See short description and definitions on kidney
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.
When time allows more information will be added.
Quinoxyfen
- Fungicide - CAS No. 124495-18-7
** 040 - 181140 "XDE-795:
Two-Year Dietary Chronic Toxicity/Oncogenicity Study in Fischer
344 Rats-Final Report," (Redmond, J.M.,
Quast, J.F., Bond, D.M., Ormand, J.R.; The Toxicology Research
Laboratory, Health and Environmental Sciences Ð The Dow
Chemical Company, Midland, MI; Laboratory ID#: DR-0325-7474-007;
6/29/95). XDE-795 (5,7-dichloro-4-[4-flurophenoxy]quinoline;
97.4% pure) was fed in diet to Fischer 344 rats at 0, 5, 20 or
80 mg/kg/day for 1 Ð 2 years. XDE-795 was administered for 2 years
to 50/sex/dose for chronic/oncogenicity assessment. A satellite
group (15/sex/dose) was sacrificed at 12 months (10/sex/dose for
interim assessment of chronic toxicity; 5/sex/dose to assess neurotoxicity).
NOEL = 20 mg/kg (Females at 80 mg/kg had increased perineal soiling
(satellite & main group). Both sexes had decreased bodyweights
and bodyweight gains at 80 mg/kg throughout the study. Urea nitrogen
was increased in males at 80 mg/kg at 18 and 24 months. Alanine
amino transferase (80 mg/kg) was decreased in males at 24 months.
Females had cholesterol levels that were statistically significantly
increased at 80 mg/kg at 18 and 24 months.
Liver and kidney
weights (absolute & relative) were statistically significantly
increased in both sexes at 80 mg/kg at 12 months.
Relative brain weights in both sexes were increased at 80 mg/kg
by 24 months. Males had increased absolute and relative testes
weights at 80 mg/kg and females had decreased relative heart and
increased relative kidney weights at 80 mg/kg at 24 months. There
was an increased incidence in chronic progressive
glomerulonephropathy in males at 80 mg/kgÑ37 versus 19
in control, p < 0.05.) No adverse effects. Acceptable. M. Silva,
8/21/01
-- 034 - 181176 "XDE-795: One Year Chronic Dietary Toxicity
Study in Beagle Dogs," (Cosse, P.F.,
Stebbins, K.E., Redmond, J.M., Ormand, J.R.; The Toxicology Research
Laboratory, Health and Environmental Sciences Ð The Dow
Chemical Company, Midland, MI; Laboratory ID#: DR-0325-7474-011;
4/21/95). XDE-795 (5,7-dichloro-4-[4-flurophenoxy]quinoline;
97.4% pure) was fed in diet to Beagle dogs (4/sex/dose) at 0,
5, 20 or 200 mg/kg/day for 1year. NOEL = 20 mg/kg (A male at 200
mg/kg was killed moribund, due to a severe
weight decrease (2 kg), decreased hemoglobin and RBC counts. Both
sexes had significantly decreased body weights and food consumption
at 200 mg/kg. The report stated it was due to unpalatability of
diet at the high dose, which persisted throughout the majority
of the study. A treatment-related hematological effect was observed
in 1/sex at 200 mg/kg. Alkaline phosphatase in both sexes at 200
mg/kg was statistically significantly increased. Liver weights
(absolute & relative) were significantly increased in both sexes
at 200 mg/kg. Statistically significantly
increased relative organ weights
were observed in both sexes at 200 mg/kg (brain, kidney,
pituitary). Liver histopathology
was observed in 3/sex at 200 mg/kg, primarily in the midzonal
region (diffuse, increased size in hepatocytes, enlarged nuclei
and prominent nucleoli). At 200 mg/kg, 1/sex had increased hepatocyte
size, increased bile in centrilobular canaliculi. Possible adverse
effect: At 200 mg/kg, 1/sex showed erythroid
proliferation in spleen and liver, due to treatment-related anemia.)
Acceptable. M. Silva, 8/15/01
-- ** 035 - 181177 "XDE-795: Potential Tumorigenic Effects
in Prolonged Dietary Administration to CD-1 Mice," (Bellringer,
M.E.; J.R.; Huntingdon Research Centre,
Ltd., Cambridgeshire, UK; HRC Project ID#: DWC/657; 6/5/95).
XR-795 (5,7-dichloro-4-[4-flurophenoxy]quinoline;
97.4% pure) was fed in diet to Crl:CD-1 (ICR)BR mice (50/sex/dose)
at 0, 20, 80 and 250 mg/kg/day for 80 weeks. NOEL = 80 mg/kg (There
was a significantly decreased bodyweight gain in both sexes
at 250 mg/kg (primarily females). The effect was intermittent
in males throughout the study. Relative (to bodyweight)
liver and kidney weights were significantly
increased in females at 250 mg/kg.) There were no histological
(neoplastic or non-neoplastic) effects due to treatment. No adverse
effects. Acceptable. M. Silva, 8/24/01
-- ** 039 Ð 181139 "XDE-795: Two-Generation Dietary Reproduction
Study in Sprague-Dawley Rats," (Liberacki,
A.B., Breslin, W.J., Zwinker, G.M., Johnson, K.A., Freshour, N.L.;
The Toxicology Research Laboratory, Health and Environmental Sciences,
The Dow Chemical, Midland, MI; Laboratory
ID#Õs: DR-0325- 7474-013 [P1, F0, W1, FB, WB, P2, F2 & W4]; 5/23/95).
XDE-795 (97.4% pure) was fed in diet to Sprague-Dawley rats (30/sex/dose)
at 0, 5, 20 and 100 mg/kg/day, 7 days/week for 2 generations.
Systemic NOEL = 20 mg/kg (Kidney pathology
was observed in P1 and P2 females at 100 mg/kg. Males showed
liver, kidney and
epididymal histopathology at 100 mg/kg in P1 and
P2 adults.) Reproductive NOEL = 100 mg/kg/day (There were no treatment-related
reproductive effects in either sex.) Pup
NOEL = 20 mg/kg/ (F1a & F1b pups showed decreased bodyweights
at 21 days of lactation and this was considered to be due
to excessive dose and decreased food consumption.) No adverse
effect. Acceptable. M. Silva, 8/9/01
-- 030; 181170; "XR-795: Four Week Dietary Toxicity Study
in Fischer 344 Rats" (Szabo, J.R. and
Davis, N.L., Health and Environmental Sciences-Texas Lake Jackson
Research Center, The Dow Chemical Company,
Freeport, Texas, Laboratory Project Study ID TXT: DR-0325-7474-002,
10/12/92). XR-795 (TSN100003, DECO-36-106, purity = 97.6%)
was admixed to the diet at dose levels of 0 (untreated diet only),
250, 500, or 1000 mg/kg/day and fed continuously to 5 Fischer
344 rats per sex per dose for 4 weeks. No clinical signs were
observed. A treatment-related decrease in
mean body weight at all dose levels in both sexes was observed.
Treatment-related increases in mean relative liver (in
both sexes at all dose levels) and in mean
relative kidney (in males at all dose levels and in females
at 500 and 1000 mg/kg/day) weights and a treatment-related decrease
in mean relative testes weight at 1000 mg/kg/day
were observed. Macroscopic examination revealed bilateral testicular
atrophy in 3/5 animals at 1000 mg/kg/day. Microscopic examination
revealed a moderate to severe decrease in spermatogenesis in 4/5
animals at 1000 mg/kg/day. Possible adverse effect indicated:
testicular atrophy with a decrease in spermatogenesis. NOEL (M/F)
< 250 mg/kg/day (based on body weight and mean relative
organ weight data). Supplemental (only 5 animals per sex per dose
were used and the animals were only dosed for 4 weeks). (Corlett,
8/27/01)
Ref: October 4, 2001. SUMMARY OF TOXICOLOGY
DATA QUINOXYFEN (XDE-795 & XR-795). California EPA, Department
of Pesticide Regulation, Medical Toxicology Branch.
http://www.fluoridealert.org/pesticides/quinoxyfen.ca.epa.2001.pdf
Sodium
bifluoride - Insecticide, Former US EPA
List 3 Inert -
CAS No.
1333-83-1
In addition to cardiovascular,
neuromuscular and gastrointestinal derangements, acute fluoride
poisoning causes major adverse effects on
two other organ systems, the brain and the kidneys. The
more critical dysfunctions are those of the brain. Toxic
signs occasionally include headache, excessive salivation, nystagmus
and dilated pupils. Transient convulions have been described,
but lethargy, stupor and coma are far more common, and death is
often ascribed to respiratory failure, presumably of central origin.
Whatever the causes of these brain derangements, it is noteworthy
that coma and respiratory arrest may develop in the presence of
a normal blood pressure. Apparently
the central neural effects of fluoride are not solely secondary
to an inadequate cerebral circulation.
/Fluoride/ [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical
Toxicology of Commercial Products. 5th ed. Baltimore: Williams
and Wilkins, 1984.,p. III-187]
Ref:
Hazardous Substances Data Bank for SODIUM HYDROGEN DIFLUORIDE CASRN:
1333-83-1
http://www.fluorideaction.org/pesticides/sodium.bifluoride.toxnet.htm
Sodium
fluorosilicate
(Sodium Hexafluorosilicate) - Insecticiide;
Wood Preservative; EPA List 3 Inert - CAS No. 16893-85-9
-- Mice orally given
sodium hexafluorosilicate (70 mg/kg; 0.37 mmol/kg) exhibited toxic
effects in the peripheral nerves, sensation, and in behavior.
In rats, an oral dose (248 mg/kg; 1.32 mmol/kg) administered intermittently
for one month produced toxic effects in
the kidney, ureter, and/or bladder, as well
as musculoskeletal and biochemical effects
(RTECS, 1997). Using guinea pigs, inhalation experiments (13-55
mg/m 3 [1.7-7.2 ppm] sodium hexafluorosilicate in air for ¥6 hours)
resulted in pulmonary irritation; the lowest concentration that
caused death was
33 mg/m 3 (4.3 ppm) (Patty, 1963; cited by HSDB, 2000b).
-- Mouse strain, 70 mg/ kg (LD 50 ; 0.37 mmol/ kg); Toxic effects
were observed in the peripheral nerves and
sensation (flaccid paralysis without anesthesia, generally neuromuscular
blockage) and in behavior (ataxia and muscle contraction
or spasticity). RTECS* (1997)
-- Rats, oral; 248 mg/ kg (1.32 mmol/ kg) for 30 days intermittent;
Toxic effects in the kidney,
ureter, and/ or bladder (other changes in urine
composition) were observed. Musculoskeletal
(other changes) and biochemical (enzyme inhibition, induction,
or changes in blood or tissue [phosphatases] levels) effects were
seen. RTECS* (1997)
-- Rats, 70 mg/ kg (LD Lo ; 0.37 mmol/ kg); Fatty liver degeneration
and other changes in the liver and
toxic
effects in the kidney, ureter, and bladder
primarily changes in glomeruli were
observed. RTECS* (1997)
Ref: Review of Toxicological Literature.
October 2001. Sodium Hexafluorosilicate [CASRN 16893-85-9] and
Fluorosilicic Acid [CASRN 16961-83-4]. Prepared for Scott Masten,
Ph.D. National Institute of Environmental Health Sciences P.O.
Box 12233 Research Triangle Park, North Carolina 27709. Contract
No. N01-ES-65402. Submitted by Karen E. Haneke, M.S. (Principal
Investigator) Bonnie L. Carson, M.S. (Co-Principal Investigator)
Integrated Laboratory Systems P.O. Box 13501 Research Triangle
Park, North Carolina 27709.
http://www.fluoridealert.org/pesticides/fluorosilicates.nih.2001.pdf
Sulfluramid
- Acaricide, Insecticide - CAS No. 4151-50-2
Abstract: BIOSIS COPYRIGHT:
BIOL ABS. The cellular effects of sulfluramid (N-ethylperfluorooctane
sulphonamide, NEPFOS) and its major metabolite perfluorooctane
sulphonamide (PFOS) were examined using a suspension of rabbit
renal proximal tubules as a model. NEPFOS and PFOS were potent
stimulators of proximal tubule basal oxygen consumptions (QO2),
with initial effects exhibited at 5-10 muM and maximal effects
at 50-200 muM. The increase in basal QO2 was ouabain insensitive,
which suggests that NEPFOS and PFOS may
act by uncoupling oxidative phosphorylation. Exposure of
tubule suspensions to NEPFOS or PFOS concentrations of 100 muM
or higher for 60 min produced tubule death,
indicated by an increase in the release of lactate dehyrogenase.
The tubule death did not appear to result from alkylation or lipid
peroxidation, since glutathione and malondialdehyde levels were
unaffected. To determine the mechanism by which NEPFOS and PFOS
increased tubule QO2, the effects of NEPFOS and PFOS on isolated
renal cortical
Ref:
SCHNELLMANN RG (1990). The cellular effects
of a unique pesticide sulfluramid (N-ethylperfluorooctanesulfonamide)
on rabbit renal proximal tubules. TOXICOL IN VITRO; 4 (1)..
71-74.
Sulfuryl fluoride
- Fumigant
insecticide - CAS No. 2699-79-8
-- In
2-week inhalation studies in rats, dogs and rabbits, different
target organs were affected. In rats, the
primary target organ was the kidneys, in which severe histopathological
lesions were observed. These lesions included papillary
necrosis, hyperplasia of the epithelial cells of the papillae,
and degeneration/regeneration of collecting tubules and proximal
tubules...
-- In subchronic (90-day) inhalation studies
in rats, dogs, rabbits and mice, the brain
was the major target organ. Malacia
and/or vacuolation were observed in the white matter of the brain
in all four species. The portions of the brain most often affected
were the caudate-putamen nucleus in the basal ganglia, the white
fiber tracts in the internal and external capsules, and the globus
pallidus of the cerebrum. In dogs and rabbits, clinical signs
of neurotoxicity (including tremors, tetany, incoordination, convulsions
and/or hind limb paralysis) were also observed. Inflammation of
the nasal passages and histiocytosis of the lungs were observed
in rats and rabbits; but not in dogs, in which species inflammation
of the upper respiratory tract was more prominent in the
2-week study. In rats, kidney
damage was also observed...
-- In chronic (1-2 year) inhalation studies
in rats, dogs and mice, target organs were the same as in the
90-day studies. In rats, severe kidney damage
caused renal failure and mortalities in many animals. Additional
gross and histopathological lesions in numerous organs and tissues
were considered to be secondary to the primary
effect on the kidneys...
-- In a developmental
toxicity inhalation study in rats, no developmental toxicity
was observed in the pups. Although no maternal toxicity was observed
in this study at the highest dose tested (225 ppm), significant
maternal toxicity (decreased body weight, body weight gain and
food consumption; increased water consumption and kidney
weights; and gross pathological changes
in the kidneys and liver)
was observed in a previously conducted range-finding study at
a slightly higher dose level (300 ppm)...
Ref:
Federal Register: September 5, 2001 (Volume 66, Number 172). Sulfuryl
Fluoride; Proposed Pesticide Temporary Tolerances.
http://www.fluorideaction.org/pesticides/sulfuryl.flu.fr.sept.5.2001.htm
The primary effects
of sulfuryl fluoride in humans are respiratory irritation and
central nervous system depression, followed by excitation and
possibly convulsions. Rabbits exposed via inhalation (6 hours/day,
5 days/week, for 2 weeks) to sulfuryl fluoride showed hyperactivity,
convulsions and vacuolation of the cerebrum at 600 ppm (2.5 mg/L).
Renal lesions were present in all rats exposed
by inhalation (6 hours/day, 5 days/week, for 2 weeks) to 600 ppm
(2.5 mg/ L) sulfuryl fluoride. Minimal renal changes were
noted in rats exposed to 300 ppm (1252 mg/L), whereas no effects
occurred at 100 ppm (4.2 mg/ L). Convulsions at near lethal concentrations
were reported in rabbits, mice, and rats. In a 30-day inhalation
study, loss of control, tremors of the hind quarters, and histopathological
changes in the lung, liver, and kidney
were reported in rabbits exposed to 400 ppm (1.6 mg/L)
for 7 hours/day, 5 days/week for 5 weeks. The NOEL was 200 ppm
(0.83 mg/L). Cerebral vacuolation and/or malacia and inflammation
of nasal tissues were observed in rabbits exposed by inhalation
to 100 or 300 ppm (0.4 or 1.25 mg/L) for 13 weeks. The NOEL was
30 ppm (0.125 mg/L). Rats exposed by inhalation to 100 to 600
ppm (0.4 to 0.25 mg/L) sulfuryl fluoride for 13 weeks developed
mottled teeth (indicative of fluoride toxicity), renal and respiratory
effects, and cerebral vacuolation. EPA believes that there is
sufficient evidence for listing sulfuryl fluoride on EPCRA section
313 pursuant to EPCRA section 313(d)(2)(B) based on the available
neurological, renal, and respiratory 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.
http://www.epa.gov/tri/frnotices/59fr1788.htm
Tembotrione - Herbicide - CAS No. 335104-84-2
• The primary target organs were the eyes, liver and kidneys. In the kidney, increased weight, and papillary mineralization were observed in the rat and mouse following chronic exposure (page 6).
• 90-Day Oral Toxicity - Rat study : In females, the following microscopic changes were observed at an increased incidence: multifocal corticotubular basal vacuolation (slight) in the kidneys occurred in a dose-dependent manner 1-6/10 in all treated groups compared to 0/10 in controls; diffuse hypertrophy of the interstitial gland in the ovaries was observed in the 1500 ppm and 7000 ppm groups (3/10) compared to 0/10 in controls. These effects were considered treatment-related (page 56).
• In a combined chronic/carcinogenicity study (MRID 46695708) Wistar male rats/dose in the dietat dose levels of 0, 1, 20, 200 or 800 ppm (equivalent to 0, 0.04, 0.79, 8.3 or 31.7 mg/kg bw/day) in the diet for 104 weeks. In the kidney, a minimal to severe chronic nephropathy was significantly increased (p≤0.01) in the 20, 200, and 800 ppm group, (87%, 87%, 92%, and 83%, respectively) compared to in the control group (63%). Changes within the kidney included one or more of the following changes: tubular cell regeneration, thickened basement membranes (glomerular and tubular), interstitial fibrosis, inflammation, dilated/cystic tubules, protein casts, pigmentation, mineralization, debris, mesangial proliferation, glomerular sclerosis, and hypertrophy/hyperplasia of tubular epithelium. Severity grades moderate or higher generally reflected a kidney with most of the above- mentioned changes, some reflecting end-stage renal disease (probable cause of death) (page 72).
Reference: Tembotrione. Human-Health Risk Assessment for Proposed Uses on Field Corn, Sweet Corn and Popcorn. USEPA. September 7, 2007.
• Dose and Endpoint for Establishing RfD: (page 22)
------ Study Selected: Chronic Toxicity/Carcinogenicity (Feeding)/Rat MRID No.: 46695708
------ The NOAEL of 0.04 mg/kg/day was based on neovascularization and edema of the cornea and snow flake-like corneal opacity, unilateral or bilateral keratitis of the eye, decreased mean body weight and mean body-weight gain, increased total cholesterol, higher ketone levels and lower pH values, higher protein levels, increased kidney weight, kidney to body weight and kidney to brain weight ratios, chronic nephropathy and atrophy of the sciatic nerve observed in the male at 0.79 mg/kg/day (LOAEL).
------ UF(s): An UF of 100 was applied to account for interspecies extrapolation (10X)
------ Comments about Study/Endpoint/UF: This study provided the lowest NOAEL in the database (most sensitive endpoint) and will also provide the most protective limits for human effects.
• Thyroid gland toxicity was observed in the 21/28-day dermal toxicity study in the rat and chronic oral toxicity study in the dog. Dermal exposure (21/28-day study) resulted in colloid alteration and hypertrophic follicular epithelium in the thyroid gland in the rat. Also observed were degenerative changes in the pancreas, increased proteinacious material in the Ratche pouch in the pituitary gland and basophilic tubules in the kidneys. Pigmentation of the thyroid gland along with hematological changes and microscopic changes in the sciatic nerve were observed in the dog.
Reference: Tembotrione. Human-Health Risk Assessment for Proposed Uses on Field Corn, Sweet Corn and Popcorn. USEPA. September 7, 2007.
Tetraconazole
- Fungicide - CAS No. 112281-77-3
Chronic Toxicity: The liver and
kidney are the primary target organs of tetraconazole.
Ref: April 2005. Pesticide Fact Sheet: Tetraconazole.
US EPA.
http://www.fluorideaction.org/pesticides/tetraconazole.epa.2005.facts.pdf
• Metbolism and Toxicokinetics. Tetraconazole
was broadly distributed to all organs and tissues tested, with
the highest level detected in the liver, followed by kidneys,
gonads, brain and bones. Low residual levels
were still detected in the liver and gastrointestinal tract (sometimes
bones) at 72 hr.
• Chronic & Carcinogenicity Studies.
Dogs received 0, 22.5, 90 or 360 ppm of tetraconazole in the diet
for 1 year. Histopathology detected apparent hepatocyte enlargement,
eosinophilic inclusions in hepatocytes, centrilobular hepatocyte
rarefaction, or centrilobular fat in the liver at 90 and 360 ppm,
and cortical tubular hypertrophy and apoptotic
bodies in the kidneys at 360 and/or 90 ppm. The NOEL was
22.5 ppm (0.7 mg/kg bw/day). (page 5)
• Sub-chronic studies. Rats received 0, 10, 60 or
360 ppm of tetraconazole in the diet for 13 weeks. Enlarged or
swollen liver was seen at 360 ppm. Increased liver weight was
associated with minimal centrilobular hepatocyte enlargement at
60 and 360 ppm, and a higher incidence of liver fat deposition
at 360 ppm. Increased kidney weight in females
and reduced testes weight in males
were also observed at 360 ppm. The NOEL was 10 ppm (0.7 mg/kg
bw/day).
-- Mice received 0, 5, 25, 125 or 625 ppm of tetraconazole in
the diet for 13 weeks. Some males at 625
ppm showed lymphocyte aggregation and foci in the kidneys. The
NOEL was 5 ppm (1 mg/kg bw/day). (page 4)
Ref: August
2005 - Evaluation of Tetraconazole in the product Domark 40ME
Fungicide. Australian Pesticides and Veterinary Medicines Authority.
http://www.fluorideaction.org/pesticides/tetraconazole.2005.report.australia.pdf
1,1,1,2-Tetrafluoroethane
(HFC-134a) - Propellant, US
EPA List 4B Inert - CAS No. 811-97-2
Comparative potency
studies showed that 1,1,1,2-tetrafluoroethane, dichlorodifluoromethane,
or 1,1,2,2-tetrafluoro-1,2-dichloroethane (25% gas phase) inhibited
gluconeogenesis about equally while as little as 300 ppm
halothane was effective and 1,1,1,2,2-pentafluoro-2-chloroethane
(25%) was without effect. Considering that the threshold for alteration
of the rate of glucose metabolism in this in vitro paradigm is
about 12.5% 1,1,1,2-tetrafluoroethane, it was concluded that toxicologically
significant alteration of glucose-linked bioenergetics is unlikely
at the levels of 1,1,1,2-tetrafluoroethane exposure anticipated
in workplace or environment. [Olson MJ et al; Fundam Appl Toxicol
15 (2): 270-80 (1990)]
Note from FAN: Definition
Gluconeogenesis: The process of making glucose (sugar) from its
own breakdown products or from the breakdown products of lipids
(fats) or proteins. Gluconeogenesis occurs mainly in cells of
the liver or kidney.
Ref: Hazardous Substances Data Bank for 1,1,1,2-TETRAFLUOROETHANE
CASRN: 811-97-2.
http://www.fluorideaction.org/pesticides/1,1,1,2-tetrafluoroe.toxnet.htm
-- groups of 16 male
and 16 female rats were exposed at concentrations of 9, 1000,
10,000, or 50,000 ppm 6 h/d for 20 d of a 28-d period (Riley
et al. 1979). No treatment-related effects were observed
with regard to body weight, clinical signs, hematology, blood
chemistry, urine composition, or ophthalmoscopy.
Changes in liver,
kidney, and gonad weights of male
rats in the group exposed
to 50,000 ppm were noted with a significant increase in liver
weight in the 10,000-ppm group also. In the absence of pathological
changes in these organs, Riley et al. (1979)
considered these changes physiological adaptations to treatment.
-- Riley
RA, Bennett IP, Chart IS, Gore CW, Robinson M, Weight TM. 1979.
Arcton-134a: Subacute toxicity to the rat by inhalation.
ICI Report No. CTL/P/463. Central Toxicology Laboratory,
Alderly Park, Macclesfield, Cheshire, UK.
Ref:
National Research Council. 2002. Acute Exposure Guideline Levels
for Selected Airborne Chemicals. Volume 2. Subcommittee on Acute
Exposure Guideline Levels. Committee on Toxicology, Board of Environmental
Studies and Toxicology, Division of Earth and Life Studies. National
Academy Press, Washington DC. Available from: National Academy
Press, 2101 Constitution Ave, NW, Box 285, Washington DC 20055.
ISBN 0-309-08511-X. Online at:
http://books.nap.edu/books/030908511X/html/index.html
Thiazopyr
- Herbicide - CAS No. 117718-60-2
Group
C -- Possible Human Carcinogen. Statistically
significant increase in thyroid follicular
cell tumors (M). Increases in renal
tubular adenomas (M & F); however statistically significant
positive trend in F only; Sprague-Dawley 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
-- A two year rat carcinogenicity
study at doses of 0, 0.04, 4.4, 44.2 or 136.4 mg/kg/day (Males)
0, 0.06, 0.6, 5.6, 56.3 or 177.1 mg/kg/day (female) with a NOEL
of 4.4 mg/kg/day. The effects were protruding
eyes, evidence of mild anemia, increased
GGT and cholesterol, increased absolute and relative liver, kidney
and thyroid weights and significant increase in microscopic lesions
in the liver (hypertrophy and vacuolar changes), kidney
(nephropathy) and thyroid (hypertrophy and hyperplasia);
decreased mean body weight and body weight gain and food consumption.
A statistically significant increase in thyroid follicular cell
adenomas/cystadenomas were observed in males at 44.2 and 136.4
mg/kg/day. A nonsignificant increase
in renal tubular adenomas in high-dose females was considered
to be equivocal.
-- Thiazopyr technical produced organ toxicity following multiple
exposures at high doses. The primary target
organs for thiazopyr toxicity in the rat, mouse and dog
were the liver, thyroid, kidney
and blood,
with the liver being the most sensitive indicator of toxicity.
In chronic dietary feeding studies, the dog was the most
sensitive species. An RfD for thiazopyr of 0.008 mg/kg/day was
established by the RfD Committee of the USEPA Health Effects Division,
based on the NOEL of 0.8 mg a.i./kg/day (20 ppm) from the chronic
dog study and a 100-fold safety factor to account for intraspecies
extrapolation and intraspecies variability.
-- 90-day Oral (Rat): NOEL (systemic) =100 ppm (6.60 mg /kg/day
and 7.99 mg/kg/day for males and females, respectively). The LOEL
was 1000 ppm (68 - 79 mg/kg/day in males and females, respectively)
based on increased liver, thyroid and kidney
weights, changes in clinical chemistry and hematological
parameters and on gross and microscopic changes observed in the
liver and thyroid at does levels of 68 mg/kg/day and higher. At
the 201 mg/kg/day dose diffused thyroid follicular cell hypertrophy/
hyperplasia was observed.
-- A 3 week dermal study in rabbits at 0, 100, 500 and 1000 mg/kg/day
with a NOEL of 100 mg/kg/day. The effects were increased mean
absolute and relative kidney weights
and minimal multifocal or periportal hypatocyte vacuolation.
-- A mouse carcinogenicity study at doses
of 0, 0.17, 1.6, 16.9, 66.3 or 128.4 mg/kg/day (males) and 0,0.24,
2.6, 26.8, 108.1 or 215.9 mg/kg/day (female) with a systemic NOEL
of 0.1 mg/kg/day. The effects were hepatocellular hypertropy and
amyloid deposition. At 66.3 mg/kg/day
the same lesions plus increased liver
weights, random and periportal hepatocellular vacuolation were
observed. At 128.4 mg/kg/day the same lesions
plus distended abdonen, slight increase in ALP, SGOT and SGPT,
abnormal coloration and enlargement of liver, decrease in absolute
and relative spleen weights, increase in absolute and relative
kidney weights, increase in eosinophilia
in hepatocytes, kidney nephropathy
and lymphocytic hyperplasia of the nesenteric
lymph nodes were observed.
There was no evidence of oncoenicity at any dose level.
Ref: US EPA. Pesticide Fact Sheet. Thiazopyr
Reason for Issuance: Registration of a New Chemical Date Issued:
February 20, l997.
http://www.epa.gov/opprd001/factsheets/thiazopyr.pdf
Tolylfluanid
- Fungicide - CAS No. 731-27-1
--
Carcinogenicity
rodents (mouse).
NOAEL = 76.3/123.9 mg/ kg/day (M/F) LOAEL
= 375.8/610.8 mg/kg/day (M/F), based on skeletal, liver, and kidney
changes No evidence of carcinogenicity
Ref:
Federal Register: September 25, 2002. Tolylfluanid; Pesticide
Tolerance. Final Rule. Federal Register.
http://www.fluoridealert.org/pesticides/tolylfluanid.fr.sept25.2002.htm
Chronic toxicity. Chronic
toxicity studies on tolylfluanid were done in the rat, mouse and
dog. Tolylfluanid was tested in two rat chronic dietary studies.
Increased growth of the incisors of the upper jaw and skeletal
changes (hyperostosis in the skull and ribs) resulted from the
high fluorine content of the compound. Hepatotoxicity and renal
toxicity were seen in rats, mice, and dogs. Hepatotoxicity
was evidenced by hepatocellular cytoplasmic changes, vacuolation,
and focal fatty changes in rats, hepatocellular hypertrophy and
single cell necrosis in mice, decreased liver enzymes in rats,
and increased liver enzymes in mice and dogs. Renal
toxicity (microscopic kidney lesions, increased relative kidney
weights, effects on urinalysis parameters) was probably
attributable to the effects of fluoride on renal tubules. A second
chronic toxicity study in dogs is currently ongoing (results not
yet available).
Ref: Federal Register: August 11, 1997 (Volume
62, Number 154). Page 42980-42986. Notice of Filing of Pesticide
Petitions.
http://www.fluoridealert.org/pesticides/tolyfluanid.fr.august.1997.htm
Transfluthrin
- Insecticide - CAS
No. 118712-89-3
-- The target organs
were the liver (rat,
mouse and dog) and kidney
(rat). There was evidence of
liver hypertrophy in the rat from 250 mg kg d (28 study) and after
administration for 90 d at 500 ppm (equivalent to 40 mg
kg d), in the dog from 350 ppm (equivalent to 14 mg kg d) after
90 d administration and from 30 ppm (equivalent to1 mg kg d) after
1 yr and in the mouse, from 1000 pppm (equivalent to 280 mg kg
d) after 2 yr administration. Increased kidney
weights, proximal tubule degeneration
and regenertion and increases in protein in the urine were observed
in male rats from 50 ppm and in females
from 500 ppm. Similar pathological findings were seen after
2 yr dietary administrationwith focal hyperplasia in the urinary
bladder in both sexes at 2000 ppm in the rat and hepatocyte hypertrophy
at 1000 ppm in the mouse. In the rat, increases in fluoride content
of teeth and bone were observed from 50 ppm in oral studies and
at 200 mg m3 following inhalation exposure in 90 d studies.
-- In 2 yr studies the NOEL for non-neoplastic findings in the
rat was 20 ppm (1 mg kg d) based on efffects in the kidney
(increased organ weight, pigment
deposition and glomerulonephrosis) at 200 ppm and above).
In the mouse, the NOEL was 10 ppm in males
(based on increases in liver weight, hepatocyte hypertrophy at
1000 ppm and fluoride accumulation at 100 ppm). It was not possible
to set a NOEL for females as increases in serum cholesterol, protein
and albumin were reported at the lowest dose.
-- Reproductive Toxicity. Developmental studies in both the rat
and rabbit provided no evidence of teratogenicity when
transfluthrin was administered at 125 and 150 mg kg d respectively.
One death occurred at 125 mg kg d in the rat study and 2 deaths
(1 each at 50 and 150 mg kg d) occurred in the rabbit study.
NOELs of 15 and 15 mg kg d were established for maternal toxicity
in the rat and rabbit respectively. These were based tremors at
55 mg kg d in the rat and mortality (following severe tremors)
at 50 mg kg d in the rabbit. In a dietary multi-generation reproductive
toxicity study in the rat there was no evidence of teratogenicity,
foetotoxicity or maternal reproductive toxicity in rats administered
transfluthrin at doses up to 191 mg kg d. NOELS of 62-191 and
9-38 mg kg d were established for maternal reproductive and parental
toxicity respectively. The NOEl for parental toxicity was based
on the following observations at 1000 ppm: - decreased body weight
and body weight gain, increased absolute and relative liver and
kidney weights, increased relative
kidney weight, decreased hepatic
triglyceride content, increased incidence of tubular
pigmentation, tubular casts and pelvic
calcinosis.
-- 3.2.2.1 Oral Route ... At 250 mg kg and 28 d, in both sexes,
there were absolute and body weight relative increases
in liver (15-20%) and kidney
weights (~ 10%). In males absolute and body weight relative
thyroid weight increases were also observed (20-25%). These changes
were reversed by 56 d. Of animals dying during treatment that
could be examined (5/7), the females exhibited slight congestion
and haemorrhage of the lung with 2 cases of focal alveolar emphysema
and 1 of alveolar oedema. The male had congested
kidneys. There was no other treatment-related pathology
during treatment or at the end of the post-treatment periods.
The NOEL was 50 mg kg d based on the effects seen at 250 mg kg
d (organ weight changes in both sexes which had reversed by 46
d).
-- In a 90 d study Bor: WISW (SPF Cpb) rats
(10 animals/sex/group) were administered diets containing 0, 10,
50, 500 or 5000 ppm transfluthrin (95% pure) in food moistened
with peanut oil to avoid dust. The main study groups were treated
for 13 w and 2 satellite groups had been intended as recovery
groups from weeks 14-18 but were treated by accident. Animals
were observed twice daily and clinical laboratory examinations
carried out at 1 and 3 months. An opthalmological examination
was carried out at the start of the study, at 13 w and in the
satellite group at 17 w. At necropsy fluoride levels in teeth
and bone were measured. During the study 2 female, treated at
10 and 0 ppm, died during weeks 6 and 18 respectively. One died
during blood sampling, the other was sacrified due to eye trauma...
There was a dose-dependent increase in tooth fluoride content
(significant above 50 ppm) reaching ~ 525% in males, ~350% in
females at 14 w. ... At necropsy there was evidence of
effects on the liver and
kidney at 500 and 5000 ppm... In addition at 5000 ppm there
was a significant increase (50%) in the numbers of animals of
both sexes with degenerated hepatocytes.
Relative and absolute kidney
weights were increased in males at
13 and 19 w by 10-15% at and above 50 ppm. In females a slight
increase (! 5%) was reported in relative weight only at 19 w.
Histopathological examination showed proximal
convoluted tubule degeneration in both sexes at 13 w not
19 w and a significant increase (~ 30%) in animals with basophilic
tubules. In all males at 500 ppm and
5000 ppm and in three males treated for 19 w the thyroid follicular
epithelium was hypertrophied and colloid was depleted. The NOEL
for this study was 10 ppm (0.85 mg kg d) based on the effects
at and above 50 ppm (4.0 mg kg d) of significant increase in fluoride
levels in teeth and bone in both sexes and evidence of
kidney toxicity (based on absolute
and relative weight increases in both sexes and urinary protein
content increases in males). In addition
liver and thyroid toxicity was noted at 500 and 5000 pm.
-- 3.2.2.2 Dermal. In a repeat dose study groupsof HC:NZW New
Zealand white rabbits (5 animals/sex/group)
received applications of 0, 20, 200 or 1000 mg kg transflurthrin
(95% pure) in cremophor E1 (2 ml kg) under a gauze dressing for
6 h d 5 d w for 3 w. Further groups were treated with 0 and 1000
mg kg and then observed for a further 14 day. ... At necropsy
white, yellow, glazing and/or cratering
were noted in kidneys at the end of both the treatment
and post treatment periods. Kidney weights
were increased by ~ 35% relative in males at 20 mg kg at the end
of the treatment period but not at the end of the post-treatment
period. These were attributed to an infestation of Nosema cuniculi.
Histopathological examination revealed effects on the kidney
(unspecified nephropathy at the end of both treatment and post
treatment in all groups)...
-- 3.3.3.4 Summary ... Following oral administratin
the major target organ in the rat and dog was the liver, with
evidence of kidney toxicity also
seen in the rat.
Fluoride determinations were undertaken in the rat only and showed
evidence of accumulation in teeth and bone from 50 ppm (4 mg kg
d). In the rat, mortalities and body tremors were seen at 250
mg kg d following gavage dosing. ... In the liver, absolute and
relative organ weight increases (recovering following cessation
of treatment) together with clinical chemistry and histopathological
evidence of hepatocyte hypertrophy were observed from 500 ppm
and at 250 mg kd d. There was also evidence of
kidney toxicity from 50 ppm (absolute and body weight relative
increases in kidney weight in both sexes ...
In the thyroid, hypertrophy of the thyroid follicular epithelium
and colloid depletion was reported from 500 ppm. The NOEl was
10 ppm (0.85 kg d).
-- 3.2.4 Carcinogenicity Studies. ... In a combined chronic toxicity
and carcinogenicity study, groups of 60 Wistar
rats (strain Bor:WISW (SPF Cpb) of both sexes were administered
transfluthrin (94.5-95% pure) in the diet at concentrations of
0, 20, 200 or 2000 ppm for 109 weeks. In addition, groups of 10
male and 10 female rats were treated identically for full interim
necropsy at 52 weeks.... Fluoride accumulation
occurred in both teeth and bone (femur) at 200 and 2000 ppm in
males and females at 1 and 2 yr. The reported increases were approximately
2 and 5 fold for teeth (from 0.1 to 0.8 mg F/g ash) and 2 and
4 fold for bone (0.5-3 mg F/g ash). The
main target organs were the liver and kidney. ... A NOEL
for non-neoplastic findings is 20 ppm ( 1 mg kg d, based on effects
in the kidney (increased organ weight, pigment
deposition and glomerulonephrosis) at 200 ppm and above).
-- 3.2.4 Carcinogenicity Studies. The two available studies, in
the rate and mouse both combine chronic toxicity and carcinogenicity...
Single incidences of tumours occurring in treated groups but not
controls were reported in the kidneys,
ovaries, brain, parathyroid and skeletal muscle. Neither these,
nor the occasional incidences of systemic tumors presented in
Table 3.3 were considered to be treatment related (page 23).
Ref: Evaluation on: Transfluthrin Use as
a Public Hygiene Insecticide. September 1997. Prepared by: the
UK Health and Safety Executive, Biocides & Pesticides Assessment
Unit, Magdalen House, Stanley Precinct, Bootle, Merseyside L20
3QZ. Available from: Department for Environment, Food and Rural
Affairs, Pesticides Safety Directorate, Mallard House, Kings Pool,
3 Peasholme Green, York YO1 7PX. UK.
Also at http://www.pesticides.gov.uk/citizen/evaluations/165_confirm-box.htm
• Note:
This was transcribed from the copy available on the web. While
one can easily read this report on the web, the report is inaccessible,
or locked, to any attempt to copy it. Any errors are mine. EC.
Trifloxystrobin
- Fungicide - CAS No. 141517-21-7
-- Short
term toxicity. Target / critical
effect: Decreased bodyweight & food consumption. Liver:
increased weight, hepatocellular hypertrophy and necrosis. Kidney:
increased weight and acute tubular lesions. Pancreas: atrophy.
Lowest relevant oral NOAEL / NOEL: 90-day rat: 100 ppm (6.4 mg/kg
bw/day) Lowest relevant dermal NOAEL / NOEL: 28-day rat: 100 mg/kg
bw/day Lowest relevant inhalation NOAEL / NOEL: No study - not
required
-- Long term toxicity and carcinogenicity.
Target / critical effect: Decreased
bodyweight & food consumption. Liver: increased weight, hepatocellular
hypertrophy, fatty change and necrosis. Kidney:
increased weight. Lowest relevant NOAEL: 2-yr rat: 250
ppm (9.8 mg/kg bw/day) Carcinogenicity: No carcinogenic potential
Ref:
Review report for the active substance trifloxystrobin. Trifloxystrobin.
SANCO/4339/2000-Final. 7 April 2003. Finalised in the [European
Commission] Standing Committee on the Food Chain and Animal Health
at its meeting on 15 April 2003 in view of the inclusion of trifloxystrobin
in Annex I of Directive 91/414/EEC.
http://www.fluorideaction.org/pesticides/trifloxystrobin.eu.april.03.pdf
Trifloxysulfuron-sodium
- Herbicide - CAS No. 199119-58-9
-- In a 2-year chronic
toxicity and carcinogenicity study, rats were fed diets containing
trifloxysulfuron-sodium that resulted in average (sexes combined)
daily test substance intakes of 0, 2.08, 22.0, 91.0 or 464 mg/kg/day...
At
terminal sacrifice, the testes to body weight ratio was increased
by 19% in the 464 mg/kg/day group. Microscopical
examination revealed a non-dose responsive increase in the incidence
of kidney tubular atrophy in the two top
dose groups of female rats, and an increase
in Leydig cell hyperplasia in high dose males only.
Both treatment-related lesions occurred late in age/ treatment,
and were not seen in animals sacrificed in the initial year of
the study... In conclusion, the MTD was reached or exceeded at
464 mg/kg/day for the 2-year rat feeding study. The
NOAEL in males was 82.6 mg/kg/day based on the increased incidence
of Leydig cell hyperplasia, and 23.7
mg/kg/day in females based on the increased incidence of kidney
tubular atrophy. There was no evidence of a carcinogenic
effect after 2 years of treatment with trifloxysulfuron-sodium
in rats.
Ref:
Federal Register: March 21, 2003. Trifloxysulfuron-sodium; Notice
of Filing a Pesticide Petition to Establish a Tolerance for a
Certain Pesticide Chemical in or on Food.
http://www.fluoridealert.org/pesticides/trifloxysulfuron-s.mar21.03.htm
Triflumizole
- Fungicide - CAS No. 68694-11-1
-- Reproduction and
fertility effects (rat): Reproductive NOAEL = not identified LOAEL
= 3.5 mg/kg/ day based on increased gestation
length in P. Offspring NOAEL = 8.5 mg/kg/ day LOAEL = 21
mg/kg/ day based on decreased pup body weight, survival indices,
and litter sizes and a slight increased incidence of hydronephrosis
in F1a pups.
Ref: Federal Register: June 12, 2002. Triflumizole;
Pesticide Tolerance. Final Rule. http://www.fluoridealert.org/pesticides/triflumizole.fr.june12.2002.htm
-- Chronic feeding/oncogenicity
studies were conducted in both the rat and mouse. The chronic
feeding study in the rat suggests that the
liver is the main target organ with the
ovary and kidney as secondary target
organs...
-- A 2-year feeding/oncogenicity study with Sprague-Dawley rats
was conducted. Rats were fed 0, 5, 20 or 80 mg/kg/day doses of
triflumizole equivalent to 0, 100, 400 and 1600 ppm triflumizole
for 104 weeks with an interim sacrifice at 52 weeks. Numerous
organ weights, clinical chemistry and hematology parameters and
microscopic changes indicate the main target organ is the
liver, with fatty vacuolization and periacinar hepatic
hypertrophy seen at all dose levels tested. Ovarian organ weights
as well as well-developed follicles indicate the
ovary as a target. Kidney weights
were affected as well with increased cortical cysts seen in the
kidneys of mid and high dose animals. The NOEL is greater
than 100 ppm, based on fatty vacuolization and periacinar hepatic
hypertrophy seen at all dose levels tested. An increase in tumor
incidence was not noted in any treatment groups.
Ref: Ref: EPA Pesticide Fact Sheet September
1991. Triflumizole (Terraguard, Procure).
http://pmep.cce.cornell.edu/profiles/fung-nemat/tcmtb-ziram/triflumizole/fung-prof-triflumizole.html
Trifluralin
- Herbicide - CAS No. 1582-09-8
Group
C -- Possible Human Carcinogen. Thyroid
(follicular celladenomas & carcinomas); Neoplasms of the
renal pelvis (M); Benign urinary
bladder tumors (F); Fischer 344 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
• Long term toxicity and carcinogenicity (Annex IIA, point
5.5). Carcinogenicity.
Evidence of carcinogenic
potential in Fischer 344 rat, (tumour
formation in various tissues, i.e. kidney, urinary
bladder, thyroid, Leydig cell). The mechanism of tumour formation
is not identified. R40. (page
46)
• Absorption,
distribution, excretion and metabolism in mammals (Annex IIA,
point 5.1). Widely distributed;
highest concentration in adrenals, fat, kidneys,
liver, skin and blood (page 45)
Ref: March 14, 2005. European
Food Safety Authority: Conclusion regarding the
peer review of the pesticide risk assessment of the active substance
trifluralin. EFSA Scientific Report (2005) 28, 1-77.
http://www.fluoridealert.org/pesticides/trifluralin.eu.long.2005.pdf
Cancer Classification
The OPP Carcinogenicity Peer Review Committee evaluated all the
available carcinogenicity data on trifluralin (April 4, 1986),
and it concluded that there is limited evidence of carcinogenicity
in male and female rats based upon an increase in combined malignant
and benign urinary bladder tumors in females,
renal pelvis carcinomas in male rats,
and thyroid gland follicular cell tumors
(adenomas plus carcinomas combined) in males. Trifluralin
has been classified as a Group "C"
possible human carcinogen with a Q of 0.0077 (mg/kg/day)
. The upper bound 1 * -1 dietary cancer risk is is approximately
1.0 x 10 . -6
Ref: Reregistration Eligibility Decision
(RED) Trifluralin. US EPA, Office of Prevention, Pesticides and
Toxic Substances. EPA 738-R-95-040. April 1996.
http://www.fluoridealert.org/pesticides/trifluralin.red.1996.epa.pdf
•
Definition
of Renal Pelvis - The area at the center of the kidney. Urine
collects here and is funneled into the ureter, the tube that
connects the kidney to the bladder.
High doses of trifluralin
are associated with increases in kidney,
bladder, and thyroid tumors.
Ref: March 2000. CERCLIS # WAD058619255.
Draft for Public Comment.. Prepared by: Washington State Department
of Health Under Cooperative Agreement with the Agency for Toxic
Substances and Disease Registry.
Public Health Assessment Cenex Supply and Marketing, Inc. Quincy,
Washington.
Also available at
http://www.doh.wa.gov/ehp/oehas/Cenex%20PHA%20Draft%20Public%20Review.pdf
-- 002, 003 952930,
952931 "The chronic toxicity of compound 36352 (trifluralin) given
as a component of the diet to Fischer 344 rats for two years."
(Lilly research, 9/16/80, R-87 and R-97) Trifluralin, 100%, no
nitrosamine, lots P-65469 and 326EF8; 60 Fischer 344 Rats/sex/group,
30 in each of two replicate studies; fed at 0, 813, 3250 or 6500
ppm in the diet - dose selection based on NCI study (Record no.
027205); diet analyses at 11 intervals; adverse effects: microcytic
anemia (both sexes) at 3250 and 6500 ppm, transitional cell carcinoma
of renal pelvis epithelium and bladder (both sexes) and thyroid
follicular adenoma and carcinoma (males only); sys NOEL = 813
ppm (decreased body weight gain), chronic NOEL < 813 ppm (progressive
glomerulonephroses, renal calculi); Complete; ACCEPTABLE.
(JPC, 5/21/85 and JG, 5/18/87). No EPA one-liner available. [In
the Guidance for the Reregistration of Pesticide Products Containing
Trifluralin as the Active Ingredient, August 1986, CDFA Record
#51346, Document 207-097, this study is
discussed with the footnote that additional data in the Fischer
344 rat is required to resolve the adverse kidney effects "since
a NOEL for non-oncogenic kidney effects was not demonstrated...."
The EPA states at least one dose should be lower than 813
ppm. JG, 5/14/87.]
-- 109 062079, 062080, "A Special Urinalysis Study in Fischer
344 Rats Maintained on Diets Containing Trifluralin (Compound
36352) for Three Months", (Lilly Research Laboratories, study
# R04785, August 1985 and 1986), trifluralin, 96.45% purity, administered
in the diet for 3 months to males only with 60/group at 0 and
2.6 mg/kg/day, and with 40/group at 10.7, 42.2, 170.2, and 342.1
mg/kg/day time-weighted average. NOEL for non-oncogenic
kidney effects in male Fischer 344 rats
= 2.6 mg/kg/day (approx. 50 ppm) (increased urinary K, Ca, AST,
LDH, and Alpha 1, Alpha 2 and Beta globulins; increased renal
tubular epithelial hyaline droplets). Some were continued on the
diets for 4 months followed by 6 weeks on control diet. Treatment
effects were reversible in all but the highest dose group. Note:
this study was conducted to determine a NOEL for the non-oncogenic
kidney effects of trifluralin in the Fischer 344 rat. This question
surfaced in the combined rat feeding study record #Õs 952930,
952927, and 952931 previously reviewed (JPC, 5/21/85 and JG, 5/18/87,
10/9/88).
Ref:
SUMMARY OF TOXICOLOGY DATA TRIFLURALIN. California EPA, Department
of Pesticides, Medical Toxicology Branch. Revised as of 11/29/95.
http://www.cdpr.ca.gov/docs/toxsums/pdfs/597.pdf
|