Brain - Adverse Effects
Fluorinated and Fluoride Pesticides

beginning with A-E F • G-P Q-Z
Brain Structures Function From the excellent website: Neuroscience for Kids
* 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.
As time allows more information will be added.

Gliftor - Rodenticide - Rodenticide - CAS No. 8065-71-2

Abstract. Acute poisoning with gliftor, a pesticide composed of 30% glycerol chlorofluorohydrin and 70% glycerol difluorohydrin, was studied in three tractor drivers who, mistaking it for alcohol, ingested 30 ml each of this liquid. Motor disorders comprising complex chloreiform hyperkinesis (Kulenkampff-Tarnow syndrome) due to lesions in the cortical and subcortical structures of the corpus striatum and of the limbicoreticular portion of the brain, were the principal poisoning symptoms. There were no symptoms of fluorine poisoning. One patient, who presented the first symptoms 48 hr after ingestion of the poison, died in respiratory collapse 6 days later. Leukocytosis (up to 20% rod neutrophilis) hyperglycemia, a serum potassium level of 2.7 mEq/liter, proteinuria, pyuria, and hematuria were observed. Histopathological examination revealed acute circulatory disturbances in the internal organs, parenchymatous dystrophy, and dystrophic changes in the central nervous system.
Ref: Three cases of gliftor poisoning; by Kovalenko LI, Bulkina VA, Panteleev RI. Gig. Tr. Prof. Zabol. (12): 53-54; 1975. [Abstract from Toxline at Toxnet.]

Halfenprox - Acaricide; Insecticide - CAS No. 111872-58-3

• No toxicological data available as of February 2005.
• Note:
This pesticide contains both bromine and fluorine; a combination that has the potential to produce severe adverse effects - particularly to the brain.

• Other fluorinated pesticides that contain both bromine and fluorine are:

1H-Pyrrole-3-carbonitrile, 4-bromo-2-(4-chlorophenyl)-5-trifluoromethyl

Indoxacarb - Insecticide - CAS No. 173584-44-6

Pyrazoline-type insecticides (PTIs) are potent neurotoxicants that cause cessation of feeding, abnormal movement, and paralysis in arthropods. Indoxacarb, the first insecticide in this class to achieve commercial registration, is a proinsecticide that is selectively activated in insects to form the insecticidal N-decarbomethoxyllated metabolite, DCJW is another pyrazoline-type compound that is an effective insecticide but was not registered for use due to its unacceptable mammalian toxicity ([Meier et al., 1992], [Silver and Soderlund, 2005a] and [Silver and Soderlund, 2005b]).
Ref: Silver KS, Soderlund DM (2007). Point mutations at the local anesthetic receptor site modulate the state-dependent block of rat Nav1.4 sodium channels by pyrazoline-type insecticides. NeuroToxicology 28:3 655-663. (Available at ScienceDirect.)
See also: Action of pyrazoline-type insecticides at neuronal target sites. Silver KS, Soderlund DM (2007). Pesticide Biochemistry and Physiology 81:2 136-143. (Available at ScienceDirect.)

52425-040 162205 ŇOncogenicity Study with DPX-JW062-106 (50% DPX-KN128, 50% DPX-KN127) Eighteen-Month Feeding Study in MiceÓ(Frame, S. 832-E. I. du Pont de Nemours and Company, Haskell Laboratory, Elkton Road, Newark, Delaware, Study HLR 799-96, 3/24/97). DPX-JW062-106 technical (Batch DPX-JW062-106, approximately 48% DPX-KN128) was given in the diet daily to 70 Crl:CD ¨ -1(ICR)BR mice/sex/dose at 0, 20, 100, or 125/150/200 ppm for 18 months (200 ppm level reduced to 150 ppm on day 126 and to 125 ppm on day 287 due to excessive mortality). The cause of death was either central nervous system disorder (determined from clinical signs of abnormal gait/mobility and head tilt) or heart inflammation/ necrosis (males only) ... Non-neoplastic changes were noted in the brain of both sexes and in the heart of males only of mice that died or were sacrificed in extremis. Neuronal necrosis was reported in two high-dose males and two females and in one female at 100 ppm. Both high-dose males were sacrificed in extremis, one while receiving the 150 ppm diet (day 133) and the other while receiving the 125 ppm diet (test day 302). The two affected females died or were killed in extremis (day 83 and 108, respectively) while receiving 200 ppm. Residual vacuolation of the piriform cortex was observed in 2 female high-dose mice that survived to the 18-month scheduled sacrifice.
March 11, 1999: Summary of Toxicology Data - Indoxycarb. California EPA Department of Pesticide Regulation, Medical Toxicology Branch.

Based on animal data from DPX-JW062 (50% KN128 [Indoxacard], Active Ingredient), the following chronic effects may occur in animals with DPX-MP062. Ingestion of DPX-JW062 by dogs for one-year caused hemolytic anemia with secondary histopathological changes and decreased body weights. The NOEL for both male and female dogs was 40 ppm. Effects in male and female rats that were fed DPX-JW062 in their diets for two-years include decreased body weight, in addition females also had some hemolysis. The NOEL for the two-year rat feeding study was 60 ppm for male rats and 40 ppm for female rats. Male and female mice fed DPX-JW062 for eighteen months had decreased body weight, in addition females showed signs of neurotoxicity, some mortality, and a few incidences of histopathologic changes in the brain (probably secondary to seizures). The NOEL for the eighteen month mouse feeding study was 20 ppm in male and female mice.
Ref: Dupont's Material Safety Data Sheet for STEWARD insecticide. January 2001.

Abstract: Indoxacarb is a newly developed insecticide with high insecticidal activity and low toxicity to non-target organisms. Its metabolite, DCJW, is known to block compound action potentials in insect nerves and to inhibit sodium currents in cultured insect neurons. However, little is known about the effects of these compounds on the sodium channels of mammalian neurons. We compared the effects of indoxacarb and DCJW on tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-resistant (TTX-R) sodium channels in rat dorsal root ganglion neurons by using the whole-cell patch clamp technique. Indoxacarb and DCJW at 1-10 microM slowly and irreversibly blocked both TTX-S and TTX-R sodium channels in a voltage-dependent manner. The sodium channel activation kinetics were not significantly modified by 1 microM indoxacarb or 1 microM DCJW. The steady-state fast and slow inactivation curves were shifted in the hyperpolarization direction by 1 microM indoxacarb or 1 microM DCJW indicating a higher affinity of the inactivated sodium channels for these insecticides. These shifts resulted in an enhanced block at more depolarized potentials, thus explaining voltage-dependent block, and an apparent difference in the sensitivity of TTX-R and TTX-S channels to indoxacarb and DCJW near the resting potential. Indoxacarb and its metabolite DCJW cause toxicity through their action on the sodium channels.
Ref: Zhao X et al. (2003). Voltage-dependent block of sodium channels in mammalian neurons by the oxadiazine insecticide indoxacarb and its metabolite DCJW. Neurotoxicology. Jan;24(1):83-96

Abstract: The effects of the oxadiazine insecticide indoxacarb and its N-decarbomethoxylated metabolite (DCJW) on tetrodotoxin-resistant (TTX-R) voltage-gated sodium channels in rat dorsal ganglion neurons were studied using the whole-cell patch clamp technique. Indoxacarb and DCJW suppressed the peak amplitude of action potentials, and DCJW exhibited a faster time course and higher potency than indoxacarb in the blocking effects. In voltage-clamp experiments, indoxacarb and DCJW suppressed TTX-R sodium currents in a time-dependent manner without a steady-state level of suppression. IC50 values for indoxacarb and DCJW on TTX-R sodium currents were estimated to be 10.7 and 0.8 microM after 25 min of bath application, respectively. DCJW was about 10 times more potent than indoxacarb in blocking TTX-R sodium currents. Although the suppressive effects of indoxacarb were partially reversible after washout with drug-free external solution, no recovery of sodium current was observed in DCJW treated neurons after prolonged washout. In current-voltage relationships, both indoxacarb and DCJW blocked the sodium currents to the same degree in the entire range of membrane potentials. The sodium conductance-voltage curve was not shifted along the voltage axis by indoxacarb and DCJW at 10 microM. In contrast, the steady-state inactivation curves were shifted in the hyperpolarizing direction by indoxacarb as well as by DCJW. Based on these results, it was concluded that indoxacarb and DCJW potently blocked the TTX-R sodium channel in rat DRG neurons with hyperpolarizing shifts of the steady-state inactivation curves, suggesting preferential association of the insecticides to the inactivated state of sodium channels. The small structural variation between indoxacarb and DCJW resulted in clear differences in potency for blocking sodium channels and reversibility after washout.
Ref: Tsurubuchi Y, Kono Y (2003). Modulation of sodium channels by the oxadiazine insecticide indoxacarb and its N-decarbomethoxylated metabolite in rat dorsal root ganglion neurons. Pest Manag Sci. Sep;59(9):999-1006.

Methanesulfonyl fluoride - Fumigant, Insecticide - CAS No. 558-25-8

Abstract: TD3: This citation summarizes a one-page announcement of technology available for utilization. Chemicals that markedly inhibit the enzyme cholinesterase (ChE) in the rat brain but relatively little in other tissues have been discovered by Dr. Donald E. Moss and his colleagues at the University of Texas at EL Paso (UTEP). Dr. Moss and his colleagues found that phenylmethanesulfonyl fluoride (PMSF) and methanesulfonyl fluoride (MSF) inhibited 90 percent of ChE activity in the rat brain but less than 35 percent in other tissues. The enzyme hydrolyzes acetylcholine, a vital neurotransmitter. Acetylcholine is markedly deficient in the brains of patients with Alzheimer disease, due at least in part to decreased synthesis, Dr. Moss points out. 'A therapeutic strategy, therefore, would be to cut down ChE's destructive action so that the little bit of neurotransmitter that is being synthesized lasts longer,' he says. Dr. Moss points out that a big advantage of MSF and PMSF over other drugs is their apparent l
Ref: New Chemicals Markedly Inhibit Cholinesterase. Authors: Anon. Author Address: National Institutes of Health, Bethesda, MD. Source: Govt Reports Announcements & Index (GRA&I), Issue 23, 1986. Order Number: NTIS/NTN86-0746, FOR ADDITIONAL INFORMATION: Contact: Research Resources Information Center, 1601 Research Blvd, Rockville, MD; (301)984-2870, Refer to X, No. 1., 1p. As cited at Toxnet.

BIOSIS COPYRIGHT: BIOL ABS. Mice were injected with an anticholinesterase, methanesulfonyl fluoride (MSF, 1.5 mg/kg) or O,O-dimethyl O-(2,2-dichlorovinyl) phosphate (DDVP, 10 mg/kg) singly or repeatedly and examined for synaptic activities on the cerebral cholinergic system and behavior. MSF inhibited the activity of cerebral acetylcholinesterase (AChE) more slowly but more irreversibly than DDVP. Although a single injection of DDVP increased the concentrations of total, extraterminal, intraterminal and cytoplasmic acetylcholine (ACh) remarkably shortly after injection, MSF was still as effective at 24 h as 3 h after administration in increasing the concentrations of fractional ACh. Repeated injection of MSF for 3 d showed a significant reduction in the activity of AChE one day after cessation with a slight recovery 5 d later. Repeated administration of DDVP for 10 days showed a less significant reduction in the ac tivity of AChE one day after cessation with considerable recovery 14 d later. Although a single injection of DDVP showed suppressive effects on locomotor activity, rectal temperature and rotarod performance in mice, the administration of MSF did not produce any significant effects, while DDVP suppressed locomotor activity and rectal temperature during and after the term of repeated injection. MSF showed a significant suppressive effect only at the 3rd day without causing any other changes during or after the term of repeated injection. In conclusion, MSF causes similar, but longer lasting effects on cholinergic mechanisms than DDVP and has fewer suppressive effects on behavioral parameters than DDVP.
Ref: KOBAYASHI H et al. (1999).
Effects of a central anticholinesterase, methanesulfonyl fluoride on the cerebral cholinergic system and behavior in mice: Comparison with an organophosphate DDVP. JOURNAL OF HEALTH SCIENCE; 45 (4). 1999. 191-202. As cited on Toxnet.

Mipafox - Acaricide, Insecticide - CAS No. 371-86-8

There are many abstracts pertaining to Mipafox effects on brain - see

Excerpts: ... At ten times the concentration of mipafox that causes a 50% inhibition of NTE (5x10-5 M/day) mipafox was found to significantly decrease neurite length in differentiated cells while paraoxon and OPH-hydrolyzed paraoxon at the same concentration did not.
... While some organophosphorus (OP) compounds including paraoxon produce acute toxicity through acetylcholinesterase inhibition, others such as mipafox produce OP-induced delayed neurotoxicity (OPIDN), which is characterized anatomically by Wallerian-type "dying back" neuropathy in the axon and myelin.
... Protein expression of NF200 was shown to be a new biomarker by which the neurotoxic effects of mipafox and paraoxon on SY5Y cells were distinguishable at the molecular level.
... The current study shows that organophosphorus compounds produce not only antiesterase activity but also modifications in protein. Evidence presented suggests that mipafox caused shortening of neurites in differentiated SY5Y cells by a degeneration process, whereas paraoxon inhibited neurite growth in the cells.
Research Project (April 2001 - April 2006): Organophosphate Insecticide Damage to the Mature and Developing Nervous Systems: in Vitro Systems for Detection and Remediation. Principal Investigator: E. Tiffany-Castiglioni. Texas A&M University.

...ACETYLCHOLINESTERASE INHIBITOR, LIKE PARATHION. AFTER ACUTE PHASES OF POISONING, DEGENERATIVE LESIONS MAY BECOME APPARENT IN CENTRAL & PERIPHERAL NERVOUS SYSTEMS. [Gosselin, R.E., H.C. Hodge, R.P. Smith, and M.N. Gleason. Clinical Toxicology of Commercial Products. 4th ed. Baltimore: Williams and Wilkins, 1976.,p. II-196]
Ref. Hazardous Substances Data Bank for MIPAFOX CASRN: 371-86-8. Available at Toxnet.

... In a study of alkyl phosphate poisoning, Pasi and Leuzinger came to the conclusion that delayed lesions only occur, if at all, after severe cerebral anoxia [176]. As regards anatomical changes in the brain (demyelination), these delayed lesions correspond to those caused by peripheral neuropathy in acute and chronic ortho-tricresyl phosphate poisoning and are confined to fluorine- containing alkyl phosphates - for example, mipafox, DFP, sarin and soman. A synoptic evaluation of 536 civilian cases of alkyl phosphate poisoning made by the above-mentioned authors led them to the conclusion that acute poisoning by civilian alkyl phosphates did not result in delayed lesions. It should be noted, however, that their period of observation of two to three years was inadequate for investigations of delayed lesions beside the scale of Spiegelberg and others [p 40].
Ref: Delayed Toxic Effects of Chemical Warfare Agents. A SIPRI (Stockholm international Peace Research Institute) Monograph. 1975. ISBN 91-85114-29-4.

PubMed abstract: A single injection of mipafox was administered to both Long-Evans hooded rats and White Leghorn hens in dosages which inhibited the activity of brain neurotoxic esterase 30-50%, 60-80%, or greater than 80% four hr after intoxication. All animals were monitored for clinical evidence of organophosphorus induced delayed neuropathy for 21 days, euthanatized, and regions of the nervous system were histologically evaluated. Only hens manifested clinical signs of neuropathy; however, light and electron microscopic lesions were present in the nervous systems of both species. In rats, these lesions were well developed in only the highest dosage group and confined to the rostral level of the fasciculus gracilis in the medulla oblongata. Swollen axons containing a single vacuole filled with flocculent material were the most prominent lesion in rats. Hens manifested more extensive and varied fiber breakdown in multiple spinal cord tracts, with the intensity of degeneration increasing with increasing dosages of mipafox. Both marked Wallerian-like degeneration and swollen axons filled with aggregates of cellular debris were observed in the nervous systems of hens. This study indicates that both rats and hens are susceptible to OPIDN. However, there are qualitative and quantitative differences in both clinical manifestations and histologic appearances between the two species.
Comparative dose-response studies of organophosphorus ester-induced delayed neuropathy in rats and hens administered mipafox; by Dyer KR, Jortner BS, Shell LG, Ehrich M. Neurotoxicology 1992 Winter;13(4):745-55.

PubMed abstract: Adult male Long-Evans rats and White Leghorn hens were given 30 mg/kg mipafox ip. Administration of this organophosphorus ester resulted in > or = 89% inhibition of brain and spinal cord neurotoxic esterase activity in both species 4 hr after dosing. Our sequential, comparative study of the bilateral mipafox-induced neuropathy in the medulla and cervical spinal cord in hens and rats demonstrated that the rats had well-developed, vacuolar axonopathic lesions in the fasciculus gracilis by post-dosing day 7. Severely affected rats with such lesions were noted through day 21, but not subsequently (days 28 and 35). The hen had a slower developing, but more severe, consistent and longer lasting neuropathy than the rat. In these birds, lesions in the medulla and rostral cervical spinal cord levels were more extensive, involving large regions of both the spinocerebellar tracts and fasciculus gracilis. Neuropathic changes, including myelinated fiber axonopathy and Wallerian-like degeneration, were prominent from days 14 - 35 in hens, and were associated with prominent gliosis in the later stages.
Comparative evolution of mipafox-induced delayed neuropathy in rats and hens; by Carboni D, Ehrich M, Dyer K, Jortner BS. Neurotoxicology 1992 Winter;13(4):723-33.

• Definitions:
Fasciculus gracilis.
White matter in the dorsal, medial area of the spinal cord. It forms the entire dorsal column in the lumbar and sacral levels and the medial division of the dorsal column in the thoracic and cervical regions. It carries sensory information from the lower extremities. In the thoracic and cervical regions it is located between the fasciculus cuneatus and the dorsal median fissure. In the lumbar and sacral regions it is found between the dorsal horn and the dorsal median fissure.
The production of a dense fibrous network of neuroglia; includes astrocytosis, which is a proliferation of astrocytes in the area of a degenerative lesion.
Gliosis - excerpt from PubMed Abstract:
... Our results show that chronic gliosis is associated with altered processing of the amyloid precursor protein in vivo and thus may initiate or exacerbate pathological changes associated with Alzheimer's disease.
Ref: Bates KA et al (2002). Chronic gliosis triggers Alzheimer's disease-like processing of amyloid precursor protein. Neuroscience: 113(4):785-96.
lower or hindmost part of the brain; continuous with spinal cord; (`bulb' is an old term for medulla oblongata); "the medulla oblongata is the most vital part of the brain because it contains centers controlling breathing and heart functioning"

Abstract: The effects of multiple low doses of ecothiopate (513100), paraoxon (311455), and mipafox (371868) on organophosphate target enzymes in the brain and diaphragm were studied in mice. Male albino-mice were injected subcutaneously once with 0 or 110 micromoles per kilogram (micromol/kg) mipafox, 0.5micromol/kg ecothiopate, or 1.5micromol/kg paraoxon or with 0 or 44micromol/kg mipafox, 0.2micromol/kg ecothiopate, or 0.6micromol/kg paraoxon daily for 5 days or 27.5micromol/kg mipafox daily for 8 day s. The mice were killed 3 hours (hr) after the single dose or 3 or 24hr after each of the multiple doses and the brain and diaphragms were removed... Mipafox and paraoxon inhibited brain AChE activity by 55 and 73%, respectively... Only mipafox inhibited brain NTE activity, by 66%. Brain AChE activity was progressively inhibited by 17 to 46% by multiple dosing with 27.5micromol/kg mipafox, by 23 to 49% by multiple injection with 44micromol/kg mipafox, and by 20 to 55% by multiple dosing with paraoxon... Mipafox also produced a progressive inhibition of brain NTE activity, the cumulative inhibitory effect, 74 and 76%, being similar after the two dosing protocols. The authors conclude that exposure to multiple low doses of mipafox, ecothiopate, and paraoxon produces additive inhibition of AChE activity. These results have implications for humans as humans are generally exposed to low levels of organophosphates for extended periods of time.
Williams FM et al (1997. The Effects of Multiple Low Doses of Organophosphates on Target Enzymes in Brain and Diaphragm in the Mouse. Human and Experimental Toxicology, Vol. 16, No. 2, pages 67-71. Abstract available at

Nissol (also known as MNFA or MNAF) - Acaricide, Insecticide - CAS NO. 5903-13-9

Abstract. The relationship between the characteristic electroencephalographic findings and the blood sugar levels in Nissol (N-methyl-N (10naphthyl) monofluoroacetamide) poisoning has been noted recently. States of both acute and chronic intoxication by Nissol were produced in male albino rabbits to study the compound's effects on the brain, together with hematologic, renal and postmortem histological manifestations. In the acute experiment, 2 ml of a 25% emulsion was applied to the skin surface. In the chronic toxicity test, a 1000-fold dilution of the 25% emulsion was applied to the skin once daily until the animals succumbed. In the acute toxicity test, there were no remarkable findings in the blood cell count, hemoglobionmetry or livr function tests but the blood sugar decreased from the pretreatment level of 122 to 78 and 56 mg/dl in 3 and 7 hr, respectively. In the chronic toxicity test, the erythrocyte count decreased to 3,310,000 and hemoglobin dropped to 50% in 8 months. The liver function tests, blood sugar analysis and electrocardiography did not show any remarkable changes. The electroencephalogram in the acute toxicity test exhibited a transient convulsive wave in all leads 5 hr following the application of Nissol which then gradually lapsed to a slow-voltage pattern, while the blood sugar level dropped to 56 mg/dl. In the chronic experiment, the electroencephalographic tracings showed a low-voltage pattern which fell into regular waves in the eighth month without convulsions or a decrease in blood sugar levels. I.P. injection of 20% glucose caused the temporary development of an alpha wave. The visceral organs were characterized by congestion, atrophy and degeneration both in the chronic and the acute toxicity tests, Ischemic changes in the cerebral cortex, hippocampus and Purkinje cells of the cerebellum were more pronounced in the chronic experiment. From the above studies, it is concluded that there is a cause-effect relationship between the fall of the blood sugar level, the electroencephalographic findings and the ischemic changes in the brain in Nissol intoxication.
Ref: Organic fluorine poisoning, by Nanba M JR et al. Nippon Rinsho; 29(2):864-70 1971. [Abstract from Toxnet.]

Abstract. The accumulation of citrate was studied in spider-mites, house-flies and mice after treatment with the acaricide Nissol (5903139). Male Swiss-Webster-mice were injected with various concentrations of Nissol. House-flies were treated topically with Nissol at various concentrations or received thoracic injections. A slide/dip technique was used to dose two-spotted-spider mites with Nissol. Mortality was recorded at 24 hours after treatment and the median lethal dose (LD50) was calculated for each species. The citric-acid (77929) content was determined in homogenates of whole mice in brains, hearts, livers, and kidneys photospectrometrically. Citric-acid content was also determined in homogenates of flies and mites. The LD50 for intraperitoneal administration in mice was 200 milligrams per kilogram (mg/kg). The topical LD50 in house-flies was 525mg/kg and the injected LD50 was 14mg/kg. The LD50 for contact administration to spider mites was 250 parts per million. Citric-acid increased substantially in each species even by 3 hours after dosing. The maximum accumulation in mice occurred at 6 hours. Flies and mites continued to show increased accumulation through 12 hours. In the mouse citric-acid was accumulated in decreasing order in the heart, kidney, brain, and liver. The authors conclude that mites, flies and mice accumulate citrate when treated with Nissol. The toxicity of this acaricide may be related to inhibition of aconitase which catalyzes transformation of citric-acid.
Ref. Citrate Accumulation In Twospotted Spider Mites, House Flies, And Mice Following Treatment With The Acaricide 2-Fluoro-N-methyl-N-(1-naphthyl) Acetamide; by Johannsen FR. Knowles CO. Journal of Economic Entomology, Vol. 65, No. 6, pages 1754-1756, 14 references, 1972.

Abstract. The effects of a single dose and repeated doses of N-methyl-N- ( 1- naphthyl ) monofluoroacetamide (MNFA) on the fluctuation of citrate in animals and the replationship between the activity of MNFA hydrolysis and the acute toxicity of MNFA in various species were investigated. MNFA was administered intraperitoneally at 25 mg/kg to male Wistar strain rats, 2.0 mg/kg to guinea pigs and 300 mg/kg to monkeys. At specified periods after dosing, the animals were sacrificed and the citrate content of heart, kidneys, liver and brain was determined. For the multiple dose study, MNFA was administered orally to male rats at doses of 0.625, 1.25, 2.5, 5.0 and 10.0 mg/kg/ day for 180 days and the citrate content was determined in the brain, heart, liver, kidney, testis and blood. In the rat, after a single dose of MNFA, the citrate level increased to 27, 10, 10 and negligible times the normal value in heart, kidneys, brain and liver, respectively. In the chronic toxicity experiment, the only increase (3 times the control value) was in the testes of rats receiving 10 mg/ kg/day of MNFA. In all other groups, the level in liver and kidney decreased significantly in comparison with the levels in animals receiving a single dose. It is suggested that this difference was due to metabolism and to the detoxification mechanism of the liver and kidney which may have been accelerated by the chronic administration of MNFA. The citrate level in the monkeys after a single dose was much lower than in the rat. In guinea pigs it increased to the maximum at 9 hr when it reached 30 times the control value in the kidney, 10 times in the heart, 6 times in the brain while no appreciable increase was found in the liver. The hydrolysis of MNFA by liver homogenates was closely related to the acute toxicity and the product of the hydrolysis was determined as N-methyl-1-naphthylamine. The enzyme activity in the guinea pig was about 35 times that of the rat or mouse. The LD50 of MNFA was 3.1 times that of N- ( 1-naphthyl ) monofluoroacetamide ( NFA ) and the amount hydrolyzed after 30 min incubation was about one- fifth.
Ref: Studies of the biochemical lesions caused by a new fluorine pesticide, N-methyl-N- ( 1-naphthyl )
monofluoroacetamide; by Noguchi T, Hashimoto Y, Miyata H. Toxicol. Appl. Pharmacol.; 13(2), 189-98, 1968.

Abstract. The selective toxicity of N-methyl-N- ( 1-naphthyl ) monofluoroacetamide ( MNFA ) in various species of animals and the effects of the compound on the central action, the peripheral action and the fluctuations in the cardiovascular and respiratory systems were investigated. Tabulated data present the physiological function or activity investigated, the test animal, the dosage of MNFA administered and the route of administration. Results showed that below the toxic level, MNFA had little or no general pharmacologic effect and only a minute effect on the central and peripheral nervous systems and various peripheral organs of the differenct animals tested. When a toxic dose of MNFA was administered, respiratory depression, a fall of blood pressure and body temperature and a decrease in heart rate were generally observed. Both the rat and cat developed convulsions. Just prior to death, a flat wave was observed in the electrical activity of the brain which was indicative of a serious impediment. A drop in blood pressure of about 30% was observed at 24 hr in rats that received 50 mg/kg of MNFA orally. Cardiac response revealed the characteristic feature of this compound to be cardiac depression in every species tested. In addition, among animals that have a high sensitivity to MNFA, such as the guinea pig, dog and cat, bigeminal or trigeminal ventricular premature beats were observed. An enhancement of epinephrine activity by MNFA was also noted. MNFA had a slight effect on the red cell count, but the white cell count in rabbits decreased markedly accompanied by a decrease of pseudoeosinophils and an increase of lymphocytes. The blood sugar level in mice showed an initial increase prior to a final decrease, while in rats and guinea pigs there was a decrease and the value remained unchanged in rabbits and dogs. Ketone bodies were only detected in the mouse.
Ref. Some pharmacologic properties of a new fluorine pesticide, N-methyl- N- ( 1-Naphthyl ) monofluoroacetamide; by Hasimoto Y, Noguchi T, Mori T, Kitagawa H. Toxicol. Appl. Pharmacol.; 13(2), 174-88, 1968.

Ref: ChemIDplus for Nissol. Available at Toxnet.
Test Type Route Reported Dose (Normalized Dose) Effect Source
cat LD50 skin 4mg/kg (4 mg/kg)



Nippon Yakurigaku Zasshi. Japanese Journal of Pharmacology. Vol. 65, Pg. 182, 1969.

Link to PubMed

dog LD50 skin 2750ug/kg (2.75 mg/kg)



Nippon Yakurigaku Zasshi. Japanese Journal of Pharmacology. Vol. 65, Pg. 182, 1969.
Link to PubMed
dog LDLo intraperitoneal 2mg/kg (2 mg/kg)



Toxicology and Applied Pharmacology. Vol. 12, Pg. 536, 1968.
guinea pig LD50 skin 5mg/kg (5 mg/kg)


Toxicology and Applied Pharmacology. Vol. 12, Pg. 536, 1968.
guinea pig LDLo subcutaneous 1mg/kg (1 mg/kg)


Toxicology and Applied Pharmacology. Vol. 12, Pg. 536, 1968.
monkey LDLo intraperitoneal 100mg/kg (100 mg/kg)



Toxicology and Applied Pharmacology. Vol. 12, Pg. 536, 1968.
monkey LDLo skin 800mg/kg (800 mg/kg)



Toxicology and Applied Pharmacology. Vol. 12, Pg. 536, 1968.
monkey LDLo subcutaneous 150mg/kg (150 mg/kg)



Toxicology and Applied Pharmacology. Vol. 12, Pg. 536, 1968.
mouse LD50 intraperitoneal 164mg/kg (164 mg/kg)


Toxicology and Applied Pharmacology. Vol. 12, Pg. 536, 1968.
mouse LD50 subcutaneous 216mg/kg (216 mg/kg)



Toxicology and Applied Pharmacology. Vol. 12, Pg. 536, 1968.
rabbit LD50 oral 1500ug/kg (1.5 mg/kg)


Experimental Animals. Jikken Dobutso Iho. Vol. 21, Pg. 88, 1972.
rabbit LDLo intravenous 5mg/kg (5 mg/kg)


Toxicology and Applied Pharmacology. Vol. 12, Pg. 536, 1968.
rat LD50 subcutaneous 41mg/kg (41 mg/kg)


Toxicology and Applied Pharmacology. Vol. 12, Pg. 536, 1968.


Noviflumuron -Insecticide - CAS No. 121451-02-3

-- REPRODUCTION, RAT. “XDE-007: Two-Generation Dietary Reproduction Toxicity Study in CD Rats,” (Carney, E.W., Zablotny, C.L., Liberacki, A.B., Yano, B.L.;Toxicology & Environmental Research and Consulting, The Dow Chemical Company, Midland, MI; 3/22/04). XDE -007 (97.9% pure) was fed in diet to Crl:CD (SD) IGS BR rats (30/sex/dose/generation) at 0, 0.5, 5 or 25 mg/kg/day continuously from pre-mating of parental generation 1 (P1) through weaning of offspring through 2 generations (2 matings for P2 generation) to F2b weaning. . ... . F2a male weanlings had statistically significantly decreased body weights, relative brain and absolute spleen weights at 25 mg/kg. Neonates at 25 mg/kg in both F1 and F2 generations showed tonoclonic convulsions, as well as in 1 litter of F2a at 5.0 mg/kg. P2 females (1, 1, 5 and 7 at 0, 0.5, 5.0 and 25 mg/kg, respectively) failed to litter, so the female is considered to be an affected sex.) Possible adverse effects on reproduction, fertility and pup survival, along with numerous other toxicologically relevant effects. M. Silva, 6/18/04
-- “XDE-007: Two-year Dietary Chronic Toxicity/Oncogenicity and Chronic Neurotoxicity Study in Fischer 344 Rats,” (Yano, B.L., Dryzga, M.D., Thomas, J.; Toxicology & Environmental Research and Consulting, The Dow Chemical Company, Midland, MI; Laboratory Project Study ID: 011168; 4.22.05). Noviflumuron ((N-[3,5-dichloro-2-fluoro-4(1,1,2,3,3,3-hexafluoropropoxy)phenyl]-N’-(2,6-difluorobenzoyl)urea; XDE-007, 97.9% pure) was fed in diet to Fischer 344 rats (75/sex/dose) for 90 days, 1 or 2 years at 0, 0.1, 1.0, 75 or 300 mg/kg/day. Subchronic toxicity was assessed after 90 days of treatment on 10/sex/dose at 0 and 1.0 mg/kg/day doses only. At 1 year,10/sex/dose (chronic toxicity group), and 5/sex/dose (chronic neurotoxicity group) were necropsied. The remaining 50/sex/dose were necropsied after 2 years (oncogenicity group). Chronic NOEL = 1.0 mg/kg/day (At > 75 mg/kg/day there were decreased body weights and body weight gains along with increases or decreases in absolute and/or relative organ weights (liver, kidney, brain, heart, adrenal, testes, spleen, epididymides were affected) at 12 and/or 24 months.
Ref: August 2005 - Summary of toxicological data. California EPA, Department of Pesticide Regulation, Medical Toxicology Branch.

-- 52905-009 186501, "XR-007: Whole Embryo Culture Teratogenicity Screen", (E. W. Carney, Health and Environmental Research Laboratories, The Dow Chemical Company, Midland, MI, Report # 971083, 31 July 1997). Seven non-pregnant female rats (serum donors) received 1000 mg/kg/day of the test article (XR-007, 98%) in 0.5% Methocel by gavage for 3 consecutive days. Four hours after the last dose, rats were exsanguinated and their blood centrifuged to obtain serum. Six control rats were similarly treated with vehicle and bled... Statistically significant increases in crown-rump length and somite number for treated embryos were reportedly due to a lower than usual growth rate in control embryos. Morphological abnormality was limited to an abnormal curvature of the anterior neural tube which distorted the head in one treated embryo (8.3%). No historical control data. This is supplemental information. (Green and Gee, 10/3/02).
Ref: September 26, 2002. Summary of Toxicology Data for Noviflumuron ((XDE-007) or N-(((3,5-dichloro-2-fluoro-4-(1,1,2,3,3,3-hexafluoropropoxy)phenyl)amino)carbonyl)-2,6- diflurobenzamide. California EPA, Department of Pesticide Regulation, Medical Toxicology Branch.

• Note from FAN- some definitions:

"Predominately anterior neural tube defects, occuring early in gestation. The anterior neural tube fails to close properly, or does not divide into two hemispheres. The generic name for this category of malformations is arrhinencephaly. Ref: Developmental and Perinatal Disorders of the CNS. Weill Medical College of Cornell University.
-- "... trisomy 13 is closely linked to midline malformations, including
arrhinencephaly, agenesis of the corpus callosum, and holoprosencephaly, and is the single most common chromosomal defect underlying holoprosencephaly." -
-- "Trisomy 13 Syndrome is a genetic disorder with onset before birth. It occurs approximately 1/5000 live births. Infants affected with Trisomy 13 tend to be small at birth. Spells of interrupted breathing (apnea) in early infancy are frequent, and mental retardation is usually severe. Many affected children appear to be deaf. A moderately small head (microcephaly) with sloping forehead, wide joints and openings between parietal bones of the head are present. Gross anatomic defects of the brain, especially failure of the forebrain to divide properly (holoprosencephaly) are common. A hernial protrusion of the cord and its meninges through a defect in the vertebral canal (myelomeningocele) is found in almost 50% of cases. The entire eye is usually small (microphthalmia), and a defect of the iris tissue (coloboma), and faulty development of the retina (retinal dysplasia) occur frequently. The supraorbital ridges are shallow and palapebral fissures are usually slanted. Cleft lip, cleft palate, or both are present in most cases. The ears are abnormally shaped and unusually low-set." -

Oxyfluorfen - Herbicide - CAS No. 42874-03-3

Absolute and relative thymus weights were decreased in mid-dose males (-14%/-10%)and high-dose males (-32%/- 18%)...Vacuolation of the adrenal cortex was present in high-dose females. Thymic atrophy occurred in high-dose males and females.... Fine vacuolation of adrenal glands (slight)and cortical atrophy of the thymus (slight) were increased in high-dose males... Absolute and/or relative organ weights in the high-dose groups that showed statistically significant changes relative to control weights (thyroid gland in both sexes and kidney in females at 12 months and brain, pituitary, and spleen in females sacrificed at 24 months) had no microscopic correlates and are not considered toxicologically significant.
Ref: US EPA. Toxicology Chapter for RED. August 8, 2001.

PFOS - PFOS - Insecticide, US EPA List 3 Inert

Due to length, click here for effects page

1H-Pyrrole-3-carbonitrile, 4-bromo-2-(4-chlorophenyl)-5-trifluoromethyl - Antifoulant, Fungicide - CAS No. 122454-29-9

• No toxicological data available as of February 2005.
• Note:
This pesticide contains both bromine and fluorine; a combination that has the potential to produce severe adverse effects - particularly to the brain.

• Other fluorinated pesticides that contain both bromine and fluorine are:


Fluoride Action Network | Pesticide Project | 315-379-9200 |