| See short description and definitions on kidney
use of high doses increases the likelihood that potentially
significant toxic effects will be identified. Findings of
adverse effects in any one species do not necessarily indicate
such effects might be generated in humans. From a conservative
risk assessment perspective however, adverse findings in
animal species are assumed to represent potential effects
in humans, unless convincing evidence of species specificity
Food and Agricultural Organization of the United Nations
This is not an exhaustive list.
When time allows more information will be added.
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
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.
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.
- Herbicide - CAS No. 69806-40-2
-- 3) 13-Week
Feeding - monkey: Dietary levels tested: 0, 2, 10, and 30 mg/kg/day;
Cynomolgus monkeys (4/sex/dose level) were administered haloxyfop-
methyl by nasogastric intubation for 13 weeks. A statistically significant
decrease in triglyceride values was reported for males and females
dosed at 2 mg/kg/day. The statistically significant decrease in
triglyceride values in males and females dosed at 10 mg/kg/day was
accompanied by a nonsignificant decrease (15%) in cholesterol values
for females at this level. Female livers appeared pale with an accentuated
lobular pattern. Slight hepatocellular hypertrophy was observed
for male and females at this level. Relative
kidney weights were significantly increase for males and females
by 12 and 37%, respectively. The LEL for systemic toxicity
is 2 mg/kg/day, the lowest dose tested, based on a statistically
significant decrease in triglyceride values in males and females.
A NOEL for systemic toxicity was not established; core grade minimum
(Dow Chemical Co., 1987b)
-- 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
-- 4) 2-Year Feeding (carcinogenicity) - rat: Dietary levels tested:
Male: 0, 0.01, 0.03, 0.065, and 0.1 mg/kg/day; Female: 0, 0.01,
0.03, 0.065, and 1.0 mg/kg/day; CDF Fischer 344 rats (50/sex/dose)
were administered haloxyfop- methyl in the diet for 2 years. No
effects were observed in the male at any dose tested. The LEL for
systemic toxicity is 1 mg/kg/day based on a significant
decrease in female absolute (8%) and relative (9%) kidney weights
accompanied by a significant increase in the incidence (24/50) in
renal pigmentation reported for females of this level. Kidney
function was not impaired as the urinalysis parameters between test
and control values were comparable. The NOEL for systemic toxicity
is 0.065 mg/kg/day; core grade guideline for chronic toxicity (Dow
Chemical U.S.A., 1984b)
Health Assessment. US EPA Integrated Risk Information System (IRIS).
polymer with tetrafluoroethylene -
EPA List 3 Inert - CAS No. 25067-11-2
Tetrafluoroethylene was tested for carcinogenicity in one
study in mice and one study in rats by inhalation... In
rats of both sexes, it increased the incidence of hepatocellular
carcinomas and kidney tubule cell adenomas.
Other relevant data
Tetrafluoroethylene is metabolized by hepatic glutathione
S-transferase and the resulting cysteine conjugate is further
metabolized by renal b-lyase. This pathway results in the
formation of a reactive thiol that causes
kidney toxicity in rats.
is sufficient evidence in experimental animals for the
carcinogenicity of tetrafluoroethylene.
is possibly carcinogenic to humans (Group 2B).
International Agency for Cancer Research (IARC):
- Insecticide, Plant Growth Regulator - CAS No. 86479-06-3
Health Effects: eye irritant, liver and kidney
Ref: Physical Properties And Health Effects
of Pesticides Used On National Park Service Collections. Conserve
O Gram. U.S. National Park Service. September 2001. Number
- Insecticide - CAS No. 67485-29-4
- In a 90 day feeding study in rats, MRID 00032641, groups of
20 male and 20 female Sprague-Dawley rats were dosed with hydramethylnon
in their feed at 0, 50, 100, 200, or 400 ppm (equivalent to 0,
2.5, 5.0, 10.0 or 20.0 mg/kg/day). Due to significant decreases
in body weight gain and food consumption during the first two
weeks of the study at the highest dose (400 ppm, 20 mg/kg/day),
this dose level was reduced to 25 ppm (1.25 mg/kg/day) on study
day 15. Thus, the dose levels tested were 0, 25, 50, 100, or 200
ppm (0, 1.25, 2.5, 5.0, or 10.0 mg/kg/day)... On study day 68,
a 50 ppm male was sacrificed moribund, and a 200 ppm (10.0 mg/kg/day)
female died. The 200 ppm female had a blood
urea nitrogen (BUN) value 4-fold higher than that of the controls
on day 45. Histopathologic evaluation of this female revealed
nephrocalcinosis and hydronephrosis...
-- In a carcinogenicity study, MRID 00101563, groups of 50 male
and 50 female Charles River CD-1 mice received diets containing
hydramethylnon at dose levels of 0, 25, 50, 100, or 200 ppm (0,
3.57, 6.93, 14.2, or 28.6 mg/kg/day in males, and 0, 4.45, 6.87,
17.3, or 33.1 mg/kg/day in females, based on food consumption)
for 18 months. The 200 ppm males and females were sacrificed after
55 weeks because of high mortality. Survival after 18 months at
the 50 and 100 ppm doses was 72% and 46% in males, and 66% and
46% in females (compared to control survival of 86% in males and
76% in females)... Dose-related amyloidosis
was seen in the kidneys of the 50 and 100 ppm females.
-- In a chronic toxicity/carcinogenicity study, MRID 00101565,
groups of 50 male and 50 female Charles River CD rats were fed
diets containing hydramethylnon at dose levels of 0, 25, 50, 100,
or 200 ppm (0, 1.2, 2.4, 4.9, or 10.0 mg/kg/day in males, and
0, 1.5, 3.0, 6.2, or 12.1 mg/kg/day in females, respectively based
on food consumption) for two years... Body
weights in the males were as much as 17% less than the controls
at 200 ppm, and 5% at 100 ppm. Body weights in the females were
as much as 42% less than the controls at 200 ppm, and 22% at 100
ppm. Body weights were comparable in the other groups. Food consumption
was reduced an average of 7% in the 200 ppm males, and 16% in
the 200 ppm females. The other groups were comparable...
Glomerulonephrosis was greater in the treated
males and females than in the controls, but there was no
Ref: US EPA. Reregistration Eligibility
Decision (RED) Hydramethylnon. EPA 738-R-98-023. December 1998. http://www.fluoridealert.org/pesticides/hydramethylnon.red.1998.pdf
18-Month Feeding (oncogenic)
- mouse: Systemic NOEL=25 ppm (2.75 mg/kg/day); Systemic LEL=50
ppm (3.75 mg/kg/day) (increased testicular lesions, decreased
body weight gain, increased renal amyloidosis);
core grade minimum (American Cyanamid, 1982d).
Ref: US EPA IRIS for Amdro (CASRN
In an 18-month cancer assay, hydramethylnon at about 3.8 mg/kg/day
was associated with amyloidosis, a syndrome
in which abnormal protein deposition in the kidney fitration unit
(glomerulus) results in damage .
E X T O X N E T Extension Toxicology Network Pesticide Information
Profiles for Hydramethylnon.
- Insecticide - CAS No. 173584-44-6
Toxicity Study of DPX-JW062-106 (50% DPX-KN128, 50% DPX-KN127)
One Year Feeding Study in Dogs"
(Mertens, J. 831-WIL Research Laboratories,
Inc. Ashland, Ohio. Study HLO 885-96, 11/19/97). DPX-JW062-106
technical (Batch DPX-JW062- 106, 47.5% DPX-KN128) was administered
orally (via the feed) to 5 Beagle dogs/sex/dose at levels of 0,
40, 80, 640 and 1280 ppm for 52 weeks. There was a treatment-related
decrease in body weight, body weight gain and food consumption
in 1280 ppm dogs during the first three months of the study. Reduced
mean hemoglobin, RBC count and hematocrit was noted in the 80,
640 and 1280 ppm groups during all periods tested; increased Heinz
bodies in these groups indicated hemolysis. Increased mean reticulocyte
counts and MCV and decreased corpuscular hemoglobin concentration,
erythrocyte morphologic changes and increased mean platelet counts
indicated responses to hemolytic anemia. Significantly decreased
RBC counts were also reported in 40 ppm males at week 25 and 51.
Females at 40 ppm also showed reductions in RBC, but the differences
were not statistically significant. Mean liver weights were increased
in males (640 and 1280 ppm groups) and females (1280 ppm only).
Microscopic changes in groups 40 ppm and above included increased
pigment (hemosiderin) in liver Kupffer cells,
kidney tubule epithelium, spleen and bone marrow and increased
extramedullary hematopoiesis in the spleen and bone marrow hyperplasia.
NOEL (M/F)=40 ppm (males: 1.1 mg/kg/day; females: 1.3 mg/kg/day
based on biologically significant hemolytic anemia at 80 ppm and
above). Acceptable. Kellner, 1/12/99.
11, 1999: Summary
of Toxicology Data - Indoxycarb.
California EPA Department of Pesticide Regulation, Medical Toxicology
- Herbicide - CAS No. 77501-63-4
Chronic toxicity--dogs. NOAEL = 0.79 mg/kg/day. LOAEL = 3.96
mg/kg/day based on increased incidence of proteinaceous
casts in the kidneys, and statistically
significant increases in the absolute weights of the thyroid and
adrenal glands in males.
Sept 24, 2004. Lactofen. Pesticide Tolerance. Final Rule. Federal
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.
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 Toxicity- A
complete chronic data base supported by appropriate subchronic
studies for lactofen is available to the Agency. Lactofen Technical
causes adverse health effects when administered to animals for
extended periods of time. These effects include proliferative
changes in the liver, spleen, and kidney;
hematological changes; and blood biochemistry changes. Based on
the Lowest Effect Level (LEL) of 1.5 mg/ kg/day in the 18-month
mouse feeding study and an uncertainty factor of 1,000, a reference
dose (RfD) of 0.002 mg/kg/day has been established for lactofen.
An uncertainty factor of 1,000 was used since a clear NOEL was
-- Reproduction-- Rats. Groups of male and female rats were fed
0, 50, 500 or 2,000 ppm of Lactofen Technical continuously in
their diets for 2-generations. Adult systemic toxicity (mortality,
reduced body weight, increased liver and spleen weight, decreased
kidney weight and histological changes
in the liver and testes) was observed at levels of 500 ppm and
-- 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.
Ref: Federal Register: February 25, 1998
[Page 9532-9540]. Notice of Filing of Pesticide Petition.
diethanolamine salt - Herbicide - CAS
The studies reviewed
below were conducted with either the free acid or the diethanolamine
salt of mefluidide. The diethanolamine salt is the registered
active ingredient in California. Possible toxicological differences
between the free acid and diethanolamine salt were not considered
in the following reviews. The free acid and diethanolamine salt
have been grouped by the US EPA (Morris, 10/5/93)...
-- ** 386-026 037397, "Twelve Month Diet Feeding Study of MBR-12325
in Dogs", (Riker Laboratories, experiment no. 0280CD0021, 11/1/82).
Technical MBR-12325 (Mefluidide), purity 93% and 91% at pre-study
and post-study, respectively, fed at 0, 60, 600 or 6000 ppm in
the diet to Beagle dogs, 6/sex/group for one year. Positive
for adverse effects on kidney at high dose. NOEL kidney
= 600 ppm; body weight = 60 ppm. Nephrosis
or degeneration of proximal convoluted renal tubular epithelium
in 4/12 at high dose. Record 059988 contains the diet analyses
for content, stability and homogeneity. ACCEPTABLE. (Gee, 3/17/86
and 7/14/88). EPA one-liner: Minimum. NOEL = 60 ppm (weight loss);
LEL = 600 ppm (cortical nephrosis). EPA one-liner: Minimum. NOEL
= 60 ppm (weight loss); LEL = 600 ppm (cortical nephrosis).
Ref: Mefluidide, diethanolamine salt: Summary
of Toxicology Data. 1986. California EPA, Department of Pesticide
Regulation, Medical Toxicology Branch.
(also known as MNFA) - Acaricide, Insecticide - CAS
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.
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.
- Herbicide - CAS No. 27314-13-2
-- A two-year carcinogenicity
study was conducted in male and female CD-1 HaM/ICR Swiss mice
in which 125 mice/sex/dose were administered technical norflurazon
in the diet at dose levels of 0, 85, 340, or 1360 ppm (0, 12.8,
58.7, or 218.8 mg/kg/day) for 100-104 weeks... 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...
-- A chronic toxicity and carcinogenicity study was conducted
in Sprague-Dawley rats. In this study, technical norflurazon was
administered in the diet at dose levels of 0, 125, 375, or 1025
ppm (0, 6.25, 18.75, or 51.25 mg/kg/day) for 104 weeks...
The systemic LEL was determined to be 1025 ppm (51.25 mg/kg/day)
in both sexes, based on the increased kidney
weight and accompanying microscopic pathologic changes,
as well as the increase in liver weight
in male and female rats and the increase in thyroid weight
-- 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
-- A nine-month oral toxicity study (MRID 00091056) was conducted
using the F generation of rats from a two-year carcinogenicity
study (MRID 00082019). In this study, rats were given technical
norflurazon in the diet at dose levels of 0, 125, 250, or 500
ppm (0, 6.25, 12.5, and 25 mg/kg/day) for 39 weeks... Kidney weight
was not significantly affected, but the incidence of hyaline
pigment deposition (many tubules) in male rats and hyaline pigment
deposition (few tubules) in female rats was increased,
as was the incidence of medullary congestion
in high dose female rats. The incidence of tubular
degeneration was increased in both sexes at the 500 ppm
dose level. ... The systemic LEL was determined to be 500 ppm
(25 mg/kg/day) in both sexes, based on the dose-related increase
in liver weight in male and female rats at 39 weeks, the increase
in gonad weight of females, and the microscopic
changes observed in kidneys of both sexes. Although dramatic
effects on thyroid weight were observed at 250 ppm in both sexes,
there were no data indicating any alteration in histology of this
organ. Thus, the weight change, while indicative of an effect
of norflurazon, is not supported as a toxic effect based on available
data (guideline: non-guideline study; classified as core supplementary;
Ref: US EPA REREGISTRATION ELIGIBILITY DECISION
NORFLURAZON. LIST A. CASE 0229.
- Insecticide - CAS No. 121451-02-3
-- “XDE-007: Two-year Dietary Chronic
Toxicity/Oncogenicity and Chronic Neurotoxicity Study in Fischer
344 Rats,” (Yano, B.L., Dryzga, M.D., Thomas, J.;
Toxicology & Environmental Research and Consulting, The Dow
Chemical Company, Midland, MI; Laboratory Project Study ID: 011168;
4.22.05). Noviflumuron ((N-[3,5-dichloro-2-fluoro-4(1,1,2,3,3,3-hexafluoropropoxy)phenyl]-N’-(2,6-difluorobenzoyl)urea;
XDE-007, 97.9% pure) was fed in diet to Fischer 344 rats (75/sex/dose)
for 90 days, 1 or 2 years at 0, 0.1, 1.0, 75 or 300 mg/kg/day.
Subchronic toxicity was assessed after 90 days of treatment on
10/sex/dose at 0 and 1.0 mg/kg/day doses only. At 1 year,10/sex/dose
(chronic toxicity group), and 5/sex/dose (chronic neurotoxicity
group) were necropsied. The remaining 50/sex/dose were necropsied
after 2 years (oncogenicity group). Chronic NOEL = 1.0 mg/kg/day
(At > 75 mg/kg/day there were decreased body weights and body
weight gains along with increases or decreases
in absolute and/or relative organ weights
(liver, kidney, brain, heart, adrenal,
testes, spleen, epididymides were affected) at 12 and/or 24 months.
Skin/tail papules and pustules were observed in males (300 mg/kg/day)
and females (> 75 mg/kg/day) in the second year. Females showed
an increase in phthisis bulbi at 300 mg/kg/day. Prothrombin time
in males and cholesterol levels in females were increased at >
75 mg/kg/day at 24 months. ALP activities were increased in both
sexes at > 75 mg/kg/day at 24 months. Urine specific gravity
was decreased (both sexes at > 75 mg/kg/day) and urine volume
was increased (M 300 mg/kg/day and F > 75 mg/kg/day) at 24
months. Lung inflammation, hepatocytic hypertrophy (both sexes
> 75 mg/kg/day), mineralization of renal
pelvic epithelium (M > 75 mg/kg/day), epididymal aspermia*
(M > 75 mg/kg/day), atrophy of seminiferous tubules
(300 mg/kg/day), tail hyperkeratosis +/- inflammation (both sexes
300 mg/kg/day), tail tip necrosis (M 300 mg/kg/day) and hyperplasia
of renal pelvic epithelium (M 300 mg/kg/day) were observed
at 24 months. Leukemia was decreased in both sexes at > 75
mg/kg/day at 24 months.) Possible adverse effect: Hepatocellular
adenomas (benign, M 300 mg/kg/day), uterine stromal polyps (F
> 75 mg/kg/day), and liver foci (M > 75 mg/kg/day) were
increased at 24 months. Acceptable. Silva, 8/19/05
-- “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. P1
male relative kidney weights, P2 female absolute kidney weights,
P2 male relative spleen and thyroid weights and P2 female absolute
and relative adrenal weights were increased at 25 mg/kg.) ...
August 2005 - Summary of toxicological data. California EPA, Department
of Pesticide Regulation, Medical Toxicology Branch.
- Herbicide - CAS No. 42874-03-3
Renal toxicity was most severe in the 2-generation reproduction
study in rats,in
which pelvic mineralization occurred.Other studies had indications
of renal toxicity:increases in organ weight and occasional histopathological
-- In a third subchronic dietary toxicity study (MRID 00117603),oxyfluorfen
(72%) was administered to 10 CRJ-CDF rats/group at dietary concentrations
of 0,200,1000,or 5000 ppm for 13 weeks.Doses corresponded to
0,14,71,or 361 mg/kg/day in males and 0,18,75,or 396 mg/kg/day
in females... At necropsy,dark-brown livers and/or kidneys
in mid-and high-dose males and females were noted... Microscopic
kidney lesions in high-dose males and mid-and high-dose females
included calcium deposition,vacuolar degeneration of distal tubules,hypertrophy/hyperplasia
of transitional epithelium,and yellow pigment in renal tubular
epithelium.The microscopic liver and kidney lesions were
generally classified slight in mid-dose animals and slight
to moderate in high-dose animals... The NOAEL is 200 ppm
(males:14 mg/kg/day; females:18 mg/kg/day).The
LOAEL is 1000 ppm (males:71 mg/kg/day);females:75 mg/kg/day)based
upon brown livers and kidneys in
males and females, increased relative liver weights in males,
decreased absolute and relative thymus weights in males, and microscopic
liver and kidney lesions in males
and females (classified slight).
-- Reproductive Toxicity. Adequacy of data base for Reproductive
Toxicity: There is an acceptable reproductive study with 71%technical
material. The data base for reproductive toxicity is complete
and no additional studies are required at this time. Parental
toxicity included mortality, body weight decrements, and microscopic
liver and kidney lesions. The kidney
lesion was microscopic mineralization, which was not observed
in other rat feeding studies.
-- Reproduction and Fertility Effects -Rat Goal Herbicide (71.4%a.i.)was
administered to groups of 25 male and 25 female Crl:CD ®BR rats
in the diet at concentrations of 0,100,400,or
1600 ppm of active ingredient for two generations (MRID
42014901).One litter was produced in each generation. Premating
doses for the adult F0 males were 0,7.8,30.9,and 120.0 mg/kg/day
and for the F0 females were 0,8.5,32.8,and 131.2 mg/kg/day,respectively.
Premating doses for the adult F1 males were 0, 8.9,36.4,and 146.3
mg/kg/day and for the F1 females were 0,8.9,35.7,and 151.3 mg/kg/day,
respectively.F1 pups chosen to produce the F2 litters were weaned
onto the same diets as their parents .Animals were given test
or control diet for 10 (F0)or 14 (F1)weeks then mated within the
same dose group... Gritty material was observed in the renal
pelvis of 2/25 high-dose F0 males and in 1/25 and 5/25 mid- and
high-dose F1 males, respectively. This was not observed
in any control or low-dose males. Dose-related increases in the
incidence rates of liver and kidney lesions
were observed in males and females of both generations...
The incidence rates of mineralization of
the renal pelvis were 0/25,1/25,3/25,7/25 (p #0.01)in F0
males;4/25,2/25,3/25,7/25 in F0 females; 1/25,1/25,5/25,11/25
(p #0.01)in F1 males; and 3/25,2/25,8/25,13/25 (p #0.01)in F1
females, respectively. In the kidney of high-dose F1 animals,
there were increased incidences of dilatation
of the collecting ducts (0/25,0/25,2/25,11/25 [p #0.01
] males and 1//25,0/25,0/25, 9/25 [p #0.01 ] females)) and hyperplasia
of the pelvic/papillary epithelium (4/25,5/25,6/25, 11/25 [p #0.05
] males and 1//25,3/25,2/25,8/25 [p #0.05 ] females)). The NOAEL
for parental toxicity is 400 ppm (males:30.9 mg/kg/day;females:32.8
mg/kg/day).The LOAEL for parental toxicity is 1600 ppm (males:120.0
mg/kg/day; females:131.2 mg/kg/day) based on mortality, body weight
decrements, and microscopic kidney and
-- 870.4100a (870.4300)Chronic Toxicity
– Rat In a chronic toxicity/carcinogenicity study (MRID
00083445,00135072,92136061),RH- 2915 technical (82.2%and 85.7%a.i.)was
administered in the diet to groups of 50 male and 50 female Long
Evans rats at concentrations of 1.0,20.0,or 400.0 ppm for weeks
1 –2;1.4,28.3,or 565.6 ppm for week 3 –4;2.0,40.0,or 800.0 ppm
for weeks 5 –56 (800 ppm was actually 686 ppm for weeks 6-48);and
2.0,40.0,or 1600 ppm for weeks 57 –104. Based on %active ingredient,doses
in males were approximately equivalent to 0,0.10,1.94,and 56.96
mg/kg/day, and in females were 0,0.12,2.43,and 72.57 mg/kg/day,in
the respective dose groups. The mortality rate at study termination
was 54,48,52,and 40%for male and 22,40,26, and 20%for females
administered the control ,low,mid,and high doses,respectively;no
treatment-related effect was observed... Absolute and/or relative
organ weights in the high-dose groups that showed
statistically significant changes relative to control weights
(thyroid gland in both sexes and kidney
in females at 12 months and brain, pituitary, and spleen
in females sacrificed at 24 months) had no microscopic correlates
and are not considered toxicologically significant. Gross lesions
were not observed in animals sacrificed at 12 or 24 months...
The changes that were statistically increased
in the 24-month group were polypoid hyperplasia of the papillary
epithelium in the kidney of high dose females (20/40 vs
13/45 controls,p<0.05) and cortical cysts
in the kidney of mid-and high-dose males (6/25 (p<0.01)
and 4/40 (p<0.05)vs 0/45 for controls). The lack of a dose-response
relationship for the changes in males and the high background
for the finding in females suggest that the microscopic findings
were not treatment related.
Ref: August 8,2001. OXYFLUORFEN. Toxicology
Chapter for RED. Submission No.S549936. P.C.Code:111601. Tox.Chem.No.188AAA.
- Herbicide - CAS No. 219714-96-2
-- Subchronic toxicity.
Dietary exposure to penoxsulam identified the
liver and/or urinary tract (kidneys
as target organs in rats, mice, and
dogs following a 4-week and 13-week administration... Effects
noted in the kidneys included crystal
deposition, most likely from precipitation of penoxsulam from
the urine, with resultant irritation, inflammation, and hyperplasia
of renal pelvic transitional epithelium. Other
than the crystal deposition in the kidneys, all effects
following subchronic exposure to rats appeared to be reversible...
-- 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...
-- 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.
-- Endocrine Disruption. For penoxsulam, effects which indicate
potential endocrine disruption include kidney
lesions (crystals) in female rats and delay in preputial
separation in male rats. When the appropriate
screening and/or testing protocols being considered under the
Agency‘s EDSP have been developed, penoxsulam may be subjected
to additional screening and/or testing to better characterize
effects related to endocrine disruption.
Reference: September 2004. US EPA Fact Sheet
on Penoxsulam. Page 4.
PFOA - Insecticide,
US EPA List 3 Inert
of rat kidney to the challenges by perfluorooctanoic acid (PFOA)
was studied using microsomal 1-acyglycerophosphocholine (1-acyl-GPC)
acyltransferase as a parameter. Marked induction
of the enzyme was brought about in kidney of male rats, whereas
the induction in kidney of female rats was far less pronounced.
The sex-related difference in the response of kidney to PFOA was
much more marked than those seen with p-chlorophenoxyisobutyric
acid (clofibric acid) or 2,2'-(decamethy-lenedithio)diethanol
(tiadenol). Hormonal manipulations revealed
that the sex-related difference in the response of kidney to PFOA
was strongly dependent on the state of gonadal hormones of rats.
Even after a prolonged administration of PFOA for up to 26 weeks,
this sex-related difference was still evident. Induction of peroxisomal
beta-oxidation was brought about concurrently with microsomal
1-acyl-GPC acyltransferase and a high correlation was confirmed
between the inductions of these two parameters.
Ref: 1991. Biochem
Pharmacol Oct 24;42(10):1921-6. Induction by perfluorooctanoic
acid of microsomal 1-acylglycerophosphocholine acyltransferase
in rat kidney. Sex-related difference; by Kawashima Y, Matsunaga
T, Uy-Yu N, Kozuka H.
3.5 Reproductive Toxicity
Studies in Animals
York (2002) conducted an oral two-generation reproductive toxicity
study of APFO, which is summarized below. Although this preliminary
risk assessment focuses on developmental toxicity, the summary
below of the two generation reproductive toxicity study includes
all endpoints. Five groups of 30 Sprague-Dawley rats per sex per
dose group were administered APFO by gavage at doses of 0,1,3,10,
and 30 mg/kg/day six weeks prior to and during mating. Treatment
of the F0 male rats continued until mating was confirmed,and treatment
of the F0 female rats continued throughout gestation, parturition,
F1 Males ...
... Necroscopic examination revealed statistically significant
treatment-related effects at 3,10,and 30 mg/kg/day ranging from
tan areas in the lateral and median lobes of the liver to moderate
to slight dilation of the pelvis of one or both kidneys...
The absolute weights of the left and/or right kidneys were significantly
increased in the 1 and 3 mg/kg/day dose groups and significantly
decreased in the 30 mg/kg/day dose group...
10, 2003: Preliminary
Risk Assessment of the Developmental Toxicity associated with
Exposure to Perfluorooctanoic Acid and its Salts. US
EPA Office of Pollution Prevention and Toxics. 63 pages.
bifluoride - Wood preservative -
CAS No. 7789-29-9
Ingestion: May cause
osseous fluorosis (increased radiographic
density of the bones). May cause
kidney damage, asthma and symptoms resembling rheumatism.
Target Organ Effects: Chronic ingestion
may cause kidney damage.
Ref: Material Safety Data Sheet for Potassium
Hydrogendifluoride [synonym]. LA-CO INDUSTRIES, Inc./Markal Co.
Product Name: SILVER BRAZING FLUX PASTE Revision #: 1.5 Date Prepared:
March 1, 1995. Date Revised: August 6, 2002.
-- 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) .
Rats fed dietary doses of about 180 mg/kg/day over 90 days showed
effects similar to those noted in dogs, as well as spleen weight
increases . In another study, doses of 480 mg/kg/day in rats
over 18 months produced increased incidence of tooth disorders,
chronic nephritis (kidney damage),
and testicular atrophy . In two 18-month studies in mice, testicular
atrophy, chronic nephritis, and increased tooth and bone disorders
were seen at doses of 180 mg/kg/day and 360 mg/kg/day,
-- Organ toxicity: Target organs
identified in animal studies include the
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.
- Herbicide - CAS No. 129630-19-9
-- Short term toxicity
Target / critical effect:
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)
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
- Insecticide - CAS No. 179101-81-6
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
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.
-- 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
Ref: Federal Register: December 5, 2003. Pyridalyl; Notice of
Filing a Pesticide Petition.