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Activity: Insecticide (Benzoylurea)
Structure:

Adverse Effects:
Blood
Body Weight Decrease
Bone
Brain
Cancer: LIVER, LUNG
Endocrine: Adrenal
Endocrine: Testicular
Endocine: Uterine
Eye
Kidney
Liver
Lung
Reproductive
Spleen
Stomach
Teratogen
Environmental: highly toxic to freshwater invertebrates

Blood and Cholesterol (click on for all fluorinated pesticides)

-- “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)... Both sexes at > 0.225% had statistically significantly increased mean platelet count. There was a significant increase in ALP at 0.225% in females at 3 and 12 months.
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

-- 007; 186499; "XDE-007: 28-Day Dietary Toxicity Study in CD-1 Mice" (Yano, B.L. and Day, S.J., Toxicology & Environmental Research and Consulting, The Dow Chemical Company, Midland, MI, Laboratory Project Study ID 001248, 6/12/01). XDE-007 (Lot, Reference No. F0031-148, TSN102332, purity = 98.4%) was admixed to the feed and fed to 5 CD-1 mice per sex per dose at dose levels of 0, 10, 100, 500, or 1000 mg/kg/day (0, 10.8, 110, 538, 1060 mg/kg/day, respectively for males and 0, 11.2, 113, 504, 1140 mg/kg/day, respectively for females) for 28 days. No mortalities occurred. No treatment-related clinical signs were observed. Treatment-related increases in mean platelet level and mean cholesterol level were observed in both sexes at 100, 500, and 1000 mg/kg/day. A treatment-related increase in mean relative liver weight was observed at in males at 100, 500, and 1000 mg/kg/day and in females at 500 and 1000 mg/kg/day. Microscopic examination revealed treatment-related hepatocellular hypertrophy with altered tinctorial properties (centrilobular/midzonal to panlobular) in males at 500 and 1000 mg/kg/day and very slight vacuolation (consistent with fatty change) of the periportal hepatocytes in males at 500 and 1000 mg/kg/day and in females at 1000 mg/kg/day. No adverse effects. NOEL (M) = 10.8 mg/kg/day and NOEL (F) = 11.2 mg/kg/day (based on increases in mean platelet and mean cholesterol levels). Supplemental (because only 5 animals per sex per dose were used and because the animals were treated for only 28 days). (Corlett, 9/30/02)
Ref: September 26, 2002. Summary of Toxicology Data for Noviflumuron ((XDE-007) or N-(((3,5-dichloro-2-fluoro-4-(1,1,2,3,3,3-hexafluoropropoxy)phenyl)amino)carbonyl)-2,6- diflurobenzamide. California EPA, Department of Pesticide Regulation, Medical Toxicology Branch.
http://www.fluoridealert.org/pesticides/Noviflumuron.CA.EPA.2002.pdf

Body Weight Decrease (click on for all fluorinated pesticides)

-- “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

Bone (click on for all fluorinated pesticides)

-- “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

Brain (click on for all fluorinated pesticides)

-- 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. . ... . 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
-- “XDE-007: Two-year Dietary Chronic Toxicity/Oncogenicity and Chronic Neurotoxicity Study in Fischer 344 Rats,” (Yano, B.L., Dryzga, M.D., Thomas, J.; Toxicology & Environmental Research and Consulting, The Dow Chemical Company, Midland, MI; Laboratory Project Study ID: 011168; 4.22.05). Noviflumuron ((N-[3,5-dichloro-2-fluoro-4(1,1,2,3,3,3-hexafluoropropoxy)phenyl]-N’-(2,6-difluorobenzoyl)urea; XDE-007, 97.9% pure) was fed in diet to Fischer 344 rats (75/sex/dose) for 90 days, 1 or 2 years at 0, 0.1, 1.0, 75 or 300 mg/kg/day. Subchronic toxicity was assessed after 90 days of treatment on 10/sex/dose at 0 and 1.0 mg/kg/day doses only. At 1 year,10/sex/dose (chronic toxicity group), and 5/sex/dose (chronic neurotoxicity group) were necropsied. The remaining 50/sex/dose were necropsied after 2 years (oncogenicity group). Chronic NOEL = 1.0 mg/kg/day (At > 75 mg/kg/day there were decreased body weights and body weight gains along with increases or decreases in absolute and/or relative organ weights (liver, kidney, brain, heart, adrenal, testes, spleen, epididymides were affected) at 12 and/or 24 months.
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

-- 52905-009 186501, "XR-007: Whole Embryo Culture Teratogenicity Screen", (E. W. Carney, Health and Environmental Research Laboratories, The Dow Chemical Company, Midland, MI, Report # 971083, 31 July 1997). Seven non-pregnant female rats (serum donors) received 1000 mg/kg/day of the test article (XR-007, 98%) in 0.5% Methocel by gavage for 3 consecutive days. Four hours after the last dose, rats were exsanguinated and their blood centrifuged to obtain serum. Six control rats were similarly treated with vehicle and bled... Statistically significant increases in crown-rump length and somite number for treated embryos were reportedly due to a lower than usual growth rate in control embryos. Morphological abnormality was limited to an abnormal curvature of the anterior neural tube which distorted the head in one treated embryo (8.3%). No historical control data. This is supplemental information. (Green and Gee, 10/3/02).
Ref: September 26, 2002. Summary of Toxicology Data for Noviflumuron ((XDE-007) or N-(((3,5-dichloro-2-fluoro-4-(1,1,2,3,3,3-hexafluoropropoxy)phenyl)amino)carbonyl)-2,6- diflurobenzamide. California EPA, Department of Pesticide Regulation, Medical Toxicology Branch.
http://www.fluoridealert.org/pesticides/Noviflumuron.CA.EPA.2002.pdf

[Note from FAN- some definitions:
"Predominately anterior neural tube defects, occuring early in gestation. The anterior neural tube fails to close properly, or does not divide into two hemispheres. The generic name for this category of malformations is arrhinencephaly. Ref: Developmental and Perinatal Disorders of the CNS. Weill Medical College of Cornell University. http://edcenter.med.cornell.edu/CUMC_PathNotes/Neuropathology/Neuropath_II/dev2.html
-- "... trisomy 13 is closely linked to midline malformations, including arrhinencephaly, agenesis of the corpus callosum, and holoprosencephaly, and is the single most common chromosomal defect underlying holoprosencephaly." - http://128.100.71.82/neurosurgery/developmental.html
-- "Trisomy 13 Syndrome is a genetic disorder with onset before birth. It occurs approximately 1/5000 live births. Infants affected with Trisomy 13 tend to be small at birth. Spells of interrupted breathing (apnea) in early infancy are frequent, and mental retardation is usually severe. Many affected children appear to be deaf. A moderately small head (microcephaly) with sloping forehead, wide joints and openings between parietal bones of the head are present. Gross anatomic defects of the brain, especially failure of the forebrain to divide properly (holoprosencephaly) are common. A hernial protrusion of the cord and its meninges through a defect in the vertebral canal (myelomeningocele) is found in almost 50% of cases. The entire eye is usually small (microphthalmia), and a defect of the iris tissue (coloboma), and faulty development of the retina (retinal dysplasia) occur frequently. The supraorbital ridges are shallow and palapebral fissures are usually slanted. Cleft lip, cleft palate, or both are present in most cases. The ears are abnormally shaped and unusually low-set." -
http://www.trisomy.org/html/trisomy_13_facts.htm

Cancer (click on for all fluorinated pesticides)

“XDE-007: 18-Month Oncogenicity Study in CD-1 Mice,” (Johnson, K.A.; Toxicology & Environmental Research and Consulting, The Dow Chemical Company, Midland, MI; 4/25/05). XDE-007 technical (N-[3,5-dichloro-2-fluoro-4-(1,1,2,3,3,3hexafluoropropoxy)phenyl]-N’-(2,6-difluorobenzoyl)urea), 97.9% pure) was fed in diet to CD-1 mice (50/sex/dose) at 0, 0.5, 3 (males only), 30 and 100 (females only) mg/kg/day for up to 18 months. Systemic NOEL = 3 mg/kg/day (males) and 30 mg/kg/day (females) There was an increase in mortality for females at 100 mg/kg/day (M: 56% vs 32%). There was an increased incidence in tonoclonic convulsions (primarily in females) at the high dose. There was an increase in relative and absolute liver weights in females at > 30 mg/kg/day. Males had an absolute liver weight increase at 30 mg/kg/day and a relative increase at > 3 mg/kg/day. Both sexes showed an increase in all severities of liver hypertrophy (hepatocytic, centrilobular/midzonal, diffuse) at 30 mg/kg/day (male) and at 100 mg/kg/day (female)... Possible adverse effect indicated: There was an increased incidence in hepatocytic adenomas and in hepatocytic adenomas plus carcinomas (slight in males, statistically significant in females) at 30 mg/kg/day (5, 7, 4, 12 of 50) and 100 mg/kg/day (F: 0, 1, 0, 4** of 50 by Peto’s mortality adjusted statistics ). Females showed an increased incidence in lung carcinomas (non-metastatic) at 100 mg/kg/day (0, 0, 1, 2** by Peto’s statistics).
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

Endocrine: Adrenal (click on for all fluorinated pesticides)

-- “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 a statistically significant increase in absolute adrenal weights (analyzed across both sexes) at 0.225% without histological findings.
-- “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
-- “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. Parental Systemic NOEL = 5.0 mg/kg/day (There were increased absolute and relative liver weights in both sexes of P1 and P2 adults at 25 mg/kg and in P1 female liver weights at 5.0 mg/kg. P1 male relative kidney weights, P2 female absolute kidney weights, P2 male relative spleen and thyroid weights and P2 female absolute and relative adrenal weights were increased at 25 mg/kg.) ...
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

Endocrine: Testicular (click on for all fluorinated pesticides)

-- 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.. ... Reproduction and Fertility NOEL = 5.0 mg/kg/day (There was an increased proportion of abnormal P2 sperm at 25 mg/kg. Although not statistically significant, there were decreased mating and fertility indices in both sexes of P2a and P2b adults at > 5.0 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
-- “XDE-007: Two-year Dietary Chronic Toxicity/Oncogenicity and Chronic Neurotoxicity Study in Fischer 344 Rats,” (Yano, B.L., Dryzga, M.D., Thomas, J.; Toxicology & Environmental Research and Consulting, The Dow Chemical Company, Midland, MI; Laboratory Project Study ID: 011168; 4.22.05). Noviflumuron ((N-[3,5-dichloro-2-fluoro-4(1,1,2,3,3,3-hexafluoropropoxy)phenyl]-N’-(2,6-difluorobenzoyl)urea; XDE-007, 97.9% pure) was fed in diet to Fischer 344 rats (75/sex/dose) for 90 days, 1 or 2 years at 0, 0.1, 1.0, 75 or 300 mg/kg/day. Subchronic toxicity was assessed after 90 days of treatment on 10/sex/dose at 0 and 1.0 mg/kg/day doses only. At 1 year,10/sex/dose (chronic toxicity group), and 5/sex/dose (chronic neurotoxicity group) were necropsied. The remaining 50/sex/dose were necropsied after 2 years (oncogenicity group). Chronic NOEL = 1.0 mg/kg/day (At > 75 mg/kg/day there were decreased body weights and body weight gains along with increases or decreases in absolute and/or relative organ weights (liver, kidney, brain, heart, adrenal, testes, spleen, epididymides were affected) at 12 and/or 24 months. Skin/tail papules and pustules were observed in males (300 mg/kg/day) and females (> 75 mg/kg/day) in the second year. Females showed an increase in phthisis bulbi at 300 mg/kg/day. Prothrombin time in males and cholesterol levels in females were increased at > 75 mg/kg/day at 24 months. ALP activities were increased in both sexes at > 75 mg/kg/day at 24 months. Urine specific gravity was decreased (both sexes at > 75 mg/kg/day) and urine volume was increased (M 300 mg/kg/day and F > 75 mg/kg/day) at 24 months. Lung inflammation, hepatocytic hypertrophy (both sexes > 75 mg/kg/day), mineralization of renal pelvic epithelium (M > 75 mg/kg/day), epididymal aspermia* (M > 75 mg/kg/day), atrophy of seminiferous tubules (300 mg/kg/day), tail hyperkeratosis +/- inflammation (both sexes 300 mg/kg/day), tail tip necrosis (M 300 mg/kg/day) and hyperplasia of renal pelvic epithelium (M 300 mg/kg/day) were observed at 24 months. Leukemia was decreased in both sexes at > 75 mg/kg/day at 24 months.) Possible adverse effect: Hepatocellular adenomas (benign, M 300 mg/kg/day), uterine stromal polyps (F > 75 mg/kg/day), and liver foci (M > 75 mg/kg/day) were increased at 24 months. Acceptable. Silva, 8/19/05
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

* Definition: Aspermia = the complete absence of semen.

Endocrine: Uterine (click on for all fluorinated pesticides)

-- “XDE-007: Two-year Dietary Chronic Toxicity/Oncogenicity and Chronic Neurotoxicity Study in Fischer 344 Rats,” (Yano, B.L., Dryzga, M.D., Thomas, J.; Toxicology & Environmental Research and Consulting, The Dow Chemical Company, Midland, MI; Laboratory Project Study ID: 011168; 4.22.05). Noviflumuron ((N-[3,5-dichloro-2-fluoro-4(1,1,2,3,3,3-hexafluoropropoxy)phenyl]-N’-(2,6-difluorobenzoyl)urea; XDE-007, 97.9% pure) was fed in diet to Fischer 344 rats (75/sex/dose) for 90 days, 1 or 2 years at 0, 0.1, 1.0, 75 or 300 mg/kg/day. Subchronic toxicity was assessed after 90 days of treatment on 10/sex/dose at 0 and 1.0 mg/kg/day doses only. At 1 year,10/sex/dose (chronic toxicity group), and 5/sex/dose (chronic neurotoxicity group) were necropsied. The remaining 50/sex/dose were necropsied after 2 years (oncogenicity group). Chronic NOEL = 1.0 mg/kg/day (At > 75 mg/kg/day there were decreased body weights and body weight gains along with increases or decreases in absolute and/or relative organ weights (liver, kidney, brain, heart, adrenal, testes, spleen, epididymides were affected) at 12 and/or 24 months. Skin/tail papules and pustules were observed in males (300 mg/kg/day) and females (> 75 mg/kg/day) in the second year. Females showed an increase in phthisis bulbi at 300 mg/kg/day. Prothrombin time in males and cholesterol levels in females were increased at > 75 mg/kg/day at 24 months. ALP activities were increased in both sexes at > 75 mg/kg/day at 24 months. Urine specific gravity was decreased (both sexes at > 75 mg/kg/day) and urine volume was increased (M 300 mg/kg/day and F > 75 mg/kg/day) at 24 months. Lung inflammation, hepatocytic hypertrophy (both sexes > 75 mg/kg/day), mineralization of renal pelvic epithelium (M > 75 mg/kg/day), epididymal aspermia (M > 75 mg/kg/day), atrophy of seminiferous tubules (300 mg/kg/day), tail hyperkeratosis +/- inflammation (both sexes 300 mg/kg/day), tail tip necrosis (M 300 mg/kg/day) and hyperplasia of renal pelvic epithelium (M 300 mg/kg/day) were observed at 24 months. Leukemia was decreased in both sexes at > 75 mg/kg/day at 24 months.) Possible adverse effect: Hepatocellular adenomas (benign, M 300 mg/kg/day), uterine stromal polyps (F > 75 mg/kg/day), and liver foci (M > 75 mg/kg/day) were increased at 24 months. Acceptable. Silva, 8/19/05
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

Eye (click on for all fluorinated pesticides)

-- “XDE-007: Two-year Dietary Chronic Toxicity/Oncogenicity and Chronic Neurotoxicity Study in Fischer 344 Rats,” (Yano, B.L., Dryzga, M.D., Thomas, J.; Toxicology & Environmental Research and Consulting, The Dow Chemical Company, Midland, MI; Laboratory Project Study ID: 011168; 4.22.05). Noviflumuron ((N-[3,5-dichloro-2-fluoro-4(1,1,2,3,3,3-hexafluoropropoxy)phenyl]-N’-(2,6-difluorobenzoyl)urea; XDE-007, 97.9% pure) was fed in diet to Fischer 344 rats (75/sex/dose) for 90 days, 1 or 2 years at 0, 0.1, 1.0, 75 or 300 mg/kg/day. Subchronic toxicity was assessed after 90 days of treatment on 10/sex/dose at 0 and 1.0 mg/kg/day doses only. At 1 year,10/sex/dose (chronic toxicity group), and 5/sex/dose (chronic neurotoxicity group) were necropsied. The remaining 50/sex/dose were necropsied after 2 years (oncogenicity group). Chronic NOEL = 1.0 mg/kg/day (At > 75 mg/kg/day there were decreased body weights and body weight gains along with increases or decreases in absolute and/or relative organ weights (liver, kidney, brain, heart, adrenal, testes, spleen, epididymides were affected) at 12 and/or 24 months. Skin/tail papules and pustules were observed in males (300 mg/kg/day) and females (> 75 mg/kg/day) in the second year. Females showed an increase in phthisis bulbi* at 300 mg/kg/day...
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

* Definition: Phthisis bulbi is an end-stage ocular response to severe ocular disease, inflammation, or insult.  Clinically, the globe will be soft and hypotonus with minimal or no vision and loss of much of the normal architecture of the eye.  Histopathologically, the globe is small and shrunken with marked thickening of the sclera, as well as disorganization and atrophy of much of the intraocular contents.  The intraocular contents are markedly dirupted and difficult to recognize.  Commonly, the retinal pigment epithelium may undergo a metaplasia leading to intraocular ossification or bone formation in the end-stage of phthisis bulbi.
Ref: University of Utah. John A. Moran Eye Center.
http://insight.med.utah.edu/opatharch/uvea/phthisis_bubli.htm

Kidney (click on for all fluorinated pesticides)

-- “XDE-007: Two-year Dietary Chronic Toxicity/Oncogenicity and Chronic Neurotoxicity Study in Fischer 344 Rats,” (Yano, B.L., Dryzga, M.D., Thomas, J.; Toxicology & Environmental Research and Consulting, The Dow Chemical Company, Midland, MI; Laboratory Project Study ID: 011168; 4.22.05). Noviflumuron ((N-[3,5-dichloro-2-fluoro-4(1,1,2,3,3,3-hexafluoropropoxy)phenyl]-N’-(2,6-difluorobenzoyl)urea; XDE-007, 97.9% pure) was fed in diet to Fischer 344 rats (75/sex/dose) for 90 days, 1 or 2 years at 0, 0.1, 1.0, 75 or 300 mg/kg/day. Subchronic toxicity was assessed after 90 days of treatment on 10/sex/dose at 0 and 1.0 mg/kg/day doses only. At 1 year,10/sex/dose (chronic toxicity group), and 5/sex/dose (chronic neurotoxicity group) were necropsied. The remaining 50/sex/dose were necropsied after 2 years (oncogenicity group). Chronic NOEL = 1.0 mg/kg/day (At > 75 mg/kg/day there were decreased body weights and body weight gains along with increases or decreases in absolute and/or relative organ weights (liver, kidney, brain, heart, adrenal, testes, spleen, epididymides were affected) at 12 and/or 24 months. Skin/tail papules and pustules were observed in males (300 mg/kg/day) and females (> 75 mg/kg/day) in the second year. Females showed an increase in phthisis bulbi at 300 mg/kg/day. Prothrombin time in males and cholesterol levels in females were increased at > 75 mg/kg/day at 24 months. ALP activities were increased in both sexes at > 75 mg/kg/day at 24 months. Urine specific gravity was decreased (both sexes at > 75 mg/kg/day) and urine volume was increased (M 300 mg/kg/day and F > 75 mg/kg/day) at 24 months. Lung inflammation, hepatocytic hypertrophy (both sexes > 75 mg/kg/day), mineralization of renal pelvic epithelium (M > 75 mg/kg/day), epididymal aspermia* (M > 75 mg/kg/day), atrophy of seminiferous tubules (300 mg/kg/day), tail hyperkeratosis +/- inflammation (both sexes 300 mg/kg/day), tail tip necrosis (M 300 mg/kg/day) and hyperplasia of renal pelvic epithelium (M 300 mg/kg/day) were observed at 24 months. Leukemia was decreased in both sexes at > 75 mg/kg/day at 24 months.) Possible adverse effect: Hepatocellular adenomas (benign, M 300 mg/kg/day), uterine stromal polyps (F > 75 mg/kg/day), and liver foci (M > 75 mg/kg/day) were increased at 24 months. Acceptable. Silva, 8/19/05
-- “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. Parental Systemic NOEL = 5.0 mg/kg/day (There were increased absolute and relative liver weights in both sexes of P1 and P2 adults at 25 mg/kg and in P1 female liver weights at 5.0 mg/kg. P1 male relative kidney weights, P2 female absolute kidney weights, P2 male relative spleen and thyroid weights and P2 female absolute and relative adrenal weights were increased at 25 mg/kg.) ...
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

Liver (click on for all fluorinated pesticides)

“XDE-007: 18-Month Oncogenicity Study in CD-1 Mice,” (Johnson, K.A.; Toxicology & Environmental Research and Consulting, The Dow Chemical Company, Midland, MI; 4/25/05). XDE-007 technical (N-[3,5-dichloro-2-fluoro-4-(1,1,2,3,3,3hexafluoropropoxy)phenyl]-N’-(2,6-difluorobenzoyl)urea), 97.9% pure) was fed in diet to CD-1 mice (50/sex/dose) at 0, 0.5, 3 (males only), 30 and 100 (females only) mg/kg/day for up to 18 months. Systemic NOEL = 3 mg/kg/day (males) and 30 mg/kg/day (females) There was an increase in mortality for females at 100 mg/kg/day (M: 56% vs 32%). There was an increased incidence in tonoclonic convulsions (primarily in females) at the high dose. There was an increase in relative and absolute liver weights in females at > 30 mg/kg/day. Males had an absolute liver weight increase at 30 mg/kg/day and a relative increase at > 3 mg/kg/day. Both sexes showed an increase in all severities of liver hypertrophy (hepatocytic, centrilobular/midzonal, diffuse) at 30 mg/kg/day (male) and at 100 mg/kg/day (female)... Possible adverse effect indicated: There was an increased incidence in hepatocytic adenomas and in hepatocytic adenomas plus carcinomas (slight in males, statistically significant in females) at 30 mg/kg/day (5, 7, 4, 12 of 50) and 100 mg/kg/day (F: 0, 1, 0, 4** of 50 by Peto’s mortality adjusted statistics ). Females showed an increased incidence in lung carcinomas (non-metastatic) at 100 mg/kg/day (0, 0, 1, 2** by Peto’s statistics).
-- “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. Parental Systemic NOEL = 5.0 mg/kg/day (There were increased absolute and relative liver weights in both sexes of P1 and P2 adults at 25 mg/kg and in P1 female liver weights at 5.0 mg/kg...
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

-- (Oral) 008; 186500; "XR-007: 4-Week Dietary Toxicity Study in Fischer Rats" (Lick, S.J. et al., Health & Environmental Research Laboratories, The Dow Chemical Company, Midland, MI, Laboratory Project Study ID 971106, 10/9/97). XR-007 (Lot # DECO-615-112, purity = 99.6%) was admixed to the feed and fed to 5 Fischer 344 rats per sex per dose at dose levels of 0, 1, 10, 100, 500, or 1000 mg/kg/day (0, 1.0, 10.4, 101.4, 512.6, 1029.1 mg/kg/day, respectively for males and 0, 1.1, 10.9, 105.1, 520.6, 1055.6 mg/kg/day, respectively for females) for 4 weeks... A treatment-related increase in mean relative liver weight was observed in both sexes at 500 and 1000 mg/kg/day. Microscopic examination revealed treatment-related hepatocellular hypertrophy (centrilobular) in males at 1000 mg/kg/day and in females at 500 and 1000 mg/kg/day. No adverse effects. NOEL (M) = 101.4 mg/kg/day and NOEL (F) = 105.1 mg/kg/day (based on an increase in mean relative liver weight and hepatocellular hypertrophy). Supplemental (because only 5 animals per sex per dose were used, the animals were treated for only 4 weeks, no ophthalmological examinations were conducted, and no analysis of the dosing material was conducted). (Corlett, 10/3/02)
-- 007; 186499; "XDE-007: 28-Day Dietary Toxicity Study in CD-1 Mice" (Yano, B.L. and Day, S.J., Toxicology & Environmental Research and Consulting, The Dow Chemical Company, Midland, MI, Laboratory Project Study ID 001248, 6/12/01). XDE-007 (Lot, Reference No. F0031-148, TSN102332, purity = 98.4%) was admixed to the feed and fed to 5 CD-1 mice per sex per dose at dose levels of 0, 10, 100, 500, or 1000 mg/kg/day (0, 10.8, 110, 538, 1060 mg/kg/day, respectively for males and 0, 11.2, 113, 504, 1140 mg/kg/day, respectively for females) for 28 days. No mortalities occurred. No treatment-related clinical signs were observed. Treatment-related increases in mean platelet level and mean cholesterol level were observed in both sexes at 100, 500, and 1000 mg/kg/day. A treatment-related increase in mean relative liver weight was observed at in males at 100, 500, and 1000 mg/kg/day and in females at 500 and 1000 mg/kg/day. Microscopic examination revealed treatment-related hepatocellular hypertrophy with altered tinctorial properties (centrilobular/midzonal to panlobular) in males at 500 and 1000 mg/kg/day and very slight vacuolation (consistent with fatty change) of the periportal hepatocytes in males at 500 and 1000 mg/kg/day and in females at 1000 mg/kg/day. No adverse effects. NOEL (M) = 10.8 mg/kg/day and NOEL (F) = 11.2 mg/kg/day (based on increases in mean platelet and mean cholesterol levels). Supplemental (because only 5 animals per sex per dose were used and because the animals were treated for only 28 days). (Corlett, 9/30/02)
Ref: September 26, 2002. Summary of Toxicology Data for Noviflumuron ((XDE-007) or N-(((3,5-dichloro-2-fluoro-4-(1,1,2,3,3,3-hexafluoropropoxy)phenyl)amino)carbonyl)-2,6- diflurobenzamide. California EPA, Department of Pesticide Regulation, Medical Toxicology Branch.
http://www.fluoridealert.org/pesticides/Noviflumuron.CA.EPA.2002.pdf

Lung (click on for all fluorinated pesticides)

“XDE-007: 18-Month Oncogenicity Study in CD-1 Mice,” (Johnson, K.A.; Toxicology & Environmental Research and Consulting, The Dow Chemical Company, Midland, MI; 4/25/05). XDE-007 technical (N-[3,5-dichloro-2-fluoro-4-(1,1,2,3,3,3hexafluoropropoxy)phenyl]-N’-(2,6-difluorobenzoyl)urea), 97.9% pure) was fed in diet to CD-1 mice (50/sex/dose) at 0, 0.5, 3 (males only), 30 and 100 (females only) mg/kg/day for up to 18 months. Systemic NOEL = 3 mg/kg/day (males) and 30 mg/kg/day (females)... There was an increased incidence in evidence of inflammation in lung in both sexes at the high dose... Females showed an increased incidence in lung carcinomas (non-metastatic) at 100 mg/kg/day (0, 0, 1, 2** by Peto’s statistics).
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

Reproductive (click on for all fluorinated pesticides)

-- “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
-- “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. Parental Systemic NOEL = 5.0 mg/kg/day (There were increased absolute and relative liver weights in both sexes of P1 and P2 adults at 25 mg/kg and in P1 female liver weights at 5.0 mg/kg. P1 male relative kidney weights, P2 female absolute kidney weights, P2 male relative spleen and thyroid weights and P2 female absolute and relative adrenal weights were increased at 25 mg/kg.) Reproduction and Fertility NOEL = 5.0 mg/kg/day (There was an increased proportion of abnormal P2 sperm at 25 mg/kg. Although not statistically significant, there were decreased mating and fertility indices in both sexes of P2a and P2b adults at > 5.0 mg/kg.) Pup NOEL = 5.0 mg/kg (There was a decrease in F1 survival (not statistically significant) on lactation days 14 and 21 at 25 mg/kg. F2a pups had statistically significantly decreased survival of lactation days 7, 14 and 21at 25 mg/kg. 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

Spleen (click on for all fluorinated pesticides)

-- 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. . ... . 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

Stomach (click on for all fluorinated pesticides)

-- Chronic Study: “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). NOEL = 0.003% (0.74 mg/kg/day - Males; 0.94 mg/kg/day - Females) (Mean corpuscular volume in males (compared with controls at each time interval) and reticulocytes in both sexes were increased at 0.225% throughout the study. Both sexes at > 0.225% had statistically significantly increased mean platelet count. There was a significant increase in ALP at 0.225% in females at 3 and 12 months. There was a statistically significant increase in absolute adrenal weights (analyzed across both sexes) at 0.225% without histological findings. 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). There was a dose-related increase in severity of stomach mucosal lymphoid hyperplasia in the fundus and pylorus in both sexes at > 0.3%.) No adverse effect. Acceptable. (M. Silva, 6/21/04).
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

Teratogen (click on for all fluorinated pesticides)

-- 52905-009 186501, "XR-007: Whole Embryo Culture Teratogenicity Screen", (E. W. Carney, Health and Environmental Research Laboratories, The Dow Chemical Company, Midland, MI, Report # 971083, 31 July 1997). Seven non-pregnant female rats (serum donors) received 1000 mg/kg/day of the test article (XR-007, 98%) in 0.5% Methocel by gavage for 3 consecutive days. Four hours after the last dose, rats were exsanguinated and their blood centrifuged to obtain serum. Six control rats were similarly treated with vehicle and bled... Statistically significant increases in crown-rump length and somite number for treated embryos were reportedly due to a lower than usual growth rate in control embryos. Morphological abnormality was limited to an abnormal curvature of the anterior neural tube which distorted the head in one treated embryo (8.3%). No historical control data. This is supplemental information. (Green and Gee, 10/3/02).
Ref: September 26, 2002. Summary of Toxicology Data for Noviflumuron ((XDE-007) or N-(((3,5-dichloro-2-fluoro-4-(1,1,2,3,3,3-hexafluoropropoxy)phenyl)amino)carbonyl)-2,6- diflurobenzamide. California EPA, Department of Pesticide Regulation, Medical Toxicology Branch.
http://www.fluoridealert.org/pesticides/Noviflumuron.CA.EPA.2002.pdf

[Note from FAN- some definitions:
"Predominately anterior neural tube defects, occuring early in gestation. The anterior neural tube fails to close properly, or does not divide into two hemispheres. The generic name for this category of malformations is arrhinencephaly. Ref: Developmental and Perinatal Disorders of the CNS. Weill Medical College of Cornell University. http://edcenter.med.cornell.edu/CUMC_PathNotes/Neuropathology/Neuropath_II/dev2.html
-- "... trisomy 13 is closely linked to midline malformations, including arrhinencephaly, agenesis of the corpus callosum, and holoprosencephaly, and is the single most common chromosomal defect underlying holoprosencephaly." - http://128.100.71.82/neurosurgery/developmental.html
-- "Trisomy 13 Syndrome is a genetic disorder with onset before birth. It occurs approximately 1/5000 live births. Infants affected with Trisomy 13 tend to be small at birth. Spells of interrupted breathing (apnea) in early infancy are frequent, and mental retardation is usually severe. Many affected children appear to be deaf. A moderately small head (microcephaly) with sloping forehead, wide joints and openings between parietal bones of the head are present. Gross anatomic defects of the brain, especially failure of the forebrain to divide properly (holoprosencephaly) are common. A hernial protrusion of the cord and its meninges through a defect in the vertebral canal (myelomeningocele) is found in almost 50% of cases. The entire eye is usually small (microphthalmia), and a defect of the iris tissue (coloboma), and faulty development of the retina (retinal dysplasia) occur frequently. The supraorbital ridges are shallow and palapebral fissures are usually slanted. Cleft lip, cleft palate, or both are present in most cases. The ears are abnormally shaped and unusually low-set." -
http://www.trisomy.org/html/trisomy_13_facts.htm

Environmental (click on for all fluorinated pesticides) The data indicate that noviflumuron is relatively non-toxic to vertebrate animals, birds, moderately toxic to fish and highly toxic to freshwater invertebrates. The proposed label does bear precautionary statements regarding the high toxicity to freshwater invertebrates. The environmental fate data indicates noviflumuron is strongly bound to soil and has low water solubility indicating a low potential for soil leaching. The proposed use for noviflumuron as a self contained bait to control termites around structures, fence posts, utility poles and landscape plantings is not expected to pose a treat to wildlife. Ref: 2003. Noviflumuron. California Department of Pesticide Regulation. Public Report 2003-5. http://www.fluorideaction.org/pesticides/noviflumuron.ca.epa.2003.pdf