Summary of Toxicity Studies With Pyridaben
Hajime IGARASHI and Satoru SAKAMOTO
Regulatory Affairs, Agricultural Division, Nissan Chemical Industries, Ltd.
(Received August 20, 1994)

DESCRIPTION OF PYRIDABEN
Pyridaben, a pyridazinone derivative, is a new acaricide and insecticide discoveredby Nissan Chemical Industries, Ltd. for control of mites and some insects such as
white flies, aphids and thrips. Pyridaben has been developed for application to fruits
as a 20% wettable powder (WP) and for vegetables, tea and ornamentals as a 20%
suspension concentrate (SC) in Japan. Technical information given in this summary
was used to register pyridaben as Sanmite® in Japan.
Pyridaben has the following chemiclal and physical properties.
Common name : Pyridaben
Code No. : NC-129, NCI-129
Chemical name : 2-tert-Butyl-5-(4-tert-butylbenzylthio)-4-chloropyridazin3(2H)-one
Chemical structure :
CH3
H3C

O

N
CH3 N

Cl
SCH2

CH3
CH3
CH3

Molecular formula : C19H25ClN2OS

Specific gravity : d20 1.2

Molecular weight : 364.9

Melting point : 111-112˚C

Physical state : White crystalline solid

Vapor pressure : 1.9 x 10-6 mmHg (20˚C)

Solubility (g/1, 20˚C) : Water, 1.2 x l0-5; acetone, 460; acetonitrile, 69;
ethyl acetate, 400; dichloromethane, 1530; n-hexane, l0Partition coefficient (n-octanol/water) : log P ow = 6.37 (23˚C)
Stability : In water, stable at pH 4-9; to heat, no decomposition at 50˚C for 3
months; to light, relatively unstable; in organic solvents, stable in most organic solvents.

ACUTE TOXICITY STUDIES
Pyridaben has been studied for acute toxicity in different species and via various
routes. The median lethal doses are summarized in Table 1 and the results show
pyridaben to be of moderate to low toxicity. No mortality occurred and there wereminimal signs seen in percutaneous tests. On the other hand, mortality occurred mostfrequently within 1 day of dosing in oral and intraperitoneal tests. Major clinicalsigns observed were decreased spontaneous motor activity, abnormal gait,prone/recumbent posture, arched back posture, eye closing, piloerection and bradypnea.
The surviving animals rapidly returned to normality. In the inhalation test, there weremortalities within 1 day after exposure and clinical signs were also reversible insurviving animals.

Table 1 Acute toxicity studies with technical material.
Testing facility(Reporting year)

Species Route

Sex

LD50
(mg/kg)Rat

Orala)

M
F

1100
570

Preclinic Research Laboratories, Central
Institute for Experimental Animals (1990)

Rat

Orala)

M
F

1350
820

Life Science Research, Ltd. (1989)

Mouse

Orala)

M
F

424
383

Preclinic Research Laboratories, Central
Institute for Experimental Animals (1990)

Mouse

Orala)
Dermal253.1
205.3> 2000> 2000> 2000> 200067.6
58.1
0.66d)
0.62d)

Nissan Chemical Industries, Ltd. (1989)

Rat

M
F
M
F
M
F
M
F
M
F

Rabbit Dermal
Rat

Intraperitonealb)

Rat

Inhalationc)a)An-Pyo Center (1986)
Life Science Research, Ltd. (1987)
Nissan Chemical Industries, Ltd. (1988)
The Institute of Environmental
Toxicology (1987)

The test material was suspended in 1 % w/v aqueous carboxymethylcellulose solution.
The test material was suspended in corn oil.
c)
A pulverized mixture of 100 parts of the test material and 8 parts (w/w) of white carbon wasused.
d)
The LC50 (mg/1) was determined in dust aerosol study by whole body exposure.
b)

PRIMARY DERMAL IRRITATION STUDY
The potential of pyridaben to cause inflammatory or corrosive changes upon firstcontact with skin was assessed by semi-occluded application of 0.5 g of the test
material to the shaven dorsa of 6 female New Zealand White rabbits for 4 hr. Dermal
reactions were assessed 1, 24, 48 and 72 hr after removal of the dressings, according
to the method of Draize. No dermal irritation responses were observed in any animal
at any time during the 72 hr observation period. Pyridaben was classified as non-irritantto skin.
(Life Science Research, Ltd., 1986)

PRIMARY EYE IRRITATION STUDY
The potential of pyridaben to cause damage to conjunctivae, iris or cornea wasassessed in 6 female New Zealand White rabbits, each subject to a single ocularinstillation of 0.1 g of test material. Ocular reactions were examined 1, 24, 48 and 72
hr after treatment, according to the modified method of Draize. A well defined orslight injection of the conjunctival blood vessels and a slight chemosis and oculardischarge were observed. These signs of mild irritation disappeared 72 hr after treatment.
Ocular effects were largely confined to slight reversible conjunctivitis and pyridaben
can be considered to be non-irritant to the eye.
(Life Science Research, Ltd., 1986)

DERMAL SENSITIZATION STUDIES
1. Maximization Test
The sensitizing potential of pyridaben was evaluated in accordance with Magnusson
and Kligman method using female Dunkin-Hartley guinea pigs. Induction doses ofpyridaben mixed with prepared Freund's Complete Adjuvant (FCA/sterile water), as
well as the test substance in peanut oil and the prepared FCA alone, were injected
intradermally on day zero in the clipped shoulder region of 20 female Dunkin-Hartley
guinea pigs. The concentration of the test substance was 5% w/v. A negative vehicle
control group of 20 animals was treated in the same manner as the test group, except
no test substance was administered. A closed patch topical application dose of 25%
w/w test substance in petrolatum or petrolatum alone was applied to the re-clipped
same shoulder area on day 7. The exposure period was 48 hr. On day 21 , all test andnegative control animals were challenged by 24 hr occluded topical application of
2.5% w/w pyridaben in petrolatum and petrolatum alone to the clipped flank. Dermalresponses to the challenge procedure were assessed 24, 48 and 72 hr after challenge
patch removal. There were no positive signs of erythema (i.e., score l) and no
edema observed at the test sites of any animal in the negative control or test substancegroup. Positive control test was conducted within 6 months of this study.
Pyridaben did not produce any skin reaction and can be considered to be
non-sensitizing under the conditions of this test.
(International Research and Development Corporation, 1987)

2. Modified Buehler Test
The potential of pyridaben to cause delayed contact hypersensitivity in guinea
pigs was assessed by a modified version of the method of Buehler. The shaven left
flanks of 10 male and 10 female Dunkin-Hartley guinea pigs were subjected to 6 hr
occluded topical application of 50% w/v pyridaben in paraffin oil on day l, 8 and 15.
On day 29, all test and control animals were challenged by 6 hr occluded topicalapplication of 50 and 10% pyridaben in paraffin oil to the shaven right flank.
Dinitrochlorobenzene (DNCB) was used as a positive control. Dermal responses tothe challenge procedure were assessed approximately 24 and 48 hr after applicationof the occlusive dressings. Challenge application of 50 and 10% w/v pyridaben inparaffin oil caused a significant reaction (faint erythema or more marked response) in
2 control and 2 test animals. These changes were considered to reflect an irritation
reaction rather than hypersensitivity response. Challenge application of 0.l% w/v
DNCB caused a significant reaction in 5 of the 10 positive control animals. No
response was observed in the irritation controls. It is concluded that, under conditionsof this study, repeated occluded dermal applications of pyridaben did not causedelayed contact hypersensitivity in guinea pigs. (Life Science Research, Ltd., 1990)

SUBACUTE AND SUBCHRONIC STUDIES
1. 13-Week Feeding Study in Rats
Pyridaben was administered continuously, via the diet, to groups of 10 male and
10 female CD rats at concentrations of 0, 30, 65, 155 or 350 ppm for 13 weeks. An
additional 10 animals per sex were assigned to the highest and control groups for a
4-week reversibility period. There were no dosage-related clinical signs or mortality.
There was a dosage-related effect on bodyweight gain, food consumption and food

conversion efficiency in males and females receiving 155 or 350 ppm. In females
receiving 65 ppm, the bodyweight gain and the efficiency of food conversion werealso affected. Following withdrawal of treatment, the bodyweight gain and the efficiency
of food conversion of animals which had previously received 350 ppm were significantly
higher than in the respective control group. No evidence of toxicologically significant
effects of treatment was noted at the ophthalmoscopic and haematological examinations.
A number of changes were noted in blood chemistry parameters and organ weights inanimals receiving 155 and 350 ppm, but these changes were considered to be secondary
to the nutritional state and growth performance. No dosage-related microscopic changes
were observed. The no-effect level was considered to be 30 ppm (equivalent to meanachieved dosages of 2.30 and 2.64 mg/kg/day, for males and females respectively).
(Life Science Research, Ltd., 1988)

2. 13-Week Feeding Study in Mice
Pyridaben was administered continuously, via the diet, to groups of 12 male and
12 female CD-1 mice at concentrations of 0, 30, 90, 270 or 810ppm for 13 weeks.
There were no dosage-related clinical signs or mortality. Lower bodyweight gain andfood utilization efficiency were noted for males receiving 90 ppm or greater and forfemales receiving 270 or 810 ppm and at concentrations above 270 ppm food andwater consumptions were reduced. Ophthalmoscopic examination revealed no evidenceof response to treatment. At higher doses some haematological parameters wereslightly affected and blood chemistry investigation revealed a number of differences
between control and treated animals. These were considered to be associated with theeffect on nutritional status at these dosages. In association with the marked effect on
bodyweight, the bodyweight-relative liver weight was increased in animals receiving
270 or 810 ppm. This was not associated with any microscopic changes, and was notconsidered to be of toxicological significance. No-effect level was 30 ppm (equivalent
to mean achieved dosages of 4.07 and 4.92 mg/kg/day for males and females
respectively).
(Life Science Research, Ltd., 1988)

3. 13-Week Oral Study in Dogs
Pyridaben was administered orally in gelatin capsule to groups of 4 male and 4
female dogs at dosage levels of 0, 0.5, 1, 4 or 16mg/kg/day for 13 weeks. There were
no effects on survival. Salivation was seen in some dogs at the upper 2 dose levels.

Slight emesis was seen in several animals at 16 mg/kg/day and some females at 4
mg/kg/day. Decreased bodyweight gain was noted for males at the dose levels of 16
and 4 mg/kg/day; bodyweight loss was recorded for one animal in each of thesegroups. There was no dosage-related decrease in food consumption and there was noclear effect on food conversion efficiency. No changes were observed at
ophthalmoscopic examination, and the results of haematology, blood chemistry andurinalysis showed no treatment-related effects. There were no test substance-related
effects seen macroscopically, on organ weights or on microscopic examination. The
no-effect level can be considered to be 1 mg/kg/day.
(International Research and Development Corporation, 1989)

4. 4-Week Inhalation Study in Rats
Pyridaben (92.6% active ingredient, 7.4% white carbon) was administered byinhalation as a respirable dust to groups of 5 male and 5 female CD rats at concentrationsof 1, 3 or 10 mg/m3 under whole body exposure conditions. The exposure time was 6
hr per day, 5 days per week over a 4 weeks period. An additional 5 animals per sex
were assigned to the highest and control groups for a 2-week reversibility period.
There were no effects on survival. Clinical signs during exposure included a slightincrease among the treated animals of dried red nasal discharge, and similar signs
were noted after exposure at 3 and 10 mg/m3. These signs abated during the recovery
period. Lower bodyweight gain and food consumption were recorded for animals
exposed at the highest level but only during the first week of exposure. Haematology
evaluations were generally unremarkable. Clinical chemistry results showedsignificantly decreased serum glutamic pyruvic transaminase (SGPT) and albumin at
the highest exposure. These effects were slight at 3 mg/m3 and reversible. There wereno macroscopic or microscopic findings seen. Some organ weights were decreased
but in the absence of supporting evidence from microscopic findings or clinicallaboratory evaluations, no explanation for this effect was apparent. The no-effectlevel was considered to be 1 mg/m3.
(Bio-dynamics, 1989)

CHRONIC TOXICITY AND ONCOGENICITY STUDIES
1. 104-Week Feeding Study in Rats
Pyridaben was administered continuously, via the diet, to groups of 50 male and50 female CD rats comprising the oncogenicity phase at concentrations of 4, 10, 28
or 80 ppm for 104 weeks. A further 35 male and 35 female rats were assigned to eachof the groups treated at 4, 10 or 28 ppm, to the controls, and to an additional groupwhich received 120 ppm. These animals comprised the toxicity phase. Each group in
this toxicity phase was composed of 23 males and 23 females scheduled for sacrifice
after 104 weeks of treatment (terminal sacrifice) and 12 males and 12 females whichwere sacrificed after 53 weeks of treatment (interim sacrifice). These rats also provided
blood and urine samples for clinical pathology investigation at 12, 23 and 50 weeks(interim animals), and at 76 and 104 weeks (terminal animals). The appearance andbehaviour, mortality and cause of death of animals of the toxicity and oncogenicity
phases were unaffected by treatment with pyridaben. Bodyweight gain and foodconsumption in rats which received 80 or 120 ppm were significantly lower thanthose of their controls. The efficiency of food conversion over the first 14 weeks oftreatment was also reduced in the both sexes at 80 and 120 ppm. No evidence oftreatment-related change was noted at the ophthalmoscopic, haematological, clinicalchemical, macroscopic or microscopic investigations. There was no evidence of any
oncogenic potential for pyridaben in this study. It was considered that the changes inrats receiving 80 or 120 ppm were toxicologically significant and that the maximum
tolerated dosage level was therefore 80 ppm. A specific target organ was not, however,identified. The no-effect level was considered to be 28 ppm (equivalent to meanachieved dosages of approximately 1.1 and 1.5 mg/kg/day for males and females,
respectively) .
(Life Science Research, Ltd., 1990)

2. 78-Week Feeding Study in Mice
Pyridaben was administered continuously, via the diet, to groups of 52 male and52 female CD-1 mice at concentrations of 2.5, 8, 25 or 80 ppm for 78 weeks. Another12 animals per sex in each dose group were sacrificed after 53 weeks of treatment.
The appearance and behaviour of animals were unaffected by treatment with pyridaben.
A slightly higher incidence of mortality was noted in males which received 80 ppm
than the controls. The overall bodyweight gain of mice which received 80 ppm wassignificantly lower than that of their controls. This was associated with the slightly
low food consumption and reduced food utilization efficiency noted for these animals.
A slight impairment in food utilization efficiency was also noted for males which
received 25 ppm. Haematological investigations after 52 and 78 weeks of treatment

revealed no changes that could be clearly related to treatment. Macroscopic examinationand organ weights revealed no changes that could be clearly related to treatment.
Microscopic examination revealed a low incidene of distended coagulation glands inmales of the terminal phase which had received 80 ppm, when compared with therespective control. No evidence of any oncogenic potential of pyridaben was noted inthis study. Evidence of treatment-related effects was noted in mice which received 25
or 80 ppm and the maximum tolerated dosage was considered to be within the rangeof these concentrations. A specific target organ was not, however, identified. The noeffect level for mice was considered to be 8 ppm (equivalent to mean achieved
dosages of 0.81 and 0.91 mg/kg/day for males and female.
(Life Science Research, Ltd., 1990)

3. 53-Week Oral Study in Dogs
Pyridaben was administered orally in gelatin capsule to groups of 4 male and 4
female dogs at dose levels of 0, 1, 4, 16 or 32 mg/kg/day for 1 year. There were noeffects on survival. Salivation and emesis were seen in the treated groups, but theincidence was low and not considered to be related to treatment. Bodyweight gains in
all treated groups were slightly lower than in the control group, but the differencesfrom control were statistically significant. Individual animals receiving 4 mg/kg/day
or greater showed thinness, but there was no clear relation to dosage. Food consumption
and food conversion efficiency values were variable. There were no test substancerelated effects on ophthalmoscopy. There were no apparent treatment related findings
for haematology, blood chemistry or urinalysis values. Macroscopic changes wereseen only in one female receiving 32 mg/kg/day and histopathological examination of
the animal revealed hepatocellular hypertrophy. In conclusion, the bodyweight
depression in the 1 mg/kg/day group was slight and this is considered to be the noadverse effect level.
(International Research and Development Corporation, 1990)

REPRODUCTIVE STUDY IN RATS
Pyridaben was administered continuously, via the diet, to groups of 25 male and25 female CD rats at concentrations of 0, 10, 28 or 80 ppm throughout two successive
generations. Both sexes (F0 generation) received 14 weeks treatment before pairingand 25 male and 25 female offspring were selected to form the F1 generation. F1

animals were also mated to produce F2 litters. The bodyweight gain of rats receiving
80 ppm was clearly reduced, although that of females showed a recovery duringlactation. There was also a slight reduction in food consumption. Reproductive
performance was unaffected. Necropsy of the F0 Parents, F 1 adults and F2 offspring
revealed no macroscopic changes that were considered to be related to treatment.
Although the weights of reproductive organs were slightly increased at 80 ppm,
microscopic examination of the reproductive organs revealed no signiflcant findings.
The maximum tolerated level was 80 ppm. The no effect level was considered to be
28 ppm (equivalent to mean achieved dosages of 2.02 and 2.50 mg/kg/day for F0
males and females, respectively, and 2.37 and 2.80 mg/kg/day for F1 males andfemales, respectively).
(Life Science Research, Ltd., 1990)

TERATOLOGY STUDIES
1. RatPyridaben was administered by gavage to groups of 22 pregnant CD rats at doselevels of 2.5, 5.7, 13 or 30 mg/kg/day from day 6 to day 15 of gestation inclusive.
Groups receiving 13 or 30 mg/kg/day showed significant reductions in maternal
weight gain during the treatment period. There was no effect at 2.5 and 5.7 mg/kg/day.
Food consumption during the treatment period showed a dose-related reduction at 13
and 30 mg/kg/day, but was unaffected at lower dose levels. There was no effect onlitter size or on pre- and post-implantation loss. Foetal and placental weights werereduced at 30 mg/kg/day and as a secondary effect a slightly retarded foetal development
was seen at this level. A slight increase in the number of small foetuses was recorded
and there were indications of visceral and skeletal immaturity, but no morphologicalchanges were recorded that were considered to be related to treatment. There was noevidence of teratogenic effect in rats. The no-effect level was considered to be 5.7
mg/kg/day for maternal response, and 13 mg/kg/day for foetal response.
(Life Science Research, Ltd., 1988)

2. Rabbit
Pyridaben was administered by gavage to groups of at least 12 pregnant New
Zealand White rabbits at dose levels of 1.5, 5 or 15 mg/kg/day from day 6 to day 19
of gestation inclusive. Pregnant rabbit receiving 15 mg/kg/day showed a transient,marked loss of bodyweight gain during the early part of the dosing period which was
followed by a rapid, but partial recovery. This was accompanied by reduced foodconsumption and faecal output. Abortion was observed at the highest level. No consistentfindings upon foetal development or survival in vitro that were attributable to treatment
were recorded. There was no evidence of teratogenicity in rabbits. The no-effect level
was considered to be 1.5 mg/kg/day for maternal response and 15 mg kg/day for
foetal response.
(Life Science Research, Ltd., 1988)

MUTAGENICITY STUDIES
Pyridaben has been evaluated for mutagenic potential based on 3 endpoints asshown in Table 2. Pyridaben did not induce point mutations in bacterial or mammaliansystems, tests for chromosomal aberration in vitro and micronucleus in vivo were
negative, and pyridaben exhibited no effect on DNA damage in bacterial systems.

Table 2 Mutagenicity studies.
MethodAmes test

Species,cell type

Test conditions

Results

Testing facility(Reporting year)

Salmonella typhimurium TA98, 100,
1535, 1537
Escherichia coli
WP2 uvrA

Without S-9mix
With S-9mix

Negative
Negative

Life Science
Research, Ltd.
(1986)

Without S-9mix
With S-9mix

Negative
Negative

Point mutationin mammaliancell system

Chinese hamster
V79 cells

Without S-9mix
With S-9mix

Negative
Negative

Life Science
Research, Ltd.
(1989)

Chromosomal
aberrationin vitro

Chinese hamsterlung (CHL) cells

Without S-9mix
With S-9mix

Negative
Negative

Nissan Chemical
Industries, Ltd.
(1988)

Micronucleus
test in vivo

Male and female
mice

Mortalities/clinical Negative
signs at thehighest dose

Nissan Chemical
Industries, Ltd.
(1988)

Lethal DNA
damage inE. coli

Escherichia coli
WP2, WP67,
CM871

Without S-9mix
With S-9mix

No incidence Life Scienceof lethal DNA Research, Ltd.
damage(1986)

Rec-assay

Bacillus subtilis
M45 (rec-),
H17 (rec+)Without S-9mix
With S-9mix

Negative
Negative

Nissan Chemical
Industries, Ltd.
(1988)

RAT METABOLISM STUDIES
Absorption, distribution, excretion and metabolism in rats were studied using
pyridaben labeled with 2 separate 14C-labels, in either the pyridazinone or the benzyl
ring. When a single dose of 3 mg/kg was orally administered to rats, elimination ofpyridaben was rapid and almost complete within 96 hr. Absorption was between 38
and 46% of the dose administered and more than 80% of the absorbed pyridaben,labeled in either position, was excreted in the bile. The blood concentration was
extremely low (maximum 0.04 ppm) and there were no significant residues in tissues.
The pharmacokinetics of both a single oral dose of 30 mg/kg and repeated oral doseof 3 mg/kg was very similar to that of a single oral dose of 3 mg/kg in rats. Pyridaben
was extensively metabolized to more than 30 metabolites, most of which were lessthan 3% of the dose. Pyridaben was metabolized by oxidation of the tert-butyl groupand cleavage of the sulphur bond. A small amount of the cleavage moieties wereconjugated with glucuronic acid or mercapturic acid.
(Life Science Research, Ltd., 1989 and Nissan Chemical Industries, Ltd., 1989)

PHARMACOLOGICAL STUDIESThe influence of pyridaben on body functions was examined in mice, rats, guinea
pigs, rabbits and dogs. Since pyridaben is extremely insoluble in water, the test
substance was suspended with 1 % w/v sodium carboxymethyl cellulose and intragastrically administered in the case of experiments in vivo. In the in vitro experiments
on isolated organs or blood etc., pyridaben was dissolved in 99.5% ethanol. Pyridaben
had diarrhoea-producing effect at relatively low doses (3 to 10mg/kg). Suppression offood consumption, hypothermia, bradycardia, decrease of urine excretion volume andbradypnoea were precipitated from the minimum acute toxic dose or near that dose(at 30 mg/kg or more for mice and 100 mg/kg or more for rats). At 300 mg/kg or
more, greater effects were observed, and the central nervous and cardiovascularfunctions were markedly suppressed. However, no influence was observed on motor
functions such as motor coordination, muscle strength or transmission at theneuromusceular junction even at doses causing severe toxic signs. No effects wereobserved on sensory and digestive organ function, on coagulation function in the
blood at such dose levels, nor did it precipitate haemolysis. Pyridaben did not directly
influence male or female reproductive organs. Emergency measures for the acutetoxicity of pyridaben have been examined in rats, and gastric lavage in the early stage

was found to be highly effective to prevent acute oral toxicity. Measures to treat
diarrhoea which develops at relatively low doses of pyridaben have also been examined.
In rats, loperamide produced marked antidiarrhoeal effects when administered prior
to pyridaben and even when administered afterwards. No specific antidote for acutetoxicity of pyridaben has been found to date.
(Preclinical Research Laboratories, Central Institute for Experimental Animals,
1987, 1988, andPreclinical Research Laboratories, Inc., 1992)

FORMULATION TOXICITY STUDIES
1. A cute Studies
Acute studies were conducted on 20% WP and 20% SC formulations. The results
are shown in Tables 3 and 4.
2. Primary Dermal Irritation Studies
The studies were conducted in accordance with Japanese MAFF guideline and themethod of Draize. Neither formulation had any primary irritating potential on theskin of rabbits.
(The Institute of Environmental Toxicology, 1 989)
3. Primary Eye Irritation Studies
The studies were conducted in accordance with Japanese MAFF guideline and themethod of Draize. The WP formulation caused slight to mild irritation of the eye
mucosa of rabbits. The SC formulation did not cause eye irritation in the rabbits.
(The Institute of Environmental Toxicology, 1 989)
4. Dermal Sensitization Studies
4.1. Maximization test
The studies were conducted in accordance with the maximization method. Bothformulations had moderate sensitizing potential in guinea pigs.
(The Institute of Environmental Toxicology, 1 989)
4.2. Modified Buehler test
The studies were conducted in accordance with a modified version of the methodof Buehler. Neither formulations elicited a de-layed contact hypersensitivity in guinea
pigs.
(Life Science Research, Ltd., 1 990)

Table 3 Acute studies with 20% Sanmite® WP.
Species Route
Rat

Sex

Testing facility(Reporting year)

LD50(mg/kg)

M 3350The Institute of EnvironmentalToxicology
F 3020(1989)
Mouse Oral
M 2911The Institute of Environmental Toxicology
F
2600(1989)
Rat
Dermal
M > 2000
The Institute of Environmental Toxicology
F > 2000(1989)
Rat
Inhalation M
1.68a) The Institute of Environmental Toxicology
F
1.44a)(1989)a)Oral

The LC50 (mg/l) was determined in dust aerosol study by whole body exposure.

Table 4 Acute studies with 20% Sanmite® SC.
Species Route
Rat

Testing facility(Reporting year)

LD50(mg/kg)

M 3090F
3162
Mouse Oral
M 2198F
2042
Rat
Dermal
M > 2000
F > 2000
Rat
Inhalation M
0.95a)
F
0.23a)
a)

Oral

Sex

The Institute of Environmental Toxicology(1989)The Institute of Environmental Toxicology(1989)The Institute of Environmental Toxicology(1989)The Institute of Environmental Toxicology(1989)The LC50 (mg/l) was determined in mist aerosol study by whole body exposure.

SUMMARY
The safety of pyridaben for users and consumers can be summarized as follows.
The acute studies with technical material showed pyridaben to have moderate to low
toxicity. Pyridaben caused no irritation of skin and eye and no contact sensitization.
Pyridaben did not show mutagenic potential, was not oncogenic in rats and mice, did
not affect reproductive performance in rats and was not teratogenic in rats and rabbits

although decreases in bodyweight and food consumption were seen in teratology
studies. In addition, the main effects seen in subchronic to chronic toxicity studies
were the reduction of body-weight gain, depression of food consumption and impairmentof food conversion efficiency. A specific target organ, however, was not identified.
The NOEL's for chronic studies in rats, mice and dogs on a mg/kg bodyweight basis
were comparable. The minimum value of the maximum no-effect level was 8 ppm inthe oncogenicity study of mice. In conclusion, there were no adverse toxicologicalfindings based on the above studies. Sanmite® WP and Sanmite® SC containing 20%
pyridaben were registered by Japanese MAFF in 1991 as an acaricide and insecticide
for various fruits as well as for tea. Pyridaben and its formulations were specified by
Japanese MHW as harmful substances because of the acute toxicity data. However,the products are not considered to be a cause for concern in the safety of users andconsumers provided they are used carefully and in accordance with the establishedstandard for safe use.

Contact
Regulatory Affairs, Agricultural Division, Nissan Chemical Industries, Ltd., KowaHitotsubashi Building, 3-7-1, Kanda-Nishiki-cho, Chiyoda-ku, Tokyo 101, Japan

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