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 hþmoglobinþmische
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.
Gliftor -
Rodenticide - Rodenticide - CAS No. 8065-71-2
Abstract. Rats were subjected to chronic inhalation of gliftor
(I; 110, 64, 13, and 1 mg/m-3). A dose of 110 mg/m-3 beginning
with the 30th day of poisoning caused pronounced
leukocytosis (maximum on the 72nd day), eosinophilia, and lymphopenia.
The contents of Hb, erythrocytes, and monocytes were close to
the control values. A dose of 64 mg/m-3 caused less leukocytosis
and insignificant changes of the content of neutrophils and lymphocytes.
With a dose of 1 mg/m-3 there was a significant increase of the
relative number of eosinophils and decrease of the number of lymphocytes.
This dose was considered the threshold. With single cutaneous
applications the LD5- for rabbits was 66 plus or minus 10 mg/kg.
The recommended maximum allowable concentration of I for worker
exposure in the air of production rooms in 0.05 mg/m-3 (1/20 of
the threshold value).
Ref: Change of the morphological composition
of the peripheral blood in gliftor poisoning; by TKACH NZ, MILOVANOVA
VI, KNYSH VS. TR INST KRAEV PATOL AKAD NAUK KAZ SSR; 22 1971 12-16.
[Abstract from Toxline at Toxnet.]
• Definition: Leukocytosis is a
condition characterized by an elevated number of white cells
in the blood.
Abstract. Under conditions of the acute inhalation effect of
the vapors of gliftor (I) the LD50 for rats was 580 plus or minus
65 and for mice 1260 plus or minus 15 mg/m-3. The threshold concentration
(TC) for rats with respect to brief disturbance of the functional
state of the CNS was 50 and the subthreshold 10 mg/m-3; for mice
the TC was 190 mg/m-3. Chronic (4 mo.) inhalation
by rats of I in a concentration of 110 and 64 mg/m-3
disturbed the functional state of the CNS and antitoxic and protein-forming
functions of the liver and reduced oxidation-reduction processes.
I in a concentration of 1.0 mg/m-3 increased
the concent of eosinophils and reduced the number of lymphocytes
by the end of the poisoning period. I is
a hazardous compound. A maximum allowable concentration of I of
0.05 mg/m-3 in the air of production shops is recommended for
worker exposure.
Ref: Effect of gliftor on certain metabolic
processes of experimental animals under inhalation poisoning conditions;
by TKACH NZ, KNYSH VS, MILOVANOVA VI, SHISHKOVA NK, SLEPOVA LI.
TR INST KRAEV PATOL AKAD NAUK KAZ SSR; 22 1971 5-12. [Abstract
from Toxline at Toxnet.]
Abstract. The threshold concentration with respect to the effect
of gliftor (I) on the organoleptic properties of water is at the
1 mg/l level. I has feeble cumulative properties. Rabbits tolerated
the chronic oral administration with water of 1/10 and 1/20 LD50
of I, receiving in all 11.2-5.6 LD50. In this case leukocytosis,
an increase of the quantity of coproporphyrin
excreted in the urine, and an increase
of the blood nucleic acid level were noted. The threshold
dose is close to 0.15 mg/mg (3.0 mg/l). The organoleptic sign
is the limiting factor in establishing the maximum allowable concentration
of I in water.
Ref: Effect of gliftor on rabbits under
conditions of chronic oral poisoning; by ALIEV KA, TKACH NZ, SHISHKOVA
NK, KOLOD'KO TP. TR INST KRAEV PATOL AKAD NAUK KAZ SSR; 22 1971
17-23. [Abstract from Toxline at Toxnet.]
Haloxyfop
- Herbicide - CAS No.
69806-34-4
The subchronic toxicity
of haloxyfop (2-(4-((3-chloro-5-(trifluoromethyl)-2- pyridinyl)oxy)phenoxy)propanoic
acid) herbicide, a peroxisome proliferator,
was evaluated in rats, mice, dogs and monkeys. Male rats given
0.2 or 2.0 mg/kg/day and female rats given 2.0 mg/kg/day in feed
for 16 weeks had peroxisome associated hepatocellular hypertrophy.
Male and female rats given 2.0 mg/kg/day for 37 weeks also had
increased renal tubular pigment. Mice given 2.0 mg/kg/day in feed
for 13 weeks had peroxisome associated hepatocellular hypertrophy.
Dogs fed 20 mg/kg/day and monkeys gavaged with 30 mg/kg/day for
13 weeks had hepatocellular hypertrophy, decreased size of thyroid
follicles, and decreased red blood
cell counts and serum cholesterol. Hepatocellular effects
in dogs and monkeys were not associated with peroxisome proliferation.
No-observed effect levels were between 0.02 and 0.2 mg/kg/day
for rats, 0.2 mg/kg/day for mice, and 2 mg/kg/day for dogs and
monkeys. There were no effects on reproduction in rats at dose
levels up to 1.0 mg/kg/day or evidence of teratogenicity in rats
or rabbits at dose levels up to 7.5 or 20 mg/kg/day, respectively.
Ref:
Subchronic and reproductive toxicity and teratology of haloxyfop
herbicide. Authors: Quast JF Yano BL Dietz FK Marler RM Hayes
WC. Source: Toxicologist 1990 Feb;10(1):175. As cited at Toxnet.
Hexaflumuron
- Insecticide; Plant Growth Regulator - CAS No. 86479-06-3
Abstract: A toxicological
evaluation of a new insecticide Sonet was realized. It was established
that by its toxicity Sonet belongs to hazardous substances of
class III. The main manifestations of its toxic effect on the
body warm-blooded animals is its influence on the erythropoiesis
and functional
state of the liver.
Ref: Sviatnyi IM et al. (1992). [A hygienic
evaluation of the insecticide Sonet and the characteristics of
the mechanism of its toxic action in an experiment] [Article in
Russian]. Lik Sprava. Jan;(1):84-7.
http://www.fluorideaction.org/pesticides/hexaflumuron.abstracts.htm
•
Definition:
Erythropoiesis is the process of red blood
cell production (which occurs in red bone marrow).
Hydramethylnon
- Insecticide - CAS No. 67485-29-4
PubMed abstract: Holstein
calves (3 to 5 months of age) were used to develop an animal model
sensitive to environmental toxicants. In the present study, the
fire ant toxicant AMDRO was fed (113.5
g/day/calf) to weanling castrated calves (9 test and 9 controls)
for 7 weeks. As early as 14 days after the start of the AMDRO
feeding, leukopenia was observed.
Differential counts revealed significant non-transient decreases
in lymphocytes and eosinophils. Eosinopenia
was observed from days 21 to 49 of AMDRO treatment. Variability
in hematocrit and hemoglobin values in treated and control calves
precluded making a determination of trends due to toxicant exposure...
Ref: Am J Vet Res 1984 May;45(5):1023-7;
Hematologic
and immunologic responses of Holstein calves to a fire ant toxicant,
by Evans DL, Jacobsen KL, Miller DM.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6732007&dopt=Abstract
In a 21-day dermal
toxicity study in rabbits, MRID 00101559, groups of 10 male and
10 female New Zealand White rabbits received a total of 15 repeated
dermal applications of hydramethylnon at doses of 0 (control),
10, 50, or 250 mg/kg/day, 6 hours/day, 5 days/week over a three
week period... Toxicity
observed at the highest dose tested (250 mg/kg/day) included decreased
food consumption in males and females as well as thrombocytopenia
(a persistent decrease in the number of blood platelets that is
usually associated with hemorrhagic conditions) in females. Although
thrombocytopenia was observed at this dose (250 mg/kg/day), it
was not considered to be an adverse, or biologically significant
effect because it was seen in the presence of skin irritation
in animals having abraded skins. In addition, alterations in hematological
parameters are often seen in dermal toxicity studies in the presence
of skin irritation. Therefore, the 250 mg/kg/day (the highest
dose tested), in spite of the presence of this effect, is considered
to be the NOAEL for dermal and systemic toxicity; a LOAEL was
not established. MRID 00101559 is classified as acceptable and
satisfies guideline requirement 82-2 for a 21-dermal toxicity
study in rats.
Ref: US EPA. Reregistration Eligibility
Decision (RED) Hydramethylnon. EPA 738-R-98-023. December 1998.
http://www.fluoridealert.org/pesticides/hydramethylnon.red.1998.pdf
Indoxacarb
- Insecticide - CAS No. 173584-44-6
-- The
substance causes damage to haemoglobin, resulting in an
increased turn over of red blood cells. At low exposure levels,
some fluctuations in isolated red blood cell parameters were observed,
which are of unclear biological significance and may be incidental.
Based on a weight of evidence consideration of all available short
and long term studies an overall NOEL of 10 ppm or 0.6 mg/kg was
proposed for the effects on blood parameters in rats. The U.S.
EPA has recently reached a similar conclusion and selected 40
ppm as a NOEL.
-- 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.
July
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.
http://www.fluorideaction.org/pesticides/indoxacarb.eu.july.18.2002.pdf
-- 90-Day oral toxicity
in nonrodents. DPX-JW062 NOAEL = 5.0 mg/kg/day LOAEL = 19 mg/kg/
day based on hemolytic anemia, as
indicated by decrease in HGB, RBCs; increases
in platelets, increased reticulocytes; and secondary histopathologic
findings indicative of blood breakdown (pigment in Kupffer cells,
renal tubular epithelium, and spleen and bone marrow macrophages);
increase in splenic EMH; and RBC hyperplasia in
bone marrow
in dogs
-- 21/28-Day dermal toxicity. DPX-MP062 NOAEL = 2,000 mg/kg/ day
LOAEL = < 2,000 mg/ kg/day in 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.
-- Chronic toxicity rodents. DPX-JW062
NOAEL = M 5, F 2.1 mg/kg/day LOAEL = M 10, F 3.6 mg/kg/day based
on decreased body weight, body weight gain,
and food consumption and food efficiency; decreased
HCT, HGB and RBC at 6 months in F only No evidence of carcinogenic
potential
-- Chronic toxicity dogs. DPX-JW062
NOAEL = M 2.3, F 2.4 mg/kg/day LOAEL = M 18, F 19 mg/kg/day based
on decreased HCT, HGB nd RBC; increased
Heinz bodies and reticulocytes and associated secondary microscopic
changes in the liver, kidneys, spleen, and bone marrow; increased
absolute and relative liver weights
Ref: Federal Register: July 18, 2002. Indoxacarb;
Pesticide Tolerance. Final Rule. Federal Register.
http://www.fluoridealert.org/pesticides/indoxacarb.fr.july.18.2002.htm
Isoxaflutole
- Herbicide - CAS No.
141112-29-0
Short term toxicity.
Target / critical effect: Periacinar
hypertrophy in liver, ocular lesions, haematological
effects. Lowest relevant oral NOAEL / NOEL: 3 mg/kg bw/d,
rat. Lowest relevant dermal NOAEL / NOEL: 100 mg/kg bw/d, 21d
rat. Lowest relevant inhalation NOAEL / NOEL: no data available,
not required.
April
2003 - Review report for the active substance isoxaflutole. Isoxaflutole
Sanco/3136/99-Final. 7 April 2003. Finalised in the Standing Committee
on the Food Chain and Animal Health at its meeting on 15 April
2003 in view of the inclusion of isoxaflutole in Annex I of Directive
91/414/EEC.
http://www.fluorideaction.org/pesticides/isoxaflutole.eu.april.2003.pdf
Nissol
(also known as MNFA) - Acaricide, Insecticide - CAS
NO. 5903-13-9
A health survey was carried out on 181 farmers before and after
the pesticidal application of Nissol (MNFA). Questionnaires on
general health, determination of blood pressure and body weight,
examination of urine and liver functions, physical examinations,
indirect chest roentgenography, blood picture, blood sugar level,
and ECG were recorded for some farmers.
Forty-five percent of the farmers complained of subjective symptoms
at the second examination (4 days after the application), unrelated
to the duration of working hours. The major subjective symptoms
were general malaise, headache, nausea, loss of appetite, diarrhea,
insomnia, abdominal pain, and tachypnea in that order. On the
average, body weight loss appeared in 33.6% of the farmers three
weeks after the application. Hemoglobin increased in 4.6%, decreased
in 18.7%, and did not change in 77% of the farmers.
Red cell count decreased in about 52% of the farmers. Leukocyte
count increased in less than fifty percent of the farmers with
a noticeable increase of neutrophils. Some
increase of urobilinogen and glycosuria were noticed while proteinuria
remained stable. Clinically
questionable findings were not obtained in liver functions. The
findings on ECG were a slight decrease of heart rate and a slight
elongation of PQ; however, no arrhythmia was found.
Ref: Studies of organofluorine pesticide
intoxication. II. Results of health examinations of farmers using
an organofluorine pesticide; by Hashida K. Okayama Igakkai Zasshi
(J. Okayama Med. So; 83(7-8): 295-310; 1971. [Abstract from Toxnet.]
Abstract. The selective toxicity of N-methyl-N- ( 1-naphthyl
) monofluoroacetamide ( MNFA ) in various species of animals and
the effects of the compound on the central action, the peripheral
action and the fluctuations in the cardiovascular and respiratory
systems were investigated. Tabulated data present the physiological
function or activity investigated, the test animal, the dosage
of MNFA administered and the route of administration. Results
showed that below the toxic level, MNFA had little or no general
pharmacologic effect and only a minute effect on the central and
peripheral nervous systems and various peripheral organs of the
differenct animals tested. When a toxic dose of MNFA was administered,
respiratory depression, a fall of blood pressure and body temperature
and a decrease in heart rate were generally observed.
Both the rat and cat developed convulsions.
Just prior to death, a flat wave was observed in the electrical
activity of the brain which was indicative of a serious impediment.
A drop in blood pressure
of about 30% was observed at 24 hr in rats that received 50 mg/kg
of MNFA orally. Cardiac response revealed
the characteristic feature of this compound to be cardiac depression
in every species tested. In addition,
among animals that have a high sensitivity to MNFA, such as the
guinea pig, dog and cat, bigeminal or trigeminal ventricular premature
beats were observed. An enhancement of epinephrine activity
by MNFA was also noted. MNFA had a slight effect on the red cell
count, but the white
cell count in rabbits decreased markedly accompanied by a decrease
of pseudoeosinophils and an increase of lymphocytes. The
blood sugar level in mice showed an initial increase prior to
a final decrease, while in rats and guinea pigs there was a decrease
and the value remained unchanged in rabbits and dogs. Ketone bodies
were only detected in the mouse.
Ref. Some pharmacologic properties
of a new fluorine pesticide, N-methyl- N- ( 1-Naphthyl ) monofluoroacetamide;
by Hasimoto Y, Noguchi T, Mori T, Kitagawa H. Toxicol. Appl. Pharmacol.;
13(2), 174-88, 1968.
Lactofen
- Herbicide - CAS No. 77501-63-4
Renal dysfunction and
decreased hemoglobin and hematocrit levels
and red blood cell counts (the LOEL was 25/75 mg/ kg/day;
the NOEL was 5 mg/kg/day) were observed in a 1-year feeding study
in dogs. Increased renal and hepatic pigmentation (the LOEL was
50 mg/kg/day; the NOEL was 25 mg/kg/day) were noted in a 2-year
feeding study in rats. In a 90-day mouse study, increased alkaline
phosphatase, serum glutamate oxaloacetate transaminase (SGOT),
and serum gleutanic pyruvic transaminase (SGPT) activities, increased
liver weight, hepatic necrosis, biliary hyperplasia, decreased
hematocrit and hemoglobin levels and red blood cell counts,
extramedullary hematopoiesis, and kidney nephrosis and fibrosis
(the LOEL was 26 mg/kg/day; the NOEL was not determined) were
seen. Decreased hemoglobin and hematocrit
levels, decreased red blood cell counts, and brown pigment
in the kidney and liver (the LOEL was 50 mg/kg/day) were noted
in a 90-day feeding study in rats. EPA believes that there is
sufficient evidence for listing lactofen on EPCRA section 313
pursuant to EPCRA section 313(d)(2)(B) based on the available
carcinogenicity data and hepatic, renal, and 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.
Lithium
perfluorooctane sulfonate
(LPOS) - Insecticide, Adjuvant - CAS
No. 29457-72-5
-- Based on the findings
of the 90-day subchronic toxicity study, it appears that LPOS
suppresses the formation of blood in males.
This endpoint is not of concern because subchronic or chronic
exposure is not expected from this use. Based on the results of
the developmental studies, there does not appear to be any increased
sensitivity of the pups in comparison to the maternal parents.
-- In an unacceptable subchronic oral toxicity study in rats,
the LOAEL was found to be 0.60 mg/kg/day in females, based on
increased liver weight and 0.30 mg/kg/day in males, based on decreased
triglycerides and hepatocytic vacuolization. The NOAEL is 0.20
mg/kg/day in females. No NOAEL was determined in males.
It appears that LPOS suppresses hematopoiesis
(blood production) in males as indicated by significant decreases
in RBCs, hemoglobin, hematocrit, and the finding of extramedullary
hematopoiesis. This study was classified as unacceptable
for the following reasons: 1) a NOAEL was not determined in males;
2) an analysis of blood coagulation factors which is required
for a subchronic study was not measured in the animals; 3) the
mean food and water consumption calculated as g/week is not correct
in the study (it is actually g/day) which raises the possibilities
of potential errors in compound consumption, since the test substance
was administered in drinking water; and 4) a range finding study
was not performed in order to develop a rationale for the appropriate
selection of doses in males and females.
Ref: US EPA. New Pesticide Fact Sheet. Lithium
perfluorooctane sulfonate (LPOs). August 1999. http://www.epa.gov/opprd001/factsheets/lithium.pdf
Metaflumizone
(BAS 320 I) - Insecticide
- CAS
No. 139968-49-3
--
In the beagle dog, treatment by oral gavage with BAS 320
I for a subchronic duration (90-day
timepoint in the chronic toxicity study) resulted in
reduced body weight gain and/or decreased
food consumption in several dogs at 30 mg/kg b.w./day and slightly
decreased mean cell
hemoglobin concentration (MCHC) at 30 mg/kg b.w./day. Under the
conditions of the study, the NOAEL for oral administration of
BAS 320 I for 90 days was 12 mg/kg b.w./day.
-- In the beagle dog, treatment
via gelatin capsules with BAS 320 I for a 12-month
chronic duration resulted in reduced
body weight gain and/or decreased food consumption in several
dogs at 30 mg/kg b.w./day and slightly
decreased mean MCHC at 30 mg/kg b.w./day. Under the conditions
of the study, the NOAEL for oral administration
of BAS 320 I for 12 months was 12 mg/kg b.w./day.
Ref: October 27,
2004. Federal Register. Pesticide
tolerance petition.
http://www.fluorideaction.org/pesticides/metaflumizone.fr.oct.27.04.htm
Methanesulfonyl
fluoride - Fumigant,
Insecticide - CAS No. 558-25-8
Range of Toxicity:
-- Minimum lethal human exposure is unknown. In rats exposed by
inhalation to a concentration of 2.2 ppm for 1 hour, only minimal
salivation was seen; at 5 ppm for the same duration, copious salivation,
eye and nose exudates, diarrhea, depression,
ataxia, and tremors were observed.
-- Only subclinical alterations of blood
glucose, serum creatinine, total bilirubin, and depression
of acetylcholinesterase were noted in rats exposed by inhalation
to 19 or 91 ppb of methanesulfonyl fluoride for 61 exposures,
each lasting 7 hours.
-- ACUTE EXPOSURE. Methanesulfonyl fluoride is an irreversible
inhibitor of acetylcholinesterase in vitro. It also inhibits butyrylcholinesterase
and trypsinogen in vitro.
Ref: TOXNET profile from Hazardous Substances
Data Base.
http://www.fluoridealert.org/pesticides/methanesulfonyl.fluo.toxnet.htm
Norflurazon
- Herbicide - CAS No. 27314-13-2
--Chronic Toxicity
and Carcinogenicity. In a 6-month toxicity study, norflurazon
technical was administered in the diet to male and female beagle
dogs (4/sex/group) at dose levels of 0, 50, 150, or 450 ppm (0,
1.53, 5.02, and 14.27 mg/kg for males; 0, 1.58, 4.77, and 17.75
mg/kg for females). At the 150 ppm dose
level, liver weight was increased by 38% in male dogs and by 23%
in female dogs. Thyroid weight was increased by 33% in male dogs
and 37% in female dogs at this dose level. Also noted at the 150
ppm dose level were increases in cholesterol in both sexes (23-40%
in males, 6-34% in females), a decrease
in SGPT (36-38% in males, 13-20% in females) and
SGOT (4-23% in males, 13-23% in females). At the 450 ppm
dose level, similar changes were observed in male and female dogs,
with the additional observation of a decrease
in red cell count in female dogs (79-92% of control). The
systemic NOEL was determined to be 50 ppm (1.53 mg/kg/day [males];
1.58 mg/kg/day [females] )...
Ref: US EPA REREGISTRATION ELIGIBILITY DECISION
NORFLURAZON. LIST A. CASE 0229.
http://www.fluoridealert.org/pesticides/norflurazon.red.epa.pdf
Novaluron
- Insecticide - CAS No. 116714-46-6
Toxicology Summary... The main toxicological effect noted in
the animal database was oxidative stress and destruction of red
blood cells (RBCs), most likely due to the
action of an aniline metabolite (3-chloro-4-(1,1,2-trifluoromethoxy)
aniline). As a result of erythrocyte destruction, secondary
effects were observed in associated blood tissues/organs and included
pigmentation in Kupffer cells in the liver as well as macrophages
in the spleen. At higher doses, the effect on red blood cell parameters
was of a sufficient magnitude to result in hemolytic anaemia and
provoke a regenerative response as evidenced by an increase in
reticulocytes, Howell-Jolly Bodies and/or Heinz bodies, with accompanying
hyperplastic response in the bone marrow and spleen... (pages
10-11)
Ref: Proposed
Registration Decision. PRD2006-05. Health Canada Pest Management
Regulatory Agency. December 22, 2006.
http://www.fluorideaction.org/pesticides/novaluron.canada.12-22-06.pdf
-- 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 PeriodÓ; (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. No treatment-related mortality resulted.
No treatment-related effects on clinical signs, food consumption
or body weight were evident. The red blood
cell was the target of toxicity. The mean red blood cell
count was decreased in a dose-related manner
((M) 10000 ppm and above,
p<0.001 at 10000 ppm), (F)
50 ppm and above, p<0.05 at 50 ppm). Likewise, hemoglobin
content was decreased in a dose-related manner ((M)
10000 ppm and above, p<0.01 at 10000 ppm, (F)
100 ppm and above, p<0.001 at 100 ppm). For the females the packed
cell volume was lower for the 100 ppm treatment group and above
(p<0.001). In conjunction with these effects on the red blood
cells, the % of methemoglobin was increased
in the 10000 and 20000 ppm groups (p<0.001). As a response to
this effect, the % of reticulocytes was
increased in these two groups (p<0.05 or p<0.001)...
-- DERMAL: 52846-038; 178971; ÒÒRimonÓ Technical: Toxicity Study
by Dermal Administration to CD Rats for 4 WeeksÓ; (P.B. Rees;
Huntingdon Life Sciences Ltd, Eye, Suffolk, England; Project ID.
MAK/478; 9/14/98); The skin of 5 CD rats/sex/group was treated
with 0, 75, 400 or 1000 mg/kg/day of RIMON Technical (batch no.
970211/4, purity: 99.7%) for 6 hours/day for 28 days. The test
material was suspended in 1.0% (w/v) aqueous methylcellulose.
No mortality resulted from the treatment. The mean body weight
and food consumption values for the 1000 mg/kg group males were
less than those of the control animals. The methemoglobin
concentration was greater for the 1000 mg/kg males (p<0.05)
and the 400 (p<0.01) and 1000 mg/kg (p<0.001) females. No treatment-related
effects were noted in the ophthalmology, clinical chemistry, or
urinalysis. There were no treatment-related lesions in either
the gross or microscopic examinations. No adverse effect indicated.
NOEL: (Systemic) (M) 400 mg/kg/day (based upon the lower mean
body weight and food consumption and increased
methemoglobin level noted for the 1000 mg/kg males) (F)
75 mg/kg/day (based upon increased methemoglobin
level noted for the 400 mg/kg females); (Dermal) 1000 mg/kg/day
(no effect evident at the highest dose tested). Study acceptable.
(Moore, 3/20/01)
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.
http://www.fluoridealert.org/pesticides/novaluron.caepa.toxtst.2001.pdf
--
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).
Re:
June 2, 2004. Novaluron; Pesticide Tolerance. Final Rule. Federal
Register.
http://www.fluoridealert.org/pesticides/novaluron.fr.june.2.2004.htm
Noviflumuron
-Insecticide - CAS No. 121451-02-3
-- “XDE-007: One-Year Dietary Toxicity
Study in Beagle Dogs,” (Stebbins, K.E., Day, S.J.,
Thomas, J.; Toxicology & Environmental Research and Consulting,
The Dow Chemical Company, Midland, MI; Laboratory Project Study
ID #: 142640; 3/5/04). XDE-007 (97.9% pure) was fed in diet to
Beagle dogs (4/sex/dose) for 1 year at 0, 0.003, 0.03 or 0.225%
(equivalent to 0, 0.74, 9.3 and 69 mg/kg/day - Males and 0, 0.94,
8.7 and 70 mg/kg/day - females)... Both
sexes at > 0.225% had statistically significantly increased
mean platelet count. There was a significant increase in ALP at
0.225% in females at 3 and 12 months.
Ref:
August 2005 - Summary of toxicological data. California EPA, Department
of Pesticide Regulation, Medical Toxicology Branch.
http://www.fluorideaction.org/pesticides/noviflumuron.ca.epa.2005.pdf
-- 007; 186499; ÒXDE-007:
28-Day Dietary Toxicity Study in CD-1 MiceÓ (Yano, B.L. and Day,
S.J., Toxicology & Environmental Research and Consulting, The
Dow Chemical Company, Midland, MI, Laboratory Project Study
ID 001248, 6/12/01). XDE-007 (Lot, Reference No. F0031-148, TSN102332,
purity = 98.4%) was admixed to the feed and fed to 5 CD-1 mice
per sex per dose at dose levels of 0, 10, 100, 500, or 1000 mg/kg/day
(0, 10.8, 110, 538, 1060 mg/kg/day, respectively for males and
0, 11.2, 113, 504, 1140 mg/kg/day, respectively for females) for
28 days. No mortalities occurred. No treatment-related clinical
signs were observed. Treatment-related increases in mean platelet
level and mean cholesterol level were observed in both
sexes at 100, 500, and 1000 mg/kg/day. A treatment-related increase
in mean relative liver weight was observed
at in males at 100, 500, and 1000 mg/kg/day and in females at
500 and 1000 mg/kg/day. Microscopic examination revealed treatment-related
hepatocellular hypertrophy with altered tinctorial properties
(centrilobular/midzonal to panlobular) in males at 500 and 1000
mg/kg/day and very slight vacuolation (consistent with fatty change)
of the periportal hepatocytes in males at 500 and 1000
mg/kg/day and in females at 1000 mg/kg/day. No adverse effects.
NOEL (M) = 10.8 mg/kg/day and NOEL (F) = 11.2 mg/kg/day (based
on increases in mean platelet and mean cholesterol
levels). Supplemental (because only 5 animals per sex per
dose were used and because the animals were treated for only 28
days). (Corlett, 9/30/02)
Ref:
September 26, 2002. Summary of Toxicology Data for Noviflumuron
((XDE-007) or N-(((3,5-dichloro-2-fluoro-4-(1,1,2,3,3,3-hexafluoropropoxy)phenyl)amino)carbonyl)-2,6-
diflurobenzamide. California EPA, Department of Pesticide Regulation,
Medical Toxicology Branch.
http://www.fluoridealert.org/pesticides/noviflumuron.ca.epa.2002.pdf
Oxyfluorfen
- Herbicide - CAS No. 42874-03-3
Human
Health Assessment. Toxicity, Oxyfluorfen is of low acute oral,
dermal, and inhalation toxicity. The primary toxic effects are
alterations in blood parameters (anemia)
and in the liver. Oxyfluorfen is classified as a possible human
carcinogen based on combined hepatocellular adenomas/carcinomas
in the mouse carcinogenicity study. A cancer potency factor (Q1*)
was used to estimate human risk. The FQPA Safety Factor for protection
of infants and children was reduced to 1X for all population subgroups
as there was no increased susceptibility in animals due to pre-
or post-natal exposure to oxyfluorfen.
-- Toxicity was similar for subchronic and
chronic rat, mouse, and dog studies in both sexes. Oxyfluorfen
inhibits heme production, which
results in a variety of anemias. Heme is the part of the
hemoglobin molecule that contains iron and binds oxygen. In the
1997 subchronic rat study which used the current 98% a.i. formulation,
the red blood cell count was normal, but the red
blood cell mass was decreased due to the small size of the red
blood cells, presumably because of inhibition of the protoporphyrinogen
oxidase enzyme. The anemia was generally mild in other
studies, with varying hematologic abnormalities described in the
rat, mouse, and dog studies.
-- It should be noted that older
toxicity studies with oxyfluorfen used technical material of approximately
71% or 85% purity. The newer toxicity studies used a technical
material of approximately 98% purity, which is the basis for the
current registrations of oxyfluorfen. The newer technical material
has similar impurities to the older technical material, but in
reduced concentrations. Toxicity was less severe for studies with
the 98% product than for the 71% product; however,
one mammal developmental study with the 98% technical was submitted
in which animals experienced the most severe anemia and related
hematologic effects of any of the mammalian studies. When
there were studies with both the new and old technical material,
preference for an endpoint for risk assessment purposes was generally
given to the newer, 98% technical material (current registrations).
Ref: US EPA Reregistration Eligibility Decision (RED) OXYFLUORFEN.
EPA738-R-02-014 October 2002.
http://www.epa.gov/oppsrrd1/REDs/oxyfluorfen_red.pdf
--
Phototoxicity. Oxyfluorfen may pose risks to animals not conveyed
by standard guideline toxicity studies because oxyfluorfen's mode
of action suggests it may be more toxic in the presence of light
(phototoxic). Oxyfluorfen,
and other light-dependent peroxidizing herbicides, act in plants
by producing phototoxic compounds. Toxicity studies
with oxyfluorfen and other similar herbicides suggest the same
phototoxic compounds may occur in animals as a result of herbicide
exposure. Because guideline toxicity studies
are normally conducted under relatively low, artificial light
conditions, the effects of being exposed simultaneously to oxyfluorfen
and sunlight are not known. To provide information on the
magnitude of this effect, EFED is currently requesting fish phototoxicity
studies be conducted for light-dependent peroxidizing herbicides
(Appendix D).
-- Phototoxicity is a concern for terrestrial organisms as well.
Although oxyfluorfen inhibits heme synthesis, the anemia described
in all but one of the mammalian sub-chronic studies was generally
mild, with varying hematologic abnormalities. The anemia described
one subchronic study with rats (MRID 449331-01) was more severe.
The red blood cell count was normal, but the red blood cell mass
was decreased because of the small size of the red blood cells,
presumably because of inhibition of the protoporphyrinogen oxidase
enzyme. In wild mammal populations, these
hematologic effects have the potential to magnify since the lack
of natural sunlight in the laboratory does reduce the likelihood
of activating the phototoxic effects of oxyfluorfen.
-- US EPA identified the herbicides Acifluorfen,
Azafenidin, Carfentrazone-ethyl, Flumiclorac-penty, Flumioxazin,
Fluthiacet-methyl, Fomesafen, Lactofen, Oxadiargyl, Oxadiazon,
Oxyfluorfen, Sulfentrazone,
Thidiazimin as phototoxic
pesticides [10 out of the 13 pesticides
that EPA identified are organofluorines].
SEE
http://www.fluoridealert.org/pesticides/phototoxicity.page.htm
Ref:
December 11, 2001 - US EPA.
Revised
Environmental Fate and Effects Division Preliminary Risk Assessment
for the Oxyfluorfen Reregistration Eligibility Decision Document
(also at: http://www.epa.gov/oppsrrd1/reregistration/oxyfluorfen/oxyefedchap.pdf
).
Penoxsulam
- Herbicide - CAS No. 219714-96-2
-- Chronic toxicity.
Chronic exposure in the dog indicated that the renal effects were
not exacerbated with long-term exposure. Following long-term exposure
in rats, the kidneys and urinary bladder
were the primary target organs. Histologic changes seen at the
end of 2 years of exposure consisted of inflammation and hyperplasia
of the renal pelvic transitional epithelium, crystal deposition
in the kidneys and urinary bladder, and hyperplasia of the mucosa
of the urinary bladder. In
the mouse, the liver was the primary target organ, and histologic
changes consisted of hepatocellular hypertrophy. There were no
treatment-related increases in tumors in either rats or mice.
The
incidence of mononuclear cell leukemia (Fischer rat leukemia)
was increased in all groups of treated male
rats compared to the concurrent controls. However, the
incidences in the treated groups were identical across a 50-fold
increase in dosage, and well within the range of control values
reported in the literature.
Ref: August 6, 2003. Federal Register: August
6, 2003 (Volume 68, Number 151)] [Notices] [Page 46609-46613].
Penoxsulam; Notice of Filing a Pesticide Petition To Establish
a Tolerance for a Certain Pesticide Chemical in or on Food.
http://www.fluorideaction.org/pesticides/penoxsulam.fr.aug.6.2003.htm
Picolinafen
- Herbicide - CAS No. 137641-05-5
-- In the rat 2-generation
reproduction study, reproduction function, reproductive parameters
and litter parameters were not influenced by treatment in the
first and second generation (P1/P2) parental animals at any dose
level up to and including 500 ppm (equal to 39 and 42 mg/kg bw/d
in males and females, respectively), the highest dose tested.
Hematological findings, increased
spleen weights, and histopathological findings indicative of
regenerative hemolytic anemia were noted for P1/P2 males
and females at 250 ppm (equal to 19 and 21 mg/kg bw/d for males
and females, respectively) and above. Hematological findings including
lower red blood cell count, hemoglobin,
and hematocrit were also noted for male and female second
generation (F2) pups at 250 ppm and above on lactation day 21
(only time point evaluated). Although the hematological findings
noted in the F2 offspring may be secondary to maternal toxicity,
a direct treatment-related effect cannot be dismissed; therefore,
these findings were considered to be toxicologically relevant.
The NOAEL for parental and offspring toxicity was 50 ppm (equal
to 3.7 and 4.0 mg/kg bw/d in males and females, respectively).
On the basis of the parental and offspring NOAELs in the rat 2-generation
reproductive toxicity study (one litter/generation), there was
no indication that neonates were quantitatively more sensitive
than adults to the toxic effects of picolinafen.
-- Hematological and histopathological findings indicative of
regenerative hemolytic anemia were noted
in all species tested. The most sensitive species appears
to be the rat. The most appropriate NOAEL for regenerative hemolytic
anemia is 50 ppm (equal to 2.4 and 3.0 mg/kg bw/d for males and
females, respectively), as determined in the 2-year rat dietary
study. The MOE for regenerative hemolytic anemia is 171 compared
to the ADI.
Ref:
February 17, 2003 - Canada. Picolinafen. Regulatory Note REG2003-02.
Alternative Strategies and Regulatory Affairs Division, Pest Management
Regulatory Agency.
http://www.fluorideaction.org/pesticides/picolinafen.canada.feb.2003.pdf
Potassium
hexafluorosilicate - Insecticide, Wood
Preservative - CAS No. 16871-90-2
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
Primisulfuron-methyl
- Fungicide,
Herbicide- CAS
No. 86209-51-0
In a 90-day dog feeding
study, reduced thyroid weights accompanied by colloid depletion
and parafollicular hyperplasia and anemia were observed at the
LOEL of 25 mg/kg/day. The NOEL was 0.625 mg/kg/day. In a 1-year
dog study, dietary administration of 250/125 mg/kg/day (LOEL:
the dose was changed after week 10 in the study) produced thyroid
hyperplasia, anemia, increased
platelet levels, vacuolar changes, and increased absolute
and relative liver weights. The NOEL was 25 mg/kg/day. In an 18-month
study in mice, dietary administration of 1.7 mg/kg/day produced
increased absolute and relative liver weights in females. No NOEL
was established...
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.
Prosulfuron
- Herbicide - CAS No. 94125-34-5
-- Short term toxicity
Target / critical effect: Liver (hepatocyte
hypertrophy), heart (myocardial degeneration),
hematopoietic system (red blood cells
decreased) Lowest relevant oral NOAEL / NOEL: NOAEL = 6
mg/kg b.w./day (90-day, dog)
Ref: July 2, 2002 - Review report for the
active substance prosulfuron. Finalised in the Standing Committee
on the Food Chain and Animal Health at its meeting on 26 February
2002 in view of the inclusion of prosulfuron in Annex I of Directive
91/414/EEC.European Commission Health & Consumer Protection
Directorate-General.
http://www.fluoridealert.org/pesticides/prosulfuron.eu.july.2002.pdf
Chronic toxicity. In
the 1-year dog chronic dosing study,
the NOAEL was 1.84 mg/kg/day based on hematologic and clinical
chemistry effects and incidence of lipofuscin
accumulation in the liver at 18.6 mg/kg/day.
Ref: Federal Register: December 31, 2002.
Prosulfuron; Notice of Filing Pesticide Petitions to Establish
Tolerances for a Certain Pesticide Chemical in or on Food.
http://www.fluorideaction.org/pesticides/prosulfuron.fr.dec.31.2002.htm
-- A 2-year chronic
feeding/carcinogenicity study in rats
fed dosages of 0, 0.4, 7.9, 79.9 or 160.9 (males), and 0, 0.5,
9.2, 95.7 or 205.8 mg/kg/day (females) was conducted. There was
uncertain evidence of carcinogenicity with slight increases in
the incidence of mammary gland adenocarcinomas
in females at 95.7 and 205.8 mg/kg/day, slight increase in incidence
of benign testicular interstitial cell tumors at 79.9 and 160.9
mg/kg/day (significant trend only). A systemic NOAEL of
7.9 mg/kg/day was based on decreased body
weight and body weight gain, hematopoietic
effects (males), and possibly increased
serum GGT and decreased liver, kidney and adrenal weights
(females) at 79.9 mg/kg/ day.
Ref: Federal Register: August 25, 1999.
[PF-882; FRL-6093-7]. Notice of Filing a Pesticide Petition to
Establish a Tolerance for Certain Pesticide Chemicals in or on
Food.
http://www.fluorideaction.org/pesticides/prosulfuron.fr.aug.25.1999.htm
Pyraflufen-ethyl
- Herbicide - CAS No. 129630-19-9
-- Short term toxicity
Target / critical effect:
Liver,
kidney,
red blood cells. Lowest relevant
oral NOAEL / NOEL: 200 ppm (20 mg/kg bw/d) 90 day mouse (satellite
group in 78 wk study)
-- Long term toxicity and carcinogenicity Target / critical effect:
Red blood cells and liver in mice,
urinary and biliary tract in rats.
Ref: July 2, 2002 - Review report for the
active substance pyraflufen-ethyl. Finalised in the Standing Committee
on Plant Health at its meeting on 29 June 2001 in view of the
inclusion of Pyraflufen-ethyl in Annex I of Directive 91/414/EEC.
SANCO/3039/99-FINAL. European Commission Health & Consumer
Protection Directorate-General.
http://www.fluoridealert.org/pesticides/Pyraflufen-eth.EU.July.2002.pdf
Pyridalyl
- Insecticide - CAS No. 179101-81-6
Subchronic toxicity.
-- Pyridalyl technical was tested in rats
in a 3-month feeding study. Effects included decreased body weight
gain, altered blood biochemistry,
increased relative liver weight and histopathological
changes in the liver, ovary, adrenal and lung. The NOAEL is 100
ppm (5.56 mg/kg/day in males and 6.45 mg/kg/day in females).
-- A 13-week
feeding study in mice was
conducted. Effects included decreased
body weight gain, hematological and blood biochemical effects,increased
liver weight, decreased kidney and ovary weights and histopathological
changes in liver, kidney, ovary and adrenal. The
NOAEL is 70 ppm in males (8.169 mg/kg/day)
and 700 ppm in females (86.78 mg/kg/day).
--
A 13-week oral (capsule) toxicity study
was conducted in dogs. Effects
included decreased body weight gain, clinical
signs indicative of respiratory distress,
hematological and blood biochemistry effects,
increased liver, lung and kidney weights and histopathological
alterations of the lung, kidney, adrenal and liver. The NOAEL
was 10 mg/kg/day.
Chronic toxicity.
-- In a 104-week combined chronic/oncogenicity
study in rats,
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).
-- Pyridalyl was administered for 12-months
by capsule to dogs. There
were alterations in blood biochemistry
(alkaline phosphatase and alanine aminotransaminase) and
increased liver weights. The NOAEL of the study was 20
mg/kg/day.
Ref: Federal Register: December 5, 2003.
Pyridalyl; Notice of Filing a Pesticide Petition.
http://www.fluorideaction.org/pesticides/pyridalyl.fr.dec.5.2003.htm
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