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The hypothalamus is an area of the brain
that produces the "controlling" hormones. These
hormones regulate body processes such as metabolism, and
control the release of hormones from glands like the thyroid,
the adrenals and the gonads (testes or ovaries).
Ref: http://www.nlm.nih.gov/medlineplus/ency/imagepages/9417.htm
See more information on the hypothalamus
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
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Note:
This is not an exhaustive list.
When time allows more information will be added.
J
Neurosci Methods 1983 Apr;7(4):317-28
An application of neutron activation analysis to small
biological samples: simultaneous determination of thirty elements
in rat brain regions.
Chan AW, Minski MJ, Lai JC.
Thirty elements in 7 rat brain regions were determined by
instrumental neutron activation analysis (INAA). The samples
were irradiated by thermal neutrons using 3 different sets
of conditions, depending on the nuclear characteristics of
the elements. Analysis of the resulting radionuclides was
by gamma-ray spectrometry using a high resolution Ge(Li) detector
and Nuclear Data 6600 multichannel analyzer, which was fully
computerized to give quantitative results for the gamma-ray
spectra. This paper demonstrates the use of INAA for small
biological samples and to show its potential elements, 7 rat
brain regions are listed. It is interesting to note that certain
elements, e.g. fluorine and potassium
showed high and low regional differences respectively,
and hypothalamus and hippocampus had
higher elemental concentrations than other brain regions.
However, since this paper is essentially an analytical one,
no attempt is made to assess these data, which are preliminary,
and the possible functional role of these elements will be
discussed elsewhere.
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PFOS - Insecticide,
US EPA List 3 Inert
Abstract: Perfluorooctane
sulfonate (PFOS) is a degradation product of sulfonyl-based fluorochemicals
that are used extensively in industrial and household applications.
Humans and wildlife are exposed to this class of compounds from
several sources. Toxicity tests in rodents have raised concerns
about potential developmental, reproductive, and systemic effects
of PFOS. However, the effect of PFOS on the neuroendocrine system
has not been investigated thus far. In this study, adult female
rats were injected intraperitoneally with 0, 1, or 10 mg PFOS/kg
body weight (BW) for 2 weeks. Food and water intake, BW, and estrous
cycles were monitored daily. At the end of treatment, PFOS levels
in tissues were measured by high-performance liquid chromatography
(HPLC) interfaced with electrospray mass spectrometry. Changes
in brain monoamines were measured by HPLC with electrochemical
detection, and serum corticosterone and leptin were monitored
using radioimmunoassay. Treatment with PFOS
produced a dose-dependent accumulation of this chemical in various
body tissues, including the brain. PFOS exposure decreased food
intake and BW in a dose-dependent manner. Treatment with PFOS
affected estrous cyclicity and increased serum corticosterone
levels while decreasing serum leptin concentrations. PFOS
treatment also increased norepinephrine
concentrations in the paraventricular nucleus of the hypothalamus.
These results indicate that exposure to
PFOS can affect the neuroendocrine system in rats.
Ref: Environ Health Perspect. 2003 Sep;111(12):1485-9.
Neuroendocrine
effects of perfluorooctane sulfonate in rats; by Austin ME,
Kasturi BS, Barber M, Kannan K, MohanKumar PS, MohanKumar SM.
Sodium
fluoride -
Insecticide, Wood preservative, US EPA List 4B Inert
- CAS No. 7681-49-4
1993 Abstract: Summary: Animal models
of subacute and chronic fluorosis in female rats were developed
with injection of large doses of NaF(IP)
and with drinking water containing 100 ppm F-, respectively. The
serotonin or 5-hydroxytryptamine (5-HT) content and turnover rate
in the hypothalamus were determined with spectrofluorometry combined
with degradation blockade. The 5-HT turnover rate decreased during
both subacute and chronic fluorosis. The 5-HT content increased
during subacute fluorosis, but decreased during chronic fluorosis.
These results suggest that the influences of 5-HT metabolism of
the two kinds of fluorosis are not completely identical. The
decrease of 5-HT turnover rate in hypothalamus may be one of possible
mechanisms of deficiency of pituitary prolactin (PRL) and milk
secretion during fluorosis.
Ref: Fluoride 1993; 26(1):57-60.
Changes of serotonin content and turnover rate in hypothalamus
of female rat during fluorosis; by Yuan
SD, Xie QW, Lu FY
1991 Abstract: The effect of fluorosis
on lactation, lactotroph function and ultrastructure were studied
in lactating rats. The results were as follows:
1) Inhibition of lactation in lactating rats with chronic fluorosis
was assessed by stunting growth of pups and decrease in the amount
of milk suckled by pups in 30 min. Metoclopramide, a blocker of
dopamine receptor, could improve lactation in these rats.
2) During chronic fluorosis serum PRL level was decreased, however,
PRL content in pituitary was increased. Electronmicroscopic examination
showed accumulation of large mature secretory granules and appearance
of extremely large abnormal secretory granules in lactotroph cytoplasma.
These findings indicate that hormone release of pituitary lactotrophs
is obstructed in lactating rats with fluorosis, and
the toxic effect of fluoride is mediated by an enhanced function
of dopaminergic system in hypothalamus.
Ref: Sheng Li Xue Bao 1991 Oct;43(5):512-7.
[An
experimental study of inhibition on lactation in fluorosis rats];
by Yuan SD, Song KQ, Xie QW, Lu FY. [Article in Chinese]
1990 Abstract: The phosphoinositide
(PI) transduction system has proven to be of major importance
in several regions of mammalian brain. In this report, we examined
in rats whether a PI system is present in the hypothalamic suprachiasmatic
nuclei (SCN), the site of a biological clock that generate circadian
rhythms. Autoradiographic localization of phorbol ester binding
revealed moderate levels of protein kinase C, a component of the
PI system, in the SCN. Hypothalamic explants containing SCN showed
substantial incorporation of [3H]myoinositol into lipids. AlF4-,
a non-specific activator of G proteins, produced a dose-dependent
increase in inositol monophosphate (IP1) levels in the explants
in calcium-free medium, with a maximum increase
of 216% of control at 50 mM NaF. Medium containing 1.8
mM calcium stimulated a similar increase in IP1 levels, but the
stimulatory effects of AlF4- and calcium were not additive, so
that the effect of Al4- was obscured in medium containing calcium.
AlF4- stimulated accumulation of IP1, as well as inositol bis-,
and trisphosphate, over a 40-min time course in the presence and
absence of lithium (10 mM LiCl). Lithium, a known inhibitor of
phosphatases in the inositol phosphate recycling pathway, raised
levels of all 3 inositol phosphates in SCN explants both at baseline
(without A1F4-) and after 30 min AlF4- stimulation. The results
show the existence of a lithium-sensitive PI system within the
suprachiasmatic region of the rat hypothalamus.
Brain Res 1990 Jan 22;507(2):181-8. Aluminum
fluoride reveals a phosphoinositide system within the suprachiasmatic
region of rat hypothalamus; by Nadakavukaren JJ, Welsh DK,
Reppert SM.
1989 Abstract: The mechanism of
sodium fluoride (NaF) induced hypothermia was investigated on
relations between the monoamine synthesis and metabolism in the
rabbit brain. Five male rabbits per a group, weighing about 2.5kg
and having rectal temperatures of 38.4 to 39.3 degrees C, were
used in this experiment. The rectal temperature measurements were
made by means of an electric thermometer for 5 hours at intervals
of 15 or 30 minutes. Through this experiment, animals were housed
in a room kept at 22 to 23 degrees C. The following drugs were
used in this experiment: NaF (40 mg/kg i.v.), barbital sodium
(0.1 g/kg s.c.), hexamethonium bromide (C6, 10 mg/kg i.v.), ergotamine
tartrate (30 mg/kg s.c.), phenoxybenzamine hydrochloride (15 mg/kg
i.v.), propranolol hydrochloride (5 mg/kg s.c.), pindolol (0.3
mg/kg s.c.), atropine sulfate (30 mg/kg s.c.), 2, 4-dinitrophenol
(DNP, 20 mg/kg i.v.), l-DOPA (20 mg/kg i.v.), 5-HTP (20 mg/kg
i.v.) Results
1. Intravenous injection of 30 mg/kg of NaF induced a drop of
0.66 degrees C in rectal temperature.
2. Pretreatment with 0.1 mg/kg of barbital sodium or 10 mg/kg
of C6 prominently inhibited the NaF-induced hypothermia.
3. The alpha-blockade caused by ergotamine tartrate and phenoxybenzamine
or the beta blockade by propranolol hydrochloride and pindolol
resulted in an approximate 50% inhibition of maximum drop in body
temperature induced by NaF administration. Both alpha- and beta-blockades
caused by ergotamine tartrate and propranolol or by phenoxybenzamine
and pindolol, however, made a remarkable inhibition of the NaF
effect. Cholinergic blockade brought on by atropine sulfate, on
the other hand, had no effect against NaF-induced hypothermia.
4. Bilateral splanchnicotomy completely inhibited drops in rectal
temperature.
5. Intravenous injection of NaF 40 mg/kg failed to counteract
the rise of rectal temperature caused by DNP 20 mg/kg.
6. Pretreatment with l-DOPA made a prominent inhibition of NaF-induced
hypothermia. The inhibiting effects of 5-HTP, however, were slight.
7. Administration of NaF made a significant
decrease in norepinephrine levels in the rabbit hypothalamus,
but had no effect on 5-HT levels.
Ref: Shikwa Gakuho 1989 Mar;89(3):607-26.
[The
rabbit thermo-regulatory system. Effects of high dose of sodium
fluoride]; by Machida H.[Article in Japanese]
1986 Abstract. Hormone-sensitive
adenylate cyclase is believed to exist as a complex consisting
of a catalytic subunit, guanine nucleotide binding regulatory
unit and a hormone or neurotransmitter receptor. The diterpene
compound, forskolin, is a potent stimulator of adenylate cyclase
activity presumably interacting with a site directly on the catalytic
subunit. Guanine nucleotides and sodium fluoride stimulate adenylate
cyclase through a stimulatory guanine nucleotide binding regulatory
subunit. In order to examine the role of the forskolin binding
site in the rat brain, the distribution of [3H]forskolin binding
sites has been compared with those of a radiolabeled guanine nucleotide
analog. [3H]Forskolin densely labeled a few discrete brain regions
including the caudate-putamen, nucleus accumbens, olfactory tubercle,
globus pallidus and substantia nigra. Specific [3H]guanylyl-5'-imidodiphosphate
([3H]Gpp(NH)p) binding sites were found in high densities in not
only these areas but also in the cerebral cortex, thalamus, hypothalamus
and midbrain regions. In the hippocampal formation, guanine nucleotide
binding sites were seen in the stratum oriens, stratum radiatum,
stratum lacunosum molecular and the molecular layer of the dentate
gyrus. On the other hand, forskolin labeled the hilus and the
pyramidal cell layer of CA3 and CA4 with high density, a region
where guanine nucleotide binding was relatively low. Sodium fluoride
and Gpp(NH)p were found to enhance forskolin binding in regions
in which [3H]Gpp(NH)p binding sites were present. These results
indicate that most, but not all forskolin binding sites in the
brain, are allosterically coupled with the stimulatory guanine
nucleotide binding protein. Conversely, it has also been demonstrated
that some forskolin binding sites in the hippocampus are probably
not guanine nucleotide regulated.
Ref: J Pharmacol Exp Ther 1986 Dec;239(3):952-8.
Regional
modulation of [3H]forskolin binding in the rat brain by guanylyl-5'-imidodiphosphate
and sodium fluoride: comparison with the distribution of guanine
nucleotide binding sites; by Gehlert DR.
Sodium
fluoroacetate (also
known as 1080)
- Rodenticide, Insecticide - CAS No. 62-74-8
Fluoroacetate,
a selective inhibitor of the glia tricarboxylic acid cycle, attenuated
the release of luteinizing hormone-releasing hormone from the
hypothalamus of ovariectomized rats.
Ref: Ann N Y Acad Sci 1991;633:626-7
Wu TJ, McArthur NH, Harms PG.
Department of Animal Science, Texas A&M University, College
Station 77843.
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: |
| (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) |
| (870.4300) |
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) |
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