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to Carfentrazone-ethyl
Index Page
Activity: Herbicide
(unclassified)
Structure
for Carfentrazone-ethyl:
Adverse
Effects:
Blood
Body Weight Decrease
Bone
Endocrine: Thymus
Kidney
Liver
Spleen
Environmental
Blood
(click on for all fluorinated pesticides)
-- Repeat-dose studies
indicate that the primary targets for carfentrazone-ethyl toxicity
are the liver, kidney, and
the red blood cell forming system... Effects
on the red blood cell forming system were seen in most studies.
These effects included a reduction in the number of
red cells in blood and an associated increase in the products
of red blood cell degradation appearing
in the urine and liver.
-- Short-Term Studies In mice fed carfentrazone-ethyl at
concentrations up to 20000 ppm for 28 days, decreased defecation
was observed at 14000 and 20000 ppm. Blood
haemoglobin concentration was reduced in females at concentrations
¥ 4000 ppm and mean corpuscular volume and mean corpuscular haemoglobin
were reduced at the highest concentration...
-- Short-Term Studies... The body weight
of dogs (1/sex) given 1000 mg/kg bw/day carfentrazone-ethyl
in capsules for 14 days was reduced;
food consumption of the female also reduced.
Mean corpuscular haemoglobin and mean corpuscular volume were
reduced. In the female,
haematocrit was also reduced with white blood cell counts and
neutrophils increased. The female had a pale
kidney and the male had reduced relative spleen and testes weights.
-- Short-Term Studies... In mice fed up to 20 000 ppm dietary
carfentrazone-ethyl for 90 days, a pink/brown staining of the
litter tray was observed at concentrations ¥ 14000 ppm. Although
red blood cell counts were increased
in males at concentrations ¥ 14000 ppm, mean
corpuscular volume and mean corpuscular haemoglobin were reduced
in males at concentrations ¥ 8000 ppm and in females at
concentrations ¥14000 ppm. In addition, mean corpuscular haemoglobin
concentration was reduced in females at the highest concentration.
Aspartate aminotransferase and alanine aminotransferase activities
were increased at 20000 ppm and albumin was increased in females
at concentrations ¥ 1400 ppm...
-- Short-Term Studies... In rats fed up to 20 000 ppm carfentrazone-ethyl
in the diet for 90 days, abdominogenital staining and pink-brown
discolouration of the cage-pan liner was observed at concentrations
4000 ppm. Body weight and food consumption
were reduced in males at concentrations ¥ 8000 ppm and in females
at concentrations ¥ 8000 and 4000 ppm respectively. Erythrocyte
parameters (Hb, Hct, MCV, MCH) were reduced at concentrations
¥ 8000 ppm and platelets were increased in males at the same concentrations.
Plasma ALT, AST, potassium, phosphorus and bilirubin were increased
at concentrations ¥ 8000 ppm whereas glucose was reduced...
-- Short-Term Studies... Dogs given capsules containing carfentrazone-ethyl
at doses up to 1000 mg/kg bw/day for 90 days exhibited subdued
behaviour, salivation and vomiting at the highest dose. Mean
corpuscular haemoglobin was reduced at doses ¥ 500 mg/kg
bw/day and mean corpuscular volume was reduced in males at this
dose. Red blood cell count was increased
in males receiving the highest dose. Total urinary porphyrins
were increased at doses ¥ 500 mg/kg bw/day and liver weight was
increased in females at this dose....
-- Long-Term Studies. Mice fed carfentrazone-ethyl at concentrations
of 0, 70, 700 or 7000 ppm for 80 weeks had increased mortality
at concentrations ¥ 700 ppm. Body weights
and body weight gains were reduced at 7000 ppm in females and
in all treated males. Red blood cell
count and haematocrit were reduced and mean corpuscular
volume was increased in females at concentrations ¥ 70 ppm. Haemoglobin
was reduced at concentrations ¥ 700 ppm and mean corpuscular volume
and mean corpuscular haemoglobin concentration were increased
in males at concentrations ¥ 70 ppm. Haemosiderosis,
porphyrin deposits and treatment related histopathological changes
were observed in males at concentrations ¥ 700 ppm and in females
at the highest concentration. A NOEL was not established for this
study, because reduced body weight gain was observed in males
at the lowest concentration tested (70 ppm, equal to 10 mg/kg
bw/day).
-- Long-Term Studies... In rats fed 0, 50, 200, 800 or
4000 ppm carfentrazone-ethyl for 52 or 104 weeks slight decreases
in red blood cell counts in males
and increases in mean corpuscular haemoglobin and mean corpuscular
haemoglobin concentration were observed at ¥ 200 ppm...
-- Long-Term Studies... In dogs given carfentrazone-ethyl in capsules
at doses of 0, 50, 150, 500 or 10000 mg/kg bw/day for 52 weeks,
increased urinary porphyrins were observed at doses ¥ 150 mg/kg
bw/day. A slight reduction in mean corpuscular haemoglobin
and mean corpuscular haemoglobin concentration was observed
in males at the same doses and an increase in liver to body weight
ratio was observed in females at doses ¥ 500 mg/kg bw/day. The
NOEL for this study was 50 mg/kg bw/day based on the slight increase
in urinary porphyrins at 150 mg/kg bw/day.
Ref:
April 2000 - Australia. Evaluation of the new active CARFENTRAZONE-ETHYL
in the product AFFINITY 400 DF HERBICIDE. National Registration
Authority for Agricultural and Veterinary Chemicals. NRA Ref.
51555.
http://www.fluorideaction.org/pesticides/carfentrazone-e.aus.2000rpt.pdf
Also
available at http://www.apvma.gov.au/publications/prscar.pdf
Body
Weight Decrease (click
on for all fluorinated pesticides)
In a developmental
toxicity study in rabbits, evidence of treatment-related maternal
toxicity consisted of unthriftiness and emaciation
in two does at 300 mg/kg/day. The maternal LOAEL is 300 mg/ kg/day;
the maternal NOAEL is greater than or equal to 150 mg/kg/day.
There was no evidence of treatment-related prenatal developmental
toxicity: The developmental LOAEL was not determined; the developmental
NOAEL is greater than or equal to 300 mg/kg/day.
Ref: Federal Register: June 12, 2002. Carfentrazone-ethyl;
Pesticide Tolerances for Emergency Exemptions. Final Rule.
http://www.fluoridealert.org/pesticides/Carfentrazone-E.FR.June2002.htm
-- A 90-day subchronic
feeding study was conducted in rats at intake levels of 0, 58,
226, 470, 831 and 1197 mg/kg/day for males and 0, 72, 284, 578,
1008 and 1427 mg/kg/day in females, respectively. The NOEL was
226 mg/kg/day in males and 284 mg/kg/day in females. The LOEL
was 470 mg/kg/day in males and 578 mg/kg/day in females based
on decreases in body weight, reductions
in food consumption and histopathological lesions.
-- A 90-day subchronic feeding study in dogs administered by dietary
admix doses of 0, 50, 150, 500 and 1000 mg/kg/day. The NOEL was
50 mg/kg/day and the LOEL was 150 mg/kg/day based on systemic
toxicity (decrease in the rate of weight
gain in females and an increase in porphyrin levels in
both sexes).
Ref: US EPA Pesticide Fact Sheet. Carfentrazone-ethyl
Reason for Issuance:New Chemical Registration Date Issued: September
30, 1998.
http://www.epa.gov/opprd001/factsheets/carfentrazone.pdf
Bone
(click
on for all fluorinated pesticides)
Developmental toxicity
study - rat... Examination of fetuses for alterations of external,
visceral, and skeletal development
revealed significantly increased litter
incidences of wavy and thickened ribs in the 1,250 mg/kg/day
treatment group. The developmental LOAEL is 1,250 mg/kg/day (based
upon a significant increase in the
litter incidences of wavy and thickened
ribs); the developmental NOAEL is 600 mg/kg/day.
Ref: Federal Register. August 1, 2001. Carfentrazone-ethyl;
Pesticide Tolerances for Emergency Exemptions. Final Rule.
http://www.fluoridealert.org/pesticides/Carfentrazone-e.FR.Aug1.01.htm
-- Reproduction and
Developmental Studies... Carfentrazone-ethyl was orally administered
to pregnant female rabbits, at doses of 0, 10, 40, 150 or 300
mg/kg bw/day from day 7 to day 19 of gestation. Slight increases
in abdominogenital, and pink or red pan liner staining were recorded
at doses ¥150 mg/kg bw/day. Skeletal variations
in rabbits (angulated hyoids, unilateral and floating ribs, and
non-ossified 6th sternabrae in rabbit litters), were slight and
not dose-related at materno-toxic doses. Maternal and foetal
NOELs were 40 and 10 mg/kg bw/day respectively, in rabbits.
Ref:
April 2000 - Australia. Evaluation of the new active CARFENTRAZONE-ETHYL
in the product AFFINITY 400 DF HERBICIDE. National Registration
Authority for Agricultural and Veterinary Chemicals. NRA Ref.
51555.
http://www.fluorideaction.org/pesticides/carfentrazone-e.aus.2000rpt.pdf
Also
available at http://www.apvma.gov.au/publications/prscar.pdf
Endocrine:
Thymus
(click
on for all fluorinated pesticides)
Short-Term Studies...
In dogs (1/sex/group) given capsules containing carfentrazone-ethyl
at doses up to 1000 mg/kg bw/day for 28 days, food consumption
and body weight gain were decreased, plasma
urea was slightly increased and plasma glucose was slightly decreased.
Total urinary porphyrins were elevated in the male at 1000 mg/kg
bw/day and in females at ¥ 500 mg/kg bw/day. Decreased
thymus weight and cortical atrophy were observed in animals
at 1000 mg/kg bw/day and decreased uterus
weights were observed in females at this dose.
Ref:
April 2000 - Australia. Evaluation of the new active CARFENTRAZONE-ETHYL
in the product AFFINITY 400 DF HERBICIDE. National Registration
Authority for Agricultural and Veterinary Chemicals. NRA Ref.
51555.
http://www.fluorideaction.org/pesticides/carfentrazone-e.aus.2000rpt.pdf
Also
available at http://www.apvma.gov.au/publications/prscar.pdf
Kidney
(click
on for all fluorinated pesticides)
-- Repeat-dose studies
indicate that the primary targets for carfentrazone-ethyl toxicity
are the liver, kidney,
and the red blood cell
forming system... Increased kidney weight and the presence of
pigment in kidney cells typified
kidney toxicity in rats and dogs...
Ref:
April 2000 - Australia. Evaluation of the new active CARFENTRAZONE-ETHYL
in the product AFFINITY 400 DF HERBICIDE. National Registration
Authority for Agricultural and Veterinary Chemicals. NRA Ref.
51555.
http://www.fluorideaction.org/pesticides/carfentrazone-e.aus.2000rpt.pdf
Also
available at http://www.apvma.gov.au/publications/prscar.pdf
Liver
(click
on for all fluorinated pesticides)
-- A 2-year
rat chronic toxicity/carcinogenicity study was conducted
in rats at intake levels of 0, 2, 9, 37 and 188 mg/kg/day for
males and 0, 3, 12, 49 and 242 mg/kg/day for females. The study
found the compound to be noncarcinogenic to rats under the conditions
of the study. The no-observed- effect level (NOEL) was 200 ppm
(9 mg/kg/day ) for males and 50 ppm (3 mg/kg/day) for females
respectively and the lowest-observed-effect-level (LOEL) was 800
ppm (37 mg/kg/day) for males and 200 ppm (12 mg/kg/day) for females,
based on liver histopathology and
total urinary porphyrin.
-- Chronic Toxicity. An 18-month mouse
carcinogenicity study was conducted in mice at dietary intake
doses of 0, 10, 110 and 1090 mg/kg/day for males and 0, 12, 119
and 1296 mg/kg/day for females). The study found the compound
to be noncarcinogenic to mice under the conditions of the study.
The systemic NOEL was 70 ppm (equivalent to 10 mg/kg/day for males
and 12 mg/kg/day for females), and the systemic LOEL was 700 ppm
(equivalent to 110 mg/kg/day for males and 119 mg/kg/day for females)
based on increased mortality and microscopic signs of
hepatotoxicity.
Ref: US EPA Pesticide Fact Sheet for Carfentrazone-ethyl.
September
30, 1998.
http://www.fluorideaction.org/pesticides/carfentrazone.epa.fact.1998.pdf
-- Subchronic oral
toxicity study in the dog. LOAEL
= 150 mg/kg/day based on decreased body weight gain and increased
porphyrin levels. -- -- Chronic toxicity study in rats. LOAEL
= 12 mg/kg/day based on liver histopathology
and increased urinary porphyrin levels.
Ref: Federal Register: June 12, 2002. Carfentrazone-ethyl;
Pesticide Tolerances for Emergency Exemptions. Final Rule.
http://www.fluoridealert.org/pesticides/Carfentrazone-E.FR.June2002.htm
--- Repeat-dose studies
indicate that the primary targets for carfentrazone-ethyl toxicity
are the liver, kidney,
and the red blood cell
forming system. Liver toxicity in all tested
species was characterised by increased liver weight, microscopic
changes in liver cells and increases in plasma levels of liver
enzymes...
--- NOEL/ADI The lowest overall NOEL for carfentrazone-ethyl was
3 mg/kg bw/day. This NOEL was established in the 2-year rat study,
based on pigment deposition, red fluorescence and histopathological
changes in the liver of rats at the
next highest dose. A safety factor of 100 is considered appropriate
for the ADI, due to the extensive, high quality toxicology database
for carfentrazone-ethyl. This results in an ADI of 0.03 mg/kg
bw/day.
Ref:
April 2000 - Australia. Evaluation of the new active CARFENTRAZONE-ETHYL
in the product AFFINITY 400 DF HERBICIDE. National Registration
Authority for Agricultural and Veterinary Chemicals. NRA Ref.
51555.
http://www.fluorideaction.org/pesticides/carfentrazone-e.aus.2000rpt.pdf
Also
available at http://www.apvma.gov.au/publications/prscar.pdf
Spleen
(click
on for all fluorinated pesticides)
-- Short-Term Studies
In mice fed carfentrazone-ethyl at concentrations up to 20000
ppm for 28 days, decreased defecation was observed at 14000 and
20000 ppm. Blood haemoglobin concentration
was reduced in females at concentrations ¥ 4000 ppm and mean corpuscular
volume and mean corpuscular haemoglobin were reduced at the highest
concentration. Liver weight was increased in both males
and females at concentrations ¥ 8000 ppm and spleen
weights were reduced in males at the highest concentration.
-- Short-Term Studies... The body weight
of dogs (1/sex) given 1000 mg/kg bw/day carfentrazone-ethyl in
capsules for 14 days was reduced; food consumption of the female
also reduced. Mean corpuscular haemoglobin and mean corpuscular
volume were reduced. In the female, haematocrit was also reduced
with white blood cell counts and neutrophils increased. The female
had a pale kidney and the male had
reduced relative spleen and testes weights.
-- Short-Term Studies... In mice fed up to 20 000 ppm dietary
carfentrazone-ethyl for 90 days, a pink/brown staining of the
litter tray was observed at concentrations ¥ 14000 ppm. Although
red blood cell counts were increased in males at concentrations
¥ 14000 ppm, mean corpuscular volume and mean corpuscular haemoglobin
were reduced in males at concentrations ¥ 8000 ppm and in females
at concentrations ¥14000 ppm. In addition, mean corpuscular haemoglobin
concentration was reduced in females at the highest concentration.
Aspartate aminotransferase and alanine aminotransferase activities
were increased at 20000 ppm and albumin was increased in females
at concentrations ¥ 1400 ppm. Liver weights were increased at
concentrations ¥ 8000 ppm and spleen
weights were decreased in all treated females... A
NOEL was not established for this study, because a reduction in
spleen weights was observed in females at the lowest concentration
tested (1000 ppm, equivalent to 150 mg/kg bw/day)
Ref:
April 2000 - Australia. Evaluation of the new active CARFENTRAZONE-ETHYL
in the product AFFINITY 400 DF HERBICIDE. National Registration
Authority for Agricultural and Veterinary Chemicals. NRA Ref.
51555.
http://www.fluorideaction.org/pesticides/carfentrazone-e.aus.2000rpt.pdf
Also
available at http://www.apvma.gov.au/publications/prscar.pdf
Environmental (click
on for all fluorinated pesticides)
--
Plants. In terrestrial plant testing, the onion is the most
sensitive plant with regard to seedling emergence (EC25
0.009 lb/A a.i.) and the tomato is the most sensitive in
regard to vegetative vigor (EC25 0.0012 lb/a.i.). On the
basis of the NOEL's the radish and lettuce were most sensitive;
both had vegetative vigor NOEL's of 0.0004 pounds a.i./A.
Carfentrazone-ethyl is highly toxic
to aquatic plants.
Ref: US EPA Pesticide Fact
Sheet. Carfentrazone-ethyl Reason for Issuance:New Chemical
Registration Date Issued: September 30, 1998.
http://www.epa.gov/opprd001/factsheets/carfentrazone.pdf
Phototoxic
Pesticide.
Light-dependent peroxidizing herbicides
(LDPHs). US
EPA identified the herbicides Acifluorfen, Azafenidin, Carfentrazone-ethyl,
Flumiclorac-penty, Flumioxazin, Fluthiacet-methyl,
Fomesafen, Lactofen, Oxadiargyl, Oxadiazon, Oxyfluorfen,
Sulfentrazone, Thidiazimin as phototoxic
pesticides that act by inhibiting protoporphyringen
oxidase in the heme and chlorophyll biosynthetic pathway.
[10 out of the 13 pesticides that EPA identified are organofluorines].
SEE http://www.fluoridealert.org/pesticides/PHOTOTOXICITY.PAGE.htm
Ref: December 11, 2001 - US EPA. Revised
Environmental Fate and Effects Division Preliminary Risk
Assessment for the Oxyfluorfen Reregistration Eligibility
Decision Document - also at: http://www.epa.gov/oppsrrd1/reregistration/oxyfluorfen/oxyefedchap.pdf
Environmental
aspects... its major metabolites are mobile to very highly
mobile in soil and have potential to leach, though significant
downward leaching was not detected in field trials.
Ref:
April 2000 - Australia. Evaluation of the new active CARFENTRAZONE-ETHYL
in the product AFFINITY 400 DF HERBICIDE. National Registration
Authority for Agricultural and Veterinary Chemicals. NRA
Ref. 51555.
http://www.fluorideaction.org/pesticides/carfentrazone-e.aus.2000rpt.pdf
Also available at http://www.apvma.gov.au/publications/prscar.pdf
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