See some background information and definitions on liver
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 the single inhalation effect
of vapors of the zoocide gliftor (I; 50, 100, 350, 520, and 1100
mg/m-3). Morphological changes were noted beginning with a concentration
of 350 mg/m-3. In a chronic experiment (4 mo.) the rats were subjected
to I poisoning in a concentration of 10, 13, 64, and 110 mg/m-3.
Distinct morphological changes in the organs were noted under
the effect of concentrations 64 and 110 mg/m-3. Under
the chronic effect of I there were considerable circulatory disorders
and destructive changes of the interanl organs, especially in
the liver, lungs, spleen, and kidneys.
Ref: Pathomorphological changes in
internal organs of white rats under the inhalation effect of gliftor;
by KNYSH VS, TKACH NZ, TSAREVSKII LP, MILOVANOVA VI. TR INST KRAEV
PATOL AKAD NAUK KAZ SSR; 22 1971 23-28. [Abstract from Toxline
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.
Abstract: The potential
of haloxyfop [2-(4-((3-chloro-5-(trifluoromethyl)-2- pyridinyl)oxy)phenoxy)propanoic
acid; HAL] to induce the proliferation of hepatocellular peroxisomes
(PP) was examined in rats, mice, dogs, and monkeys. Chemically
induced PP is associated with the development of
liver tumors in rodents via an apparent species-dependent,
nongenotoxic mechanism of action. HAL is nongenotoxic yet has
been shown to cause liver tumors in female B6C3F1 mice. Ingestion
of HAL by rats and/or mice (0.1-14 mg/kg/day for 2 to 4 weeks)
resulted in significant dose-related PP as evidenced by hepatocellular
hypertrophy, increased peroxisome volume density (VD),
and induction of peroxisomal enzymes and CYP4A1. Only a relatively
weak induction of PP was noted at a carcinogenic dosage in female
mice...
Ref: Fundam Appl Toxicol 1995 Nov;28(1):71-9.
Species-dependent
induction of peroxisome proliferation by haloxyfop, an aryloxyphenoxy
herbicide. Stott WT, Yano BL, Williams DM, Barnard SD, Hannah
MA, Cieszlak FS, Herman JR.
PubMed Abstract: The
CoA esters of diclofop, haloxyfop and fluazifop are
up to 425-fold more potent than the corresponding unconjugated
herbicides as inhibitors of rat liver acetyl-CoA carboxylase (EC
6.4.1.2); the most potent inhibitor is (R)-fluazifopyl-CoA2 (Ki
= 0.03 microM).
Ref: Life Sci 1992;50(7):533-40. Coenzyme
A esters of 2-aryloxyphenoxypropionate herbicides and 2-arylpropionate
antiinflammatory drugs are potent and stereoselective inhibitors
of rat liver acetyl-CoA carboxylase. Kemal C, Casida JE.
Haloxyfop-methyl
- Herbicide - CAS No. 69806-40-2
Group
B2--Probable Human Carcinogen.
Reviewed 9/ 18/ 89.
Ref:
List of Chemicals Evaluated for Carcinogenic Potential. Science
Information Management Branch, Health Effects Division, Office
of Pesticide Programs, U. S. Environmental Protection Agency.
March 15, 2002.
http://www.biomuncie.org/chemicals_evaluated_for_carcinog.htm
"There are eight
diphenyl ethers that are structurally similar to diclofop-methyl.
Of the chemicals, fomesafen sodium, haloxyfop-methyl
(Verdict), oxyfluorfen, acifluorfen
sodium, nitrofen, and lactofen were reviewed in the initial
CPRC report. All of these chemicals induced
liver adenomas and carcinomas in rats and/or mice..."
Ref: May 24, 2000 - Cancer Assessment Document.
Evaluation of the Carcinogenic Potential of Diclofop-Methyl. (Second
Review). Final Report. Cancer Assessment Review Committee, Health
Effects Division, US EPA Office of Pesticide Programs.
http://www.fluoridealert.org/pesticides/Cancer.EPA.Assess.May.2000.pdf
-- 1) 2-Year Feeding
(carcinogenicity) - mouse: Dietary levels tested: 0, 0.03, 0.065,
and 0.6 mg/kg/day; B6C3F1 mice (50/sex/dose) were administered
haloxyfop-methyl in the diet for 24 months. High-dose males exhibited
a reduced body weight gain, elevated
alkaline phosphatase levels, and an increase
in relative liver weights. Histopathological observations
of the livers from high-dose males and females were characterized
by an alteration of the tinctorial staining
properties of the hepatocytes. Based on the above effects
the LEL for systemic toxicity is 0.6 mg/kg/day. The NOEL for systemic
toxicity is 0.065 mg/kg/day.; core grade minimum (Dow Chemical
U.S.A., 1985c)
-- 4) 16-Week Feeding - rat: Dietary levels tested: 0, 0.002,
0.02, 0.2, and 2 mg/kg/day; CDF Fischer 344 rats (15/sex/group)
were administered haloxyfop- methyl in the diet for 16 weeks.
A significant dose-related increase in relative liver weight was
reported for male rats of the 0.002, 0.02, 0.2, and 2.0
mg/kg/day levels by 4, 5, 11, and 44%, respectively. Female relative
liver weights were increased significantly (4%) at the 2.0 mg/kg/day
levels. Males fed the 0.2 and 2.0 mg/kg/day levels showed enlarged
hepatocytes and increased cytoplasmic homogeneity. An increase
in hepatocellular cytoplasmic homogeneity was reported for females
at 2.0 mg/kg/day. A significant decrease
in relative testes weight (5%) accompanied by atrophy of the seminiferous
tubules were reported for males fed the 2.0 mg/kg/day level. The
LEL for systemic toxicity is 0.002 mg/kg/day, the lowest dose
tested, based on a dose related increase
in relative liver weight in males. A NOEL for systemic
toxicity was not established.; core grade minimum (Dow Chemical
U.S.A., 1982a)
-- 7) 36-Week Feeding - mouse: Dietary levels tested: 0, 0.02,
and 2.0 mg/kg/day; B6C3F1 mice (10/sex/group) were administered
haloxyfop-methyl in the diet for 9 months. A significant increase
in serum alkaline phosphatase was reported for males at the 2.0
mg/kg/day level with a slight increase in serum alkaline phosphatase
for females. The liver was slightly enlarged and darkened for
both males and females at 2.0 mg/kg/day. A
significant increase in the liver absolute weight and organ-to-body
weight ratio of both males and females fed 2.0 mg/kg/day was observed.
Males also exhibited a significant decrease in kidney and heart
weights compared with the control organ weight. Livers
of males and females at the 2.0 mg/kg/day dose exhibited an enlargement
of centrilobular hepatocytes cells with an increase cytoplasmic
homogenity and increased eosinophilia. Kidneys
of males fed 2.0 mg/kg/day showed a decrease of cytoplasmic vacuolation
of the proximal convoluted tubular cells.
Based on the above effects, the LEL for systemic toxicity
is 2.0 mg/kg/day. The NOEL for systemic toxicity is 0.02 mg/kg/day;
core supplementary (Dow Chemical U.S.A., 1982d)
-- Critical Effect: Reduced relative kidney
weights in F0, F1, and F2b adults; Reduced fertility in
the F1/F2b generation. 3-Generation Rat Reproduction Study. Dow
Chemical U.S.A.,1985a. NOEL: 0.005 mg/kg/day; LEL: 0.05 mg/kg/day....
Signs of toxicity in parental rats at 1 mg/kg/day level
were reduced body weight gain and reduced food consumption without
increased mortality or obvious toxicity to the offspring. In addition,
a significant increase in relative
liver weight and enlarged livers were observed, however
this finding was more frequent in males
than females. A significant decrease
in relative kidney weight was observed at 0.05 and 1 mg/kg/day,
but it again occurred more frequently in the F0, F1, and F2b adult
male rats. Renal pigmentation was also reported at 1 mg/kg/day
for male and female adult rats after the gross and histopathological
examinations. Based on decreases in relative kidney weights, the
LEL for systemic toxicity is 0.05 mg/kg/day. The NOEL for systemic
toxicity is 0.005 mg/kg/day.
Ref:
Health Assessment. US EPA Integrated Risk Information System (IRIS).
http://www.fluoridealert.org/pesticides/Haloxyfop.Methyl.IRIS.htm
Hexafluoropropene,
polymer with tetrafluoroethylene -
EPA List 3 Inert - CAS No. 25067-11-2
Animal
carcinogenicity data
Tetrafluoroethylene was tested for carcinogenicity in one
study in mice and one study in rats by inhalation. In both sexes
of mice, it increased the incidence of hepatocellular
carcinomas, histiocytic sarcomas and haemangiosarcomas
in the liver. In rats of both sexes, it increased the incidence
of hepatocellular carcinomas and kidney tubule cell adenomas.
Evaluation
There
is sufficient evidence in experimental animals for the
carcinogenicity of tetrafluoroethylene.
Overall
evaluation
Tetrafluoroethylene
is possibly carcinogenic to humans (Group 2B).
Ref:
International Agency for Cancer Research (IARC):
http://www-cie.iarc.fr/htdocs/monographs/vol71/048-tetrafluo.html
Hexaflumuron
- Insecticide, Plant Growth Regulator - CAS No. 86479-06-3
In
long-term (chronic) feeding tests, hexaflumuron increased the
incidence and severity of a liver cell abnormality
(U.S. EPA. Office of Pesticide Programs. 1994. Pesticide fact
sheet: Hexaflumuron. Washington, D.C. Mar. 10).
Ref: Subterranean Termites. Part 2, by Caroline
Cox. Journal of Pesticide Reform / Summer 1997. Vol. 17, No. 2
http://www.pesticide.org/subtermites2.pdf
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).
Indoxacarb
- Insecticide - CAS No. 173584-44-6
COMBINED, RAT **52425-054
162226 "Combined
Chronic Toxicity/Oncogenicity Study with DPX-JW062-106 (50% DPX-KN128,
50% DPX-KN127) Two-Year Feeding Study in Rats"
(Frame, S. 835-E. I. du Pont de Nemours and Company, Haskell Laboratory,
Elkton Road, Newark, Delaware, Study HLR 1174-96,
11/19/97). DPX-JW062-106 technical (Batch DPX-JW062-106, 47.5%
DPX-KN128) was given in the diet daily to males at 0, 20, 40,
60, 125 or 250 ppm and females at 0, 10, 20, 40, 60 or 125 ppm
for 24 months. Deaths of one female at 60 ppm and seven at 125
ppm during the first year were associated with bone marrow atrophy,
splenic lymphoid depletion and thymic necrosis. Decreases in mean
body weight/weight gain in males at 125 and 250 ppm and females
at 60 and 125 ppm correlated with decreased food consumption.
Hemolytic anemia at 60 ppm and above (males) and 40 ppm and above
(females): RBC mass, hemoglobin and hematocrit were decreased
and linked with increased reticulocyte counts and increased MCV.
Bone marrow regenerative response was increased bone marrow hyperplasia
in the one-year interim sacrifice 125 ppm females. Spleen weights
were increased in both sexes at the respective high-dose levels
and other non-neoplastic changes were secondary physiological
responses to test substance-related hemolysis; increased
pigment observed within the Kupffer cells of female livers (125
ppm) and the macrophages of the spleen (both sexes at 60
ppm and above) indicated increased RBC turnover. Increased hematopoiesis
was reported in the spleen of interim sacrifice males at 125 ppm
and above and in the bone marrow of high-dose males and females.
After two years, secondary changes were seen in the
liver, spleen, bone marrow, kidneys and thymus in high
dose groups. Increased pigment was observed
in the Kupffer cells of female livers at 40 ppm and above;
in males, increases were noted at 250 ppm only. Increased
splenic pigment was seen in all compound-treated male groups and
in females at 60 ppm and above; a slight increase in splenic congestion
was seen in 250 ppm males. No evidence of an oncogenic effect
was reported. NOEL(M)= 40 ppm; (F)=20 ppm (M: 1.59 mg/kg/day;
F: 1.04 mg/kg/day based on hemolytic anemia). Acceptable. Kellner,
1/29/99.
Ref:
March
11, 1999: Summary
of Toxicology Data - Indoxycarb.
California EPA Department of Pesticide Regulation, Medical Toxicology
Branch.
http://www.fluorideaction.org/pesticides/indoxacarb.ca.epa.1999.pdf
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
Isoxaflutole
- Herbicide - CAS No. 141112-29-0
Likely
to be carcinogenic to Humans. Statistically
significant increases in liver tumors
in both sexes of CD-1 mice & Sprague-Dawley rats; statistically
significant increases in thyroid tumors
in male rats.
Ref: April
26, 2006 . Chemicals Evaluated for Carcinogenic Potential by the
Office of Pesticide Programs. From: Jess Rowland, Chief Science
Information Management Branch Health Effect Division (7509C) Office
of Pesticide Programs, USEPA.
http://www.fluorideaction.org/pesticides/pesticides.cancer.potential.2006.pdf
-- Isoxaflutole demonstrates
developmental toxicity and has been classified as a Group
B2 carcinogen (probable human carcinogen).
-- In a combined chronic toxicity/carcinogenicity study in rats,
evidence of systemic toxicity was observed at 500 mg/kg/day and
included: abnormal gait, limited use of limbs,
lower body weight gains and food consumption, decreased food efficiency
during the first 14 weeks of the study, elevated cholesterol levels
throughout the 104-week study, increased absolute and relative
liver weights, and
thyroid hyperplasia. Increased incidence of periacinar
hepatocytic hypertrophy, portal tract (senile) bile duct
changes, focal cystic degeneration of the
liver was observed in males at 20 mg/kg/day and greater,
females at 500 mg/kg/day. Eye
opacity, gross necropsy changes in eyes, corneal lesions, degeneration
of sciatic nerve and thigh muscles was observed in males at 20
mg/kg/day and higher doses and in females at 500 mg/kg/day.
The chronic LOAEL is 20 mg/kg/day based on liver,
thyroid, ocular, and nervous system toxicity in males and
liver toxicity in females. The chronic NOEL is 2.0 mg/kg/day.
-- Under the conditions of this study, isoxaflutole induced benign
and malignant tumors of the liver in both sexes at 500 mg/kg/day
hepatocellular adenomas and hepatocellular carcinomas.
Combined incidences of liver adenoma/carcinoma in males and females
showed animals bearing carcinomas in the
majority...
-- In a 78-week carcinogenicity study, isoxaflutole had no significant
effect on the survival of animals. Systemic signs of toxicity
in the treated groups included: decreased
body weight gain in both sexes at 500 ppm and 7,000 ppm and for
females at 25 ppm group; food consumption was unaffected
except food efficiency was lower for both sexes at 7000 ppm during
the first 14 weeks of the study; absolute and relative/body liver
weights were significantly increased in both sexes at 7,000 ppm
and at 500 ppm relative liver weight was
increased in males at 52 weeks and in females at 78 weeks;
gross necropsy at 78-week sacrifice revealed increased occurrences
of liver masses in both sexes at
7,000 ppm; non-neoplastic lesions of the
liver occurred at 52-week sacrifice in males at 500 ppm
and in males and females at 7,000 ppm. At termination, the 500
ppm group males exhibited increased incidence of hepatocyte
necrosis. At 7,000 ppm, significant
increase in non-neoplastic lesions in both sexes included periacinar
hepatocytic hypertrophy, necrosis, and erythrocyte-containing
hepatocytes. In addition, males at the high dose had pigment-laden
hepatocytes and Kupffer cells, basophilic foci, and increased
ploidy; extramedullary hemopoiesis in the spleen was noted in
both sexes; increase incidences of hepatocellular
adenoma and carcinoma were observed in both sexes at 7,000
ppm in the 52-week and 78-week studies.
-- Among scheduled and unscheduled deaths in the 78-week study,
there were significant occurrences of hepatocellular
adenomas in 52% of the males and 29% of the females, and carcinomas
in 33% of the males and 8% of the females (non-significant).
The incidences of these tumors exceeded
the corresponding historical incidence with this species in the
laboratory. Combined adenoma and carcinoma incidences at
7,000 ppm were 73% for males and 35% for
females. At 500 ppm, the incidences
of 17% adenomas and 15% carcinomas in males and 2% adenomas in
females were not statistically significant, but exceeded the means
for historical controls. The 52- and 78-week studies revealed
a dose-related decrease in the first occurrence of carcinomas
in males; the earliest carcinomas were observed
at 78, 71, 52, and 47 weeks at the 0 through 7,000 ppm doses.
There were no carcinomas in females up to 78 weeks at 0, 25, or
500 ppm, although, the earliest finding at 7000 ppm was at 60
weeks. The LOAEL for this study is 64.4 mg/kg/day for males and
77.9 mg/kg/day for females (500 ppm), based on decreased
body weight gains, increased liver
weights, and increased incidences of histopathological
liver changes. The NOEL is 3.2 mg/kg/day for males and
4.0 mg/kg/day for females (25 ppm). Although body weight was decreased
marginally in females at 25 ppm, there were no corroborating findings
of toxicity at this dose. Under conditions of this study, isoxaflutole
appears to induce hepatocellular adenomas
and carcinomas in male and female CD-1 mice. The chemical
was tested at doses sufficient to measure its carcinogenic potential.
-- Reproductive Toxicity. In a 2-generation reproduction study
in rats, evidence of toxicity was observed in the male and female
parental rats of both generations: at 20 and 500 mg/kg/day, increased
absolute and relative liver weights
associated with liver hypertrophy
was observed.. The Systemic LOAEL is 17.4 mg/kg/day for males
and females, based upon increased liver
weights and hypertrophy and the Systemic NOEL is 1.76 mg/kg/day
for males and females...
Ref: US EPA. Pesticide Fact Sheet. Isoxaflutole
Reason for Issuance: Conditional Registration Date Issued: September
15, 1998.
http://www.epa.gov/opprd001/factsheets/isoxaflutole.pdf
Lactofen
- Herbicide - CAS No. 77501-63-4
Likely
to be Carcinogenic to Humans at High Doses.
Not Likely to be Carcinogenic to Humans at Low Doses. Hepatocellular
carcinomas
(M); Hepatocellular adenomas & carcinomas (M & F); CD-mice.
Liver neoplastic nodules; Sprague-Dawley rats (M & F). MOE
approach should be used for estimating human cancer risk, using
a NOAEL of 2 ppm (0.3 mg/kg/day).
Ref: April
26, 2006 . Chemicals Evaluated for Carcinogenic Potential by the
Office of Pesticide Programs. From: Jess Rowland, Chief Science
Information Management Branch Health Effect Division (7509C) Office
of Pesticide Programs, USEPA.
http://www.fluorideaction.org/pesticides/pesticides.cancer.potential.2006.pdf
Lactofen acts via a peroxisome proliferation mechanism of action.
Likely to be carcinogenic to humans at high enough doses to cause
these biochemical and histopathological effects (peroxisome
proliferation) in the livers of rodents but unlikely to
be carcinogenic at doses below those causing these changes. Lactofen
is considered to be a threshold carcinogen. NOAEL = 0.3
mg/kg/day based on increased activities
of liver enzymes and increased incidence of liver histopathological
findings at the LOAEL of 1.5 mg/kg/day.
Ref:
Sept 24, 2004. Lactofen. Pesticide Tolerance. Final Rule. Federal
Register.
http://www.fluorideaction.org/pesticides/lactofen.fr.sept.24.2004.htm
Lactofen meets the
criteria of an EPA Group B2 compound, i.e., a probable human carcinogen.
This conclusion was based on an increased incidence of hepatocellular
carcinomas in males and combined incidence of hepatocellular
adenomas and carcinomas in both sexes of CD-1 mice following
dietary administration of lactofen. In CD rats, there was increased
incidence of liver neoplastic nodules in
both sexes. Four structurally similar chemicals, acifluorfen,
nitrofen, oxyfluorfen, and fomesafen, all produced hepatocellular
tumors in rodents. Results of several subchronic and chronic studies
indicated the liver and kidney as
target organs for lactofen. Increased absolute and relative liver
weight and hepatocytomegaly (the LOEL was 1.5 mg/kg/day;
the NOEL was not determined) were observed in
male mice fed lactofen for 78 weeks. At 37.5 mg/kg/day,
there was also an increased incidence of cataracts and renal pigmentation.
Based on the LOEL, an oral RfD of 0.002 mg/kg/day was derived.
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.
Chronic/carcinogenicity
feeding study-- Mouse-- 24-month. In a dietary 18-month oncogenicity
study in mice at dosages of 10, 50 and 250 ppm Lactofen Technical,
an increase in liver adenomas and
carcinomas, cataracts and liver pigmentation
was observed at 250 ppm. The lowest dose, 10 ppm, was the LOEL
based on increased liver weight and hepatocytomegaly.
-- Chronic/carcinogenicity feeding study-- Rat-- 24-month. In
a 2- year chronic feeding/oncogenicity study of Lactofen Technical
in rats at dosages of 0, 500, 1,000 and 2,000 ppm in the diet,
an increase in liver neoplastic nodules
and foci of cellular alteration was observed in both sexes at
2,000 ppm. The NOEL for systemic toxicity is 500 ppm based on
kidney and liver pigmentation.
-- Carcinogenicity. The Toxicology Branch Peer Review Committee
has determined that lactofen meets the criterion for a B2 (possible
human) carcinogen since it caused an increase in liver
tumors (adenomas and/or carcinomas) in two species. Based
on the mouse oncogenicity study, a human upper-bound potency estimate
(Q1*) was calculated as 0.17 (mg/kg/day).
-- More importantly, evidence summarized above suggest that carcinogenic
effects observed in rodent liver related to long term lactofen
consumption are attributable to peroxisomal
proliferation as opposed to a direct genotoxic effect.
This mechanism of action would more appropriately be regulated
as a threshold effect (similar to RfD comparisons) as opposed
to a non-threshold effect with a quantitative potency factor derived
from low dose extrapolations. This change in the hazard assessment
process for lactofen would have a profound effect on the exposure
and risk assessments for this chemical.
Ref: Federal Register: February 25, 1998
[Page 9532-9540]. Notice of Filing of Pesticide Petition.
http://www.fluoridealert.org/pesticides/Lactofen.FR.Feb.1998.htm
Lithium
perfluorooctane sulfonate
(LPOS) - Insecticide, Adjuvant - CAS
No. 29457-72-5
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
PFOS
is persistent, bioaccumulative and toxic to mammalian species.
There are species
differences in the elimination half-life
of PFOS; the half-life is 100 days in rats, 200 days in monkeys,
and years in humans. The toxicity profile of PFOS is similar
among rats and monkeys. Repeated exposure results in hepatotoxicity
and mortality; the dose-response curve is very steep for
mortality. This occurs in animals of all
ages, although the neonate may be more sensitive. In addition,
a 2-year bioassay in rats has shown that exposure to PFOS results
in hepatocellular adenomas and thyroid
follicular cell adenomas; the hepatocellular
adenomas do not appear to be related to peroxisome proliferation.
Further work to elucidate the species differences in toxicokinetics
and in the mode of action of PFOS will increase our ability to
predict risk to humans.
Ref:
November 21, 2002 report:
Hazard Assessment of Perfluorooctane sulfonate (PFOS) and its
salts.
Organisation for Economic Co-operation and Development. ENV/JM/RD(2002)17/FINAL.
http://www.fluorideaction.org/pesticides/pfos.final.report.nov.2002.pdf
Mefluidide
and its potassium and diethanolamine salts - Herbicide,
Plant growth regulator - CAS Nos. 53780-34-0,
53780-36-2, 83601-83-6)
"Lifetime Carcinogenicity Study in Mice", (International
Research and Development Corporation, report no. 102-026, 5/14/1979).
Mefluidide, purity 93%, fed at 0, 600, 1800 or 6000 ppm in diet
to 60/sex/group for 18-19 months. Positive
adverse chronic effect of liver toxicity. No evidence of
oncogenicity. NOEL for hepatotoxicity is 600 ppm. UNACCEPTABLE.
(J. Christopher, 7/1/85). Evaluated as possibly upgradeable with
submission of pathology data adjusted according to time of death,
complete histopathology for the mid dose group and organ weights.
Rebuttal (#059987 in 034) discusses the requirements for an oncogenicity
study as opposed to a combined and contains diet analyses. See
Summary statement below. (Updated, Kishiyama and Gee, 7/14/88).
...Significant adverse effects consisted of increased mortality
in the 6000 ppm (high) dose group and liver
nodular hyperplasia in the 6000 and 1800 (intermediate) dose groups.
The liver alterations were called "reparative or regenerative
responses to toxic liver injury" and no oncogenic
effect was claimed. Two consultant pathologist re-read the slides
and generally agreed with the diagnoses of the IRDC pathologist.
While no oncogenic effects were found, the
reduced survival in the high dose group confounds interpretation.
The pathology data need to be adjusted according to time of death
rather than be lumped into singular incidence values irrespective
of time of death or sacrifice. Appropriate statistics could then
be performed. In any event, the report is still incomplete and
unacceptable due to study conduct deficiencies originally outlined
in Dr. Christopher’s review. F. Martz, 4/16/86.
Ref:
Summary of Toxicology Data. 11-21-94 Revision. California EPA,
Department of Pesticide Regulation, Medical Toxicology Branch.
http://www.fluoridealert.org/pesticides/Mefluidide.CA.EPA.1986.pdf
21-Day Dermal toxicity - rabbit (4 rabbits/sex/dose). Acceptable/Non-guideline
(NOAEL was not observed). Systemic LOAEL = 240 mg/kg/day, based
on clinical chemistry (increased alkaline phosphatase and alanine
aminotransferase) and organ weights (decreased spleen weight in
females and increased liver weights in males).
Edema and swelling with myelin loss in sciatic nerve was seen
in 720 and 2400 mg/kg/day dose group. Dehydration observed at
2400 mg/kg/day dose. Dermal and systemic NOAELs were not established.
Ref:
USEPA. Mefluidide - Toxicology
section for the Reregistration Eligibility Decision Document (RED)
(January 31, 2007)
http://www.fluoridealert.org/pesticides/docket/EPA-HQ-OPP-2007-0431-0009.pdf
Metaflumizone
(BAS 320 I) - Insecticide
- CAS
No. 139968-49-3
--
Chronic toxicity. In the Sprague-Dawley
rat, treatment by oral gavage with
BAS 320 I for a 2-year chronic duration resulted in dose-related
increased incidences of hepatocellular centrilobular
hypertrophy in the livers of males and females at 60 mg/kg
b.w./day and at 300/200 mg/kg b.w./day and hepatocellular
basophilic alteration in males at 60 and 300 mg/kg b.w./day.
(Note: Beginning the first day of Week 3, the dose level of the
high-dose females was lowered from 300 to 200 mg/kg b.w./day,
due to an adverse effect of -71% decreased
body weight gain as compared to controls.)
Ref: October 27,
2004. Federal Register. Pesticide
tolerance petition.
http://www.fluorideaction.org/pesticides/metaflumizone.fr.oct.27.04.htm
Nissol
(also known as MNFA) - Acaricide, Insecticide - CAS
NO. 5903-13-9
Abstract. The effects of a single dose and repeated doses of
N-methyl-N- ( 1- naphthyl ) monofluoroacetamide (MNFA) on the
fluctuation of citrate in animals and the replationship between
the activity of MNFA hydrolysis and the acute toxicity of MNFA
in various species were investigated. MNFA
was administered intraperitoneally at 25 mg/kg to male Wistar
strain rats, 2.0 mg/kg to guinea pigs and 300 mg/kg to monkeys.
At specified periods after dosing, the animals were sacrificed
and the citrate content of heart, kidneys, liver and brain was
determined. For the multiple dose study, MNFA was administered
orally to male rats at doses of 0.625, 1.25, 2.5, 5.0 and 10.0
mg/kg/ day for 180 days and the citrate content was determined
in the brain, heart, liver, kidney, testis and blood.
In the rat, after a single dose of MNFA, the citrate level increased
to 27, 10, 10 and negligible times
the normal value in heart, kidneys, brain and liver, respectively.
In the chronic toxicity experiment, the only increase
(3 times the control value) was in the testes of rats receiving
10 mg/ kg/day of MNFA. In all other
groups, the level in liver and kidney decreased significantly
in comparison with the levels in animals receiving a single dose.
It is suggested that this difference was due to metabolism and
to the detoxification mechanism of the liver
and kidney which may have been accelerated by the chronic administration
of MNFA. The citrate level in the monkeys after a single dose
was much lower than in the rat. In guinea pigs it
increased to the maximum at 9 hr when it reached 30 times the
control value in the kidney, 10 times in the heart,
6 times in the brain while no appreciable increase was found in
the liver. The hydrolysis of MNFA by liver
homogenates was closely related to the acute toxicity and the
product of the hydrolysis was determined as N-methyl-1-naphthylamine.
The enzyme activity in the guinea pig was about 35 times that
of the rat or mouse. The LD50 of MNFA was 3.1 times that
of N- ( 1-naphthyl ) monofluoroacetamide ( NFA ) and the amount
hydrolyzed after 30 min incubation was about one- fifth.
Ref: Studies of the biochemical lesions
caused by a new fluorine pesticide, N-methyl-N- ( 1-naphthyl )
monofluoroacetamide; by Noguchi T, Hashimoto Y, Miyata H. Toxicol.
Appl. Pharmacol.; 13(2), 189-98, 1968.
Abstract. The accumulation of citrate was studied in spider-mites,
house-flies and mice after treatment with the acaricide Nissol
(5903139). Male Swiss-Webster-mice were injected with various
concentrations of Nissol. House-flies were treated topically with
Nissol at various concentrations or received thoracic injections.
A slide/dip technique was used to dose two-spotted-spider mites
with Nissol. Mortality was recorded at 24 hours after treatment
and the median lethal dose (LD50) was calculated for each species.
The citric-acid (77929) content was determined in homogenates
of whole mice in brains, hearts, livers, and kidneys photospectrometrically.
Citric-acid content was also determined in homogenates of flies
and mites. The LD50 for intraperitoneal administration in mice
was 200 milligrams per kilogram (mg/kg). The topical LD50 in house-flies
was 525mg/kg and the injected LD50 was 14mg/kg. The LD50 for contact
administration to spider mites was 250 parts per million. Citric-acid
increased substantially in each species even by 3 hours after
dosing. The maximum accumulation in mice occurred at 6 hours.
Flies and mites continued to show increased accumulation through
12 hours. In the mouse citric-acid was accumulated
in decreasing order in the heart, kidney, brain, and liver. The
authors conclude that mites, flies and mice accumulate citrate
when treated with Nissol. The toxicity of
this acaricide may be related to inhibition of aconitase which
catalyzes transformation of citric-acid.
Ref. Citrate Accumulation In Twospotted
Spider Mites, House Flies, And Mice Following Treatment With The
Acaricide 2-Fluoro-N-methyl-N-(1-naphthyl) Acetamide; by Johannsen
FR. Knowles CO. Journal of Economic Entomology, Vol. 65, No. 6,
pages 1754-1756, 14 references, 1972.
Norflurazon
- Herbicide - CAS No. 27314-13-2
Group
C -- Possible Human Carcinogen. Statistically
significant increase in comparison to controls in liver
adenomas & combined liver adenomas & carcinomas, as well
as the statistically significant positive trend for these hepatocellular
adenomas & combined adenomas & carcinomas; CD-1 mice (M).
Ref: April
26, 2006 . Chemicals Evaluated for Carcinogenic Potential by the
Office of Pesticide Programs. From: Jess Rowland, Chief Science
Information Management Branch Health Effect Division (7509C) Office
of Pesticide Programs, USEPA.
http://www.fluorideaction.org/pesticides/pesticides.cancer.potential.2006.pdf
-- A two-year carcinogenicity
study was conducted in male and female CD-1 HaM/ICR Swiss mice
in which 125 mice/sex/dose were administered technical norflurazon
in the diet at dose levels of 0, 85, 340, or 1360 ppm (0, 12.8,
58.7, or 218.8 mg/kg/day) for 100-104 weeks... Liver
weight was increased by 9% and 15% in male and female mice at
the 340 ppm dose level, and by 27% and 21% at the 1360 ppm dose
level, respectively. The liver to
body weight ratio was increased by 19% and 4% in male and female
mice at the 340 ppm dose level, and by 43% and 19% at the 1360
ppm dose level, respectively. Increased incidences of
enlarged spleen, nephritis, swollen/enlarged
liver, and nodular enlargement of the liver were observed in high
dose male mice, while increased incidences of
pyelonephritis, enlarged
liver, and cystic ovaries were observed
in high dose female mice. Carcinogenic
potential was evidenced by an increased incidence of hepatic
adenoma and combined adenoma/carcinoma in high dose male mice.
The systemic NOEL was determined to be 12.8 mg/kg/day (85 ppm)
for male mice, and 58.7 mg/kg/day (340 ppm) for female mice. The
systemic LEL was determined to be 58.7 mg/kg/day (340 ppm) for
male mice, based on the increased incidence of
enlarged spleen,
increased absolute and relative liver weight,
and increased incidence of nephritis.
The systemic
LEL was determined to be 218.8 mg/kg/day (1360 ppm) for female
mice, based on the increased incidence of
enlarged liver and cystic ovaries,
the increased
absolute and relative liver weight,
and the increased incidence of pyelonephritis
(guideline ¤83-2; MRID 00111649).
-- As
a result of the July 18, 1990 meeting of the OPP/Health
Effects Division Carcinogenicity Peer Review Committee, norflurazon
was classified as a non quantifiable Group C - possible
human carcinogen - based upon statistically significant
pair-wise comparisons of the incidence of liver
adenomas and combined liver adenomas/ carcinomas as well as statistically
positive trends for these lesions in male CD-1 mice receiving
218.8 mg/kg/day norflurazon technical in the diet for up to 104
weeks (MRID 00111649).
-- A 2-generation reproductive toxicity study was conducted in
male and female Wistar rats. In this study, norflurazon technical
was administered in the diet at dose levels of 0, 150, 750, or
1500 ppm over 2 generations (0, 10.2, 50.8, or 102.5 mg/kg/day
for F males; 0, 12.1, 0 62.0, or 129.7 mg/kg/day for F females;
0, 13.2, 67.8, or 138.6 0 mg/kg/day for F males; 17.1, 81.7, and
173.0 mg/kg/day for F1 1 females). The NOEL for systemic toxicity
was determined to be 150 ppm (10.2 mg/kg/day for males and 12.1
mg/kg/day for females), and the systemic toxicity LEL was determined
to be 750 ppm (50.8 mg/kg/day for males and 62.0 mg/kg/day for
females), based on significant increases
in liver and kidney weights observed in both generations
of parental rats and the increased incidence of hepatocellular
hypertrophy in both generations of parental rats...
Ref: US EPA REREGISTRATION ELIGIBILITY DECISION
NORFLURAZON. LIST A. CASE 0229.
http://www.fluoridealert.org/PESTICIDES/Norflurazon.RED.EPA.pdf
Congestion of the
liver, hepatocyte swelling and increased liver weights,
and increase in colloid vacuole in the thyroid
were observed in dogs fed 450 ppm (10.25 mg/kg/day) norflurazon
for 6 months. The NOEL was 150 ppm (3.75 mg/kg/day). An oral RfD
of 0.04 mg/ kg/day has been determined. Increased relative liver
weight and hypertrophy of the thyroid with depletion of
colloid were seen in rats fed 2,500 ppm (125 mg/kg/day) norflurazon
for 90 days. The NOEL was 500 ppm (25 mg/kg/day). Hepatic
hyperplasia and hypertrophy and increased relative liver weight
were noted in a 28-day feeding study in rats. The LOEL was 1,000
ppm (50 mg/kg/day) and the NOEL was 500 ppm (25 mg/kg/ day). Increased
relative liver weight and diffuse and smooth
granular livers were seen in a 28-day feeding study in
mice. The LOEL was 2,520 ppm (328 mg/kg/day) and the NOEL was
420 ppm (55 mg/kg/day). EPA believes that there is sufficient
evidence for listing norflurazon on EPCRA section 313 pursuant
to EPCRA section 313(d)(2)(B) based on the available
hepatic and thyroid toxicity data.
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.
The chronic NOAEL of
1.5 mg/kg/day was established based on increased absolute and
relative liver weight and increased
cholesterol in both sexes in a 6-month feeding study in dogs at
the LOAEL of 4.77 mg/kg/day... The acute and chronic dietary exposure
analyses are based on the Dietary Exposure Evaluation Model (DEEM
TM .) The acute dietary exposure estimates used the entire distribution
of single day food consumption. The chronic dietary exposure estimates
the three day average consumption for each population subgroup.
The DEEM TM analysis was conducted using consumption data from
the USDA 1989-92 Continuing Surveys for Food Intake by Individuals
(CSFII).
Ref: US EPA May 31, 2002. Tolerance Reassessment
Progress and Risk Management Decision.
http://www.fluoridealert.org/pesticides/Norflurazon.TRED.May31.2002.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... (page 10)
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
--
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).
-- Chronic toxicity - dog.
NOAEL= 10 mg/kg/day. LOAEL=100 mg/kg/day
based on hematologic changes associated with
histopathological changes in liver
and spleen.
-- Short-term, Intermediate-term and Long-term
inhalation: 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: 18-Month Oncogenicity Study
in CD-1 Mice,” (Johnson, K.A.; Toxicology & Environmental
Research and Consulting, The Dow Chemical Company, Midland, MI;
4/25/05). XDE-007 technical (N-[3,5-dichloro-2-fluoro-4-(1,1,2,3,3,3hexafluoropropoxy)phenyl]-N’-(2,6-difluorobenzoyl)urea),
97.9% pure) was fed in diet to CD-1 mice (50/sex/dose) at 0, 0.5,
3 (males only), 30 and 100 (females only) mg/kg/day for up to
18 months. Systemic NOEL = 3 mg/kg/day (males) and 30 mg/kg/day
(females) There was an increase in mortality for females at 100
mg/kg/day (M: 56% vs 32%). There was an increased incidence in
tonoclonic convulsions (primarily in females) at the high dose.
There was an increase in relative and absolute liver weights in
females at > 30 mg/kg/day. Males had an absolute liver weight
increase at 30 mg/kg/day and a relative increase at > 3 mg/kg/day.
Both sexes showed an increase in all severities of liver hypertrophy
(hepatocytic, centrilobular/midzonal, diffuse) at 30 mg/kg/day
(male) and at 100 mg/kg/day (female)... Possible
adverse effect indicated: There was an increased incidence in
hepatocytic adenomas and in hepatocytic adenomas plus carcinomas
(slight in males, statistically significant in females) at 30
mg/kg/day (5, 7, 4, 12 of 50) and 100 mg/kg/day (F: 0, 1, 0, 4**
of 50 by Peto’s mortality adjusted statistics ).
Females showed an increased incidence in lung carcinomas (non-metastatic)
at 100 mg/kg/day (0, 0, 1, 2** by Peto’s statistics).
-- “XDE-007: Two-Generation Dietary
Reproduction Toxicity Study in CD Rats,” (Carney,
E.W., Zablotny, C.L., Liberacki, A.B., Yano, B.L.;Toxicology &
Environmental Research and Consulting, The Dow Chemical Company,
Midland, MI; 3/22/04). XDE -007 (97.9% pure) was fed in diet to
Crl:CD (SD) IGS BR rats (30/sex/dose/generation) at 0, 0.5, 5
or 25 mg/kg/day continuously from pre-mating of parental generation
1 (P1) through weaning of offspring through 2 generations (2 matings
for P2 generation) to F2b weaning. Parental Systemic NOEL = 5.0
mg/kg/day (There were increased absolute
and relative liver weights in both sexes of P1 and P2 adults at
25 mg/kg and in P1 female liver weights at 5.0 mg/kg...
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
-- (Oral) 008; 186500;
"XR-007: 4-Week Dietary Toxicity Study in Fischer Rats"
(Lick, S.J. et al., Health & Environmental Research Laboratories,
The Dow Chemical Company, Midland,
MI, Laboratory Project Study ID 971106, 10/9/97). XR-007 (Lot
# DECO-615-112, purity = 99.6%) was admixed to the feed and fed
to 5 Fischer 344 rats per sex per dose at dose levels of 0, 1,
10, 100, 500, or 1000 mg/kg/day (0, 1.0, 10.4, 101.4, 512.6, 1029.1
mg/kg/day, respectively for males and 0, 1.1, 10.9, 105.1, 520.6,
1055.6 mg/kg/day, respectively for females) for 4 weeks... A treatment-related
increase in mean relative liver weight
was observed in both sexes at 500 and 1000 mg/kg/day. Microscopic
examination revealed treatment-related hepatocellular
hypertrophy (centrilobular) in males at 1000 mg/kg/day
and in females at 500 and 1000 mg/kg/day. No adverse effects.
NOEL (M) = 101.4 mg/kg/day and NOEL (F) = 105.1 mg/kg/day (based
on an increase in mean relative liver weight
and hepatocellular hypertrophy). Supplemental (because
only 5 animals per sex per dose were used, the animals were treated
for only 4 weeks, no ophthalmological examinations were conducted,
and no analysis of the dosing material was conducted). (Corlett,
10/3/02)
-- 007; 186499; "XDE-007: 28-Day Dietary Toxicity Study in
CD-1 Mice" (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
Nuarimol
- Fungicide - CAS No. 63284-71-9
Abstract: Early
hepatic changes
induced by nuarimol (63284719) were studied in rats. Male
Wistar-rats were administered 0, 31.5, 62.5, or 125mg/kg nuarimol
orally daily for up to 5 days. Selected rats were killed after
1, 3, or 5 days of exposure or 10 days after the last dose and
weighed. The livers were removed and weighed and liver tissues
were assayed for p-nitroanisole-O-demethylase (PNAD). The DNA
was isolated and the effects of nuarimol on DNA synthesis were
evaluated by measuring uptake of tritiated thymidine. Fragments
of liver tissue were examined for histopathological changes. The
number of hepatocytes undergoing mitosis was determined. Nuarimol
did not affect body weight. Administration of three doses of 62.5
and 125mg/kg nuarimol significantly increased relative liver weight.
The 31.5mg/kg dose did not affect liver weight. PNAD
activity was significantly increased after the first doses of
62.5 and 125mg/kg nuarimol. Three doses of 31.5mg/kg nuarimol
were required to induce a significant increase in PNAD activity.
Single doses of nuarimol caused a dose dependent
increase in DNA synthesis and the mitotic index. After
three and five doses, the level of DNA synthesis decreased, returning
to the control level after five doses. After five doses of 31.5,
62.5, and 125mg/kg nuarimol mitotic activity returned to the control
value. Nuarimol caused time dependent increases in the number
of binucleated hepatocytes. One and
three administrations caused a dose related increase in cytoplasmic
vacuolization and focal destruction of centrilobular hepatocytes.
These changes partially disappeared after five doses. The authors
conclude that the early hepatic effects of nuarimol include increases
in PNAD activity and cellular hyperplasia, as manifested
by increases in the level of DNA synthesis and mitotic activity.
The increase in the number of binucleated hepatocytes and signs
of necrosis suggest that the hepatomitogenic
effect of nuarimol may reflect a regeneration response.
Ref: Kostka G et al (1994). Early Hepatic
Changes Induced by Nuarimol in Rats. Journal of Applied Toxicology,
Vol. 14, No. 5, pages 337-342. As cited at Toxnet.
Exposure to nuarimol
causes both acute and chronic effects. It is moderately acutely
toxic, with a WHO classification of Class III, or "slightly hazardous"
and a rat oral LD50 of 1250 mg/kg. (24) DowElanco data indicates
a single oral as well as inhalation exposure of the product caused
laboratory rats to exhibit reduced activity, clonic convulsion
(muscle contraction), ataxia (loss of balance
and coordination), labored breathing, reduced weight gain,
and coma. Laboratory animals exhibited increases in liver
weight and enzyme activity and microscopic liver
cell changes when repeatedly exposed to the product. (8)
The product is also an eye irritant. (8,16,21) As mentioned above,
EPA has concerns over the product's ability to cause cancer and
birth defects in lab animals. (10)
Ref: NEVER-REGISTERED PESTICIDES: Rejected
Toxics Join the "Circle of Poison." Greenpeace USA Pesticide Campaign
report. By Sandra Marquardt, Laura Glassman and Elizabeth Sheldon.
February 1992.
http://www.fluoridealert.org/pesticides/Nuarimol.Greenpeace.1992.htm
Oxyfluorfen
- Herbicide - CAS No. 42874-03-3
Group
C -- Possible Human Carcinogen. Liver (adenomas,
carcinomas 7 combined adenomas and/or carcinomas); CD-1 mice (M).
Ref: April
26, 2006 . Chemicals Evaluated for Carcinogenic Potential by the
Office of Pesticide Programs. From: Jess Rowland, Chief Science
Information Management Branch Health Effect Division (7509C) Office
of Pesticide Programs, USEPA.
http://www.fluorideaction.org/pesticides/pesticides.cancer.potential.2006.pdf
Oxyfluorfen is a phenoxyphenyl-type
herbicide. Several chronic oral toxicity studies suggest that
oxyfluorfen may be hepatotoxic. Hepatic effects (e.g. increased
absolute liver weight, necrosis, regeneration, and hyperplastic
nodules) were observed in mice fed diets containing greater
than 3 mg/kg/day oxyfluorfen for 20 months (the NOEL was 0.3 mg/kg/day).
Based on these findings, an oral RfD value of 0.003 mg/kg/ day
was derived. This study was supported by other chronic feeding
studies that demonstrated increases in liver
weight, alkaline phosphatase activity, and bile pigmented hepatocytes
(the LOEL was 15 mg/kg/day; the NOEL was 2.5 mg/kg/day) in dogs,
and minimal hypertrophy of centrilobular hepatocytes (the LOEL
was 40 mg/kg/day; the NOEL was 2 mg/kg/day) in rats. EPA believes
that there is sufficient evidence for listing oxyfluorfen on EPCRA
section 313 pursuant to EPCRA section 313(d)(2)(B) based on the
hepatotoxic effects of 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.
Microscopic changes
observed at 12 months included binucleate hepatocytes (6/10),
central lobular hepatocyte hypertrophy
(7/10), and enlarged hepatocyte nuclei (6/10) in high dose females
compared to 0/5 for controls. Similar changes were not seen at
the terminal sacrifice, despite the fact that the animals received
higher doses during the last 12 months of the study. Therefore
the findings at 12 months may be an adaptive effect... The microscopic
liver and kidney lesions were generally
classified slight in mid-dose animals and slight to moderate in
high-dose animals... The only treatment-related histopathological
lesion in the liver was slight to
moderate bile pigmented hepatocytes in both sexes after 104 weeks
(n.s.) and hepatocellular vacuolization was seen in high-dose
females.
Ref: US EPA. Toxicology Chapter for RED.
August 8, 2001.
http://www.epa.gov/oppsrrd1/reregistration/oxyfluorfen/oxytoxchapter.pdf
Penoxsulam
- Herbicide - CAS No. 219714-96-2
-- Subchronic toxicity.
Dietary exposure to penoxsulam identified the
liver and/or urinary tract (kidneys
and bladder) as target organs in rats, mice, and dogs following
a 4-week and 13-week administration. Effects on the liver were
reflected in increased liver weights and hepatocellular
hypertrophy, but these effects were not associated with
increases in mixed function oxidase (MFO) enzyme activity... Other
than the crystal deposition in the kidneys, all effects
following subchronic exposure to rats appeared to be reversible.
Very high doses were associated with significant decreases in
body weight, weight gain, and feed consumption.
-- Reproductive and developmental toxicity. Penoxsulam did not
have any effect on reproductive parameters at dose levels that
induced treatment-related effects in parental rats. At the highest
dosage tested (HDT) (300 mg/kg/day), body
weights and weight gains in both males and females were depressed,
liver and/or kidney weights were
increased, and histologic changes were noted in the
liver (males) and kidneys (females). At 100 mg/kg/day,
increased liver weights were recorded in
males, with no histologic correlate, and
histologic changes noted in the kidneys of females...
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
Perfluidone
- Herbicide - CAS
No. 37924-13-3
-- Subchronic toxicology
effects of perfluidone are as follows: - A 90-day dog feeding
study showed liver disorders (hepatic lesions,
hepatocyte vacuolation, hyaline degeneration, and biliary
stasis) at the two highest dose levels (400 and 800 ppm).
-- The Agency (US EPA) is not conducting a tolerance reassessment
on perfluidone, because the only use is on flue-cured tobacco.
This use is a nonfood and non-feed use which does not require
a tolerance. Therefore, the Agency will not require residue chemistry
data on the metabolism of perfluidone and related metabolite(s)
in crops and animals.
Ref: Chemical Fast Sheet for Perfluidone.
Number 74. Date Issued: September 30, 1985.
http://www.fluoridealert.org/pesticides/Perfluidone.Fact.Sheet.1985.htm
Abstract: The influence
of perfluidone (37924133) on oligomycin inhibited mitochondrial
respiration was investigated in-vitro. Mitochondria were prepared
from albino Wistar-rats and incubated with pyruvate-malate, succinate,
or ascorbate N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD) as
substrate. Aliquots of 50 nanomolar adenosine-diphosphate, oligomycin,
and perfluidone at concentrations from 0 to 160 millimolar (mM),
or carbonylcyanide-p-trifluoromethoxyphenyl-hydrazone (FCCP),
a classic protonophore, were added at specific time intervals.
Oxygen consumption was measured polarographically. The effect
of varying concentrations of perfluidone on oligomycin sensitive
mitochondrial adenosine-triphosphatase (ATPase) was also determined.
With succinate as substrate, respiratory rates increased from
29.5 nanogram atoms oxygen/milligram mitochondrial protein/minute
(ng/mg/minute) to 85.4ng/mg/minute after adding 40mM perfluidone.
The extent of respiration stimulation by perfluidone increased
with increasing concentrations. After adding FCCP at 1microM,
the oligomycin inhibited respiratory rate of 31.4ng/mg/minute
was increased to 151.3ng/mg/minute. The respiratory rate was increased
in a dose dependent fashion at perfluidone concentrations up to
80microM which gave a maximum stimulation of about 5 fold. At
higher concentrations of perfluidone the extent of stimulation
of respiration decreased. Similar results were obtained when respiration
was supported by pyruvate-malate. Maximum sensitivity to perfluidone,
about 5 fold stimulation, was obtained at 100microM and decreased
at higher concentrations. When ascorbate TMPD was used as the
substrate, a 2 fold stimulatory effect was obtained at 20microM
perfluidone; maximum effect was apparent at 80microM perfluidone
and respiration was decreased at higher concentrations. The authors
conclude that perfluidone probably increases the permeability
of the inner mitochondrial membrane to protons, as does FCCP,
and acts as a classic protonophore.
Ref: Olorunsogo OO et al. (1985). Sensitivity
Of Oligomycin-Inhibited Respiration Of Isolated Rat Liver Mitochondria
To Perfluidone, A Fluorinated Arylalkylsulfonamide. Toxicology,
Vol. 35, No. 3, pages 231-240
Picolinafen
- Herbicide - CAS No. 137641-05-5
-- Fat, liver
and kidneys contained the highest amounts of picolinafen metabolites
labelled on the pyridine ring, whereas the blood,
liver, spleen and lungs contained the highest amounts of
picolinafen metabolites labelled on the aniline ring.
-- Short-Term Studies All mice fed picolinafen at dietary concentrations
of 0, 100, 1000, 2000, 3500 or 7000 ppm for 28 days... Discolouration
of the extremities, discoloured organs (kidney,
liver, lungs, testes and heart) and haematological changes
(increased MCH, MCHC, reticulocyte and Heinz bodies numbers) were
observed at 3500 and 7000 ppm. Spleen and liver
weights were increased at ¥ 2000 ppm and the breakdown products
of blood cells accumulated in the liver
and spleen and the production of blood cells in the spleen were
increased in males at ¥ 1000 ppm and females at ¥ 2000 ppm. The
severity of these histopathological changes increased in a dose-related
manner.
-- In a study in which groups of two dogs per sex were fed picolinafen
at dietary concentrations of 0, 100, 1000, 2000, or 10000 ppm
for 28 days, ... Livers were enlarged,
liver weights and liver glycogen
increased and serum cholesterol was increased in males at ¥ 1000
ppm and females at ¥ 2000 ppm.
-- In mice fed picolinafen at dietary concentrations of 0, 50,
500, 1000 or 2000 ppm for 13 week... Liver
weight and pigment deposition were increased at 2000 ppm with
other histopathological changes observed in the liver
of males at ¥ 500 ppm and females at ¥1000 ppm. The spleens of
some mice were enlarged and spleen weights were increased in females
at ¥1000 ppm...
- In rats fed picolinafen at dietary concentrations of 0, 80,
400 or 800 ppm ... Liver to body
weight ratios were increased in males at 800 ppm and females at
400 and 800 ppm. Pigment deposition was increased in the liver
and spleen at 400 and 800 ppm. The NOEL in this study was 80 ppm,
equal to 6.4 mg/kg bw/day in males and 6.8 mg/kg bw/day in females.
-- Long-Term Studies In mice fed picolinafen at dietary concentrations
of 0, 40, 400 or 800 ppm for 18 months, there was no increase
in the incidence of neoplasms... Increased liver
weights and histopathological changes were observed in females
at 800 ppm with histopathological changes observed in the
livers of males at 400 and 800 ppm.
Ref: Public Release Summary on Evaluation
of the new active PICOLINAFEN in the products SNIPER HERBICIDE
& PARAGON HERBICIDE. Australia. National Registration Authority
for Agricultural and Veterinary Chemicals November 2000.
http://www.nra.gov.au/publications/prspic.pdf
Following subchronic
and chronic administration, mice also exhibited treatment-related
findings in the liver, including centrilobular
hepatocellular hypertrophy and hepatocellular vacuolation.
These were noted following 28-day, 90-day and 78-week dietary
administration. The NOAELs for mice were 23.4, 10.2, and 6.9 mg/kg
bw/d following 28-day, 90-day, and 78-week dietary administration,
respectively.
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
Primisulfuron-methyl
- Fungicide,
Herbicide- CAS
No. 86209-51-0
-- Chronic toxicity:
Doses of 125 mg/kg/day administered in the diet to dogs over a
1-year period produced decreased body weight gain, anemia, increased
liver weight, and thyroid hyperplasia
(abnormal growth) [15]...
-- Reproductive effects: Changes in the function of the testes
were noted in rats fed high doses (250 mg/kg/day) of primisulfuron-methyl
over two generations. There was also a decrease in the body weight
of the offspring. No compound-related effects on reproduction
were noted at doses below 50 mg/kg/day [15]. Testicular atrophy
was seen in rats in chronic studies (see above), which
could result in reproductive effects. The available data suggest
that reproductive effects in humans due to primisulfuron are not
likely under normal circumstances.
-- Organ toxicity: Target organs identified in animal studies
include the liver, kidneys,
spleen, and testes,
as well as the skeleton.
Ref: E X T O X N E T Extension Toxicology
Network Pesticide Information Profiles. Revised June 1996.
http://ace.ace.orst.edu/info/extoxnet/pips/primisul.htm
-- Chronic toxicity.
EPA has established the RfD for primisulfuron- methyl at 0.006
milligrams/kilogram/day (mg/kg/day). This RfD is based on an 80-week
mouse feeding study with a LOEL of 1.7 mg/kg/day based on increased
absolute and relative liver weights.
An uncertainty factor of 300 was used because a NOEL was not achieved.Carcinogenicity.
Primisulfuron-methyl has been classified as a Group D chemical
incomplete evidence based on liver
tumors in mice.
Ref: Federal Register: December 17, 1997.Primisulfuron-methyl;
Pesticide Tolerances for Emergency Exemptions. Final Rule.
http://www.fluoridealert.org/pesticides/Primisulfuron-methyl.FR.97.htm
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. Based on this study, an oral RfD of 0.006
mg/kg/day was derived. In a 2-year mouse study, increases in absolute
and relative liver weights were observed
at 408 mg/kg/day in males and 1.7 mg/kg/day in females. The systemic
LOEL and NOEL in males was 408 mg/kg/day and 40.2 mg/kg/day, respectively.
The systemic LOEL in females was 1.7 mg/kg/day
and a NOEL could not be established. EPA believes that there is
sufficient evidence for listing primisulfuron on EPCRA section
313 pursuant to EPCRA section 313(d)(2)(B) based on the available
thyroid and liver 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.
Prodiamine
- Herbicide - CAS No. 29091-21-2
--
Chronic/Subchronic Toxicity Studies. Prodiamine: Liver
(alteration and enlargement) and thyroid effects (hormone
imbalances) at high dose levels (rats); decreased body weight
gains.
-- Carcinogenic Potential. Prodiamine: Benign thyroid tumors (rat).
None observed (mouse).
-- Target Organs. Prodiamine: Liver
and Thyroid.
Ref: Material Safety Data Sheet for Barricade
65WG Herbicide. Novartis. February 28, 2000.
http://www.fluoridealert.org/pesticides/Prodiamine.MSDS.2000.pdf
Profluralin
- Herbicide
- CAS No. 26399-36-0
(FAN
NOTE: Very little Tox data available)
-- Lifetime feeding studies with high dose levels of profluralin
technical have produced an increased incidence of hepatic
tumors in mice.
Ref: March 1985. Profile of Herbicide (Tolban).
Pesticide Management Education Program at Cornell Univeristy.
http://www.fluoridealert.org/pesticides/Profluralin.Tolban.1985.fct.htm
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)
-- Long term toxicity and carcinogenicity Target / critical effect:
Liver (hepatocellular hypertrophy in mice), indication
of hormonal disruption (uterus and mammalian gland in rats) at
high dose levels Lowest relevant NOAEL: NOAEL = 1,7 mg/kg bw/day
(18-month, mouse) Carcinogenicity: No carcinogenic potential
Ref: July 2, 2002 - Review report for the
active substance prosulfuron. European Commission Health &
Consumer Protection Directorate-General.
http://www.fluoridealert.org/pesticides/Prosulfuron.EU.July.2002.pdf
-- In an 18-month mouse
carcinogenicity study, prosulfuron was administered at dose levels
of 0, 1.71, 81.4, 410 or 832 mg/kg/day (males), and 0, 2.11, 100,
508 or 1,062 mg/kg/day (females). There was no evidence of carcinogenic
effects up to 1,062 mg/kg/day, the HDT. The NOAEL was 1.71 mg/kg/day
in males, and 100 mg/kg/day in females based on increased incidence/severity
of centrilobular hepatocellular hypertrophy.
-- Chronic toxicity. Prosulfuron was fed to dogs at dosages of
0, 0.33, 1.95, 18.6 or 41.0 mg/kg/day (males) and 0, 0.31, 1.84,
20.2, or 48.8 mg/kg/day (females) for 1-year. 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: 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
Likely
to be Carcinogenic to Humans. Hepatocellular adenomas
and combined adenomas, carcinomas and/or hepatoblastomas
in male and female (SPF) ICR (Crj:CD-1) mice.
Ref: April
26, 2006 . Chemicals Evaluated for Carcinogenic Potential by the
Office of Pesticide Programs. From: Jess Rowland, Chief Science
Information Management Branch Health Effect Division (7509C) Office
of Pesticide Programs, USEPA.
http://www.fluorideaction.org/pesticides/pesticides.cancer.potential.2006.pdf
-- 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.Lowest relevant NOAEL: 200 ppm
(20 mg/kg bw/d ) 2 year mice study 400 ppm ( 20 mg/kg bw/d) 2
year rat study. Carcinogenicity: Increased incidence of hepatocellular
adenomas in mice at hepatotoxic doses, not carcinogenic
in rats. Classification and labelling not appropriate.
-- Other toxicological studies. Accumulation of porphyrins in
all organs except skin and Harderian glands.
Inhibitor of some liver P450 dependent activities; inhibitor
of catalase. Induction of liver single cell
necrosis followed by mitosis.
Ref: July 2, 2002 - Review report for the
active substance pyraflufen-ethyl. 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.
-- Pyridalyl was administered in the diet
to mice for
78-weeks. Effects included
decreased body weight gain and food consumption/efficiency,
and increased liver and
kidney weights. The
NOAEL of the study was 50 ppm (5.04 mg/kg/day in males and 4.78
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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