Body Weight Decrease - Adverse Effects
Fluorinated and Fluoride Pesticides
beginning with
A-E F-G • H-P Q-Z
 
 
• 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

PFOS - PFOS - Insecticide, US EPA List 3 Inert

Due to length, click here for effects page

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

 
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