Brain Structures |
Function |
From the excellent
website: Neuroscience
for Kids |
Cerebral
Cortex |
* Thought
* Voluntary movement
* Language
* Reasoning
* Perception |
The word "cortex" comes from the
Latin word for "bark" (of a tree). This is because
the cortex is a sheet of tissue that makes up the outer layer
of the brain. The thickness of the cerebral cortex varies from
2 to 6 mm. The right and left sides of the cerebral cortex are
connected by a thick band of nerve fibers called the "corpus
callosum." In higher mammals such as humans, the cerebral
cortex looks like it has many bumps and grooves. A bump or bulge
on the cortex is called a gyrus (the plural of the word gyrus
is "gyri") and a groove is called a sulcus (the plural
of the word sulcus is "sulci"). Lower mammals, such
as rats and mice, have very few gyri and sulci. |
Cerebellum |
* Movement
* Balance
* Posture |
The word "cerebellum" comes from
the Latin word for "little brain." The cerebellum
is located behind the brain stem. In some ways, the cerebellum
is similar to the cerebral cortex: the cerebellum is divided
into hemispheres and has a cortex that surrounds these hemispheres.
|
Brain stem |
* Breathing
* Heart Rate
* Blood Pressure |
The brain stem is a general term for the area
of the brain between the thalamus and spinal cord. Structures
within the brain stem include the medulla, pons, tectum, reticular
formation and tegmentum. Some of these areas are responsible
for the most basic functions of life such as breathing, heart
rate and blood pressure. |
Hypothalamus |
* Body Temperature
* Emotions
* Hunger
* Thirst
* Circadian Rhythms |
The hypothalamus is composed of several different
areas and is located at the base of the brain. Although it is
the size of only a pea (about 1/300 of the total brain weight),
the hypothalamus is responsible for some very important functions.
One important function of the hypothalamus is the control of
body temperature. The hypothalamus acts as a "thermostat"
by sensing changes in body temperature and then sending signals
to adjust the temperature. For example, if you are too hot,
the hypothalamus detects this and then sends a signal to expand
the capillaries in your skin. This causes blood to be cooled
faster. The hypothalamus also controls the pituitary. |
Thalamus |
* Sensory processing
* Movement |
The thalamus receives sensory information and
relays this information to the cerebral cortex. The cerebral
cortex also sends information to the thalamus which then transmits
this information to other areas of the brain and spinal cord. |
Limbic System |
* Emotions |
The limbic system (or the limbic areas) is
a group of structures that includes the amygdala, the hippocampus,
mammillary bodies and cingulate gyrus. These areas are important
for controlling the emotional response to a given situation.
The hippocampus is also important for memory. |
Hippocampus |
* Learning
* Memory |
The hippocampus is one part of the limbic system
that is important for memory and learning. |
Basal Ganglia |
* Movement |
The basal ganglia are a group of structures,
including the globus pallidus, caudate nucleus, subthalamic
nucleus, putamen and substantia nigra, that are important in
coordinating movement. |
Midbrain |
* Vision
* Audition
* Eye Movement
* Body Movement |
The midbrain includes structures such as the
superior and inferior colliculi and red nucleus. There are several
other areas also in the midbrain. |
|
The
use of high doses increases the likelihood that potentially
significant toxic effects will be identified. Findings of
adverse effects in any one species do not necessarily indicate
such effects might be generated in humans. From a conservative
risk assessment perspective however, adverse findings in
animal species are assumed to represent potential effects
in humans, unless convincing evidence of species specificity
is available.
--
Food and Agricultural Organization of the United Nations
|
Note:
This is not an exhaustive list.
When time allows more information will be added.
Quinoxyfen
- Fungicide - CAS No. 124495-18-7
-- 040 - 181140 "XDE-795:
Two-Year Dietary Chronic Toxicity/Oncogenicity Study in Fischer
344 Rats-Final Report," (Redmond, J.M.,
Quast, J.F., Bond, D.M., Ormand, J.R.; The Toxicology Research
Laboratory, Health and Environmental Sciences Ð The Dow
Chemical Company, Midland, MI; Laboratory ID#: DR-0325-7474-007;
6/29/95). XDE-795 (5,7-dichloro-4-[4-flurophenoxy]quinoline;
97.4% pure) was fed in diet to Fischer 344 rats at 0, 5, 20 or
80 mg/kg/day for 1 Ð 2 years. XDE-795 was administered for 2 years
to 50/sex/dose for chronic/oncogenicity assessment. A satellite
group (15/sex/dose) was sacrificed at 12 months (10/sex/dose for
interim assessment of chronic toxicity; 5/sex/dose to assess neurotoxicity).
NOEL = 20 mg/kg (Females at 80 mg/kg had increased perineal soiling
(satellite & main group). Both sexes had decreased bodyweights
and bodyweight gains at 80 mg/kg throughout the study. Urea nitrogen
was increased in males at 80 mg/kg at 18 and 24 months. Alanine
amino transferase (80 mg/kg) was decreased in males at 24 months.
Females had cholesterol levels that were statistically significantly
increased at 80 mg/kg at 18 and 24 months. Liver and kidney weights
(absolute & relative) were statistically significantly increased
in both sexes at 80 mg/kg at 12 months. Relative
brain weights in both sexes were increased at 80 mg/kg
by 24 months. Males had increased absolute and relative testes
weights at 80 mg/kg and females had decreased relative heart and
increased relative kidney weights at 80 mg/kg at 24 months. There
was an increased incidence in chronic progressive glomerulonephropathy
in males at 80 mg/kgÑ37 versus 19 in control, p < 0.05.) No adverse
effects. Acceptable. M. Silva, 8/21/01
-- ** 034 - 181176 "XDE-795: One Year Chronic Dietary Toxicity
Study in Beagle Dogs," (Cosse, P.F., Stebbins, K.E., Redmond,
J.M., Ormand, J.R.; The Toxicology Research Laboratory, Health
and Environmental Sciences Ð The Dow Chemical Company, Midland,
MI; Laboratory ID#: DR-0325-7474-011; 4/21/95). XDE-795 (5,7-dichloro-4-[4-flurophenoxy]quinoline;
97.4% pure) was fed in diet to Beagle dogs (4/sex/dose) at 0,
5, 20 or 200 mg/kg/day for 1year. NOEL = 20 mg/kg (A male at 200
mg/kg was killed moribund, due to a severe weight decrease (2
kg), decreased hemoglobin and RBC counts. Both sexes had significantly
decreased body weights and food consumption at 200 mg/kg. The
report stated it was due to unpalatability of diet at the high
dose, which persisted throughout the majority of the study. A
treatment-related hematological effect was observed in 1/sex at
200 mg/kg. Alkaline phosphatase in both sexes at 200 mg/kg was
statistically significantly increased. Liver weights (absolute
& relative) were significantly increased in both sexes at 200
mg/kg. Statistically significantly increased
relative organ weights were observed in both sexes at 200
mg/kg (brain, kidney, pituitary).
Liver histopathology was observed in 3/sex at 200 mg/kg, primarily
in the midzonal region (diffuse, increased size in hepatocytes,
enlarged nuclei and prominent nucleoli). At 200 mg/kg, 1/sex had
increased hepatocyte size, increased bile in centrilobular canaliculi.
Possible adverse effect: At 200 mg/kg, 1/sex showed erythroid
proliferation in spleen and liver, due to treatment-related anemia.)
Acceptable. M. Silva, 8/15/01
Ref: October 4, 2001 - SUMMARY
OF TOXICOLOGY DATA QUINOXYFEN (XDE-795 & XR-795). California
EPA, Department of Pesticide Regulation, Medical Toxicology Branch.
Sodium
bifluoride - Insecticide, Former US EPA
List 3 Inert -
CAS No.
1333-83-1
In addition to cardiovascular,
neuromuscular and gastrointestinal derangements, acute fluoride
poisoning causes major adverse effects on
two other organ systems, the brain and the kidneys. The
more critical dysfunctions are those of the brain. Toxic
signs occasionally include headache, excessive salivation, nystagmus
and dilated pupils. Transient convulions have been described,
but lethargy, stupor and coma are far more common, and death is
often ascribed to respiratory failure, presumably of central origin.
Whatever the causes of these brain derangements, it is noteworthy
that coma and respiratory arrest may develop in the presence of
a normal blood pressure. Apparently the
central neural effects of fluoride are not solely secondary to
an inadequate cerebral circulation. /Fluoride/ [Gosselin,
R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial
Products. 5th ed. Baltimore: Williams and Wilkins, 1984.,p. III-187]
Ref:
Hazardous Substances Data Bank for SODIUM HYDROGEN DIFLUORIDE CASRN:
1333-83-1
http://www.fluorideaction.org/pesticides/sodium.bifluoride.toxnet.htm
Sodium
fluoroacetate
(also known as Sodium monofluoroacetate, Compound 1080)
- Insecticide, Rodenticide - CAS No.
62-74-8
PubMed abstract: The
case reported developed an acute brain syndrome,
including cerebellar signs, shortly after the ingestion of sodium
monofluoroacetate. After insiduous improvement of the clinical
symptoms, the patient remained with an "end-stage"
cerebellar ataxia for 18 months following the acute intoxication.
The development of brain atrophy,
proven by computed tomography, is considered to represent a direct
influence of sodium monofluoroacetate on the brain
and to reflect the unique disturbances in cellular metabolism
of glucose.
Ref: J
Toxicol Clin Toxicol 1983 Mar;20(1):85-92; Computed
tomography demonstration of brain damage due to acute sodium monofluoroacetate
poisoning; Trabes J, Rason N, Avrahami E.
A case study reported
a deliberate ingestion of an unspecified dose of sodium fluroacetate
by a healthy female. The woman experienced nausea, vomiting, and
abdominal pain 30 minutes after ingestion, with subsequent seizures
occurring 60 minutes after the initial onset of symptoms. Neurological
examination after 2 weeks revealed severe
cerebellar dysfunction. By 18 months, memory disturbances
and depressive behavior persisted... EPA believes that there is
sufficient evidence for listing sodium fluoroacetate on EPCRA
section 313 pursuant to EPCRA section 313(d)(2)(B) based on the
neurologic, reproductive, and myocardial toxicity data for this
chemical.
Ref:
USEPA/OPPT. Support Document for the Health and Ecological Toxicity
Review of TRI Expansion Chemicals. U. S. Environmental Protection
Agency, Washington, DC (1993). As cited by US EPA in:
Federal
Register: January 12, 1994. Part IV.
40 CFR Part 372. Addition of Certain Chemicals; Toxic Chemical
Release Reporting; Community Right-to-Know; Proposed Rule.
--
Sodium fluoroacetate and fluoroacetamide are readily absorbed
by the gut, but only to a limited extent across skin. The toxic
mechanism is distinct from that of fluoride salts. Three molecules
of fluoroacetate or fluoroacetamide are combined in the liver
to form a molecule of fluorocitrate, which poisons critical enzymes
of the tricarboxylic acid (Krebs) cycle, blocking cellular respiration.
The heart, brain, and kidneys are
the organs most prominently affected... Crimidine and sodium fluoroacetate
are no longer registered for use as pesticides.
Ref: US EPA. Rodenticides. Chapter 17.
http://www.epa.gov/oppfead1/safety/healthcare/handbook/Chap17.pdf
Abstract: To clarify
the contribution of glial cells to octanoate uptake into the brain,
we determined the effects of fluoroacetate,
a selective inhibitor of glial metabolism, on in vitro
brain uptake of [1-14C]octanoate, using rat brain slices. The
[1-14C]octanoate uptake significantly decreased, depending on
the concentration of fluoroacetate (p = 0.001). The [1-14C]octanoate
uptakes at 5 mM (0.23 +/- 0.05% uptake/mg slice) and 25 mM fluoroacetate
(0.12 +/- 0.01% uptake/mg slice) were significantly lower than
that at control (0.29 +/- 0.02% uptake/mg slice, p < 0.05 and
p < 0.001, respectively). The results demonstrate the contribution
of glial cells to octanoate uptake into the brain. The potential
of [1-11C]octanoate as a PET tracer for studying glial functions
is suggested.
Ref: Kuge Y et al. (2002).
In vitro uptake of [1-14C]Octanoate in brain slices of rats: basic
studies for assessing [1-11C]Octanoate as a PET tracer of glial
functions. Nucl Med Biol 2002 Apr;29(3):303-6.
Abstract:
The effect of sodium-fluoroacetate (62-74-8) on electrical activity
in the brain was investigated in rats. Electrical activity was
recorded in the reticular nucleus of the thalamus and in the caudate
nucleus of male albino-rats using bipolar electrodes.
Twenty four hours after electrode implantation, animals
were dosed intraperitoneally with sodium-fluoroacetate at 5 milligrams
per kilogram. At various times thereafter, the complete electrical
activity was recorded in selected brain structures using a loop
oscillograph. The electrical activity was summed with an integrator
enabling relative changes in complete electrical activity to be
detected. Readings were taken for 5 minutes, every 15 minutes.
Control animals showed characteristic slow waves, 4 to 6 per second,
mainly in the reticular nucleus of the thalamus throughout the
6 hour experiment. Upon sodium-fluoroacetate treatment, slow waves
were recorded and later faster waves, 12 to 15 per second, superceded
the slow waves. At the end of the first hour and thereafter waves
of slow frequency disappeared and those of faster frequency prevailed.
Later, the frequency and amplitude of waves increased,
particularly pronounced in the period of paroxysms in the reticular
nucleus of the thalamus. After 3 hours, the fast waves
were depressed and the complete electrical activity was not reversible.
The authors conclude that the increase in complete electrical
activity after the initial stage reflects participation of the
central nervous system in compensatory processes evoked by deepening
hypothermia and anoxia caused by sodium-fluoroacetate poisoning.
(Russian)
Ref: Combined Electrical Activity
Of Some Subcortical Structures In The Brain Of Albino Rats At
Various Stages Of Sodium Fluoroacetate Poisoning; by Artyushkova
VA, Kirzon MV, Timeiko VN. Byulleten' Eksperimental'noi Biologii
i Meditsiny, Vol. 67, No. 4, pages 69-73, 9 references, 1969.
[From Toxline at Toxnet]
Sulfentrazone - Herbicide - CAS No. 122836-35-5
TERATOLOGY, RABBIT **52988-0038 217369, “F6285 Technical,
Teratology Study in Rabbits (Oral)”, ©. Freeman, FMC
Corporation, Toxicology Laboratory, Princeton, NJ., Study No.
A92-3540, 22 June 1993). 20 mated female New Zealand White rabbits
per group received F6285 Technical (94.2 ± 0.5% sulfentrazone)
by oral gavage at 0 (corn oil), 100, 250, and 375 mg/kg/day on
gestation days 7 through 19. There were no treatment-related deaths.
Two dams per group at 100 and 250 mg/kg/day died due to misdosing.
One 375 mg/kg/day dam was sacrificed due to misdosing. Five dams
at 375 mg/kg/day aborted (two on day 21 and one each on days 22,
23, and 24). The mean number of implants and the mean number of
early resorptions were significantly increased at 250 and 375
mg/kg/day. 13, 13, 16, and 18 dams at 0, 100, 250, and 375 mg/kg/day
respectively exhibited decreased feces during the study and hematuria
was recorded for 1 and 16 dams at 250 and 375 mg/kg/day respectively.
Significantly reduced bodyweights were recorded for dams at 250
and 375 mg/kg/day on gestation days 19 and 29 compared to controls
and bodyweight gains were significantly reduced during the dosing
period and overall for days 0 through 29. Fetal weights were significantly
reduced at 250 and 375 mg/kg/day. No treatment-related findings
for fetal external and internal exams. Two treatment related skeletal
malformations were noted at 375 mg/kg/day. One
fetus had incompletely or not ossified frontals,
parietals, interparietals, suppraoccipital bones, and execenphaly. Although not statistically significant, the findings were considered
treatment-related since they occurred only at the high dose and
because execenphaly is uncommon in the rabbit strain.
Additionally, 3 fetuses from 3 different dams had fused caudal
vertebrae. The incidence was statistically significant and was
higher than the historical control values. Treatment-related skeletal
variations included statistically significant litter and fetal
incidences of partially fused nasal bones at 375 mg/kg/day. Also,
4 litter mates at 375 mg/kg/day had unossified pubes. Finally,
the average number of ossified sternal centers, tarsal bones,
forepaw and hindpaw phlanges and metacarpal bones was significantly
reduced in fetuses at 375 mg/kg/day. Maternal NOEL = 100 mg/kg/day
(reduced bodyweight). Developmental NOEL = 100 mg/kg/day (reduced
fetal weight, increased early resorptions). No teratogenicity.
Acceptable. (Green and Leung, 12/13/05)
Note from EC: Was execenphaly a spelling error? Should
it read exencephaly? Definition exencephaly - A condition in which the skull is defective, causing exposure
or extrusion of the brain.
Ref: January
13, 2006: Summary of toxicology data: Sulfentrazone (F2685). California
EPA. Department of Pesticide Regulation. Medical Toxicology Branch.
http://www.fluorideaction.org/pesticides/sulfentrazone.ca.epa.2006.pdf
Sulfuryl
fluoride -
Fumigant insecticide - CAS No. 2699-79-8
Ref:
January
23, 2004. Sulfuryl Fluoride; Pesticide Tolerance.
40 CFR Part 180 [OPP-2003-0373; FRL-7342-1]. Final
Rule. Federal Register |
Excerpts
from: Table 1.--Subchronic,
Chronic, and Other Toxicity |
Study
Guideline |
Type
of Study |
NOAEL
mg/kg/day |
LOAEL
mg/kg/day |
Based
on: |
None
cited |
2-Week inhalation study--rabbit |
30/30
(M/F) |
90/90
(M/F) |
malacia
(necrosis) in cerebrum, vacuolation
of cerebrum |
None
cited |
2-Week inhalation study--rabbit |
- |
180/180
(M/F) |
malacia
(necrosis)
in cerebrum, vacuolation
of cerebrum |
(870.3100) |
90-Day
inhalation toxicity--rat |
24/25
(M/F) |
90/90
(M/F) |
malacia
(necrosis) in cerebrum, vacuolation
of cerebrum |
(870.3100) |
90-Day
inhalation toxicity--rat |
- |
180/180
(M/F) |
malacia
(necrosis)
in cerebrum, vacuolation
of cerebrum |
(870.3100) |
90-Day
inhalation toxicity--rat |
- |
240/250
(M/F) |
vacuolation
of caudate-putamen nucleus and
white
fiber tracts of the internal capsule of the brain |
(870.3100) |
90-Day
inhalation toxicity--mouse |
38/36
(M/F) |
125/121
(M/F) |
miscroscopic
lesions in caudate-putamen nucleus and
external capsule of the brain |
(870.3150) |
90-Day inhalation toxicity--dog |
25/26
(M/F) |
50/51
(M/F) |
slight
histopathology of the caudate nucleus
of the basal ganglia |
(870.3150) |
90-Day inhalation toxicity-- rabbit |
8.6/8.5
(M/F) |
29/28
(M/F) |
vacuolation
of white matter of the brain
(F only) |
(870.3150) |
90-Day
inhalation toxicity-- rabbit |
- |
86/85
(M/F) |
malacia
(necrosis) and vacuolation of
putamen, globus pallidus and
internal and external capsules in the
brain |
(870.4100) |
Chronic toxicity--rodents |
3.5
for M
16 for
F |
14
for M
62
for F |
histopathology
in brain (vacuolation in cerebrum
and
thalmus/hypothalmus) |
(870.4100) |
1-Year chronic inhalation toxicity--dog
|
5.0/5.1
(M/F) |
50/51
(M/F) |
malacia
(necrosis) in caudate nucleus
of brain |
(870.4200) |
18-Month carcinogenicity inhalation study--mouse |
25/25
(M/F) |
101/101
(M/F) |
cerebral
vacuolation in brain |
(870.4300) |
2-Year combined chronic/
carcinogenicity--rat |
3.5
for M
16 for
F |
14
for M
62
for F |
histopathology
in brain (vacuolation
in cerebrum and
thalmus/hypothalmus) |
Ref:
January
23, 2004. Sulfuryl Fluoride; Pesticide Tolerance.
40 CFR Part 180 [OPP-2003-0373; FRL-7342-1]. Final
Rule. Federal Register |
Excerpts: Table 2.--Summary
of Toxicological Dose and Endpoints for sulfuryl fluoride
for Use in Human Risk |
Exposure
Scenario |
Dose
Used in Risk Assessment, Interspecies and Intraspecies and
any Traditional UF |
Special
FQPA SF and Level of Concern for Risk Assessment |
Study
and Toxicological Effects |
Chronic dietary (all populations) |
NOAEL
= 8.5 mg/kg/day
UF = 3,000...
Chronic RfD = 0.003 mg/kg/day. |
Special
FQPA SF = 1X
cPAD = chronic RfD/
Special FQPA SF = 0.003 mg/kg/day. |
Rabbit
- 90-Day inhalation
LOAEL = 28 mg/kg/day based on vacuolation
of white matter in the brain of females. |
Short-term inhalation (1 to 30 days) |
Inhalation
study
NOAEL = 30 mg/kg/day
(100 ppm; 0.42 mg/L). |
Residential
LOC for MOE = 1,000 Occupational
LOC = 100 |
Rabbit
- 2-Week inhalation
LOAEL = 90 mg/kg/day (300 ppm; 1.25 mg/L) based on malacia
(necrosis) and vacuolation in
brain, inflammation of nasal tissue and trachea |
Intermediate-term inhalation (1 to 6 months) |
Inhalation
study
NOAEL = 8.5 mg/kg/day (100 ppm; 0.42mg/L). |
Residential
LOC for MOE = 1,000
Occupational LOC for MOE = 100. |
Rabbit
- 90-Day inhalation
LOAEL = 28 mg/kg/day (100 ppm; 0.42 mg/L) based on vacuolation
of white matter in the brain of females. |
Long-term inhalation (>6 months) |
Inhalation
study
NOAEL = 8.5 mg/kg/day
(30 ppm; 0.13 mg/L). |
Residential
LOC for MOE = 3,000
Occupational LOC for MOE = 300.
|
Rabbit
- 90-Day inhalation
LOAEL = 28 mg/kg/day based on vacuolation
of white matter in the brain of females |
Federal
Register: September 5, 2001. Sulfuryl Fluoride; Proposed
Pesticide Temporary Tolerances. Volume 66, Number 172. Proposed
Rules. Page 46415-46425.
Excerpt
from Table 1.
Summary of Toxicological Doses and Endpoints for sulfuryl
fluoride for Use in Human Risk Assessment
|
Exposure
Scenario \1\ |
Dose
(mg/kg/day) |
Endpoint |
Study |
Chronic
Dietary (General Population including Infants and Children) |
NOAEL
= 8.5;
UF = 300;
FQPA Factor = 3 |
Vacuolation
of white
matter
in the brain
of females.
Chronic RfD = 0.028 mg/ kg/day
Chronic Population- Adjusted Dose (cPAD) = 0.0093 mg/kg/day |
90-Day
inhalation- rabbits |
Inhalation
Short-Term (Occupational) |
NOAEL
= 30;
MOE = 100;
FQPA Factor = N/A |
Malacia
(necrosis) and vacuolation in the cerebrum,
inflammation of nasal tissues and trachea. |
2-Week
inhalation- rabbits |
Inhalation
Short-Term (Residential) |
NOAEL
= 30;
MOE = 300;
FQPA Factor = 3 |
Malacia
(necrosis) and vacuolation in the cerebrum,
inflammation of nasal tissues and trachea. |
2-Week
inhalation- rabbits |
Inhalation
Intermediate-Term (Occupational) |
NOAEL
= 8.5;
MOE = 100;
FQPA Factor = N/A |
Vacuolation
of white matter in the brain
of females. |
90-Day
inhalation- rabbits |
Inhalation
Intermediate-Term (Residential) |
NOAEL
= 8.5;
MOE = 300;
FQPA Factor = 3 |
Vacuolation
of white matter in the brain
of
females. |
90-Day
inhalation- rabbits |
\*\
The reference to the FQPA Safety Factor refers to any additional
safety factor retained due to concerns unique to the FQPA. |
\1\
The only significant route of exposure for inorganic fluoride
is dietary exposure, which includes residues in drinking water.
This risk assessment uses the maximum concentration limit
goal (MCLG) of 4.0 ppm for fluoride as the basis for a maximum
allowable exposure to inorganic fluoride (see the Cryolite
Reregistration Eligibility Decision, 8/96, EPA- 738-R-96-016).
Using the Agency default values of body weight (70 kg) and
water consumption (2 liters/day), the MCLG converts to an
exposure limit of 0.114 mg/kg/day. This exposure is used as
the cPAD for inorganic fluoride in this risk assessment.
|
-- In 2-week inhalation studies in
rats, dogs and rabbits, different target organs were affected...
In rabbits, the primary target organ was
the brain, in which malacia (necrosis) and vacuolation were observed
in the cerebrum...
-- In subchronic (90-day)
inhalation studies in rats, dogs, rabbits and mice,
the brain was the major target organ. Malacia and/or vacuolation
were observed in the white matter of the brain in all four species.
The portions of the brain most often affected were the caudate-putamen
nucleus in the basal ganglia, the white fiber tracts in the internal
and external capsules, and the globus pallidus of the cerebrum.
In dogs and rabbits, clinical signs of neurotoxicity (including
tremors, tetany, incoordination, convulsions and/or hind limb
paralysis) were also observed...
-- In chronic (1-2 year) inhalation studies
in rats, dogs and mice, target organs were
the same as in the 90-day studies. In rats, severe kidney
damage caused renal failure and mortalities in many animals. Additional
gross and histopathological lesions in numerous organs and tissues
were considered to be secondary to the primary effect on the kidneys.
Other treatment-related effects in rats
included effects in the brain (vacuolation
of the cerebrum and thalamus/hypothalamus) and respiratory
tract (reactive hyperplasia and inflammation of the respiratory
epithelium of the nasal turbinates, lung congestion, aggregates
of alveolar macrophages).
In dogs and mice, increased mortalities, malacia
and/or vacuolation in the white matter in the brain, histopathology
in the lungs, and follicular cell hypertrophy in the thyroid gland
were observed.
-- In specially designed acute and subchronic
inhalation neurotoxicity studies in rats, several electrophysiological
parameters (EEGs) were recorded in addition to observations for
clinical signs of neurotoxicity, functional observational battery
(FOB) and motor activity testing, and/or neurohistopathologic
examination. Following two exposures on consecutive days for 6
hours/day at 300 ppm of sulfuryl fluoride (354 mg/kg/day), no
treatment-related neurotoxic effects were noted. In a 90-day study,
changes in some EEG patterns were observed at 100 ppm (80 mg/kg/day)
and in several additional patterns at 300 ppm (240 mg/kg/day).
Vacuolation of the white matter in the cerebrum
was also observed at 300 ppm in this study. In a specially designed
1-year chronic inhalation neurotoxicity study in rats, no treatment-related
neurotoxic effects were observed at 80 ppm (56 mg/kg/ day). EEGs
were not recorded in this study.
Ref:
Federal Register: September 5, 2001 (Volume 66, Number 172). Sulfuryl
Fluoride; Proposed Pesticide Temporary Tolerances.
http://www.fluorideaction.org/pesticides/sulfuryl.flu.fr.sept.5.2001.htm
Vikane, sulfuryl fluoride,
Lot No. TWP 830919-408, 99.8%, was administered to New Zealand
White rabbits via inhalation for 6 hours/day, 5 days/week for
13 weeks at 0, 30, 100 or 300 ppm. Seven animals per sex per group.
NOEL = 30 ppm; [cerebral vacuolation in
regions of internal and external capsules, putamen, and globus
pallidus of one female: and nasal tissue inflammation in
one male]. At 300 ppm, common brain findings
were vacuolation to severe malacia of cerebrum (both sexes, in
the above regions), and gliosis and/or hypertrophy of vascular
endothelial cells in some females in the same regions.
Ref: CA EPA, Summary of Toxicolgy Data,
August 1, 1986. http://www.cdpr.ca.gov/docs/toxsums/pdfs/618.pdf
The primary effects
of sulfuryl fluoride in humans are respiratory irritation and
central nervous system depression, followed by excitation and
possibly convulsions. Rabbits exposed via inhalation (6 hours/day,
5 days/week, for 2 weeks) to sulfuryl fluoride showed hyperactivity,
convulsions and vacuolation of the cerebrum
at 600 ppm (2.5 mg/L). Renal lesions were present in all rats
exposed by inhalation (6 hours/day, 5 days/week, for 2 weeks)
to 600 ppm (2.5 mg/ L) sulfuryl fluoride. Minimal renal changes
were noted in rats exposed to 300 ppm (1252 mg/L), whereas no
effects occurred at 100 ppm (4.2 mg/ L). Convulsions at near lethal
concentrations were reported in rabbits, mice, and rats. In a
30-day inhalation study, loss of control, tremors of the hind
quarters, and histopathological changes in the lung, liver, and
kidney were reported in rabbits exposed to 400 ppm (1.6 mg/L)
for 7 hours/day, 5 days/week for 5 weeks. The NOEL was 200 ppm
(0.83 mg/L). Cerebral vacuolation
and/or malacia and inflammation of nasal tissues were observed
in rabbits exposed by inhalation to 100 or 300 ppm (0.4 or 1.25
mg/L) for 13 weeks. The NOEL was 30 ppm (0.125 mg/L). Rats exposed
by inhalation to 100 to 600 ppm (0.4 to 0.25 mg/L) sulfuryl fluoride
for 13 weeks developed mottled teeth (indicative of fluoride toxicity),
renal and respiratory effects, and cerebral
vacuolation. EPA believes that there is sufficient evidence
for listing sulfuryl fluoride on EPCRA section 313 pursuant to
EPCRA section 313(d)(2)(B) based on the available neurological,
renal, and respiratory toxicity data for this chemical.
Ref:
USEPA/OPP. Support Document for the Addition of Chemicals from
Federal Insecticide, Fungicide, Rodenticide Act (FIFRA) Active
Ingredients to EPCRA Section 313. U. S. Environmental Protection
Agency, Washington, DC (1993). As cited by US EPA in: Federal
Register: January 12, 1994. Part IV. 40 CFR Part 372. Addition
of Certain Chemicals; Toxic Chemical Release Reporting; Community
Right-to-Know; Proposed Rule.
PubMed abstract:
This study assessed
the health effects associated with occupational exposure to methyl
bromide and sulfuryl fluoride among
structural fumigation workers... Sulfuryl
fluoride exposure over the year preceding examination was associated
with significantly reduced performance
on the Pattern Memory Test and on olfactory
testing...
Occupational sulfuryl fluoride exposures may be associated with
subclinical effects on the central nervous system, including effects
on olfactory and some cognitive functions.
Ref: Am J Public Health 1998 Dec;88(12):1774-80.
Health
effects associated with sulfuryl fluoride and methyl bromide exposure
among structural fumigation workers by
Calvert GM et al.
Teflon
(PTFE: polytetrafluoroethylene) - EPA List 3 Inert -
CAS No. 9002-84-0
Note: tetrafluoroethylene
is a major thermal breakdown product of Teflon.
Abstract: The toxic
properties of the tetrafluoroethylene (9002-84-0)
monomer and of products of the thermal treatment of the tetrafluoroethylene
polymer in acute experiments on cats, rabbits, albino rats and
albino mice are reported. In rats and rabbits
the inhalation of monomer induced hyperemia of organs, especially
the brain, hemorrhage
in the spleen and lungs, and dystrophic changes in the kidneys.
Emphysema
and atelectasis was observed in the lungs, desquamation of the
epithelium in the bronchi also was observed. The threshold mortality
for the monomer was 2.5 volume percent for albino rats and 4.0
volume percent for rabbits. The pyrolytic decomposition of tetrafluoroethylene
polymer was lethal to cats, rabbits, mice, and rats. Death was
caused by acute pulmonary edema, sometimes accompanied by pneumonia.
Renal dystrophy was observed in the cats. There was acute irritation
of the upper respiratory tract mucosa in all test animals. It
is concluded that the pathology observed upon inhalation of the
products of thermal decomposition of the polymer is apparently
explained by the presence
in the pyrolyses gas of difluorophosgene, perfluoroisobutylene
(382-21-8), and other highly toxic hydrocarbons. (Russian: English
translation available)
Ref: Toxicity of Tetrafluoroethylene
by Zhemerdi A. Trudy Leningradskogo Sanitarno-gigienicheskogo
Meditsinskogo Instituta, Vol. 44, pages 164-176, 1958. Document
Number: NIOSH/00080478.
Tefluthrin
- Insecticide - CAS No. 79538-32-2
In a 3-month rat study,
dietary administration of 10 mg/kg/day produced plasma, red blood
cell, and brain cholinesterase inhibition.
The NOEL was 5 mg/kg/day. In a 6-month dog study, dietary administration
of 10 mg/kg/day (LOEL) produced plasma cholinesterase inhibition.
The NOEL was 1 mg/kg/day.
Ref:
USEPA/OPP. Support Document for the Addition of Chemicals from
Federal Insecticide, Fungicide, Rodenticide Act (FIFRA) Active
Ingredients to EPCRA Section 313. U. S. Environmental Protection
Agency, Washington, DC (1993). As cited by US EPA in: Federal
Register: January 12, 1994. Part IV. 40 CFR Part 372. Addition
of Certain Chemicals; Toxic Chemical Release Reporting; Community
Right-to-Know; Proposed Rule.
Tembotrione - Herbicide - CAS No. 335104-84-2
-- Evidence of neurotoxicity was noted in the subchronic and chronic toxicity studies in the dog and the acute and developmental neurotoxicity studies in the rat (page 20).
-- Rats: decreased absolute brain weight (pp 7, 16, 20, 56, 68, 88).
-- Developmental Neurotoxicity/ Rat study: brain morphometric changes and decreased acoustic startle response were observed in offspring at the lowest dose tested (0.8 mg/kg/day). These effects were observed at a dose lower than that which caused maternal toxicity (16.3 mg/kg/day, corneal opacity). (p 16) ... the brain morphometric changes were presumed to occur following a single exposure (p 21-22).
-- Relative brain weight was significantly (p<0.01) increased in both males and females by 11 and 12% respectively, at 7000 ppm. Absolute brain weight decreased significantly (p<0.001) by 6% in 7000 ppm males only and was comparable to controls in females (p 56).
-- absolute brain weights were dose-dependently decreased (p≤0.05) in both sexes in both generations. In F1 male and female pups, absolute brain weights significantly decreased 3-10% in all treatment groups. In the F2 generation, absolute brain weights significantly decreased 5-9% in males and females at ≥ 200 ppm. Relative brain weights were significantly increased (p≤0.05) in only F1 males and females by 8-9% at ≥200 ppm (p 68).
-- In an acute neurotoxicity study (MRID 46695723), groups of non- fasted, young-adult Wistar rats (12/sex/dose) were given a single oral (gavage; 10 mL/kg) dose of AE 0172747 at doses of 0, 200, 500 or 2000 mg/kg (limit dose) and observed for 14 days. The brain and peripheral nervous system tissues collected from the perfused animals in the control and 2000 mg/kg groups were subjected to histopathological evaluation. Positive control data were not provided; however, data previously reviewed by the Agency have been included in this DER. (p 85)
* [definition of morphometric: (Science: technique) method that involves measurement of shape.]
Reference: Tembotrione. Human-Health Risk Assessment for Proposed Uses on Field Corn, Sweet Corn and Popcorn. USEPA. September 7, 2007.
• Dose and Endpoint for Establishing RfD: (page 22)
------ Study Selected: Chronic Toxicity/Carcinogenicity (Feeding)/Rat MRID No.: 46695708
------ The NOAEL of 0.04 mg/kg/day was based on neovascularization and edema of the cornea and snow flake-like corneal opacity, unilateral or bilateral keratitis of the eye, decreased mean body weight and mean body-weight gain, increased total cholesterol, higher ketone levels and lower pH values, higher protein levels, increased kidney weight, kidney to body weight and kidney to brain weight ratios, chronic nephropathy and atrophy of the sciatic nerve observed in the male at 0.79 mg/kg/day (LOAEL).
------ UF(s): An UF of 100 was applied to account for interspecies extrapolation (10X)
------ Comments about Study/Endpoint/UF: This study provided the lowest NOAEL in the database (most sensitive endpoint) and will also provide the most protective limits for human effects.
• Evidence of neurotoxicity was seen in the subchronic and chronic toxicity studies in the dog (uncoordinated movement, disturbance in locomotion) and in the acute (decreased arousal, decreased body temperature, decreased motor and locomotor activities) and developmental neurotoxicity (brain morphometric changes, decreased acoustic startle response) studies in the rat. In the developmental neurotoxicity study in rats, increased susceptibility was observed as fetal neurological effects and occurred at a dose that was lower than the dose at which maternal toxicity occurred (corneal opacity). (page 6-7)
• The decreased accoustic startle response observed in adult rats was statistically significant at the mid and high dose but not at the low dose.
Reference: Tembotrione. Human-Health Risk Assessment for Proposed Uses on Field Corn, Sweet Corn and Popcorn. USEPA. September 7, 2007.
Tetraconazole
- Fungicide - CAS No. 112281-77-3
• Metbolism nd Toxicokinetics. Tetraconazole
was broadly distributed to all organs and tissues tested, with
the highest level detected in the liver, followed by kidneys,
gonads, brain and bones.
Low residua levels were still detected in the liver and gastrointestinal
tract (sometimes bones) at 72 hr.
• Chronic & Carcinogenicity Studies.
Dorsal compression was seen in the brain
of some mice at 1250 ppm, and thickening
of compact bones in the cranium, ribs and
collar bones, myelofibrosis, pale, thickened, broken, chipped
and/or overgrown incisors
were observed at 800 and 1250 ppm, indicating abnormal
bone metabolism. (pp 4-5)
-- Rats received 0, 10, 80, 640 or 1280 ppm (the last dose to
males only) of tetraconazole in the diet for 2 years...
In the brain of males at 640 and 1280 ppm, dorso-lateral
compression, dilated ventricles, and white
thickened cranium and parietal bones were probably secondary to
the osseous hypertrophy. Increased numbers of rats had
pale, thickened and overgrown incisors at 640 and 1280 ppm. (page
5)
Ref: August
2005 - Evaluation of Tetraconazole in the product Domark 40ME
Fungicide. Australian Pesticides and Veterinary Medicines Authority.
http://www.fluorideaction.org/pesticides/tetraconazole.2005.report.australia.pdf
1,2,4-triazole targets the nervous
system, both central and peripheral, as
brain lesions (most notably in the cerebellum)
were seen in both rats and mice, and peripheral nerve degeneration
was also seen in the subchronic neurotoxicity study in rats. In
addition, brain weight decreases were
seen in several studies, including in the offspring in the reproductive
toxicity study. In the subchronic/neurotoxicity study, there
is evidence that effects progress over time, with an increase
in incidence of clinical signs (including tremors and muscle fasciculations)
during weeks 8 and 13 that were not seen during earlier evaluations.
Effects were also seen on reproductive organs in both sexes, most
notably ovaries (in rats) and testes (in rats and mice), in both
the reproductive toxicity and subchronic toxicity studies. Hematological
changes, including slightly decreased hemoglobin and/or hematocrit,
have also been seen in multiple studies and species (in rats at
doses of 33 mg/kg/day and above, and in mice at doses of 487 mg/kg/day
and above). Studies depicting the effects of chronic exposure
to free triazole or its conjugates are not currently available.
Ref: Human
Health Aggregate Risk Assessment for Triazole-derivative Fungicide
Compounds (1,2,4-Triazole, Triazole Alanine, Triazole Acetic
Acid). US EPA, February 7, 2006.
1,1,1,2-Tetrafluoroethane
(HFC-134a) - Propellant, US
EPA List 4B Inert - CAS No. 811-97-2
-- NEUROLOGIC 0.2.7.1.
ACUTE EXPOSURE - Headache, dizziness, and disorientation are common.
Cerebral edema may be found on autopsy.
A syndrome of impaired psychomotor speed, impaired memory and
learning, and emotional lability has been described in workers
with chronic occupational exposure to fluorinated hydrocarbons.
-- THERE IS A SIGNIFICANT
ACCUMULATION OF FLUOROCARBONS IN BRAIN, LIVER & LUNG COMPARED
TO BLOOD LEVELS, SIGNIFYING A TISSUE DISTRIBUTION OF FLUOROCARBONS
SIMILAR TO THAT OF CHLOROFORM. /FLUOROCARBONS/ [Clayton, G. D.
and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology:
Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons,
1981-1982. 3076]
Ref: Hazardous Substances Data Bank for
1,1,1,2-TETRAFLUOROETHANE CASRN: 811-97-2.
http://www.fluorideaction.org/pesticides/1,1,1,2-tetrafluoroe.toxnet.htm
Transfluthrin
- Insecticide - CAS
No. 118712-89-3
-- 3.2.4 Carcinogenicity
Studies. The two available studies, in the rate and mouse both
combine chronic toxicity and carcinogenicity... Single incidences
of tumours occurring in treated groups but not controls were reported
in the kidneys, ovaries, brain, parathyroid
and skeletal muscle. Neither these, nor the occasional incidences
of systemic tumors presented in Table 3.3 were considered to be
treatment related (page 23).
Ref: Evaluation on: Transfluthrin Use as
a Public Hygiene Insecticide. September 1997. Prepared by: the
UK Health and Safety Executive, Biocides & Pesticides Assessment
Unit, Magdalen House, Stanley Precinct, Bootle, Merseyside L20
3QZ. Available from: Department for Environment, Food and Rural
Affairs, Pesticides Safety Directorate, Mallard House, Kings Pool,
3 Peasholme Green, York YO1 7PX. UK. Also at http://www.pesticides.gov.uk/citizen/evaluations/165_confirm-box.htm
• Note: This was transcribed
from the copy available on the web. While one can easily read
this report on the web, the report is inaccessible, or locked,
to any attempt to copy it. Any errors are mine. EC.
Tributyltin
fluoride - Antifoulant, Fungicide, Microbiocide
- CAS
No. 1983-10-4
... In
rats given a single oral dose of 40 mg/kg tributyltin fluoride
(15 mg Sn/kg), transient elevations in tributyltin, dibutyltin,
monobutyltin, and inorganic tin were observed in brain and liver
over the 8-day period following the dose, indicating that dealkylation
had occurred (Iwai et al. 1981, see Section 3.4.3). ..
Ref: DRAFT TOXICOLOGICAL PROFILE FOR TIN
AND COMPOUNDS. U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES. Public
Health Service Agency for Toxic Substances and Disease Registry.
September 2003.
http://www.atsdr.cdc.gov/toxprofiles/tp55.pdf
Trichlorofluoromethane
- Insecticide, Fungicide, Propellant, US EPA List 2 Inert
- CAS No. 75-69-4
--
Chronic effects ... Chronic Effects Chronic use of Freon
11 has been linked to diseases of the mucous membranes, lungs,
and central nervous system (Hazardtext, 2003B). In the occupational
setting, chronic fluorocarbon exposure has been associated with
a syndrome of impaired psychomotor speed, impaired
memory and learning, and emotional instability (Reprotext,
2003). Repeated or prolonged skin contact may cause dermatitis
(NIOSH, 2001E; NIOSH, 2001D).
Ref:
September 24, 2003 (Revised)
- FREON [11, 12, 113].
Technical Support Document: Toxicology. Clandestine
Drug Labs/ Methamphetamine. Volume 1, Number 11. California EPA,
Office of Environmental Health Hazard Assessment (OEHHA), Department
of Toxic Substances Control.
-- An estimated BCF
of 49 was calculated for trichlorofluoromethane(SRC), using a
log Kow of 2.53(1) and a regression-derived equation(2). According
to a classification scheme(3), this BCF suggests the potential
for bioconcentration in aquatic organisms is moderate. The levels
of trichlorofluoromethane in three species of mollusks and five
species of fish are only slightly enriched (usually 2-25 times
on a dry weight basis) over the seawater levels(4). The
usual order of enrichment was found to be brain > liver > gill
> muscle(4). [(1) Hansch C et al; Exploring QSAR. Hydrophobic,
Electronic, and Steric Constants. ACS Prof Ref Book. Heller SR,
consult. ed., Washington, DC: Amer Chem Soc p. 3 (1995) (2) Meylan
WM et al; Environ Toxicol Chem 18: 664-72 (1999) (3) Franke C
et al; Chemosphere 29: 1501-14 (1994) (4) Dickson AG, Riley JP;
Mar Pollut Bull 7: 167-9 (1976)]
-- There is a significant accumulation of
propellant in the brain, liver and lung compared to blood
levels, signifying a tissue distribution of propellant similar
to that of chloroform. /Fluorocarbons/ [Clayton, G.D., F.E. Clayton
(eds.) Patty's Industrial Hygiene and Toxicology. Volumes 2A,
2B, 2C, 2D, 2E, 2F: Toxicology. 4th ed. New York, NY: John Wiley
& Sons Inc., 1993-1994. 1203]
-- Aerosol sprays containing fluorocarbon propellants are another
source of solvent intoxication. Prolonged exposure or daily use
may result in damage to several organ systems. Clinical problems
include cardiac arrhythmias, bone marrow
depression,
cerebral degeneration,
and damage to liver, kidney, & peripheral nerves. Death occasionally
has been attributed to inhalant abuse, probably via the mechanism
of cardiac arrhythmias, especially accompanying exercise or upper
airway obstruction. /fluorocarbon propellants/ [Hardman, J.G.,
L.E. Limbird, P.B. Molinoff, R.W. Ruddon, A.G. Goodman (eds.).
Goodman and Gilman's The Pharmacological Basis of Therapeutics.
9th ed. New York, NY: McGraw-Hill, 1996. 575]
Ref: Hazardous Substances Data Base for
TRICHLOROFLUOROMETHANE.
http://www.fluoridealert.org/pesticides/Trichlorofluorometha.TOXNET.htm
Trichlorotrifluoromethane
(CFC
113)
- Solvent, US EPA List 2 Inert - CAS No. 76-13-1
.. A single case /was
reported/ of sensorimotor neuropathy in a woman who had worked
as a laundress with trichlorotrifluoroethane (Freon
113) for several years. Weakness, pain, and paresthesias
were most severe distally in the legs. Electrodiagnostic testing
was consistent with axonal damage.
Removal from exposure to trichlorotrifluoroethane
resulted in gradual recovery. [O'Donoghue, J.L. (ed.).
Neurotoxicity of Industrial and Commercial Chemicals. Volume II.
Boca Raton, FL: CRC Press, Inc., 1985. 110]
-- There is a significant
accumulation of fluorocarbons in brain, liver and lung
compared to blood levels, signifying a tissue distribution of
fluorocarbons similar to that of chloroform. [Clayton, G.D., F.E.
Clayton (eds.) Patty's Industrial Hygiene and Toxicology. Volumes
2A, 2B, 2C, 2D, 2E, 2F: Toxicology. 4th ed. New York, NY: John
Wiley & Sons Inc., 1993-1994. 1203]
Ref:
Hazardous Substances Data Bank for 1,1,2-TRICHLORO-1,2,2-TRIFLUOROETHANE
CASRN: 76-13-1.
http://www.fluorideaction.org/pesticides/trichlorotrifluorome.toxnet.htm
Chronic
effects ... In the occupational setting, chronic fluorocarbon
exposure has been associated with a syndrome of impaired psychomotor
speed, impaired memory and learning,
and emotional instability (Reprotext, 2003). Repeated or prolonged
skin contact may cause dermatitis (NIOSH, 2001E; NIOSH, 2001D).
Ref:
September 24, 2003 (Revised)
- FREON [11, 12, 113].
Technical Support Document: Toxicology. Clandestine
Drug Labs/ Methamphetamine. Volume 1, Number 11. California EPA,
Office of Environmental Health Hazard Assessment (OEHHA), Department
of Toxic Substances Control.
Triflusulfuron-methyl
- Herbicide
- CAS No. 126535-15-7
In a rat reproduction
study (2-generation, 1 litter/generation), the NOEL for systemic
(parental) toxicity was 5.81 mg/kg bw/d based on lower body weights
and food consumption. The NOEL for reproductive toxicity was 44
mg/kg bw/d (750 ppm) based on lower pup body weights and
histopathological effects on the cerebellum consistent with undernutrition
(decreased cellularity in the internal granular layer and increased
cellularity in the external germinal layer) in
the 2500 ppm group...
Ref:
Dec 3, 1999 - Report on Triflusulfuron methyl. Regulatory Note
REG99-03. Pest Management Regulatory Agency, Health Canada, Ottawa.
http://www.fluorideaction.org/pesticides/triflusulfuron.methy.canada.pdf
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