Return to
Index Page
Abstracts

ACTIVITY: Acaricide, Insecticide (organofluorine)

Note: Out-dated pesticide

CAS Name: 2-fluoro-N-methyl-N-(1-naphthalenyl)acetamide

Structure:

Adverse Effects:
Blood
Body Weight Decrease
Brain
Endocrine: Testes
Heart
Kidney
Liver
Lung

Blood (click on for all fluorinated pesticides)

A health survey was carried out on 181 farmers before and after the pesticidal application of Nissol (MNFA). Questionnaires on general health, determination of blood pressure and body weight, examination of urine and liver functions, physical examinations, indirect chest roentgenography, blood picture, blood sugar level, and ECG were recorded for some farmers. Forty-five percent of the farmers complained of subjective symptoms at the second examination (4 days after the application), unrelated to the duration of working hours. The major subjective symptoms were general malaise, headache, nausea, loss of appetite, diarrhea, insomnia, abdominal pain, and tachypnea in that order. On the average, body weight loss appeared in 33.6% of the farmers three weeks after the application. Hemoglobin increased in 4.6%, decreased in 18.7%, and did not change in 77% of the farmers. Red cell count decreased in about 52% of the farmers. Leukocyte count increased in less than fifty percent of the farmers with a noticeable increase of neutrophils. Some increase of urobilinogen and glycosuria were noticed while proteinuria remained stable. Clinically questionable findings were not obtained in liver functions. The findings on ECG were a slight decrease of heart rate and a slight elongation of PQ; however, no arrhythmia was found.
Ref: Studies of organofluorine pesticide intoxication. II. Results of health examinations of farmers using an organofluorine pesticide; by Hashida K. Okayama Igakkai Zasshi (J. Okayama Med. So; 83(7-8): 295-310; 1971. [Abstract from Toxnet.]

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.

Body Weight Decrease (click on for all fluorinated pesticides)

Abstract: A health survey was carried out on 181 farmers before and after the pesticidal application of Nissol (MNFA). Questionnaires on general health, determination of blood pressure and body weight, examination of urine and liver functions, physical examinations, indirect chest roentgenography, blood picture, blood sugar level, and ECG were recorded for some farmers. Forty-five percent of the farmers complained of subjective symptoms at the second examination (4 days after the application), unrelated to the duration of working hours. The major subjective symptoms were general malaise, headache, nausea, loss of appetite, diarrhea, insomnia, abdominal pain, and tachypnea in that order. On the average, body weight loss appeared in 33.6% of the farmers three weeks after the application. Hemoglobin increased in 4.6%, decreased in 18.7%, and did not change in 77% of the farmers. Red cell count decreased in about 52% of the farmers. Leukocyte count increased in less than fifty percent of the farmers with a noticeable increase of neutrophils. Some increase of urobilinogen and glycosuria were noticed while proteinuria remained stable. Clinically questionable findings were not obtained in liver functions. The findings on ECG were a slight decrease of heart rate and a slight elongation of PQ; however, no arrhythmia was found.
Ref: Studies of organofluorine pesticide intoxication. II. Results of health examinations of farmers using an organofluorine pesticide; by Hashida K. Okayama Igakkai Zasshi (J. Okayama Med. So; 83(7-8): 295-310; 1971. [Abstract from Toxnet.]

Brain (click on for all fluorinated pesticides)

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.

TOXICITY Ref: ChemIDplus for Nissol. Available at Toxnet.
Organism	Test Type	Route	Reported Dose (Normalized Dose)	Effect	Source
cat	LD50	skin	4mg/kg (4 mg/kg)	BEHAVIORAL: CONVULSIONS OR EFFECT ON SEIZURE THRESHOLD BEHAVIORAL: EXCITEMENT	Nippon Yakurigaku Zasshi. Japanese Journal of Pharmacology. Vol. 65, Pg. 182, 1969. Link to PubMed
dog	LD50	skin	2750ug/kg (2.75 mg/kg)	BEHAVIORAL: CONVULSIONS OR EFFECT ON SEIZURE THRESHOLD BEHAVIORAL: EXCITEMENT	Nippon Yakurigaku Zasshi. Japanese Journal of Pharmacology. Vol. 65, Pg. 182, 1969. Link to PubMed
dog	LDLo	intraperitoneal	2mg/kg (2 mg/kg)	BEHAVIORAL: CONVULSIONS OR EFFECT ON SEIZURE THRESHOLD BEHAVIORAL: EXCITEMENT	Toxicology and Applied Pharmacology. Vol. 12, Pg. 536, 1968.
guinea pig	LD50	skin	5mg/kg (5 mg/kg)	BEHAVIORAL: CONVULSIONS OR EFFECT ON SEIZURE THRESHOLD	Toxicology and Applied Pharmacology. Vol. 12, Pg. 536, 1968.
guinea pig	LDLo	subcutaneous	1mg/kg (1 mg/kg)	BEHAVIORAL: CONVULSIONS OR EFFECT ON SEIZURE THRESHOLD	Toxicology and Applied Pharmacology. Vol. 12, Pg. 536, 1968.
monkey	LDLo	intraperitoneal	100mg/kg (100 mg/kg)	BEHAVIORAL: "HALLUCINATIONS, DISTORTED PERCEPTIONS" BEHAVIORAL: CONVULSIONS OR EFFECT ON SEIZURE THRESHOLD	Toxicology and Applied Pharmacology. Vol. 12, Pg. 536, 1968.
monkey	LDLo	skin	800mg/kg (800 mg/kg)	BEHAVIORAL: "HALLUCINATIONS, DISTORTED PERCEPTIONS" BEHAVIORAL: CONVULSIONS OR EFFECT ON SEIZURE THRESHOLD	Toxicology and Applied Pharmacology. Vol. 12, Pg. 536, 1968.
monkey	LDLo	subcutaneous	150mg/kg (150 mg/kg)	BEHAVIORAL: "HALLUCINATIONS, DISTORTED PERCEPTIONS" BEHAVIORAL: CONVULSIONS OR EFFECT ON SEIZURE THRESHOLD	Toxicology and Applied Pharmacology. Vol. 12, Pg. 536, 1968.
mouse	LD50	intraperitoneal	164mg/kg (164 mg/kg)	BEHAVIORAL: EXCITEMENT BEHAVIORAL: COMA	Toxicology and Applied Pharmacology. Vol. 12, Pg. 536, 1968.
mouse	LD50	subcutaneous	216mg/kg (216 mg/kg)	BEHAVIORAL: EXCITEMENT BEHAVIORAL: COMA	Toxicology and Applied Pharmacology. Vol. 12, Pg. 536, 1968.
rabbit	LD50	oral	1500ug/kg (1.5 mg/kg)	BEHAVIORAL: CONVULSIONS OR EFFECT ON SEIZURE THRESHOLD	Experimental Animals. Jikken Dobutso Iho. Vol. 21, Pg. 88, 1972.
rabbit	LDLo	intravenous	5mg/kg (5 mg/kg)	BEHAVIORAL: CONVULSIONS OR EFFECT ON SEIZURE THRESHOLD	Toxicology and Applied Pharmacology. Vol. 12, Pg. 536, 1968.
rat	LD50	subcutaneous	41mg/kg (41 mg/kg)	BEHAVIORAL: EXCITEMENT BEHAVIORAL: COMA	Toxicology and Applied Pharmacology. Vol. 12, Pg. 536, 1968.

Endocrine: Testes (click on for all fluorinated pesticides)

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 actue toxicity of N-methyl-N- ( 1-napthyl ) fluoroacetamide ( MNFA, Nissol ) was determined in detail in different species of animals and its subacute toxicity was determined in the rat. The LD50 of Nissol and its active ingredient MNFA were determined in male and female mice by oral, subcutaneous, dermal, intraperitoneal and intravenous administration; in male rats and guinea pigs by oral, dermal and subcutaneous administration; in male rats and guinea pigs by oral, dermal and subcutaneous administration; in male cats and dogs by oral and dermal routes; in adult monkeys by oral, dermal, subcutaneous, intraperitoneal and intravenous administration and orally in hens. Fish toxicity was investigaged in carp and inhalation toxicity tests were made in mice, rats and guinea pigs. The tabulated results show that the toxicity varied markedly with species. The toxicity of MNFA in mice, rats or monkeys was 1/100 to 1/200 of that in rabbits, guinea pigs, cats or dogs. In mice the oral LD50 ranged from 250-370 mg/kg, while by subcutaneous and intraperitoneal administration, the LD50 values were about 250 mg/kg or less. The approximate toxicity of MNFA for monkeys was less than for other species, the oral minimum lethal dose ( MLD ) being 300 mg/kg, subcutaneous MLD 150 mg/kg, intraperitoneal MLD 100 mg/kg and dermal MLD 800 mg/kg. The toxic symptoms produced by MNFA were charcteristic or organic fluorine poisoning in mammals. In the subacute toxicity tests, five groups of rats, 12 male and 12 female in each group were given oral daily doses of 0.625, 1.25, 2.50, 5 and 10 mg/kg MNFA for 6 months. Blood and urine tests were taken at 40-day intervals and pathological examination during autopsy revealed aspermatogenesis in some tubules of the testis from the rats of the two high dose groups. Destruction of the germinal epithelium was more striking in mature cell series than in immature cells. Does below 2.5 mg/kg did not produce significant changes in the testis. A dose dependent decline in the systolic arterial blood pressure was noticed. The reduction ranged from 5 to 20% of the normal blood pressure. The blood pressure reduction was not accompanied by gross or microscopic changes of morphology of the cardiovascular system or kidney. The serum level of SGOT also was reduced in the treated rats.
Ref. Acute an/ subchronic toxicity of a new fluorine pesticide, N-methyl- N-( 1-naphthyl ) fluoracetamide; by Hashimoto Y, Makita T, Miyata H, Noguchi T, Ohta G. Toxicol, App. Pharmacol.; 12(3), 536-47, 1968.

Heart (click on for all fluorinated pesticides)

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.

Abstract. General aspects of pesticide intoxication and therapy have been reported previously. Since most pesticides act on the nervous system, appreciable pathological alterations can be produced there, especially in the CNS. Four cases of pesticide intoxication are described: one with endrin, two with ceresin(!) (O-methyl O-cyclohexyl S(p-chlorophenyl)thiophosphate), and one with Nissol (MNFA)... In the MNFA intoxication case the patient's condition was serious with unconsiousness and a very low blood sugar value (50 mg/dl). The EEGs recorded on the first and seventh days of hospitalization showed flat, low-voltage waves without any slow waves or spikes. Intravenous administration of 40 ml of 40% glucose solution restored the alpha-waves, although at low-voltage, and the EEG returned to normal after one month. ...
Ref. Electroencephalograms in pesticide poisoning cases; by Hiraki K, Iwasaki, Namba M. Rinsho Noha (Clin. Electroencephalog.) ; 14(6): 333-340; 1972. [Abstract from Toxnet.].

Abstract. A brief discussion of the use of fluoroacetic acid as a pesticide, and a brief history of studies on this acid are given. More detailed discussions include those of MNFA, comparative toxicity of MNFA, pre-clinical test of antidotes, fluoroacetic poisoning of men and antidote treatment, the mechanism of detoxication, and various experiments of fluoroacetic acid effects on the brains of mice. The effects that have been detected on men include: mild nausea, vomiting, headache, dizziness; medium ataxia, clouding of consciousness, epileptic convulsion, repetition of tonic and clonic convulsion, decrease in heart rate; and serious coma, cyanosis, lack of abdominal reflex, arrhythmia, increase of tracheal secretion, and hypotension. Clinical findings include: sudden decrease or increase of blood sugar, increase of hemogram leucocyte, increase of pseudo acidophils, lymphocytes, and decrease of electrolyte K. The blood pressure gradually decreases, and various types of premature beats, myocardial infarction, and coronary insufficiency are found on electrocardiogram, as the heart rate increases and respiration decreases, In hepatic function, GOT and GPT gradually or slightly increase. Electroencephalogram shows a slow malfunction, or irregular slow wave; when serious, a flat pattern appears. The body temperature increases temporarily and then gradually decreases. The article is a review of previously published material by other researchers.
Ref. Pre-clinical evaluation of detoxication of organic fluoride toxins; by Hashimoto Y. Eisei Kagaku (Journal of Hygienic Chemistr; 17(6): 363-379; 1971. [Abstract from Toxnet.].

Abstract. The effects of N-methyl-N-(1-naphthyl)-monofluoroacetamide (MNFA) on cardiac function were studied in rabbits. Rabbits received 5 milligrams per kilogram (mg/kg) MNFA orally, or 2mg/kg MNFA subcutaneously (sc). Electrocardiographic (ECG) recordings were made from subcutaneously implanted electrodes before and up to 2 hours after oral MNFA, and for up to 10 hours after sc MNFA. Serum electrolytes and enzymes were determined 30 minutes before and after, and 3 and 6 hours after MNFA. One hour after oral MNFA, and ECG showed small deflections and almost discernible P-waves and T-waves in lead 1, with tall peaked T-waves in leads 2, 3, and aVF; after 2 hours, the QRS complex was widened and the ST junction was lowered. Leads 1 and aVL had ST depression consisting of wide S-waves and inverted T-waves. One hour after sc MNFA, the ECG revealed tachycardia; after 3 hours the ST junction was lowered. Leads 1 and aVL had ST depression consisting of wide S-waves and inverted T-waves. One hour after sc MNFA, ECG revealed tachycardia; after 3 hours the ST junction was lowered and T-waves were flattened or inverted. After 6 hours, there were wide S-waves and QRS was prolonged in leads 1, 2, and aVF. At 10 hours R-deflections were decreased in most leads, and tachycardia and ST junction depression were improved. Serum calcium was decreased slightly 6 hours after MNFA, but serum levels of sodium, potassium, chlorine, transaminases, and lactic-dehydrogenase were not affected. The authors conclude that the ECG changes of the QRS, ST, and T-waves are probably caused mainly by metabolic disturbances during MNFA intoxication.
Ref. Agricultural Organofluoride Poisoning: II. Cardiac Damage; by Iwasaki I, Nawa H, Hara A, Takagi S, Hyodo KFluoride, Vol. 3, No. 3, pages 127-130, 1970.

Abstract. Patients suffering from severe organofluoride intoxication (MNFA, Oxylan) were treated with glucose. Prior to treatment the electroencephalograms (EEG) demonstrated flat curves. Dysrhythmic patterns were observed in less severely affected patients which suggest the presence of impaired cerebral function associated with abnormal carbohydrate metabolism. The appearance of paroxysmal waves is also indicative of organofluoride poisoning. It is evident that EEG findings are valuable in the prognostic evaluation and diagnosis of organofluoride poisoning.
Ref: Studies on organofluoride poisoning IV. Electroencephalographic (EEG) observations; by Iwasaki I, Namba, Nawa H, Hara, Tagaki S, Hyodo K. Fluoride; 3(3): 133-136; 1970.

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.

TOXICITY Ref: ChemIDplus for Nissol. Available at Toxnet.
Organism	Test Type	Route	Reported Dose (Normalized Dose)	Effect	Source
dog	LDLo	intraperitoneal	2mg/kg (2 mg/kg)	BEHAVIORAL: CONVULSIONS OR EFFECT ON SEIZURE THRESHOLD BEHAVIORAL: EXCITEMENT CARDIAC: CARDIOMYOPATHY INCLUDING INFARCTION	Toxicology and Applied Pharmacology. Vol. 12, Pg. 536, 1968.

Kidney (click on for all fluorinated pesticides)

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.

Liver (click on for all fluorinated pesticides)

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 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. 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.

Lung (click on for all fluorinated pesticides)

TOXICITY Ref: ChemIDplus for Nissol. Available at Toxnet.
Organism	Test Type	Route	Reported Dose (Normalized Dose)	Effect	Source
guinea pig	LD50	skin	5mg/kg (5 mg/kg)	LUNGS, THORAX, OR RESPIRATION: DYSPNEA	Toxicology and Applied Pharmacology. Vol. 12, Pg. 536, 1968.
guinea pig	LDLo	subcutaneous	1mg/kg (1 mg/kg)	LUNGS, THORAX, OR RESPIRATION: DYSPNEA	Toxicology and Applied Pharmacology. Vol. 12, Pg. 536, 1968.
mouse	LD50	intraperitoneal	164mg/kg (164 mg/kg)	LUNGS, THORAX, OR RESPIRATION: RESPIRATORY DEPRESSION	Toxicology and Applied Pharmacology. Vol. 12, Pg. 536, 1968.
mouse	LD50	subcutaneous	216mg/kg (216 mg/kg)	LUNGS, THORAX, OR RESPIRATION: RESPIRATORY DEPRESSION	Toxicology and Applied Pharmacology. Vol. 12, Pg. 536, 1968.
rabbit	LD50	oral	1500ug/kg (1.5 mg/kg)	LUNGS, THORAX, OR RESPIRATION: OTHER CHANGES	Experimental Animals. Jikken Dobutso Iho. Vol. 21, Pg. 88, 1972.
rabbit	LDLo	intravenous	5mg/kg (5 mg/kg)	LUNGS, THORAX, OR RESPIRATION: DYSPNEA	Toxicology and Applied Pharmacology. Vol. 12, Pg. 536, 1968.
rat	LD50	subcutaneous	41mg/kg (41 mg/kg)	LUNGS, THORAX, OR RESPIRATION: RESPIRATORY DEPRESSION	Toxicology and Applied Pharmacology. Vol. 12, Pg. 536, 1968.