Bone - Adverse Effects
Fluorinated and Fluoride Pesticides

beginning with
A-E F-G • H-P Q-Z
 
 
See short description and defintions on bone

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

Reproductive Effects: In rats, oral doses of 10 and 50 mg/kg/day of haloxyfop-ethoxyethyl from days 6 to 16 of pregnancy reduced the number of live offspring per litter and caused vaginal bleeding in the mother (5). Teratogenic Effects: Oral doses of 50 mg/kg/day of haloxyfop-ethoxyethyl in rats between days 6 and 16 of pregnancy caused developmental abnormalities in the offspring's urogenital system and death to the fetus (5). Oral doses of 7.5 mg/kg/day of haloxyfop-methyl given to rats from days 6 to 15 of pregnancy caused delayed bone formation in the offspring (6).
Ref: EXTOXNET Pesticide Information Profile

http://pmep.cce.cornell.edu/profiles/extoxnet/haloxyfop-methylparathion/haloxyfop-ext.html

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.

Haloxyfop-methyl - Herbicide - CAS No. 69806-40-2

-- 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)
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

Decreased fetal weight was observed in the offspring of rats administered 30 mg/kg/day (LOEL). The NOEL was 10 mg/kg/day. Increased post implantation loss and decreased fetal viability were observed in the offspring of rabbits administered 15 mg/kg/day (LOEL). The NOEL was 5 mg/kg/day. Vertebral anomalies were seen in the offspring of rabbits administered 10 mg/kg/day (LOEL). The NOEL was 5 mg/kg/day.
Ref: USEPA/OPP. Support Document for the Addition of Chemicals from Federal Insecticide, Fungicide, Rodenticide Act (FIFRA) Active Ingredients to EPCRA Section 313. U. S. Environmental Protection Agency, Washington, DC (1993). As cited by US EPA in: Federal Register: January 12, 1994. Part IV. 40 CFR Part 372. Addition of Certain Chemicals; Toxic Chemical Release Reporting; Community Right-to-Know; Proposed Rule
.

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... Skeletal variations were generally comparable in all groups, although the high-dose fetuses had an increase in the incidence of rudimentary structures and \incompletely ossified supraoccipitals... At 30 mg/kg/day, a 16% decrease in maternal body weight, increased incidence of clinical signs (nasal mucus, alopecia, soft stool, staining of the ano-genital fur), yellowish discoloration of the fat, and small thymus were observed. 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.
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

-- 90-Day oral toxicity in dogs: NOAEL = 5.0 mg/kg/day nonrodents-- LOAEL = 19 mg/kg/ day based on hemolytic anemia, as indicated by decreased in HGB, RBCs; increases in platelets, increased reticulocytes; and secondary histopathologic findings indicative of blood breakdown (pigment in Kupffer cells, renal tubular epithelium, and spleen and bone marrow macrophages); increased in splenic EMH; and RBC hyperplasia in bone marrow in dogs.
-- Chronic toxicity- dogs. NOAEL = M 2.3, F 2.4 mg/ kg/day LOAEL = M 18, F 19 mg/kg/day based on decreased. HCT, HGB and RBC; increased Heinz bodies and reticulocytes and associated secondary microscopic changes in the liver, kidneys, spleen, and bone marrow; increased absolute and relative liver weights.
-- Prenatal developmental in nonrodents--rabbitts. Developmental NOAEL = 500 mg/kg/ day LOAEL = 1,000 mg/kg/day based on decr. fetal body weights and reduced ossification of the sternebrae.
Ref:
Federal Register. September 29, 2000. Indoxacarb; Pesticide Tolerance. Final Rule. http://www.fluoridealert.org/pesticides/indoxacarb.fr.sept.2000.htm

COMBINED, RAT **52425-054 162226 ”Combined Chronic Toxicity/Oncogenicity Study with DPX-JW062-106 (50% DPX-KN128, 50% DPX-KN127) Two-Year Feeding Study in Rats” (Frame, S. 835-E. I. du Pont de Nemours and Company, Haskell Laboratory, Elkton Road, Newark, Delaware, Study HLR 1174-96, 11/19/97). DPX-JW062-106 technical (Batch DPX-JW062-106, 47.5% DPX-KN128) was given in the diet daily to males at 0, 20, 40, 60, 125 or 250 ppm and females at 0, 10, 20, 40, 60 or 125 ppm for 24 months. Deaths of one female at 60 ppm and seven at 125 ppm during the first year were associated with bone marrow atrophy, splenic lymphoid depletion and thymic necrosis. Decreases in mean body weight/weight gain in males at 125 and 250 ppm and females at 60 and 125 ppm correlated with decreased food consumption. Hemolytic anemia at 60 ppm and above (males) and 40 ppm and above (females): RBC mass, hemoglobin and hematocrit were decreased and linked with increased reticulocyte counts and increased MCV. Bone marrow regenerative response was increased bone marrow hyperplasia in the one-year interim sacrifice 125 ppm females. Spleen weights were increased in both sexes at the respective high-dose levels and other non-neoplastic changes were secondary physiological responses to test substance-related hemolysis; increased pigment observed within the Kupffer cells of female livers (125 ppm) and the macrophages of the spleen (both sexes at 60 ppm and above) indicated increased RBC turnover. Increased hematopoiesis was reported in the spleen of interim sacrifice males at 125 ppm and above and in the bone marrow of high-dose males and females. After two years, secondary changes were seen in the liver, spleen, bone marrow, kidneys and thymus in high dose groups. Increased pigment was observed in the Kupffer cells of female livers at 40 ppm and above; in males, increases were noted at 250 ppm only. Increased splenic pigment was seen in all compound-treated male groups and in females at 60 ppm and above; a slight increase in splenic congestion was seen in 250 ppm males. No evidence of an oncogenic effect was reported. NOEL(M)= 40 ppm; (F)=20 ppm (M: 1.59 mg/kg/day; F: 1.04 mg/kg/day based on hemolytic anemia). Acceptable. Kellner, 1/29/99.
-- -- **52425-047 162215 “Chronic Toxicity Study of DPX-JW062-106 (50% DPX-KN128, 50% DPX-KN127) One Year Feeding Study in Dogs” (Mertens, J. 831-WIL Research Laboratories, Inc. Ashland, Ohio. Study HLO 885-96, 11/19/97). DPX-JW062-106 technical (Batch DPX-JW062- 106, 47.5% DPX-KN128) was administered orally (via the feed) to 5 Beagle dogs/sex/dose at levels of 0, 40, 80, 640 and 1280 ppm for 52 weeks. There was a treatment-related decrease in body weight, body weight gain and food consumption in 1280 ppm dogs during the first three months of the study. Reduced mean hemoglobin, RBC count and hematocrit was noted in the 80, 640 and 1280 ppm groups during all periods tested; increased Heinz bodies in these groups indicated hemolysis. Increased mean reticulocyte counts and MCV and decreased corpuscular hemoglobin concentration, erythrocyte morphologic changes and increased mean platelet counts indicated responses to hemolytic anemia. Significantly decreased RBC counts were also reported in 40 ppm males at week 25 and 51. Females at 40 ppm also showed reductions in RBC, but the differences were not statistically significant. Mean liver weights were increased in males (640 and 1280 ppm groups) and females (1280 ppm only). Microscopic changes in groups 40 ppm and above included increased pigment (hemosiderin) in liver Kupffer cells, kidney tubule epithelium, spleen and bone marrow and increased extramedullary hematopoiesis in the spleen and bone marrow hyperplasia. NOEL (M/F)=40 ppm (males: 1.1 mg/kg/day; females: 1.3 mg/kg/day based on biologically significant hemolytic anemia at 80 ppm and above). Acceptable. Kellner, 1/12/99.
-- -- ** 036; 162201; “Subchronic Oral Toxicity:90-Day Study with DPX-JW062-106 (Approximately 50% DPX-KN128, 50% DPX-KN127) Feeding Study in Dogs” (Mertens, J.J.W.M., WIL Research Laboratories, Inc., Ashland, OH, Haskell Laboratory Project ID: HLO 494-95, Performing Laboratory Project ID: WIL-189016, 11/19/97). 821. DPX-JW062 Technical (Batch No. DPX-JW062- 106, 47.5% DPX-KN128) was admixed to the feed at concentrations of 0, 40, 80, 160, or 640 ppm (0, 1, 2, 5, or 18 mg/kg/day, respectively, for males, and 0, 1, 3, 5, or 17 mg/kg/day, respectively, for females) and fed to 4 outbred beagle dogs per sex per dose level for 13 weeks. No animals died during the study interval. No treatment-related clinical signs were observed. Statistically significant and treatment-related decreases in mean red blood cell and hemoglobin levels in males at 160 and 640 ppm, and females at 640 ppm and statistically significant and dose-related increases in mean cell volume in males beginning at 160 ppm and in females beginning at 80 ppm and percent reticulocytes in males at 640 ppm and in females at 160 and 640 ppm were observed. Treatment-related increases in Heinz bodies and mean total bilirubin levels were observed in males and females at 160 and 640 ppm. Microscopic examination revealed a treatment-related increase in pigment in the spleen beginning in males at 40 ppm and in females at 80 ppm, increased extramedullary hematopoiesis in the spleen beginning in males and females at 160 ppm, treatment-related erythrocytic hyperplasia and an increase in pigment in the bone marrow in males beginning at 80 ppm and in females beginning at 40 ppm, and a treatment-related increase in pigment in the liver in males and females beginning at 80 ppm. No adverse effects. NOEL (M/F)< 1 mg/kg/day (40 ppm) (based on a treatment-related increase in pigment in the spleen in males, and on
a treatment-related increase in extramedullary hematopoiesis in the spleen, and treatment-related erythrocytic hyperplasia and a treatment-related increase in pigment in the bone marrow in females). Acceptable. (Corlett, 2/10/99)

Ref: March 11, 1999: Summary of Toxicology Data - Indoxycarb. California EPA Department of Pesticide Regulation, Medical Toxicology Branch.
http://www.fluorideaction.org/pesticides/indoxacarb.ca.epa.1999.pdf

The haemosiderin deposits in spleen and liver, and spleen and bone marrow hyperplastic response should be considered to be secondary physiological responses to the increased RBC turn over. The very shallow dose-response curve also indicates that the compensatory mechanism of the haemopoietic system was not overcome (except at high doses in the dog) and the effect of indoxacarb in rats and dogs can be described as a compensated haemolytic effect.
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

Developmental studies conducted in rats and rabbits demonstrated that the rat was more susceptible than the rabbit to the maternal and fetal effects of DPX- MP062. Developmental toxicity was observed only in the presence of maternal toxicity. The NOAEL for maternal and fetal effects in rats was 2 mg/kg/day based on body weight effects and decreased food consumption at 4 mg/kg/day. The NOAEL for developmental effects in fetuses was >4 mg/kg/day. In rabbits, the maternal and fetal NOAELS were 500 mg/kg/day based on body weight effects, decreased food consumption in dams and decreased weight and delayed ossification in fetuses at 1,000 mg/kg/day.
Ref: Federal Register: January 25, 2002 [Page 3700-3706]. Notice of Filing a Pesticide Petition to Establish a Tolerance for a Certain Pesticide Chemical in or on Food
http://www.fluoridealert.org/pesticides/dpx-mp062.fr.jan.25.2002.htm

Isoxaflutole - Herbicide - CAS No. 141112-29-0

-- 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.
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). 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.
-- Rat Developmental Toxicity Study. LOAEL = 150 mg/kg/day based on decreased fetal weight and skeletal abnormalities.
Ref: Sept 24, 2004. Lactofen. Pesticide Tolerance. Final Rule. Federal Register.
http://www.fluorideaction.org/pesticides/lactofen.fr.sept.24.2004.htm

Developmental toxicity-- Rats. Pregnant rats were administered oral doses of 0, 15, 50 and 150 mg/kg/day Lactofen Technical on days 6- 19 of gestation. Maternal toxicity (death, abortion and reduced body weight gain) was observed at 150 mg/kg/day. Developmental toxicity (reduced fetal weight, slightly reduced ossification, bent ribs and bent limb bones) was also observed at 150 mg/kg/day. The NOEL for this study was 50 mg/kg/day."
Ref: Federal Register, February 25, 1998. [PF-789; FRL-5767-5]

http://www.fluoridealert.org/pesticides/lactofen.fr.feb.1998.htm

Lithium perfluorooctane sulfonate (LPOS) - Insecticide, Adjuvant - CAS No. 29457-72-5

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 Factsheet. Lithium Perfluorooctane sulfonate (LPOS). August 1990. EPA-730-F-99-009.
http://www.fluoridealert.org/pesticides/lithium.per..epa.facts.1999.pdf

Abstract (rat): Lithium Perfluorooctane sulfonate (LPOS) was administered by gavage at 3, 6, or 12 mg/kg to mated Crl:CDĄBR VAF/PlusĄ 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: Toxicologist 1994 Mar;14(1):162; Developmental toxicity study with lithium perfluorooctane sulfonate in rats; by Henwood SM, Costello AC, Osimitz TG

Abstract (rabbit): Lithium perfluorooctane sulfonate (LPOS) was administered by gavage at 1, 2, or 4 mg/kg to mated New Zealand White female rabbits once daily on Days 7 through 19 of gestation. Body weights and clinical observations were made on Days 0, 7, 10, 13, 16, 20, 24, and 29 of gestation. Cesarean sections were done on surviving animals on Day 29 of gestation, and the fetuses were removed for examination. The does were necropsied following sacrifice. Treatment at the 4-mg/kg level resulted in abortions; premature deliveries; and lower mean body weights, lower body weight gains, and lower gravid uterine weights than those of the control groups. Cesarean sections revealed a treatment-related increase in postimplantation losses at the 4-mg/kg level. Mean fetal body weight (mean = 10.01 g, n = 11) at the 4-mg/kg level was lower than that of controls (mean = 39.93 g, n = 16) and represents developmental toxicity. Fetal morphological examinations disclosed no evidence of teratogenicity of LPOS in rabbits at any level. There were increased incidences of unossified skeletal structures at the 2- and 4-mg/kg levels. These variations along with the lower fetal body weights suggest retarded development at the 4-mg/kg level. The no-observable-effect level of LPOS for developmental toxicity in rabbits is considered to be 2 mg/kg.
Ref: Henwood SM et al. (1994). Developmental toxicity study with lithium perfluorooctane sulfonate in
rabbits. Teratology 1994 May;49(5):398.

 Metaflumizone (BAS 320 I) - Insecticide - CAS No. 139968-49-3

-- In a developmental (teratology) toxicity study in the Himalayan rabbit, the results indicated that the NOAEL for maternal toxicity was 100 mg/kg b.w./day, based on several clinical symptoms of toxicity (including ataxia and poor general state) occurring in 4 of 25 does at 300 mg/kg b.w./day, for which 2 of these 4 does had abortions prior to being sacrificed early, with a third doe at 300 mg/kg b.w./day being sacrificed moribund. Similarly, the NOAEL for fetal (prenatal)/ developmental toxicity was 100 mg/kg b.w./day, based on slightly decreased mean fetal body weights as well as an increased rate for a certain skeletal variation, namely incomplete ossification of sternabrae.
Ref: October 27, 2004. Federal Register.
Pesticide tolerance petition.
http://www.fluorideaction.org/pesticides/metaflumizone.fr.oct.27.04.htm

Norflurazon - Herbicide - CAS No. 27314-13-2

For females (13-50 years) population subgroup, the acute No Observed Adverse Effects Level (NOAEL) of 10 mg/kg/day was established based on increased incidence in skeletal variations observed in the developmental toxicity study in rabbits at the Lowest Observed Adverse Effect Level (LOAEL) of 30 mg/kg/day... The FQPA safety factor to account for the enhanced sensitivity of infants and children be reduced to 3X based on increased incidence in skeletal variations observed in the developmental toxicity study in rabbits. This determination is based on the following: the toxicity database is adequate; the development toxicity studies in the rat and rabbit are acceptable as an multi-generation study; a developmental neurotoxic study is not required because there is no indication of increased susceptibility in young rats to norflurazon exposure; and there are currently no residential uses for norflurazon. The FQPA safety factor is applicable to only females 13-50 population subgroup for acute dietary risk assessment.
Ref: US EPA May 31, 2002. Tolerance Reassessment Progress and Risk Management Decision.

http://www.fluoridealert.org/pesticides/norflurazon.tred.may31.2002.pdf

A developmental toxicity study was conducted in New Zealand White rabbits, which received either 0, 10, 30, or 60 mg/kg/day norflurazon technical by oral gavage on gestation days 7 through 19 inclusive... The developmental toxicity NOEL was determined to be 30 mg/kg/day, and the developmental toxicity LEL was determined to be 60 mg/kg/day, based on statistically significant increases in the fetal incidence of incompletely ossified frontal bones, 16 caudal vertebrae, unossified first metacarpal, unossified middle phalanx of the fifth digit of the forelimb, and unossified proximal epiphysis of the tibia at the 60 mg/kg/day dose level.
Ref: US EPA Reregistration Eligibility Decision: Norflurazon. http://www.fluoridealert.org/pesticides/norflurazon.red.epa.pdf

-- A nine-month oral toxicity study (MRID 00091056) was conducted using the F generation of rats from a two-year carcinogenicity study (MRID 00082019). In this study, rats were given technical norflurazon in the diet at dose levels of 0, 125, 250, or 500 ppm (0, 6.25, 12.5, and 25 mg/kg/day) for 39 weeks. There were no significant effects of norflurazon on survival, body weight, body weight gain, food consumption, food efficiency, hematology, or clinical chemistry in male or female rats at any dose level tested. At 500 ppm, liver weight was increased by 14% and 23% in male and female rats respectively, at 39 weeks. Kidney weight was not significantly affected, but the incidence of hyaline pigment deposition (many tubules) in male rats and hyaline pigment deposition (few tubules) in female rats was increased, as was the incidence of medullary congestion in high dose female rats... (guideline: non-guideline study; classified as core supplementary; MRID 00091056).
-- 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. Developmental toxicity was suggested at the 400 mg/kg/day dose level in the form of an increase in bipartite thoracic vertebrae (10th-13th) and an increase in rudimentary 14th ribs. However, these increases were not statistically significant and are believed to be secondary to maternal effects at the high dose (guideline 83-3; MRID 00063621).
-- A developmental toxicity study was conducted in New Zealand White rabbits, which received either 0, 10, 30, or 60 mg/kg/day norflurazon technical by oral gavage on gestation days 7 through 19 inclusive. The maternal toxicity NOEL was determined to be 30 mg/kg/day, and the maternal toxicity LEL was determined to be 60 mg/kg/day, based on decreased body weight gain and clinical toxicity (abortion) at this dose level. The developmental toxicity NOEL was determined to be 30 mg/kg/day, and the developmental toxicity LEL was determined to be 60 mg/kg/day, based on statistically significant increases in the fetal incidence of incompletely ossified frontal bones, 16 caudal vertebrae, unossified first metacarpal, unossified middle phalanx of the fifth digit of the forelimb, and unossified proximal epiphysis of the tibia at the 60 mg/kg/day dose level. A 12% decrease in mean fetal weight was also observed at the 60 mg/kg/day dose level (guideline 83-3; MRID 00131151 and 00131152).
-- 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.
-- Toxic Endpoints of Concern Identified for Use in Risk Assessment. The Health Effects Division's (HED) Less than Lifetime Committee selected the following toxicology endpoints for use in risk assessment for norflurazon (Toxicology Endpoint Selection Document, 4/21/95): The endpoint selected for the acute dietary risk assessment is a NOEL of 30 mg/kg/day. This is the developmental NOEL based on increased skeletal variations observed at the dose of 60 mg/kg/day in a rabbit developmental toxicity study.
Ref: US EPA REREGISTRATION ELIGIBILITY DECISION NORFLURAZON. LIST A. CASE 0229.

http://www.fluoridealert.org/pesticides/norflurazon.red.epa.pdf

Noviflumuron -Insecticide - CAS No. 121451-02-3

-- “XDE-007: 90-Day Dietary Toxicity Study with 28-Day Recovery in Beagle Dogs,” (Stebbins, K.E., Thomas, J., Baker, P.C.; Toxicology & Environmental Research and Consulting, The Dow Chemical Company, Midland, MI; Laboratory Project Study ID #: 011194; 5/9/03). XDE-007 (98.4% pure) was fed in diet to Beagle dogs (4/sex/dose) for 90 days at 0, 0.003, 0.3 or 3.0% (equivalent to 0, 0.913, 115 and 1040 mg/kg/day - Males and 0, 1.06, 113 and 1150 mg/kg/day - females). Recovery groups (4/sex/dose) were fed XDE-007 in diet at 0 or 3% for 90 days, then were maintained on control diet for 28 days. ... There was an increased incidence in bone marrow hyperplasia (erythroid cell) at > 0.3% XDE-007 in the main dose group that persisted after recovery.
-- “XDE-007: One-Year Dietary Toxicity Study in Beagle Dogs,” (Stebbins, K.E., Day, S.J., Thomas, J.; Toxicology & Environmental Research and Consulting, The Dow Chemical Company, Midland, MI; Laboratory Project Study ID #: 142640; 3/5/04). XDE-007 (97.9% pure) was fed in diet to Beagle dogs (4/sex/dose) for 1 year at 0, 0.003, 0.03 or 0.225% (equivalent to 0, 0.74, 9.3 and 69 mg/kg/day - Males and 0, 0.94, 8.7 and 70 mg/kg/day - females)... There was an increased incidence in bone marrow erythroid hyperplasia (erythroid cell) at > 0.3% XDE-007 (males, 0, 0, 4, 4 --each dose level) and at 0.225% (females: 0, 0, 0, 1 --each dose level).
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

Oxyfluorfen - Herbicide - CAS No. 42874-03-3

-- Renal toxicity was most severe in the 2-generation reproduction study in rats,in which pelvic mineralization occurred.Other studies had indications of renal toxicity:increases in organ weight and occasional histopathological observations.
-- In a developmental toxicity study (MRID 41806501),oxyfluorfen (71.4%), was administered by gavage to pregnant Crl:CD BR rats from gestation days 6-15.There were 27 rats/group.Doses were 0,18,183,or 848 mg/kg/day (adjusted for analytical results).... There were 12 litters in the mid-dose group with skeletal malformations which included bent scapula,fused sternebrae,and bent bones in hindlimbs and forelimbs compared to 0 litters in the control group with skeletal malformations. The NOAEL for maternal toxicity is 18 mg/kg/day;the maternal LOAEL is 183 mg/kg/day based on clinical signs (red vaginal discharge,soft feces,scant feces). The NOAEL for developmental toxicity is 18 mg/kg/day.The LOAEL for developmental toxicity is 183 mg/kg/day based on increased early resorptions,decreased fetal weight,and increased incidence of fetal visceral and skeletal variations and malformations.
-- 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.
tudy which would not meet current guideline requirements.The study was,however,adequate to determine a NOAEL value.
... 90-Day Oral Toxicity -Mouse In a 3-month dietary toxicity study (MRID 00117602),Goal (72.5% ) was administered to Charles River CD-1 mice (15/sex/group)at dietary concentrations of 0,200,800,or 3200 ppm for 13 weeks.Doses were equivalent to 0,32.0,134.5,or 490.5 mg/kg/day in males and 0,44.4, 166.6,or 520.9 mg/kg/day in females... Bone marrow hyperplasia was present in low-dose males and mid-and high-dose males and females.Vacuolation of the adrenal cortex was present in high-dose females.Thymic atrophy occurred in high-dose males and females.
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

PFOS - PFOS - Insecticide, US EPA List 3 Inert

Due to length, click here for effects page


Picolinafen - Herbicide - CAS No. 137641-05-5

-- In a developmental study, picolinafen was given to rabbits by oral gavage at 0, 5, 20 or 50 mg/kg bw/day on days 6-28 of gestation... The number of resorptions was slightly increased at 50 mg/kg bw/day and an increased incidence of fused sternal centra was observed in foetuses at 50 mg/kg bw/day. The NOEL for maternal toxicity in this study was 5 mg/kg bw/day and the NOEL for embryotoxicity and foetotoxicity was 20 mg/kg bw/day.
-- -- Picolinafen was given to pregnant rats by oral gavage at 0, 100, 500 or 1000 mg/kg bw/day on days 6 to 19 of gestation... The incidence of bipartite ossification in the thoracic vertebrae in foetuses at 1000 mg/kg bw/day was increased, but no other alterations were observed. Since a NOEL for maternal toxicity was not established in this study, a follow-up study using 0, 5, 25 or 50 mg/kg bw/day was conducted. No treatment-related effects were observed on dams or on foetal development... In a developmental study, picolinafen was given to rabbits by oral gavage at 0, 5, 20 or 50 mg/kg bw/day on days 6-28 of gestation. Soft or liquid faeces were observed at 50 mg/kg bw/day and body weight gain and food consumption were reduced at 20 and 50 mg/kg bw/day... The number of resorptions was slightly increased at 50 mg/kg bw/day and an increased incidence of fused sternal centra was observed in foetuses at 50 mg/kg bw/day. The NOEL for maternal toxicity in this study was 5 mg/kg bw/day and the NOEL for embryotoxicity and foetotoxicity was 20 mg/kg bw/day.
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

Histopathological findings were generally characterized by increased incidence/severity of hemosiderin deposition in the spleen and/or Kupffer cells of the liver and extramedullary hematopoiesis in the spleen and/or liver. Under normal physiological conditions a certain amount of hemosiderin deposition is routinely observed in the spleen due to normal breakdown of effete red blood cells; however, for all species tested, increased incidence/severity were noted for both sexes at the higher dose levels. The increased incidence/severity of extramedullary hematopoiesis was most likely a compensatory response to the increased hemolysis of red blood cells noted for all species tested. Other histopathological findings associated with regenerative hemolytic anemia included increased erythropoietic activity in the bone marrow and liver at higher doses. This was noted in rats following 28-day dietary administration at 1000 ppm and was indicated by a change in the myeloid:erythroid ratio from 2:1 in the controls to 1:1 in rats at 1000 ppm. For males, this shift to a more immature, stronger population of red cells at 1000 ppm was considered to account for the slight but significant decrease in erythrocyte osmotic fragility. For females, this correlated with an increased incidence of erythropoiesis in the bone marrow (femur/joint and sternum).
Ref: February 17, 2003 - Canada. Picolinafen. Regulatory Note REG2003-02. Alternative Strategies and Regulatory Affairs Division, Pest Management Regulatory Agency.
http://www.fluorideaction.org/pesticides/picolinafen.canada.feb.2003.pdf

Picoxystrobin - Fungicide - CAS No. 117428-22-5

-- 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
-- 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"

Potassium bifluoride - Wood preservative - CAS No. 7789-29-9

Chronic exposure may cause mottling of teeth and bone damage (osteosclerosis) and fluorosis. Symptoms of fluorisis include brittle bones,weight loss, anemia, calcified ligaments, general ill health and joint stiffness.
Ref: POTASSIUM BIFLUORIDE. Material Data Safety Sheet.
http://www.kingwaychem.com/MSDSflu7.html

Ingestion: May cause osseous fluorosis (increased radiographic density of the bones). May cause kidney damage, asthma and symptoms resembling rheumatism. Target Organ Effects: Chronic ingestion may cause kidney damage.
Ref: Material Safety Data Sheet for Potassium Hydrogendifluoride [synonym]. LA-CO INDUSTRIES, Inc./Markal Co. Product Name: SILVER BRAZING FLUX PASTE Revision #: 1.5 Date Prepared: March 1, 1995. Date Revised: August 6, 2002.
http://www.fluorideaction.org/pesticides/potassium.bifluoride.msds.pdf

Potassium fluorosilicate - Insecticide, Wood Preservative - CAS No. 16871-90-2

Title: [Potassium hexafluorosilicate]
Source: English/French versions: Internet documents, 1999. Spanish version: Instituto Nacional de Seguridad e Higiene en el Trabajo, Ediciones y Publicaciones, c/Torrelaguna 73, 28027 Madrid, Spain, 1991. 2p. Illus.
Abstract: International Chemical Safety Card. Exposure routes: inhalation and ingestion. Short term exposure effects: irritation of the skin, eyes and respiratory tract; effects on the calcium metabolism, resulting in cardiac disorders and impaired function. Long-term exposure effects: effects on the bone, resulting in fluorosis. Threshold limit value: 2.5mg/m3 (TWA) as fluorine (ACGIH 1997-1998).
Ref: Toxline at Toxnet.

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].
-- Teratogenic effects: No teratological effects were seen in offspring of rabbits given doses of up to 600 mg/kg/day. In one study of rats, delayed skeletal development and lack of ossification was seen in offspring of pregnant rats given doses of 500 mg/kg/day, while in another, 100 mg/kg/day produced incomplete ossification of the pubic bone [15]. The available evidence suggests that primisulfuron-methyl is not teratogenic except at very high doses.
-- Organ toxicity: Target organs identified in animal studies include the liver, kidneys, spleen, and testes, as well as the skeleton.
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

-- Acute toxicity. For acute dietary risk assessment, the Agency used a NOEL of 100 mg/kg/day, based on delayed or absent ossification effects in fetuses at the LEL of 500 mg/kg/day, from the oral developmental study in rats. This risk assessment will evaluate acute dietary risk to the population subgroup of concern, females 13+ years of age... Acute risk. The finding of developmental effects in the rat study absent ossification required that an acute dietary risk assessment be performed for females 13+ years of age. The calculated MOE of 71,000 demonstrated that acute pre-natal developmental risks were below EPA's level of concern.
Ref: Federal Register: December 17, 1997.Primisulfuron-methyl; Pesticide Tolerances for Emergency Exemptions. Final Rule.
http://www.fluoridealert.org/pesticides/primisulfuron-methyl.fr.97.htm

Prosulfuron - Herbicide - CAS No. 94125-34-5

-- Reproductive toxicity. Developmental toxicity: Skeletal variations (rat) and resorptions (rabbit) at maternal toxic doses. Lowest relevant developmental NOAEL / NOEL: NOAEL = 10 mg/kg b.w./day (rabbit)
Ref: July 2, 2002 - Review report for the active substance prosulfuron. European Commission Health & Consumer Protection Directorate-General.

 
Fluoride Action Network | Pesticide Project | 315-379-9200 | pesticides@fluoridealert.org