Some
Definitions:
Anisocytosis:
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
hydroxyurea). http://www.kumc.edu/instruction/medicine/pathology/ed/keywords/kw_anisocyt.html
Erythrocyte:
A mature red blood cell. SYN. haemacyte, hemacyte, red
blood cell, red corpuscle.•
Erythropoiesis
is the process of red blood cell production (which occurs
in red bone marrow).•
Haemangioma
(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
Heinz'
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 Innenkšrper (German) Ehrlich hşmoglobinşmische
Innenkšrper (German) Heinz-Ehrlich bodies http://www.whonamedit.com/synd.cfm/658.html
Hematopoietic.
SYN hemopoietic (see below).
Hemopoietic.
Pertaining to or relted to
the formation of blood cells. SYN haemoplastic, hematogenic
(1), hematogenous, hematoplastic, hematopoietic, hemogenic,hemoplastic,
sanguifacient.•
Hematopoietic
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.•
Hypochromasia:
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
Leukocyte
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
Lipofuscin.
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"
pigment.
http://www.nlm.nih.gov/medlineplus/ency/article/002242.htm
Methemoglobinemia.
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
Microcytic
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.
http://www.cariboo.bc.ca/schs/medtech/RICE/intromicroanemia.html
Polychromasia:
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
crisis. http://www.kumc.edu/instruction/medicine/pathology/ed/keywords/kw_polychro.html
Sulfhemoglobinemia.
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 ed
|
The
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
is available.
--
Food and Agricultural Organization of the United Nations
|
Note:
This is not an exhaustive list.
As time allows more information will be added.
Ammonium
fluosilicate-
Insecticide, Miticide Wood Preservative,
EPA List 3 Inert
-
CAS No. 16919-19-0
LD50 ranges of sodium,
potassium, or ammonium fluorosilicates administered intragastrically
in rats and mice were 89-128 and 45-64 mg fluoride ion/kg, respectively.
Severe cornea damage was observed 3 hr after the administration
of 50 mg of any of the salts into rabbits' eyes. Min toxic dose
(intragastric) of fluorosilicic acid in rats was 8 mg/kg. Min
toxic concn in 4 hr inhalation of the salt aerosols were 7.4-9.6
mg/cu m; nontoxic concn was 0.8 mg/cu m. Main toxic effects were
decreased activities of cholinesterase and
lactate dehydrogenase in blood serum.
The intragastric effects of the fluorosilicates were similar to
and additive with those of sodium fluoride. [Rumyantser GI et
al; Oig Sanit (11): 80-2 (1988)]
Ref: TOXNET profile from Hazardous Substances
Data Bank for AMMONIUM SILICOFLUORIDE.
http://www.fluoridealert.org/pesticides/ammonium.silicofluor.toxnet.htm
Chronic: Causes severe
skin irritation and burns. Ingestion or inhalation may be harmful
and possibly fatal depending on severity and length of over-exposure.
Chronic over- exposure may cause fluorosis. Product may be absorbed
through the skin and produce signs of fluorosis such
as weight loss, brittleness of bones, anemia,
weakness and stiffness of joints. Internal
bleeding may develop. First aid procedures should be followed
even in cases of suspected contact.
Ref:
Ammonium fluorosilicate Material Safety Data Sheet from LCI, Ltd.
http://www.fluorideaction.org/pesticides/ammonium.fluosilicate.msds.htm
Benfluralin
(Benefin) - Herbicide -
CAS No. 1861-40-1
Increased relative
liver weights, decreased red blood cell
counts and decreased hematocrit and
hemoglobin levels were observed in dogs orally administered
benfluralin at a dose of 125 mg/kg/day for 2 years. The NOAEL
was 25 mg/kg/day. Based on the NOAEL, EPA has established an oral
RfD of 0.003 mg/kg/day. EPA believes that there is sufficient
evidence for listing benfluralin on EPCRA section 313 pursuant
to EPCRA section 313(d)(2)(B) based on the available hematological
toxicity data for this chemical.
Ref:
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.
Boron
Trifluoride
- Fumigant -
CAS No. 7637-07-2
-- Target Organs: Lungs,
blood, bones
and teeth.
Ref: Material Safety Data Sheet for Boron
Trifluoride (BF3). May 2001.
http://www.fluoridealert.org/pesticides/boron.trifluoride.msds.htm
Butafenacil
-
Herbicide - CAS No. 134605-64-4
The
most susceptible species in long term studies was the mouse. A
NOEL for butafenacil-allyl of 0.36 mg/kg bw/day was found for
males in an 18 month study, essentially based on
haematological effects mostly in males and liver toxicity
in animals of both sexes. A rat 2-year study revealed a NOEL of
1.14 mg/kg bw/day for males, based on liver toxicity in animals
of both sexes. A safety factor of 100 is considered appropriate
for the ADI, due to the extensive toxicology database for butafenacil-allyl.
This results in an ADI of 0.004 mg/kg bw/day (p 10).
Long-Term Studies. Mice received butafenacil in the diet at concentrations
of 0, 1, 3, 10 and 60 ppm over 18 months.
Haematological effects included lower mean values for erythrocyte
count, haemoglobin concentration and haematocrit in males at 60
ppm at weeks 53 and 79, respectively, and for erythrocyte count,
haemoglobin and haematocrit at week 79 in males at 10 ppm. Males
also had slightly increased neutrophil and monocyte counts at
60 ppm, and a slight thrombocytosis. Mean absolute and
relative liver weights were increased in both sexes at 60 ppm.
The incidence of enlarged liver was increased in males at 60 ppm
and in females at 10 and 60 ppm. Microscopic examination revealed
an increased incidence of hepatocyte necrosis and hyperplasia
of Kupffer cells in the liver of males at 10 and 60 ppm, and of
females at 60 ppm. In addition, an increased incidence of lipofuscin
deposition, and inflammatory cell infiltration was seen in males
at 60 ppm. There was no treatment-related increase in the incidence
of neoplasms at any dose. Butafenacil was not carcinogenic in
mice. The NOEL was 3 ppm in males and 10 ppm in females, equivalent
to 0.36 and 1.20 mg/kg bw/day for males and females, respectively
(p7-8)....
Ref:
Public Release Summary on Evaluation of the new active BUTAFENACIL
in the products LOGRAN B-POWER HERBICIDE & TOUCHDOWN B-POWER HERBICIDE.
National Registration Authority for Agricultural and Veterinary
Chemicals. Australia. February 2002.
Also available at:
http://www.nra.gov.au/publications/prsbuta.pdf
Some
excerpts from Table 3.--Toxicological Dose and Endpoints for
Butafenacil
- a summary of the toxicological endpoints used for human
risk assessment
Ref: Butafenacil;
Pesticide Tolerance. Final Rule. Federal Register. September
19, 2003.
http://www.fluorideaction.org/pesticides/butafenacil.fr.sept.19.2003.htm
|
-- Exposure Scenario
-- Dose Used in Risk Assessment, UF
-- Special FQPA SF* and Level of Concern
for Risk Assessment |
Study
and Toxicological Effects |
--
Chronic dietary (All populations)
-- NOAEL= 1.2 mg/kg/day UF = 100
-- Chronic RfD = 0.012 mg/ kg/day.
-- Special FQPA
SF = 1 cPAD = chronic RfD
-- Special FQPA SF = 0.012 mg/kg/day. |
Mouse
oncogenicity study.
The LOAEL is 6.96 mg/kg/. day, based on enlarged
livers with increased
weights, and hepatic microscopic lesions including Kupffer
cell hyperplasia, inflammatory cell infiltration, and single
cell necrosis in both sexes and on deposits of
lipofuscin in males |
--
Short-term inhalation (1 to 30 days)
-- Oral NOAEL = 18.8 mg/kg/ day
-- Residential LOC for MOE = 100
-- Occupational = 100 |
90-day
rat feeding study.
The LOAEL for this study is 62.3 mg/kg/ day based on decreased
hemoglobin,
hematocrit, mean corpuscular hemoglobin, mean corpuscular
volume, increased red cell volume distribution width,
and increased incidence of bone marrow
hypercellularity |
--
Short-term incidental oral (1 to 30 days)
-- Intermediate-term incidental oral (1- 6 months)
-- LOAEL = 18.8 mg/kg/day
-- Residential LOC for MOE = 100
-- Occupational = NA |
90-day
rat feeding study.
The LOAEL for this study is 62.3 mg/kg/ day, based on decreased
hemoglobin, hematocrit,
mean corpuscular hemoglobin, mean corpuscular volume, increased
red cell volume distribution width, and increased
incidence of bone marrow hypercellularity |
--
Short-term inhalation (1 to 30 days)
-- Intermediate-term inhalation (1 to 6 months)
-- Oral NOAEL = 18.8 mg/kg/day
-- Residential
LOC for MOE = 100
-- Occupational = 100 |
Same
as above |
Some excerpts from Table 2.--Subchronic,
Chronic, and Other Toxicity
Ref:
Butafenacil; Pesticide Tolerance. Final
Rule. Federal Register. September 19, 2003.
http://www.fluorideaction.org/pesticides/butafenacil.fr.sept.19.2003.htm
|
Study
type
[Guideline number] |
Results |
90-Day
oral (dietary) toxicity rodents
(rat) - [870.3100] |
NOAEL
= 300 ppm (18.8/20.6 mg/kg/ day M/F). LOAEL = 1,000 ppm (62.3/69.3
mg/kg/ day M/F) based on decreased body weight gains, decreased
hemoglobin, hematocrit, mean corpuscular hemoglobin (MCH),
mean corpuscular volume (MCV), increased red cell volume,
increased bone marrow hypercellularity;
increased bilirubin and urobilinogen; increased alanine
aminotransferase; hepatocyte necrosis;
inflammatory liver cell infiltration |
90-Day
oral (capsule) toxicity in non- rodents (dog)
- [870.3150] |
NOAEL
= 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 |
1-Year chronic oral (capsule) toxicity
(dog) - [870.4100] |
NOAEL = 500 mg/kg/day M/F LOAEL = 1,000 mg/kg/ day M/F, based
on decreased body weight gain in males, decreased
MCV, MCH, and mean corpuscular hemoglobin concentration (MCHC);
increased thrombocytes and red cell volume distribution width;
hepatic histopathology: glycogen disposition, inclusion bodies
in cytoplasm, and pigment disposition in both sexes, and
focal vaculolation in females |
18-Month
carcinogenicity dietary study
(mouse) - [870.4200] |
NOAEL
= 10 ppm (1.17/1.20 mg/kg/day M/F) LOAEL = 60 ppm (6.96/ 6.59
mg/kg/day M/ F), based on enlarged livers
with increased weights, and hepatic microscopic lesions
including Kupffer cell hyperplasia, inflammatory cell infiltration,
and single cell necrosis in both sexes and on deposits of
lipofuscin in males No evidence
of carcinogenicity |
Mechanistic studies - [870.7485] |
Effects
on enzymes of cultured mouse, rat, and/or human hepatocytes
involved with heme biosynthesis |
Mechanistic studies - [870.7485] |
Effects
on liver microsomal and plasma
protox activity and its metabolic
conversion |
Mechanistic studies - [870.7485] |
Effects on porphyrin profile in rats; treatment induced porphyria,
consisting of accumulation of selected porphyrins in the
liver, spleen, and plasma
and increased excretion in urine and feces |
Mechanistic studies - [870.7485] |
Test
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 P450 system |
Carfentrazone-ethyl - Herbicide - CAS No. 128639-02-1
-- Repeat-dose studies
indicate that the primary targets for carfentrazone-ethyl toxicity
are the liver, kidney, and
the red blood cell forming system... Effects
on the red blood cell forming system were seen in most studies.
These effects included a reduction in the number of
red cells in blood and an associated increase in the products
of red blood cell degradation appearing
in the urine and liver.
-- 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...
-- 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...
-- Short-Term Studies... In rats fed up to 20 000 ppm carfentrazone-ethyl
in the diet for 90 days, abdominogenital staining and pink-brown
discolouration of the cage-pan liner was observed at concentrations
4000 ppm. Body weight and food consumption
were reduced in males at concentrations ¥ 8000 ppm and in females
at concentrations ¥ 8000 and 4000 ppm respectively. Erythrocyte
parameters (Hb, Hct, MCV, MCH) were reduced at concentrations
¥ 8000 ppm and platelets were increased in males at the same concentrations.
Plasma ALT, AST, potassium, phosphorus and bilirubin were increased
at concentrations ¥ 8000 ppm whereas glucose was reduced...
-- Short-Term Studies... Dogs given capsules containing carfentrazone-ethyl
at doses up to 1000 mg/kg bw/day for 90 days exhibited subdued
behaviour, salivation and vomiting at the highest dose. Mean
corpuscular haemoglobin was reduced at doses ¥ 500 mg/kg
bw/day and mean corpuscular volume was reduced in males at this
dose. Red blood cell count was increased
in males receiving the highest dose. Total urinary porphyrins
were increased at doses ¥ 500 mg/kg bw/day and liver weight was
increased in females at this dose....
-- Long-Term Studies. Mice fed carfentrazone-ethyl at concentrations
of 0, 70, 700 or 7000 ppm for 80 weeks had increased mortality
at concentrations ¥ 700 ppm. Body weights
and body weight gains were reduced at 7000 ppm in females and
in all treated males. Red blood cell
count and haematocrit were reduced and mean corpuscular
volume was increased in females at concentrations ¥ 70 ppm. Haemoglobin
was reduced at concentrations ¥ 700 ppm and mean corpuscular volume
and mean corpuscular haemoglobin concentration were increased
in males at concentrations ¥ 70 ppm. Haemosiderosis,
porphyrin deposits and treatment related histopathological changes
were observed in males at concentrations ¥ 700 ppm and in females
at the highest concentration. A NOEL was not established for this
study, because reduced body weight gain was observed in males
at the lowest concentration tested (70 ppm, equal to 10 mg/kg
bw/day).
-- Long-Term Studies... In rats fed 0, 50, 200, 800 or
4000 ppm carfentrazone-ethyl for 52 or 104 weeks slight decreases
in red blood cell counts in males
and increases in mean corpuscular haemoglobin and mean corpuscular
haemoglobin concentration were observed at ¥ 200 ppm...
-- Long-Term Studies... In dogs given carfentrazone-ethyl in capsules
at doses of 0, 50, 150, 500 or 10000 mg/kg bw/day for 52 weeks,
increased urinary porphyrins were observed at doses ¥ 150 mg/kg
bw/day. A slight reduction in mean corpuscular haemoglobin
and mean corpuscular haemoglobin concentration was observed
in males at the same doses and an increase in liver to body weight
ratio was observed in females at doses ¥ 500 mg/kg bw/day. The
NOEL for this study was 50 mg/kg bw/day based on the slight increase
in urinary porphyrins at 150 mg/kg bw/day.
Ref:
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.
51555.
http://www.fluorideaction.org/pesticides/carfentrazone-e.aus.2000rpt.pdf
Also
available at
http://www.apvma.gov.au/publications/prscar.pdf
Clodinafop-propargyl
-
Herbicide - CAS No. 105512-06-9
-- Carcinogenicity.
In accordance with the EPA Proposed EPA Weight-of-the-Evidence
Categories, August 1999, the Agency's Cancer Assessment Review
Committee (CARC) classified clodinafop-propargyl as "likely
to be carcinogenic to humans" by the oral route based on
the occurrence of prostate tumors in male rats, ovarian tumors
in female rats, and liver tumors in both
sexes of mice, as well as blood vessel tumors
in female mice. For the quantification of human cancer
risk, the CARC recommended a linear low-dose extrapolation approach
based on the most potent of these tumor types. This approach is
supported by possible genotoxic potential and the lack of confirmation
of the mode of action of clodinafop-propargyl. The most potent
unit risk, Q1 * (mg/kg/day) -1 , of those calculated for clodinafop-propargyl
is that for male mouse liver benign hepatoma and/or carcinoma
combined tumor rates at 0.129 (mg/kg/day) -1 in human equivalents.
SUBCHRONIC AND CHRONIC TOXICITY
Ref:
US EPA Pesticide Fact Sheet. Reason for Issuance: Conditional
Registration. June 6, 2000.
http://www.epa.gov/opprd001/factsheets/clodinafop.pdf
Cloransulam-methyl
- Herbicide - CAS No. 147150-35-4
-- In the rat Chronic
Feeding / Carcinogenicity study the NOEL was equal to 75 mg/kg/day
and the Lowest Observed Effect Level (LOEL) was 325 mg/kg/day
based on significant increase in hemoglobin,
hematocrit, and red cell count in males, activities of
the liver enzymes aspartate and alanine
aminotransferase as well as alkaline phosphatase were decreased
in males, cholesterol was decreased in females, specific gravity
of urine was decreased in females, increased relative wight in
liver and relative weight of testes in males, males exhibited
an increased incidence of collecting duct hypertrophy and females
exhibited increased incidence of vacuolation in the kidney. There
was no evidence of carcinogenicity for cloransulam-methyl in this
study. In the mouse carcinogenicity study the NOEL was 10 mg/kg/day
and the LOEL was 108 mg/kg/day based on based on a decrease in
renal tubule vacuolation in male mice, increased size of centrilobular
and midzonal hepatocytes accompanied by altered tinctorial properties
in females and centrilobular hepatocyte hypertrophy in males.
Total tumor incidence (adenoma + carcinoma) was not increased
by dosing with cloransulam-methyl.
-- 21-day dermal (rabbit): Dermal Irritation NOEL 1000 mg/kg/day
Systemic NOEL = 500 mg/kg/day Systemic LOEL = 1000 mg/kg/day based
on decreased red cell count, hemoglobin
and hematocrit, anisocytosis and macrocytosis of red cells for
females.
-- Chronic Feeding/ Carcinogenicity (rat): NOEL = 75 mg/kg/day
LOEL = 325 mg/kg/day based on significant
increase in hemoglobin, hematocrit, and red cell count in males,
activities of the liver enzymes aspartate
and alanine aminotransferase as well as alkaline phosphatase were
decreased in males, cholesterol was decreased in females, specific
gravity of urine was decreased in females, increased relative
wight in liver and relative weight of testes in males, males exhibited
an increased incidence of collecting duct hypertrophy and females
exhibited increased incidence of vacuolation in the kidney. There
was no evidence of carcinogenicity for cloransulam-methyl
in this study.
Ref: USEPA. Pesticide Fact sheet. Cloransulam-methyl.
Reason for Issuance: Conditional Registration Date Issued: October
29, 1997.
http://www.epa.gov/opprd001/factsheets/cloransulam.pdf
... Cloransulam-methyl
84% DF was not found to be carcinogenic, teratogenic or to cause
reproductive effects. In-vitro and animal mutagenicity studies
were negative. Target organ effects have
been reported in the blood, kidney, liver,
testes and thyroid gland...
Ref: Material Safety Data Sheet for Gauntlet
Herbicide. MSDS Ref. No: F18-20-2. Date Approved: 09/25/2000.
Revision No. 1. FMC Corporation, Agricultural Products Group,
1735 Market Street, Philadelphia, PA 19103, USA.
http://www.fluoridealert.org/pesticides/gauntlet.herbicidemsds.2000.pdf.
Also available at http://www.cdms.net/ldat/mp48J001.pdf
Cyfluthrin
-
Insecticide - CAS No. 68359-37-5
-- Cyfluthrin. 28-Day
oral toxicity NOAEL = 15.0 (males & females) based on minimal
decrease in
blood glucose.
LOAEL = 50 based on, gait abnormalities, salivation, nervousness,
decrease in body weight, food consumption, changes
in hematological, clinical chem. & urinalysis parameters,
increases in selected organ wts., cytoplasmic swelling of glandular
epithelium of submaxillary gland, minimal
degrees of fiber degeneration in sciatic nerve (# not reported)
which disappeared after recovery period.
-- Cyfluthrin (93.8% a.i.). 4-Week inhalation toxicity study--rats.
NOAEL = 0.00044 mg/L (0.12 mg/kg/day; males & females) LOAEL =
0.006 mg/L (1.6 mg/kg/day; males & females) based on
decreases in body weight and body weight gain in males, hypothermia,
reduction in leukocyte counts (F)
and low serum protein.
Ref: Federal Register.
September 27, 2002. Cyfluthrin; Pesticide Tolerance. Final Rule.
http://www.fluoridealert.org/pesticides/cyfluthrin.fr.sept.27.2002.htm
Groups of 18 rats (strain
unspecified) of each sex received diets containing 0, 100, 300,
or 1000 mg/kg cyfluthrin for one month, when 12 rats of each sex
per group were sacrificed; the remainder were killed after one
month of recovery on control diet... Total protein and blood glucose
levels were significantly decreased
in male rats given 300 mg/kg feed. No effects were seen
on macroscopic examination... On the basis of the depressed
blood glucose levels in male rats at 300 mg/kg feed, the
NOEL was 100 mg/kg feed, equivalent to 5 mg/kg bw (Watanabe et
al., 1982a)...
In separate studies, the NOEL in rats ranged from 5 mg/kg bw per
day on the basis of depressed blood glucose
levels to 20 mg/kg bw per day on the basis of mortality
and decreased body-weight gain.
Ref: Toxicological evaluation of certain
veterinary drug residues in food. 1997. WHO FOOD ADDITIVES SERIES
39.
http://www.fluoridealert.org/pesticides/cyfluthrin.who.tox.eval.97.htm
DFP:
Diisopropyl fluorophosphate
- Insecticide - CAS No. CAS No. 55-91-4
The study
examined the relationship between inhibition of cholinesterase
activity (CA) and thermoregulatory response in the rat following
exposure to the organophosphate (OP), diisopropyl fluorophosphate
(DFP). Male Long-Evans rats were injected with DFP dissolved in
peanut oil in doses ranging from 0 to 1.5 mg/kg (s.c.). Colonic
T(sub col) and tail skin temperature T(sub tail) were recorded
at 0, 1, 2, and 3 hr post-injection. At 3 hr post-injection the
rat was sacrificed and a blood sample was taken by cardiac puncture
and analyzed for CA. There was a biphasic dose effect of DFP on
T(sub col) with slight but significant elevation in T(sub col)
in the dose range of 0.01 to 0.5 mg/kg and a significant depression
in T(sub col) at doses of 1.0 and 1.5 mg/kg. There
was a dose-dependent fall in CA with DFP administration in the
erythrocyte, plasma, and whole blood fractions. Hypothermia
was associated with 80 to 87% inhibition in CA, whereas the elevation
in T(sub col) was associated with 20 to 70% [abstract truncated]
Ref:
1991 - Relationship between Cholinesterase Inhibition and Thermoregulation
Following Exposure to Diisopropyl Fluorophosphate in the Rat;
by Gordon CJ, Fogelson L, Richards J, Highfill J. Report No. NTIS/PB92-158658
from The National Technical Information Service.
Dichlofluanid
- Wood
Preservative, Antifoulant, Fungicide, Acaracide -
CAS No. 1085-98-9
-- One-year Study.
A repeat-exposure study using Beagles (4/dose/sex) is available;
it was GLP and OECD Annex V compliant. Animals were administered
either vehicle or 2.5, 12.5 or 37.5/62.5 mg kg -1 d -1 of dichlofluanid
(90 % purity) in capsule form for one year. The top dose was reduced
at week 15 to 37.5 mg kg -1 d -1 because of excessive toxicity.
As a NOEL could not be established with the initial dosing regime,
a subsequent study was carried out in which 0 or 1.25 mg kg -1
d -1 dichlofluanid was used. Interim blood samples were taken
at 13, 26, 39 and 52 week (terminal bleed); in addition samples
were taken from some animals in the top-dose group at 14, 15 and
19 weeks... The haematology findings in males receiving 37.5 mg
kg -1 d -1 from 6 months onwards were decreased
numbers of erythrocytes (4 %), haemoglobin concentration (7.5
%) and haematocrit (7.4 %). Mild to moderate hepatic haemosiderin
deposition was reported and was particularly extensive in two
animals. None of these effects achieved statistical significance.
However, as they were outside the range of supplied historical
control data they were considered to be
treatment related. The following data, in animals at the
top dose, outside the range of supplied historical control data
(¥¥¥¥¥2SD), except BUN, creatinine, and triglyceride levels in
females. This clinical chemistry data refers to the first study
and unless otherwise stated the data were collected at study termination.
Increases in ALP (215 % and 18 % males and
females respectively), AST (81 % males only*), ALT (595 % and
293 % males and females respectively) and gammaGT (360 % males
only) levels were reported in animals 37.5 mg kg -1 d -1 . An
increase in ALT levels (350 % males only) at 12.5 mg kg -1 d -1
was also reported. Serum concentrations of cholesterol were elevated
in animals receiving 12.5 mg kg -1 d -1 (20 % and 23 % males and
females respectively) and 37.5 mg kg -1 d -1 (132 %* and 89 %
males and females respectively). The serum concentration of triglycerides
were elevated in females only (63 % and 59 % at 12.5 mg kg -1
d -1 and 37.5 mg kg -1 d -1 respectively). Elevated BUN (males
only 114 %) and creatanine levels were reported (77 %* and 22
%* males and females respectively) at 37.5 mg kg -1 d -1 . One
male receiving 12.5 mg kg -1 d -1 was also reported to have elevated
BUN and creatanine levels (*statistically significant)...
Ref: January
2003 - Evaluation
on: Booster biocides in antifouling products. Full review of Dichlofluanid.
No. 206. Evaluation of Fully Approved or Provisionally Approved
Products. Prepared by : The 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 available
at:
http://www.pesticides.gov.uk/citizen/Evaluations/206_dichlofluanid.pdf
1,1-Difluoroethane
-
Propellent, EPA List 2 Inert - CAS
No. 75-37-6
McAlack, J.W. and P.W. Schneider, Jr. 1982. Two-year inhalation
study with ethane, 1,1-difluoro (FC-152a) in rats. E.I. Du
Pont de Nemours and Co., Inc. Haskell Laboratory for Toxicology
and Industrial Medicine. Haskell Laboratory Report No. 8-82. CD
rats (30/sex/group) were exposed to 0, 2000, 10,000, or 25,000
ppm 1,1- difluoroethane (HCFC-152a) (99.88% pure) (0, 5399, 26,994,
or 67,485 mg/cu.m, respectively) for 6 hours/day, 5 days/week,
for 2 years (McAlack and Schneider, 1982). Duration-adjusted concentrations
are 0, 964, 4821, or 12,051 mg/cu.m, respectively. Interim sacrifices
were performed on 10 rats/sex/group after 3 or 12 months of exposure.
The animals were exposed in 4.6-cu.m stainless steel and glass
chambers using a one-pass, flow-through mode of air flow (air
flow rate = 1200 L/minute). The test atmosphere was generated
by diluting HCFC-152a vapor with air. The concentration of the
test atmosphere was analyzed approximately every 30 minutes during
each exposure period by gas chromatography, and mean chamber concentrations
were found to be within 15% of nominal concentrations. Animals
were observed twice daily and several times during exposure for
clinical signs of toxicity and moribundity. Body weights and food
consumption were measured biweekly for the first 14 weeks and
monthly thereafter. Hematology, clinical chemistry, and urinalysis
were conducted at 1, 3, 6, 12, 18, and 24 months on 10 rats/sex/group.
Gross and microscopic evaluation of approximately 40 tissues was
conducted in all animals at terminal sacrifice and in the high-concentration
and control animals at the 3- and 12-month sacrifices (10 rats/sex).
Kidney and nasal tissues from the low- and intermediate-concentration
groups were also examined microscopically. The number of cross-sections
examined in the nasal tissue ranged from three to six (Trochimowicz,
1992).
There were no statistically significant exposure-related effects
on survival or body weight gain. Clinical signs noted at a higher
incidence, when summed across exposure periods, in both sexes
exposed to 25,000 ppm HCFC- 152a included ocular/nasal discharges
and wet/stained perinea. The 25,000-ppm females also exhibited
significantly elevated incidences of stained body/face. These
observations suggested chronic low-level irritation or stress
in the animals exposed to HCFC-152a at the highest exposure level
but were not observed consistently across exposure periods or
exposure levels nor supported by histopathology. Although
several statistically significant hematological changes were noted,
none were considered to be toxicologically significant.
For example, females exposed to 10,000 and 20,000 ppm HCFC-152a
exhibited increased mean corpuscular volumes,
and all exposed females exhibited increased serum bilirubin; increased
hematocrits and mean corpuscular volumes were seen in males exposed
to 10,000 and 25,000 ppm HCFC-152a. However, hematopoietic tissues
and red blood cell counts were normal in these animals, which
does not support the hemolytic effect that is suggested by the
changes listed above. Statistically significant
reductions in eosinophils and monocytes also were observed in
some of the treated groups...
Ref: US EPA IRIS for 1,1-Difluoroethane.
http://www.fluorideaction.org/pesticides/1,1-difluoroethane.epa.iris.htm
Definitions:
• Eosinophil - A
white blood cell that contains granules filled with chemicals
damaging to parasites, and enzymes that damp down inflammatory
reactions.
• MONOCYTE - a
large white blood cell that plays a role in immune defense by
acting as a scavenger that destroys invading microorganisms.
Monocytes circulate in the bloodstream; when they migrate to
the tissues, they mature into macrophages.
1,2-Difluoroethane
(Freon 152) - List 3 Inert - CAS No. 624-72-6
Abstract: The inhalation toxicity of a series of fluorinated
ethanes which are metabolized to fluoroacetate (144490) were studied
in the male CD-rat. When the rats were exposed
by inhalation to 1,2-difluoroethane (624-72-6), 1-chloro-2-fluoroethane
(762505), 1-bromo-2-fluoroethane (762492), or 1-chloro-1,2-difluoroethane
(338647) for 4 hours, the lethal concentrations for each compound
were less than 100 parts per million (ppm). Tests with
1,1-difluoroethane (75376) showed a 4 hour median lethal dose
of over 400,000ppm in rats. Clinical signs of fluoroacetate toxicity
were noted including lethargy, hunched posture, and convulsions.
Concentrations of citrate increased in serum and heart tissue
on exposure to 1,2-difluoroethane, 1-chloro-2-fluoroethane,
1-chloro-1,2-difluoroethane, and 1-bromo-2-fluoroethane. Fluoroacetate
was present in the urine of rats exposed to each of the toxic
compounds. Rats exposed to 1,2-difluoroethane showed fluorocitrate
in the kidneys. Rats exposed to 1,2-difluoroethane
showed a concentration related elevation of serum and heart citrate
up to 1000 ppm of the compound. Serum citrate was up five fold
and heart citrate 11 fold over control levels. The authors
suggest that the metabolism of the toxic fluoroethane was initiated
at the carbon/hydrogen bond, with metabolism to fluoroacetate
via an aldehyde or an acyl fluoride. The authors conclude that
1-(di)halo-2-fluoroethanes are highly toxic to rats and should
be viewed as a hazard to humans.
Ref: Fluoroacetate-Mediated Toxicity of
Fluorinated Ethanes; by Keller DA, Roe DC, Lieder PH. Fundamental
and Applied Toxicology, Vol. 30, No. 2, pages 213-219, 1996.
Abstract: The 18-year-old white male driver and 17-year-old white
male passenger of an automobile were killed when their vehicle
crossed the median of a 4-lane highway and collided with a minivan.
A can of airbrush propellant was found in the automobile of the
deceased. The only drug detected during initial toxicological
analyses was 130 mg/L ethanol in the blood of the driver. When
performing ethanol analysis by headspace gas chromatography, an
unidentified peak was observed in the blood of both deceased.
This peak was identified as difuoroethane (Freon
152), the propellant in the aerosol can found in the automobile.
The concentrations of difluoroethane in
the blood of the driver and passenger were 78 mg/L and 35 mg/L,
respectively. Based on a literature search we believe that this
is the first report of the quantitation of difluoroethane in biological
samples.
Publication Types: • Case Reports
Ref: Two traffic fatalities related to the
use of difluoroethane. Broussard LA, Brustowicz T, Pittman T,
Atkins KD, Presley L. J Forensic Sci. 1997 Nov;42(6):1186-7.
Dichlorofluoromethane
(CFC-21)
- Propellant, EPA List 2 Inert - CAS
No. 75-43-4
--
TSCA Test Submissions: A subchronic inhalation toxicity study
was conducted with groups of male (35) and female (35) albino
rats (strain not reported) receiving whole body exposure to dichloromonofluoromethane
at a nominal concentration of 0, 50, 150 or 500ppm in a dynamic
air flow chamber for 6 hours per day, five days per week for approximately
90 days. On day 45 and day 90, 5 animals per sex and 20 animals
per sex, respectively were sacrificed. The remaining animals were
observed for an additional 30 days and
then sacrificed. Four high dose males were found dead during the
exposure period and one female and six males from the high dose
group were found dead during the recovery period. High dose rats
were observed to have statistically significant (p < 0.01) lower
body weights than controls during the exposure period, but were
comparable after the 30 day recovery period. Hematology, clinical
chemistry and urine analysis values were similar between all dosed
animals and control animals, with the exception of a slightly
higher total blood leukocytes counts and elevated mean SAP and
SGPT values for high dose animals at approximately 45, 90 and
120 days. A dose related increase
in urine fluoride levels was also observed. Histopathology evaluation
of treated animals revealed portal cirrhosis of the liver, interstitial
edema of the pancreas and degeneration of the seminiferous epithelium.
Three cases of leukemia were observed
in high dose male rats. [Industrial Bio-Test
Laboratories; Subacute Inhalation Toxicity Study with Genetron
21 in Albino Rats, (1979), EPA Document No. FYI-OTS-0779-0045,
Fiche No. OTS0000045-0 ] **UNREVIEWED**
Ref: TOXNET profile from Hazardous
Substances Data Base for DICHLOROFLUOROMETHANE
http://www.fluoridealert.org/pesticides/dichlorofluoromethan.toxnet.htm
Diflubenzuron
-
Chemosterilant, Insecticide - CAS No. 35367-38-5
--
90-Day oral toxicity rodents. NOAEL < 8 mg/kg/day LOAEL = 8 mg/kg/day
based on increased methemoglobinemia, and
signs of hemolytic anemia, erythrocyte destruction in the
spleen and liver and regeneration of erythrocytes in the bone
marrow.
-- 90-Day oral toxicity in nonrodents. NOAEL = 2 mg/kg/day LOAEL
= 6.24 mg/kg/day based on methemoglobinemia.
-- 21/28-Day dermal toxicity NOAEL = 500 mg/kg/day LOAEL = 1,000
mg/kg/day based on methemoglobinemia
(limit dose).
-- Reproduction and fertility effects. Parental/Systemic NOAEL
< 36 mg/kg/day (LDT) LOAEL = 36 mg/kg/day based on dose-related
decreased hematocrit, hemoglobin concentration,
red blood cell count and an increase in percent methemoglobin,
changes in cell morphology and brown pigment in Kupffer
cells. Reproductive NOAEL> 4254 mg/kg/day (HDT) LOAEL was not
established. Offspring NOAEL = 427 mg/kg/day LOAEL = 4254 mg/kg/day
based on Significant decrease in F-1 pup
weights on day 4, 8 and 21 of lactation.
-- Chronic toxicity dogs NOAEL = 2 mg/kg/day LOAEL = 10 mg/kg/day
based on methemoglobinemia and sulfhemoglobinemia.
-- Carcinogenicity mice NOAEL = 2.4 mg/kg/day LOAEL = 12 mg/kg/day
based on increased methemoglobin and sulfhemoglobin
levels. No evidence of carcinogenicity
-- Special studies. In acute oral toxicity study in rats CPA at
62 mg/kg caused significant increase in
methemoglobinemia while CPU at 200 mg/kg did not cause
methemoglobinemia.
Ref: Federal Register: September 19, 2002.
Diflubenzuron; Pesticide Tolerances. Final Rule. Federal Register.
http://www.fluoridealert.org/pesticides/diflubenzuron.fr.sept19.02.htm
In a 2-year study in
which beagle dogs received diflubenzuron daily in gelatin capsules,
the LOAEL for increases in sulfhemoglobin
and methemoglobin was 10 mg/kg/day and the NOAEL was 2
mg/kg/day. EPA has derived an oral RfD of 0.02 mg/kg/day for this
chemical from this study. Similar effects were noted in two separate
2-year rat feeding studies (the LOAEL was 7.8 to 8 mg/kg/day;
the NOAEL was 2 mg/kg/day), and in a lifetime oral study in mice
(the LOAEL was 12 mg/kg/day; the NOAEL was 2.4 mg/kg/day). EPA
believes that there is sufficient evidence for listing diflubenzuron
on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based
on the available hematological toxicity
data. Measured aquatic acute toxicity data for diflubenzuron include
a 48-hour LC 50 of 4.55 ppb for daphnids. EPA believes that
there is sufficient evidence for listing diflubenzuron on EPCRA
section 313 pursuant to EPCRA section 313(d)(2)(C) based on the
environmental toxicity data for this chemical.
Ref:
USEPA/OPPT. Support Document for the Health and Ecological Toxicity
Review of TRI Expansion Chemicals. 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.
Chronic dietary (all
populations) - Chronic toxicity study (dog): LOAEL = 10 mg/kg/day
based on methemoglobinemia and
sulfhemoglobinemia
Ref: Federal Register. February 15,
2002. Diflubenzuron; Pesticide Tolerance in or on Pear at 0.50
ppm. Final Rule.
http://www.fluoridealert.org/pesticides/diflubenzron.fr.feb.15.2002.htm
-- To assess subacute
dermal toxicity, diflubenzuron was applied to the backs of male
and female CD rats for 3 weeks at dose levels of 20, 500, and
1,000 mg/kg/day. Hematology evaluation showed reductions in
red blood cell (RBC), hemoglobin (Hgb) and hematocrit values
at 500 and 1,000 mg/kg/day. An increased incidence of
polychromasia, hypochromasia,
and anisocytosis was seen at 500 and 1,000 mg/kg/day.
An increase in methemoglobin and sulfhemoglobin
values was seen at 1,000 mg/kg/day. The NOAEL for systemic
toxicity was 20 mg/kg/day. Also, a dermal absorption factor of
0.5%, for systemic absorption, was derived from a study where
rats were dosed with either 0.005 or 0.05 mg/cm\2\ of (\14\C)
diflubenzuron technical. This value can be used for converting
dermal exposure to oral equivalents.
-- Chronic toxicity. Diflubenzuron was given by capsule to male
and female Beagle dogs for 1 year at dose levels of 0, 2, 10,
50, and 250 mg/kg/day. Body weight (bwt) gain was slightly reduced
in females at 250 mg/kg/day. Absolute liver and spleen weights
were increased in males given 50 and 250 mg/kg/day. A
reduction in hemoglobin and mean corpuscular hemoglobin concentration,
with an elevation in reticulocyte count, was seen at 50 and 250
mg/kg/day. Methemoglobin and sulfhemoglobin values were increased
at doses of 10 mg/kg/day and greater. Histopathological
findings were limited to pigmented macrophages and Kupffer cells
in the liver at doses of 50 and 250
mg/ kg/day. The NOAEL for chronic toxicity in dogs was 2 mg/kg/day.
-- Diflubenzuron was fed to male and female Sprague Dawley rats
for 2 years at dose levels of 0, 156, 625, 2,500, and 10,000 ppm.
Methemoglobin values were elevated in female
rats at all dose levels and in male rats at the two highest dose
levels. Sulfhemoglobin was elevated in females, only, at dose
levels of 2,500 and 10,000 ppm. Mean corpuscular volume (MCV)
and reticulocyte counts were increased in high dose females...
In another study diflubenzuron was administered to male and female
CD rats for 2 years at dose levels of 0, 10, 20, 40, and 160 ppm.
Elevated methemoglobin levels were seen
in high dose males and females. No additional effects,
including carcinogenic findings, were observed. The NOAEL for
chronic toxicity in rats was 40 ppm (2 mg/kg/ day).
-- 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 pigmented
Kupffer cells. A NOAEL for these effects was 16 ppm (2 mg/kg/day).
-- Diflubenzuron was fed to male and female Sprague Dawley rats
for 2 years at dose levels of 0, 156, 625, 2,500, and 10,000 ppm.
Methemoglobin values were elevated in female
rats at all dose levels and in male rats at the two highest dose
levels. Blood sulfhemoglobin was elevated in females, only, at
dose levels of 2,500, and 10,000 ppm. MCV and reticulocyte counts
were increased in high dose females. Spleen and liver weights
were elevated at the two highest doses. Histopathological examination
demonstrated an increase in hemosiderosis
of the liver and spleen, bone marrow and erythroid hyperplasia,
and areas of cellular alteration in the liver. There was no increase
in tumor formation. In another study, diflubenzuron was administered
to male and female CD rats for 2 years at dose levels of 0, 10,
20, 40, and 160 ppm. Elevated methemoglobin
levels were seen in high dose males and females. No additional
effects, including carcinogenic findings, were observed.
-- In single dose treatments, after 7 days, 20% and 3% of the
applied dose 5 and 100 mg/kg, respectively, were excreted in urine,
while 79% and 98% of the applied dose 5 and 100 mg/ kg, respectively,
were eliminated in the feces. Very little bioaccumulation in the
tissues was observed. In the feces, only unchanged parent compound
was detected. Several metabolites were observed
in the urine which are, among others, 2,6-diflurobenzoic acid
(DFBA), 2,6-difluorophippuric acid, 2,6-difluorobenzamide (DFBAM),
and 2-hydroxydiflubenzuron (2-HDFB).
-- 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...
-- 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.
http://www.fluoridealert.org/pesticides/diflubenzuron.fr.dec14.2001.htm
Abstract: Five benzoylphenylurea
insecticides were administered to male Wistar rats for 28 days
at oral doses of 100 mg kg-1 each. Elevation
of methaemoglobin was found only in the diflubenzuron- and triflumuron
treated groups. The number of reticulocytes was increased
in all of the treated groups.
Ref: J Appl Toxicol. 1993 Jan-Feb;13(1):67-8.
Comparative
study on the effects of five benzoylphenylurea insecticides on
haematological parameters in rats. Tasheva M, Hristeva V.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8440876&dopt=Abstract
"Diflubenzuron
causes methaemoglobinaemia and sulfhaemo-
globinaemia. Dose-related methaemoglobinaemia has been
demonstrated after oral, dermal or inhalatory exposure to diflubenzuron
in various species. This effect is the most sensitive toxicological
end-point in experimental animals. The NOEL based on methaemoglobin
formation is 2 mg/kg body weight per day in rats and dogs and
2.4 mg/kg body weight per day in mice. In long-term toxicity studies
with mice and rats, treatment-related changes were principally
associated with oxidation of haemoglobin or with hepatocyte changes...
It is attributable to the metabolite, 4-chloroaniline,
which is known to induce methaemoglobin formation in several animal
species and in humans."
Ref: ENVIRONMENTAL HEALTH CRITERIA 184:
International Programme on Chemical Safety http://www.inchem.org/documents/ehc/ehc/ehc184.htm
Ethalfluralin
- Herbicide - CAS No. 55283-68-6
1-year
oral toxicity study in dogs. NOAEL = 4.0 mg/kg/day. LOAEL = 20
mg/kg/day based on altered red cell morphology and urinary bilirubin.
Ref: Federal Register: August 8, 2001. Ethalfluralin;
Pesticide Tolerances for Emergency Exemptions. Final Rule.
http://www.fluoridealert.org/pesticides/ethalfluralin.fr.aug8.2001.htm
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