Shaped much like a loose fist and tucked
under the left side of the diaphragm, the spleen is the
most ignored and misunderstood of all organs. After all,
we read numerous times that someone in an automobile accident
or a fight has a ruptured spleen so the spleen is removed
(splenectomy) and life goes on.
What we don't read about is that splenectomized people later
have problems with overwhelming bacterial infections of
the blood (sepsis). What does this suggest as the function
of the spleen?
The spleen receives blood from an artery off of the aorta.
After passing through an intricate meshwork of tiny blood
vessels, the blood continues to the liver. The blood vessels
of the spleen are surrounded by nests of B lymphocytes -
mainly of the memory type. As the blood slowly moves through
the spleen, it is monitored by T-cells for any non-self
invaders. If some suspicious cell or molecule is detected,
it is presented to the resident B-cells for a match to an
appropriate memory B-cell. Once a matching B-cell is activated,
the cell divides rapidly and begins producing antibodies
directed against the invading antigen.
The spleen blood vessels are also lined with macrophages
which swallow and digest debris in the blood such as worn
out red blood cells and platelets. In a disease such as
mononucleosis, the macrophages in the spleen become overactive
and trap a higher number of white blood cells. In the process,
the spleen becomes swollen and may even rupture. Ref:
For more detailed information
on the spleen go to: http://www.bartleby.com/107/278.html
use of high doses increases the likelihood that potentially
significant toxic effects will be identified. Findings of
adverse effects in any one species do not necessarily indicate
such effects might be generated in humans. From a conservative
risk assessment perspective however, adverse findings in
animal species are assumed to represent potential effects
in humans, unless convincing evidence of species specificity
Food and Agricultural Organization of the United Nations
This is not an exhaustive list.
When time allows more information will be added.
- Acaricide, Insecticide - CAS No.
STUDIES 1. Rats Study by Dietary Repeat Dose for 90 Days Followed
by a 28-Day Recovery Period Group of 20 male and 20 female CD
(SD) rats were fed diet containing 0, 30, 100 or 300 ppm of acrinathrin
for 90 days... Other microscopic findings observed were lymphoid
deletion in the spleen and thymus
in 5 females of the 300 ppm group and medullar [marrow] atrophy
in 2 females of the 300 ppm group... The No Observed Effect Level
(NOEL) for this study was considered to be 30 ppm (male: 2.4 mg/kg/day;
female: 3.1 mg/kg/day) (Centre International de Toxicologie, 1988).
Ref: Summary of Toxicological Studies on
Acrinathrin Market Development, AgrEvo Japan Limited (Received
January 26, 1998 ; Accepted March 20, 1998).
(Benefin) - Herbicide - CAS
"Benefin: 13-Week Oral
Toxicity Study in Beagle Dogs", (D.W. Dalgard, Hazleton Washington,
HWA 174-135, 12/28/93). Benefin, purity 95.8%, administered via
capsule at concentrations of 0, 5, 25, 125 mg/kg/day to 4 Beagle
dogs/sex/group for 13 weeks. Emesis (compound colored) was slightly
increased at all dose levels for females and for mid and high
dose males. Liver weights was increased for high dose males; and
the incidence of hepatocellular hypertrophy was increased for
high dose males and females. Increased incidence
of hemosiderin pigment was observed in the liver at the
high dose and the spleen at mid and
high dose levels. NOAEL = 5 mg/kg/day. Acceptable (Kishiyama,
J., and P. Iyer, 5/12/98).
Ref: Summary of Toxicology Data for Benefin.
California EPA, Department of Pesticide Regulation, Medical Toxicology
Herbicide - CAS No. 134605-64-4
Some excerpts from Table 2.--Subchronic,
Chronic, and Other Toxicity
Butafenacil; Pesticide Tolerance. Final Rule.
Federal Register. September 19, 2003.
oral (capsule) toxicity in non- rodents (dog)
= 200 mg/kg/ day M/F LOAEL = 1,000 mg/kg/ day M/F, based
on decreases in MCV and MCH in males; increases in RDW, HDW,
platelets and triglycerides in males; and hemosiderosis
in spleen and
liver and extramedullary
hematopoiesis the spleen in males
studies - [870.7485]
on porphyrin profile in rats; treatment induced porphyria,
consisting of accumulation of selected porphyrins in the
and plasma and
increased excretion in urine and feces
studies - [870.7485]
substance interferes with heme biosynthesis
in rats, as evidenced by dose- dependent, pronounced porphyria
in the liver, spleen,
and plasma; increased porphyrin excretion, and decreased activity
of various isoenzymes of the hepatic microsomal cytochrome
- Herbicide - CAS No. 128639-02-1
-- Short-Term Studies
In mice fed carfentrazone-ethyl at concentrations up to 20000
ppm for 28 days, decreased defecation was observed at 14000 and
20000 ppm. Blood haemoglobin concentration
was reduced in females at concentrations ¥ 4000 ppm and mean corpuscular
volume and mean corpuscular haemoglobin were reduced at the highest
concentration. Liver weight was increased in both males
and females at concentrations ¥ 8000 ppm and spleen
weights were reduced in males at the highest concentration.
-- Short-Term Studies... The body weight
of dogs (1/sex) given 1000 mg/kg bw/day carfentrazone-ethyl in
capsules for 14 days was reduced; food consumption of the female
also reduced. Mean corpuscular haemoglobin and mean corpuscular
volume were reduced. In the female, haematocrit was also reduced
with white blood cell counts and neutrophils increased. The female
had a pale kidney and the male had
reduced relative spleen and testes weights.
-- Short-Term Studies... In mice fed up to 20 000 ppm dietary
carfentrazone-ethyl for 90 days, a pink/brown staining of the
litter tray was observed at concentrations ¥ 14000 ppm. Although
red blood cell counts were increased in males at concentrations
¥ 14000 ppm, mean corpuscular volume and mean corpuscular haemoglobin
were reduced in males at concentrations ¥ 8000 ppm and in females
at concentrations ¥14000 ppm. In addition, mean corpuscular haemoglobin
concentration was reduced in females at the highest concentration.
Aspartate aminotransferase and alanine aminotransferase activities
were increased at 20000 ppm and albumin was increased in females
at concentrations ¥ 1400 ppm. Liver weights were increased at
concentrations ¥ 8000 ppm and spleen
weights were decreased in all treated females... A
NOEL was not established for this study, because a reduction in
spleen weights was observed in females at the lowest concentration
tested (1000 ppm, equivalent to 150 mg/kg bw/day)
April 2000 - Australia. Evaluation of the new active CARFENTRAZONE-ETHYL
in the product AFFINITY 400 DF HERBICIDE. National Registration
Authority for Agricultural and Veterinary Chemicals. NRA Ref.
available at http://www.apvma.gov.au/publications/prscar.pdf
Chemosterilant, Insecticide - CAS No. 35367-38-5
p (or 4-chloraniline) is a metabolite of Diflubenzuron.
In 2006, USEPA classified chloroaniline, p as
a "Group B2 -- Probable Human Carcinogen." "Spleen
hemangiosarcomas & osteosarcomas) (M); Adrenal
(pheochromocytomas (M & F); F344/N rats. Hepatocellular
adenomas/carcinomas (M); Hemangiosarcomas
in spleen and/or liver (M) in B6C3F1 mice."
26, 2006 . Chemicals Evaluated for Carcinogenic Potential by the
Office of Pesticide Programs. From: Jess Rowland, Chief Science
Information Management Branch Health Effect Division (7509C) Office
of Pesticide Programs, USEPA.
Effects attributed to diflubenzuron metabolites : PCA and CPU
-- In a 28-day feeding study technical grade diflubenzuron was
administered in the diet to rats at dose levels of 0 (control),
800, 4000, 20000 or 100000 ppm (equivalent to 0, 40, 200, 1000
or 5000 mg/kg/day). Methemoglobin was increased in males at all
dose levels and in females at dose levels of 200 mg/kg/day and
higher. Sulfhemoglobin was increased in all treated males and
females. At 5000 mg/kg/day males and females experienced decreased
erythrocyte counts, packed cell volumes and hemoglobin. Dose-related
increases in spleen weights at all dose levels and in liver
weights at dose levels of 200 mg/kg/day and higher were also observed.
No NOEL was established in this study since treatment-related
effects were observed at 40 mg/kg/day, the lowest dose level tested.
The LEL is 40 mg/kg/day, based on increased methemoglobin in males,
increased sulfhemoglobin in males and females and increased spleen
weights in males and females. (MRID 00070018)
-- At all dose levels, histopathological examinations indicated
dose related increases of hemosiderosis
and congestion of the spleen, hemosiderosis and chronic
hepatitis of the liver, and mild erythroid hyperplasia of the
bone marrow... Male rats at 6 and 18 mg/kg/day and female rats
at 18 mg/kg/day had blue extremities indicative of cyanosis. Histopathological
examinations indicated non-neoplastic treatment-related effects
in the spleen, liver, bone marrow
and adrenal gland... (National Toxicology Program (NTP) Report
No. 351; July, 1989)..."
Ref: US EPA RED. August 1997.
-- A 91-week carcinogenicity
study in CFLP mice was conducted at doses of 0, 16, 80, 400, 2,000,
and 10,000 ppm. There was no increase in
tumor incidence as a result of diflubenzuron administration. Target
organ effects included: Increased methemoglobin and sulfhemoglobin
values, Heinz bodies, increased liver and spleen weight,
hepatocyte enlargement, and vacuolation,
extramedullary hemopoiesis in the liver and spleen, siderocytosis
in the spleen and
cells. A NOAEL for these effects was 16 ppm (2 mg/kg/day).
- PCA [p-chloroaniline; a metabolite of
Diflubenzuron] was administered 5 days/week by oral gavage,
as a hydrochloride salt in water, to male and female F344/N rats
at doses of 0, 2, 6, or 18 mg/kg/day. Mean body weights of dosed
rats were generally within 5% of those of controls throughout
the study. High dose animals generally showed mild hemolytic anemia
and dose-related methemoglobinemia. Non- neoplastic lesions seen
were bone marrow hyperplasia, hepatic hemosiderosis, and splenic
fibrosis, suggesting treatment-related effects on the hematopoietic
system. Adrenal medullary hyperplasia was observed in high dose
female rats. The incidence of uncommon sarcomas
of the spleen was significantly increased in high dose male rats.
A marginal increase in pheochromocytomas of the adrenal gland
was seen in high dose male and female rats. It was concluded that,
under the conditions of this 2-year gavage study, there was clear
evidence of carcinogenic activity of PCA hydrochloride for male
F344/N rats and equivocal evidence of carcinogenic activity of
PCA hydrochloride for female F344/N rats.
-- PCA [p-chloroaniline;
a metabolite of Diflubenzuron] hydrochloride was administered
5 days/week by oral gavage to male and female B6C3F1 mice at doses
of 0, 3, 10, or 30 mg/kg/day. Mean body weights of high dose male
and female mice were generally within 5% of those of controls
throughout the study. The incidence of hepatocellular adenomas
or carcinomas (combined) was increased in a non-dose-dependent
manner in treated male mice. Metastasis of carcinoma to the lung
was seen in the high dose group. An increased incidence of hemangiosarcomas
of the liver or spleen was seen in high dose male mice.
It was concluded that, under the conditions of this 2-year gavage
study, there was some evidence of carcinogenic activity of PCA
hydrochloride for male B6C3F1 mice and no evidence of carcinogenic
activity of PCA hydrochloride for female B6C3F1 mice.
-- In addition to PCA,
4-chlorophenylurea (CPU) is also
a potential minor metabolite of diflubenzuron. By association
with PCA, EPA has concluded that CPU has carcinogenic potential
and the same carcinogenic potency (q\1\*) as PCA. In the
NTP report of the PCA bioassay, it is proposed that PCA undergoes
N-hydroxylation to form the corresponding N-hydroxylamine [[Page
64827]] metabolites; N-hydroxylation of aromatic amines is a well
know mechanism of aromatic amine carcinogenicity. This metabolite,
or proximate carcinogen, is then conjugated to form the ultimate
carcinogen capable of ionizing and reacting with DNA to form adducts
which result in splenic tumor formation.
An alternate mechanism involving toxicity resulting in erythrocyte
damage, splenic scavenging, hemorrhage,
hyperplasia and fibrosis and ultimately splenic tumor formation
is also proposed, but both mechanisms
are based on the formation of N-hydroxy PCA.
Ref: Federal Register: December 14, 2001.
(Volume 66, Number 241)] [Notices] [Page 64823-64828]. Notice
of Filing Pesticide Petitions to Establish a Tolerance for a Certain
Pesticide Chemical in or on Food.
- Herbicide - CAS No. 109293-97-2
1-Year non-rodent (dog). Beagle dogs were dosed with diflufenzopyr
at 0, 750, 7,500 and 15,000 ppm in the diet for one year. The
NOEL was determined to be 750 ppm (26 mg/kg/day) in males and
(28 mg/kg/day) in females. The LOAEL was 7,500 ppm (299 mg/ kg/day)
in males and (301 mg/kg/day) in females. This is based on an erythropoietic
response in bone marrow and increased hemosiderin
deposits in spleen, liver and kidneys.
Ref: Federal Register: November 21, 1997
(Volume 62, Number 225) [Notices] [Page 62304-62308]. Notice of
Filing of Pesticide Petitions
- Herbicide -
CAS No. 97886-45-8
The following results
were presented by a Monsanto scientist.
-- Four-week Feeding Study in Mice. Dithiopyr
was administered via the diet to groups of 6 male and 6 female
CD-1 mice for 4 weeks at concentrations of 0, 300, 1000, 3000,
10,000 and 30,000 ppm... Liver enlargement and discoloration,
adrenal enlargement, and atrophy of the thymus,
spleen, seminal vesicles, ovaries and uterus were noted
on gross post-mortem examination... (The Institute of Environmental
-- Eighteen-month Feeding Study in Mice ¥In an oncogenicity study,
dithiopyr was administered via the diet to groups of 70 male and
70 female CD-1 mice for 78 weeks at concentrations of 0, 3, 30
and 300 ppm... Other findings included : increased adrenal weights,
adrenal cortical swelling, spleen enlargement
and increased splenic extramedullary
hematopoiesis. The chronic NOEL in mice is considered to be 3
ppm (equivalent to a daily intake of 0.31 mg/kg b.w. in males
and 0.37 mg/kg b.w. in females). (The Institute of Environmental
Ref: Summary of Toxicology Studies With
Dithiopyr Dennis P. WARD. Toxicology Department, The Agricultural
Grop, A Unit of Monsanto Company (Received February 20, 1993)
- Insecticide - CAS No. 158062-67-0
-- In the multi-generation
rat reproduction study, the NOAEL was 300 ppm for both parental
animals (13.5-32.8 and 16.3-67.0 mg/kg/day, respectively, for
males and females) and their offspring. The effects at the highest
dose of 1,800 ppm included the following: increased
kidney weights and gross and histopathological
alterations in the kidney.
Findings noted in the top dose females included delayed vaginal
opening and increased liver,
kidney and spleen weights in the
F1 generation and reduced ovary and adrenal weights in the parental
generation and decreased uterine weights in the F1 female weanlings.
There was an increase in the FSH and LH levels in F1 females tested
for these endpoints. These findings did not affect the reproductive
performance or survival of offspring in the study.
-- In a 13-week mouse study, the NOAEL was 100 ppm (15.25 mg/kg/day
in males and 20.1 mg/kg/day in females). The LOAEL is 1,000 ppm
(153.9 mg/kg/day in males and 191.5 mg/kg/day in females) based
on hematology effects and changes
in glucose, creatinine, bilirubin, sodium, chloride and potassium
levels, increased liver
and spleen weights and histopathology findings in
the bone marrow, spleen
-- In the 18-month mouse
study, effects were observed in the lung,
liver, spleen and bone marrow at
250 ppm or higher. Findings included, centrilobular
hepatocellular hypertrophy, extramedullary hematopoiesis and
pigment deposition in the spleen and decreased
cellularity (hypocellularity) in the bone marrow...
Federal Register: May 23, 2003 (Volume 68, Number 100)] [Notices]
[Page 28218-28222]. Flonicamid; Notice of Filing a Pesticide Petition
to Establish a Tolerance for a Certain Pesticide Chemical in or
oral toxicity rodents (mice).
LOAEL is 1,000 ppm in
(males: 153.9 mg/kgbw/day; females: 191.5 mg/kg bw/ day) based
on extramedullary hematopoiesis of the spleen.
Many of the tissues/organs recommended by
Guideline 870.3100 were not histologically examined in any dose
group, but this study is not required and serves as a range-finding
study for the mouse carcinogenicity study.Therefore, it is classified
as acceptable, non-guideline study.
August 31, 2005. Flonicamid; Pesticide Tolerance. Final Rule.
- Herbicide - CAS No. 69806-50-4
Fluazifop butyl was
evaluated for reproductive and developmental effects in 2 successive
generations of Charles River Wistar strain rats (30/sex/group)
exposed continuously to 0, 10, 80 and 250 ppm in the diet. Each
respective parent generation had received treatment for a minimum
of 100 days (F0) and 120 days (F1) prior to mating. F0 and F1
dams weaned their progeny for 25 days postpartum to time of offspring
selection for mating and continued study (F1) or sacrifice (F1,
F2). Thirty days after sacrifice of their offspring, the surviving
F1 females and select F1 males were sacrificed and with representative
F1 and F2 offspring were examined histologically.... F2 female
progeny of 250 ppm exposed parents were found with significantly
increased absolute and relative spleen weights... [ICI
AMERS INC; Fluazifop butyl: Effects Upon Reproductive Performance
of Rats Treated Continuously Through 2 Generations (Final Report);
03/17/81; EPA Doc No. 88-920006849; Fiche No. OTS05543854]
Ref: TOXNET profile from Hazardous Substances
Data Bank for FLUAZIFOP-BUTYL.
- Herbicide - CAS No. 79241-46-6
In a 3-generation reproductive study in rats, effects included
reductions in weight gain, fetal weight, ossification, testicular
weight, spleen weight, increased
prostate weight and gestational length. No Effect Level (NEL)
was 1 mg/kg/day...
Chronic/Subcrhonic Toxicity Studies: Chronic toxicity studies
in rodents have shown liver changes (cellular hypertrophy). The
No Effect Level (LEL) in rats is 10 ppm (0.5 mg/kg/day). Long
term feeding studies in dogs produced a range of potentially serious
effects at high dose rates (red cell, bone marrow and lymphadenopathy
changes and liver and spleen damage)
with a No Effect Level of 25 mg/kg/day.
Target Organs: Liver, skin, kidney, eye, bone marrow, blood, reproductive
Ref: Material Safety Data Sheet for Fusilade
DX (active indredient Fluazifop-P-Butyl). Syngenta. January 21,
- Insecticide - CAS No. 272451-65-7
of a reproductive toxicity study in rats (exposure route not stated):
Thyroid, liver, uterine, thymus, and spleen
weight changes in 2000 and 20000 ppm F1 and F2 pups.
Ref: TSCA Health & Safety Study
Cover Sheet "Public Display Copy"
document was cited at EPA's
site: "TSCA 8(e) and FYI Submissions Received from 11-15-04-11-26-04".
It is important to note this as the document itself does not identify
flubendiamide or its CAS No.
study was conducted in the laboratory of The Institute of Environmental
Toxicology - Japan
•• Source of Data/Study
Sponsor: Bayer Material Science Corporation, 100 Bayer Road, Pittsburg
Acaracide, Insecticide - CAS No. 70124-77-5
-- Groups of 6 male
and 6 female Beagle dogs received technical flucythrinate (87.3%
pure) in the diet at 0, 30, 100, or 300 ppm daily for 24 months...
At sacrifice, the relative liver, kidney, and pituitary weights
were increased in both high-dose males and females, while increases
in relative spleen, testis and lung
weights were noted for high-dose males only...
(Spicer et al., 1984).
Ref: 1985 World Health Organization Review
- Fungicide - CAS No. 131341-86-1
A carcinogenicity study
in mice administered in the diet nominal dose levels at 0, 10,
100, 1,000, and 3,000 ppm (0, 1.1, 11.3, 112, and 360 mg/kg/day
for male mice; 0, 1.4, 13.5, 133, and 417 mg/kg/day for female
mice). Male mice at the 3,000 ppm level exhibited clinical toxicity
in the form of an incidence of male mice which ``convulsed'' when
handled. No significant effects on body weight, weight gain, food
consumption, hematology, or microscopic non-neoplastic pathology
was reported in either sex. Increased liver weight (9%) and spleen
weight (34%) were observed in male mice at the 3,000 ppm dose
level, which correlated with the macroscopic observations of enlarged
spleen and raised foci of their liver.
Female mice showed a statistically significant increase in liver
weight at the 3,000 ppm dose level, and this is also supported
by the macroscopic observation of enlarged liver at the 3,000
ppm dose level in female mice. Other macroscopic changes in female
mice were an increased incidence of enlarged thymus, spleen,
mediastinal lymph node, and liver, and an increased incidence
of lymphoma in these organs.
Ref: Federal Register: October 29, 1997
(Volume 62, Number 209) [Rules and Regulations] [Page 56075-56082].
Pesticide Tolerance. Final Rule.
- Herbicide - CAS No. 142459-58-3
Chronic feeding studies
in dog and rat showed structural or functional alterations in
liver, kidney, haematology, spleen,
and thyroid. Flufenacet induces neuropathogical changes in the
brain and spinal cord (axonal swelling) in rat and dog. The overall
evaluation of the observed changes demonstrates that these effects
occur only after repeated and prolonged exposure to high dose
levels of flufenacet, which saturate metabolic pathways, and exceed
the animal capacity to rapidly metabolise and excrete it. The
liver was considered the primary target organ, with increases
in organ weight, cell size and number, and/or associated changes
in liver function tests.
Ref: European Commission, Health & Consumer
Protection Directorate-General, Scientific Committee on Plants,
October 17, 2001. SCP/FLUFEN/002-Final.
-- In the rat chronic feeding / carcinogenicity study the NOEL
was less than 1.2 mg/kg/day in males and less than 1.5 mg/kg/day
in females and the LOEL was 1.2 mg/kg/day in males and 1.5 mg/kg/day
in females based on methemoglobinemia
and multi-organ effects in blood, kidney,
heart, and uterus.
Under experimental conditions the treatment did not alter the
spontaneous tumor profile. In the mouse carcinogenicity study
the NOEL was less than 7.4 mg/kg/day in males and was 9.4 mg/kg/day
for females and the LOEL was 7.4 mg/kg/day for males and was 38.4
mg/kg/day for females
based on cataract incidence and severity.
There was no evidence of carcinogenicity for flufenacet
in this study.
Ref: US EPA. Pesticide Fact Sheet. Flufenacet
Reason for Issuance: Conditional Registration Date Issued: April
- CAS No. 101463-69-8
dose mammalian studies.
were 28 d rat, 90 d rat/mouse/dog, 12 and 24 month rat, and 12
month dog. In both the rat and dog there was evidence of regenerative
anaemia and increased methaemoglobin levels
with NELs of 5 mg.kg-1 (rat 28- and 90- day) and 2.5 mg.kg-1.d-1
(dog 12 month). In mice the NEL was 7.5 mg.kg-1.d-1 based on increased
plasma bilirubin. Plasma bilirubin was also increased in rats
(24 month). Evidence of regenerative anaemia (increased methaemoglobin,
decreased erythrocyte parameters, increased reticulocytes,
increased marrow cellularity and increased
spleen weight) was seen in most studies.
In addition at higher doses triglycerides were decreased and heart
weight increased in the rat.
-- Carcinogenicity. Rat. Groups of 50/sex/group Fischer 344 rats
were administered 0, 500, 5000 or 50000 ppm flllufenoxuron in
the diet for 24 months... In
males relative spleen weight was reduced in all treatment groups
(respectively 14, 29 and 32 %)...In
the females there was a significant increase in adrenal weight
in all treatment groups (respectively 9, 7 and 15%).
data. Adequately conducted carcinogenicity studies in the rat
and mouse have been reported. Flufenoxuron was not carcinogenic
in the rat. The NOEL for non-neoplastic effects (body weight and
relative spleen weight changes) was 25 mg-1.kg-1.d-1. In the mouse
there was an increased incidence of haemangiosarcoma
in the liver (males) and
spleen (females) at 50000 ppm, and
an apparent increase in hepatocellular carcinoma
in males at all dose levels. The
apparent increase in liver tumors was due to an abnormally low
control incidence, and therefore flufenoxuron had no significant
carcinogenic activity in the mouse. No NEL was established in
1995. Evaluation of Flufenoxuron use as a public hygiene insecticide.
UK: Health and Safety Executive, Biocides & Pesticides Assessment
Unit. Available at http://www.pesticides.gov.uk/citizen/evaluations/evallist_alphabet.htm
- Acaricide - CAS No. 69770-45-2
-- IN GLP repeated-dose
toxicity study, groups of 20/sex/dose Wistar rats were fed diets
containing 0, 10, 40 or 160 mg/kg feed flumethrin for up to 15
weeks. During mixing of the diets, 1% peanut oil was added to
minimise dust formation. At 160 mg/kg feed,
body weight gain was significantly reduced. Sever skin lesions
were observed in the 160 mg/kg feed group. Some mild skin lesions
were also observed in the 40 mg/kg feed group. Decreased red cell
values and increased leucocyte counts in the 160 mg/kg feed group
were probably associated with the skin lesions. At termination,
histopathological examination revealed ulcerative skin lesions
in all rats given 160 mg/kg feed and some rats from the 40 mg/kg
feed group. Increased extramedullary
haematopoiesis and reduced haemosiderin storage in the spleen
were also observed in the 160 mg/kg feed group. The NOEL was 10
mg/kg feed, equivalent to 0.7/0.8 mg/kg bw per day in males/females
Ref: Committee for Veterinary Medicinal
Products. Flumethrin. Summary Report (1). June 1998. EMEA/MRL/469/98-FINAL.
The European Agency for the Evaluation of Medicinal Products.
- Herbicide - CAS No. 2164-17-2
The spleen, kidney, and liver appear
to be the organs consistently affected
following exposure to moderate doses of fluometuron in rats and
dogs in subchronic, chronic, developmental, and reproductive studies.
February 1, 2005. US EPA: Fluometuron: Revised HED Risk Assessment
for Phase III of the Reregistration Eligibility Decision. Docket
Identification Number: OPP-2004-0372-0008.
E. Subchronic Studies. Subchronic feeding studies were conducted
to determine the two concentrations (referred to in this report
as "low" and "high" doses) to be used in the
chronic studies. Fluometuron was administered in the diet for
90 days at doses of 0, 250, 500, 1,000, 2,000, 4,000, 8,000, or
16,000 ppm to groups consisting of 10 males and 10 females of
each species (Tables 1 and 2) (page 5) ... A second 90-day subchronic
study, described in Table 3, was undertaken to investigate in-depth
the effects of feed containing 0 to 4,000 ppm fluometuron on the
spleens of rats.... Gross lesions observed
at necropsy included varying degrees of splenomegaly in all dosed
groups. This change was dose related with the spleens being larger,
heavier, darker, and firmer than the control spleens. In male
rats, an increase in the mean weights of spleens occurred at 1,000
ppm, and the mean spleen weight at 4,000 ppm was twice that of
the control. In female rats, the mean weight of spleens in the
group receiving 250 ppm was greater than that of the control,
and those of the groups receiving 2,000 ppm or 4,000 ppm were
respectively twice and almost three times that of the control.
A dose-related increased incidence of red
blood cells with polychromasia and anisocytosis was observed for
both male and female rats. Microscopically, the pathologic changes
were congestion of the red pulp with corresponding decrease of
white pulp. (page 8)
Reference: 1980. Bioassay of fluometuron
for possible carcinogenicty. NCI-CG-TR-195. NTPO-80-11. National
Cancer Institute. Carcinogenesis. Technical Report Series No.
195. NTP No. 80-11.
-- CHRONIC TOXICITY.
Rats were fed 7.5, 75, or 750 mg/kg/day for 90 days. At the 750
mg/kg dose, decreased body weight and
congestion in the spleen,
adrenals, liver, and kidneys
were evident. The NOAEL for this study was 7.5 mg/kg/day (100
ppm). When doses of 1.5, 15 or 150 mg/kg/day were fed to puppies
for 90 days, congestion of the liver, kidneys and
at the 150 mg/kg dose. No effects were seen at 15 mg/kg/day (400
Ref: Flumeturon. EXTOXNET. Pesticide Information
Profile. March 1994.
- Fungicide - CAS No. 193740-76-0
chronic toxicity / carcinogenicity--rats. decreased
body weight, decreased body weight gain, and decreased food efficiency
in both sexes; decreased spleen weight in
males; and microscopic lesions in
the uterus of females. The apparent increase in tumors in the
uterus and thyroid were addressed and resolved by an Agency committee,
which concluded that no carcinogenic concern exists for
Ref: Federal Register. September 16, 2005.
Fluoxastrobin; Pesticide Tolerances. Final Rule.
- Herbicide - CAS No. 96525-23-4
-- Two-year dietary
study in mice. In a carcinogenicity study, groups CD-1 mice (60/sex/dose)
were fed diets containing 0, 30, 300, 3500 and 7000 ppm flurtamone
(91.9% purity) for at least 78 weeks... The mean intake of flurtamone
for males and females was estimated to be 4.5, 45, 525 and 1050
mg/kg bwday at 30, 300, 3500 and 7000 ppm, respectively. After
78 weeks of treatment, the mortality rate for the 7000 ppm female
mice was significantly higher than controls and a significant
negative survival trend was found in both sexes. The test laboratory
pathologist considered systemic amyloidosis to be the major cause
of death (Table 5.34) [page 102]... The
severity and incidence of extramedullary
haematopoiesis was increased in the spleens
of the 7000 ppm males and females
2000 . Evaluation on: Flurtamone.
No. 196. Department for Environment, Food and Rural Affairs, Pesticides
Safety Directorate, Mallard House, Kings Pool, 3 Peasholme Green,
York YO1 7PX, UK. Available
- Fungicide - CAS No.
toxicity. A 84-day rat feeding study with a No Observed Effect
Level ( NOEL) less than 100 ppm [6.0 mg/kg/day] for males and
a NOEL of 100 ppm [7.2 mg/kg/day] for females and with a Lowest
Observed Effect Level (LOEL) of 100 ppm [6.8 mg/kg/day] for males
based on suppression of thyroxine (T4) level and a LOEL of 400
ppm [28.8 mg/kg/day] for females based on hematology and clinical
chemistry findings. A 13-week mouse feeding study with a NOEL
of 100 ppm [18.2 mg/kg/day for males and 24.5 mg/kg/day for females]
and a LOEL of 400 ppm [64.2 mg/kg/day for males and 91.3 mg/kg/day
for females] based on histopathology of the liver, spleen
and thyroid. A 13-week dog dietary study with a NOEL of 50 ppm
[1.70 mg/kg/day for males and 1.67 mg/kg/day for females] and
a LOEL of 200 ppm [6.90 mg/ kg/day for males and 7.20 mg/kg/day
for females] based on evidence that the bio-transformation capacity
of the liver has been exceeded, (as indicated by increase in LDH,
liver weight, ALK and hepatomegaly), globulin and
spleen pigment in females, decreased T4 and [[Page 34180]]
ALT values in both sexes, decreased albumin in males, and decreased
serum glucose in females. A 21-day rabbit dermal study with the
dermal irritation NOEL of 1,000 mg/kg/day for males and females
and a systemic NOEL of 20 mg/kg/day for males and 150 mg/kg/day
for females and a systemic LOEL of 150 mg/kg/day for males and
1,000 mg/kg/day for females based on clinical chemistry data (decreased
T4 and FT4 levels in both sexes) and centrilobular hepatocytomegaly
Federal Register: June 23, 1998 [Page 34176-34184]. Notice of
Filing of Pesticide Petitions.
Rodenticide - Rodenticide - CAS No. 8065-71-2
Abstract. The single administration of
gliftor (I; internally, 40-160 mg/kg) caused considerable destructive
changes and circulatory disorders in the internal organs of rats.
The maximum tolerance dose of I (60 mg/kg) caused hyperplasia
of the cells of the RES in the spleen, proliferation of
local cells, and inflammatory cellular infiltration of the alveolar
walls in the lungs.
Ref: Morphological changes of internal
organs of experimental animals after oral administration of gliftor;
by KNYSH VS, TKACH NZ, TSAREVSKII LP. TR INST KRAEV PATOL AKAD
NAUK KAZ SSR; 22 1971 28-30. [Abstract from Toxline at Toxnet.]
Abstract. Rats were subjected to the single inhalation effect
of vapors of the zoocide gliftor (I; 50, 100, 350, 520, and 1100
mg/m-3). Morphological changes were noted beginning with a concentration
of 350 mg/m-3. In a chronic experiment (4 mo.) the rats were subjected
to I poisoning in a concentration of 10, 13, 64, and 110 mg/m-3.
Distinct morphological changes in the organs were noted under
the effect of concentrations 64 and 110 mg/m-3. Under
the chronic effect of I there were considerable circulatory disorders
and destructive changes of the interanl organs, especially in
the liver, lungs, spleen, and kidneys.
Ref: Pathomorphological changes in
internal organs of white rats under the inhalation effect of gliftor;
by KNYSH VS, TKACH NZ, TSAREVSKII LP, MILOVANOVA VI. TR INST KRAEV
PATOL AKAD NAUK KAZ SSR; 22 1971 23-28. [Abstract from Toxline
- Insecticide - CAS No. 173584-44-6
The haemosiderin deposits
in spleen and liver, and spleen and
bone marrow hyperplastic response should be considered to be secondary
physiological responses to the increased RBC turn over. The very
shallow dose-response curve also indicates that the compensatory
mechanism of the haemopoietic system was not overcome (except
at high doses in the dog) and the effect of indoxacarb in rats
and dogs can be described as a compensated haemolytic effect.
18, 2002: Opinion of the Scientific Committee on Plants on specific
questions from the Commission concerning the evaluation of Indoxacarb.
European Commission. Health & Consumer Protection Directorate-General.
COMBINED, RAT **52425-054
Chronic Toxicity/Oncogenicity Study with DPX-JW062-106 (50% DPX-KN128,
50% DPX-KN127) Two-Year Feeding Study in Rats"
(Frame, S. 835-E. I. du Pont de Nemours and Company, Haskell Laboratory,
Elkton Road, Newark, Delaware, Study HLR 1174-96, 11/19/97). DPX-JW062-106
technical (Batch DPX-JW062-106, 47.5% DPX-KN128) was given in
the diet daily to males at 0, 20, 40, 60, 125 or 250 ppm and females
at 0, 10, 20, 40, 60 or 125 ppm for 24 months. Deaths of one female
at 60 ppm and seven at 125 ppm during the first year were associated
with bone marrow atrophy, splenic lymphoid
depletion and thymic necrosis.
Decreases in mean body weight/weight gain in males at 125 and
250 ppm and females at 60 and 125 ppm correlated with decreased
food consumption. Hemolytic anemia at 60 ppm and above (males)
and 40 ppm and above (females): RBC mass, hemoglobin and hematocrit
were decreased and linked with increased reticulocyte counts and
increased MCV. Bone marrow regenerative response was increased
bone marrow hyperplasia in the one-year interim sacrifice 125
ppm females. Spleen weights were increased
in both sexes at the respective high-dose levels and other
non-neoplastic changes were secondary physiological responses
to test substance-related hemolysis; increased pigment observed
within the Kupffer cells of female livers (125 ppm) and the macrophages
of the spleen (both sexes at 60 ppm and above) indicated
increased RBC turnover. Increased hematopoiesis was reported in
the spleen of interim sacrifice males at 125 ppm and above and
in the bone marrow of high-dose males and females. After
two years, secondary changes were seen in the liver, spleen, bone
marrow, kidneys and thymus in high dose groups. Increased
pigment was observed in the Kupffer cells of female livers at
40 ppm and above; in males, increases were noted at 250 ppm only.
Increased splenic pigment was seen in all compound-treated male
groups and in females at 60 ppm and above; a slight increase
in splenic congestion was seen in
250 ppm males. No evidence of an oncogenic effect was reported.
NOEL(M)= 40 ppm; (F)=20 ppm (M: 1.59 mg/kg/day; F: 1.04 mg/kg/day
based on hemolytic anemia). Acceptable. Kellner, 1/29/99.
-- **52425-047 162215 "Chronic
Toxicity Study of DPX-JW062-106 (50% DPX-KN128, 50% DPX-KN127)
One Year Feeding Study in Dogs"
(Mertens, J. 831-WIL Research Laboratories, Inc. Ashland, Ohio.
Study HLO 885-96, 11/19/97). DPX-JW062-106 technical (Batch DPX-JW062-
106, 47.5% DPX-KN128) was administered orally (via the feed) to
5 Beagle dogs/sex/dose at levels of 0, 40, 80, 640 and 1280 ppm
for 52 weeks... Microscopic changes in groups
40 ppm and above included increased pigment (hemosiderin) in liver
Kupffer cells, kidney tubule epithelium, spleen and bone marrow
and increased extramedullary hematopoiesis in the spleen and bone
marrow hyperplasia. NOEL (M/F)=40 ppm (males: 1.1 mg/kg/day;
females: 1.3 mg/kg/day based on biologically significant hemolytic
anemia at 80 ppm and above). Acceptable. Kellner, 1/12/99.
-- REPRODUCTION, RAT **52425-046
Generation Reproduction/Fertility Study with DPX-JW062-106 in
Rats" (Breslin, W. 834-MPI Research, Mattawan, MI, Report#
HLO 115-96, 11/3/97). DPX-JW062- 106 (Batch no. DPX-JW062-106,
47.7% DPX-KN128, dissolved in acetone) was administered orally
via the feed to 26 Crl:CD ¨ VAF/Plus ¨ rats/sex/dose at levels
of 0, 20, 60, 100 ppm beginning 70 days prior to mating and continuing
until euthanasia for 2 generations... Necropsy findings included
increased spleen weights in the F0 and F1
males at 100 ppm and in the F0 and F1 females at 60 and 100 ppm.
Maternal NOEL= 20 ppm (0.856-4.141 mg/kg/day,
based on increased spleen weights in females at 60 and 100 ppm).
There were no apparent compound-related effects on gonad function,
estrous cycling or mating behavior in either the F0 or F1 animals.
In F1 females at 100 ppm, slight decreases in fecundity and fertility
index were noted. While mean F1 pup weights in the 60 and 100
ppm groups were statistically reduced during the lactation period,
corresponding weights in the F2 generation showed no compound-related
effect. Developmental NOEL= 20 ppm (based on decreased F1 pup
weights during lactation at 60 and 100 ppm). No Adverse Effects;
decrease in F1 fecundity and fertility indices were not statistically
significant, not seen during F0 mating and not accompanied by
effects in sperm or estrous cycle evaluations. Reproductive NOEL=
60 ppm (1.734-11.610 mg/kg/day; based on slight reduction in F1
fertility index at 100 ppm). Acceptable. Kellner,
-- ** 034; 162199; "Subchronic
Oral Toxicity:90-Day Study with DPX-MP062 (Approximately 75% DPX-KN128,
25% DPX-KN127) Feeding Study in Rats"
(MacKenzie, S.A., Haskell Laboratory for Toxicology and Industrial
Medicine, E.I. du Pont de Nemours and Company, Newark, DE, Laboratory
Project ID DuPont HL-1997-00056, 3/24/97). 821. DPX-MP062 (Batch
No. DPX-MP062- 51A, 74.7% DPX-KN128) was admixed to the feed at
concentrations of 0, 10, 25 (females only), 50, 100, or 200 (males
only) ppm (0, 0.620, 3.09, 6.01, or 15.0 mg/kg/day, respectively,
for males and 0, 0.760, 2.13, 3.78, or 8.94 mg/kg/day, respectively,
for females) and fed to 10 Crl:CD ¨ (SD)BR rats per sex per dose
level for approximately 90 days. 5 females at 100 ppm died or
were sacrificed in extremis. No dose-related clinical signs were
observed in males; among females at 100 ppm, ataxia (in 2 of the
mortalities), weakness (in 4 animals), and tremors (in 1 of the
mortalities) were observed. Treatment-related decreased mean body
weight and decreased mean body weight gain in males at 200 ppm
and in females at 50 and 100 ppm were observed. Statistically
significant and dose-related decreases in mean red blood cell,
hemoglobin, and hematocrit levels in males beginning at 100 ppm,
50 ppm, and 100 ppm, respectively, and in females beginning at
25 ppm, 10 ppm, and 10 ppm, respectively, were observed. Microscopic
examination revealed treatment-related increased
pigment and increased extramedullary hematopoiesis in the spleen
in males at 50, 100, and 200 ppm, and in females at all dose levels.
No adverse effects. NOEL (M)=0.620 mg/kg/day (10 ppm) and (F)<
0.760 mg/kg/day (10 ppm) [based on treatment-related decreased
mean hemoglobin (males and females) and hematocrit (females) levels
and histologic effects in the spleen).
Acceptable. (Corlett, 1/19/99
-- ** 035; 162200; "Subchronic
Oral Toxicity:90-Day Study with DPX-JW062-34 (50% DPX-KN128, 50%
DPX-KN127) Feeding Study in Mice"
[Malek, D.E., Haskell Laboratory for Toxicology and Industrial
Medicine, E.I. du Pont de Nemours and Company, Newark, DE, Haskell
Laboratory Report No. 750-93 (Revision No. 1), 1/22/97]. 821.
DPX-JW062-34 Technical (Batch No. DPX-JW062-34, 47.4% DPX-KN128)
was admixed to the feed at concentrations of 0, 10/300 (started
at 10 ppm and increased to 300 ppm on Day 42 of feeding), 35,
75, or 150 ppm (0, 1.7/44, 5.5, 12, or 23 mg/kg/day, respectively,
for males and 0, 2.1/51, 7.0, 16, or 30 mg/kg/day, respectively,
for females) and fed to 10 Crl:CD-1 ¨ (ICR)BR mice per sex per
dose level for approximately 90 days. One male at 300 ppm was
found dead on day 85. Treatment-related clinical signs included
animals leaning to one side (in males at 300 ppm and in females
at 150 and 300 ppm), abnormal gait or mobility (in females at
300 ppm), and tremors (in one male at 300 ppm). Treatment-related
decreases in mean body weight (in males at 300 ppm), mean body
weight gain (in males at 300 ppm), and mean daily food consumed
per mouse (in males at 300 ppm and in females at 150 and 300 ppm)
were observed. Treatment-related increases in mean reticulocyte
(in males and females at 300 ppm), mean cell volume (in males
at 300 ppm and in females at 150 and 300 ppm), and mean white
blood cell (in males and females at 300 ppm) levels, and the treatment-related
presence of Heinz bodies (in males and females at 150 and 300
ppm) were observed. Microscopic examination revealed treatment-related
increased pigment in the spleen in males
and females beginning at 75 ppm. No adverse effects. NOEL
(M)=5.5 mg/kg/day (35 ppm) and (F)=7.0 mg/kg/day (35 ppm) (based
on treatment-related increased pigment in the spleen).
Acceptable. (Corlett, 1/28/99)
-- ** 036; 162201; "Subchronic
Oral Toxicity:90-Day Study with DPX-JW062-106 (Approximately 50%
DPX-KN128, 50% DPX-KN127) Feeding Study
in Dogs" (Mertens, J.J.W.M., WIL Research Laboratories,
Inc., Ashland, OH, Haskell Laboratory Project ID: HLO 494-95,
Performing Laboratory Project ID: WIL-189016, 11/19/97). 821.
DPX-JW062 Technical (Batch No. DPX-JW062- 106, 47.5% DPX-KN128)
was admixed to the feed at concentrations of 0, 40, 80, 160, or
640 ppm (0, 1, 2, 5, or 18 mg/kg/day, respectively, for males,
and 0, 1, 3, 5, or 17 mg/kg/day, respectively, for females) and
fed to 4 outbred beagle dogs per sex per dose level for 13 weeks.
No animals died during the study interval. No treatment-related
clinical signs were observed. Statistically significant and treatment-related
decreases in mean red blood cell and hemoglobin levels in males
at 160 and 640 ppm, and females at 640 ppm and statistically significant
and dose-related increases in mean cell volume in males beginning
at 160 ppm and in females beginning at 80 ppm and percent reticulocytes
in males at 640 ppm and in females at 160 and 640 ppm were observed.
Treatment-related increases in Heinz bodies and mean total bilirubin
levels were observed in males and females at 160 and 640 ppm.
Microscopic examination revealed a treatment-related
increase in pigment in the spleen beginning in males at 40 ppm
and in females at 80 ppm, increased extramedullary hematopoiesis
in the spleen beginning in males and females at 160 ppm, treatment-related
erythrocytic hyperplasia and an increase in pigment in the bone
marrow in males beginning at 80 ppm and in females beginning at
40 ppm, and a treatment-related increase in pigment in the liver
in males and females beginning at 80 ppm. No adverse effects.
NOEL (M/F)< 1 mg/kg/day (40 ppm) (based on a
treatment-related increase in pigment in the spleen in males,
and on a treatment-related increase in
extramedullary hematopoiesis in the spleen, and treatment-related
erythrocytic hyperplasia and a treatment-related increase in pigment
in the bone marrow in females). Acceptable. (Corlett, 2/10/99)
11, 1999: Summary
of Toxicology Data - Indoxycarb.
California EPA Department of Pesticide Regulation, Medical Toxicology
28-Day dermal toxicity
-- rats: DPX--MP062 / NOAEL = 50
mg/kg/day LOAEL = 500 mg/kg/ day based on decreased body weights,
body weight gains, food consumption, and food efficiency in F,
and changes in hematology parameters (increased reticulocytes),
the spleen (increased
absolute and relative weight M only, gross discoloration),
clinical signs of toxicity in both sexes in rats.
Ref: Federal Register: September 29, 2000.
Indoxacarb; Pesticide Tolerance. Final Rule.
In a 2-generation rat
reproduction study, the parental NOEL was 1.3 and 1.5 mg/kg/day
for males and females, respectively. The parental NOEL was based
on observations of reduced weight gain and food consumption for
the higher concentration groups of the F0 generation and potential
treatment-related changes in spleen weights
for the higher groups of the F1 generation.
Ref: Federal Register: April 16, 1998 [Page
18912-18919]. Notice of Filing of Pesticide Petitions.
- Herbicide - CAS No. 77501-63-4
Subchronic feeding-- Mice-- 3-month. Groups of Male and female
mice were fed diets containing Lactofen Technical at concentrations
of 0, 40, 200, 1,000, 5,000, and 10,000 for 13-weeks. At week
5, the dosage of the 40 ppm groups was increased to 2,000 ppm.
Treatment related mortality occurred at dosages above 1,000 ppm.
The LOEL was 200 ppm based on: increased WBC; decreased hematocrit,
hemoglobin and RBC; increased alkaline phosphatase, SGOT, SGPT,
cholesterol and total serum protein levels; increased weights
or enlargement of the spleen, liver, adrenals, heart and kidney;
histopathological changes of the liver, kidney, thymus,
spleen, ovaries and testes. In general, effects were slight
in the 200 ppm groups, and moderate to severe in the 1,000 ppm
-- Reproduction-- Rats. Groups of male and female rats were fed
0, 50, 500 or 2,000 ppm of Lactofen Technical continuously in
their diets for 2-generations. Adult systemic toxicity (mortality,
reduced body weight, increased liver and
spleen weight, decreased kidney weight and histological
changes in the liver and testes) was observed
at levels of 500 ppm and greater.
Ref: Federal Register: February 25, 1998
[Page 9532-9540]. Notice of Filing of Pesticide Petition.
and its potassium and diethanolamine salts - Herbicide,
Plant growth regulator - CAS Nos. 53780-34-0,
21-Day Dermal toxicity - rabbit (4 rabbits/sex/dose). Acceptable/Non-guideline
(NOAEL was not observed). Systemic LOAEL = 240 mg/kg/day, based
on clinical chemistry (increased alkaline phosphatase and alanine
aminotransferase) and organ weights (decreased
spleen weight in females and increased
liver weights in males). Edema and
swelling with myelin loss in sciatic nerve was seen in 720 and
2400 mg/kg/day dose group. Dehydration observed at 2400
mg/kg/day dose. Dermal and systemic NOAELs were not established.
USEPA. Mefluidide - Toxicology
section for the Reregistration Eligibility Decision Document (RED)
(January 31, 2007)
- Herbicide - CAS No. 27314-13-2
- A two-year carcinogenicity
study was conducted in male and female CD-1 HaM/ICR Swiss mice
in which 125 mice/sex/dose were administered technical norflurazon
in the diet at dose levels of 0, 85, 340, or 1360 ppm (0, 12.8,
58.7, or 218.8 mg/kg/day) for 100-104 weeks. No significant effects
were observed on body weight, body weight gain, clinical toxicity,
or food consumption at any dose level tested.
Liver weight was increased by 9% and 15% in male and female mice
at the 340 ppm dose level, and by 27% and 21% at the 1360 ppm
dose level, respectively. The liver to body weight ratio was increased
by 19% and 4% in male and female mice at the 340 ppm dose level,
and by 43% and 19% at the 1360 ppm dose level, respectively. Increased
incidences of enlarged spleen, nephritis,
swollen/enlarged liver, and nodular enlargement of the liver were
observed in high dose male mice,
while increased incidences of pyelonephritis, enlarged liver,
and cystic ovaries were observed in high dose female mice. Carcinogenic
potential was evidenced by an increased incidence of hepatic adenoma
and combined adenoma/carcinoma in high dose male mice. The
systemic NOEL was determined to be 12.8 mg/kg/day (85 ppm) for
male mice, and 58.7 mg/kg/day (340 ppm) for female mice. The systemic
LEL was determined to be 58.7 mg/kg/day (340 ppm) for male mice,
based on the increased incidence of enlarged
spleen, increased absolute and relative
liver weight, and increased incidence of nephritis.
The systemic LEL was determined to be 218.8 mg/kg/day (1360 ppm)
for female mice, based on the increased incidence of enlarged
liver and cystic ovaries, the increased absolute and relative
liver weight, and the increased incidence of pyelonephritis (guideline
¤83-2; MRID 00111649).
-- A chronic toxicity and carcinogenicity study was conducted
in Sprague-Dawley rats. In this study, technical norflurazon was
administered in the diet at dose levels of 0, 125, 375, or 1025
ppm (0, 6.25, 18.75, or 51.25 mg/kg/day) for 104 weeks.,, Other
microscopic alterations observed at the high dose included an
increased incidence of parathyroid hyperplasia
(both sexes), hemosiderin pigment deposition in the spleen
(males only) and liver (both sexes), and endometritis
and squamous metaplasia of the uterus (females). The
systemic NOEL was determined to be 375 ppm (18.75 mg/kg/day) for
Ref: US EPA REREGISTRATION ELIGIBILITY DECISION
NORFLURAZON. LIST A. CASE 0229.
- Insecticide - CAS No. 116714-46-6
-- SUBCHRONIC STUDIES
(Oral) 52846-002; 174427; " 'Rimon' Technical: Toxicity Study
by Dietary Administration to CD Rats for 13 Weeks Followed by
a 4 Week Reversibility Period":; (P.W. East; Huntingdon Life
Sciences Ltd, Eye, Suffolk, England; Report No. MAK399/972319;
4/2/98); Ten CD rats/sex/group were fed 0, 50, 100, 10000 or 20000
ppm of Rimon Technical (Novaluron Technical) (batch no. 031068069,
purity: 99.8% (pre-study analysis)) in the diet for 13 weeks ((M):
0, 4.2, 8.3, 818.5, 1666.9 mg/kg/day, (F): 0, 4.7, 8.9, 871.0,
1820.6 mg/kg/day). An additional 5 animals/sex/group in the 0,
50 and 20000 ppm groups were maintained for 4 more weeks after
the termination of dosing in order to assess the reversibility
of treatment-related effects... Microscopic examination of the
spleen revealed increased extramedullary erythropoesis (50 ppm
and above) and increased hemosiderosis (M)
and above (p<0.01), (F)
50 ppm and above (p<0.05 at 50 ppm). In the livers
of the 10000 and 20000 ppm females, pigmented Kupffer cells were
noted (p<0.05 at 10000 ppm). At the conclusion of the 4 week recovery
period, the methemoglobin levels were still slightly elevated
for the 20000 ppm group (p<0.05), the relative spleen
weight was increased for the 20000 ppm females (p<0.05),
and there was still increased hemosiderosis
in the spleen of the 20000 ppm females (p<0.01). No adverse
effect indicated. NOEL: (M/F) < 50 ppm ((M) 4.2 mg/kg/day, (F)
4.7 mg/kg/day (based upon the increased incidence of splenic
extramedullary erythropoesis noted for the 50 ppm treatment
group); Study acceptable. (Moore, 11/1/00)
Ref: 2001. Summary of Toxicology Data for
Novaluron. California Environmental Protection Agency, Department
of Pesticide Regulation, Medical Toxicology Branch. Chemical Code
# 5754, Tolerance # 52846 3/23/01.
Short-term incidental oral (1-30 days);
Intermediate-term incidental oral (1-6 months); and Intermediate-term
inhalation (1 to 6 months): 90-day feeding study in rat.
LOAEL = 8.64 mg/kg/day based on clinical chemistry (decreased
hemoglobin, hematocrit and RBC counts) and histopathology
(increased hematopoiesis and hemosiderosis in spleen and liver).
-- Reproduction and fertility-
rat. Parental NOAEL= Not established;
(M/F)= 74.2/84.0 mg/kg/day based on increased
absolute and relative spleen weights. Offspring
NOAEL= Not established; LOAEL (M/F)= 74.2/84.0 mg/
kg/day based on increased absolute
and relative spleen weights.
June 2, 2004. Novaluron; Pesticide Tolerance. Final Rule. Federal
- Insecticide - CAS No. 121451-02-3
-- REPRODUCTION, RAT. “XDE-007: Two-Generation
Dietary Reproduction Toxicity Study in CD Rats,”
(Carney, E.W., Zablotny, C.L., Liberacki, A.B., Yano, B.L.;Toxicology
& Environmental Research and Consulting, The Dow Chemical
Company, Midland, MI; 3/22/04). XDE -007 (97.9% pure) was fed
in diet to Crl:CD (SD) IGS BR rats (30/sex/dose/generation) at
0, 0.5, 5 or 25 mg/kg/day continuously from pre-mating of parental
generation 1 (P1) through weaning of offspring through 2 generations
(2 matings for P2 generation) to F2b weaning. . ... . F2a
male weanlings had statistically significantly decreased body
weights, relative brain and absolute
spleen weights at 25 mg/kg.
Neonates at 25 mg/kg in both F1 and F2 generations showed
tonoclonic convulsions, as well as in 1 litter of F2a at 5.0 mg/kg.
P2 females (1, 1, 5 and 7 at 0, 0.5, 5.0 and 25 mg/kg, respectively)
failed to litter, so the female is considered
to be an affected sex.) Possible adverse effects on reproduction,
fertility and pup survival, along with numerous other toxicologically
relevant effects. M. Silva, 6/18/04
August 2005 - Summary of toxicological data. California EPA, Department
of Pesticide Regulation, Medical Toxicology Branch.
- Herbicide - CAS No. 42874-03-3
and relative thymus weights were decreased in mid-dose males (-14%/-10%)and
high-dose males (-32%/- 18%)...Vacuolation of the adrenal cortex
was present in high-dose females. Thymic atrophy occurred in high-dose
males and females.... Fine vacuolation of adrenal glands (slight)and
cortical atrophy of the thymus (slight) were increased in high-dose
males... Absolute and/or relative organ weights in the high-dose
groups that showed statistically significant changes relative
to control weights (thyroid gland in both sexes and kidney in
females at 12 months and brain, pituitary, and spleen
in females sacrificed
at 24 months) had no microscopic correlates and are not considered
Ref: US EPA. Toxicology Chapter for RED.
August 8, 2001.
PFOS - PFOA
- Insecticide, US EPA List 3 Inert
The effects of peroxisome
proliferators on the immune system of male C57B1/6 mice have been
investigated. Significant atrophy of the
thymus and spleen was observed in animals treated with potent
peroxisome proliferators (e.g. perfluorooctanoic acid (PFOA),
di(2-ethylhexyl)phthalate (DEHP), Wy-14643 and nafenopin), whereas
the effects of a moderate peroxisome proliferator (i.e. acetylsalicylic
acid (ASA)) were relatively weak. The time course of thymic and
splenic atrophy caused by PFOA was found to resemble the time
course of the increase in liver weight and of peroxisome proliferation...
Interestingly, in vitro exposure to PFOA for up to 24 h did not
produce analogous effects in either thymocytes or splenocytes.
Thus, the thymic and splenic atrophy caused
by PFOA appears to involve an indirect pathway."
Ref: 2000. Clin Exp Immunol Nov;122(2):219-26. Effects
of peroxisome proliferators on the thymus and spleen of mice;
by Yang Q, Xie Y, Depierre JW.
In the rat subchronic study, Goldenthal et al. (1978b) administered
CD rats, 5/sex/group, dietary
levels of 0, 30, 100,
300, 1000 or 3000 ppm PFOS (FC-95) for 90 days. The males
232 g and the females weighed 165-206 g at study initiation. The
dietary levels were equivalent
to doses of 0, 2, 6, 18, 60 and 200 mg/kg/day... The rats were
sacrificed after 90 days of treatment and a gross necrospy was
conducted... All of the rats in the 300,
1000 and 3000 ppm groups died. Death occurred between days 13-25
and days 18-28 for the males and females, respectively, in the
300 ppm group...
The rats in all groups showed signs of toxicity including emaciation,
handling, hunched back, red material around the eyes, yellow material
around the anogenital
region, increased sensitivity to external stimuli, reduced activity
and moist red material around
the mouth or nose. Three males and two females in the 100 ppm
group died prior to scheduled sacrifice. Two of the males and
the two females died during week 5 and the third male died during
week 11 of the study... All rats in the 30 ppm group survived
until the end of the study... Histologic examination also showed
lesions in all treated groups. Centrilobular to midzonal cytoplasmic
hypertrophy of hepatocytes and focal necrosis was observed in
the liver; the incidence and relative severity were greater in
the males. In addition, especially among rats in the 300, 1000
and 3000 ppm groups, treatment related histologic lesions were
noted in the primary (thymus, bone marrow)
and secondary (spleen,
mesenteric lymph nodes) lymphoid organs,
stomach, intestines, muscle and skin. In the thymus, this consisted
of depletion in the number and size of the lymphoid follicles
and in the bone marrow hypocellularity was noted. The
spleen was slightly atrophied with
a corresponding decrease in the size and number of lymphoid follicles
and cells and a similar depletion was noted in the mesenteric
Ref: August 31, 2000.
SUBJECT: Hazard Assessment of PFOS. FROM: Jennifer Seed, Branch
Chief, Existing Chemical Assessment Branch, Risk Assessment Division
(7403). THRU: Oscar Hernandez , Division Director, Risk Assessment
Division (7403). TO: Charlie Auer, Division Director, Chemical
Control Division (7405).
- Herbicide - CAS No. 137641-05-5
-- Fat, liver and kidneys
contained the highest amounts of picolinafen metabolites labelled
on the pyridine ring, whereas the blood, liver, spleen
and lungs contained the highest amounts of picolinafen metabolites
labelled on the aniline ring.
-- Short-Term Studies. All mice fed picolinafen at dietary concentrations
of 0, 100, 1000, 2000, 3500 or 7000 ppm for 28 days survived,
but body weight gain was reduced in males at 7000 ppm... Spleen
and liver weights were increased at ¥ 2000 ppm and the breakdown
products of blood cells accumulated in the liver and spleen
and the production of blood cells in the spleen
were increased in males at ¥ 1000 ppm and females at ¥ 2000 ppm.
The severity of these histopathological changes increased in a
-- In mice fed picolinafen at dietary concentrations of 0, 50,
500, 1000 or 2000 ppm for 13 weeks, food consumption was decreased
in males at 1000 and 2000 ppm... The spleens
of some mice were enlarged and spleen
weights were increased in females at ¥1000 ppm. Pigment deposition
was increased in the spleen at ¥
500 ppm and extramedullary haematopoiesis was increased in females
at ¥ 500 ppm males at ¥1000 ppm. The NOEL in this study was 50
ppm, equal to 10 mg/kg bw/day in males and 13 mg/kg bw/day in
-- In mice fed picolinafen at dietary concentrations of 0, 50,
500, 1000 or 2000 ppm for 13 weeks, food consumption was decreased
in males at 1000 and 2000 ppm... The spleens
of some mice were enlarged and spleen weights were increased in
females at ¥1000 ppm. Pigment deposition was increased in the
spleen at ¥ 500 ppm and extramedullary
haematopoiesis was increased in females at ¥ 500 ppm males at
¥1000 ppm. The NOEL in this study was 50 ppm, equal to 10 mg/kg
bw/day in males and 13 mg/kg bw/day in females.
-- In rats fed picolinafen at dietary concentrations of 0, 80,
400 or 800 ppm for 13 weeks body weight gain was slightly reduced
in females at 800 ppm... Spleen weights
were increased at 400 and 800 ppm in males and 800 ppm in females.
Liver to body weight ratios were increased in males at 800 ppm
and females at 400 and 800 ppm. Pigment deposition was increased
in the liver and spleen at 400 and
800 ppm. The NOEL in this study was 80 ppm, equal to 6.4 mg/kg
bw/day in males and 6.8 mg/kg bw/day in females.
-- Long-Term Studies In mice fed picolinafen at dietary concentrations
of 0, 40, 400 or 800 ppm for 18 months, there was no increase
in the incidence of neoplasms... Splenic
enlargement was slightly increased in incidence in females at
400 and 800 ppm. Extramedullary haematopoiesis was observed in
the spleens of mice at 800 ppm with
increased pigment deposition observed in males at 800 ppm and
females at 400 and 800 ppm. The NOEL in this study was 40 ppm,
equal to 6.9 mg/kg bw/day for males and 8.2 mg/kg bw/day for females.
-- In rats fed picolinafen at dietary concentrations of 0, 50,
250, or 500 ppm for 24 months there was no increase in the incidence
of neoplasms. Haemoglobin, Hct and RBC were reduced at 3 and 6
months only at 250 and 500 ppm. Spleen
weights were increased at 500 ppm and the amount of brown pigment
observed in the spleen was increased
at 250 and 500 ppm at both 12 and 24 months. The NOEL in this
study was 50 ppm, equal to 2.4 mg/kg bw/day for males and 3.0
mg/kg bw/day for females.
-- Rats were fed picolinafen at dietary concentration of 0, 50,
250 or 500 ppm in a two-generation reproduction study... The spleen
also showed congestion, increased amounts of brown pigment and
extramedullary haematopoiesis at 250 and 500 ppm... The NOEL in
this study is 50 ppm, equal to 3.7 mg/kg bw/day for males and
4.2 mg/kg bw/day for females.
-- Picolinafen was given to pregnant rats by oral gavage at 0,
100, 500 or 1000 mg/kg bw/day on days 6 to 19 of gestation. One
dam at 1000 mg/kg bw/day appeared emaciated and body weight losses
associated with reduced food consumption were observed on days
6-12 of gestation at ¥ 500 mg/kg bw/day. Spleen
weights were increased in dams at ¥100 mg/kg bw/day and
liver to body weight ratios were slightly increased at ¥ 500 mg/kg
bw/day... The incidence and severity of
extramedullary haematopoiesis and haemosiderosis in the spleen
was increased in a dose dependent manner in all treated groups...
-- In a developmental study, picolinafen was given to rabbits
by oral gavage at 0, 5, 20 or 50 mg/kg bw/day on days 6-28 of
gestation... Congestion and haemosiderosis in the spleen
were increased in incidence and severity at 20 and 50 mg/kg bw/day
and increased extramedullary haematopoiesis was observed at 50
Ref: Public Release Summary on Evaluation
of the new active PICOLINAFEN in the products SNIPER HERBICIDE
& PARAGON HERBICIDE. Australia. National Registration Authority
for Agricultural and Veterinary Chemicals November 2000.
Herbicide - CAS
Organ toxicity: Target
organs identified in animal studies include
the liver, kidneys, spleen,
as well as the skeleton.
Ref: E X T O X N E T Extension Toxicology
Network Pesticide Information Profiles. Revised June 1996.
- Insecticide - CAS No. 179101-81-6
a 104-week combined chronic/oncogenicity study in
effects included decreased body weight gain,
increased frequency of rearing (high
dose females only), hematological alterations
and histopathological alterations of the spleen.
No oncogenicity was found. The NOAEL for this study is 100 ppm
(3.4 mg/kg/day in males and 4.1 mg/kg/day in females).
Register: December 5, 2003. Pyridalyl; Notice of Filing a Pesticide
preservative, EPA List 4B Inert - CAS No. 7681-49-4
Objective: To examine
qualitatively and quantitatively the histological changes in spleen
of rats given sodium fluoride.
Material and Methods: Seventy-five female Wistar rats, each weighing
approx. 200 g, were divided into three equal groups. Animals in
groups 1 and 2 received intraperitoneally daily doses of 0.5 and
5 mg NaF, respectively, whereas group 3 (control) received physiological
saline. The experiments were run for a period of 3 months.1
Afterwards, the spleen was removed for histological and histochemical
examination and fixed in 1 0% formaldehyde solution. Histological
sections were stained with haematoxylin and eosin, picrosirius
red F3BA,2,3 and silver reagent according
to Gomori. The ultrastructural changes in collagen fibres were
investigated by optical polarisation methods.
Results: The lymphoid tissue mass of the spleen decreased and
the relative proportion of reticulin and collagen structures increased.
These changes correlated with the dose of
Conclusions and Interpretation: The absolute
and relative proportion of lymphoid tissue in spleen of rats given
NaF decreased in a dose-related manner. Loss of lymphoid tissue
may play an important role in the diminished reactivity of the
organism and may be regarded as a consequence of fluoride toxicity.
Lymphoid depletion of spleen due to experimental fluorosis in
rats; by M
Bely. Fluoride 2000; 33(1):S1-S2. [XXIIIrd ISFR Conference abstracts,
Szczecin, Poland, June 11-14 2000]. Full
report available at:
(Sodium Hexafluorosilicate) - Insecticiide,
Wood Preservative, EPA List 3 Inert - CAS No. 16893-85-9
-- Sheep, Awassi breed,
1- to 3- yr- old, 5F technical sodium hexafluorosilicate, 25,
50, 200, 1500, and 2000 mg/ kg (0.13, 0.27, 1.06, 7.976, and 10.63
mmol/ kg) suspended in water; duration and observation period
n. p. With the 25- and 50- mg/ kg doses, animals exhibited grinding
of teeth (an indication of pain), dullness, and mild diarrhea.
At 200 mg/ kg, additional symptoms were experienced and included
staggering and severe diarrhea. Animals
died on day 6. With the two higher doses, licking of the lips,
kicking of the belly, grinding of the teeth, falling down (after
1.5 h), frothing at the mouth, congested conjunctiva, protrudation
of the tongue, forced and labored breathing, fever, and increased
respiration and heart rates were observed. Animals died 3 h after
administration of 1500 mg/ kg and 2.5 h after administration of
2000 mg/ kg. Post- mortem examination showed serous pericardial
fluid (few milliliters), a slightly friable liver, mild edema
in the lungs, and froth in the trachea.
Hemorrhages occurred on the spleen and mucosal folds of
the abomasum, and a gelatinous fluid was present in the colon.
For the 1500 mg/ kg- dose group, the change in GOT went from 132%
(of pretreatment activity) at 1.5 hours to 230% at 2.5 hours.
For LDH, the change was 158% at death. The serum ICDH change increased
from 168% after one hour to 984% at death. Egyed and Shlosberg
Ref: Review of Toxicological Literature.
October 2001. Sodium Hexafluorosilicate [CASRN 16893-85-9] and
Fluorosilicic Acid [CASRN 16961-83-4]. Prepared for Scott Masten,
Ph.D. National Institute of Environmental Health Sciences P.O.
Box 12233 Research Triangle Park, North Carolina 27709. Contract
No. N01-ES-65402. Submitted by Karen E. Haneke, M.S. (Principal
Investigator) Bonnie L. Carson, M.S. (Co-Principal Investigator)
Integrated Laboratory Systems P.O. Box 13501 Research Triangle
Park, North Carolina 27709.
Sulfentrazone - Herbicide
- CAS No. 122836-35-5
A prenatal oral developmental
toxicity study in the rat with dose levels at 25.0 or 50.0 mg/kg/day
established a maternal NOEL of 25 mg/kg/day based on decreased
body weight gain, increased spleen
weight, and microscopic changes in the spleen,
and a fetal NOEL of 10 mg/kg/day was based on fetal death, reduced
body weights, and alterations in skeletal development at higher
doses... Risk to infants and children was determined by use of
developmental toxicity studies in rats and a two-generation reproduction
study in rats. The oral developmental toxicity studies resulted
in a maternal NOEL of 25 mg/kg/day based on decreased body weight
gain, increased spleen weight, and
microscopic changes in the spleen,
and a fetal NOEL of 10 mg/kg/day based on fetal death, reduced
body weights, and alterations in skeletal development at higher
Ref: Federal Register: March 10, 1997.
Sulfentrazone; Establishment of Tolerances. Final Rule. Federal
-- 90-Day oral toxicity
rodents (mice) - [870.3100] NOAEL
= 60 mg/kg/day for males and 79.8 mg/kg/day for females LOAEL
= 108.4 mg/ kg/day for males and 143.6 mg/kg/ day for females
based on decreased body weights, body weight gains, red blood
cells, hemoglobin, hematocrit, and severity
of splenic micropathology (increased incidence and severity of
-- 90-Day oral toxicity in nonrodents (dogs)
- [870.3150] NOAEL = 28 mg/kg/day LOAEL = 57 mg/kg/ day for males
and 73 mg/kg/day for females based on decreased body weights (7-10%)
and body weight gains during first 5 weeks of study; decreased
hemoglobin, hematocrit, mean cell volume, mean cell hemoglobin
and mean cell hemoglobin concentration, and increased absolute
liver weights and alkaline phosphatase levels, and microscopic
changes in the liver and spleen (pigmented
sinusoidal microphages in the liver, swollen centrilobular hepatocytes
and pigmented reticuloendotheli al cells in the spleen)
-- Prenatal developmental in rodents (rats)
- [870.3700] Maternal NOAEL = 25 mg/kg/day LOAEL = 50 mg/kg/ day
based on increased relative splenic extramedullary
-- Subchronic neurotoxicity screening battery - [870.6200] NOAEL
= 30 mg/kg/day for males and 37 mg/kg/day for females LOAEL =
150 mg/kg/ day for males and 180 mg/kg/day for females based on
increased incidence of clinical signs; decreased body weight,
body weight gains, and food consumption in females; and increased
motor activity in females. At 5,000 ppm, included increased mortality;
decreased body weights, and body weight gains in males; decreased
hindlimb grip strength and increased tail flick latency in males
at week 8; distended bladders with red fluid and enlarged
spleen. No evidence of neuropathology at 2,500 and 5,000
Ref: Federal Register: September 24, 2003.
Sulfentrazone; Pesticide Tolerances. Final Rule.
- Insecticide - CAS
(60/group/sex) received 0, 10, 100 or 1000 ppm mg kg transfluthrin
(94.8-95%) pure in the diet for up to 104 weeks with 10/sex/dose
killed after one yar. Two additional groups(10/sex) received 0
or 1000 ppm for 13 weeks... Serum cholesterol
levels were significantly raised from 13 weeks at 1000 ppm (20%
in males and 54% in females) and from 100 ppm from week 53 (approximately
11 - 30%) and at week 103 from 10 ppm in females (approximately
50 - 70%) and at 1000 ppm in males )~ 20%)... The incidences
of hepatocellular carcinoma were within
the historical control range for the laboratory (1 - 5 in females
for studies using 50 animals), whereas the adenoma incidence of
13/50 exceeded the range (1 - 9). The low incidences of other
tumours (haemangiosarcoma in the spleen,
sarcoma of the subcutis and adenoma
of the harderian gland) observed
at the top dose in females were not statistically significant...
Ref: Evaluation on: Transfluthrin Use as
a Public Hygiene Insecticide. September 1997. Prepared by: the
UK Health and Safety Executive, Biocides & Pesticides Assessment
Unit, Magdalen House, Stanley Precinct, Bootle, Merseyside L20
3QZ. Available from: Department for Environment, Food and Rural
Affairs, Pesticides Safety Directorate, Mallard House, Kings Pool,
3 Peasholme Green, York YO1 7PX. UK. Also at
This was transcribed from the copy available on the web. While
one can easily read this report on the web, the report is inaccessible,
or locked, to any attempt to copy it. Any errors are mine. EC.
- Fungicide - CAS No. 141517-21-7
4. Subchronic toxicity.
In subchronic studies, several mortality related changes were
reported for the top dose in dogs (500 mg/kg) and rats (800 mg/kg).
At these dose levels, excessive toxicity has resulted in body
weight loss and mortality with the associated and non-specific
changes in several organs (such as atrophy in the thymus, pancreas,
bone marrow, lymph node, and spleen)
which are not considered specific target organs for the test compound.
In the dog, specific effects were limited to hepatocellular hypertrophy
at 150 mg/kg and hyperplasia of the epithelium of the gall bladder
at 500 mg/kg. Target organ effects in the rat were noted as hepatocellular
hypertrophy (200 mg/kg) and the related liver weight increase
(50 mg/kg). In the mouse, target organ effects included single
cell necrosis (300 mg/kg) and hypertrophy (1,050 mg/ kg) in the
liver and extramedullary hematopoiesis (300 mg/ kg) and hemosiderosis
in the spleen (1,050 mg/kg). In general,
definitive target organ toxicity, mostly in the liver, was seen
at high feeding levels of over 100 mg/kg for an extended treatment
period. At the lowest observed adverse effect level (LOAEL), no
serious toxicity was observed other than mostly non-specific effects
including a reduction in body weight and food consumption or liver
hypertrophy. 5. Chronic toxicity. The liver appears to be the
major primary target organ based on the chronic studies conducted
in mice, rats, and dogs. It was identified as a target organ in
both the mouse and the dog studies with trifloxystrobin. However,
no liver effect was seen in the chronic rat study which produced
the lowest NOAEL of 2.5 mg/kg based on reduced body weight gain
and food consumption seen at higher dose levels.
Ref: Federal Register. November 14, 2001.
- Herbicide - CAS No. 199119-58-9
Dogs were given trifloxysulfuron at doses of 0, 50, 200 or 500
mg/kg bw/day in gelatin capsules for 28 days. There were no mortalities,
changes in food consumption, clinical signs of toxicity or effects
on body weight gain. A white material in the faeces of animals
at 500 mg/kg bw/day was confirmed by analysis to be the test material.
Red blood cell count, haematocrit, haemoglobin, platelet counts
and clotting times, plasma bilirubin, protein and albumin were
lower and globulin and chloride were higher in both sexes at 500
mg/kg bw/day. Plasma bilirubin was also lower in females at 200
mg/kg bw/day and plasma potassium and calcium were lower in males
at 500 mg/kg bw/day. Liver weights were higher in both sexes at
200 and 500 mg/kg bw/day. Thymus weights were marginally lower
with one of two males and one of two females at 500 mg/kg bw/day
having slight cortical atrophy in the thymus. Testes weight was
lower in one of the two males at 500 mg/kg bw/day along with markedly
reduced spermatogenesis and some single cell necrosis of tubular
cells. This male also had slight follicular hypertrophy in the
thyroid. Spleen weights were higher in females
at 500 mg/kg bw/day with lymphoid hyperplasia observed in the
spleen of males at 200 and 500 mg/kg bw/day and females at all
doses. Pneumonia was observed in dogs at 500 mg/kg
Ref: August 2002 -
Evaluation of the new active Trifloxysulfuron-sodium in the product
ENVOKE HERBICIDE. Public Release Summary.
National Registration Authority for Agricultural and Veterinary
Chemicals 2002 ISSN1443-1335.