyl was
barely active, and dihexyl was inactive.
ANIMALS:
Humans: anecdotal and personal experiences
ANIMALS: Human
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Identification and quantitation analyses, still not complete
as reported, indicate that 200 ml of drink (normal dose)
includes 30 mg harmine, 10 mg TH-harmine and 25 mg DMT
(relative amounts in separate ingredients found to be
different), taken up to 10 times/mo or more.
ROUTE AND SITE: oral
CONTROL INFORMATION: None
PREPARATION AND DOSE
or HISTORY OF PATIENT: 1 mg/kg
ROUTE AND SITE: ns
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: Expedition, duration ns
EXAM. TYPE: Behavior, analytical chemistry
DURATION OF EXPERIMENT: ns
EXAM. TYPE: ns
527
528
-------
COMPOUND: Indole, 3-(2-(dimethylamino)ethyl)-5-methoxy-
(5-methoxydimethyltryptamlne)
REFERENCE: Gallagher, C.H., Koch, J.H. and Hoffman, H.
Int. J. Neuropharmacol. 6: 223-228, 1967.
COMPOUND: Indole, 3-(2-dlpropyl amlno)ethyl)-
000061529
REFERENCE: Szara, S.
Biochem. Pharm. 8: 32, 1961,
OBSERVED NEUROTOXIC EFFECTS:
Convulsions, spasms. The authors showed that the
convulsions originated in the brain and that the
spasms originated in the spinal cord.
OBSERVED NEUROTOXIC EFFECTS:
Treatment caused disturbances of the autonomic, emotional,
perceptual and thinking systems, dependent on the 6-
hydroxylation rate in liver; dealkylation, for instance,
produced inactive metabolites. Thus diethyl, dimethyl,
and dipropyl homologs were active, while dibutyl was
barely active, and dihexyl was inactive.
ANIMALS: Sheep, surgically prepared
ANIMALS: Human
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Dimethyl tryptamine (1) and 5-methoxydimethyltryptamine (2)
were administered as HC1 derivatives; 5-hydroxydimethy1trypt-
amine (3) as a bioxalate derivative. 0.05-0:1 mg/kg of each,
mixed, or 0.05-0.1 mg/kg of (2), or 0.25-0.5 mg/kg of (3)
were equivalent doses. One sheep that was poisoned while
grazing was obtained.
ROUTE AND SITE: I.V., jugular; oral.
CONTROL INFORMATION: ns
PREPARATION AND DOSE
or HISTORY OF PATIENT: l mg/kg
ROUTE AND SITE: ns
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Electrophysiology, pharmacology
DURATION OF EXPERIMENT: ns
EXAM. TYPE: ns
529
530
-------
COMPOUND:
Indol-5-ol-3-02-(dimethylamino)ethylo-
0000487934
REFERENCE: Gallagher, C.H., Koch, J.H. and Hoffman, H.
Int. J. Neuropharmacol. 6: 223-228, 1967.
COMPOUND: Indol-4-ol, 3(2-(dimethyl amino)ethyl)-
000520536
REFERENCE: Horita, A. and Weber, L.J.
Tox. Appl. Phann. 4: 730-737, 1962.
(Psylocin)
OBSERVED NEUROTOXIC EFFECTS: Convulsions, spasms. The authors showed that the
convulsions originated in the brain and that the
spasms originated in the spinal cord.
OBSERVED NEUROTOXIC EFFECTS:
After administration of psilocybin, psylocin (4-hydroxy
analog of psilocybin) appeared in tissues including
brain, brain peak 25-30 min after dose. Piloerection,
exophthalmos, motor incoordination followed brain levels
of psylocin. Pretreatment with B-glycerophosphate did
not alter distribution of psylocin nor behavior.
Interpreted to mean that psilocybin was rapidly dephos-
phorylated, and central nervous system effects exerted
by the psylocin metabolite.
ANIMALS: Sheep, surgically prepared
ANIMALS: Mice, albino, 25-35g, 6/group
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Dimethyl tryptamine (1) and 5-methoxydimethyltryptamine (2)
were administered as HC1 derivatives; 5-hydroxydimethyltrypt-
amine (3) as a bioxalate derivative. 0.05-0.1 mg/kg of each,
mixed, or 0.05-0.1 mg/kg of (2), or 0.25-0.5 mg/kg of (3)
were equivalent doses. One sheep that was poisoned while
grazing was obtained.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
100 mg/kg, equalling 0.35 mmole/kg
ROUTE AND SITE: I.V., jugular; oral.
CONTROL INFORMATION: ns
ROUTE AND SITE: I.P.
CONTROL INFORMATION: "Normal mice", details ns
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Electrophysiology, pharmacology
DURATION OF EXPERIMENT: Serial to 30 min
EXAM. TYPE: Biochemistry, behavior
531
532
-------
COMPOUND' Indol-4-ol, 3-(2-(dimethylamino)ethyl)-, dihydrogen phosphate (Psilocybln)
000520525
REFERENCE: Horita, A. and Weber, L.J.
Tox. Appl. Pharm. 4: 730-737, 1962.
OBSERVED NEUROTOXIC EFFECTS: After administration of psilocybin, psylocin (4-hydroxy
analog of psilocybin) appeared in tissues including
brain, brain peak 25-30 min after dose. Piloerection,
exophthalmos, motor incoordination followed brain levels
of psylocin. Pretreatment with B-glycerophosphate did
not alter distribution of psylocin nor behavior.
Interpreted to mean that psilocybin was rapidly dephos-
phorylated, and central nervous system effects exerted
by the psylocin metabolite.
COMPOUND: Indol-4-ol, 3-(2-(dimethylamino)ethyl)-, dihydrogen phosphate
000520525
REFERENCE: Spooner, C.E. and Winters, W.D.
Int. J. Neuropharmacol. 5: 217-236, 1966
OBSERVED NEUROTOXIC EFFECTS: compound produced excitement, abnormal postures,
: arousal EEGs, then depression.
ANIMALS: Mice, albino, 25-35g, 6/group
ANIMALS: 200 Cockerels, White Leghorn, ages 5-14 d, 45-100 g
PREPARATION AND DOSE
or HISTORY OF PATIENT: 72 mg/kg, equalling 0.35 mmole/kg
PREPARATION AND DOSE
or HISTORY OF PATIENT: 1-50 mg/kg
ROUTE AND SITE: I.P.
CONTROL INFORMATION: "Normal mice", details ns
ROUTE AND SITE: s.C. near axillary vein; I.P. for doses over 0.05 ml
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: Serial to 30 min
EXAM. TYPE: Biochemistry, behavior
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Behavior, EEC
533
534
-------
COMPOUND:
Isocyanic acid, p-bromophenyl ester
COMPOUND: Isoglutamlne, L-
REFERENCE: Lessel, B. and Towlerton, R.G.
Fd. Cosmet. Toxicol. 5:741-743, 1967.
REFERENCE: Curtis, D.R. and Watkins, J.C.
J. Neurochem. 6:117-141, 1960.
OBSERVED NEUROTOXIC EFFECTS:
Swaying gait, ataxia, weak hindlimbs, and swelling-
degeneration of the axons. Demyelination of spinal
cord. Neuronal degeneration. Death. Spinal
cord lesions.
OBSERVED NEUROTOXIC EFFECTS:
Treatment caused excitation or depression of
neuronal activity. Excitatory ranking: glutamic,
B-aminoglutaric, aspartic, cysteic, cysteine-
sulfinic acids, B-hydroxyglutamic, N-methylaspartic,
N-formiminoaspartlc acids.
Depressant ranking: 6-alanine, GABA, taurine,
N-methyl-6-alanine, 6-amino-B-hydroxybutyric,
glycine, a-alanine, 6-aminovaleric, jJ-aminoisobutyric
acids.
Structure-activity relationships established.
ANIMALS: 16 Lambs, 8 wk, 19-24 kg.
ANIMALS:
Cats, surgically prepared to exposed motoneurones, Renshaw cells or
dorsal horn interneurones in lumbar cord.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
150-200 mg/kg/d.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Qualitative doses.
ROUTE AND SITE: Oral
CONTROL INFORMATION:
ROUTE AND SITE: Topical, ionophoresis
CONTROL INFORMATION: Laboratory
DURATION OF EXPERIMENT:
EXAM. TYPE: Dissection
Sacr.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry, electrophysiology
535
536
-------
COMPOUND: Isonicotinic acid, 2-(2-(benzylcarbamoyl)ethyl)hydrazide
Q00051127
REFERENCE: Quinton, R.M.
Br. J. Phannac. 21:51-66, 1963.
COMPOUND: Isonicotinic acid, hydrazlde
000054853
REFERENCE: Alder, S. and Zbinden, G.
Agents and Actions 3/4: 233-243, 1973,
OBSERVED NEUROTOXIC EFFECTS: The compound enhanced the effect of Yohimbine
and lowered its lethal dosage.
OBSERVED NEUROTOXIC EFFECTS:
Water intake increased at weekends (no dose given),
normal during treatment. In Hot Plate Test, delayed
response; in Foot Print Test, gait not altered; in
Rotating Rod Test performance impaired in some rats.
All rats had peripheral neuropathy after 5 d, all
doses: degenerative changes, especially of myelin.
Brain and cord no changes. Thymus moderate atrophy
with 600 mg/kg.
ANIMALS:
Mice, TT, M, 18-25 g.
ANIMALS: Rats, CFN Zu, F. 38-53g, 6 groups of 8-10 each.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
ED5Q 9 mg/kg
ED
50
dose producing a 50% mortality of mice injected
S.C. with yohimbine hydrochloride (20 mg/kg).
PREPARATION AND DOSE
or HISTORY OF PATIENT: 200, 400, 600 mg/kg, 5d/wk, for 5-26 doses.
ROUTE AND SITE: S.C., Oral
CONTROL INFORMATION: Various
ROUTE AND SITE: Oral
CONTROL INFORMATION: 6 groups given water orally.
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Behavior, electrophysiology, biochemistry
DURATION OF EXPERIMENT: Serial sacr 1-5 wk.
EXAM. TYPE: Behavior, histology
537
538
-------
COMPOUND: Isonicotinic acid, hydrazlde
000054853
REFERENCE: Botta, J.A., Jr. and Carlton, W.W.
Tox. Appl. Pharm. 11:35-48, 1967.
OBSERVED NEUROTOXIC EFFECTS: Excitement, ataxia, convulsions; cerebellar lesions.
Dose-relationships with symptoms and pathology
are explored.
ANIMALS: Drakes, Pekin and Rouen, 30-36 hr old
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.1-6.3% in diet; 40-1250 mg/kg/d i.p. 7 d; 0.001-0.1%
in diet.
ROUTE AND SITE: Oral, I.P.
CONTROL INFORMATION: Untreated
DURATION OF EXPERIMENT: Up to 3 mo. or more.
EXAM. TYPE: Mortality, behavior, pathology
539
COMPOUND: Isonicotinic acid, hydrazide
000054853
REFERENCE: Carlton, W.W. and Kreutzberg, G.
Am. J. Path. 48:91-98, 1966.
OBSERVED NEUROTOXIC EFFECTS: Tremors, ataxia. Spongy degeneration (vacuoles,
demyelination) in cerebellar white matter, also in optic lobe, hemispheres,
cord. Local axonal degeneration, proliferation of glia, edema of astrocytes.
No protection from pyridoxal.
ANIMALS: Drakes, Pekin, day-old, 4 grps of 10, 3 grps treated.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 1 g/kg in diet with 0, 0.2, 1 g/kg of pyridoxal hydro-
chloride.
ROUTE AND SITE: Oral
CONTROL INFORMATION: 1 group untreated.
DURATION OF EXPERIMENT: 4 wk.
EXAM. TYPE: Behavior, histology
540
-------
COMPOUND: Isonicotinic acid, hydrazide
000054853
REFERENCE: Carlton, W.W.
Avian Dis. 11:241-254, 1967.
COMPOUND: Isonicotinic acid, hydrazide
000054853
REFERENCE: Cavanagh, J.B.
J. Neurol. Neurosurg. Psychiat. 30:26-33, 1967.
OBSERVED NEUROTOXIC EFFECTS: Neuropathy (taxia, tremor, convulsions) severe
only with 0.15 and 0.30% feeding. Central Nervous System spongy degeneration
especially in cerebellar medulla, less in medulla oblongata, optic lobes
and cord. No protection if 0.2% pyridoxine was fed. Growth depressed in all,
mortality 25-85% dose-related.
OBSERVED NEUROTOXIC EFFECTS: Weakness and wasting of hindlimb muscles, varying
degrees. Denervation of mainly motor, also sensory nerves in distal muscles,
medium sized fibers specially. Pattern like that in acute intermittent
porphyria in man, unlike that from organophosphourses.
ANIMALS: Chicks: broiler stock, M, day-old, grps of 20.
ANIMALS: Rats, Wistar, M, 270-300 g (12), av. 68 g (12), av. 73 g (8).
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.05-0.30% of diet.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 250 mg/kg/d in diet or in two doses B.C.
ROUTE AND SITE: oral
CONTROL INFORMATION: Diet only
ROUTE AND SITE: Oral or s.c.
CONTROL INFORMATION: None reported
DURATION OF EXPERIMENT: 8 wk
EXAM. TYPE: Behavior, histology
DURATION OF EXPERIMENT: Serial sacr to 12 wk
EXAM. TYPE: Behavior, histology
541
542
-------
COMPOUND: Isonicotinlc acid, hydrazide
000054853
REFERENCE: Gammon, G.D., Burge, F.W. and King, G.
Arch. Neurol. Psychiat. 70:64-69, 1953.
OBSERVED NEUROTOXIC EFFECTS: Signs of peripheral neuropathy, regressed on
stopping the drug. Inducing dose 4.5-13.5 mg/kg, "in the range in which
toxicity is to be excepted."
ANIMALS: Human: 14 cases selected from 46 "with similar complaints" in
a series of 408 treated with isoniazid.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 300-700 mg/d, duration ns.
ROUTE AND SITE: Oral
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Clinical
543
COMPOUND: Isonicotinic acid, hydrazide
000054853
REFERENCE: Hildebrand, J., Joffroy, A. and Goers, C.
Arch. Neurol. 19:60-70, 1968.
OBSERVED NEUROTOXIC EFFECTS: At 3 d, 10% of sciatic nerve fibers damaged and
conduction reduced; at 7 d myelin disruped in 32% of fibers, axonal
fragmentation, collateral sprouting of subterminal fibers, altered
muscle action potentials; at 13 d 76% of fibers damaged, slower motor
condution, large group atrophy of muscles. After 37 d of no treatment
much nerve damage persisted, no recovery of muscles. Collateral
branching explained continued motor activity.
ANIMALS: 19 Rats, S-D, M, Age 3 mo. 260-300 g
PREPARATION AND DOSE
or HISTORY OF PATIENT: 90 mg/rat/d, 3-13 d
ROUTE AND SITE: i.e.
CONTROL INFORMATION: 23 Matched rats, 280-320 g
DURATION OF EXPERIMENT: Sacr after 4-50 d observation
EXAM. TYPE: Electrophysiology, histology
544
-------
COMPOUND: Isonicotinic acid, hydrazide
000054853
REFERENCE: Jenney, E.H. and Pfeiffer, C.C.
J. Pharm. Exp. Ther. 122: 110-123, 1958.
COMPOUND: Isonicotinic acid, hydrazide
000054853
REFERENCE: Jones, W.A. and Jones, G.P.
Lancet:1073-1074, 1953.
OBSERVED NEUROTOXIC EFFECTS: Convulsions
OBSERVED NEUROTOXIC EFFECTS: Polyneuropathy of limbs, resembling pellagra and
attributed to competitive inhibition of nicotinic acid and perhaps other
B-vitamins by the drug.
ANIMALS: Mice, Harlan, 19-21 g
ANIMALS: Human: 2 case-reports, M aged 23 and F aged 18
PREPARATION AND DOSE
or HISTORY OF PATIENT: l.i mM/kgm
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) 300 mg/d (5 mg/kg/d) for over 6 wk, admitted to
hospital 4 wk after treatment ended.
(2) 450 mg/d (12 mg/kg/d) for 3 mo., repeated after
4 mo. interval, admitted 2 wk later.
ROUTE AND SITE: I.P., i.v.
CONTROL INFORMATION: ns
ROUTE AND SITE: Oral
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: Acute
EXAM. TYPE: Clinical
DURATION OF EXPERIMENT: (1) 1 mo. observation, (2) 3 wk.
EXAM. TYPE: clinical
545
546
-------
COMPOUND: Isonicotinic acid, hydrazlde
000054853
REFERENCE: Noel, P.R.B., Worden, A.N. and Palmer, A.C.
Tox. Appl. Pharm. 10:183-198, 1967.
OBSERVED NEUROTOXIC EFFECTS: No constant evidence of peripheral nervous system
damage. Brain damage mainly due to subcortical
myelin of hemispheres, considered edematous.
COMPOUND: Isonicotinic acid, hydrazide
000054853
REFERENCE: Ochoa, J.
Brain 93:831-850, 1970.
OBSERVED NEUROTOXIC EFFECTS: Peripheral neuropathy; sural nerves myelinated
and unmyelinated fibers were damaged, with differences; regeneration and
degeneration of regenerated fibers were seen.
ANIMALS:
12 Dogs, Pembroke Corgi, 6M, 6F
ANIMALS: 9 Humans, M and F, aged 35-70 yr.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 25 or 50 mg/kg/d in gelatin capsules, 6d/wk.
High dose reduced to 40 mg/kg due to convulsions, and
then both groups reduced to 5 or 25 mg. Continued
treatment resulted in death, so 25 mg/kg reduced to 15 mg/kg.
ROUTE AND SITE: Oral
CONTROL INFORMATION: 6 undosed controls.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 300-500 mg/d; 1 patient given 2 g/d for 5 d in error.
ROUTE AND SITE: Oral
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: 195 d
EXAM. TYPE: Clinical, biochemistry, autopsy
DURATION OF EXPERIMENT: Up to about 3 yr.
EXAM. TYPE: Clinical and lab, histology (biopsy)
547
548
-------
COMPOUND: Isonicotinic acid, hydrazide
000054853
REFERENCE: Palmer, A.C. and Noel, P.R.B.
Nature 205:506-507, 1965.
OBSERVED NEUROTOXIC EFFECTS: Seperation of fibers in subcortical rayelin,
ballooning, but axons intact, activation of
microglia and hypertrophy of astrocytes.
COMPOUND: Isonicotinic acid, hydrazide
000054853
REFERENCE: Ramakrishna, T. and Smith, B.H.
Neurology 20:1142-1145, 1970.
OBSERVED NEUROTOXIC EFFECTS: Generalized convulsions, abnormal EEC.
ANIMALS: Dogs
ANIMALS: Human: 2 case-reports (F, 14 yr; F, 22 yr)
PREPARATION AND DOSE
or HISTORY OF PATIENT:
5 or 15 mg/kg/d for up to 6 mo.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Two attempted suicides: 2.4 g and about 5 g, single doses
(50 and 93 mg/kg)
ROUTE AND SITE: Oral
CONTROL INFORMATION: Control dogs, no details.
ROUTE AND SITE: Oral
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: Up to 6 mo.
EXAM. TYPE: Histology
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Clinical, EEC
549
550
-------
COMPOUND: Isonicotinic acid, hydrazide
000054853
REFERENCE: Schlaepfer, W.W. and Hager, H.
Am. J. Path. 45:209-216, 1964.
OBSERVED NEUROTOXIC EFFECTS: Primary axonal degeneration with swelled mitochon-
dria in peripheral nerves; changes in axoplasm.
COMPOUND: Isonicotinic acid, hydrazide
000054853
REFERENCE: Schlaepfer, W.W. and Hager, H.
Am. J. Path. 45:423-430, 1964.
OBSERVED NEUROTOXIC EFFECTS: Specific report on breakdown of myelin. Collapse
of cylinder, myelin globules formed within Schwann cell cytoplasm with reactive
changes and phagosome-like vacuoles; products transferred to macrophages.
ANIMALS: 20 rats, S-D, F, 250-400 g
ANIMALS: 20 rats, S-D, F
PREPARATION AND DOSE
or HISTORY OF PATIENT: 250 mg/kg/d for 6-16 d.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 350 mg/kg/d for 6-16 d.
ROUTE AND SITE: Gavage
CONTROL INFORMATION: "Normal rats" number and treatment ns.
ROUTE AND SITE: Oral
CONTROL INFORMATION: 4 "normal rats" as control.
DURATION OF EXPERIMENT: Serial sacr to 16 d
EXAM. TYPE: Histology
DURATION OF EXPERIMENT: Serial sacr to 154 d.
EXAM. TYPE: Histology
551
552
-------
COMPOUND: Isonicotinic acid, hydrazide
000054853
REFERENCE: Schlaepfer, W.W. and Hager, H.
Am. J. Path. 45:679-686, 1964.
COMPOUND: Isonicotinic acid, hydrazide
000054853
REFERENCE: Sea, C.P. and Peterson, E.G.
Exp. Neurol. 48:.252-260, 1975.
OBSERVED NEUROTOXIC EFFECTS: Focal disruption of axons and myelin sheaths.
Regeneration studied: mild fibrosis of endoneurium, shcwann-cell pro-
liferation, regeneration of axons interacting with schwann-cell processes and
remyelinat ion.
OBSERVED NEUROTOXIC EFFECTS: Portions of both sciatic nerves (one for histology,
the other for biochemistry); neuropathy varied axon to axon and rat to rat.
Degeneration of myelin; Schwann cells appeared to transform into macro-
phages. Loss of the main protein band (electrophoresis).
ANIMALS: 20 rats, S-D, F
ANIMALS: 30 Rats, S-D, M, 200-300 g.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 350 mg/kg/d for 6-15 d.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 270 mg/kg/d till hyperactivity seen (usually 6 d), then
200 mg/kg/d to day 14.
ROUTE AND SITE: Oral
CONTROL INFORMATION: 4 "Normal rats" as control.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: 2 Controls, saline treated.
DURATION OF EXPERIMENT: Serial sacr to 154 d
EXAM. TYPE: Histology
DURATION OF EXPERIMENT: Serial sacr to 14 d
EXAM. TYPE: Histology, biochemistry
553
554
-------
COMPOUND: Isonicotinic acid, hydra-ide
100054653
REFERENCE: Smith, B.
J. Neurol. Neurosurg. Psychiat. 30: 506-510, 1967.
COMPOUND: Isonicotinic acid, hydrazide
000054853
REFERENCE:
Terman, D.S. and Teitelbaum, D.T.
Neurology 20:299-304, 1970.
OBSERVED NEUROTOXIC EFFECTS: The myenteric plexus was examined, and histological
changes were found. The author suggests her method
for screening for neurotoxicity by looking for damage
to the myenteric plexus in the large intestine.
OBSERVED NEUROTOXIC EFFECTS: Intractable convulsions, metabolic acidosis.
All recovered eventually.
ANIMALS: 45 Mice, TO, CFW and Porton strains, 20-25 g
ANIMALS: Human: 4 cases (M, 35; M, 21; F, 16; F, 20)
PREPARATION AND DOSE
or HISTORY OF PATIENT: f, r.g twice weekly fcr 5-20 doses, 9 mice
Acute study: 10 mg I.P. or 2 mg I.V. one dose
PREPARATION AND DOSE
or HISTORY OF PATIENT: Single doses: (1) amt unknown, (2) 30 g, (3) approx 10 g
plus pyridoxine, (4) amt unknown. In each case self-administered, thought
to 'be over 7 g.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: ns
ROUTE AND SITE: oral
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: 2 d to 3 mo after last dose. Acute: 20 min.
EXAM. TYPE: Histology
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: clinical, hospital lab.
556
-------
COMPOUND: Isonicotinic acid, hydrazide
000054853
REFERENCE: Tomkin, G.H.
Practitioner 211:773-777, 1973.
COMPOUND: Isonicotinic acid 2-lsopropyl hydrazide phosphate
REFERENCE: Quinton, R.M.
Br. J. Pharnac. 21:51-66, 1963.
OBSERVED NEUROTOXIC EFFECTS: Loss of strength in arms and legs, absent
tendon reflexes, plantar responses flexor, impaired sensation to pinpricks.
Complication: sideroblastic anemia. After all drugs were discontinued and
blood and pyridoxlne given, patient began recovery. In 3 wk patient walked
unaided, in 4 mo. sensations and tendon reflexes except ankle-jerk were
normal.
OBSERVED NEUROTOXIC EFFECTS: The compound enhanced the effect of Yohimbine
and lowered its lethal dosage.
ANIMALS: 1 Human, M, aged 67 yr.
ANIMALS:
Mice, XT, M, 18-25 g.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Dose 300 mg/d as antituberculosis therapy, after 2 yr
complained of limb numbness; was found unable to walk unaided.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
ED5Q 200 mg/kg
ED,n - dose producing a 50% mortality of mice injected
"50
S.C. with yohimbine hydrochloride (20 mg/kg).
ROUTE AND SITE: ns.
CONTROL INFORMATION: ns.
ROUTE AND SITE: S.C., Oral
CONTROL INFORMATION: Various
DURATION OF EXPERIMENT: 2 yr of drug therapy, follow up.
EXAM. TYPE: Hospital
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Behavior, electrophysiology, biochemistry
557
558
-------
COMPOUND: Isonicotinic acid, 2-(sulfomethyl)hydrazide, sodium salt
003804895
REFERENCE: Noel, P.R.B., Worden, A.N. and Palmer, A.C.
Tox. Appl. Pharm. 10:183-198, 1967.
COMPOUND: Isonicotinic acid, 2-(sulfomethvl) hvdraziHe, sodium salt
003804895
REFERENCE: Palmer, A.C. and Noel, P.R.B.
Nature 205:506-507, 1965.
OBSERVED NEUROTOXIC EFFECTS: No constant evidence of peripheral nervous system
damage. Brain damage mainly due to subcortical
myelin of hemispheres, considered edematous.
OBSERVED NEUROTOXIC EFFECTS:
Seperation of fibers in subcortical myelin, ballooning,
but axons Intact, activation of microglia and
hypertrophy of astrocytes. Severe laminar necrosis
of cerebral cortex.
ANIMALS:
18 Dogs, Pembroke Corgi, 9 M, 9 F
ANIMALS: Dogs
PREPARATION AND DOSE
or HISTORY OF PATIENT: 6, 30 or 60 mg/kg/d in gelatin capsules, 6d/wk. High
dose reduced to 48 mg/kg due to convulsions, and then to
. •• 40 mg/kg. Deaths caused further reduction to 20 or 10
mg/kg/d.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
6, 10, or 20 mg/kg/d.
ROUTE AND SITE: Oral
CONTROL INFORMATION: 6 undosed controls.
ROUTE AND SITE: Oral
CONTROL INFORMATION: Control dogs, no details
DURATION OF EXPERIMENT: 195 d
EXAM. TYPE: Clinical, biochemistry, autopsy
DURATION OF EXPERIMENT: Up to 6 mo.
EXAM. TYPE: Histology
559
560
-------
COMPOUND:
Lactic acid, hydrazide
REFERENCE: Jenney, E.H. and Pfeiffer, C.C.
J. Pharm. Exp. Ther. 122: 110-123, 1958.
COMPOUND: Lead
007439921
REFERENCE: Anku, V.D. and Harris, J.W.
J. of Pediatrics 85(3):337-340, 1974.
OBSERVED NEUROTOXIC EFFECTS: Convulsions
OBSERVED NEUROTOXIC EFFECTS: Peripheral neuropathy, fatigue, headache,
epistaxis, clumsiness and limb weakness.
ANIMALS: Mice, Harlan, 19-21 g
ANIMALS: 1 Human, M, 6 yrs.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 9.6 nM/kgm
PREPARATION AND DOSE
or HISTORY OF PATIENT: Ingestion of lead-base paint chips.
ROUTE AND SITE: i.P.
CONTROL INFORMATION: ns
ROUTE AND SITE: Oral
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: Acute
EXAM. TYPE: Clinical
DURATION OF EXPERIMENT: 5 mo.
EXAM. TYPE: Clinical, hematology.
561
562
-------
COMPOUND: Lead
007439921
REFERENCE: Baloh, R., Sturm, R., Green, B. and Gleser, G.
Arch. Neurol. 32:326-330, 1975.
OBSERVED NEUROTOXIC EFFECTS:
All subjects asymptomatic when evaluated. Hyper-
activity correlated with increased lead levels, but
quantitative tests did not. Authors comment
about "uncontrolled variables."
COMPOUND: Lead
007439921
REFERENCE: Beattie, A.D., Briggs, J.D., Canavan, J.S.F., Doyle, D., Mullin, P.J.
and Watson, A.A.
Quart. J. Med. 44(174): 275-284, 1975.
OBSERVED NEUROTOXIC EFFECTS: Two of the cases showed severe neuropathy character-
ized by sudden flaccid paralysis 15 days after the
dose, with quadriplegia and respiratory paralysis.
Peripheral nervous system motor end plates lacked
innervation and showed degenerated axons and myelin.
ANIMALS: Human children aged over 3 1/2 yr with 2 blood tests over 50 mcg/Pb/100
ANIMALS: Human: 5 cases, all associated
PREPARATION AND DOSE
or HISTORY OF PATIENT:
History, physical exam, blood Pb determination, and
psychological tests (motor, perceptual-motor, verbal-
cognitive, memory, quantitative).
PREPARATION AND DOSE
or HISTORY OF PATIENT: Self-administration of lead-opium pills obtained by
burglary, ground, suspended, and injected (3-712 pills)
one dose.
ROUTE AND SITE: N/A
CONTROL INFORMATION: Controls matched from files (m of age, sex, race, background)
and screened at under 30 meg Pb/100 ml blood.
ROUTE AND SITE: I.V.
CONTROL INFORMATION: Absent
DURATION OF EXPERIMENT: as.
EXAM. TYPE: History, physical, hematological, behavioral
DURATION OF EXPERIMENT: About 2 wk
EXAM. TYPE: Clinical, biochemistry, histology (autopsy)
563
564
-------
COMPOUND: Lead
007439921
REFERENCE: Carson, T.L., Van Gelder, G.A., Karas, G.C. and Buck, W.B.
Arch. Env. Hlth. 29:154-156, 1974.
COMPOUND: Lead
007439921
REFERENCE: David, O.J.
Lancet i, 866, 1974.
OBSERVED NEUROTOXIC EFFECTS:
Blood lead of controls 4.7, lows 18.6, highs 34.8
meg/100 ml; of lambs at 2-4 wk of age controls 6.0,
lows 17.0, highs 25.0 meg/100 ml; of lambs
at 10-12 wk controls 4.0, lows 9.0, highs 14.0
meg/100 ml. Rate of learning six visual discrimination
problems: highs but not lows significantly slower
than controls.
OBSERVED NEUROTOXIC EFFECTS:
ANIMALS: Lambs born to ewes fed high or low lead diets:
7 in high group, 8 in low group.
Used eventually: 4 control, 8 low, and 6 high lambs.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
High: dams fed 4.5 mg/kg/d.
Low: dams fed 2.3 mg/kg/d.
Lambs weaned at 3 mo.-exposure ceased.
ANIMALS: Humans
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Criticisms of paper by Lansdown et al., Lancet i_,
538, 1974. (1) Blood lead does not signify lead
burden, without lead mobilization tests.
(2) Behaviorial controls should be outside the
affected area, and methods should be justified
for purpose (lead-free population, and scale
intended to measure hyperkinesis). (3) Sex
imbalance in expected frequencies of behavior
disturbance (boys more than girls) should be
considered in selecting the study sample and
in data-processing; same with age-imbalance
(omission of cases under 6 yr old). Therefore,
conclusions are not proved by data (may still be
correct, but issue unresolved).
Industrial exposure to emissions from a lead smelter
ROUTE AND SITE: Diet
CONTROL INFORMATION: Lambs from ewes fed normal diet: 9 lambs.
ROUTE AND SITE: ns.
CONTROL INFORMATION: Subject of argument
DURATION OF EXPERIMENT: About 15 mo.
EXAM. TYPE: Behavioral, blood chemistry
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Subject of argument
565
566
-------
COMPOUND: Lead
007439921
REFERENCE: Krigman, M.R.
Env. Hlth. Persp. 4:98, 1973. (Abstracts).
COMPOUND: Lead
007439921
REFERENCE: Lansdown, R.G., Shepherd, J., Clayton, B.E., Delves, H.T., Graham, P.J.
and Turner, W.C.
Lancet 1:538-541, 1974.
OBSERVED NEUROTOXIC EFFECTS:
Thinner cortical mantle, smaller neurons, less
developed neuropil, fewer synapses but larger.
Lead retarded neuronal growth but not maturation,
whereas undernourishment affected both growth and
maturation.
OBSERVED NEUROTOXIC EFFECTS:
Weak positive correlation of blood lead with distance
of home from source of pollution. No relationship
between blood lead and level of mental functioning
by any of several measurements (dysfunction was
found to be related to social factors).
ANIMALS: Rats, Long-Evans, age 30 d.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Amt ns;, to undernourished litters.
ANIMALS: Human: whole population under 17 in working-class area, 317; 275
of these available for testing, 232 (84%) were tested, 215 (78%) had
blood tests, 227 (82%) were behavior-rated, social-worker data were
obtained on 218 (79%); 1% did not take part (parents refused).
PREPARATION AND DOSE
or HISTORY OF PATIENT: Exposure to airborne emissions and dust from a smelting
factory for whole life, gauged by distance of home from
. source in steps of 100 m from 0-500 and 500+.
ROUTE AND SITE: Oral
CONTROL INFORMATION: Mentioned, not described
ROUTE AND SITE: Inhalation of airborne emissions and of dusts in homes and on
roads, ingestion of dusts.
CONTROL INFORMATION: '. . , .
Another, non-exposed, population
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Histology
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior, blood chemistry
567
568
-------
COMPOUND: Lead
007439921
REFERENCE: Moore, J.F., Mushak, P. and Krigman, M.R.
Env. Hlth. Persp. 10:266, 1975 (Abstract).
COMPOUND: Lead
007439921
REFERENCE: O'Tuama, L.A., Howard, J.L., Kim, C.S. Mushak, P.M. and Krigman, M.R.
Env. Hlth. Persp. 10:266, 1975 (Abstract).
OBSERVED NEUROTOXIC EFFECTS:
Level of lead In cerebrum increased just before onset
of convulsions, in nuclei and mitochondria more
than in other organelles.
OBSERVED NEUROTOXIC EFFECTS:
At 5 min lead was strongly concentrated in choroid
plexus and meninges; low concentration in brain;
ouabain reduced choroid plexus level to 2%,
meninges to 13%, brain to 70% of controls. At
240 min these tissue-to-blood ratios had fallen
and ouabain had no effect. Interpreted in terms
of lead transport and its importance in lead encephalopathy.
ANIMALS: Guinea-pigs
ANIMALS: Guinea-pigs
PREPARATION AND DOSE
or HISTORY OF PATIENT:
"large doses"
PREPARATION AND DOSE
or HISTORY OF PATIENT:
0.01 mcCi/kg with/without ouabain
ROUTE AND SITE: Oral
CONTROL INFORMATION: ns.
ROUTE AND SITE: ns.
CONTROL INFORMATION: Lead regarded as control
DURATION OF EXPERIMENT: 5 d
iXAM. TYPE: Biochemistry
DURATION OF EXPERIMENT: 240 min
EXAM. TYPE: Biochemistry
569
570
-------
COMPOUND: Lead
007439921
REFERENCE: Popoff, N., Keinberg, S. and Feigin, I.
Neurology 13:101-112, 1963.
COMPOUND: Lead
007439921
REFERENCE: Pueschel, S.M.
Env. Hlth. Persp. 7:13-16, 1974.
OBSERVED NEUROTOXIC EFFECTS:
Clinically: vomiting, headache, stupor,
papilledema, coma, convulsions. Edema of brain, petechial
hemorrhages in cortex, demyelination and astrocytic
and nicroglial reactions. Authors concluded
that vascular damage contributed to the encephalopathy.
OBSERVED NEUROTOXIC EFFECTS:
23-27% found to have neurological dysfunction
and motor impairment; assessed as low average
mental abilities at first examination, some
improvement reported at reexamination 1 1/2 -
3 yr later.
ANIMALS: Human: 6 cases aged 1 1/2-3
ANIMALS:
Human: 58 children diagnosed as lead-poisoned in a survey of 705
children in Boston. Analysis of hair, then blood.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
History of eating paint for 4-6 mo.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Evaluation, then reexamination 11/2-3 yr later.
ROUTE AND SITE: Oral
CONTROL INFORMATION: ns.
ROUTE AND SITE: ns.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: 5 died in 9 hr to 8 d of hospitalization, one lived
39 d.
EXAM. TYPE: Autopsy, histology
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Clinical, behavior
571
572
-------
COMPOUND: Lead
007439921
REFERENCE: Roberts, T.M., Hutchlnson, T.C., Paciga, J., Chattopadhyayt, A.,
Jervis, R.E. and Van Loon, J.
Science 186:1120-1123, 1974.
COMPOUND: Lead
007439921
REFERENCE:
Rosenblaum, W.I.
Acta Neuropathologlca. 5:54-60, 1965.
OBSERVED NEUROTOXIC EFFECTS:
2 cases of neuropathy, 3 of slow nerve conduction;
increased absorption not enough to cause clear-cut
symptoms but "may cause metabolic and subtle neurological
changes, "found in 10-15% of 21 selected children
with excessive lead loads.
OBSERVED NEUROTOXIC EFFECTS:
Lead caused dilation of pial arteries and
inhibited the contractile response to barium.
At lower doses, the responses were reversible,
but at concentrations of 2% or higher the
arteries never regained their responsiveness
to barium.
ANIMALS:
Humans:
286 residents of zone contaminated by lead smelter A, 1425
close to smelter B.
ANIMALS: Mice, Swiss-Webster, Male, 20 g
PREPARATION AND DOSE
or HISTORY OF PATIENT:
ROUTE AND SITE:
Emissions estimated from A: 15,000 kg/yr, from B:
30,000 kg/yr. Soil near A contained 40 mg lead/g, soil near
B contained 16 mg/g. More dust than fumes. Blood lead
levels near source A: 27 meg/100 ml, near B: 28 meg/100 ml,
but levels over 40 occured in <1% of controls, in 28%
near source A (summer) and 13% near source B (winter).
Inhalation, skin contact, ingestion
CONTROL INFORMATION:
1232 socioeconomically matched urbanites not exposed.
Urban control soil content 0.1-0.5 mg/g. Mean blood lead
level of control children was 19 meg/100 ml.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Clinical, biochemistry
PREPARATION AND DOSE
or HISTORY OF PATIENT: 7.0 mg/100 g
ROUTE AND SITE: Injection
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Dissection
573
574
-------
COMPOUND: Lead
007439921
REFERENCE: Sachs, H.K.
Env. Hlth. Persp. 7:41-45, 1974.
COMPOUND: Lead
007439921
REFERENCE: SeppalHinen, A.M., Tola, S., Hernberg, S. and Kock, B.
Arch. Env. Hlth. 30:180-183, 1975.
OBSERVED NEUROTOXIC EFFECTS:
Symptoms found in 12.2% of subjects in year 1,
falling to 4.2% in year 5 of study: drowsiness,
vomiting, irritability, g-i, behavior, ataxia,
convulsions, stupor peripheral neuropathy; only one
death.
OBSERVED NEUROTOXIC EFFECTS:
Blood lead regularly monitored and never above 70 meg/
100 ml (accepted safety norm). Yet nerve-conduction
in selected muscles was slower (P<0.001) than in
controls. As no complaints were involved, authors
term findings "subclinical neuropathy" and suggest
that safety norms be reconsidered.
ANIMALS:
Human: -6804 (3.2%) of 213,598 screened who had ^50 meg/100 ml of
blood, in Chicago.
ANIMALS:
Human: 26 workers (18 M, 8 F) at a battery factory in Finland.
PREPARATION AND DOSE
or HISTORY OF PATIENT: History of eating paint or plaster 80%, x-ray finding
of paint chips in abdomen in another 10%.
PREPARATION AND DOSE
or HISTORY OF PATIENT: No previous exposure, current exposures (4.6 yr range 13 mo.-
17 yr. slight or moderate. Clinical exam, and electromyography
ROUTE AND SITE: Oral mainly
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: Several yr.
EXAM. TYPE: Clinical, blood chemistry
ROUTE AND SITE: Occupational exposure, inhalation.
CONTROL INFORMATION: Age-sex-matched data from normals (blue-collar) assembled
at Inst. Occupational Hlth., Helesinki, about 200; Blood
lead estimated 10-13 meg/100 ml.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Electrophysiology
575
576
-------
COMPOUND:
Lead (Pb210)
REFERENCE: Thomas, J.A., Dallenbach, F.D. and Thomas, M.
J. Path. 109:45-50, 1973.
COMPOUND: Lead
007439921
REFERENCE:
Zaworskl, R.E. and Oyasu, R.
Arch. Env. Hlth. 27:383-386, 1973.
OBSERVED NEUROTOXIC EFFECTS: study to localize lead In developing cerebellum:
in cytoplasm of capillary endothelial cells, later
in astrocyte foot-processes. After 72 hr lead
associated with edema.
OBSERVED NEUROTOXIC EFFECTS: By atomic absorption: 0.5 + .68 ppm in wet
tissue of normals; increase in first two decades
of life. 0.34 + 0.03 ppm in tumor brains,
statistically non-significant.
ANIMALS: t> Rats, Wistar, F, each with litter aged 1 d; 2 grps trtd.
ANIMALS: Humans: Autopsy material (brains) from 4 hospitals, only R frontal
lobes studied: 191 normal brains, 9 with tumors.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 5 or 10 mcCi.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
No known industrial exposure to lead, childhood exposure
unknown. Samples obtained from ten patient with
brain tumors and 191 normals.
ROUTE AND SITE: I.p.
CONTROL INFORMATION: 2 grps
ROUTE AND SITE: ns.
CONTROL INFORMATION: 191 Control brains, lead content undetectable to 7.9 ppm
DURATION OF EXPERIMENT: Serial sacr to 168 hr.
EXAM. TYPE: Autoradiography after histology
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Chemistry
577
578
-------
COMPOUND: Lead acetate, trihydrate
REFERENCE: Roy> s., Hirano, A., Kochen, J.A. and Zimmerman, H.M.
Acta Neuropath. 30: 287-294, 1974.
OBSERVED NEUROTOXIC EFFECTS: Attenuated endothelial cells of cerebral vessels
with altered ultrastrueture.
COMPOUND: Lead, bis (acetato)tetrahydrooxytri
001335326
REFERENCE: Clasen, R.A., Hartmann, J.F., Coogan, P.S., Pandolfi, S., Laing, I.
and Decker, R.
Env. Hlth. Persp. 7:175-185, 1974.
OBSERVED NEUROTOXIC EFFECTS:
At 6-18 wk onset of ataxia, nystagmus, weakness,
convulsions; rise of blood Pb and urinary ALA,
fall of Hb. Central nervous system edema of white matter
of hemispheres and cerebellum; granular precipitate
with expanded extracellular space; axonal swelling
in cortex only.
ANIMALS: Chick eggs
ANIMALS: 4 Rhesus monkeys (3 M, 1 F) age 5-6 mo. newly weaned.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 50-75 meg inj into yolksac on d 4 of incubation.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.5 g with 1000 IU vitamin D in corn oil 3 doses/wk.
ROUTE AND SITE: Ini, yolksac
CONTROL INFORMATION: ns.
ROUTE AND SITE: Gavage
CONTROL INFORMATION: 2 animals given vitamin D alone.
DURATION OF EXPERIMENT: Living embryos sacrificed serially 5-18 d of incubation
EXAM. TYPE: Histology.
DURATION OF EXPERIMENT: Up to 18 wk.
EXAM. TYPE: Behavior, histology
579
580
-------
COMPOUND:
Lead carbonate
000598630
COMPOUND: Lead carbonate
000598630
REFERENCE:
Hopkins, A.
Br. J. Indust. Med. 27:130-140, 1970.
REFERENCE: Hopkins, A.P. and Dayan, A.D.
Br. J. Indust. Med. 31:128-133, 1974.
OBSERVED NEUROTOXIC EFFECTS:
Ten adults died, 2 were killed; 2 infants died, 1
was killed; 8 convulsed, 3 had limb weakness;
no peripheral nervous system abnormality found,
nor anemia nor punctate basophilia. Central nervous
system findings to be given elesewhere; author
discusses species differences.
OBSERVED NEUROTOXIC EFFECTS:
Seizures, widespread cerebral edema, focal
cortical necroses.
ANIMALS: Baboons, 3 M, 9 F, 7.2-13.6 kg, F adult, M not full-grown; and
3 infant F, 2.8-3.3 kg.
ANIMALS: 3 Baboons: 1 F, 11.7 kg; 1 F, 10.7 kg; 1 F, 2.8 kg.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 50-135 mg/kg for 39-362 d, single and multiple doses.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 1. 86 mg/kg, 5 doses in 122 d and 1 dose on d 137.
2. 94 mg/kg, 8 doses in 234 d.
3. 54 mg/kg, 1 dose and 2 larger doses in 84 d.
ROUTE AND SITE: Intratracheal
CONTROL INFORMATION: Starting data and 12 healthy baboons used in other
studies
ROUTE AND SITE: Intratracheal
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: up to 362 d.
EXAM. TYPE: Behavior, electrophysiology, histology
DURATION OF EXPERIMENT: Death on d 156, 265 and 117 respectively.
EXAM. TYPE: Behavior, histology
581
582
-------
COMPOUND: Lead carbonate
000598630
REFERENCE: Krigman, K.R., Druse, M.J., Traylor, T.D., Wilson, M.H., Newell, L.R.
and Hogan, E.L.
J. Neuropath. Exp. Neurol. 33(l):58-73, 1974.
OBSERVED NEUROTOXIC EFFECTS:
Neural tissue growth retarded. Myelin formation
altered and its cerebral content reduced. Axons
and number of myelin lamellae in the sheaths
were reduced. Hypomyelination. Caudal paraplegia
and medullary cysts. Abnormally small brains.
COMPOUND: Lead carbonate
000598630
REFERENCE: Krigman, M.R. and Hogan, E.L.
Env. Hlth. Persp. 7:187-199, 1974.
OBSERVED NEUROTOXIC EFFECTS: Brain growth retarded (mass, not cell numbers),
with slow maturation, fewer synapses, hypomyelination,
but essentially normal chemistry.
ANIMALS:
Rats, Long-Evan newborns
ANIMALS: Rats, Long-Evans, neonates with dams.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 4% lead carbonate to nursing mothers and then to weanlings
via diet.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 4% in diet fed to dams and, at weaning, to litters.
ROUTE AND SITE: Oral
CONTROL INFORMATION: 8 pups - no lead as controls.
ROUTE AND SITE: oral
CONTROL INFORMATION: Controls similarly treated, no lead.
DURATION OF EXPERIMENT: Sacr. after 30 d post-natal.
EXAM. TYPE: Biochemical, Histology, Ultra structural.
DURATION OF EXPERIMENT: 30 d
EXAM. TYPE: Histology, biochemistry
583
584
-------
COMPOUND: Lead carbonate
000598630
REFERENCE: Lampert, P.W. and Schochet, S.S.
J. Neuropath. Exp. Neurol. 27: 527-545, 1968.
OBSERVED NEUROTOXIC EFFECTS: Proliferation and degeneration of Schwann cells,
with disintegration of myelin lamellae, new lamellae are formed and
disintegrate, leaving remnants of basement membrane. Schwann cells
proliferate along this membrane.
COMPOUND: Lead carbonate
000598630
REFERENCE: Rosenblum, W.I. and Johnson, M.G.
Arch. Path. 85: 640-648, 1968.
OBSERVED NEUROTOXIC EFFECTS:
Neonates exhibited an altered gait and loss of
righting reflex. Neuropathologic findings induced
excesses of fibrous intercapillary strands in
cerebral sites, astrocytosis in the hippocampus, and
altered properties of glia and/or cerebral tissues.
ANIMALS: 26 Long-Evans rats average 100 g
ANIMALS: Mice, Balb/c, pregnant F.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 4% in chow diet.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Diet contained 1% (in 3 cases 0.5%) lead carbonate after
delivery.
ROUTE AND SITE: Oral
CONTROL INFORMATION: Chow only, "parallel groups"
ROUTE AND SITE: Oral
CONTROL INFORMATION: No lead carbonate
DURATION OF EXPERIMENT: Serial sacr 2-12 mo.
EXAM. TYPE: Histology
DURATION OF EXPERIMENT: Suckling neonates were killed at 14, 17, 20, 23d of age.
EXAM. TYPE: Clinical, histology
585
586
-------
COMPOUND: Lead carbonate
000598630
REFERENCE: Sauerhoff, M.W. and Michaelson, I.A.
Science 182:1022-1024, 1973.
OBSERVED NEUROTOXIC EFFECTS: Hyperactivity, aggression, stereotype-behavior in
neonates exposed via dam, starting at 4 wk of age; brain lead increased
8-fold, 20% less dopamine, no change in norepinephrine. Authors infer
relationship of lead, dopamine, and behavior. (This report retracted in
1975 by Goiter and Michaelson, see under Lead acetate).
ANIMALS: Rats, S-D, F, pregnant 16 d
PREPARATION AND DOSE
or HISTORY OF PATIENT: 4% in diet for 16 d, then 40 ppm.
ROUTE AND SITE: oral
CONTROL INFORMATION: Pair-fed, matched controls
DURATION OF EXPERIMENT: Neonates serially sacr up to 29 d of age.
EXAM. TYPE: Behavior, biochemistry
587
COMPOUND: Lead (II) nitrate (1:2)
010099748
REFERENCE: Markov, D.V. and Dimova, R.N.
Acta Neuropath. 28:25-35, 1974.
OBSERVED NEUROTOXIC EFFECTS: Ultrastructural changes seen only in microglial
cells of parietal cortex: hypertrophy especially of endoplasmic reticulum,
lipid inculsions.
ANIMALS: Rats, 11 littermates M and F, newborn.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.4% in drinking water from birth.
ROUTE AND SITE: Oral
CONTROL INFORMATION: Mentioned-not described
DURATION OF EXPERIMENT: 9 mo.
EXAM. TYPE: Histology
588
-------
COMPOUND: Leurocristine
000057227
REFERENCE: Anderson, P.J. Song, S.K. and Slotwlner, P.
J. Neuropath. Exp. Neurol. 26(1):15-24, 1967.
OBSERVED NEUROTOXIC EFFECTS: Peripheral and terminal motor endplates were de-
generated when paralysis was maximal; interpretation uncertain according to
authors. Other wise no peripheral nervous system abnormalities.
ANIMALS: 20 Rats, S-D, M, 150-250 g.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.3-0.4 mg/kg/d up to 4 d
ROUTE AND SITE: I.P.
CONTROL INFORMATION: Matched controls untreated.
DURATION OF EXPERIMENT: 4 d
EXAM. TYPE: Histology
589
COMPOUND: Leurocristine
000057227
REFERENCE: Bradley, W.G.
J. Neurol. Sci. 10:133-162, 1970.
OBSERVED NEUROTOXIC EFFECTS: Acute: axonal degeneration in sciatic, posterior
tibial, digital and intramuscular nerves; minor changes in dorsal root
ganglia and anterior horn and in motor endplate axons. Chronic: Similar
changes with denervation and terminal regeneration. Sciatic nerve conduction
reduced to 81%.
ANIMALS: 27 Guinea-pigs, M, young (200-300 g), and old (>500 g) , outbred.
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) 1 mg/kg one dose to 10 animals.
(2) 0.03 mg/kg, 2/wk to 17 animals.
ROUTE AND SITE: I>P.
CONTROL INFORMATION: 25 untreated controls.
DURATION OF EXPERIMENT: Up to 14 wk.
EXAM. TYPE: Electrophysiology, histology
590
-------
COMPOUND: Leurocristine
000057227
REFERENCE: Bradley, W.G., Lassman, L.P., Pearce, G.W. and Walton, J.N.
J. Neurol. Sci. 10:107-131, 1970.
OBSERVED NEUROTOXIC EFFECTS: All treated over 2 mo. had mixed sensorimotor
peripheral neuropathy, children less sensitive. Distal nerve conduction:
increased latency to complete block. Main nerve trunks unaffected. Sural
nerve biopsy: axonal degeneration. In 5 autopsies, distal muscles denervated.
No signs of CNS damage, but ultrastructure not studied.
COMPOUND: Leurocristine
000057227
REFERENCE: Gottschalk, P.G., Dyck, P.J. and Kiely, J.M.
Neurol. 18: 875-882, 1968.
OBSERVED NEUROTOXIC EFFECTS: During third week of vincristine therapy, paresthesias
in the fingers and toes appeared. Mild generalized
muscle weakness and absence of muscle stretch reflexes
noted at the end of seven weeks.
ANIMALS: Human: Cancer patients - 23 adults aged 26-63 year, 14 children aged
14 mo. to 13 yr. Follow-up data. Studied personally: 2 adults, 3 children.
ANIMALS: 1 Human, F, age 63 yr
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.05 mg/kg/wk (one dose/wk) for up to 20 mo.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 12 mg in 7 wk
ROUTE AND SITE: I.V.
CONTROL INFORMATION: ns.
ROUTE AND SITE: I.V. . .
CONTROL INFORMATION: Group of rats, not described
DURATION OF EXPERIMENT: 20 mo.
EXAM. TYPE: Clinical, electrophysiology, histology (biopsy)
DURATION OF EXPERIMENT: 7 wk
EXAM. TYPE: Neurological, physiological
591
592
-------
COMPOUND: Leurocristine
000057227
REFERENCE: Joneja, M. and Ungthavorn, S.
Teratology 2:235-240, 1969.
COMPOUND: Leurocristine
000057227
REFERENCE: Levitt, L.P. and Prager, D.
Neurology 25:894-895, 1975.
OBSERVED NEUROTOXIC EFFECTS: Of 222 surviving fetuses, 36 had exencephaly,
encephalocele, anopthalmia especially in C3H mice. 115/222 abnormal in some
way.
OBSERVED NEUROTOXIC EFFECTS: "Mononeuropathy," acute, followed each of the
last 2 single doses. Different nerve on each occasion. Claimed first
report of an additional neurotoxic manifestation of vincristine.
ANIMALS: Mice: Inbred C3H/HeJ and DBA/2J and randombred Swiss ICR/Ha, F,
pregnant.
ANIMALS: Human: one case, leukemic M aged 3 yr.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.01% in saline on d 9 of gestation.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 2 mg/28 d for 9 mo. with no ill effect; 18 mo. later
one dose of 2 mg, repeated after 6 mo.
ROUTE AND SITE: i.P.
CONTROL INFORMATION: Saline only
ROUTE AND SITE: i.v.
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: 8 d
EXAM. TYPE: Teratological
DURATION OF EXPERIMENT: Over 3 mo. from last dose.
EXAM. TYPE: Behavior, electrophysiology
593
594
-------
COMPOUND: Leurocristine
000057227
REFERENCE: McLeod, J.G. and Penny, R.
J. Neurol. Neurosurg. Psychlat. 32: 297-304, 1969.
COMPOUND: Leurocristine
000057227
REFERENCE: Moress, G.R., D'Agostino, A.N. and Jarcho, L.W.
Arch. Neurol. 16:377-384, 1967.
OBSERVED NEUROTOXIC EFFECTS: The patients suffered paresthesias, areflexias (ankle)
and slow motor and impaired sensory conduction in per-
ipheral nerves which progressed or reversed after ex-
posure stopped. Biopsy revealed demyelination and
axonal degeneration in sural nerves; regeneration
occurred after exposure stopped.
OBSERVED NEUROTOXIC EFFECTS: Clinical neuropathy, mainly lower extremities,
progressing to quadriparesis, time-related to
compound. Necropsy: demyelination and axonal
degeneration.
ANIMALS: . Human: 9 patients, M & F, 18-79
ANIMALS: Human: 3 cases of acute lymphoblastic leukemia
PREPARATION AND DOSE
or HISTORY OF PATIENT: 5-15.5 mg (total) in 0.02-0.05 mg doses, no more than
5 doses/course
PREPARATION AND DOSE
or HISTORY OF PATIENT:
0.05 mg/kg, 0.1 mg/kg, 2 or more doses.
ROUTE AND SITE: I.V. •
CONTROL INFORMATION: None
ROUTE AND SITE: I.V.
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Clinical, electrophysiology, histology
DURATION OF EXPERIMENT: Lifetime of patients
EXAM. TYPE: Clinical, histology (necropsy)
595
596
-------
COMPOUND: Leurocristine
000057227
REFERENCE: Shelanski, M.L. and Wisniewski, H.
Arch. Neurol 20:199-206, 1969.
OBSERVED NEUROTOXIC EFFECTS:
Neurofibrillary proliferation found in all 3
cases. Authors feel effects were due to leurocristine
and not the other chemotherapeutic agents administered.
COMPOUND: Leurocristine
000057227
REFERENCE: Uy, Q.L., Moen, T.H., Johns, R.J. and Owens, A.H., Jr.
Johns Hopkins Med. J. 121:349-360, 1967.
OBSERVED NEUROTOXIC EFFECTS: Mice and rats: hindlimb paralysis; chromoatolysis
of dorsal root ganglia; later, degeneration of myelin and axis cylinders
of sciatic nerves. No Impairment of neuromuscular transmission or nerve
conduction.
ANIMALS:
3 Humans, acute leukemics, M 7 yr., F 13 yr and M 17 yr.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Dosage varied 1.0 mg-0.5 mg from Feg and Aug.
1.7 mg, 3 doses, plus mercaptopurine 150 mg by
mouth for 3 d and 75 mg after.
3. 2.7 mg, preceded by treatment with prednisone,
mercaptopurine, and cyclophosphamide.
ROUTE AND SITE: 1. I.V., 2. ns., 3. I.V.
CONTROL INFORMATION: Control specimens mentioned, no details
ANIMALS: Mice: BDF (C57BL/6 x DBA/2), F, 20-25 g.
Rats: Lewis, F, 180-200 g.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Mice: 1-8 rag/kg, one dose.
Rats: 0.25-1 mg/kg, one dose.
ROUTE AND SITE: Mice I.P., rats I.V.
CONTROL INFORMATION: starved untreated animals.
DURATION OF EXPERIMENT: Weeks
EXAM. TYPE: Clinical exam, histopathology at autopsy.
DURATION OF EXPERIMENT: serial sacr to 30 d
EXAM. TYPE: Behavior, histology, electrophysiology
597
598
-------
COMPOUND: Leurocristine, sulfate (1:1) (salt)
2068782
REFERENCE: Clarke, J.T.R., Karpati.G., Carpenter, S. and Wolfe, L.E.
J. Neuropath. Exp. Neurol 31(2):247-266, 1972.
COMPOUND: Leurocristine, sulfate (1:1) (salt)
2068782
REFERENCE: Gottschalk, P.G., Dyck, P.J. and Kiely, J.M.
Neurol. 18: 875-882, 1968.
OBSERVED NEUROTOXIC EFFECTS: Lethargy, ataxia, paraplegia and quadriplegia
after 24 hrs.
OBSERVED NEUROTOXIC EFFECTS: Peripheral neurophathy was produced. Axonal type
degeneration of myelinated fibers. Most rats receiving
more than 0.15 mg/kg/d died within four days. Those
receiving 0.1 mg/kg/d died between eight and thirty days
after initial injection.
ANIMALS: Rats, Wistar, M, 100-150 gm.
ANIMALS: 70 Rats, S-D, M, 10-12 wk old, 174-300 gm
PREPARATION AND DOSE
or HISTORY OF PATIENT:
(1) 0.4 mg/kg for chemistry study.
(2) 0.3-0.4 mg/kg/d for 3 d as 0.1 mg/'ml saline soln
for histochemical studies.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 2 doses 2/wk which equal 0.05-0.5 mg/kg/d
ROUTE AND SITE: I.P.
CONTROL INFORMATION:
ROUTE AND SITE: ns
CONTROL INFORMATION: Untreated controls
DURATION OF EXPERIMENT: (1) Sacr after 28 hr. (2) 4 d
EXAM. TYPE: Histochemistry, ultrastructural, chemistry
DURATION OF EXPERIMENT: 5-6d after admin to time of disorder manifestation
EXAM. TYPE: Behavior, histology
599
60C
-------
COMPOUND: Leurocristine, sulfate (1:1) (salt)
2068782
REFERENCE: Schlaepfer, W.W.
.1. Neuropath. Exp. Neurol. 30(3): 488-505, 1971.
COMPOUND: Leurocristine, sulfate (1:1) (salt)
2068782
REFERENCE: Schochet, S.S., Jr., Lampert, P.W. and Earle, K.M.
J. Neuropath. Exp. Neurol. 27:645-658, 1968.
OBSERVED NEUROTOXIC EFFECTS: Axonal alterations of peripheral nerve. Axonal neuro-
tubular disruption. Wallerian degeneration in the distal
segment of nerve fibers.
OBSERVED NEUROTOXIC EFFECTS: 1. Human: seizures, neuronal changes (clumped
Nissl substance, clear areas, acidophilic rhombohedral crystals)
2. Rabbits: similar effects: the clear areas were skeins of neurofilaments
ANIMALS: Rats, Albino, M, 300-350 gm.
ANIMALS: 1. Human: 1 case, F, Aged 2 1/2, acute leukemia, ending in autopsy.
2. 20 Rabbits, NZ White, 2.5 kg.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 1 x 10~3 M, 1 x 10 M or 1 x 10 M in saline solution.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 1. Human: 15 mo. history of cytotoxic drugs including
vincristine i.v.; then 3 mg given intrathecally, and 200 ml of cerebrospinal
fluid exchanged for 200 ml saline.
2. Rabbits: 0.001-0.2 mg/kg one dose intracisternally.
ROUTE AND SITE: Endoneural inj.
CONTROL INFORMATION: None
ROUTE AND SITE: See above
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: Serial sacr 0.5-72 hr
EXAM. TYPE: Histochemistry, cytochemistry, ultrastructural
DURATION OF EXPERIMENT: Rabbits: 1-4 d
EXAM. TYPE: Autopsy, histology
601
602
-------
COMPOUND: Leurocristine sulfate
REFERENCE: Sell, F.J. and Lampert, P.W.
Exp. Neurol. 21: 219-230, 1968
COMPOUND: Leurocristine, sulfate (1:1) (salt)
2068782
REFERENCE: Sell, F.J., Lampert, P.W. and Klatzo, I.
J. Neuropath. Exp. Neurol. 28: 74-85, 1969.
OBSERVED NEUROTOXIC EFFECTS: Neurofibrillary tangles and neuronal degeneration;
starting with clumping of argentophilic neurofilaments
around the nucleus. Persistent after withdrawal of
compound.
OBSERVED NEUROTOXIC EFFECTS: Induced neurofibrillary spheroids filled the cytoplasm
of the cells exposed to aluminum phosphate, and the
nuclei were displaced. The spheroids were compared
with those induced hy vincristine sulfate. The author
claimed the former were like those of postencephalitic
parkinsonism and the latter like those of Alzheimer's
disease.
ANIMALS: In vitro cultures of fetal rabbit spinal cord and dorsal root ganglia
ANIMALS: In vitro cultures of spinal cord and dorsal root ganglia from fetal
NZ White rabbits.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.5-20 ng/drop of medium, changed twice a week, starting
serially at 17-26 d in vitro. Exposures lasted in all 31 hr
to 14 d.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.5-20 ng/drop of medium for 31hr to 14 d, medium
renewed twice weekly
ROUTE AND SITE: in vitro
CONTROL INFORMATION: Laboratory
ROUTE AND SITE: In vitro
CONTROL INFORMATION: Untreated cultures
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Histology
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Light and electron microscopy
603
604
-------
COMPOUND: Lithium carbonate
000554132
REFERENCE: Vacaflor, L., Lehmann, H.E. and Ban, T.A.
J. Clin. Pharm. 10: 387-389, 1970.
COMPOUND: Lithium chloride
007447418
REFERENCE: Benowitz, L.J. and Sperry, R.W.
Exp. Neurol. 40:540-546, 1973.
OBSERVED NEUROTOXIC EFFECTS:
The patients experienced toxic confusion within 2 wk
of treatment (impaired consciousness, clonic limb
movements), which reversed in 1 wk after treatment was
stopped and did not reappear after treatment was
reinstituted. One case (gravida 7 mo, history of
mania) given 900-1200 mg/d developed hand tremor,
whereupon treatment was stopped; after delivery she
took unknown amount of unprescribed compound (serum
SmEq/liter) and had 5 d of coma, spasticity of limbs,
and convulsions.
OBSERVED NEUROTOXIC EFFECTS:
No effect on memory 20 min after treatment, but
amnesia 24 hr afterwards, if treated 4 min before
training (less so if treated 2 min before, and no
effect if treated 10 min after training). Delayed
effect on development of long term memory in chicks.
ANIMALS: Human: 5 cases of side-effects attributed to compound, all over 50 yr old ANIMALS: Cockerels, White Leghorn, 1 d old
PREPARATION AND DOSE
or HISTORY OF PATIENT: 600 mg/d increasing to 900-1200 mg/d, producing only serum
0.97-1.53 mEq/liter
PREPARATION AND DOSE
or HISTORY OF PATIENT:
0.245 mg/chick, before or after memory-training
ROUTE AND SITE: Oral
CONTROL INFORMATION: None
ROUTE AND SITE: Injected into 2 cerebral hemispheres, 1/2-dose to each
CONTROL INFORMATION: Vehicle only (some), sham training (others)
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Clinical
DURATION OF EXPERIMENT: 10 sec to 2 hr.
EXAM. TYPE: Behavior
605
606
-------
COMPOUND: D-Lyseramide, N-N-diethyl ester, tartrate (LSD)
COMPOUND: Malic acid, L(+)-
REFERENCE: Diab, I.M., Freedman, D.X. and Roth, L.J.
Science 173:1022-1024, 1971.
REFERENCE: Curtis, D.R. and Watkins, J.C.
J. Neurochem. 6:117-141, 1960.
OBSERVED NEUROTOXIC EFFECTS:
Free LSD generally distributed in pituitary,
pineal, cerebellum, hippocampus, choroid plexus.
Bound LSD localized in cortical neurons, caudate
nucleus, midbrain, medulla, epithelium of choroid
plexus.
OBSERVED NEUROTOXIC EFFECTS:
Treatment caused excitation or depression of
neuronal activity. Excitatory ranking: glutamic,
g-aminoglutaric, aspartic, cysteic, cysteine-
sulfinic acids, 6-hydroxyglutamic, N-methylaspartic,
N-formiminoaspartic acids.
Depressant ranking: 6-alanine, GABA, taurine,
N-methyl-B-alanine, 6-amino-B-hydroxybutyric,
glycine, a-alanine, 6-aminovaleric, B-aminoisobutyric
acids.
Structure-activity relationships established.
ANIMALS: Rats, S-D, M, 100-125 g
ANIMALS: Cats, surgically prepared to expose, motoneurones, Renshaw cells or
dorsal horn interneurones in lumbar cord.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
1 mcg/g, or 1.7 mcg/g of labeled compound.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Qualitative doses.
ROUTE AND SITE: i.V.
CONTROL INFORMATION: None
ROUTE AND SITE: Topical, ionophoresis
CONTROL INFORMATION: Laboratory
DURATION OF EXPERIMENT: Serial sacr 5-60 min.
EXAM. TYPE: Autoradiography
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry, electrophysiology
607
608
-------
COMPOUND: Maicmic acid
000141822
REFERENCE: Curtis, D.R. and Watkins, J.C.
J. Neurochem. 6:117-141, I960.
OBSERVED NEUROTOXIC EFFECTS:
'ANIMALS:
Treatment caused excitation or depression of
neuronal activity. Excitatory ranking: glutamic,
8-aminoglutaric, aspartic, cysteic, cysteins-
sulfinic acids, 6-hydroxyglutamic, N-methylaspartic,
N-formiminoaspartic acids.
Depressant ranking: 8-alanine, GABA, taurine,
N-methyl-3-alanine, 6-amino-6-hydroxybutyric,
glycine, a-alanine, 6-aminovaleric, 6-amirioisobutyric
acids.
Structure-activity relationships established.
Cats, surgically prepared to expose;., motoneurones, Renshaw cells or
dorsal horn interneurones in lumbar cord.
COMPOUND: Malonic acid, amino-
REFERENCE:
Curtis, D.R. and Watkins, J.C.
J. Neurochem. 6:117-141, 1960.
OBSERVED NEUROTOXIC EFFECTS:
ANIMALS:
Treatment caused excitation or depressicn of
neuronal activity. Excitatory ranking: glutamic,
B-amiaoglutaric, aspartic, cysteic, cysteine-
sulfinic acids, S-hydroxyglutamic, N-methylaspartic,
N-fonniminoaspartic acids.
Depressant ranking: B-alanine, GABA, taurine,
N-methyl-S-alanine, 6-amino-S-hydroxybutyric,
glycine, a-alanine, 6-aminovaleric, 6-aininoisQbutyric
acids.
Structure-activity relationships established.
Cats, surgically prepared to expose motoneurones, Renshaw cells or
dorsal horn interneurones in lumbar cord.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Qualitative doses.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Qualitative doses.
ROUTE AND SITE: Topical, ionophoresis
CONTROL INFORMATION: Laboratory
ROUTE AND SITE: Topical, ionophoresis
CONTROL INFORMATION: Laboratory
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry, electrophysiology
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry, electrophysiology
609
610
-------
COMPOUND: Malonic acid, aminoethyl-
COMPOUND: Mandelic acid, hydrazide
REFERENCE: Curtis, D.R. and Watkins, J.C.
J. Neurochem. 6:117-141, 1960.
OBSERVED NEUROTOXIC EFFECTS:
ANIMALS:
Treatment caused excitation or depression of
neuronal activity. Excitatory ranking: glutamic,
B-aminoglutaric, aspartic, cysteic, cysteine-
sulfinic acids, 6-hydroxyglutamic, N-methylaspartic,
N-formiminoaspartic acids.
Depressant ranking: 6-alanine, GABA, taurine,
N-methyl-B-alanine, 6-amino-B-hydroxybutyric,
glycine, a-alanine, 6-aminovaleric, B-aminoisobutyric
acids.
Structure-activity relationships established.
Cats, surgically prepared to expose motoneurones, Renshaw cells or
dorsal horn interneurones in lumbar cord.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Qualitative doses.
REFERENCE: Jenney, E.H. and Pfeiffer, C.C.
J. Pharm. Exp. Ther. 122: 110-123, 1958.
OBSERVED NEUROTOXIC EFFECTS: Convulsions
ANIMALS: nice, Harlan, 19-21 g
PREPARATION AND DOSE
or HISTORY OF PATIENT: 6.0 mM/kgm
ROUTE AND SITE: Topical, ionophoresis
CONTROL INFORMATION: Laboratory
ROUTE AND SITE: i.p.
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry, electrophysiology
DURATION OF EXPERIMENT: Acute
EXAM. TYPE: Clinical
612
-------
COMPOUND: Manganese
007439965
REFERENCE: Cotzias, G.C., Horiuchi, K., Fuenzalida, S. and Mena, I.
Neurology 18:376-382, 1968.
OBSERVED NEUROTOXIC EFFECTS:
"Healthy" miners had more tissue manganese
and cleared Manganese faster than controls or
chronic-poisoned grps from tissues, although
clearance from bloodstream was slower. Neuropathy
continued in poisoned grp. Authors conclude that higl
tissue Manganese not needed for neuropathy
to continue; thus chelation therapy logically
useless.
COMPOUND: Manganese
007439965
REFERENCE: Mena, I., Marin, 0., Fuenzallda, S. and Cotzias, G.C.
Neurology 17: 128-136, 1967.
OBSERVED NEUROTOXIC EFFECTS: Transient psychiatric symptoms (long list)
followed by permanent neurologic (partly extrapyramidal) changes, only
in the poisoned group. "Healthy" miners eliminated labeled Mn faster than
either poisoned or non-exposed control groups.
ANIMALS: Humans: 20 healthy miners M, aged 23-60 yr.
18 patients with chronic Manganese poisoning M, aged 18-56 yr.
19 hospital staff, M and F, aged 20-30 yr.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
(1) 1-20 yr industrial exposure continuing.
(2) Exposure terminated 2-27 yr before study.
(3) No exposure.
All given Manganese for clearance studies.
ROUTE AND SITE: 1%v.f antecubital
CONTROL INFORMATION: Grps (1) and (3) treated as controls.
ANIMALS: Human: 114 Mn miners, clinically "healthy", of whom 14 were selected
for isotope studies: M ages 20-60 (av. 37 yr).
13 in-patients with chronic Mn poisoning; ages 18-56 yr (av. 50)
PREPARATION AND DOSE
or HISTORY OF PATIENT: Industrial exposure; clinical histories and lab studies
performed.
ROUTE AND SITE: Mainly inhalation of dusts
CONTROL INFORMATION: Medical workers, 4 M, 4 F, aged 20-30.
DURATION OF EXPERIMENT: About 1 mo.
EXAM. TYPE: Biochemical
DURATION OF EXPERIMENT: 20-30 d for each case
EXAM. TYPE: Behavior, laboratory, isotope studies.
613
614
-------
COMPOUND: Manganese
007439965
REFERENCE: Nichols, R.A. and Nakajima, Y.
Brain Res. 86: 493-498, 1975.
COMPOUND: Manganese
007439965
REFERENCE- Prakash, N.J., Fontana, J. and Henkin, R.I.
Life Sci. 12(1):249-259, 1973.
OBSERVED NEUROTOXIC EFFECTS:
Manganese inhibited the generation of the IPSP (sic)
of the stretch receptor neuron but did not affect the
action potential of the soma and had no effect on GABA-
induced increase of conductance. Manganese was inter-
preted to affect coupling of excitation with GABA
secretion at the presynaptic site of the inhibitory
synapse.
OBSERVED NEUROTOXIC EFFECTS:
Inhibited (Na+ + K+) ATPase, although never more
than 20%, even at 0.2 mM. Inhibition involved
blockage of norepinephrine.
ANIMALS: In vitro: slow adapting stretch receptors from 8th thoracic segment
of lobster (II. americanus) and crayfish (Oronectes) , or from
the 2nd-3rd abdominal segment of crayfish.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Mn at 0-5 mM
ANIMALS:
Rat brain synaptosomes in vitro
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Mn chloride added to medium in various expts.
ROUTE AND SITE: In vitro
CONTROL INFORMATION: Zero treatment
ROUTE AND SITE: in vitro
CONTROL INFORMATION: Lab
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Biochemistry, electrophysiology
DURATION OF EXPERIMENT: Minutes
EXAM. TYPE: Biochemistry
615
616
-------
COMPOUND: Manganese
007439965
REFERENCE: Prasad, K.N.
Exp. Neurol. 45:554-557, 1974.
OBSERVED NEUROTOXIC EFFECTS: Adenyl cyclase inhibited, cAMP phosphodiesterase
stimulated by manganese. Differentiated cells more
sensitive to manganese than undifferentiated.
COMPOUND: Manganese
007439965
REFERENCE: Rosenstock, H.A., Simons, D.G. and Meyer, J.S.
J. Am. Med. Assn. 217:1354-1358, 1971.
OBSERVED NEUROTOXIC EFFECTS:
Impairment of gait and station, dysarthric speech
and deterioration of fine motor coordination.
Headaches, anxiety and irritability.
ANIMALS: In vitro cultured mouse neuroblastoma cells
ANIMALS:
Human: one, M, 22 yr.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 1 or 10 mM in medium
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Exposure to fumes present in a steel foundry over a two
year period. After that too disabled to work, 14 yr
later was confined to wheelchair.
ROUTE AND SITE: In vitro
CONTROL INFORMATION: Mentioned, no details.
ROUTE AND SITE: Inhalation
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: 3 or more d
EXAM. TYPE: Biochemistry
DURATION OF EXPERIMENT: 14 mo. of exposure
EXAM. TYPE: Clinical
617
618
-------
COMPOUND: Manganese
007439965
REFERENCE: Smyth, L.T., Ruhf, R.C., Whitman, N.E. and Dugan, T.
J. Occup. Med. 15:101-109, 1973.
OBSERVED NEUROTOXIC EFFECTS:
5 Subjects with signs of Parkinsonism were examined,
removed from exposure, and reexamined after 3 mo.
Reversible manifestations (loss of associated
arm movements) had disappeared, irreversible
ones had not progressed. Authors concluded that
Manganese exposure was the cause, although urine
values were not high (but bile is the main route
of excretion of Manganese). Blood chemistry was
inconclusive.
ANIMALS: Human: 142 employees of a steelworks producing ferromanganese alloy,
71 directly exposed, 71 not directly exposed.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Exposure to fume and dust, 0.12-13.3 mg/m (TLV = 5
mg/m3) up to 26 yr. Fume was mainly Mn,0, <2 me in s
Dust was mainly FeMn, also MnO, Mn.O, and Fe~0, , 95%
size.
<5 me in size, and respirable.
ROUTE AND SITE: Inhalation, skin contact
CONTROL INFORMATION: The 71 not exposed were carefully matched.
DURATION OF EXPERIMENT: Over 3 mo.
EXAM. TYPE: Clinical
619
COMPOUND: Manganese
007439965
REFERENCE: Tanaka, S. and Lieben,
J. Arch. Env. Hlth. 19:674-684, 1969.
OBSERVED NEUROTOXIC EFFECTS: Weakness, tremors, disturbed gait, motor impairment
of extremities. Recovery, none to partial.
ANIMALS: Human, 3 selected cases of industrial exposure
PREPARATION AND DOSE
or HISTORY OF PATIENT: Up to >100 mg/m in air (dust) for 1-17 yr.
ROUTE AND SITE: Inhalation and skin contact
CONTROL INFORMATION: None
-X
DURATION OF EXPERIMENT: Years
EXAM. TYPE: Clinical, clinicochemical
620
-------
COMPOUND: Manganese (II) chloride (1:2)
0096250
REFERENCE: Chandra, S.V. and Sur, R.N.
Env. Res. 3:417-424, 1970.
OBSERVED NEUROTOXIC EFFECTS: Convulsions, EEC changes, scattered degeneration
of neurons in cerebral and cerebellar cortex.
COMPOUND: Manganese (II) chloride (1:2)
0096250
REFERENCE: Meiri, U. and Rahamimoff, R.
Science 176:308-309, 1972.
OBSERVED NEUROTOXIC EFFECTS: Managanese ions blocked synaptic transmission at
the neuromuscular junction. The inhibition
produced is reversible.
ANIMALS: 40 Rabbits, M, av. 1.5 kg. 30 had surgical impl of brain cannulae.
ANIMALS: In vitro preparation of frog sartorius muscle.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
0.5 mg in 0.1 ml saline/2 d for 15 d
PREPARATION AND DOSE
or HISTORY OF PATIENT:
1 mM MnCl ; 0.07-1 mM Mn
2+
ROUTE AND SITE: intravehtricular
CONTROL INFORMATION: 10 normal controls, 10 had cannula impl and 0.1 ml
saline inj.
ROUTE AND SITE: In vitro
CONTROL INFORMATION: Laboratory
DURATION OF EXPERIMENT: Serial sacr 0 hr to 15 d
EXAM. TYPE: Behavior, autopsy, histology
DURATION OF EXPERIMENT: Minutes
EXAM. TYPE: Electrophysiology
621
622
-------
COMPOUND: Manganese, cyclopentadienyltricarbonyl
012079651
REFERENCE: Arkhipova, O.G.
Fed. Proc. 23: T51-T54, 1964.
OBSERVED NEUROTOXIC EFFECTS: Damage to nervous system indicated by trembling, paresis
of limbs and reduced neuromuscular excitability.
COMPOUND:
3-Mercaptopropionic acid
REFERENCE: Arnaiz, G.R. deL., de Canal, M.A. and DeRobertis, E.
J. Neurochem. 19:1379-1385, 1972.
OBSERVED NEUROTOXIC EFFECTS: Dose-related convulsant properties studied in
cerebellum. Glutamate decarboxylase and GABA fell,
GABA-aminotransferase rose, and dose-related changes
were seen in Purkinje cells. From these and other
enzyme and amino-acid changes the authors inferred
that the compound causes imbalance among the excitatory-
inhibitory amino acids.
ANIMALS: Rats, white; Mice, white; Rabbits; Guinea-pigs
ANIMALS: Rats, Wistar, 100-150 g
PREPARATION AND DOSE
or HISTORY OF PATIENT: Rats: LD,n was 80 mg/kg, MLD 40 mg/kg
Mice: LD^ was 150 mg/kg, MLD 80-100 mg/kg
Rats, rabbits, guinea-pigs: Exposed to 0.0007-0.001 mg/liter
of air for 10 mo
ROUTE AND SITE: Inhalation. Route of LD and MLD doses ns (but not inhalation).
CONTROL INFORMATION: Yes, but not described
PREPARATION AND DOSE
or HISTORY OF PATIENT: 35-150 mg/kg
ROUTE AND SITE: I.P.
CONTROL INFORMATION: Controls no treatment.
DURATION OF EXPERIMENT: 10 mo
EXAM. TYPE: Clinical
DURATION OF EXPERIMENT: 60 min
EXAM. TYPE: Biochemistry, histology, behavior
623
624
-------
COMPOUND: Manganese dioxide
001313139
REFERENCE: Abd el Naby, S. and Hassanein, M.
J. Neurol. Neurosurg, Psychiat. 28:
282-288, 1965.
OBSERVED NEUROTOXIC EFFECTS:
The subjects experienced insidious onset with fatigue
and inertia; then weak, stiff gait, parkinsonian-type
imbalance, motor signs cerebellar, pyramidal, and/or
extrapyramidal; sleep disturbances, psychoses and
emotional lability. Permanent disabilities included
the use of legs, and neurological signs continued to
progress after exposure stopped; only psychic changes
regressed.
COMPOUND:
3-Mercaptopropionic acid
REFERENCE: Horton, R.W. and Meldrum, B.S.
Br. J. Pharmac. 49: 52-63, 1973.
OBSERVED NEUROTOXIC EFFECTS: Seizures, photic stimulation, EEC changes, inhibition
of brain glutamate carboxylase were caused by 3-mer-
captopropionic acid more strongly than by allylglycine
or 4-deoxypryidoxine HC1. Thus the authors concluded
that seizures were due to depletion of glycine and Y-
aminobutyric acid (GABA).
ANIMALS: Human: 45 miners, M, 21-54
ANIMALS: Mice, CFW or BALB/C, M, 20-30 g
10 Baboons (Papio papio) , adolescent, from Senegal, 3-6 kg
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Exposure to dust for 5 mo to 25 yr
PREPARATION AND DOSE
or HISTORY OF PATIENT: Mice: EP5Q and latency 0.27 mmol/kg, 4.5 min.
Baboons: ED and latency 0.28 mmol/kg, 4 min.
ROUTE AND SITE: Dermal, inhalation, possibly ingestion too.
CONTROL INFORMATION: None
.ROUJE AND SITE: Mice I.*., Baboons I.V.
.CONTROL INFORMATION: Timed studies
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Clinical
.DURATION OF .EXPERIMENT: Various
EXAM. TYPE: Mice: behavior, biochemistry; baboons: polygraph.
625
626
-------
3-Mercaptopropionic acid
RL!'LntNCC: Olnoy, J.W. , Ho, 0.1.. nm! iilicc, V.
Exp. lir.-iin Kcs. 1';: i?l-'/(i, 19V.I.
OBSERVED NEURCTOX1C EFFECTS: No cytotoxicity was observed.
COMPOUND: Mercuric bichloride
007487947
REFERENCE: Chang, L.W., Desnoyers, P.A., and Hartmann, H.A.
J. Neuropath. Exp. Neurol. 31(3):489-501, 1972.
OBSERVED NEUROTOXIC EFFECTS:
Poisoning produced initial decrease in RKA content
followed by partial increase of RNA after prolonged
intoxication. Cell volume decreased. Moderate
increase in RNA was noted in anterior horn
motoneurons.
ANIMALS: Rice, Swiss-wcbster a^c 10 d, total 250
ANIMALS: 18 Rats
PREPARATION AND DOSE
or HISTORY OF PATIENT: Initially 12 iimiolcs/kg, then range established Cor
each coinpound.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Daily dosage of 1.2 mg/kg body weight.
ROUTE AND SITE: s.C.
CONTROL INFORMATION: Compounds compared with monosodium L-plutnnate (MSG)
potency for selectively necrosing neurons in retina
and brain (hypothalamus)
DURATION OF EXPERIMENT: 5 hr or serial intervals including 5 hr.
EXAM. TYPE: Histology
ROUTE AND SITE: Oral, stomach tube, S.C.
CONTROL INFORMATION: 6 Rats
DURATION OF EXPERIMENT: Serial sacr 1 wk, 2 wks, 6 wks
EXAM. TYPE: Histology, quantitative, cytochemical
627
628
-------
COMPOUND: Mercuric bichloride
007487947
REFERENCE: Chang, L.W. and Hartmann, H.A.
Exp. Neurol. 35:122-137, 1972.
COMPOUND:
Mercuric bichloride
007487947
REFERENCE: Takeda, Y., Kunugi, T., Hoshino, 0. and Ukita, T.
Tox. Appl. Pharm. 13: 156-164, 1968.
OBSERVED NEUROTOXIC EFFECTS:
General distribution of mercury parallel to
gross neuropathology; intracellular binding
to membraneous structures in cytoplasm, minimally
in nucleus.
OBSERVED NEUROTOXIC EFFECTS: Alkyl mercury compounds excreted more slowly than inorganic
or aryl compounds. Metabolism varied with C-chain length.
Distribution in brain and reported neurotoxlcity were re-
lated to structure of compound.
ANIMALS: Rats, S-D, adult M
ANIMALS: Rats, Donryu, aged 7 wk
PREPARATION AND DOSE
or HISTORY OF PATIENT:
1 mg/kg/d
PREPARATION AND DOSE
or HISTORY OF PATIENT: Compounds labeled with iuJHg; mercuric chloride 3 mg/kg,
others 10 mg/kg (one dose).
203,,
ROUTE AND SITE: Gavage or S.C.
CONTROL INFORMATION: Mentioned, not described
ROUTE AND SITE: S.C.
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: 1 d to 11 wk, serial
EXAM. TYPE: Histochemistry
DURATION OF EXPERIMENT: Serial 1-8 d
EXAM. TYPE: Biochemistry
629
630
-------
COMPOUND: Mecuric (II) nitrate
010045940
REFERENCE: Fox, J.H., Patel-Mandlik, K. and Cohen, M.M.
J. Neurochem 24:757-762, 1975.
OBSERVED NEUROTOXIC EFFECTS: No effect on respiration or metabolism.
COMPOUND Mercury
007439976
REFERENCE: Chang, L.W., Optiz, J.M., Pallister, P.D., Gilbert, E.F. and Viseskul, C.
Acta Neuropath. (Berl.) 26:275-284, 1973.
OBSERVED NEUROTOXIC EFFECTS:
Disintegration of granular layer, disapperance of
Purkinje cells with Bergmann's fiber proliferation
and demyelination of fiber tracts observed in
cerebellum. Extensive proliferation of astrocyte
fibers and characteristic focal demyelination and
loosening of tayelin sheaths in many nerve fibers.
ANIMALS: Guinea-pig brain slices, in vitro.
ANIMALS: 1 case study of 21 yr female.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.1-1.0 mM in medium.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Accidental exposure to mercury-containing herbicide
during childhood.
ROUTE AND SITE: In vitro incubation
CONTROL INFORMATION: Mercury-free medium used for control.
ROUTE AND SITE: Ingestion
CONTROL INFORMATION: Experimental rat poisoned with mercury.
DURATION OF EXPERIMENT: 1 hr in some cases
EXAM. TYPE: Biochemistry
DURATION OF EXPERIMENT: 19 yrs.
EXAM. TYPE: Light and election microscopy.
631
632
-------
COMPOUND Mercury
007439976
REFERENCE: Danziger, S.J. and Fossick, P.A.
J. Occup. Med. 15:15-20, 1973.
OBSERVED NEUROTOXIC EFFECTS:
Symptoms: 6 insomnia, 5 hard-of-hearing, 4 oral
phenomena, 3 peripheral neuropathy, 2 depression,
1 severe oral and sensory disturbance with tremors
and irritability. Signs: 59 myopia, 12 dermograph-
ism, 9 hearing loss, 2 hyperesthesia, 1 dental
oral and ocular disorders. High urine Hg and 6
cases of proteinuria.
COMPOUND:
REFERENCE:
Mercury
00743996
Prakash, N.J., Fontana, J. and Henkin, R.I.
Life Sci. 12(1):249-259, 1973.
OBSERVED NEUROTOXIC EFFECTS:
At concentrations over 0.01 mM, Hg"*"1" completely
inhibited (Na+ + K+) ATPase. Inhibition
involved blockage of norepinephrine and choline
uptake.
ANIMALS: Human: 75 workers (gender ns) calibrating lab glassware in 13
factories in New Jersey, ages 20-60+
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Exposure from 0.5 to 40+ y, skin contact; vapor 0-0.3
Kg/m3 in breathing zone, tc 1.03 elsewhere. (TLV is
0.1, 0.05 proposed).
ANIMALS:
Rat brain synaptosomes in vitro
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Hg chloride added to medium in various expts.
ROUTE AND SITE: skin, inhalation, perhaps ingestion
CONTROL INFORMATION: 4 foremen claiming to work in uncontaminated areas, and the
research team.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Clinical, behavior, blood and urinalysis. environmental
ROUTE AND SITE: Xn vitro
CONTROL INFORMATION: Lab
DURATION OF EXPERIMENT: Minutes
EXAM. TYPE: Biochemistry
634
-------
COMPOUND:
Mercury
007439976
REFERENCE: Smith, E.G., Vorwald, A.J., Patll, L.S. and Mooney, T.F.
Am. Indust. Hyg. Assn. J. 31:687-700, 1970.
OBSERVED NEUROTOXIC EFFECTS: Anorexia, insomina, tremors, other signs.
COMPOUND Mercury
007439976
REFERENCE: Vroom, F.Q. and Greer, M.
Brain 95: 305-318, 1972.
OBSERVED NEUROTOXIC EFFECTS: Irritability and poor concentration (transient), memory
defects (permanent), suggesting temporal lobe lesions;
neuropsychology suggesting general cortical dysfunction;
abnormal EEG; parkinsonianism; severe tremors in all;
peripheral nervous system involvement; electromyography
indicating denervation.
ANIMALS:
Human: 642 workers from 21 chloralkali plants in U.S. and Canada.
ANIMALS: Human: 9 selected employees of a thermometer factory where industrial
negligence had produced an epidemic of signs.
PREPARATION AND DOSE , 3
or HISTORY OF PATIENT: Time-weighted av exposures approx. 0 to 0.27 mg/m , 85%
_< 0.1 mg/m3.
PREPARATION AND DOSE
or HISTORY OF PATIENT: About 3 yr exposure, less in some cases.
ROUTE AND SITE: Inhalation, skin contact
CONTROL INFORMATION: 382 non-exposed workers
ROUTE AND SITE: Inhalation, skin contact, ingestion
CONTROL INFORMATION: Up to 40 normal subjects for various tests
DURATION OF EXPERIMENT: 1 vr-
EXAM. TYPE: Full medical.
DURATION OF EXPERIMENT: Up to 20 mo after diagnosis
EXAM. TYPE: Electrophysiology, neuropsychology, behavior, chemistry
635
636
-------
COMPOUND: Mercury, (acetato)methyl-
COMPOUND: Mercury, (acetato)methyl-
REFERENCE: Carraichael, N., Cavanagh, J.B. and Rodda, R.A.
Acta. Neuropath. 32(2):115-125, 1975.
REFERENCE: Kim, S.U.
Exp. Neurol. 32:237-246, 1971.
OBSERVED NEUROTOXIC EFFECTS:
Severe ataxia. Degenerative changes seen in
primary sensory ganglion cells, in both Purkinje
and granule cells of the cerebellum, and in cells
of the forebrain. Wallerian degeneration of
sensory neurones, widespread pyknosis of cerebellum,
symmetrical changes in cerebral cortex.
OBSERVED NEUROTOXIC EFFECTS: Vacuolar degeneration especially in granule and
Purkinje cells. Axonx and melin sheaths degen-
erated, cytoplasmic organelles affected but not
nuclear structures.
ANIMALS: Rabbits, New Zealand, White, M and F, young 1.0-2.5 kg.
ANIMALS: Slices of newborn mouse cerebellum in vitro
PREPARATION AND DOSE
or HISTORY OF PATIENT: 7.5 mg/kg/d for 3-4 d, total 22.5 or 30 mg/kg.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 10 mM in medium
ROUTE AND SITE: I. Tub.
CONTROL INFORMATION: 2 rabbits.
ROUTE AND SITE: In vitro
CONTROL INFORMATION: Laboratory
DURATION OF EXPERIMENT: Serial sacr: 1, 2, 8 d
EXAM. TYPE: Histology, vascular
DURATION OF EXPERIMENT: 5 h to 24 d
EXAM. TYPE: Histology
637
638
-------
COMPOUND: Mercury, butyl-chloro-
000543635. ,
REFERENCE: Takeda, Y., Kunugi, T., Hoshino, 0. and Uklta, T.
Tox. Appl. Pharm. 13: 156-164, 1968«
COMPOUND: Mercury (I) chloride
007546307
REFERENCE: Davis, L.E., Wands, J.R., Weiss, S.A., Price, D.L. and Girling, E.F.
Arch. Neurol. 30:428-431, 1974
OBSERVED NEUROTOXIC EFFECTS: Alkyl mercury compounds excreted more slowly than inorganic
l or aryl compounds. Metabolism varied with C-chain length.
' Distribution in brain and reported neurotoxlcity were re-
lated to structure of compound.
OBSERVED NEUROTOXIC EFFECTS: Dementia, recent memory loss, sensorineural loss,
ataxia, coarse tremors. Autopsy revealed small brains, loss of cerebellar
granular cells, Hg in neuronal cytoplasm (especially choroid plexus).
ANIMALS: Rats, Donryu, aged 7 wk
ANIMALS: 2 Human patients: (1) F, 63 yr and (2) F, 56 yr.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Compounds labeled with iuJHg; mercuric chloride 3 mg/kg,
others 10 mg/kg (one dose).
203.,
PREPARATION AND DOSE
or HISTORY OF PATIENT: 120 mg as laxative tablet, twice daily for: (1) 25 yr,
(2) 6 yr prior to death.
ROUTE AND SITE: S.C.
CONTROL INFORMATION: ns
ROUTE AND SITE: Oral
CONTROL INFORMATION: No controls
DURATION OF EXPERIMENT: Serial 1-8 d
EXAM. TYPE: Biochemistry
DURATION OF EXPERIMENT: (1) 25 yr, (2) 6 yr
EXAM. TYPE: Behavior, Hospital investigations.
639
640
-------
COMPOUND: Mercury (II) chloride
007487947
REFERENCE: Chang, L.W. and Hartmann, H.A.
Acta Neuropath. 20:316-334, 1972.
OBSERVED NEUROTOXIC EFFECTS:
Pathological manifestations in dorsal and ventral
root fibers and sciatic nerve. Axonal degeneration.
Disoriented myelin layers.
COMPOUND: Mercury, chloroethyl-
000107277
REFERENCE: Hay, W.J., Rickards, A.G., McMenemey, W.H. and Cumings, J.N.
J. Neuro. Neurosurg. Psychiat. 26: 199-202, 1963.
OBSERVED NEUROTOXIC EFFECTS:
The brain cortex was selectively damaged, especially the
calcarine, parastriate, motor and sensory areas and the
caudal part of first temporal gyrus. A loss of neurons,
a porous underlying white matter, swollen oligodendro-
cytes were observed. There was a high concentration of
mercury in the corpus callosum. The patient experienced
blurred vision, deafness, ataxic dysarthria, incoordin-
ation and weakness of arms and legs.
ANIMALS: Rats, Adult, M
ANIMALS: Human: M, 29 (one case)
PREPARATION AND DOSE
or HISTORY OF PATIENT:
1.0 mg/kg/d.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Occupational exposure of 7 wk before onset of symptoms, died
25 wk after first exposure
ROUTE AND SITE: Oral and injections
CONTROL INFORMATION: ns.
ROUTE AND SITE: ns
CONTROL INFORMATION: None
DURATION OF EXPERIMENT:Serial sacr. 5 hr, 12 hr, 1 d, 4 d, 1 wk, 6 wk, 11 wk.
EXAM. TYPE: Ultrastructural, histology
DURATION OF EXPERIMENT: 25 wk
EXAM. TYPE: Clinical, histology
641
642
-------
COMPOUND: Mercury, chloroethyl-
000107277
REFERENCE: Kasuya, M.
Tox. Appl. Pharm. 32:347-354, 1975.
OBSERVED NEUROTOXIC EFFECTS:
Compound inhibited outgrowth. Vitamin E pro-
tected against toxicity, less potently against
ethylmercuric chloride than methylmercuric chloride.
Interpreted that alkyl mercurials interact with
membranes to produce nerve degeneration.
COMPOUND: Mercury, chloroethyl-
000107277
REFERENCE: Takeda, Y., Kunugi, T., Hoshino, 0. and Ukita, T.
Tox. Appl. Pharm. 13: 156-164, 1968.
OBSERVED NEUROTOXIC EFFECTS: Alkyl mercury compounds excreted more slowly than inorganic
or aryl compounds. Metabolism varied with C-chain length.
Distribution in brain and reported neurotoxicity were re-
lated to structure of compound.
ANIMALS: In vitro slices of newborn rat cerebella
ANIMALS: Rats, Donryu, aged 7 wk
PREPARATION AND DOSE
or HISTORY OF PATIENT:
6 x 10 to 2 x 10 M; in presence of ethanol 0.1-0.4%,
glucose 550 mg/100 ml, and vitamin E (DL-a-tocopherol
acetate) 0-2 x 10~5 M.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Compounds labeled with ^UJHg; mercuric chloride 3 mg/kg,
others 10 mg/kg (one dose).
203.,
ROUTE AND SITE: Culture medium
CONTROL INFORMATION: Zero levels of various additives to medium
ROUTE AND SITE: S.C.
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: 4 d
EXAM. TYPE: Microscopic outgrowth of neurons and fibroblasts
DURATION OF EXPERIMENT: Serial 1-8 d
EXAM. TYPE: Biochemistry
643
644
-------
COMPOUND: Mercury, chloromethyl-
000115093
REFERENCE: Carmichael, N., Cavanagh, J.B., and Rodda, R.A.
Acta Neuropath. 32(2):115-125, 1975.
COMPOUND: Mercury, chloromethyl-
000115093
REFERENCE: Chang, L.W. Desnoyers, P.A., and Hartmann, H.A.
J. Neuropath. Exp. Neurol. 31(3):489-501, 1972.
OBSERVED NEUROTOXIC EFFECTS:
Severe ataxia. Primary sensory ganglion cells,
cerebellar Purkinje and granule cell and forebrain
cell degeneration. Wallerian degeneration of
sensory neurones, widespread pyknosis of cerebellum,
symmetrical changes in cerebral cortex.
OBSERVED NEUROTOXIC EFFECTS:
Continuous decrease in RNA content in spinal
ganglion neurons. Except for cell swelling
during first week of methylmercury poisoning,
cell volume decreased after poisoning. Moderate
increase in RNA after poisoning was noted in
anterior horn motoneurons.
ANIMALS:
Rabbits, New Zealand, White, M and F, young 1.0-2.5 kg.
ANIMALS: 9 Rats, S-D (Holtzman), 150 g
PREPARATION AND DOSE
or HISTORY OF PATIENT: 7.5 mg/kg/d for 3-4 d, as suspension (5 mg/tnl)
in 50% polyethylene glycol 400. Total 22.5 or 30 mg/kg.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Daily dosage of 1.0 mg/kg body weight
ROUTE AND SITE: s.C., neck
CONTROL INFORMATION: 2 rabbits
ROUTE AND SITE: Orally, stomach tube, S.C.
CONTROL INFORMATION: 6 Rats
DURATION OF EXPERIMENT: Serial sacr: l,2,8d.
EXAM. TYPE: Histology, vascular.
DURATION OF EXPERIMENT: Serial sacr 1 wk, 2 wks, 6 wks, 11 wks.
EXAM. TYPE: Histology, quantitative, cytochemical studies.
645
646
-------
COMPOUND: Mercury, chloromethyl-
000115093
REFERENCE: Chang, L.W. and Hartmann, H.A.
Exp. Neurol. 35:122-137, 1972.
OBSERVED NEUROTOXIC EFFECTS:
General distribution of mercury parallel to
gross neuropathology; intracellular binding
to membraneous structures in cytoplasm, minimally
in nucleus.
ANIMALS: Rats, S-D, adult M
PREPARATION AND DOSE
or HISTORY OF PATIENT:
1 mg/kg/d
ROUTE AND SITE: Gavage or S.C.
CONTROL INFORMATION: Mentioned, not described
DURATION OF EXPERIMENT: 1 d to 11 wk, serial
EXAM. TYPE: Histochemistry
647
COMPOUND: Mercury, chloromethyl-
000115093
REFERENCE: Chang, L.W. and Hartmann, H.A.
Acta Neuropath. 20:316-334, 1972.
OBSERVED NEUROTOXIC EFFECTS:
After 4 days, mercury apparent in axoplasm. Dorsal
root fiber pathology after 1 wk. Axonal de-
generation with destruction of myelin. Limited
damage to ventral root fibers and extensive damage
to sciatic nerve in 2nd wk. Phagocytosis by
Schwann cells observed.
ANIMALS:
Rats, adult M
PREPARATION AND DOSE
or HISTORY OF PATIENT: 1 mg/kg/d
ROUTE AND SITE: oral or I.P.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: Serial to 11 wk.
EXAM. TYPE:
Histology
648
-------
COMPOUND: Mercury, chloromethyl-
COMPOUND: Mercury, chloromethyl-
000115093
REFERENCE: Fehling, C., Abdulla, M., Brun, A., Dictor, M., Schutz, A. and Skerfving, S.
Toxicol. Appl. Pharm. 33:27-37, 1975.
OBSERVED NEUROTOXIC EFFECTS: Waddling gait, cross of hindlimbs and severe
involvement of righting reflexes. Wallerian
degeneration and edema and degeneration of
sensory ganglia. Partial reversible peripheral
neuropathy.
REFERENCE: Carman, R.H., Weiss, B. and Evans, H.L.
Acta Neuropath. 32:61-74, 1975.
OBSERVED NEUROTOXIC EFFECTS:
Neuronal damage in cerebral cortex, eosimophilic
neuron degeneration, loss of Nissl substance,
impairment of touch and vision. Loss of pro-
prioceptive sense, incoordination, astereognosis.
'ANIMALS: 30 Rats, Wistar, M, 135-170 g.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 20 or 40 mg Hg/kg/d as soln with dilute sodium hydroxide
and 20% (w/w) egg albumin.
ANIMALS: 14 Squirrel Monkeys, Saimiri sciureus, Male
6 Monkeys, Macaca, Male
PREPARATION AND DOSE
or HISTORY OF PATIENT:
0.4-4 mg Hg/kg/wk.
ROUTE AND SITE: I. Tub.
CONTROL INFORMATION: 10 controls mercury-free albumin soln.
ROUTE AND SITE: Oral
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: 15 d
EXAM. TYPE: Neurological, chemical, nerve conduction velocity, histopathology.
DURATION OF EXPERIMENT: Sacr. at various intervals.
EXAM. TYPE: Clinicopathology, autoradiography, necropsy, histology
649
650
-------
COMPOUND: Mercury, chloromethyl-
000115093
REFERENCE: Harris, S.B., Wilson, J.G. and Printz, R.H.
Teratology 6:139-142, 1972.
OBSERVED NEUROTOXIC EFFECTS: Hydrocephalus among surviving fetuses. Compound
produced significant amounts of embryotoxicity, and also produced some maternal
toxicity.
COMPOUND: Mercury, chloromethyl-
000115093
REFERENCE: Iverson, F., Downie, H., Paul, C. and Trenholm, H.L.
Tox. Appl. Pharm. 24:545-554, 1973.
OBSERVED NEUROTOXIC EFFECTS:
Loss of muscular control (neurotoxiclty) 1-2
wk after treatment, some cases. In Central nervous
system levels ranked cerebrum, cerebellum, cord,
dose-related; decay (elimination) rate not dose-
related but biphasic.
ANIMALS: Golden hamsters, F, pregnant, at least 134
ANIMALS:
Guinea-pigs, English, F, 400-500 g
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) 2-8 mg/kg in carboxymethylcellulose (0.2%) one time,
d 5-10 of pregnancy;
(2) Groups of 20 given 8 mg/kg on d 5, 8 or 9.
(3) 10 animals given 4 mg/kg on d 8.
(4) Chronic: 1, 4, or 2 mg/kg/d for 14 d.
ROUTE AND SITE: i.p.
CONTROL INFORMATION: Control group vehicle only.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Acute toxicity
I.P.: 1.5-9.1 mg Hg/kg
P.O.: 4-30 mg Hg/kg
in 5mM sodium carbonated at 0.5 ml/100 g to 10 animals each dose.
ROUTE AND SITE: Oral, i.p.
CONTROL INFORMATION: Controls: sodium carbonate treatment.
DURATION OF EXPERIMENT: Sacr on d 15 of pregnancy
EXAM. TYPE: Teratological
DURATION OF EXPERIMENT: Serial sacr, 1-49 d after dose.
EXAM. TYPE: Mortality, biochemistry
651
652
-------
COMPOUND: Mercury, chloromethyl-
000115093
REFERENCE: Kasuya, M.
Tox. Appl. Pharm. 32:347-354, 1975.
COMPOUND:
Mercury, chloromethyl-
000115093
REFERENCE: Khera, K.S.
Teratology 8:293-304, 1973.
OBSERVED NEUROTOXIC EFFECTS:
Compound Inhibited outgrowth. Vitamin E pro-
tected against toxicity, less potently against
ethylmercuric chloride than methylmercuric chloride.
Interpreted that alkyl mercurials interact with
membranes to produce nerve degeneration.
OBSERVED NEUROTOXIC EFFECTS: Mercury 6.6 ppm in maternal brain. Fetal cerebellum:
transient external granular layer thinner than in controls; cell aggregates
in incipient molecular layer more common than in controls, changes dose-
related, mainly in 0.25 mg/kg grp.
ANIMALS: In vitro slices of newborn rat cerebella
ANIMALS: Cats of random origin, 2.2-3.5 kg.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
10 M; in presence of ethanol 0.1-0.4%, glucose
550 mg/100 ml, and vitamin E (DL-o-tocopherol acetate)
0-2 x 10~5 H.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.03-0.75 mg/kg/d in corn oil d 10-58 of pregnancy.
ROUTE AND SITE: Culture medium
CONTROL INFORMATION: Zero levels of various additives to medium
ROUTE AND SITE: Oral in gelatin capsules
CONTROL INFORMATION: Controls treated corn oil alone
DURATION OF EXPERIMENT: 4 d
EXAM. TYPE: Microscopic outgrowth of neurons and fibroblasts
DURATION OF EXPERIMENT: Sacr on d 59 of pregnancy
EXAM. TYPE: Teratological
653
654
-------
COMPOUND: Mercury, chloromethyl-
000115093
REFERENCE: Khera, K.S., Iverson, F., Hierlihy, L., Tanner, R. and Trivett, G.
Teratology 10:69-76, 1974.
OBSERVED NEUROTOXIC EFFECTS: Clinical: 0.5 mg/d and over, ataxia, visual,
sensory and righting-reflex losses. High brain levels of mercury.
Cerebral degeneration, especially in white matter of cortex and internal
granular layer of cerebellum.
ANIMALS: Cats, age 4-9 d
PREPARATION AND DOSE
or HISTORY. OF PATIENT:
up to 184 d.
0.25-1.0 mg/kg dissolved in 0.05%, NaHCO-, daily,
ROUTE AND SITE: Gavage
CONTROL INFORMATION: Control treatment vehicle only
DURATION OF EXPERIMENT: Maximum 184 d.
EXAM. TYPE: Biochemistry, histology
655
COMPOUND: Mercury, chloromethyl-
000115093
REFERENCE: Ware, R.A., Chang, L.W. and Burkholder, P.M.
Acta Neuropath 30:211-224, 1974.
OBSERVED NEUROTOXIC EFFECTS: infrastructure damage and subsequent dysfunction
of blood-brain barrier induced 4-6 hr after administration. Horseradish
peroxidase demonstrated: tracer extravasation into brain parenchyma after
4 hr and, tracer permeation into neurons and axons after 10-12 hr.
ANIMALS: 72 Rats, S-D, M, adult, av 200 g.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 10 mg/kg, followed 10 min prior to sacr by Horseradish
peroxidase: 10 mg in 0.25 ml saline, i.v.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: 18 rats, 1 ml saline as controls.
DURATION OF EXPERIMENT: Serial sacr 0.5-24 hr.
EXAM. TYPE: Histochemistry, Histology
656
-------
COMPOUND: Mercury, chlorophenyl
000100561 •
REFERENCE: Takeda, Y., Kunugl, T., Hoshino, 0. and Ukita, T.
Tox. Appl. Pharm. 13: 156-164, 1968.
OBSERVED NEUROTOXIC EFFECTS: Alkyl mercury compounds excreted more slowly than Inorganic
I or aryl compounds. Metabolism varied with C-chain length.
Distribution in brain and reported neurotoxicity were re-
lated to structure of compound.
COMPOUND: Mercury, (3-cyanoguanidino)methyl-
000502396
REFERENCE: Cavanagh, J.B. and Chen, F.C.K.
Acta Neuropath. 19:208-215, 1971.
OBSERVED NEUROTOXIC EFFECTS: Early loss of hindlimb control, recovery complete
5 wk after stopping doses (5 mg/kg). Gross ataxia of all limbs at 14-16
d, recovery always incomplete, some died (7.5 mg/kg). By 10th-12th d
Wallerian degeneration in peripheral nerves, then spinal ganglion cells,
then axonal degeneration in cord, then discrete degeneration in cerebellum
(Purkinje cells normal, no other brain findings).
ANIMALS: Rats, Donryu, aged 7 wk
ANIMALS: Rats, WAG/C, S-D, and Porton, M and F
PREPARATION AND DOSE
203,,
or HISTORY OF PATIENT: Compounds labeled with Hg; mercuric chloride 3 mg/kg,
others 10 mg/kg (one dose).
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.25 mg/ml, in 50% polyethyleneglycol 400
(1) 5 mg/kg/d for 8 d.
(2) 7.5 mg/kg/d for 8 d.
ROUTE AND SITE: S.C.
CONTROL INFORMATION: ns
ROUTE AND SITE: Gavage
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: Serial 1-8 d
EXAM. TYPE: Biochemistry
DURATION OF EXPERIMENT: "Many months"
EXAM. TYPE: Histology, behavior
657
658
-------
COMPOUND: Mercury, (3-cyanoguanidino)methyl-
000502396
REFERENCE: Diamond, S.S. and Sleight, S.D.
Tox. Appl. Pharm. 23:197-207, 1972.
COMPOUND: Mercury, (3-cyanoguanidino) methyl-
000502396
REFERENCE: Magos, L. and Butler, W.H.
Fd. Cosmet. Toxicol. 10: 513-517, 1972.
OBSERVED NEUROTOXIC EFFECTS: Demyelination of sciatic nerve, atrophy of
cerebellum granular cells, Neuronal degeneration
in cerebrum, hippocampus and cervical spinal
cord. Peripheral nervous system and cerebellum
lesions.
OBSERVED NEUROTOXIC EFFECTS:
Dose-time-related linear accumulation of methyl
mercury in the brain . Granular-layer necrosis was
observed in the cerebellum with white-matter edema.
Ataxia was apparent.
ANIMALS: 84 Fats, S-D, M, lOOg
ANIMALS:
Rats, Porton, F, 200 g
PREPARATION AND DOSE
or HISTORY OF PATIENT:
(1) 0.5-25.0 mg/100 g bw, single dose.
(2) 20 rats given U>50> 1.:
(3) 1.0 mg/100 g bw, 1/wk.
(2) 20 rats given U>50> 1.335 mg/100 g bw.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.84 mg Hg/kg/d, 5 d/wk for up to 59 doses
1.68 mg Hg/kg/d, 5 d/wk for up to 34 doses
3.36 mg Hg/kg/d, 5 d/wk for up to 16 doses
ROUTE AND SITE: I.P.
CONTROL INFORMATION: (2) 6 rats distilled water
ROUTE AND SITE: Oral
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: (1) 1 wk,
EXAM. TYPE: Clinical, histology
DURATION OF EXPERIMENT: Sacrificed after last dose if surviving
EXAM. TYPE: Behavior, histology, chemistry
659
660
-------
COMPOUND: Mercury, (3-cyanoguanldino) methyl-
000502396
REFERENCE:Spyker, J.M.
Federation Proc. 34:1835-1844, 1975.
OBSERVED NEUROTOXIC EFFECTS: Offspring of 6 mo-yr whose mothers were exposed to
8 mg/kg displayed tremors, ataxia, difficulty
righting. Those of mothers exposed to a smaller
dose underwent retarded growth and development.
Mothers unaffected.
COMPOUND: Mercury, cysteinylethyl-
REFERENCE: Mukai, N.
Acta Neuropath. 22:102-109, 1972.
OBSERVED NEUROTOXIC EFFECTS: Accretion in central nervous; predicatable selective
necrosis of small granular neurons in koniocortex and neostriatum. Astroglial
cell compartment believed to transport mercury protein complex into neurons.
ANIMALS: Mice, Strain 129/SvSl: nulliparous, F, offspring
ANIMALS: Mice: 24 C3H and 27 CD-I, 20-25 g
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.5-8 mg/kg in saline.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.3 mg/d in 0.5 ml saline x 8 d, labeled with tritium.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: Females with saline gave birth to offspring which developed
normally.
DURATION OF EXPERIMENT: 1 yr.
EXAM. TYPE: Behavior, neurochemical analysis
ROUTE AND SITE: I.P.
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: 15 d
EXAM. TYPE: Histology, autoradiography
661
662
-------
COMPOUND:
Mercury, ((2,3-dihydroxypropyl)thio)methyl-
REFERENCE: Charlton, K.M.
Can. J. Comp. Med. 38:75-81, Jan. 1974.
COMPOUND: • Mercury, hydroxymethyl-
001184572
REFERENCE: Berlin, M., Grant, C.A., Hellberg, J. and SchUtz, A.
Arch. Env. Hlth. 30:340-348, 1975.
OBSERVED NEUROTOXIC EFFECTS:
Gait disturbance. Peripheral nervous system:
Wallerian degeneration in sensory fibers and
neuronal degeneration in dorsal root ganglia.
Lesions caused by neuronal-axonal degeneration.
Central nervous system: Ischemic neuronal
degeneration glial degeneration,and gliosis.
OBSERVED NEUROTOXIC EFFECTS:
Operant behavior tests, filmed. As blood mercury was
increased, sudden visual disorder was seen, suggesting
tissue threshold for mercury toxicity. Typical cerebral
cortical lesions always involved visual cortex, and the
tissue methylmercury level was claimed to be the
lowest associated with such lesions yet seen.
ANIMALS: 20 Pigs, Yorkshire, 7 M and 13 F, 10 wk old.
ANIMALS:
Squirrel monkeys, M and F, 500-1000 g.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.24-5.76 mg Hg/kg/d.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.2-0.8 mg/monkey/wk, adjusted to produce desired level
in blood; 4 levels apparently aimed at (0.6-1.8 mcg/g);
in some expts labeled methylmercury given.
ROUTE AND SITE: Oral
CONTROL INFORMATION: 4 untreated controls.
ROUTE AND SITE: Gavage
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: 2 sacr at 1 d, others left to die.
EXAM. TYPE: Histology, necropsy.
DURATION OF EXPERIMENT: Approx 9 mo.
EXAM. TYPE: Behavior, biochemistry, histology
663
664
-------
COMPOUND: Mercury, hydroxymethyl-
001184572
REFERENCE: Falk, S.A., Klein, R., Baseman, J.K., Sanders, G.M., Talley F.A.
and Lira, D.J.
Arch. Path. 97:297-305, 1974.
OBSERVED NEUROTOXIC EFFECTS: Only wt. loss, lethargy clinically; slow
increase of brain mercury; pyknotic neurons in cerebellum.
COMPOUND: Mercury, hydroxymethyl-
001184572
REFERENCE: Herman, S.P., Klein, R., Talley, F.A. and Krigman, M.R.
Lab. Invest. 28(1):104-118, 1973.
OBSERVED NEUROTOXIC EFFECTS: Ataxic hindlimb gait, selective Wallerian-like
degeneration in sensory fibers in dorsal root, sciatic
nerve, brachial plexus and sural nerve. Sensory
polyneuropathy in peripheral nerves, spinal
ganglia and cord. Wallerian degeneration in
peripheral sensory axons and central nervous
system neuronal necrosis.
ANIMALS: Guinea-pigs, Hartley, M, 250-300 g
ANIMALS: 16 Rats, albino, C-D, M
PREPARATION AND DOSE
or HISTORY OF PATIENT: 2 mg/kg/d, 5 d/wk, for 1-6 wk
PREPARATION AND DOSE
or HISTORY OF PATIENT: 2 mg Hg/kg/d, 5 d/wk for 1-3 wk.
ROUTE AND SITE: s.C.
CONTROL INFORMATION: Uttermates, total 55, no details.
ROUTE AND SITE: S.C.
CONTROL INFORMATION: 6 Rats treated sterile water.
DURATION OF EXPERIMENT: Serial sacr to 11 wk.
EXAM. TYPE: Clinical, biochemical, histology
DURATION OF EXPERIMENT: Sacr 1-24 d
EXAM. TYPE: Ultrastructural, histology, clinical
665
666
-------
COMPOUND: Mercury, hydroxymethyl-
001184572
REFERENCE: Null, D.H., Gartside, P.S. and Wei, E.
Life Sci. 12(2):65-72, 1973.
OBSERVED NEUROTOXIC EFFECTS: Mercury cone in fetal brains "at least twice"
that in dams or nonpregnant adults. Interpreted by authors to explain
greater susceptibility of fetus to compound.
COMPOUND: Mercury, mercaptomethyl-
REFERENCE: Miyakawa, T., Deshimaru, M., Sumiyoshi, S., Teraoka, A., Udo, N.,
Hattori, E. and Tatetsu, S.
Acta Neuropath. 15:45-55, 1970.
OBSERVED NEUROTOXIC EFFECTS:
Pathological changes in peripheral sensory nerve
fibers: swelling and degeneration of Schwann cells;
changes in both myelin sheaths and axons (beginning
at nodes of Ranvier).
ANIMALS: 20 Rats, F, 200-220 g, pregnant and non-pregnant.
ANIMALS: Rats, adult, M, 100-115 g, 4 x 3 (rats & groups)
PREPARATION AND DOSE
or HISTORY OF PATIENT: 5-40 mg Hg/kg to pregnant (d 13 gestation) and non-
pregnant rats. Preliminary tests showed highest mercury concentration
in brain found 5-9 d after treatment.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 1 mg/rat/d
ROUTE AND SITE: S.c.
CONTROL INFORMATION: Control: saline only.
ROUTE AND SITE: Oral
CONTROL INFORMATION: 4 Rats
DURATION OF EXPERIMENT: 7 d after treatment
EXAM. TYPE: Chemistry
DURATION OF EXPERIMENT: Sacrifice on d 4, 8, 12, 20.
EXAM. TYPE: Histology
667
668
-------
COMPOUND: Mercury, mercaptomethyl-
COMPOUND: Mercury, methjl-
REFERENCE: Mlkayawa, T., Deshimaru, M., Sumiyoshl, S., Teraoka, A. and Tatetsu, S.
Acta Neuropath. 17:6-13, 1971.
REFERENCE:
Abe, T., Haga, T. and Kurokawa, M.
Brain Res. 86:504-508, 1975.
OBSERVED NEUROTOXIC EFFECTS:
Day 7: Mitosis of Schwann cells. Day 250: Decreased
number of myelinated fibers; some regeneration
(peripheral nervous system). Posterior nerve root
ganglion cells intact.
OBSERVED NEUROTOXIC EFFECTS: Blockage of axoplasmic transport. Depolymerized
cerebral microtubules in vitro.
ANIMALS: 6 Rats, adult, M, 100-115 g
ANIMALS: Frogs, R. catesbeiana
PREPARATION AND DOSE
or HISTORY OF PATIENT: 1 mg/rat/d for 20 d.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
(1) 5 mcl of 5mM methyl mercury 2 hr after labeled leucine.
(2) 108.5 mcM to purified microtubule protein from pig brain.
ROUTE AND SITE: oral
CONTROL INFORMATION: 2 Rats
ROUTE AND SITE: Inj., 9th dorsal root ganglion; In vitro
CONTROL INFORMATION: Vehicle only
DURATION OF EXPERIMENT^ Rats sacrificed 7 d after last dose, 3 sacrificed 250 d
afterwards. 1 rat/gp control.
EXAM. TYPE: Histology
DURATION OF EXPERIMENT: 38 hr.
EXAM. TYPE: Biochemistry
669
670
-------
COMPOUND: Mercury, methyl-
COMPOUND:
Mercury, methyl-
REFERENCE: Albanus, L., Frankenberg, L., Grant, C., von Haartman, U.,
Jernelov, A., Nordberg, G., Rydalv, M., Schutz, A. and Skerfving, S.
Env. Res. 5:425-442, 1972.
OBSERVED NEUROTOXIC EFFECTS:
Gait and visual field impairment, convulsions.
Over 90% of mercury was absorbed, 20% found in hair,
1% of remainder in brain (18 meg/kg, all as
methyl-mercury, comparable with compound as
administered in lab experiments.
REFERENCE:
Fox, H.H., Patel-Mandlik, K. and Cohen, M.M.
J. Neurochem. 24:757-762, 1975.
OBSERVED NEUROTOXIC EFFECTS:
Decreased oxygen uptake and carbon dioxide
production, increased production of pyruvate
and lactate. Authors propose inhibition of
tricarboxylic acid cycle as basis of organomercury
neurotoxicity.
ANIMALS: Pike (Esox lucius) from contaminated and uncontaminated waters;
Cats, European short-haired, 9 F and 6 M in 3 grps of 3 F and 2 M.
ANIMALS:
Guinea-pig brain slices in vitro.
PREPARATION AND DOSE
Or HISTORY OF PATIENT: The pike were fed to the cats. Contaminated fish had
been exposed to phenyl mercury acetate. Trace amounts
of methylmercury hydroxide sprayed on homogenized
contaminated and uncontaminated fish. Amount added
corresponded to 0.6% of mercury present originally.
ROUTE AND SITE: Oral
CONTROL INFORMATION: Noncontaminated fish, homogenized and frozen without
further treatment.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.01-0.5 mM in medium
ROUTE AND SITE: In vitro incubation
CONTROL INFORMATION: Mercury-free medium used for control.
DURATION OF EXPERIMENT: Up to 82 d
EXAM. TYPE: Behavior, biochemistry
DURATION OF EXPERIMENT: 1 hr in some cases.
EXAM. TYPE: Biochemistry
671
672
-------
COMPOUND: Mercury, methyl-
COMPOUND: Mercury, methyl-
REFERENCE: Ganther, H.E., Goudie, C., Sunde, M.L., Kopecky, M.J., Wagner, P.
Oh, S-H. and Hoekstra, W.G.
Science 175:1122-1124, 1972.
OBSERVED NEUROTOXIC EFFECTS: Death rate from mercury diminished by selenium
in amounts reported.
REFERENCE: Iwata, H., Okamoto, H. and Ohsawa, Y.
Res. Comn. Chem. Path. Pharm. 5(3):673-680, 1973.
OBSERVED NEUROTOXIC EFFECTS:
A dose of 0.5 mg/kg sodium selenite given S.C.
with the compound increased immediate accumulation
of mercury in the brain but not in other organs;
after 1 wk this accumulation was decreased. The
authors concluded that selenium complexing with
mercury hastened excretion of mercury.
ANIMALS: 360 Japanese quail (Coturnix coturnix japonica). day-old, in 8 grps of 45.
ANIMALS: Rats, Wistar, M, 140-160 g
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0-20 ppm Hg as methylmercury in diets (various)
with/without natural Se or Se supplement 0.5 ppm as
PREPARATION AND DOSE
or HISTORY OF PATIENT:
10 mg/kg/d 8-10 d
ROUTE AND SITE: Oral
CONTROL INFORMATION: Yes
ROUTE AND SITE: Oral
CONTROL INFORMATION:
DURATION OF EXPERIMENT: Serial sacr to 7 wk
EXAM. TYPE: Epidemiology, behavior
DURATION OF EXPERIMENT: 24 hr or 1 wk
EXAM. TYPE: Behavior, mortality, biochemistry
673
674
-------
COMPOUND: Mercury, methyl-
COMPOUND: Mercury, methyl-
REFERENCE: Klein, R., Herman, S.P. Brubaker, P.E., Lucier, G.W. and
Krigman, M.R.
Arch. Path. 93:408-418, 1972.
OBSERVED NEUROTOXIC EFFECTS: Ataxia, hindlimb-crossing; advanced peripheral
neuropathy, vacuoles and neurophagia in anterior horns, fewer neurons in
parts of brainstem, pyknotic nuclei in internal granular layer of cerebellum.
REFERENCE: Matsumoto, H., Koya, G. and Takeuchi, T.
J. Neuropath. Exp. Neurol. 24(4):563-574, 1965.
OBSERVED NEUROTOXIC EFFECTS: Small brains (650 g vs normal 960 g at 2.5 yr;
630 g vs 1125 g normal at 6 yr. Disorganized cellular structure of cortex,
no active demyleination but poor corpora callosa, atrophy of cerebellum;
no great changes in brain stem, few in cord, retina intact. However,
pyramidal tracts were demyelinated, in brain and cord. Picture claimed
typical of Minamata disease.
ANIMALS:
Rats, Chalres Rvier, M, 280-365 g, total 28 in 4 grps
ANIMALS: 2 Human autopsies
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) 6 rats, 20 mg/kg in 2 doses 1/d, killed on d 3.
(2) 6 rats, 50 mg/kg in 5 doses 1/d, killed on d 6.
(3) 6 rats, 70 mg/kg in 7 doses 1/d, killed on d 8.
(4) 10 rats, 70 mg/kg in 7 doses 1/d, killed on d 15.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 2 F human children inferred to have been exposed in utero.
Autopsy findings at 2.5 and 6 yr respectively. Families had histories of
Minamata disease, no exposure of subjects.
ROUTE AND SITE: s.C.
CONTROL INFORMATION: 26 in 4 grps, paired with above.
ROUTE AND SITE: Transplacental
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: Serial sacr to 15 d
EXAM. TYPE: Behavior, histology
DURATION OF EXPERIMENT:
EXAM. TYPE: Histopathology
675
676
-------
COMPOUND: Mercury, methyl-
COMPOUND: Mercury, methyl-
REFERENCE:
Rustam, H. and Hamdi, T.
Brain 97:499-510, 1974.
REFERENCE: Rustam, H., Von Burg, R., Amin-Zaki, L. and El Haasani, S.
Arch. Env. Hlth. 30:190-195, 1975.
OBSERVED NEUROTOXIC EFFECTS:
Multiple system involvement in most cases,
severity varied within families. In coordination,
ataxic gait, dysarthria and nystagmus. Reduced
visual acuity, blindness and some speech
disturbance. Sensory changes like peripheral
neuropathy were not confirmed electrophysiologically.
OBSERVED NEUROTOXIC EFFECTS: Selective muscle weakness was uncovered; neostigmine
produced clinical improvement that was transient, suggesting
direct/indirect action of methyl mercury on transmitter
release.
ANIMALS:
53 Humans, 30 F, 23 M, 5-60 yr.
ANIMALS:
Human: 3 cases (F 25, M 10, F 10) from the 1972 outbreak with
delayed recovery.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Consumption of bread made from wheat treated with
compound. Grain eaten within 1-3 mo, and 2-8 wk
intervened between last poisoned meal and onset of
symptoms. Patients selected from 6,530 admitted to
hospital.
ROUTE AND SITE: Oral
CONTROL INFORMATION: ns.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Effects of neostigmine therapy on electromyography were
tested. 0.25-0.5 mg neostigmine and 0.3-0.6 mg atropine
sulfate were given.
ROUTE AND SITE: i.M.
CONTROL INFORMATION: Alternate drug and placebo periods in each case.
DURATION OF EXPERIMENT:
EXAM. TYPE:
Cases occured between 1956-1962.
Clinical, physiological, clinical laboratory.
DURATION OF EXPERIMENT: Months
EXAM. TYPE: Electrophysiology, behavior
677
678
-------
COMPOUND: Mercury, methyl-
COMPOUND: Mercury, methyl-
REFERENCE: Salvaterra, P., Lown, B., Morganti, J. and Massaro, E.J.
Acta Pharmacol. Toxicol. 33: 177-190, 1973.
OBSERVED NEUROTOXIC EFFECTS: Open field tests and alterations of selected glycolytic
pathway intermediates corresponded and were dose-related,
at 1 and 3 hr after doses; by 72 hr all normal.
REFERENCE: Somjen, G.G., Herman, S.P., Klein, R. and Krigman, M.R.
Env. Hlth. Persp. 4:99, 1973. (Abstract).
OBSERVED NEUROTOXIC EFFECTS:
Sensory neurons of dorsal root ganglia damaged
first and most, accumulate methyl mercury more
avidly. Neurons held more mercury than glia,
satellite cells or Schwann cells.
ANIMALS: Mice, Swiss-Webster, M, 25-32 g, 6/grp.
ANIMALS:
Rats
PREPARATION AND DOSE
or HISTORY OF PATIENT:
(1) 1, 5, 10 mg Hg/kg as chloride salt.
(2) 10 mg Hg/kg (single doses).
PREPARATION AND DOSE
or HISTORY OF PATIENT:
ROUTE AND SITE: I.P.
CONTROL INFORMATION: NaCl treated controls.
ROUTE AND SITE: ns.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: (1) Serial sacr to 74 hr. (2) Serial sacr to 7 d.
EXAM. TYPE: Behavior, biochemistry
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior, electrophysiology, radlosotope studies
679
680
-------
COMPOUND:
Mercury, methyl(methylthio)-
COMPOUND:
Mercury, Methyl(thioacetamido)-
REFERENCE' Miyakawa, T., Sumiyoshi, S. and Deshimaru, M.
Acta Neuropath. 30:33-41, 1974.
OBSERVED NEUROTOXIC EFFECTS: Destruction of myelin sheath, slight ataxia in
hindlimbs, slight involvement of dorsal root
ganglia fibers, morphological changes in nodes of
Ranvier axons and Wallerian or segmental degeneration
of nerve fibers. Involvement of the sural nerve.
REFERENCE: Okinaka, S., Yoshikawa, M., Mozai, T., Mizuno, Y., Terao, T., Watanabe, H.,
Ogihara, Y.., Hirai.'S., Yoshino, Y., Inose, T., Anzai, S. and Tsuda, M.
Neurology 14: 69-76, 1964.
OBSERVED NEUROTOXIC EFFECTS:
Clinical effects: numbness, speech disturbances, ataxia, paralysis,
restriction of visual fields. Levels of Hg in blood, hair, liver, kidney,
brain increased up to 40-fold. Widespread denervation of cerebral cortex
granular layers, especially calcarine and superior temporal convolution,
in cerebellar cortex (layer adjacent to Purkinje cells, but not Golgi
cells), and in anterior horn of cord.
ANIMALS: 10 Rats, Wistar, M, 100-110 g.
ANIMALS: Human: 3 cases, M, 17-35
PREPARATION AND DOSE
or HISTORY OF PATIENT: 1 mg/kg/d x 10.
PREPARATION AND DOSE
or HISTORY OF PATIENT: skin application for widespread fungal infection
ROUTE AND SITE: Oral
CONTROL INFORMATION: 5 control rats
ROUTE AND SITE: Topical, limbs and trunk
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: Sacr 600 d
EXAM. TYPE: Ultrastructural, histology
\
DURATION OF EXPERIMENT: 2 mo (fatal cases), 8 mo (surviving case)
EXAM. TYPE: Autopsy (histology), clinical
681
682
-------
COMPOUND:
Mercury, methyl (thioacetamido)-
COMPOUND:
Mercury, methyl (thioacetamido)-
REFERENCE: Yoshlno, Y., Mozai, T. and Nakao, K.
J. Neurochem. 13: 397-406, 1966.
REFERENCE: Yoshino, Y., Mozai, T. and Nakao, K.
J. Neurochem. 13: 1223-1230, 1966.
OBSERVED NEUROTOXIC EFFECTS:
(1) The highest mercury level and the greatest histo-
logical changes occurred in the calcarine area.
(2) Almost all label was found in the protein fraction
of the brain; little in the lipid or nucleic acid fractions.
Subcellular distribution: mitochondrias > microsomes >
supernatant. A lag time was noted from peak concentra-
tions to onset of nervous symptoms.
OBSERVED NEUROTOXIC EFFECTS:
Protein synthesis in brain cortex slices was markedly
inhibited before the onset of neurological signs;
oxygen consumption, glycolysis, and sulfhydryl-enzyme
activities were unchanged. After the onset of neurological
signs, oxygen and aerobic glycolysis decreased. At
advanced stages, activity of succinate dehydrogenase de-
creased. Thus, the compound exerted selective inhibition
of enzyme synthesis.
ANIMALS: (1) Dogs, adult, 6.1-16 kg
(2) Rats, Wistar, 120 g
ANIMALS: Rats, Wistar, M, 120 g
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) 30-60 mg/kg
(2) ns rUJHg)
PREPARATION AND DOSE
or HISTORY OF PATIENT: 75 mg/kg
ROUTE AND SITE: I.v.
CONTROL INFORMATION: ns
ROUTE AND SITE: i.p.
CONTROL INFORMATION: Untreated.
DURATION OF EXPERIMENT:
EXAM. TYPE:
Dogs: 2-19 d
Rats: 48 hr or 6hr to 16 d
Histology, biochemistry
DURATION OF EXPERIMENT: up to 5-7 d
EXAM. TYPE: Biochemistry in vitro
683
684
-------
COMPOUND: Methane, bromo-
000074839
REFERENCE: Collins, R.P.
California Med. 103: 112-116, 1965.
OBSERVED NEUROTOXIC EFFECTS: Exposure caused progressive sensorimotor weakness of
the fingers and toes. Nine months after exposure
ceased, a slight residual weakness of muscles persisted.
COMPOUND: Methane, bromo-
000074839
REFERENCE: Kantarjian, A.D., and Shaheen, A.S.
Neurologj 13:1054-1058, 1963.
OBSERVED NEUROTOXIC EFFECTS: Numbness of extremeties, unsteadiness on walking,
some with ataxia. Deep reflexes absent or sluggish.
ANIMALS: Human: 1 case, M, 22, a fumigator
ANIMALS: 8 humans, M, 18-43 years.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Exposures possible over 18 mo before medical consultation
and progressed for 4 mo until exposure ceased
PREPARATION AND DOSE
or HISTORY OF PATIENT:
6-8 hrs daily, 6 d/wk, for 3 mo., dose believed to be low.
ROUTE AND SITE: Probably dermal
CONTROL INFORMATION: None
ROUTE AND SITE: Exposure by date fumigation process.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: 13 mo
EXAM. TYPE: Clinical
DURATION OF EXPERIMENT: 6-8 mo.
EXAM. TYPE: Behavioral, biochemistry
685
686
-------
COMPOUND: Methane, chloro-
000074873
REFERENCE: Scharnweber, B.C., Spears, G.N. and Cowles, S.R.
J. Occup. Med. 16:112-113, 1974.
OBSERVED NEUROTOXIC EFFECTS:
Ataxia, disorientatlon, combativeness, lethargy,
loss of short-term memory, blurred vision, stated
to be nonspecific signs, with progression only in
Central Nervous System. Recovery in 6 wk to 3 mo.
Physical and neurologic examination and laboratory
studies "usually completely normal."
COMPOUND: Methane, dichloro-
REFERENCE: Steward, R.D., Fisher, T.N., Hosko, M.J., Peterson, J.E., Baretta, E.D.,
and Dodd, B.C.
Arch. Env. Hlth. 25: 342-348, 1972.
OBSERVED NEUROTOXIC EFFECTS: Sustained elevation of carboxyhemoglobin in all subjects,
altered Visual Evoked Responses and other Central Nervous
System signs in 2 subjects.
ANIMALS: Human: 6 cases, M, 24-58 yr.
ANIMALS: 11 Humans, healthy M, 23-43 yr old, nonsmokers
PREPARATION AND DOSE
or HISTORY OF PATIENT: Workers with foam plastics, exposed to 200-400 ppm for
2-3 wk or more before onset of symptoms (TLV is 100 ppm).
PREPARATION AND DOSE
or HISTORY OF PATIENT: 986 ppm in air for 2 hr.
ROUTE AND SITE: Inhalation, possibly skin contact
CONTROL INFORMATION: None
ROUTE AND SITE: Inhalation
CONTROL INFORMATION: Previous tests.
DURATION OF EXPERIMENT: 6 wk to 3 mo. per case.
EXAM. TYPE: Clinical
DURATION OF EXPERIMENT: 2 hr.
EXAM. TYPE: Biochemistry
687
688
-------
COMPOUND: Methane, dichloro-
REFERENCE: Weiss, G.
Abstr. Hyg. 43: 1123, 1968, abstracting from
Zentbl. Arbmed. Arbschutz. 17: 282-285, 1967 (Ger.).
OBSERVED NEUROTOXIC EFFECTS: Disturbed cerebral functions and hallucinations (optic
and acoustic) attributed to toxic encephalitis caused by
the compound.
COMPOUND: 4,7-Methanoindene, l,4,5,6,7,8,8-heptachloro-3a, 4,7,7a-tetrahydro-
000076448
REFERENCE:
Ryan, W.H. and Shankland, D.L.
Life Sci. 10(1):193-200, 1971.
OBSERVED NEUROTOXIC EFFECTS:
Instability and block of activity •"•. ;;i.ant fibers;
no direct action on axonal membrane. Exo-acetoxy
analog of aldrin was nontoxic. DDT with other
compounds produced effects not seen with any compound
alone.
ANIMALS: Human: 1 case, a distiller of compound
PREPARATION AND DOSE
or HISTORY OF PATIENT: Vapor 900-3600 ppm in air, "several" hr/d for 3 yr before
symptoms and then 2 yr more. Compound was 98-100% pure.
ANIMALS:
Cockroach (Periplaneta ame_ricana), surgically prepared
Housefiles, NAIDM strain
PREPARATION AND DOSE
or HISTORY OF PATIENT: DDT 10~ M, other compounds (aldrin, dieldrin, endrin,
heptachlor) 2 x iO~6 to 5 x 10~4 M (cockroaches). Up to
300 mcg/g (houseflies).
ROUTE AND SITE: Inhalation, skin contact
CONTROL INFORMATION: None
ROUTE AND SITE: Irrigation of exposed nerves (cockroaches), topical (houseflies)
CONTROL INFORMATION: Three types (described)
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Clinical
DURATION OF EXPERIMENT: Several hours
EXAM.. TYPE: Electrophysiology
689
690
-------
COMPOUND: 4,7-Methanoindene, l,4,5,6,7,8,8-heptachloro-3a, 4,7,7a- tetrahydro-
(heptachlor)
000076448
REFERENCE: St. Omer, V.
J. Neurochem. 18: 365-374, 1971U
OBSERVED NEUROTOXIC EFFECTS:
Convulsions, starting in some cases during injection.
Intensity and other signs were directly related to
increases of brain ammonia. Toxicity ranking:
llndane > dieldrin > heptachlor > DDT. Brain gluta-
mlne increases resulting from conversion of ammonia
to glutamine were related to the toxicity ranking,
suggesting that the 4 compounds produced convulsions by
one mechanism involving interference with the production
and/or utilization of ammonia.
COMPOUND:
REFERENCE:
4,7-Methanoisobenzofuran, 1,3,4,5,6,7,8,8-octachloro-l,3,3a,4,7,7a-
hexahydro
000297789
Worden, A.N.
Tox. Appl. Pharm. 14:556-573, 1969.
OBSERVED NEUROTOXIC EFFECTS:
LD50 between 1.6 and 10 mg/kg for single oral dose,
with central nervous system symptoms like those
from other chlorinated hydrocarbons. Chronic
toxicity for rats less than that of endrin or of
1,2,3,4,10,10-hexachloro-6,7-epoxy-l,4,4a,5,6,
7,8,8a-octahydro-l,4-endo-5,8-endodlmethanonaphthalene.
Symptoms: twitching, frothing, opisthotonus,
convulsions.
ANIMALS: Rats, adult F, Wistar, 250-300 g, surgically prepared.
Cockerels, White Leghorn or Barred Plymouth Rock, 12 wk, 1.4-1.6 kg,
surgically prepared.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Rats: mg/kg — lindane 11.5, DDT 50, dieldrin 6, heptachlor 13.
Cockerels: mg/kg — lindane 6.3, DDT 30, dieldrin 6, heptachlor 6.3.
The compounds stated to be structurally unrelated.
ANIMALS: Rats, Hooded Lister and S-D
Mice, Schofield
Guinea-pigs, albino
Hamsters, golden
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Rabbits, Dutch
Cats, mongrel
Dogs, mongrel
Chickens, Light Sussex
Acute: single dose by gavage to find U>50
single dose S.C. (mice and rats, M and F, 10 each)
Chronic: dermal 2 mg/kg 1 dose to 0.3 mg/kg/d 30 d (rats,
rabbits, guinea-pigs); 25-100 ppm in diet up to
78 d (rats), 5-30 ppm for 2 yr (rats), 0.025 and 0.1
mg/kg/d by gavage (dogs).
ROUTE AND SITE: Intra-arteriai (carotid) at 1 ml/min
CONTROL INFORMATION: Vehicle only
ROUTE AND SITE: Gavage, S.C. left flank.
CONTROL INFORMATION: Various including endrin equivalent
DURATION OF EXPERIMENT: Up to 60 min, in controls 7 d
EXAM. TYPE: Behavior, biochemistry
DURATION OF EXPERIMENT: Up to 2 yr.
EXAM. TYPE: Clinical, behavior, mortality, biochemistry
691
692
-------
COMPOUND: Methanol
000067561
REFERENCE: Bennett, I.L., Jr., Gary, F.H., Mitchell, G.L., Jr. and Cooper, M.N.
Medicine 32:431-463, 1953.
OBSERVED NEUROTOXIC EFFECTS: Cerebral edema, optic tracts ganglia degenerated
but not optic nerves.
COMPOUND: Methanol
000067561
REFERENCE: Erlanson, P., Fritz, H., Hagstam, K-E., Liljenberg, B., Tryding, N.
and Voigt, G.
Acta Med. Scand. 177:393-408, 1965.
OBSERVED NEUROTOXIC EFFECTS:
Acidosis, blindness, cerebral damage (massive
necrosis). Hemorrhages into putamen. No reaction of glia.
4th case below: symmetrical slit-shaped
cysts in putamina, residual damage; cerebellar
loss of Purkinje cells could not be definitely
attributed to the methanol.
ANIMALS: Humans: 323 cases (308 Black, 15 White; 210 M, 113 F) ages 10-78 yr.
ANIMALS: Human: 4 cases of accidental poisoning.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Bootleg "whiskey" ingested in a 5-d period, October 1951,
Atlanta, Ga. 90 gall distributed, 35-40% MeOH, under 4% EtOH in composition.
Patients presented selves to hospitals.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Accidental poisoning. All treated within
29-44 hr with alkali, ethanol, dialysis;
3 cases fatal, 4th died later; all were autopsied.
ROUTE AND SITE: oral
CONTROL INFORMATION: None
ROUTE AND SITE: oral
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: 5 d
EXAM. TYPE: Clinical, autopsy (10 of 41 deaths)
DURATION OF EXPERIMENT: Up to 1.5 yr.
EXAM. TYPE: Behavior, chemistry, histology
693
694
-------
COMPOUND: Methanol
000067561
REFERENCE: Guggenheim, M.A., Couch, J.R. and Welnberg, W.
Arch. Neurol. 24:550-554, 1971.
OBSERVED NEUROTOXIC EFFECTS: Immediate and permanent nervous system damage:
bilateral optic atrophy, rigidity, spasticity, hypokinesis. Administration
of levodopa improved condition.
COMPOUND:
Methanol
000067561
REFERENCE: Riegel, H., and Wolf, G.
Food and Cosmet. Tox. 5:828-829, 1967.
OBSERVED NEUROTOXIC EFFECTS:
Unconscious for 3 days, unable to swallow or speak.
Eyesight permanently and severely damaged.
Brain damage involving movement and walking distur-
bances still seen 20 years later. Symptoms similar
to those of Parkinson's syndrome.
ANIMALS: One Human, F, age 13 yr, 10 no.
ANIMALS: 1 Human, F
PREPARATION AND DOSE ... • .
or HISTORY OF PATIENT: ,-Ingeati.on of 90 and 240 .ml antifreeze contg 60Z
• - methanol, no* heavy metals, as suicide atteapt.
• PREPARATION AND DOSE
or HISTORY OF PATIENT: Intake of "spirit" at a party.
ROUTE AND SITE: oral
CONTROL INFORMATION: None
ROUTE AND SITE: Oral
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: Approx. 1 yr follow-up and therapy.
EXAM. TYPE: Hospital neurological exam.
DURATION OF EXPERIMENT: Appears follow-up of 2 yr.
EXAM. TYPE: Clinical
695
696
-------
COMPOUND: Methanol
000067561
REFERENCE: Roach, M.K., Davis. D.L., Pennington, W. and Nordyke, E.
Life Sci. 12(1):433-441, 1973.
COMPOUND: 16-Methylpregna-l,4-diene-3,20-dione, 9-fluoro-11,17,21-trihydroxy
REFERENCE: Miyakawa, T., Sumiyoshi, S. and Deshimaru, M.
Acta Neuropath. 30:85-89, 1974.
OBSERVED NEUROTOXIC EFFECTS:
Methanol inhibited active transport of probable
neurotransmitters of the central nervous systems
by synaptosomes. Authors conclude that alcohol inter-
acts with membrane lipids of synaptosome.
OBSERVED NEUROTOXIC EFFECTS: Dose-related changes both groups: thalamus and
hypothalamus vacuolar degeneration, hypertrophic
mitochondria, astrocyte edema, more free ribosomes;
Group (1) rats but not group (2) became restless.
ANIMALS: Rats, S-D, M, 200-250 g; brains removed and homogenates
incubated in vitro.
ANIMALS: Rats, Wistar, M, 100-120 g
PREPARATION AND DOSE
Or HISTORY OF PATIENT: Graded amounts added to incubation medium; concentration not
specified.
PREPARATION AND DOSE
or HISTORY OF PATIENT: (D 0.5 mg/kg for 30 d.
(2) 0.05 mg/kg for 130 d.
ROUTE AND SITE: in vitro
CONTROL INFORMATION: Control: incubation in medium with no alcohol.
ROUTE AND SITE: Oral
CONTROL INFORMATION: Controls mentioned, no details
DURATION OF EXPERIMENT: Laboratory procedure
EXAM. TYPE: Biochemistry.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior, histology
697
698
-------
COMPOUND: 2-Methyoxyacridine, 6-chloro-9-[[4-(diethylamino)-l-methylbutyl]amino]-,
dimethane sulfonate
REFERENCE: Smith, B.
J. Neurol. Neurosurg. Psychlat. 30: 506-510, 1967.
OBSERVED NEUROTOX1C EFFECTS: The myenteric plexus was examined, and hlstologlcal
changes were found. The author suggests her method
for screening for neurotoxicity by looking for damage
to the myenteric plexus in the large intestine.
COMPOUND: Morphinan-3,6-alpha-diol 17-allyl-7,8 didehydro-4,5-alpha-epoxy-, HC1
000062679
REFERENCE: Spooner, C.E. and Winters, W.D.
Int. J. Neuropharmacol. 5: 217-236, 1966
OBSERVED NEUROTOXIC EFFECTS: Compound produced depression and associated slow-wave
EEGs.
ANIMALS: 45 Mice, TO, CFW and Porton strains, 20-25 g
ANIMALS: 200 Cockerels, White Leghorn, ages 5-14 d, 45-100 g
PREPARATION AND DOSE
or HISTORY OF PATIENT: 3 mg/d for 5 d, 18 mice
Acute study: 10 mg I.P. or 2 mg I.V. one dose
PREPARATION AND DOSE
or HISTORY OF PATIENT: 10 mg/kg
ROUTE AND SITE: I.p.
CONTROL INFORMATION: ns
ROUTE AND SITE: s.C. near axillary vein; I.P. for doses over 0.05 ml
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: 2 d to 3 mo after last dose. Acute: 20 min.
EXAM. TYPE: Histology
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Behavior, EEC
699
700
-------
COMPOUND: Morphinan-3,6-alpha-diol, 7,8-didehydro-4,5-alpha-epoxy-17-methy1-
000057272
REFERENCE: Davis, W.M. and Khalsa, J.H.
Res. Comm. Chem. Path. Pharm. 6: 867-872, 1973,
OBSERVED NEUROTOXIC EFFECTS: Tropolone, which inhibits catecholamine-0-methyltrans-
ferase, reduced the morphine LD5Q to 54 mg/kg. The
authors concluded that the release of brain catecholamines
was a strong factor in morphine toxicity.
COMPOUND: Morphinan-3,6-diol, 7,8-didehydro-4,5-epoxy-17-methyl-, hydrochloride,
(5-alpha-6-alpha)-
000052266
REFERENCE: Quinton, R.M.
Br. J. Pharmac. 21:51-66, 1963.
OBSERVED NEUROTOXIC EFFECTS: The compound enhanced the effect of Yohimbine
and lowered its lethal dosage.
ANIMALS: Rats, Holtzman, M, 350-450 g
ANIMALS:
Mice, TT, M, 18-25 g.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 10-640 mg/kg; LD5Q 292 mg/kg
PREPARATION AND DOSE
or HISTORY OF PATIENT:
ED5() >80 mg/kg
ED_n = dose producing a 50% mortality of mice injected
S.C. with yohimbine hydrochloride (20 mg/kg).
ROUTE AND SITE: I.P.
CONTROL INFORMATION: The LD. served as control for tests of modifying drugs
ROUTE AND SITE: S.C., Oral
CONTROL INFORMATION: Various
DURATION OF EXPERIMENT: Up to 24 hr.
EXAM. TYPE: Mortality
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Behavior, electrophysiology, biochemistry
701
702
-------
COMPOUND: Morphinan-3,6-alpha-diol, 7,8-didehydro-4,5-alpha epoxy-17-methyl-, sulfate
000064313
REFERENCE: Ross, D.H., Medina, M.A. and Cardenas, H.L.
Science 186:63-65, 1974.
OBSERVED NEUROTOXIC EFFECTS:
Regional Ca depletion (from 55-60 to 33-39 mcg/g)
in hypothalamus, hippocampus, corpus striatum,
and cortex; antagonized by naloxone. Ca considered
important in release of transmitters and neuron
stimulation.
COMPOUND: Morphinan-3,6-alpha-diol, 7,8-didehydro-4,5-alpha epoxy-17-methyl-, sulfate
000064313
REFERENCE: Spooner, C.E. and Winters, W.D.
Int. J. Neuropharmacol. 5: 217-236, 1966
OBSERVED NEUROTOXIC EFFECTS: Compound produced depression and associated slow-wave
EEGs.
ANIMALS: Rats, S-D, M, 150-200 g, groups of 3
ANIMALS: 200 Cockerels, White Leghorn, ages 5-14 d, 45-100 g
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Morphine sulfate 25 mg/kg, 30 min antemortem
Ethanol 1.5 mg/kg 120 min antemortem
Other treatments also given.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 5-20 mg/kg
ROUTE AND SITE: i.p.
CONTROL INFORMATION: Untreated, 1:1, each expt replicated 3 or more times
ROUTE AND SITE: s.C. near axillary vein; I.P. for doses over 0.05 ml
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Behavior, EEC
703
704
-------
COMPOUND: Morphinan-6-one, 4-5-epoxy-3,14-dihydroxy-17-(2-propenyl)-, hydrochloride,
(5-alpha)-
000357084
REFERENCE: Tseng, L.F., Menon, M.K. and Loh, H.H.
Neuropharmacology 14: 247-250, 1975.
OBSERVED NEUROTOXIC EFFECTS: Naloxone precipitated abstinence signs, teeth chatter-
ing, myoclonic twitch, and repetitive shaking. Bilateral
transverse lesions suggested that the different signs
originated in different brain areas.
COMPOUND: Morpholine, 2-chloroethyl-, hydrochloride
REFERENCE: Goldin, A., Now, H.A., Landing, B.H., Shapiro, D.M. and Goldberg, B.
J. Pharm. Exp. Ther. 94:249-261, 1958.
OBSERVED NEUROTOXIC EFFECTS:
Waltzing syndrome was produced by dialkyl and hetero-
cyclic B-chloroethylamines but not when (a) OH
or bromine replaced the B chlorine, (b) a 8-phenyl
group replaced one of the 6 hydrogens in the
chlorinated chain, or (c) phenyl groups were introduced
into the dialkyl carbons. No effect from primary/
secondary B-chloroethylamines, related quaternary
compounds, or bis-, tris-, or tetrakis-B-chloro-
ethylamines. Piperidine and morpholine analogs and
arsacetin produced waltzing. Cerebellar and
axial lesions found consistent with behavior.
ANIMALS: Rats, S-D, M, 350-400 g, morphine-dependent and surgically prepared
ANIMALS:
Mice, CF1, M, 2-3m, 18-25 g; also CF1 F and C3H M.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 4 mg/kg
PREPARATION AND DOSE
or HISTORY OF PATIENT:
1-625 mg/kg in saline or (insolubles) 10% acacia,
various schedules.
ROUTE AND SITE: i.p.
CONTROL INFORMATION: Sham-operated rats
ROUTE AND SITE: I.P.
CONTROL INFORMATION: Vehicle alone
DURATION OF EXPERIMENT: 30 min each test
EXAM. TYPE: Behavior
DURATION OF EXPERIMENT: At least 10 d after treatment.
EXAM. TYPE: Behavior, histology.
705
706
-------
COMPOUND: Morphollnium, 2,2'-(4,4'-biphenylylene)bis(2-hydroxy-4,4-dimethyl-, dibromide)
COMPOUND:
stilus edulis toxins
REFERENCE: Shellenberger, M.K. and Domino, E.F.
Int. J. Neuropharmacol. 6: 283-291, 1967f
REFERENCE: Evans, M.H.
Br. J. Pharmac. 40: 847-865, 1970.
OBSERVED NEUROTOXIC EFFECTS: Treatment produced seizures with a 20 min latency.
The authors inferred that the compound exerted direct
action on possible cholinergic receptors, rather than
acting by way of acetylcholinesterase inhibition.
OBSERVED NEUROTOXIC EFFECTS:
Outbreak of paralytic poisoning in about 80 subjects
in NW England in May, 1968. Assays and signs in
animals and nerve preparations were used to try to
identify the toxins.
ANIMALS: Dogs, beagle-like mongrel, M and F, 8-12 kg, surgically prepared
PREPARATION AND DOSE
or HISTORY OF PATIENT: 5 mg (basis not given)
ANIMALS: Humans: about 80 who suffered paralytic shellfish poisoning
Mice, rabbits, and desheathed sciatic nerves from rat, frog and newt,
and rat cauda equina nerves.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Humans: unwitting ingestion.
Animals and in vitro preparations: assay of crude extracts
and part-purified toxins.
ROUTE AND SITE: Intraventricular
CONTROL INFORMATION: None
ROUTE AND SITE: Various
CONTROL INFORMATION: Various
DURATION OF EXPERIMENT: At peak response, duration ns
EXAM. TYPE: EEC, biochemistry
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Behavior, electrophysiology, chemistry
707
708
-------
COMPOUND: Naphthalene methanol, alpha-(isopropylamino) methyl-, hydrochloride
001722516
REFERENCE: Quinton, R.M.
Br. J. Pharmac. 21:51-66, 1963.
OBSERVED NEUROTOXIC EFFECTS: The compound enhanced the effect of Yohimbine
and lowered its lethal dosage.
COMPOUND: Napthalimlde, N-hvdroxy-.diethyl phosphate
001491414
REFERENCE: Sherman, M., Herrick, R.B., Ross, E. and Chang, M.T.Y.
Toxicol. Appl. Pharm. 11: 49-67, 1967.
OBSERVED NEUROTOXIC EFFECTS: Ataxia, paralysis, convulsions.
ANIMALS:
Mice, IT, M, 18-25 g.
ANIMALS: Cockerels, Single Comb White Leghorn, 10-12 d old
PREPARATION AND DOSE
or HISTORY OF PATIENT:
ED5Q >40 mg/kg
ED,. = dose producing a 50% mortality of mice injected
S.C. with yohimbine hydrochloride (20 mg/kg).
ROUTE AND SITE: s.C., Oral
CONTROL INFORMATION: Various
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) Acute: LD 43.3 mg/kg
(2) Subacute: 50-800 ppm in diet, 20 chicks/grp, for 2 wk
ROUTE AND SITE: Oral
CONTROL INFORMATION: Untreated control grps
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Behavior, electrophysiology, biochemistry
DURATION OF EXPERIMENT: 1-3 wk
EXAM. TYPE: Behavior, mortality
709
710
-------
COMPOUND:
Neomycin
001404042
REFERENCE: Tang, A.H. and Schroeder, L.A.
Tox. Appl. Pharm. 12:44-47, 1968.
OBSERVED NEUROTOXIC EFFECTS: (1) Depressed neuromuscular transmission of doses of
25 and 50 mg/kg. (2) Immediate ataxia in chicks.
COMPOUND:
REFERENCE:
Nickel
007440020
Prakash, N.J., Fontana, J. and Henkin, R.I.
Life Sci. 12(1):249-259, 1973.
OBSERVED NEUROTOXIC EFFECTS:
Inhibited (Na+ + K ) ATPase, although never
more than 20%, even at 0.2 mM. Inhibition
involved blockage of norepinephrine and
choline uptake.
ANIMALS:
(1) 6 Rabbits
(2) Chickens
•PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) 25 mg/kg followed by 50 mg/kg, in saline.
(2) 50-100 mg/kg
ANIMALS:
Rat brain synaptosomes in vitro
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Ni chloride added to medium in various expts.
ROUTE AND SITE: l.v.
CONTROL INFORMATION: ns.
ROUTE AND SITE: Jn vitro
CONTROL INFORMATION: Lab
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Electrophysiology, behavior
DURATION OF EXPERIMENT: Minutes
EXAM. TYPE: Biochemistry
711
712
-------
COMPOUND: Nitrous acid, pentyl ester
000463047
REFERENCE: Dewey, W.L., Tucker, L.S., Prange, A., Spaulding, T. and Chau, T.T.
Res. Comm. Chem. Path. Pharm. 5(3):889-892, 1973.
OBSERVED NEUROTOXIC EFFECTS:
Inhalation: tremors, ataxia, short duration.
I.V.: generalized convulsion in 30 sec, died in
1 min. Vomiting, defecation and other "unpleasant"
effects reported.
COMPOUND: 2.Norbornene, 1,2,3,4,7,7-hexachloro-5,6-bis(chloromethyl)-
REFERENCE: Sherman, M., Herrick, R.B., Ross, E. and Chang, M.T.Y.
Toxicol. Appl. Pharm. 11: 49-67, 1967.
OBSERVED NEUROTOXIC EFFECTS: Ataxia, paralysis, convulsions.
Acute: No mortality at highest dose level (5000 mg/kg),
and no signs of intoxication.
ANIMALS: Mice for ID studies
Dogs, 5-10.5 kg
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Various doses, I.V. or by inhalation (dogs)
ANIMALS: Cockerels, Single Comb White Leghorn, 10-12 d old
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) Acute: LD5Q > 5000 mg/kg
(2) Subacute: 50-800 ppm in diet, 20 chicks/grp, for 2 wk
ROUTE AND SITE: I.V., inhalation
CONTROL INFORMATION: No controls
ROUTE AND SITE: Oral
CONTROL INFORMATION: Untreated control grps
DURATION OF EXPERIMENT: i d
EXAM. TYPE: Behavior
DURATION OF EXPERIMENT: 1-3 wk
EXAM. TYPE: Behavior, mortality
713
714
-------
COMPOUND:
Notechis scutatus scutatus venom
COMPOUND:
Notechis scutatus scutatus venom, toxin from
REFERENCE: Datyner, M.E. and Gage, P.W.
Br. J. Pharmac. 49: 340-354, 1973.
REFERENCE: Harris, J.B., Karlsson, E. and Thesleff, S.
Brit. J. Pharmac. 47: 141-146, 1973.
OBSERVED NEUROTOXIC EFFECTS:
50 meg/ml blocked elicited twitches without affecting
compound action potentials. 1-10 meg/ml reduced
amplitude of endplate potentials and inhibited depolar-
izations by carbachol. The authors concluded that a
venom fraction was bound to acetylcholine. Other in
vitro effects were observed.
OBSERVED NEUROTOXIC EFFECTS:
The resting membrane potentials and action potentials
were normal. There was a low frequency of miniature
endplate potentials (amplitude unchanged). The toxin
was almost ineffective in vitro. In vivo, adminis-
tration caused deaths by respiratory paralysis.
ANIMALS: Isolated sciatic-sartorius nerve-muscle preparations from Queensland
cane toads (Bufo marinus)
ANIMALS: Mice, NMR1, M, 25-30 g
PREPARATION AND DOSE
or HISTORY OF PATIENT: 1-200 meg/ml of Ringer solution
PREPARATION AND DOSE
or HISTORY OF PATIENT: 10 meg/mouse
ROUTE AND SITE: in vitro
CONTROL INFORMATION: Laboratory
ROUTE AND SITE: i.V., tail vein
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: Minutes to 6 hr
EXAM. TYPE: Electrophysiology
DURATION OF EXPERIMENT: Various
EXAM. TYPE:
In vitro studies on hemidiaphragm and digitorum longus nerve-muscle
preparations dissected from mice intoxicated in vivo
715
716
-------
COMPOUND: Organophosphate pesticides
REFERENCE:
Rodnitzky, R.L., Levin, H.S., Mick, D.L.
Arch. Env. Hlth. 30:98-103, 1975.
COMPOUND: Ouabain
000036066
REFERENCE: Doggett, N.S.
Life Sci. 12(1):121-129, 1973.
OBSERVED NEUROTOXIC EFFECTS:
Behavior tasks performed as well as by controls,
blood ChE in normal range though lower in some
subjects than control values. Conclusion: that
"higher nervous system functions" have "relative
resistance" to mild chronic exposures.
OBSERVED NEUROTOXIC EFFECTS: Hypothermia did not involve brain noradrenergic
systems but possible direct action on thermoregulation
including interference with amine function.
ANIMALS:
23 Humans (12 farmers, 11 commercial applicators)
ANIMALS: Mice, TO, M, 16-20 g
PREPARATION AND DOSE
Or HISTORY OF PATIENT: Regularly used organophosphates, had applied them personally
to at least 500 acres and who had used them in the previous
2 wk every working day.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.1-0.25 meg/mouse with one or more of: noradrenaline,
phentolamine, a-methylmetatyrosine, (+)-amphetamine.
ROUTE AND SITE: Inhalation, skin contact
CONTROL INFORMATION: Age-education-matched farmers whose pesticides, if any,
were applied for them by contractors.
ROUTE AND SITE: Intracerebroventricular
CONTROL INFORMATION: Controls saline treated
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior tasks, blood chemistry
DURATION OF EXPERIMENT: Hours
EXAM. TYPE: Biochemistry
717
718
-------
COMPOUND:
Ouabain
000036066
REFERENCE: Grasso, A. and Majorl, G.
J. Econ. Entomol. 62: 944-945, 1969.
COMPOUND: Ouabain
000036066
REFERENCE: Towfighi, J. and Gonatas, N.K.
Lab. Invest. 28:170-180, 1973.
OBSERVED NEUROTOXIC EFFECTS: Ouabain is known to inhibit the Na+/K+-dependent
ATPase found in the ventral nerve cord of cockroaches.
By inference, such was presumed to be the basis of
ouabain toxicity in the housefly.
OBSERVED NEUROTOXIC EFFECTS:
Edema corresponding to spread of labeled
more in adults than juveniles, central zone of
swollen dendrites, Golgi, and rough endoplasmic
reticulum, marginal zone of swollen astrocytes,
presynaptic terminals, and dark neurons. Central
zone interpreted as primary effect, marginal as
secondary to pressure or ischemia.
ANIMALS: Houseflies (Musca domestica), adult, 22 mg
ANIMALS: 129 Rats, Osborne-Mendel, M and F, adult and juvenile.
PREPARATION AND DOSE
or HISTORY OF PATIENT: LD5Q found to be: Feeding 270-690 rag/kg
Topical 292-1600 mg/kg
Injected 0.9-2.25 mg/kg
Ranges of averages of three groups: susceptible to resistant.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.0006-0.00125 mg/rat (1-5 d old); 0.0025 mg/rat (older);
in buffered saline pH 7.2.
ROUTE AND SITE: Injection into thorax; dermal to dorsal surface; feeding in sucrose
by calibrated micropipet method.
CONTROL INFORMATION: ......
Vehicles
ROUTE AND SITE: Intracerebral
CONTROL INFORMATION: Vehicle only.
DURATION OF EXPERIMENT: 24 hr
EXAM. TYPE: Count of knocked-down insects
DURATION OF EXPERIMENT: 2 hr.
EXAM. TYPE: Histology, histochemistry
719
720
-------
COMPOUND: Oxalic acid, bis(cyclohexylidenehydrazide)
000370810
REFERENCE: Carlton, W.W.
Life Sci 6:11-19, 1967.
COMPOUND: Oxalic acid, Bis(Cyclohexylidenehydrazide)
REFERENCE: Pattison, I.H., Clarke, M.C., Haig, D.A. and Jebbett, J.N.
Res. Vet. Sci. 12: 478-480, 1971.
OBSERVED NEUROTOXIC EFFECTS:
Hydrocephalus and spongy degeneration of brain,
cord and sciatic nerve. Copper reduced hydrocephalus
but not edema, spongy degeneration or astrogliosis.
Liability to hydrocephalus decreased with age.
Myelin loss occurred late, spongy degeneration
early, glial proliferation in-between.
OBSERVED NEUROTOXIC EFFECTS: Cultured brain cells from mice treated with the
compound or with scrapie but not controls tended to
adhere to glass.
ANIMALS:
Mice, M, albino, weanling aged 21-28 d (groups of 10)
ANIMALS: Mice, BSVS, aged 4-6 wk
PREPARATION AND DOSE
or HISTORY OF PATIENT:
ROUTE AND SITE: Oral
CONTROL INFORMATION:
(1) 0.5% in diet of Cuprizone precursors: cyclohexanone
and oxaldihydrazide.
(2) 0.5% in diet, plus vitamins at lOOOx the recommended
requirements.
(3) 0.5% in diet, plus diuretic, Diurill, 0.5 and 1 gm/kg.
(4) 0.2% in diet, plus copper 130 and 260 ppm.
(5) 0.5% in diet for 8 wk.
(3) Diurill treatment only
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.5% of diet
ROUTE AND SITE: Oral
CONTROL INFORMATION: Untreated, treated with scrapie agent
DURATION OF EXPERIMENT: Maximum 9 wk
EXAM. TYPE: Histology, hematology
DURATION OF EXPERIMENT: Over 16 d
EXAM. TYPE: Biophysics in vitro
721
722
-------
COMPOUND: Oxalic acid, bis(cyclohexylidenehydrazide)
000370810
REFERENCE: Pattison, I.H. and Jebbett, J.N.
J. Path. 109:245-250, 1973.
COMPOUND: Oxalic acid, bis(cyclohexylidenehydrazide)
000370810
REFERENCE: Suzuki, K. and Kikkawa, Y.
Am. J. Path. 54:307-325, 1969.
OBSERVED NEUROTOXIC EFFECTS:
Scrapie-like spongiform encephalopathy; functional
recovery in "a few days," histological recovery
in 34 d; apparent correlation with microglial
proliferation.
OBSERVED NEUROTOXIC EFFECTS: Inactive at 1-2 wk, hindlimb weakness, most died
at 3 wk. Spongy degeneration in CNS: brainstem
and cerebellar white matter. Vacuoles in myelin
and glia.
ANIMALS:
Mice, BSVS, F aged 3-6 wk, weaned.
ANIMALS: 30 Mice, Swiss-Webster, M
PREPARATION AND DOSE
or HISTORY OF PATIENT:
ROUTE AND SITE: Oral
CONTROL INFORMATION: None
(1) 0.5% in diet, up to 15 mg/mouse/d, for 7, 14,
21 d then 60 d untrtd.: 3 grps of 12
clinically abnormals.
(2) Similar test, adding 28 and 35 d trtmts.
(3) 37 d trtmt (max), 52 d no trtmt, 38 d (max) trtmt,
and then 52 d no treatment.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.5 g/100 g diet.
ROUTE AND SITE: Oral
CONTROL INFORMATION: 10 untreated controls
DURATION OF EXPERIMENT: Serial sacr to 179 d
EXAM. TYPE: Histology, behavior
DURATION OF EXPERIMENT: About 3 wk
EXAM. TYPE: Behavior, histology
723
724
-------
COMPOUND:
Oxalic acid, dihydrazide
REFERENCE: Jenney, E.H. and Pfeiffer, C.C.
J. Phann. Exp. Ther. 122: 110-123, 1958.
OBSERVED NEUROTOXIC EFFECTS: Convulsions
COMPOUND: 2H-l,3,2-oxazaphosphorine, 2-(bis(2-chloroethyl)amino) tetrahydro-, 2-oxide
000050180
REFERENCE:Levine, S. , and Sowinski, R.
J. Neuropath. Exp. Neurol 32(3), 365-370, 1973.
OBSERVED NEUROTOXIC EFFECTS: Lesions of the choroid plexus were well developled
after 24-48 hours and were characterized by
severe edema, hemorrhage, and focal leukocytic
infiltration. Progressed to necrosis of individual
villi and hemorrhage infarction of an entire
plexus after 4-6 days. Plexitis was greatest in
plexus of 4th ventricle.
ANIMALS: Mice, Harlan, 19-21 g
PREPARATION AND DOSE
or HISTORY OF PATIENT: 1.7 mM/kgm
ANIMALS: Rats, Lewis strain: (1) 38 rats, 100-300 g.
(2) 8 rats, 100-175 g.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 125-500 mg/kg in saline.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: ns
ROUTE AND SITE: S.C. or I.P.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: Acute
EXAM. TYPE: Clinical
DURATION OF EXPERIMENT: 7 d.
EXAM. TYPE: Histology
725
726
-------
COMPOUND:
2-Oxazolidinone, 5-((0-methoxyphenoxy)methyl)
000070075
REFERENCE: Benitz, K-F., Moraski, R., Roepke, R.R. and Wozniak, L.A.
Tox. Appl. Pharm. 4:220-237, 1962.
OBSERVED NEUROTOXIC EFFECTS:
(1) Dogs, ataxia and emesis on 480 or 600 mg/kg/d.
(2) Rats, no neural signs.
ANIMALS: (1) 6 Dogs, beagle, 1 M and 1 F/group, 3 groups.
(2) 80 Rats, Sherman, 10 M and 10 F/group, 4 groups.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
(1) Short term - 70, 200, 600 mg/kg/d for 30 d.
Long term - 30, 120, 480 mg/kg/d for 6 mo.
(2) 0.0625, 0.25, 1% in diet.
ROUTE AND SITE: oral (dogs and rats)
CONTROL INFORMATION: i Group untreated (dogs and rats)
DURATION OF EXPERIMENT: (i) 30 d and 6 mo.
(2) 30 d
EXAM. TYPE: Behavior, pathology (at sacrifice)
727
COMPOUND: 2-Oxazoline, 2-amino-5-phenyl-
002207503
REFERENCE: Borbely, F., Past, A. and Velvart, J.
Arch. Toxikol. 26:117-124, 1970.
OBSERVED NEUROTOXIC EFFECTS: Ataxia, cramps, convulsions; transient.
ANIMALS: 30 human cases
PREPARATION AND DOSE
or HISTORY OF PATIENT: 1-2 mg/kg estimated as toxic for central nervous system.
ROUTE AND SITE: oral
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: 2 hr.
EXAM. TYPE: Clinical
728
-------
COMPOUND: Oxygen
REFERENCE: Barnard, E.E.P.
Proc. Roy. Soc. Med. 64: 874-876, 1971.
OBSERVED NEUROTOXIC EFFECTS:
Men: convulsions, susceptibility (threshold, taken
as 1.7 atm) varied day-to-day. Mice: Time course
of minor convulsions, slow onset, duration 5-10 sec;
major convulsions, rapid onset, preceded by spinning,
duration 30-60 sec followed by tonic spasm for
15-30 sec; normal movements then till next convul-
sion. Dose-response (atm) and major-minor relation-
ships reported.
ANIMALS: Human: Naval volunteers
Mice: unspecified.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Diving experiments, no details
Mice: chamber experiments, no details
ROUTE AND SITE: inhalation
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: ns
EXAM. TYPE: clinical
729
COMPOUND: Oxygen
REFERENCE: Joanny, P., Corriol, J. and Brue, F.
Science 167:1508-1510, 1970.
OBSERVED NEUROTOXIC EFFECTS: Less oxidation by tissues, fall of phosphocreatine
and ATP, and rise of lipid peroxides. The increased
lipid peroxides is attributed to the toxic
effects of hyperbaric oxygen.
ANIMALS: Guinea-pig, brain cortex slices in vitro.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Incubation in presence of 1-10 atm of pure
and labeled substrates.
ROUTE AND SITE: In vitro
CONTROL INFORMATION: Laboratory methods
DURATION OF EXPERIMENT: 60 min
EXAM. TYPE: Biochemistry
730
-------
COMPOUND: Oxygen
COMPOUND: Oxygen.
REFERENCE: Walter, D.C., Underwood, B.C. and Nelson, S.R.
Comp. Gen. Pharm. 5: 165-167, 1974.
REFERENCE: Wood, J.D.
J. Neurochem. 17: 573-579, 1970.
OBSERVED NEUROTOXIC EFFECTS: Tremors, loss of righting reflex, 6 hr survival
limit. The authors report much variation among
species.
OBSERVED NEUROTOXIC EFFECTS:
Susceptibility to 0- convulsions rose with age at
exposure (1-23 d), and brain y-aminobutyric acid
(GABA) changed less with age. The rate of GABA deple-
tion was related to the time of convulsions. Injected
GABA protected young chicks more than old, consistent
with decreasing permeability of blood-brain barrier
to GABA with age.
ANIMALS: Cockroach (Periplaneta americana), adult M & F
ANIMALS: Cockerels, White Leghorn, age 1 d
PREPARATION AND DOSE
or HISTORY OF PATIENT: 6 atm (75 psi), 0-6 hr
PREPARATION AND DOSE
or HISTORY OF PATIENT: C>2: exposure to 60 psi for 5-38 min
GABA: 1-20 mmoles/kg 30 min before exposure to 0. or sacrifice
ROUTE AND SITE: Inhalation
CONTROL INFORMATION: Untreated
ROUTE AND SITE: 02> inhalation; GABA, I.P.
CONTROL INFORMATION: One or other treatment omitted
DURATION OF EXPERIMENT: Serial to 6 hr.
EXAM. TYPE: Behavior, physiology
DURATION OF EXPERIMENT: About 1 hr
EXAM. TYPE: Behavior, biochemistry
731
732
-------
COMPOUND: Ozone
010028156
REFERENCE: Kulle, T.J. and Cooper, G.P.
Arch. Env. Hlth 30:237-243, 1975.
COMPOUND:
OBSERVED NEUROTOXIC EFFECTS:
Examined effects of prolonged exposure. Ozone
increased response to amyl alcohol; perfuslon
with air for 1 hr. partly normalized the response.
Pentaborane (9)
019624227
REFERENCE: Feinsilver, L., Lawson, L.H., Yevich, P.P. and Jacobson, K.H.
U.S. Army CWL Report CWLR 2367, 1960.
OBSERVED NEUROTOXIC EFFECTS: LC5Q under conditions were:
j Rats - 6ppm; mice - 3ppm. Signs included ataxia;
depression, prostration, tremors, clonic convulsions,
interpreted as "marked effects upon" the central
nervous system.
ANIMALS: Rats, S-D, M, 250-400 g, surgically prepared for testing of nasopalatine
nerve twigs.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 5 ppm for 1 hr. Repeated tests in many animals, for
total exposure of 5 hr.
ANIMALS: Rats, ages 8-10 wk, M
Mice, 8-10 wk, F
Dogs, beagle, M.
PREPARATION AND DOSE
PREPARATION AND DOSE
or HISTORY OF PATIENT: Exposed to vapors of compounds in LC5Q study, 2-4 hr
ROUTE AND SITE: Gas drawn through nasal cavities by vacuum pump.
CONTROL INFORMATION:
DURATION OF EXPERIMENT:
Several hr.
EXAM. TYPE: Electrophysiology
Pre-exposure control responsiveness determined by test
series of amyl alcohol (0.3, 0.7, 1.0, 3.3, 6.7, 10.0 pph)
and then test repeated after exposure to test compound. Air
controls also run.
ROUTE AND SITE: Inhalation
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: Observation to 7 d after exposure
EXAM. TYPE: Behavior, pathology
733
734
-------
COMPOUND: Pentaborane (9)
019624227
REFERENCE: Schoettlin, C.E., Clanko, G.M., Walter, R.D. and Freedman, T.
ASD Tech. Report 61-438 (DSAF), 1961.
OBSERVED NEUROTOXIC EFFECTS:
Mental confusion, lack of coordination; EEC changes
reversible about 1 yr after exposure. One or more
expsoures produced abnormalities. EEC's not
specific for boranes.
ANIMALS: Humans: 119 rocket fuel handlers
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Symptoms and signs recorded, plus a total 333 EEC's.
Composition of fuels ns.
ROUTE AND SITE: Inhalation, skin contact
CONTROL INFORMATION: 22 controls
DURATION OF EXPERIMENT: Over 1 yr
EXAM. TYPE: Behavior, EEC
735
COMPOUND: 2-Pentanone, 4-methyl-
000108101
REFERENCE: Spencer, P.S., Schaumburg, H.H., Raleigh, R.L. and Terhaar, C.J.
Arch. Neurol. 32: 219-222, 1975.
OBSERVED NEUROTOXIC EFFECTS: Compound produced no clinical signs, no histological
damage except in distal tibial and ulnar nerves, which were not degenerated.
ANIMALS: 6 Rats, young adult
PREPARATION AND DOSE
or HISTORY OF PATIENT: 1,500 ppm commercial grade in air, exposed 6 hr/d,
5 d/wk for up to 5 mo. Approx. 3% MBK contaminant.
ROUTE AND SITE: inhalation
CONTROL INFORMATION: Normal control rats
DURATION OF EXPERIMENT: 5 mo.
EXAM. TYPE: Behavior, histology
736
-------
COMPOUND: Pesticides (unspecified)
REFERENCE: Drenth, H.J., Ensberg, I.F.G., Roberts, D.V. & Wilson, A.
Arch. Env. Hlth. 25:395-398, 1972.
OBSERVED NEUROTOXIC EFFECTS: Abnormal electromyographic (EMG) exam in 40%
indicating disturbed peripheral nervous system
function. No abnormal blood cholinesterase or
other biological data.
ANIMALS:
Human: 102 agric. workers with pesticides, M, aged 17-59.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Exposure varied from 1 compound daily for 7 d to
several compounds/d. Screening study for blood
cholinesterase and EMG function.
ROUTE AND SITE: Skin, inhalation, oral
CONTROL INFORMATION: 130 industrial workers not exposed to pesticides
DURATION OF EXPERIMENT: 2 screenings 2 mo apart.
EXAM. TYPE: Electomyography, blood chemistry
737
COMPOUND: Phenethylamine, p-chloro-alpha, alpha-dimethyl
000461789
REFERENCE: Lullmann-Rauch, R.
Acta Neuropath. (Berl)29: 237-249, 1974.
OBSERVED NEUROTOXIC EFFECTS: Significant ultrastructural alterations of nerve
cells, both in spinal cord and in cerebellar cortex.
ANIMALS: Rats, Wistar, M., Young Adult.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 40 mg/kg b.w., 5d/wk in saline 0.5ml/100g bw, for 5 wk.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: Controls inj. saline
DURATION OF EXPERIMENT: 5 wk
EXAM. TYPE: Histology
738
-------
COMPOUND:
Phenethylamine, 4-chloro-2-methyl-, DL-
COMPOUND:
Phenethylamine, 4-chloro-alpha-methyl-
REFERENCE: Harvey, J.A., McMaster, S.E. and Yunger, L.M.
Science 187:841-843, 1975.
REFERENCE: Sanders-Bush, E., Bushing, J.A. and Sulser, F.
Biochetn. Pharmacol. 21:1501-1510, 1972.
OBSERVED NEUROTOXIC EFFECTS:
Dissolution of neurons in ventral midbrain
tegmentum (B-9 serotonergic cell group) and in
substantla nigra, starting at 1 d and progressing
to 30 d. Damage interpreted to explain effects
of compound on 5-HT and tryptophan-5-hydroxylase.
OBSERVED NEUROTOXIC EFFECTS:
Dose-related inhibition of tryptophan hydroxylase.
Authors claim that this explains the prolonged
reductions of 5-hydroxytrptamine and 5-hydroxy-
indoleacetic acid produced by this compound.
ANIMALS: 25 Rats, Holtzman, M, 150-200 g
ANIMALS:
Rats, S-D, M, 180-220 g.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 2.5-20 mg/kg in saline to 1 ml.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Pretreatment (some experiments) 2-10 mg/kg 16 hr before
sacrifice (2i rats) , in one expt 6 d.
In vitro: homogenized brainstems used to assay tryptophan
hydroxylase activity with/without £-chloroamphetamine.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: Vehicle only
ROUTE AND SITE: Pretreatment: I.P.
CONTROL INFORMATION: Pretreatment: 5 rats no dose.
DURATION OF EXPERIMENT: Serial sacr to 30 d
EXAM. TYPE: Histology
DURATION OF EXPERIMENT:
EXAM. TYPE: Biochemical
Pretreatment 16 hr., or less, one expt. 6 d.
739
740
-------
COMPOUND: Phenethylamlne, 2-chloro-2-methyl-, (±)-
COMPOUND: Phenethylamlne, 3-chloro-2-methyl-, (±)-
REFERENCE: Wong, D.T., Horng, J-S., and Fuller, R.W.
Biochem. Phannacol. 22:311-322, 1973.
REFERENCE: Wong, D.T., Horng, J-S., and Fuller, R.W.
Biochem. Pharmacol. 22:311-322, 1973.
OBSERVED NEUROTOXIC EFFECTS: Synaptosomes accumulated serotonin by (a) high-
affinity and (b) low-affinity processes.
2-chloroamphetamine inhibited both processes.
OBSERVED NEUROTOXIC EFFECTS:
Synaptosomes accumulated serotonin by (a) high-
affinity and (b) low-affinity processes.
3-chloroamphetamine inhibited both processes.
ANIMALS:
Rat brain in vitro
ANIMALS:
Rat brain in vitro
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Synaptosomes isolated from homogenized whole brains,
and uptake of labeled serotonin or norepinephin measured
in presence/absence of the amphetamine. Some rats
pretreated with the amphetamine.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Synaptosomes insolated from homogenized whole brains,
and uptake of- labeled serotonin or norepinephin measured
in presence/absence of the amphetamine. Some rats
pretreated with the amphetamine.
ROUTE AND SITE: Addition to incubation medium
CONTROL INFORMATION: Laboratory controls
ROUTE AND SITE: Addition to incubation medium.
CONTROL INFORMATION: Laboratory controls.
DURATION OF EXPERIMENT: Pretreatment up to 22.5 hr; in vitro 5 sec to 30 min.
EXAM. TYPE: Biochemical
DURATION OF EXPERIMENT:
EXAM. TYPE: Biochemical
Pretreatment up to 22.5 hr; in vitro 5 sec to 30 min.
741
742
-------
COMPOUND: Phenethylamine, 4-chloro-2-methyl-, (±)-
REFERENCE: Wong, D.T., Horng, J-S., and Fuller, R.W.
Biochem. Pharmacol. 22:311-322, 1973.
OBSERVED NEUROTOXIC EFFECTS:
Synaptosomes accumulated serotonin by (a) high-
affinity and (b) low-affinity processes.
4-chloroamphetamine strongly inhibited (a)
and inhibited (b) to a lesser extent.
ANIMALS:
Rat brain in vitro
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Synaptosomes isolated from homogenized whole brains,
and uptake of labeled serotonin or norepinephin
measured in presence/absence of the amphetamine. Some
rats pretreated with the amphetamine.
ROUTE AND SITE: Addition to incubation medium
CONTROL INFORMATION: Laboratory controls
DURATION OF EXPERIMENT:
EXAM. TYPE: Biochemical
Pretreatment up to 22.5 hr; in vitro 5 sec to 30 min.
743
COMPOUND' Phenethylamine, N-alpha-dimethyl-, hydrochloride, (-)-
REFERENCE: Kasirsky, G. and Tansy, M.F.
Teratology 4:131-134, 1971.
OBSERVED NEUROTOXIC EFFECTS: Both mice and rabbits showed excitement within
5 min after ttmt, continuing for 6-7 hr. Fetal anomalies: exencephaly,
anophthalmia, microphthalmia greater in all treated litters of mice; exencephaly
and microphthalmia in rabbits litters.
ANIMALS: Mice, CF1, pregnant; Rabbits, New Zealand white, F, pregnant
and M, sires.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Mice: 5 or 10 mg/kg/d for 3, 4, or 7 d during d 9-15
of gestation.
Rabbits: 1.5 mg/kg for 4, 6, or "18 d during d 12-30 of gestation. Males: 1.5,
3.0, or 5.0 mg/kg/d for 3 mo. prior mating.
ROUTE AND SITE: I.V. Mice: tail, Rabbits: ear.
CONTROL INFORMATION: Untreated and saline ttd groups for mice and rabbits.
DURATION OF EXPERIMENT: Mice sacr day 19, Rabbits (F) sacr day 30.
EXAM. TYPE: Teratological
744
-------
COMPOUND: Phenethylamine, N-alpha-dimethyl-, hydrochloride, (-)-
COMPOUND: Phenethylamlne, alpha-methyl-(+)-amphetamine
REFERENCE:Schuster, C.R., and Fischmann, M.W.
Federation Proceedings 34:1845-1451, 1975.
REFERENCE: Wong, D.T., Horng, J-S., and Fuller, R.W.
Biochem. Pharmacol. 22:311-322, 1973.
OBSERVED NEUROTOXIC EFFECTS: Dose of 9.0 and 5.0 mg/kg caused collapse with no
sympathomimetic symptoms in contrast to the dose
of 2.5 and 3.0 mg/kg which brought on piloerection,
pupillary dilation, salvation, tremors in
extremities.
OBSERVED NEUROTOXIC EFFECTS:
Synaptosomes accumulated serotonin by (a) high-
affinity and (b) low-affinity processes. Compound
weakly inhibited both processes.
ANIMALS: 19 Monkeys, Rhesus, M
ANIMALS:
Rat brain in vitro
PREPARATION AND DOSE
or HISTORY OF PATIENT: 1 ml I.V. over 10 sec. Dose range 9.0-1.0 mg/kg.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Synaptosomes isolated from homogenized whole brains,
and uptake of- labeled serotonin or norepinephin measured
in presence/absence of the amphetamine. Some rats
pretreated with the amphetamine.
ROUTE AND SITE: i.v.
CONTROL INFORMATION: ns.
ROUTE AND SITE: Addition to incubation medium.
CONTROL INFORMATION: Laboratory controls
DURATION OF EXPERIMENT: ns.
EXAM. TYPE Behavioral
DURATION OF EXPERIMENT:
EXAM. TYPE: Biochemical
Pretreatment up to 22.5 hr; in vitro 5 sec to 30 min.
745
746
-------
COMPOUND: Phenethylamine, alpha-methyl-sulphate (2:1),(+,-)-
000060139
REFERENCE: Quinton, R.M.
Br. J. Pharmac. 21:51-66, 1963.
COMPOUND: Phenethylamine, alpha-methyl-, sulphate (2:1), (+-)-
REFERENCE: Spooner, C.E. and Winters, W.D.
Int. J. Neuropharmacol. 5: 217-236, 1966
OBSERVED NEUROTOXIC EFFECTS: The compound enhanced the effect of Yohimbine
and lowered its lethal dosage.
OBSERVED NEUROTOXIC EFFECTS: Compound produced increased locomotion, abnormal
postures and arousal EEGs. Atropine sulfate and atropine
methylnitrate potentiated the effects of this compound.
Chlorpromazine HC1, reserpine phosphate, diphenhydramine
HC1, cycllzine, chlorpheniramine maleate, promethazine
HC1, meprobamate, phenoxybenzamine HC1 blocked the effects
of this compound.
ANIMALS:
Mice, IT, M, 18-25 g.
ANIMALS: 200 Cockerels, White Leghorn, ages 5-14 d, 45-100 g
PREPARATION AND DOSE
or HISTORY OF PATIENT:
ED,
2 mg/kg
ED,- = dose producing a 50% mortality of mice injected
S.C. with yohimbine hydrochloride (20 mg/kg).
PREPARATION AND DOSE
or HISTORY OF PATIENT: 1-50 mg/kg
ROUTE AND SITE: S.C., Oral
CONTROL INFORMATION: Various
ROUTE AND SITE: S.C. near axillary vein; I.P. for doses over 0.05 ml
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Behavior, electrophysiology, biochemistry
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Behavior, EEC
747
748
-------
COMPOUND: Phenethylamine, 3,4,5,-trimethoxy-
000054046
REFERENCE: Dill, R.E. and Campbell, K.M.
Res. Comm. Chem. Path. Pharm. 6: 975-982, 1973.
COMPOUND: Phenethylamine, 3,4,5,-trimethoxy-
000054046
REFERENCE: Seller, N. and Demisch, L.
Biochem. Pharmacol. 23:273-287, 1974.
OBSERVED NEUROTOXIC EFFECTS: Treatment produced tremors in the contralateral limbs
lasting 1/2-hour.
OBSERVED NEUROTOXIC EFFECTS:
Probable formation of trimethoxyphenylacetic acids
in the brain.
ANIMALS: Squirrel monkeys
Rats (details ns)
ANIMALS: Mice, NMR1, M, 30-35 g (groups of 10)
PREPARATION AND DOSE
Of HISTORY OF PATIENT: 161 or 540 nMoles/monkey
About 200-800 nMoles/rat
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Various labeled compounds including 2,6-mescaline HC1
120 mg/kg.
ROUTE AND SITE: Monkeys: direct application to putamen
Rats: intrastriatal
CONTROL INFORMATION: „
Homovanillic acid or saline
ROUTE AND SITE: I.P.
CONTROL INFORMATION: Laboratory controls
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Clinical (behavior)
DURATION OF EXPERIMENT: 1-24 hr. serial
EXAM. TYPE: Biochemical
749
750
-------
COMPOUND: Phenethylamine, 3,4,5,-trimethoxy-
000054046
REFERENCE: Shah, N.S. and Neely, A.E.
Biochem. Phannacol. 22:1535-1538, 1973.
COMPOUND: Phenethylamine, 3,4,5rtrimethoxy-, hemlsulfate
REFERENCE: Spooner, C.E. and Winters, W.D.
Int. J. Neuropharmacol. 5: 217-236, 1966
OBSERVED NEUROTOXIC EFFECTS: Nontoxic doses of chlorpromazine caused "marked
and prolonged retention" of compound blocking its
disappearance from brain of both mother and fetuses.
OBSERVED NEUROTOXIC EFFECTS: Compound produced excitement, abnormal postures,
arousal EEGs, then depression.
ANIMALS: Mouse, Swiss-Webster, pregnant F (number ns.)
ANIMALS: 200 Cockerels, White Leghorn, ages 5-14 d, 45-100 g
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Labeled mescaline 8.33 micromoles/kg. Chlorpromazine
up to 15 mg/kg, serially. Various schedules. Days
15-18 of gestation.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 5-100 mg/kg
ROUTE AND SITE: I.P.
CONTROL INFORMATION: Incorporated into schedules
ROUTE AND SITE: s.C. near axillary vein; I.P. for doses over 0.05 ml
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: 4 hr after mescaline, sacrifice
EXAM. TYPE: Biochemical
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Behavior, EEC
751
752
-------
COMPOUND: Phenol
000108952
REFERENCE: Berry, K. and Olszewski, J.
Neurology 13: 152-154, 1963.
OBSERVED NEUROTOXIC EFFECTS: The treatment gave scant relief of pain, but caused
severe demyelination, especially in the outer zone
of the posterior roots, affecting fibers of all sizes.
. Phenol, p-(2-aminoethyl)-3-methoxy-
COMPOUND:
REFERENCE: Dill, R.E. and Campbell, K.M.
Res. Comm. Chem. Path. Pharm. 6: 975-982, 1973.
OBSERVED NEUROTOXIC EFFECTS: Treatment produced tremors in the contralateral limbs
lasting 1/2-hour.
ANIMALS: Human: 3 terminal cancer patients with intractable pain.
ANIMALS: Squirrel monkeys
Rats (details ns)
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.5-0.6 ml of 5% compound
PREPARATION AND DOSE
or HISTORY OF PATIENT: 161 or 540 nMoles/monkey
About 200-800 nMoles/rat
ROUTE AND SITE: Intrathecal
CONTROL INFORMATION: None
ROUTE AND SITE: Monkeys: direct application to putamen
Rats: intrastriatal
CONTROL INFORMATION: „ ,,,_,
Homovanillic acid or saline
DURATION OF EXPERIMENT: 12 d to 1°-1/2 wk
EXAM. TYPE: Clinical, autopsy (histology)
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Clinical (behavior)
753
754
-------
COMPOUND: Phenol, m-(N-(2-imidazolin-2-ylmethyl)-p-toluidino)-,
monoethanesulfonate (salt)
000065281
REFERENCE: Qulnton, R.M.
Br..J. Pharmac. 21:51-66, 1963.
OBSERVED NEUROTOXIC EFFECTS: The compound enhanced the effect of Yohimbine
and lowered its lethal dosage.
COMPOUND: Phenol, 2,2' -methylenebis (3,4,6-trichloro)-
000070304
REFERENCE: Alder, S. and Zbinden, G.
Agents and Actions 3/4: 233-243, 1973.-
OBSERVED NEUROTOXIC EFFECTS: Spongiform encephalopathy of brain and cord after 5 doses
(10 and 15mg levels), severe after 9 doses; occasional
degeneration of sciatic nerve. Mild atrophy of pancreas
at 5 mg level. Hind leg paresis at 10 and 15mg levels.
Slight delay on Hot Plate Test, no effects on Foot Print
Test, failures of Rotating Rod Test after 4 (15mg level)
and 10 (lOmg level) days.
ANIMALS:
Mice, TT, M, 18-25 g.
ANIMALS: Rats: CFN Zu, F, 38-53g, 8 groups 10-12 each
PREPARATION AND DOSE
or HISTORY OF PATIENT:
ED5Q 46 mg/kg
ED,- = dose producing a 50% mortality of mice injected
S.C. with yohimbine hydrochloride (20 mg/kg).
PREPARATION AND DOSE
or HISTORY OF PATIENT: 5, 10, 15 mg/kg, 5 d/wk, 2 groups/level, 5-50 doses
ROUTE AND SITE: S.C., Oral
CONTROL INFORMATION: Various
ROUTE AND SITE: Oral
CONTROL INFORMATION: 2 groups water orally
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Behavior, electrophysiology, biochemistry
DURATION OF EXPERIMENT: Serial sacr 1-10 wk
EXAM. TYPE: Behavior, histology
755
756
-------
COMPOUND: Phenol, 2,2'-methylenebis (3,4,6-trichloro)
(Hexachlorophene)
000070304
REFERENCE: DeJesus, P.V., Jr. and Pleasure, D.E.
Arch. Neurol. 29:180-182, 1973.
OBSERVED NEUROTOXIC EFFECTS:
Low-Hexachlorophene rats few signs but motor
nerve conduction velocity (MNCV) diminished,
and yield of myelin sulfatide was low.
High-Hexachlorophene rats had hind limb
weakness and muscle-wasting (recovered in 1-2
wk),MNCV 72% diminished, and still lower yield
of myelin sulfatide.
ANIMALS: Rats, Osborne-Mendel, adult, 3 grps
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Low-Hexachlorophene fed diet giving 25-35
mg/kg/d. High-Hexachlorophene diet gave
50-75 mg/kg/d. Sciatic nerves extracted,
on termination.
ROUTE AND SITE: Oral
CONTROL INFORMATION: Untreated group.
DURATION OF EXPERIMENT: About 2 mo.
EXAM. TYPE: Behavior; nerve-conduction; biochemistry
757
COMPOUND: Phenol, 2,2'-methylenebis (3,4,6-trichloro)-
000070304
REFERENCE: Hall, G.A. and Reid, I.M.
J. Path. 114:241-246, 1974.
OBSERVED NEUROTOXIC EFFECTS: Incoordination, varied extent(none to fatal).
White-matter vacuolation in Central and Peripheral Nervous System, rapid
onset, severe in some clinically normal animals.
ANIMALS: Sheep, Herdwick or (Suffolk x Clun Forest), F and castrated M
yearlings, 3 studies with 9, 6, and 11 sheep.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 20 mg/kg/d as 5% w/v in paraffin.
ROUTE AND SITE: Oral (1,2); injection into rumen (3).
CONTROL INFORMATION: Paraffin only
DURATION OF EXPERIMENT: Serial sacr to 12 d
EXAM. TYPE: Behavior, histology
758
-------
COMPOUND: Phenol, 2,2'-methylenebis (3,4,6-trichloro)-(hexachlorophene)
000070304
REFERENCE: Herter, W.B.
Kaiser Fdn. Hosp. Bull. 7:59, 1959.
COMPOUND: . Phenol, 2,2'-methylenebis (3,4,6-trichloro)-
000070304
REFERENCE: Kimbrough, R.D. and Gaines, T.B.
Arch. Env. Hlth. 23:114-118, 1971.
OBSERVED NEUROTOXIC EFFECTS: Twitching, nystagmus, convulsions; recovery started
on d 4 of hospital stay. On d 6, left facial
paralysis; recovered by d 16. Author stated that
no similar case of hexachlorophene poisoning
was found in published reports.
OBSERVED NEUROTOXIC EFFECTS: Leg weakness at 2 wk, paralysis at 3-5 wk, recovery
in 6 wk. Brain wt increased and returned to normal. Cerebral white-matter
edema, diffuse spongy degeneration.
ANIMALS: Human: baby, 5 d old
ANIMALS: Rats, Sherman, adult F
PREPARATION AND DOSE
or HISTORY OF PATIENT:
3% lotion applied and left there daily for 4 d.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 500 ppm in diet (25 mg/kg/d)
ROUTE AND SITE: Topical, after bath, all over skin.
CONTROL INFORMATION: None
ROUTE AND SITE: oral
CONTROL INFORMATION: Matched untreated controls
DURATION OF EXPERIMENT: 11
EXAM. TYPE: Clinical
DURATION OF EXPERIMENT: serial sacr to 14 wk
EXAM. TYPE: Behavior, histology
759
760
-------
COMPOUND: Phenol, 2,21-methvlenebis (3,4,6-trichloro)-
000070304
REFERENCE: Lampert, P., O'Brien, J. and Garrett, R.
Acta Neuropath. 23:326-333, 1973.
COMPOUND: Phenol, 2,2'-methylenebis (3,4,6-trichloro)-
000070304
REFERENCE: Martinez, A.J., Boehm, R. and Hadfield, M.G.
Acta Neuropath. 28:93-103, 1974.
OBSERVED NEUROTOXIC EFFECTS: Lethargy, dragging hindlegs after 2 wk. Gross
cerebral edema, especially white-matter (corpus callosum). Widely-
spaced myelinated axons. Wide clear spaces within myelin sheaths (between
lamellae). Spaces disappeared on recovery. Water content of brain had
been increased, as had proportion of ganglioside GM . Little axonal
. degeneration.
OBSERVED NEUROTOXIC EFFECTS: Anorexia, nausea, vomiting; blurred vision,
blindness; later somnolence, disorientation. Decerebrate posturing,
respiratory and cardiac arrest. EEG slowed at 40 hr after admission,
isoelectric at 71 hr. Demyelination and axonal degeneration throughout
optic pathways, considered secondary to edema. Optic tract localization
shown dependent on oral route, as in animal models.
ANIMALS: 10 Rats (Sherman) and 40 mice
ANIMALS: 1 Human: M, aged 7 yr
PREPARATION AND DOSE
or HISTORY OF PATIENT: 700-1000 ppm respectively in diet
PREPARATION AND DOSE
or HISTORY OF PATIENT: Accidental administration of 6 doses totaling approx. 45 ml
67-21 hr before admission to hospital.
ROUTE AND SITE: Oral
CONTROL INFORMATION: 20 mice transferred to normal diet after 2 wk and so fed
for up to 12 wk. Some normal-diet controls.
ROUTE AND SITE: Oral
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: 14 wk
EXAM. TYPE: Behavior, histology, biochemistry
DURATION OF EXPERIMENT: Death 83 hr after admission
EXAM. TYPE: Behavior; Histology
761
762
-------
COMPOUND: Phenol. 2,2'-methylenebis (3,4,6-trichloro)-
(Hexachlorophene)
000070304
REFERENCE: Matthieu, J-M., Zimmerman, A.W., Webster, H.deF., Ulsamer, A.G.,
Brady, R.O. and Quarles, R.H.
Exp. Neurol. 45:558-575, 1974.
OBSERVED NEUROTOXIC EFFECTS:
500 ppm fed d 1-10 had proved lethal. Now,
lethargy, incontinence of urine, and spastic
paraplegia in pups and dams, but pups placed
on control diet at d 18 recovered in 4 wk.
Central Nervous System white-matter was
demyelinated, apparently following degradation
of a myelin glycoprotein.
ANIMALS:
Rats, S-D, 16 litters (9-10/litter) aged 2 d, randomized.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
ROUTE AND SITE: Oral
300 ppm in SPF diet (15 mg/kg/d) days 2-10,
then 500.ppm (25 mg/kg/d) days 11-18, fed
to dams; same fed to pups days 19-21. On d
21 pups were injected intracerebrally with
labeled fucose and sacrificed 16 hr later
(d 22) .
CONTROL INFORMATION: Fed SPF diet without hexachlorophene.
DURATION OF EXPERIMENT: 22 d
EXAM. TYPE: Histology and biochemistry; behavior.
763
COMPOUND: Phenol, 2,2'-methylenebis (3,4,6-trichloro)-
000070304
REFERENCE: NaKaue, H.S., Dost, F.N. andBuhler, D.R.
Tox. Appl. Pharm. 24:239-249, 1973.
OBSERVED NEUROTOXIC EFFECTS: Lethargy, posterior paralysis, histopathological
change in the brain, characterized by extensive
vacuolization and edema of myelinated areas. Hind
limb weakness, brain lesions and death.
ANIMALS: Rats, albino, Wistar, M and F, 4 wk old.
PREPARATION AND DOSE
or HISTORY OF PATIENT: I.P.: 21.8-39.9 mg/kg/d.
Oral: 63.0-87.0 mg/kg/d.
ROUTE AND SITE: I.P. and oral
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: Sacr 16 weeks, others demised.
EXAM. TYPE: Histology, hematology.
764
-------
COMPOUND: Phenol, 2,2'-methylenebls (3,4,6-trichloro)-
000070304
REFERENCE: Pilapil, v.R.
Am. J. Dis. Child. 11:333-336, 1966.
COMPOUND: Phenol, 2,2'-methylenebis (3,4,6-trichloro)-
(Hexachlorophene)
00007034
REFERENCE: Pleasure, D., Towfighi, J.,Silberberg, D. and Parris, J.
Neurology 24:1068-1075, 1974.
OBSERVED NEUROTOXIC EFFECTS: Neuromuscular signs by d 3-4, progressing to
seizures. After correction of error, spastic flexion of extremities persisted
at 1 wk, slight at 1 mo. (EEC normal at 2 wk, no observed residual signs at
6 mo.
OBSERVED NEUROTOXIC EFFECTS: (1) In vivo: hindlimb weakness in 2-3 wk, sciatic
nerve demyelination, loss of about 40% of myelin.
(2) In vitro (rat brain): disruption of myelin within 12 hr.
(3) Chick embryo sciatic nerves: hexachlorophene was bound rapidly,
inhibited protein and lipid synthesis after 1 hr and depleted the nerves of
ATP.
ANIMALS: Human: one case, neonate, M
PREPARATION AND DOSE
or HISTORY OF PATIENT: 3% prep, 20 drops 4/d for 2 d, 25 drops 4/d, for 5 d,
by mistake for sulfisoxazole (misbottling).
ROUTE AND SITE: Oral, gavage
CONTROL INFORMATION: None
ANIMALS: (1) Rats, Osborne-Mendel, adult, 30 including controls.
(2) Cultures of newborn rat cerebellum, 47 including control cultures.
(3) Sciatic nerves from chick embryos, 18 d old.
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) 0.1% in diet (w/w).
(2) Selected cultures exposed to 0.3-10 meg/ml of medium
for 48 hr on d 14-19 in vitro. x
(3) Incubated for 2 hr with labeled myelin precursors and "sufficient"
HCP, or with labeled HCP.
ROUTE AND SITE: (1) oral (2 and 3) in medium in vitro.
CONTROL INFORMATION: Controls as above without hexachlorophene.
DURATION OF EXPERIMENT: 7 d plus 6 mo. follow-up
EXAM. TYPE: Clinical
DURATION OF EXPERIMENT: (1) up to 4 wk, (2) 48 hr (3) 2 hr.
EXAM. TYPE: Behavior, biochemistry, histology
765
766
-------
COMPOUND: Phenol, 2,2'-methylenebis (3,4,6-trichloro)-
(Hexachlorophene)
000070304
REFERENCE: Rose, A.L., Wisniewski, H.M., and Cannner, W.
J. Neurol. Sci. 24:425-435, 1975.
COMPOUND: Phenol, 2,2'-methylenebis (3,4,6-trichloro)-
(Hexachlorophene)
000070304
REFERENCE: Shuman, R.M., Leech, R.W., and Alvord, B.C.
Arch. Neurol. 32: 315-319, 1975.
OBSERVED NEUROTOXIC EFFECTS: Paralysis of hindlimbs. Survivor's vision
was impaired. Myelin was vacuolated in central and peripheral nervous system
with axonal degeneration, especially in optic nerves. After treatment stopped,
poisoned infants had hydrocephalus, optic nerve atrophy. 50% of dams
and 75% infants died. Hexachlorophene in blood: dams 4.7-6 meg/ml,
infants 2-2.5 meg/ml.
OBSERVED NEUROTOXIC EFFECTS: Inactivity decreased feeding, weakness, coarse
tremor; "extremely susceptible" at age 6-22 d, not susceptible after
d 26, or before d 2. Vacuolar encephalopathy was produced by 2 washes
only between d 13 and 22. Vacuolization and disruption of myelin, no
damage to nonmyelinated nuclear areas. "Age-dose-response curves are
. similar to those in humans."
ANIMALS: 23 Rats, S-D, F with nursing litters (20 were ttd).
ANIMALS: Rats aged 0-33 d kept with dams
PREPARATION AND DOSE
or HISTORY OF PATIENT: 500 ppm in dams' diet (50 mg/kg/d) from 9th d postpartum.
Young received same diet from weaning.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Daily wash with 3% hexachlorophene in detergent, 2-3 ml.
ROUTE AND SITE: oral
CONTROL INFORMATION: 3 dams and litters untreated, diet alone.
ROUTE AND SITE: Topical
CONTROL INFORMATION: 2 litters washed with detergent only, one litter unwashed.
DURATION OF EXPERIMENT: Serial sacr to 180 d.
EXAM. TYPE: Behavior, biochemistry, histology
DURATION OF EXPERIMENT: 33 d, serial termination.
EXAM. TYPE: Behavior, histology
767
768
-------
COMPOUND: Phenol. 2,2'-methylenebis (3,4,6-trichloro)-
(Hexachlorophene)
000070304
REFERENCE: Shuman, R.M., Leech, R.W. and Alvord, E.G.
Arch. Neurol. 32: 320-325, 1975.
OBSERVED NEUROTOXIC EFFECTS: whole-body bathing repeatedly in 3% hexachloro-
phene (history) significantly associated with vacuolar encephalopathy of
brainstera reticular formation; prevalence related to number of exposures,
concentration of hexachlorophene, thoroughness of rinsing, and exposure
to UV.
COMPOUND: Phenol, 2.2'-methvlenebis (3.4.6-trichloro)-
000070304
REFERENCE: StenbHck, F.
Arch. Env. Hlth. 30:32-35, 1975.
OBSERVED NEUROTOXIC EFFECTS:
Hindlimb tremor, paralysis, convulsions, death
(22% in 2 wk, thereafter mortality unremarkable).
Symptoms vanished after 2-6 wk, epidermis at site
thickened. Autopsies showed edema and cystic lesions
in Central Nervous System white-matter; some of the
lesions persisted after symptoms had vanished.
ANIMALS: Human neonates under 1.4 kg birthweight that survived 4 or more d
and were autopsied from 1/1/66 through 6/30/73; total of 46, in
2 hospitals.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Available brain sections, with 2 or more brainstem
levels (medulla and either pons or midbrain). Histories
examined independently and then matched with histology
data.
ANIMALS: Mice, random-bred Swiss, F, age 8 wk.
PREPARATION AND DOSE , c fn
or HISTORY OF PATIENT: 5, 25 or 50% in 0.2 ml acetone, 2 doses/wk for life, 50
mice/cone. -.
ROUTE AND SITE: Topical (washing)
CONTROL INFORMATION: Blind review of 2 sets of data.
ROUTE AND SITE: Topical, dorsal skin between flanks, shaved regularly
CONTROL INFORMATION: One control group.
DURATION OF EXPERIMENT: 18 mo.
EXAM. TYPE: Histology and history
DURATION OF EXPERIMENT: Lifetime
EXAM. TYPE: Behavior, clinical, autopsy, histology
769
770
-------
COMPOUND: Phenol, 2,2'-methvlenebis (3,4,6-trichloro)-
000070304
REFERENCE: Udall, V.
Proc. Roy. Soc. Med. 65: 197-199, 1972
COMPOUND: Phenol, 2,2'-methylenebis (3,4,6-trichloro)-
000070304
REFERENCE' Webster, Henry DeF., Ulsamer, A.G. and O'Connell, M.F.
J. Neuropath. Exp. Neurol. 33(1):144-170, 1970.
OBSERVED NEUROTOXIC EFFECTS: Signs 12-30 hours after dose included loss of visual
acuity and pupil response (no recovery after 4 mo),
transient optic disc edema, no retino-EEG action
potentials, exophthalmos, cerebral edema.
OBSERVED NEUROTOXIC EFFECTS:
Large optical lesions, myelin sheath splitting
at axonal and extracellular surfaces, vacuolation
in myelin sheaths, ventral tail nerve fibers exhibited
focal splitting and lesions on peripheral myelin sheath.
Loss of some motor activity.
ANIMALS: Sheep and Cattle
ANIMALS: 25-40 groups Tadpoles, Xenopus, 45-55th development stage.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 20-80 mg/kg
PREPARATION AND DOSE
or HISTORY OF PATIENT: Immersed in 0.1-0.2 meg Compound/ml.
ROUTE AND SITE: Oral, abomasal, or ruminal
CONTROL INFORMATION: ns
ROUTE AND SITE: Absorption via immersion
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Behavior, physiology
DURATION OF EXPERIMENT:Sacr 1, 3, 5, 6 or 7 d.
EXAM. TYPE: Ultrastruetural, histology
771
772
-------
COMPOUND:
Phenolphthalein
COMPOUND: Phenothiazine drugs (unspecified)
REFERENCE:
Steer, H.W. and Colin-Jones, D.G.
J. Path. 115:199-205, 1975
REFERENCE: Myrianthopoulos, N.C., Kurland, A.A. and Kurland, L.T.
Arch. Neurol. 6: 19-23, 1962.
OBSERVED NEUROTOXIC EFFECTS: More lysosomal activity and lysosomes in Schwann
cells and neurons of submucosal plexus in colonic
OBSERVED NEUROTOXIC EFFECTS: 13 cases of parkinsonism found among relatives of
propositi, 3 among relatives of controls; numbers too
small for analysis but suggested some hereditary
susceptibility to parkinsonian side-effects of
ataractic drugs.
ANIMALS: Human: 7 aged 24-80 with melanosis coli who took purgatives;
1 who had taken purgatives for only 1 m.
ANIMALS: Human: 728 relatives of 59 propositi
PREPARATION AND DOSE
or HISTORY OF PATIENT: Rectal biopsy before and 3-7 m after stopping medication
PREPARATION AND DOSE
or HISTORY OF PATIENT: History of high doses of compounds with parkinsonian
side-effects
ROUTE AND SITE: oral
CONTROL INFORMATION:
7 aged 27-70 with other gut disorders who had taken no
purgatives for 3 m.
ROUTE AND SITE: oral
CONTROL INFORMATION: 777 relatives of 67 controls
DURATION OF EXPERIMENT: About 7 m.
EXAM. TYPE: Histology, histochemistry
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Epidemiology
773
774
-------
COMPOUND: Phenothiazine, 2-chloro-10-3(3-dimethylamino)propyl)- (chloropromazine)
000050533
REFERENCE: Brosnan, C.F., Bunge, M.B. and Murray, M.R.
J. Neuopath. Exp. Neurol. 24(3):337-353, 1970.
OBSERVED NEUROTOXIC EFFECTS: Chlorpromazine affected the lysosomal system,
inducing acid Pase activity; compound appeared to be concentrated within
the multilaminated dense bodies of the lysosomal system. The purpose of
the study was to explore the mode of action of chloropromazine.
COMPOUND: Phenothiazine, 2-c'hloro-10-3(3-dimethylamino)propyl)-
000050533
REFERENCE: Shah, N.S. and Neely, A.E.
Biochem. Pharmacol. 22:1535-1538, 1973.
OBSERVED NEUROTOXIC EFFECTS:
Nontoxic doses of Chlorpromazine caused "marked
and prolonged retention" of mescaline, blocking its
disappearance from brain of both mother and fetuses.
ANIMALS: Rat ganglia from 18-19 d fetuses, cultured in vitro.
ANIMALS: Mouse, Swiss-Webster, pregnant F (number ns.)
PREPARATION AND DOSE _. _4
or HISTORY OF PATIENT: 7-0 x 10 M or 1.4 x 10 M in salt solution, 74
cultures examined.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Labeled mescaline.8.33 micromoles/kg. Chlorpromazine
up to 15 mgVkg, serially. Various schedules. Days
15-18 of gestation.
ROUTE AND SITE: In vitro
CONTROL INFORMATION: Controls with substrate alone, or no substrate.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: Incorporated into schedules
DURATION OF EXPERIMENT: Weeks
EXAM. TYPE: Cytology, biochemistry
DURATION OF EXPERIMENT: 4 hr after mescaline. sacrifice
EXAM.| TYPE: Biochemical
775
776
-------
COMPOUND: Phenothiazine, 2-chloro-10-3(3-dimethylamino)propyl)-
000050533
REFERENCE: Stunnan, G.
Br. J. Pharmac. 50: 153-155, 1974.
COMPOUND: Phenothiazine, 2-chloro-10-(3-(dlmethylamlno)propyl)-,mono-hydrochlorlde
000069090
REFERENCE: Qulnton, R.M.
Br. J. Pharmac. 21:51-66, 1963.
OBSERVED NEUROTOXIC EFFECTS:
Mice: Pretreatment 1 hour beforehand with piperazine
enhanced the acute toxicity of chlorpromazine but not
of prochlorperazine. Rats: Pretreatment with piper-
azine enhanced catatonia from chlorpromazine but not
from prochlorperazine. Piperazine did not alter the
EEC changes induced by chlorpromazine or prochlor-
perazine. In sum: piperazine potentiated the central
nervous system effects of chlorpromazine but not of
prochlorperazine.
OBSERVED NEUROTOXIC EFFECTS:
The compound enhanced the effect of Tohimbine
and lowered its lethal dosage.
ANIMALS: Mice, no details
Rats, F, no other details
ANIMALS:
Mice, TT, M, 18-25 g.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Piperazine: 0, 1, 2.5 or 5 g/kg~i followed after 1 or 24
hr by various doses of chlorpromazine or prochlorperazine
-1
ROUTE AND SITE: Piperazine: S.C.; chlorpromazine and prochlorperazine: I.P.
CONTROL INFORMATION: No piperazine given
PREPARATION AND DOSE
or HISTORY OF PATIENT:
7 mg/kg
ED-- «• dose producing a 50% mortality of mice injected
50 S.C. with yohimbine hydrochloride (20 mg/kg).
ROUTE AND SITE: s.C., Oral
CONTROL INFORMATION: Various
DURATION OF EXPERIMENT: Hours
EXAM. TYPE: Behavior
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Behavior, electrophysiology, biochemistry
777
778
-------
COMPOUND: Phenothiazine, 2-chloro-10-(3-(dimethylamino)propyl)-, mono-hydrochloride
000069090
REFERENCE: Spooner, C.E. and Winters, W.D.
Int. J. Neuropharmacol. 5: 217-236, 1966.
OBSERVED NEUROTOXIC EFFECTS: Compound produced depression and associated slow-
wave EEGs.
COMPOUND: Phenothiazine, 2-chloro-10-(3-(4-methyl-l-piperazinyl) propyl
000058388
REFERENCE: DeSilva, K.L., Muller, P.J. and Pearce, J.
Practitioner 211: 316-320, 1973.
OBSERVED NEUROTOXIC EFFECTS: Extrapyramidal signs, spasms especially of face, tongue
and jaws, torticollis, opisthotonus, trismus; onset in
2-60 hrs. commonest in young. No dose relationship,
recovery after withdrawal. One case had added dienceph-
alic features. Authors comment that etiology still
unknown, and suggest idlosyncracy to class of drugs
(phenothiazines).
ANIMALS: 200 Cockerels, White Leghorn, ages 5-14 d, 45-100 g
ANIMALS: Human: 10 cases, M & F, 14-30, selected from 20 cases treated at a
hospital serving 500,000 population, over 2 yrs
PREPARATION AND DOSE
or HISTORY OF PATIENT: 2.5-50 mg/kg
PREPARATION AND DOSE
or HISTORY OF PATIENT: 3 cases: 15 mg P.O., 12.5 to 25 mg I.M.
Adverse drug reaction.
ROUTE AND SITE: s.C. near axillary vela; I.P. for doses over 0.05 ml
CONTROL INFORMATION: ns
ROUTE AND SITE: I.M. and P.O. (see above)
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Behavior, EEC
DURATION OF EXPERIMENT: 2-24 hrs.
EXAM. TYPE: Clinical
779.
780
-------
COMPOUND: Phenothiazlne, 2-chloro-10-(3-(4-methyl-l-piperazinyl)propyl- (prochlorperazine)
OOOOS8388
REFERENCE: Stunnan, G.
Br. J. Phannac. 50: 153-155, 1974.
OBSERVED NEUROTOXIC EFFECTS:
Mice: Pretreatment 1 hour beforehand with piperazine
enhanced the acute toxicity of chlorpromazine but not
of prochlorperazine. Rats: Pretreatment with piper-
azine enhanced catatonia from chlorpromazine but not
from prochlorperazine. Piperazine did not alter the
EEC changes induced by chlorpromazine or prochlor-
perazine. In sum: piperazine potentiated the central
nervous system effects of chlorpromazine but not of
prochlorperazine.
COMPOUND: Phenothiazine, 10-(2-diethylamino) propyl)-
000522009
REFERENCE: pfeiffer, C.C., Murphree, H.B., Jenney, E.H., Robertson, M.G.,
Randall, A.H. and Bryan, L.
Neurology 9: 249-250, 1959.
OBSERVED NEUROTOXIC EFFECTS:
The authors concluded that synthetic atropines are more
active hallucinogens than atropine or scopolamine, pro-
ducing effects lasting 24-48 hr. Synthetic antitremor
drugs had fewer peripheral nervous system side-effects,
but central nervous system side-effects (hallucinations)
may have been exaggerated.
ANIMALS: Mice, no details
Rats, F, no other details
ANIMALS: Human: prison volunteers, drug-sophisticated, no other details
PREPARATION AND DOSE
or HISTORY OF PATIENT: Piperazine: 0, 1, 2.5 or 5 g/kg"-1 followed after 1 or 24
hr by various doses of chlorpromazine or prochlorperazine
-1
PREPARATION AND DOSE
or HISTORY OF PATIENT: 50 mg/man
ROUTE AND SITE: Piperazine: S.C.; chlorpromazine and prochlorperazine: I.P.
CONTROL INFORMATION: No piperazine given
ROUTE AND SITE: Oral
CONTROL INFORMATION: LSD-25: 0, 25, 50, 100 meg/man
DURATION OF EXPERIMENT: Hours
EXAM. TYPE: Behavior
DURATION OF EXPERIMENT: Up to 3 d
EXAM. TYPE: Opinion of volunteers
781
782
-------
COMPOUND: Phenothiazlne, 10-(2-dimethylamino propyl)
000060877
REFERENCE: Qulnton, R.M.
Br. J. Pharmac. 21:51-66, 1963.
OBSERVED NEUROTOXIC EFFECTS: the compound enhanced the effect of Yohimbine
and lowered its lethal dosage.
COMPOUND: Phenothiazine, 10-(3-(dimethylamino)propyl)-, monohydrochloride (promazine)
000053601
REFERENCE: Barsa, J.A. and Kline, N.S.
Am. J. Psychiatry 113: 654, 1957.
OBSERVED NEUROTOXIC EFFECTS: "A few" developed mild rigidity; 2 patients had grand
mal seizures. When the dose was reduced to 200 mg
four times per day, there were no adverse reactions. An
EEC taken in 1 case was normal.
ANIMALS:
Mice, TT, M, 18-25 g.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
ED50 16 mg/kg
ED,n = dose producing a 50% mortality of mice injected
S.C. with yohimbine hydrochloride (20 mg/kg).
ANIMALS: Human: schizophrenics, subjects of a clinical pharmacology trial,
ages 25-68, hospitalized 2-24 yr, total 21 subjects
PREPARATION AND DOSE
or HISTORY OF PATIENT: All had been receiving chlorpromazine for 6 mo or more.
Promazine given 25-300 mg four times per day.
ROUTE AND SITE: s.C., Oral
CONTROL INFORMATION: Various
ROUTE AND SITE: Oral
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Behavior, electrophysiology, biochemistry
DURATION OF EXPERIMENT: 3 mo or more
EXAM. TYPE: Clinical
783
784
-------
COMPOUND: Phenothiazine, 10-(3-(dimethylamino)propyl)-, monohydrochloride
000053601
REFERENCE: Quinton, R.M.
Br. J. Phannac. 21:51-66, 1963.
OBSERVED NEUROTOXIC EFFECTS: The compound enhanced the effect of Yohimbine
and lowered its lethal dosage.
COMPOUND: Phenothiazine, 10-(2-(dimethylamino) propyl)-, monohydrochloride
000058333
REFERENCE: Quinton, R.M.
Br. J. Pharmac. 21:51-66, 1963.
OBSERVED NEUROTOXIC EFFECTS: The compound enhanced the effect of Yohimbine
and lowered its lethal dosage.
ANIMALS: Mice, TT, M, 18-25 g.
ANIMALS:
Mice, TT, M, 18-25 g.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
^50
ED_. ° dose producing a 50% mortality of mice injected
S.C. with yohimbine hydrochloride (20 mg/kg).
PREPARATION AND DOSE
or HISTORY OF PATIENT:
ED5Q >50 mg/kg
ED = dose producing a 50% mortality of mice injected
S.C. with yohimbine hydrochloride (20 mg/kg).
ROUTE AND SITE: S.C., Oral
CONTROL INFORMATION: Various
ROUTE AND SITE: S.C., Oral
CONTROL INFORMATION: Various
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Behavior, electrophysiology, biochemistry
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Behavior, electrophysiology, biochemistry
785
786
-------
COMPOUND: Phenothiazine, 2-(ethylthio)-10-(3-(4-methyl-l-piperazinyl)propyl)-'
COMPOUND: Phenothiazine, 10-(3-(4-methyl-l-piperazinyl)propyl)-2-(trifluoromethyl)-
REFERENCE: DeSilva, K.L., Muller, P.J. and Pearce, J.
Practitioner 211: 316-320, 1973.
REFERENCE: DeSilva, K.L., Muller, P.J. and Pearce, J.
Practitioner 211: 316-320, 1973.
OBSERVED NEUROTOXIC EFFECTS: Extrapyramidal signs, spasms especially of face, tongue
and jaws, torticollis, opisthotonus, trismus; onset in
2-60 hrs. commonest in young. No dose relationship,
recovery after withdrawal. One case had added dienceph-
alic features. Authors comment that etiology still
unknown, and suggest idiosyncracy to class of drugs
(phenothiazines).
OBSERVED NEUROTOXIC EFFECTS:
Extrapyramidal signs, spasms especially of face, tongue
and Jaws, torticollis, opisthotonus, trismus; onset in
2-60 hrs. commonest in young. No dose relationship,
recovery after withdrawal. One case had added dienceph-
alic features. Authors comment that etiology still
unknown, and suggest idiosyncracy to class of drugs
(phenothiazines).
ANIMALS: Human: 10 cases, M & F, 14-30, selected from 20 cases treated at
hospital serving 500,000 population, over 2 yrs
ANIMALS: Human: 10 cases, M & F, 14-30, selected from 20 cases treated at a
hospital serving 500,000 population, over 2 yrs
PREPARATION AND DOSE
or HISTORY OF PATIENT: 1 case: 10 mg, t.d.s., P.O.
Adverse drug reaction.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 1 case: 1 mg, b.d., P.O.
Adverse drug reaction.
ROUTE AND SITE: T.d.s., P.O. (see above)
CONTROL INFORMATION: None
ROUTE AND SITE: B.d., P.O. (see above)
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: 60 hrs.
EXAM. TYPE: Clinical
DURATION OF EXPERIMENT: 60 hrs.
EXAM. TYPE: Clinical
787
788
-------
COMPOUND: Phenothiazine, 10-(3-(4-methyl-l-piperazinyl)propyl)-2-trifluoromethyl)-.
COMPOUND: /
3-Phosphabicyclo(4.4.0) decane, p-chloro-2,4-dioxa-5-methyl-p-thiono-
REFERENCE: Romasenko, V.A. and Jacobson, I.S.
Acta Neuropath. 12:23-32, 1969.
OBSERVED NEUROTOXIC EFFECTS: "Sluggishness, motor inhibition, and catalepsy"
reversed on stopping the drug. Vascular changes and hyperchromic and
"wrinkled" nerve cells in cerebral cortex. Increased RNA, proteins,
SH-groups, and polysaccharides. Diminished activities of acid phosphatase
and succinic dehydrogenase. Some Purkinje cells affected in cerebellum.
Author concluded changes are very slight and reversible.
REFERENCE: Sherman, M., Herrick, R.B., Ross, E. and Chang, M.T.Y.
Toxicol. Appl. Pharm. 11: 49-67, 1967.
OBSERVED NEUROTOXIC EFFECTS: Ataxia, paralysis, convulsions.
Acute: Significant growth depression even at levels
lower than the LD....
ANIMALS: 96 Rats, white, M, 150-250 g
ANIMALS: Cockerels, Single Comb White Leghorn, 10-12 d old
PREPARATION AND DOSE
or HISTORY OF PATIENT: 1- Chronic: 1, 5, or 20-25 mg/kg for 1-5 wk.
2. Acute and subacute: 50-250 mg/kg, one dose.
3. Observational only.
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) Acute: LD5Q 25.6 mg/kg
(2) Subacute: 50-800 ppm in diet, 20 chicks/grp, for 2 wk
ROUTE AND SITE: 1- Oral: gavage or in diet. 2. I.M.
CONTROL INFORMATION: Mentioned, not described.
ROUTE AND SITE: Oral
CONTROL INFORMATION: Untreated control grps
DURATION OF EXPERIMENT: 1. about 2 mo. 2. 30 min. 3. 1 mo. after (1)
EXAM. TYPE: Behavior, biochemistry, histology
DURATION OF EXPERIMENT: 1-3 wk
EXAM. TYPE: Behavior, mortality
789
790
-------
COMPOUND: Phosphine oxide, tri-o-tolyl-
REFERENCE: Hine, C.H., Dunlap, M.K., Rice, E.G. Coursey, M.M., Gross, R.M.
and Anderson, H.H.
J. Pharm. Exp. Ther. 116:227, 1956.
OBSERVED NEUROTOXIC EFFECTS: None had paralysis.
ANIMALS:
22 Chickens, White Leghorn, M, 0.75-1.3 kg
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) 0.5 gm/kg.
(2) 1.0 gm/kg
ROUTE AND SITE: (i) s.C. (2) Oral
CONTROL INFORMATION: One group of 5 per experimental group.
DURATION OF EXPERIMENT: 14-36 d after treatment.
EXAM. TYPE: Behavior, histology
791
COMPOUND: Phosphofluoridic acid, methyl-, isopropyl ester
000107448
REFERENCE: Bajgar, J.
Tox. and App. Pharm. 22:93-96, 1972.
OBSERVED NEUROTOXIC EFFECTS: Acetylcholinesterase inhibition in blood and
subcellular fractions of medulla oblong gata.
ANIMALS: Rats, Wistar/Mezno, F, 150-170 g
PREPARATION AND DOSE
or HISTORY OF PATIENT:
0.2 mg/kg (approxamating LD,-).
ROUTE AND SITE: I.M.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: Immediately
EXAM. TYPE: Histological, biochemical
792
-------
COMPOUND:
Phosphollpase A
REFERENCE:
Chang, C.C., Chuang, S-T., Lee, C.Y., Wei, J.W.
Br. J. Pharmac. 44:752-764, 1972.
OBSERVED NEUROTOXIC EFFECTS: Ineffective on axonal conduction. Synergistic
effect on cardiotoxin's blocking action due to
aceleration rather than potentiation of its
action. 90 meg/ml completely depolarized
superficial muscle fibers. High concentrations
' of CaCl2 enhanced the depolarizing effect.
ANIMALS:
Phrenic nerve-diaphragm preparation from Long-Evans rats.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Various doses in vitro.
ROUTE AND SITE: in vitro.
CONTROL INFORMATION: Laboratory
DURATION OF .EXPERIMENT: Various
EXAM. TYPE: Electrophysiology, chemistry.
793
COMPOUND:
Fhosphonic acid, decyl-, ethyl p-nitrophenyl ester
REFERENCE:
Aldridge, W.N. and Barnes, J.M.
Biochemical Pharm. 15:541-548, 1966.
OBSERVED NEUROTOXIC EFFECTS: Weakened limbs. Histological changes in the
spinal cord and sciatic nerves. Inhibition of
CNS esterase.
ANIMALS:
Hens, grps of 2-4, RIR x Light Sussex, 2-3 kg
PREPARATION AND DOSE
or HISTORY OF PATIENT: Mostly 1 dose, amount varied by compound
ROUTE AND SITE: oral, s.c., or l.p.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: 14-21 d
EXAM. TYPE: Biochemistry, histology
794
-------
COMPOUND:
Phosphonic acid, ethyl-, 2-chloroethyl 2,2-dichlorovinyl ester
COMPOUND: Phosphonic acid, 0-ethy1-0-(4-nitrophenyl)-ethyl ester
REFERENCE:
Aldridge, W.N. and Barnes, J.M.
Biochemical Pharm. 15:541-548, 1966.
REFERENCE: Rosic, N., Lonax, P. and Kovacevic, N.
Comp. Gen. Pharm. 5: 187-189, 1974.
OBSERVED NEUROTOXIC EFFECTS: Weakened limbs. Histological changes in the
spinal cord and sciatic nerves. Inhibition of
CNS esterase.
OBSERVED NEUROTOXIC EFFECTS: Avoidance behavior was depressed up to 6 hr after
treatment with recovery by 24 hr. Brain cholinesterase
was down 20% by 2 hr, returning after 6 hr, and re-
covered by 24 hr. The authors suggest these findings
are related.
ANIMALS:
Hens, grps of 2-4, RIR x Light Sussex, 2-3 kg
ANIMALS: Fish (Serranus scriba). 15-25 g
PREPARATION AND DOSE
or HISTORY OF PATIENT: Mostly 1 dose, amount varied by compound
PREPARATION AND DOSE
or HISTORY OF PATIENT: 60 meg/kg after avoidance training (half LD5Q)
ROUTE AND SITE: Oral, s.c., or i.p.
CONTROL INFORMATION: ns.
ROUTE AND SITE: S. C.
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: 14-21 d
EXAM. TYPE: Biochemistry, histology
DURATION OF EXPERIMENT: Serial to 24 hr
EXAM. TYPE: Behavior, biochemistry
795
796
-------
COMPOUND:
Phosphonic acid, pentyl-, ethyl p-nitrophenyl ester
COMPOUND: Phosphonic acid, 2-phenylethyl-, ethyl p-nitrophenyl ester
REFERENCE:
Aldridge, W.N. and Barnes, J.M.
Biochemical Pharm. 15:541-548, 1966.
REFERENCE:
Aldridge, W.N. and Barnes, J.M.
Biochemical Pharm. 15:541-548
OBSERVED NEUROTOXIC EFFECTS: Weakened limbs. Histological changes in the
spinal cord and sciatic nerves. Inhibition
of CNS esterase.
OBSERVED NEUROTOXIC EFFECTS: Weakened limbs. Histological changes in the spinal
cord and sciatic nerves. Inhibition of CNS
esterase.
ANIMALS: Hens, grps of 2-4, RIR x Light Sussex, 2-3 kg
ANIMALS:
Hens, grps of 2-4, RIR x Light Sussex, 2-3 kg
PREPARATION AND DOSE
or HISTORY OF PATIENT: Mostly 1 dose, amount varied by compound
PREPARATION AND DOSE
or HISTORY OF PATIENT: Mostly 1 dose, amount varied by compound
ROUTE AND SITE: Oral, s.c., or i.p.
CONTROL INFORMATION: ns.
ROUTE AND SITE: oral, s.c., or i.p.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: 14-21 d
EXAM. TYPE: Biochemistry, histology
DURATION OF EXPERIMENT: 14-21 d
EXAM. TYPE: Biochemistry, histology
797
798
-------
COMPOUND: Phosphonic acid, phenylmethyl-, ethyl p-nitrophenyl ester
COMPOUND:
Phosphonic acid, 3-phenylpropyl-, ethyl p-nitrpphenyl ester
REFERENCE: Aldridge, W.N. and Barnes, J.M.
Biochemical Pharm. 15: 541-548, 1966.
OBSERVED NEUROTOXIC EFFECTS: Weakened limbs. Histological changes in the
spinal cord and sciatic nerves. Inhibition of CNS esterase.
REFERENCE:
Aldridge, W.N. and Barnes, J.M.
Biochemical Pharm. 15:541-548, 1966.
OBSERVED NEUROTOXIC EFFECTS: Weakened limbs. Histological changes in the spinal
cord and sciatic nerves. Inhibition of CNS
esterase.
ANIMALS: Hens, grps of 2-4, RIR x Light Sussex, 2-3 kg
ANIMALS:
Hens, grps of 2-4, RIR x Light Sussex, 2-3 kg
PREPARATION AND DOSE
or HISTORY OF PATIENT: Mostly 1 dose, amount varied by compound
PREPARATION AND DOSE
or HISTORY OF PATIENT: Mostly 1 dose, amount varied by compound
ROUTE AND SITE: oral, B.C., or i.p,
CONTROL INFORMATION: ns.
ROUTE AND SITE: Oral, B.C.. or i.p.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: 14-21 d
EXAM. TYPE: Biochemistry, histology.
DURATION OF EXPERIMENT: 14-21 d
EXAM. TYPE: Biochemistry, histology
799
800
-------
COMPOUND: Phosphonic acid, (2,2,2-trichloro-l-hydroxyethyl)-, dimethyl ester
000052686
REFERENCE: Rayner, M.D., Popper, J.S., Carvalho, E.W. and Hurov, R.
Res. Comm. Chem. Path. Phann. 4: 595-606, 1972.
OBSERVED NEUROTOXIC EFFECTS: The force generated by the achilles tendon reflex was
subnormal in exposed subjects. The authors suggest
! that this hyporeflexia may be a sensitive indicator of
chronic exposure to organophosphates.
COMPOUND: Phosphonodithioic acid, chloromethyl-, S-(p-chlorophenyl)0-isopropyl ester
001713979
REFERENCE: Sherman, M., Herrick, R.B., Ross, E. and Chang, M.T.Y.
Toxicol. Appl. Pharm. 11: 49-67, 1967.
OBSERVED NEUROTOXIC EFFECTS: Ataxia, paralysis, convulsions.
ANIMALS: Humans, Japanese ancestry, M, ages 22-59 (orchid farmers)
ANIMALS: Cockerels, Single Comb White Leghorn, 10-12 d old
PREPARATION AND DOSE
or HISTORY OF PATIENT: Exposure of more than 4 hr/d, 2 d/wk, 52 wk/yr for 5 yr except
one case (2 yr). Other types of pesticide also used, but
authors judged organophosphates exposures to be primary.
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) Acute: LD 30.9 mg/kg
(2) Subacute: 50-800 ppm in diet, 20 chicks/grp, for 2 wk
ROUTE AND SITE: Skin contact, inhalation
CONTROL INFORMATION: Matched non-exposed subjects, so far as could be ascertained
ROUTE AND SITE: Oral
CONTROL INFORMATION: Untreated control grps
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Physiological
DURATION OF EXPERIMENT: 1-3 wk
EXAM. TYPE: Behavior, mortality
801
802
-------
COMPOUND: Phosphonodithiotic acid, 0-isopropyl-S-p-tolyl chloromethyl ester
COMPOUND: Phcisphonofluoridic acid, methyl-, isopropyl ester
REFERENCE: Sherman, M., Herrick, R.B., Ross, E. and Chang, M.T.Y.
Toxicol. Appl. Pharm. 11: 49-67, 1967.
OBSERVED NEUROTOXIC EFFECTS: Ataxia, paralysis, convulsions.
REFERENCE: Loomis, T.A.
Tox. Appl. Pharm. 5:489-499, 1963.
OBSERVED NEUROTOXIC EFFECTS: Motor activity in activity-cage decreased.
ANIMALS: Cockerels, Single Comb White Leghorn, 10-12 d old
ANIMALS: Mice, white, 25-30 g, and 2 dogs (no details)
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) Acute: LD 34.1 mg/kg
(2) Subacute: 50-800 ppm in diet, 20 chicks/grp, for 2 wk
PREPARATION AND DOSE
or HISTORY OF PATIENT: 40 meg/kg.
ROUTE AND SITE: Oral
CONTROL INFORMATION: Untreated control grps
ROUTE AND SITE: i.p.
CONTROL INFORMATION: Saline treated controls.
DURATION OF EXPERIMENT: 1-3 wk
EXAM. TYPE: Behavior, mortality
DURATION OF EXPERIMENT:Serial sacr to 25 min.
EXAM. TYPE: Biochemistry, behavior
803
804
-------
COMPOUND: Phosphonofluoridic acid, methyl-, isopropyl ester
REFERENCE: Loomls, T.A. and Salafsky, B.
Tox. Appl. Pharm. 5:685-701, 1963.
OBSERVED NEUROTOXIC EFFECTS: Acetylcholinesterase inhibition.
COMPOUND: Phosphonofluoridic acid, methyl-, 1,2,2-trimethylpropyl ester
000096640
REFERENCE: Loomis, T.A. and Salafsky, B.
Tox. Appl. Pharm. 5:685-701, 1963.
OBSERVED NEUROTOXIC EFFECTS: Acetylcholinesterase inhibition
ANIMALS: Mice, C^B, 25-35 g
PREPARATION AND DOSE
or HISTORY OF PATIENT:
0.01 ml
ANIMALS: Mice, CJl, 25-35 g
PREPARATION AND DOSE
or HISTORY OF PATIENT:
0.01 ml
ROUTE AND SITE: Dermal
CONTROL INFORMATION: ns.
ROUTE AND SITE: Dermal
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Mortality, electrophysiology
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Mortality, electrophysiology
805
806
-------
COMPOUND: Phosphonothioic acid, ethyl-, di(2-chloroethyl) ester.
REFERENCE: Aldridge, W.N. and Barnes, J.M.
Biochemical Pharra. 15:541-548, 1966.
COMPOUND: Phosphonothioic acid, ethyl-, 0-ethyl 0-(2,4,5-trichlorophenyl)
ester
000327980
REFERENCE:
Aldridge, W.N. and Barnes, J.M.
Biochemical Pharm. 15:541-548, 1966.
OBSERVED NEUROTOXIC EFFECTS: Weakened limbs. Histological changes in the
spinal cord and sciatic nerves. Inhibition
of CNS esterase.
OBSERVED NEUROTOXIC EFFECTS: Weakened limbs. Histological changes in the spinal
cord and sciatic nerves. Inhibition of CNS
of esterase.
ANIMALS: Hens, grps of 2-4, RIR x Light Sussex, 2-3 kg
ANIMALS:
Hens, grps of 2-4, RIR x Light Sussex, 2-3 kg
PREPARATION AND DOSE
or HISTORY OF PATIENT: Mostly 1 dose, amount varied by compound
PREPARATION AND DOSE
or HISTORY OF PATIENT: Mostly 1 dose, amount varied by compound
ROUTE AND SITE: oral, B.C., or i.p.
CONTROL INFORMATION: ns.
ROUTE AND SITE: Oral, s.c., or i.p.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: 14-21 d
EXAM. TYPE: Biochemistry, histology
DURATION OF EXPERIMENT: 14-21 d
EXAM. TYPE: Biochemistry, histology.
807
808
-------
COMPOUND: Phosphonothioic acid, ethyl-, 0-ethyl 0-(2,4,5-trichlorophenyl) ester
000327980
REFERENCE: Sherman, M., Herrick, R.B., Ross, E. and Chang, M.T.Y.
Toxicol. Appl. Pharm. 11: 49-67, 1967.
OBSERVED NEUROTOXIC EFFECTS: Ataxia, paralysis, convulsions.
COMPOUND: Phosphonothioic acid, methyl-, 2,4-dichlorphenyl methyl ester
REFERENCE: Aldridge, W.N. and Barnes, J.M.
Biochemical Pharm. 15:541-548, 1966.
OBSERVED NEUROTOXIC EFFECTS: Weakened limbs. Histological changes in the
spinal cord and sciatic nerves. Inhibition of
CNS esterase.
ANIMALS: Cockerels, Single Comb White Leghorn, 10-12 d old
ANIMALS:
Hens, grps of 2-4, RIR x Light Sussex, 2-3 kg
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) Acute: LD5Q 12.3 mg/kg
(2) Subacute: 50-800 ppm in diet,' 20 chicks/grp, for 2 wk
PREPARATION AND DOSE
or HISTORY OF PATIENT: Mostly 1 dose, amount varied by compound
ROUTE AND SITE: Oral
CONTROL INFORMATION: Untreated control grps
ROUTE AND SITE: Oral, B.C.,'or l.p.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: 1-3 wk
EXAM. TYPE: Behavior, mortality
DURATION OF EXPERIMENT: 14-21 d
EXAM. TYPE: Biochemistry, histology
809
810
-------
COMPOUND: Phosphonothioic acid, phenyl.-0-ethyl ester, 0-ester with p-hydroxybenzonitrile COMPOUND: ' Phosphonothioic acid, phenyl-,0-ethyl 0- (p-nitrophenyl)ester
013067931 002104645
REFERENCE: Sherman, M., Herrick, R.B., Ross, E. and Chang, M.T.Y.
Toxicol. Appl. Pharm. 11: 49-67, 1967.
REFERENCE: Gaines, T.B.
Tox. Appl. Pharm. 14: 515-534, 1969.
OBSERVED NEUROTOXIC EFFECTS: Ataxia, paralysis, convulsions.
OBSERVED NEUROTOXIC EFFECTS: 80 mg/kg produced leg weakness
ANIMALS: Cockerels, Single Comb White Leghorn, 10-12 d old
ANIMALS: Chickens, White Leghorn, F
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) Acute: LD 20.3 mg/kg
(2) Subacute: 50-800 ppm in diet, 20 chicks/grp, for 2 wk
PREPARATION AND DOSE
or HISTORY OF PATIENT: 15 mg/kg atropine sulfate orally 15 min prior to compound;
graded doses compound in peanut oil
ROUTE AND SITE: Oral
CONTROL INFORMATION: Untreated control grps
ROUTE AND SITE: S.C., under right wing
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: 1-3 wk
EXAM. TYPE: Behavior, mortality
DURATION OF EXPERIMENT: 1 yr
EXAM. TYPE: Clinical
811
812
-------
COMPOUND: Phosphonothiooic acid, 0-ethyl S-(2-dimethyl amino ethyl methyl ester
COMPOUND: Phosphonotrithioic acid, S,S-dlpropyl methyl
REFERENCE: Bajgar, J.
Br. J. Pharmac. 45: 368-371, 1972.
OBSERVED NEUROTOXIC EFFECTS: Acetylcholinesterase Inhibition in 3 parts of the
medulla oblongata proceeded at different rates.
The author concluded that.penetration of the compound
through corresponding parts of the blood-brain
barrier was not uniform.
REFERENCE: Sherman, M., Herrick, R.B., Ross, E. and Chang, M.T.Y.
Toxicol. Appl. Pharm. 11: 49-67, 1967.
OBSERVED NEUROTOXIC EFFECTS: Ataxia, paralysis, convulsions.
ANIMALS: Rats, Wistar, F, 150-170 g
ANIMALS: Cockerels, Single Comb White Leghorn, 10-12 d old
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.035 mg/kg
PREPARATION AND DOSE • - .
or HISTORY OF PATIENT: (1) Acute: LD5Q 11.6 mg/kg
(2) Subacute: 50-800 ppm in diet, 20 chicks/grp, for 2 wk
ROUTE AND SITE: I.M.
CONTROL INFORMATION: None
ROUTE AND SITE: Oral
CONTROL INFORMATION: Untreated control grps
DURATION OF EXPERIMENT: 1-30 min
EXAM. TYPE: Biochemistry
DURATION OF EXPERIMENT: 1-3 wk
EXAM. TYPE: Behavior, mortality
813
814
-------
COMPOUND:
Phosphonotrithiolc acid, methyl-, S-propyl-S-diethy1.
-------
COMPOUND:
Phosphoramldic acid, methyl-4-tert-butyl-2-chlorophenyl methyl-ester
000299865
REFERENCE: Khan, M.A.
Res. Vet. Sci. 15: 180-185, 1973.
OBSERVED NEUROTOXIC EFFECTS: The animals exhibited dullness, ataxia and muscular
fasciculation, with recovery in 72 hr (1 case 1 wk).
The signs were related to inhibition of whole-blood
cholinesterases.
COMPOUND: Phosphoramidothioic acid, isopropyl-,0-2,4-dichlorophenyl 0-methyl ester
000299854
REFERENCE: Sherman, M., Ross, E. and Chang, M.T.Y.
Tox. Appl. Pharm. 6:147-153, 1964.
OBSERVED NEUROTOXIC EFFECTS:
-------
COMPOUND: Phosphoric acid, aluminum salt
COMPOUND: Phosphoric acid, bis(2-ethylhexyl) o-tolyl ester
REFERENCE: Seil, F.J., Lampert, P.W. and Klatzo, I.
J. Neuropath. Exp. Neurol. 28: 74-85, 1969.
OBSERVED NEUROTOXIC EFFECTS: Induced neurofibrillary spheroids filled the cytoplasm
of the cells exposed to aluminum phosphate, and the
nuclei were displaced. The spheroids were compared
with those induced by vincristine sulfate. The author
claimed the former were like those of postencephalitic
parkinsonism and the latter like those of Alzheimer's
disease.
REFERENCE: Hine, C.H., Dunlap, M.K., Rice, E.G., Coursey, M.M., Gross, R.M.
and Anderson, H.H.
J. Pharm. Exp. Ther. 116:227, 1956.
OBSERVED NEUROTOXIC EFFECTS: No paralysis reported.
ANIMALS: In vitro cultures of spinal cord and dorsal root ganglia from fetal
NZ White rabbits.
ANIMALS: * Chickens, White Leghorn, M, 0.75-1.3 kg
PREPARATION AND DOSE
or HISTORY OF PATIENT:
1:100 suspension every 4 d after 20-22 d in vitro:
time of exposure 6-11 d in each cycle of 20 d
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) 0.5 gm/kg
(2) 1.0 gm/kg
ROUTE AND SITE: In vitro
CONTROL INFORMATION: Untreated cultures
ROUTE AND SITE: (i) s.C. (2) Oral
CONTROL INFORMATION: one group of 5 per experimental group.
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Light and electron microscopy
DURATION OF EXPERIMENT: 14-36 d after treatment. .
EXAM. TYPE: Behavior, histology
819
820
-------
COMPOUND: Phosphoric acid, bis(p-ethylphenyl) ester
COMPOUND: Phosphoric acid, bis(4-ethylphenyl) 2-propylphenyl ester
REFERENCE: Bondy, H.F., Field, E.J., Worden, A.N. and Hughes, J.P.W.
Brit. J. Indust. Med. 17: 190-200, 1960.
REFERENCE: Aldridge, W.N. and Barnes, J.M.
Biochem. Pharm. 6: 177-188, 1961.
OBSERVED NEUROTOXIC EFFECTS: (D All birds were severely paralyzed.
(2) All birds developed ataxia within 12 days.
(3) All birds developed ataxia within 10 days.
OBSERVED NEUROTOXIC EFFECTS: Neurotoxicity independent of cholinesterase inhibition
in vivo; the latter was found and attributed to some
metabolite (unidentified). Little structure-activity
relationship seen between triaryl phosphates. Most
common sign of toxicity was ataxia.
ANIMALS: (D 12 Chickens
(2) 3 Chickens
(3) 3 Chickens
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) 1,000 mg/kg
(2) 500 mg/kg
(3) 100 mg/kg
ANIMALS: Chickens, F, aged over 4 mo, usually 6-12 mo, various breeds
PREPARATION AND DOSE
or HISTORY OF PATIENT: 50-5000 mg/kg
ROUTE AND SITE: Gavage
CONTROL INFORMATION: Controls mentioned but not described
ROUTE AND SITE: Oral
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: Up to 1 yr
EXAM. TYPE: Behavior, histology
DURATION OF EXPERIMENT: 24 hr to 21 d
EXAM. TYPE: Behavior
821
822
-------
COMPOUND: Phosphoric acid, bis(2-ethylphenyl) p-tolyl ester
COMPOUND: Phosphoric acid, bis(o-propylphenyl) p-tolyl ester
REFERENCE: Aldridge, W.N. and Barnes, J.M.
Biochem. Pharm. 6: 177-188, 1961.
REFERENCE: Bondy, H.F., Field, E.J., Worden, A.N. and Hughes, J.P.W.
Brit. J. Tndust. Med. 17: 190-200, 1960.
OBSERVED NEUROTOXIC EFFECTS: Neurotoxicity independent of cholinesterase inhibition
i in vivo; the latter was found and attributed to some
! metabolite (unidentified). Little structure-activity
relationship seen between triaryl phosphates. Most
common sign of toxicity was ataxia.
OBSERVED NEUROTOXIC EFFECTS: All birds developed ataxia within 10 days.
ANIMALS: Chickens, F, aged over 4 mo, usually 6-12 mo, various breeds
ANIMALS: 6 Chickens
PREPARATION AND DOSE
or HISTORY OF PATIENT: 50-5000 mg/kg
PREPARATION AND DOSE
or HISTORY OF PATIENT: 500 mg/kg
ROUTE AND SITE: Oral
CONTROL INFORMATION: ns
ROUTE AND SITE: Gavage
CONTROL INFORMATION: Controls mentioned but not described
DURATION OF EXPERIMENT: 24 hr to 21 d
EXAM. TYPE: Behavior
DURATION OF EXPERIMENT: Up to 1 yr
EXAM. TYPE: Behavior, histology
823
824
-------
COMPOUND: Phosphoric acid, bis (3,5-xylyl) 2-ethylphenyl ester
COMPOUND: Phosphoric acid, 2-chloro-l-(2,4-dibromophenyl) vinyl dimethyl ester
REFERENCE: Aldridge, W.N. and Barnes, J.M.
Biochem. Pharm. 6: 177-188, 1961.
OBSERVED NEUROTOXIC EFFECTS: Neurotoxicity independent of cholinesterase inhibition
in vivo; the latter was found and attributed to some
metabolite (unidentified). Little structure-activity
relationship seen between triaryl phosphates. Most
common sign of toxicity was ataxia.
REFERENCE:
Morallo, B.D. and Sherman, M.
J. Econ. Entomol. 60:509-515, 1967.
OBSERVED NEUROTOXIC EFFECTS:
The order of resistance to the insecticide was:
fleshfly > house fly > anthomyiid fly > blow fly.
This insecticide caused 50% mortality in the
anthomyiid fly within one hour, but was much slower
with the other species. It caused a low level of
inhibition of cholinesterase in house flies, but
caused high levels in the other species, with maximum
inhibition occurring within 30 minutes. Recovery
was not very complete in anthomyiid flies and flesh
flies.
ANIMALS: Chickens, F, aged over 4 mo, usually 6-12 mo, various breeds
PREPARATION AND DOSE
or HISTORY OF PATIENT: 50-5000 mg/kg
ROUTE AND SITE: Oral
CONTROL INFORMATION: ns
ANIMALS: Housefly, Musca domestica, adult F, 3-4 d old
Anthomyiid fly, Fannia pusio, adult F, 3-4 d old
Blowfly, Chrysoma megacephala, adult F, 3-4 d old
Flesh fly, parasarcophaga argyrostoma, adult F, 3-4 d old
PREPARATION AND DOSE
or HISTORY OF PATIENT: In vitro: The LD50 (0.26-21.6 mcg/g), 10-20 flies/
group or dose-level, each test replicated
3 or more times.
In vivo: 10 groups of 50 each of houseflies and
anthomyiid flies, and 10 groups of 20 each
of blowflies and flesh flies.
ROUTE AND SITE: Applied topically, venter of thorax.
CONTROL INFORMATION:
Untreated fly heads
DURATION OF EXPERIMENT: 24 hr to 21 d
EXAM. TYPE: Behavior
DURATION OF EXPERIMENT: Serial to 24 hr.
EXAM. TYPE: Biochemistry, mortality
825
826
-------
COMPOUND: Phosphoric acid, 2-chloro-l-(2,4-dichlorophenyl) vinyl diethyl ester
00047096
REFERENCE: Sherman, M., Herrick, R.B., Ross, E. and Chang, M.T.Y.
Toxicol. Appl. Pharm. 11: 49-67, 1967.
OBSERVED NEUROTOXIC EFFECTS: Ataxia, paralysis, convulsions.
ANIMALS: Cockerels, Single Comb White Leghorn, 10-12 d old
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) Acute: LD 29.1 mg/kg
(2) Subacute:5050-800 ppm in diet, 20 chicks/grp, for 2 wk
ROUTE AND SITE: oral
CONTROL INFORMATION: Untreated control grps
DURATION OF EXPERIMENT: 1-3 wk
EXAM. TYPE: Behavior, mortality
827
COMPOUND: Phosphoric acid, 2-chloro-l-(2,4-dichlorophenyl) vinyl dimethyl ester
002274671
REFERENCE:
Morallo, B.D. and Sherman, M.
J. Econ. Entomol. 60:509-515, 1967.
OBSERVED NEUROTOXIC EFFECTS:
The order of resistance to the insecticide was
flesh fly >house fly >anthomyiid fly >blow fly. This
insecticide is a relatively rapid toxicant, with
50% mortality occurring within one hour. 100%
inhibition of cholinesterase occurred in the flesh
fly within 5 minutes. Inhibition was higher and
recovery less complete in dead flies than in living
flies.
ANIMALS: Housefly, Muaca domestica, adult F, 3-4 d old
Anthomyiid fly, Fannia pusio, adult F, 3-4 d old
Blowfly, Chrysoma mcgacephala, adult F, 3-4 d old
Flesh fly, parasarcophaga argyrostoma, adult F, 3-4 d old
PREPARATION AND DOSE
or HISTORY OF PATIENT: In vitro: The LD50 (0.26-21.6 mcg/g), 10-20 flies/
group or dose-level, each test replicated
3 or more times.
In vivo: 10 groups of 50 each of houseflies and
anthornylid flies, and 10 groups of 20 each
of blowflies and flesh flies.
ROUTE AND SITE: Applied topically, venter of thorax.
CONTROL INFORMATION:
Untreated fly heads
DURATION OF EXPERIMENT: Serial to 24 hr.
EXAM. TYPE: Biochemistry, mortality
828
-------
COMPOUND: Phosphoric acid, 2-chloro-l-(2,5-dichlorophenyl) vinyl dimethyl ester
COMPOUND:
Phosphoric acid, 2-chloroethyl 2,2-dichlorovinyl methyl ester
REFERENCE:
Morallo, B.D. and Sherman, M.
J. Econ. Entomol. 60:509-515, 1967.
REFERENCE:
Aldridge, W.N. and Barnes, J.M.
Biochemical Pharm. 15:541-548, 1966.
OBSERVED NEUROTOXIC EFFECTS:
The order of resistance to the insecticide was:
flesh fly > house fly > anthomyiid fly > blow fly.
This toxicant caused 50% mortality in all flies
within 2 hours. Within 5 minutes, 90% inhibition
of cholinesterase occurred in both house flies and
flesh flies. Anthomyiid flies took 2 hours to reach
maximum inhibition (49%). The recovery of the flesh
fly was very slow with 50% inhibition after 24 hours.
OBSERVED NEUROTOXIC EFFECTS: Weakened limbs. Histological changes in the
spinal cord and sciatic nerves. Inhibition of
CNS esterase.
ANIMALS: Housefly, Musca domestica, adult F, 3-4 d old
Anthomyiid fly, Fannia pusio, adult F, 3-4 d old
Blowfly, Chrysoma megacephala, adult F, 3-4 d old
Flesh fly, parasareophaga argyrostoma, adult F, 3-4 d old
PREPARATION AND DOSE
or HISTORY OF PATIENT: In vitro: The LD50 (0.26-21.6 mcg/g), 10-20 flies/
group or dose-level, each test replicated
3 or more times.
In vivo: 10 groups of 50 each of houseflies and
anthomyiid flies, and 10 groups of 20 each
of blowflies and flesh flies.
ROUTE AND SITE: Applied topically, venter of thorax.
CONTROL INFORMATION:
ANIMALS:
Hens, grps of 2-4, RIR x Light Sussex, 2-3 kg
Untreated fly heads
PREPARATION AND DOSE '
or HISTORY OF PATIENT: Mostly 1 dose, amount varied by compound
ROUTE AND SITE: Oral, s.c., or i.p.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: Serial to 24 hr.
EXAM. TYPE: Biochemistry, mortality
DURATION OF EXPERIMENT: 14-21 d
EXAM. TYPE: Biochemistry, histology
829
830
-------
COMPOUND: Phosphoric acid, 2-chloroethyl 2-dichlorovinyl methyl ester
COMPOUND:
Phosphoric acid, 2-chloroethyl ethyl p-nitrophenyl ester
REFERENCE: Sherman, M., Ross, E. and Chang, M.T.Y.
Tox. Appl. Pharm. 6:147-153, 1964.
REFERENCE:
Aldridge, W.N. and Barnes, J.M.
Biochemical Pharm. 15:541-548, 1966.
OBSERVED NEUROTOXIC EFFECTS: (1) Convulsions and death within 18 hrs. Survivors
were lethargic for 6-19 hrs. post treatment.
(2) 50% Cholinesterase inhibited by doses of >800 ppm
OBSERVED NEUROTOXIC EFFECTS: Weakened limbs. Histologlcal changes in the
spinal cord and sciatic nerves. Inhibition of
CNS esterase.
ANIMALS: Cockerels, White Leghorn, single-comb, 10-50/grp, 12 d old
ANIMALS:
Hens, grps of 2-4, RIR x Light Sussex, 2-3 kg
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) Acute: LD (37.8 mg/kg) as gelatin capsule.
(2) Subacute: 50-800 ppm in feed.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Mostly 1 dose, amount varied by compound
ROUTE AND SITE: Oral
CONTROL INFORMATION: Untreated diet.
ROUTE AND SITE: oral, s.c., or i.p.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: 1 wk
EXAM. TYPE: Mortality, behavior, blood ChE
DURATION OF EXPERIMENT: 14-21 d
EXAM. TYPE: Biochemistry, histology
831
832
-------
COMPOUND:
Phosphoric acid, o-chlorophenyl diphenyl ester
REFERENCE: Hine, C.H., Dunlap, M.K., Rice, E.G., Coursey, M.M., Gross, R.M.
and Anderson, H.H.
J. Pharm. Exp. Ther. 116:227, 1956.
OBSERVED NEUROTOXIC EFFECTS: NO paralysis.
COMPOUND: Phosphoric acid, l-((p-chlorophenyl)thio) vinyl dimethyl ester
002595531
REFERENCE: Sherman, M., Herrick, R.B., Ross, E. and Chang, M.T.Y.
Toxicol. Appl. Pharm. 11: 49-67, 1967.
OBSERVED NEUROTOXIC EFFECTS: Ataxia, paralysis, convulsions.
ANIMALS: 4 Chickens, White Leghorn, M, 0.75-1.3 kg
ANIMALS: Cockerels, Single Comb White Leghorn, 10-12 d old
PREPARATION AND DOSE
or HISTORY OF PATIENT: (i) o.5 gm/kg
(2) 1.0 gm/kg
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) Acute: LD 51.3 mg/kg
(2) Subacute: 50-800 ppm in diet, 20 chicks/grp, for 2 wk
ROUTE AND SITE: (1) S.C. (2) Oral
CONTROL INFORMATION: One group of 5 per experimental group.
ROUTE AND SITE: Oral
CONTROL INFORMATION: Untreated control grps
DURATION OF EXPERIMENT: 14-36 d after treatment.
EXAM. TYPE: Behavior, histology
DURATION OF EXPERIMENT: 1-3 wk
EXAM. TYPE: Behavior, mortality
833
834
-------
COMPOUND:
Phosphoric acid, 2-chloro-l-(2,4,5-trichloro-phenyl)vinyl dimethyl ester
000961115
COMPOUND: Phosphoric acid, o-cresyl diphenyl ester
REFERENCE: Sherman, M., Herrick, R.B., Ross, E. and Chang, M.T.Y.
Toxicol. Appl. Pharm. 11: 49-67, 1967.
REFERENCE: Johnson, M.K. and Barnes, J.M.
Biochem. Pharm. 19:3045-3047, 1970.
OBSERVED NEUROTOXIC EFFECTS: Ataxia, paralysis, convulsions.
OBSERVED NEUROTOXIC EFFECTS:
Toxic to adult hens at 0.1 rag/kg. Repeated doses
produced ataxia and "characteristic" lesions in
cord and peripheral nerves.
ANIMALS: Cockerels, Single Comb White Leghorn, 10-12 d old
ANIMALS: Chickens, various breeds, sex not stated.
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) Acute: LD,. 2528 mg/kg
(2) Subacute: 50-800 ppm in diet, 20 chicks/grp, for 2 wk
PREPARATION AND DOSE
or HISTORY OF PATIENT:
0.5 ml/kg, then 0.1 ml/kg up to 6 doses.
ROUTE AND SITE: Oral
CONTROL INFORMATION: Untreated control grps
ROUTE AND SITE: Oral
CONTROL INFORMATION: Mentioned, not described
DURATION OF EXPERIMENT: 1-3 wk
EXAM. TYPE: Behavior, mortality
DURATION OF EXPERIMENT: Up to 63 d
EXAM. TYPE: Behavior, then histology. Also, in vitro bioassay.
835
836
-------
COMPOUND:
Phosphoric acid, cyclic methylene-o-phenylene o-tolyl ester
REFERENCE: Baron, R.L. and Casida, J.E.
Biochem. Pharm. 11: 1129-1136, 1962.
OBSERVED NEUROTOXIC EFFECTS: Ataxic doses inhibited selectively nerve esterases
hydrolyzing butyryl esters of choline, glycerol and
phenols. TOCP more persistent than metabolite.
Oxidation of succinate^ pyruvate, a-ketoglutarate
by nerve and brain preparations was not affected.
ANIMALS: Chickens, White Leghorn, 1-2 y, 1.5-2.5 kg
PREPARATION AND DOSE
or HISTORY OF PATIENT: 20mg/kg
ROUTE AND SITE: TOCP: gavage; DFP and metabolite: I.P.
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Biochemistry
837
COMPOUND: Phosphoric acid, cyclic methylene-o-phenylene tolyl ester
REFERENCE: Baron, R.L.,-Bennett, D.R. and Casida, J.E.
Br. 3. Pharmacol. 18:465-474, 1962.
OBSERVED NEUROTOXIC EFFECTS: clinical and neurological comparison was made
between this compound and tri-ortho-cresyl phosphate.
Ataxia was present with both, higher doses increased
the degree of peripheral neuropathy. Demyelination
of the spinal cord occurred at doses below those
effecting peripheral nerve degeneration. Axon
and myelin damage was prominent with both agents.
ANIMALS: 24 Chickens, White Leghorn, aged 12-18 mo, av 2 kg.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
8-400 mg/kg in corn oil, single dose.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Histology
838
-------
COMPOUND:
Phosphoric acid, cyclic methylene-o-phenylene o-tolyl ester
COMPOUND: Phosphoric acid, l,2-dibromo-2,2-dichloroethyl dimethyl ester
000300765
REFERENCE: Taylor, J.D.
Tox. Appl. Pharmac. 11:538-545, 1967.
OBSERVED NEUROTOXIC EFFECTS:
(1) Paralysis as from TOCP in 21 d. (2) Doses over
75 mg/kg to adults produced ataxia and an abnormal
reflex; no effect on kittens. Axonal degeneration
in cord, as from TOCP, found in cats.
REFERENCE: Rayner, M.D., Popper, J.S., Carvalho, E.W. and Hurov, R.
Res. Comm. Chem. Path. Pharm. 4: 595-606, 1972.
OBSERVED NEUROTOXIC EFFECTS: The force generated by the achllles tendon reflex was
subnormal in exposed subjects. The authors suggest
that this hyporeflexia may be a sensitive indicator of
chronic exposure to organophosphates.
ANIMALS: (1) One White Leghorn chicken
(2) 18 Cats, adult M, random-bred, castrated, and 8 kittens
ANIMALS: Humans, Japanese ancestry, M, ages 22-59 (orchid farmers)
PREPARATION AND DOSE
or HISTORY OF PATIENT:
(1) 10 mg/kg, one dose.
(2) 15-200 mg/kg, one dose.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Exposure of more than 4 hr/d, 2 d/wk, 52 wk/yr for 5 yr except
one case (2 yr). Other types of pesticide also used, but
authors judged organophosphates exposures to be primary.
ROUTE AND SITE:(l)ns.
CONTROL INFORMATION:
(2) I.M. in shoulder
(1) One control chicken
(2) 4 of the 8 kittens.
ROUTE AND SITE: Skin contact, inhalation
CONTROL INFORMATION: Matched non-exposed subjects, so far as could be ascertained
DURATION OF EXPERIMENT: Up to 190 d.
EXAM. TYPE: Behavior, histology
DURATION OF EXPERIMENT: ns
EXAM. TYPE: . Physiological
839
840
-------
COMPOUND:
Phosphoric acid, di(2-chloroethyl) 2,2-dichlorovlnyl ester
REFERENCE:
Aldridge, W.N. and Barnes, J.M.
Biochemical Pharm. 15:541-548, 1966.
OBSERVED NEUROTOXIC EFFECTS: Weakened limbs. Histological changes in the
spinal cord and sciatic nerves. Inhibition of
CNS esterase.
ANIMALS: Hens, grps of 2-4, RIR x Light Sussex, 2-3 kg
PREPARATION AND DOSE
or HISTORY OF PATIENT: Mostly 1 dose, amount varied by compound
ROUTE AND SITE: oral, B.C., or i.p.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: 14-21 d
EXAM. TYPE: Biochemistry, histology
841
COMPOUND:
Phosphoric acid, di(2-chloroethyl) p-nitrophenyl ester
REFERENCE:
Aldridge, W.N. and Barnes, J.M.
Biochemical Pharm. 15:541-548, 1966.
OBSERVED NEUROTOXIC EFFECTS: Weakened limbs. Histological changes in the
spinal cord and sciatic nerves. Inhibition of
CNS esterase.
ANIMALS:
Hens, grps of 2-4 RIR x Light Sussex, 2-3 kg
PREPARATION AND DOSE
or HISTORY OF PATIENT: Mostly 1 dose, amount varied by compound
ROUTE AND SITE: Oral, s.c., or i.p.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: 14-21 d
EXAM. TYPE: Biochemistry, histology
842
-------
COMPOUND: Phosphoric acid, di(2-chloroethyl) 2,3,5-trichlorophenyl ester
REFERENCE:
Aldridge, W.N. and Barnes, J.M.
Biochemical Pharm. 15:541-548, 1966.
OBSERVED NEUROTOXIC EFFECTS: Weakened limbs. Histological changes in the
spinal cord and sciatic nerves. Inhibition
of CNS esterase.
ANIMALS:
Hens, grps of 2-4, RIR x Light Sussex, 2-3 kg
PREPARATION AND DOSE
or HISTORY OF PATIENT: Mostly 1 dose, amount varied by compound
ROUTE AND SITE: oral, s.c., or i.p.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: 14-21 d
EXAM. TYPE: Biochemistry, histology
843
COMPOUND: Phosphoric acid, di-o-chlorophenyl phenyl ester
REFERENCE: Hine, C.H., Dunlap, M.K., Rice, E.G., Coursey, M.M., Gross, R.M.
and Anderson, H.H.
J. Pharm. Exp. Ther. 116:227, 1956.
OBSERVED NEUROTOXIC EFFECTS: No paralysis.
ANIMALS: 4 Chickens, White Leghorn, M, 0.75-1.3 kg
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) 0.5 gin/kg
(2) 1.0 gm/kg
ROUTE AND SITE: (i) s.C. (2) Oral
CONTROL INFORMATION: One group of 5 per experimental group.
DURATION OF EXPERIMENT:14-36 d after treatment.
EXAM. TYPE: Behavior, histology
844
-------
COMPOUND: Phosphoric acid, 2-2-dichlorovinyl dimethyl ester
000062737
REFERENCE: Aldridge, W.N. and Barnes, J.M.
Biochemical Pharm. 15:541-548, 1966.
COMPOUND: Phosphoric acid, diethyl p-nitrophenyl ester
000311455
REFERENCE: Murphy, S.D., Lauwerys, R.R. and Cheever, K.L.
Tox. Appl. Pharm. 12: 22-35, 1968.
OBSERVED NEUROTOXIC EFFECTS: Weakened limbs. Histological changes in the
spinal cord and sciatic nerves. Inhibition of
CNS esterase.
OBSERVED NEUROTOXIC EFFECTS: Inhibits brain cholinesterase.
Sensitivities: birds> mammals > fish.
ANIMALS: Hens, grps of 2-4, RIR x Light Sussex, 2-3 kg
PREPARATION AND DOSE
or HISTORY OF PATIENT: Mostly 1 dose, amount varied by compound
In vitro brains of rats,
guinea pigs, sparrows, small-
mouth bass, flounder, sculpin
and monkey.
ANIMALS- Mlce> Swiss-Webster, M, 25-30g
Chickens, White Rock X N.H. Red, M, 5BO-700g
Sunfish, M and F, 40-80g
Bullfish, M and F, 40-80g
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.1-1500 mg/kg, various schedules (I.P.) in mice, chickens,
sunfish and bullheads; 0.1-200 mg/kg (orally) in sunfish;
0.001-4 picomoles of malaoxon in vitro.
ROUTE AND SITE: oral, B.C.. or i.p.
CONTROL INFORMATION: ns.
ROUTE AND SITE: See above
CONTROL INFORMATION: Brain cholinesterase determined in controls
DURATION OF EXPERIMENT: u_2i a
EXAM. TYPE: Biochemistry, histology
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Biochemistry
845
846
-------
COMPOUND: Phosphoric acid, di(o-ethylphenyl) p-tolyl ester
COMPOUND: Phosphoric acid, diethyl o-tolyl ester
REFERENCE: Bondy, H.F., Field, E.J., Worden, A.N. and Hughes, J.P.W.
Brit. J. Indust. Med. 17: 190-200, 1960.
OBSERVED NEUROTOXIC EFFECTS: Three out of four birds became paralyzed.
REFERENCE: Hine, C.H., Dunlap, M.K., Rice, E.G., Coursey, M.M., Gross, R.M.
and Anderson, H.H.
J. Pharm. Exp. Ther. 116:227, 1956.
OBSERVED NEUROTOXIC EFFECTS: No paralysis
ANIMALS: 4 Chickens
ANIMALS:
It Chickens, White Leghorn, M, 0.75-1.3 kg
PREPARATION AND DOSE
or HISTORY OF PATIENT: 5 x 500 mg/kg
PREPARATION AND DOSE
or HISTORY OF PATIENT:
(1) 0.5 gm/kg.
(2) 1.0 gm/kg.
ROUTE AND SITE: Gavage
CONTROL INFORMATION: Controls mentioned but not described
ROUTE AND SITE: (1) S.C. (2) Oral
CONTROL INFORMATION: One group of 5 per experimental group.
DURATION OF EXPERIMENT: Up to 1 yr
EXAM. TYPE: Behavior, histology
DURATION OF EXPERIMENT: 14-36 d after treatment.
EXAM. TYPE: Behavior, histology
847
848
-------
COMPOUND: Phosphoric acid, dimethyl (l-(dimethylphosphonyl)vinyl) ester
REFERENCE: Sherman, M., Ross, E. and Chang, M.T.Y.
Tox. Appl. Pharm. 6:147-153, 1964.
OBSERVED NEUROTOXIC EFFECTS: (i) Convulsions and death within 18 hrs.
Survivors were lethargic for 6-19 hrs. post
treatment.
(2) 50% Cholinesterase inhibited by doses of 45 ppm.
COMPOUND: Phosphoric acid, dimethyl ester, ester with (E)-3hydroxy-N-methyl
crotonamide
000919448
REFERENCE: Sherman, M., Herrick, R.B., Ross, E. and Chang, M.T.Y.
Toxicol. Appl. Pharm. 11: 49-67, 1967.
OBSERVED NEUROTOXIC EFFECTS: Ataxia, paralysis, convulsions.
ANIMALS: Cockerels, White Leghorn, single-comb, 10-50/grp, 12 d old
ANIMALS: Cockerels, Single Comb White Leghorn, 10-12 d old
PREPARATION AND DOSE
or HISTORY OF PATIENT: (i) Acute: LD (43.9 rag/kg) as gelatin capsule.
(2) Subacute: 50-800 ppm in feed.
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) Acute: LD5_ 3.54 mg/kg
(2) Subacute: 50-800 ppm in diet, 20 chicks/grp, for 3 wk
ROUTE AND SITE: Oral
CONTROL INFORMATION: Untreated diet.
ROUTE AND SITE: Oral
CONTROL INFORMATION: Untreated control grps
DURATION OF EXPERIMENT: 1 wk
EXAM. TYPE: Mortality, behavior, blood ChE
DURATION OF EXPERIMENT: 1-3 wk
EXAM. TYPE: Behavior, mortality
849
850
-------
COMPOUND: Phosphoric acid, diphenyl o-tolyl ester
COMPOUND: Phosphoric acid, diphenyl o-tolyl ester
REFERENCE:
Aldridge, W.N. and Barnes, J.M.
Biochemical Pharm. 15:541-548, 1966.
OBSERVED NEUROTOXIC EFFECTS: Weakened limbs. Histological changes in the
spinal cord and sciatic nerves. Inhibition
of CNS esterase.
REFERENCE: Hine, C.H., Dunlap, M.K., Rice, E.G., Coursey, M.M., Gross, R.M.
and Anderson, H.H.
J. Pharm. Exp. Ther. 116:227, 1956.
OBSERVED NEUROTOXIC EFFECTS: All had paralysis.
ANIMALS:
Hens, grps of 2-4, RIR x Light Sussex, 2-3 kg
ANIMALS: 4 Chickens, White Leghorn, M, 0.75-1.3 kg
PREPARATION AND DOSE
or HISTORY OF PATIENT: Mostly 1 dose, amount varied by compound
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) 0.5 gin/kg.
(2) 1.0 gm/kg.
ROUTE AND SITE: Oral, s.c., or i.p.
CONTROL INFORMATION: ns.
ROUTE AND SITE: (1) S.C. (2) Oral
CONTROL INFORMATION: One group of 5 per experimental group.
DURATION OF EXPERIMENT: 14-21 d
EXAM. TYPE: Biochemistry, histology
DURATION OF EXPERIMENT: 14-36 d after treatment.
EXAM. TYPE: Behavior, histology
851
852
-------
COMPOUND: Phosphoric acid, di-o-tolyl ester
COMPOUND: Phosphoric acid, di-p-tolyl 2-ethylphenyl ester
REFERENCE: Hine, C.H., Dunlap, M.K., Rice. E.G., Coursey, M.M., Gross, R.M.
and Anderson, H.H.
J. Pharm. Exp. Ther. 116:227, 1956.
OBSERVED NEUROTOXIC EFFECTS: No paralysis.
REFERENCE: Aldridge, W.N. and Barnes, J.M.
Biochem. Pharm. 6: 177-188, 1961.
OBSERVED NEUROTOXIC EFFECTS: Neurotoxicity independent of cholinesterase inhibition
in vivo; the latter was found and attributed to some
metabolite (unidentified). Little structure-activity
relationship seen between triaryl phosphates. Most
common sign of toxicity was ataxia.
ANIMALS:
4 Chickens, White Leghorn, M, 0.75-1.3
ANIMALS: 'Chickens, F, aged over A mo, usually 6-12 mo, various breeds
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) 1.0 gm/kg
(2) 2.5 gm/kg in 5 aliquots over 10 d period.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 50-5000 mg/kg
ROUTE AND SITE: (1) Oral
CONTROL INFORMATION: One group of 5 per experimental group.
ROUTE AND SITE: Oral
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: 14-36 d after treatment.
EXAM. TYPE: Behavior, histology
DURATION OF EXPERIMENT: 24 hr to 21 d
EXAM. TYPE: Behavior
853
854
-------
COMPOUND: Phosphoric acid, di-p-tolyl o-ethylphenyl ester
COMPOUND: Phosphoric acid, di-o-tolyl m-tolyl ester
REFERENCE: Bondy, H.F., Field, E.J., Worden, A.M. and Hughes, J.P.W.
Brit. J. Indust. Med. 17: 190-200, 1960.
REFERENCE: Aldridge, W.N. and Barnes, J.M.
Biochem. Pharm. 6: 177-188, 1961.
OBSERVED NEUROTOXIC EFFECTS: All chickens were .paralyzed.
OBSERVED NEUROTOXIC EFFECTS: Neurotoxicity independent of cholinesterase inhibition
in vivo; the latter was found and attributed to some
metabolite (unidentified). Little structure-activity
relationship seen between triaryl phosphates. Most
common sign of toxicity was ataxia.
ANIMALS: (l) 5 Chickens
(2) 3 Chickens
ANIMALS: Chickens, F, aged over 4 mo, usually 6-12 mo, various breeds
PREPARATION AND DOSE
or HISTORY OF PATIENT:
-------
COMPOUND: Phosphoric acid, di-p-tolyl o-tolyl ester
COMPOUND: Phosphoric acid, di-o-tolyl p-tolyl ester
REFERENCE: Aldridge, W.N. and Barnes, J.M.
Biochem. Pharm. 6: 177-188, 1961.
OBSERVED NEUROTOXIC EFFECTS: Neurotoxicity independent of cholinesterase inhibition
I in vivo; the latter was found and attributed to some
metabolite (unidentified). Little structure-activity
relationship seen between triaryl phosphates. Most
common sign of toxicity was ataxia.
REFERENCE: Hine, C.H., Dunlap, M.K., Rice, E.G., Coursey, M.M., Gross, R.M.
and Anderson, H.H.
J. Pharm. Exp. Ther. 116:227, 1956.
OBSERVED NEUROTOXIC EFFECTS: Paralysis seen in all groups.
ANIMALS: Chickens, F, aged over 4 mo, usually 6-12 mo, various breeds
ANIMALS:
22 Chickens, White Leghorn, M, 0.75-1.3 kg
PREPARATION AND DOSE
or HISTORY OF PATIENT: 5075000 mg/kg
ROUTE AND SITE: Oral
CONTROL INFORMATION: ns
PREPARATION AND DOSE (1) 0.4 gm/kg
or HISTORY OF PATIENT: (2) 0.2 gm/kg
(3) 0.1 gm/kg
(4) 0.05 gm/kg
(5) 0.025 gm/kg
(6) 2.5 gm/kg in 5 aliquots over 10 d period.
ROUTE AND SITE: Oral
CONTRfll INFORMATION: One group of 5 per experimental group.
DURATION OF EXPERIMENT: 24 hr to 21 d
EXAM. TYPE: Behavior
DURATION OF EXPERIMENT: 14-36 d after treatment.
EXAM. TYPE: Behavior, histology
857
858
-------
COMPOUND: Phosphoric acid, di-p-tolyl o-tolyl ester
COMPOUND: Phosphoric acid, di(3,5-xylyl) o-tolyl ester
REFERENCE: Hine, C.H., Dunlap, M.K., Rice, E.G., Coursey, M.M., Gross, R.M.
and Anderson, H.H.
J. Pharm. Exp. Ther. 116:227, 1956.
OBSERVED NEUROTOXIC EFFECTS: (1, 2 and 5) All had paralysis, (3) 1 had paralysis
(A) None had paralysis.
REFERENCE: Aldridge, W.N. and Barnes, J.M.
Biochem. Pharm. 6: 177-188, 1961.
OBSERVED NEUROTOXIC EFFECTS: Neurotoxicity independent of cholinesterase inhibition
in vivo; the latter was found and attributed to some
metabolite (unidentified). Little structure-activity
relationship seen between triaryl phosphates. Most
common sign of toxicity was ataxia.
ANIMALS: 18 Chickens, White Leghorn, M, 0.75-1.3 kg
ANIMALS: Chickens, F, aged over 4 mo, usually 6-12 mo, various breeds
PREPARATION AND DOSE
or HISTORY OF PATIENT:
(1) 0.2 gin/kg
(2) 0.1 gm/kg
(3) 0.05 gm/kg
(4) 0.025 gm/kg
(5) 2.5 gm/kg in 5 aliquots over 10 d period.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 50-5000 mg/kg
ROUTE AND SITE: Oral
CONTROL INFORMATION: One group of 5 per experimental group.
ROUTE AND SITE: Oral
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: 14-36 d after treatment.
EXAM. TYPE: Behavior, histology
DURATION OF EXPERIMENT: 24 hr to 21 d
EXAM. TYPE: Behavior
859
860
-------
COMPOUND:
Phosphoric acid, o-hydroxyphenyl phenyl ester
REFERENCE:
Aldridge, W.N. and Barnes, J.M.
Biochemical Pharm. 15:541-548, 1966.
OBSERVED NEUROTOXIC EFFECTS: Weakened limbs. Histological changes in the
spinal cord and sciatic nerves. Inhibition of
CNS esterase.
ANIMALS:
Hens, grps of 2-4, RIR x Light Sussex, 2-3 kg
PREPARATION AND DOSE
or HISTORY OF PATIENT: Mostly 1 dose, amount varied by compound
ROUTE AND SITE: Oral, s.c., or i.p.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: 14-21 d
EXAM. TYPE: Biochemistry, histology
861
COMPOUND: Phosphoric acid, tolyl ester
REFERENCE: Smith, H.V. and Spalding, J.M.K,
Lancet 2: 1019-21, 1959.
OBSERVED NEUROTOXIC EFFECTS: Distal weakness and paresthesias. No deaths
reported, most patients were expected to recover.
ANIMALS: Humans, more than 2,000 cases.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Exposure via "olive oil" used in food preparation.
Later exam, of sample showed oil to contain 3% mixed
cresyl phosphates, mainly meta and para compounds.
ROUTE AND SITE: Oral
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: Weeks
EXAM. TYPE: Behavior
862
-------
COMPOUND: phosphoric acid, o-tolyl ester
COMPOUND: Phosphoric acid, triaryl ester
REFERENCE: Vora, D.D., Dastur, D.K., Braganca, B.M., Parihar, L.M., Iyer, C.G.S.,
Fodekar, R.B. and Prabhakaran, K.
J. Neurol. Neurosurg. Psychiat. 25: 234-242, 1962.
OBSERVED NEUROTOXIC EFFECTS: Glove-and-stocking type sensory impairment, distal
muscle paralysis with characteristic gait; degeneration
of intramuscular and intradermal nerve twigs, increased
plasma cholinesterase.
REFERENCE: Siegel, J., Rudolph, H.S., Getzkin, A.J. and Jones, R.A.
Tox. Appl. Pharm. 7: 543-549, 1965.
OBSERVED NEUROTOXIC EFFECTS: Neurotoxic signs in chickens over 23 mg/m , in rabbits
at 102 mg/m , but none in rats, dogs or monkeys at
levels tested.
ANIMALS: Human: 32 of 58 reported cases in Bombay in 1960.
PREPARATION AND DOSE
or HISTORY OF PATIENT: History noncontributory. Later investigation showed that
oil from some sources was contaminated with 0.65-32.5 mg
OCP/100 g oil or with 2-12% of mineral oil containing OCP.
ANIMALS: 53 hens, White Vantress, 6 mo, 2-2 1/2 kg 21 squirrel monkeys, 0.5-1 kg
50 rats, Long-Evans, 200-250 g
31 rabbits, NZ White, 3-4 kg
18 dogs, beagle, 6-10 kg
PREPARATION AND DOSE
or HISTORY OF PATIENT: ,
(1) 1.8-110 mg/m of air, 24 hr/d, 36-163 d
(2) 25 and 50 mg/m of air, 8 hr/d, 5 d/wk, total 30 exposures.
ROUTE AND SITE: Oral or skin contact (oil used for massaging body).
CONTROL INFORMATION: Epidemiological data
ROUTE AND SITE: Inhalation
CONTROL INFORMATION: 24 chickens, 30 rabbits, 10 monkeys
DURATION OF EXPERIMENT: Admissions over a 5-mo period
EXAM. TYPE: Clinical, lab, and histology of biopsy specimens.
DURATION OF EXPERIMENT: Up to 1 yr after exposures
EXAM. TYPE: Behavior, autopsy (gross and histological)
863
864
-------
COMPOUND: Phosphoric acid, tri(o-biphenylyl) ester
REFERENCE: Hine, C.H., Dunlap, M.K., Rice, E.G., Coursey, M.M., Gross, R.M.
and Anderson, H.H.
J. Pharm. Exp. Ther. 116:227, 1956.
OBSERVED NEUROTOXIC EFFECTS: No paralysis.
COMPOUND: Phosphoric acid, tributyl ester
000126738
REFERENCE: Chambers, H.W. and Casida, J.E.
Tox. Appl. Pharm. 10:105-118, 1967.
OBSERVED NEUROTOXIC EFFECTS:
Ataxia, paralysis; protection interpreted in terms
of structure-activity relationships.
ANIMALS: 4 Chickens, White Leghorn, M, 0.75-1.3 kg
ANIMALS:
Mice, Swiss albino, M, 14-17 g.
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) 0.5 gm/kg
(2) 1.0
PREPARATION AND DOSE
or HISTORY OF PATIENT:
850-1000 mg/kg
Study tested 21 nicotinic acid analogs for protection
against neurotoxicity of compound.
ROUTE AND SITE: (1) S.C. (2) Oral
CONTROL INFORMATION: One group of 5 per experimental group.
ROUTE AND SITE: Mice: I.P.
CONTROL INFORMATION: Various parameters
DURATION OF EXPERIMENT: 14-36 d after treatment.
EXAM. TYPE: Behavior, histology
DURATION OF EXPERIMENT: Up to 10 d
EXAM. TYPE: Clinical, biochemistry
865
866
-------
COMPOUND:
Phosphoric acid, triethyl ester
COMPOUND:
Phosphoric acid, tri-p-ethylphenyl ester
REFERENCE: Gumbmann, M.R., Gagne, W.E. and Williams, S.N.
Tox. Appl. Pharm. 12:360-371, 1968.
OBSERVED NEUROTOXIC EFFECTS:
Adverse effects on growth (at 5%) and reproduction
(at 1%), minimal changes in blood or brain
cholinesterase (10% grp was excluded for anorexia),
no brain changes reported.
REFERENCE: Aldridge, W.N. and Barnes, J.M.
Biochem. Pharm. 6: 177-188, 1961.
OBSERVED NEUROTOXIC EFFECTS: Neurotoxicity independent of cholinesterase inhibition
i in vivo; the latter was found and attributed to some
metabolite (unidentified). Little structure-activity
relationship seen between triaryl phosphates. Most
common sign of toxicity .was ataxia.
ANIMALS:
S-D, 5 M and 5 F/grp, initially 71-79 g, and their litters
ANIMALS: Chickens, F, aged over A mo, usually 6-12 mo, various breeds
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.1-10% in diet.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 50-5000 mg/kg
ROUTE AND SITE: oral
CONTROL INFORMATION: ns.
ROUTE AND SITE: Oral
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: Original M killed at 120 d, F at 150 d.
EXAM. TYPE: Behavior, biochemistry, necropsy
DURATION OF EXPERIMENT: 24 hr to 21 d
EXAM. TYPE: Behavior
867
868
-------
COMPOUND: Phosphoric acid, tri-p-ethylphenyl ester
COMPOUND: Phosphoric acid, tri-4-ethyl nhenyl ester
REFERENCE: Bondy, H.F., Field, E.J., Worden, A.M. and Hughes, J.P.W.
Brit. J. Indust. Med. 17: 190-200, 1960.
REFERENCE: Cavanagh, J.B., Davies, D.R., Holland, P. and Lancaster, M.
Porton Tech. Paper #760, 1961.
OBSERVED NEUROTOXIC EFFECTS: Birds paralyzed with significant demyelination.
OBSERVED NEUROTOXIC EFFECTS:
Threshold dose was "about" 150 mg/kg; between 150
and 500 mg/kg, signs were delayed till 20-30
d and preceded by typical "high stepping gait,"
followed by ataxla. Sciatic nerves always
damaged severely, but ventral cord little. Relative
absence of anticholinesterase.
ANIMALS: 30 chickens
ANIMALS:
Hens, White Leghorn, ages 1-2 yr.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 200 mg/kg - 5 x 500 mg/kg
ROUTE AND SITE: Gavage
CONTROL INFORMATION: Controls mentioned but not described
PREPARATION AND DOSE
or HISTORY OF PATIENT:
ROUTE AND SITE: I.M.
Triparethylphenylphosphate, TOCP, or diisopropyl-
fluoridate at: (1) 150-750 mg/kg, (2) 30-400 mg/kg,
(3) 0.3-1 mg/kg. (With Triparaethylphenylphosphate
500-1000 mg/kg ataxia and paralysis occur after 10-20
d and signs and results resemble those of TOCF and
diisopropylfluoridate; aim of present study was to
find threshold dose).
breast muscle; oral
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: Up to 1 yr
EXAM. TYPE: Behavior, histology
DURATION OF EXPERIMENT: 1 mo.
EXAM. TYPE: Behavior, histology
869
870
-------
COMPOUND: Phosphoric acid, tri-o-ethylphenyl ester
REFERENCE: Hine, C.H., Dunlap, M.K., Rice, E.G., Coursey, M.M., Gross, R.M.
and Anderson, H.H.
J. Pharm. Exp. Ther 116:227, 1956.
OBSERVED NEUROTOXIC EFFECTS: No paralysis.
ANIMALS:
4 Chickens, White Leghorn, M, 0.75-1.3 kg
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) 1.0 gm/kg
(2) 2.5 gm/kg
ROUTE AND SITE: (1) S.C. (2) Oral
CONTROL INFORMATION: One group of 5 per experimental group.
DURATION OF EXPERIMENT: u-36 d after treatment.
EXAM. TYPE: Behavior, histology
871
COMPOUND: Phosphoric acid, triphenyl ester
000115866
REFERENCE: Hine, C.H., Dunlap, M.K., Rice, E.G., Coursey, M.M., Gross, R.M.
and Anderson, H.H.
J. Pharm. Exp. Ther. 116:227, 1956.
OBSERVED NEUROTOXIC EFFECTS: No paralysis.
ANIMALS: 4 Chickens, White Leghorn, M, 0.75-1.3 kg
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) 0.5 gm/kg
(2) 1.0 gm/kg
ROUTE AND SITE: (1) s.C. (2) Oral
CONTROL INFORMATION: One group of 5 per experimental group.
DURATION OF EXPERIMENT: 14-36 d after treatment.
EXAM. TYPE: Behavior, histology
872
-------
COMPOUND: Phosphoric acid, tritolyl ester
001330785
REFERENCE: Ahmed, M.M.
Acta Neuropath. 17:302-309, 1971.
COMPOUND: Phosphoric acid, tritolyl ester
001330785
REFERENCE: Ahmed, M.M., and Glees, P.
Acta Neuropath. 19:94-98, 1971.
OBSERVED NEUROTOXIC EFFECTS: Anterior horn of spinal cord examined. Synaptic
vesicles and mitochondria of pre-synaptic bag were
degenerated.
OBSERVED NEUROTOXIC EFFECTS: Ataxia and motor paralysis of hindlimbs. Large
number of chromatolytic neurones in the lumbar segments of the spinal cord.
Axonal degeneration in the long tracts and peripheral nerves.
ANIMALS: 7 Hens, adult
ANIMALS: 4 Slow loris, adults, 218-360 g.
PREPARATION AND DOSE
Or HISTORY OF PATIENT: 0.5 ml painted on comb, one dose, to 4 hens.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.2 ml/kg/d for 10 d to 3 animals.
ROUTE AND SITE: Topical, comb
CONTROL INFORMATION: 3 hens untreated.
ROUTE AND SITE: Topical, back of neck
CONTROL INFORMATION: One untreated animal.
DURATION OF EXPERIMENT: 3 wk
EXAM. TYPE: Histology
DURATION OF EXPERIMENT: 11 wk.
EXAM. TYPE: Behavior; histology
873
874
-------
COMPOUND: Phosphoric acid, tritolyl ester
001330785
REFERENCE: Bondy, H.F., Field, E.J., Worden, A.N. and Hughes, J.P.W.
Brit. J. Indust. Med. 17: 190-200, 1960C
OBSERVED NEUROTOXIC EFFECTS: (D Birds became ataxic. (2) Five birds became para-
lyzed, histological examination of one showed demyelin-
ation. (3) and (4) No adverse effects seen.
COMPOUND: Phosphoric acid, tri-m-tolyl ester
REFERENCE: Hine, C.H., Dunlap, M.K., Rice, E.G., Coursey, M.M., Gross, R.M.
and Anderson, H.H.
J. Pharm. Exp. Ther. 116:227, 1956.
OBSERVED NEUROTOXIC EFFECTS: No paralysis reported.
ANIMALS:
(1) 2 Chickens
(2) 6 Chickens
(3) 1 Chicken
(4) 3 Chickens
ANIMALS: g Chickens, White Leghorn, M, 0.75-1.3 kg
PREPARATION AND DOSE Ester contained only: m-cresol, p-cresol, 2:4 and 2:5 di-
or HISTORY OF PATIENT: methylphenol.
(1) 250 mg/kg, daily for 2 d
(2) 500 mg/kg, two daily doses
(3) 2,500 mg/kg single dose of tri-m-tolyl phosphate
(4) As above, except tri-p-tolyl phosphate
ROUTE AND SITE: Gavage
CONTROL INFORMATION: Controls mentioned but not described
PREPARATION AND DOSE
or HISTORY OF PATIENT: (i) 5.0 gin/kg
(2) 1.0 gm/kg
(3) 5.0 gm/kg in 5 aliquots over 10 d period.
ROUTE AND SITE: Oral
CONTROL INFORMATION: One group of 5 per experimental group.
DURATION OF EXPERIMENT: "P to 1 yr
EXAM. TYPE: Behavior, histology
DURATION OF EXPERIMENT: 14-36 d after treatment.
EXAM. TYPE: Behavior, histology
875
876
-------
COMPOUND: Phosphoric acid, tri-o-tolyl ester
REFERENCE: Aldridge, W.N. and Barnes, J.M.
Biochem. Pharm. 6: 177-188, 1961.
COMPOUND: Phosphoric acid, tri-o-tolyl ester
000078308
REFERENCE:
Baron, R.L., Bennett, D.R. and Casida, J.E.
Br. J. Pharmacol. 18:465-474, 1962.
OBSERVED NEUROTOXIC EFFECTS: Neurotoxicity independent of cholinesterase inhibition
in vivo; the latter was found and attributed to some
metabolite (unidentified). Little structure-activity
relationship seen between triaryl phosphates. Most
common sign of toxicity was ataxia.
OBSERVED NEUROTOXIC EFFECTS: Clinical and neurological comparison was made
between this compound and its major cyclic phosphate
metabolite. Ataxia was present with both, higher
doses increased the degree of peripheral neuropathy.
Axon and myelin damage was prominent with both agents.
ANIMALS: Chickens, F, aged over 4 mo, usually 6-12 mo, various breeds
ANIMALS: 14 Chickens, White Leghorn, aged 12-18 mo., av. 2 kg.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 50-5000 mg/kg
PREPARATION AND DOSE
or HISTORY OF PATIENT:
1 ml/kg, one dose.
ROUTE AND SITE: Oral
CONTROL INFORMATION: ns
ROUTE AND SITE: oral
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: 24 hr to 21 d
EXAM. TYPE: Behavior
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Histology
877
878
-------
COMPOUND: Phosphoric acid, tri-o-tolyl ester (TOCP)
000078308
REFERENCE: Baron, R.L. and Casida, J.E.
Biochem. Pharm. 11: 1129-1136, 1962.
OBSERVED NEUROTOXIC EFFECTS: Ataxic doses inhibited selectively nerve esterases
hydrolyzing butyryl esters of choline, glycerol and
phenols. TOCP more persistent than metabolite.
Oxidation of succinate, pyruvate, a-ketoglutarate
by nerve and brain preparations was not affected.
ANIMALS: Chickens, White Leghorn, 1-2 y, 1.5-2.5 kg
PREPARATION AND DOSE
or HISTORY OF PATIENT: TOCP 1 ml/kg
ROUTE AND SITE: TOCP: gavage; DFP and metabolite: I.P.
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Biochemistry
879
COMPOUND: Phosphoric acid, tri-o-tolyl ester
000078308
REFERENCE: Beresford, W.A. and Glees, P.
Acta Neuropath. 3: 108-118, 1963.
OBSERVED NEUROTOXIC EFFECTS: Paralysis; fiber degeneration in central nervous
system (in cats only the cord was studied). Start: 9-14 d (hens),
3-4 wk (cats). Both ascending and descending degeneration is reported.
ANIMALS: 10 Hens, adult; 4 cats.
PREPARATION AND DOSE
Or HISTORY OF PATIENT: Hens: 0.2 ml/kg to 9 hens, 0.1 ml/kg to 1 hen, one dose.
Cats: 0.1 or 0.2 ml/d.
ROUTE AND SITE: Hens: Oral; Cats: Top. sk, neck
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: Serial sacr: hens 9-23d, cats 3-4 wk
EXAM. TYPE: Behavior, histology
880
-------
COMPOUND:
Phosphoric acid, tri-o-tolyl ester
COMPOUND: Phosphoric acid, tri-o-tolyl ester
000078308
REFERENCE: Berry, J.F. and Cevallos, W.H.
J. Neurochem. 13: 117-124, 1966.
OBSERVED NEUROTOXIC EFFECTS:
Treatment produced demyelination with the following
changes in lipid classes: increases in cholesterol
esters, mono-or diglycerides, and lecithin; decrease
in cerebrosides. Changes in fatty acid compositions
of lipid classes were as follows: decrease of 15:0
and increase of 18:1 in cholesterol esters; increase of
16:0 in sphingomyelin; decrease of 22:0, 24:0, and 24:1
in cerebrosides; and decrease of 18:0 in phosphotidyl-
serine.
REFERENCE: Bischoff, A.
Acta Neuropath. 9:158-174, 1967.
OBSERVED NEUROTOXIC EFFECTS: Weakness on standing appeared by 10-14 d, then
paralysis of extensors and toes, progressed 4-6d then ceased. Axoplasm
of sciatic nerves with moderate damage to myelin: neurolfilaments and
endoplasmic reticulum distorted. Unmyelinated nerves also affected.
Severity of the disease is the same on all levels of the peripheral nerves.
There is an evident proportional correlation between the severity of
morphological alterations and severity of clinical symptoms.
ANIMALS: Chickens, not further described
Chicken nerves from NMRI, Bethesda
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Aerosols, not measured.
ANIMALS: 24 Chickens, Leghorn and sexlinked cross Rhode Island Red/Barred
Plymouth Rock, aged 6 and 12 wk.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.5-1 mg/kg.
ROUTE AND SITE: Inhalation
CONTROL INFORMATION: Untreated
ROUTE AND SITE: Oral
CONTROL INFORMATION: Age-matched untreated controls.
DURATION OF EXPERIMENT: Onset of paralysis, usually 2 wk
EXAM. TYPE: Biochemistry
DURATION OF EXPERIMENT: Sacr 1-20 d after first appearance of neuropathology
EXAM. TYPE: Behavior, histology
881
882
-------
COMPOUND: Phosphoric acid, tri-o-tolyl ester
000078308
REFERENCE: Bischoff, A.
Acta Neuropath. 15:142-155, 1970.
OBSERVED NEUROTOXIC EFFECTS: Slight but definite paralysis of distal leg
muscles. Diseased axons in the white matter of spinal cord: proliferation
of endoplasmic reticulum and disintegration of neurofilaments. Severe
structural alterations in the boutons terminaux in grey substance of the
anterior horn; swelling of axosomatic synapses.
ANIMALS: 16 chickens, Leghorn and sexlinked cross Rhode Island Red/Barred
Plymouth Rock, aged 8 wk.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.5-1 ml/kg.
ROUTE AND SITE: Oral
CONTROL INFORMATION: Breed-matched untreated controls.
DURATION OF EXPERIMENT: Sacr d 1, 6 and 14 after first neurological signs.
EXAM. TYPE: Behavior, histology
883
COMPOUND: Phosphoric acid, tri-o-tolyl ester
000078308
REFERENCE: Cavanagh, J.B
J. Path. Bact. 87: 365-383, 1964
OBSERVED NEUROTOXIC EFFECTS: Ataxia, abnormal gait and Wallerian degeneration in
peripheral nerves. Axonal and Myelin sheath frag-
mentation. Distal degeneration of sensory nerve
endings.
ANIMALS: Cats: young F and castrated M of known parentage.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.01-0.75 mg/kg as oil
ROUTE AND SITE: s.C., flank
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: Maximum 17 wk
EXAM. TYPE: Behavior, histology .
884
-------
COMPOUND: Phosphoric acid, tri-o-tolyl ester
000078308
REFERENCE: Cavanagh, J.B. and Patangia, G.N.
Brain 88: 165-181, 1965
OBSERVED NEUROTOXIC EFFECTS: Weakness and ataxia in hind limbs. "Dying back"
process in long pathway nerve fibers. Degeneration in long ascending and
descending spinal tracts. Axonal degeneration with swelling, increased
argyrophilia, eosinophilic change and fragmentation. Degeneration in
spino cerebellar tract above C.7 spinal level.
COMPOUND: Phosphoric acid, tri-o-tolyl ester
000078308
REFERENCE: Chambers, H.W. and Casida, J.E.
Tox. Appl. Pharm. 10:105-118, 1967.
OBSERVED NEUROTOXIC EFFECTS:
Ataxia, paralysis; protection interpreted in terms
of structure-activity relationships.
ANIMALS: Cats: young F and castrated M of known parentage.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.01-0.75 mg/kg as oil
ROUTE AND SITE: S.C., flank
CONTROL INFORMATION: ns.
ANIMALS: Adult hens, 1.5-2.5 kg.
Mice, Swiss albino, M, 14-17 g.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Hens: 0.5 ml/kg
Mice: 50 mcl/mouse
Study tested 21 nicotinic acid analogs for protection
against neurotoxicity of compounds.
ROUTE AND SITE: Hens: gavage. Mice: I.P.
CONTROL INFORMATION: Various parameters
DURATION OF EXPERIMENT: Maximum 17 wk
EXAM. TYPE: Behavior, histology
DURATION OF EXPERIMENT: Up to 10 d
EXAM. TYPE: Clinical, biochemistry
885
886
-------
COMPOUND: Phosphoric acid, tri-o-tolyl ester
REFERENCE: Glees, P. and Janzik, H.
Progr. Brain Res. 14:97-121, 1965.
OBSERVED NEUROTOXIC EFFECTS: Flaccid paralysis and death (LD study). Ascending
and descending nerve fiber degeneration especially
in the reticulo-cerebellar systems.
COMPOUND: Phosphoric acid, tri-o-tolyl ester
000078308
REFERENCE: Glees, P. and White, W.G.
J. Neurol. Neurosurg. Psychiat. 24: 271-274, 1961.
OBSERVED NEUROTOXIC EFFECTS: Characteristic paralysis of leg extensors with 0.1
ml/kg. Selected cord degeneration of myelin and
axons; even one dose of 0.05 ml/kg caused some degen-
eration in anterior medial tract; no peripheral nervous
system (leg) degeneration seen, at these dosages.
ANIMALS: chicks (not fully described)
ANIMALS: 40 mature hens and cocks, 3-5 kg
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.1-0.2 ml/kg
PREPARATION AND DOSE
or HISTORY OF PATIENT: Up to (1) 0.2 ml/bird, one or more doses at day-intervals
(2) 0.1-0.3 ml/kg orally
ROUTE AND SITE: Topical (comb)
CONTROL INFORMATION: ns.
ROUTE AND SITE: (1) Painted on comb, (2) oral.
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: Follow-up for 5.5 mo.
EXAM. TYPE: Behavior, histology
DURATION OF EXPERIMENT: About 2 mo.
EXAM. TYPE: Behavior, histology
887
888
-------
COMPOUND:
Phosphoric acid, tri-o-tolyl ester
REFERENCE: Hine, C.H., Dunlap, M.K., Rice, E.G., Coursey, M.M., Gross, R.M.
and Anderson, H.H.
J. Pharm. Exp. Ther. 116:227, 1956.
OBSERVED NEUROTOXIC EFFECTS:
Paralysis seen in all groups.
COMPOUND: Phosphoric acid, tri-o-tolyl ester
000078308
REFERENCE: Illis, L., Patangia, G.N. and Cavanagh, J.B.
Exp. Neurol. 14:160-174, 1966.
OBSERVED NEUROTOXIC EFFECTS:
Changes in boutons termlnaux corresponded with
onset of ataxia, more pronounced in lumbar than
in cervical cord segments. Changes occurred mainly
in intermediate greymatter. Preterminal degeneration
started 5 d after onset of ataxia.
ANIMALS:
22 Chickens, White Leghorn, M, 0.75-1.3 kg
ANIMALS: 6 cats, M & F, 1.5-3.5 kg
PREPARATION AND DOSE
or HISTORY OF PATIENT:
ROUTE AND SITE: Oral
CONTROL INFORMATION:
(1) 0.4 gm/kg, 0.8
(2) 0.2 gm/kg
(3) 0.1 gm/kg
(4) 0.05 gm/kg
(5) 0.025 gm/kg
(6) 2.5 gm/kg in 5 aliquots over 10 d period
One group of 5 per experimental group.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
0.1-0.25 mg/kg
ROUTE AND SITE: S.C.
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: 14-36 d after treatment.
EXAM. TYPE: Behavior, histology
DURATION OF EXPERIMENT: 8-327 d
EXAM. TYPE: Histology
889
890
-------
COMPOUND: Phosphoric acid, tri-o-tolyl ester
000078308
REFERENCE: LeVay, S., Meier, C. and Glees, P.
Acta Neuropath. 17:103-113, 1971.
COMPOUND: Phosphoric acid, tri-o-tolyl ester
000078308
REFERENCE: prlneas, J.
J. Neuropath. Exp. Neurol. 28(4):571-597, 1969.
OBSERVED NEUROTOXIC EFFECTS: Neurological symptoms appeared after 8 d.
After 6 d about 25% of the large myelinated fibers of peripheral nerves
contained an abnormal system of membranous tubules and vacuoles; degeneration
progressed. Membranous proliferation was followed 4-9 d later by massive
changes in the spinal ganglia; by a hypertrophy of the endoplasmic reticulum
in some cells and of neurofilaments in others.
OBSERVED NEUROTOXIC EFFECTS: Progressive weakness, impaired tail response,
ataxia, Electronmicroscopical peripheral nervous system changes preceded
behavior or photomicroscopical changes, in motor nerve terminals; small
myelinated fibers of spinal gray matter also affected. Then neuromuscular
junctions and anterior horns showed changes in endoplasmic reticulum.
Demyelination starting distally always along with other degenerative
changes. Described as dying-back polyneuropathy.
ANIMALS: . 9 Hens, White Leghorn, Adult.
ANIMALS: 13 Cats, M and F, young and old, 2.25-5.75 kg
PREPARATION AND DOSE
or HISTORY OF PATIENT: 6 Hens given 2 ml/kg.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.5-3.0 ml/kg, TOCP 99% pure (impurities were mixed
esters of phenol and orthocresol).
ROUTE AND SITE: oral
CONTROL INFORMATION: 3 untreated
ROUTE AND SITE: s.C., left thigh
CONTROL INFORMATION: 4 cats, treatment n.
DURATION OF EXPERIMENT: Serial sacr 6-16 d
EXAM. TYPE: Behavior, histology
DURATION OF EXPERIMENT: 42 d
EXAM. TYPE: Behavior, histology
891
892
-------
COMPOUND: Phosphoric acid, tri-o-tolyl ester
000078308
REFERENCE: Taylor, J.D.
Can. J. Physiol. Pharm. 43: 715-721, 1965.
OBSERVED NEUROTOXIC EFFECTS: Demyelination, verified histologically, was found in
cervical and caudal cord sections to involve increases
of phospholipid content and of the phosphatidylethanol-
amine fraction of phospholipids (proportion of other
fractions unaltered). The increase was shown to involve
synthesis.
COMPOUND: Phosphoric acid, tri-o-tolyl ester
000078308
REFERENCE:
Vij, S. and Kanagasuntheram, R.
Acta Neuropath. 20:150-159, 1972.
OBSERVED NEUROTOXIC EFFECTS: Unsteady movements. Most notable finding in
afferent nerve endings dealt, with cholinesterase activity: reduction of
specific activity, almost complete absence of non-specific activity. Degen-
eration of taste bud cells, and degenerative changes in the sensory nerve
terminations.
ANIMALS:
Cats, adult M
ANIMALS: Slow loris, 2 adult, one "very young"
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.4 ml/kg in peanut oil
Slices of spinal cord from treated cats in incubation system
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.25 ml applied every 4th day for 12 applications
(1 adult, 1 young). Other adult given 0.25 ml oral, one dose.
ROUTE AND SITE: I.M., left forelimb
CONTROL INFORMATION: None
ROUTE AND SITE: Topical, back of neck; oral.
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: Average 8 d plus in vitro studies
EXAM. TYPE: Biochemistry
DURATION OF EXPERIMENT: Maximum survival 50 d.
EXAM. TYPE: Behavior, histology, histochemistry
893
894
-------
COMPOUND: Phosphoric acid, tri-p-tolyl ester
COMPOUND: Phosphoric acid, trixylyl ester
REFERENCE: Hine, C.H., Dunlap, M.K., Rice, E.G., Coursey, M.M., Gross, R.M.
and Anderson, H.H.
J. Pharm. Exp. Ther. 116:227, 1956.
OBSERVED NEUROTOXIC EFFECTS: No paralysis.
REFERENCE: Bondy, H.F., Field, E.J., Worden, A.N. and Hughes, J.P.W.
Brit. J. Indust. Med. 17: 190-200, 1960.
OBSERVED NEUROTOXIC EFFECTS: Four of twelve birds developed ataxia.
ANIMALS: 6 Chickens, White Leghorn, M, 0.75-1.3 kg
ANIMALS: 12 Chickens
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) 5.0 gm/kg
(2) 1.0 gm/kg
(3) 5.0 gm/kg given in 5 aliquots over 10 d period.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 5 x 500 mg/kg
ROUTE AND SITE: Per os.
CONTROL INFORMATION: One group of 5 per experimental group.
ROUTE AND SITE: Gavage
CONTROL INFORMATION: Controls mentioned but not described.
DURATION OF EXPERIMENT: 14-36 d after treatment.
EXAM. TYPE: Behavior, histology
DURATION OF EXPERIMENT: Up to 1 yr
EXAM. TYPE: Behavior, histology
895
896
-------
COMPOUND: Phosphoric acid, tri-2,4-xylyl ester
REFERENCE: Hine, C.H., Dunlap, M.K., Rice, E.G., Coursey, M.M., Gross, R.M.
and Anderson, H.H.
J. Pharm. Exp. Ther. 116:227, 1956.
OBSERVED NEUROTOXIC EFFECTS: No paralysis
ANIMALS:
4 Chickens, White Leghorn, M, 0.75-1.3 kg
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) 1.0 gm/kg
(2) 2.5 gm/kg
ROUTE AND SITE: (1) s.C. (2) Oral
CONTROL INFORMATION: One group of 5 per experimental group.
DURATION OF EXPERIMENT: 14-36 d after treatment.
EXAM. TYPE: Behavior, histology
897
COMPOUND: Phosphoric acid, tri-2,5-xylyl ester
REFERENCE: Hine, C.H., Dunlap, M.K., Rice, E.G., Coursey, M.M., Gross, R.M.
and Anderson, H.H.
J. Pharm. Exp. Ther. 116:227, 1956.
OBSERVED NEUROTOXIC EFFECTS: No paralysis.
ANIMALS: 4 Chickens, White Leghorn, M, 0.75-1.3 kg
PREPARATION AND DOSE
or HISTORY OF PATIENT: (D 1.0 gm/kg
(2) 2.5 gm/kg
ROUTE AND SITE: (1) S.C. (2) Oral
CONTROL INFORMATION: One group of 5 per experimental group.
DURATION OF EXPERIMENT: 14-36 d after treatment.
EXAM. TYPE: Behavior, histology
898
-------
COMPOUND: Phosphoric acid, tri-2,6-xylyl ester
REFERENCE: Hine, C.H., Dunlap, M.K., Rice, E.G., Coursey, M.M., Gross, R.M.
and Anderson, H.H.
J. Pharm. Exp. Ther. 116:227, 1956.
OBSERVED NEUROTOXIC EFFECTS: No paralysis.
ANIMALS: 4 Chickens, White Leghorn, M, 0.75-1.3 kg
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) 1.0 gm/kg
(2) 2.5 gm/kg
ROUTE AND SITE: (1) S.C. (2) Oral
CONTROL INFORMATION: One group of 5 per experimental group.
DURATION OF EXPERIMENT: 14-36 d after treatment.
EXAM. TYPE: Behavior, histology
899
COMPOUND: Phosphoric acid, tri-3,5-xylyl ester
REFERENCE: Hine, C.H., Dunlap, M.K., Rice, E.G., Coursey, M.M., Gross, R.M.
and Anderson, H.H.
J. Pharm. Exp. Ther 116:227, 1956.
OBSERVED NEUROTOXIC EFFECTS: No paralysis.
ANIMALS: 4 Chickens, White Leghorn, M, 0.75-1.3 kg
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) 0.5 gm/kg
(2) 1.0 gm/kg
ROUTE AND SITE: (1) S.C. (2) Oral
CONTROL INFORMATION: One group of 5 per experimental group.
DURATION OF EXPERIMENT: 14-36 d after treatment.
EXAM. TYPE: Behavior, histology
900
-------
COMPOUND: Phosphorochloridic acid, di-o-toly] ester
COMPOUND: Phosphorochloridous acid, bis(3,5-xylyl)ester
REFERENCE: Hine, CH., Dunlap, M.K., Rice, E.G., Coursey, M.M., Gross, R.M.
and Anderson, H.H.
J. Pharm. Exp. Ther. 116:227, 1956.
OBSERVED NEUROTOXIC EFFECTS: No paralysis.
REFERENCE: Hine, C.H., Dunlap, M.K., Rice, E.G., Coursey, M.M., Gross, R.M.
and Anderson, H.H.
J. Pharm. Exp. Ther. 116:227, 1956.
OBSERVED NEUROTOXIC EFFECTS: Anticholinesterase effects studied in vivo
and in vitro. No cholinesterase inhibition in
fowl plasma, however compound was active against the
enzymes of human plasma.
ANIMALS: 8 Chickens, White Leghorn, M, 0.75-1.3 kg
ANIMALS: (i) 5 Cockerels (2) Human erythrocytes and plasma
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) 0.5 gm/kg
(2) 1.0 gm/kg
(3) 2.5 gm/kg in 5 a'liquots over 10 d period.
PREPARATION AND DOSE
or HISTORY OF PATIENT: (i) i gm/kg.
(2) Laboratory method, no details.
ROUTE AND SITE: Oral
CONTROL INFORMATION: One group of 5 per experimental group.
ROUTE AND SITE: (i) oral (2) In vitro
CONTROL INFORMATION: (1) 5 untreated birds
DURATION OF EXPERIMENT: 14-36 d after treatment.
EXAM. TYPE: Behavior, histology
DURATION OF EXPERIMENT:, (i) 24 hr.
EXAM. TYPE: Biochemical
901
902
-------
COMPOUND: Phosphorodlamidic fluoride, N,N'-dlbutyl-
COMPOUND: Phosphorodichloridic acid, o-tolyl ester
REFERENCE: Johnson, M.K. and Barnes, J.M.
Biochem. Pharm. 19:3045-3047, 1970.
OBSERVED NEUROTOXIC EFFECTS:
4 or 5 doses (0.2 mg/kg) produced marginal response.
6 doses resulted in frequent collapse and inability
to stand. Regression occurred rapidly in chicks,
slowly in adults. Severely ataxic chicks had
characteristic lesions in both peripheral nerve
and spinal cord.
REFERENCE: Hine, C.H., Dunlap, M.K., Rice, E.G., Coursey, M.M., Gross, R.M.
and Anderson, H.H.
J. Pharm. Exp. Ther. 116:227, 1956.
OBSERVED NEUROTOXIC EFFECTS:
All died.
ANIMALS: Chickens, various breeds, sex not stated.
ANIMALS: 22 Chickens, White Leghorn, M, 0.75-1.3 kg
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Vehicle: 10% ethanol, various.schedules, premedication with
atropine or eserine.
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) 0.5 gm/kg.
(2) 1.0 gm/kg.
ROUTE AND SITE: s.C.
CONTROL INFORMATION: Mentioned, not described
ROUTE AND SITE: (1) S.C. (2) Oral
CONTROL INFORMATION: One group of 5 per experimental group.
DURATION OF EXPERIMENT: Up to 63 d.
EXAM. TYPE: Behavior, then histology. Also, in vitro bioassay.
DURATION OF EXPERIMENT: 14-36 d after treatment.
EXAM. TYPE: Behavior, histology
903
904
-------
COMPOUND:
Phosphorodithioic acid, S.S'-benzylidene bis-O.O-dimethyl
REFERENCE: Sherman, M., Herrick, R.B., Ross, E. and Chang, M.T.Y.
Toxicol. Appl. Pharm. 11: 49-67, 1967.
OBSERVED NEUROTOXIC EFFECTS: Ataxia, paralysis, convulsions.
COMPOUND: Phosphorodithioic acid, S,S'-benzylidene 0,0,0',0'-tetramethyl ester
002732709
REFERENCE: Gaines, T.B.
Tox. Appl. Pharm. 14: 515-534, 1969.
OBSERVED NEUROTOXIC EFFECTS: 300 mg/kg produced leg weakness
ANIMALS: Cockerels, Single Comb White Leghorn, 10-12 d old
ANIMALS: Chickens, White Leghorn, F
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) Acute: LD5Q 5096 mg/kg
(2) Subacute: 50-800 ppm in diet, 20 chicks/grp, for 2 wk
PREPARATION AND DOSE
or HISTORY OF PATIENT: 15 mg/kg atropine sulfate orally 15 min prior to compound;
graded doses compound in peanut oil
ROUTE AND SITE: Oral
CONTROL INFORMATION: Untreated control grps
ROUTE AND SITE: S.C., under right wing
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: 1-3 wk
EXAM. TYPE: Behavior, mortality
DURATION OF EXPERIMENT: 1 yr
EXAM. TYPE: Clinical
905
906
-------
COMPOUND:
Phorphorodithioic acid, bis(4-chlorophenyl)methyl-0,0-diethyl
REFERENCE: Sherman, H., Herrlck, R.B., Ross, E. and Chang, M.T.Y.
Toxicol. Appl. Pharm. 11: 49-67, 1967.
OBSERVED NEUROTOXIC EFFECTS: Ataxia, paralysis, convulsions.
Acute: Chicks appeared normal until 6 days post treatment,
then leg paralysis lasting up to 5 days. The highest
dosage levels given resulted in only 30% mortality.
Significant growth depression even at levels lower than
the LD,
'50'
COMPOUND: phosphorodithioic acid, S-(p-chlorophenyl)thio methyl 0,0-diethyl ester
000786196
REFERENCE: Gaines, T.B.
Tox. Appl. Pharm. 14: 515-534, 1969.
OBSERVED NEUROTOXIC EFFECTS: 640 rag/kg produced leg weakness
ANIMALS: Cockerels, Single Comb White Leghorn, 10-12 d old
ANIMALS: Chickens, White Leghorn, F
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) Acute: LD5Q > 3000 mg/kg
(2) Subacute: 50-800 ppm in diet, 20 chicks/grp, for 2 wk
PREPARATION AND DOSE
or HISTORY OF PATIENT: 15 mg/kg atropine sulfate orally 15 min prior to compound;
graded doses compound in peanut oil
ROUTE AND SITE: Oral
CONTROL INFORMATION: Untreated control grps
ROUTE AND SITE: S.C., under right wing
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: 1-3 wk
EXAM. TYPE: Behavior, mortality
DURATION OF EXPERIMENT: 1 yr
EXAM. TYPE: Clinical
907
908
-------
COMPOUND: Phosphorodithioic acid, S-(((p-chlorophenyl)thio) methyl) O.cf-diethyl ester
000786196
REFERENCE: Sherman, M., Herrick, R.B., Ross, E. and Chang, M.T.Y.
Toxicol. Appl. Phann. 11: 49-67, 1967.
OBSERVED NEUROTOXIC EFFECTS: Ataxia, paralysis, convulsions.
COMPOUND: Phosphorodithioic acid, S-(((p-chlorophenyl)thio)methyl) 0,0-dimethyl ester
000953173
REFERENCE: Gaines, T.B.
Tox. Appl. Pharm. 14: 515-534, 1969.
OBSERVED NEUROTOXIC EFFECTS: 800 rag/kg produced leg weakness
ANIMALS: Cockerels, Single Comb White Leghorn, 10-12 d old
ANIMALS: Chickens, White Leghorn, F
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) Acute: LD Q 57.2 mg/kg
(2) Subacute: 50-800 ppm in diet, 20 chicks/grp, for 2 wk
PREPARATION AND DOSE
or HISTORY OF PATIENT: 15 mg/kg atropine sulfate orally 15 min prior to compound;
graded doses compound in peanut oil
ROUTE AND SITE: Oral
CONTROL INFORMATION: Untreated control grps
ROUTE AND SITE: S.C., under right wing
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: 1-3 wk
EXAM. TYPE: Behavior, mortality
DURATION OF EXPERIMENT: 1 yr
EXAM. TYPE: Clinical
909
910
-------
COMPOUND: Phosphorodithioic acid, S(((p-chlorophenyl)thio)methyl)0,0-dimethyl ester
000953173
REFERENCE: Sherman, H., Ross, E. and Chang, M.T.Y.
Tox. Appl. Pharm. 6:147-153, 1964.
OBSERVED NEUROTOXIC EFFECTS:
(1) Chicks were highly excitable and exhibited
a "flying" syndrome at lower dose levels. After
several hours syndrome was followed by paralysis
and dehydration of leg tissue. Compound caused
death over a 2-day period. (2) 50% cholinesterase
inhibition by dose of >800 ppm.
COMPOUND: Phosphorodithioic acid, S-((4,6-diamino-S-triazin-2-yl)methyl)0,0-dimethyl ester
000078579
REFERENCE: Gaines, T.B.
Tox. Appl. Pharm. 14: 515-534, 1969.
OBSERVED NEUROTOXIC EFFECTS: 600 mg/kg produced leg weakness
ANIMALS: Cockerels, White Leghorn, single-comb, 10-50/grp, 12 d old
ANIMALS: Chickens, White Leghorn, F
PREPARATION AND DOSE n . ,
or HISTORY OF PATIENT: (1) Acute: LD (544.3 mg/kg) in gelatin capsule, 4-5
dose levels used.
(2) Subacute: 50-800 ppm in feed.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 15 mg/kg atropine sulfate orally 15 min prior to compound;
graded doses compound in peanut oil
ROUTE AND SITE: Oral
CONTROL INFORMATION: Untreated diet.
ROUTE AND SITE: S.C., under right wing
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: 1 wk
EXAM. TYPE: Mortality, behavior, blood ChE
DURATION OF EXPERIMENT: 1 yr
EXAM. TYPE: Clinical
911
912
-------
COMPOUND: phosphorodithioic acid, S-(((2,5-dichlorophenyl)thio)methyl) 0,0-diethyl ester
COMPOUND: Phosphorodithioic acid, (((3,4-dichlorophenyl)thio)methyl) 0,0-diethyl .ester
REFERENCE: Sherman, M., Herrick, R.B., Ross, E. and Chang, M.T.Y.
Toxicol. Appl. Pharm. 11: 49-67, 1967.
OBSERVED NEUROTOXIC EFFECTS: Ataxia, paralysis, convulsions.
Acute: the highest dosage levels given resulted in only
20% mortality.
REFERENCE: Sherman, M., Herrick, R.B., Ross, E. and Chang, M.T.Y.
Toxicol. Appl. Pharm. 11: 49-67, 1967.
OBSERVED NEUROTOXIC EFFECTS: Ataxia, paralysis, convulsions.
ANIMALS: Cockerels, Single Comb White Leghorn, 10-12 d old
ANIMALS: Cockerels, Single Comb White Leghorn, 10-12 d old
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) Acute: LDgQ > 5000 mg/kg
(2) Subacute: 50-800 ppm in diet, 20 chicks/grp, for 2 wk
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) Acute: LD50 143.0 mg/kg
(2) Subacute: 50-800 ppm in diet, 20 chicks/grp, for 2 wk
ROUTE AND SITE: Oral
CONTROL INFORMATION: Untreated control grps
ROUTE AND SITE: Oral
CONTROL INFORMATION: Untreated control grps
DURATION OF EXPERIMENT: 1-3 wk
EXAM. TYPE: Behavior, mortality
DURATION OF EXPERIMENT: 1-3 wk
EXAM. TYPE: Behavior, mortality
913
914
-------
COMPOUND: Phosphodithioic acid, S-((3,4-dichlorophenylthio)methyl) 0,0-dimethyl ester
REFERENCE: Sherman, M., Herrick, R.B., Ross, E. and Chang, M.T.Y.
Toxicol. Appl. Pharm. 11: 49-67, 1967.
OBSERVED NEUROTOXIC EFFECTS: Ataxia, paralysis, convulsions.
COMPOUND: phosphorodithioic acid, 0,0-diethyl ester, S,S-diester with p-dioxane-
2,.1-Hithinl
000078342
REFERENCE: Gaines, T.B.
Tox. Appl. Pharm. 14: 515-534, 1969.
OBSERVED NEUROTOXIC EFFECTS: 320 rag/kg produced leg weakness
ANIMALS: Cockerels, Single Comb White Leghorn, 10-12 d old
ANIMALS: Chickens, White Leghorn, F
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) Acute: LD 693.7 mg/kg
(2) Subacute: 50-800 ppm in diet, 20 chicks/grp, for 2 wk
PREPARATION AND DOSE
or HISTORY OF PATIENT: 15 mg/kg atropine sulfate orally 15 min prior to compound;
graded doses compound in peanut oil
ROUTE AND SITE: Oral
CONTROL INFORMATION: Untreated control grps
ROUTE AND SITE: S.C., under right wing
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: 1-3 wk
EXAM. TYPE: Behavior, mortality
DURATION OF EXPERIMENT: 1 yr
EXAM. TYPE: Clinical
915
916
-------
COMPOUND: Phosphorodithiolc acid, 0,0-diethyl ester, S-ester with 3-(mercaptomethyl)-
l,2,3-benzotriazin-4(3H)one
002642719
REFERENCE: Sherman, M., Herrick, R.B., Ross, E. and Chang, M.T.Y.
Toxicol. Appl. Pharm. 11: 49-67, 1967.
OBSERVED NEUROTOXIC EFFECTS: Ataxia, paralysis, convulsions.
COMPOUND: Phosphorodithioic acid, 0,0-diethyl S-(2 ethylthio)ethyl)ester
000298044
REFERENCE: Gaines, T.B.
Tox. Appl. Pharm. 14: 515-534, 1969.
OBSERVED NEUROTOXIC EFFECTS: >50 mg/kg produced leg weakness
ANIMALS: Cockerels, Single Comb White Leghorn, 10-12 d old
ANIMALS: Chickens, White Leghorn, F
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) Acute: LD5Q 34.4 mg/kg
(2) Subacute: 50-800 ppm in diet, 20 chicks/grp, for 2 wk
PREPARATION AND DOSE
or HISTORY OF PATIENT: 15 mg/kg atropine sulfate orally 15 min prior to compound;
graded doses compound in peanut oil
ROUTE AND SITE: Oral
CONTROL INFORMATION: Untreated control grps
ROUTE AND SITE: S.C., under right wing
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: 1-3 wk
EXAM. TYPE: Behavior, mortality
DURATION OF EXPERIMENT: 1 yr
EXAM. TYPE: Clinical
917
918
-------
COMPOUND: Phosphorodithioic acid, 0,0-dlethyl S-(2 ethylthio)ethyl) ester
000298044
REFERENCE: Redhead, I.H.
Lancet 1: 686-688, 1968,
OBSERVED NEUROTOXIC EFFECTS: The subject experienced headaches, nausea and
dizziness. Clinical examination showed abnormally
low cholinesterase.
COMPOUND: Phosphorodithioic acid, 0,0-diethyl S-(ethylthio)methyl ester
000298022
REFERENCE: Gaines, T.B.
Tox. Appl. Pharm. 14: 515-534, 1969.
OBSERVED NEUROTOXIC EFFECTS: 48 mg/kg produced leg weakness
ANIMALS: Human, M, 48 yr
ANIMALS: Chickens, White Leghorn, F
PREPARATION AND DOSE
or HISTORY OF PATIENT: Occupational exposure to dimeton and disulfoton for 5 yr
PREPARATION AND DOSE
or HISTORY OF PATIENT: 15 mg/kg atropine sulfate orally 15 min prior to compound;
graded doses compound in peanut oil
ROUTE AND SITE: Inhalation, topical
CONTROL INFORMATION: ns
ROUTE AND SITE: S.C., under right wing
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: 5 yr
EXAM. TYPE: Clinical
DURATION OF EXPERIMENT: 1 yr
EXAM. TYPE: Clinical
919
920
-------
COMPOUND:
Phosphorodithioic acid, 0,0-dimethyl ester, S-ester with 2-mercapto-N-
(2-methoxyacetyl) acetamide
000919766
REFERENCE: Sherman, M., Herrick, R.B., Ross, E. and Chang, M.T.Y.
Toxicol. Appl. Pharm. 11: 49-67, 1967.
OBSERVED NEUROTOXIC EFFECTS: Ataxia, paralysis, convulsions.
ANIMALS: Cockerels, Single Comb White Leghorn, 10-12 d old
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) Acute: LD50 94.0 mg/kg
(2) Subacute: 50-800 ppm in diet, 20 chicks/grp, for wk
ROUTE AND SITE: Oral
CONTROL INFORMATION: Untreated control grps
DURATION OF EXPERIMENT: 1-3 wk
EXAM. TYPE: Behavior, mortality
921
COMPOUND: Phosphorodithioic acid, 0,0-dimethyl ester, S-ester with 2-mercapto-
N-methylacetaraide (Dimeton)
000060515
REFERENCE: Redhead, I.H.
Lancet 1: 686-688, 1968.
OBSERVED NEUROTOXIC EFFECTS: The subject experienced headaches, nausea and
dizziness. Clinical examination showed abnormally
low cholinesterase.
ANIMALS: Human, M, 48 yr
PREPARATION AND DOSE
or HISTORY OF PATIENT: Occupational exposure to dimeton and disulfoton for 5 yr
ROUTE AND SITE: Inhalation, topical
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: 5 yr
EXAM. TYPE: Clinical
922
-------
COMPOUND: Phosphorodithioic acid, 0-0-dimethyl ester, S-ester with 3(mercaptomethyl)-
l,2,3-benzotriazin-4(3H)-one
000086500
REFERENCE: Gaines, T.B.
Tox. Appl. Pharm. 14: 515-534, 1969.
OBSERVED NEUROTOXIC EFFECTS: 150 mg/kg produced leg weakness
COMPOUND: Phosphorodithioic acid, 0,0-dimethyl ester, S-ester with 3-
(mercapto-methyl)-l,2,3 benzotriazin-4(3H)-one
000086500
REFERENCE: Murphy, S.D., Lauwerys, R.R. and Cheever, K.L.
Tox. Appl. Pharm. 12: 22-35, 1968.
OBSERVED NEUROTOXIC EFFECTS: Poor inhibitor of brain cholinesterase.
Metabolized to Gutoxon which is an inhibitor.
ANIMALS: Chickens, White Leghorn, F
PREPARATION AND DOSE
or HISTORY OF PATIENT: 15 mg/kg atropine sulfate orally 15 min prior to compound;
graded doses compound in peanut oil
In vitro brains of rats,
guinea pigs, sparrows, small-
mouth bass, flounder, sculpin
and monkey.
ANIMALS- Mice, Swiss-Webster, M, 25-30g
Chickens, White Rock X N.H. Red, M, 500-700g
Sunfish, M and F, 40-80g
Bullfish, M and F, 40-80g
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.1-1500 mg/kg, various schedules (I.P.) in mice, chickens,
sunfish and bullheads; 0.1-200 mg/kg (orally) in sunfish;
0.001—4 picomoles of malaoxon in vitro.
ROUTE AND SITE: S.C., under right wing
CONTROL INFORMATION: ns
ROUTE AND SITE: See above
CONTROL INFORMATION: Brain cholinesterase determined in controls
DURATION OF EXPERIMENT: 1 yr
EXAM. TYPE: Clinical
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Biochemistry
923
924
-------
COMPOUND: Phosphorodithioic acid, 0,0-dimethyl ester, S-ester with
3-(mercaptomethyl)-l,2,3-benzotriazin-4(3H)-one
REFERENCE: Sherman, M., Herrick, R.B., Ross, E. and Chang, M.T.Y.
Toxicol. Appl. Pharm. 11: 49-67, 1967.
OBSERVED NEUROTOXIC EFFECTS: Ataxia, paralysis, convulsions.
COMPOUND: Phosphorodithioic acid, 0,0-dimethyl ester, S-ester with N-(mercaptomethyl)
ohthallmide
000732116
REFERENCE: Sherman, M., Ross, E. and Chang, M.T.Y.
Tox. Appl. Pharm. 6:147-153, 1964.
OBSERVED NEUROTOXIC EFFECTS: (D Caused death within 18 hrs, any survivors
lethargic or paralyzed for as long as 2 d
post treatment. (2) 50% cholinesterase Inhibition
by dose of 400 ppm.
ANIMALS: Cockerels, Single Comb White Leghorn, 10-12 d old
ANIMALS: Cockerels, White Leghorn, single-comb, 10-50/grp, 12 d old
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) Acute:LD . 277.2 mg/kg
(2) Subacute: 50-800 ppm in diet, 20 chicks/grp, for 2 wk
PREPARATION AND DOSE
or HISTORY OF PATIENT: (D Acute: LD (707.0 mg/kg) in gelatin capsule.
(2) Subacute: 50-800 ppm in diet.
ROUTE AND SITE: ' Oral
CONTROL INFORMATION: Untreated control grps
ROUTE AND SITE: Oral
CONTROL INFORMATION: Untreated diet.
DURATION OF EXPERIMENT: 1-3 wk
EXAM. TYPE: Behavior, mortality
DURATION OF EXPERIMENT: 1 wk
EXAM. TYPE: Mortality, behavior, blood ChE
925
926
-------
COMPOUND: Phosphorodithioic acid, 0-ethyl S, S-dipropyl ester
013194484
REFERENCE: Sherman, M., Herrick, R.B., Ross, E. and Chang, M.T.Y.
Toxicol. Appl. Pharm. 11: 49-67, 1967.
OBSERVED NEUROTOXIC EFFECTS: Ataxia, paralysis, convulsions.
COMPOUND: Phosphorodithioic acid, S.S'-methylene 0,0,0',0'-tetraethyl ester
000563122
REFERENCE: Comstock, E.G., Bickel, L., and McCormick, R.A., Jr.
Texas Medicine 63: 71-75, 1967.
OBSERVED NEUROTOXIC EFFECTS: Generalized flaccid paralysis and areflexia;
respiratory distress.
ANIMALS: Cockerels, Single Comb White Leghorn, 10-12 d old
ANIMALS: Human, M, 6 mo.
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) Acute: LD5Q 5.5 mg/kg
(2) Subacute: 50-800 ppm in diet, 20 chicks/grp, for 2 wk
PREPARATION AND DOSE
or HISTORY OF PATIENT: 15.7 mg/kg
ROUTE AND SITE: Oral
CONTROL INFORMATION: Untreated control grps
ROUTE AND SITE: Oral
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: 1-3 wk
EXAM. TYPE: Behavior, mortality
DURATION OF EXPERIMENT: 1 yr
EXAM. TYPE: Clinical
927
928
-------
COMPOUND:
COMPOUND. Phosphorodithiolc acid, S.S'methylene 0,0,0' ,0'-tetraethyl ester
000563122
REFERENCE: Gaines, T.B.
Tox. Appl. Pharm. 14: 515-534, 1969.
OBSERVED NEUROTOXIC EFFECTS: 1200 mg/kg produced leg weakness
Phosphonodithioic acid, methyl-, 0-phenyl S-propyl ester
REFERENCE: Sherman, M., Herrick, R.B., Ross, E. and Chang, M.T.Y.
Toxicol. Appl. Pharm. 11: 49-67, 1967.
OBSERVED NEUROTOXIC EFFECTS: Ataxia, paralysis, convulsions.
ANIMALS: Chickens, White Leghorn, F
PREPARATION AND DOSE
or HISTORY OF PATIENT: 15 mg/kg atropine sulfate orally 15 min prior to compound;
graded doses compound in peanut oil
ANIMALS: Cockerels, Single Comb White Leghorn, 10-12 d old
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) Acute: LD 8.1 mg/kg
(2) Subacute: 50-800 ppm in diet, 20 chicks/grp, for 2 wk
ROUTE AND SITE: S.C., under right wing
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: 1 yr
EXAM. TYPE: Clinical
ROUTE AND SITE: Oral
CONTROL INFORMATION: Untreated control grps
DURATION OF EXPERIMENT: 1-3 wk
EXAM. TYPE: Behavior, mortality
929
930
-------
COMPOUND: Phosphorofluorldic acid, bis(l-methylethyl) ester
000055914
REFERENCE: Baron, R.L. and Casida, J.E.
Biochem. Pharm. 11: 1129-1136, 1962.
OBSERVED NEUROTOXIC EFFECTS: Ataxlc doses Inhibited selectively nerve esterases
hydrolyzing butyryl esters of choline, glycerol and
phenols. TOCP more persistent than metabolite.
Oxidation of succinate, pyruvate, a-ketoglutarate
by nerve and brain preparations was not affected.
COMPOUND: Phosphorofluoridic acid, bis(l-methylethyl) ester
000055914
REFERENCE: Johnson, M.K. and Barnes, J.M.
Biochem. Pharm. 19:3045-3047, 1970.
OBSERVED NEUROTOXIC EFFECTS:
1 mg/kg in hens aged 12 mo or more caused
frequent collapse and inability to stand. 2-5
mg/kg in chicks aged 7-49 d produced no effect,
but given at 60-130 d was increasingly toxic.
Repeated doses produced ataxia and "characteristic"
lesions in cord and peripheral nerves.
ANIMALS: . Chickens, White Leghorn, 1-2 y, 1.5-2.5 kg
ANIMALS: Chickens, various breeds, sex not stated.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 2mg/kg
PREPARATION AND DOSE
or HISTORY OF PATIENT:
0.5 ml/kg, then 0.1 ml/kg up to 6 doses.
ROUTE AND SITE: TOCP: gavage; DFP and metabolite: I.P.
CONTROL INFORMATION: ns
ROUTE AND SITE: S.c.
CONTROL INFORMATION: Mentioned, not described
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Biochemistry
DURATION OF EXPERIMENT: Up to 63 d.
EXAM. TYPE: Behavior, then histology. Also, in vitro bioasssay.
931
932
-------
COMPOUND: Phosphorofluoridic acid, methyl-,isopropyl ester (Sarin)
000107448
REFERENCE: Grob, D. and Johns, R.J.
Neurology 8: 897-902, 1958.
OBSERVED NEUROTOXIC EFFECTS: Overdoses of sarin resulted in neuromuscular block
from cholinesterase inhibition; partly relieved by
certain oximes.
COMPOUND: Phosphorothioic acid, 0-(2-(sec-butoxymethylthio)ethyl) 0,0-diethyl ester
REFERENCE: Sherman, M., Ross, E. and Chang, M.T.Y.
Tox. Appl. Pharm. 6:147-153, 1964.
OBSERVED NEUROTOXIC EFFECTS: (1) Convulsions followed by death within 18 hr.
Survivors were lethargic for 6-19 hrs post treatment.
(2) 50% cholinesterase inhibition by dose 280 ppm.
ANIMALS: Human: "many instances"
ANIMALS: Cockerels, White Leghorn, single-comb, 10-50/grp, 12 d old
PREPARATION AND DOSE
or HISTORY OF PATIENT: Patients with myasthenia medicated with compound, doses ns.
PREPARATION AND DOSE
or HISTORY OF PATIENT: (i) Acute: LD (28.6 mg/kg) in gelatin capsule.
(2) Subacute: 50-800 ppm in feed.
ROUTE AND SITE: . Probably intraarterial
CONTROL INFORMATION: ns
ROUTE AND SITE: Oral
CONTROL INFORMATION: Untreated diet.
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Electrophysiology, clinical.
DURATION OF EXPERIMENT: 1 wk
EXAM..TYPE: Mortality, behavior, blood ChE
933
934
-------
COMPOUND: Phosphorothioic acid, 0-(2-chloro-l-(2,4-dichlorophenyl) vinyl 0,0-
di--ethvl ester
COMPOUND: Phosphorothioic acid, 0-(2-chloro-4-nitrophenyl) 0,0-dimethyl ester
REFERENCE:
Morallo, B.D. and Sherman, M.
J. Econ. Entomol. 60:509-515, 1967.
REFERENCE: Gaines, T.B.
Tox. Appl. Pharm. 14: 515-534, 1969.
OBSERVED NEUROTOXIC EFFECTS:
The order of resistance to the insecticide was:
flesh fly > house fly > anthomyiid fly > blow fly.
This insecticide is a relatively rapid toxicant with
50% mortality occurring within 1 hour for blow flies
and house flies and within 4 hours for the other
two flies. There was significant inhibition of
cholinesterase in house flies and flesh flies, but
had little effect on the others. Recovery was just
about complete in 24 hours. Dead flies showed more
pronounced effects than living flies.
OBSERVED NEUROTOXIC EFFECTS: 300 mg/kg produced leg weakness
ANIMALS: Housefly, Musca domestica, adult F, 3-4 d old
Anthomyiid fly, Fannia pusio, adult F, 3-4 d old
Blowfly, Chrysoma megacephala, adult F, 3-4 d old
Flesh fly, parasarcophaga argyrostoma, adult F, 3-4 d old
PREPARATION AND DOSE
or HISTORY OF PATIENT: In vitro: The LD50 (0.26-21.6 mcg/g), 10-20 flies/
group or dose-level, each test replicated
3 or more times.
In vivo: 10 groups of 50 each of houseflies and
anthomyiid flies, and 10 groups of 20 each
of blowflies and flesh flies.
ROUTE AND SITE: Applied topically, venter of thorax.
CONTROL INFORMATION:
Untreated fly heads
ANIMALS: Chickens, White Leghorn, F
PREPARATION AND DOSE
or HISTORY OF PATIENT: 15 mg/kg atropine sulfate orally 15 min prior to compound;
graded doses compound in peanut oil
ROUTE AND SITE: S.C., under right wing
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: Serial to 24 hr.
EXAM. TYPE: Biochemistry, mortality
DURATION OF EXPERIMENT: 1 yr
EXAM. TYPE: Clinical
935
936
-------
COMPOUND: Phosphorothioic acid, O-(p-cyanophenyl) 0,0-dimethyl ester
REFERENCE: Sherman, M., Herrick, R.B., Ross, E. and Chang, M.T.Y.
Toxicol. Appl. Pharm. 11: 49-67, 1967.
COMPOUND: Phosphorothioic acid, 0-(2,4-dichlorophenyl)-0,0-diethyl ester
000097176
REFERENCE: Sherman, M., Herrick, R.B., Ross, E. and Chang, M.T.Y.
Toxicol. Appl. Pharm. 11: 49-67, 1967.
OBSERVED NEUROTOXIC EFFECTS: Ataxia, paralysis, convulsions.
OBSERVED NEUROTOXIC EFFECTS: Ataxia, paralysis, convulsions.
ANIMALS: Cockerels, Single Comb White Leghorn, 10-12 d old
ANIMALS: Cockerels, Single Comb White Leghorn, 10-12 d old
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) Acute: LD 23.5 mg/kg
(2) Subacute: 50-800 ppm in diet, 20 chicks/grp, for 2 wk
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) Acute: LD 148.2 mg/kg
(2) Subacute: 50-800 ppm in diet, 20 chicks/grp, for 2 wk
ROUTE AND SITE: Oral
CONTROL INFORMATION: Untreated control grps
ROUTE AND SITE: Oral
CONTROL INFORMATION: Untreated control grps
DURATION OF EXPERIMENT: 1-3 wk
EXAM. TYPE: Behavior, mortality
DURATION OF EXPERIMENT: 1-3 wk
EXAM. TYPE: Behavior, mortality
937
938
-------
COMPOUND: Phosphorothioic acid, 0,0-diethyl 0-(2-isopropyl-6-methyl-4-pyrimidinyl) ester
000333415
REFERENCE: Rayner, M.D., Popper, J.S., Carvalho, E.W. and Hurov,- R.
Res. Comm. Chem. Path. Pharm. 4: 595-606, 1972.
OBSERVED NEUROTOXIC EFFECTS: The force generated by the achilles tendon reflex was
. subnormal in exposed subjects. The authors suggest
! that this hyporeflexia may be a sensitive indicator of
chronic exposure to organophosphates.
COMPOUND: Phosphorothioic acid, 0,0-diethyl-0-(4-(methylthio)-3,5-xylyl) ester
REFERENCE: Sherman, M., Herrick, R.B., Ross, E. and Chang, M.T.Y.
Toxicol. Appl. Pharm. 11: 49-67, 1967.
OBSERVED NEUROTOXIC EFFECTS: Ataxia, paralysis, convulsions.
ANIMALS: Humans, Japanese ancestry, M, ages 22-59 (orchid farmers)
ANIMALS: Cockerels, Single Comb White Leghorn, 10-12 d old
PREPARATION AND DOSE
or HISTORY OF PATIENT: Exposure of more than 4 hr/d, 2 d/wk, 52 wk/yr for 5 yr except
one case (2 yr). Other types of pesticide also used, but
authors judged organophosphates exposures to be primary.
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) Acute: LD5Q 17.9 mg/kg
(2) Subacute: 50-800 ppm in diet, 20 chicks/grp, for 3 wk
ROUTE AND SITE: Skin contact, inhalation
CONTROL INFORMATION: Matched non-exposed subjects, so far as could be ascertained
ROUTE AND SITE: Oral
CONTROL INFORMATION: Untreated control grps
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Physiological
DURATION OF EXPERIMENT: 1-3 wk
EXAM. TYPE: Behavior, mortality
939
940
-------
COMPOUND: Phosphorothiolc acid, 0,0-diethyl O-(p-nitrophenyl) ester
REFERENCE: McFarland, L.Z. and Lacy, P.B.
Tox. Appl. Pharm. 12:105-114, 1968.
COMPOUND: Phosphorothioic acid, 0,0-dlethyl O-(p-nitrophenyl) ester
000056382
REFERENCE: Murphy, S.D., Lauwerys, R.R. and Cheever, K.L.
Tox. Appl. Pharm. 12: 22-35, 1968.
OBSERVED NEUROTOXIC EFFECTS: Death in 30 min to 2 hr. Salivation, tremors,
clonic convulsions and ataxia. (Parasympathomimetic
responses.)
OBSERVED NEUROTOXIC EFFECTS: P00r inhibitor of brain cholinesterase. Metabolized
to paraoxon which is an inhibitor.
ANIMALS: (1) 46 Japanese quail, adult
(2) 7 Pintail ducks, adult
(3) 36 Mallard ducks, adult
PREPARATION AND DOSE
or HISTORY OF PATIENT:
(1) 3.9-5.7 mg/kg
(2) 1.6-2 mg/kg
(3) 0.6-1.7 mg/kg
In vitro brains of rats,
guinea pigs, sparrows, small-
mouth bass, flounder, sculpin
and monkey.
ANIMALS' Mice, Swiss-Webster, M, 25-30g
Chickens, White Rock X N.H. Red, M, 5CO-700g
Sunfish, M and F, 40-80g
Bullfish, M and F, 40-80g
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.1-1500 mg/kg, various schedules (I.P.) in mice, chickens,
sunfish and bullheads; 0.1-200 mg/kg (orally) in sunfish;
0.001-4 picomoles of malaoxon in vitro.
ROUTE AND SITE: I.V.
CONTROL INFORMATION: ns.
ROUTE AND SITE: See above
CONTROL INFORMATION: Brain cholinesterase determined in controls
DURATION OF EXPERIMENT: 2 hr.
EXAM. TYPE: Behavior, physiology
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Biochemistry
941
942
-------
COMPOUND: Phosphorothioic acid, 0,0-diethyl O-(p-nitrophenyl) ester
000056382
REFERENCE: Rayner, M.D., Popper, J.S., Carvalho, E.W. and Hurov, R.
Res. Comm. Chem. Path. Pharm. 4: 595-606, 1972t-
OBSERVED NEUROTOXIC EFFECTS: The force generated by the achilles tendon reflex was
subnormal in exposed subjects. The authors suggest
that this hyporeflexia may be a sensitive indicator of
chronic exposure to organophosphates.
COMPOUND: Phosphorothioic acid, 0,0-diethyl 0-(3,5,6-trichloro-2-pyridyl) ester
002921882
REFERENCE: Gaines, T.B.
Tox. Appl. Pharm. 14: 515-534, 1969.
OBSERVED NEUROTOXIC EFFECTS: 200 mg/kg produced leg weakness, delayed 3-18 days
after dosing
ANIMALS: Humans, Japanese ancestry, M, ages 22-59 (orchid farmers)
ANIMALS: Chickens, White Leghorn, F
PREPARATION AND DOSE
or HISTORY OF PATIENT: Exposure of more than 4 hr/d, 2 d/wk, 52 wk/yr for 5 yr except
one case (2 yr). Other types of pesticide also used, but
authors judged organophosphates exposures to be primary.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 15 mg/kg atropine sulfate orally 15 min prior to compoun.
graded doses compound in peanut oil
ROUTE AND SITE: Skin contact, inhalation
CONTROL INFORMATION: Matched non-exposed subjects, so far as could be ascertained
ROUTE AND SITE: S.C., under right wing
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Physiological
DURATION OF EXPERIMENT: 1 yr
EXAM. TYPE: Clinical
943
944
-------
COMPOUND: Phosphorothioic acid, 0,0-diethyl 0-(3,5,6-trichloro-2-pyridyl) ester
002921882
REFERENCE: Sherman, M., Herrick, R.B., Ross, E. and Chang, M.T.Y.
Toxicol. Appl. Pharm. 11: 49-67, 1967.
OBSERVED NEUROTOXIC EFFECTS: Ataxia, paralysis, convulsions.
ANIMALS: Cockerels, Single Comb White Leghorn, 10-12 d old
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) Acute: LD,n 25.4 mg/kg
(2) Subacute:5050-800 ppm in diet, 20 chicks/grp, for 2 wk
ROUTE AND SITE: Oral
CONTROL INFORMATION: Untreated control grps
DURATION OF EXPERIMENT: 1-3 wk
EXAM. TYPE: Behavior, mortality
945
COMPOUND: Phosphorothioic acid, 0,0-diethyl 0-1,2,2-trimethyl propyl ester
REFERENCE: Sherman, M., Ross, E. and Chang, M.T.Y.
Tox. Appl. Pharm. 6:147-153, 1964.
OBSERVED NEUROTOXIC EFFECTS: (1) Convulsions followed in many by death within
18 hr. Survivors were lethargic for 6-19 hrs.
post treatment. (2) 50% cholinesterase inhibition
by doses of >800 ppm.
ANIMALS: Cockerels, White Leghorn, single-comb, 10-50/grp, 12 d old
PREPARATION AND DOSE
or HISTORY OF PATIENT: (D Acute: LD (1633.0 mg/kg) in gelatin capsule.
(2) Subacute:. 50-800 ppm in feed.
ROUTE AND SITE: Oral
CONTROL INFORMATION: Untreated diet.
DURATION OF EXPERIMENT: 1 wk
EXAM. TYPE: Mortality, behavior, blood ChE
946
-------
COMPOUND: Phosphorothiolc acid, 0,0-diisopropyl 0-(4-methylsulfinyl phenyl) ester
COMPOUND: Phosphorothioic acid, 0,0-dimethyl ester, 0,0-diester with 4,4'-thiodiphenol
REFERENCE: Sherman, M., Ross, E. and Chang, M.T.Y.
Tox. Appl. Pharm. 6:147-153, 1964.
OBSERVED NEUROTOXIC EFFECTS: (i) Convulsions followed in many by death within
18 hrs. Survivors were lethargic for 6-19
hrs post treatment.
(2) 50% cholinesterase inhibition by doses of 90 ppm.
REFERENCE: Gaines, T.B.
Tox. Appl. Pharm. 14:515-534, 1969.
OBSERVED NEUROTOXIC EFFECTS: 1000 mg/kg produced leg weakness.
ANIMALS: Cockerels, White Leghorn, single-comb, 10-50/grp, 12 d old
ANIMALS: Chickens, White Leghorn, F.
PREPARATION AND DOSE
or HISTORY OF PATIENT: (j.) Acute: LD (32.6 mg/kg) in gelatin capsule.
(2) Subacute: 50-800 ppm in feed.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 15 mg/kg atropine sulfate orally 15 min. prior to compound;
graded doses compound in peanut oil
ROUTE AND SITE: Oral
CONTROL INFORMATION: Untreated diet.
ROUTE AND SITE: S.C., under right wing
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: 1 wk
EXAM..TYPE: Mortality, behavior, blood ChE
DURATION OF EXPERIMENT: 1 yr.
EXAM. TYPE: Clinical
947
948
-------
COMPOUND:
Phosphorothloic acid, 0,0-dimethyl S-(2-(ethylsulfinyl) ethyl) ester
COMPOUND: Phosphorothioic acid, 0,0-dimethyl S-(2-(ethylsulfonyl)ethyl) ester
REFERENCE: Sherman, M. , Ross, E. and Chang, M.T.Y.
Tox. Appl. Pharm. 6:147-153, 1964.
OBSERVED NEUROTOXIC EFFECTS:
(1) Convulsions followed in many by death
within 18 hrs. Survivors were lethargic 6-19
hr post treatment.
(2) 50% cholinesterase inhibition by dose of
>800 ppm.
REFERENCE: DuBois, K.P and Plzak, G.J.
Tox. Appl. Pharm. 4: 621-630, 1962,
OBSERVED NEUROTOXIC EFFECTS: Inhibited brain cholinesterase in vitro. Sublethal
doses inhibited cholinesterase of central nervous
system and peripheral nervous system in vitro.
ANIMALS: Cockerels, White Leghorn, single-comb, 10-50/grp, 12 d old
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) Acute: LD (79.6 mg/kg) in gelatin capsule.
. (2) Subacute: 50-800 ppm in feed.
ANIMALS: Rats, S-D, M and F, 200-275g
Mice, CF adult M and F
Guinea pigs, young M, 200-300g
PREPARATION AND DOSE
or HISTORY OF PATIENT: LD5Q and other schedules
ROUTE AND SITE: Oral
CONTROL INFORMATION: Untreated diet.
ROUTE AND SITE: Oral, I.P., skin contact
CONTROL INFORMATION: Various
DURATION OF EXPERIMENT: 1 wk
EXAM.:TYPE: Mortality, behavior, blood ChE
DURATION OF EXPERIMENT: Up to 72 hr
EXAM. TYPE: Biochemistry
949
950
-------
COMPOUND: Phosphorothiolc acid, 0,0-dimethyl S-(2-ethylthioethyl) ester
COMPOUND: Phosphorothioic acid, 0,0-dimethyl S-(2-(isopropylsulfino) ethyl) ester
REFERENCE: DuBois, K.P and Plzak, G.J.
Tox. Appl. Pharm. 4: 621-630, 1962.
REFERENCE: DuBois, K.P and Plzak, G.J.
Tox. Appl. Pharm. 4: 621-630, 1962.
OBSERVED NEUROTOXIC EFFECTS: Inhibited brain cholinesterase in vitro. Sublethal
doses inhibited cholinesterase of central nervous
system and peripheral nervous system in vitro.
OBSERVED NEUROTOXIC EFFECTS: Inhibited brain cholinesterase in vitro. Sublethal
doses Inhibited cholinesterase of central nervous
system and peripheral nervous system in vitro.
ANIMALS: Rats, S-D, M and F, 200-275g
Mice, CF-, adult M and F
Guinea pigs, young M, 200-300g
PREPARATION AND DOSE
or HISTORY OF PATIENT: LD5Q and other schedules
ANIMALS: Rats, S-D, M and F, 200-275g
Mice, CF adult M and F
Guinea pigs, young M, 200-300g
PREPARATION AND DOSE
or HISTORY OF PATIENT: LD5Q and other schedules
ROUTE AND SITE: Oral, I.P., skin contact
CONTROL INFORMATION: Various
ROUTE AND SITE: Oral, I.P., skin contact
CONTROL INFORMATION: Various
DURATION OF EXPERIMENT: Up to 72 hr
EXAM. TYPE: Biochemistry
DURATION OF EXPERIMENT: Up to 72 hr
EXAM. TYPE: Biochemistry
951
952
-------
COMPOUND: ?hosphorothioic acid, 0,0-dimethyl 0-(p-methylsulfinyl)phenyl) ester
000115913
REFERENCE: Sherman, M. , Ross, E. and Chang, M.T.Y.
Tox. Appl. Pharm. 6:147-153, 1964.
OBSERVED NEUROTOXIC EFFECTS: (D Convulsion followed in many by death within
18 hr. Survivors were lethargic for 6-19 hr post
treatment. (2) 50% Cholinesterase inhibition by
dose of >800 ppm.
COMPOUND: _ Phosphorothioic acid, 0,0-dlmethyl-,0-(4-methylthio)-m-tolyl) ester (DMTP)
000055389
REFERENCE: DuBois, K.P. and Kinoshita, F.
Tox. Appl. Pharm. 6: 86-95, 1964.
OBSERVED NEUROTOXIC EFFECTS: Brain anticholinesterase inhibited for prolonged
periods, exposures cumulative, toxicity potentiated
by combination with 2,3-£-dioxanedithiol-j[,j[-bis-(0^0-
diethyl phosphorodithioate) (Delnav) or O^CV-diethyl
Or 3-chloro-4-methy 1-2-oxo-211-l-benzopyran-7-yl
phosphorothioate (Co-Ral), or Malathion.
ANIMALS: Cockerels, White Leghorn, single-comb, 10-50/grp, 12 d old
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) Acute: LD (2.32 mg/kg) in gelatin capsule.
(2) Subacute: 50-800 ppm in feed.
ANIMALS: Rats, S-D, M and F, 175-275 g
Guinea pigs, M, 200-300 g
Mice, CF-p adult M and F
PREPARATION AND DOSE
or HISTORY OF PATIENT: In diet: 1% (mice) or 0.1% (rats, guinea pigs) of body weight;
I.P.: 10-100 mg/kg (rats); Topical: up to 500 mg/kg
DMTP + other compounds, equitoxic combinations.
ROUTE AND SITE: Oral
CONTROL INFORMATION: Untreated diet.
ROUTE AND SITE: Oral (diet), I.P., topical (shaved back, rats)
CONTROL INFORMATION: Zero doses
DURATION OF EXPERIMENT: 1 wk
EXAM. TYPE: Mortality, behavior, blood ChE
DURATION OF EXPERIMENT: Up to 60 d
EXAM. TYPE: Mortality, behavior, biochemistry
953
954
-------
COMPOUND: phosphorothiolc acid, 0,0-dimethyl-,0-(4-methylthio)-m-tolyl) ester
000055389
REFERENCE: Gaines, T.B.
Tox. Appl. Pharm. 14: 515-534, 1969.
OBSERVED NEUROTOXIC EFFECTS: 40 mg/kg produced leg weakness
COMPOUND: Phosphorothioic acid, 0,0-dimethyl 0-(4-methylthio)-3,5-xylyl) ester
000055378
REFERENCE: Sherman, M., Herrick, R.B., Ross, E. and Chang, M.T.Y.
Toxicol. Appl. Pharm. 11: 49-67, 1967.
OBSERVED NEUROTOXIC EFFECTS: Ataxia, paralysis, convulsions.
ANIMALS: Chickens, White Leghorn, F
ANIMALS: Cockerels, Single Comb White Leghorn, 10-12 d old
PREPARATION AND DOSE
or HISTORY OF PATIENT: 15 mg/kg atropine sulfate orally 15 min prior to compound;
graded doses compound in peanut oil
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) Acute: LD5Q 102.8 mg/kg
(2) Subacute: 50-800 ppm in diet, 20 chicks/grp, for 3 wk
ROUTE AND SITE: S.C., under right wing
CONTROL INFORMATION: ns
ROUTE AND SITE: Oral
CONTROL INFORMATION: Untreated control grps
DURATION OF EXPERIMENT: 1 yr
EXAM. TYPE: Clinical
DURATION OF EXPERIMENT: 1-3 wk
EXAM. TYPE: Behavior, mortality
955
956
-------
COMPOUND: Phosphorothioic acid, 0,0-dimethyl-0-(p-nitrophenyl)ester
000298000
REFERENCE: Gaines, T.B.
Tox. Appl. Pharm. 14: 515-534, 1969.
OBSERVED NEUROTOXIC EFFECTS: 200 mg/kg produced leg weakness
COMPOUND: Phosphorothioic acid, 0,0-dimethyl 0-(4-nitro-m-tolyl) ester
000122145
REFERENCE: Sherman, M., Herrick, R.B., Ross, E. and Chang, M.T.Y.
Toxicol. Appl. Pharm. 11: 49-67, 1967.
OBSERVED NEUROTOXIC EFFECTS: Ataxia, paralysis, convulsions.
ANIMALS: Chickens, White Leghorn, F
ANIMALS: Cockerels, Single Comb White Leghorn, 10-12 d old
PREPARATION AND DOSE
or HISTORY OF PATIENT: 15 mg/kg atropine sulfate orally 15 min prior to compound;
graded doses compound in peanut oil
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) Acute: LD 279.5 mg/kg
(2) Subacute: 50-800 ppm in diet, 20 chicks/grp, for 2 wk
ROUTE AND SITE: S.C... under right wing
CONTROL INFORMATION: ns
ROUTE AND SITE: Oral
CONTROL INFORMATION: Untreated control grps
DURATION OF EXPERIMENT: 1 yr
EXAM. TYPE: Clinical
DURATION OF EXPERIMENT: 1-3 wk
EXAM. TYPE: Behavior, mortality
957
958
-------
COMPOUND: Phosphorothloic acid, 0,0-dimethyl S-((4-oxo-l,2,3-benzotriazin-3(4H)-
yDmethyl) ester
000961228
REFERENCE: Murphy, S.D., Lauwerys, R.R. and Cheever, K.L.
Tox. Appl. Pharm. 12: 22-35, 1968.
COMPOUND:
Phosphorothloic acid, 0-0-dimethyl 0(2,4,5-trichlorophenyl)
'ester
000299843
REFERENCE: Gaines, T.B.
Tox. Appl. Pharm. 14: 515-534, 1969.
OBSERVED NEUROTOXIC EFFECTS: Inhibits brain cholinesterase.
Sensitivities: f ish > mammals* birds.
OBSERVED NEUROTOXIC EFFECTS: 1600 mg/kg produced leg weakness
ANIMALS- Mice, Swiss-Webster, M, 25-30g
Chickens, White Rock X N.H. Red, M, 5jDO-700g
Sunfish, M and F, 40-80g
Bullfish, M and F, 40-80g
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.1-1500 mg/kg, various schedules (I.P.) in mice, chickens,
sunfish and bullheads; 0.1-200 mg/kg (orally) in sunfish;
0.001-4 picomoles of malaoxon in vitro.
In vitro brains of rats, ANIMALS: Chickens, White Leghorn, F
guinea pigs, sparrows, small-
mouth bass, flounder, sculpin
and monkey.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 15 mg/kg atroplne sulfate orally 15 min prior to compound;
graded doses compound in peanut oil
ROUTE AND SITE: See above
CONTROL INFORMATION: Brain cholinesterase determined in controls
ROUTE AND SITE: S.C., under right wing
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Biochemistry
DURATION OF EXPERIMENT: 1 yr
EXAM. TYPE: Clinical
959
960
-------
COMPOUND: Phosphorotrithioic acid, 0-methyl S,S-dipropyl e'ster
REFERENCE: Sherman, M., Herrick, R.B., Ross, E. and Chang, M.T.Y.
Toxicol. Appl. Pharm. 11: 49-67, 1967.
OBSERVED NEUROTOXIC EFFECTS: Ataxia, paralysis, convulsions.
Acute: Significant growth depression even at levels lower
than the LD
COMPOUND: Phosphorotrithioic acid, S.S.S-tributyl ester
000078488
REFERENCE: Gaines, T.B.
Tox. Appl. Pharm. 14: 515-534, 1969.
OBSERVED NEUROTOXIC EFFECTS: 200 mg/kg produced leg weakness, delayed 14-24 days
after dosing
ANIMALS: Cockerels, Single Comb White Leghorn, 10-12 d old
ANIMALS: Chickens, White Leghorn, F
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) Acute: LD,- 9.6 mg/kg
(2) Subacute: 50-800 ppm in diet, 20 chicks/grp, for 2 wk
PREPARATION AND DOSE
or HISTORY OF PATIENT: 15 mg/kg atropine sulfate orally 15 min prior to compound;
graded doses compound in peanut oil
ROUTE AND SITE: Oral
CONTROL INFORMATION: Untreated control grps
ROUTE AND SITE: S.C., under right wing
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: 1-3 wk
EXAM. TYPE: Behavior, mortality
DURATION OF EXPERIMENT: 1 yr
EXAM. TYPE: Clinical
961
962
-------
COMPOUND: Phosphorotrithious acid, tributyl ester
000150505
REFERENCE: Gaines, T.B.
Tox. Appl. Pharm. 14: 515-534, 1969.
OBSERVED NEUROTOXIC EFFECTS: 600 mg/kg produced leg weakness, delayed 3-21 days
| after dosing
COMPOUND: Phosphorous acid, trl-o-tolyl ester
REFERENCE: Hine, C.H., Dunlap, M.K., Rice, E.G., Coursey, M.M., Gross, R.M.
and Anderson, H.H.
J. Pharm. Exp. Ther. 116:227, 1956.
OBSERVED NEUROTOXIC EFFECTS: All died.
ANIMALS: Chickens, White Leghorn, F
ANIMALS: 22 Chickens, White Leghorn, M, 0.75-1.3 kg.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 15 mg/kg atropine sulfate orally 15 min prior to compound;
graded doses compound In peanut oil
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) 0.5 gm/kg
(2) 1.0 gm/kg
ROUTE AND SITE: S.C., under right wing
CONTROL INFORMATION: ns
ROUTE AND SITE: (1) S.C. (2) Oral
CONTROL INFORMATION: One group of 5 per experimental group.
DURATION OF EXPERIMENT: 1 yr
EXAM. TYPE: Clinical
DURATION OF EXPERIMENT: 14-36 d after treatment.
EXAM. TYPE: Behavior, histology
963
964
-------
COMPOUND: Phthalate plasticizers (mixture)
REFERENCE: Mllkov, L.E., Aldyreva, M.V., Popova, T.B., Lopukhova, K.A.,
Malarenko, Y.L., Malyar, L.M. and Shakhova, T.K.
Env. Hlth. Persp. 3:175-178, 1973. (Trans from Gig. Trud. 13:14, 1969).
OBSERVED NEUROTOXIC EFFECTS:
Limb weakness and sensory disturbance after 6-7 yr exposure,
progressive. Polyneuritis (32 in autonomic nervous
system, 15 mixed), function disturbed in 22. High
pain threshold in 66.7%, low sensitivity to vibrations
in 33.8%, 78% of 81 subjects examined for vestibular
disorder had it, 82% olfactory changes, no auditory
disturbances.
COMPOUND: Phthalimide,N-(2,6-dioxo-3-piperidyl)-
000050351
REFERENCE:
McBride, W.G.
Teratology 10:283-292, 1974.
OBSERVED NEUROTOXIC EFFECTS: Fetal spinal ganglia were examined. Treated
group produced: 37 normals, 7 with reduction deformities, 49 resorptions;
control group; 22 normals, no deformities. Dorsal root ganglia of the
deformed fetuses showed degenerative changes particularly in the cervical
and lumbar regions of the cord. Reduction in number of sensory neurons,
believed to be causative of, or consequent to, the reduction deformities
of the forelimbs.
ANIMALS: .147 Humans, 60 M and 87 F, 75% younger than 40.
ANIMALS: Rabbits, NZ White, F, 3.5-5 kg, pregnant.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Exposure to mixture of compounds, levels of mixed esters
10-66 mg/m. 54 exposed 0.5-5 yr, 28 for 6-10 yr and 28
for 10-19 yr.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 90-1000 mg/kg/d from d 7, 8, or 11 of pregnancy.
ROUTE AND SITE: Inhalation, skin contact
CONTROL INFORMATION: ns.
ROUTE AND SITE: Oral; gavage or capsule
CONTROL INFORMATION: Untreated controls
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Survey, electrophysiology, clinical, biochemical.
DURATION OF EXPERIMENT: 29 d
EXAM. TYPE: Teratological
965
966
-------
COMPOUND:
Phthalimide, N-(2,6-dioxo-3-piperidyl)-
000050351
REFERENCE: McCredie, J. and McLeod, J.G.
Lancet ii:llll (1974)
OBSERVED NEUROTOXIC EFFECTS:
Immature ganglion strucutre vs. mature In controls,
resembling human fetus at 3-4 mo., interpreted as
developmental arrest of embryonic dorsal-root
ganglia. Concluded that reduction deformities are
due to embryonic sensory neuropathy, caused by compound.
COMPOUND: Phthalimide, N-hydroxy-,0-ethyl 0-isopropyl phosphorothioate
003733844
REFERENCE: Sherman, M., Ross, E. and Chang, M.T.Y.
Tox. Appl. Pharm. 6:147-153, 1964.
OBSERVED NEUROTOXIC EFFECTS: (1) Convulsions followed in many by death within
18 hr. Survivors were lethargic for 6-19 hrs.
post treatment. (2) 50% cholinesterase inhibition
by dose of 150 ppm.
ANIMALS:
Rabbits, newborn, of dams treated with compound.
ANIMALS: Cockerels, White Leghorn, single-comb, 10-50/grp, 12 d old
PREPARATION AND DOSE
or HISTORY OF PATIENT:
to dams ns.
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) Acute: LD.- (111.1 mg/kg) in gelatin capsule.
(2) Subacute: 50-800 ppm In feed.
ROUTE AND SITE: ns.
CONTROL INFORMATION: Matched untreated controls
ROUTE AND SITE: Oral
CONTROL INFORMATION: Untreated diet.
DURATION OF EXPERIMENT:
EXAM. TYPE: Histology
DURATION OF EXPERIMENT: 1 wk '
EXAM..TYPE: Mortality, behavior, blood ChE
967
968
-------
COMPOUND: Picolinlc acid, 5-amino-6-(7-amino-5,8-dihydro-6-methoxy-5,8-
dioxo-2-quinolyl)-4-(2-hydroxy-3,4-dimethoxyphenyl)-3-methyl
003930196
REFERENCE: Warkany, J. and Takacs, E.
Arch. Path. 79(l):65-79, 1965.
OBSERVED NEUROTOXIC EFFECTS: Inlencephaly with many related brain and cord
defects.
COMPOUND: Picolinic acid, hydrazide
REFERENCE: Jenney, E.H. and Pfeiffer, C.C.
J. Pharm. Exp. Ther. 122: 110-123, 1958.
OBSERVED NEUROTOXIC EFFECTS: Convulsions
ANIMALS: Rats, F, pregnant (2 strains).
ANIMALS: Mice, Harlan, 19-21 g
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.24-0.34 mg/kg one dose.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 2.2 mM/kgm
ROUTE AND SITE: I.P.
CONTROL INFORMATION: ns.
ROUTE AND SITE: i.p.
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: End of pregnancy
EXAM. TYPE: Teratology
DURATION OF EXPERIMENT: Acute
EXAM. TYPE: Clinical
969
970
-------
COMPOUND: 2-Picolinium, l-((4-amlno-2-propyl-5-pyrimidinyl)methyl)-, chloride,
hydrochloride
hydrochlorid
REFERENCE: Morgan, K.T.
J. Path. 112:229-236, 1974.
COMPOUND: 2-Plcollnium, l-((4-amino-2-propyl-5-pyrimldinyl)methyl)-, chloride,
hydrochloride
REFERENCE: Morgan, K.T., Coop, R.L. and Doxey, D.L.
J. Path. 116:73-81, 1975.
OBSERVED NEUROTOXIC EFFECTS: Ataxia, convulsions; cerebrocortical malacia with
edema of astrocytes, neuronal degeneration;
disruption of meylin sheaths in white-matter
OBSERVED NEUROTOXIC EFFECTS: Encephalopathy preceded by reduced cerebrocortical
transketolase activity.
ANIMALS: 21 Lambs, Suffolk x Dorset, M and F, aged 24 hr: 12 treated, 9 controls.
ANIMALS: 24 Sheep: Suffolk x Dorset lambs aged 24 hr, M and F
PREPARATION AND DOSE
or HISTORY OF PATIENT:
280 mg/kg/d
PREPARATION AND DOSE
or HISTORY OF PATIENT:
280 mg/kg/d in aqueous soln.
ROUTE AND SITE: Oral
CONTROL INFORMATION: 4 given thiamine 1 mg/d, 5 untreated.
ROUTE AND SITE: Oral
CONTROL INFORMATION: 12 matched untreated controls.
DURATION OF EXPERIMENT: Serial sacr 2-36 hr after neurotoxic signs.
EXAM. TYPE: Behavior, pathology, histology
DURATION OF EXPERIMENT: Sacr at 7, 14, 21 d.
EXAM. TYPE: Histology, biochemistry
971
972
-------
COMPOUND: Plcrotoxin
000124878
REFERENCE: Hill, R.G. and Miller, A.A.
Br. J. Pharmac. 50: 425-427, 1974.
OBSERVED NEUROTOXIC EFFECTS: The compound reduced presynaptlc inhibition produced
by peripheral stimulation, and is a known convulsant.
The authors infer that both folic acid and picrotoxin
act by the same mechanism.
COMPOUND: Picrotoxin
000124878
REFERENCE: Hill, R.G., Simmonds, M.A. and Straughan, D.W.
Br. J. Pharmac. 45: 176P-177P, 1972 (Abstract of proceedings)
OBSERVED NEUROTOXIC EFFECTS: The convulsive threshold was reached in 20 min;
abnormal electrographs were seen before GABA antagon-
ism, and were related with seizures. GABA was
Ineffective in preventing convulsions.
ANIMALS: 6 piebald Lister rats, adult, surgically prepared
ANIMALS: Cats, surgically prepared
PREPARATION AND DOSE
or HISTORY OF PATIENT: Concentrations: 0.2% w/v (about 3mM)
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.15 mg
ROUTE AND SITE: Cannulated onto the surface of the cuneate nucleus
CONTROL INFORMATION: ns
ROUTE AND SITE: i.v. infusion
CONTROL INFORMATION: Leptazol (6 mg) used as control
DURATION OF EXPERIMENT: About 2 hr per test
EXAM. TYPE: Electrophysiology
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Biochemistry, behavior
973
974
-------
COMPOUND: Picrotoxin
000124878
REFERENCE: Johnston, G.A.R. and Mitchell, J.F.
J. Neurochem. 18:2441-2446, 1971.
COMPOUND: Piperazine
000110850
REFERENCE: Sturtnan, G.
Br. J. Pharmac. 50: 153-155, 1974.
OBSERVED NEUROTOXIC EFFECTS:
All four compounds Influenced the release of GABA,
but not its uptake. Biculline, at 10~5 M (not
more or less) potentiated evoked release of GABA
but not the resting release. Metrazol inhibited
the electrically resting release but not the
electrically evoked release. Strychnine and
picrotoxin inhibited the electrically evoked
release of GABA.
OBSERVED NEUROTOXIC EFFECTS:
Mice: Pretreatment 1 hour beforehand with piperazlne
enhanced the acute toxicity of chlorpromazine but not
of prochlorperazine. Rats: Pretreatment with piper-
azine enhanced catatonia from chlorpromazine but not
from prochlorperazine. Piperazine did not alter the
EEC changes induced by chlorpromazine or prochlor-
perazine. In sum: piperazine potentiated the central
nervous system effects of chlorpromazine but not of
prochlorperazine.
ANIMALS: In vitro slices of rat cerebral cortex
ANIMALS:
Mice, no details
Rats, F, no other details
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Preincubated with compounds for 15 min, then with labeled
GABA for 10 min.
-1
PREPARATION AND DOSE
or HISTORY OF PATIENT: Piperazine: 0, 1, 2.5 or 5 g/kg"4" followed after 1 or 24
hr by various doses of chlorpromazine or prochlorperazine
ROUTE AND SITE: in vitro
CONTROL INFORMATION: Lab
ROUTE AND SITE: Piperazine: S.C.; chlorpromazine and prochlorperazine: I.P.
CONTROL INFORMATION: No piperazine given
DURATION OF EXPERIMENT: 25 min
EXAM. TYPE: Biochemistry
DURATION OF EXPERIMENT: Hours
EXAM. TYPE: Behavior
975
976
-------
COMPOUND: 1-Piperazineethanol, 4-(3-(2-chlorophenothiazin-10-yl)propyl)-
000058399
REFERENCE: Quinton, R.M.
Br. J. Pharaac. 21:51-66, 1963.
OBSERVED NEUROTOXIC EFFECTS: The compound enhanced the effect of Tfohimbine
and lowered its lethal dosage.
ANIMALS:
Mice, TT, M, 18-25 g.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
ED5Q 50 mg/kg
ED.. = dose producing a 50% mortality of mice injected
S.C. with yohimbine hydrochloride (20 mg/kg).
ROUTE AND SITE: s.c., oral
CONTROL INFORMATION: Various
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Behavior, electrophysiology, biochemistry
977
COMPOUND: 1-Piperazineethanol, 4-(3-(2-chlorophenothiazin-10-yl)propyl)-,
heptanoate
REFERENCE: Pakkenberg, H. and Fog, R.
Psychapharmacologia (Berl) 40:165-169, 1974.
OBSERVED NEUROTOXIC EFFECTS: No significant effects except in (1) where compound
increased labeling of nuclei. Authors refer to related paper where 12 mo.
of treatment caused 20% loss of cells in basal ganglia and conclude that
treatment must be "relatively prolonged."
ANIMALS: 40 Rats, Wistar, approx. 250 g.
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) 3.4 mg/kg in sesame oil, 3 times in 6 wks to 10 rats.
(2) As above, except 5 inj. to 10 rats.
ROUTE AND SITE: S.C.
CONTROL INFORMATION: 10 rats .treated sesame oil 3 times in 6 wk, sacr 3 d
after last inj.
10 rats treated sesame oil 5 times.
DURATION OF EXPERIMENT: (1) 6.5 wk, (2) 10.5 wk.
EXAM. TYPE: Autoradiography
978
-------
COMPOUND:2-Piperidineacetic acid, a-phenyl-, methyl ester hydrochloride
COMPOUND:
Piperidine, 2-chloroethyl-, hydrochloride
REFERENCE: Qulnton, R.M.
Br. J. Pharmac. 21:51-66, 1963.
OBSERVED NEUROTOXIC EFFECTS: The compound enhanced the effect of Yohimbine
and lowered its lethal dosage.
REFERENCE: Goldin, A., Now, H.A., Landing, B.H., Shapiro, D.M. and Goldberg, B.
J. Pharm. Exp. Ther. 94:249-261, 1958.
OBSERVED NEUROTOXIC EFFECTS:
Waltzing syndrome was produced by dialkyl and hetero-
cyclic B-chloroethylamines but not when (a) OH
or bromine replaced the 6 chlorine, (b) a B-phenyl
group replaced one of the B hydrogens in the
chlorinated chain, or (c) phenyl groups were introduced
into the dialkyl carbons. No effect from primary/
secondary g-chloroethylamines, related quaternary
compounds, or bis-, tris-, or tetrakis-B-chloro-
ethylamines. Piperidine and morpholine analogs and
arsacetin produced waltzing. Cerebellar and
axial lesions found consistent with behavior.
ANIMALS:
Mice, IT, M, 18-25 g.
ANIMALS:
Mice, CF1, M, 2-3m, 18-25 g; also CF1 F and C3H M.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
>5Q 15 mg/kg
ED
ju
ED,.. = dose producing a 50% mortality of mice injected
S.C. with yohimbine hydrochloride (20 mg/kg).
PREPARATION AND DOSE
or HISTORY OF PATIENT:
1-625 mg/kg in saline or (insolubles) 10% acacia,
various schedules.
ROUTE AND SITE: S.C., Oral
CONTROL INFORMATION: Various
ROUTE AND SITE: I.P.
CONTROL INFORMATION: Vehicle alone
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Behavior, electrophysiology, biochemistry
DURATION OF EXPERIMENT: At least 10 d after treatment.
EXAM. TYPE: Behavior, histology.
979
980
-------
COMPOUND: 2-piperidineethenol, alpha, alpha-diphenyl-1-methyl-hydrochloride.
REFERENCE: pfeiffer, C.C., Murphree, H.B., Jenney, E.H., Robertson, M.G.,
Randall, A.H. and Bryan, L.
Neurology 9: 249-250, 1959.
OBSERVED NEUROTOXIC EFFECTS: The authors concluded that synthetic atropines are more
active hallucinogens than atropine or scopolamine, pro-
ducing effects lasting 24-48 hr. Synthetic antitremor
drugs had fewer peripheral nervous system side-effects,
but central nervous system side-effects (hallucinations)
may have been exaggerated.
COMPOUND: 1-Piperidine propanol, alpha-cyclohexyl alpha-phenyl-, hydrochloride
000052493
REFERENCE: Pfeiffer, C.C., Murphree, H.B., Jenney, E.H., Robertson, M.G.,
Randall, A.H. and Bryan, L.
Neurology 9: 249-250, 1959.
OBSERVED NEUROTOXIC EFFECTS: The authors concluded that synthetic atropines are more
I active hallucinogens than atropine or scopolamine, pro-
ducing effects lasting 24-48 hr. Synthetic antitremor
drugs had fewer peripheral nervous system side-effects,
but central nervous system side-effects (hallucinations)
may have been exaggerated.
ANIMALS: Human: prison volunteers, drug-sophisticated, no other details
ANIMALS: Human: prison volunteers, drug-sophisticated, no other details
PREPARATION AND DOSE
or HISTORY OF PATIENT: 150 mg/man
PREPARATION AND DOSE
or HISTORY OF PATIENT: 5, 10 mg/man
ROUTE AND SITE: Oral
CONTROL INFORMATION: LSD-25: 0, 25, 50, 100 meg/man
ROUTE AND SITE: Oral
CONTROL INFORMATION: LSD-25: 0, 25, 50, 100 meg/man
DURATION OF EXPERIMENT: Up to 3 d
EXAM. TYPE: Opinion of volunteers
DURATION OF EXPERIMENT: Up to 3 d
EXAM. TYPE: Opinion of volunteers
981
982
-------
COMPOUND:
1-Piperidine propanol, alpha-cyclopentyl-alpha-phenyl-
COMPOUND: 3-Piperidinol, 1-methyl-, citrate
REFERENCE: pfeiffer, C.C., Murphree, H.B., Jenney, E.H., Robertson, M.G.,
Randall, A.H. and Bryan, L.
Neurology 9: 249-250, 1959.
OBSERVED NEUROTOXIC EFFECTS: The authors concluded that synthetic atropines are more
active hallucinogens than atropine or scopolamine, pro-
ducing effects lasting 24-48 hr. Synthetic antitremor
drugs had fewer peripheral nervous system side-effects,
but central nervous system side-effects (hallucinations)
may have been exaggerated.
REFERENCE: Pfeiffer, C.C., Murphree, H.B., Jenney, E.H., Robertson, M.G.,
Randall, A.H; and Bryan, L.
Neurology 9: 249-250, 1959.
OBSERVED NEUROTOXIC EFFECTS: The authors concluded that synthetic atropines are more
active hallucinogens than atropine or scopolamine, pro-
ducing effects lasting 24-48 hr. Synthetic antitremor
drugs had fewer peripheral nervous system side-effects,
but central nervous system side-effects (hallucinations?
may have been exaggerated.
ANIMALS: Human: prison volunteers, drug-sophisticated, no other details
ANIMALS: Human: prison volunteers, drug-sophisticated, no other details
PREPARATION AND DOSE
or HISTORY OF PATIENT: 5 mg/man
PREPARATION AND DOSE
or HISTORY OF PATIENT: 100 mg/man
ROUTE AND SITE: Oral
CONTROL INFORMATION: LSD-25: 0, 25, 50, 100 meg/man
ROUTE AND SITE: Oral
CONTROL INFORMATION: LSD-25: 0, 25, 50, 100 meg/man
DURATION OF EXPERIMENT: Up to 3 d
EXAM. TYPE: Opinion of volunteers
DURATION OF EXPERIMENT: Up to 3 d
EXAM. TYPE: Opinion of volunteers
983
984
-------
COMPOUND: Plumbane, tetraethyl-
000078002
REFERENCE: Cremer, J.E.
Nature (Lond.) 195: 607-608, 1962.
(with reply by Vardanis, A. and Quastel, J.H., ibid, p.
608).
COMPOUND: Plumbane, tetraethyl-
000078002
REFERENCE: Niklowitz, W.J. and Yeager, D.W.
Life Sci. 13: 897-905, 1973.
OBSERVED NEUROTOXIC EFFECTS:
The compound produced tremors with intermittent con-
vulsions, different from hindlimb paralysis from
triethyl lead, an in-vivo metabolite of tetraethyl
lead. Glucose was taken up but not oxidized by
brain slices (Cremer). There was normal oxidation
by less susceptible hooded rats who survive longer,
and oxidation is depressed only by triethyl lead
(Vardanis and Quastel).
OBSERVED NEUROTOXIC EFFECTS:
Acute intoxication in frontal cortex, cerebellum, and
hippocampus. All contained approx. 33 meg lead/g
dry wt, with significant losses of copper, iron and
zinc. Lead: copper movement ratio: was 1:1, lead:
iron was 1:2, lead: zinc varied. Convulsions and
encephalopathy.
ANIMALS: Rats, (strain ns), M, 200 g (Cremer)
Rats, hooded, M, bred at McGill (Vardanis & Quastel)
ANIMALS: - Rabbits, NZ White, M, 2.5-3.5 kg.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
10 mg/kg/d for 3 d (Cremer)
10 mg/kg/d for 6 d (Vardanis & Quastel)
PREPARATION AND DOSE
or HISTORY OF PATIENT: 100 mg/kg, one dose.
ROUTE AND SITE: I.p.
CONTROL INFORMATION: ns
ROUTE AND SITE: I.P.
CONTROL INFORMATION: Mentioned, not described.
DURATION OF EXPERIMENT: 3-6 d
EXAM. TYPE: Behavior, biochemistry
DURATION OF EXPERIMENT: Sacr 18-24 hr.
EXAM. TYPE: Biochemistry
985
986
-------
COMPOUND: Plumbane, tetraethyl-
000078002
REFERENCE: Niklowitz, W.J.
Neurology 25:927-934, 1975.
OBSERVED NEUROTOXIC EFFECTS: Hippocampus, frontal and cerebellar cortex were
examined for ultrastructural changes. Classic neurofibrillary tangles
developed in hydropic degenerating neurons and comprised mainly bundles
of smooth tubules 200 A diam. and of "enormous length."
COMPOUND: Pregn-4-ene-3,20-dione, 17,21-dihydroxy-, succinate, sodium salt
REFERENCE: Heuser, G., Ling, G.M. and Buchwald, N.A.
Arch. Neurol 13:195-203, 1965.
OBSERVED NEUROTOXIC EFFECTS: (1) Low doses (5 mg/kg) produced slow wave EEC
and intermittent sedation. Doses of 20-70 mg/kg resulted in sleep-like be-
havior. Complete recovery was observed within several hours. Total of 100-200
mg/kg produced seizures, from which 3/4 animals recovered, 1 died. (2) Dose of
40-70 mg/kg resulted in syndrome of alternating periods of sedation and alertness.
Acute doses of 200 mg/kg elicited repeated myoclonic jerks, and tonic-clonic
seizures were seen after doses of 300 mg/kg or more. (3) Dose of 40-70 mg/kg
produced sedation and slow wave activity, 100-150 mg/kg produced tonic seizures
and falling spells, 200 mg/kg and greater gave tonic-clonic convulsions.
ANIMALS: 16 Rabbits, NZ White, M, 2.5-3.5 kg, quarantined for 2 wk.
ANIMALS:
Monkeys: (1) Cebus (2) Rhesus (3) Squirrel
PREPARATION AND DOSE
or HISTORY OF PATIENT: 100 mg/kg, one dose.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Varying doses, approx 5-200 mg/kg.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: Serial Sacr 6-12 hr.
EXAM. TYPE: Histology
ROUTE AND SITE:
I.V. or I.P.
CONTROL INFORMATION: Sham inj as well as saline and sodium bicaronate
soln were used as controls. Control inj did not produce
sedative or convulsion effects.
DURATION OF EXPERIMENT: Up to approx 30 min/test
EXAM. TYPE: Electrophysiology, behavior
987
988
-------
COMPOUND:
Proline, 5-oxo-
REFERENCE: Curtis, D.R. and Watkins, J.C.
J. Neurochem. 6:117-141, 1960.
OBSERVED NEUROTOXIC EFFECTS:
Treatment caused excitation or depression of
neuronal activity. Excitatory ranking: glutamic,
g-aminoglutaric, aspartic, cysteic, cysteine-
sulfinic acids, B-hydroxyglutamic, N-methylaspartic,
N-formiminoaspartic acids.
Depressant ranking: B-alanine, GABA, taurine,
N-methyl-B-alanine, 6-amino-B-hydroxybutyric,
glycine, a-alanine, 6-aminovaleric, S-aminoisobutyric
acids.
Structure-activity relationships established.
COMPOUND: 1,2-Propanediol, dinitrate
006423434
REFERENCE: Stewart, R.D., Peterson, J.E., Newton, P.E., Hake, C.L., Hosko, M.J.,
Lebrun, A.J., and Lawton, G.M.
Toxicol. Appl. Phannacol. 30: 377-395, 1974.
OBSERVED NEUROTOXIC EFFECTS: 0.2ppm or more caused headache and disruption of
the visual evoked response. O.Sppm for 6.5 hours
produced impairment in balance.
ANIMALS:
Cats, surgically prepared to exposed motoneurones, Renshaw cells or
dorsal horn interneurones in lumbar cord.
ANIMALS: Human, 19 M aged 22-51 yr, 1 F aged 24 yr
PREPARATION AND DOSE
or HISTORY OF PATIENT: Qualitative doses.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.03 to l.Sppm for 1 to 8 hr
ROUTE AND SITE: Topical, ionophoresis
CONTROL INFORMATION: Laboratory
ROUTE AND SITE: Inhalation
CONTROL INFORMATION: Subjects prior to exposure
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry, electrophysiology
DURATION OF EXPERIMENT:
EXAM. TYPE: Clinical
989
990
-------
COMPOUND' 1,3-Propanediol, 2-methyl-2-propyl-, dicarbamate
000057534
REFERENCE: Meyerowitz, S. and Satran, R.
Neurology 10: 1103-1105, 1960.
COMPOUND: l-Propene-l,l,3-tricarbonltrile, 2-amino-
REFERENCE:
Davenpor t, J. W.
Science 167:1007-1009, 1970.
OBSERVED NEUROTOXIC EFFECTS: The subject exhibited high-voltage fast activity in
his EEC at 28 hr, less at 44 hr, abnormalities at 91 hr,
and persistent occasional slow activity at 14 d.
OBSERVED NEUROTOXIC EFFECTS: Poor performance of closed-field maze tests
during and long after treatment. Eight learning
tests were not helped by treatment with compound.
ANIMALS: Human, 1 M, 19
ANIMALS: Rats, Holtzman, pregnant F d 5 gestation.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Overdose of 160 g
PREPARATION AND DOSE
or HISTORY OF PATIENT: (i) 1.5 g/kg diet.
(2) 1.0 g/kg diet.
Diets fed during gestation and lactation, and to offspring
after weaning until ages 130 or 212 d.
ROUTE AND SITE: Oral
CONTROL INFORMATION: None
ROUTE AND SITE: oral
CONTROL INFORMATION: (1) Control rats with plain mash diet.
(2) 2 grps: plain diet or diet with 1.0 g thiouracil/kg diet.
DURATION OF EXPERIMENT: 14 d
EXAM. TYPE: Clinical, EEC
DURATION OF EXPERIMENT: Until offspring were (1) 130 d -or- (2) 212 d old.
EXAM. TYPE: Behavior
991
992
-------
COMPOUND: Propionic acid, 2-amino-3-hydroxy-, phosphonate, (ester)
COMPOUND: Propionic acid, 2-amino-3-sulfino-, L-
REFERENCE: Olney, J.W., Ho, O.L. and Rhee, V.
Exp. Brain Res. 14:61-76, 1971.
OBSERVED NEUROTOXIC EFFECTS: The compound was toxic to non-neurol components
(glia, etc.), but not to neurons.
REFERENCE:Curtis, D.R. and Watkins, J.C.
J. Physiol. 166:1-14, 1963.
OBSERVED NEUROTOXIC EFFECTS: N-methyl-D-aspartic and D-homocysteic acids were
stronger excitants of depolarization than all
others. With some compounds the action was
prolonged for many seconds after the stimulus
was terminated, notably N-jv-propyl-D-aspartic
acid. There were no differences among types of
neurons tested; structure-activity relationship
was observed.
ANIMALS: Mice, Swiss-webster age 10 d, total 250
PREPARATION AND DOSE
or HISTORY OF PATIENT: Initially 12 rranoles/kg, then range established for
each compound.
ANIMALS: Cats prepared for electrophoretic application of chemicals to single
central nervous system neurons.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Dilutions 0.1-0.5 M of 31 compounds mainly of aspartic,
glutamic and cysteic acids listed in order of
potency of results.
ROUTE AND SITE:
S.C.
CONTROL INFORMATION: Compounds compared with monosodium L-glutamate (MSG)
potency for selectively necrosing neurons in retina
and brain (hypothalamus)
DURATION OF EXPERIMENT: 5 hr or serial intervals including 5 hr.
EXAM. TYPE: Histology
ROUTE AND SITE: Electrophoretic application, various sites in central nervous
system.
CONTROL INFORMATION:
None
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Electrophysiological
993
994
-------
COMPOUND:
Propionic acid, beta-N-oxalyl-L-alpha, beta-diamino
(Lathyrus sativus neurotoxin;
COMPOUND: Propionic acid, beta-N-oxalyl-L-alpha, beta-diamino-
REFERENCE:
Cheema, P.S., Padmanaban, G. and Sarma, P.S.
J. Neurochem. 18:2137-2144, 1971.
REFERENCE: Rao, S.L.N. and Sanaa, P.S.
Biochera. Pharm. 16: 218-220, 1967,
OBSERVED NEUROTOXIC EFFECTS:
Lathyrism involves tremors and convulsions.
Increases of brain adenylic acid deaminase,
glutaminase, transglutaminase, acid protease,
aspartate-a-ketoglutarate transaminase, and aspartate-
pyruvate transaminase were found; glutamate
dehydrogenase was diminished slightly; glutamine
synthetase was unchanged. Authors concluded that
ODAP-induced protein degradation might have liberated
excess ammonia.
OBSERVED NEUROTOXIC EFFECTS: Ataxia and paralysis
ANIMALS: Rats (breed ns.), aged 12 d, 15-20 g
PREPARATION AND DOSE
or HISTORY OF PATIENT:
1.4 mmol/kg in saline
ANIMALS: Cockerels, adult, 650-750 g
Rats, Adult, 100-120 g
Mice, adult, 30-35 g
A monkey, M, 1.5 kg
PREPARATION AND DOSE
or HISTORY OF PATIENT: Prepared cockerels, 100 mg of compound (controls aspartic acid)
Rats and mice: 500 mg/kg
Monkey: 200 mg
ROUTE AND SITE: i.p.
CONTROL INFORMATION: Vehicle only
ROUTE AND SITE: I.P.
CONTROL INFORMATION: Yes, but no details
DURATION OF EXPERIMENT: 7 or 60 min after treatment
EXAM. TYPE: Biochemistry
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Behavior, biochemistry
995
996
-------
COMPOUND: Propionitrile, 3-diamino-
REFERENCE: Hartmann, H.A. and Stitch, H.F.
Science 125:445, 1975.
COMPOUND: Propionitrile, 3,3'-iminodi-
000111944
REFERENCE: Chou, S-M. and Hartmann, H.A.
Acta Neuropath. 3: 428-450, 1964.
OBSERVED NEUROTOXIC EFFECTS: Hyperactivity and abnormal movements in rats for
next 5 mo., mice became "waltzing"; birds hyperactive and moved abnormally;
fish brief hyperactivity and abnormal posture, reevokable later; grass-
hoppers leapt further and tetrahymena migrated faster than normal.
OBSERVED NEUROTOXIC EFFECTS: No deaths; waltzing syndrome and body weight loss
within 48 hr of last dose, many symptoms persisted for 1 yr. Affected
nerves: brain-stem least myelinated large neuron axons in reticular system,
Vlllth nerve nuclei, cord anterior horns, cranial nerves, especially neurons
in which enzyme transport depends on axonal flow. Good correlation between
behavior and histology.
Grasshoppers (Melanopus
Protozoan (Tetrahymena)
ANIMALS: Rats: S-D - 200 g, Long-Evans - 280 g.
Mice: Albino
Birds: (Melopsittacus undulatus)
Fish: (Lepomus gibbosus)
PREPARATION AND DOSE
OP HISTORY OF PATIENT: Rats 0.1-10 g/kg one dose; mice 1.5-2 g/kg one dose;
Birds 2 g/kg; fish 2 g/kg; grasshoppers 1-2 g/kg;
Tetrahymena 0.01% in medium.
ANIMALS: 40 rats, S-D, M, 200 g
PREPARATION AND DOSE
or HISTORY OF PATIENT: 2 g/kg (in one dose or in 4 doses at 3-d intervals) in buffer
ROUTE AND SITE: Rats, mice, birds: I.P. Fish and grasshoppers: intraabdominal
CONTROL INFORMATION: ns.
ROUTE AND SITE: i.p.
CONTROL INFORMATION: Mentioned, not described
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior
DURATION OF EXPERIMENT: Serial sacr 2 d to 6 mo (1 yr observation of some)
EXAM. TYPE: Behavior, histology
997
998
-------
COMPOUND: Propionitrile, 3,3'-iminodi-
000111944
REFERENCE: Chou, S-M and Hartmann, H.A.
Acta Neuropath. 4:590-603, 1965.
OBSERVED NEUROTOXIC EFFECTS: All developed waltzing syndrome. Electron-
microscopical description of axonal balloon lesions: edema and degeneration.
ANIMALS: 5 Rats, S-D, M, 100-200 g.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.5 g/kg every 3 d for 6 doses.
ROUTE AND SITE: i.p.
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: Serial sacr 6-11 wk.
EXAM. TYPE: Behavior, histology
999
COMPOUND: Propionitrile, 3,3'-iminodi-
REFERENCE: Hartmann, H.A., Lalich, J.J. and Akert, K.
J. Neuropath. Exp. Neurol. 17:298-304, 1958.
OBSERVED NEUROTOXIC EFFECTS: After 3-4 wk characteristic jerking and rotational
movements of heads. After 8 wk ataxia and paresis of the hind-limb.
Degeneration of intraspinal axons of the anterior motor horn cells.
ANIMALS: 12 Rats, S-D, 75 g.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 20 mg/rat/d in diet
ROUTE AND SITE: Oral
CONTROL INFORMATION: 12 rats unttd.
DURATION OF EXPERIMENT: Serial sacr 9, 12, 15 wk
EXAM. TYPE: Behavior, histology
1000
-------
COMPOUND: Propionltrile, 3,3'-iminodi-
000111944
REFERENCE: Slagel, D.E. and Hartmann, H.A.
J. Neuropath. Exp. Neurol. 24(4): 599-620, 1965.
COMPOUND: Propionitrlle, 3,3'-iminodi-
000111944
REFERENCE: Tews, J.K., Kopf, G.M. and Stone W.E.
Int. J. Neuropharmacol. 7: 29-34, 19681
OBSERVED NEUROTOXIC EFFECTS: Extensor hypertonus of neck and forelimb, retro-
pulsion, choreoathetotic head movements, rapid circling. Axonal swelling
in brain and cord; lateral and medial vestibular nuclei, caudal pontine
reticular nucleus, ventral horn (lumbar, thoracic and cervical); spinal,
accessory, hypoglossal, vagus, parafacial, abducens, motor Vth, mesen-
cephalic Vth, trochlear, and oculomotor nuclei. Neurology and behavior
were correlated.
OBSERVED NEUROTOXIC EFFECTS:
(1) Brains analyzed for 30 (total) free amino acids and
other compounds showed only (a) low valine, and (b)
a tendency toward increased phosphorylation of nucleosides
(more triphosphates, less diphosphates).
(2) and (3) Cats and dogs showed no hyperactivity but
ataxia, depression, anorexia and retropulsion. EEC
changes in cats were not related to clinical symptoms.
ANIMALS: (1) 7 mice, Swiss Webster, (2) 14 mice
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.2 g/ml in 0.9% saline pH 7.0 (HC1), 2-3 g/kg, 4-9 doses.
ANIMALS: (1) Mice, Rolfsmeyer, F, 7-8 wk old
(2) Cats, surgically prepared
(3) Three Dogs
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) Hyperactivity doses of 3 g/kg and up
(2) Mostly single doses 200-400 mg/kg
(3) 100-300 mg/kg
ROUTE AND SITE: Injections
CONTROL INFORMATION: 7 controls, saline only; (2) 10 mice
ROUTE AND SITE: (1) S.C.; (2) I.P.; (3) ns
CONTROL INFORMATION: (1) Untreated (2, 3) ns
DURATION OF EXPERIMENT: 4-10 wk
EXAM. TYPE: Behavior; histology
DURATION OF EXPERIMENT: 7-11 d
EXAM. TYPE: (1) Biochemistry; (2) EEC; (3) Behavior
1001
1002
-------
COMPOUND: Pronionitrlle, 3,3'-iminodi-
000111944
REFERENCE: Vivanco, F., Busturia, M.A., Ramos, F. and Sanchez-Martin, J.A.
J. Neurochem. 19:563-565, 1972.
OBSERVED NEUROTOXIC EFFECTS: Cyanoacetic acid (metabolite of compound)
in plasma and brain of poisoned rats lower than in
thyroxine-protected rats. Thyroxine rats excreted
more metabolite in urine.
COMPOUND: Propyl alcohol (Propanol)
000071238
REFERENCE: Roach, M.K.> Davis, D.L., Pennington, W. and Nordyke, E.
Life Sci. 12(1):433-441, 1973.
OBSERVED NEUROTOXIC EFFECTS:
Propanol inhibited active transport of probable
neurotransmitters of the central nervous system
by synaptosomes. Authors conclude that alcohol
interacts with membrane lipids of synaptosome.
ANIMALS: 27 Rats, M, 100-150 g.
ANIMALS: Rats, S-D, M, 200-250 g, brains removed and homogenates incubated in vitro.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 60 mg/rat/d, for 2 d (15 rats)
PREPARATION AND DOSE
or HISTORY OF PATIENT: Propanol added as 25% soln, at start of preincubation period.
Propanol cone 5-30 mg/ml. Incubated in vitro with labeled
norepinephrine, GABA and glutamate.
ROUTE AND SITE: s.C.
CONTROL INFORMATION: 12 rats pretreated with 0.2 mg/d Na-L-thyroxinate for 5 d
ROUTE AND SITE: in vitro
CONTROL INFORMATION: Control: incubation in medium with no alcohol.
DURATION OF EXPERIMENT: 3 d (1 d after last dose of compound)
EXAM. TYPE: Biochemistry
DURATION OF EXPERIMENT: Laboratory procedure.
EXAM. TYPE: Biochemistry
1003
1004
-------
COMPOUND: Propylamlne
000107108
REFERENCE: Curtis, D.R. and Watkins, J.C.
J. Neurochem. 6:117-141, 1960.
OBSERVED NEUROTOXIC EFFECTS:
Treatment caused excitation or depression of
neuronal activity. Excitatory ranking: glutamic,
6-aminoglutaric, aspartic, cysteic, cysteine-
sulfinic acids, $-hydroxyglutamic, N-methylaspartic,
N-formiminoaspartlc acids.
Depressant ranking: 6-alanine, GABA, taurine,
N-methyl-B-alanine, 6-amino-B-hydroxybutyric,
glycine, a-alanine, 6-aminovaleric, B-aminoisobutyric
acids.
Structure-activity relationships established.
COMPOUND: Pseudomona tabaci exotoxin .
REFERENCE: Sinden, S.L. Durbin, R.D., and Uchytil, T.F.
Toxic. Appl. Pharmac. 14: 82-88, 1969.
OBSERVED NEUROTOXIC EFFECTS: (1) Severe convulsions with minimal dose of 0.025 mmole/kg
I.P.; became uncoordinated; and then spastic.
(2) Severe convulsions with minimal dose .0003 mmoles/kg
in rats intracisternally.
ANIMALS:
Cats, surgically prepared to exposed motoneurones, Renshaw cells or
dorsal horn interneurones in lumbar cord.
ANIMALS: (1) Mice, weanling SW, lOg
(2) Rats, Holtzman, 135g
PREPARATION AND DOSE
or HISTORY OF PATIENT: Qualitative doses.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.5 ml toxin soln (methanol extracts of concentrated culture
filtrate 3% pure by weight) and doses of 0.0125-0.3 mmoles/kg
I.P. ; 0.00015-0.0006 mmoles/kg intracisternally. Doses were
heated.
ROUTE AND SITE: Topical, ionophoresis
CONTROL INFORMATION: Laboratory
ROUTE AND SITE: I.P. and intracisternally
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry, electrophysiology
DURATION OF EXPERIMENT: .1-12 hrs I.P.; 10-20 mins intracisternally
EXAM. TYPE: Behavior
1005
1006
-------
COMPOUND: 3-Pyridenecarboxamide, 6-amlno-
000329895
REFERENCE: Chamberlain, J.G.
Teratology 3:377-388, 1970.
OBSERVED NEUROTOXIC EFFECTS: Central nervous system and growth retardation at
24 hr, with fluid movement into ventricles. Normal pressure by d 21,
and evidence of early hemorrhage nearly gone.
COMPOUND: 3-Pyridenecarboxamide, 6-amino-
000329895
REFERENCE: Turbow, M.M., Clark, W.H., and DiPaolo, J.A.
Teratology 4:427-432, 1971.
OBSERVED NEUROTOXIC EFFECTS: Multiple defects: exencephaly, anophthalmia
and hydrocephalus. Day 8 and 9 embryos responded to 5 meg, day 7
embryos needed 50-100 meg.
ANIMALS: Rats, Long-Evans, F, av 100 d old, 225 g, bred with males.
ANIMALS: Hamsters, F, 8-12 wk age
PREPARATION AND DOSE
or HISTORY OF PATIENT: 8 mg/kg on d 13, single dose.
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) 5-100 meg in 5 or 10 mcl water to 1/2 or 1/3 of
implantation sites once during d 7-9 of pregnancy; remaining sites given one
of 3 control treatments.
(2) 8 mg/kg once during d 7-9 of pregnancy.
ROUTE AND SITE: I.p.
CONTROL INFORMATION: Controls fasted or given sterile H20, i.p.
ROUTE AND SITE: (1) Intraamniotic inj.
(2) I.P.
CONTROL INFORMATION: Implanted embryos given 5 mcl water, needle-puncture
only, or no treatment. In one group all implantations were so treated.
DURATION OF EXPERIMENT: Serial sacr .25 to 8 d after dose.
EXAM. TYPE: Histology, biochemistry
DURATION OF EXPERIMENT: 14 d.
EXAM. TYPE: Teratological
1007
1008
-------
COMPOUND: 3-Pyridenecarboxamide, 6-amino-
000329895
REFERENCE: Chamberlain, J.G. and Nelson, M.M.
Teratology 3(4):285-292, 1970.
OBSERVED NEUROTOXIC EFFECTS: Cellular changes in fetal brains 24 hr after dose.
Hydrocephalus frequent. Prevented by equal
injections of nicotinamide.
ANIMALS: Rats, Long-Evans, F, age 100 d, 225 g, bred. One group treated
d 9-20 of pregnancy.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 8 mg/kg, 1 dose in water.
ROUTE AND SITE: i.p.
CONTROL INFORMATION: 14 rats received water, i.p.
DURATION OF EXPERIMENT: 21 d
EXAM. TYPE: Teratological
1009
COMPOUND: 3-Pyridenecarboxamide, 6-amino-
000329895
REFERENCE: wolf, A., and Cowen, D.
Bull. N.Y. Acad. Med. 35:814-816, 1959.
OBSERVED NEUROTOXIC EFFECTS: Progressive limb weakness starting in hindlimbs and
extending to other muscles, speed of onset dose-related, no convulsions;
grey-matter of cord (not white-matter or PNS), focal lesions of geniculate
bodies, thalamus and corpus striatum; degeneration of axons and myelin
(rats). Additional degeneration of brain cortex and sciatic nerve (cats).
. Similar lesions to rats (dogs).
ANIMALS: 15 rats, 4 cats, 2 dogs, and additional rats.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 8 mg/kg (16 rats), 16-64 mg/kg (additional rats), 30
mg/kg (cats) - all single doses. 4 mg/kg "repeatedly" (dogs)
ROUTE AND SITE: I.P. (rats), I.V. or I.P. (cats), I.V. (dogs)
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: Serial sacr to 10 d (rats and dogs) or 20 d (cats)
EXAM. TYPE: Behavior, histology
1010
-------
COMPOUND: Pyrldine, 2-((2-(dimethylamino)ethyl)(p-methoxybenzyl)amino)-,
maleate (1:1)
REFERENCE: Qulnton, R.M.
Br. J. Pharmac. 21:51-66, 1963.
COMPOUND: 3-Pyridinemethanol, 5-hydroxy-4,6-dimethyl-, hydrochloride (4-Deoxypyridoxine HCL'.
000148516
REFERENCE' Horton, R.W. and Meldrum, B.S.
Br. J. Pharmac. 49: 52-63, 1973.
OBSERVED NEUROTOXIC EFFECTS: The compound enhanced the effect of Yohimblne
and lowered its lethal dosage.
OBSERVED NEUROTOXIC EFFECTS:
Seizures, photic stimulation, EEC changes, inhibition
of brain glutamate carboxylase were caused by 3-mer-
captopropionic acid more strongly than by allylglycine
or 4-deoxypyridoxine HC1. Thus the authors concluded
that seizures were due to depletion of glycine and y-
aminobutyric acid (GABA).
ANIMALS:
Mice, TT, M, 18-25 g.
ANIMALS: Mice, CFW or BALB/C, M, 20-30 g
10 Baboons (Papio papio), adolescent, from Senegal, 3-6 kg
PREPARATION AND DOSE
or HISTORY OF PATIENT:
ED5Q >50 mg/kg
ED,- = dose producing a 50% mortality of mice injected
S.C. with yohimbine hydrochloride (20 mg/kg).
PREPARATION AND DOSE
or HISTORY OF PATIENT: Mice: ED5Q and latency 1.1 mmole/kg, 42.3 min.
Baboons: ED__ and latency 0.53 mmol/kg, 46 min.
ROUTE AND SITE: S.C., Oral
CONTROL INFORMATION: Various
ROUTE AND SITE: Mice I.P., Baboons I.V.
CONTROL INFORMATION: Timed studies
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Behavior, electrophysiology, biochemistry
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Mice: behavior, biochemistry; baboons: polygraph.
1011
1012
-------
COMPOUND: Pyridinium, 2-formyl-l-methyl-, chloride, oxime
REFERENCE: Crook, J.W., Cresthull, P., O'Neil, H.W. and Oberst, F.W.
Tox. Appl. Pharm. 6: 310-315, 1964,
OBSERVED NEUROTOXIC EFFECTS: Occasional ataxia, collapse, tremors in dogs, no
changes in red-cell cholinesterase, no signs in
rabbits, no pathology by photomicroscopy.
ANIMALS: 3 mongrel dogs, 7-11 kg
5 white rabbits, ca. 2.5 kg
PREPARATION AND DOSE
or HISTORY OF PATIENT: Dogs: 25 mg/kg twice daily, 5 d/w for 6 w
Rabbits: 50 mg/kg/d, 5d/w for 6 w
ROUTE AND SITE: I.V.
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: 6 wk
EXAM. TYPE: Behavior, blood tests, autopsy
1013
COMPOUND:
Pyridinium, 2-formyl-l-methyl-, methanesulfonate, oxime
REFERENCE: Crook, J.W., Cresthull, P., O'Neil, H.W. and Oberst, F.W.
Tox. Appl. Pharm. 6:310-315, 1964.
OBSERVED NEUROTOXIC EFFECTS: Occasional ataxia, collapse, tremors in dogs,
no changes in red-cell cholinesterase, no signs
in rabbits, no pathology by photomicroscopy.
ANIMALS:
3 mongrel dogs, 7-11 kg
5 white rabbits, ca. 2.5 kg
PREPARATION AND DOSE
or HISTORY OF PATIENT: Dogs: 25 mg/kg twice daily, 5 d/w for 6 w
Rabbits: 50 mg/kg/d, 5d/w for 6w
ROUTE AND SITE: i.v.
CONTROL INFORMATION:
None
DURATION OF EXPERIMENT: 6 wk
EXAM. TYPE: Behavior, blood tests, autopsy
1014
-------
COMPOUND:
(3H-Pyrido-(3,4-b)indole, 4,9-dihydro-7-methoxy-l-methyl-
000304212
REFERENCE: Rivier, L. and Lindgren, J-E.
Econ. Bot. 26: 101-129, 1972•
OBSERVED NEUROTOXIC EFFECTS: Hallucinatory (visual)
COMPOUND:
9H-Pyrido(3,4-b)indole,-7-methoxy-l-methyl-
000442513
REFERENCE: Rivier, L. and Lindgren, J-E.
Econ. Bot. 26: 101-129, 1972.
OBSERVED NEUROTOXIC EFFECTS: Hallucinatory (visual)
ANIMALS:
Humans: anecdotal and personal experiences
ANIMALS:
Humans: anecdotal and personal experiences
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Identification and quantitation analyses, still not complete
as reported, indicate that 200 ml of drink (normal dose)
includes 30 mg harmine, 10 mg TH-harmine and 25 mg DMT
(relative amounts in separate ingredients found to be
different), taken up to 10 times/mo or more.
ROUTE AND SITE: oral
CONTROL INFORMATION: None
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Identification and quantitation analyses, still not complete
as reported, indicate that 200 ml of drink (normal dose)
Includes 30 mg harmine, 10 mg TH-harmine and 25 mg DMT
(relative amounts in separate ingredients found to be
different), taken up to 10 times/mo or more.
ROUTE AND SITE: oral
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: Expedition, duration ns
EXAM. TYPE: Behavior, analytical chemistry
DURATION OF EXPERIMENT: Expedition, duration ns
EXAM. TYPE: Behavior, analytical chemistry
1015
1016
-------
COMPOUND: 9H-Pyrido(3,4-b) indole, 7-methoxy-l-methyl-, hydrochloride
COMPOUND:
9H-Pyrido(3,4-b)indole, l,2,3,4-tetrahydro-7-methoxy-l-methyl
REFERENCE: Spooner, C.E. and Winters, W.D.
Int. J. Neuropharmacol. 5: 217-236, 1966
OBSERVED MEUROTOXIC EFFECTS: Compound produced excitement, abnormal postures,
arousal EEGs, then depression.
REFERENCE: Rlvier, L. and Llndgren, J-E.
Econ. Botw 26: 101-129, 1972.
OBSERVED NEUROTOXIC EFFECTS: Hallucinatory (visual)
ANIMALS: 200 Cockerels, White Leghorn, ages 5-14 d, 45-100 g
ANIMALS: Humans: anecdotal and personal experiences
PREPARATION AND DOSE
or HISTORY OF PATIENT: 10-50 mg/kg
ROUTE AND SITE: S.C. near axillary vein; I.P. for doses over 0.05 ml
CONTROL INFORMATION: ns
PREPARATION AND DOSE
or HISTORY OF PATIENT: Identification and quantltation analyses, still not complete
as reported, indicate that 200 ml of drink (normal dose)
Includes 30 mg harmine, 10 mg TH-harmine and 25 mg DMT
(relative amounts in separate ingredients found to be
different), taken up to 10 times/mo or more.
ROUTE AND SITE: oral
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Behavior, EEC
DURATION OF EXPERIMENT: Expedition, duration ns
EXAM. TYPE: Behavior, analytical chemistry
1017
1018
-------
COMPOUND:
9H-PyrIdo(3,4-b)indole, 1,2,3,4-tetrahydro-2-methy1-
COMPOUND:
9H-Pyrido(3,4-b)indol-7-ol, 1-methyl-
REFERENCE: Rlvier, L. and Lindgren, J-E.
Econ. Bot. 26: 101-129, 1972.
REFERENCE: Rlvier, L. and Lindgren, J-E.
Econ. Bot. 26: 101-129, 1972.
OBSERVED NEUROTOXIC EFFECTS: Hallucinatory (visual)
OBSERVED NEUROTOXIC EFFECTS: Hallucinatory (visual)
ANIMALS:
Humans: anecdotal and personal experiences
ANIMALS:
Humans: anecdotal and personal experiences
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Identification and quantitation analyses, still not complete
as reported, indicate that 200 ml of drink (normal dose)
includes 30 mg harmine, 10 mg TH-harmine and 25 mg DMT
(relative amounts in separate ingredients found to be
different), taken up to 10 times/mo or more.
ROUTE AND SITE: oral
CONTROL INFORMATION: None
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Identification and quantitation analyses, still not complete
as reported, indicate that 200 ml of drink (normal dose)
includes 30 mg harmine, 10 mg TH-harmine and 25 mg DMT
(relative amounts in separate ingredients found to be
different), taken up to 10 times/mo or more.
ROUTE AND SITE: oral
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: Expedition, duration ns
EXAM. TYPE: Behavior, analytical chemistry
DURATION OF EXPERIMENT: Expedition, duration ns
EXAM. TYPE: Behavior, analytical chemistry
1019
1020
-------
COMPOUND: Pyridoxol hydrochloride
COMPOUND: Pyridoxol, methoxy-
REFERENCE: Alder, S. and Zbinden, G.
Agents and Actions 3/4: 233-243, 1973.
OBSERVED NEUROTOXIC EFFECTS: Irritability after 1 wk on 2 x 500 mg/kg. Hot Plate
Test positive after 8-18 d and on day 25 (500 mg level);
Foot Print Test ns, but Rotating Rod Test was failed by
rats on 500 mg level. Sciatic nerve degeneration seen
after 10 x 500 mg doses, no changes in brain and cord,
moderate effects on bone-marrow.
REFERENCE: Purpura, D.P. and Gonzalex-Monteagudo, 0.
J. Neuropath. Exp. Neurol. 19(3):421-432, 1960.
OBSERVED NEUROTOXIC EFFECTS: Generalized seizures in 30-45 min, monitored by EEC
recorded epidurally from neocortex. Hippocampal pyramidal neurons damaged
within 2 hr (shrunken with loss of internal structure). In Ammon's horn
CA--CAi(endblade) neurons altered selectively. Same sort of changes also
seen at 6 hr after dose.
ANIMALS: Rats, CFN Zu, F, 38-53g, 6 groups 10-12 each
ANIMALS: 51 Cats, adult, 2.4 kg.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 100, 250, 500 mg/kg, 5d/wk, 2 groups/level, 5-40 doses
PREPARATION AND DOSE
or HISTORY OF PATIENT: 18 cats given 50 mg/kg.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: 2 groups saline I.P.
ROUTE AND SITE: i.v.
CONTROL INFORMATION: 32 controls given various treatments.
DURATION OF EXPERIMENT: Serial sacr 1-8 wk
EXAM. TYPE: Behavior, histology
DURATION OF EXPERIMENT: Observation 2-6 hr after dose, then sacr.
EXAM. TYPE: Behavior; histology.
1021
1022
-------
COMPOUND: 4-Pyrimidinecarboxylic acid. l,2,3,6-tetrahydro-2,6-dioxo-5-fluoro-
COMPOUND: 4-Pyrimidinecarboxylic acid, l,2,3,6-tetrahydro-2,6-dioxo-5-fluoro-
REFERENCE: Koenig, H.
Science 127:1238-1239, 1958.
REFERENCE: Kury, G. and Craig, J.M.
Arch. Path. 81: 166-173, 1966.
OBSERVED NEUROTOXIC EFFECTS: Severe ataxia of trunk and extremities, fatal
in some. Not seen in "control studies".
Advanced chromatolysis of Purkinje cells of
cerebellum.
OBSERVED NEUROTOXIC EFFECTS: Exencephaly with severe brain malformations, neuraxis
with necrotic neuroblasts. Microphthalmia and necrotic
neurons in neuraxis.
ANIMALS: Cats
ANIMALS: Eggs, White Leghorn, fertilized
PREPARATION AND DOSE
or HISTORY OF PATIENT: 3-10 mg, one dose, in some cases repeated to make
total of 5-15 mg (per cat).
PREPARATION AND DOSE
or HISTORY OF PATIENT: Teratogenic dosage schedules, from d 1 to d 4
ROUTE AND SITE: Intracisternal
CONTROL INFORMATION: Not described, except that orotic acid and i.p. injections
were mentioned as "control studies".
ROUTE AND SITE: Inoculation
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior, histology (incomplete at time of writing).
DURATION OF EXPERIMENT: 21 d
EXAM. TYPE: Teratological
1023
1024
-------
COMPOUND: 4,6(lH,5H)-Pyrimidinedlone, 5-ethyldlhydro-5-phenyl- (Primidone)
000125337
REFERENCE: Brillman, J., Gallagher, B.B. and Mattson, R.H.
Arch. Neurol. 30:255-258, 1974.
OBSERVED NEUROTOXIC EFFECTS: Central Nervous System depression and disequilibrium,
due "mostly" to primidone itself, rather than its metabolites phenobarbital
and/or phenylethylmalonamide.
COMPOUND: Pyrocatechol, 4-(2-aminoethyl)-5.-hydroxy-
REFERENCE: Sachs, C. and Jonsson, G.
Res. Comm. Chem. Path. Pharm. 4: 203-220, 1972.
OBSERVED NEUROTOXIC EFFECTS: Compound produced a permanent, though incomplete,
chemical sympathectomy. The compound penetrated the
blood-brain barrier in newborn animals and depressed
norepinephrine uptake by selected nerves. Cortex and
cord neurons were more susceptible than those in the
hypothalamus.
ANIMALS: 2 Human cases of overdose, 1M age 51 an epileptic, 1 F age 18.
ANIMALS: Rats, S-D, newborn
Mice, N.M.R.I., newborn
PREPARATION AND DOSE
or HISTORY OF PATIENT: Male: estimated intake 5 g; Female: 22.5 g in 12 hr.
Commercial preparation.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 100 mg/kg in sodium chloride
0.05 ml per rat or mouse within 4 hr of birth and at 24-hr
intervals for 3 doses
ROUTE AND SITE: Oral
CONTROL INFORMATION:
ROUTE AND SITE: s.C.
CONTROL INFORMATION: Matched controls
DURATION OF EXPERIMENT: Male 23 d, Female 7 d.
EXAM. TYPE: Behavior, clinical laboratory
DURATION OF EXPERIMENT: 10-14 wk
EXAM. TYPE: Biochemistry
1025
1026
-------
COMPOUND: Pyrocatechol, 4-(2-aininoethyl)-5-hydroxy~
COMPOUND: Pyrocatechol, 4-(2-aminoethyl)-5-hydroxy-
REFERENCE: Simon, H., LeMoal, M., Galey, D. and Cardo, B.
Exp. Brain Res. 20: 375-384, 1974.
OBSERVED NEUROTOXIC EFFECTS: Treatment caused terminal degeneration in nucleus
caudatus-putamen or nucleus accumbens, depending on
injection site.
REFERENCE: Votavova, M., Boullin, D.J. and Costa, E.
Life Sci. 10(1):87-91, 1971.
OBSERVED NEUROTOXIC EFFECTS: Noradrenaline depleted in peripheral neurons,
5-HT not affected. Author's conclude failure
to affect 5-HT indicates that indolylalkylamine
is definitely not present in sympathetic nerves.
ANIMALS: 9 rats, S-D, no other details
ANIMALS: Cats, F, 2.5-4.5 kg.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.5 and 1 meg
PREPARATION AND DOSE
or HISTORY OF PATIENT: 20 mg/kg, in 0.5 ml soln containing 6 mg/ml ascorbic acid,
followed after 14 d with 50 mg/kg. 200,000 I.U. of
procaine penicillin, i.m., followed each inj.
ROUTE AND SITE: Injection into ventral mesencephalic tegmentum
CONTROL INFORMATION: ns
ROUTE AND SITE: I.V.
CONTROL INFORMATION: 5 cats inj with ascorbic acid.
DURATION OF EXPERIMENT: 3d
EXAM. TYPE: Histology
DURATION OF EXPERIMENT: 21 d
EXAM. TYPE: Biochemistry
1027
1028
-------
COMPOUND: Pyrophosphoric acid, tetraethyl ester
000107493
COMPOUND: Pyrrole, 2,4-dimethyl-3-ethyl-
REFERENCE: Rayner, M.D., Popper, J.S., Carvalho, E.W. and Hurov, R.
Res. Comm. Chem. Path. Pharm. 4: 595-606, 1972,
OBSERVED NEUROTOXIC EFFECTS: The force generated by the achilles tendon reflex was
subnormal in exposed subjects. The authors suggest
that this hyporeflexia may be a sensitive indicator of
chronic exposure to organophosphates.
REFERENCE: Walker, J.L.
Phannac. Biochem. Behav. 3: 243-250, 1975.
OBSERVED NEUROTOXIC EFFECTS: Treatment caused ataxia, hyperventilation, locomotor
depression and catalepsy. EEC teats showed low frequency
hypersynchronous changes intermittent with acute asyn-
chronous spiking activity. The author concluded that the
compound caused major central nervous system dysfunction
on the lines of drug-induced psychoses.
ANIMALS:
Humans, Japanese ancestry, M, ages 22-59 (orchid farmers)
ANIMALS: Rats, hooded, 311-465 g, total 10, surgically prepared
PREPARATION AND DOSE
or HISTORY OF PATIENT: Exposure of more than 4 hr/d, 2 d/wk, 52 wk/yr for 5 yr except
one case (2 yr). Other types of pesticide also used, but
authors judged organophosphates exposures to be primary.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 10-90 mcl/kg (9.1-82 mg/kg) per d for up to 8 d
ROUTE AND SITE: Skin contact, inhalation
CONTROL INFORMATION: Matched non-exposed subjects, so far as could be ascertained
ROUTE AND SITE: I.P.
CONTROL INFORMATION: Pre-drug data
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Physiological
DURATION OF EXPERIMENT: Up to 8 d
EXAM. TYPE: Behavior, EEC, histology
1029
1030
-------
COMPOUND:
3-Pyrrolidine acetic acid, 2-carboxy-4-isopropenyl
REFERENCE: Olney, J.W., Rhee, V. and Ho, O.L.
Brain Res. 77:507-512, 1974.
COMPOUND: Pyrrolidine, l,l-(2-butynylene) di-
000051730
REFERENCE: Brumlik, J. and Means, E.D.
Brain 92:157-190, 1969.
OBSERVED NEUROTOXIC EFFECTS:
Convulsions: infants from 15 mln, some at 1 mg/kg
s.c., all at 5 mg/kg or more, and orally, some at
3 mg/kg, all at 7 mg/kg or more. Adults s.c., none
at 20 mg/kg, all at 40 mg/kg; orally, some at
40 mg/kg, and 60% at 100 mg/kg. Lesions in arcuate
'nucleus of hypothalamus, some in hippocampus; none
in controls.
OBSERVED NEUROTOXIC EFFECTS:
Tremors compared in detail with those of virus-
induced acute cerebellar ataxia in man and with
parkinsonism.
ANIMALS: 16 litters of mice aged 7 d; 126 adult mice aged 6-8 wk.
ANIMALS: Dogs, F, adult, 3
PREPARATION AND DOSE
or HISTORY OF PATIENT:
1-10 mg/kg (infants), 10-100 mg/kg (adults), 6 animals/dose
and /route, 1 dose/animal.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 5 mg/kg
ROUTE AND SITE: Gavage or s.c.
CONTROL INFORMATION: 6 Infants, 6 adults, NaCl
ROUTE AND SITE: I.P.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: 1-3 hr.
EXAM. TYPE: Behavior, histology
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior, electrophsiology
1031
1032
-------
COMPOUND: Pyrrolidine, 1,1 -(2-butynylene)di-
000051730
REFERENCE: McColl, J.D. and Rice, W.B.
Tox. Appl. Pharm. 4:263-268, 1962.
OBSERVED NEUROTOXIC EFFECTS: ED for producing tremors was 5.8 (4.7-7.1)
mg7fcg.
COMPOUND:
1-Pyrrolidine propanol, alpha-cyclohexyl-alpha-phenyl-
000077372
REFERENCE: pfeiffer, C.C., Murphree, H.B., Jenney, E.H., Robertson, M.G.,
Randall, A.H. and Bryan, L.
Neurology 9: 249-250, 1959.
OBSERVED NEUROTOXIC EFFECTS: The authors concluded that synthetic atropines are more
active hallucinogens than atropine or scopolamine, pro-
ducing effects lasting 24-48 hr. Synthetic antitremor
drugs had fewer peripheral nervous system side-effects,
but central nervous system side-effects (hallucinations)
• •..' , - may have been exaggerated.
ANIMALS: .. Mice, CFW, ,20 g
ANIMALS: Human: prison volunteers, drug-sophisticated, no other details
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Graded doses
PREPARATION AND DOSE
or HISTORY OF PATIENT: 15 mg/man
ROUTE AND SITE: I.P.
CONTROL INFORMATION: Untrtd, trtd with antagonists
ROUTE AND SITE: Oral
CONTROL INFORMATION: LSD-25: 0, 25, 50, 100 meg/man
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior
DURATION OF EXPERIMENT: Up to 3 d
EXAM. TYPE: Opinion of volunteers
1033
1034
-------
COMPOUND- 4(3H)-Quinazolinone, 2-methyl-3-o-tolyl-
000072446
REFERENCE: Geldmacher-Mallinckrodt, M. and Lautenbach, L.
Arch. Toxikol. 20:31-37, 1963.
COMPOUND: 4(3H)-Quinazolinone, 2-methyl-3-o-tolyl-
000072446
REFERENCE:
Marks, P.
Practitioner 212:
721-722, 1974.
OBSERVED NEUROTOXIC EFFECTS: Case 1 died after 40 hr, case 2 made a slow
recovery, case 3 recovered in 48 hr. Clonic
convulsions noted.
OBSERVED NEUROTOXIC EFFECTS:
The subject experienced "glove" paresthesia and
weakness of hands and loss of tendon reflexes from
immediately after the first dose. Tendon reflexes
returned in 24 hr after cessation of intake, sen-
sations in 24 hr, power in 36 hr, and paresthesias
disappeared after 48 hr. Conclusion: bilateral
symmetrical peripheral neuropathy of mixed type,
reversible.
ANIMALS: Humans: 3 cases of overdoses.
ANIMALS: Human: one case, M, 50
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) M, 25, took 20 tablets, total 8 g; (2) M, 26 took 60
tablets; (3) F, 24, took 20 tablets.
PREPARATION AND DOSE
or HISTORY OF PATIENT: History noncontributory. 250 mg/night for sleeping.
4 nights.
ROUTE AND SITE: Oral
CONTROL INFORMATION: Hone
ROUTE AND SITE: Oral
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Clinical
DURATION OF EXPERIMENT: 6 d
EXAM. TYPE: Clinical
1035
1036
-------
COMPOUND: Quinine, monohydrochloride
000130892
REFERENCE: Hoffmann, F.A.
Archiv. Exp. Path. Pharm. (Berlin) 17: 363-366, 1883.
OBSERVED NEUROTOXIC EFFECTS: The injections produced convulsions, which the author
attributed to a central nervous system reaction.
COMPOUND: Quinolines, 8-amino- (not specified)
REFERENCE: Udall, V.
Proc. Roy. Soc. Med. 65: 197-199, 1972.
OBSERVED NEUROTOXIC EFFECTS: Functional blindness, no retinal damage, extensive
brain damage including lateral geniculate nucleus.
ANIMALS: Humans: used to reduce pyrexia of typhus, 2 cases of adverse reactions
ANIMALS: Monkeys, rhesus or cynomolgus
PREPARATION AND DOSE
or HISTORY OF PATIENT: 1.8 .grains; 2 doses of 40 and 60 grains
PREPARATION AND DOSE
or HISTORY OF PATIENT: ns, used against malaria
ROUTE.AND SITE: i.v.
CONTROL INFORMATION: None
ROUTE AND SITE: Oral
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Clinical
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Histology
1037
1038
-------
COMPOUND: Quinoline, 7-chloro-4-(4-diethylamino-1-methy1-butylamino)-diphosphate
000050635
REFERENCE: Klinghardt, G.W.
Acta Neuropath. 28: 117-141, 1974
COMPOUND: Quinoline, 7-chloro-4((4-(diethyl amino) -l-methylbutyl)amino)-
00054057
REFERENCE:
Tischner, K.H.
Acta Neuropath. 22:208-221, 1972.
OBSERVED NEUROTOXIC EFFECTS: "Neuronal storage dystrophy:" mainly in posterior
root and trigeminal ganglia. Some differences between rats and rabbits.
Axonal dystrophy in central nervous system. Myelin breakdown in peripheral
nervous system. Considered due to phospholipidosis.
OBSERVED NEUROTOXIC EFFECTS: Perikarya contained many multilamellated bodies;
also found in Schwann cells, fibroblasts and axons; myelin lamellae were
split and degenerated; in 10% of neurons nuclei had 2 types of granular
inclusions and the nucleoli could not be found but nucleolar satellites
persisted (claimed as a new finding).
ANIMALS: (D Rats, Wistar-Stamm, 100-200 g or 40-50 g
(2) 14 Rabbits, 0.9-1.4 kg
ANIMALS: Dorsal root ganglia from Wistar fetal rat in culture.
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) 250, 375 mg/kg/d, estimated uptake 200 mg/kg/d
(2) 100-165 mg/kg/d
PREPARATION AND DOSE
or HISTORY OF PATIENT: 2 x 10 M in media for 6-21 d
ROUTE AND SITE: Gavage
CONTROL INFORMATION: None found (full translation not performed)
ROUTE AND SITE: in vitro.
CONTROL INFORMATION: Laboratory controls
DURATION OF EXPERIMENT: 47-290 d (rats); 138 d (rabbits).
EXAM. TYPE: Histology, histochemistry
DURATION OF EXPERIMENT: 6-21 d
EXAM. TYPE: Microscopy
1039
1040
-------
COMPOUND' Quinoline, 8-((4-diethylamino)-l-methylbutyl) amino)-6-methoxy-
REFERENCE: D'Agostino, A.N.
Neurology 14: 114-124, 1964.
OBSERVED NEUROTOXIC EFFECTS: Focal degeneration of (a) neurons, with loss of Nissl
substance, mitochondrial edema and (Schwann cells)
cytoplasmic inclusions, and (b) axons, resembling
wallerian degeneration.
ANIMALS: 8 albino rats, adult
PREPARATION AND DOSE
or HISTORY OF PATIENT: 40 mg/kg initially; then 20 mg/kg at 6 h intervals
ROUTE AND SITE: I.P.
CONTROL INFORMATION: Yes, but no details, except saline dose.
DURATION OF EXPERIMENT: Serial to 48 hr
EXAM. TYPE: Histology
1041
COMPOUND: Quinoline, 6-methoxy-8-(3-diethylaminopropylamino)-
REFERENCE: Schmidt, I.G. and Schmidt, L.H.
J. Neuropath. Exp. Neurol. 7:368-398, 1948
OBSERVED NEUROTOXIC EFFECTS: Selective degeneration in the central nervous
system: acute - in proprioceptive pathways;
subacute - damage more selective. At 1/2
MTD lesions limited to cord and brainstem
(proprioceptive nuclei). Chronic low-dose exposures
and long recovery showed massed microglia, astrocytes
and neuroglia in injured areas.
ANIMALS: :22 Rhesus monkeys (Macaca mulatta)
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.125 to 6.0 mg base/kg, every 8 hr., in soln as
hydroiodide salt.
ROUTE AND SITE: Gavage
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: Acute: 6 hr, chronic: 22d
EXAM. TYPE: Histology
1042
-------
COMPOUND: 8-Quinolinol
000148243
COMPOUND: 8-Qulnolinol, 5-chloro-3'-hydroxy-2'-naphthoate
REFERENCE: Bernstein, E.H., Pienta, P.W. and Gershon, H.
Tox. Appl. Pharm. 5:599-604, 1963.
REFERENCE: Bernstein, E.H., Pienta, P.W. and Gershon, H.
Tox. Appl. Pharm. 5:599-604, 1963.
OBSERVED NEUROTOXIC EFFECTS: This study included8-quinolinol, selected salts
and copper chelates. 8-quinolinol was shown to be
more toxic than its salts. The introduction of the
copper chelate decreased the toxicity of 8-quinolinol,
but increased the toxicity of the derivatives.
The salts, generally, manifested their toxicities
within 72 hours. The toxic reactions to the chelates
were, generally, more delayed. Some of these
compounds appear to show sex specificity in their
toxic manifestations. Symptoms included: confusion,
respiratory difficulty, convulsions and some
paralysis.
ANIMALS: Mice, Swiss, random-bred albino, 18-22 g
10 animals per dose level, 5 M and 5 F.
OBSERVED NEUROTOXIC EFFECTS: This study included8-quinolinol, selected salts
and copper chelates. 8-quinolinol was shown to be
more toxic than its salts. The introduction of the
copper chelate decreased the toxicity of 8-quinolinol,
but increased the toxicity of the derivatives.
The salts, generally, manifested their toxicities
within 72 hours. The toxic reactions to the chelates
were, generally, more delayed. Some of these
compounds appear to show sex specificity in their
toxic manifestations. Symptoms included: confusion,
respiratory difficulty, convulsions and some
paralysis.
ANIMALS: Mice, Swiss, random-bred albino, 18-22 g
10 animals per dose level, 5 M and 5 F.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
ID
SO"
48 mg/kg in 0.5% methylcellulose.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
LD
SO'
215 mg/kg in 0.5% methylcellulose.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: 10 controls treated with methyl cellulose.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: 10 controls treated with methyl cellulose.
DURATION OF EXPERIMENT: At least 3 wk.
EXAM. TYPE: Clinical.
DURATION OF EXPERIMENT: At least 3 wk.
EXAM. TYPE: Clinical.
1043'
1044"
-------
COMPOUND' 8-Quinolinol, 5-chloro-3'-hydroxy-2'-napthalate, copper (II) chelate
COMPOUND: 8 Quinolinol,5-chloro-7-iodo-
000130267
REFERENCE: Bernstein, E.H., Pienta, P.W. and Gershon, H.
Tox. Appl. Pharm. 5:599-604, 1963.
OBSERVED NEUROTOXIC EFFECTS: This study included 8-quinolinol, selected salts
and copper chelates. 8-quinolinol was shown to be
more toxic than its salts. The introduction of the
copper chelate decreased the toxicity of 8-quinolinol,
but increased the toxicity of the derivatives.
The salts, generally, manifested their toxicities
within 72 hours. The toxic reactions to the chelates
were, generally, more delayed. Some of these
compounds appear to show sex specificity in their
toxic manifestations. Symptoms included: confusion,
respiratory difficulty, convulsions and some
paralysis.
ANIMALS: . Mice, Swiss, random-bred albino, 18-22 g
10 animals per dose level, 5 M and 5 F.
PREPARATION AND DOSE
or HISTORY OF PATIENT: LD
50'
39 mg/kg in 0.5% methylcellulose.
REFERENCE: Castaigne, P., Rondot, P., Lenoel, Y., Ribadeau Dumas, J.-L., and Autret,
Therapie 28:393-400, 1973.
OBSERVED NEUROTOXIC EFFECTS: Paraplegia, sphincter disturbance, withdrawal
reflexes, peripheral amyotrophy, optic neuritis.
No change during 4 mo. of observation in hospital.
Syndrome labeled subacute myelo-optico-neuritis.
ANIMALS: ' 1 Human, F, aged 55 yr.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
1500 mg/d for 1 mo. as Enterovioform.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: 10 controls treated with methyl cellulose.
ROUTE AND SITE: Oral
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: At least 3 wk.
EXAM. TYPE: Clinical.
DURATION OF EXPERIMENT: 4 mo.
EXAM. TYPE: Clinical and biochemistry
1045'
1046
-------
COMPOUND: 8 quinolinol,5-Chloro-7-iodo-
000130267
REFERENCE: Ferrier, T.M. and Eadie, M.J.
Med. J. Aust. 2: 1008-1009, 1973.
COMPOUND:
8 quinolinol,5-Chloro-7-iodo-
000130267
REFERENCE: Jones, E.L., Searle, C.E. and Smith, W.T.
Acta Neuropath. 24:256-262, 1973.
OBSERVED NEUROTOXIC EFFECTS:
The compound produced sudden severe failure of
recent memory, with headache and confusion. The
EEC remained normal and recovery began on the third
day, but a memory gap persisted throughout the
study. The author comments on permanent losses and
. hippocampal damage in animals .
ANIMALS: Human: F, 43 and M, 32
OBSERVED NEUROTOXIC EFFECTS:
Unsteady gait to hindlimb paralysis early as 114 wk
In paralyzed rats sciatic nerves more damaged
than brachial. Loss of myelinated fibers,
Wallerian degeneration; patchy vacuolization
throughout cord white-matter (authors say possibly
artifact), and degeneration in gracile fasciculi
of posterior columns that looked like ascending
demyelination. In 1 rat brain necrosis in
thalamus and central white-matter. Mild peripheral
lesions. Some lesions in controls. Optic nerves
all intact.
ANIMALS: Rats, Wistar, 12 M and 8 F, age 7 wk.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 1500 mg; 2 g
PREPARATION AND DOSE
or HISTORY OF PATIENT:
0.1% in diet of maize, intake approx. 50 mg/kg.
ROUTE AND SITE: Oral
CONTROL INFORMATION: Hone
ROUTE AND SITE: Oral
CONTROL INFORMATION: 6M, 6F maize diet only.
DURATION OF EXPERIMENT: To 1 mo
EXAM. TYPE: Clinical, EEC
DURATION OF EXPERIMENT: Serial sacr to 132 wk.
EXAM. TYPE: Behavior, histology
1047
1048
-------
COMPOUND: 8-Quinolinol, 5-chloro-7-iodo-
000130267
REFERENCE: Tateishi, J., Ikeda, H., Saito, A., Kuroda, S. and Otsuki, S.
Neurology 22:702-709, 1972.
OBSERVED NEUROTOXIC EFFECTS: Acute: death with convulsions. Chronic: ataxia,
hindlimb motor paralysis after 20-28 d, symmetrical degeneration of long
tracts of cord and spinal rrot ganglia.
COMPOUND:
8 quinolinol,5-Chloro-7-iodo-
000130267
REFERENCE: Tateishi, J., Kuroda, S., Saito, A. and Otsuki, S.
Acta Neuropath. 24:304-320, 1973.
OBSERVED NEUROTOXIC EFFECTS:
Some died with acute convulsions, others
developed muscle weakness judged by gait,
3 dogs showed no signs. Distal degeneration
in posterior cord and optic tract; axons,
then demyelination, then spinal root ganglia,
and peripheral nerves. Both strain and
specific differences, reported.
ANIMALS: 11 Dogs: 8 treated (2 grps), 3 controls
PREPARATION AND DOSE
Or HISTORY OF PATIENT: 72-125 mg/kg/d for 1.5-62 d; 56-128 mg/kg/d with con-
stipating drugs for 2-64 d.
ROUTE AND SITE: Oral
CONTROL INFORMATION: 2 dogs untreated, 1 given constipating drugs only
ANIMALS: Dogs: 20 mongrels, 8 purebred F beagles aged 14 mo, 27 cats,
1 monkey.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
(1) 20 Mongrels: Japanese-made clioquinol
suspened in milk, 2 x d.
(2) 4 Beagles: Japanese-made, twice daily.
(3) 4 Bealges: Swiss-made compound, twice daily.
(4) 22 Cats: Compound in food.
(5) Monkey: Water .suspension Japanese-made compound
—ce dally.
ROUTE AND SITE: Oral or nasal tube (monkey)
CONTROL INFORMATION: 4 mongrels, 4 beagles, 5 cats, 1 monkey.
DURATION OF EXPERIMENT: About 2 mo.
EXAM. TYPE: Behavior, histology
DURATION OF EXPERIMENT: 1-383 d
EXAM. TYPE: Behavior, histology
1049
1050
-------
COMPOUND: 8-Quinolinol, 5-chloro-7-iodo-
000130267
REFERENCE: Tsubaki, T., Honma, Y. and Hoshl, M.
Lancet 1:696-697, 1971.
COMPOUND: 8-Quinolinol, copper(II)chelate
REFERENCE: Bernstein, E.H., Pienta, P.W. and Gershon, H.
Tox. Appl. Pharm. 5:599-604, 1963.
OBSERVED NEUROTOXIC EFFECTS:
Of 110 given compound for >14 d 35.4% had neuropathy;
of 153 given it for <13 d, 2.6% had neuropathy;
controls 0%. Symptoms: leg paresthesia, gait,
and signs identical with subacute myelo-
optico-neuropathy (includes axonal damage and
demyelination of optic nerve).
ANIMALS:
263 Humans
OBSERVED NEUROTOXIC EFFECTS: This study included8-quinolinol, selected salts
and copper chelates. 8-quinolinol was shown to be
more toxic than its salts. The introduction of the
copper chelate decreased the toxicity of 8-quinolinol,
but increased the toxicity of the derivatives.
The salts, generally, manifested their toxicities
within 72 hours. The toxic reactions to the chelates
were, generally, more delayed. Some of these
compounds appear to show sex specificity in their
toxic manifestations. Symptoms included: confusion,
respiratory difficulty, convulsions and some
paralysis.
ANIMALS: Mice, Swiss, random-bred albino, 18-22 g
10 animals per dose level, 5 M and 5 F.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.6-1.6 g/d as treatment to patients with digestive
disorders.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
U50'
67 mg/kg in 0.5% methylcellulose.
ROUTE AND SITE: Oral
CONTROL INFORMATION: 706 disorder-matched patients not given the compound.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: 10 controls treated with methyl cellulose.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Clinical
DURATION OF EXPERIMENT: At least 3 wk.
EXAM. TYPE: Clinical.
1051
1052
-------
COMPOUND- 8-Quinolinol, 4,5'-dichloro-3'-hydroxy-2'-napthoate
COMPOUND: 8-Quinolinol, 5-iodo-4'-chloro-3'-hydroxy-2'-napthoate, copper(II) chelate
REFERENCE: Bernstein, E.H., Pienta, P.W. and Gershon, H.
Tox. Appl. Phartn. 5:599-604, 1963.
REFERENCE: Bernstein, E.H., Pienta, P.W. and Gershon, H.
Tox. Appl. Pharm. 5:599-604, 1963.
OBSERVED NEUROTOXIC EFFECTS: This studyiicluded-; 8-quinolinol, selected salts
and copper chelates. 8-quinolinol was shown to be
more toxic than its salts. The introduction of the
copper chelate decreased the toxicity of 8-quinolinol,
but increased the toxicity of the derivatives.
- The salts, generally, manifested their toxicities
within 72 hours. The toxic reactions to the chelates
were, generally, more delayed. Some of these
compounds appear to show sex specificity in their
toxic manifestations. Symptoms included: confusion,
respiratory difficulty, convulsions and some
paralysis.
ANIMALS: Mice, Swiss, random-bred albino, 18-22 g
10 animals per dose level, 5 M and 5 F.
OBSERVED NEUROTOXIC EFFECTS: This study included.-8-quinolinol, selected salts
and copper chelates. 8-quinolinol was shown to be
more toxic than its salts. The introduction of the
copper chelate decreased the toxicity of 8-quinolinol,
but increased the toxicity of the derivatives.
The salts, generally, manifested their toxicities
' • ' within 72 hours. The toxic reactions to the chelates
were, generally, more delayed. Some of these
compounds appear to show sex specificity in their
toxic manifestations. Symptoms included: confusion,
: ' respiratory difficulty, convulsions and some
paralysis.
ANIMALS: Mice, Swiss, random-bred albino, 18-22 g
10 animals per dose level, 5 M and 5 F.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
LD
SO'
350 mg/kg in 0.5% methylcellulose.
PREPARATION AND DOSE
or HISTORY OF PATIENT:.
LD
50'
110 mg/kg in 0.5% methylcellulose.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: 10 controls treated with methyl cellulose.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: 10 controls treated with methyl cellulose.
DURATION OF EXPERIMENT: At least 3 wk.
EXAM. TYPE: Clinical.
DURATION OF EXPERIMENT: At least 3 wk.
EXAM. TYPE: Clinical.
1053
1054-
-------
COMPOUND: 8-Quinolinolium 7'-bromo-3'-hydroxy-2'naphthoate, copper (II) chelate
COMPOUND: 8-Quinolinolium A',7'-dibromo-3'-hydroxy-2'-naphthoate
REFERENCE: Bernstein, E.H., Pienta, P.W. and Gershon, H.
Tox. Appl. Pharm. 5:599-604, 1963.
REFERENCE: Bernstein, E.H., Pienta, P.W. and Gershon, H.
Tox. Appl. Pharm. 5:599-604, 1963.
OBSERVED NEUROTOXIC EFFECTS: This study included8-quinolinol, selected salts
and copper chelates. 8-quinolinol was shown to be
more toxic than its salts. The introduction of the
copper chelate decreased the toxicity of 8-quinolinol,
but increased the toxicity of the derivatives.
The salts, generally, manifested their toxicities
within 72 hours. The toxic reactions to the chelates
were, generally, more delayed. Some of these
compounds appear to show sex specificity in their
toxic manifestations. Symptoms included: confusion,
respiratory difficulty, convulsions and some
paralysis.
ANIMALS: Mice, Swiss, random-bred albino, 18-22 g
10 animals per dose level, 5 M and 5 F.
OBSERVED NEUROTOXIC EFFECTS: This study included 8-quinolinol, selected salts
and copper chelates. 8-quinolinol was shown to be
more toxic than its salts. The introduction of the
copper chelate decreased the toxicity of 8-quinolinol,
but increased the toxicity of the derivatives.
The salts, generally, manifested their toxicities
within 72 hours. The toxic reactions to the chelates
were, generally, more delayed. Some of these
compounds appear to show sex specificity in their
toxic manifestations. Symptoms included: confusion,
respiratory difficulty, convulsions and some
paralysis.
ANIMALS: Mice, Swiss, random-bred albino, 18-22 g
10 animals per dose level, 5 M and 5 F.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
LD
50
26 mg/kg in 0.5% methylcellulose
PREPARATION AND DOSE
or HISTORY OF PATIENT:
ID,-: 85 mg/kg in 0.5% methylcellulose.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: 10 controls treated with methyl cellulose.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: 10 controls treated with methyl cellulose.
DURATION OF EXPERIMENT: At least 3 wk.
EXAM. TYPE: Clinical.
DURATION OF EXPERIMENT: At least 3 wk.
EXAM. TYPE: Clinical.
1055'
1056"
-------
COMPOUND: 8-Quinolinolium 4', 7'-dibromo-3'-hydroxy-2'-naphthoate, copper(II)chelate
COMPOUND: 8-Quinollnolium l'-hydroxy-2'-naphthoate
REFERENCE: Bernstein, E.H., Pienta, P.W. and Gershon, H.
Tox. Appl. Pharm. 5:599-604, 1963.
OBSERVED NEUROTOXIC EFFECTS: This study tocludei 8-quinolinol, selected salts
and copper chelates. 8-quinolinol was shown to be
more toxic than it's salts. The introduction of the
copper chelate decreased the toxicity of 8-quinolinol,
but increased the toxicity of the derivatives.
The salts, generally, manifested their toxicities
within 72 hours. The toxic reactions to the chelates
were, generally, more delayed. Some of these
compounds appear to show sex specificity in their
• . toxic manifestations. Symptoms included: confusion,
respiratory difficulty, convulsions and some
paralysis.
ANIMALS: Mice, Swiss, random-bred albino, 18-22 g
10 animals per dose level, 5 M and 5 F.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
LD
50'
39 mg/kg in 0.5% methylcellulose.
REFERENCE: Bernstein, E.H., Pienta, P.W. and Gershon, H.
Tox. Appl. Pharm. 5:599-604, 1963.
OBSERVED NEUROTOXIC EFFECTS: This study included 8-quinolinol, selected salts
and copper chelates. 8-quinolinol was shown to be
more toxic than its salts. The introduction of the
copper chelate decreased the toxicity of 8-quinolinol,
but increased the toxicity of the derivatives.
The salts, generally, manifested their toxicities
within 72 hours. The toxic reactions to the chelates
were, generally, more delayed. Some of these
compounds appear to show sex specificity in their
toxic manifestations. Symptoms included: confusion,
respiratory difficulty, convulsions and some
paralysis.
ANIMALS: Mice, Swiss, random-bred albino, 18-22 g
10 animals per dose level, 5 M and 5 F.
PREPARATION AND DOSE
or HISTORY .OF PATIENT:
LD
50'
72 mg/kg in 0.5% methylcellulose.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: 10 controls treated with methyl cellulose.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: 10 controls treated with methyl cellulose.
DURATION OF EXPERIMENT: At least 3 wk.
EXAM. TYPE: Clinical.
DURATION OF EXPERIMENT: At least 3 wk.
EXAM. TYPE: Clinical.
1057
1058'
-------
COMPOUND: 8-Quinolinolium 3'-hydroxy-2'-naphthoate
COMPOUND: 8-Quinolinolium l'-hydroxy-2'-naphthoate, copper (II) chelate
REFERENCE: Bernstein, E.H., Pienta, P.W. and Gershon, H.
Tox. Appl. Pharm. 5:599-604, 1963.
REFERENCE: Bernstein, E.H., Pienta, P.W. and Gershon, H.
Tox. Appl. Pharm. 5:599-604, 1963.
OBSERVED NEUROTOXIC EFFECTS: This study included8-quinolinol, selected salts
and copper chelates. 8-quinolinol was shown to be
more toxic than its salts. The introduction of the
copper chelate decreased the toxicity of 8-quinolinol,
but increased the toxicity of the derivatives.
The salts, generally, manifested their toxicities
within 72 hours. The toxic reactions to the chelates
were, generally, more delayed. Some of these
compounds appear to show sex specificity in their
toxic manifestations. Symptoms included: confusion,
respiratory difficulty, convulsions and some
paralysis.
ANIMALS: Mice, Swiss, random-bred albino, 18-22 g
10 animals per dose level, 5 M and 5 F.
OBSERVED NEUROTOXIC EFFECTS: This study included 8-quinolinol, selected salts
and copper chelates. 8-quinolinol was shown to be
more toxic than its salts. The introduction of the
copper chelate decreased the toxicity of 8-quinolinol,
but increased the toxicity of the derivatives.
The salts, generally, manifested their toxicities
within 72 hours. The toxic reactions to the chelates
were, generally, more delayed. Some of these
compounds appear to show sex specificity in their
toxic manifestations. Symptoms included: confusion,
respiratory difficulty, convulsions and some
paralysis.
ANIMALS: Mice, Swiss, random-bred albino, 18-22 g
10 animals per dose level, 5 M and 5 F.
PREPARATION AND DOSE •
or HISTORY OF PATIENT:
LD :61 mg/kg in 0.5% methylcellulose.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
LD
50'
27 mg/kg in 0.5% methylcellulose
ROUTE AND SITE: I.P.
CONTROL INFORMATION: 10 controls treated with methyl cellulose.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: 10 controls treated with methyl cellulose.
DURATION OF EXPERIMENT: At least 3 wk.
EXAM. TYPE: Clinical.
DURATION OF EXPERIMENT: At least 3 wk.
EXAM. TYPE: Clinical.
1059
1060
-------
COMPOUND: 8-Quinolinolium 3'-hydroxy-2'-naphthoate, copper (II) chelate
COMPOUND: 8-Quinolinolium salicylate
REFERENCE: Bernstein, E.H., Pienta, P.W. and Gershon, H.
Tox. Appl. Pharm. 5:599-604, 1963.
REFERENCE: Bernstein, E.H., Pienta, P.W. and Gershon, H.
Tox. Appl. Pharm. 5:599-604, 1963.
OBSERVED NEUROTOXIC EFFECTS: This study included 8-quinolinol, selected salts
and copper chelates. 8-quinolinol was shown to be
more toxic than its salts. The introduction of the
copper chelate decreased the toxicity of 8-quinolinol,
but increased the toxicity of the derivatives.
The salts, generally, manifested their toxicities
within 72 hours. The toxic reactions to the chelates
were, generally, more delayed. Some of these
compounds appear to show sex specificity in their
toxic manifestations. Symptoms included: confusion,
respiratory difficulty, convulsions and some
paralysis.
ANIMALS: Mice, Swiss, random-bred albino, 18-22 g
10 animals per dose level, 5 M and 5 F.
OBSERVED NEUROTOXIC EFFECTS: This studyincluded 8-quinolinol, selected salts
and copper chelates. 8-quinolinol was shown to be
more toxic than its salts. The introduction of the
• copper chelate decreased the toxicity of 8-quinolinol,
but increased the toxicity of the derivatives.
The salts, generally, manifested their toxicities
within 72 hours. The toxic reactions to the chelates
were, generally, more delayed. Some of these
compounds appear to show sex specificity in their
toxic manifestations. Symptoms included: confusion,
respiratory difficulty, convulsions and some
paralysis.
ANIMALS: Mice, Swiss, random-bred albino, 18-22 g
10 animals per dose level, 5 M and 5 F.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
LD
SO'
23 mg/kg in 0.5% methylcellulose.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
LD
50-
58 mg/kg in 0.5% methylcellulose.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: 10 controls treated with methyl cellulose.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: 10 controls treated with methyl cellulose.
DURATION OF EXPERIMENT: At least 3 wk.
EXAM. TYPE: Clinical.
DURATION OF EXPERIMENT: At least 3 wk.
EXAM. TYPE: 'Clinical.
1061
1062
-------
COMPOUND: 8-Quinolinolium salicylate, copper (II) chelate
COMPOUND: Reserpine phosphate
REFERENCE: Bernstein, E.H., Pienta, P.W. and Gershon, H.
Tox. Appl. Pharm. 5:599-604, 1963.
REFERENCE: Spooner, C.E. and Winters, W.D.
Int. J. Neuropharmacol. 5: 217-236, 1966
OBSERVED NEUROTOXIC EFFECTS: This study included 8-quinolinol, selected salts
and copper chelates. 8-quinolinol was shown to be
more toxic than its salts. The introduction of the
copper chelate decreased the toxicity of 8-quinolinol,
but increased the toxicity of the derivatives.
The salts, generally, manifested their toxicities
within 72 hours. The toxic reactions to the chelates
were, generally, more delayed. Some of these
compounds appear to show sex specificity in their
toxic manifestations. Symptoms included: confusion,
respiratory difficulty, convulsions and some
paralysis.
,.'.L:.: Mice, Swiss, random-bred albino, 18-22 g
10 animals per dose level, 5 M and 5 F,
OBSERVED NEUROTOXIC EFFECTS: Compound produced depression and associated slow-
wave EEGs.
ANIMALS: 200 Cockerels, White Leghorn, ages 5-14 d, 45-100 g
PREPARATION AND DOSE
or HISTORY OF PATIENT:
LD
50'
13.1 mg/kg in 0.5% methylcellulose.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 1-5 mg/kg
ROUTE AND SITE: I.P.
CONTROL INFORMATION: 10 controls treated with methyl cellulose.
ROUTE AND SITE: S.C. near axillary vein; I.P. for doses over 0.05 ml
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: At least 3 wk.
EXAM. TYPE: Clinical.
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Behavior, EEC
1063
1064
-------
COMPOUND:
Resorclnol, 2-p-mentha-l,8-dien-3-yl-5-pentyl-
COMPOUND- Resorcinol, 2-p-mentha-l,8-dien-3-yl-5-pentyl-
REFERENCE: Christensen, H.D., Freudenthal, R.I., Gidley, J.T., Rosenfeld, R.,
Boegli, G., Testino, L., Brine, D.R., Pitt, C.G. and Wall, M.E.
Science 172: 165-167, 1971.
OBSERVED NEUROTOXIC EFFECTS: The biological activity of the above compound, and
other cannabinoids was compared to that of A9-Tetrahydrocannabinol. Similar
neurological and behavioral responses were found for all, provided that high
concentrations were given. The potency of the compounds varied depending on
structure and route of administration. Behavioral pattern was character-
ized by irritability, decrease in activity, reduced sensorimotor responses.
Intracerebral admin, increased potency.
REFERENCE: Karler, R., Cely, W. and Turkanis, S.A.
Res. Comm. Chem. Path. Pharm. 7(2):353-358, 1974.
OBSERVED NEUROTOXIC EFFECTS:
Bar-walk test gave decreasing order of toxicity
as dimethyIheptylpyran, A9-tetrahydrocannabinol,
cannabidiol; anticonvulsant and "toxic" actions
concluded to be separable.
ANIMALS: Mice
ANIMALS: ' Mice, ICR, 4-5 wk old
PREPARATION AND DOSE
or HISTORY OF PATIENT: Amount ns., table included comparing relative potency of
A9THC to compound tested.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
100-200 mg/kg
ROUTE AND SITE: i.V. or Intracerebral
CONTROL INFORMATION: ns.
ROUTE AND SITE: i.p.
CONTROL INFORMATION:
Own controls
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior
DURATION OF EXPERIMENT:
EXAM. TYPE: Behavior
1065
1066
-------
COMPOUND: Retinol, all trans-
000068268
REFERENCE: Langman, J. and Welch, G.W.
J. Comp. Neurol. 128: 1-16, 1966.
COMPOUND: Retinol, all trans-
000068268
REFERENCE: Langman, J. and Welch, G.W.
J. Comp. Neurol. 131: 15-26, 1967.
OBSERVED NEUROTOXIC EFFECTS:
Anencephaly and/or myeloschisis was observed in 26% of
the implanted rat embryos after 3 x 10 USP units (most
effective dose); mouse results were inconsistent. The
internal limiting membrane for diencephalon and mesence-
phalon was disrupted at day 12, with displacement of
tissue and then degeneration. The neural groove was
prevented from closing.
OBSERVED NEUROTOXIC EFFECTS:
Treatment caused interference with the mitosis of neuro-
epithelial cells bordering the neural groove in embryos,
resulting in exencephaly and anencephaly at birth. Upon
treatment, fewer cells were formed and existing cells
degenerated; differentiation of developing cells was
affected; abnormal behavior was also observed.
ANIMALS: (1) Rats, Wistar, F, 200-250 g, bred
(2) Mice, Swiss Webster, F, bred
ANIMALS: Mice, Swiss-Webster, 23-28 g, F.
PREPARATION AND DOSE 4
or HISTORY OF PATIENT: (D Rats: 3-6 x 10 USP units on d 8,9,10 of gestation
(2) Mice: 3-7.5 x 10 USP units/d, 1-3 doses, d 7-9 of
gestation.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 10,000 USP units/d on d 14 and 15 of gestation
or for 2-3 d starting d 11
ROUTE AND SITE: Gavage
CONTROL INFORMATION: (D Rats: vehicle or saline.
(2) Mice: none.
ROUTE AND SITE: Oral
CONTROL INFORMATION: Untreated with compound
DURATION OF EXPERIMENT: Serial, to term.
EXAM. TYPE: Teratology
DURATION OF EXPERIMENT: 1 hr to full-term
EXAM. TYPE: Histology, behavior
1067
1068
-------
COMPOUND: Salicylic acid, monsodium salt
000054217
REFERENCE: Ryder, H.W., Shaver, M. and Ferris, E.B.
New Eng. J. Med. 232:617-621, 1945.
OBSERVED NEUROTOXIC EFFECTS: Toxic encephalopathy (6 hr postmortem), cortical
edema, pyramidal degeneration extending to basal
ganglia, substantia nigra and brainstem. Excesses
of microglia, swollen oligodendroglia in white-
matter. Other damage secondary to hemorrhages.
Clinical evidence of salicylate toxicity included
hyperpnea and respiratory alkalosis.
ANIMALS:
Human: 1 case, F, 16 yr
PREPARATION AND DOSE
or HISTORY OF PATIENT:
26 g given over 6 d in hospital (0.7 g/kg)
and death occured on d 8.
Autopsy disclosed active rheumatic heart disease.
ROUTE AND SITE: Oral
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: 8 d
EXAM. TYPE: Clinical, autopsy
1069
COMPOUND: Saxitoxin
REFERENCE: Bull, R.J. and Trevor, A.J.
J. Neurochem. 19:999-1009, 1972.
OBSERVED NEUROTOXIC EFFECTS: Inhibited increase of lactate and redistribution
of sodium and potassium from electrical stimulation
in vitro.
ANIMALS: Rats, S-D, M, 200-250 g, brain cortex slices in vitro.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 10 - 10 M in incubation medium.
ROUTE AND SITE: m vitro
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: Hours
EXAM. TYPE: Biochemistry
1070
-------
COMPOUND: Saxitoxin
REFERENCE: Narahashi, T., Haas, H.G. and Therrien, E.F.
Science 157: 1441-1442, 1967.
OBSERVED NEUROTOXIC EFFECTS: Saxitoxln blocks conduction with no change in resting
potential. The mechanism of the blockage is similar
to that caused by tetrodotoxin, but recovery of washed
axons is faster.
COMPOUND: Scopolamine
000051343
REFERENCE: Pfeiffer, C.C., Murphree, H.B., Jenney, E.H., Robertson, M.G.,
Randall, A.H. and Bryan, L.
Neurology 9: 249-250, 1959.
OBSERVED NEUROTOXIC EFFECTS: The authors concluded that synthetic atropines are more
active hallucinogens than atropine or scopolamine, pro-
ducing effects lasting 24-48 hr. Synthetic antitremor
drugs had fewer peripheral nervous system side-effects,
but central nervous system side-effects (hallucinations)
may have been exaggerated.
ANIMALS: Lobster (Homarus americanus)
ANIMALS: Human: prison volunteers, drug-sophisticated, no other details
PREPARATION.AND DOSE
or HISTORY OF PATIENT: Partly isolated giant axons treated with saxitoxin at
3 x 10~ to 3 x 10 moles/liter of medium.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 2 mg/man .,
ROUTE AND SITE: Semi-in vitro
CONTROL INFORMATION: Laboratory
ROUTE AND SITE: Oral
CONTROL INFORMATION: LSD-25: 0, 25, 50, 100 meg/man
DURATION OF EXPERIMENT: Up to 100 min
EXAM. TYPE: Electrophysiology
DURATION OF EXPERIMENT: Up to 3 d
EXAM. TYPE: Opinion of volunteers
1071
1072
-------
COMPOUND: Scopolamlne bromide
REFERENCE: Spooner, C.E. and Winters, W.D.
Int. J. Neuropharmacol. 5: 217-236, 1966
OBSERVED NEUROTOXIC EFFECTS: Compound produced locomotor ataxia and arousal EEGs.
COMPOUND: Semicarbazide .
000057567
REFERENCE: Jenney, E.H. and Pfeiffer, C.C.
J. Pharm. Exp. Ther. 122: 110-123, 1958.
OBSERVED NEUROTOXIC EFFECTS: Convulsions
ANIMALS: 200 Cockerels, White Leghorn, ages 5-14 d, 45-100 g
PREPARATION AND DOSE
or HISTORY OF PATIENT: 2-4 mg/kg
ANIMALS: Mice, Harlan, 19-21 g
PREPARATION AND DOSE
or HISTORY OF PATIENT: 1.6 mM/kgm
ROUTE AND SITE: S.C. near axillary vein; I.P. for doses over 0.05 ml
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Behavior, EEC
ROUTE AND SITE: i.p.
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: Acute
EXAM. TYPE: Clinical
1073
1074
-------
COMPOUND: Semicarbazide, 4,4-diethyl-, hydrochloride
REFERENCE: Jenney, E.H. and Pfeiffer, C.C.
J. Phann. Exp. Ther. 122: 110-123, 1958.
OBSERVED NEUROTOXIC EFFECTS: Convulsions
ANIMALS: Mice, BarIan, 19-21 g
PREPARATION AND DOSE
or HISTORy OF PATIENT: 0.66 mM/kgm
ROUTE AND SITE: I
-------
COMPOUND: Semicarbazide, thio-
000079196
REFERENCE: Knyihar, E., Kiss, J. and Csillik, B.
Res. Coram. Chem. Path. Pharm. 2: 392-405, 1971.
OBSERVED NEUROTOXIC EFFECTS: This semlcarbazlde produced typical convulsions after
30-45 min at which time the label was concentrated in
the hippocampus glial cells. The authors inferred that
thiosemicarbazide-sensitive enzymes for GABA metabolism
are located at glio-neuronal interfaces.
COMPOUND: Semioxamazide
REFERENCE: Jenney, E.H. and Pfeiffer, C.C.
J. Pharm. Exp. Ther. 122: 110-123, 1958.
OBSERVED NEUROTOXIC EFFECTS: Convulsions
ANIMALS: 8 Rats, R-Amsterdam, 150 g
ANIMALS: Mice, Harlan, 19-21 g
PREPARATION AND DOSE
or HISTORY OF PATIENT: 20 mg/kg, labeled
PREPARATION AND DOSE
or HISTORY OF PATIENT: 1.8 mM/kgm
ROUTE AND SITE: I.P.
CONTROL INFORMATION: None
ROUTE AND SITE: i.p.
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: 55 min
EXAM. TYPE: Behavior, autoradiography (histological)
DURATION OF EXPERIMENT: Acute
EXAM. TYPE: Clinical
1077
1078
-------
COMPOUND:
Senna
COMPOUND: Serine, dihydrogen phosphate (ester), L-
REFERENCE:
Steer, H.W. and Colin-Jones, D.G.
J. Path. 115:199-205, 1975
REFERENCE: Curtis, D.R. and Watklns, J.C.
J. Neurochem. 6:117-141, 1960.
OBSERVED NEUROTOXIC EFFECTS: More lysosomal activity and lysosomes in Schwann
cells and neurons of submucosal plexus of colonic
mucosa.
OBSERVED NEUROTOXIC EFFECTS:
Treatment caused excitation or depression of
neuronal activity. Excitatory ranking: glutamic,
fj-aminoglutaric, aspartic, cysteic, cysteine-
sulfinic acids, 8-hydroxyglutamic, N-methylaspartic,
N-formiminoaspartic acids.
Depressant ranking: B-alanine, GABA, taurine,
N-methyl-B-alanine, 6-amino-B-hydroxybutyric,
glycine, a-alanine, 6-aminovaleric, B-aminoisobutyric
acids.
Structure-activity relationships established.
ANIMALS: Human: 7 aged 24-80 with melanosis coli who took purgatives;
1 who had taken purgatives for only 1 m.
ANIMALS: Cats, surgically prepared to exposed motoneurones, Renshaw cells or
dorsal horn interneurones in lumbar cord.
PREPARATION AND DOSE
Or HISTORY OF PATIENT: Rectal biopsy before and 3-7 m after stopping medication
PREPARATION AND DOSE
or HISTORY OF PATIENT: Qualitative doses.
ROUTE AND SITE: oral
CONTROL INFORMATION:
7 aged 27-70 with other gut disorders who had taken no
purgatives for 3m.
ROUTE AND SITE: Topical, ionophoresis
CONTROL INFORMATION: Laboratory
DURATION OF EXPERIMENT: About 7 m.
EXAM. TYPE: Histology, histochemistry
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry, electrophysiology
1079
1080
-------
COMPOUND: Shigella Shigae toxin
COMPOUND:
Sodium azide
026628228
REFERENCE: Masek, K., Smetana, R. and Raskova, H.
Int. J. Neuropharmacol. 1: 71-77, 1962.
REFERENCE:
Mettler, F.A. and Sax, D.S.
Brain 95:505-516, 1972.
OBSERVED NEUROTOXIC EFFECTS: The mice exhibited a dose-related depression of brain
norepinephrine after a 48-hr lag period. Brain serotonin
was also depressed.
OBSERVED NEUROTOXIC EFFECTS:
Acute syndrome giving ataxia due to cerebellar
cortical destruction (authors state that subacute
effects are well known and chronic effects
less well known), claimed first description.
ANIMALS: Mice, Konarovice, M and F, 16-18 g
ANIMALS: 11 Rhesus monkeys
PREPARATION AND DOSE , ,
or HISTORY OF PATIENT: 0.2 x 10"b to 0.4 x 10~ ml/mouse
PREPARATION AND DOSE
or HISTORY OF PATIENT:
8-16 mg/kg one dose; followed by other trtmts; pretrtmt
with thiamytal or succinylcholine chloride before NaN ,
or oil of wormwood instead of NaN,.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: Yes, but not described.
ROUTE AND SITE: I.V., saphenous vein at ankle
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: Serial 6-48 hr
EXAM. TYPE: Biochemistry
DURATION OF EXPERIMENT: Approx 1 hr/experiment
EXAM. TYPE: Behavior, histology
1081
1082
-------
COMPOUND: Sodium azide
026628228
REFERENCE: Miyoshi, K.
Acta Neuropathol. 9:199-216, 1967.
COMPOUND:
Stannane, acetoxytriphenyl-
000900958
REFERENCE: Verschuuren, H.G., Kroes, R., Vink, H.H., and Van Esch, G.J.
Food Cormet. Toxicol. 4: 35-45, 1966.
OBSERVED NEUROTOXIC EFFECTS: Selective vulnerability of basal ganglia to striatal
necrosis. Necrosis in corpus striatum (35 rats), pallidum (13 rats), cortex
(5); demyelination of optic tract (7). Diffuse and complete loss of oxidative
enzyme activities, in necrotic tissues.
OBSERVED NEUROTOXIC EFFECTS: Doubtful edema in spinal cord in 3 rats on 10 ppm,
2 on 25 ppm and 1 on 50 ppm accompanying increase
in water content of the brain and spinal cord.
Doubtful edema in brain of 1 guinea-pig on 5 ppm
and 1 on 50 ppm. Brain weights increased in
guinea-pigs with 20 ppm.
ANIMALS: Rats> albino, 110-130 g, 64 used.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.1% dilutions, 3 mg/kg, 4/d at 30 min intervals, in 50
rats for 4 d.
ANIMALS: p0r each experiment, 4-6 groups of 20 or more animals, 1/2 F, 1/2 M:
Rats, Wistar, 4 wk old, 40-60 g.
Guinea-pigs, albino, 3 wk old, 130-200 g.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0,5,10,25 and 50 ppm in rats.
0,5,10,20 and 50 ppm in guinea-pigs.
ROUTE AND SITE: I>P.
CONTROL INFORMATION: ns.
ROUTE AND SITE: Oral
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: Serial sacr: 14 rats within 24 hr, 50 rats 3-50 d after
last dose.
EXAM. TYPE: Histology, histochemistry
DURATION OF EXPERIMENT: 6-90 day studies for 1 1/2 yr
EXAM. TYPE: Behavior, pathology, histology
1083
1084
-------
COMPOUND: Stannane, chlorotriethyl-
REFERENCE: Robinson, I.M.
Fd. Cosmet. Toxicol. 7: 45-52, 1969
COMPOUND: Stannane, dibutyloxo-
000818086
REFERENCE: Robinson, I.M.
Fd. Cosmet. Toxicol. 7: 45-52, 1969
OBSERVED NEUROTOXIC EFFECTS: Treatment caused hlndllmb paralysis, depression,
death; lowered brain eplnephrlne, noreplnephrlne and
serotonin for 48 hours.
OBSERVED NEUROTOXIC EFFECTS: Treatment lowered brain epinephrine, norepinephrine
and serotonin for 48 hours.
ANIMALS: Rats, Osborne-Mendel, F, 190-220 g, 18/group
ANIMALS: Rats, Osborne-Mendel, F, 190-220 g, 18/group
PREPARATION AND DOSE
or HISTORY OF PATIENT: 10 mg/kg in corn oil
PREPARATION AND DOSE
or HISTORY OF PATIENT: 80 mg/kg in corn oil
ROUTE AND SITE: I.P.
CONTROL INFORMATION: Equivalent corn oil
ROUTE AND SITE: I.P.
CONTROL INFORMATION: Equivalent corn oil
DURATION OF EXPERIMENT: Serial to 48 hr
EXAM. TYPE: Behavior, biochemistry
DURATION OF EXPERIMENT: Serial to 48 hr
EXAM. TYPE: Behavior, biochemistry
1085
1086
-------
COMPOUND: Stannane, hydroxytriethyl-
REFERENCE: Vershuuren, H.G., Kroes, R., Vink, H.H. and Van Esch, G.J.
Food Cosmet. Toxicol. 4: 35-45, 1966
COMPOUND: Stannane, hydroxytriphenyl-
000076879
REFERENCE: Verschuuren, H.G., Kroes, R., Vlnk, H.H., and Van esch, G.J
Food Cosnet. Toxicol. 4: 35-45, 1966
OBSERVED NEUROTOXIC EFFECTS: Paralysis and protonation of hindlegs observed
in 3-8 wk old rats at 10, 20 ppm and 1-3 wk old
guinea-pigs. Alopecia in 2 rats given 10 ppm.
Induced interstitial edema in brain and spinal
cord of rats.
OBSERVED NEUROTOXIC EFFECTS:
Paralysis and protonation of hindlimb. Doubtful
edema in spinal cord of 3 rats on 10 ppm, 2 on 25
ppm and 1 on 50 ppm accompanying increase in water
content of brain and spinal cord. Doubtful edema
in brain of 4 guinea-pigs on 20 ppm and 2 on 50
ppm.
ANIMALS: For each experiment, 4-6 groups of 20 or more animals, 1/2 F, 1/2 M.
Rats, Wistar, 4 wk old, 40-60 g.
Guinea-pigs, Albino, 3 wk old, 130-200 g.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0,5,10,20 ppm in rats
0,5,10,20 ppm in guinea-pigs
ANIMALS: For each experiment, 4-6 groups of 20 or more animals, 1/2 F, 1/2 M.
Rats, Wistar, 4 wk old, 40-60 g.
Guinea-pigs, Albino, 3 wk old, 130-200 g.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0,5,10,25 and 50 ppm in rats.
0,2.5,5,10,20 and 50 ppm in guinea-pigs.
ROUTE AND SITE: oral
CONTROL INFORMATION: ns
ROUTE AND SITE: Oral
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: 6-90 d studies for 1 1/2 yr.
EXAM. TYPE: Behavior, pathology, histology
DURATION OF EXPERIMENT: 6-90 d studies for 1 1/2 yr
EXAM. TYPE: Behavior, pathology, histology
1087
1088
-------
COMPOUND: Stannane, triethyl-
COMPOUND: Stannane, triethyl-
REFERENCE: Hirano, A., Dembitzer, H.M., Becker, N.H. and Zimmerman, H.M.
J. Neuropath. Exp. Neurol. 28(3):507-511, 1969.
OBSERVED NEUROTOXIC EFFECTS: Splitting of myelin sheath in the central
nervous system.
REFERENCE:
Levy, W.A., Taylor, J.M., Herzog, I. and Scheinberg, L.C.
Arch. Heurol. 13:58-64, 1965.
OBSERVED NEUROTOXIC EFFECTS: Diffuse edema of cerebral white matter with diffuse
splitting and distension of the myelin sheaths.
Urea diminished intensity of tin effects.
ANIMALS: Rats, Albino; 200-300 g
ANIMALS: ' Rabbits, NZ White, 2.5-3.5 kg
PREPARATION AND DOSE
or HISTORY OF PATIENT: 5 mg/kg x 1.
PREPARATION AND DOSE
or HISTORY. OF PATIENT: 0.5% in a dose of 1.mg/kg, 1/d for 6 d, followed on
d 6 by urea, 30% soln i.v., 4 gm/kg.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: ns.
ROUTE AND SITE: i.p.
CONTROL INFORMATION: Controls treated with urea only.
DURATION OF EXPERIMENT: Sacr at 24 hr.
EXAM. TYPE: Histology, Histochemistry, Ultrastructural
DURATION OF EXPERIMENT: Serial sacr to 6 hr.
EXAM. TYPE: Histology, biochemistry
1089
1090
-------
COMPOUND: Stannane, triethyl-
COMPOUND: Stannane, triethyl-
REFERENCE: Magee, P.N., Stoner, H.B. and Barnes, J.M.
J. Path. Bact. 73:107-124, 1957.
OBSERVED NEUROTOXIC EFFECTS: Reversible interstital edema of brain and cord white-matter
without gross neuronal damage.
REFERENCE: Smith, M.E.
J. Neurochemistry 21:357-372, 1973.
OBSERVED NEUROTOXIC EFFECTS: Brain and spinal cord edema, paralysis and
death. Spinal cord more edematous than brain. Severe myelin loss.
Swelling of astrocytes, axons and cleft development in myelin. Brain myelin
loss 16% in M, 25% in F.
ANIMALS: Rats, Porton, age 30-70 d.
ANIMALS: Rats, Wistar, M and F, 2 mo. age.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Acute: triethyltin sulfate 10 mg/kg, dichloride 20
mg/kg.
Chronic: 20 ppm in diet 14 d, then 10 ppm.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 10 mg/l/d in drinking water.
ROUTE AND SITE: Acute: I.E. Chronic: Oral
CONTROL INFORMATION: Pair fed groups.
ROUTE AND SITE: Oral
CONTROL INFORMATION: Matched control water ttd.
DURATION OF EXPERIMENT: Up to 5 mo.
EXAM. TYPE: Biochemistry, histology
DURATION OF EXPERIMENT: Serial sacr 7-11 wk.
EXAM. TYPE: Histology, Histochemistry, Ultrastructural
1091
1092
-------
COMPOUND:
Stannane, triethyl-
COMPOUND:
Strychnine
000057249
REFERENCE: Torack, R., Gordon, J. and Prokop, J.
Int. Rev. Neurobiol. 12:45-86, 1970.
REFERENCE:
Johnston, G.A.R. and Mitchell, J.F.
J. Neurochem. 18:2441-2446, 1971.
OBSERVED NEUROTOXIC EFFECTS:
Weakness, stupor in all except the 4 mg/kg group,
9 mg/kg was fatal. Cerebral edema, especially
of corpus callosum; swollen astrocytes, focal
dilatation of axons, oligodendrites not affected.
Reduced ATFase activity. Fluid accumulation.
Splitting of myelin sheaths.
OBSERVED NEUROTOXIC EFFECTS:
All four compounds influenced the release of GABA,
but not its uptake. Biculline, at 10~5 M (not
more or less) potentiated evoked release of GABA
but not the resting release. Metrazol inhibited
the electrically resting release but not the
electrically evoked release. Strychnine and
picrotoxin inhibited the electrically evoked
release of GABA.
ANIMALS: (1) Rats, albino, M, 300-350 g.
(2) Rats, S-D, 375-425 g.
ANIMALS: In vitro slices of rat cerebral cortex
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) 4-9 mg/kg, single dose.
(2) 7 mg/kg, single dose, with labeled substrates;
1 mg/kg/d for 7-10 d (1 grp).
PREPARATION AND DOSE
or HISTORY OF PATIENT: Preincubated with compounds for 15 min, then with labeled
GABA for 10 min.
ROUTE AND SITE: I.p.
CONTROL INFORMATION: Normal rats
ROUTE AND SITE: in vitro
CONTROL INFORMATION: Lab
DURATION OF EXPERIMENT: Serial sacr (1) 6-24 hr (2) 4-22 hr or 7-10 d
EXAM. TYPE: Biochemistry, histology
DURATION OF EXPERIMENT: 25 min
EXAM. TYPE: Biochemistry
1093
1094
-------
COMPOUND: Strychnine
000057249
REFERENCE: Yagi, K. and Sawaki, Y.
Brain Res. 84:155-159, 1975.
COMPOUND:
REFERENCE:
Strychnine, sulfate (2:1)
000060413
Luse, S.A., Goldring, S. and O'Leary, J.
Arch. Neurol. 11:296-302, 1964.
OBSERVED NEUROTOXIC EFFECTS: Rat hypothalamus tuber-Infundibular neurons
(controlling adenohypophysis functions) were recurrently facilitated
in presence/absence of compound. No effects, suggesting that this neural
circuit is resistant to compound.
OBSERVED NEUROTOXIC EFFECTS: 82% of 50 cortical neurons had marked dilation
of ergastoplasmic sacs of perikaryon and dendrites;
controls showed only occasional edema.
ANIMALS: Rats, Wistar, F cyclic, 191-340 g, surgically prepared
ANIMALS:
6 Rabbits, 1.5-2 kg, surgically prepared.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.2 mg/kg and up to 0.5 mg/kg.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.5-3.5 rag/rabbit.
ROUTE AND SITE: i.v.
CONTROL INFORMATION: Control 0.4 ml of gallamine triethlodide soln (2% w/v)
or Locke's soln, repeatedly inj.
ROUTE AND SITE: I.V.
CONTROL INFORMATION:
Same animals, biopsy and recordings before compound;
also doses of 4 other convulsive compound.
DURATION OF EXPERIMENT: Various short-term intervals.
EXAM. TYPE: Electrophysiological
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior, electrophysiology, histology
1095
1096
-------
COMPOUND: Strychnine, sulfate (2:1)
000060413
REFERENCE: Spooner, C.E. and Winters, W.D.
Int. J. Neuropharmacol. 5: 217-236, 1966
OBSERVED NEUROTOXIC EFFECTS: ^ compound produced convulsions and a desynchronized
EEC.
COMPOUND: Succinamic acid, alpha-amino-, L-
REFERENCE: Curtis, D.R. and Watkins, J.C.
J. Neurochem. 6:117-141, 1960.
OBSERVED NEUROTOXIC EFFECTS:
Treatment caused excitation or depression of
neuronal activity. Excitatory ranking: glutamic,
B-aminoglutaric, aspartic, cysteic, cysteine-
sulfinic acids, B-hydroxyglutamic, N-methylaspartic,
N-formiminoaspartic acids.
Depressant ranking: B-alanine, GABA, taurine,
N-methyl-B-alanine, 6-amino-B-hydroxybutyric,
glycine, a-alanine, 6-aminovaleric, B-aminoisobutyric
acids.
Structure-activity relationships established.
ANIMALS: 200 Cockerels, White Leghorn, ages 5-14 d, 45-100 g
ANIMALS:
Cats, surgically prepared to expose, motoneurones, Renshaw cells or
dorsal horn interneurones in lumbar cord.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.25-1 mg/kg
PREPARATION AND DOSE
or HISTORY OF PATIENT: Qualitative doses.
ROUTE AND SITE: s.C. near axillary vein; i;p. for doses over 0.05 ml
CONTROL INFORMATION: ns
ROUTE AND SITE: Topical, ionophoresis
CONTROL INFORMATION: Laboratory
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Behavior, EEC
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry, electrophysiology
1097
1098
-------
COMPOUND: Succlnamic acid, alpha-amino-, L-
REFERENCE: Olney, J.W., Ho, O.L. and Rhee, V.
Exp. Brain Res. 14:61-76, 1971.
OBSERVED NEUROTOXIC EFFECTS: No cytotoxicity was observed.
ANIMALS: Mice, Swiss-webster age 10 d, total 250
PREPARATION AND DOSE
or HISTORY OF PATIENT: Initially 12 mmoles/kg, then range established for
each compound.
COMPOUND: Succinic acid
000110156
REFERENCE: Curtis, D.R. and Watkins, J.C.
J. Neurochem. 6:117-141, 1960.
OBSERVED NEUROTOXIC EFFECTS:
Treatment caused excitation or depression of
neuronal activity. Excitatory ranking: glutamic,
B-aminoglutaric, aspartic, cysteic, cysteine-
sulfinic acids, 6-hydroxyglutamic, N-methylaspartic,
N-formiminoaspartic acids.
Depressant ranking: 6-alanine, GABA, taurine,
N-methyl-B-alanine, 6-amino-B-hydroxybutyric,
glycine, a-alanine, 6-aminovaleric, B-aminoisobutyric
acids.
Structure-activity relationships established.
ANIMALS: Cats, surgically prepared to exposed motoneurones, Renshaw cells or
dorsal horn interneurones in lumbar cord.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Qualitative doses.
ROUTE AND SITE:
S.c.
CONTROL INFORMATION: Compounds compared with monosodium L-gluts; -te (MSG)
potency for selectively necrosing neurons i:> retina
and brain (hypothalamus)
DURATION OF EXPERIMENT: 5 hr or serial intervals including 5 hr.
EXAM. TYPE: Histology
ROUTE AND SITE: Topical, ionophoresis
CONTROL INFORMATION: Laboratory
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry, electrophysiology
1099
1100
-------
COMPOUND: Succinic acid, 2-aminomethyl-, DL-
COMPOUND: Succinic acid, 2,3-diamino-, meso-
REFERENCE: Curtis, D.R. and Watkins, J.C.
J. Neurochem. 6:117-141, 1960.
REFERENCE: Curtis, D.R. and Watkins, J.C.
J. Neurochem. 6:117-141, 1960.
OBSERVED NEUROTOXIC EFFECTS:
Treatment caused excitation or depression of
neuronal activity. Excitatory ranking: glutamic,
B-aminoglutaric, aspartic, cysteic, cysteine-
sulfinic acids, B-hydroxyglutamic, N-methylaspartic,
N-formiminoaspartic acids.
Depressant ranking: 8-alanine, GABA, taurine,
N-methyl-B-alanine, 6-amino-B-hydroxybutyric',
glycine, a-alanine, 6-aminovaleric, B-aminoisobutyric
acids.
Structure-activity relationships established.
OBSERVED NEUROTOXIC EFFECTS:
Treatment caused excitation or depression of
neuronal activity. Excitatory ranking: glutamic,
B-aminoglutaric, aspartic, cysteic, cysteine-
sulfinic acids, B-hydroxyglutamic, N-methylaspartic,
N-formiminoaspartic acids.
Depressant ranking: B-alanine, GABA, taurine,
N-methyl-B-alanine, 6-amino-B-hydroxybutyric,
glycine, a-alanine, 6-aminovaleric, B-aminoisobutyric
acids.
Structure-activity relationships established.
ANIMALS: Cats, surgically prepared to expose motoneurones, Renshaw cells or
dorsal horn interneurones in lumbar cord.
ANIMALS:
Cats, surgically prepared to exposed motoneurones, Renshaw cells or
dorsal horn interneurones in lumbar cord.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Qualitative doses.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Qualitative doses.
ROUTE AND SITE: Topical, ionophoresis
CONTROL INFORMATION: Laboratory
ROUTE AND SITE: Topical, ionophoresis
CONTROL INFORMATION: Laboratory
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry, electrophysiology
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry, electrophysiology
1101
1102
-------
COMPOUND: Succinic acid, mercapto-.diethyl ester, S-ester with 0,0-dimethyl
phosphorodithioate
(Malathion)
000121755
REFERENCE: Casida, J.E., Baron, R.L., Eto, M. and Engel, J.L.
Biochem. Pharm. 12: 73-83, 1963.
OBSERVED NEUROTOXIC EFFECTS: Malathion was potentiated by: triphenyl phosphates
and phosphonates with o- and 2r> methyl and ethyl
substituents; some diphenylphosphonates and N-
methyl phosphoramidates; J3,j^,j[,-trialkyl phosphoro-
trithioites and phosphorotrithioates; saligenic
cyclic P esters. The last two groups produced
ataxia readily in hens.
COMPOUND: Succinic acid, mercapto-, diethyl ester, S-ester with 0,0-dimethyl
phosphorodithioate
000121755
REFERENCE: Gaines, T.B.
Tox. Appl. Pharm. 14: 515-534, 1969.
OBSERVED NEUROTOXIC EFFECTS: 1000 mg/kg produced leg weakness
ANIMALS: Mice, Rolfsmeyer, F, 25 g
Hens, White Leghorn, 6-18 mo, 1.4-2.2 kg
PREPARATION AND DOSE
or HISTORY OF PATIENT: Mice: Tests to determine effect of various compounds in
malathion toxiclty and antiesterase activity.
Hens: Acute lethal and minimal ataxia dosages studied.
ANIMALS: Chickens, White Leghorn, F
PREPARATION AND DOSE
or HISTORY OF PATIENT: 15 mg/kg atropine sulfate orally 15 min prior to compound;
graded doses compound in peanut oil
ROUTE AND SITE: I.P. (mice); I.P. or oral (hens).
CONTROL INFORMATION: Various
ROUTE AND SITE: S.C., under right wing
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Mortality, clinical, in vitro biochemical
DURATION OF EXPERIMENT: 1 yr
EXAM. TYPE: Clinical
1103
1104
-------
COMPOUND: Succinic acid, mercapto-, diethyl ester, S-ester with 0,0-dimethyl
phosphorodithioate
000121755
REFERENCE: Murphy, S.D., Lauwerys, R.R. and Cheever, K.L.
Tox. Appl. Pharm. 12: 22-35, 1968.
COMPOUND: Succinic acid, mercapto-, diethyl ester, S-ester with 0,0-dimethyl
phosphorodithioate
000121755
REFERENCE: Rayner, M.D., Popper, J.S., Carvalho, E.W. and Hurov, R.
Res. Comm. Chem. Path. Pharm. 4: 595-606, 1972.
OBSERVED NEUROTOXIC EFFECTS:
Poor inhibitor of brain cholinesterase.
to malaoxon which is an inhibitor.
Metabolized
OBSERVED NEUROTOXIC EFFECTS:
The force generated by the achilles tendon reflex was
subnormal in exposed subjects. The authors suggest
that this hyporeflexia may be a sensitive indicator of
chronic exposure to organophosphates.
In vitro brains of rats,
guinea pigs, sparrows, small-
mouth bass, flounder, sculpin
and monkey.
ANIMALS- Mice, Swiss-Webster, M, 25-30g
Chickens, White Rock X N.H. Red, M, 500-700g
Sunfish, M and F, 40-80g
Bullfish, M and F, 40-80g
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.1-1500 mg/kg, various schedules (I.P.) in mice, chickens,
sunfish and bullheads; 0.1-200 mg/kg (orally) in sunfish;
0.001-4 picomoles of malaoxon in vitro.
ANIMALS: Humans, Japanese ancestry, M, ages 22-59 (orchid farmers)
PREPARATION AND DOSE
or HISTORY OF PATIENT: Exposure of more than 4 hr/d, 2 d/wk, 52 wk/yr for 5 yr except
one case (2 yr). Other types of pesticide also used, but
authors judged organophosphates exposures to be primary.
ROUTE AND SITE: See above
CONTROL INFORMATION: Brain cholinesterase determined in controls
ROUTE AND SITE: Skin contact, inhalation
CONTROL INFORMATION: Matched non-exposed subjects, so far as could be ascertained
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Biochemistry
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Physiological
1105
1106
-------
COMPOUND: Sulfoximine, S-(3-amino-3-carboxypropyl)-S-methyl-
COMPOUND:
Sulfoximine, S-(3-amlno-3-carboxypropyl)-S-methyl
REFERENCE: DeRobertis, E., Bellinger, O.Z., Arnais, G.R. deL., Alberici, M. and
Zieher, L.M.
J. Neurochem. 14:81-89, 1967.
OBSERVED NEUROTOXIC EFFECTS: Mode-of-action study. Most bound drug was in the
mitochondrial fraction. Some increase of activity of catechol-0-methyltransferase;
strong inhibition of alanine aminotransferase and glutamine synthetase
(especially in synaptic membranes). infrastructure changes included
swollen nerve-endings and loss of synaptic vesicles. Authors conclude an
action on glutamate-glutamine-GABA metabolism in nerve-endings.
REFERENCE:
Harris, B.
Arch. Neurol. 11:388-407, 1964.
OBSERVED NEUROTOXIC EFFECTS:
Cortex but not white-matter was vacuolated after
1-4 hr of seizures; vacuoles contained osmiophillc
granules, which was also found in distended cytoplasm
between inner rayelin lamellae and axons.
ANIMALS: Rats, white, adult, 150 g
ANIMALS:
Rabbits and dogs, adults, surgically prepared
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.15 ml of solution containing 8.7 mg/mg (labeled),
to produce convulsions.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Rabbits: 1 g, dogs: 5 g (per animal).
ROUTE AND SITE: Intrathecal
CONTROL INFORMATION: None
ROUTE AND SITE: l.V.
CONTROL INFORMATION: Rabbits, normals, and treated in various ways.
DURATION OF EXPERIMENT: 1-1.5 hr
EXAM. TYPE: Brain cortex fractions studied in vitro.
DURATION OF EXPERIMENT: About 30 min per experiment.
EXAM. TYPE: Behavior, electrophysiology, histology
1107
1108
-------
COMPOUND:
Sulfoximlne, S-(3-amino-3-carboxypropyl)-S-methyl-
COMPOUND: Sulfoximine, S-(3-amino-3-carboxypropyl)-S-methyl-
REFERENCE:
Lamar, C. , Jr. and Sellinge.r, O.Z.
Biochem. Pharm. 14:489-506, 1965.
REFERENCE: Rizzuto, N. and Gonatus, N.K.
J. Neuropath. Exp. Neurol. 33(2):237-250, 1974
OBSERVED NEUROTOXIC EFFECTS:
Treatment produced inhibition of cerebral cortex
glutamine synthetase and glutamine transferase
within 30 minutes. The degree of inhibition
was progressive with time. Rats not sacrificed in
4 hours experienced convulsions.
OBSERVED NEUROTOXIC EFFECTS:
Ataxia, weakness, seizures. After severe and
prolonged seizures there was clearing and swelling
of 10% presynaptic endings and glial edema.
Alteration of presynaptic terminals suggested as
metabolic effect of seizures rather than direct drug-
effect. Administration to developing rats did
not result in seizures or morphological changes in
presynaptic terminals, some glial swelling.
ANIMALS: Rats, Holtzman, M, 150-200 g
ANIMALS: Rats, Osborne-Mendel, M and F (1) 8 adults, (2) 2 adults, (3) 2 ten-d
old, (4) 3 developing rats.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
400 mg/kg followed by serial sacrifice up to 4 hr.
PREPARATION AND DOSE
or HISTORY OF PATIENT: (i) 400-600 mg/kg, single convulsant dose.
(2) 100 mg/kg, two subconvulsant doses at 24 hr intervals.
(3) Single adult convulsant dose
(4) 100 mg/kg, daily from birth to 24th d.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: ns.
ROUTE AND SITE: (1-3) I.P. (4) S.C.
CONTROL INFORMATION: (1) 3 controls, (2) 2 controls, (3) 1 control, (4) 2 control rats.
DURATION OF EXPERIMENT: 4 hr
EXAM. TYPE: Biochemistry
DURATION OF EXPERIMENT: Serial sacr various time intervals.
EXAM. TYPE: Behavior, ultrastructural, histopathological
1109
1110
-------
COMPOUND: Sulfoximine, S-(3-amino-3-carboxypropyl)-S-methyl-
REFERENCE: Sinden, S.L., Durbin, R.D., and Uchytil, T.F.
Toxic. Appl. Pharmac. 14: 82-88, 1969.
OBSERVED NEUROTOXIC EFFECTS: (1) Convulsions with minimal dose of 0.25 mmoles/kg
I.P. and became uncoordinated and then spastic.
(2) Convulsions with minimal dose of .00038 mmoles/kg.
ANIMALS: (1) Mice, weanling Swiss Webster, lOg
(2) Rats, Holtzman, 135g
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) 0.25-4.0 mmoles/kg I.P.
(2) .0015-.006 mmoles/kg intracisternally.
ROUTE AND SITE: I.P. and intracisternally.
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: 2-10 hrs. I.P.; 60-75 mins. intracisternally.
EXAM. TYPE: Behavior
1111
COMPOUND: Tellurium
REFERENCE: Duckett, S.
Exp. Neurol. 31:1-16, 1971.
OBSERVED NEUROTOXIC EFFECTS: 24 of 30 produced litters, 20 litters all hydrocephalic,
6 litters all normal. Pathology mainly in ependyma
and subependyma, later the white-matter of survivors
is edematous, cortex gradually destroyed, and connective
tissue present.
ANIMALS: 30 Rats, Wistar, F, mated
PREPARATION AND DOSE
or HISTORY OF PATIENT:
3000 ppm in diet fed through gestation.
ROUTE AND SITE: Oral
CONTROL INFORMATION: 20 similar controls.
DURATION OF EXPERIMENT: Pregnancy
EXAM. TYPE: Teratology
1112
-------
COMPOUND: Tellurium
COMPOUND: Tellurium tetrachloride
REFERENCE: Lampert, P., Garro, F. and Pentschew, A.
Acta Neuropath. 15:308-317, 1970.
OBSERVED NEUROTOXIC EFFECTS: Segmental demyelination of sciatic nerves and
spinal roots resulting in hindlimb paralysis. Edema of nerves and vacuolar
degeneration of Schwann cells, followed by disintegration and removal of
myelin segments. Recovery from paralysis and remyelination occurred despite
continued treatment. Group treated at 20 d age showed less hind leg
weakness, than those treated at 17 d age.
REFERENCE: Carlton, W.W. and Kelly, W.A.
Tox. Appl. Pharm. 11:203-214, 1967.
OBSERVED NEUROTOXIC EFFECTS:
Necrosis in cerebral cortex, brain lesions.
Focal neuronal rarefaction and extensive thinning
of cortical tissue.
ANIMALS: Rats, Long-Evans, 21 from different litters, weanlings.
ANIMALS: Drakes, Pekin, 1 d old
PREPARATION AND DOSE
or HISTORY OF PATIENT: 1% in diet
PREPARATION AND DOSE
or HISTORY OF PATIENT:
50-1000 ppm in diet.
ROUTE AND SITE: Oral
CONTROL INFORMATION: 4 rats
ROUTE AND SITE: Oral
CONTROL INFORMATION: Weight and species matched, untreated.
DURATION OF EXPERIMENT: 25 d
EXAM. TYPE: Behavior, histology
DURATION OF EXPERIMENT: Up to 4 wks.
EXAM. TYPE: Necropsy, histology
1113
1114
-------
COMPOUND:
Tetanus toxin
COMPOUND: Tetanus toxin
REFERENCE' Fedinec, A.A. and Shank, R.P.
J. Neurochem. 18:2229-2234, 1971.
REFERENCE: Webster, R.A.
Int. J. Neuropharmacol. 6: 207-215, 1967.
OBSERVED NEUROTOXIC EFFECTS:
Local and generalized tetany ran its course. No
changes in levels of glycine, GABA, glutamate,
aspartate, or other amino acids in cord or either
half of it, so that the amino acid pool was stable
throughout. Authors conclude that if glycine is a
spinal inhibitory neurotransmitter released by
tetanized interneurons, then the toxin should
interfere with its release rather than deplete the
pool.
OBSERVED NEUROTOXIC EFFECTS:
The toxin exaggerated polysynaptic but not monosynaptic
reflexes. In ventral root and motor nerve filaments,
alpha but not gamma motorneurones became more excitable,,
No increase of afferent input from muscle spindles was
observed. The author concluded that the toxin acted by
abolishing inhibitions of alpha motorneurones.
ANIMALS: Eats, Wistar, M, 250-350 g
ANIMALS: Rabbits, no details, surgically prepared.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
10 mouse MID/kg in 5 mcl 0.15 M-NaCl/dose, one dose.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 1250 mouse m.l.d.
ROUTE AND SITE: I.M., left gastrocnemius
CONTROL INFORMATION: 3 non-injected rats
ROUTE AND SITE: I.M., left gastrocnemius
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: Serial to 45 hr.
EXAM. TYPE: Biochemistry, behavior
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Electromyography
1115
1116
-------
COMPOUND: 5H-Tet.razoloazepine, 6,7,8,9-tetrahydro- (Metrazol)
000054955
REFERENCE:
Johnston, G.A.R. and Mitchell, J.F.
J. Neurochem. 18:2441-2446, 1971.
COMPOUND: 5H-Tetrazoloazepine, 6,7,8,9-tetrahydro
000054955
REFERENCE: Nahorski, S.R., Roberts, D.J. and Stewart, G.G.
J. Neurochem. 17: 621-631, 1970.
OBSERVED NEUROTOXIC EFFECTS:
All four compounds influenced the release of GABA,
but not its uptake. Biculline, at 10~5 M (not
more or less) potentiated evoked release of GABA
but not the resting release. Metrazol inhibited
the electrically resting release but not the
electrically evoked release. Strychnine and
picrotoxin inhibited the electrically evoked
release of GABA.
ANIMALS: In vitro slices of rat cerebral cortex
OBSERVED NEUROTOXIC EFFECTS:
Treatment caused irregular clonus of the forehead
and limbs 75-90 sec after treatment, progressing to
the rest of body and to tonic flexion; about 100
sec after treatment, a full tonic extensor seizure
lasted 10 sec; then sedation with death or recovery
in 20 min. Levels of 25 brain metabolites were
measured. Glycolysis was accelerated, energy
reserves fell; alanine rose, citrate fell; finally
GABA rose slightly and other metabolites moved toward
normal. The authors propose that convulsions result
from disordered brain metabolism.
ANIMALS:
Rats, Hooded-Lister, M, 90-120 g
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Preincubated with compounds for 15 min, then with labeled
GABA for 10 min.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
70 mg/kg
ROUTE AND SITE: in vitro
CONTROL INFORMATION: Lab
ROUTE AND SITE: i.p.
CONTROL INFORMATION: Saline
DURATION OF EXPERIMENT: 25 min
EXAM. TYPE: Biochemistry
DURATION OF EXPERIMENT: Serial to 150 sec; some rats were allowed to recover
EXAM. TYPE: Behavior, biochemistry
1117
1118
-------
COMPOUND: 5H-Tetrazoloazepine, 6,7,8,9-tetrahydro
000054955
REFERENCE:
Nishie, K., Waiss, A.C.,and Keyl, A.C.
Tox. Appl. Pharm. 41:301-307, 1969.
COMPOUND: 5H-Tetrazoloazepine, 6,7,8,9-tetrahydro
000054955
REFERENCE: Palfal, T., Kurtz, P. and Gutman, A.
Pharm. Bicchem. Behav. 2: 261-262, 1974.
OBSERVED NEUROTOXIC EFFECTS: Convulsions, varying degrees of tremor, opisthotonus
and tonic extensor seizures. Authors note higher
pH correspond to lower CD5Q values.
OBSERVED NEUROTOXIC EFFECTS: The compound reduced the brain norepinephrine con-
centration at 5 but not at 1440 minutes after injection.
The time course of induced convulsions and amnesia for
memory-task correlated with the brain norepinephrine
concentration.
ANIMALS:
Mice, albino, M, 20-25 g.
ANIMALS: Mice, M, 70-100 d old, total 84
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Data reported:
CD5Q - 38.5 mg/kg I.P., 75 mg/kg P.O.
LD - 134 mg/kg I.P.,214 mg/kg P.O.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 50 mg/kg
ROUTE AND SITE: I.P., P.O.
CONTROL INFORMATION: Saline or other parameter.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: Distilled water; electric foot-shock.
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Behavior, electrophysiology.
DURATION OF EXPERIMENT: Serial, 5-1440 min
EXAM. TYPE: Behavior, biochemistry
1119
1120
-------
COMPOUND: 5H-Tetrazoloazepine, 6,7,8,9-tetrahydro
000054955
REFERENCE:
Sequin, J., Fretz, N., Manax, S., Stavrky, G.
Arch. Neurol. 5(3):314-319, 1961.
COMPOUND: 5H-Tetrazoloazepine, 6,7,8,9-tetrahydro
000054955
REFERENCE: Spooner, C.E. and Winters, W.D.
Int. J. Neuropharmacol. 5: 217-236, 1966
OBSERVED NEUROTOXIC EFFECTS: CDso 33 mg/kg with isolated twitches of limbs and
head, some had clonic convulsions with ventro-
flexion of head. Convulsant threshold lowered,
latent period prolonged and clonic and repeated
convulsions more frequent than in control animals.
(2) CD5Q 35 mg/kg.
OBSERVED NEUROTOXIC EFFECTS: This compound produced different EEC changes according
; to dose and behavior changes.
ANIMALS:
Rats, S.D., M, divided into 3 groups.
ANIMALS: 200 Cockerels, White Leghorn, ages 5-14 d, 45-100 g
PREPARATION AND DOSE
or HISTORY OF PATIENT:
55 mg/cc stock in saline diluted to .5 cc. Range
for estimation of €050 25, 29, 34, 40 and 47 mg/kg.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 50-100 mg/kg
ROUTE AND SITE: s.C.
CONTROL INFORMATION:
(1) Corpus collusum sectioned under anesthesia
(2) Control, left intact
(3) Sham trepanation.
DURATION OF EXPERIMENT: 5 months
EXAM. TYPE: Behavior
ROUTE AND SITE: s.C. near axillary vein; I.P. for doses over 0.05 ml
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Behavior, EEC
1121
1122
-------
COMPOUND: Tetrodotoxin
011005699
REFERENCE: Bull, R.J. and Trevor, A.J.
J. Neurochem. 19:999-1009, 1972.
OBSERVED NEUROTOXIC EFFECTS: Inhibited increase of lactate and redistribution
of sodium and potassium from electrical stimulation
in vitro. Inhibited the influx of calcium in the
absence of electrical stimulation.
ANIMALS: Rats, S-D, M, 200-250 g, brain cortex slices in vitro
PREPARATION AND DOSE
„-?
or HISTORY OF PATIENT: 10 ' - 10 " M in incubation medium.
ROUTE AND SITE: In vitro
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: Hours
EXAM. TYPE: Biochemistry
1123
COMPOUND: Tetrodotoxin
011005699
REFERENCE: Koizumi, K., Levine, D.G. and Brooks, C. McC.
Neurology 17:395-404, 1967.
OBSERVED NEUROTOXIC EFFECTS: Depressed spinal monosynaptic and postsynaptic
reflexes but not afferent stimuli nor neuromuscular transmission. Motor
actions not blocked; cortical evoked potentials less readily depressed.
ANIMALS: Cats
PREPARATION AND DOSE
or HISTORY OF PATIENT: "Usually" 1-3 meg/kg in solution of 10 meg/ml, one dose.
Repeated doses and larger doses are mentioned.
ROUTE AND SITE: I.V. (radial vein) or application to surgically prepared nerves.
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior, electrophysioiogy
1124
-------
COMPOUND: Tetrodotoxin
011005699
REFERENCE: Narahashl, 1., Haas, H.G. and Therrlen, E.F.
Science 157: 1441-1442, 1967.
OBSERVED NEUROTOXIC EFFECTS: Tetrodotoxin blocks conduction with no change in
resting potential. The mechanism of the blockage
is similar to that caused by saxitoxin, but recovery
of washed axons is slower.
COMPOUND: Thallium
REFERENCE: Zook, B.C. and Gilmore, C.E.
J. Am. Vec. Med. Assn. 151(2): 206-217, 1967.
OBSERVED NEUROTOXIC EFFECTS: The animals exhibited depression, vomiting, anorexia,
neuropathy and esophageal paralysis. Autopsy revealed
scattered neuronal degeneration throughout the cerebrum
and cerebellum, and moderate hydrocephalus. Focal
axonal degeneration and swelling of the myelin sheaths
were observed in the peripheral nervous system.
ANIMALS: Lobster (Homarus americanus)
ANIMALS: 34 dogs, mean age 3 yr (range 6 mo to 8 yr)
PREPARATION AND DOSE
or HISTORY OF PATIENT: Partly isolated giant axons treated with tetrodotoxin at
1 x 10 moles/liter.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Presented at clinic with accidental poisoning with thallium-
containing compounds.
ROUTE AND SITE: Semi-in vitro
CONTROL INFORMATION: Laboratory
ROUTE AND SITE: Unknown
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: Up to 100 min
EXAM. TYPE: Electrophysiology
DURATION OF EXPERIMENT: Cases occurred over a 10 yr period
EXAM. TYPE: Behavior, autopsy
1125
1126
-------
COMPOUND: Thallium
REFERENCE: Bank, W.J., Pleasure, D.E., Suzuki, K., Nigro, M. and Katz, R.
Arch. Neurol. 26:456-463, 1972.
COMPOUND: Thallium sulfate
010031591
REFERENCE: Arena, J.M., Watson, G.A. and Sakhadeo, S.S.
Clin. Pediat. 4: 267-270, 1965.
OBSERVED NEUROTOXIC EFFECTS:
Axonal degeneration, segmental demyelination, mild
peripheral neuropathy, autonomic dysfunction with
tachycardia and hypertension. Alopecia.
OBSERVED NEUROTOXIC EFFECTS: The subject suffered convulsions, stupor, and coma.
At autopsy, the brain (1600 g) seemed swollen but no
microscopic lesions were identified.
ANIMALSKumans: (1)25 yr. old F (2) 27 yr. old M (3) Chronic, 44 yr. old M
(4) 7 yr. old M (5) 3 yr. old F
ANIMALS:
Human: one M, age 5, 43 Ib
PREPARATION AND DOSE
or HISTORY OF PATIENT:
(1&2) Unknown (3) Ingestion of rat poison-1 tsp.
(4&5) Ingestion of unknown amt. of rat poison
PREPARATION AND DOSE
or HISTORY OF PATIENT: Exposure to TAT Home Guard Roach Poison, 1% of compound, by
playing with empty (?) cans, 6 having been used in home during
2 wk. Urine contained thallium of 20.2 mg/1.
ROUTE AND SITE: oral
CONTROL INFORMATION: ns.
ROUTE AND SITE: Oral and/or dermal
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: Symptoms cleared after 10 wks for 1&2. (3) 8 wks
(4) patient died 78 days after ingestion (5) patient symptoms
EXAM. TYPE: almost cleared after 30 days.
Neurologic, urinalysis
DURATION OF EXPERIMENT: About 2 wk
EXAM. TYPE: Clinical and autopsy
1127
1128
-------
COMPOUND: Thallium sulfate
010031591
REFERENCE' Spencer, P.S., Peterson, E.R., Madrid, R. and Raine, C.S.
J. Cell Biol. 58: 79-95, 1973,
OBSERVED NEUROTOXIC EFFECTS: Mitochondria in axons of peripheral nerve fibers were
enlarged after 2 hours, then mitochondria swelled to
become axonal vacuoles, which coalesced, and the
outer membranes had affinity for thallium which is
electron-dense. Swelling made myelin retract from
nodes of Ranvier, but there was no degeneration, and
conduction was not lost. There were similar changes,
but less severe, in dorsal root ganglia and central
fibers, but not in other cell types.
COMPOUND: Theobromine, 1-allyl-
REFERENCE: Scott, C.C., Anderson, R.C. and Chen, K.K.
J. Pharm. Exp. Ther. 86: 113-119, 1946.
OBSERVED NEUROTOXIC EFFECTS: Produced tetanic convulsions.
ANIMALS: In vitro cross-sections of fetal mouse spinal cord with dorsal root
ganglia, 14 d in utero
ANIMALS: nice
PREPARATION AND DOSE
or HISTORY OF PATIENT: 5-10 meg/ml = 1-2 x 10~5M
PREPARATION AND DOSE
or HISTORY OF PATIENT: 35.7 mg/kg (median convulsive dose)
ROUTE AND SITE: m vitro
CONTROL INFORMATION: Laboratory
ROUTE AND SITE: I.V., tail vein
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: Cultures grown for 12 wk, exposed to thallium for up to 4 d
EXAM. TYPE: Histology
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Clinical
1129
1130
-------
COMPOUND: Theobromine, l-(2-butenyl)-
REFERENCE: Scott, C.C., Anderson, R.C. and Chen, K.K.
J. Pharm. Exp. Ther. 86: 113-119, 1946.
OBSERVED NEUROTOXIC EFFECTS: Produced tetanic Convulsions.
ANIMALS: Mice
PREPARATION AND DOSE
or HISTORY OF PATIENT:
56.1 mg/kg (median convulsive dose)
ROUTE AND SITE: I.V., tall vein
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Clinical
1131
COMPOUND: Theobromine, 1-ethyl-
REFERENCE: Scott, C.C., Anderson, R.C. and Chen, K.K.
J. Pharm. Exp. Ther. 86: 113-119, 1946.
OBSERVED NEUROTOXIC EFFECTS: Produced tetanic; convulsions.
ANIMALS: Mice
PREPARATION AND DOSE
or HISTORY OF PATIENT:
54.1 mg/kg (median convulsive dose)
ROUTE AND SITE: I.V., tail vein
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Clinical
1132
-------
COMPOUND: Theobromlne, l-(2'-methoxyethyl)-
REFERENCE: Scott, C.C., Anderson, R.C. and Chen, K.K.
J. Pharm. Exp. Ther. 86: 113-119, 1946.
OBSERVED NEUROTOXIC EFFECTS: Produced tetanic convulsions.
ANIMALS: Mice
PREPARATION AND DOSE
or HISTORY OF PATIENT: 240.0 mg/kg (median convulsive dose)
ROUTE AND SITE: I.V., tail vein
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Clinical
1133
COMPOUND: Theobromine, l-(2'-methylallyl-)
REFERENCE: Scott, C.C., Anderson, R.C. and Chen, K.K.
J. Pharm. Exp. Ther. 86: 113-119, 1946.
OBSERVED NEUROTOXIC EFFECTS: Produced tetanic, convulsions.
ANIMALS: Mice
PREPARATION AND DOSE
or HISTORY OF PATIENT: 119.0 mg/kg (median convulsive dose)
ROUTE AND SITE: I.V., tail vein
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Clinical
1134
-------
COMPOUND: Theobromine, 1-propyl
REFERENCE: Scott, C.C., Anderson, R.C. and Chen, K.K.
J. Pharm. Exp. Ther. 86: 113-119, 1946.
COMPOUND: 4-Thla-l-azabicyclo(3.2.0)heptane-2-carboxylic acid, 3,3-dimethyl-
7-oxo-6-(2-phenylacetamido)-
000061336
REFERENCE: Fossieck, B. and Parker, R.H.
J. Clin. Pharm. 14: 504-512, 1974.
OBSERVED NEUROTOXIC EFFECTS: Produced tetanic'convulsions.
OBSERVED NEUROTOXIC EFFECTS: The subject exhibited asterixis and twitching of
the limb extremities and the face. The compound
found in: cerebrospinal fluid 26 U/ml, cortex 11
and cerebellum 45 U/ml.
ANIMALS: Mice
ANIMALS: Human: one case, M, 43
PREPARATION AND DOSE
or HISTORY OF PATIENT: 96.3 mg/kg (median convulsive dose)
PREPARATION AND DOSE
or HISTORY OF PATIENT: Complications following heart surgery, normal EEC, read-
mission and intensive antibiotics; compound was the 3rd
sp. administered: 8 x 10 units/d
ROUTE AND SITE: I.V., tail vein
CONTROL INFORMATION: ns
ROUTE AND SITE: Continuous I.V. infusion
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Clinical
DURATION OF EXPERIMENT: 4 d (patient died)
EXAM. TYPE: Clinical, biochemistry
1135
1136
-------
COMPOUND: 4-Thia-l-azabicyclo(3.2.0) heptane-2-carboxylic acid, 3,3-dimethyl-
7-oxo-6-(2-phenvlacet amido)-
000061336
REFERENCE: Raichle, M.E., Kutt, H., Louis, S. and McDowell, F.
Arch. Neurol. 25:232-239, 1971.
COMPOUND: 4-Thia-l-azabicyclo(3.2.0) heptane-2-carboxylic acid, 3,3-dimethyl-
7-OXO-6-(2-phenylacetamido)-
000061336
REFERENCE: Tang, A.H. and Schroeder, L.A.
Tox. Appl. Pharm. 12:44-47, 1968.
OBSERVED NEUROTOXIC EFFECTS:
In 1 human case, encephalopathy followed by g
recovery on stopping treatment. In cats, 1.3 x 10
units/kg produced encephalopathy with myoclonus,
more produced status epilepticus and death.
In rats, 4.5 x 10^ units/kg and more produced same,
but if anesthetized (ether) only 3 x 10" units/kg
were needed. Encephalopathy was reversed by
penicillinase, i.v. Labeled penicillin was
concentrated mainly in membranal-nuclear fraction
of homogenates; peak reached 5-10 mins after dose.
OBSERVED NEUROTOXIC EFFECTS: Produced little blockade of neuromuscular transmission
at doses given.
ANIMALS:
1 Human patient; 19 adult cats, 2.5-4 kg; 48 Wistar rats, 200-300 g.
ANIMALS: 6 Rabbits
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Human: Postsurgery, 10 x 10 units 2/d, for 14 d.
Cats: 0.5-1.5 x 10 units/kg "or more" repeated in some
animals.,
Rats: 3-5 x 10 units/kg.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 25 mg/kg followed by 50 mg/kg, in saline.
ROUTE AND SITE: I.V., by catheter in cats (femoral veins) and rats (jugular).
CONTROL INFORMATION: Human: removal, reinstatement, and again removal of therapy.
Cats and rats: similar techniques, no control groups mentioned.
ROUTE AND SITE: i.v.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: Minutes to weeks
EXAM. TYPE: Behavior, EEC, biochemistry
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Electrophysiology, behavior
1137
1138
-------
COMPOUND: 4-Thia-l-azabicyclo(3.2.0) heptane-2-carboxylic acid, 3,3-dimethyl-7-oxo-
6-(2-phenylacetamido)-, monopotassium and monosodium salts
REFERENCE: Okada, K., Ayala, G.F. and Sung, J.H.
J. Neuropath. Exp. Neurol. 30(3):337-353, 1971.
OBSERVED NEUROTOXIC EFFECTS:
EEC: Periodic cortical paroxysm, ipsilateral only,
only with penicillin-G.
Histology: Cortical lesions, progressive with
time, similar in 1st and 2nd groups; streptococcal
exotoxin caused different lesions, sucrose nil.
COMPOUND: 4H-Thieno(2,3-b)(l,4)benzothiazine
REFERENCE: Grol, C.J. and Rollema, H.
J. Med. Chem. 18:857-861, 1975.
OBSERVED NEUROTOXIC EFFECTS: This compound gave positive results in a
neurotoxicity screening test in which the
criteria were ptosis, sedation and -catalepsy.
ANIMALS: 34 adult cats in 4 groups: 16, 6, 8, 4.
ANIMALS:
Hats and mice, no details
PREPARATION AND DOSE
or HISTORY OF PATIENT:
ROUTE AND SITE:
CONTROL INFORMATION:
Bilateral burr-holes to expose pericruciate gyrus of
cortex; topical applications on one side. 1st group
received paste as above; 2nd, in Ringer solution
(isotonic); 3rd received streptococcal paste or hypertonic
sucrose; 4th same plus trypan blue I.V.
The second side was not treated, stated to act as control.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 40 mg/kg.
ROUTE AND SITE: i.P.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: Order of 60-90 min per experiment
EXAM. TYPE: EEC, then histology.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior screening tests
1139
1140
-------
COMPOUND: 9H-Thieno(3,4-b)(l,4)benzothiazine
REFERENCE:
Grol, C.J. and Rollema, H.
J. Med. Chem. 18:857-861, 1975.
OBSERVED NEUROTOXIC EFFECTS: This compound gave positive results in a
neurotoxicity screening test in which the
criteria were ptosis, sedation and catalepsy.
ANIMALS:
Rats and mice, no details
PREPARATION AND DOSE
or HISTORY OF PATIENT: 40 mg/kg.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior screening tests
1141
COMPOUND: 9H-Thieno(3,2-b)(l,4)benzothiazine, 9-acetyl-
REFERENCE:
Grol, C.J. and Rollema, H.
J. Med. Chem. 18:857-861, 1975.
OBSERVED NEUROTOXIC EFFECTS: This compound gave positive results in a
neurotoxicity screening test in which the
criteria were ptosis, sedation and catalepsy.
ANIMALS:
Rats and mice, no details
PREPARATION AND DOSE
or HISTORY OF PATIENT: 40 mg/kg.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior screening tests
1142
-------
COMPOUND: 9H-Thieno(3,4-b)(l,4)benzothiazine-9-carboxaldehyde
REFERENCE:
Grol, C.J. and Rollema, H.
J. Med. Chem. 18:857-861, 1975.
OBSERVED NEUROTOXIC EFFECTS: This compound gave positive results in a
neurotoxicity screening test in which the
criteria were ptosis, sedation and catalepsy.
ANIMALS:
Rats and mice, no details
PREPARATION AND DOSE
or HISTORY OF PATIENT: 40 mg/kg.
ROUTE AND SITE: i.P.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior screening tests
1143
COMPOUND: 4H-Thieno(2,3-b)(l,4)benzothiazine-4-carboxaldehyde, 6-chloro
REFERENCE:
Grol, C.J. and Rollema, H.
J. Med. Chem. 18:857-861, 1975.
OBSERVED NEUROTOXIC EFFECTS: This compound gave positive results in a
neurotoxicity screening test in which the
criteria were ptosis, sedation and catalepsy.
ANIMALS: Rats and mice, no details
PREPARATION AND DOSE
or HISTORY OF PATIENT: 40 mg/kg.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior screening tests
1144
-------
COMPOUND: 9H-Thieno(3,2-b)(l,4)benzothiazine-9-carboxaldehyde, 7-chloro
REFERENCE:
Grol, C.J. and Rollema, H.
J. Med. Chem. 18:857-861, 1975.
OBSERVED NEUROTOXIC EFFECTS: This compound gave positive results in a
neurotoxicity screening test in which the
criteria were ptosis, sedation and catalepsy.
ANIMALS:
Rats and mice, no details
PREPARATION AND DOSE
or HISTORY OF PATIENT: 40 mg/kg.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior screening tests
1145
COMPOUND: 9H-Thieno(3,4-b) (l,4)benzothiazine-9-carboxaldehyde, 7- chloro
REFERENCE:
Grol, C.J. and Rollema, H.
J. Med. Chem. 18:857-861, 1975.
OBSERVED NEUROTOXIC EFFECTS: This compound gave positive results in a
neurotoxicity screening test in which the
criteria were ptosis, sedation and catalepsy.
ANIMALS: Rats and mice, no details
PREPARATION AND DOSE
or HISTORY OF PATIENT: 40 mg/kg.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior screening tests
1146
-------
COMPOUND: 4H-Thieno(2,3-b) (l,4)benzothiazine-4-carboxaldehyde, 6-(trlfluoromethyl)-
COMPOUND: 9H-Thieno(3,2-b) (l,4)benzothiazine-9-carboxaldehyde, 7-(trifluoromethyl)-
REFERENCE:
Grol, C.J. and Rollema, H.
J. Med. Chem. 18:857-861, 1975.
REFERENCE:
Grol, C.J. and Rollema, H.
J. Med. Chem. 18:857-861, 1975.
OBSERVED NEUROTOXIC EFFECTS: This compound gave positive results in a
neurotoxicity screening test in which the
criteria were ptosis, sedation and catalepsy.
OBSERVED NEUROTOXIC EFFECTS: This compound gave positive results in a
neurotoxicity screening test in which the
criteria were ptosis, sedation and catalepsy.
ANIMALS: Rats and mice, no details
ANIMALS:
Rats and mice, no details
PREPARATION AND DOSE
or HISTORY OF PATIENT: 40 mg/kg.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 40 mg/kg.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: ns.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior screening tests
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior screening tests
1147
1148
-------
COMPOUND: 9H-Thieno(3,4-b)(l,4)benzothiazine-9-carboxaldehyde, 7(trifluoromethyl)-
COMPOUND: 4H-Thieno(2,3-b)(l,4)benzothiazine, 6-chloro-
REFERENCE:
Grol, C.J. and Rollema, H.
J. Med. Chem. 18:857-861, 1975.
OBSERVED NEUROTOXIC EFFECTS: This compound gave positive results in a
neurotoxicity screening test in which the
criteria were ptosis, sedation and catalepsy.
REFERENCE:
Grol, C.J. and Rollema, H.
J. Med. Chem. 18:857-861, 1975.
OBSERVED NEUROTOXIC EFFECTS: This compound gave positive results in a
neurotoxicity screening test in which the
criteria were ptosis, sedation and catalepsy.
ANIMALS:
Rats and mice, no details
ANIMALS:
Rats and mice, no details
PREPARATION AND DOSE
or HISTORY OF PATIENT: 40 mg/kg.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 40 mg/kg.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: ns.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior screening tests
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior screening tests
1149
1150
-------
COMPOUND: 9H-Thieno(3,2-b)(l,4)benzothiazine, 7-chloro-
REFERENCE:
Grol, C.J. and Rollema, H.
J. Med. Chem. 18:857-861, 1975.
OBSERVED NEUROTOXIC EFFECTS: This compound gave positive results in a
neurotoxicity screening test in which the
criteria were ptosis, sedation and catalepsy.
ANIMALS:
Rats and mice, no details
PREPARATION AND DOSE
or HISTORY OF PATIENT: 40 mg/kg.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior screening tests
1151
COMPOUND: 9H-Thieno(3,4-b)(l,4)benzothiazine, 7-chloro
REFERENCE:
Grol, C.J. and Rollema, H.
J. Med. Chem. 18:857-861, 1975.
OBSERVED NEUROTOXIC EFFECTS: This compound gave positive results in a
neurotoxicity screening test in which the
criteria were ptosis, sedation and catalepsy.
ANIMALS:
Rats and mice, no details
PREPARATION AND DOSE
or HISTORY OF PATIENT: 40 mg/kg.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior screening tests
1152
-------
COMPOUND: 4H-Thieno(2,3-b)(l,4)benzothiazine, 7-chloro-4-(3-dimethylaminopropyl)-,
hydrochloride
REFERENCE:
Grol, C.J. and Rollema, H.
J. Med. Chem. 18:857-861, 1975.
OBSERVED NEUROTOXIC EFFECTS: This compound gave positive results in a
neurotoxicity screening test in which the
criteria were ptosis, sedation and catalepsy.
COMPOUND: 9H-Thieno(3,4-b)(l,4)benzothiazine, 7-chloro-9-(3-dimethylaminopropyl)-
hydrochloride
REFERENCE:
Grol, C.J. and Rollema, H.
J. Med. Chem. 18:857-861, 1975.
OBSERVED NEUROTOXIC EFFECTS: This compound gave positive results in a
neurotoxicity screening test in which the
criteria were ptosis, sedation and catalepsy.
ANIMALS:
Rats and mice, no details
ANIMALS: Rats and mice, no details
PREPARATION AND DOSE
or HISTORY OF PATIENT: 40 mg/kg.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 40 mg/kg.
ROUTE AND SITE: i.P.
CONTROL INFORMATION: ns.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior screening tests
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior screening tests
1153
1154
-------
COMPOUND:
. 9H-Thieno(3,4-b)(l,4)benzothiazine, 9-(3-dimethylaminopropyl)-, hydrochlorlde
COMPOUND: 9H-Thieno(3,4-b)(l,4)benzothiazine, 4-(3-dimethylaminopropyl)-6-
(trifluoromethyl)-, hydrochloride
REFERENCE:
Grol, C.J. and Rollema, H.
J. Med. Chem. 18:857-861, 1975.
REFERENCE:
Grol, C.J. and Rollema, H.
J. Med. Chem. 18:857-861, 1975.
OBSERVED NEUROTOXIC EFFECTS: This compound gave positive results in a
neurotoxicity screening test in which the
criteria were ptosis, sedation and catalepsy.
OBSERVED NEUROTOXIC EFFECTS: This compound gave positive results in a
neurotoxicity screening test in which the
criteria were ptosis, sedation and catalepsy.
ANIMALS:
Rats and mice, no details
ANIMALS:
Rats and mice, no details
PREPARATION AND DOSE
or HISTORY OF PATIENT: 40 mg/kg.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 40 mg/kg.
ROUTE AND SITE: . i.P.
CONTROL INFORMATION: ns.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior screening tests
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior screening tests
1155
1156
-------
COMPOUND: 9H-Thieno(3,4-b)(l,4)benzothiazine, 9-(3-dimethylaminopropyl)-7-
(trlfluoromethyl)-, hydrochloride
REFERENCE:
Grol, C.J. and Rollema, H.
J. Med. Chem. 18:857-861, 1975.
OBSERVED NEUROTOXIC EFFECTS: This compound gave positive results in a
neurotoxicity screening test in which the
criteria were ptosis, sedation and catalepsy.
ANIMALS: Rats and mice, no details
PREPARATION AND DOSE
or HISTORY OF PATIENT: 40 rag/kg.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior screening tests
1157
COMPOUND: 4H-Thieno(2,3-b)(l,4)benzothiazine, 6-(trifluoromethyl)-
REFERENCE:
Grol, C.J. and Rollema, H.
J. Med. Chem. 18:857-861, 1975.
OBSERVED NEUROTOXIC EFFECTS: This compound gave positive results in a
neurotoxicity screening test in which the
criteria were ptosis, sedation and catalepsy.
ANIMALS: Rats and mice, no details
PREPARATION AND DOSE
or HISTORY OF PATIENT: 40 mg/kg.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior screening tests
1158
-------
COMPOUND:
9H-Thieno(3,2-b)(l,4) benzothiazine, 7-(trifluoromethyl)-
REFERENCE:
Grol, C.J. and Rollema, H.
J. Med. Chem. 18:857-861, 1975.
OBSERVED NEUROTOXIC EFFECTS: This compound gave positive results in a
neurotoxicity screening test in which the
criteria were ptosis, sedation and catalepsy.
ANIMALS:
Rats and mice, no details
PREPARATION AND DOSE
or HISTORY OF PATIENT: 40 mg/kg.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior screening tests
1159
COMPOUND: 9H-Thieno(3,4-b)(1,4) benzothiazine, 7-(trifluoromethyl)-
REFERENCE:
Grol, C.J. and Rollema, H.
J. Med. Chem. 18:857-861, 1975.
OBSERVED NEUROTOXIC EFFECTS: This compound gave positive results in a
neurotoxicity screening test in which the
criteria were ptosis, sedation and catalepsy.
ANIMALS: Rats and mice, no details
PREPARATION AND DOSE
or HISTORY OF PATIENT: 40 mg/kg.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior screening tests
1160
-------
COMPOUND: Thiophene, 3-(2-amino-4-chlorophenyl)Chio-
REFERENCE:
Grol, C.J. and Rollema, H.
J. Med. Chem. 18:857-861, 1975.
OBSERVED NEUROTOXIC EFFECTS: This compound gave positive results in a
neurotoxicity screening test in which the
criteria were ptosis, sedation and catalepsy.
ANIMALS:
Rats and mice, no details
PREPARATION AND DOSE
or HISTORY OF PATIENT: 40 mg/kg.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior screening tests
1161
COMPOUND: Thiophene, 2-(2-amino-4-chlorophenyl) thio-3-bromo-
REFERENCE:
Grol, C.J. and Rollema, H.
J. Med. Chem. 18:857-861, 1975.
OBSERVED NEUROTOXIC EFFECTS: This compound gave positive results in a
neurotoxicity screening test in which the
criteria were ptosis, sedation and'catalepsy.
ANIMALS:
Rats and mice, no details
PREPARATION AND DOSE
or HISTORY OF PATIENT: 40 mg/kg.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior screening tests
1162
-------
COMPOUND: Thiophene, 3-(2-amino-4-chlorophenyl)thio-4-bromo
REFERENCE:
Grol, C.J. and Rollema, H.
J. Med. Chem. 18:857-861, 1975.
OBSERVED NEUROTOXIC EFFECTS: This compound gave positive results in a
neurotoxicity screening test in which the
criteria were ptosis, sedation and catalepsy.
ANIMALS:
Rats and mice, no details
PREPARATION AND DOSE
or HISTORY OF PATIENT: 40 mg/kg.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior screening tests
1163
COMPOUND:
Thiophene, 3-(2-aminophenyl) thio-
REFERENCE:
Grol, C.J. and Rollema, H.
J. Med. Chem. 18:857-861, 1975.
OBSERVED NEUROTOXIC EFFECTS: This compound gave positive results in a
neurotoxicity screening test in which the
criteria were ptosis, sedation and catalepsy.
ANIMALS:
Rats and mice, no details
PREPARATION AND DOSE
or HISTORY OF PATIENT: 40 mg/kg.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior screening tests
1164
-------
COMPOUND:
Thiophene, 2-(2-aminopheny1)thio-3-bromo-
REFERENCE:
Grol, C.J. and Rollema, H.
J. Med. Chem. 18:857-861, 1975.
OBSERVED NEUROTOXIC EFFECTS: This compound gave positive results in a
neurotoxicity screening test in which the
criteria were ptosis, sedation and catalepsy.
ANIMALS:
Rats and mice, no details
PREPARATION AND DOSE
or HISTORY OF PATIENT: 40 mg/kg.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior screening tests
1165
COMPOUND:
Thiophene, 3-(2-aminophenyl)thio-4-bromo-
REFERENCE:
Grol, C.J. and Rollema, H.
J. Med. Chem. 18:857-861, 1975.
OBSERVED NEUROTOXIC EFFECTS: This compound gave positive results in a
neurotoxicity screening test in which the
criteria were ptosis, sedation and catalepsy.
ANIMALS: Rats and mice, no details
PREPARATION AND DOSE
or HISTORY OF PATIENT: 40 mg/kg.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior screening tests
1166
-------
COMPOUND: Thlophene, 3-((2-amino-(alpha, alpha, alpha-trifluoro-p-tolyl)))thio-
COMPOUND: Thiophene, 2-((2-amino-(alpha, alpha, alpha-trifluoro-p-tolyl)))thio-3-bromo-
REFERENCE:
Grol, C.J. and Rollema, H.
J. Med. Chem. 18:857-861, 1975.
REFERENCE:
Grol, C.J. and Rollema, H.
J. Med. Chem. 18:857-861, 1975.
OBSERVED NEUROTOXIC EFFECTS: This compound gave positive results in a.
neurotoxicity screening test in which the
criteria were ptosis, sedation and catalepsy.
OBSERVED NEUROTOXIC EFFECTS: This compound gave positive results in a
neurotoxicity screening test in which the
criteria were ptosis, sedation and catalepsy.
ANIMALS:
Rats and mice, no details
ANIMALS: Rats and mice, no details
PREPARATION AND DOSE
or HISTORY OF PATIENT: 40 mg/kg.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 40 mg/kg.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: ns.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior screening tests
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior screening tests
1167
1168
-------
COMPOUND: Thiophene, 3-((2-amino-(alpha, alpha, alpha-trifluoro-p-tolyl)))thio-4-bromo- COMPOUND:
Thiophene 3-bromo-2-(4-chloro-2-nitrophenyl)thio-
REFERENCE:
Grol, C.J. and Rollema, H.
J. Med. Chem. 18:857-861, 1975.
REFERENCE:
Grol, C.J. and Rollema, H.
J. Med. Chem. 18:857-861, 1975.
OBSERVED NEUROTOXIC EFFECTS: This compound gave positive results in a
neurotoxicity screening test in which the
criteria were ptosis, sedation and catalepsy.
OBSERVED NEUROTOXIC EFFECTS: This compound gave positive results in a
neurotoxicity screening test in which the
criteria were ptosis, sedation and catalepsy.
ANIMALS:
Rats and mice, no details
ANIMALS: Rats and mice, no details
PREPARATION AND DOSE
or HISTORY OF PATIENT: 40 mg/kg.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 40 mg/kg.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: ns.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior screening tests
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior screening tests
1169
1170
-------
COMPOUND:
Thiophene, 3-bromo-4-(4-chloro-2-nitrophenyl)thio-
REFERENCE: Grol, C.J. and Rollema, H.
J. Med. Chem. 18:857-861, 1975.
OBSERVED NEUROTOXIC EFFECTS: This compound gave positive results in a
neurotoxicity screening test in which the
criteria were ptosis, sedation and catalepsy.
ANIMALS:
Rats and mice, no details
PREPARATION AND DOSE
or HISTORY OF PATIENT: 40 rag/kg.
ROUTE AND SITE: i.P.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior screening tests
1171
COMPOUND: Thiophene, 3-bromo-2-(2-nitrophenyl)thio-
REFERENCE:
Grol, C.J. and Rollema, H.
J. Med. Chem. 18:857-861, 1975.
OBSERVED NEUROTOXIC EFFECTS: This compound gave positive results in a
neurotoxicity screening test in which the
criteria were ptosis, sedation and catalepsy.
ANIMALS:
Rats and mice, no details
PREPARATION AND DOSE
or HISTORY OF PATIENT: 40 mg/kg.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: ns.
HRATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior screening tests
1172
-------
COMPOUND: Thiophene, 3-bromo-4-(2-nitrophenylthio)-
REFERENCE:
Grol, C.J. and Rollema, H.
J. Med. Chem. 18:857-861, 1975.
OBSERVED NEUROTOXIC EFFECTS: This compound gave positive results In a
neurotoxicity screening test in which the
criteria were ptosis, sedation and catalepsy.
ANIMALS: Rats and mice, no details
PREPARATION AND DOSE
or HISTORY OF PATIENT: 40 mg/kg.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior screening tests
1173
COMPOUND:
REFERENCE:
Thiophene, 3-bromo-2-((2-n itro-(alpha,alpha,alpha-trifluoro-p-
tolyDthio)-
Grol, C.J. and Rollema, H.
J. Med. Chem. 18:857-861, 1975.
OBSERVED NEUROTOXIC EFFECTS: This compound gave positive results in a
neurotoxicity screening test in which the
criteria were ptosis, sedation and catalepsy.
ANIMALS:
Rats and mice, no details
PREPARATION AND DOSE
or HISTORY OF PATIENT: 40 mg/kg.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior screening tests
1174
-------
COMPOUND:
REFERENCE:
Thiophene, 3-bromo-4-((2-nitro-(alpha,alpha,alpha-trifluoro-p-
tolyl)thio)-
Grol, C.J. and Rollema, H.
J. Med. Chem. 18:857-861, 1975. ' .
OBSERVED NEUROTOXIC EFFECTS: This compound gave positive results in a
neurotoxicity screening test in which the
criteria were ptosis, sedation and catalepsy.
ANIMALS: Rats and mice, no details
PREPARATION AND DOSE
or HISTORY OF PATIENT: 40 mg/kg.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior screening tests
1175
COMPOUND: Thiophene, 3-(4-chloro-2-nitrophenyl) thio-
REFERENCE:
Grol, C.J. and Rollema, H.
J. Med. Chem. 18:857-861, 1975.
OBSERVED NEUROTOXIC EFFECTS: This compound gave positive results in a
neurotoxicity screening test in which the
criteria were ptosis, sedation and catalepsy.
ANIMALS:
Rats and mice, no details
PREPARATION AND DOSE
or HISTORY OF PATIENT: 40 mg/kg.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior screening tests
1176
-------
COMPOUND: Thiophene hydrazide
REFERENCE: Jenney, E.H. and Pfeiffer, C.C.
J. Phann. Exp. Ther. 122: 110-123, 1958.
COMPOUND:
REFERENCE:
Thiophene, 3-(2-nitrophenylthio)
Grol, C.J. and Rollema, H.
J. Med. Chem. 18:857-861, 1975.
OBSERVED NEUROTOXIC EFFECTS: Convulsions
OBSERVED NEUROTOXIC EFFECTS: This compound gave positive results in a
neurotoxicity screening test in which the
criteria were ptosis, sedation and catalepsy.
ANIMALS: Mice, Harlan, 19-21 g
ANIMALS:
Rats and mice, no details
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.56 mM/kgm
PREPARATION AND DOSE
or HISTORY OF PATIENT: 40 rag/kg.
ROUTE AND SITE: i.P.
CONTROL INFORMATION: ns
ROUTE AND SITE: I.P.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: Acute
EXAM. TYPE: Clinical
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior screening tests
1177
1178
-------
COMPOUND' Thiophene, 3-(2-nitro-alpha, alpha, alpha-trifluoro-p-
tolyl)thio-
REFERENCE: Grol, C.J. and Rollema, H.
J. Med. Chem. 18:857-861, 1975.
OBSERVED NEUROTOXIC EFFECTS: This compound gave positive results in a
neurotoxicity screening test in which the
criteria were ptosis, sedation and catalepsy.
COMPOUND: Thiopyrophosphoric acid, tetrapropyl ester
003244904
REFERENCE: Sherman, M., Ross, E. and Chang, M.T.Y.
Tox. Appl. Pharm. 6:147-153, 1964.
OBSERVED NEUROTOXIC EFFECTS:
(1) Convulsions followed in many by death within
18 hr. Survivors were lethargic for 6-19 hr post
treatment. (2) 50% cholinesterase inhibition
by dose of 380 ppm.
ANIMALS:
Rats and mice, no details
ANIMALS: Cockerels, White Leghorn, single-comb, 10-50/grp, 12 d old
PREPARATION AND DOSE
or HISTORY OF PATIENT: 40 mg/kg.
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) Acute: LD (436.1 mg/kd) in gelatin capsule.
(2) Subacute: 50-800 ppm in feed.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: ns.
ROUTE AND SITE: Oral
CONTROL INFORMATION: Untreated diet.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Behavior screening tests
DURATION OF EXPERIMENT: 1 wk
EXAM. TYPE: Mortality, behavior, blood ChE
1179
1180
-------
COMPOUND: Thioxanthene-delta.(sup):-gamma-propylamine, 2-chloro-N,N-dimethyl,
hydrochlorlde
001229385
REFERENCE: Quinton, R.M.
Br. J. Pharmac. 21:51-66, 1963.
OBSERVED NEUROTOXIC EFFECTS: The compound enhanced the effect of Yohimbine
and lowered its lethal dosage.
COMPOUND: Tin, dioctyl-, acetate
REFERENCE: Robinson, I.M.
Fd. Cosmet. Toxicol. 7: 45-52, 1969.
OBSERVED NEUROTOXIC EFFECTS: Treatment lowered brain epinephrine, norepinephrine
and serotonin for 48 hours.
ANIMALS:
Mice, TT, M, 18-25 g.
ANIMALS: Rats, Osborne-Mendel, F, 190-220 g, 18/group
PREPARATION AND DOSE
or HISTORY OF PATIENT:
ED5Q 18 mg/kg
"50
dose producing a 50% mortality of mice injected
S.C. with yohimbine hydrochloride (20 mg/kg).
PREPARATION AND DOSE
or HISTORY OF PATIENT:
800 mg/kg in corn oil
ROUTE AND SITE: s.C., Oral
CONTROL INFORMATION: Various
ROUTE AND SITE: I.P.
CONTROL INFORMATION: Equivalent corn oil
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Behavior, electrophysiology, biochemistry
DURATION OF EXPERIMENT: Serial to 48 hr
EXAM. TYPE: Behavior, biochemistry
1181
1182
-------
COMPOUND: Tin, triethyl-, sulphate
REFERENCE: Aleu, F.P., Katzman, R. and Terry, R.D.
J. Neuropath. Exp. Neurol. 22(3):403-413, 1963.
OBSERVED NEUROTOXIC EFFECTS: Generalized neuromuscular weakness in hindlimbs
and immobilization. Continued injections lead to quadriplegia and death.
Severe cerebral edema.
ANIMALS: 21 Rabbits, M, 3 kg
PREPARATION AND DOSE
or HISTORY OF PATIENT: 1 mg/kg/d in saline soln.
ROUTE AND SITE: i.p.
CONTROL INFORMATION: 11 rabbits, treatment ns.
DURATION OF EXPERIMENT: Sacr 6-7 d
EXAM. TYPE: Histology, histochemlstry, ultrastructural
1183
COMPOUND:
Tin'
-- sulphate
REFERENCE: Graham, D.I. and Gonatas, N.K.
Laboratory Investigation 29(6):628-632, 1973.
OBSERVED NEUROTOXIC EFFECTS: Sciatic nerve splitting, nerve fibers underwent
Wallerian degeneration. Produced lesions in the peripheral nervous system.
Motor dysfunction, spastic paresis of hindllmb. Progressive paraplegia
and quadriplegia. Swollen and edamatous brains. Myelln splitting.
ANIMALS: 12 Rats, Osbourne-Mendell, M and F, (6) 3 mo. old and (6) 12 mo. old.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 20 mg/1 in drinking water
ROUTE AND SITE: Oral
CONTROL INFORMATION: 12 matched for age and sex.
DURATION OF EXPERIMENT: Sacr by 22nd
EXAM. TYPE: Ultrastructural, clinical, histology
1184
-------
COMPOUND:
Tin, triethyl-, sulphate
REFERENCE:
Katzman, R. Aleu, F. and Wilson, C.
Arch. Neurol. 9:178-187, 1963.
OBSERVED NEUROTOXIC EFFECTS:
Water content of white-matter (dry-matter basis)
rose by 91%; no change in Na-Mg-dependent ATP ase;
this, other chemistry, and histology indicated
that edema fluid was located in intramyelinic
vacuoles.
ANIMALS: 40 rabbits, white, M, 2-3 kg.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 1 mg/kg in saline.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: 20 untreated controls.
DURATION OF EXPERIMENT: Up to 7 hr.
EXAM. TYPE: Biochemistry, histology
1185
COMPOUND: . Tin, triethyl-, sulphate
REFERENCE: Suzuki, K.
Exp. Neurol. 31:207-213, 1971.
OBSERVED NEUROTOXIC EFFECTS: All acute rats died in 3 d, hemorrhagic
encephalopathy. Chronic rats no behavior signs
but spongy degeneration found throughout the
central nervous system white-matter.
ANIMALS: Rats, Wlstar Acute: 20 newborn, 10 eight d old, 2 two mo. old.
Chronic: 8 newborn, their dam, 2 two mo. old.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Acute: 5 mg/kg/d for 3 d.
Chronic: 5 mg/1 in water for 4 mo.
ROUTE AND SITE: Acute: I.P.
CONTROL INFORMATION: ns.
Chronic: Oral
DURATION OF EXPERIMENT: 3 d and 4 mo.
EXAM. TYPE: Histology and behavior
1186
-------
COMPOUND:
Tin, trioctyl-, dllaurate
REFERENCE: Robinson, I.M.
Fd. Cosmet. Toxicol. 7: 45-52, 1969
OBSERVED NEUROTOXIC EFFECTS: Treatment lowered brain epinephrine, norepinephrine
and serotonin for 48 hours.
COMPOUND: p-Toluamlde, N-isopropyl-alpha-(2-methylhydrazino)
000671169
REFERENCE: Chaube, S. and Murphy, M.L.
Teratology 2: 23-32, 1969.
OBSERVED NEUROTOXIC EFFECTS: Exencephaly, encephalocele, and acephaly, seen
after treatment on d 9 only, after doses of 1/2 to 1/45 of the female
lethal dose of 550 mg/kg.
ANIMALS: Rats, Osborne-Mendel, F, 190-220 g, 18/group
ANIMALS: Rats, CF Wistar, F in estrus, 200-250 g, total 275
PREPARATION AND DOSE
or HISTORY OF PATIENT: 800 mg/kg
PREPARATION AND DOSE
or HISTORY OF PATIENT: 5-550 mg/kg in 0.85% NaCl, one dose on 5-17th d of
gestation.
ROUTE AND SITE: i.P.
CONTROL INFORMATION: Equivalent corn oil
ROUTE AND SITE: I.P.
CONTROL INFORMATION: 23 controls vehicle only.
DURATION OF EXPERIMENT: Serial to 48 hr
EXAM. TYPE: Behavior, biochemistry
DURATION OF EXPERIMENT: Sacr 21d
EXAM. TYPE: Histology of fetuses
1187
1188
-------
COMPOUND: p-Toluamide, N-isopropyl-alpha-(2-methylhydrazlno)-
000671169
REFERENCE: Herman, E.H., Lee, I.
Toxicol. Appl. Pharmacol. 22:484-496, 1972.
COMPOUND:
Toluene
000108883
REFERENCE: Grabski, D.A.
Am. J. Psychiat.
118: 461-426, 1961.
OBSERVED NEUROTOXIC EFFECTS:
Central nervous system depression observed In anesthetized
and unanesthetized animals. (1) Anesthetized
monkeys showed decrease in EEC activity. (2) Unanesth-
etized animals given similar doses induced
somnolence with concurrent synchronization of the
EEC pattern, producing ataxia.
OBSERVED NEUROTOXIC EFFECTS:
The subject showed a gait characteristic of cerebellar
damage, intention tremor of the hands and feet, and rebound
phenomena in all limbs. There was no abnormality of
olfaction, vision, orientation, memory, mentation, or of
cranial nerves 5,7,9,11,12 or of posterior column signs,
toe position or vibratory sense. The author inferred
Irreversible cerebellar damage, probably to the lateral
lobes .
ANIMALS: Monkeys, M, 3.5-4.5 kg (1) 12 (2) 3 (3) 15 animals
ANIMALS: Human, 1 case, M, 19 at start
PREPARATION AND DOSE
or HISTORY OF PATIENT: (1) Anesthetized: d25, 50, 100, 200 or 400 mg/kg in saline.
(2) Unanesthetized: 100 mg/kg, preceded 15 min by dl-propanolol
or d-propanolol 0.5 mg/kg.
(3) Unanesthetized: 25, 50, 200, 400 mg/kg. (3 animals per dose)
PREPARATION AND DOSE
or HISTORY OF PATIENT: Addictive pattern of self administration over 6 yr
ROUTE AND SITE: I.V.
CONTROL INFORMATION: ns.
ROUTE AND SITE: Inhalation
CONTROL INFORMATION: None
DURATION OF EXPERIMENTED mins.
EXAM. TYPE: Electroencephalography, electrocardiography
DURATION OF EXPERIMENT: 6 yr
EXAM. TYPE: Behavior, clinical, neurological
1189
1190
-------
COMPOUND: Toluene
000108883
REFERENCE: Knox, J.W. and Nelson, J.R.
New Eng. J. Med. 275: 1494-1496, 1966.
OBSERVED NEUROTOXIC EFFECTS:
Ataxia, tremors, emotional lability, right Babinski
sign, diffuse EEG slowing, diffuse cerebral atrophy
by pneumoencephalography, .interpreted as permanent
brain damage.
COMPOUND:
Triethylcholine
REFERENCE: Hartung, R. and"'Cornish, H.H.
Tox. Appl. Phartn. 12:486-494, 1968,
OBSERVED NEUROTOXIC EFFECTS:
This compound was tested with a group of other
aminoethanols and choline analogs, all of which in-
hibited cholinesterase in vitro. In vitro inhibition
increases as the number of carbon atoms attached
on the nitrogenous head of the 2-aminoethanol I
molecule. In the in vivo tests the oral IJ>50's were
uniformly higher than the i.p. LD values.
ANIMALS:
Human: 1 case, M, 33
ANIMALS: Rats, S-D, M
PREPARATION AND DOSE
or HISTORY OF PATIENT: History of glue- or pure toluene-sniffing for 14 yr with
exposure estimated at about 1 gallon/mo; minimal alcohol
consumption, one episode of carbon tetrachloride intoxi-
cation, frequent admissions to mental hospitals.
ROUTE AND SITE:• Inhalation
CONTROL INFORMATION: None
PREPARATION AND DOSE
or HISTORY OF PATIENT: In vitro:
In vivo:
ROUTE AND SITE: Oral, i.p., in vitro
CONTROL INFORMATION: ns.
to 10 .
an<^ l°wer doses.
DURATION OF EXPERIMENT: 14 yr
EXAM. TYPE: Behavioral, EEG, pneumoencephalography
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry
1191
1192
-------
COMPOUND: l-alpha-H,5-alpha-H-tropane-2-beta-carboxylic acid, 3-beta-
hydroxy-methyl ester, benzoate (ester) hydrochloride
000053214
REFERENCE: Quinton, R.M.
Br. J. Pharmac. 21:51-66, 1963.
OBSERVED NEUROTOXIC EFFECTS: The compound enhanced the effect of Yohimbine
and lowered its lethal dosage.
COMPOUND: l-alpha-H,5-alpha-H-tropane, 3-alpha-(diphenyl methoxy)
REFERENCE: pfeiffer, C.C., Murphree, H.B., Jenney, E.H., Robertson, M.G.,
Randall, A.H. and Bryan, L.
Neurology 9: 249-250, 1959.
OBSERVED NEUROTOXIC EFFECTS: The authors concluded that synthetic atropines are more
j active hallucinogens than atropine or scopolamine, pro-
ducing effects lasting 24-48 hr. Synthetic antitremor
drugs had fewer peripheral nervous system side-effects,
but central nervous system side-effects (hallucinations)
may have been exaggerated.
ANIMALS:
Mice, TT, M, 18-25 g.
ANIMALS: Human: prison volunteers, drug-sophisticated, no other details
PREPARATION AND DOSE
or HISTORY OF PATIENT:
ED5Q 15 mg/kg
EDeg = dose producing a 50% mortality of mice injected
S.C. with yohimbine hydrochloride (20 mg/kg).
PREPARATION AND DOSE
or HISTORY OF PATIENT: 2 mg/man
ROUTE AND SITE: s.c., Oral
CONTROL INFORMATION: Various
ROUTE AND SITE: Oral
CONTROL INFORMATION: LSD-25: 0, 25, 50, 100 meg/man
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Behavior, electrophysiology, biochemistry
DURATION OF EXPERIMENT: Up to 3 d
EXAM. TYPE: Opinion of volunteers
1193
1194
-------
COMPOUND:
Tropanium, 3-alpha-hydroxy-9-methyl, p-tolylacetate
COMPOUND: Tropanol aryl esters, (unspecified)
REFERENCE: Friess, S.L. and Anderson, J.B.
Tox. Appl. Pharm. 22: 208-212, 1972.
OBSERVED NEUROTOXIC EFFECTS:
With tropine-p_-tolylacetate or its quaternary methiodide
separately, there was reversibility of induced blockade
on washing depending on the extent of N-substitution,
quaternary methiodide being more reversible than the
tertiary ester. But 1 mM of tropine-p_-tolylacetate
added to 5mM of its quaternary methiodide halved the
reversibility of quaternary methiodide blockade. More
than 1 mM of tropine-£-tolylacetate had no more effect.
REFERENCE: Friess, S.L., Durant, R.C., Baldridge, H.D. and Reber, L.J.
Tox. Appl. Pharm. 7:694-707, 1965.
OBSERVED NEUROTOXIC EFFECTS:
Stereospecific effects obtained at synaptic
chemoreceptors, features of intoxication syndrome,
interpreted in terms of .chemical configuration
of receptor sites.
ANIMALS:
In vitro excitable nodes of Ranvier in single fibers of frog sciatic
nerve.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 5mM for separate incubations with tropine-£-tolylacetate and
its quaternary methiodide; tropine-p_-tolylacetate:the quater-
nary methiodide ratios in mixed incubations 1:5, 2:5, and
3:5 in mM.
ANIMALS: Rats: Long-Evans, M: in vivo and phrenic nerve-diaphragm preparations.
Cats: In situ denervated gastrocnemius-soleus preparations
Frogs: In vitro, nodes of Ranvier in single fibers of sciatic nerve.
PREPARATION AND DOSE . , 7 ' ,
or HISTORY OF PATIENT: 10"^ to 10~J M; in some tests 10"'to 5 x 10 *• M.
ROUTE AND SITE: In vitro
CONTROL INFORMATION: Laboratory
ROUTE AND SITE: Prepared
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Incubation, removal, washing, observing by electrophysiology
DURATION OF EXPERIMENT:ns.
EXAM. TYPE: Electrophysiology
1195
1196
-------
COMPOUND:
Tropine, and aryl esters (unspecified)
COMPOUND: 2-d-Tropine, p-nitrophenylacetate, (ester)
REFERENCE: Reber, L.J., Allen, C.H., Durant, R.C. and Friess, S.L.
Tox. Appl. Pharm. 5: 625-636, 1963.
REFERENCE: Friess, S.L., Baldridge, H.D., Durant, R.C. and Reber, L.J.
Tox. Appl. Pharm. 7:794-803, 1965.
OBSERVED NEUROTOXIC EFFECTS: Convulsions, paralysis (i.v.), dose-related. In vitro
potentiation of evoked twitch responses, interpreted in
terms of chemoreceptor structure-activity relationships.
OBSERVED NEUROTOXIC EFFECTS: Behaviorally and electrically less toxic than the
3-tropanyl isomers; interpreted in terms of chemical
configuration of synaptic receptor sites.
ANIMALS: Mice, white, M, 18-22 g, 10/group
Rat phrenic nerve-diaphragm preparations
Cats, no details
PREPARATION AND DOSE
or HISTORY OF PATIENT: Two new esters were synthesized, described structurally.
I-IJ/-HC1, mice 32.7 mg/kg (LD ), cats 10-25.5 mg/kg (dose)
II-i|)-HCl, mice 35 mg/kg (LD ;, cats 25 mg/kg (dose)
Rat PD-prep:
, "50'
10 to > 5 x 10 M in medium
ANIMALS: Mice, NMRI, intact
Cats, mongrel, intact and denervated gastronemius muscle preparation
Rats, in vitro phrenic nerve-diaphragm preparations
PREPARATION AND DOSE
or HISTORY OF PATIENT: Mice: LD (23-63 mg/kg)
Cats: 30255 mg/kg ,
In vitro: 10~5 to 10 M
ROUTE AND SITE: I.V., in vitro
CONTROL INFORMATION: ns
ROUTE AND SITE: I.V., in vitro
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: ns
EXAM. TYPE: Biochemistry, electrophysiology
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Electrophysiology
1197
1198
-------
COMPOUND: 2-alpha-Tropine, p-tolylacetate, (ester)
COMPOUND: Turpentine
REFERENCE: Friess, S.L., Baldridge, H.D., Durant, R.C. and Reber, L.J.
Tox. Appl. Pharm. 7:794-803, 1965.
REFERENCE: Sperling, F., Marcus, W.L. and Collins, C.
Tox. Appl. Pharm. 10:8-20, 1967.
OBSERVED NEUROTOXIC EFFECTS: Behaviorally and electrically less toxic than the
3-tropanyl isomers; interpreted in terms of chemical
configuration of synaptic receptor sites.
OBSERVED NEUROTOXIC EFFECTS:
LC-n for rats, 1-6 hr exposures, were 12-20 mg/liter;
2-hr LC_Q for mice was 29 mg/liter; highest
concentration was in brain. Ataxia, tremors,
convulsions produced by I.V., sometimes by inhalation.
ANIMALS: Mice, NMRI, intact
Cats, mongrel, intact and denervated gastronemlus muscle preparations
Rat, in vitro phrenic nerve-diaphragm preparations
PREPARATION AND DOSE
or HISTORY OF PATIENT: Mice: LDQ(23-63 mg/kg)
Cats: 30-45 mg/kg _,
In vitro: 10"5 to 10 M
ANIMALS: Rats, Wistar, M, 140-200 g
Mice, Groups of 10, Swiss-Webster, M, 25-30 g
PREPARATION AND DOSE
or HISTORY OF PATIENT:
Vapors generated at 25-27°, various concentrations to
measure LC for 1-6 hr. ^>cn for I-v- in mice.
ROUTE AND SITE: i.v., in vitro
CONTROL INFORMATION: ns.
ROUTE AND SITE: Inhalation, I.V.
CONTROL INFORMATION: Various
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Electrophysiology.
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Clinical, polygraph, biochemistry
1199
1200
-------
COMPOUND:
o-Tyrosine, DL-
REFERENCE: Curtis, D.R. and Watkins, J.C.
J. Neurochem. 6:117-141, 1960.
COMPOUND: Uracil, 5-fluoro
000051218
REFERENCE: Koeing, H. and Patel, A.
Trans. Ainer. Neurol. Assoc. 94:290-292, 1969.
OBSERVED NEUROTOXIC EFFECTS:
Treatment caused excitation or depression of
neuronal activity. Excitatory ranking: glutamic,
6-aminoglutaric, aspartic, cysteic, cysteine-
sulfinic acids, B-hydroxyglutamic, N-methylaspartic,
N-form±minoaspartic acids.
Depressant ranking: (3-alanine, GABA, taurine,
N-methyl-g-alanine, 6-amino-g-hydroxybutyric,
glycine, a-alanine, 6-aminovaleric, B-aminoisobutyric
acids.
Structure-activity relationships established.
OBSERVED NEUROTOXIC EFFECTS:
Neuronal and glial lesions in cerebellar and
vestibular structures, onset of cerebellar ataxia
and convulsions caused by formation of fluoroacetate
with consequent blockage of the Krebs cycle.
ANIMALS: Cats, surgically prepared to exposed motoneurones, Renshaw cells or
dorsal horn interneurones in lumbar cord.
ANIMALS: Cats
PREPARATION AND DOSE
or HISTORY OF PATIENT: Qualitative doses.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 7.5-30 mg/kg
ROUTE AND SITE: Topical, ionophoresis
CONTROL INFORMATION: Laboratory
ROUTE AND SITE: i.v.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemistry, electrophysiology
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Biochemical, histological
1201
1202
-------
COMPOUND: Uracil, 5-fluoro
000051218
REFERENCE:
Koenig, H. and Patel, A.
Arch. Neurol. 23:155-160, 1970.
COMPOUND: Uracil, 5-fluoro
000051218
REFERENCE: Kury, G. and Craig, J.M.
Arch. Path. 81: 166-173, 1966*
OBSERVED NEUROTOXIC EFFECTS:
Citrate in brain elevated. In 2 patients,
citrate in whole blood was elevated. Inter-
preted as inhibition of citrate-isocitrate step
of Krebs cycle (aconitase-catalyzed). Fluorouracil
thought metabolized to fluoracetate. Return
to normal 5 d after treatment.
OBSERVED NEUROTOXIC EFFECTS: Exencephaly with severe brain malformations, neuraxis
with necrotic neuroblasts. Some microphthalmia arid
necrotic neurons in neuraxis.
ANIMALS: 24 Cats, adult, M and F, 2-3 kg. 2 Human patients.
ANIMALS: Eggs, White Leghorn, fertilized
PREPARATION AND DOSE
or HISTORY OF PATIENT:
7.5-30 rag/kg i.v. or 20 mg/kg i.p. Also a-fluoro-
alanine 5-10 mg/kg i.p., and fluoroacetate
0.1-0.4 mg/kg. Patients 15 mg/kg/d for 5 d,
or 7.5 mg/2 d.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Teratogenic dosage schedules, from d 1 to d 4
ROUTE AND SITE: I.V. or I.P. Human: I.V.
CONTROL INFORMATION: Saline controls.
ROUTE AND SITE: Inoculation
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: Serial sacr to 48 hr.
EXAM. TYPE: Biochemical "
DURATION OF EXPERIMENT: 21 d
EXAM. TYPE: Teratological
1203
1204
-------
COMPOUND: Uracil. 5-fluoro
000051218
REFERENCE: Riehl, J-L., and Brown, W.J.
Neurology 14: 961-967, 1964.
COMPOUND: Urea, ((p-bromophenyl)acetyl)-
30241862
REFERENCE: Chen, F.C.K. and Cavanagh, J.B.
Br. J. Exp. Path. 52:315-321, 1971.
OBSERVED NEUROTOXIC EFFECTS:
Acute cerebellar syndrome seen In humans, reversed
on stopping or lowering dosage of compound; autopsies
showed chromatolysis of neurons of olivary and dentate
nuclei, and sparse cells in granular layer of cere-
bellum. Cats showed multifocal edema and destruction
of Purklnje cells and granular layer of cerebellum;
myelin and axons were affected.
OBSERVED NEUROTOXIC EFFECTS:
Liver damage studies indicated that substance was
neurotoxic per se; adults over 9—10 wk old more
susceptible than juveniles, no sex differences.
Substance was probably detoxified by liver but
not by microsomal enzymes induced by barbiturates.
Paresis in limbs dose—related.
ANIMALS: Human: 4 cases, 46-69, and 2 autopsies
Cats: 3 healthy, 3-3.5 kg
ANIMALS: Hats, Porton, M and F, 180-250 g.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Humans: Up to 15 mg/kg/d, subsequently lowered
Cats: 15 mg/kg/d
PREPARATION AND DOSE
or HISTORY OF PATIENT:
50-400 mg/kg/d for 2 d.
Bats prepared in various ways with neurotoxic treatments.
ROUTE AND SITE: I.V.
CONTROL INFORMATION: ns
ROUTE AND SITE: Gavage
CONTROL INFORMATION: 28 healthy rats.
DURATION OF EXPERIMENT: Humans: various. Cats: to 7 d
EXAM. TYPE: Behavior, histology
DURATION OF EXPERIMENT: 2 wk
EXAM. TYPE: Behavior, enzyme determinations.
1206
1205
-------
COMPOUND: Urea, ((p-bromophenyl)acetyl)-
30241862
REFERENCE: Blakemore, W.F. and Cavanagh, J.B.
Brain 92:789-804, 1969.
OBSERVED NEUROTOXIC EFFECTS: "Neuroaxonal dystrophy" In "dying back"
process from second wk, persisting for at least
10 wk after treatment.
ANIMALS: Rats, SPF, M, about 200 g.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 200 mg/kg/d in DMSO.
ROUTE AND SITE: Oral, via cannula
CONTROL INFORMATION: D1ISO only, number ns.
DURATION OF EXPERIMENT: Serial sacr 5 d to 10 wk.
EXAM. TYPE: Histology
1207
COMPOUND: Urea, ethyl nitroso-
000759739
REFERENCE: Cravioto, H., Weiss, J.F., Weiss E. de C., Goebel, H.H. and
Ransohoff, J.
J. Acta Neuropath. 23:265-280, 1973.
OBSERVED NEUROTOXIC EFFECTS: Peripheral nervous system tumors in 80%,
Central nervous system in 16% of treated rats. Mostly trigeminal nerve
in peripheral nerves: Schwann cells behaving as if malignant. Transplants,
direct or cultured, behaved similarly, similar cell composition.
ANIMALS: Rats, 10 CFE and 6 inbred BD-IX, F
PREPARATION AND DOSE
or HISTORY OF PATIENT:
and transplanted.
20 mg/kg in last 5 d of gestation. Tumors cultured
ROUTE AND SITE: I.V., Transplants intracerebral or i.p., or s.c.
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Cytology, electronmicroscopy
1208
-------
COMPOUND: Urea, ethyl nitroso-
000759739
REFERENCE: Fornatto, L. and Schiffer, D.
Acta Neuropath. 20:199-206, 1972.
COMPOUND: Urea, ethyl nitroao-
000759739
REFERENCE: Grossi-Paoletti, E., Paoletti, P., Schiffer, D. and Fabiani, A.
J. Neurol. Sci. 11:573-581, 1970.
OBSERVED NEUROTOXIC EFFECTS: Five neurinomas were produced. Abundant spindle
cells, mitoses, necroses, and cysts; signs of high invasiveness. Activities
of acid phosphatase, B-glucuronidase, lysosomes, and plnocytosis were
characterized.
OBSERVED NEUROTOXIC EFFECTS: Tumors in 41 (89Z) offspring, total 58:
40 intracranial, 18 spinal. Types: 35 neurinomas, 20 oligodendrogliomas,
2 ependymomas, 1 glioblastoma.
ANIMALS: Rats, Long-Evans, newborn
ANIMALS: Rats, Long-Evans, F at d 17 of pregancy: 46 young.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 50 mg/kg.
Five neurinomas of. the Vth cranial nerve cultured in vitro, with 4-30 particle
explanatations each.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 10 mg/kg one dose on d 17 of pregnancy.
ROUTE AND SITE: Intracerebral; s.c.
CONTROL INFORMATION: 2 Human neurinomas of the Vlllth cranial nerve with 28
particle explanations.
ROUTE AND SITE: I.V.
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: 20 d of culture followed by histochemistry
EXAM. TYPE: Histology, histochemistry
DURATION OF EXPERIMENT: 150-400 d
EXAM. TYPE: Autopsy, histology
1209
1210
-------
COMPOUND: Urea, ethyl nitroso-
000759739
REFERENCE: Jones, E.L., Searle, C.E. and Smith, W.T.
J. Path. 109:123-139, 1973.
OBSERVED NEUROTOXIC EFFECTS: 33 Of 34 had 71 tumors; 62 cranial, 9 spinal.
ANIMALS: Rats, Wistar and hooded-Norway, newborn, total 38; 34 survived
weaning..
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.02 ml/rat 24 hr after birth (10 mg/kg).
ROUTE AND SITE: S.C.
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: 191-680 d sacr when neuropathology seen.
EXAM. TYPE: Histology, pathology
1211
COMPOUND: Urea, ethyl nitroso-
000759739
REFERENCE: Lantos, P.L.
J. Path. 116:107-115, 1975.
OBSERVED NEUROTOXIC EFFECTS: 39 of 40 offspring developed either gliomas
or malignant schwannomas. Ultrastructure of resultant macrophages is
reported.
ANIMALS: 9 rats, BD-IX, F, pregnant d 15
PREPARATION AND DOSE
or HISTORY OF PATIENT: 30 mg/kg one dose in citrate buffer
ROUTE AND SITE: i.v.
CONTROL INFORMATION: 2 rats buffer only.
DURATION OF EXPERIMENT: 160-300 d
EXAM. TYPE: Histology
1212
-------
COMPOUND: Urea, ethyl nitroso-
000759739
REFERENCE:
Pfaffenroth, M.J., Das, G.D. and McAllister, J.P.
Teratology 9:305-316, 1974.
OBSERVED NEUROTOXIC EFFECTS: Mlcroencephaly, especially of cortex and
cerebellum. The earlier the injection, the greater the decrease. No
recovery in adulthood. At 4 mo. some brain tumors observed.
COMPOUND: Urea, ethyl nitroso-
000759739
REFERENCE: Wechsler, W., Pfeiffer, S.E., Swenberg, J.A. and Koestner, A.
Acta Neuropath. 24: 287-303, 1973.
OBSERVED NEUROTOXIC EFFECTS: 18 brain tumors, 1 cord tumor and 22 peripheral nervous
system tumors were studied. S-100 protein isolated from
16 central nervous system and 21 peripheral nervous system
tumors, but found in only 1/10 non-neurogenic tumors.
Authors claim that S-100 protein is "definitive indication"
of nerve cell participation in a tumor.
ANIMALS: Rats, Wistar, F, pregnant
ANIMALS: Rats, CD, CDF, or BDIX, pregnant F, 3rd period gestation.
PREPARATION AND DOSE
or HISTORY OFqPATIENT: 60 mg/kg/d on d 14-21 of gestation in saline at pH 4.5.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 1, 5, 20 or 50 mg/kg to produce tumors in offspring.
ROUTE AND SITE: i.v., tail
CONTROL INFORMATION: None
ROUTE AND SITE: I.V.
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: Progeny killed 0-75 d after birth (7 groups, 2/gp);
some observed for 4 mo.
EXAM. TYPE: Macroscopical (histology to be reported elsewhere)
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Histology, biochemistry.
1213
1214
-------
COMPOUND: Urea, hydroxy-
000127071
REFERENCE: Perm, V.H.
Arch. Path. 81: 174-177, 1966.
OBSERVED NEUROTOXIC EFFECTS: Exencephaly and failure of neural tube to close after
administration of compound, more so after i.v. treatment.
COMPOUND: Urea, methyl nitroso-
000684935
REFERENCE: Schiffer, D., Fabiani, A., Grossi-Paolettl, E. and Paoletti, P.
J. Neurol. Sci. 11:559-572, 1970.
OBSERVED NEUROTOXIC EFFECTS: 29 (80%) rats developed central nervous system
tumors: total of 46 intracranial and 8 cord tumors. Cranial mostly
oligodendrogliomas and other gliomas. Cord: 6 gliomas, 2 neurinomas.
ANIMALS: Golden hamsters, F, pregnant, 100-125 g
ANIMALS: 36 Rats, Long-Evans; M, aged 1-2 mo.
PREPARATION AND DOSE
or HISTORY OF PATIENT: 50 mg/hamster on d 9, 10, 11 or 12
PREPARATION AND DOSE
or HISTORY OF PATIENT: 25 mg/kg/mo (one dose/mo.) for 8 mo.
ROUTE AND SITE: i.v. lingual vein
CONTROL INFORMATION: ns
ROUTE AND SITE: I.V. tail vein
CONTROL INFORMATION: ns.
DURATION OF EXPERIMENT: 24-72 hr. after treatment.
EXAM. TYPE: Teratological
DURATION OF EXPERIMENT: 8 mo.
EXAM. TYPE: Clinical, histology
1215
1216
-------
COMPOUND: Urea, methyl nitroso-
000684935
REFERENCE: Wechsler, W., Pfeiffer, S.E., Swenberg, J.A. and Koestner, A.
Acta Neuropath. 24: 287-303, 1973.
COMPOUND: Urea, (2-phenylbutyryl)-
000090493
REFERENCE: Orloff, M.J., Feldman, P.E., Shaiova, C.H. and Pfeiffer, C.C.
Neurology 1: 377-385, 1951.
OBSERVED NEUROTOXIC EFFECTS: 18 brain tumors, 1 cord tumor and 22 peripheral nervous
system tumors were studied. S-100 protein isolated from
16 central nervous system and 21 peripheral nervous system
tumors, but found in only 1/10 non-neurogenic tumors.
Authors claim that S-100 protein is "definitive indication"
of nerve cell participation in a tumor.
OBSERVED NEUROTOXIC EFFECTS: Doses used to control grand mal seizures produced
"extreme toxiclty": cramps, anorexia, dizziness,
ataxia, disorientation, athetoid movements. The
effects were not persistent.
ANIMALS: (1) Rats, Charles River, adult, CD and CDF (all SPF)
ANIMALS: Humans: 10 Institutionalized epileptics
PREPARATION AND DOSE
or HISTORY OF PATIENT: 180 mg/kg as 5 mg/kg/wk, carcinogenic dose
PREPARATION AND DOSE
or HISTORY OF PATIENT: Humans: 1.2-7.2 g/patient/d with other drugs, various
periods
ROUTE AND SITE: Oral, i.p., i.v., or s.c.
CONTROL INFORMATION: None
ROUTE AND SITE: Oral
CONTROL INFORMATION: None
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Histology, biochemistry
DURATION OF EXPERIMENT: 4-64 d
EXAM. TYPE: Clinical
1217
1218
-------
COMPOUND:
Urease
COMPOUND: Urldine, 2'-deoxy-5-fluoro
REFERENCE: Gibson, G.E., Zimber, A., Krook, L., Richardson, E.P., Visek, W.J.
J. Neuropath, and Exper. Neurol. 33(2):201-211, 1974.
REFERENCE: Kury, G. and Craig, J.M.
Arch. Path. 81: 166-173, 1966.
OBSERVED NEUROTOXIC EFFECTS:
Brain tissue examined 30-38 hr after injection
showed increases in size and number of astrocytic
nuclei; the astrocytes were typical in appearance of
Alzheimer II cells. Spongy vacuolation of neurophil.
Behavioral changes included coma with or without
generalized convulsive seizures.
OBSERVED NEUROTOXIC EFFECTS: Exencephaly with severe brain malformations, neuraxis
I with necrotic neuroblasts, no abnormalities of cord
and autonomic ganglia.
ANIMALS:
Mice, S.W., M, 18-21 g
ANIMALS: Eggs, White Leghorn, fertilized
PREPARATION AND DOSE
or HISTORY OF PATIENT:
0.2 ml of crystalline jackbean urease injected twice
with 0.4 units of urease per mouse. Others received
55 units/kg body wt. - LD-
PREPARATION AND DOSE
or HISTORY OF PATIENT: Teratogenic dosage schedules, from d 1 to d 4
ROUTE AND SITE: I.P.
CONTROL INFORMATION: Injected with .85% NaCl.
ROUTE AND SITE: Inoculation
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT:
EXAM. TYPE: Histological
Approx. 36 hrs after injection depending on behavior
conditions.
DURATION OF EXPERIMENT: 21 d
EXAM. TYPE: Teratological
12.19
1220
-------
COMPOUND: Uridine, 2'-deoxy-5-fluoro
COMPOUND: Valeric acid, 2-amino-5-sulfo-, 0L-
REFERENCE: Maruyama, S., Chiga, M. and D'Agostino, A.N.
J. Neuropath. Exp. Neurol. 27:96-107, 1968.
OBSERVED NEUROTOXIC EFFECTS:
Necrosis in central nervous system progressive
from 3 hr. In cord dorsal columns and horns,
in brain the telencephalon, hippocampi, and
corpus callosum were most affected. Interpreted
as selective effects on cells in S phase in
presence of DNA inhibition.
REFERENCE:Curtis, D.R. and Watkins, J.C.
J. Physiol. 166:1-14, 1963.
OBSERVED NEUROTOXIC EFFECTS:
N-methyl-D-aspartic and D-homocysteic acids were
stronger excitants of depolarization than all
others. With some compounds the action was
prolonged for many seconds after the stimulus
was terminated, notably N-n_-propyl-D-aspartic
acid. There were no differences among types of
neurons tested; structure-activity relationship
was observed.
ANIMALS: 22 Rats, S-D, pregnant F, about 300 g.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
60 mg in water (average 200 mg/kg). Histology
on 5 fetuses per litter.
ANIMALS: Cats prepared for electrophoretic application of chemicals to single
central nervous system neurons.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Dilutions 0.1-0.5 M of 31 compounds mainly of aspartic,
glutamic and cysteic acids listed In order of
potency of results.
ROUTE AND SITE: I.P.
CONTROL INFORMATION: Fetuses from 1 rat/d on days 13, 14, 15 and 17.
ROUTE AND SITE: Electrophoretic application, various sites In central nervous
system.
CONTROL INFORMATION:
None
DURATION OF EXPERIMENT: Serial sacr 30 min to 4 d.
EXAM. TYPE: Histology
DURATION OF EXPERIMENT: ns.
EXAM. TYPE: Electrophysiologlcal
1221
1222
-------
COMPOUND: Valeric acid, 2,2-diphenyl-, 2-(diethylamino) ethyl ester
COMPOUND: Veratrum alkaloids (Unspecified)
REFERENCE: Gaitonde, B.B. and Borison, H.L.
Tox. Appl. Pharm. 8:118-125, 1966.
REFERENCE: Kolb, E.J. and Korein, J.
Neurology 11: 159-163, 1961
OBSERVED NEUROTOXIC EFFECTS: 25 mg/kg cause clonic convulsions; repeated doses
i.p. cumulative, causing anorexia, convulsions
and death. Intracarotid doses stimulated forebrain;
doses into vertebral artery depressed respiratory
center in lower brainstem. Peripheral nervous system
effects as well.
OBSERVED NEUROTOXIC EFFECTS: In 3 cases, produced reversible episodic myotonic
syndrome, dose-related intensity; in one case
episodic peripheral neuropathy.
ANIMALS: Cats, no details, some surgically prepared.
ANIMALS: Human: 4 patients, M, with hypertension
PREPARATION AND DOSE
or HISTORY OF PATIENT: 2-25 mg/kg i.v. or intracarotid, or in vertebral artery;
10 or 40 mg/kg intraportal; 25-200 mg/kg i.p.
PREPARATION AND DOSE
or HISTORY OF PATIENT: Up to 1 mg 3 times/d
ROUTE AND SITE: I.V. or intracarotid, intraportal, i.p.
CONTROL INFORMATION: ns.
ROUTE AND SITE: Oral
CONTROL INFORMATION: None
DURATION OF EXPERIMENT:Various time schedules.
EXAM. TYPE: Clinical, physiograph, autopsy
DURATION OF EXPERIMENT: Months
EXAM. TYPE: Clinical
1223
1224
-------
COMPOUND: Vincaleukoblastine
000865214
REFERENCE: 'Gottschalk, P.G., Dyck, P.J. and Kiely, J.M.
Neurol. 18: 875-882, 1968 *
COMPOUND: Vincaleukoblastine, sulfate (1:1) (salt)
000143679
REFERENCE: Smith, B.
J. Neurol. Neurosurg. Psychiat. 30: 506-510, 1967.
OBSERVED NEUROTOXIC EFFECTS: Generalized weakness, numbness of toes, decreased muscle
stretch reflexes. Death occured four weeks after end of
treatment. Sural nerves contained unusually large fibers,
and other signs of Wallerian degeneration were found.
OBSERVED NEUROTOXIC EFFECTS: The myenteric plexus was examined, and histologlcal
changes were found. '
ANIMALS: 1 Human, F, age 46 yr
ANIMALS: 45 Mice, TO, CFW and Porton strains, 20-25 g
PREPARATION AND DOSE
or HISTORY OF PATIENT: 80 mg in 8 wk
PREPARATION AND DOSE
or HISTORY OF PATIENT: 0.005 or 0.05 mg/d for 3-6 d, 18 mice
Acute study: 10 mg I.P. or 2 mg I.V. one dose
ROUTE AND SITE: I.V.
CONTROL INFORMATION: Group of rats, not described
ROUTE AND SITE: I.P.
CONTROL INFORMATION: ns
DURATION OF EXPERIMENT: 8 wk
EXAM. TYPE: Histology
DURATION OF EXPERIMENT: 2 d to 3 mo after last dose. Acute: 20 min.
EXAM. TYPE: Histology
1225
1226
-------
COMPOUND: Xylitol
REFERENCE: Evans, GW., Phillips, G., Mukherjee, T.M., Snow, M.R., Lawrence, J.R.
and Thomas, D.W.
J. Clin. Path. 26: 32-36, 1973
OBSERVED NEUROTOXIC EFFECTS: Calcium oxalate crystals deposited in midbrain,
almost certainly as indirect result of xylitol.
COMPOUND: Yohimbam-16-alpha-carboxylic acid, 17-alpha-hydroxy-, methyl ester
000146485
REFERENCE: Quinton, R.M.
Br. J. Pharmac. 21:51-66, 1963.
OBSERVED NEUROTOXIC EFFECTS: Treatment produced ptosis, sedation, prostration,
and clonic, but never tonic, convulsions. It
also decreased brain norepinephrine, but had no
effect on monoamine oxidase activity.
ANIMALS: Human: 1 M, 58
ANIMALS: Mice, TT, M, 18-25 g
PREPARATION AND DOSE
or HISTORY OF PATIENT: Kidney transplant 3 mo earlier; acute pancreatitis, severe
hypertension, epigastric mass. 3 infusions of cpd, followed
by 2 dialyses. Total dose: 1000 ml of 25% and 500 ml of
50% solutions.
PREPARATION AND DOSE
or HISTORY OF PATIENT:
20 mg/kg and up to l^ (43.9 mg/kg).
ROUTE AND SITE: I.V.
CONTROL INFORMATION: None
ROUTE AND SITE: s.C.
CONTROL INFORMATION: Various
DURATION OF EXPERIMENT: About 2 wk
EXAM. TYPE: Autopsy, histology of midbrain sections
DURATION OF EXPERIMENT: Various
EXAM. TYPE: Behavior, electrophysiology, biochemistry
1227
1228
-------
COMPOUND' 3-beta,20-alpha-Yohimban-16-beta-carboxylic acid, 18-beta-hydroxy-
11,17-alpha-dimethoxy-, methyl ester, 3,4,5-trimethoxybenzoate (ester)
000050555
REFERENCE: Young, R.L., Albano, R.F., Charnecki, A.M., Opar, G.E. and
Sheppard, H.
Res. Comm. Chem. Path. Pharm. 5(2):237-286, 1973.
OBSERVED NEUROTOXIC EFFECTS: Treated mice were cataleptic; neuraxis contained
defects of phospho-creatine and ATP metabolism,
differing according to thermic conditions. The
authors concluded that reserpine affects high-
energy phosphate compounds of the brain and inter-
• acts with temperature-regulation.
ANIMALS: Mice, CF-IS, M, 17-23 g
PREPARATION AND DOSE
or HISTORY OF PATIENT: 5 mg/kg
ROUTE AND SITE: I.P.
CONTROL INFORMATION: Vehicles only
DURATION OF EXPERIMENT: 4.5 hr
EXAM. TYPE: Neurochemistry
1230
1229
-------
Index
This index is an alphabetical listing of all of the
chemicals for which extracts are presented, and some of their
synonyms, and a tabular review of their chemical classes and
induced effects. All of the studies in which human exposure
was reported are also indicated.
The tabular review is not "all-inclusive." That is, not
all chemical classes or types of effects are listed - only those
that are of particular interest with respect to neurotoxicity.
The codes for the chemical classes used are listed in Table 1.
Brief definitions of the effects indexed are presented in
Table 2.
1231
-------
Table 1. Chemical Class Codes
A Acrylamides
Al Aluminum and aluminum compounds
As Arsenic and arsenic compounds
Au Gold and gold compounds
B Barbiturates
C Carbamates
Ca Calcium and calcium compounds
Cd Cadmium and cadmium compounds
CN Cyanides and nitriles
Co Cobalt and cobalt compounds
Cu Copper and copper compounds
Ga Gallium and gallium compounds
Hg Mercury and mercury compounds
HZ Hydrazides
K Ketones
Li Lithium and lithium compounds
LSD Lysergic acid derivatives
Mn Manganese and manganese compounds
Ni Nickel and nickel compounds
OP Organophosphates
Pb Lead and lead compounds
Sn Tin and tin compounds
TA Toxins, animal
TB Toxins, bacterial
Te Tellurium and tellurium compounds
TF Toxins, fungus
Tl Thallium and thallium compounds
TP Toxins, plant
X Halogenated hydrocarbons
Zn Zinc and zinc compounds
1232
-------
Table 2. Effects
CNS structural damage - gross or microscopic changes
in the physical composition of the brain or
spinal cord.
PNS structural damage - gross or microscopic changes
in the physical composition of the peripheral
nervous system.
Gross dysfunction - observed impaired or abnormal
neuronal functioning that is discernable with-
out special testing; for example, paralysis or
convulsions.
Performance dysfunction - observed impaired or
abnormal neuronal functioning that is discer-
nable only by special performance tests, such
as bar-walking or swimming tests.
Instrument detectable dysfunction - impaired or
abnormal neuronal functioning that is detecta-
ble by direct instrumental measurement; for
example, nerve conduction inhibition or EEC
changes.
Cholinesterase inhibition - reduced activity and/or
levels of cholinesterase.
Effects in offspring - abnormalities of the nervous
system of offspring induced by exposure of the
mother to the compound during gestation.
1233
-------
N>
UJ
*-
iChemical
Class
Codes
OP
OP
HZ
HZ
•
Chemical Name Pages
Abate, see: Phosphorothioic acid, 0,0- 948
dimethyl ester, 0,0-diester with 4,4'-
thiodiphenol
Abathion, see: Phosphorothioic acid, 948
0,0-dimethyl ester, 0,0-diester with
4 , 4 ' -thiodiphenol
Acetaldehyde 1
Acetaldehyde, chloro-, (2,4-dinitrophenyl) 2
hydrazone
Acetamide, 2-fluoro-N-methyl-N-l-napthyl 3
Acetanilide, 2'^(2'bromo-3-thienyl)thio- 4
Acetanilide, 4l-(4-(3-dimethyl amino) 5
propyl ) -1-piperazinyl) -
Acetanilide, 2'-(3-thienyl)thio- 6
Acethydrazide 7
Acetic acid, bis(p-chlorophenyl)- 8
Acetic acid, cyano-, hydrazide 9
Acetic acid, (2,3-dichloro-4-(2-methylene- 10
butyrl)phenoxy)-
Acetic acid, 2,4-dichlorophenoxy- 11-13
Acetic acid, (2,4-dichlorophenoxy)-, 14
compound with dimethylamine (1:1)
CNS
Structural
Damage _
•
5
PNS
Structural
Damacte
Gross
Dysfunction
2
3
4
6
7
9
10
11
12
13
14
Performance
Dysfunction
Instrument
Detectable
Dysfunction
Cholin-
esterase
Inhibition
Effects in
Offspring
Reported
Human
Incidence
10
13
14
-------
Chemical
Class
Codes
Pb
OP
Tl
Zn
K
HZ
HZ
HZ
HZ
K
HZ
Chemical Name Pages
Acetic acid, (ethylene-dinitrilo) tetra- 15
Acetic acid, fluoro-, sodium salt 16
Acetic acid, Iminodi 17
Acetic acid, lead (2+) salt 18-24
Acetic acid, mercaptophenyl-, ethyl ester 25
S-ester with 0,0-dimethyl phosphorodithioate
Acetic acid, thallium (1) salt e 26
Acetic acid, p-tolyl-, 3-alpha-tropanyl 27
ester
Acetic acid, zinc salt 28
Acetone 29
Acetone, allophanylhydrazone 30
Acetone semicarbazone 31
Acetone, thiocarbohydrazone 32
Acetone, thiocarbohydrazonodi- 33
Acetone thiosemicarbazone 34
Acetophenone, 2-chloro 35
Acetophenone, thiocarbohydrazone 36
CNS
Structural
Damage
15
22
PNS
Structural
Damace
23
26
Gross
Dysfunction
21
22
24
25
29
30
31
32
33
34
36
Performance
Dysfunction
19
Instrument "1
Detectable
Dysfunction |
17
Cholin-
esterase
Inhibition
25
Effects in
Offspring
15
9
Reported
Human
Incidence
29
-------
to
Co
rH
id
u
•H 05 to
B a ^
P-i O
44
c
4-1 •
MOO
c
o
-------
Chemical
Class
Codes
X
HR
Chemical Name Pages
Agrocide, see: Cyclohexane, 1,2,3,4,5,6- 251-252
hexachloro-, gamrna-isomer
Alanine, 3-(3,4-dihydroxyphenyl)-, L 63
Alanine, 3-mercapto-, hydrogen sulfate 64
(ester)
Alanine, N-methyl-3-sulfo-, L- 65
Alanine, phenyl-, L- 66-67
Alanine, 3-sulfino- 68-69
Alanine, 3-sulfo-, D- 70
Alanine, 3-sulfo-, L- 71-73
Alanine, 3-(2-thienyl)- 74
Alanine, 2,4,5-trihydroxyphenyl- 75-76
Alanine, 2,4,5-trihydroxyphenyl-, 77
hydrohromide
Aldrin, see: l,4:5,8-dimethanonapthalene, 293-294
l,2,3,4,10,10-hexachloro-l,4,4a,5,8,8a-
hexahydro-endo, endo-
Alkyl mercury 78
Allocaine, see: Benzoic acid, p-amino-2- 146
(diethylamino) ethyl ester
CNS
Structural
Damage _
64
66
69
73
76
78
PNS
Structural
Damage
76
78
Gross
Dysfunction
65
70
72
78
Performance
Dysfunction
75
Instrument
Detectable
Dysfunction
Cholin-
esterase
Inhibition
Effects in
Offspring
74
•
Reported
Human
Incidence
-------
NJ
W
CD
Chemical
Class
Codes
HZ
TP
Al
Chemical Name Pages
Allophanic acid, hydrazide 79
Aloes 80
Aluminum hydroxide 81
N-Allylnormorphine HC1, see: Morphinan- 700
3,6-alpha-diol, 17-allyl-7,8 didehydro-
4,5-alpha-epoxy-, HC1
DL-alpha-Aminoadipic acid, see: Hexane- 454-456
dioic acid, 2-amino-, DL-
6-Aminonicotinamide, see: 3-Pyridine- J.007-1010
carboxamide, 6-amino-
DL-alpha-Aminopimelic acid, see: Heptane- 450-451
dioic acid, 2-amino-, DL-
gamma-Aminopimelic acid, see: Heptane- 449
dioic acid, 4-amino-
Amitriptyline, see: 5H-Dibenzo(a,d) cyclo- 267
heptene-delta(sup 5) ,pamma-Propylamine,
10,ll-dihydro-N,N-dimethyl-
Amitriptyline HC1, see: 5H-Dibenzo(a,d) 268
cycloheptene-delta(sup 5) , gamma-propyl-
amine, 10,ll-dihydro-N,N-dimethyl-,
hydrochloride
Ammonium, (O-bromobenzyl)ethyldimethyl-, 82
p-toluenesulfonate
CNS
Structural
Damage _
81
PNS
Structural
Damace
Gross
Dysfunction
79
Performance
Dysfunction
Instrument
Detectable
Dysfunction
Cholin-
esterase
Inhibition
Effects in
Offspring
•
Reported
Human
Incidence
80
-------
VO
'Chemical I
Class
Codes 1
Ca
•
Chemical Name Pages
Ammonium, (3-carboxypropyl) trimethyl-, 83
carboxylate
Ammonium, dibutyl(2-hydroxyethyl)methyl- 84
Ammonium, diethyl(2-hydroxyethyl)me.thyl- 85
Ammonium, (2-hydroxyethyl)triethyl- 86
Ammonium, (2-hydroxyethyl)triethyl-, p- 87
toluenesulf onate ,3,4, 5-tr imethoxy-
benzoate
Ammonium, (m-hydroxyphenyl) trimethyl-, 88
bromide, dimethylcarbamate
Ammonium ion (+1) 89
Amphetamine, see: Phenethylamine, alpha- 746
methyl- (+) -amphetamine
dl-Amphetamine S04, see: Phenethylamine, 747-748
alpha-methyl-, sulphate (2:1), (+,-)-
i
Amprolium, see: 2-Picolinium, l-((4- 971-972
Amino-2-propyl-5-pyrimidinyl)methyl)-,
chloride, hydrochloride
Amyl nitrite, see: Nitrous acid, pentyl 713
ester
Androst-5-en-3-heta-ol, 17-beta-((3- 90
(dimethylamino)propyl)methylainino)-
CNS
Structural
Damage
90
PNS
Structural
Daraaee
Gross
Dysfunction
86
87
Performance
Dysfunction
[Instrument
betec table
Pysfunction
Cholin-
esterase
Inhibition
84
85
Effects in
Offspring
•
Reported
Human
Incidence
-------
ho
*>
o
[Chemical
Class
Codes
OP
As
Chemical Name Pages
Androst-5-en-17-one, 3-beta-hydroxy-, 91
succinate, sodium salt
Angiotonin, see: 5H-Tetrazoloazepine, 1117-1122
6,7,8, 9-tetrahydro-
Aniline, 4,4'-sulfonyldi- 92
o-Anisamlde, 4-amino-5-chloro-N-(2- 93
d iethylamino) ethyl ) -
Anthraquinone, dihydroxy- 94
Aprobit, see: Phenothiazine, 10-(2- 782-783
d imethylaminopropyl ) -
Armin, see: Phosphonic acid, O-ethyl-0- 796
(4-nitrophenyl) -ethyl ester
Arsenic 95-96
Artane, see: 1-Piperidinepropanol, alpha- 982
cyclohexyl alpha-phenyl-, hydrochloride
L-Asparagine, see: Succinamic acid, alpha-1098-1099
amino— , L—
Aspartic acid 97
Aspartic acid, D- 98-100
Aspartic acid, DL- 101
CNS
Structural
Damage _
97
100
PNS
Structural
Daroace
92
94
95
Gross
Dysfunction
91
92
93
95
96
93
99
101
Performance
Dysfunction
Instrument
Detectable
Dysfunction
Cholin-
esterase
Inhibition
Effects in
Offspring
Reported
Human
Incidence
92
93
94
95
96
-------
H
CO
0
•H 0) Cfl
a to w
0) CO T>
X iH O
U W CJ
Chemical Name Pages
Aspartic acid, L- 102-104
Aspartic acid, N-acetyl-, L- 105-106
Aspartic acid, N-carbamoyl-, DL- 107
Aspartic acid, N,N-dimethyl-, D- 108
Aspartic acid, N,N-dimethyl-, DL- 109-110
Aspartic acid, N-ethyl, D- 111
Aspartic acid, N-ethyl-, DL- 112
Aspartic acid, N-ethyl, L- 113
Aspartic acid, N-formimino-, L- 114
Aspartic acid, N-iminomethyl-, D- 115
Aspartic acid, N-iminomethyl-, L- 116
Aspartic acid, N-methyl-, D- 117
Aspartic acid, N-methyl, DL- 118-119
Aspartic acid, alpha-methyl-, DL- 120
Aspartic acid, N-methyl-, DL- 121-122
Aspartic acid,' N-methyl-, L- 123
Aspartic acid, N-propyl-, D- 124
Aspartic acid, N-propyl-, L- 125
t-H
«
n
t-l 0)
U oc
s «
w w e
ss 4J «
U VJ Q
104
.
121
122
t-i
Cfl
M
4J CU
0 tl
3 cfl
W VJ E
55 4J co
PM c/> Q
,
0
O
•H
4-1
U
c
eo o
CO M-l
o co
H ^
o o
102
108
109
111
114
117
118
119
124
M P O
c
O
Q> -H
1 CO 4J
C « -rl
•H Vl JD
fH
-------
•H
a
u
•H en co
B CO 01
>
u o
128
130
131
132
133
135
136
01 ft
u o
C i-l
W 4-1
go
c
O 3
M O
o> ^
P-i O
126
c
4-1 0> O
C t-i n
CU ^ 4J
B CO U
3 4-i B
M 0 3
CO 4-1 CO
C -
MOO
C
o
0) i-l
I CO 4J
C rt i-l
i-t h J3
iH
ID O
01 C
p C T3
O CO -H
O. 3 CJ
-------
N>
*-
U)
1 Chemical
Class
Codes
B
HZ
Chemical Name Pages
Barbituric acid, 5-ethyl-5-phenyl- 137
Eenadryl, see: Ethylamine, 2-(diphenyl- 357
methoxy)-N,N-dimethyl-
Benzamide, p-amino-n-(2-(diethylamino)ethyl))- 138
Benzenearsonic acid, 4-hydroxy-3-nitro- 139
Benzilic acid, l-tnethyl-3-piperidyl 140
ester, hydrochloride
2-Benzimidazolinone, l-(l-(3-(p-f luoro- 141
benzoyl)propyl ) -1,2,3, 6-tetrahydro-4-
pyridyl)-
3H-l,4-Benzodiazepine, 7-chloro-2-methyl- 142-143
amino)-5-phenyl-, 4-oxide
2H-l,4-Benzodiazepin-2-one-7-chloro-l,3- 144
d ihydro-l-methyl-5-phenyl-
Benzoic acid 145
Benzole acid, p-amino-, 2-(diethylamino) 146
ethyl ester
Benzole acid, hydrazide 147
Benzoxazole, 2-amino-5-chloro- 148
Benzydamine, see: 1H, Indazole, 1-Benzyl- 514
3 (3-(dimethylatnino)propoxy)-
CNS
Structural
Damage
137
.
145
IPNS
Structural
iDaraane
139
Gross
Dysfunction
138
139
141
143
144
145
146
147
148
Performance
Dysfunction
142
Instrument
Detectable
Dysfunction
Cholin-
esterase
Inhibition
Effects in j
Offspring
•
Reported
Human
Incidence
138
140
141
143
144
-------
Chemical
Class
Codes
X
OP
CN
OP
OP
Chemical Name Pages
Benzyl alcohol, 3,4-dichloro-alpha- 149
((Isopropyl-amino)methyl)-, HC1
Benzyl alcohol, m-hydroxy-alpha- (methyl- 150
amino)methyl-, hydrochloride, (-)-
Benzylamine, N-(2-chloroethyl)-N-(l- 151
methyl-2-phenoxyethyl) -
Benzylamine, N-methyl-N-2-propynyl-, HC1 152
Bicuculline 153-155
o .
Biculline, see: Bicuculline 153-155
Biphenyl 156-157
Biphenyl, chloro 158
Birlane, see: Phosphoric acid, 2-chloro 827
-l-(2,4-dichlorophenyl)vinyl) diethyl
ester
Bis (p-aminophenoxy) alkane series 159
Bis-beta-cyanoethylamine, see: Propio- 998-1003
nitrile, 3,3'-iminodi-
Bis (3 , 5-d imethylphenyl) chlorophosphite , 902
see: Phosphorochloridous acid, bis (3,5-
xylyl) ester
Bithion, see: Phosphorothioic acid, 0,0- 948
dimethyl ester, 0,0-diester with 4,4'-
thiodiphenol
CNS
Structural
Damage
•
159
IPNS
Structural
iDamape
150
Gross
Dysfunction
150
153
154
156
157
158
Performance
Dysfunction
156
[Instrument
betectable
[Dysfunction
Cholin-
esterase
Inhibition
Effects in
Offspring
«
Reported
Human
Incidence f
150
156
157
158
-------
H
0)
U
•H 05 tO
§0) n)
PM to O
16A
167
c
O
•H
4-1
0
c
(0 3
(0 14-1
O (0
Vi ^
O Q
160
161
162
163
164
165
166
168
169
.
PH O
170
c
4J 0) O
C f-l -H
4J
6 rt o
3 •!-• C
PUS
4J 0) IM
(0 4-> CO
c .
M O Q
C
O
at -H
1 CO 4-1
c « 1*
•H n ua
t-l CU -H
O 4J &
JZ co c
U
T3 O
0) C
4-1 CD
M C -a
O CO «H
a. e o
-------
M
4S
C^
Ichemical
Class
Codes
OP
OP
Cd
TP
Ca
Chemical Name Pages
2-Butanol, 4-(dimethylamino)-3-methyl- 171-172
l,2-diphenyl-,propionate(ester),HCl(+)-
Butiphos, see: Phosphorotrithioic acid, 962
S,S,S-tributyl ester
Butyl alcohol 173
n-Butylcholine, see: Ammonium, dibutyl 84
(2-hydroxyethyl) methyl-
Butyric acid, 4-amino 174
Butyric acid, 2-amino-4-hydroxy-, phos- 175
phonate, (ester)
Butyric acid, 2-amino-4-sulf ino-, DL- 176
Butyric acid, 2-hydrazino-2-methyl- 177
Butyric acid, 2-(methlyamino)-4-sulfo-, DL- 178
Cadmium chloride 179-181
Caffeine 182
Calcium chloride 183
Cannabidiol, see: Resorcinol, 2-p-mentha- 1065-1066
1 , 8-dien-3-yl-5-pentyl-
CNS
Structural
Damage _
179
180
181
PNS
Structural
Damaee
Gross
Dysfunction
171
172
177
182
Performance
Dysfunction
Instrument
Detectable
Dysfunction
Cholin-
esterase
Inhibition
Effects in
Offspring
*
Reported
Human
Incidence
172
-------
rH
n)
u
i-t m co
0 co 01
v a -o
X r-l O
u u u
C
C
C
C
C
C
C
C
C
C
C
Chemical Name Pages
Carbamic acid, diethylthio-, sodium salt 184-189
Carbamic acid, ethyl ester 190
Carbamic acid, dimethyl-6-methyl-2- 191
propyl-4-pyrimidnyl ester
Carbamic acid, methyl-, benzo(b)thien- 192-193
4-yl-ester .
Carbamic acid, methyl-, 5-sec-butyl-2- 194
chlorophenyl ester
Carbamic acid, methyl -m-sec-butylphenyl 195
ester
Carbamic acid, methyl-, m-cumenyl ester 196
Carbamic acid, methyl-, 2,3-dihydro-2,2- 197
dimethyl-7-henzofuranyl ester
Carbamic acid, methyl-, 4-dimethyl- 198
amino-3,5-xylyl ester
Carbamic acid, methyl-, m-(l-methyl- 199
butyl)phenyl ester
Carbamic acid, methyl-, 1-naphthyl ester 200-201
i
iH
W
li
4J 4)
U 6C
3 (Q
M >-i 6
Z 4-1 (0
u e/j o
184
185
186
187
188
189
.
201
iH
«
W
4-1 t
O Q
188
191
192
193
194
195
196
197
198
199
200
201
(U C
u o
C -H
CO 4J
E g
O 3
>4-l M-l
M n
0) >>
P-, Q
C
4J
M Q O
C
o
01 i-l
1 CO 4-1
C « -H
•H H ^3
iH 4» -H
O 4J J=
J= W C
O 0) M
201
C
•H 00
C
co t-i
4-1 Vl
U P.
-------
ro
•e-
oo
[Chemical
Class
Codes
C
C
c
HZ
HZ
X
•
Chemical Name Pages
Carbamic acid, methyl-, 3,4-5-trimethyl 202-203
ester
Carbaryl, see: Carbamic acid, methyl-, 200-201
1-naphthyl ester
Carbofuran, see: Carbamic acid, methyl- 197
2 , 3-d ihydro-2 , 2-d imethyl-7-benzo-
furanyl ester
Carbohydrazide 204
Carbohydrazide, thio- 205
Carbon dioxide 206
Carbon disulfide 207-213
Carbonic acid, dithio-, cyclic S,S- 214
(6-methyl-2,3-quinoxalinediyl) ester
Carbon monoxide 215-218
-
Carbon tetrachloride 219-222
CNS
Structural
Damage _
.
207
208
212
216
218
219
222
PNS
Structural
Damace
209
217
218
Gross
Dysfunction
202
203
204
205
206
207
208
209
210
211
213
214
215
216
217
218
222
Performance
Dysfunction
Instrument
Detectable
Dysfunction
Cholin-
esterase
Inhibition
Effects in
Offspring
«
Reported
Human
Incidence
210
215
217
218
219
222
-------
N>
Chemical
Class
Codes
OP
c
c
Chemical Name Pages
Carbophenothion, see: Phosphorodithioic 908
acid, S-(p-chlorophenyl)thio methyl
0,0-diethyl ester
Cardiotoxin 223
Cascara 224
Chevron RE 5305, see: Carbamic acid, 195
methyl-, m-sec-butylphenyl ester
Chevron RE 5655, see: Carbamic acid, 194
methyl-, 5-sec-butyl-2-chlorophenyl
ester
Chloramine, see: Diethylamine, 2,2'- 286
d ichloro-N-methyl-
Chlordiazepoxide, see: 3H-l,4-Benzo- 142-143
diazepine, 7-chloro-2-(methylamino)-5-
phenyl-, 4-oxide
1-Chloro-amitriptyline, see: 5H-Dibenzo- 266
• (a,d)cycloheptene-delta(sup5, gamma)
propyl-amine, l-chloro-10,ll-dihydro-
N,N-dimethyl-
2-Chloroamphetainine, see: Phenethylamine, 741
2-chloro-2-raethyl-, (+-)-
3-Chloroamphetamine, see: Phenethylatnine, 742
3-chloro-2-methyl-, (+-)-
4-Chloroamphetamine, see: Phenethylair.ine, 743
4-chloro-2-methyl-, (H — )-
CNS
Structural
Damage
'
PNS n
Structural
Damage 1
224
Gross
Dysfunction
Performance
Dysfunction
[Instrument
betectable
[Dysfunction
223
Cholin-
esterase
Inhibition
Effects in
Offspring
Reported
Human
Incidence
224
-------
Ul
O
1 Chemical
Class
Codes
OP
OP
Chemical Name Pages
DL-p-Chloroamphetamine, see: Phenethyl- 739
amine, 4-chloro-2-methyl-, DL-
p-Chloroamphetamine, see: Phenethylamine, 743
4-chloro-2-methyl-
beta-Chloroethylamine, ethyl-n-propyl-, HC1 225
Chlorof eninphos , see: Phosphoric acid, 827
2-chloro-l-(2,4-dichlorophenyl)vinyl
diethyl ester
Chloroquine, see: Quinoline, 7-chloro- 1040
4 ((4-diethylamino)-l-i!iethylbutyl)amino)-
Chloroquine diphosphate, see: Quinoline, 1039
7-chloro-4-(4-diethylamino-l-methyl-
butylamino ) -d iphospha te
Chlorphentermine, see: Phenethylamine 738
p-chloro-alpha , alpha- * dimethyl -
Chlorpromazine, see: Phenothiazine, 2- 775-777
chloro-10-3 (3-d imethylamino ) pr opyl ) -
Chlorpromazine HC1, see: Phenothiazine, 778-779
2-chloro-10-(3-(dimethylamino)propyl)-,
mono-hydrochloride
Chlorprothixene HC1, see: Thioxanthene- 1181
delta (sup9)-gamma-propylamine, 2-chloro-
N,N-dimethyl, hydrochloride
Choralose, alpha 226
CNS
Structural
Damage
225
.
PNS
Structural
Damage
Gross
Dysfunction
225
226
Performance
Dysfunction
Instrument
Detectable
Dysfunction
Cholin-
esterase
Inhibition
Effects in
Offspring
Reported
Human
Incidence
-------
ho
ichemical
Class
Codes
Co
TA
TP
Chemical Name Pages
Cicutoxin, see: (-)-Heptadeca-trans-S, 448
10,12-triene-4,6-diyne-l,14-diol
Ciodrin, see: Crotonic acid, 3-hydroxy-, 245
alpha-methylbenzyl ester dimethyl
phosphate, (E)-
Citric acid, fluoro- 227-228
Clioquinol, see: 8-Ouinolinol, 5-chloro- 1046-1051
7-iodo-
Clomipramine, see: 5H-Dibenz(b,f )azepine, » 263
3-chloro-5-(3-(dimethylamino)propyl)-
10,11-dihydro-
Cobalt ion (+2) 229-230
Cobra toxin 231
Cocaine HC1, see: l-alpha-H,5-alpha-H- 1193
Tropane-2-beta-carboxylic acid, 3-beta-
hydroxy-methyl ester, benzoate (ester)
hydrochloride
Cocaine muriate, see: (same as above) 1193
Cogent in, see: l-alpha-H,5-alpha-H Tropane 1194
3-alpha-(diphenyl methoxy)
Colchinine 232-233
CNS
Structural
Damage
227
232
233
PNS ~1
Structural
Damace 1
Gross
Dysfunction
227
228
233
Performance
Dysfunction
[Instrument
betec table
[Dysfunction
Choi in- ~|
esterase
Inhibition j
Effects in
Offspring
«
Reported
Human
Incidence
-------
ISJ
(Jl
M
[Chemical
Class
Codes
Cu
Cu
Cu
Cu
TP
OP
OP
OP.
OP
OP
«
Chemical Name Pages
Copper (II) chloride 234
Copper ion (+2) 235
Copper II sulphate 236
Copper (II) sulfate pentahydrate (1:1:5) 237
Cortisol 238
Cortisol, 21-acetate 239
Cottonseed oil 240
Coumaphos, see: Coumarin, 3-chloro-7- 242
hydroxy-4-methyl, 0-ester with 0,0-
diethyl phosphorothioate
Coumarin, 3-chloro-7-hydroxy-4-methyl-, 241
bis (2-chloroethyl ) phosphate
Coumarin , 3-chloro-7-hydroxy-4-methyl-,
0-ester with 0,0-diethyl phosphorothioate 242
Coumarin, 7-hydroxy-4-methyl-, bis (2- 243
chloropropyl) phosphate
0-Cresol, 4,6-dinitro- 244
Cresyl phosphate, see: Phosphoric acid, 862
tolyl ester
Crotonic acid, 3-hydroxy-, alpha-methyl- 245
henzylester, dimethyl phosnhate, (E)-
CNS
Structural
Damage
236
237
239
243
PNS
Structural
Damage
241
243
Gross
Dysfunction
240
241
242
243
244
245
Performance
Dysfunction
Instrument
Detectable
Dysfunction
234
Cholin-
esterase
Inhibition
Effects in
Offspring
•
Reported
Human
Incidence _,
244
-------
M
10
tji
OJ
Chemical
Class
Codes
TP
OP
HZ
CN
CN
X
Chemical Name Pages
.Crotyl theobromine, see: Theobromine, 1131
l-(2-butenyl)-
Cruf ornate, see: Phosphoramidic acid, methyl 816-817
-4-tert-butyl-2-chlorophenyl methyl ester
Cuprizone, see: Oxalic acid, bis(cyclo- 721-724
hexy 1 id enehyd r a z i d e )
Cyanic acid 246
Cyanide 247-249
Cycasin, see: beta-D-Glucopyranoside, 381-384
(methyl-ONN-azoxy)methyl)-
1,3,5-Cycloheptatriene 250
Cyclohexane, 1,2,3,4,5,6-hexachloro-, 251-252
pamma-i somer
Cycloheximide, see: Glutaramidp, 3-(2- 430-431
(3,5-dimethyl-2-oxocyclohexy)-2-
hydroxyethyl)-
Cycloleucine, see: Cyclopentanecar- 254
boxylic acid, 1-amino
5H-Cyclooct(b)indole, 5- (3- (dimethyl- 253
amino)propyl)-6,7,8,9,10,ll-hexahydro-
Cyclopentanecar boxylic acid, 1-amino 254
CNS
Structural
Damage _
247
248
253
254
PNS
Structural
Damace
Gross
Dysfunction
249
250
252
Performance
Dysfunction
Instrument
Detectable
Dysfunction
251
Cholin-
esterase
Inhibition
Effects in
Offspring
*
Reported
Human
Incidence
251
-------
ro
(ji
->
Ichemical
Class
Codes
OP
Chemical Name Pages
Cyclopentane carboxylic acid, 1-phenyl-, 255
2-(diethylamino)ethyl ester, HC1
Cyclophosphamide, see: 2H-l,3,2-Oxazaphos- 726
phorine, 2-(bis(2-chloroethyl)amino)
tetrahydro-, 2-oxide
ryclopropylamine, 2-phenyl-, sulfate 256
trans- (+,-)-, (2:1)
D-Cysteic acid, see: Alanine, 3-sulfo-,D- 70
L-Cysteic acid, see: Alanine, 3-sulfo-,L- 71-73
Cysteine, L- " 257-258
Cysteine, N-acetyl-, L- 259
L-Cysteine sulfinic acid, see: Alanine, 68-69
3-sulf ino-
Cysteine-S- Sulphate, see: Alanine, 3- 64
mercapto-, hydrogen sulfate (ester)
Dapsone, see: Aniline, 4,4'-sulfonyldi- 92
Darvon hydrochloride, see: 2-Butanol, 4- 171-172
(dimethylamino)-3-TTiethyl-l,2-diphenyl-,
propionate (ester), hydrochloride, (+)-
DCPA, see: Acetic acid, 2,4-dichloro- 11-13
phenoxy-
DDA, see: Acetic acid, bis(p-chlorophenyl)- 8
CNS
Structural
Damage
257
258
PNS
Structural
Damace
Gross
Dysfunction
Performance
Dysfunction
255
(Instrument
petectable
[Dysfunction
Cholin-
esterase
Inhibition
Effects in
Offspring
*
Reported
Human
Incidence
255
-------
1-1
CO
0
•H n co
0 co 10 T)
x: IH o
o u u
A.
OP
.
Chemical Name Pages
DDT, see: Ethane, l,l,l-trichloro-2,2-bis 314-322
(p-chlorophenyl ) -
Deanol, see: Ethanol, 2-dimethylatnino- 327
Decaborane (14) 260
Decaborane, ethyl 261
DEF, see: Phosphorotrithioic acid, 962
S,S,S-tributyl ester
Dehydroepiandrosterone, sodium succinate 91
salt, see: Androst-5-en-17-one, 3-beta-
hydroxy-, succinate, sodium salt
4-Deoxypyridoxine HC1, see: 3-Pyridine- 1012
methanol, 5-Hydroxy-4,6-dimethyl-,
hydrochloride
ll-Desoxy-17-hydroxycorticosterone, sodium 988
succinate salt, see: Prepn-4-ene-3 , 20-
' dione, 17,21-dihydroxy-, succinate,
sodium salt
Dextropropoxyphene hydrochloride, see: 171-172
2-Butanol , 4- (d iraethylamino-3-tnethyl -1 ,
2-diphenyl-, propionate (ester), hydro-
chloride (+)-
L-alpha-epsilon, 5th-Diaminopimelic acid 452
see: Heptane.dioic acid, 2,5-diamino-,L-
l,4-Diazabicyclo(2,2,2)octane. 262
i
i-H
cd
n
4J 0)
0 OC
3 CO
to (-1 B
2 u ta
O CO Q
,
i-l
CO
M
3
4J 0,
0 tl
3 CO
w vi e
Z 4J CO
fx, co o
c
o
•H
4J
0
c
(0 3
(0 M-l
O (0
M ^
O O
260
261
0) C
u o
C -H
CO tJ
00
c
O 3
U-l U-l
M 01
>-
M Q 0
262
c
o
0) -H
1 (0 4-1
C CO -H
•H W ^3
iH 0» -H
o *-• ^:
J= W C
O
O C-
-------
I-1
NJ
cr>
Ichemical
Class
Codes
OP
Chemical Name Pages
20, 25-Diazacholesterol, see: Androst-5- 90
en-3-beta-ol , 17-beta-((3-(dimethylamino)
pr opyl )methylamino ) -
Diazepam, see: 2H-l,4-Benzodiazepin-2- 144
one, 7-chloro-l,3-dihydro-l-methyl-5-
phenyl-
Diazinon, see: Phosphorothioic acid, 0,0- 939
diethyl 0-(2-isopropyl-6-inethyl-4-
pyrimidnyl) ester
Dibenamine, see: Dibenzylatnine, N-(2- 285
chloroethyl)-
5H-Dibenz(b,f)azepine, 3-chloro-5-(3- 263
• (d imethylaminopr opyl ) -10 , 11-d ihydr o-
5H-Dibenz(b,f)azepine, 5-(3-(dimethyl- 264
amino ) propyl ) -10 , 11-d ihydro-
5H-Dibenz(b,f)azepine, 5-(3-(dimethyl- 265
atnlno) propyl )-10, 11-d ihydro-mono-
hydrochloride
5H-Dibenzo-(a,d)cycloheptene-delta (sup 5) 266
gamma-propylamine l-chloro-10,11-
dihydro-N,N-dimethyl-
5H-Dibenzo(a,d)cycloheptene-delta (sup 5), 267
gamma-propylamine, 10,11-dihydro-
N,N-dimetbyl-
5H-Dibenzo(a,d)cycloheptene-delta (sup 5), 268
pamma-propylanine, 10,11-dibydro-
N,N-dimethyl-, bydrochloride
CNS
Structural
Damage
•
263
266
PNS
Structural
Damace
Gross
Dysfunction
Performance
Dysfunction
264
Instrument
Detectable
Dysfunction
Cholin-
esterase
Inhibition
Effects in
Offspring
•
Reported
Human
Incidence
-------
Chemical
Class
Codes
Chemical Name Pages
5H-Dibenzo(a,d)cyclohepten-5-one, 10,11- 269
dihydro-,o-(2-(dimethylamino) ethyl )oxiipe
Dibenzo-p-dioxin, 2 ,3,7, 8-tetrachloro 270
6H-Dibenzo(b,d)pyran-l-ol,3-(l'2'-di- 271
methylheptyl ) -7,8,9, 10-tetrahydr o-
6,6,9-trimethyl-
6H-Dibenzo(b,d)pyran-l-ol, 6a,7,10,10a- 272
tetrahydro-7-alpha, 11-dihydroxy-
6,6, 9-trimethyl-3-pentyl
6Tl-Dibenzo(b,d)pyran-l-ol, 6a,7,10,10a- • 273
tetrahydro-7-beta, 11-dihydroxy-
6,6,9-trimethyl-3-pentyl-
6H-Dibenzo(b,d)pyran-l-ol, 6a,7,8,10a- 274
tetrahydro-8 , 11-d ihydroxy-6 ,6,9-
trimethyl-3-pentyl-
6R-Dibenzo(b,d)pyran-l-ol, 6a,7,10,10a- 275
tetrahydro-ll-hydroxy-6 , 6 , 9-tr imetbyl-
3-pentyl-
6H-Dibenzo(b,d)pyran-l-ol, 6a,7,10,10a- 276-277
tetrahydro-6, 6, 9-trimethyl-3-pentyl-
6H-Dibenzo(b,d)pyran-.l-ol, 6a,7,8,10a- 27R-28A
tetrahydro-6, 6, 9-tr imethyl-3-pentyl-,
(6 aR-trans)-
Dibenzylamine, N-(2-chloroethyl)- 285
n-Dibutylcholine, see: Ammonium, dibutyl 84
(2-hydroxyethyl )methyl-
CNS
Structural
Damage
PNS
Structural
Damage
Gross
Dysfunction
270
272
273
274
275
276
277
279
282
284
Performance
Dysfunction
271
278
. 280
283
Instrument
Detectable
Dysfunction
281
282
Cholin-
esterase
Inhibition
Effects in
Offspring
•
Reported
Human
Incidence
270
278
-------
to
01
CO
'Chemical
Class
Codes
Sn
OP
OP
Chemical Name Pages
Dibutyltin oxide, see: Stannane, 1086
dibutyloxo-
N,N-Dibutyltryptatnine, see: Indole, 3- 523
(2-(dibutylamino)ethyl)-
Dicapthon, see: Phosphorothioic acid, 0- 936
(2-chloro-4-nitrophenyl)0,0-dimethyl
ester
Dichloroisoprenaline HC1, see: Benzyl 149
alcohol , 3 , 4-d ichloro-alpha- ( (Isopropyl-
amino)raethyl)-, hydrochloride
Dieldrin, see: l,4:5,8-Dimethanonapthal- 290-292
ene ,1,2,3,4, 10, 10-hexachloro-6 , 7 , epoxy-
l,4,4a,5,6,7,8,8a-octahydro,endo,exo-
Diethion, see: Phosphorodithioic acid, 928-929
S,S' -methyl ene 0,0,0' ,0'-tetraethyl ester
Diethylamine, 2,2'-dichloro-N-methyl- 286
beta-Diethylaminoethyl diphenylpropyl- 1223
acetate, see: Valeric acid, 2,2-di-
phenyl-, 2-(diethylamino)ethyl ester
Biethylcholine, see: Ammonium, diethyl -85
(2-hyd roxyethyl )methyl ) -
Diethyl ether, see: Ethane, l,l'-oxybis- 312-313
N,N-diethyltryptamine, see: Indole, 3- 524
(2- (d iethylamino ) ethyl ) -
CNS
Structural
Damage
•
286
PNS
Structural
Damace
Gross
Dysfunction
286
Performance
Dysfunction
Instrument
Detectable
Dysfunction
Cholin-
esterase
Inhibition
Effects in
Offspring
•
Reported
Human
Incidence
-------
Chemical
Class
Codes
•
Chemical Name Pages
Dip.lycine, see: Acetic acid, iminodi 17
N,N-Dihexyltryptamine, see: Indole, 3- 525
(2-dihexylaminoethyl .)-
6,7-Dihydrodipyrido(l,2-a:2',l'-c) pyra- 287
zidiinium dibromide
7-alpha,ll-Dihydroxy-delta(Sup8)tetrahydro- 272
cannabinol, see: 6H-Dibenzo(b,d)pyran-
l-ol , 6a , 7 , 10, 10a-tetrahydro-7-alpha , 11-
dihydroxy-6, 6 , 9-trimethyl-3-pe.ntyl-
7-beta-ll-Dihydroxy-delta (Sup8) tetrahydro- 273
cannabinol, see: 6H-Dibenzo(b,d)pyran-
l-o 1, 6a,7,10,10a-tetrahydro-7-beta,ll-
dihydroxy-6,6,9-trimethyl-3-pentyl-
8,ll-Dihydroxy-delta(Sup9)tetrahydrocanna- 274
binol, see: 6H-Dibenzo(b,d)pyran-l-ol,
6a ,7 , 8, 10a-tetrabydro-8 , 11-dihydroxy-
6,6, 9-tr imethyl-3-pentyl-
5., 6-Dihydroxytryptamine, see: Indole, 516-518
3- ( 2-aminoetbyl ) -5 , 6-d ihydr oxy-
5,7-Dihydroxytryptamine, see: Indole, 519
3-(2-aminoethyl)-5,7-dihydroxy-
Dilantin, see: Hydantoin, 5,5-diphenyl-, 488
mono sodium salt
Dimazine, see: Hydrazine, 1,1-dimethyl- 499-500
l,4:5,8-Dlmethanonaphthalene, acetoxy-1, 288
2,3,4,10,10-hexachloro-l,4,4a,5,8,8a-
llUli-lllUlll II-L U.ll-
CNS
Structural
Damage _
PNS
Structural
Damace
Gross
Dysfunction
287
Performance
Dysfunction
Instrument
Detectable
Dysfunction
288
Cholin-
esterase
Inhibition
Effects in
Offspring
«
Reported
Human
Incidence _,
-------
to
a*
o
iChemical
Class
Codes
OP
OP
Chemical Name Pages
l,4:5,8-Dimethanonapthalene, 1,2,3,4,10, 289
8 , 8a-octahydro-, endo,endo-
l,4:5,8-Dimethanonapthalene, 1,2,3,4,10, 290-292
8 , 8a-oc tahydr o , endo , exo-
l,4:5,8-Dimethanonapthalene, 1,2,3,4,10, 293-294
10-hexachloro-l , 4 , 4a , 5 , 8 , 8a-hexa-hydro-
endo,endo-
4-Dimethylamino-3 , 5 xylyl methylcarba- 295
mate, 22.3% emulsifiable concentrate
Dimethylheptylpyran, see: 6H-Dibenzo(b,d) 271
pyran-l-ol,3-(l' ,2'-dimethylheptyl)-7,
8,9, 10-tetrahydro-6 , 6 , 9-tr imethyl
Dimethyl tryptamine, see: Indole, 3-(2- 526-528
d imethylaminoethyl ) -
Dimeton, see: Phosphorodithioic acid, 922
0,0-dimethyl ester, S-ester with 2-
mercapto-N-methylacetamide
Dioxathion, see: Phosphorodithioic acid, 916
0,0-diethyl ester, S,S-diester with
r»-dioxane-2,3-dithiol
Diquat, see: 6,7-Dihydrodipyrido(l,2-a: 287
2' ,l'-c)pyrazidiinium dibromide
Disipal, see: Ethylamine, N,N-dimethy3- 355
2-(o-nethyl-alpha-phenylbenzyl-oxy)-
CNS
Structural
Damage ^
292
*
PNS
Structural
Damage
Gross
Dysfunction
291
293
295
Performance
Dysfunction
[Instrument
[Detectable
[Dysfunction
289
290
294
Cholin-
esterase
Inhibition
Effects in
Offspring
Reported
Human
Incidence t
293
-------
ON
Chemical
Class
Codes
OP
OP
OP
Chemical Name Pages
Distannoxane, hexabutyl- 296
Disulfide, bis(diethylthiocarbamoyl) 297
0
Disulfiram, see: Disulfide, bis(diethyl- 297
thiocarbamoyl)
Disulfoton, see: Phosphorodithioic acid, 918
0,0-diethyl S-(2 ethylthio)ethyl)ester
L-Dopa, see: Alanine, 3-(3,4-dihydroxy- 63
phenyl ) - , L-
Dormutil, see: 4(3H)-Quinazolinone, 2- "1035-1036
methyl-3-o-tolyl-
Droperidol, see: 2-Benzimidazolimme, 1- 141
(1- (3- (p-f luorobenzoyl ) pr opyl ) -1 , 2 , 3 , 6-
tetrahydro-4-pyr idyl ) -
Dursban, see: Phosphorothioic acid, 0,0- 944-945
diethyl 0-(3,5,6-trichloro-2-pyridyl)
ester
Dyvon, see: Phosphonic acid, (2,2,2-tri- 801
chloro-1-hydroxyethyl)-, dimethyl ester
Edrophonium chloride, see: Ethyl (m-hy- 362
droxyphenyl)dimethylammonium chloride
EDTA, see: Acetic acid, (Ethylene- 15
. d±nitrilo)tetra-
Emhutal, see: Barbituric acid, 5-ethyl- 134-135
5-(l-methylbutyl)-, sodium salt
CNS
Structural
Damage
PNS
Structural
Damage
Gross
Dysfunction
297
Performance
Dysfunction
[Instrument
[Detectable
bysfunction
Cholin-
esterase
Inhibition
Effects in
Offspring
Reported
Human
Incidence ^
297
-------
NJ
ON
N>
Chemical
Class
Codes
OP
LSD
D
X
•
Chemical Name Pages
Endrin, see: l,4:5,8-Dimethanonapthalene, 290-292
1,2,3,4,10, 10-hexachloro-6 , 7-epoxy-l , A ,
4a,5,6,7,8,8a-octahydro-,endo,endo-
Ephedrine KC1 298
EPN, see: Phosphonothioic acid, phenyl-, 812
0-ethyl O-(p-nitrophenyl) ester
Erp,olinf>-8-beta-carboxaroide, 2-bromo-9 , 10- 299-305
didehydro-N,N-diethyl-6-methyl-
Erj»oline-8-beta-carboxylic acid, 9,10- 306
didehydro-6-methyl-, morpholide
Erpotamine, dihydro-, monomethanesul- 307
fonate
D-Erythro-D-palacto-octo pyranoside, 308
methyl 6,8-dideoxy-6-(l-methyl-4-propyl-
2-pyrrolidine carboxamido)-l-thio-
Ethacrynic acid, see: Acetic acid, (2,3- 10
. dichloro-4-(2-methylenebutryl)phenoxy)-
Ethanamine 309
Ethane, 2-bromo-2-chloro-l,l,l-trif luoro- 310-311
Ethane, l,l'-oxybis- (ether) 312-313
CNS
Structural
Damage _
.
310
312
PNS
Structural
Damane
Gross
Dysfunction
305
306
308
312
313
Performance
Dysfunction
302
Instrument
Detectable
Dysfunction
308
309
Cholin-
esterase
Inhibition
Effects in
Offspring
311
•
Reported
Human
Incidence
306
312
-------
Chemical
Class
Codes
X
OP
Chemical Name Pages
Ethane, l,l,l-trichloro-2,2-bis (p-chloro- 314-322
phenyl)-
Ethanol, see: Ethyl alcohol 333-350
Ethanol, 2-hutylamino 323
Ethanol, 2-(p-chlorophenyl)-l-(p-(2- 324
. (diethylamino)ethoxy)phenyl)-l-p-tolyl-
Ethanol, 2-(dibutylarcino)- 325
E-thanol, 2-(diethylamino)- 326
Ethanol, 2-dimethylamino- 327
Ethanol, 2-(ethylamino)- 328
Ethanol, 2-methoxy- 329-330
Ethanol, 2-(methylamino)- 331
Ether, see: Ethane, l,l'-oxyhis- 312-313
Ether, chloromethyl methyl 332
Ethion, see: Phosphorodithioic acid, 928-929
. S,S'-methylene 0,0,0*0'-tetraethyl ester
CNS
Structural
Damage
324
332
PNS
Structural
Damage
Gross
Dysfunction
314
317
319
320
321
322
330
Performance
Dysfunction
329
330
[Instrument
petec table
[Dysfunction
316
318
320
321
Cholin-
esterase
Inhibition
323
325
326
327
328
331
Effects in
Offspring
Reported
Human
Incidence
330
-------
IChemical
Class
Codes
Chemical Name Pages
Ethyl alcohol 333-350
Ethylamine, see: Ethanamine 309
Ethylamine, 2-chloro-N,N-dimethyl-, 351
hydrochloride
Ethylamine, 2-chloro-N,K-dipropyl- 352
Ethylamine, 2-chloro-N-ethyl-N-methyl-, * 353
hydrochloride
Ethylamine, N-chloro-methyl-N-propyl-2-, 354
hydrochloride
Ethylamine, N,N-di™ethyl-2-(o-methyl- 355
alpha-phenylbenzyl-oxy ) -
Ethylamine, N,K-dime.thyl-2-( (o-methyl- 356
alpha-phenylbenzyl)oxy)-, hydrochloride
Ethylamine, 2-(diphenylmethoxy)-N,N- 357
dimethyl-
Ethylcholine, see: Ethyl (beta-hydroxy 361
ethyl) trimethylammonium hydroxide
F.thylenediaminetetraacetic acid, see: 15
Acetic acid, (ethylene-dionitrilo)tetra-
Ethylene elycol monomethyl ether, see: 329-330
Ethanol, 2-methoxy-
CNS
Structural
Damage __
334
351
352
353
354
PNS
Structural
Damage
344
350
Gross
Dysfunction
333
343
344
346
349
351
352
353
354
356
Performance
Dysfunction
337
355.
357
[Instrument
betec table
[Dysfunction
346
350
Cholin-
esterase
Inhibition
Effects in
Offspring
•
Reported
Human
Incidence ^
337
344
346
350
355
356
357
-------
to
ON
U1
Chemical
Class
Codes
X
X
OP
x
Chemical Name Pages
Ethylene, tetrachloro- 358
Ethylene, trichloro- 359-360
Ethyl (beta-hydroxy ethyl )trimethyl- 361
ammonium hydroxide
Ethyl (m-hydroxyphenyl) dimethyl- 362
ammonium chloride
alpha-Ethyl tryptamine acetate, see: 515
Indole, 3-(2-aminobutyl)-, monoacetate
Ethylurethan, see: Carbamic acid, ethyl 190
ester
Etryptamine, see: Indole, 3-(2-amino- 515
butyl)-, monoacetate
Fenthion, see: Phosphorothioic acid, 954-955
0,0-dimethyl-,0-(4-methylthio)-ro-
tolyl) ester
5-Fluoroorotic acid, see: 4-Pyrimidine 1023-1024
carboxylic acid, l,2,3,6-tetrahydro-2,
6-dioxo-5-f luoro-
Fluorothane, see: Ethane, 2-bromo-2- 310-311
chloro-l,l,l-trif luoro-
Folic acid 363
Folic acid, sodium salt 364
CNS
Structural
Damage
359
PNS
Structural
Damage
Gross
Dysfunction
358
359
360
363
Performance
Dysfunction
Instrument
Detectable
Dysfunction
[Cholin-
esterase
llnhibition
361
Effects in
Offspring
Reported
Human
Incidence
358
359
360
-------
NJ
O\
(^
Chemical
Class
Codes
C
HZ
Chemical Name Pages
Formaldehyde 365
Formamidine, see: Imidazole 509
Formanilide, 2'-(3-bromo-2-thienyl)thio- 366
Formanilide, 2'-(3-bromo-A-thienyl)thio- 367
Formanilide, 2f-(2-bromo-3-thienyl)thio- 368
5'-chloro-
Formanilide, 2l-(3-bromo-2-thienyl)thio- 369
5 ' -chloro-
Formanilide, 2'-(3-bromo-4-thienyl)thio- 370
S'-chloro-
Formanilide, 2'-(2-bromo-3-thienyl)thio- 371
5 ' - ( tr if luorome thyl ) -
Formanilide, 5'-chloro-2'-(3-thienyl)thio- 372
Formanilide, 2'-(3-thienyl)thio-5'- 373
(trifluoromethyl)-
Furacin, see: Benzyl alcohol, m-Hydroxy- 150
alpha- (methylamino)methyl)-, hydro-
chloride, (-)-
Furadan, see: Carbamic acid, methyl-, 2, 197
. 3-dihydro-2,2-diinethyl-7-beTizofuranyl
ester
Furoyl hydrazide 374
HABA, see: Butyric acid, 4-amino 174
CNS
Structural
Damage _
PNS
Structural
Damane
Gross
Dysfunction
366
367
368
369
370
371
372
373
374
Performance
Dysfunction
Instrument
Detectable
Dysfunction
Cholin-
esterase
Inhibition
Effects in
Offspring
•
Reported
Human
Incidence
-------
l-t
R)
u
•H CO CO
QUO*
V CO T)
A f-l O
U 0 0
Ga
OP
Chemical Name Pages
Galactose 375
D-Galactose 376-377
Galactosiduronic acid, methyl-, methyl 378
ester, polymer of sulfated sodium salt
Gallium fluoride 379
Gasoline 380
beta-D-Glucopyranoside, (methyl-CNN- 381-384
azoxy)methyl ) -
e
Glue vapors 385
Glutaconic acid, 3-hydroxy-, dimethyl 386
ester, dimethyl phosphate
Glutamic acid 387-388
Glutamic acid, D- 389-391
Glutamic acid, DL- 392
Glutamic acid, L- 393-395
Glutamic acid, N-acetyl 396
Glutamic acid, N-acetyl, L- 397
Glutamic acid, 3-amino- 398
.H
td
M
4-1 -! g
Z 4-> W
CJ c/1 O
381
382
384
387
391
395
f-H
CO
M
3
4J (U
U ti
3 CO
W M B
23 4J co
Pu c/3 o
385
0
O
•H
4-1
O
CO 3
CD 14-1
o u
n >>
O Q
378
379
381
382
383
384
385
386
(U B
O O
C -H
CO 4J
g S
O 3
U-l M-J
1J W
.
p^ a
B
4J a> o
C t-( -H
MOO
380
389
390
392
393
394
396
398
c
o
01 iH
1 CO 4-1
C « i-(
•H H J3
i-l tt» iH
o *J j:
j: co c
O CU M
B
•H 60
B
CO -H
4-1 »j
CJ P-
(U (0
IM «4-l
M-l 14-1
W O
«
-------
Ichemlcal
Class
Codes
•
Chemical Name Pages
Glutamic acid, N-carbamoyl- , L- 399
Glutamic acid, N-(p-(((2,4-diamino-6- 400-401
pteridnyl).methyl)methylaroino)benzoyl)-
L-
Glutamic acid, N,N-dimethyl-, L- 402
Glutamic acid, hydrazide, L- 403
Glutamic acid, beta-hydroxy 404
Glutamic acid, N-methyl-, D- 405
Glutamic acid, alpha-methyl-, DL- 406-407
Glutamic acid, N-methyl-, DL- 408-410
Glutamic acid, alpha-methyl ester, L- 411
Glutamic acid, gamma-methyl ester, L- 412
Glutamic acid, monosodium salt, L-(+)- 413-424
Glutamic acid, sodium salt 425
Glutamine, L- 426-427
CNS
Structural
Damage _
400
401
410
414
415
416
417
418
419
420
421
424
PNS
Structural
Damage
Gross
Dysfunction
400
413
414
420
Performance
Dysfunction
[Instrument
betectable
[Dysfunction
399
402
403
404
405
406
408
409
411
412
413
425
426
Cholin-
esterase
Inhibition
Effects in
Offspring
•
Reported
Human
Incidence _,
401
-------
ON
'Chemical ^j
Class 1
Codes J
HZ
Chemical Name Pages
•Glutamine, N,N-dimethyl-, L- 428
Glutamine, N-methyl-, L- 429
alpha-Glutarobetaine, see: Ammonium, 83
(3-Carboxypropyl)trircethyl-, carboxylate
Glutaramide, 3-(2-(3,5-dimethyl-2- 430-431
oxocyclohexyl)-2-hydroxyrnethyl)-
Glutaric acid 432
Glutaric acid, 2-oxo- 433
Glutarimide, 3-(2-(3,5-dimethyl-2- 434
oxocyc lohexyl ) - 2-hyd r oxye thyl )
Olutarimide, 3-ethyl-3-methyl- 435
Gluterimide, 2-ethyl-2-phenyl- 436-438
Clutethimide, see: Gluterimide, 2-ethyl- 436-438
2-phenyl-
Glycine, N-allyl- 439-440
Glycine, N-(pamma-pJutamyl)-, L- 441
Clycolic acid, hydrazide 442
Glyoxalin, see: Imidazole 509
CNS
Structural
Damage
440
PNS
Structural
Damace
Gross
Dysfunction
430
435
436
437
438
439
440
442
Performance
Dysfunction
430
434
[Instrument
betec table
IDysfunction
428
429
432
435
437
439
440
441
Choi in- ~j
esterase
Inhibition |
431
Effects in
Offspring
•
Reported
Human
Incidence g
431
435
436
437
-------
to
^J
o
[Chemical
Class
Codes
Au
OP
OP
X
OP
x
Chemical Name Pages
Gold 443
Guanethidine S04, see: Guanidine, (2- 444
(hexahydro-1 (2K) azocinyl) ethyl) - ,
sulphate (2:1)
Guanidine, (2-hexahydro-l(2H)azocinyl) 444
ethyl)-, sulphate (2:1)
Guthion, see: Phosphorodithioic acid, 923-925
0,0-dimethyl ester, S-ester with 3-
(mercapto-Tnethyl)-l,2,3 benzotriazin-4
(3F)-one
Gutoxon, see: Phosphorothioic acid, 0,0- 959
dimethyl S-((4-oxo-l,2,3-benzotriazin-
3(4H)-yl)methyl) ester
Halothane, see: Ethane, 2-bromo-2-chloro- 310-311
1,1,1-trifluoro-
Haloxon, see: Coumarin, 3-chloro-7-hydroxy- 241
4-methyl-, bis(2-chloroethyl) phosphate
Halsan, see: Ethane, 2-bromo-2-chloro- 310-311
1,1,1-trifluoro-
Harmidine, see: 3H-Pyrido-(3,4-b) indole, 1015
4 , 9-dihydro-7-methoxy-l-methyl-
Harmine, see: 9H-Pyrido(3,4-b) indole, 1016
7 -TTiethoxy-l-methyl-
Rarmine FG1, see: 9F.-Pyrido(3,4-b) indole, 1017
7-methoxy-l-methyl-, hydrochloride
CNS
Structural
Damage
PNS
Structural
Damage
443
1
Gross
Dysfunction
443
Performance
Dysfunction
Instrument
Detectable
Dysfunction
443
Cholin-
esterase
Inhibition
Effects in
Offspring
Reported
Human
Incidence
443
-------
Chemical
Class
Codes
TB
X
•
Chemical Name Pages
Harmol, see: 9H-Pyrido(3,4-b)indol-7-ol, 1020
1-methyl-
Harrisite 445
HCP, see: Phenol, 2,2'-methylene bis 756-772
(3,4,6-trichloro)-
HEF-2 (mix of alkylpentaborane derivatives) 446
He.micholinium-3, see: Mornholinium, 2,2'- 707
(4,4'-biphenylylene)bis(2-hydroxy-4,4-
dimethyl-, dibromide
alpha-Hemolysin from staphylococcus aureus 447
F.eptachlor, see: 4,7-Methanoindene, 1,4,5, 690-691
6,7,8, 8-heptachloro-3a ,4,7, 7a-tetrahydro-
(-)-Heptadeca-trans-8,10,12-triene-4,6- 448
diyne.-l,14-diol
Heptanedioic acid, 4-amino- 449
*
Reptanedioic acid, 2-amino-, DL- 450-451
Heptanedioic acid, 2,5-diamino-, L- 452
gamrna-Hexachlorocyclohexane, see: Cyclo- 251-252
hexane, 1,2,3,4,5,6-hexachloro-, gamma
isomer
Hexachlorophane , see: Phenol, 2,2'- 756-772
methyl enebis (3,4, 6-tr ichloro ) -
CNS
Structural
Damage
PNS
Structural
Damace
Gross
Dysfunction
445
446
448
Performance
Dysfunction
Instrument
betectable
[Dysfunction
445
447
448
449
450
452
Cholin-
esterase
Inhibition
Effects in
Offspring
«
Reported
Human
Incidence
445
448
-------
•vj
N3
•H
CO
U
1-1 co CJ
453
458
461
463
464
465
c
0
•H
4-1
0
W 3
CO IM
O (0
w. s*
o o
453
457
458
459
460
462
463
464
465
466
01 C
0 O
C -H
CO 4J
E g
O 3
U-l >4-l
>J 0]
o> >>
P-. Q
C
4-1 U O
C i-l -H
tU X> *J
E CO 0
3 *J C
Wi U 3
4J (U «4-l
CO 4-1 CO
c 0) M
C
•H 00
C
CO -H
4-1 M
U 0-
cu co
IW tM
4-1 M-l
U o
•
0)
•O 0
-------
rH
CO
O
•H OJ 05
0 CO
4J 0>
CJ M
3 A
l/> Wi 6
2 4J CO
O cn o
473
474
475
436
48R
iH
0)
p
4J m
0 Cl
9 TO
CO |-i £
a *j «
PH 00 Q
490
494
496
497
0
O
•H
4J
U
c
(0 3
co yj
O (0
^ >>
0 P
472
473
474
475
476
477
478
479
483
484
485
488
491
492
494
495
496
497
499
500
501
504
a, c
0 O
C -H
CO 4-1
es
0 3
«4-l <4-l
M (0
%
P-i O
C
4-1 -
MOO
472
479
480
481
482
483
484
485
486
490
492
493
498
c
o
14
u c-
01 (0
U-l U-l
M-l M-l
w o
*
0>
•a o
-i C -a
o « -H
p. 0 o
0) 3 C
Vi 33 M
472
475
476
477
478
479
481
482
483
484
485
488
489
491
492
493
494
495
496
497
498
-------
S3
-J
Ichemical
Class
Codes
CN
OP
•
Chemical Name Pages
Hydrocyanic acid 505-506
Hydrogen selenide 507
Hydrogen sulfide 508
5-Eydroxydimethyltryptamine, see: Indol- 531
5-ol, 3-02-(dimethylamino)ethylo-
6-Hydroxydopa, see: Alan in e., 2, A, 5- 75-76
t r ihydr oxyphenyl -
6-Hydroxydopamine, see: Pyrocatechol, 1026-1028
4-(2-aminoethyl)-5-hydroxy-
6-Hydroxydopamine hydrobromide, see: 77
Alanine , 2,4, 5-tr ihydroxyphenyl- ,
hydrobromide
ll-Hydroxy-delta(Sup8)tetrahydrocannabinol, 275
see: 6H-Dibenzo(b,d)pyran-l-ol, 6a,7,
10,10a-tetrahydro-ll-hydroxy-6,6,9-
• triTnethyl-3-pentyl-
Hyminal, see. 4(3H)-Quinazolinone, 2- 1035-1036
methyl-3-o-tolyl-
Imidan, see.: Phosphorodithioic acid, 926
0,0-dimethyl ester, S-ester witb N-
(nercaptomethyl) phthalimide
CNS
Structural
Damage
505
506
PNS
Structural
Damace
Gross
Dysfunction
507
508
Performance
Dysfunction
Instrument
Detectable
Dysfunction
Cholin-
esterase
Inhibition
Effects in
Offspring
«
Reported
Human
Incidence
507
508
-------
K3
^J
Ul
'Chemical
Class
Codes
OP
Chemical Name Pages
•Imidazol? 509
Inidazole, 1-methyl- 510
Iroidazole, 2 -methyl- 511
Imidazole, 4-methyl- 512
2-Imidazoline-2-hentyl-hydrochloridp 513
Imipramine, see: 5H-Dibenz(b,f )azepine, 264
5- (3- (dimethylamino) propyl ) -1 0 , 11 -
dihydro-
Iroipramine HC1, see: 5H-Dibenz(b,f ) 265
azepine, 5- (3- (dimethylamino) propyl ) -
10,11-dihydro-, roonohydrochloride
IH-Indazole, 1 -benzyl -3 (3- (dimethylamino) 514
propoxy)-
Indocybin, see: Indol-4-ol, 3- (2- (dimethyl 533-534
amino) ethyl)-, dihydropen phosphate
Indole, 3-(2-atninobutyl)-, monoacetate 515
Indole, 3-(2-aminoethyl)-5,6-dihyr1roxy- 516-518
Indole, 3-(2-aminoethyl)-5,7-dihydroxy- 519
Indole, 3-(2-aininoethyl)-5-methoxy- 520
Indole, 3-(2-aminoethyl)-f;-nPthoxy- 521
Indole, 3-(2-aminopropyl)-, acetate 522
CNS
Structural
Damage
519
PNS
Structural
Damace
Gross
Dysfunction
509
510
511
512
514
519
Performance
Dysfunction
520
521
Instrument
Detectable
Dysfunction
509
510
511
512
515
522
Cholin-
esterase
Inhibition
Effects in
Offspring
«
Reported
Human
Incidence
520
521
-------
1-\
«o
0
•H cn to
a w o>
0) CO *O
43 r-t O
0 U CJ
OP
HZ
Chemical Name Pages
^
'Indole, 3-(2-(dibutylamino)ethyl)- 523
Indole, 3-(2-(diethylamino) ethyl)- 524
Indole, 3-(2-dihexylaminoethyl)- 525
Indole, 3-(2-dimethylaminoethyl)- 526-528
Indole, 3-(2-(dimethylamino)ethyl)-5- 529
methoxy-
Indole, 3-(2-dipropyl amino)ethyl)- 530
Indol-5-ol, 3-(2-(dimethylamino)ethyl)- 531
Indol-4-ol, 3(2-(dimethyl amino)ethyl)- 532
Indol-4-ol, 3-(2-(dimethylamino)ethyl)-, 533-534
dihydrogen phosphate
Ipr indole, see5H-Cyclooct(b) indole, 253
5- (3-(d imethylamino)propyl) -6 ,7,8,9,
10 , 11-hexahydro-
Iproniazid P04, see: Isonicotinic acid, 558
2-isopropyl hydrazide phosphate
Isocyanic acid, p-bromophenyl ester 535
Isocycloheximide, see: Glutarimide, 3- 434
(2-(3,5-dimethyl-2-oxocyclohexyl)-2-
hydroxy ethyl) -
tH
CO
n
4-1 0)
0 t>C
3 cd
to »•! 6
2; 4J re
O C/3 O
-
535
t-H
CO
M
4-1 0)
U Ci
9 CO
to (-1 £
a 4J «
PJ CO Q
13
O
•H
4-1
CJ
c
W 3
(0 14-1
O (0
VJ >.
e> o
523
524
525
526
528
529
530
531
532
533
534
535
01 G
0 0
C «H
CO 4-1
E g
0 3
«4-< M-l
t-l M
0) >>
PU Q
527
£
4-1 0) O
C iH -H
01 JO 4J
e co o
3 4J C
M U 3
4J 01 «4-l
(0 4J W
c
MQO
526
529
531
534
c
o
0> -H
1 CO 4-1
C CO -H
•H h J3
rH O> -H
O 4J J=
J3 CO p
U O» M
C
•H 60
C
W l-l
4-1 P
U P.
Ol (0
«4-l U-J
U-l <4-l
w o
*
01
tJ O
-------
rH
CO
o
•H « en
§03 cu
CO T3
J= iH O
U 0 U
OP
OP
HZ
HZ
HZ
HZ
HZ
Chemical Name Pages
Isoglutaraine, L- 536
Isomethylsystox, see: Phosphorothioic 951
acid, 0,0-dimethyl S-(2-ethylthioethyl)
ester
Isomethylsystox sulfone, see: Phosphoro- 950
thioic acid, 0,0-dimethyl S-(2-(ethyl
sulfonyl) ethyl) ester
Isoniazid, see: Isonicotinic acid, 538-557
hydra zide
Isonicotinic acid, 2-(2-(benzylcarbamoyl) 537
ethyl) hydrazide " °
Isonicotinic acid, hydrazide 538-557
Isonicotinic acid 2-isopropyl hydrazide 558
phosphate
Isonicotinic acid, 2-(sulfomethyl) 559-560
hydrazide, sodium salt
JB-336, see: Benzilic acid, l-nethyl-3- 140
piperidyl ester, hydrochloride
i
tH
CO
M
4J 0)
U OC
3 CO
w M e
ss 4J co
U M O
-
539
540
541
547
549
560
r-4
CO
M
4J QJ
U tl
a w
V3 (-1 E
z; 4-> «
PM CO O
538
542
544
548
551
552
553
554
555
c
o
•rt
4J
U
C
CO D
(0 IM
o u
h ^
o o
539
540
541
542
543
545
546
550
556
557
0) C
0 O
c -H
« 4J
e s
O 3
«4-l <4-l
M <0
01 ^
PH O
538
c
4-1 01 O
C »H -H
0) U3 *J
e ca o
3 4J C
M O 3
4J 0) U-l
CO *J CO
C 4) S-
M O G
536
544
550
c
o
0> -H
1 CO 4-1
C « -H
•H M U3
r-1 O) -H
O 4J X
JB co c
CJ 01 M
C
•H 00
C
CO -H
4-1 M
0 PL.
v co
IW U-J
«W <4-l
U O
•
0)
•o o
01 C
4-1 0)
P C -0
O CO -H
&. B o
0) 3 C
Pi W M
543
546
548
550
556
557
-------
to
»J
oo
•H
«
u
•H to en
§to v
B) -a
J3 i-l O
o u u
HZ
T>b
Pb
Pb
•
Chemical Name Pages
JB-468, see: 3-Piperidinol, 1-methyl-, 984
citrate
Kainic acid, see: 3-Pyrrolidineacetic 1031
acid, 2-carboxy-4-isopropenyl
Keraadrin, see: 1-Pyrrolidine propanol, 1034
a Ipha-cyc lohexyl-a Ipha-pbenyl-
Alpha-Ketop,lutaric acid, see: Glutaric 433
acid, 2-oxo-
Kryptopyrrole, see: Pyrrole, 2,4-ditnethyl 1030
-3-ethyl-
Lactic acid, hydrazide 561
Lead 562-578
*
Lead acetate, tribydrate 579
Lead, bis (acetato) tetrabydrooxytri 580
i
t-t
CO
)-i
4J 0)
U 00
S CO
W W B
a w co
u co a
567
571
577
579
580
1-1
CO
p
4J ft)
O ti
9 «J
w H B
a w to
PJ C/3 O
564
c
o
•H
4J
U
c
01 3
CO M-4
O CO
>-. ^
0 P
561
562
564
569
571
572
575
580
CU c
u o
C -H
CQ 4J
E 8
O 3
MH <4-J
(-. CO
0) >.
PI a
565
573
c
.p at o
C t-l -H
MQO
573
576
c
o
0) i-l
1 CO 4-1
C CO -H
•H »J 43
iH 01 1H
O *J J2
4= W C
o at M
c
•H Mr
C
CO -H
4-1 M
CJ (X
at co
14-1 14-1
M-l IW
W O
«
a>
•o o
(U
>-c c -a
o « -H
P. 8 0
« 3 C
oi w M
562
563
564
566
568
571
572
573
575
576
578
-------
NJ
->4
<£>
Chemical
Class
Codes
Pb
Pb
Pb
TP
TP
X
Chemical Name Pages
•Lead carbonate 581-587
Lead (II) nitrate (1:2) 588
Lead subacetate, see: Lead, bis(acetato) 580
tetrahydrooxytri
Leurocristine 589-598
Leurocristine, sulfate (1:1) (salt) 599-604
Librium, see: 3H-l,4-Benzodiazepine, 7- 142-143
chloro-2-(methylamino)-5-phenyl-,
4-oxide
Lincomycin, see: D-Erythro-D-Galacto- 308
octo pyranoside, methyl 6,8-dideoxy-6-
(l-methyl)-4-propyl-2-pyrrolidine-
carboxamido)-l-thio
Lindane, see: Cyclohexane, 1,2,3,4,5,6- 251-252
hexachloro-, pamma isomer
CNS
Structural
Damage _
581
582
583
584
585
586
588
593
598
604
PNS
Structural
Damage
589
590
591
595
596
597
598
600
601
602
603
Gross
Dysfunction
581
582
583
589
592
595
596
598
599
600
602
Performance
Dysfunction
586
587
591
595
Instrument
Detectable
Dysfunction
591
594
595
Cholin-
esterase
Inhibition
Effects in
Offspring
586
587
593
594
•
Reported
Human
Incidence
591
592
594
595
596
597
602
-------
NJ
oo
o
Chemical
Class
Codes
OP
Li
Li
Li
B
LSD
LSD
D
,
HZ
Chemical Name Pages
Lindol, see: Phosphoric acid, tritolyl 873-875
ester
Lithane, see: Lithium carbonate 605
Lithium carbonate 605
Lithium chloride 606
Luminal, see: Barbituric acid, 5- 137
ethyl-5-phenyl-
D-Lyseramide, N-N-diethyl ester, tartrate 607
ft
Lysergic acid diethylamide tartarate, see: 607
D-Lyseramide, N-N-diethyl ester, tartrate
d-Lysergic acid, morpholide, see: Ergoline 306
-S-beta-carboxylic acid,9,10-didehydro-
6-methyl-, morpholide
Malathion, see: Succinic acid, mercapto-, 1103-1106
diethyl ester, S-ester with 0,0-di-
methyl phosphorodithioate
Malic acid, L(+)- 608
Malonic acid 609
Malonic acid, amino- 610
Halonic acid, aminoethyl- 611
Mandelic acid, hydrazide 612
CNS
Structural
Damage _
PNS
Structural
Damaee
Gross
Dysfunction
605
612
Performance
Dysfunction
606
Instrument
Detectable
Dysfunction
608
609
610
611
Cholin-
esterase
Inhibition
Effects in
Offspring
Reported
Human
Incidence
605
-------
OO
Chemical
Class
Codes
Mn
Mn
Mn
OP
Mn
C
Chemical Name Pages
Manganese 613-620
Manganese (II) chloride (1:2) 621-622
•
Manganese, cyclopentadienyltricarbonyl 623
Menazon, see: Phosphorodithioic acid, S- 912
((4,6-diamino-S-triazin-2-yl)methyl)
0,0-dimethyl ester
o
3-Mercaptopropionic acid 624
Manganese dioxide 625
Mepesulfate, see: Galactosiduronic acid, 378
methyl-, methyl ester, polymer of sul-
fated sodium salt
Mephenolaxone, see: 2-Oxazolidinone, 5- 727
( (O-methoxyphenoxy)inethyl)
Meprobamate, see: 1,3-Propanediol, 2- 991
methyl-2-nropyl-, dicarbamate
Mepyramine raaleate, see: Pyridine, 2- 1011
(dimethylamino) ethyl) (p-methoxybenzyl)
anino)-, maleate (1:1)
CNS
Structural
Damage
621
•
PNS
Structural
Damage
Gross
Dysfunction
613
614
618
619
620
621
623
624
625
Performance
Dysfunction
Instrument
Detectable
Dysfunction
615
621
622
Cholin-
esterase
Inhibition
Effects in
Offspring
•
Reported
Human
Incidence
613
614
618
619
620
625
-------
rH
CO
u
•H CO CO
Sen
U 5C
3 CO
1/3 Vi 6
2 4J CO
0 C/3 O
628
629
632
637
638
640
641
642
643
t-H
CO
M
4J (U
U tl
S cfl
CO M g
a *j S
PM eo o
641
0
O
•H
4-1
g
W 3
CO U-l
O CO
n >.
0 0
626
633
635
636
637
640
642
(U C
0 O
C -H
CO 4J
eg
O 9
U-l IW
M CO
.
PU Q
C
4J 0) O
CS i-( -H
•
MOO
626
636
c
o
01 -H
I CO 4J
C «0 -H
•rt >j X>
i-H 0) -H
O 4J .C
J= CO C
O CD M
C
•H 00
C
CO TH
4J »J
U 0.
CU M
U-l U-l
U-l U-l
W 0
•
0>
•o o
(U C
4J (U
>-i C -O
O CO -H
Cu 0 0
-------
1-1
CO
u
•H CD W
0 CO Q)
O> CO T>
4= i-H 0
U O O
HR
«B
HS
HS
TIB
He
HR
Hg
HP,
Chemical Name Pages
.
7!ercury, chloromethyl- 645-656
Mercury, chlorophenyl 657
Mercury, (3-cyanoguanidlno)methyl- 658-661
Mercury, cysteinylethyl- 662
Mercury, ((2,3-dihydroxypropyl)thio) 663
methyl-
Mercury, hydroxymethyl- 664-667
"
Mercury, tnercaptomethyl- 668-669
Mercury, methyl- 670-680
Mercury, methyl (methylthio)- 681
i
rH
CO
p
4J 0)
U 60
a n
w M B
a 4J «
U OT Q
645
646
648
650
651
652
653
654
655
658
659
660
662
663
664
665
666
675
676
681
•H
ec
M
3
4J 0)
O Ci
a co
w M E
25 *J CO
PL4 CO O
649
658
659
663
666
668
.669
681
a
o
•H
4J
U
to 3
(0 UH
O (0
H 5^
O O
649
650
652
658
660
661
666
671
675
.677
678
(U C
0 O
C -H
« *J
ES
O 3
M-4 U-l
M U
(U ^
P-. Q
655
663
664
665
679
680
c
4-1 (U O
C i-H 1-1
-
MOO
678
680
i
c
o
0) -H
1 (0 4-1
C « -H
•H (-1 .£>
l-t
-------
ichemical
Class
Codes
HR
OP
OP
X
X
X
Chemical Name Pages
Mercury, methyl (thioacetamido)- 682-684
Merphos, see: Phosphorotrithious acid, 963
tributyl ester
Mescaline, see: Phenethylamine, 3,4,5- 749-751
trimethoxy-
Mescaline hemisulfate, see: Phenethyl- 752
amine, 3,4,5-trimethoxy-, hemisulfate
Metasystox-R, see: Phosphorothioic acid, 949
0,0-dimethyl S-(2-(ethylsulf inyl)ethyl)
ester
Metamphetamine hydrochloride, see: 744-755
Phenethylamine , N-alpha-d imet hyl- ,
hydrochloride, (-)-
Methane, bromo- 685-686
Methane, chloro- 687
Methane, dichloro- 688-689
4,7-Methanoindene, 1,4,5,6,7,8,8-hepta- 690-691
chloro-3a , 4 , 7 , 7a-tetrahydro-
4,7-Methanoisobenzofuran, 1,3,4,5,6,7,8, 692
CNS
Structural
Damage _
682
683
690
PNS
Structural
Damage
Gross
Dysfunction
682
683
685
686
687
691
692
Performance
Dysfunction
688
689
Instrument
Detectable
Dysfunction
Cholin-
esterase
Inhibition
Effects in
Offspring
Reported
Human
Incidence
682
685
686
687
688
689
-------
oo
Ul
Chemical
Class
Codes
OP
X
*
Chemical Name Pages
Methanol 693-697
Methaqualone, see: 4(3H)-Ouinazolinone, 1035-1036
2-methyl-3-o-tolyl-
beta-Methasone, see: 16-methylprepna- 698
l,4-diene-3,20-dione, 9-f luoro-11,17,
21-trihydroxy-
Methion, see: Phosphorothioic acid, 958
0,0-dime.thyl 0-(4-nitro-m-tolyl) ester
Methionine sulfoxitnine, see: Sulfoximine, 1107-1111
S-(3-amino-3-carboxypropyl)-S-methyl-
Methotrexate, see: Glutamic acid, 11- 400-401
(p- ( ( (2 , 4-diamino-6-pteridnyl)methyl)
methylamino)benzoyl)- L-
5-Methoxydimethyltryptamine, see: Indole, 529
3- (2-d imethylanino) ethyl ) -5-methoxy-
5-Methoxy tryptamine , see: Indole, 3- (2- 520
aminoethyl)-5-methoxy-
6-Methoxy tryptamine, see: Indole, 3-(2- 521
aminoethyl)-6-methoxy-
3-Methoxytyramine, see: Phenol, p-(2- 754
aminoethyl)-3-methoxy-
Methyl bromide, see: Methane., bromo- 685-636
CNS
Structural
Damage
693
694
PNS
Structural
Damace
Gross
Dysfunction
694
695
696
Performance
Dysfunction
(Instrument
betectable
(Dysfunction
Cholin-
esterase
Inhibition
Effects in
Offspring
*
Reported
Human
Incidence
693
694
695
696
-------
Ichemical
Class
Codes
K
X
X
Hp,
Hp.
Hp
Hp,
Chemical Name Pages
Methyl-N-butyl ketone, see: 2-Hexanone 459-465
Methyl cellosolve, see: Ethanol, 2- 329-330
methoxy-
Methyl chloride, see: methane, chloro- 687
N-Methyl-L-cysteic acid, see: Alanine, 65
N-methyl-3-sulfo-, L-
Methylene chloride, see: Methane, 688-689
dichloro-
Methyl pjycol, see: Ethanol, 2-methoxy- 329-330
TJ-Methyl-DL-homocysteic acid, see: Butyric 178
. acid, 2-(methylamino)-4-sulfo-, DL-
Methyl iso-hutyl ketone, see: 2-Pentanone, 736
4-methyl-
Methyl mercuric acetate, see: Mercury, 637-638
(acetato)methyl-
Methylmercuric sulfide, see: Mercury, 668-669
mercaptomethyl-
Methylmercury dicyandiamide, see: Mercury, 658-661
(3-cyanop.uanidino) methyl-
Methyl tiethylnercury sulfide, see: 681
Mercury, methyl (methyl thio)-
CNS
Structural
Damage _
.
PNS
Structural
Daraace
Gross
Dysfunction
Performance
Dysfunction
Instrument
petec table
[Dysfunction
Cholin-
esterase
Inhibition
Effects in
Offspring
*
Reported
Human
Incidence _,
-------
00
Chemical
Class
Codes
OP
TP
OP
C
Chemical Name Pages
Methyl parathion, see: Phosphorothioic 957
acid, 0,0-dimethyl O-(p-nitrophenyl)
ester
Methyl phenidate HCl, see: 2-Piperidine 979
acetic acid, alpha -phenyl-, methyl ester,
hydrochloride
16-Methylpregna-l,4-diene-3,20-dione, 698
9-f luoro-11 , 17 , 21-tr ihydroxy
Methyl theobromine, see: Caffeine 182
Methyl trithion, see: Phosphor odithioic 0 910-911
ac id , S- ( ( (p-chlorophenyl ) thio )methyl )
0,0-dimethyl ester
alpha-Methyl tryptamine acetate, see: 522
Indole, 3-(2-aminopropyl)-, acetate
2-Methyoxyacridine, 6-chloro-9-((4- 699
(d iethylamino) -1-methylbutyl ) amino) - ,
dimethane sulfonate
Metoclopramide, see: o-Anisamide, 4- 93
amino-5-chloro-N-(2-d iethylamino) ethyl)
Metrazol, see: 5H-Tetrazoloazepine, 1117-1122
6 » 7 , 8 , 9-tetrahydro
Miazole, see: Imidazole 509
Mohara, see: Carbamic acid, methyl-, 192-193
benzo (b) thien-4-yl-ester
CNS
Structural
Damage _
698
PNS
Structural
Damace
Gross
Dysfunction
Performance
Dysfunction
698
Instrument
Detectable
Dysfunction
Cholin-
esterase
Inhibition
Effects in
Offspring
•
Reported
Human
Incidence
-------
OO
C»
ichemical
Class
Codes
Chemical Name Pages
Morestan, see: Carbonic acid, dithio-, 214
cyclic S,S-(6-methyl-2,3-quinoxaline-
diyl) ester
Morphinan-3, 6-alpha-diol,17-allyl-7, 700
8 didehydro-4,5-alpha-epoxy-, HC1
Morphinan-3, 6-alpha-diol, 7,8-didehydro- 701
4 , 5-alpha-epoxy-17-methyl-
Morphinan-3, 6-diol , 7 , 8-didehydro-4 ,5- 702
epoxy-17-methyl-, hydrochloride,
(5-alpha-6-alpha) -
Morphinan-3, 6-alpha-diol, 7,8-didehydro- 703-704
4,5-alpha epoxy-17-methyl-, sulfate
Morphinan-6-one, 4-5-epoxy-3,l4- 705
dihydroxy-17-(2-propenyl)-, hydro-
chloride, (5-alpha)-
Morphine HC1, see: Morphinan-3, 6-diol, 702
7 , 8-d idehydro-4 , 5-epoxy-17-methyl-,
1 hydrochloride, (5-alpha-6-alpha)-
Morphine sulfate, see: Morphinan-3, 6- 703-704
alpha-diol, 7 , 8-didehydro-4 , 5-alpha
epoxy-17-methyl-, sulfate
Morpholine., 2-chloroethyl-, hydrochloride 706
CNS
Structural
Damage _
706
PNS
Structural
Damace
Gross
Dysfunction
705
706
Performance
Dysfunction
Instrument
Detectable
Dysfunction
700
704
Cholin-
esterase
Inhibition
Effects in
Offspring
,
•
Reported
Human
Incidence _,
-------
N)
OO
VO
Chemical
Class
Codes
OP
OP
OP
B
Chemical Name Pages
TTorpholinium, 2,2f-(4,4'-biphenylylene) 707
bis(2-hydroxy-4,4-dimethyl-, dibromide)
MSO, see: Glutamic acid, monosodium 413-424
salt, L-(+)-
?ITX, see: Olutamic acid, N-(p-(((2,4- 400-401
diamino-6-pteridnyl)methyl)methylamino)
benzoyl)-, L-
Mustargen, see: Diethylamine, 2,2'- 286
d ichloro-N-methyl-
Mytilus edulis toxins 708
Naled, see: Phosphoric acid, 1,2-dibromo- 840
2,2-dichloroethyl dimethyl ester
Naloxone HCl, see: Morphinan-6-one, 4-5- 705
p.poxy-3,14-dihydroxy-17-(2-propenyl)-,
hydrochloride, (5-alpha)-
Napthalene methanol, alpha- (isopropyl-
amino) methyl-, hydrochloride 709
Napthalinide, N-hydroxy-, diethyl 710
phosphate
Nemacide, see: Phosphorothioic acid, 0- 938
(2,4-dichloro-phenyl)-0,0-diethyl ester
Nembutal, see: Barbituric acid, 5-ethyl- 134-135
5-(l-nethylbutyl)-, sodium salt
;!eomycin 711
CNS
Structural
Damage
PNS
Structural
Damace
Gross
Dysfunction
70S
710
711
Performance
Dysfunction
(Instrument
petec table
[Dysfunction
707
708
711
Cholin-
esterase
Inhibition
Effects in
Offspring
•
Reported
Human
Incidence
708
-------
N>
\O
O
Ichemical
Class
Codes
Ca
HZ
IIZ
OP
Ni
OP
Chemical Name Pages
Neostitonine bromide, see: Ammonium, 88
(m-hydroxyphenyl) trimethyl-, bromide
dimethylcarbamate
Neotizide, see: Isonicotinic acid, 2- 559-560
(sulfomethyl)hydrazide, sodium salt
Mialamide, see: Isonicotinic acid, 2- 537
(2-(benzylcarbamoyl)ethyl)hydrazide
Nialate, see: Phosphorodithioic acid, 928-929
S , S ' -methylene 0 ,0 , 0 ' , 0 ' -tetraethyl
ester
o
Nickel 712
TliRrin, see: Picolinic acid, 5-amino-6- 969
(7-araino-5 , 8-dibydro-6-methoxy-5 , 8-
dioxo-2-quinolyl)-4-(2-hydroxy-3,4-
dimethoxyphenyl)-3-methyl
Nissol, see: Acetamide, 2-fluoro-N-methyl- 3
N-1-napthyl-
Mitrof urantoin , see: Hydantoin, l-((5- 489-498
nitrofurfurylidene)amino)-
Nitrophos, see: Phosphorothioic acid, 958
0,0-dimethyl 0-(4-nitro-m-tolyl) ester
Nitrous acid, pentyl ester 713
Tlivemycin, see Neomycin
2,T!orbornene, 1,2,3,4,7 ,7-hexachloro-5, 6- 714
bis(chloronethyl)-
CNS
Structural
Damage _
PNS
Structural
Damage
Gross
Dysfunction
713
714
Performance
Dysfunction
Instrument
Detectable
Dysfunction
Cholin-
esterase
Inhibition
Effects in
Offspring
•
Reported
Human
Incidence _,
-------
K>
VO
Chemical
Class
Codes
TA
OP
HZ
HZ
OP
•
Chemical Name Pages
Motechis scutatus scutatus venom 715-716
Novocaine, see: Benzamide, p-amino-n- 138
(2-(diethylamino)ethyl))-
Noxiptlline, see: 5H-Dibenzo(a,d)cyclo- 269
hepten-5-one, 10,ll-dihydro-,0-(2-
(dimethylamino) ethyl )oxime
Organophosphate pesticides 717
Orphenadrine HCl, see: Ethylamine, N,N- 356
dimethyl-2-((o-methyl-alpha-phenylbenzyl)
oxy)-, hydrochloride
Orthonal, see: 4(3K)-Quinazolinone, 2- 1035-1036
methyl-3-o-tolyl-
Ouabain 718-720
Oxalic acid, bis(cyclohexylidenehydrazide) 721-724
*
Oxalic acid, dihydrazide 725
2H-l,3,2-Oxazaphosphorine, 2- (bis (2- 726
chloroethyl)amino)tetrahydro-, 2-oxide
2-Oxazolidinone, 5-((0-methoxyphenoxy) 727
methyl)
2-Oxazoline, 2-amino-5-phenyl- 728
CNS
Structural
Damage _
720
721
723
724
726
PNS
Structural
Damace
721
Gross
Dysfunction
716
719
723
724
725
727
72P>
Performance
Dysfunction
[Instrument
petec table
[Dysfunction
715
716
Cholin-
esterase
Inhibition
Effects in
Offspring
•
Reported
Human
Incidence
717
728
-------
IChemical
Class
Codes
OP
OP
OP
Chemical Name Pages
•Oxygen 729-732
Ozone 733
Pa^itane, see: 1-Piperidine propanol, 983
alpha -cyclopp.ntyl-alpha-phenyl-
2-PAMM, see: Pyridinlum, 2-formyl-l-methyl 1014
-,methanesulfonate, oxime
Panparnlt, see: cyclopentane carboxylic 255
. acid, 1-phenyl-, 2-(diethylamino)ethyl
ester, hydrochloride
Papthlon, see: Acetic acid, mercapto- 25
phenyl-, ethyl ester, S-ester with 0,0-
dimethyl phosphorodithioate
Paraoxon, see: Phosphoric acid, diethyl 846
p-nitrophenyl ester
Parathion, see: Phosphorothioic acid, 941-943
0,0-diethyl 0- (p-nitrophenyl) ester
Pargyline 1IC1, see: Benzylamine, N- 152
methyl-N-2-propynyl-, hydrochloride
Parsidol, see: Phenothiazine, 10-(2- 782-783
diethylamino)propyl)-
Penicillin G, see: 4-Thia-l-azahlcyclo 1136-1138
(3.2.0)heptane-2-carboxylic acid, 3,3-
dirnethyl-7-oxo-6- (2-phenylacetamldo) -
CNS
Structural
Damage _
PNS
Structural
Damace
Gross
Dysfunction
729
731
732
Performance
Dysfunction
Instrument
Detectable
Dysfunction
733
Cholin-
esterase
Inhibition
Effects in
Offspring
*
Reported
Human
Incidence
729
-------
NJ
\O
U)
Chemical
Class
Codes
B
Chemical Name Pages
Pentaborane (9) 734-735
Pentamethylenete.trazole, see: 5H-Tetra- 1117-1122
zoloazepine , 6,7,8, 9-tetrahydro
2-Pentanone, 4-methyl- 736
Pentaphene hydrochloride, see: Cyclo- 255
pentane carboxylic acid, 1-phenyl-,
2-(dlethylamino)ethyl ester, IIC1
Pentobarbital sodium, see: Barbituric 134-135
acid , 5-ethyl-5-(l-methylbutyl)-,
sodium salt
9
Perphenazine, see: 1-Piperazineethanol, 977
4-(3-(2-chlorophenothiazin-10-yl)propyl)
Perphenazine enanthate, see: 1-Piper- 978
azineethanol, 4-(3-(2-chlorophenothin-
zin-10-yl)propyl)-, heptanoate
Pesticides (unspecified) 737
Phenelzine RC1, see: Hydrazine, phenethyl-, 503
hydrocliloride
Phenethylamine, p-chloro-alpha, alpha- 738
dimethyl
Phenethylamine, 4-chloro-2-Tnethyl-, DL- 730
Phenethylamine, 4— chloro— alpha-methyl- 740
Phenethylanine, 2-chloro-2-nethyl-, (+-)- 741
CNS
Structural
Damage _
•
738
739
PNS
Structural
Damace
736
Gross
Dysfunction
734
735
Performance
Dysfunction
Instrument
Detectable
Dysfunction
735
737
Cholin-
esterase
Inhibition
Effects in
Offspring
*
Reported
Human
Incidence
735
737
-------
.H
CO
CJ
•H 03 03
§03 (V
CO -O
.C tH 0
U U U
B
O
•
Chemical Name Pages
Phenethylamine, 3-chloro-2-methyl-, (+-)- 742
Phenethylamine, 4-chloro-2-methyl-, (+-)- 743
Phenethylamine, N-alpha-dimethyl-, 744-745
hydrochloride, (-)-
Phenethylamine, alpha-methyl- (+)- 746
amphetamine
Phenethylamine, alpha-methyl-sulphate 747-748
(2:1), (+,-)-
Phenethylamine, 3,4,5,-trimethoxy- 749-751
Phenethylamine, 3,4,5-trimethoxy-, 752
hemisulfate
Pheniprazine RC1, see: Hydrazine, (alpha- 502
methylphenethyl)-, hydrochloride
Phenobarhital, see: Barbituric acid, 137
5-ethyl-5-phenyl-
i
Phenol 753
Phenol, p-(2-aminoethyl)-3-methoxy- 754
Phenol, m-(lI-(2-imidazolin-2-ylmethyl)-p- 755
toluidino)-, monoethanesulfonate (salt)
i-H
CO
4J 0)
U 60
3 CO
Crt l-i 6
O CO Q
753
rH
cd
Vi
4-1 OJ
O fcl
3 CO
10 t-i E
a 4J «
PH C/3 O
C
O
•H
4J
U
03 3
03 M-l
O (0
h >>
O O
744
745
749
752
754
4) C
U O
C -H
CO 4J
00
C
O 3
M-l M-4
M 03
(U >%
CU Q
74S
c
4J Q> o
C i-l -H
>
M Q O
748
752
C
o
a) -H
1 03 4J
C CO -H
i-l C
B
03 lH
4-1 »-c
0 P.
(il 03
M^ M-l
M-l M-l
W o
744
751
0)
T3 O
(U G
4-1 0)
M C -O
O CO i-l
P. 0 0
a> 3 B
OS EC M
753
-------
Chemical
Class
Codes
Chemical Name Pages
•Phenol, 2,2'-methylenebis (3,4,6- 756-772
trichloro)-
Phenolphthalein 773
Phenothiazine druRS (unspecified) 774
Phenothiazine, 2-chloro-10-3(3-dimethyl- 775-777
amino) propyl )-
Phenothiazine, 2-chloro-10-(3-(dimethyl- 773-779
amino) propyl)-, mono-hydrochloride
Phenothiazine, 2-chloro-10-(3-(4-methyl- 780-781
1-piperazinyl) propyl
Phenothiazine, 10-(2-diethylamino)propyl) 782-783
Phenothiazine, 10-(3-(dimethylamino) 784-786
propyl)-, monohydrochloride
Phenothiazine, 2-(ethylthio)-10-(3-(4- 787
methyl-1-piperazinyl ) propyl) -
CNS
Structural
Damage _
756
758
760
761
762
763
764
767
768
769
770
772
PNS
Structural
Damaee
756
758
766
767
773
Gross
Dysfunction
757
758
759
760
761
762
763
764
765
766
767
768
770
771
780
784
787
Performance
Dysfunction
779
Instrument
Detectable
Dysfunction
757
762
771
111
779
Cholin-
esterase
Inhibition
Effects in
Offspring
763
•
Reported
Human
Incidence
759
762
765
769
773
774
780
782
784
787
-------
S3
v£>
Chemical
Class
Codes
OP
OP
OP
OP
OP
OP
OP
Chemical Name Pages
Phenothiazine, 10-(3-(4-methyl-l-piper- 788-789
azinyl)propyl)-2-(trifluoromethyl)-
Phenoxybenzamine, see: Benzylamine, N- 151
(2-chloroethyl) -N- (l-methyl-2-
phenoxyethyl)-
Phentolamine methane sulphonate, see: 755
Phenol, m-(N-(2-Imidazolin-2-ylmethyl)-
p-toluidino)-, monomethanesulfonate
(salt)
Phenytoin, see: Hydantoin, 5,5-diphenyl- 472-487
Phisohex, see: Phenol, 2,2 '-methylenebis ° 756-772
(3,4,6-trichloro)-
Phorate, see: Phosphorodithioic acid, 0,0- 920
diethyl S-(ethylthio)methyl ester
3-Phosphabicyclo(4.4.0) decane, p-chloro- 790
2 ,4-dioxa-5-methyl-p-thiono-
Phosphine oxide, tri-o-tolyl- 791
Phosphofluoridic acid, methyl-, isopropyl 792
ester
Phospholipase A 793
Phosphonic acid, decyl-, ethyl p-nitro- 794
phenyl ester
Phosphonic acid, ethyl-, 2-chloroethyl 795
2,2-dichlorovinyl ester
CNS
Structural
Damage _
789
794
795
PNS
Structural
Damace
794
795
Gross
Dysfunction
738
789
790
794
795
Performance
Dysfunction
[Instrument
[Detectable
(Dysfunction
Cholin-
esterase
Inhibition
792
Effects in
Offspring
•
Reported
Human
Incidence
788
-------
Chemical
Class
Codes
OP
OP
OP
OP
OP
OP
OP
OP
OP
OP
OP
OP
•
Chemical Name Pages
Phosphonic acid, 0-ethyl-0-(4-nitro- 796
phenyl)-ethyl ester
Phosphonic acid, pentyl-, ethyl p- 797
nitrophenyl ester
Phosphonic acid, 2-phenylethyl-, ethyl p- 798
nitrophenyl ester
Phosphonic acid, phenyltnethyl-, ethyl 799
p-nitrophenyl ester
Phosphonic acid, 3-phenylpropyl-, ethyl 800
p-nitrophenyl ester
Phosphonic acid, (2,2,2-trichloro-l- 801
hydroxyethyl)-, dimethyl ester
Phosphonodithioic acid, chloromethyl- 802
S-(p-chlorophenyl)0-isopropyl ester
Phosphonodithioic acid, 0-isopropyl-S- 803
p-tolyl chloromethyl ester
Pnosphonofluoridic acid, methyl-, 804-805
isopropyl ester
Phosphonofluoridic acid, methyl-, 806
1,2,2-trimethyl propyl ester
Phosphonothioic acid, ethyl-, di(2- 807
chloroethyl) ester
Phosphonothioic acid, ethyl-, 0-ethyl 808-809
O-(2,4,5-trichlorophenyl) ester
CNS
Structural
Damage _
797
798
799
800
807
808
PNS
Structural
Damage
797
798
799
800
807
808
Gross
Dysfunction
797
798
799
800
802
803
807
80S
809
Performance
Dysfunction
796
801
804
Instrument
Detectable
Dysfunction
Cholin-
esterase
Inhibition
796
805
806
Effects in
Offspring
~*
•
Reported
Human
Incidence
801
-------
iH
CO
O
•H m co
S w 01
Q) CO T3
.C rH 0
CO 0 CJ
OP
OP
CN
OP
OP
OP
OP
OP
OP
Al
OP
op
OP
Chemical Name Pages
'Phosphonothioic acid, methyl-, 2,4- 810
dichlorophenyl methyl ester
Phosphonothioic acid, phenyl, -0-ethyl fill
ester, 0-est^r with p-hydroxybenzonitrile
Phosphonothioic acid, phenyl-, 0-ethyl 812
O-(p-nitrophenyl) ester
Phosphonothioic acid, 0-ethyl S-.(2- . 813
dimethyl amino ethyl)methyl estor
Phosphonotrithioic acid, S,S-dipropyl 814
methyl
Phosphonotrithioic acid, methyl-, S- 815
propyl-S-diethlsuccinate
Phosphoramidic acid, methyl-, A-tert- 816-817
hutyl-2-chlorophenyl methyl ester
Phosphorair.idothioic acid, isopropyl-, 818
0-2,4-dichlorophenyl 0-methyl ester
Phosphoric acid, aluminum salt 819
Phosphoric acid, bis(2-ethylhexyl) 820
o-tolyl ester
Phosphoric acid, his (p-ethylphenyl) ester 321
Phosphoric acid, his(4-ethylphenyl) 2- 822
propylphenyl ester
i
•H
co
i-i
4J CD
u oc
3 O)
u CJ
O CO
to >j E
Z *J CO
Pn C/5 O
810
C
O
•H
4-1
u
C
CO 3
CO IM
O M
Ui >>
O O
310
811
812
814
815
816
817
818
821
822
(U G
U O
C -H
CO 4J
g g
0 3
<4-l M-l
VJ CO
Q) ^
Pi O
C
4J Q> O
C i-( iH
01 J3 4J
g CO 0
5 4J C
VJ 0 3
4J 41 U-!
CO *J 10
C
MOO
C
O
-i JD
M -• C -a
O CO -H
a. e o
« 3 C
OS P3 M
-------
Chemical
Class
Codes
OP
OP
OP
OP
OP
OP
OP
op
OP
OP
OP
OP
Chemical Name Pages
Phosphoric acid, his(2-ethylphenyl) 823
p-tolyl ester
Phosphoric acid, his(o-propylphenyl) 824
p-tolyl ester
Phosphoric acid, his (3,5-xylyl) 2- 825
ethylphenyl ester
Phosphoric acid, 2-chloro-l-(2,4- 826
dibromophenyl) vinyl dimethyl ester
Phosphoric acid, 2-chloro-l-(2,4- 827
dichlorophenyl) vinyl diethyl ester 0
Phosphoric acid, 2-chloro-l-(2,4- 828
dichlorophenyl) vinyl dimethyl ester
Phosphoric acid, 2-chloro-l-(2,5- 829
dichlorophenyl) vinyl dimethyl ester
Phosphoric acid, 2-chloroethyl 2,2- 830
dichlorovinyl methyl ester
Phosphoric acid, 2-chloroethyl 2- 831
dichlorovinyl methyl ester
Phosphoric acid, 2-chloroethyl ethyl 832
p-nitrophenyl ester
Phosphoric acid, o-chlorophenyl diphenyl 333
aster
Phosphoric acid, l-((p-chlorophenyl) 834
thio) vinyl dimethyl ester
CNS
Structural
Damage
830
832
PNS
Structural
Damacte
830
832
Gross
Dysfunction
823
324
825
827
830
831
832
834
Performance
Dysfunction
(Instrument
betectable
[Dysfunction
Cholin-
esterase
Inhibition
826
828
829
831
Effects in
Offspring
«
Reported
Human
Incidence _,
-------
Chemical
Class
Codes
OP
OP
OP
OP
OP
OP
OP
OP
OP
OP
OP
OP
»
Chemical Name Pages
Phosphoric acid, 2-chloro-l-(2,4, 5-tri- 835
chloro-phenyl) vinyl dimethyl ester
Phosphoric acid, o-cresyl diphenyl ester 836
Phosnhoric acid, cyclic methylene-o- 837-839
phenylene o-tolyl ester
Phosphoric acid, l,2-dibromo-2,2- 840
dichloroethyl dimethyl ester
Phosphoric acid, di(2-chloroethyl) 2,2- 841
dichlorovinyl ester
Phosphoric acid, di(2-chloroethyl) 842
p-nitrophenyl ester
Phosphoric acid, di(2-chloroethyl) 2,3,5- 843
trichlorophenyl ester
Phosphoric acid, di-o-chlorophenyl 844
phenyl ester
Phosphoric acid, 2-2-dichlorovinyl 845
' dimethyl ester
Phosphoric acid, diethyl p-nitrophenyl 846
ester
Phosphoric acid, di(o-ethylphenyl) 847
p-tolyl ester
Phosphoric acid, diethyl o-tolyl ester 848
CNS
Structural
Damage
836
838
839
841
842
843
845
PNS
Structural
Daraace
836
838
841
842
843
845
Gross
Dysfunction
835
836
838
839
841
842
843
845
847
Performance
Dysfunction
840
Instrument
Detectable
Dysfunction
Cholin-
esterase
Inhibition
846
Effects in
Offspring
•
Reported
Human
Incidence
840
-------
Chemical
Class
Codes
OP
OP
OP
OP
OP
OP
OP
OP
OP
OP
OP
OP
OP
OP
Chemical Name Pages
•Phosphoric acid, dimethyl (1- (dimethyl 849
phosphonyl) vinyl) ester
Phosphoric acid, dimethyl ester, ester 850
with (E)-3 hydroxy-N-methyl crotonamide
Phosphoric acid, diphenyl o-tolyl ester 851-853
Phosphoric acid, di-p-tolyl 2-ethyl 854
phenyl ester
Phosphoric acid, di-p-tolyl o-ethyl 855
phenyl ester
Phosphoric acid, di-o-tolyl m-tolyl ester 856
Phosphoric acid, di-p-tolyl o-tolyl ester 857
Phosphoric acid, di-o-tolyl p-tolyl ester 858
Phosphoric acid, di-p-tolyl o-tolyl ester 859
Phosphoric acid, di(3,5-xylyl) o-tolyl 860
ester
Phosphoric acid, o-hydroxyphenyl phenyl 861
ester
Phosphoric acid, tolyl ester 862
Phosphoric acid, o-tolyl ester 863
Phosphoric acid, triaryl ester 864
CNS
Structural
Damage
851
861
PNS
Structural
Damace
851
.861
863
Gross
Dysfunction
849
850
851
852
854
855
856
857
858
859
860
861
862
863
864
Performance
Dysfunction
(Instrument
petec table
[Dysfunction
Cholin-
esterase
Inhibition
849
Effects in
Offspring
•
Reported
Human
Incidence
862
863
-------
iChemical
Class
Codes
OP
OP
OP
OP
OP
OP
op
OP
OP
OP
OP
OP
Chemical Name Pages
Phosphoric acid, tri(o-biphenylyl) ester 865
Phosphoric acid, tributyl ester 866
Phosphoric acid, triethyl ester 867
Phosphoric acid, tri-p-e.thylphenyl ester 86R-869
Phosphoric acid, tri-4-ethyl phenyl ester 870
Phosphoric acid, tri-o-ethyl phenyl ester 871
Phosphoric acid, triphenyl ester 872
Phosphoric acid, tritolyl ester • 873-875
Phosphoric acid, tri-m-tolyl ester 876
Phosphoric acid, tri-o-tolyl ester 877-894
Phosphoric acid, tri-p-tolyl ester 895
Phosphoric acid, trixylyl ester 896
CNS
Structural
Damage _
870
873
874
880
883
885
887
888
890
891
892
893
PNS
Structural
Damace
869
870
874
875
878
881
882
884
885
891
892
894
Gross
Dysfunction
866
868
869
870
874
875
877
878
880
882
883
884
885
886
887
888
889
890
891
892
896
Performance
Dysfunction
Instrument
Detectable
Dysfunction
Cholin-
esterase
Inhibition
894
Effects in
Offspring
•
Reported
Human
Incidence
-------
,_4
0
•H m co
B co ->
(X, Q
C
4J CU O
(3 rH TH
(U *JQ 4J
£ CO CJ
3 *J C
M U 3
4J (U «4-l
CO JM CO
C!
M Q 0
C
O
0) -H
1 CO 4J
C CO -H
•H »-l 43
rH CU -H
O *•* ^3
J= CO C
CJ CU M
902
911
C
•H 60
B
CO -H
0 P.
cu co
UH MH
U^ *> i
W O
0)
T3 O
CU B
4-1 CU
M B T3
O CO tH
P- 0 O
0) 3 B
Od K M
902
-------
u>
o
.£>
Chemical
Class
Codes
OP
OP
OP
OP
OP .
OP
OP
OP
OP
OP
Chemical Name Pages
Phosphorodithioic acid, S((4,6-(iiamino- 912
S-triazin-2-yl)methyl)0,0-dimethyl ester
Phosphorodithioic acid, S-(((2,5-dichloro- 913
phenyl)thio)methyl) 0,0-diethyl ester
Phosphorodithioic acid, (((3,4-dichloro- 914
phenyl)thio)methyl) 0,0-diethyl ester
Phosphodithioic acid, S-( (3,4-dichloro- 915
phenyl)thio)inethyl) 0,0-dimethyl ester
Phosphorodithioic acid, 0,0-diethyl ester, 916
S,S-diester with p-dioxane-2,3-dithiol
Phosphorodithioic acid, 0,0-diethyl ester, 917
S-ester with 3-(tnercaptomethyl)-l,2,3-
henzotr iazin-4 (311) one
Phosphorodithioic acid, 0,0-diethyl S- 918-919
(2 ethylthio) ethyl) ester
Phosphorodithioic acid, 0,0-diethyl S- 920
(ethylthio)methyl ester
Phosphorodithioic acid, 0,0-dimethyl 921
ester, S-ester with 2-mercapto-N-
(2-methoxyacetyl) acetamide
Phosphorodithioic acid, 0,0-dimethyl 922
ester, R-ester with 2-mercapto-N-
methylacetamide
CNS
Structural
Damage _
PNS
Structural
Damage
Gross
Dysfunction
912
913
914
915
916
917
918
919
920
921
922
Performance
Dysfunction
Instrument
Detectable
Dysfunction
Cholin-
esterase
Inhibition
919
922
Effects in
Offspring
•
Reported
Human
Incidence
919
922
-------
Chemical
Class
Codes
OP
OP
OP
OP
OP
OP
OP
OP
OP
OP
OP
•
Chemical Name Pages
Phosphorodithioic acid, 0,0-dimethyl ester, 923-925
S-ester with 3(mercaptomethyl)-l,2,3-
benzotriazin-4(3H)-one
Phosphorodithioic acid, 0,0-dlriethyl ester 926
S-ester with N-(mercaptomethyl)
phthalimide
Phosphorodithioic acid, 0-ethyl S,S- 927
dipropyl ester
Phosphorodithioic acid, S^'-methylene 928-929
0,0,0',0'-tetraethyl ester
Phosphonodithioic acid, methyl-, 0- 930
phenyl S-propyl ester
Phosphorofluoridic acid, bis(l- 931-932
methylethyl) ester
Phosphorofluoridic acid, methyl-, 933
isopropyl ester
Phosphorothioic acid, 0-(2-(sec-butoxy- 934
'methylthio) ethyl) 0,0-diethyl ester
Phosphorothioic acid, 0-(2-chloro-l-(2,4- 935
dichlorophenyl)vinyl 0,0-dimethyl ester
Phosphorothioic acid, 0-(2-chloro-4- 936
nitrophenyl) 0,0-dimethyl ester
Phosphorothioic acid, O-(p-cyanophenyl) 937
0,0-dimethyl ester
CNS
Structural
Damage _
. •
932
PNS
Structural
Damace
932
Gross
Dysfunction
923
925
926
927
928
929
930
931
932
934
935
936
937
Performance
(Dysfunction
[Instrument
betec table
[Dysfunction
933
Cholin-
esterase
Inhibition
924
926
933
934
935
Effects in
Offspring
Reported
Human
Incidence
928
933
-------
[Chemical
Class
Codes
OP
OP
OP
OP
OP
OP
OP
OP
OP
OP
OP
OP
OP
Chemical Name Pages
Phosphorothioic acid, 0-(2,4-dichloro- 938
pbenyl)-0,0-diethyl ester
Phosphorothioic acid, 0,0-diethyl 0-(2- 939
isopropyl-6-methyl-4-pyrimidinyl) ester
Phosphorothioic acid, 0,0-diethyl-O- 940
(4- (methylthio) -3 , 5-xylyl ) ester
Phosphorothioic acid, 0,0-diethyl 0- 941-943
(p-nitrophenyl) ester
Phosphorothioic acid, 0,0-diethyl 0- 944-945
(3,5,6-trichloro-2-pyridyl) ester
•
Phosphorothioic acid, 0,0-diethyl 0- 946
1,2,2-trimethyl propyl ester
Phosphorothioic acid, 0,0-diisopropyl 947
0-(4-methylsulfinyl phenyl) ester
Phosphorothioic acid, 0,0-dimethyl ester, 948
0,0-diester with 4,4'-thiodiphenol
Phosphorothioic acid, 0,0-dimethyl S-(2- 949
(ethylsulfinyl) ethyl) ester
Phosphorothioic acid, 0,0-dimethyl S-(2- 950
(ethylsulfonyl) ethyl)ester
Phosphorothioic acid, 0,0-dimethyl S-(2- 951
ethylthioethyl) ester
Phosphorothioic acid, 0,0-dimethyl S-(2- 952
(isopropylsulfino) ethyl) ester
Phosphorothioic acid, 0,0-dimethyl 0-(p- 953
nethylsulfinyl)phenyl) ester
CNS
Structural
Damage _
PNS
Structural
Damace
Gross
Dysfunction
938
940
941
944
945
946
947
948
949
953
Performance
Dysfunction
Instrument
Detectable
Dysfunction
939
943
Cholin-
esterase
Inhibition
942
946
947
949
950
951
952
953
Effects in
Offspring
•
Reported
Human
Incidence
939
943
-------
iChemical
Class
Codes
OP
OP
OP
OP
OP
OP
OP
OP
OP
OP
OP
•
Chemical Name Pages
Phosphorothioic acid, 0,0-dimethyl-, 0- 954-955
(4-methylthio)-m-tolyl) ester
Phosphorothioic acid, 0,0-dimethyl 0-(4- 956
methylthio)-3,5-xylyl) ester
Phosphorothioic acid, 0,0-dimethyl-O- 957
(p-nitrophenyl) ester
Phosphorothioic acid, 0,0-dimethyl 0- 958
(4-nitro-m-tolyl) ester
Phosphorothioic acid, 0,0-dimethyl S- 959
( (4-oxo-l , 2 , 3-benzotr iazin-3 (4H) -yl)
methyl) ester
Phosphorothioic acid, 0-0-dimethyl 0 960
(2,4,5-trichlorophenyl) ester
Phosphorotrithioic acid, 0-methyl S,S- 961
dipropyl ester
Phosphorotrithioic acid, S,S,S-tributyl 962
ester
Phosphorotrithious acid, tributyl ester 963
Phosphorous acid, tri-o-tolyl ester 964
Phthalate plasticizers (mixture) 965
Phthalimide, N-(2,6-dioxo-3-piperidyl)- 966-967
Phthalimide, N-hydroxy-, 0-ethyl 0- 968
isopropyl phosphorothioate
CNS
Structural
Damage _
966
967
PNS
Structural
Damace
Gross
Dysfunction
955
956
957
958
960
961
962
963
964
965
968
Performance
Dysfunction
Instrument
Detectable
Dysfunction
965
Cholin-
esterase
Inhibition
959
968
Effects in
Offspring
966
967
«
Reported
Human
Incidence ^
965
-------
UJ
o
00
Chemical
Class
Codes
•HZ
TP
Chemical Name Pages
.Picolinic acid, 5-amino-6-(7-amino-5,8- 969
dihydro-6-methoxy-5,8-dioxo-2-quinolyl-4-
(2-hydroxy-3,4-dimethoxyphenyl)-3-methyl
Picolinic acid, hydrazide 970
2-Picolinium, l-((4-amino-2-propyl-5- 971-972
pyrimidinyl)methyl)-, chloride,
hydrochloride
Picrotoxin 973-975
Piperamide, see: Acetanilide, 4 '-(4- (3- 5
dimethylamino)propyl)-l-piperazinyl)-
Piperazine 976
1-Piperazineethanol, 4-(3-(2-chloro- 977
phenothiazin-10-yl)propyl)-
1-Plperazineethanol, 4-(3-(2-chloro- 978
phenothiazin-10-yl)propyl)-,heptanoate
2-Piperidine acetic acid, alpha-phenyl-, 979
methyl ester hydrochloride
Piperidlne, 2-chloroethyl-, hydrochloride 980
2-Piperidineethanol, alpha, alpha-diphenyl- 981
1-methyl-hydrochloride
1-piperidine propanol, alpha-cyclohexyl 982
alpha-phenyl-, hydrochloride
CNS
Structural
Damage _
969
971
972
.
980
PNS
Structural
Damace
Gross
Dysfunction
970
971
974
980
Performance
Dysfunction
[Instrument
betec table
[Dysfunction
973
974
975
Cholin-
esterase
Inhibition
[Effects in
Offspring
969
•
Reported
Human
Incidence
981
982
-------
U)
o
V0
Chemical
Class
Codes
Pb
Tip,
OP
Chemical Name Pages
1-Piperidine propanol, alpha-cyclopentyl- 983
alpha-phenyl-
3-Piperidinol, 1-methyl-, citrate 984
Plasmocide, see: Quinoline, 8-((4-dlethyl- 1041
amino)-l-methylbutyl)amino)-6-nethoxy-
Plumbane, tetraethyl- 985-987
PMC, see: Mercury, chlorophenyl 657
Pregn-4-ene-3,20-dione, 17,21-dihydroxy-, 988
succinate, sodium salt
Pritnidone, see: 4,6(lH,5lI)-Pyrinidine- 1025
dione, 5-ethyldihydro-5-phenyl-
Procainamide, see: Benzair.ide, p-amino- 138
n-2-(diethyl(amino)ethyl))-
Procaine, see: Benzole acid, p-amino, 2- 146
(diethylamino) ethyl ester
Procarbazine, see: p-Toluamide, N- 1188-1189
isopropyl-alpha-(2-Tnethylhydrazino)-
Prochlorperazine, see: Phenothiazine, 730-781
. 2-chloro-10-(3-(4-methyl-l-piper-
azinyl)propyl-
Prolats, see: Phosphorodithioic acid, 926
0,0-dimethyl ester, S-ester with N-
(mercaptonethyl) phthalimide
CNS
Structural
Damage
987
PNS
Structural
Damace
Gross
Dysfunction
985
986
988
Performance
pysf unction
[Instrument
petectable
(Dysfunction
988
Cholin-
esterase
Inhibition
Effects in
Offspring
Reported
Human
Incidence
983
984
-------
1
CO
(J
•H M CO
6 to d
J= i-( "c
U U CJ
C
CM
OP
CM
Chemical Name Pages
Proline, 5-oxo- 9B9
Promazine HC1, see: Phenothiazine, 10-(3- 784-786
(dimethylamino)propyl)-, monohydrochloride
Prone.thalol HC1, see: Naphthalene 709
tnethanol, alpha- (isopropylamino) methyl-,
hydrochloride
1,2-Propanediol, dinitrate 990
1,3-Propanediol, 2-methyl-2-propyl-, 991
dicarbamate
Propanol, see: Propyl alcohol 1004
l-Propene-l,l,3-tricarbonitrile, 2-amino- 992
Propionic acid, 2-amino-3-hydroxy-, 993
phosphonate, (ester)
Propionic acid, 2-amino-3-sulf ino-, L- 994
Propionic acid, beta-N-oxalyl-L-alpha, 995-996
beta-d iamino-
Propionitrile, 3-diamino- 997
,_4
cd
3
4J CU
CJ «
3 cfl
iO )>4 fi
2 4J CO
0. c/> Q
rH
CO
3
U M
3 CO
co t~> 6
!S 4J CO
X W O
C
O
•H
4_>
U
c
eo 3
CO «4-l
O (0
1-1 >•>
o o
995
996
997
a) c
u o
(3 -H
CO 4-1
w C
O 3
H ^ i[ j
t-i (0
V >>
ft^ f^
990
992
c
4-1 0) C
C rH T
e *« t
3 4.) C
»-i o :
4-1 0) U-
CO 4J 0
c
-------
u>
Chemical
Class
Codes
CM
TE
OP
*
Chemical Name Pages
Propionitrile, 3,3f-irninodi- 998-1003
Propoxyphene hydrochloride, see: 2-Butan- 171-172
ol, 4-(diTnethylamino)-3-niethyl-l,2-di-
phenyl-, propionate (ester), hydro-
chloride (+)-,
Propyl alcohol 1004
Propylamine 1005
Pseudomona tabaci exotoxin 1006
Psilocin, see: Indol-4-OL, 3(2-(dimethyl 532
amino ) ethyl ) -
Psilocybin, see: Indol-4-OL, 3-2- (dimethyl 533-534
amino) ethyl)-, dihydrogen phosphate
Puromycin, see: Adenosine, 3 '-(alpha- 61-62
amino-p-methoxy hydrocennamamido)-
3 ' -d eoxy-N , N-d iraethyl
Pyramat, see: Carbamic acid, dimethyl-6- 191
rnethyl-2-propyl-4-pyrinidnyl ester
3-PyridenecarboxaTnide, 6-amino- 1007-1010
CNS
Structural
Damage
998
999
1000
1001
1007
1008
1009
1010
PNS
Structural
Damage
1010
Gross
Dysfunction
998
999
1000
1001
1002
1006
1010
Performance
Dysfunction
Instrument
Detectable
nysftinrf-f nn
1002
1005
Cholin-
esterase
Inhibition
Effects in
Offspring
.007
.008
.009
Reported
Human
Incidence
-------
rH
H)
u
1-1 co (o
B w 01
0) CO -O
x: r-i o
o u u
.
Chemical Name Pages
Pyridine, 2-( (2-(dinethylamino)athyl) (p- 1011
methoxybenzyl)amino)-, maleate (1:1)
3-Pyridinemethanol, 5-hydroxy-4,6-dimethyl-, 1012
hydrochloride
Pyridinium, 2-formyl-l-methyl-, chloride, 1013
oxime
Pyridinium, 2-formyl-l-methyl-, methane- 1014
sulfonate, oxime
3H-Pyrido- (3, 4-h) indole, 4, 9-dihydro-7- 1015
methoxy-1-methyl-
9T!-Pyrido(3,4-b)indole, -7-methoxy-l- 1016
methyl- .
' 9II-Pyrido(3,4-b) indole, 7-methoxy-l- 1017
methyl-, hydrochloride
9H-Pyrido (3, 4-b) indole, 1,2,3,4-tetra- 1018
hydro-7-methoxy-l-methyl
9ft-Pyrido(3,4-b)indole, 1,2,3,4-tetra- 1019
hydro-2-Tiiethyl-
9H-Pyrido(3,4-b)indol-7-ol, 1-methyl- 1020
Pyridoxol hydrochloride 1021
Pyridoxol, r.iethoxy- 1022
4-Pvrimidinecarboxylic acid, 1,2,3,6- 1023-1024
tetrahydro-2,6-dioxo-5-fluoro-
i
t-»
W
M
4J %
CJ 0
1012
1013
1014
1017
1022
1023
,
PI a
1015
1016
1018
1019
1020
c
4-> CU O
C •-! vH
01 XI 4-)
B « 0
3 4J C
»-i O 3
4J CU U-l
CO 4-1 CO
C V >
MQp
1012
1017
1021
1022
c
o
CU -H
1 CO 4-1
C « -H
•H »J 43
iH 0» -H
O 4J .C
.CMC
O 4-l
W O
1024
0)
•0 0
CU B
4J CU
>-i C T)
O « -H
&. B o
(U 3 C
pi SG l-l
1015
1016
101S
1019
1020
-------
Chemical
Class
Codes
OP
TP
TP
TP
Chemical Name Pages
4,6(lH,5!I)-Pyrinidinedione, 5-ethyldi- 1025
hydro-5-phenyl
Pyrocatechol, 4-(2-aminoethyl)-5-hydroxy- 1026-1028
Pyroglutamic acid, see: Proline, 5-oxo- 989
Pyrophosphoric acid, tetraethyl ester 1029
Pyrrole, 2,4-dimethyl-3-ethyl- 1030
3-Pyrrolidine acetic acid, 2-carboxy-4- 1031
isopropenyl
Pyrrolidine, l,l-(2-butynylene) di- 1032-1033
1-Pyrrolidine propanol, alpha-eye lohexyl- 1034
alpha-phenyl-
4(3H)-Ouinazolinone, 2-methyl-3-o-tolyl- 1035-1036
Quinine chloride, see: Quinine., mono- 1037
hydrochloride
Quinine, monohydrochloride 1037
Quinine muriate, see: Quinine, mono- 1037
hydrochloride
Ouinolines, 8-amino- (not specified) 1038
CNS
Structural
Damage _
1027
1031
1038
PNS
Structural
Damage
Gross
Dysfunction
1025
1030
1031
1032
1033
1035
J036
1037
1038
Performance
Dysfunction
1029
[Instrument
betec table
(Dysfunction
1030
Cholin-
esterase
Inhibition
Effects in
Offspring
•
Reported
Human
Incidence _,
1025
1029
1034
1035
1036
1037
-------
rH
CO
U
•H m co
g to v
4-1 0)
u oc
3 CO
co M S
sz; 4-1 to
u to Q
1039
1040
1041
1042
.
1048
1049
1050
1051
r-i
cfl
t-l
4J OJ
o w
9 CO
CO h B
Z 4J CO
P-( C/3 O
1039
1048
1050
p
o
•H
4J
C
CO 3
CO M-l
O CO
M >>
U O
1043
1044
1045
1046
1048
1049
1050
1051
1052
1053
1054
V B
CJ O
B -H
CO 4J
a H
0 3
IM <*-i
M CO
CU >.
Pi O
1047'
B
*J CU O
B iH -H
B
»-i 0 3
•u
T3 O
CU B
4-1 CU
H C T3
O CO i-l
Cu 0 O
CU 3 B
Prf K M
1046
1047
1051
-------
w
I-1
Ul
Chemical
Class
Codes
Cu
Cu
Cu
Cu
Cu
0?
•
Chemical Name Pages
8-Ouinolinolium 7 '-bromo'S'hydroxy' 2 '- 10.55
naphthoate, copper (II) chelate
8-Ouinolinolium 4' ,7 '-dibromo-3'-hydroxy-2'- 1056
naphthoate
3-Ouinolinolium 4 ' , 7 '-dihromo-3 '-hydroxy- 1057
2 '-naphthoate, copper (II) chelate
8-Quinolinolium l'-hydroxy-2' -naphthoate 1058
8-Quinolinoliuro 3 '-hydrox3'-2' -naphthoate 1059
8-Ouinolinolium l'-hydroxy-2 '-naphthoate, 1060
copper (II) chelate
o-Ouinolinoliun 3 '-hydroxy-21 -naphthoate, 1061
copper (II) chelate
8-Ouinolinolium salicylate 1062
8-Ouinolinolium salicylate, copper (II) 1063
chelate
t
Rpserpine, see: 3-beta,20-alpha-Yohimhan- 1229
].6-be>ta-carboxylic acid, 18-heta-hydroxy-
11,17-alpha-dimethoxy-, methyl ester,
3, 4,5-trimethoxybenzoate (ester)
Reserpine phosphate 106A
Resorcinol, 2-p-mentha-l,8-dien-3-yl- 1065-1066
5-pentyl-
CNS
Structural
Damage
-
PNS
Structural
Damage
Gross
Dysfunction
1055
1056
1057
1058
1059
1060
1061
1062
1063
Performance
Dysfunction
1065
1066
Instrument
Detectable
Dysfunction
1064
Cholin-
esterase
Inhibition
Effects in
Offspring
*
Reported
Human
Incidence
-------
Chemical
Class
Codes
OP
OP
OP
TP
TP
B
B
Chemical Name Pages
'Retinol, all trans- 1067-1068
Revonal, see: 4(3K)-Quinazolinone, 2- 1035-1036
methyl-3-o-tolyl-
Ronnel, see: Phosphorothioic acid, 0-0- 960
dimethyl 0(2,4,5-trichlorophenyl) ester
TUielene, see: Phosphoramidic acid, methyl-, 816-817
4-tert-butyl-2-chlorophenyl methyl ester
Salicylic acid, monsodium salt 1069
Sarin, see: Phosphonofluoridic acid, 804-805
methyl-, isopropyl ester
Sarodormin, see: Gluterimide, 2-ethyl- 436-438
2-phenyl-
Saxitoxin 1070-1071
Scopolamine 1072
Scopolamine bromide 1073
Secobarbital, see: Barbituric acid, 5- 131
allyl-5- (1-methylbutyl)
Seconal, see: Barbituric acid, 5-allyl- 131
5- (1-methylbutyl)-
Semicarbazide 1074
Semicarbazide, 4,4-diethyl-, hydrochloride 1075
CNS
Structural
Damage
1067
1068
1069
PNS
Structural
Damage
Gross
Dysfunction
1073
1074
1075
Performance
Dysfunction
1 Instrument
Detectable
Dysfunction
1071
1073
Cholin-
esterase
Inhibition
Effects in
Offspring
1067
1068
*
Reported
Human
Incidence _,
1069
1072
-------
rH
CO
CJ
•H 0) 05
§03 01
CO •«
.C tH O
U 0 CJ
OP
C
TB
B
B
B
B
Sn
Chemical Name Pages
Semicarbazide, thio- 1076-1077
Semioxamazide 1078
Senna 1079
Serine, dihydrogen phosphate (ester), L- 1080
Sevin, see: Carbamic acid, methyl-, 200-201
1-naphthyl ester
Shigella Shigae toxin 1081
Sodium azide. ' 1082
1083
Sodium methohexital, see: Barbituric 132
acid , 5-allyl-l-methyl-5-(l-methyl-
2-pentynyl)-, sodium salt
Sodium pentobarbital, see: Barbituric 134-135
acid, 5-ethyl-5-(l-methylbutyl)-,
sodium salt
Sodium pentothal, see: Barbituric acid, 136
5-ethyl-5-(l-me.thylbutyl)-2-thio-,
sodium salt
Sodium thiopental, see: Barbituric acid, 136
5-ethyl-5-(l-methylbutyl)-2-thio-,
sodium salt
Stannane, acetoxytriphenyl- 1084
f_^
CO
4^ (U
u 6c
3 co
C/5 M B
S3 4J CO
c_> to o
*..
1082
1083
i-H
h
4J >
o o
1076
1077
1078
1082
to c
u o
C i-l
CO 4J
E 8
O 3
U-l U-l
M CO
(1) >%
P-, G
0
4-1 01 O
C r-l -H
(U |£J 4*^
E cfl • O
3 4J C
Wi O 3
4J Cil U-l
CO 4J CO
(j D ^"
M Q O
1080
c
o
M
0 P.
V U
^1 I* 1
u-i u-i
W CD
0)
•o cj
1 i (y
M c -a
0 CO «H
P. B «-»
U 3 C
Pd W M
1079
-------
Chemical
Class
Codes
Sn
Sn .
Sn .
Sn
Sn
TP
TP
Chemical Name Pages
Stannane, chlorotriethyl- 1085
Stannane, dibutyloxo- 1086
Stannane, hydroxytriethyl- 1087
Stannane, hydroxytriphenyl- 1088
Stannane, triethyl- 1089-1093
Streptoni^rin, see: Picolinic acid, 5- 969
amino-6-(7-amino-5 , 8-dihydro-6-methoxy-
5,8-dioxo-2-quinolyl)-4-(2-hydroxy-3,4-
dimethoxyphenyl)-3-methyl
Strychnine 1094-1095
Strychnine, sulfate (2:1) 1096-1097
Succinanic acid, alpha-amino-, L- 1098-1099
Succinic acid 1100
Succinic acid, 2-aminomethyl-, DL- 1101
Succinic acid, 2,3-diamino-, me.so- 1102
Succinic acid, mercapto-, diethyl ester, 1103-1106
S-ester with 0,0-dimethyl phosphoro-
dithioate
CNS
Structural
Damage _
1087
1089
1090
1092
1093
1096
PNS
Structural
Damage
Gross
Dysfunction
1085
1037
1088
1092
1093
1096
1097
1103
1104
Performance
Dysfunction
(Instrument
betectable
bysfunction
1097
1098
1100
1101
1102
1106
Cholin-
esterase
Inhibition
1105
Effects in
Offspring
,
(Reported
Human
(Incidence
1106
-------
OJ
M
VO
Chemical
Class
Codes
Te
Te
OP
TB
Sn
Pb
Chemical Name Pages
'Sulfoximine, S-(3-amino-3-carboxypropyl)- 1107-1111
S-nethyl-
TED, see: l,4-Diazabicyclo(2.2.2)octane 262
Tellurium 1112-1113
Tellurium tetrachloride 1114
TFPP, see: Pyrophosphoric acid, 1029
tetraethyl ester
Tetanus toxin 1115-1116
TETH, see: Stannane, hydroxytriethyl- 1087
Tetraethyl lead, see: Plumbane, tetra- 985-987
ethyl-
delta (Supl)Tetrahydrocannabinol, see: 6H- 278-284
Dibenzo (b ,d ) pyran-1-ol , 6a , 7 , 8 , lOa-
tetrahydro-6,6,9-trimethyl-3-pentyl-,
(6aR-trans)-
delta(Sup8)-Tetrahydrocannabinol, see: 6H- 276-277
Dibenzo (b ,d ) oyran-1-ol , 6a , 7 , 10 , lOa-
tetrahydro-6 , 6 , 9-tr imethyl-3-pentyl-
delta(Sup9)-Tetrahydrocannabinol, see: 6H- 278-284
dibenzo(b,d)pyran-l-ol, 6a,7,8,10a-
tf.trahydro-6 , 6 , 9-trimethyl-3-pentyl- ,
(6aR-trans)-
CNS
Structural
Damage
1107
1108
1110
1112 .
1114
PNS
Structural
Damace
1113
Gross
Dysfunction
1108
1109
1110
1111
1113
1115
Performance
Dysfunction
[Instrument
petectable
pysf unction
1116
Cholin-
esterase
Inhibition
Effects in
Offspring
1112
«
Reported
Human
Incidence
-------
OJ
N>
O
Chemical
Class
Codes
TA
TI
TI
TP
TP
TP
TP
TP
TP
Chemical Name Pages
'5H-Tetrazoloazepine, 6,7,8,9-tetrahydro- 1117-1122
Tetrodotoxin 1123-1125
*
Thalidomide, see: Phthalimide, N-(2,6- 966-967
d ioxo-3 -p ip er id yl ) -
Thallium 1126-1127
Thallium sulfate 1128-1129
delta (SupS)THC, see: 6H-Dibenzo(b,d)pyran- 276-277
l-ol, 6a, 7,10, lOa-tetrahydr 0-6, 6,9-
trimethyl-3-pentyl-
delta(Sup9)THC, see: 6K-Dibenzo(b,d)pyran- 278-284
l-ol , 6a , 7 , 8 , lOa-tetrahydr 0-6 ,6,9-
trimethyl-3-pentyl-, (6aR-trans)
Theobromine, 1-allyl- 1130
Theobromine, l-(2-butenyl)- 1131
Theobromine, 1-ethyl- 1132
Theobromine, l-(2'-methoxye.thyl)- 1133
Theobromine, l-(2'-me.thylallyl-) 1134
Theobromine, 1-propyl 1135
,CNS
Structural
Damage
1126
PNS
Structural
Damage
1126
1127
1129
Gross
Dysfunction
1118
1119
1120
1121
1126
1128
1130
1131
1132
1133
1134
1135
Performance
Dysfunction
1120
1122
Instrument
Detectable
Dycf ti^irf-'fnn
1119
1122
1124
1125
Cholin-
esterase
Inhibition
Effects in
Offspring
Reported
Human
Incidence
L127
L128
-------
Chemical
Class
Codes
Chemical Name Pages
4-Th±a-l-azabicyclo (3.2.0) heptane-2- 1136-1138
carboxylic acid, 3,3-dimethyl-7-oxo-
6- (2-phenylacetamido ) -
4-Thia-l-azabicyclo(3.2.0) heptane-2- 1139
carboxylic acid, 3,3-dimethyl-7-oxo-
6- (2-phenylacetamido)-, monopotassium
and monosodiutn salts
4H-Thieno(2,3-b)(l,4)benzothiazine 1140
9H-Thieno(3,4-b) (l,4)benzothiazine 1141
9H-Thie.no(3,2-b)(l,4)benzothiazine, 9- t 1142
acetyl-
9H-Thieno(3,4-b) (l,4)benzothiazine-9- 1143
carboxaldehyde
4H-Thieno(2,3-b) (l,4)benzothiazine-4- 1144
carboxaldehyde, 6-chloro
9H-Thieno(3,2-b) (l,4)benzothiazine-9- 1145
carboxaldehyde, 7-chloro
9H-Thieno(3,4-b) (l,4)benzothiazine-9- 1146
carboxaldehyde, 7-chloro
4H-Thieno(2,3-b) (l,4)benzothiazine-4- 1147
carboxaldehyde, 6-(trifluoromethyl)-
9H-Thieno(3,2-b) (l,4)benzothiazine-9- 1148
carboxaldehyde, 7-(trif luoromethyl)-
,CNS
Structural
Damage
1139
PNS
Structural
Damage
Gross
Dysfunction
1136
1137
1139
1140
1141
1142
1143
1144
1145
1146
1147
1148
Performance
Dysfunction
Instrument
Detectable
T)y«? f iipf* t" 'f nji
1137
1138
Cholin-
esterase
Inhibition
Effects in
Offspring
Reported
Human
Incidence
1136
1137
-------
Chemical
Class
Codes
•
Chemical Name Pages
9H-Thieno(3,4-b)(l,4)benzothiazine-9- 1149
carboxaldehyde, 7 (trifluoromethyl)-
4H-Thieno(2,3-b)(l,4)benzothiazine, 6- 1150
chloro-
91I-Thieno(3,2-b)(l,4)benzothiazine, 7- 1151
chloro-
9H-Thieno(3,4-b)(l,4)benzothiazine, 7- 1152
chloro
4H-Thieno(2,3-b)(l,4)benzothiazine, 7- 1153
chloro-4-(3-diraethylaminopropyl)-,
hydrochloride
9H-Thieno(3,4-b)(l,4)benzothiazine, 7- 1154
chloro-9- (3-dimethylaminopropyl ) - ,
hydrochloride
9H-Thieno(3,4-b)(l,4)benzothiazine, 9- 1155
(3-dimethylaminopropyl)-, hydrochloride
9H-Thieno(3,4-b)(l,4)benzothiazine, 4- 1156
(3-dimethylaminopropyl) -6- (tr if luoro-
methyl)-, hydrochloride
9!!-Thieno(3,4-b)(l,4)benzothiazine, 9- 1157
(3-dimethylaminopropyl)-7-(trifluoro-
methyl)-, hydrochloride
4H-Thieno(2,3-b)(l,4)benzothiazine, 6- 1158
(trifluoromethyl)-
CNS
Structural
Damage
PNS
Structural
Damage
Gross
Dysfunction
1149
1150
1151
1152
1153.
1154
1155
1156
1157
1158
Performance
Dysfunction
Instrument
Detectable
nysf iinrf inn
Cholin-
esterase
Inhibition
Effects in
Offspring
Reported
Human
Incidence
-------
Chemical
Class
Codes
OP
Chemical Name Pages
' 91I-Thieno(3,2-b)(l,4) benzothiazine, 7- 1159
(trifluoromethyl)-
9H-Thieno(3,4-b)(l,4) benzothiazine, 7- 1160
(trifluoromethyl)-
Thiethylperazine, see: Phenothiazine, 2- 787
(ethylthio)-10-(3-(4-methyl-l-piper-
azinyl)propyl)-
Thiocron, see: Phosphor odithioic acid, 921
0,0-dimethyl ester, S-ester with 2-
inercapto-N-(2-methoxyacetyl)acetamide
Thiophene, 3-(2-amino-4-chlorophenyl) thio- 1161
Thiophene, 2-(2-amino-4-chlorophenyl)thio- 1162
3-bromo-
Thiophene, 3-(2-amino-4-chlorophenyl)thio- 1163
4-brorao
Thiophene, 3-(2-aminophenyl) thio- 1164
Thiophene, 2-(2-aminophenyl)thio-3-bromo- 1165
Thiophene, 3-(2-aminophenyl)thio-4-bromo- 1166
Thiophene, 3-((2-amino(alpha, alpha, alpha- 1167
trif luoro-p-tolyl) ) ) thio-
Thiophene, 2-((2-amino-(alpha, alpha, alpha- 1168
trif luoro-p-tolyl) ) ) thio-3-bromo-
Thiophene, 3-((2-amino(alpha, alpha, alpha- 1169
trif luoro-p-tolyl) ))thio-4-bromo-
,CNS
Structural
Damage
PNS
Structural
Damage
Gross
Dysfunction
1159
1160
1161
1162
1163
1164
1165
1166
1167
1168
1169
Performance
Dysfunction
Instrument
Detectable
DyfifunrMnn
Cholin-
esterase
Inhibition
Effects in
Offspring
Reported
Human
Incidence
-------
Chemical
Class
Codes
HZ
OP
Sn
Sn
Chemical Name Pages
Thiophene 3-bromo-2-(4-chloro-2-nitro- 1170
phenyl)thio-
Thiophene, 3-bromo-4-(4-chloro-2-nitro- 1171
phenyl)thio-
Thiophene, 3-bromo-2-(2-nitrophenyl)thio- 1172
Thiophene, 3-brorao-4-(2-nitrophenylthio)- 1173
Thiophenei 3-bromo-2-( (2-nitro- (alpha, 1174
alpha, alpha-trif luoro-p-tolyl) thio)-
Thiophene, 3-broroo-4-( (2-nitro- (alpha, . 1175
alpha , alpha-trif luoro-p-tolyl ) thio) -
Thiophene, 3-(4-chloro-2-nitrophenyl)thio- 1176
Thiophene hydrazide 1177
Thiophene, 3-(2-nitrophenylthio)- 1178
Thiophene, 3-(2-nitro-alpha, alpha, alpha- 1179
trif luoro-p-tolyl) thio-
Thiopyrophosphoric acid, tetrapropyl ester 1180
Thioxanthene-delta(sup9-)gamma-propylamine, 1181
2-chloro-M,N-dimethyl, hydrochloride
Tin, dioctyl-, acetate 1182
Tin, triethyl-, sulphate 1183-1186
,CNS
Structural
Damage
1183
1185
1136
PNS
Structural
Damage
1184
Gross
Dysfunction
1170
1171
1172
1173
1174
1175
1176
1177
1178
1179
1180
1183
1186
Performance
Dysfunction
Instrument
Detectable
T)y«s f npr f- •• r>n
Cholin-
esterase
Inhibition
1180
Effects in
Offspring
Reported
Human
Incidence
-------
u>
N>
(Jl
Chemical
Class
Codes
Sn
OP
DP
Chemical Name Pages
Tin, trioctyl-, dilaurate 1187
TMBDA, see: 1,3-Rutanediamine, N.N.ll'.N1- 169
tetramethyl-
TOCP, see: Phosphoric acid, tri-o-tolyl 876-895
ester
Tolazoline HC1, see: 2-Imidazoline, 2- 513
bentyl-hydrochloride
p-Toluamide, N-isopropyl-alpha-(2- 1188-1189
methylhydrazino)
Toluene 1190-1191
Transamine sulfate, see: Cyclopropylamine 256
2-phenyl-, sulfate, trans-(-f ,-)-, (2:1)
Tranylcypromine sulfate, see: Cyclopropyl- 256
amine, 2-phenyl-, sulfate, trans- (+,-)-,
(2:1)
*
Tremorine, see: Pyrrolidine, 1,1- (2- 1032-1033
butynylene) di-
Triazoic acid, see: Ilydrazoic acid 504
Tributyltin oxide, see: Distannoxane, 296
hexabutyl-
Trichlorfon, see: Phosphonic acid, (2,2, 801
2-trichloro-l-hydroxyethyl)-, dimethyl
ester
CNS
Structural
Damage
1188
PNS
Structural
Damage
Gross
Dysfunction
1190
1191
Performance
Dysfunction
Instrument
Detectable
Dyfif nnrt"fnn
1189
1191
Cholin-
esterase
Inhibition
Effects in
Offspring
1188
Reported
Human
Incidence
1190
1191
-------
OJ
Chemical
Class
Codes
OP
OP
CM
Sn
Sn
Sn
Sn
Chemical Name Pages
• Trichloronate, see: Phosphonothioic acid, 803-809
ethyl-, 0-ethyl 0-(2,4,5-trichlorophenyl)
ester
Tri-o-cresyl phosphate, see: Phosphoric 876-895
acid, tri-o-tolyl ester
Tricyanoaminopropene, see: 1-Propene- 992
1,1,3-tricarbonitrile, 2-amino-
Triethylcholine 1192
Triethylenediamine, see: 1,4-Diazabi- 262
cyclo(2.2.2) octane
Triethyltin, see: Stannane, triethyl- 1089-1093
Triethyltin hydroxide, see: Stannane, 1087
hydroxytriethyl-
Trifluoperazine, see: Phenothiazine, 788-789
10- (3- (4-nethyl-l-piperaz inyl ) pr opyl ) -
2- (tr if luoromethyl ) -
Triparanol, see: Ethanol, 2-(p-chloro- 324
phenyl ) -1- (p- (2- (d iethylamino ) e thoxy )
phenyl ) -1-p-t olyl-
Triphenyltin acetate, see: Stannane, 1084
acetoxytriphenyl-
Triphenyltin hydroxide, see: Stannane, 1088
hydroxytriphenyl-
:CNS
Structural
Damage
PNS
Structural
Damage
Gross
Dysfunction
Performance
Dysfunction
Instrument
Detectable
Hys f un f f i nn
Cholin-
esterase
Inhibition
1192
Effects in
Offspring
Reported
Human
Incidence
-------
Chemical
Class
Codes
Chemical Name Pages
1-alpha-H, 5-alpha-H-Tropane-2-beta-carboxy- 1193
lie acid, 3-beta-hydroxy-methyl ester,
benzoate (ester) hydrochloride
1-alpha-H, 5-alpha-H-Tropane, 3-alpha- 1194
(dipbenyl methoxy)
Tronaniun, 3-alpha-hydroxy-9-Tnsthyl, 1195
p-tolylacetate
Tropanol aryl esters (unspecified) 1196
Tropilidene, see: 1,3,5-Cycloheptatriene 250
Tronine, and aryl esters (unspecified) 1197
2-d-Tropine, p-nitrophenylacetate (ester) 1198
2-alpha-Tropine, p-tolylacetate (ester) 1199
Turpentine 1200
o-Tyrosine, DL- 1201
Uracil, 5-fluoro 1202-1205
Urea, ((p-bromophenyl)acetyl)- 1206-1207
Urea, ethyl nitroso- 1208-1214
,CNS
Structural
Damage
1202
1204
1205
1208
1209
1210
1211
1212
1213
1714
PNS
Structural
Damage
1207
1208
1214
Gross
Dysfunction
1197
1200
1202
1205
1206
Performance
Dysfunction
Instrument
Detectable
Tlyef iino flop
1197
1198
1199
1200
1201
Cholin-
esterase
Inhibition
Effects in
Offspring
1204
1210
1212
1213
1214
Reported
Human
Incidence
1194
1203
1205
-------
f-i
to
u
•H W «
§w a
CO "C
JS iH C
U U U
C
TP
TP
TP
TP
TP
TP
•
Chemical Name Pages
Urea, hydroxy- 1215
Urea, methyl nitroso- 1216-1217
Urea, (2-phenylbutyryl)- 1218
Urease 1219
Urethane, see: Carbamic acid, ethyl ester 190
Uridine, 2l-deoxy-5-f luoro 1220-1221
Valeric acid, 2-amino-5-sulfo-, DL- 1222
Valeric acid, 2,2-diphenyl-, 2-(diethyl- 1223
amino) ethyl ester
Valium, see: 2H-l,4-Benzodiazepin-2- 144
one, 7-chloro-l,3-dihydro-l-methyl-
5-phenyl- -
Veratrum alkaloids (Unspecified) 1224
Vinblastine, see: Vincaleukoblastine 1225
Vinblastine sulfate, see: Vincaleuko- 1226
blastine, sulfate (1:1) (salt)
Vincaleukoblastine 1225
Vincaleukoblastine, sulfate (1:1) (salt) 1226
Vincristins, see: Leurocristine 589-598
t-H
«
i-i
3
4J 0)
O ti
3 «
to vi e
tz, *J IB
CJ. 0> O
1215
1216
1217
1219
1220
1221
iH
CO
)-i
3
4J 0)
U 60
3 CO
co >-i e
2: *J ca
d* C/5 Q
1217
1225
1226
c
o
•H
4J
U
C
01 3
(0 «4-l
O U)
M >>
U O
1218
1219
1223
1224
1225
0) C
u o
C -rl
m AJ
r °
0 3
IM M-I
h (0
u >•.
(V4 O
C
4J Q) C
C -1 T
0> ^3 4-
e rt «.
3 4J C
no:
4J 0) U-
(0 4J «
C 0 >
M Q C
1222
1223
G
O
01 iH
1 (0 4J
C n) 1-1
•H Vi ,0
f-H 0) -H
0 *J J=
J= W C
O 0) H
C
*H t>0
C
W
-------
OJ
NJ
VO
Chemical
Class
Codes
TP
C
OP
Chemical Name Pages
Vincristine sulfate, see: Leurocristine, 599-604
sulfate (1:1) (salt)
Vitamin A, see: Retinol, all trans- 1067-1068
Xylitol 1227
Yohimbam-16-alpha-carboxylic acid, 17- 1228
alpha-hydroxy-, methyl ester
3-beta,20-alpha-Yohimban-16-beta-carboxy- 1229
lie acid, 18-beta-hydroxy-ll,17-alpha-
. dimethoxy-, methyl ester, 3,4,5-tri-
methoxybenzoate (ester)
Yohimbine, see: Yohimbam-16-alpha-carboxy- 1228
lie acid, 17-alpha-hydroxy-, methyl ester
Zectran, see: Carbainic acid, methyl-, 4- 198
d imethyl-amino-3 , 5-xylyl ester
Zoxazolamine, see: Renzoxazole, 2- 148
amino-5-chloro-
Zytron, see: Phosphoramidothioic acid, 818
isopropyl-, 0-2,4-dichlorophenyl 0-
methyl ester
,CNS
Structural
Damage
1227
PNS
Structural
Damage
Gross
Dysfunction
1228
1229
Performance
Dysfunction
Instrument
Detectable
nyefnnrMnr)
1228
Cholin-
esterase
Inhibition
Effects in
Offspring
Reported
Human
Incidence
1227
-------
Appendix; information sources.
Primary Journals
Acta Neuropathol
Acta Pharm et Tox
Amer J Pathol
Arch Environ Health
Arch Neurol
Arch Pathol
Arch Toxicology
Biochem Pharmacol
Brain
Brain and Nerve
Brain Research
Brit J Indust Med
British J Pharm
Can J Comp Med
Can Med Assoc J
Comparative & General Pharm
Crit Rev Toxicol
Diseases of the Nervous System
Economic Botany
Environ Health Perspect
Experimental Brain Research
Experimental Neurology
European J of Toxicology
Food and Cosmetic Toxicology
Internation J of Neuropharm
Int Rev Exp Pathol
Int Rev Neurobiol
Japanese J Pharm
John Hopkins Medical J
J Cell Biology
J Clinical Pathology
J Clinical Pharm
J Comp Neurol .
Years
Volumes
1961-1975
1970-1975
1970-1975
1970-1975
1960-1975
1965-1969
1973-1975
1964-1975
1960-1975
1970
1975
1970-1975
1960-1975
1973-1975
1974-1975
1970-1974
1971-1974
1965-1975
1960-1975
1972-1975
1966-1975
1959-1975
1969-1975
1963-1975
1962-1969
1964-1975
1965-1975
1959-1975
1970-1975
1971-1975
1960-1975 .
1970-1975
1960-1975
1-33
28-37
58-81
20-30
3-32
79-88
31-34
13-24
83-98
22
83-100
27-32
15-55
37-39
110-113
1-5
1-3
8-36
14-29
1-12
1-24
1-49
1-13
1-8
3-14
8-18
8-25
126-137
48-67
13-28
10-15
114-164
1330
-------
Years Volumes
J Comp Phys Psychology 1973-1975 84-89
J Economic Entomology 1967-1975 60-68
J Medicinal Chem 1974-1975 17-18
J Neurochem 1965-1975 12-25
J Neuropath Exp. Neurol 1960-1975 19-34
J Neurol Neurosurg Psychiatry 1960-1975 17-38
J Neurol Sci 1970-1975 13-24
J Occup Med 1970-1975 12-17
J Pathol 1970-1975 100-117
J Pharmacol Exp Ther 1970-1975 170-195
Lab Invest 1970-1975 22-33
Life Sci 1970-1975 9-17
New Eng J Med 1974 290-291
Neurology 1951-1975 1-25
Neurophann 1970-1975 9-14
Pharmacology Biochem. Beh. 1973-1975 1-3
Practitioner 1973-1975 210-215
Proceedings R. Soc. Med 1970-1975 63-68
Psychopharmacologia 1971-1975 19-45
Res Comm Chem Path Phar 1970-1975 1-12
Res Vet Science 1970-1974 13-17
Pharmacol Toxicol 1967-1970 30-33
Science 1970-1972 167-178
Teratology 1969-1975 2-12
Toxicology 1973-1975 1-5
Toxicol & Appl Pharmacol 1962-1975 4-34
World.Neurol 1960-1962 1-3
Secondary Sources
Chemical Abstracts 1950-1975 44-83
Biological Abstracts 1950-1975 24-60
Excerpta Medica, Neuri & Neurosurg 1970-1975 24-31
TOXLINE
MEDLINE
Physicians Desk Reference
Registry of Toxic Effects of Chemical Substances
PHS-149 A Survey of Compounds Which Have Been Tested for Carcinogenicity
1331
-------
TECHNICAL REPORT DATA
(Please read Instructions on the reverse before completing)
1. REPORT NO.
EPA 560/1-76-005
2.
3. RECIPIENT'S ACCESSION>NO.
4. TITLE AND SUBTITLE
Chemicals. Which Have Been Tested For Neurotoxic Effects
5. REPORT DATE
May 1976
6. PERFORMING ORGANIZATION CODE
7. AUTHOR(S)
8. PERFORMING ORGANIZATION REPORT NO.
9. PERFORMING ORGANIZATION NAME AND ADDRESS
10. PROGRAM ELEMENT NO.
Tracer Jitco, Inc.
1776 East Jefferson Street
Rockville, Maryland 20852
11. CONTRACT/GRANT NO.
68-01-3255, Task 4
12. SPONSORING AGENCY NAME AND ADDRESS
Office of Toxic Substances
U.S. Environmental Protection Agency
Washington, D.C. 20460
13. TYPE OF REPORT AND PERIOD COVERED
Final
14. SPONSORING AGENCY CODE
15. SUPPLEMENTARY NOTES
16. ABSTRACT
An extensive literature search was conducted to prepare this catalog of
chemicals which have been tested for neurotoxic effects. The text of the catalog
consists of a series of brief extracts of the experimental procedures and findings
of studies in which chemicals were tested for neurotoxic effects. The
document is indexed by chemical, class of chemical, and selected neurotoxic effects.
17.
KEY WORDS AND DOCUMENT ANALYSIS
DESCRIPTORS
b.lDENTIFIERS/OPEN ENDED TERMS
c. COSATI Field/Group
Neurotoxic chemicals
Neurotoxic effects
Neurotoxicity
13. DISTRIBUTION STATEMENT
19. SECURITY CLASS (This Report)
21. NO. OF PAGES
20. SECURITY CLASS (Thispage)
22. PRICE
EPA Form 2220-1 (9-73)
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