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]