• See Table of dramatic weight loss effects in laboratory animals exposed to fluoride and/or fluorinated pesticides.
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.
Haloxyfop-etotyl
- Herbicide - CAS No. 87237-48-7
Abstract: The developmental
toxicity of haloxyfop-ethoxyethyl-ester (87237487) (HEE) was studied
in rats. Pregnant Wistar-rats were gavaged with 5, 10, or 50mg/kg
HEE on days six to 16 of gestation. They were observed for clinical
signs of toxicity and sacrificed on gestational day 21. The uteri
were removed, examined, and the number of implantations, live
and dead fetuses, and resorption sites recorded. The live fetuses
were weighed and examined for malformations. HEE at 10 and 50mg/kg
caused vaginal bleeding in 40 and 50% of the dams, respectively.
The 10 and 50mg/kg doses significantly increased the number of
resorptions per litter and decreased the number of live fetuses
per litter. The 50mg/kg dose caused a significant
decrease in fetal weight. HEE caused a significant
dose related increase in the number of cachectic
fetuses. The proportion
of cachectic
fetuses following exposure
to 5, 10, and 50mg/kg was 2.0, 6.8, and 20.3%, respectively. Ureterohydronephrosis
was the most frequently observed soft tissue malformation, the
prevalence of this defect following the 10 and 50mg/kg doses being
42.9 and 54.8%, respectively. The 10 and 50mg/kg doses caused
skeletal malformations such as retarded ossification of the sternum
and absence of rib 13. The author concludes that haloxyfop-ethoxyethyl-ester
is embryotoxic and teratogenic. The no observable effect level
is expected to be below 5mg/kg.
Ref: Machera K (1993). Developmental Toxicity
of Haloxyfop Ethoxyethyl Ester in the Rat. Bulletin of Environmental
Contamination and Toxicology, Vol. 51, No. 4, pages 625-632. As
cited at Toxnet.
•
Definitions:
cachectic
- relating to or having the symptoms of
cachexia
cachexia - A profound and marked
state of constitutional disorder, general ill health and malnutrition.
The loss of body weight and muscle mass frequently seen in patients
with advanced diseases. Synonyms: cachexy, wasting
Haloxyfop-methyl
- Herbicide - CAS No. 69806-40-2
-- 1) 2-Year
Feeding (carcinogenicity) - mouse: Dietary levels tested:
0, 0.03, 0.065, and 0.6 mg/kg/day; B6C3F1 mice (50/sex/dose)
were administered haloxyfop-methyl in the diet for 24 months. High-dose
males exhibited a reduced body weight gain,
elevated alkaline phosphatase levels, and an increase
in relative liver weights. Histopathological observations of the
livers from high-dose males and females were characterized by an
alteration of the tinctorial staining properties of the hepatocytes.
Based on the above effects the LEL for systemic toxicity
is 0.6 mg/kg/day. The NOEL for systemic toxicity is 0.065 mg/kg/day.;
core grade minimum (Dow Chemical U.S.A., 1985c)
-- 2-Generation Reproduction - rat: Dietary levels tested: 0, 0.01,
0.65, and 1.0 mg/kg/day; Groups Sprague-Dawley rats (30/sex/dose)
were administered haloxyfop-methyl. The F0 generation was dosed
for 8 weeks and the F1 generation for 11 weeks after each generation
was mated. The only apparent effect was reduced
body weights of the offspring in the F1a litters at weaning,
at 21 days in all treatment groups, and in the 1 mg/kg/day groups
of the F1b males and females and F2a males. Although
statistically significant, the reductions are not large, amount
to 10% or less. It is questionable whether this is a true
toxic effect in all exposure groups, since it was not seen in subsequent
litters except at the high-dose. No organ weights or histopathological
examinations were performed. No maternal or reproductive toxicity
was observed at any dose tested. The LEL for developmental toxicity
is 1 mg/kg/day based on reduced weanling weight in F1a, F1b, and
F2a litters. The NOEL for developmental toxicity is 0.065 mg/kg/day.;
core grade supplementary (Dow Chemical U.S.A., 1985b)
-- 5) Developmental toxicity - rat: Dose levels tested: 0, 0.1,
1.0, 7.5, 10, and 25 mg/kg/day; Groups of pregnant Fischer 344 rats
(10/dose) were administered haloxyfop-methyl orally during days
6 through 15 of gestation. At the 7.5 mg/kg/day dose a decrease
in weight gain and food consumption accompanied by an increase
in water intake during gestation was observed. Additional maternal
toxicity was observed at 10 and 25 mg/kg/day,
including a decrease in weight gain and food consumption accompanied
by an increase in liver weight. An increase in the incidence of
resorptions was also observed at 10 and 25 mg/kg/day. At 7.5 mg/kg/day,
a significant incidence of delayed ossification of the centra of
the thoracic vertebra was observed.
The NOEL and LEL for maternal toxicity are 1 and 7.5 mg/kg/day,
respectively. The NOEL and LEL for developmental toxicity are 1
and 7.5 mg/kg/day, respectively; core grade guideline (Dow Chemical
U.S.A., 1983a)
-- 6) Developmental toxicity - rabbit: Dose levels tested: 0, 3,
7.5, and 15 mg/kg/day; Inseminated New Zealand White rabbits (Dams:
27, 28, 30, and 25 for the control, low-, mid-, and high-dose, respectively)
were administered haloxyfop-methyl by gavage on days 6 through 18
of gestation. No evidence of developmental toxicity was observed
at any dose tested. At the 7.5 mg/kg/day dose level reduced
body weight gain on days 6 to 18 was observed. Therefore
the NOEL and LEL for maternal toxicity is 3 and 7.5 mg/kg/day, respectively.;
core grade minimum (Dow Chemical Co., 1985)
-- 7) Developmental toxicity - rabbit: Dose levels tested: 0, 1.0,
7.5, and 20 mg/kg/day; Inseminated New Zealand White rabbits (30/dose)
were administered haloxyfop-methyl orally on days 6 through 18 of
gestation. At 20 mg/kg/day, 4/31 pregnant animals died between days
18 and 24 of gestation with 1/31 pregnant animals dead on day 8
of gestation. A decrease in weight gain was also observed at 20
mg/kg/day. Body weight gain at the 7.5 mg/kg/day was comparable
to controls. At 20 mg/kg/day, a significant increase in the incidence
of resorbed implantations was reported. The LEL for maternal toxicity
is 20 mg/kg/day based on dam mortality and
decreased weight gain. The NOEL for maternal toxicity is
7.5 mg/kg/day. The LEL for fetotoxicity is 20 mg/kg/day based on
the increase in resorptions. The NOEL for fetotoxicity is 7.5 mg/kg/day;
core grade guideline (Dow Chemical U.S.A., 1983b)
Ref: Health Assessment. US EPA Integrated
Risk Information System (IRIS).
http://www.fluoridealert.org/pesticides/haloxyfop.methyl.iris.htm
Hydramethylnon
- Insecticide - CAS No. 67485-29-4
-- In a subchronic
toxicity study, MRID 00061794, groups of 4 male and 4 female beagles
received gelatin capsules containing hydramethylnon at doses of
0, 3.0, 6.0, or 12.0 mg/kg/day for 91 days. None of the control
or low-dose dogs died, but 3 males and 3 females in the mid-dose
died or were sacrificed moribund between days 27 and 75, and all
high-dose dogs were sacrificed moribund between days 27 and 53.
.. Body weights in the low, mid, and high-dose
groups were decreased as much as 11%, 51%, and 34% in males; and
9%, 42%, and 37% in the females (body weight decreases were greatest
in the mid-dose dogs because they survived longer than the high-dose
dogs)... All mid and high-dose dogs were
cachectic at necropsy... The 6 mg/kg/day
dose caused lethality, as well as decreased
food consumption and body weight gain, increased SGPT,
cachexia, wasting
of muscle and subcutaneous fat, and testicular atrophy.
The LOAEL was 3 mg/kg/day (the lowest does tested) based on decreased
food consumption and body weight gain; a NOAEL was not
established.
-- In a 21-day dermal toxicity study in rabbits,
MRID 00101559, groups of 10 male and 10 female New Zealand White
rabbits received a total of 15 repeated dermal applications of
hydramethylnon at doses of 0 (control), 10, 50, or 250 mg/kg/day,
6 hours/day, 5 days/week over a three week period... Food consumption
was depressed as much as 38% and 45% in the high-dose males and
females, compared to controls. The high-dose
males and females weighed as much as 8% and 9% less than the controls...
Toxicity observed at the highest dose tested (250 mg/kg/day) included
decreased food consumption in males and females as well as thrombocytopenia
(a persistent decrease in the number of blood platelets that is
usually associated with hemorrhagic conditions) in females...
-- Chronic Toxicity and Carcinogenicity In a 6-month
study, MRID 00035529, groups of 4 male and 4 female beagles dogs
received gelatin capsules containing hydramethylnon at doses of
0, 0.33, 1.0, or 3.0 mg/kg/day for 26 weeks. The control group
received 120 mg/kg/day of lactose. No dogs died... A
high-dose male was removed from the study due to anorexia
between study days 42 and 98, and day 120 to termination.
-- In a chronic toxicity/carcinogenicity study, MRID 00101565,
groups of 50 male and 50 female Charles River CD rats were fed
diets containing hydramethylnon at dose levels of 0, 25, 50, 100,
or 200 ppm (0, 1.2, 2.4, 4.9, or 10.0 mg/kg/day in males, and
0, 1.5, 3.0, 6.2, or 12.1 mg/kg/day in females, respectively based
on food consumption) for two years... Body
weights in the males were as much as 17% less than the controls
at 200 ppm, and 5% at 100 ppm. Body weights in the females were
as much as 42% less than the controls at 200 ppm, and 22% at 100
ppm. Body weights were comparable in the other groups. Food consumption
was reduced an average of 7% in the 200 ppm males, and 16% in
the 200 ppm females. The other groups were comparable...
-- On May 28, 1998, the Agency's Cancer Peer Review Committee
concluded that the dose levels of 100 ppm in males, and 50 ppm
in females were adequate to assess the carcinogenic potential
of hydramethylnon in rats. This conclusion was based on significant
decreases in body weight at higher doses... Under the conditions
of this study, the NOAEL was 50 ppm (2.4 mg/kg/day in males, 3.0
mg/kg/day in females), and the LOAEL was 100 ppm (4.9 mg/kg/day
in males, 6.2 mg/kg/day in females) based on small, soft testes,
decreased testicular weights, and testicular atrophy in males;
and decreased body weight gain in females.
This study is classified as acceptable and satisfies guideline
requirement 83-5 for a chronic feeding/carcinogenicity study in
rodents.
-- In a carcinogenicity study, MRID 00101563, groups of 50 male
and 50 female Charles River CD-1 mice received diets containing
hydramethylnon at dose levels of 0, 25, 50, 100, or 200 ppm (0,
3.57, 6.93, 14.2, or 28.6 mg/kg/day in males, and 0, 4.45, 6.87,
17.3, or 33.1 mg/kg/day in females, based on food consumption)
for 18 months. The 200 ppm males and females were sacrificed after
55 weeks because of high mortality. Survival after 18 months at
the 50 and 100 ppm doses was 72% and 46% in males, and 66% and
46% in females (compared to control survival of 86% in males and
76% in females). Body weights in the 100
and 200 ppm groups were as much as 13% and 23% less than the controls
in males, and as much as 6% and 19% less than the controls in
females, respectively. Food consumption was reduced an
average of 14% in the 200 ppm males, and
20% in the 200 ppm females. The other groups were comparable...
-- In a prenatal developmental toxicity study, MRID 00061790,
groups of 26 pregnant female Sprague-Dawley rats were given oral
administration of hydramethylnon at doses of 0, 3, 10, or 30 mg/kg/day
on gestation days 6-15. The vehicle controls were dosed with corn
oil. The dams were sacrificed and examined on gestation day 20.
There were two maternal deaths in the high-dose, presumably due
to intubation error. The mid-dose dams weighed
as much as 8% less than the controls, and the high-dose dams weighed
as much as 16% less than the controls. Body weight gain
during the post-dosing interval (gestation days 15-20) was comparable
in all groups... Mean high-dose fetal weights
were reduced 10% for both sexes, but the other groups were
comparable... For maternal toxicity, the NOAEL was 3 mg/kg/day
and the LOAEL was 10 mg/kg/day, based on an 8% decrease
in body weight and yellowish discoloration of the fat...
For developmental toxicity, the NOAEL was 10 mg/kg/day and the
LOAEL was 30 mg/kg/day, based on decreased
mean fetal weights, increased incidence of rudimentary
structures, and increased incidence of incompletely ossified supraoccipital.
This study is classified as acceptable and satisfies guideline
requirement 83-3(a) for a developmental toxicity study in rats.
-- In a developmental toxicity study, MRID 00101558, groups of
16 impregnated New Zealand rabbits received oral administration
of hydramethylnon at doses of 0, 5, 10, or 20 mg/kg/day on gestation
days 6-18. The vehicle controls were dosed with corn oil. The
does were sacrificed and examined on gestation day 29. Two high-dose
does died during the post-treatment period of undetermined causes.
Six does aborted, 3 each in the mid and high-dose groups. Dose-related
clinical signs seen at the mid and high-dose included soft stool,
reduced amount of stool, and ano-genital matting and discharge.
The high-dose body weights were as much as 12% less than the controls
(gestation day 24). The low and mid-dose body weights were comparable,
though slightly less than the controls. The mean number of implantations,
corpora lutea, post-implantation loss, early or late resorptions,
viable fetuses, and sex distribution were comparable in all groups.
The fetal weights in the low, mid, and high-dose groups were 8%,
16%, and 25% lower than the controls; the low-dose was
within historical limits. For maternal toxicity, the LOAEL was
5 mg/kg/day based upon body weight established.
However, the incidence of soft stool, reduced amount of stool,
and body weight loss of less than 6%, at the low-dose, were not
considered adverse. At 10 mg/kg/day, ano-genital matting and discharge
was also observed, and the same findings, with increased severity,
were observed at the 20 mg/kg/day dose level. For developmental
toxicity, the NOAEL was 5 mg/kg/day and the LOAEL was 10 mg/kg/day,
based upon decreased fetal weight (16%)
mg/kg/day. The decreased fetal weight observed at the 5 mg/kg/day
was not considered to be treatment-related since the incidences
were within historical control ranges . This study is classified
as acceptable and satisfies guideline requirement 83-3(b) for
a developmental toxicity study in rabbits.
Ref:
US EPA. Reregistration Eligibility Decision (RED) Hydramethylnon.
EPA 738-R-98-023. December 1998.
http://www.fluoridealert.org/pesticides/hydramethylnon.red.1998.pdf
Indoxacarb
- Insecticide - CAS No. 173584-44-6
In an acute neurotoxicity
study in rats, alteration of some FOB (functional observational
battery) parameters (males) and in motor activity (females) were
observed at the highest dose associated with, and possibly due
to, general toxicity (reduced body weight
and body weight gain, decreased food intake, alopecia etc).
Reduced body weight gain in males,
and reduced food consumption and alopecia in females were also
observed in the mid dose. The NOAEL in this study was 25 mg/kg
bw in males and 12.5 mg/kg bw in females.
July
18, 2002: Opinion of the Scientific Committee on Plants on specific
questions from the Commission concerning the evaluation of Indoxacarb.
European Commission. Health & Consumer Protection Directorate-General.
http://www.fluorideaction.org/pesticides/indoxacarb.eu.july.18.2002.pdf
-- 90-Day oral toxicity
rodents. DPX-MP062 NOAEL = M 3.1 milligrams/ kilogram/day (mg/
kg/day) F 2.1 mg/kg/day LOAEL = M 6.0 mg/kg/ day, F 3.8 mg/kg/
day based on decreased body weight, body
weight gain, food consumption and food efficiency.
-- 21/28-Day dermal toxicity. DPX-MP062 NOAEL = 2,000 mg/kg/ day
LOAEL = < 2,000 mg/ kg/day in rats DPX-MP062 NOAEL = 50 mg/kg/
day LOAEL = 500 mg/kg/ day based on decreased
body weights, body weight gains, food consumption, and
food efficiency in F, and changes in hematology
parameters (increased reticulocytes), the spleen (increased absolute
and relative weight M only, gross discoloration), clinical signs
of toxicity in both sexes in rats.
-- Prenatal developmental in rodents. DPX-MP062 Maternal NOAEL
= 2.0 mg/kg/ day LOAEL = 4.0 mg/kg/ day based on decreased
mean body weights, body weight gains, food
consumption. Developmental
NOAEL = 2.0 mg/kg/ day LOAEL = 4.0 mg/kg/ day based on
decreased fetal weights DPX-JW062 Maternal NOAEL = 10 mg/kg/
day LOAEL = 100 mg/kg/ day based on mortality, clinical signs,
and decreased mean body weights, body weight
gains, and food consumption
Developmental NOAEL = 10 mg/kg/ day LOAEL = 100 mg/kg/ day based
on decreased numbers of live fetuses/ litter DPX-JW062
Maternal NOAEL = 1.1 mg/kg/ day LOAEL = 2.2 mg/kg/ day based
on decreased mean body weights, body weight gains, food consumption,
and food efficiency Developmental NOAEL = 1.1 mg/kg/ day
LOAEL = 2.2 mg/kg/ day based on decreased
fetal body weights
-- Prenatal developmental
in nonrodents. DPX-JW062 -
rabbits Maternal NOAEL = 500 mg/kg/ day LOAEL = 1,000 mg/kg/ day
based on slight decreases in maternal body weight gain and food
consumption Developmental NOAEL = 500 mg/kg/ day LOAEL = 1,000
mg/kg/ day based on decreased fetal body
weights and reduced ossification of the sternebrae
-- Reproduction and fertility effects.
DPX-JW062 Parental/Systemic NOAEL = 1.5
mg/kg/ day LOAEL = 4.4 mg/kg/ day based on decreased
body weights, body- weight gains, and food
consumption of F0 females, and increased spleen
weights in the F0 and F1 females Reproductive NOAEL = 6.4 mg/kg/
day LOAEL = 6.4 mg/kg/ day Offspring NOAEL = 1.5 mg/kg/ day LOAEL
= 4.4 mg/kg/ day based on decrease in the
body weights of the F1 pups during lactation.
-- Chronic toxicity rodents.
DPX-JW062 NOAEL = M 5, F 2.1 mg/kg/day LOAEL
= M 10, F 3.6 mg/kg/day based on decreased
body weight, body weight gain, and food
consumption and food efficiency;
decreased HCT, HGB and RBC at 6 months in F only
No evidence of carcinogenic potential
-- Carcinogenicity mice.
DPX-JW062 NOAEL = M 2.6, F 4.0 mg/kg/day
LOAEL = M 14, F 20 mg/kg/day based on decreased
body weight, body weight gain, and food
efficiency and clinical
signs indicative of neurotoxicity No evidence of carcinogenicity
-- DPX-MP062 No evidence of mutagenic activity at the following
concentration range: 1.56-200 [mu]g/mL; cytotoxicity
was seen at concentrations of >100 [mu]g/mL DPX-JW062 No
evidence of mutagenic activity at the following concentration
range: 0.1-50 [mu]g/mL, cytotoxicity observed
at >50 [mu]g/mL
-- Acute neurotoxicity
screening battery. DPX-MP062 NOAEL = M 100, F 12.5 mg/kg LOAEL
= M 200 mg/kg based on decreased body weight
gain, decreased food consumption, decreased forelimb grip
strength, and decreased foot splay F 50 mg/kg based on decreased
body weight, body weight gain, and food
consumption DPX-JW062
NOAEL > M 2,000 mg/ kg = F > 500 mg/kg LOAEL > M 2,000 mg/ kg
= F > 500 mg/kg based on clinical signs, decreased
body weight gains and food consumption,
and FOB effects
-- Subchronic
neurotoxicity screening battery. DPX-MP062NOAEL
= M 0.57, F 0.68 mg/kg/day LOAEL = M 5.6, F 3.3 mg/kg/day based
on decreased body weight and alopecia
Ref: Federal Register: July 18, 2002. Indoxacarb;
Pesticide Tolerance. Final Rule. Federal Register.
http://www.fluoridealert.org/pesticides/indoxacarb.fr.july.18.2002.htm
28-Day dermal toxicity
-- rats: DPX--MP062 / NOAEL = 50
mg/kg/day LOAEL = 500 mg/kg/ day based on decreased
body weights, body weight gains, food consumption, and
food efficiency in F, and changes in hematology
parameters (increased reticulocytes), the spleen (increased absolute
and relative weight M only, gross discoloration), clinical signs
of toxicity in both sexes in rats.
Ref: Federal Register: September
29, 2000. Indoxacarb; Pesticide Tolerance. Final Rule.
http://www.epa.gov/EPA-PEST/2000/September/Day-29/p25052.htm
In a 2-generation rat
reproduction study, the parental NOEL was 1.3 and 1.5 mg/kg/day
for males and females, respectively. The parental NOEL was based
on observations of reduced weight gain and
food consumption for the higher concentration groups of the F0
generation and potential treatment-related changes in spleen
weights for the higher groups of the F1 generation.
Ref: Federal Register: April 16, 1998 [Page
18912-18919]. Notice of Filing of Pesticide Petitions.
http://www.fluoridealert.org/pesticides/dpx-mp062.fr.apr16.1998.htm
Isoxaflutole
- Herbicide - CAS No. 141112-29-0
-- In a chronic toxicity
study with dogs, a LOAEL was established 453 mg/kg/day for males
and 498 mg/kg/day for females, based on reduced
weight gains compared to controls and intravascular
hemolysis
with associated
clinical chemistry and histopathological findings. The NOEL is
44.81 mg/kg/day for males and 45.33 mg/kg/day for females.
-- In a combined chronic toxicity/carcinogenicity study in rats,
evidence of systemic toxicity was observed at 500 mg/kg/day and
included: abnormal gait, limited use of limbs, lower
body weight gains and food consumption,
decreased food efficiency during the first 14 weeks of
the study, elevated cholesterol levels throughout
the 104-week study, increased absolute and relative liver weights,
and thyroid hyperplasia. Increased incidence of periacinar hepatocytic
hypertrophy, portal tract (senile) bile duct changes, focal cystic
degeneration of the liver was observed in males at 20 mg/kg/day
and greater, females at 500 mg/kg/day. Eye opacity, gross necropsy
changes in eyes, corneal lesions, degeneration of sciatic nerve
and thigh muscles was observed in males at 20 mg/kg/day and higher
doses and in females at 500 mg/kg/day. The chronic LOAEL is 20
mg/kg/day based on liver, thyroid, ocular, and nervous system
toxicity in males and liver toxicity in females. The chronic
NOEL is 2.0 mg/kg/day.
-- In a developmental toxicity study in rats, maternal toxicity
was observed at 500 mg/kg/day, manifested as an increased incidence
of salivation, decreased body weight, weight
gain, and food consumption during the dosing period. The
maternal LOAEL is 500 mg/kg/day, based on increased incidence
of clinical signs and decreased body weights,
body weight gains, and food consumption. The maternal NOEL
is 100 mg/kg/day. Developmental toxicity, observed at 100 and
500 mg/kg/day, were manifested as increased incidences of fetuses/litters
with various anomalies: growth retardations
(decreased fetal body weight; increased
incidence of delayed ossification of sternebrae, metacarpals and
metatarsals).
In addition, an increased incidence of vertebral and rib anomalies
and high incidence of subcutaneous edema were observed at 500
mg/kg/day. The incidences of these anomalies were higher than
the concurrent control values and in some cases exceeded the range
for historical controls. The LOAEL for developmental toxicity
is 100 mg/kg/day, based on
decreased fetal body weights
and increased incidences of skeletal anomalies.
The developmental NOEL is 10 mg/kg/day.
-- In a developmental toxicity study in rabbits, maternal toxicity
was observed at 100 mg/kg/day, manifested as increased incidence
of clinical signs (little diet eaten and few feces) and
decreased body weight gain and food consumption during
the dosing period. The maternal LOAEL is 100 mg/kg/day, based
on increased incidence of clinical signs, decreased
body weight gains and food consumption. The maternal NOEL
is 20 mg/kg/day. Developmental toxicity, observed at 5 mg/kg/day,
consisted of increased incidence of 27th
pre-sacral vertebrae. Additional findings noted at 20 and
100 mg/kg/day were manifested as increased number of postimplantation
loss and late resorptions, as well as growth
retardations in the form of generalized reduction in skeletal
ossification, and increased incidence of 13 pairs of ribs. At
100 mg/kg/day, an increased incidence of fetuses with incisors
not erupted was also observed. Incidences of these anomalies,
on a litter basis, were higher than the concurrent control values
and in some cases exceeded the range for historical controls.
The LOAEL for developmental toxicity is 5 mg/kg/day, based on
increased incidence of fetuses with 27th pre-sacral vertebrae.
The developmental NOEL was not established.
-- Reproductive Toxicity. In a 2-generation reproduction study
in rats, evidence of toxicity was observed in the male and female
parental rats of both generations: at 20 and 500 mg/kg/day, increased
absolute and relative liver weights associated
with liver hypertrophy was observed; at 500 mg/kg/day (HDT),
decreased body weight, body weight gain
and food consumption during premating and gestation, and
increased incidence of subacute inflammation of the
cornea of the eye
in F0 adults as well as keratitis in F1 adults were reported.
There were no other systemic effects that were attributed to treatment,
nor was there any indication, at any treatment level, of an effect
on reproductive performance of the
adults. Treatment-related effects were observed in F1 and F2 offspring:
at 20 and 500 mg/kg/day, reduction in pup survival was noted;
at 500 mg/kg/day, decrease in body weights
of F1 and F2 pups throughout lactation, increased incidence of
chronic keratitis, low incidence of inflammation of the iris,
as well as retinal and vitreous bleeding in F2 pups and weanlings
were observed. Necropsy of F1 and F2 pups culled on Day 4 revealed
an increased number of pups with no milk in the stomach and underdeveloped
renal papillae. The Systemic LOAEL is 17.4 mg/kg/day for males
and females, based upon increased liver weights and hypertrophy
and the Systemic NOEL is 1.76 mg/kg/day for males and females.
The Reproductive LOAEL is greater than 437 mg/kg/day, based on
lack of reproductive effects and the Reproductive NOEL is greater
than or equal to 437 mg/kg/day.
-- In a subchronic neurotoxicity study in rats, treatment-related
effects observed in high-dose males consisted of decreases
in body weight and body weight gain. The LOAEL was established
at 25 mg/kg/day based on significant decreases in mean hind limb
grip strength in male rats at 25 mg/kg/day (LDT) during both trials
at week 13 as well as a non-significant decrease in mean forelimb
grip strength at week 13.
Ref: US EPA. Pesticide Fact Sheet. Isoxaflutole
Reason for Issuance: Conditional Registration Date Issued: September
15, 1998.
http://www.epa.gov/opprd001/factsheets/isoxaflutole.pdf
Lactofen
- Herbicide - CAS No. 77501-63-4
Prenatal developmental--
rodents (rat)
Maternal NOAEL = 50 mg/kg/day. Maternal LOAEL = 150 mg/kg/day
based on signs of toxicity (excessive salivation, lethargy, dried
red material around the nares and inguinal regions) and statistically
significant decreases in body weight gain.
Developmental NOAEL = 50 mg/kg/day.
Developmental LOAEL = 150 mg/kg/day based on decreased
fetal weight and skeletal abnormalities (increased incidence
of bent ribs and/or limb bones) and reduced ossification of vertebral
arches.
Ref:
Sept 24, 2004. Lactofen. Pesticide Tolerance. Final Rule. Federal
Register.
http://www.fluorideaction.org/pesticides/lactofen.fr.sept.24.2004.htm
Lithium
perfluorooctane sulfonate
(LPOS) - Insecticide, Adjuvant - CAS
No. 29457-72-5
Abstract: Lithium Perfluorooctane
sulfonate (LPOS) was administered by gavage at 3, 6, or 12 mg/kg
to mated Crl:CD„BR VAF/Plus„ female rats once daily on days 6
through 15 of gestation. Body weights and clinical observations
were on days 0, 6, 9, 12, 16, 20 of gestation. Food consumption
was also measured. Cesarean sections were done on surviving animals
on day 20 of gestation, and the fetuses were removed for examination.
The dams were necropsied following sacrifice. Clear maternal toxicity
was observed in both the 6 and 12 mg/kg groups. Five out of 25
females in the 12 mg/kg group did not survive to scheduled sacrifice.
Both the 6 and 12 mg/kg groups had test material-related changes
including lower mean body weights,
body weight gains, and food consumption. Treatment at 12 mg/kg
resulted in embryolethality as evidenced by lower uterine weights,
fewer live fetuses per litter, reduced fetal
bodyweights and lower percent of live fetuses than the
control treated. There was also significant increased incidences
of cleft palate (79%), and edema (36%). Variations at this dose
included reduced ossification of bone and unossified bone. The
no-observable-effect level (NOEL) for LPOS for teratogenicity
in rats is 6 mg/kg, whereas the NOEL for maternal toxicity in
rats is 3 mg/kg.
Ref: Henwood SM et al. (1994). Developmental
toxicity study with lithium perfluorooctane sulfonate in rats.
Toxicologist 1994 Mar;14(1):162.
-- Developmental Toxicity
In the developmental study in rabbits, maternal toxicity was observed
at 1 mg/kg/day and above, based on
reduced body weight gains during
the dosing period, followed by a rebound in body weight gains
post-dosing. Developmental toxicity was observed at the highest
dose tested, 4 mg/kg/day. Effects included fetolethality, skeletal
variations (unossified skull bones, sternebrae, talus, pubis and
extra full rib) and decreased fetal
body weights. A maternal NOAEL was not established and
the maternal LOAEL was 1 mg/kg/day, based on
reduced body weight gains. The developmental NOAEL was
2 mg/kg/day.
-- In the rat developmental study, maternal toxicity was observed
at 6 mg/kg/day based on reductions in mean
body weights, mean body weight gains, food
consumption and clinical signs (hunched and few
feces in one animal). The maternal NOAEL is 3 mg/kg/day. The developmental
NOAEL is 6 mg/kg/day and the LOAEL is 12 mg/kg/day based on increased
fetolethality, lower fetal body weights,
external and soft tissue malformations, and skeletal
variations.
Ref: US EPA. New Pesticide Fact Sheet. Lithium
perfluorooctane sulfonate (LPOs). August 1999.
http://www.epa.gov/opprd001/factsheets/lithium.pdf
Mefluidide
and its potassium and diethanolamine salts - Herbicide,
Plant growth regulator - CAS Nos. 53780-34-0,
53780-36-2, 83601-83-6)
• Rat: Non-guideline range finding developmental toxicity,
gavage with diethanolamine salt of mefluidide. Developmental LOAEL:
230 mg a.i. /kg/day based on significantly decreased fetal body
weight. Developmental NOAEL: 173 mg a.i. /kg/day, The dosage levels
of 0, 50, 200 and 400 mg of the 28.78% formulation/kg/day weredefinitive
developmental study.
• Dog: A NOAEL of 1.5 mg/kg/day was selected based on chronic
toxicity (decreased body weight (15%)
and body weight gain (50%)
in the males) occurring at a LOAEL
of 15.0 mg/kg/day. This was the most sensitive
endpoint. An UF of 100X (10-fold for interspecies extrapolation,
10-fold for intraspecies variability) was applied to the NOAEL
of 1.5 mg/kg/day to derive the cRfD to give and RfD of 0.015 mg/kg/day.
• In rats and rabbits, critical effects of acute oral toxicity
occurring at doses of 100 mg/kg/day and above were tremors, hunched
posture, salivation, reduced body weight
and body weight gain.
• Mefluidide and its diethanolamine
salt subchronic and chronic toxicity are manifested
by decreased body weight and body weight gain in several
species tested (rats, rabbits and dogs). Dogs are most sensitive
to these effects, which occur at doses as low as 15 mg/kg/day
in diets fed for one year.
• Rats: The maternal toxicity included tremors, decreased
body weight, weight gain and mortality.
• In the 2-generation reproduction toxicity study, the offspring
toxicity was characterized by decreased
body weights in both sexes and both litters in all generations.
The reproductive LOAEL was not observed (NOAEL = 346/604
mg/kg bw/day).
• Evidence of maternal toxicity included transient clinical
signs (tremors, dark material around the nose, few feces, urine
stain and reddish vaginal discharge), decreased
body weight gain (11-61%)
•
At 6000 ppm, body weights were decreased by 1-8%
in males and 1-12% in females
throughout the study in the P generation, attaining
significance (p<0.05) at Week 18 in the males and Weeks
8, 18, 19, and 27 in the females. In the F1 generation at this
dose, body weights were decreased throughout
the study in the males (decr. 13-21%) and females
(decr. 10-21%), attaining significance (p<0.01) at Weeks 27,
37, and 56 in both sexes. Similarly in the F2 generation,
body weights were decreased throughout the
study in the 6000 ppm males (decr. 14-21%) and females (decr.
11-23%), attaining significance (p<0.01)
at Weeks 57, 66, and 85 in both sexes.
• Numerous absolute and relative
(to bw) organ weights in the 6000 ppm parents were significantly
(p<0.05) different from the controls, however,
none of these differences were corroborated by any macroscopic
or microscopic findings indicating these decreases were most likely
not related to treatment. Thus, it is likely that they were attributable
to decreased body weights at this dose.
Ref: USEPA.
Mefluidide - Toxicology section for the Reregistration Eligibility
Decision Document (RED) (January 31, 2007)
http://www.fluoridealert.org/pesticides/docket/EPA-HQ-OPP-2007-0431-0009.pdf
Metaflumizone
(BAS 320 I) - Insecticide
- CAS
No. 139968-49-3
--
Reproductive and developmental
toxicity. ...
a 2-generation reproduction toxicity study in Wistar
rats by oral gavage administration. Originally, the highest
dose tested (HDT) by oral gavage was 75 mg/kg b.w./day, which
induced both excessive maternal toxicity (very high incidences
of poor general health in females during premating, gestation,
and lactation; and statistically decreased
food consumption, body weights, and body weight gain) as
well as excessive developmental toxicity (statistically
impaired pup body weights and body weight gain), which
altogether resulted in high pup mortality. Consequently, a meaningful
assessment of the potential reproductive toxicity of the test
compound at this excessively toxic dose level was not possible.
Thereafter, for the next two successive parental generations of
rats, which were originally derived from the parents treated at
75 mg/kg b.w./day, the HDT was 50 mg/kg b.w./day. Subsequently,
the no observable adverse effect level (NOAEL) for parental toxicity
was 20 mg/kg b.w./day, based on the following effects for females
at 50 mg/kg b.w./day (HDT for two consecutive generations) increased
incidences of poor general health in females during premating,
gestation, and lactation; 3 of 25 dams with complete litter losses;
and statistically significantly reduced
body weights during premating, gestation, and lactation.
The NOAEL for offspring/pup toxicity was 20 mg/kg b.w./day, based
on a slight increased incidence of pup mortality at 50 mg/kg b.w./day.
Whereas the NOAEL for fertility in this study was 50 mg/kg b.w./day
(HDT for two generations), the
NOAEL for reproductive performance was considered to be 20 mg/kg
b.w./day, based on 3 of 25 dams with complete litter losses,
of which 2 of these 3 dams had indications of poor nursing
for their first generation of pups.
-- In a developmental (teratology) toxicity
study in the Wistar rat, the
results indicated that the NOAEL for maternal toxicity was 40
mg/kg b.w./day, based on statistically decreased
food consumption and body weight gains at 120 mg/kg b.w./day
(HDT). The NOAEL for fetal (prenatal) /developmental toxicity
was 120 mg/kg b.w./day (HDT).
-- Chronic toxicity. In the Sprague-Dawley
rat, treatment by oral gavage with
BAS 320 I for a 2-year chronic duration resulted in dose-related
increased incidences of hepatocellular centrilobular hypertrophy
in the livers of males and females at 60
mg/kg b.w./day and at 300/200 mg/kg b.w./day and hepatocellular
basophilic alteration in males at 60 and 300 mg/kg b.w./day.
(Note: Beginning the first day of Week 3, the dose level of the
high-dose females was lowered from 300 to 200 mg/kg b.w./day,
due to an adverse effect of -71%
decreased body weight gain as compared to controls.)
-- In the beagle dog, treatment via
gelatin capsules with BAS 320 I for a 12-month chronic duration
resulted in reduced body weight gain
and/or decreased food consumption in several dogs at 30 mg/kg
b.w./day and slightly decreased mean MCHC at 30 mg/kg b.w./day
... For BAS 320 I, the lowest NOAEL for chronic toxic effects
is 12 mg/kg b.w./day from the 12-month dog study.
-- Subchronic toxicity study with Z-Isomer.
In the Sprague-Dawley rat, treatment by oral gavage with the Z-isomer
of BAS 320 I for a subchronic (90-day) duration resulted in impaired
body weight gain only in females at the mid-dose (300 mg/kg
b.w./day) and the high-dose (1,000 mg/kg b.w./day), as compared
to controls. Several microscopic changes were observed in female
animals at these two dose levels, but all morphologic changes
were regarded to be indirect effects of the impaired
body weight gain.
Ref: October 27,
2004. Federal Register. Pesticide
tolerance petition.
http://www.fluorideaction.org/pesticides/metaflumizone.fr.oct.27.04.htm
Nissol
(also known as MNFA) - Acaricide, Insecticide - CAS
NO. 5903-13-9
--
Developmental and Reproductive Toxicity In a developmental toxicity
(teratology) study, rats of the Sprague-Dawley strain received
either 0, 100, 200, or 400 mg/kg/day norflurazon technical by
oral gavage on gestation days 6 through 15 inclusive. The maternal
toxicity NOEL was determined to be < 100 mg/kg/day, and the maternal
toxicity LEL was determined to be < 100 mg/kg/day, based on reductions
in body weight gain for the period of dosing and for the
dosing plus post-dosing period. The developmental toxicity NOEL
was determined to be > 400 mg/kg/day, and the developmental toxicity
LEL was determined to be > 400 mg/kg/day...
-- The studies examining developmental and reproductive toxicity
of norflurazon were considered by the Health Effects Division
RfD/Peer Review Committee in a meeting held March 16, 1995. Overall,
the committee concluded that treatment with norflurazon was associated
with reproductive toxicity in the form of increased pup death,
increased stillborn pups, and increased pup deaths between days
5-14 of lactation at a dose of 1500 ppm. Developmental toxicity
was not evident in treated rats, but developmental toxicity in
rabbits was evident at a dose of 60 mg/kg/day in the form of decreased
mean fetal weight, slight delays in ossification of the skull
and limbs, and an increase in the incidence of 13th ribs. These
developmental effects occurred at a dose that was maternally toxic.
Ref: US EPA REREGISTRATION ELIGIBILITY DECISION
NORFLURAZON. LIST A. CASE 0229.
http://www.fluoridealert.org/pesticides/norflurazon.red.epa.pdf
Norflurazon
- Herbicide - CAS No. 27314-13-2
--
Developmental and Reproductive Toxicity In a developmental toxicity
(teratology) study, rats of the Sprague-Dawley strain received
either 0, 100, 200, or 400 mg/kg/day norflurazon technical by
oral gavage on gestation days 6 through 15 inclusive. The maternal
toxicity NOEL was determined to be < 100 mg/kg/day, and the maternal
toxicity LEL was determined to be < 100 mg/kg/day, based on reductions
in body weight gain for the period of dosing and for the
dosing plus post-dosing period. The developmental toxicity NOEL
was determined to be > 400 mg/kg/day, and the developmental toxicity
LEL was determined to be > 400 mg/kg/day...
-- The studies examining developmental and reproductive toxicity
of norflurazon were considered by the Health Effects Division
RfD/Peer Review Committee in a meeting held March 16, 1995. Overall,
the committee concluded that treatment with norflurazon was associated
with reproductive toxicity in the form of increased pup death,
increased stillborn pups, and increased pup deaths between days
5-14 of lactation at a dose of 1500 ppm. Developmental toxicity
was not evident in treated rats, but developmental toxicity in
rabbits was evident at a dose of 60 mg/kg/day in the form of decreased
mean fetal weight, slight delays in ossification of the
skull and limbs, and an increase in the incidence of 13th ribs.
These developmental effects occurred at a dose that was maternally
toxic.
Ref: US EPA REREGISTRATION ELIGIBILITY DECISION
NORFLURAZON. LIST A. CASE 0229.
http://www.fluoridealert.org/pesticides/norflurazon.red.epa.pdf
Novaluron
- Insecticide - CAS No. 116714-46-6
-- DERMAL: 52846-038;
178971; "'Rimon' Technical: Toxicity Study by Dermal Administration
to CD Rats for 4 Weeks"; (P.B. Rees; Huntingdon Life Sciences
Ltd, Eye, Suffolk, England; Project ID. MAK/478; 9/14/98); The
skin of 5 CD rats/sex/group was treated with 0, 75, 400 or 1000
mg/kg/day of RIMON Technical (batch no. 970211/4, purity: 99.7%)
for 6 hours/day for 28 days. The test material was suspended in
1.0% (w/v) aqueous methylcellulose. No mortality resulted from
the treatment. The mean body weight
and food consumption values for the 1000 mg/kg group males
were less than those of the control animals. The
methemoglobin concentration was greater for the 1000 mg/kg males
(p<0.05) and the 400 (p<0.01) and 1000 mg/kg (p<0.001) females.
No treatment-related effects were noted in the ophthalmology,
clinical chemistry, or urinalysis. There were no treatment-related
lesions in either the gross or microscopic examinations. No adverse
effect indicated. NOEL: (Systemic) (M) 400 mg/kg/day (based
upon the lower mean body weight and food
consumption and increased methemoglobin level noted
for the 1000 mg/kg males) (F) 75 mg/kg/day (based upon increased
methemoglobin level noted for the 400 mg/kg females); (Dermal)
1000 mg/kg/day (no effect evident at the highest dose tested).
Study acceptable. (Moore, 3/20/01)
Ref: 2001. Summary of Toxicology Data for
Novaluron. California Environmental Protection Agency, Department
of Pesticide Regulation, Medical Toxicology Branch. Chemical Code
# 5754, Tolerance # 52846 3/23/01.
http://www.fluoridealert.org/pesticides/novaluron.caepa.toxtst.2001.pdf
Noviflumuron
-Insecticide - CAS No. 121451-02-3
-- “XDE-007: One-Generation Dietary
Reproduction Toxicity Study With CrossFostering in CD Rats,”
(Marty, M.S., Zablotny, C.L., Liberacki, A.B., Yano, B.L.;Toxicology
& Environmental Research and Consulting, The Dow Chemical
Company, Midland, MI; Laboratory Project Study ID: 011221; 3/23/04).
XDE -007 (97.9% pure) was fed in diet to Crl:CD (SD) IGS BR rats
(30/sex/dose) at 0, 0.5, 5 and 100 mg/kg/day continuously from
pre-mating (10 weeks) of parental generation, through breeding
(2 weeks), gestation (3 weeks) and lactation through weaning of
F1 offspring. Although designed as a 2 generation reproduction
study, it was terminated after 1 generation due to excessive F1
pup mortality at 100 mg/kg/day. Subsequently a Cross-fostering
Study was performed to determine whether the decreased survival
in pups from XDE-007 treated P1 rats resulted from in utero or
lactational exposure. Parental Systemic NOEL = 0.5 mg/kg/day (Tonoclonic
convulsions were observed in 2/30 males and 1/24 females at 100
mg/kg/day. Males had statistically significantly decreased food
consumption from day 8 until termination at 100 mg/kg. Females
had statistically significantly decreased food consumption during
lactation. Male P1 premating body weights
were statistically significantly decreased at 100 mg/kg/day. Mean
gestational body weight gain in females was statistically significantly
decreased GD 0 - 7 (but not GD 0 - 21) and lactation days
7 - 13 at 100 mg/kg/day.) Reproduction and Fertility NOEL = 0.5
mg/kg/day (P1 female gestation survival was decreased and gestation
length was increased at 100 mg/kg. Pup NOEL = 0.5 mg/kg (F1 survival
was drastically decreased throughout lactation at 100 mg/kg. Clinical
effects were increased in pups at 100 mg/kg, primarily tonoclonic
convulsions, no milk in stomach, entire litter loss and death.
Pup weights were statistically significantly
decreased at 100 mg/kg. Cross-fostering data indicate the
proximate toxicant (either XDE-007 and/or its metabolites) led
to decreased pup survival through the maternal milk and not through
exposure in utero. Possible adverse effect indicated: excessive
neonatal/pup mortality and increased tonoclonic convulsions in
pups (17/24 litters) at 100 mg/kg. These data are supplemental.
M. Silva, 7/20/04
-- REPRODUCTION, RAT. “XDE-007: Two-Generation
Dietary Reproduction Toxicity Study in CD Rats,”
(Carney, E.W., Zablotny, C.L., Liberacki, A.B., Yano, B.L.;Toxicology
& Environmental Research and Consulting, The Dow Chemical
Company, Midland, MI; 3/22/04). XDE -007 (97.9% pure) was fed
in diet to Crl:CD (SD) IGS BR rats (30/sex/dose/generation) at
0, 0.5, 5 or 25 mg/kg/day continuously from pre-mating of parental
generation 1 (P1) through weaning of offspring through 2 generations
(2 matings for P2 generation) to F2b weaning... Mean
F2a litter size was statistically significantly decreased
on lactation days 14 and 21 at 25 mg/kg. Mean
F1 pup weights were statistically significantly decreased at
25 mg/kg on lactation days 1, 14 and 21. Mean
F2a male pup weights were statistically significantly decreased
on lactation days 1 and 21 and F2a female pup weights were
decreased on lactation day 21 at 25 mg/kg. F2a
male weanlings had statistically significantly decreased body
weights, relative brain and absolute spleen
weights at 25 mg/kg. Neonates
at 25 mg/kg in both F1 and F2 generations showed tonoclonic convulsions,
as well as in 1 litter of F2a at 5.0 mg/kg. P2 females (1, 1,
5 and 7 at 0, 0.5, 5.0 and 25 mg/kg, respectively) failed
to litter, so the female is considered to be an affected sex.)
Possible adverse effects on reproduction, fertility and pup survival,
along with numerous other toxicologically relevant effects. M.
Silva, 6/18/04
Ref:
August 2005 - Summary of toxicological data. California EPA, Department
of Pesticide Regulation, Medical Toxicology Branch.
http://www.fluorideaction.org/pesticides/noviflumuron.ca.epa.2005.pdf
Nuarimol
- Fungicide - CAS No. 63284-71-9
Exposure to nuarimol
causes both acute and chronic effects. It is moderately acutely
toxic, with a WHO classification of Class III, or "slightly hazardous"
and a rat oral LD50 of 1250 mg/kg. (24) DowElanco data indicates
a single oral as well as inhalation exposure of the product caused
laboratory rats to exhibit reduced activity, clonic convulsion
(muscle contraction), ataxia (loss of balance
and coordination), labored breathing, reduced
weight gain, and coma. Laboratory animals exhibited increases
in liver weight and enzyme activity and microscopic liver cell
changes when repeatedly exposed to the product. (8) The
product is also an eye irritant. (8,16,21) As mentioned above,
EPA has concerns over the product's ability to cause cancer and
birth defects in lab animals. (10)
Ref: NEVER-REGISTERED PESTICIDES: Rejected
Toxics Join the "Circle of Poison." Greenpeace USA Pesticide Campaign
report. By Sandra Marquardt, Laura Glassman and Elizabeth Sheldon.
February 1992.
http://www.fluoridealert.org/pesticides/nuarimol.greenpeace.1992.htm
Oxyfluorfen
- Herbicide - CAS No. 42874-03-3
-- In a developmental
toxicity study (MRID 44933102),oxyfluorfen (98.0%a.i.)in 1%(w/v)methylcellulose
was administered to pregnant New Zealand White rabbits (15/dose)at
dose levels of 0,10,30,or 90 mg/kg/day by gavage on gestation
days (GDs)6 through 19. Does were sacrificed on GD 29. Two premature
deaths occurred in the control group; one female was sacrificed
in extremis on GD 20 due to an ulceration on the ventral neck
area and a second female aborted on GD 21. At 90 mg/kg,one female
was found dead on GD 28,and two other females aborted on GD 27
or GD 29; all three females displayed reduced food consumption
and fecal output from mid-gestation resulting in decreased
body weight and general thin appearance prior to death.
No treatment-related changes in body weight were noted at any
dose level tested.
-- In a developmental toxicity study (MRID 00094052),19 presumed
pregnant New Zealand White rabbits per group were administered
oxyfluorfen (26.9%ai ;Lot No.CDP 0482- 1) by gavage at dose levels
of 0 (negative control),0 (vehicle control),10,30,or 90 mg/kg/day,
on gestation days (GD)6-18,inclusive. Doses were adjusted for
per cent active ingredient. The vehicle control consisted of all
ingredients of the 25 WP formulation without the active ingredient
administered at the equivalent of a 90 mg/kg/day dose of 25 WP.
Five premature deaths and 4 abortions occurred in the 90 mg/kg/day
treatment group. Treatment related clinical signs of toxicity
consisted of anorexia and red exudate
in the cage pan at 30 and 90 mg/kg/day and hematuria and decreased
motor activity at 90 mg/kg/day of oxyfluorfen. Ulceration, erosions,
and/or petechial hemorrhages were observed at necropsy in the
stomach mucosa of 3 high-dose does which died. Body
weight gain was decreased during GD 13-18 at 30 mg/kg/day
and throughout the dosing at 90 mg/kg/day; terminal body weights
were not significantly affected at any dose level. The maternal
NOAEL is 10 mg/kg/day. The maternal LOAEL is 30 mg/kg/day based
on clinical signs of toxicity and decreased
body weight gain during treatment. Decreased
litter size and an increase in early resorptions occurred
at 90 mg/kg/day. The small number of litters (5/11 pregnant does)evaluated
precluded adequate statistical evaluation of cesarean section
data. There were no treatment-related external, visceral,or skeletal
malformations or variations observed at any treatment level. There
was no evidence for delayed fetal growth at any treatment level
compared to controls. The developmental NOAEL is 30 mg/kg/day.
The developmental LOAEL is 90 mg/kg/day
based on decreased litter size and increased early resorptions.
This study is classified acceptable/guideline and satisfies the
guideline requirements for a developmental toxicity study in rabbits.
-- Reproductive Toxicity Adequacy of data base for Reproductive
Toxicity: There is an acceptable reproductive study with 71%technical
material.The data base for reproductive toxicity is complete and
no additional studies are required at this time. Parental toxicity
included mortality, body weight decrements,
and microscopic liver and kidney lesions. The kidney lesion was
microscopic mineralization, which was not observed in other rat
feeding studies. Reproductive/offspring effects included smaller
litter size and body weight decrements on day 0 of lactation.
-- 870.3800 Reproduction and Fertility Effects -Rat Goal Herbicide
(71.4%a.i.) was administered to groups
of 25 male and 25 female Crl:CD ¨BR rats in the diet at concentrations
of 0,100,400,or 1600 ppm of active ingredient for two generations
(MRID 42014901). One litter was produced in each generation. Premating
doses for the adult F0 males were 0,7.8,30.9,and 120.0 mg/kg/day
and for the F0 females were 0,8.5,32.8,and 131.2 mg/kg/day,respectively.
Premating doses for the adult F1 males were 0, 8.9,36.4,and 146.3
mg/kg/day and for the F1 females were 0,8.9,35.7,and 151.3 mg/kg/day,
respectively. F1 pups chosen to produce the F2 litters were weaned
onto the same diets as their parents. Animals were given test
or control diet for 10 (F0)or 14 (F1) weeks then mated within
the same dose group. One high-dose F1 male was sacrificed moribund
during week 9 of treatment;treatment- related chronic pyelonephritis
secondary to pelvic mineralization was described at necropsy;
this death was attributed to treatment. No treatment-related clinical
signs of toxicity were observed in parental animals of either
generation. Several intercurrent deaths of F0 females and F1 males
and females were considered incidental to treatment. Mean body
weights,body weight gains,and food consumption by the low-and
mid-dose males and females of both generations were comparable
to their respective controls. Body weights of the high-dose F0
males were slightly (n.s.)lower than the controls throughout premating
with overall body weight gains 92%of the control level .Absolute
body weights of the high-dose F0 females were significantly (p
#0.05)less than the controls during weeks 4-7, with overall body
weight gain 88% of controls. Food consumption by the high-dose
F0 males was significantly (89-92%of control;p #0.05)less than
the controls during weeks 0,2,and 4-8 of the premating interval.
Food consumption by the high-dose F0 females was 85-94%of the
control levels during the premating period with statistical significance
(p #0.05) reached during weeks 0-6 and 8.
High-dose F1 males and females had significantly (p #0.05) lower
body weights than the controls throughout the premating
interval (84-89%and 79-93%,respectively of the controls). Overall
body weight gains were 89% and 97%, respectively, of control levels.
Food consumption was significantly (p #0.05 )less than the controls
by the high-dose F1 males during treatment weeks 0-9 and 12 and
by high-dose F1 females during weeks 0-3,5,and 8. High-dose
F0 dams had significantly (p #0.05) lower body weights than the
controls on GD 21 and on lactation day 14. Body
weights of the high-dose F1 dams were significantly (p #0.05)
less than the controls throughout gestation and on lactation
days 0,7,and 14. Body weights of the high-dose
F1 pups were significantly (78-89%of controls;p #0.05) less than
the controls throughout lactation. High-dose
F2 pups had significantly (82-89%;p #0.05)lower body weights than
the controls on lactation days 0,14,and 21.Body weight
gains by the high-dose pups of both generations were 81-85% of
the control level for lactation days 0- 14 and were 73-77%of the
control level for lactation days 14-21.Because the most pronounced
effect on pup body weight gain was after they started to eat the
test diets, the lower pup body weights are
considered a systemic effect and not a lactational effect.
-- The NOAEL for parental toxicity is 400 ppm (males:30.9 mg/kg/day;females:32.8
mg/kg/day). The LOAEL for parental toxicity is 1600 ppm (males:120.0
mg/kg/day; females:131.2 mg/kg/day) based on mortality,
body weight decrements, and microscopic kidney and liver
lesions.
Ref: August 8,2001. OXYFLUORFEN. Toxicology
Chapter for RED. Submission No.S549936. P.C.Code:111601. Tox.Chem.No.188AAA.
US EPA.
http://www.epa.gov/oppsrrd1/reregistration/oxyfluorfen/oxytoxchapter.pdf
-- Risks
to Terrestrial Organisms. The results of the risk assessment
do not suggest concern for acute risks to birds or mammals. Sub-chronic
and chronic risks to terrestrial birds and mammals present a serious
concern. These toxic effects may be manifested as reproductive,
developmental, and hemolytic consequences. The chronic LOC was
exceeded for birds in all crop scenarios and for mammals in scenarios
with the highest application rate (2 lbs ai/application). In the
bobwhite quail reproduction study, reduced chick weights were
observed, which would reduce fitness if experienced in the wild.
In the 2-generation rat reproduction study, toxic effects in adults
were mortality, decreased body weight, and liver and kidney histopathology,
and toxic effects observed in the pups were decreased body weight
and a decreased number of live pups/litter.
In three of the four developmental toxicity studies, increases
in spontaneous abortions, fetal resorptions, and fetal bone deformities
as well as decreases in litter size
were observed. Any of these effects would have an effect on the
fitness of individuals, and may have an effect on the overall
fitness of wild mammal populations exposed to oxyfluorfen.
Ref: December 11, 2001. Environmental Fate
and Effects Division's Preliminary Risk Assessment for the Reregistration
Eligibility Document for Oxyfluorfen
http://www.fluoridealert.org/pesticides/oxyfluorfen.enveffects.2001.pdf
Penoxsulam
- Herbicide - CAS No. 219714-96-2
(Pages
24-25) In a two-generation reproduction toxicity study (MRID 45830920),
XDE-638 (97.7% ai, lot #B-765-44, TSN102058) was administered
to 30 male and 30 female Crl:CD (SD) IGS BR rats/dose at dietary
concentrations that provided 0,30, 100, or 300 mg/kg/day. On litter
was produced in each generation. Fo and F1 parental animals were
administered test or control diet for 10 weeks prior to mating,
throughout mating, gestation, and lactation and until sacrifice...
Absolute body weights of the high-dose
F1 males were significantly (p≤0.05; 88-94% of controls)
less than those of the controls throughout the study...
Food consumption by the high-dose F1 males was significantly
less (p≤0.05; 92-93% of controls) than that of the
control group for the first two weeks of premating. Body weights
of the high-dose Fo and F1 dams were significantly
lower (p≤0.05; 87-94% of controls) than that of controls
from GD 21 through lactation day 14. The
most pronounced effect on body wieght gains during gestation was
for days 14-21 when the high-dose Fo and F1 dams had weight gains
79% and 82%, respectively, of the control group levels. Weight
changes by the high-dose dams during the first week of lactation
consisted of marked weight loss during days
1-4 and a lower weight gain than the controls for days
4-7.... Food consumption by the high-dose Fo dams was
significantly less (p≤0.05; 76-88% of controls) than
that of the controls on lactation days 1-11. Food consumption
by the high dose F1 dams was significantly
(p≤0.05; 70-72% of controls) less than that of the controls
on lactation days 1-7... High-dose male and female pups from both
generations had significantly lower (p≤0.05)
body weights on lactation days 4-21 compared with controls.
Ref: June 18, 2007 - Penoxsulam.
Human Health Risk Assessment for Proposed Uses on Fish and Shellfish.
Docket: EPA-HQ-OPP-2006-0076-0004. USEPA.
http://www.fluorideaction.org/pesticides/EPA-HQ-OPP-2006-0076-0004.pdf
-- Subchronic toxicity.
Dietary exposure to penoxsulam identified the
liver and/or urinary tract (kidneys and bladder) as target organs
in rats, mice, and dogs following a 4-week and 13-week administration.
Effects on the liver were reflected in increased liver weights
and hepatocellular hypertrophy, but these effects were not associated
with increases in mixed function oxidase (MFO) enzyme activity.
Effects noted in the kidneys included crystal deposition, most
likely from precipitation of penoxsulam from the urine, with resultant
irritation, inflammation, and hyperplasia of renal pelvic transitional
epithelium. Other than the crystal deposition in the kidneys,
all effects following subchronic exposure to rats appeared
to be reversible. Very high doses were associated
with significant decreases in body weight, weight gain, and feed
consumption.
-- Reproductive and developmental toxicity. Penoxsulam
did not have any effect on reproductive parameters at dose levels
that induced treatment-related effects in parental rats. At the
highest dosage tested (HDT) (300 mg/kg/day), body
weights and weight gains in both males and females were depressed,
liver and/or kidney weights were increased, and histologic
changes were noted in the liver
(males) and kidneys (females).
At 100 mg/kg/day, increased liver weights were recorded in males,
with no histologic correlate, and histologic changes noted in
the kidneys of females. Transient
decreases in pup body weights were seen at the HDT, but
dietary concentrations were targeted for adults and consumption
of treated diets by the pups resulted in dose levels to the pups
approximately 3-fold higher than in adults. A teratogenic potential
was not demonstrated for penoxsulam in either rats or rabbits.
Ref: August 6, 2003. Federal Register: August
6, 2003 (Volume 68, Number 151)] [Notices] [Page 46609-46613].
Penoxsulam; Notice of Filing a Pesticide Petition To Establish
a Tolerance for a Certain Pesticide Chemical in or on Food.
http://www.fluorideaction.org/pesticides/penoxsulam.fr.aug.6.2003.htm
Picolinafen
- Herbicide - CAS No. 137641-05-5
-- In dogs fed picolinafen
at dietary concentrations of 0, 50, 150 or 1500 ppm for 12 months
body weight gains were decreased in all
groups of treated males... Enlarged
thyroids and increased thyroid weights were observed at 1500 ppm.
Increased follicular hypertrophy in the thyroid was observed in
both sexes at 1500 ppm and hyperplasia in the thyroid was observed
in females at 1500 ppm. A NOEL could
not be established in this study since body weight gain was reduced
at all tested doses. The LOEL in this study was 50 ppm,
equal to 1.4 mg/kg bw/day in males and 1.6 mg/kg bw/day in females.
Ref: Public Release Summary on Evaluation
of the new active PICOLINAFEN in the products SNIPER HERBICIDE
& PARAGON HERBICIDE. Australia. National Registration Authority
for Agricultural and Veterinary Chemicals November 2000.
http://www.nra.gov.au/publications/prspic.pdf
Determination of Acceptable Daily Intake. The most appropriate
NOAEL of 1.4 mg/kg bw/d in the 1-year dietary study in dogs is
recommended as the basis for the acceptable daily intake (ADI).
Treatment-related findings at the lowest observed adverse effect
level (LOAEL), the next highest dose level, included lower
body weight and body-weight gain for males (approximately 20 and
48%, respectively). A safety factor of 100 to account for
intraspecies and interspecies variations was considered to be
adequate; no additional safety factors are required. The recommended
ADI is 0.014 mg/kg bw/d.
Ref:
Nov 2005 - AC 900001 (Picolinafen). Proposed Regulatory Decision
Document. PRDD2005-5. Canadian
Pest Management Regulatory Agency (PMRA).
http://www.fluorideaction.org/pesticides/picolinafen.canada.nov05.pdf
Picoxystrobin
- Fungicide
- CAS
No. 117428-22-5
--
Short term toxicity. Target / critical effect: No specific
target organ toxicity (rat, dog) Reduced
bodyweight and food consumption/ utilisation efficiency
at highest dose tested. Lowest relevant oral NOAEL / NOEL: 90-d
& 1-yr dietary, dog: 4.3 mg/kg bw/d. Lowest relevant dermal NOAEL
/ NOEL: 28-d, rat: >1000 mg/kg bw/d (limit dose)
-- Reproductive toxicity. Target / critical
effect - Reproduction: No effects on reproductive performance;
reduced body weights of offspring
at the end of the lactation period at parentally toxic doses (750
ppm). Lowest relevant reproductive NOAEL / NOEL: 2-gen, rat: >750
ppm (78.2 mg/kg bw/d), this being the highest dose tested; 200
ppm (parent rats) Target / critical effect
- Developmental toxicity: Ossification
delay and increased incidence of skeletal variants at maternally
toxic doses.
Lowest relevant developmental NOAEL / NOEL: rat: 30 mg/kg bw/day
rabbit: 25 mg/kg bw/day
-- Long term toxicity and carcinogenicity.
Target / critical effect: No significant target organ toxicity.
Reduced bodyweight and food consumption
at the highest dose tested (750 ppm). Lowest relevant NOAEL: 2-yr,
rat: 200 ppm (12.2 mg/kg bw/d). Carcinogenicity: No evidence of
carcinogenicity
-- Other
toxicological studies. o-phthalic
acid (Metabolite 15, grain): Survey of published literature
(November 2000) Acute oral LD50, rat: 7500-8400 mg/kg bw In-vitro
genotoxicity (Ames test & cytogenetic assay in CHO cells): negative.
Dominant lethal test: questionable positive test result involving
reduced male fertility and abnormal sperm morphology. Non-carcinogenic
in rats and mice according to NTP carcinogenicity programme. Reduced
foetal body weight and retarded ossification
in rats at maternal toxic doses
Ref:
July
2003 - Review report for the active substance picoxystrobin. Picoxystrobin
SANCO/10196/2003-Final. 3 June 2003. Finalised in the [European
Commission] Standing Committee on the Food Chain and Animal Health
at its meeting on 4 July 2003 in view of the inclusion of picoxystrobin
in Annex I of Directive 91/414/EEC/.
http://www.fluorideaction.org/pesticides/picoxystrobin.eu.june.2003.pdf
•
Note: This report identified o-phthalic
acid (Metabolite 15, grain)
as a "Toxicologically significant compound"
Primisulfuron-methyl
- Fungicide, Herbicide- CAS No. 86209-51-0
-- Chronic toxicity:
Doses of 125 mg/kg/day administered in the diet to dogs over a
1-year period produced decreased body weight
gain, anemia, increased liver weight,
and thyroid hyperplasia (abnormal growth) [15]. Rats fed dietary
doses of about 180 mg/kg/day over 90 days showed effects similar
to those noted in dogs, as well as spleen weight increases [24].
In another study, doses of 480 mg/kg/day in rats over 18 months
produced increased incidence of tooth disorders, chronic nephritis
(kidney damage), and testicular atrophy [4]. In two 18-month studies
in mice, testicular atrophy, chronic nephritis, and increased
tooth and bone disorders were
seen at doses of 180 mg/kg/day and 360 mg/kg/day, respectively
[4].
-- Reproductive effects: Changes in the
function of the testes were noted in rats fed high doses (250
mg/kg/day) of primisulfuron-methyl over two generations. There
was also a decrease in the body weight of
the offspring. No compound-related effects on reproduction
were noted at doses below 50 mg/kg/day [15]. Testicular atrophy
was seen in rats in chronic studies (see above), which
could result in reproductive effects. The available data suggest
that reproductive effects in humans due to primisulfuron are not
likely under normal circumstances.
Ref: E X T O X N E T Extension Toxicology
Network Pesticide Information Profiles. Revised June 1996.
http://ace.ace.orst.edu/info/extoxnet/pips/primisul.htm
Prodiamine
- Herbicide - CAS No. 29091-21-2
--
Chronic/Subchronic Toxicity Studies. Prodiamine: Liver (alteration
and enlargement) and thyroid effects (hormone imbalances) at high
dose levels (rats); decreased body weight
gains.
-- Carcinogenic Potential. Prodiamine: Benign thyroid tumors (rat).
None observed (mouse).
-- Target Organs. Prodiamine: Liver and Thyroid.
Ref: Material Safety Data Sheet for Barricade
65WG Herbicide. Novartis. February 28, 2000.
http://www.fluoridealert.org/pesticides/prodiamine.msds.2000.pdf
Prosulfuron
- Herbicide - CAS No. 94125-34-5
-- A 2-year chronic
feeding/carcinogenicity study in rats fed dosages of 0, 0.4, 7.9,
79.9 or 160.9 (males), and 0, 0.5, 9.2, 95.7 or 205.8 mg/kg/day
(females) was conducted. There was uncertain evidence of carcinogenicity
with slight increases in the incidence of
mammary gland adenocarcinomas in females at 95.7 and 205.8 mg/kg/day,
slight increase in incidence of benign testicular interstitial
cell tumors at 79.9 and 160.9 mg/kg/day (significant trend only).
A systemic NOAEL of 7.9 mg/kg/day was based on
decreased body weight and body weight gain, hematopoietic
effects (males), and possibly increased serum GGT and decreased
liver, kidney and adrenal weights (females) at 79.9 mg/kg/
day.
Ref: Federal Register: August 25, 1999.
[PF-882; FRL-6093-7]. Notice of Filing a Pesticide Petition to
Establish a Tolerance for Certain Pesticide Chemicals in or on
Food.
http://www.fluorideaction.org/pesticides/prosulfuron.fr.aug.25.1999.htm
Pyraflufen-ethyl - Herbicide - CAS
No.
129630-19-9
Developmental toxicity-
rabbit. LOAEL = 60 mg/kg/day based on decreases
in body weight and food consumption, GI observations, and
abortions.
Ref:
Federal Register: April 30, 2003. Pyraflufen-ethyl; Pesticide
Tolerance. Final Rule.
http://www.fluorideaction.org/pesticides/pyraflufen-ethy.fr.apr30.03.htm
Reproductive toxicity
Target / critical effect - Reproduction: Reduced
body weight gain of pups during lactation at parental toxic
doses. Lowest relevant reproductive NOAEL / NOEL: NOAELsyst.tox
= 1000 ppm (70.8 mg/kg bw/d) NOAELreprotox = 1000ppm ( 70.8 mg/kg
bw/d) Target / critical effect - Developmental toxicity: Implantation
loss and retardations in rabbits
at maternally toxic doses (mortality). Lowest relevant developmental
NOAEL / NOEL: 20 mg/kg bw/d
Ref: July 2, 2002 - Review report for the active substance pyraflufen-ethyl.
Finalised in the Standing Committee on Plant Health at its meeting
on 29 June 2001 in view of the inclusion of Pyraflufen-ethyl in
Annex I of Directive 91/414/EEC. SANCO/3039/99-FINAL. European
Commission Health & Consumer Protection Directorate-General.
http://www.fluoridealert.org/pesticides/pyraflufen-eth.eu.july.2002.pdf
Pyridalyl
- Insecticide - CAS No. 179101-81-6
Subchronic toxicity.
-- Pyridalyl technical was tested in rats
in a 3-month feeding study. Effects included decreased
body weight gain, altered blood biochemistry,
increased relative liver weight and histopathological changes
in the liver, ovary, adrenal and lung. The NOAEL is 100 ppm (5.56
mg/kg/day in males and 6.45 mg/kg/day in females).
-- A 13-week
feeding study in mice was
conducted. Effects included decreased body weight gain,
hematological and blood biochemical effects,increased
liver weight, decreased kidney and ovary weights and histopathological
changes in liver, kidney, ovary and adrenal. The
NOAEL is 70 ppm in males
(8.169 mg/kg/day) and 700 ppm in females (86.78 mg/kg/day).
--
A 13-week oral (capsule) toxicity study
was conducted in
dogs. Effects included decreased
body weight gain, clinical signs indicative
of respiratory distress, hematological and blood biochemistry
effects, increased liver, lung and kidney weights and histopathological
alterations of the lung, kidney, adrenal and liver. The NOAEL
was 10 mg/kg/day.
Chronic toxicity.
-- In a 104-week combined chronic/oncogenicity
study in rats,
effects included decreased body weight gain,
increased frequency of rearing (high dose
females only), hematological alterations and histopathological
alterations of the spleen.
No oncogenicity was found. The NOAEL for this study is
100 ppm (3.4 mg/kg/day in males and 4.1 mg/kg/day in females).
-- Pyridalyl was administered in the diet
to mice for
78-weeks. Effects included
decreased body weight gain
and food consumption/efficiency, and increased liver and kidney
weights. The NOAEL of the
study was 50 ppm (5.04 mg/kg/day in males and 4.78 mg/kg/day
in females)
Ref: Federal Register: December 5, 2003.
Pyridalyl; Notice of Filing a Pesticide Petition.
http://www.fluorideaction.org/pesticides/pyridalyl.fr.dec.5.2003.htm
|