Hypothalamus - Adverse Effects
Fluorinated and Fluoride Pesticides


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

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.

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
Based on:
Chronic toxicity--rodents

3.5 for M

16 for F

14 for M

62 for F

histopathology in
brain (vacuolation in cerebrum and
2-Year combined chronic/

3.5 for M

16 for F

14 for M

62 for F

histopathology in
brain (vacuolation in cerebrum and
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