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Activity: Insecticide (unclassified)

Structure for CAS Name:

Adverse Effects:
Ataxia
Blood
Body Weight Decrease
Bone
Clastogenic
Liver
Reproductive

Ataxia (click on for all fluorinated pesticides)

-- 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

Blood (click on for all fluorinated pesticides)

-- In the beagle dog, treatment by oral gavage with BAS 320 I for a subchronic duration (90-day timepoint in the chronic toxicity study) 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 cell
hemoglobin concentration (MCHC) at 30 mg/kg b.w./day. Under the conditions of the study, the NOAEL for oral administration of BAS 320 I for 90 days was 12 mg/kg b.w./day.
-- 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. Under the conditions of the study, the NOAEL for oral administration of BAS 320 I for 12 months was 12 mg/kg b.w./day.
Ref: October 27, 2004. Federal Register. Pesticide tolerance petition.
http://www.fluorideaction.org/pesticides/metaflumizone.fr.oct.27.04.htm

Body Weight Decrease (click on for all fluorinated pesticides)

-- 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

Bone (click on for all fluorinated pesticides)

-- 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

Clastogenic (click on for all fluorinated pesticides)

Genotoxicty. In a battery of three in vitro and two in vivo mutagenicity assays consisting of all required end-points (point mutation, chromosomal damage, and DNA damage and repair), the weight of the evidence for BAS 320 I indicates a lack of potential genotoxicity.
Specifically, for the battery of three in vitro mutagenicity assays with BAS 320 I, no positive responses were observed for increased revertant frequencies with and without metabolic activation bacterial reverse mutation assay or for increased mutant frequencies with and without metabolic activation Hypoxanthine guanine phophoribosyl
transferase (HGPRT) locus assay. Although there was a positive result for a statistically increased number of structurally aberrant metaphases in the chromosomes, which indicates clastogenic potential under in vitro conditions, this result was only observed without metabolic activation cytogenicity study with V79 cells.
Importantly, the potential biological significance of this apparent chromosome damage observed in vitro only without metabolic activation, was evaluated in vivo using the mouse micronucleus assay. Testing in the in vivo micronucleus study with NMRI mice was conducted at a high dose level (2,000 mg/kg b.w.) that demonstrated clinical symptoms of toxicity, including piloerection and poor general state, in 5 of 5 animals. No significant or dose-related increases in chromosomal damage were observed in this in vivo test, indicating that BAS 320 I does not cause chromosomal aberrations in intact animals.
Moreover, it has also been recognized by EPA that more weight should be placed on in vivo systems than in vitro systems as expressed in the Agency's weight of evidence for genotoxic evaluation of a chemical included in the ``Guidelines for Mutagenicity Risk
Assessment'' (Federal Register, September 24, 1986, Vol. 51: 34006-34012). Thus, the negative in vivo results (non-clastogenicity for chromosomal aberrations) observed in the mouse micronucleus assay and the rat hepatocytes assay, should override the positive results obtained in the in vitro assay only without metabolic activation. Furthermore, it has been noted that in vitro systems may simulate abnormal physiological conditions from prolonged exposure to a chemical in the absence of S-9 metabolic activation (Brusick, D.J. (editor) 1987. Genotoxicity Produced in Cultured Mammalian Cell Assay by Treatment Conditions. Mutation Research, Vol. 189, No.1: 1-69 and Sofuni, T. 1993. Japanese Guidelines for Mutagenicity Testing. Environmental and Molecular Mutagenesis, Vol. 21, No.1: 2-7). Consequently, based on the weight of the evidence presented above, BAS 320 I does not pose a genotoxic concern.
Ref: October 27, 2004. Federal Register. Pesticide tolerance petition.
http://www.fluorideaction.org/pesticides/metaflumizone.fr.oct.27.04.htm

Definitions: In vivo = In a living cell or organism. In vitro =   In an experimental situation outside the organism. Biological or chemical work done in the test tube (in vitro is Latin for "in glass") rather than in living systems.

Liver (click on for all fluorinated pesticides)

-- 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.)
Ref: October 27, 2004. Federal Register. Pesticide tolerance petition.
http://www.fluorideaction.org/pesticides/metaflumizone.fr.oct.27.04.htm

Reproductive (click on for all fluorinated pesticides)

-- 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.
Ref: October 27, 2004. Federal Register. Pesticide tolerance petition.
http://www.fluorideaction.org/pesticides/metaflumizone.fr.oct.27.04.htm