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.
Ammonium
fluoride
- Wood Preservative - CAS No. 12125-01-8
Male Wistar rats were
exposed to ammonium fluoride vapours in a toxicological chamber
for 3 months.Exposure to NH4F was for 3 months, 6 hours per day
and 5 days per week, in a toxicological chamber... a concentration
of 2 mg/m 3 was administered in the form of aerosol in air...
Biochemical tests in liver homogenate... Total cholesterol:
Ammonium fluoride caused a rise of 65% in
cholesterol
levels. Quercetin at either dose markedly
reduced the content of cholesterol
in liver. Triglycerides: Triglycerides in liver homogenate were
increased by 61% in the NH4F group. When quercetin was administered
the level of triglycerides fell to near-normal values. DISCUSSION
In this work chronic exposure of rats to ammonium fluoride led
to a sharp increase in the concentration
of total lipids, triglycerides, and cholesterol
in serum. The content of cholesterol
in the microsomal fraction rose, while the content of phospholipids
fell... Abnormal enzyme activities seem to be one of the chief
factors responsible for the rise in
serum triglycerides and cholesterol.
It appears that enzymes inhibited by fluoride, such as triglyceride
lipase, unspecific esterases, and pyro-phosphatase, were involved.
Opinions as to the influence of fluorides on cholesterol
levels are controversial. Some authors did not observe any changes
after fluoride exposure, while others have confirmed the hypercholestero-lemic
effect of fluorine compounds... CONCLUSIONS - Chronic exposure
to ammonium fluoride vapours leads to changes in lipid metabolism
in experimental animals.
Ref: B Czerny et al. (2000). The influence
of quercetin on some parameters of lipid metabolism in rats chronically
exposed to ammonium fluoride. Fluoride, Vol. 33, No. 1; 27-32.
http://www.fluoride-journal.com/00-33-1/331-27.pdf
Chlorfenapyr
-
Acaricide, Insecticide - CAS No. 122453-73-0
The 100-fold margin
of safety is adequate to assure a reasonable certainty of no harm
to infants and children from the proposed use. As stated earlier,
the NOAEL is based on the effects observed in the rat and mouse
chronic oncogenicity studies, (reduced bwt gains,
increased globulin and cholesterol
values and increased liver weights in the rat and reduced bwt
gains and vacuolation of white matter of the mouse brain), the
1-year neurotoxicity study in the rat, (reduced bwt gains and
vacuolar myelinopathy of [[Page 46680]] the brain and spinal cord
that is completely reversible following termination of treatment
and is not associated with any damage to neuronal cell bodies
or axons; vacuolation of the white matter is a consequence of
edema (water) formation between the myelin layers which result
from the unrestricted movement of ions across the cell membranes)
and the 2-generation rat reproduction study, (reduced bwt gains
for parental animals and reduced pup body weights for the F1 and
F2 litters; however no behavioral changes were observed in either
F1 or F2 offsprings in the 2-generation reproduction study)...
Ref: Federal Register: August 26, 1999 [Page
46677-46680]. Notice of Filing; Pesticide Petition.
http://www.fluoridealert.org/pesticides/chlorfenapyr.fr.aug.26.1999.htm
Chlorodifluoromethane
-
Insecticide, Fungicide, Propellant - CAS No. 75-45-6
Lee and Suzuki (1981)
exposed groups of 16 male Sprague-Dawley rats to 0 or 50,000 ppm
HCFC-22 for 5 hours/day, 7 days/week for 8 weeks (duration- adjusted
concentrations = 0 or 36,800 mg/cu.m, respectively). Six rats/group
were sacrificed at 8 weeks, and the rest were used in a fertility
study (discussed below). The only exposure-related effects noted
were a slight decrease in prostate weight (without accompanying
histopathological changes), an increase
in plasma cholesterol,
and decreases in plasma glucose and triglycerides. The toxicological
significance of these changes is not clear because functional
studies on adrenal or hepatic function were not undertaken, and
there were no histopathological changes in these organs. Nevertheless,
a LOEL of 50,000 ppm [LOEL(HEC) = 36,800 mg/cu.m] can be estimated
from this study.
Ref: US EPA IRIS (Integrated Risk Information
System).
http://www.fluoridealert.org/pesticides/chlorodifluoromethane.iris.htm
Cloransulam-methyl
- Herbicide - CAS No. 147150-35-4
In the rat Chronic
Feeding / Carcinogenicity study the NOEL was equal to 75 mg/kg/day
and the Lowest Observed Effect Level (LOEL) was 325 mg/kg/day
based on significant increase in hemoglobin, hematocrit, and red
cell count in males, activities of the liver enzymes aspartate
and alanine aminotransferase as well as alkaline phosphatase were
decreased in males, cholesterol
was
decreased in females,
specific gravity of urine was decreased in females, increased
relative weight in liver and relative weight of testes in males,
males exhibited an increased incidence of collecting duct hypertrophy
and females exhibited increased incidence of vacuolation in the
kidney.
Ref: US EPA Fact Sheet. October 29, 1997.
http://www.fluoridealert.org/pesticides/cloransulam-methyl.epa.1997.htm
Cyhalothrin,
lambda -
Insecticide - CAS No. 91465-08-6
Subchronic toxicity.
A 90-day feeding study in which rats were fed doses of 0, 50,
150, and 350 ppm with a NOEL of 50 ppm and a lowest observed effect
level (LOEL) of 150 ppm based on mild dose changes in hemoglobin,
cholesterol, and liver weight.
Ref: Federal Register: September 25, 1997
[Page 50337-50367]. Notice of Filing of Pesticide Petitions.
http://www.fluoridealert.org/pesticides/lambda-cyhalothrin.fr.1997.htm
Diflufenican
- Herbicide - CAS No. 83164-33-4
--Subacute toxicity
studies... In a 13-week oral study in the dog, the minimum effect
level was 250 mg/kg bw based on enemis and
increased cholesterol levels at the
250 mg/kg bw/day dose level. The observed effects at higher dose
levels included impaired body weight gain, emesis, increased plasma
cholesterol and increase in the relative thymus weights.
Ref: September
1995. Evaluation on Diflufenican.
Evaluation of fully approved or provisionally approved products.
Department for Environment, Food and Rural Affairs, Pesticides
Safety Directorate, Mallard House, Kings Pool, 3 Peasholme Green,
York YO1 7PX, UK. Available at:
http://www.pesticides.gov.uk/citizen/evaluations/evallist_alphabet.htm
Ethalfluralin
- Herbicide - CAS No. 55283-68-6
A three month oral
study with beagle dogs had doses of 0, 6.25, 27.5, or 125/80 mg/kg/day
by capsule. The systemic NOEL was 27.5 mg/kg/day. The systemic
LOEL was 80 mg/kg/day (the high dose) based on elevated alkaline
phosphatase, slight fatty metamorphosis of the liver,
increased cholesterol, and increased BUN. (MRID 00135193)
Ref: US EPA. Reregistration Eligibility
Decision (RED): Ethalfluralin. March 1995.
http://www.fluorideaction.org/pesticides/ethalfluralin.red.long.pdf
Fipronil
- Acaricide,
Insecticide
- CAS No. 120068-37-3
An acceptable chronic
rat feeding study identified the following effects: seizures,
including seizures resulting in death, decreased body weight gain,
decreased food consumption and food conversion efficiency, decreased
hematology measures, alterations in clinical chemistry (cholesterol,
calcium, and protein), alterations in thyroid hormones, alterations
in urine chemistry, changes on gross necropsy, increase in liver
and thyroid weights, and progressive senile nephropathy (kidney
effects). The NOEL for systemic toxicity was 0.5 ppm. The LOEL
of 1.5 ppm was based on an increase in incidence of clinical signs
and alterations in clinical chemistry and thyroid parameters.
Based on this study, the RfD Committee recommended that the RfD
be established using the NOEL and an uncertainty factor of 100
to account for the interspecies extrapolation and intraspecies
variability. The RfD was set at 0.0002 mg/kg/day.
Ref: US EPA. New Pesticide Fact Sheet. May
1996.
http://www.fluoridealert.org/pesticides/fipronil.epa.facts.may.1996.htm
Fluazifop-butyl
- Herbicide - CAS No. 69806-50-4
-- Fluazifop-butyl
(CAS # 69806-50-4) was evaluated for subchronic dietary toxicity
in Wistar rats (20/sex/group) receiving 0, 10, 100 and 2000 ppm
by dietary inclusion for 13 weeks. Mean achieved dosages during
13-week treatment were 0, 0.7, 7.1 and 144.5 mg/kg/day in males
of the respective treatment groups and 0, 0.8, 8.0 and 161.9 mg/kg/day
in females... cholesterol and total
protein concentrations were low as compared to controls. [ICI
AMERICAS INC; 13 Week Dietary Toxicity Study with PP009 in Rats
(Final Report); 05/29/80; EPA Doc No. 88-920006943; Fiche No.
OTS0545346]
-- Fluazifop-butyl (CAS # 69806-50-4) was evaluated for subacute
oral toxicity in Wistar albino rats (10/sex/group) administered
10 ml/kg doses in corn oil of 0, 4, 20, 100 and 500 mg/kg/day
by oral gavage, 5 days/week for 2 weeks. Five-day weekly treatment
periods were each followed by 2-day recovery... Blood chemistry
indicated a dose-related elevation of alkaline phosphatase activity
in 100 and 500 mg/kg/day males, elevated aspartate amino-transferase
activity in 500 mg/kg/day males, and elevated
cholesterol concentrations in 500 mg/kg/day males and females.
Conversely, enzyme activity was depressed in rats of lower dosages...
[ICI AMERS INC; 14 Day Subacute Oral Toxicity Study with PP009
in Rats; 07/11/80; EPA Doc No. 88-920007017; Fiche No. OTS0545392]
Ref: TOXNET profile from Hazardous Substances
Data Bank for FLUAZIFOP-BUTYL.
http://www.fluoridealert.org/pesticides/fluazifop-butyl.toxnet.hsdb.htm
**411-083 069476 Virgo,
D. M., "Fluazifop-butyl: 55 week oral toxicity study in beagle
dogs," Life Science Research, Stock, Essex, England, 10/15/82.
LSR Report No. 81/ILK019/620. Six dogs/sex/group were dosed for
55 weeks with Fluazifop-butyl, 99.6% purity, by gelatin capsules
at dose levels of 0, 5, 25, and 125 mg/kg/day in a chronic study.
Test article within capsules was dissolved in 0.4 ml/kg corn oil
vehicle. NOEL = 5 mg/kg/day... All
other noteworthy findings were limited to the high dose group,
as follows. Seven 125 mg/kg/day dogs (5 M, 2 F) were killed in
extremis prior to term, generally after at least 29 weeks on study
... Cholesterol
was consistently reduced. Male reproductive
toxicity included testicular tubular degeneration and reduced/absent
spermatozoa in epididymides. Possible adverse effects
(many-faceted toxicity, including mortalities, at 125 mg/kg/day).
Acceptable. Aldous, 5/20/02.
Ref: May 20, 2002. SUMMARY OF TOXICOLOGY
DATA FLUAZIFOP-P-BUTYL. California EPA. Department of Pesticide
Regulation. Medical Toxicology Branch.
http://www.fluoridealert.org/pesticides/fluazifop-p-butyl.caepa.02.pdf
Fluazinam
- Fungicide
- CAS
No. 79622-59-6
-- 21-Day dermal toxicity
rats: increased AST and cholesterol
levels in clinical chemistry determinations (males).
Special studies: 4-Week dietary (Range-finding) rats- decreased
body weight gain and food consumption, increased serum phospholipids,
increased total cholesterol,
increased relative liver weights, and liver histopathology.
-- 4-Week dietary (Range-finding) mice- decreased body weight
gain, increased serum glucose, increased
kidney weights.
-- 4-Week dietary (Range-finding) rats. NOAEL = Males: 5.1 mg/kg/day;
Females: 5.3 mg/ kg/day LOAEL = Males: 26.4 mg/kg/day; Females:
25.9 mg/ kg/day based on decreased body
weight gain and food consumption, increased serum phospholipids,
increased total cholesterol, increased
relative liver weights, and liver histopathology.
Ref: Federal Register: April 18, 2002 [Page
19120-19130]. Fluazinam; Pesticide Tolerance. Final Rule.
http://www.fluoridealert.org/pesticides/fluazinam.fr.apr.18.2002.htm
Fludioxonil
- Fungicide - CAS No. 131341-86-1
A chronic oral toxicity
study in dogs dosed for 52 weeks at 0, 100, 1,000, and 8,000 ppm
in the diet (0, 3.1, 33.1, and 297.8 mg/kg/ day in males; 3.3,
35.5, and 330.7 mg/kg/day in females. The LEL is 297.8 mg/kg/day
for male dogs based on decreased body weight, hematology alterations
(increase in platelets and fibrin), clinical chemistry alterations
(increase in cholesterol and alkaline
phosphatase) and increased liver weight. The LEL is 35.5 mg/kg/day
for female dogs based on a marked decrease in body weight gain
for weeks 1 - 13 and weeks 1 - 52 of the study. The NOEL is 33.1
mg/kg/day for male dogs and 3.3 mg/kg/day in female dogs.
Ref: Federal Register: October 29, 1997
[Page 56075-56082]. 4-(2,2-difluoro-1,3-benzodioxol-4-yl)-1H-pyrrole-3-carbonitrile;
Pesticide Tolerance. Final Rule.
http://www.fluoridealert.org/pesticides/fludioxonil.fr.oct.29.1997.htm
Flufenacet
- Herbicide - CAS No. 142459-58-3
A 1-year dog chronic
feeding study with a NOEL was 40 ppm (1.29 mg/kg/day in males
and 1.14 mg/kg/day in females) and a LOEL of 800 ppm (27.75 mg/kg/day
in males and 26.82 mg/kg/day in females) based on increased alkaline
phosphatase, kidney, and liver weight in both sexes, increased
cholesterol in males, decreased T2, T4 and ALT values in
both sexes, and increased incidences of microscopic lesions in
the brain, eye, kidney, spinal cord, sciatic nerve and liver.
Ref: Federal Register: September 23, 1998.
Flufenacet; Time-Limited Pesticide Tolerance. Final Rule.
http://www.fluoridealert.org/pesticides/Flufenacet.FR.Sept.23.1998.htm
Flumioxazin
- Herbicide - CAS No. 103361-09-7
-- 870.3150 90-Day
capsule - dog NOAEL = mg/kg/day: 10 (M & F) LOAEL = mg/kg/day:
100 (M & F) based on dose dependent increase
in total cholesterol, phospholipid & alkaline phosphatase
Ref: US EPA Pesticide Fact Sheet. April
12, 2001.
http://www.epa.gov/opprd001/factsheets/flumioxazin.pdf
Flurprimidol
- Plant Growth Regulator - CAS No. 56425-91-3
Chronic Studies. Rodent
Feeding Studies. A 2-year study in rats treated with either 0,
1.0, 3.6, 12.1 and 41.2 mg/kg/day of flurprimidol technical for
males and 0, 1.2, 4.4, 14.5, and 49.3 mg/kg/day for females the
NOEL was 3.6 mg/kg/day and the LEL was 12.1 mg/kg/day based upon
hepatocellular changes in males including enzyme induction, fatty
change, hepatocellular eosinophilic change and focal atypia. At
41.2 mg/kg/day there was also a transient body weight and weight
gain decrease (males), increased cholesterol
and triglycerides (males and females) increased hepatic enzyme
induction and liver weight, fatty change and hepatocellular eosinophilic
change (females). No oncogenic potential was observed at any dose
level.
Ref: EPA Pesticide Fact Sheet Name: Flurprimidol.
http://www.fluoridealert.org/pesticides/Flurprimidol.EPA.Facts.1989.htm
Flutolanil
- Fungicide - CAS No.
66332-96-5
Chronic toxicity. A
1-year dog chronic feeding study with a NOEL was 40 ppm [1.29
mg/kg/day in males and 1.14 mg/kg/day in females] and a LOEL of
800 ppm [27.75 mg/kg/day in males and 26.82 mg/kg/day in females]
based on increased alkaline phosphatase, kidney, and liver weight
in both sexes, increased cholesterol in
males, decreased T2, T4 and ALT values in both sexes, and
increased incidences of microscopic lesions in the brain, eye,
kidney, spinal cord, sciatic nerve and liver.
Ref: Federal Register: June 23, 1998 [Page
34176-34184]. Notice of Filing of Pesticide Petitions.
http://www.fluoridealert.org/pesticides/Flutolanil.FR.June.23.1998.htm
Haloxyfop-methyl
- Herbicide - CAS No. 69806-40-2
-- 13-Week Feeding
- dog: Dietary levels tested: 0, 2, 5, and 20 mg/kg/day; Beagle
dogs (4/sex/dose level) were administered haloxyfop-methyl in
the diet for 13 weeks. A statistically significant
decrease in serum cholesterol values was reported for males
fed 2 mg/kg/day. A statistically significant
decrease in serum cholesterol values was reported for males
and females fed 5 mg/kg/day. A significant
decrease in male and female triiodothyronine and free thyroxine
values was accompanied by a significant decrease in male and female
relative thyroid/parathyroid weights. Hepatic peroxisomal fatty
acid beta-oxidation was increased in males and females fed 5 mg/kg/day.
Histological changes reported at this level were hepatocellular
enlargement with increased glycogen content, decrease in follicular
size and hypertrophy of the follicular epithelial cells of the
thyroid, and decrease size of the testicular tubules. The LEL
for systemic toxicity is 2 mg/kg/day, the lowest dose tested,
based on decreases in serum cholesterol values in males. A NOEL
for systemic toxicity was not established; core grade minimum
(Dow Chemical Co., 1987a)
Ref:
Health Assessment. US EPA Integrated Risk Information System (IRIS).
http://www.fluoridealert.org/pesticides/Haloxyfop.Methyl.IRIS.htm
Isoxaflutole
- Herbicide - CAS No. 141112-29-0
In a combined chronic
toxicity/carcinogenicity study, isoxaflutole was continuously
administered to 75 Sprague-Dawley rats/ sex/dose at dietary levels
of 0, 0.5, 2, 20 or 500 mg/kg/day for 104 weeks. An additional
20 rats/sex/group were treated for 52 weeks, after which 10 rats/sex/group
were sacrificed and the remainder were held for a maximum of 8
weeks without treatment in order to assess reversibility of treatment-related
changes. Evidence of systemic toxicity observed at 500 mg/kg/day
in one or both sexes 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.
Ref: Federal Register: September 23, 1998.
Isoxaflutole; Pesticide Tolerance. Final Rule.
http://www.fluoridealert.org/pesticides/Isoxaflutole.FR.Sept23.1998.htm
Norflurazon
- Herbicide - CAS No. 27314-13-2
A 90-day rat feeding
study at nominal dosages of 0, 12.5, 25.0 and 125.0 mg/kg/day...
at the mid-dose level there were increases
of cholesterol in both sexes (23
to 40 percent in males, 6 to 34 percent in females), a decrease
in SGPT (36 to 38 percent in males, 13 to 20 percent in females)
and SGOT (4 to 23 percent in males, 13 to 23 percent in females).
At the highest level, similar changes were observed in male and
female dogs, with the additional observation of a decrease in
red cell count in female dogs (79 to 92 percent of control). The
systemic NOEL was determined to be 1.53 mg/kg/day for males and
1.58 mg/kg/day for females. The systemic LEL was determined to
be 5.02 mg/kg/day for males and 4.77 mg/kg/day for females, based
on increased absolute and relative liver weight and increased
cholesterol in both sexes.
Ref: Federal Register: July 29, 1996 [Page
39347-39351]. Norflurazon; Pesticide Tolerance. Final Rule.
http://www.fluoridealert.org/pesticides/Norflurazon.FR.July.29.1996.htm
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
Noviflumuron
-
Insecticide -
CAS No. 121451-02-3
-- 007; 186499; ÒXDE-007:
28-Day Dietary Toxicity Study in CD-1 MiceÓ (Yano, B.L. and Day,
S.J., Toxicology & Environmental Research and Consulting, The
Dow Chemical Company, Midland,
MI, Laboratory Project Study ID 001248, 6/12/01). XDE-007 (Lot,
Reference No. F0031-148, TSN102332, purity = 98.4%) was admixed
to the feed and fed to 5 CD-1 mice per sex per dose at dose levels
of 0, 10, 100, 500, or 1000 mg/kg/day (0, 10.8, 110, 538, 1060
mg/kg/day, respectively for males and 0, 11.2, 113, 504, 1140
mg/kg/day, respectively for females) for 28 days. No mortalities
occurred. No treatment-related clinical signs were observed. Treatment-related
increases in mean platelet level
and mean cholesterol level were observed in both sexes
at 100, 500, and 1000 mg/kg/day. A treatment-related increase
in mean relative liver weight was observed
at in males at 100, 500, and 1000 mg/kg/day and in females at
500 and 1000 mg/kg/day. Microscopic examination revealed treatment-related
hepatocellular hypertrophy with altered tinctorial properties
(centrilobular/midzonal to panlobular) in males at 500 and 1000
mg/kg/day and very slight vacuolation (consistent with fatty change)
of the periportal hepatocytes in males at 500 and 1000
mg/kg/day and in females at 1000 mg/kg/day. No adverse effects.
NOEL (M) = 10.8 mg/kg/day and NOEL (F) = 11.2 mg/kg/day (based
on increases in mean platelet and mean cholesterol
levels). Supplemental (because only 5 animals per sex per
dose were used and because the animals were treated for only 28
days). (Corlett, 9/30/02)
Ref:
September 26, 2002. Summary of Toxicology Data for Novidlumuron
((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
Quinoxyfen
- Fungicide - CAS No. 124495-18-7
** 040 - 181140 ÒXDE-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
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
Tefluthrin
- Insecticide - CAS No. 79538-32-2
In a subchronic oral
toxicity study, rats were dosed at 0, 50, 150, or 350 ppm (2.5,
7.5, or 17.5 mg/kg/day) for 90 days. The LOEL for this 90-day
feeding study is 150 ppm (equivalent to approximately 7.5 mg/kg/day)
based on changes in hemoglobin, cholesterol,
and liver weight in the mid-dose animals. The NOEL is 50 ppm (equivalent
to approximately 2.5 mg/kg/day).
Ref: Federal Register: November 26, 1997.
Tefluthrin; Pesticide Tolerance. Final Rule. http://www.fluoridealert.org/pesticides/Tefluthrin.FR.Nov.1997.htm
Tembotrione - Herbicide - CAS No. 335104-84-2
• 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. Total cholesterol concentrations were significantly increased (p≤ 0.01) at 200 and 800 ppm (46 and 52%, respectively), compared to controls during the first 18 months of treatment. The increased total cholesterol concentrations observed at 800 ppm during the first 18 months of treatment were still present after 3 months of recovery (43%, p<0.01), compared to controls (page 71).
• A treatment related increase in cholesterol was observed in males in a dose-dependent manner that reached significance at ≥75 ppm [1.25 ppm (14%), 75 ppm (22%, p<0.01), 1500 ppm (32%, p<0.001), 7000 ppm (80%, p<0.001) and increased significantly by 34% (p<0.01) in females at 7000 ppm (page 55).
• 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.
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.
A 12-month chronic oral toxicity study in Beagle dogs was conducted
with technical tetraconazole at dose levels of 0.7, 2.8, and 5.6
mg/kg/day (22.5, 90, and 360 ppm dietary concentrations, respectively).
At the highest dose, liver and kidney weights
and cholesterol levels were elevated,
and liver injury occurred based upon
increased levels of GPT, -GT and OCT. The no effect level
was 0.7 mg/kg/day, as compared with zero-dose control animals.
Ref: Federal Register: October 14, 1999.
Notice of Filing Pesticide Petitions to Establish a Tolerance
for Certain Pesticide Chemicals in or on Food. PP 9F5066, 9F6023,
and 7E4830.
http://www.fluoridealert.org/pesticides/Tetraconazole.FR.Oct14.1999.htm
Thiazopyr
- Herbicide - CAS No. 117718-60-2
-- 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.
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
Transfluthrin
- Insecticide - CAS
No. 118712-89-3
-- 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.
-- In 90 d study Beagles (4/sex/group)
were administered transfluthrin (94.5%0 pure via their food at
nominal concentrations of 0, 50, 350 or 2500 ppm. Haematological
and urine examinations were carried out on all grops pre study
and at 3, 6 and 13 w. Ophthalmological examinations were carried
out pre study, 6 and 13 w, and hearing tests were carried out
pre study and 13 w. ... The haematological and urine examinations
showed no treatment related changes. The clinical chemistry examination
indicated treatment related effects on the
liver. At 2500 ppm increases in cholesterol
levels were noted in both sexes which increased with time
(~ 35-70% in males and ~ 60-80% in females
over `- 13 w). In addition at 13
w plasma lipid and triglyceride levels were increased in both
sexes (~ 110-120%). N-demethylase activity was increased in both
sexes at 2500 ppm (~ 35%). At 13 w the examination also noted
a decrease in thyroxine levels in females (~ 45%) and a non-significant
decrease in triiodothyronine (~ 40%) at 2500 ppm. At necropsy,
gross pathological examination noted no treatment related changes.
At 2500 ppm relative (to the brain) liver weights increased in
both sexes (~ 30% in males and ~50% in females) and thyroid weight
increased non-significantly in females (~ 70%). Histopathological
examination showed centrilobular hypertrophy in all animals at
2500 ppm and 1 female from this group with minimal hepatocytic
single cell necrosis. The NOEL for this study was 50 ppm
(1.9 kg d) based on the increase in N-demethylase activity in
males at 350 ppm (14 mg kg d).
-- B6C3F1 mice (60/group/sex) received
0, 10, 100 or 1000 ppm mg kg transfluthrin (94.8-95%) pure in
the diet for up to 104 weeks with 10/sex/dose killed after one
yar. Two additional groups(10/sex) received 0 or 1000 ppm for
13 weeks... Serum cholesterol levels were
significantly raised from 13 weeks at 1000 ppm (20%
in males and 54% in females) and from 100 ppm from week
53 (approximately 11 - 30%) and at week
103 from 10 ppm in females (approximately 50 - 70%) and
at 1000 ppm in males )~ 20%). ... Based on the chronic toxicity,
in males the NOEL is 10 ppm (2 mg kg d based on increases in
liver weight and hepatocyte hypertrophy, at 1000 ppm and increased
fluoride accumulation at 100 ppm). It
is not possible to set a NOEL for females as increases in serum
cholesterol, protein and albumin were reported at the lowest dose.
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.
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