Abstracts
Nissol (also known as MNFA)
CAS No. 5903-13-9
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Adverse Effects

ACTIVITY: Acaricide, Insecticide (organofluorine)

Note: Out-dated pesticide

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

Systematic Names
Acetamide, 2-fluoro-N-methyl-N-(1-naphthyl)-
Acetamide, 2-fluoro-N-methyl-N-1-naphthalenyl- (9CI)

Structure

From Toxline at Toxnet

Nippon Rinsho; 29(2):864-70 1971; (REF:15)

Language: Japanese

Organic fluorine poisoning.

Nanba M JR, Fujii Y JR, Hara A JR, Nawa H JR, Iwasaki I JR, Hiraki K JR

HAPAB 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.

CAS Registry Numbers:
5903-13-9

 

From Dart Special at Toxnet

Chemically Induced Birth Defects 1993;2:675-721

Pesticides.

Schardein JL

International Research and Development Corporation, Mattawan, MI.

Medical Subject Headings (MeSH):
Pregnancy
Animal
Human
Female
Pesticides/*TOXICITY
*Abnormalities, Drug-Induced
2,4,5-Trichlorophenoxyacetic Acid/TOXICITY
Insecticides/TOXICITY

Substance (CAS Registry Number):
[Note: [Too many to list, however the following fluorinated pesticides were included]

Diflubenzuron (35367-38-5)
Ethalfluralin (55283-68-6)
Flusilazole (85509-19-9)
Gliftor (8065-71-2) - [Synonym: 1-Chloro-3-fluoro-2-propanol mixt. with 1,3-difluoro-2-propanol]
N-Methyl-N- 1-naphthyl fluoroacetamide [Nissol] (5903-13-9)
Sarin [Synonym: (+-)-Isopropyl methylphosphonofluoridate] (107-44-8)
Sodium fluoroacetate (62-74-8)
Sodium hexafluorosilicate [also known as Sodium fluorosilicate] (16893-85-9)
Soman [Synonym: 1,2,2-Trimethylpropyl methylphosphonofluoridate] (96-64-0)
Sulfuryl fluoride (2699-79-8)
Trifluralin (1582-09-8)


From Toxline at Toxnet

Environ. Health Perspect. 14: 93-102; 1976.(83 references)

Chemistry and toxicology of quinoxaline, organotin, organofluorine, and formamidine acaricides.

Knowles CO

PESTAB. This paper reviews existing data from studies of the chemistry and toxicology of the quinoxaline, organotin, organofluorine, and formamidine compounds. Studies indicated that cyclic dithiocarbonates usually had higher initial toxicity to spider mites than trithiocarbonates. Oxythioquinox has a broad spectrum of miticidal activity and is active against some insects and fungi. Oxythioquinox has a relatively low acute toxicity. The three organotins that possess appreciable acaricidal activity are Plictran, Vendex, and R-28627. Plictran is the only organotin currently in use for mite control. Four different types of organofluorine miticides are represented by fluenethyl, Nissol, fenazaflor, and R-10044. There are five types of formamidines of current commercial interest as acaricides and insecticides. Chlordimeform is the forerunner of this class of compounds. Arylthioformamidines are the most recent addition to this group.


From Toxline at Toxnet

Ig. Mod.65(9-10): 476-496; 1973

Language: Italian

Effetti della monofluoroacetammide (MNFA) sulla microflora dell'ambiente. Nota II. Effetti della MNFA sul ciclo del Carbonio. Effects of monofluoroacetamide (MNFA) on environmental microflora. II. Effects of MNFA on the carbon cycle.)

Cenci P, Cavazzini G

PESTAB. (32 references) (Italian) jThe effects of MNFA on microorganisms involved in the natural carbon cycle are reported. Using concentrations of 1, 10, 100, 500 and 100 gamma/ml of MNFA, microorganisms were tested for: cellulolysis (Cellvibrio viridis), growth and lactic acid production (Lactobacillus bulgaricus), growth and propionic acid production (Propionibacterium shermanii), growth and ethyl alcohol production (Saccharomyces cerevisiae var. elliposideus), growth and acetic acid production (Acetobacter aceti), growth and amylolysis (Aspergillus oryzae), growth and citric acid production (Aspergillus niger), and growth of Streptomyces sp. , Penicillus sp. and Sclerotinia fructicola. It is shown that MNFA inhibits two enzymatic reactions, both catalyzed by NADH (i. e. , ethyl alcohol and lactic acid production); however, citric acid production seems to be stimulated. The latter result supports the hypothesis that MNFA may inhibit aconitase as well as isocitric dehydrogenase, taking into consideration the possible deviation of the Krebs cycle through the glyoxalate pathway. s, [abstract truncated]


From Toxline at Toxnet

Source: Ig. Mod. 66(2): 131-149; 1973.(20 references)

Language: Italian

Effects of monofluoroacetamide (MNFA) on the microflora. III. Effects of MNFA on sulfur, phosphorus, and iron natural cycles.
:
Cenci P, Cavazzini G

PESTAB. The interaction is presented between N-methyl-(N-1-naphthyl)monofluoroacetamide and bacteria which fulfill fundamental biochemical functions in the sulfur, phosphorus, and iron natural cycles. The following are reported: oxidation of sulfur to sulfate (Thiobacillus thiooxidans and Th. thioparus); oxidation of thiosulfate to sulfur (Thiobacillus thiooxidans); growth of Desulfovibrio desulfuricans and reduction from sulfate to sulfide; growth of Bacillus megatherium var. phosphaticum and Bacillus cereus, and organic phosphorus solubilization; growth of Ferrobacillus ferrooxidans and iron oxidation. MNFA shows a toxic action on aerobic microorganisms, while it seems that the action of anaerobic bacteria is either a stimulating effect (at the higher concentrations of MNFA) or a toxic one (at the lower concentrations).


From Toxline at Toxnet

Ig. Mod. 66(3): 217-285; 1973.(11 references)

Language: Italian

Effects of monofluoroacetamide (MNFA) on the microflora. IV. Effects of MNFA on aquatic microorganisms.

Cenci P, Cavazzini G

PESTAB. The effects are presented of N-methyl-(N-1-naphthyl)monofluoroacetamide (MNFA) on bacteria and algae chemically active in fresh, saline, and waste waters. By spectrophotometry, growth and essential biochemical functions were determined in Methanococcus vannielii (CH4 production); Sphaerotilus natans and Leptothrix cholodnii (iron precipitation); Photobacterium phosphoreum (luminescent energy emission); Chlorella vulgaris, Euglena viridis, Anabaena cylindrica and Nostoc muscorum (chlorophyll a production). Results show that MNFA develops a toxic action on all the aerobic microorganisms considered. Chlorophyll production whether on Chlorophyceae or Cianophyceae, seems to be inhibited. Methanococcus vannielii behavior corroborates the hypothesis that an antagonism exists between stimulation (probably due to a mechanism of hydrogen donation) and toxicity in anaerobic reducing microorganisms.


From Toxline at Toxnet

Journal of Economic Entomology, Vol. 65, No. 6, pages 1754-1756, 14 references, 1972

Citrate Accumulation In Twospotted Spider Mites, House Flies, And Mice Following Treatment With The Acaricide 2-Fluoro-N-methyl-N-(1-naphthyl) Acetamide

Johannsen FR. Knowles CO

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.

CAS Registry Numbers:
5903-13-9
5903-13-9

77-92-9


From Toxline at Toxnet

Jikken Dobutsu (Exp. Animals); 21(2): 88-95; 1972 ; (REF:12)

A species difference in absorption of pesticides, especially a miticide, MNFA.

Language: Japanese

Hashimoto Y

HAPAB Species differences in absorption of chemicals are discussed using MNFA, N-methyl-N-(1-naphthyl)) monofluoroacetamide, a substance with a high toxicological selectivity, as an example. The LD50s in mug/kg in several experimental animals for oral and dermal administration respectively were: 250 and 370 in mouse; 110 and 300 in rat; 0.5 and 5.4 in guinea pig; 1.5 and 1.75 in rabbit; 2.5 and 4.0 in cat; 2.0 and 2.75 in dog;GT 300 and GT 800 in monkey.. No large difference in toxicity was seen due to route of administration. A metabolic study using (SUP)3H and (SUP)14C labeled MNFA indicated the toxic action is caused by the released fluoroacetate's blocking of citric acid metabolism, resulting in the accumulation of acid in internal organs. No direct relationship was seen between the amount of citric acid accumulated and the intensity of symptoms. A relationship was found between the species-specific MNFA degrading enzyme activity and the toxicity. The major degradation product of MNFA was N-methyl-l-naphthylamine in mammalian liver.


From Toxline at Toxnet

Rinsho Noha (Clin. Electroencephalog.) ; 14(6): 333-340; 1972 ; (REF:27)

Language: Japanese

Electroencephalograms in pesticide poisoning cases.

Hiraki K, Iwasaki, Namba M

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...

CAS Registry Numbers:
72-20-8
5903-13-9


From Toxline at Toxnet

Nippon Noson Igakkai Zasshi (J. Jap. Ass. ; 21(2): 236-237; 1972

Language: Japanese

Status of pesticide application and injuries in cultivators of illuminated chrysanthemum.

Rikimaru T, Goto, Ezaki H, Takamatsu M

The health of 50 families of workers in illuminated chrysanthemum growing sheds in Fukuoka prefecture was examined in May and October, 1971, to determine any relationship between contact dermatitis and pesticide applications. Examinations were made of labor conditions, diet, subjective symptoms, biometry, blood, liver function, urine, blood pressure, ECG, and general health. Patch tests with pesticides were also done (48 hr). Pesticides used in the chrysanthemum growing included dichlorvos, EPN, Estox, dithane (nabam), Lannate (methomyl), Nissol (MNFA based), and gramoxone (paraquat). These were power sprayed 55 times per year by men and 33 times by women. Illnesses included contact dermatitis, headaches, dizziness and nausea. However, the dermatitis was also induced by the leaves of the chrysanthemums, proven by patch tests. Subjective symptoms were susceptibility to fatigue, lumbago, shoulder discomfort, pruritus, and stomach disorders, the last two prevalent in men. Serum ChE activity during the October season was significantly lower in men and probably related to organophosphate pesticide application. No significant changes were found in liver function.


From Toxline at Toxnet

Source: Nogyo Gijutsu (J. Agr. Sci.); 27(3): 102-106; 1972

Language: Japanese

Recent studies on tea culture. Part 2.

Kawai S

Recent studies on tea culture in Japan are outlined, with particular reference to the development of tea-picking machinery, newly observed diseases, new studies on insect pests, and the safe use of pesticides. A fairly large number of pesticides has been registered for tea growing, and although actual standards for residues on tea leaves have not yet been established, the minimum number of weeks between application and harvest is officially fixed, based on the results of odor-disappearance (organoleptic) tests on treated and processed tea leaves. These intervals are as follows: 1 week for phosaron, naled, cartap, dichlorvos, and salithion; 2 weeks for Meobar, Fujithion, binapacryl, daconil, difolatan, Vegita, chlorfenvinphos, trichlorfon, mecarbam, and neotran; 3 weeks for azoxybenzene-Sumite, EPN, micro-carbaryl, Imidan, chlorbenzylate-dimite, Estox, fenitrothion, dicofol, Omite, Bassa, and inorganic copper; 4 weeks for cidial, Nissol, and petroleum distillate; and 7 weeks for calcium sulfide.


From Toxline at Toxnet

Eisei Kagaku (Journal of Hygienic Chemistr; 17(6): 363-379; 1971 ; (REF:117)

Language: Japanese

Pre-clinical evaluation of detoxication of organic fluoride toxins.

Hashimoto Y

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.


From Toxline at Toxnet

Okayama Igakkai Zasshi (J. Okayama Med. So; 83(7-8): 295-310; 1971 ; (REF:43)

Language: Japanese

Studies of organofluorine pesticide intoxication. II. Results of health examinations of farmers using an organofluorine pesticide.

Hashida K

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. 1971


From Toxline at Toxnet

Okayama Igakkai Zasshi (J. Okayama Med. So; 83(7-8): 273-293; 1971

Language: Japanese

Studies on organofluorine pesticide intoxication. I. Experimental and clinical studies on the therapy of organofluorine pesticide intoxication.

Hashida K

Monofluoroacetamide (MFA) was orally administered by a stomach tube to groups of Wistar rats at 20, 30, 50, and 100 mg/kg and to a group of rabbits at 30 mg/kg as a 10% aqueous solution. All the rats given 100mg and 50 mg/kg died within 24 hr. No rats given 20 and 30 mg/kg died; all the rabbits died after 2.5 hr. The symptoms in rats (50 mg/kg) were excitation with active movement, gneral convulsion, then lethargy and occasional convulsion. The symptoms in rabbits were general convulsion, cyanosis, and venticular fibrillation on ECG. Experimental therapeutic treatments were carried out on rats given MFA at 50 mg/kg and on rabbits given MFA at 30 mg/kg. The results show that acetamide was most effective for the intoxicated rats at doses of 500 mg/kg every eight hours. Ethanol, monoacetin, and glucose prolonged life somewhat while phenobarbital and procainamide were least effective. Acetamide and procainamide (500 mg/kg i.m. every two hr plus procainamide 50 mg/kg. i.m. every three hr) were most effective on rabbits, but with less success than in rats. MFA tends to lower the blood sugar of rats proportional to dose and is related to convulsions; methyl parathion and endrin increase the blood sugar. The finding gives an important criterion for the etiology in diagnosing pesticide intoxication. In humans acute intoxication by Nissol, an organofluorine, lowers the blood sugar level triggering loss of consciousness the administration of large amounts of glucose was highly effective.


From Toxline at Toxnet

Document Number: NIOSH/00161652

Fluoride, Vol. 3, No. 3, pages 127-130, 1970

Agricultural Organofluoride Poisoning: II. Cardiac Damage

Iwasaki I, Nawa H, Hara A, Takagi S, Hyodo K

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.


From Toxline at Toxnet

Fluoride; 3(3): 133-136; 1970

Studies on organofluoride poisoning IV. Electroencephalographic (EEG) observations.

Iwasaki I, Namba, Nawa H, Hara, Tagaki S, Hyodo K

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.


From Dart Special at Toxnet

OYO YAKURI(PHARMACOMETRICS) 4:463-468,1970

TERATOLOGICAL STUDIES OF N-METHYL-N-(1-NAPHTHYL)-FLUOROACETAMIDE IN MICE

MAKITA T, HASHIMOTO Y, NOGUCHI T

Taxonomic Name: MUS, ICR
Test Object: MAMMAL, MOUSE

Name of Agent (CAS RN):
N-METHYL-N-(1-NAPHTHYL)-FLUOROACETAMIDE ( 5903-13-9 )

Assay Method:
GROWTH
BEHAVIOR AND PSYCHOLOGIC PROCESSES
VIABILITY, FERTILITY AND MORTALITY
MUSCULOSKELETAL SYSTEM
CRANIUM AND FACE


From Dart Special at Toxnet

Proc. Fourth Int. Congr. Rural Med.öWhithe; 59-62; 1970 ; (REF:11)

Preclinical experiments on the antidote against monofluoroacetic acid derivatives poisoning in mammals.

Hashimoto Y, Makita, Mori T, Nishibe, Noguchi T, Watanabe S

Acetamide and glucose are used as antidotes against N-methyl-N-(1-naphthyl) monofluoroacetamide (MNFA). Intravenous and intraperitoneal injection of 500 mg/kg t.i.d. of acetamide against LD99, MNFA showed a complete cure but the oral dose has no effect at all. 100 mg/kg t.i.d. of acetamide was needed against LD 50 , FAA. Comparative effects of acetamide and glucose are considered. The most excellent antidote was found to be acetamide in 50% glucose solution administered intravenously in all species. A typical diagnosis of fluoroacetate poisoning is presented.


From Toxline at Toxnet

Fluoride; 3(3): 121-127; 1970 ; (REF:1)

Agricultural organofluoride poisoning: I. Carbohydrate metabolism.

Iwasaki I, Nawa, Hara A, Takagi, Hyodo K

There is a close association between organofluoride (MNFA) intoxication and an abnormal carbohydrate metabolism. Due to the blockage of the Krebs cycle, glucose is quickly changed into lactic acid via pyruvic acid which results in hypoglycemia. A very effective treatment of organochlorine poisoning is intravenous injection of glucose.

CAS Registry Numbers:
5903-13-9


From Toxline at Toxnet

Toxicol. Appl. Pharmacol.; 13(2), 189-98, 1968; (REF:34)

Studies of the biochemical lesions caused by a new fluorine pesticide, N-methyl-N- ( 1-naphthyl ) monofluoroacetamide

Noguchi T, Hashimoto Y, Miyata H

HAPAB 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.

CAS Registry Numbers:
5903-13-9


From Toxline at Toxnet

Toxicol, App. Pharmacol.; 12(3), 536-47, 1968; (REF:6)

Acute an/ subchronic toxicity of a new fluorine pesticide, N-methyl- N-( 1-naphthyl ) fluoracetamide.

Hashimoto Y, Makita T, Miyata H, Noguchi T, Ohta G

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 andpathological 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. TOXICOLOGY AND PHARMACOLOGY 68/12/00,20 1968

CAS Registry Numbers:
5903-13-9


From Toxline at Toxnet

Toxicol. Appl. Pharmacol.; 13(2), 174-88, 1968; (REF:33)

Some pharmacologic properties of a new fluorine pesticide, N-methyl- N- ( 1-Naphthyl ) monofluoroacetamide

Hasimoto Y, Noguchi T, Mori T, Kitagawa H

HAPAB 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. TOXICOLOGY AND PHARMACOLOGY 69/02/00, 54 1968

CAS Registry Numbers:
5903-13-9


From Science Direct

Toxicology and Applied Pharmacology; Volume 13, Issue 2 , September 1968, Pages 189-198

Studies of the biochemical lesions caused by a new fluorine pesticide, N-methyl-N-(1-naphthyl)monofluoroacetamide

Teruhisa Noguchi, Yoshinobu Hashimoto and Hiroo Miyata

Chemical Toxicology and Applied Pharmacology Laboratory, Biological Research Laboratories, Nippon Soda Company, Ltd., Oiso-machi, Kanagawa-ken, Japan

N-Methyl-N-(1-naphthyl)monofluoroacetamide (MNFA), a derivative of monofluoroacetic acid, is an effective pesticide with low toxicity for most mammals. The biochemical effect of this compound was investigated. After a single dose the citrate level rose in the heart of the rat and monkey and in the kidney of the guinea pig. A chronic toxicity experiment showed there was an increase in the citrate level only in the testis of rats receiving 10 mg/kg/day of MNFA for 180 days and a decrease in the level in the liver and kidney as compared with animals receiving a single dose. The lack of toxicity associated with chronic administration may be due to accelerated detoxication in the liver and kidney as a consequence of metabolism in the animal body. The hydrolysis of MNFA by liver homogenates was closely related to the acute toxicity. The enzyme activity in the guinea pig was about 35 times that of the rat or mouse. The product of the hydrolysis of MNFA by liver homogenates of guinea pigs, rats, and mice was N-methyl-1-naphthylamine. The LD50 of MNFA, a N-CH3 compound of NFA, was 3.1 times that of NFA, and the amount hydrolyzed after 30 minutes incubation was about one-fifth.


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=4865226

Iryo. 1967 May;21(5):612-5.

No Abstract available

[Medical study of Nissol]

[Article in Japanese]

Tsuboi S.

PMID: 4865226 [PubMed - indexed for MEDLINE]


 
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