Variation in red cell size. Normal red blood cells are 7
to 8 micrometers, and have an average volume of 90 fl, with
a normal range of 80-100 fl. RBCs which are smaller than
normal are termed microcytic (MCV 100). Macrocytic anemia
has many causes, including folate/vitamin B12 deficiency
and some drugs (e.g., methotrexate, Zidovudine (AZT), and
A mature red blood cell. SYN. haemacyte, hemacyte, red
blood cell, red corpuscle.•
is the process of red blood cell production (which occurs
in red bone marrow).•
(also known as a strawberry birthmark) is a type of birthmark
caused by an abnormal collection of abnormal blood vessels
just below the skin. http://www.heros.org.uk/health/health.ihtml?step=4&Healthpid=818
bodies Small irregular, deep purple granules in red
blood cells due to damage of the haemoglobin molecules.
Seen in premature infants, in certain forms of drug sensitivity,
characteristically in glucose-6-phosphate dehydrogenase
deficiency following administration of oxidant drugs, e.g.
primaquin. Also in certain type of hereditary haemolytic
anaemia, especially in patients with thalassaemia. The bodies
are best seen when the blood is stained with crystal violet.
Heinz reported these bodies in the blood of guinea pigs
treated with acetylphenylhydrazine. Also known as: Ehrlich's
bodies Ehrlich Innenkörper (German) Ehrlich hĢmoglobinĢmische
Innenkörper (German) Heinz-Ehrlich bodies http://www.whonamedit.com/synd.cfm/658.html
SYN hemopoietic (see below).
Pertaining to or relted to
the formation of blood cells. SYN haemoplastic, hematogenic
(1), hematogenous, hematoplastic, hematopoietic, hemogenic,hemoplastic,
system. the blood making organs;
in the embryo at different ages these are the yolk sac,
liver, thymus, spleen, lymph nodes, and bone marrow; after
birth they are principally the bone marrow, spleen, thymus,
and lymph nodes.•
Decrease in hemoglobin concentration per red cell. Morphologically,
this is reflected by increased size of the central pallor
of the RBC when observed on a peripheral blood smear. http://www.kumc.edu/instruction/medicine/pathology/ed/keywords/kw_hypochro.html
Histology • a white or colorless cell of the blood, having
a nucleus and either granular or nongranular cytoplasm;
leukocytes function as bacterial or viral phagocytes, as
detoxifiers of toxic proteins, and in the development of
immunities. Also, WHITE BLOOD CELL. http://www.academicpress.com/inscight/10011998/leukocy1.htm
This brownish pigment is left over from the breakdown and
absorption of damaged blood cells. Lipofuscin is found in
heart muscle and smooth muscles and is also called the "aging"
A condition in which the iron in the hemoglobin molecule
(the red blood pigment) is defective, making it unable to
carry oxygen effectively to the tissues. http://www.nlm.nih.gov/medlineplus/ency/article/000562.htm
Anemia These are associated with an inability to
produce hemoglobin. Hemoglobin consists of iron inserted
into the prtoporphyrin ring complex to form heme which in
turn is inserted into the globin chain. Hence these anemias
are seen in: iron deficiency - absence of iron chronic disease
- iron unavailable thalassemia - inability to produce globin
chains sideroblastic anemia- inability to produce heme.
Blue-gray coloration of young (anucleate) red cells when
observed on a Wright-stained peripheral smear, due to the
presence of residual RNA in the cytosol of the immature
red cell. Polychromatic cells which are macrocytic suggest
that this cell is a reticulocyte. Increased polychromasia
occurs when the bone marrow releases immature RBC's into
the peripheral blood in response to stress such as a hemolytic
A morbid condition due to the presence of sulfmethemoglobin
in the blood; it is marked by a persistent cyanosis, but
the blood count does not reveal any special abnormality
in blood cells; it is thought to be caused by the action
of hydrogen sulfide absorbed from the intestine.•
• Stedman's Concise Medical
Dictionary for the Health Professions. Illustrated, 4th
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.
- Insecticide - CAS No. 158062-67-0
-- In a 90-day rat
feeding study the NOAEL was established at 200 ppm (12.11 mg/kg/day)
for males and 1,000 ppm (72.3 mg/kg/day) for females. The NOAELs
were based on effects on hematology,
triglycerides, and pathology in the liver and kidney.
-- 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 and kidney.
-- Chronic toxicity. In the chronic dog study with administration
via using capsules, the NOAEL was 8 mg/kg/day. The LOAEL was 20
mg/kg/ day based on reduced body weights
in females and effects on the circulating
red blood cells.
-- In a rat 24-month combined chronic and oncogenicity study,
flonicamid technical was not carcinogenic in rats. The NOAEL was
200 ppm (7.32 mg/kg/day) for males and 1,000 ppm (44.1 mg/kg/day)
for females. The LOAEL was 1,000 ppm for males and 5,000 ppm for
females based on histopathology in the kidney,
hematology effects, hepatic
effects including changes
in biochemical parameters, increased organ weights, and histopathological
changes. Atrophy of striated muscle fibers, cataract and retinal
atrophy observed in the high dose females were considered
to be due to acceleration of spontaneous age-related lesions.
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
90-Day oral toxicity rodents (rats). 28-day
range-finding. NOAEL is 100 ppm (7.47 mg/kg/day) for males
and 1,000 ppm (81.9 mg/kg/day) for females.
LOAELs were 500 ppm (36.45 mg/kg/day) for males based on changes
in the kidney (hyaline deposition) and 5,000
ppm for females (372.6mg/kg/day) based on kidney (hyaline deposition),
liver changes (centrilobularhypertrophy),
hematological effects (anemia)
and clinical chemistry (increased cholesterol)
90-Day oral toxicity (nonrodents- dogs).
NOAEL is 8 mg/kg/day in males and 20 mg/kg/day for female. LOAEL
is 20 mg/kg/day in males and 50 mg/kg/day in females, based on
acute clinical signs in males and females (vomiting,
first observed on Day 1 and last observed on Day 90), clinical
pathology at 7 weeks (increased total protein
levels in males, lower red blood cells and higher reticulocytes
counts in females), increased adrenal
weights in males, decreased thymus gland weights in males, and
increased kidney tubular vacuolation in females at study termination
toxicity (dogs). NOAEL is 8 mg/kg/day. LOAEL is 20 mg/kg/day,
based on acute clinical signs(vomiting, mostly within the first
week), clinical pathology at 12 months (higher
reticulocytes counts) in males and females.
was not established. LOAEL is 250 ppm (equivalent to 29/38mg/kg/
day [M/F]), based on minimal to moderate centrilobular
hepatocellular hypertrophy, minimal to severe
extramedullary hematopoiesis, minimal to moderate
pigment deposition in the sternal bone marrow, and
increased incidence of tissue masses/nodules in the lungs in the
males, and minimal to moderate decreased
cellularity in the femoral bone marrow and hyperplasia/hypertrophy
of the epithelial cells of the terminal bronchioles of the females.
At the doses tested, the carcinogenic potential of IKI-220 (flonicamid)
is positive at 250 ppm in males and females based on the increased
incidence of alveolar/bronchiolar adenomas, carcinomas, and combined
adenomas/carcinomas. Dosing was considered adequate based on increased
incidence of tissue masses/nodules in the lungs and microscopic
findings in the liver, spleen, bone marrow, and lungs. However,
data were provided suggesting this effect is specific to sensitive
strains of mice. Carcinogenic in
rat. Parental LOAEL = 22 mg/kg/day based on increased kidney
weights, kidney hyaline deposition, increased
blood serum LH (F1 females)
August 31, 2005. Flonicamid; Pesticide Tolerance. Final Rule.
- Herbicide - CAS No. 69806-50-4
**411-083 069476 Virgo,
D. M., “Fluazifop-butyl: 55 week oral toxicity study in beagle
dogs,” Life Science Research, Stock, Essex, England, 10/15/82.
LSR Report No. 81/ILK019/620. Six dogs/sex/group were dosed for
55 weeks with Fluazifop-butyl, 99.6% purity, by gelatin capsules
at dose levels of 0, 5, 25, and 125 mg/kg/day in a chronic study.
Test article within capsules was dissolved in 0.4 ml/kg corn oil
vehicle. NOEL = 5 mg/kg/day... All
other noteworthy findings were limited to the high dose group,
as follows. Seven 125 mg/kg/day dogs (5 M, 2 F) were killed in
extremis prior to term, generally after at least 29 weeks on study.
Fluazifop-butyl caused ulcerations in the g.i. tract, specifically
in the tongue, lip, mouth lining, stomach pylorus, or cecum. Ulcerations
may have contributed to low RBC parameters in both sexes (reduced
HCT, Hb levels, and RBC counts, particularly in males). Platelet
counts were reduced by about half in both sexes.
taken at weeks 10 and 52 for smear analyses showed “reduced
numbers of megakaryocytes,” suggesting reduced production
as a reason for low platelet counts. Other
hematology-related findings included increased incidence/degree
of thymic involution, decreased lymphocyte counts, increased degree
of hemosiderin-laden Kupffer cells, hypercellular sternal marrow,
and severe extramedullary hematopoiesis in 4 male and 1 female
decedent. Four of the latter 5 dogs also had substantially
increased splenic weights, 'pallor'
in clinical signs as part of moribund condition, and their final
hematology red cell values (RBC count, Hb,
HCT) were very low. Eyes of eight high dose dogs had cataracts,
usually accompanied by miliary ('seed-like' appearance) vacuolation
of the lens. Liver dysfunction was indicated by periacinar hepatocytic
degeneration and thinning of hepatic cords in some dogs, other
hepatocytic changes such as vacuolation and/or granular cytoplasm,
and occasional bile plugs in the canaliculi. Most clinical chemistry
changes were plausibly related to liver toxicity, including elevated
alkaline phosphatase, ALT, and occasionally AST. Substantially
increased BSP retention was consistent with biliary disturbance.
Urine was typically bright yellow or orange due to high bile pigment
concentrations. Cholesterol was consistently
reduced. Male reproductive toxicity included testicular tubular
degeneration and reduced/absent spermatozoa in epididymides.
Possible adverse effects (many-faceted toxicity, including mortalities,
at 125 mg/kg/day). Acceptable. Aldous, 5/20/02.
Ref: May 20, 2002. SUMMARY OF TOXICOLOGY
DATA FLUAZIFOP-P-BUTYL. California EPA. Department of Pesticide
Regulation. Medical Toxicology Branch.
- Herbicide - CAS No. 79241-46-6
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
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,
- CAS No. 33245-39-5
PubMed Abstract: Basalin,
a herbicide, was administered orally to male rats at doses ranging
from 60 mg to 1.92 g/kg for 13 weeks. Oral LD50 of the compound
was 1.65 g/kg. Toxic effects included hyperexcitability and tremors.
The cumulative lethal dose (CLD50) at the end of week 13 was 135
mg/kg with a cumulative toxicity factor (CTF) of 12.22. At
1.92 g/kg, no
animals survived to 13 weeks. At 60 and 120 mg/kg, there were
no significant changes in body weight gain compared with the controls
and a significant decrease in total leukocyte
count (TLC), erythrocyte sedimentation rate (ESR) and Hb was observed.
There was a decrease in spermatogenesis
and infiltration of mononucleated cells in the liver.
Ref: Toxicol Lett 1983 Aug;18(1-2):13-8.
Subacute toxicity of Basalin in rats. Gupta PK, Singh YP, Parihar
- Herbicide - CAS No. 142459-58-3
-- 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,
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.
-- Chronic Feeding/ Carcinogenicity (rat): NOEL < 25 ppm [1.2
mg/kg/day in males and 1.5 mg/kg/day in females]. LOEL = 25 ppm
[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, spleen, heart, and uterus.
Under experimental conditions the treatment did not alter
the spontaneous tumor profile.
Ref: US EPA. Pesticide Fact Sheet. Flufenacet
Reason for Issuance: Conditional Registration Date Issued: April
- Acaracide, Insecticide, Herbicide - CAS No. 101463-69-8
The critical toxicological effects of flufenoxuron in mammals
are on the hemopoeitic [sic hematopoietic] system. These effects
include shifts in red blood cell parameters (decreased
in hemoglobin, hematocrit, red blood cells and erythroid: myloid
ratio) resulting in mild anemia and enhanced levels of
methemoglobin and sulfhemoglobin in dogs and rats. Dogs appears
to be more susceptible to the hematopoetic effects described above.
It is likely that a metabolite (aniline metabolite (4-[2chloro,
á, á, á-trifluoro-p-tolyoxy]-2-fluoroaniline)
is responsible for the formation of methemoglobin and sulfhemoglobin.
Two oncogenicity studies in mice and one in rat; were conducted
at doses exceeding 4 - 7.5x limit dose.
Reference: August 15, 2006.
US EPA Human Health Risk Assessment for proposed tolerances on
apples, pears, grapes, organges and livestock commodities imported
into US. http://www.fluorideaction.org/pesticides/flufenoxuran.hra.epa.2006.pdf
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.
dose studies. Sub-Acute Toxicity.
In an adequately conducted study 7/sex/dose Fischer 344 rats were
administered 0, 50, 500, 5000, 10000 or 50000 ppm flufenoxuron
[in] the diet for 28 days... Haematology parameters were measured
at necropsy. Methaemoglobin concentrations
were increased 100% at and above 500 ppm in males and 5000
ppm in females...
of Flufenoxuron use as a public hygiene insecticide. UK: Health
and Safety Executive, Biocides & Pesticides Assessment Unit.
- Herbicide - CAS No. 188489-07-8
-- EPA has not had
the opportunity to review the toxicity studies on flufenpyr-ethyl
and has not established toxic endpoints.
-- Subchronic toxicity. Subchronic oral toxicity studies conducted
with flufenpyr-ethyl in the rat, mouse and dog indicate a low
level of toxicity. i. Rats. Pure (99.4%) flufenpyr-ethyl was tested
in rats at dose levels of 0, 600, 2,000, 6,000, and 20,000 ppm
in the diet for 13 weeks. Effects observed included urinary incontinence,
increased food and water consumption, slight
hematological and blood biochemistry changes...
-- In an additional study, flufenpyr-ethyl technical was tested
in rats at dose levels of 0, 1,000, 10,000, and 20,000 ppm in
the diet for 13 weeks. Effects observed included urinary incontinence,
increased food and water consumption, and mild urinalysis, hematological
and blood biochemistry changes...
-- Mice. In a 4-week study, CD-1 mice were fed pure flufenpyr-
ethyl at dose levels of 0, 300, 1,000, 3,000, and 7,000 ppm. Effects
were slight anemia, changes in blood biochemistry...
-- In a 13-week study, flufenpyr-ethyl technical was administered
to mice at dose levels of 0, 300, 1,000, 3,000, and 7,000 ppm.
Slight anemia and blood biochemistry changes
-- Mice. In a 78-week oncogenicity study with mice, flufenpyr-
ethyl technical was administered at dose levels of 0, 350, 3,500,
and 7,000 ppm. Male animals exhibited slight
anemia. Females had increased liver
and kidney weights (week 53 only)...
Federal Register: June 25, 2003 (Volume 68, Number 122)] [Notices]
[Page 37813-37820]. Flufenpyr-ethyl; Notice of Filing a Pesticide
Petition to Establish a Tolerance for a Certain Pesticide Chemical
in or on Food.
- Microbiocide - CAS No. 42835-25-6
BIOLOGICAL DATA 2.1. Hepatotoxicity and carcinogenicity. In short-term
and long-term studies of toxicity that were evaluated by the Committee
at its forty-second and forty-eighth meetings, oral administration
of flumequine caused dose-related hepatotoxic
effects in rats and CD-1 mice. The liver damage was most pronounced
in male mice, and included degenerative changes with hypertrophy,
fatty vacuolation, focal necrosis and increased mitotic activity.
After cessation of treatment with flumequine, the liver damage
was reversed. Treatment with flumequine had little or no effect
on P450-dependent hepatic drugmetabolizing enzymes or on glucuronyl
transferase. Flumequine increased the plasma
activities of alanine and aspartate aminotransferases, alkaline
phosphatase and lactate dehydrogenase. The overall no-observed-effect
level (NOEL) for hepatotoxic effects in mice was 25mg/kg bw per
- Flumequine (addendum). First draft prepared by Mrs. M.E.J. Pronk,
Centre for Substances and Integrated Risk Assessment, National
Institute for Public Health and the Environment. Bilthoven, The
- Herbicide - CAS No. 87546-18-7
-- Chronic Toxicity
(Including Cancer): Studies with Flumiclorac Pentyl Technical
indicate that repeated high exposures produced changes in
liver, kidney, and red blood cells
but did not produce cancer in test animals.
-- Potentially Aggravated Condition: Individuals with preexisting
diseases of the liver, kidney, or red
blood cells may have increased susceptibility to the toxicity
of excessive exposures.
-- SUBCHRONIC: Compound-related effects noted at very high dose
levels of Flumiclorac Pentyl Technical in rodents and/or dogs
included: increased liver and kidney weights;
histological changes in the kidney and liver;
slight changes in blood biochemistry parameters; decreased red
blood cell count, hemoglobin, and hematocrit; and slight
decreases in body weight. The NOEL in rats and mice was 1000 ppm.
-- CHRONIC/CARCINOGENICITY: Effects of long-term high dose exposures
to Flumiclorac Pentyl Technical in rodents and/or dogs consisted
primarily of increases in kidney and liver
weights, slight changes in blood
biochemistry, and histological changes in
the liver. The lowest NOEL
was 300 ppm in the mouse study. Flumiclorac Pentyl Technical was
not carcinogenic in either rats or mice.
Ref: Material Safety Data Sheet for RESOURCE
- Herbicide - CAS No. 103361-09-7
and Other Toxicity
-- 870.3100 90-Day oral toxicity -rat NOAEL = mg/kg/day: 69.7
(M), 71.5 (F) LOAEL = mg/kg/day: 243.5 (M), 229.6 (F) based on
a decrease in MCV [mean corpuscular volume]
both sexes; increase in platelets F only
-- 870.3100 90-Day oral toxicity -rat NOAEL = mg/kg/day: 65.0
(M), 72.9 (F) LOAEL = mg/kg/day: 196.7 (M), 218.4 (F) based on
-- 870.4300 Combined chronic carcinogenicity - rat NOAEL = mg/kg/day:
males = 1.8, females = 2.2 LOAEL = mg/kg/day: males = 18.0, females
= 21.8 based on increased chronic nephropathy
in males and decreased hematological
parameters in females (Hgb, MCV, MCH and MCHC) No evidence
of carcinogenicity 870.5100 Gene mutation in S. typhimurium and
E. coli Neither cytotoxic nor mutagenic up to 2000 g/plate. There
were reproducible increases in revertant colonies of S. typhimurium
strains TA1538 and TA98 in S9 activated phases of the preliminary
cytotoxicity and both mutation assays. [Results considered to
Ref: US EPA Pesticide Fact Sheet. April
... Mild cholinesterase inhibitor & /causes/ ... an
increased leukocyte count in circulating blood in exposed agricultural
workers. [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical
Toxicology of Commercial Products. 5th ed. Baltimore: Williams
and Wilkins, 1984.,p. II-331]
Ref: Hazardous Substance Data Bank for Fluometuron.
Available at Toxnet
Abstract: On single
oral administration of (14)C-S-53482 [7-fluoro-6-(3,4,5, 6-tetrahydrophthalimido)-4-(2-propynyl)-2H-1,4-benzoxazin-3(
4H)-one, Flumioxazin] labeled at the 1- and 2-positions of tetrahydrophthaloyl
group to rats at 1 (low dose) or 100 (high dose) mg/kg, the radiocarbon
was almost completely eliminated within 7 days after administration
in both groups with generally very low residual (14)C tissue levels.
The predominant excretion route was via the feces. The major fecal
and urinary metabolites involved reduction or sulfonic acid addition
reactions at the 1,2-double bond of the 3,4,5,6-tetrahydrophthalimide
moiety and hydroxylation of the cyclohexene or cyclohexane ring.
One urinary and four fecal metabolites were identified using chromatographic
techniques and spectroanalyses (NMR and MS). Three of five identified
metabolites were unique forms, reduced at the 1,2-double bond
of the 3,4,5, 6-tetrahydrophthalimide moiety. On the basis of
the metabolites identified in this study, the metabolic pathways
of S-53482 in rats are proposed. To specify tissues forming reduced
metabolites, an in vitro study was conducted. Reduction
was found to take place in red blood cells.
Ref: Tomigahara Y et al. (1999).
Metabolism of 7-fluoro-6-(3,4,5,6-tetrahydrophthalimido)-4- (2-propynyl)-2H-1,4-benzoxazin-3(4H)-one
(S-53482, flumioxazin) in the rat: II. Identification of reduced
metabolites. J Agric Food Chem. Jun;47(6):2429-38.
Abstract: An N-phenylimide
herbicide, S-53482, inhibits protoporphyrinogen oxidase, an enzyme
common to chlorophyll and heme biosynthesis, and produces embryolethality,
teratogenicity [mainly ventricular septal defects (VSD) and wavy
ribs], and growth retardation in rats. In order to elucidate the
mechanism of the developmental toxicity, in particular VSD, effects
of the herbicide on rat embryonic blood cells were investigated
histologically at the light and electron microscopic levels at
6, 12, 24, 36, and 48 h after oral administration of the chemical
to pregnant rats on day 12 of gestation, the most sensitive day
for toxicity. Electron and light microscopy demonstrated mitochondrial
lesions, including abnormal iron deposits
that were probably due to inhibition of heme biosynthesis,
in erythroblasts derived from the yolk sac. Subsequently, degeneration
of these erythroblasts occurred followed by erythrophagocytosis.
Histologically hearts from exposed embryos had a thin ventricular
wall, which may reflect a compensatory reaction
to a loss of embryonic blood cells. Thus, the herbicide
may induce VSD due to hematological dysfunction
caused by the inhibition of heme biosynthesis rather than by direct
injurious effects on the heart.
Ref: Kawamura S et al (1996).
Histological changes in rat embryonic blood cells as a possible
mechanism for ventricular septal defects produced by an N-phenylimide
herbicide. Teratology. Nov;54(5):237-44.
- Herbicide - CAS No. 2164-17-2
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.
-- Organ Toxicity.
Toxic injury to the liver, kidneys, gut
and brain is induced when lethal doses of fluometuron are administered
experimentally (10). An increase in spleen weight and in the incidence
of abnormalities in red-blood cells,
and decreased weight gain in females were
observed in a 90-day study of rats (18).
-- Carcinogenic Effects. EPA has determined that there is not
enough evidence that fluometuron causes cancer in animals to justify
its classification as a carcinogen. Fluometuron is not classified
as a carcinogen by the EPA (20). An increased incidence of
liver-cell tumors in male mice
was noted in a study of rats and mice. In the same study, no carcinogenic
effects were observed in female mice or in rats of either sex
(18). Mice that were given oral doses of 87 mg/kg for two years
had evidence of liver tumors and
leukemia, a condition characterized by uncontrolled growth in
the number of white blood cells in the blood stream (7).
-- ACUTE TOXICITY. ... It may be fatal if inhaled, swallowed,
or absorbed through skin, as it is irritating to the mucous membrane
lining the skin, gastrointestinal tract, and respiratory system
(2). While there have been no reports of cases of fluometuron
poisoning in humans, this herbicide is considered a mild
inhibitor of cholinesterase. Cholinesterase is an essential
enzyme of the nervous system. Cholinesterase inhibition was observed
in guinea pigs exposed by inhalation to 588 mg/m3 for 2 hours
(18). (For more information, refer to the Toxicology Information
Brief on Cholinesterase-Inhibition). Fluometuron
caused an increased white blood cell count in agricultural workers
Ref: Flumeturon. EXTOXNET. Pesticide Information
Profile. March 1994.
-- PubMed abstract:
Twelve of fifteen 6-9-mo-old clinically healthy Desert sheep were
given single or repeated daily doses of 25
to 4000 mg cotoran/kg by drench. Cotoran poisoning was characterized
by grinding of the teeth, ruminal tympany, mydriasis, dyspnea,
staggering, paresis of the hind and forelimbs, and recumbency.
Lesions were widespread congestion and hemorrhage, hepatic fatty
change, catarrhal enteritis and degeneration of the epithelial
cells of the renal proximal convoluted tubules. These
were accompanied by significant increases in the activities of
GOT, LDH and GGT and decreases in serum total protein and calcium.
Ref: Vet Hum Toxicol 1995 Jun;37(3):214-6.
of cotoran (fluometuron) in Desert sheep; by Mohamed OS, Ahmed
KE, Adam SE, Idris OF.
In the mouse
1 and 3 month study, the rat 1 month
study and the dog 52 week study,
reductions in haemoglobin levels, red blood
cell numbers and packed cell volume were variously seen,
predominantly at the top doses. Nucleated
and polychromatic red blood cell numbers were raised in
the rat study only. These effects appeared reversible, in both
the 1 month rat and mouse studies. It would appear that any potential
haemolytic effects, possibly from aniline-derivatives, are of
secondary importance to other subchronic effects...
Evaluation on: Fluoroglycofen-ethyl. May 1992. Issue No. 50. Department
for Environment, Food and Rural Affairs, Pesticides Safety Directorate,
Former insect Chemosterilant; now used as a pharmaceutical - CAS No. 51-21-8
Major toxic effects
result from myelosuppressive action. Clinical effects are leukopenia,
thrombocytopenia, and anemia.
Loss of hair, occasionally progressing to total alopecia, nail
changes, dermatitis, and increased pigmentation and atrophy of
skin may occur.
Ref: OXNET profile from Hazardous Substances
Data Base for FLUOROURACIL.
Leukopenia - an abnormal
lowering of the white blood cell count
blood disease characterized by an abnormally small number of platelets
in the blood
- CAS No. 136426-54-5
-- Oral long-term toxicity
and carcinogenicity. 2-year dietary study in rats. groups of 50
male and 50 female outbred albino Sprague-Dawley CRL :COBS CD(SD)BR
rats were administered fluquinconazole (93.2% purity) in the diet
at concentrations of 0 (control), 1, 20 or 100 ppm. Additionally
20 animals/sex/dose designated for the interim-kill received the
test compound at concentrations of 0, 1, 5, 10 or 100 ppm for
12 months... There was a very slight reduction
in red blood cells, haemoglobin and haematocrit in females during
the first 12 months. At 24 months, the mean cell volume, mean
corpuscular haemoglobin (MCH) and haemoglobin values were statistically
significantly lower at the 100 ppm dose level than in controls.
In males, the mean cell volume, mean corpuscular haemoglobin (MCH)
and haemoglobin values were statistically significantly lower
than controls at 12 months only. The
main changes in clinical chemistry were related to serum protein
Short Term Toxicity. Oral route. Rat. (b)... Groups of 5 male
and 5 female outbrd albino Sprague-Dawley Crl:COBS CD(SD)BR rats
were each administered fluquinconazole (100% purity) either in
the diet at concentrations of 0 (control), 5, 20, 100 and 400
ppm or by gavage dissolved in 1 % aqueous methlcellulose at a
dose level of 10 mg/kg bw/day for 28 days. Due to mortalities
at the 400 ppm dose level, a supplementary gorups of 5 male and
5 female animals were administered fluquinconazole at a dose level
of 200 ppm... Minimal statistically
non-significant differences were noted in surving male rats at
the 200 ppm were reduction in white blood
cells, reduction in lymphocytes and increased mean cell haemoglobin
concentration. Changes in clinical chemistry parameters were related
primarly to plasma proteins...
-- Short Term Toxicity. Oral route. Rat. (c). In a 3-month feeding
study, groups of 10 male and 10 female outbred albino Spraque-Dawley
CRL:COBS CD(SD)BR rats were administered fluquinconazole (>96.2%
purity) at concentrations of 0 (controls), 1, 5, 15, or 100 ppm.
Additional groups of animals at the 0 (control) and 100 ppm dose
levels were kept on an untreated diet for 4 weeks in order to
invetigate the regressivity of effects. Blood samples were taken
after 6 and 13 weeks of treatment for haematological and clinical
chemistry investigations... Haematology,
clinical chemistry and urinalysis parameters showed
incidences of statistically significant changes which were
considred to be of limited toxicological significance because
they were either not dose-related or were reported to be withing
the range of historical data.
Ref: Evaluation on: Fluquinconazole. May
1999. No. 184. Evaluation of Fully Approved or Provisionally Approved
Products. Department for Environment, Food and Rural Affairs,
Pesticides Safety Directorate, Mallard House, Kings Pool, 3 Peasholme
Green, York YO1 7 PX, UK. Available online:
- Fungicide -
CAS No. 85509-19-9
-- In a one-year feeding study, dogs were given flusilazole in
the diet at concentrations of 0, 5,20, and 75 pprn (MRID 400421
13). There were treatment-related effects
on hematological parameters at 75 pprn including increased white
blood cell count, ALP activity, and serum cholesterol. Serum total
protein and albumin levels were lower in the male high dose group.
Relative liver weight was increased at 75 ppm. Treatment-related
histopathological changes included liver centrilobular hepatocellular
enlargement and centrilobular inflammation and hyperplasia in
the lymphoid nodules of the gastric mucosa observed in the high
dose. In summary, the effects of feeding flusilazole to dogs for
one year were a dose-related trend towards mild to moderate hepatotoxicity
and a mild leucocytosis (inflammatory) response. The effects were
mainly seen in the high dose group and most pronounced in males.
The liver hypertrophy was considered likely to be an adaptive
response to increased metabolic demand. Based on minimal liver
histology at the mid-dose, 20 ppm (0.7 mgkglday) is considered
a NOAEL. (Pages 18-19)
-- Short-term exposure toxicity of flusilazole was investigated
in rats (gavage and dietary), mice (dietary), dogs (dietary) and
in rabbits (dermal application). The targets
identified were the blood system, liver and urinary bladder.
The dog was found to be the most sensitive species to the hepatotoxicity
and bladder toxicity of flusilazole. Degenerative
liver disorder and evidence of cellular proliferation (hyperplasia)
in the urinary bladder were seen at 125 ppm (4.3 mgikglday) in
the dog. The NOAEL was 0.9 mgkgiday. (Page
Ref: DuPont Punch (Active ingredient: Flusilazole)
and DuPont Charisma (Active ingredients: Flusilazole and Famoxadone):
Summary of data compiled in support of a
Section 18 Emergency Exemption request for control of Asian soybean
rust on soybeans. By DuPont authors: Cosgrove T, Czochor L, Dinter
A, Jemberg K, Klemens A, Marcon A, McInnes B, Mullin L, Russell
M, Ryan D, Singles S, Vanderbroeck V. Revision No. 1: February
- Herbicide - CAS No. 117337-19-6
-- 90-day oral Toxicity,
rats and mice. Rats: NOAEL = 6.19 milligrams/ kilograms day (mg/
kg/day) in males 6.80 mg/ kg/day in females LOAEL = 216 mg/ kg/day
in males 249 mg/ kg/day in females Mice: NOAEL = 1.3 mg/kg/ day
in males 1.6 mg/ kg/day in females LOAEL = 66 mg/kg/ day in males
83 mg/kg/ day in females. Based on decreased
body weight gains as well as effects
on hematology, clinical
parameters, liver weights and microscopic pathology in rats; and
on effects on the erythropoietic system and liver in mice.
-- Carcinogenicity rats. NOAEL in males = 2.1 mg/kg/day LOAEL
in males = 130 mg/kg/day NOAEL in females = 2.5 mg/kg/day LOAEL
in females = 154 mg/kg/dayIn males there were
decreased body weight, liver toxicity, pancreatic toxicity
and microcytic anemia. In females
there were liver toxicity, uterine toxicity
and slight microcytic anemia.
In males only at 130 and 219 mg/kg/day there was respectively,
an increase in the trend toward pancreatic
exocrine adenomas and pancreatic islet cell adenomas.
-- In a 90-day rat feeding study the NOAEL was 6.19 mg/kg/day
for males and 6.80 mg/kg/day for females. In a 6-week dog dietary
study the NOAEL was 236 mg/kg/day for males and 77.7 mg/kg/day
for females. In a 28-day rat dermal study the NOAEL was 1000 mg/kg/day
[HDT]. In a 1-year dog chronic feeding study, the NOAEL was 57.6
mg/kg/day for males and 30.3 mg/kg/day for females and the Lowest
Observed Adverse Effect Level (LOAEL) was 582 mg/kg/day for males
and 145 mg/kg/day for females based on effects observed in the
erythropoietic system [red blood cells]
and the liver.
-- Chronic toxicity NOAEL in males = dogs 57.6 mg/kg/day LOAEL
in males = 582 mg/kg/day NOAEL in females = 30.3 mg/kg/day LOAEL
in females = 145 mg/kg/day The LOAELs were based on effects observed
in the erythropoietic system and
Ref: Federal Register: December
21, 2001. Fluthiacet-methyl; Pesticide Tolerance. Final Rule.
- Acaracide, Insecticide - CAS No. 69409-94-5
of 2.5 mg/kg/day to rats for 13 weeks produced anemia
in blood parameters (decreased hematocrit, hemaglobin, and red
blood cells). The NOEL was 1.0 mg/kg/day. Dietary administration
of 30 mg/kg/day (LOEL) to rats for 3 months produced decreased
hemoglobin, hematocrit, and red blood cell count in rats.
The NOEL was 3 mg/kg/day... EPA believes that there is sufficient
evidence for listing fluvinate on EPCRA section 313 pursuant to
EPCRA section 313(d)(2)(B) based on the available developmental,
dermal, and hematological toxicity
data for this chemical.
USEPA/OPP. Support Document for the Addition of Chemicals from
Federal Insecticide, Fungicide, Rodenticide Act (FIFRA) Active
Ingredients to EPCRA Section 313. U. S. Environmental Protection
Agency, Washington, DC (1993). As cited by US EPA in: Federal
Register: January 12, 1994. Part IV. 40 CFR Part 372. Addition
of Certain Chemicals; Toxic Chemical Release Reporting; Community
Right-to-Know; Proposed Rule.
- Herbicide - CAS No. 72178-02-0
plasma cholesterol and triglycerides and increased liver
weights (reversible at 7 days post-treatment) were observed at
50 mg/kg/day (only dose tested) when administered in the diet
of rats for 4 weeks.
USEPA/OPP. Support Document for the Addition of Chemicals from
Federal Insecticide, Fungicide, Rodenticide
Act (FIFRA) Active Ingredients to EPCRA Section 313. U. S. Environmental
Protection Agency, Washington, DC (1993). As cited by US EPA in:
Register: January 12, 1994. Part IV. 40 CFR Part 372. Addition
of Certain Chemicals; Toxic Chemical Release Reporting; Community
Right-to-Know; Proposed Rule.