Note: This is not an exhaustive list.
When time allows more information will be added.

Sodium bifluoride - Insecticide, Former US EPA List 3 Inert - CAS No. 1333-83-1

Effects of Overexposure. Inhalation of dust or mist may cause severe mucous membrane irritation, burns and, with prolonged or repeated exposure, may cause fluorosis. Eye and skin exposure causes irritation and burns. Product may be absorbed through the skin and produce signs of fluorosis such as weight loss, brittleness of bones, anemia, weakness and stiffness of joints. Ingestion is harmful due to acid burns and fluoride poisoning. Internal bleeding may develop. Effects may not be immediately apparent, especially with dilute solutions.
Ref: Material Safety Data Sheet for Sodium bifluoride. Rev. March 29, 1996. Chemtech Products, Inc., St. Louis MO 63131
http://www.fluorideaction.org/pesticides/sodium.bifluoride.msds.1996.pdf

-- CHRONIC EXPOSURE o Hydrogen fluoride and hydrofluoric acid are extreme irritants to any part of the body that they contact. The main route of exposure to hydrogen fluoride is inhalation, followed by dermal contact for acute exposure and ingestion for chronic exposure. Symptoms of the chronic effects of hydrofluoric acid include weight loss, malaise, anemia, leukopenia, discoloration of teeth, and osteosclerosis.
-- MUSCULOSKELETAL 0.2.15.1 ACUTE EXPOSURE - Acute exposure may cause decalcification and corrosion of the bone beneath the area of dermal burn. 0.2.15.2 CHRONIC EXPOSURE - Fluorosis is characterized by skeletal changes such as increased bone density of the spin and pelvis, calcification of ligaments, and hyperostosis although clinical fluorosis is unlikely before 10 years of exposure to fluoride.
Ref: Hazardous Substances Data Bank for SODIUM HYDROGEN DIFLUORIDE CASRN: 1333-83-1
http://www.fluorideaction.org/pesticides/sodium.bifluoride.toxnet.htm

Sodium fluorosilicate (Sodium Hexafluorosilicate) - Insecticiide, Wood Preservative; EPA List 3 Inert - CAS No. 16893-85-9

-- Toxicological Data. Human Data. Chronic exposure to sodium hexafluorosilicate dust at levels above the eight-hour TWA can result in severe calcification of the ribs, pelvis, and spinal column ligaments; effects on the enzyme system; pulmonary fibrosis; stiffness; irritation of the eyes, skin, and mucous membranes; weight loss; anorexia; anemia; cachexia; wasting; and dental effects. Long-term or repeated exposure to the skin can result in skin rash. A probable oral lethal dose of 50-500 mg/kg, classified as very toxic, has been reported for a 150-pound (70-kg) person receiving between 1 teaspoon and 1 ounce of sodium hexafluorosilicate. Cases of sodium hexafluorosilicate ingestion reported symptoms such as acute respiratory failure, ventricular tachycardia and fibrillation, hypocalcemia, facial numbness, diarrhea, tachycardia, enlarged liver, and cramps of the palms, feet, and legs.
-- Mice orally given sodium hexafluorosilicate (70 mg/kg; 0.37 mmol/kg) exhibited toxic effects in the peripheral nerves, sensation, and in behavior. In rats, an oral dose (248 mg/kg; 1.32 mmol/kg) administered intermittently for one month produced toxic effects in the kidney, ureter, and/or bladder, as well as musculoskeletal and biochemical effects (RTECS, 1997). Using guinea pigs, inhalation experiments (13-55 mg/m 3 [1.7-7.2 ppm] sodium hexafluorosilicate in air for ¥6 hours) resulted in pulmonary irritation; the lowest concentration that caused death was 33 mg/m 3 (4.3 ppm) (Patty, 1963; cited by HSDB, 2000b).
Ref: Sodium Hexafluorosilicate [CASRN 16893-85-9] and Fluorosilicic Acid [CASRN 16961-83-4]. Review of Toxicological Literature. October 2001. Prepared for Scott Masten, Ph.D. National Institute of Environmental Health Sciences P.O. Box 12233 Research Triangle Park, North Carolina 27709 Contract No. N01-ES-65402. Submitted by Karen E. Haneke, M.S. (Principal Investigator) Bonnie L. Carson, M.S. (Co-Principal Investigator) Integrated Laboratory Systems P.O. Box 13501 Research Triangle Park, North Carolina 27709.
http://www.fluoridealert.org/pesticides/fluorosilicates.nih.2001.pdf

Sulfentrazone - Herbicide - CAS No. 122836-35-5

-- A developmental toxicity study in rats resulted in a maternal (systemic)... The developmental (fetal) LOEL is 25.0 mg/kg/day based upon 1) decreased mean fetal weight and 2) retardation in skeletal development as evidenced by an increased number of litters with any variation and by decreased numbers of caudal vertebral and metacarpal ossification sites. The developmental (fetal) NOEL is 10.0 mg/kg/day. Evidence of treatment-related developmental toxicity consisted of decreased fetal viability, decreased fetal body weight, and increased incidence of fetal alterations, comprised, for the most part, of skeletal malformations and variations. A supplementary prenatal oral developmental toxicity study in rats confirmed the maternal and fetal findings of the previously conducted study and did not alter the study conclusions.
Ref: US EPA. Pesticide Fact Sheet. Sulfentrazone Reason for Issuance: Registration of a New Chemical Date Issued: February 27, l997.
http://www.epa.gov/opprd001/factsheets/sulfentrazone.pdf

-- Developmental Study in rats. Developmental LOAEL = 25 mg/kg/day based on decreased fetal weight and retarded skeletal development as evidenced by an increased number of litters with any variation and by decreased numbers of caudal vertebral and metacarpal ossification sites.
-- In the dermal developmental study in rats, the maternal (systemic) NOAEL was 250 mg/kg/day and a LOAEL was not determined. The developmental (fetal) NOAEL was 100 mg/kg/day, based on decreased fetal weight and increased fetal variations (hypoplastic or wavy ribs, incompletely ossified lumbar vertebral arches, incompletely ossified ischia or pubes, and reduced numbers of thoracic vertebral and rib ossification sites) at the LOAEL of 250 mg/kg/day.
Ref: Federal Register. August 1, 2001. Sulfentrazone; Pesticide Tolerances for Emergency Exemptions. Final Rule.
http://www.fluoridealert.org/pesticides/sulfentrazone.fr.aug1.2001.htm

A developmental toxicity study in rabbits was conducted at gavage dose levels of 0, 100, 250, or 375 mg/kg/day... The maternal (systemic) NOEL is 100 mg/kg/day. Skeletal evaluation in fetuses revealed dose- and treatment-related findings at the 375 mg/kg/day dose level. These included significant increases in both the fetal and litter incidences of fused caudal vertebrae (a malformation) and of partially fused nasal bones (a variation). In addition, at 375 mg/kg/day, significant treatment-related reductions in ossification site averages were observed for metacarpals and both fore- and hindpaw phalanges
Ref: Federal Register: March 10, 1997. Sulfentrazone; Establishment of Tolerances. Final Rule. Federal Register.
http://www.fluoridealert.org/pesticides/Sulfentrazone.FR.Mar10.1997.htm

Prenatal developmental in rodents (rats) - [870.3700] LOAEL = 25 mg/kg/ day based on decreased mean fetal weights, and retardation in skeletal development evidenced by an increased number of litters with any variation and by decreased number of caudal vertebral and metacarpal ossification sites Maternal NOAEL = 250 mg/kg/day LOAEL was not established. Developmental NOAEL = 100 mg/kg/ day LOAEL = 250 mg/kg/ day based on decreased fetal body weight; increased incidence of fetal variations: hypoplastic or wavy ribs, incompletely ossified lumbar vertebral arches, and incompletely ossified ischia or pubis [see definitions below]; and reduced number of thoracic vertebral and rib ossification sites.
-- Combined chronic toxicity/carcinogenicity rats - [870.4300] NOAEL = 40 mg/kg/day for males and 36.4 mg/kg/day in females LOAEL = 82.2 mg/kg/ day for males and 67 mg/kg/day for females based on dose-related decreased body weights (11 and 19%), body weight gains (13 and 26%), food consumption (13 and 19%), hemoglobin, hematocrit, mean cell volume, and mean cell hemoglobin. Increased nucleated red blood cells and reticulocytes in bone of females at 124.7 mg/kg/ day. No evidence of carcinogenicity
Ref: Federal Register: September 24, 2003. Sulfentrazone; Pesticide Tolerances. Final Rule.
http://www.fluorideaction.org/pesticides/sulfentrazone.fr.sept24.03.htm
• Definition
Ischia (plural of Ischium): The ventral and posterior of the three principal bones composing either half of the pelvis; seat bone; the huckle bone.
Pubis: one of the three sections of the hipbone; together the two pubic bones form the front of the pelvis

Sulfuryl fluoride - Fumigant insecticide - CAS No. 2699-79-8

Prenatal developmental--rabbit (870.3700) Developmental NOAEL = 75 ppm or 29/29 (M/F) mg/kg/ day LOAEL = 225 ppm or 86 (F) mg/kg/day based on decreased fetal body weight, decreased crown-rump length, possible increased fetal liver pathology (pale liver) Ref: January 23, 2004. Sulfuryl Fluoride; Pesticide Tolerance. 40 CFR Part 180 [OPP-2003-0373; FRL-7342-1]. Final Rule. Federal Register

From FAN Note the similarity of effect with the following: - EC.

Abstract: Fluoride was €rst associated with fetal malformation shortly after water �uoridation was initiated in the 1940s. Since many chemicals can interact directly with the embryo to cause malformation, the effects of �uoride on embryonic and fetal development were investigated. The effects of sodium �uoride on the development of frog embryos were studied under conditions described by the Frog Embryo Teratogenesis Assay —Xenopus (FETAX), a screening assay for teratogens. The most prominent malformations caused by sodium �uoride are reduction in the head-tail lengths and dysfunction of the neuromuscular system of the tadpoles. The values for LC50, EC50, and minimal concentration to inhibit growth (MCIG) of sodium �uoride met the limits established for a teratogen in frog embryos, showing that sodium �uoride is a direct acting teratogen on developing embryos. Since FETAX has a high degree of success in identifying mammalian teratogens, the observed teratogenic action of sodium �uoride on frog embryos would indicate a strong possibility that sodium �uoride may also act directly on developing mammalian fetuses to cause malformation. Ref: Effects of �uoride on Xenopus embryo development EH Goh, AW Neff Food and Chemical Toxicology 41 (2003)1501 –1508 • Note: The fluoride anion is the toxicological endpoint of concern for Sulfuryl fluoride.

... Rats exposed by inhalation to 100 to 600 ppm (0.4 to 0.25 mg/L) sulfuryl fluoride for 13 weeks developed mottled teeth (indicative of fluoride toxicity), renal and respiratory effects, and cerebral vacuolation. EPA believes that there is sufficient evidence for listing sulfuryl fluoride on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on the available neurological, renal, and respiratory toxicity data for this chemical.
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.

-- 90-Day inhalation toxicity--rat. NOAEL = 24/25 (M/F) mg/kg/day. LOAEL = 80/83 (M/F) mg/kg/day based on dental fluorosis*.
-- 90-Day inhalation toxicity--rabbit. NOAEL = 8.6/8.5 (M/F) mg/kg/day. LOAEL = 29/28 (M/F) mg/kg/day based on decreased body weight, decreased liver weight, dental fluorosis*, vacuolation of white matter of the brain (F only).
-- Chronic toxicity--rodents. NOAEL = 3.5 for M and 16 for F mg/kg/day. LOAEL = 20 ppm or 14 for M and 80 ppm or 62 for F mg/kg/day based on dental fluorosis* in males...
-- 1-Year chronic inhalation toxicity--dog. NOAEL = 5.0/5.1 (M/F) mg/kg/day. LOAEL = 20/20 (M/F) mg/kg/day based on decreased body weight gain, increased alveolar macrophages in lungs, dental fluorosis*.
-- 2-Year combined chronic/ carcinogenicity--rat. NOAEL = 3.5 for M and 16 for F mg/kg/day.
LOAEL = 20 ppm or 14 for M and 80 ppm or 62 for F mg/kg/day based on dental fluorosis* in males...
* = dental fluorosis is not considered an adverse health effect, and the identification of that effect in any of these toxicological studies has not served to define a safe level of exposure to sulfuryl fluoride under the FFDCA.
Ref: January 23, 2004. Sulfuryl Fluoride; Pesticide Tolerance.
40 CFR Part 180 [OPP-2003-0373; FRL-7342-1]. Final Rule. Federal Register

-- Poisonings and fatalities have been reported in humans following inhalation exposure to sulfuryl fluoride. The severity of these effects has depended on the concentration of sulfuryl fluoride and the duration of exposure. Short-term inhalation exposure to high concentrations has caused respiratory irritation, pulmonary edema, nausea, abdominal pain, central nervous system depression, and numbness in the extremities. In addition, there have been two reports of deaths of persons entering houses treated with sulfuryl fluoride. One person entered the house illegally and was found dead the next morning. A second person died of cardiac arrest after sleeping in the house overnight following fumigation. A plasma fluoride level of 0.5 mg/L (10 times normal) was found in this person following exposure. Prolonged chronic inhalation exposure to concentrations of sulfuryl fluoride gas significantly above the TLV of 5 ppm have caused fluorosis in humans because sulfuryl fluoride is converted to fluoride anion in the body. Fluorosis is characterized by binding of fluoride anion to teeth (causing mottling of the teeth) and to bone.
-- In many subchronic and chronic inhalation studies in rats, dogs, and rabbits, dental fluorosis was the most sensitive toxic effect observed in the study. In two 90-day studies in rats and rabbits, in which serum fluoride levels were determined, an increased serum level of fluoride anions was observed at even lower dose levels. The increased serum fluoride levels were due to the conversion of sulfuryl fluoride to fluoride anions in the body.
Ref: Federal Register: September 5, 2001 (Volume 66, Number 172). Sulfuryl Fluoride; Proposed Pesticide Temporary Tolerances.
http://www.fluorideaction.org/pesticides/sulfuryl.flu.fr.sept.5.2001.htm

Chronic exposure to either too low or too high a concentration of fluoride may have deleterious effects on the skeletal system. An increased in the incidence of severe osteoporosis was correlated with use of drinking water containing 0.4 mg/l fluoride. Severe skeletal fluorosis has been reported in persons living in areas of naturally high fluoride concentrations (up to 14 mg/l). Radiologically detectable osteosclerosos has been observed in about 10 percent of long term residents using water supplies containing 8 mg/l fluoride. Retardation of skeletal maturity has been observed in children using a water supply containing 3.6 mg/l fluoride. In other situations, skeletal fluorosis has not been described in populations whose water supplies contained less than 4 mg/l fluoride.
Ref: [USEPA, Office of Drinking Water; Criteria Document (Draft): Fluoride p.vi-48 (1985)] as cited in Hazardous Substances Data Bank for Ammonium fluoride
http://www.fluoridealert.org/pesticides/ammonium.fluoride.toxnet.htm

• Note: Inorganic fluoride is the toxicological endpoint of concern for Sulfuryl fluoride

tau-Fluvalinate - AcarIcide, Insecticide - CAS No. 102851-06-9

-- Teratogeniciity studies on tau fluvalinate in rabbits showed increased incidences of delayed ossification, and visceral and skeletal malformations at an overt maternotoxic dose (125 mg/kg bw). This dose salso caused increased numbers of resorptions and poorer viability of fetuses. No teratogenic effects occurred at lower doses. No reproduction studies with tau fluvalinate in other species were submitted and the compound has to be classified as possibly teratogenic.
Ref: Revised Summary Report. EMEA/MRL/021-REV1/95. Committee for Veterinary Medicinal Products. The European Agency for the Evaluation of Medicinal Products.
http://www.fluorideaction.org/pesticides/tau.fluvalinate.1995.review.pdf

Tefluthrin - Insecticide - CAS No. 79538-32-2

Reproductive and developmental toxicity. In a rat developmental study, [[Page 50363]] delayed ossification was noted in the highest dose group (5 mg/kg/day), along with significant maternal toxicity (decreased body weight (bwt)). The developmental no observed effect level (NOEL) for this study was established at 3 mg/kg/day.
Ref: Federal Register: September 25, 1997 [Page 50337-50367]. Notice of Filing of Pesticide Petitions.
http://www.fluoridealert.org/pesticides/bifenthrin.fr.sept.25.1997.htm

-- In a developmental toxicity study, rats were dosed at 0, 1, 3, or 5 mg/kg/day from days 7 through 16 of gestation. The maternal LOEL is 3 mg/kg/day, based on treatment-related decrease body weight gains during dosing. The maternal NOEL is 1 mg/kg/day. Developmental toxicity was demonstrated at 5 mg/kg/day as an increase in the fetal incidence of bilaterally unossified calcanea (92.9% vs. 87.5% in controls, p<0.05; litter incidence was not shown) and a slight increase in the pes score (3.05 vs. 2.96 in controls) indicating slight inhibition of ossification at these sites. There were no treatment-related effects on the number, growth, and survival of the young in utero. In addition, the inter-group differences in the mean numbers of corpora lutea, implantations, pre- and post- implantation deaths, live fetuses, proportion of male fetuses, and fetal weights were not remarkable. The developmental LOEL is 5 mg/kg/day, based on inhibited ossification. The developmental NOEL is 3 mg/kg/day.
-- In a developmental toxicity study, rabbits were dosed at 0, 3, 6, or 12 mg/kg/day from days 7 through 19 of gestation. The maternal LOEL is 3 mg/kg/day, based on treatment-related clinical signs of toxicity (tremors). The maternal NOEL is <3 mg/kg/day. There was no developmental toxicity demonstrated at any dose level. There were no treatment-related effects on in utero survival and growth or on litter size and sex ratio of the fetuses. The skeletal variant data showed significant (p<0.01 or 0.05) increases in incidence of extra thoracic ribs and 27 pre-sacral vertebrae among fetuses in the dosed groups; however, when the litter was used as the unit for comparison, the incidences of these respective variants were comparable between all groups. The incidences of these variants were not biologically significant. The NOEL for developmental toxicity is 12 mg/kg/day. The developmental LOEL was not observed.
Ref: Federal Register: November 26, 1997. Tefluthrin; Pesticide Tolerance. Final Rule. http://www.fluoridealert.org/pesticides/tefluthrin.fr.nov.1997.htm

Tembotrione - Herbicide - CAS No. 335104-84-2

• In a developmental toxicity study (MRID 46695647), AE0172747 (95.0% w/w; Batch# PFI 0195) in 0.5% methylcellulose 400 was administered via gavage at a dose volume of 10 mL/kg to 25 Sprague Dawley rats/dose group at dose levels of 0, 25, 125, or 500 mg/kg/day from gestation days (GD) 6-20. On GD 21, all dams were euthanized, and the uterus was removed via cesarean section and its contents examined. Fetuses were examined for external, visceral, and skeletal malformations, anomalies, and variations.
-- At >=25 mg/kg/day, fetal body weights were dose-dependently decreased (p<=0.01) by 3-16% and a dose-related increase in the number of runts (fetuses weighing less than 4.0 g) was observed compared to controls. Additionally at these doses, incidences of the following skeletal variations, indicative of altered growth and development, were increased over controls:
(i) enlarged (poor ossification) of the anterior and/or posterior fontanelle [a fontanelle -or fontanel- is one of two "soft spots" on a newborn human's skull.]
(ii) unossified 7th cervical centrum;
(iii) incomplete ossification of the 5th and/or 6th sternebrae, hemisternebra of the 5th sternebrae, or bipartite 5th sternebrae;
(iv) extra ossification points (unilateral/bilateral) on the 14th thoracic vertebra;
(v) incomplete ossification of the thoracic centrum;
(vi) unossified 3rd and/or 4th proximal phalanges on the forepaws;
(vii) incomplete ossification or unossified 5th metacarpals;
(viii) unossified 1st metatarsals; and
(ix) less than 9 sacrocaudal vertebrae ossified/9 first sacrocaudal vertebrae.
-- Additionally at >=125 mg/kg/day, incidences of the following skeletal variations and anomalies were increased over controls:
(i) bilateral incomplete ossification of the supraoccipital, interparietal, nasals, frontals, and /or parietals;
(ii) unossified 5th and/or 6th sternebrae;
(iii) unossified thoracic centrum; and
(iv) bipartite and/or dumbbell thoracic centrum and cartilage.
-- Finally at 500 mg/kg/day, incidences of the following skeletal variations were increased over controls:
(i) unossified hyoid centrum;
(ii) unossified 7th cervical centrum, cartilage bipartite;
(iii) bipartite ossification, incomplete ossification, or unossified 1st, 2nd, and/or 4th sternebrae.
-- At >=25 25 mg/kg/day, incidences of short unilateral/bilateral 14th thoracic ribs were increased over controls. Additionally at >=125 mg/kg/day, incidences of bipartite and/or dumbbell thoracic centrum and cartilage were increased over controls.
-- At 500 mg/kg/day, incidences of the following variations were increased over controls:
(i) enlarged thymus;
(ii) split, bipartite, or branched xiphoid process;
(iii) bipartite and/or dumbbell thoracic centrum; and
(iv) dumbbell 1st lumbar centrum.
Additionally at this dose, enlarged bladder and absent (unilateral) renal papilla were noted in a single fetus.
-- The developmental LOAEL is 25 mg/kg/day based on increased skeletal variations including delayed ossifications and on decreased growth and development as indicated by decreased fetal body weights, and an increased number of runts.
-- The developmental NOAEL was not observed. (pages 63-65)
Reference: Tembotrione. Human-Health Risk Assessment for Proposed Uses on Field Corn, Sweet Corn and Popcorn. USEPA. September 7, 2007.

• In a developmental toxicity study (MRIDs 46695703, 46695701, and 46695702), AE0172747 (95.0% w/w; Batch# PFI 0195) in 0.5% methylcellulose 400 was administered via gavage at a dose volume of 4 mL/kg to 25 New Zealand White rabbits/dose group at dose levels of 0, 1, 10, or 100 mg/kg bw/day from gestation days (GD) 6-28. On GD 29, all surviving does were euthanized, and the uterus was removed via cesarean section and its contents examined. Fetuses were examined for external, visceral, and skeletal malformations, anomalies, and variations...
-- At 10 and 100 mg/kg/day, incidences of the following skeletal variations and anomalies were increased over controls and indicate decreased or delayed growth and development:
(i) enlarged (poor ossification) of the anterior and/or posterior fontanelle;
(ii) unossified atlas centrum;
(iii) extra ossification site between atlas and axis centrum;
(iv) incomplete ossification of the 1st or 2nd sternebra;
(v) unilateral/bilateral incomplete ossification of the pubis;
(vi) unossified 1st or 2nd sternebra; and
(vii) extra sternebral ossification.
-- Additionally at 100 mg/kg/day, the incidence of unossified 6th sternebra was higher than controls.
-- At 10 and 100 mg/kg/day, incidences of the following skeletal variations were increased over concurrent controls:
(i) cartilage of 8th rib (unilateral/bilateral) attached to the sternum;
(ii) cartilage of 1st and 2nd rib (unilateral/bilateral) fused;
(iii) presence of 27 pre-sacral vertebrae; and
(iv) 13 thoracic rib(s) unilateral/bilateral and presence of 27 pre-sacral vertebrae.
-- Additionally at 100 mg/kg/day,
(i) unilateral/bilateral 1st ribs short;
(ii) cartilage of 1st rib (unilateral/bilateral) not attached to the sternum; and
(iii) 14 thoracic ribs (bilateral) or 14 thoracic rib (unilateral) short and/or detached.
-- Additionally at 100 mg/kg/day, incidences of the following visceral variations were increased over concurrent controls:
(i) short innominate arteries;
(ii) absent innominate arteries; and
(iii) dilated cerebral lateral ventricles (bilateral).
-- At 100 mg/kg/day, fused kidneys and retroesophageal aortic arch were noted in a single fetus (each) compared to 0 controls. Incidences of all other malformations were unrelated to dose.
-- The developmental LOAEL is 10 mg/kg bw/day based on decreased or delayed growth and/or development of the skeleton and increased incidences of other skeletal variations and anomalies.
-- The developmental NOAEL is 1 mg/kg bw/day (page 66).
Reference: Tembotrione. Human-Health Risk Assessment for Proposed Uses on Field Corn, Sweet Corn and Popcorn. USEPA. September 7, 2007.

• There was evidence of increased susceptibility following in utero and postnatal exposure in the developmental and 2-generation studies. Fetal effects were increased skeletal variations including delayed ossification and decreased fetal body weight and increased number of runts. These effects were observed at the lowest dose tested (25 mg/kg/day) and at a dose lower than that which caused marginal maternal toxicity (125 mg/kg/day, decreased body-weight gains and food consumption). page 16
• In the rabbit developmental study, decreased growth and/or delayed development of the skeleton and increased incidences of skeletal variations and anomalies in fetuses occurred at the a dose (10 mg/kg/day) lower than that which caused maternal toxicity (100 mg/kg/day, few or no feces, late abortion, decreased body weight and food consumption). In the 2-generation reproduction study in rats, parental effects occur at the lowest dose tested (1.4/1.6 mg/kg/day, M/F) and include corneal opacity, acute inflammation and neovascularization of the cornea. Offspring effects occurred at the same dose and included similar eye effects as well as increased incidences of minimal extramedullary hematopoeisis in the spleen, delayed preputial separation, and decreased absolute brain weight. There were no effects on reproduction (page 16).
• In a combined chronic/carcinogenicity study (MRID 46695708) Wistar male rats/dose in the diet at dose levels of 0, 1, 20, 200 or 800 ppm (equivalent to 0, 0.04, 0.79, 8.3 or 31.7 mg/kg bw/day) in the diet for 104 weeks. In the skeletal muscle, the incidence of minimal to moderate atrophy was significantly increased in the 800 ppm group (49%) when compared to controls (32%) (pages 71,73).
Reference: Tembotrione. Human-Health Risk Assessment for Proposed Uses on Field Corn, Sweet Corn and Popcorn. USEPA. September 7, 2007.

Tetraconazole - Fungicide - CAS No. 112281-77-3

• Metbolism nd Toxicokinetics. Tetraconazole was broadly distributed to all organs and tissues tested, with the highest level detected in the liver, followed by kidneys, gonads, brain and bones. Low residual levels were still detected in the liver and gastrointestinal tract (sometimes bones) at 72 hr.
• Chronic & Carcinogenicity Studies. Dorsal compression was seen in the brain of some mice at 1250 ppm, and thickening of compact bones in the cranium, ribs and collar bones, myelofibrosis [disease of the bone marrow], pale, thickened, broken, chipped and/or overgrown incisors were observed at 800 and 1250 ppm, indicating abnormal bone metabolism. (pp 4-5)
-- Rats received 0, 10, 80, 640 or 1280 ppm (the last dose to males only) of tetraconazole in the diet for 2 years... In the brain of males at 640 and 1280 ppm, dorso-lateral compression, dilated ventricles, and white thickened cranium and parietal bones were probably secondary to the osseous hypertrophy. Increased numbers of rats had pale, thickened and overgrown incisors at 640 and 1280 ppm. (page 5)
• Developmental Studies Pregnant rats received 0, 5, 22.5 or 100 mg/kg bw/day of tetraconazole by gavage on gestation days 6-15. Post-dosing salivation was noted in dams at 22.5 and 100 mg/kg bw/day. Increased water consumption at 100 mg/kg bw/day, and decreased food consumption and body weight gain at 22.5 and 100 mg/kg bw/day were observed. Liver and kidney weights were increased in dams at 100 mg/kg bw/day. There were no treatment-related effects on embryo/fetal loss, litter size and sex ratio of pups. Variable fetal weights within each group at 22.5 and 100 mg/kg bw/day might be associated with variation in degrees of skeletal ossification. Incidences of hydronephrosis and hydroureter at 100 mg/kg bw/day were increased. The number of fetuses with supernumerary rib(s) was higher, and ossification in skeletons tended to be advanced at 100 mg/kg bw/day. The NOEL was 5 mg/kg bw/day for maternal toxicity, and was 22.5 mg/kg bw/day for fetal development.
-- Pregnant rabbits received 0, 20, 40 or 80 mg/kg bw/day of tetraconazole in a preliminary study, and 0, 7.5, 15 or 30 mg/kg bw/day in the main study, by gavage on gestation days 6-18. Rabbits at 80 mg/kg bw/day showed minimal to nil food intake, body weight loss and deteriorated condition, and were sacrificed on day 7 of dosing showing increased early fetal loss. At 40 mg/kg bw/day, reduced food intake, body weight loss, lower fecal output and emaciation occurred during the dosing period, and increased liver and kidney weight were observed at necropsy. Abortion, death, post-implantation loss, and reduced fetal weight were seen in this group. Food consumption and body weight gain of dams were lower at 30 mg/kg bw/day. Incidences of malformation, anomalies and skeletal variants were low in all groups. The NOEL was 15 mg/kg bw/day for maternal toxicity, and was 30 mg/kg bw/day for fetal growth/development. (page 6)
Ref: August 2005 - Evaluation of Tetraconazole in the product Domark 40ME Fungicide. Australian Pesticides and Veterinary Medicines Authority.
http://www.fluorideaction.org/pesticides/tetraconazole.2005.report.australia.pdf

-- Reproductive and developmental toxicity. A developmental toxicity study with rats given oral gavage doses of 5, 22.5, and 100 mg/kg/day from days 6 through 15 of gestation resulted in a NOAEL for maternal toxicity of 5 mg/kg/day based upon bwt reduction, reduced food intake and post-dose salivation at the two higher doses, as compared with zero-dose controls. The developmental NOAEL was 22.5 mg/kg/day. Among the highest dose group there was evidence of minimal increase in the incidence of supernumerary ribs among the fetuses.
-- A chronic feeding/carcinogenicity study was conducted with tetraconazole in Crl:CD-l (ICR)BR mice at dietary levels of 10, 90, 800, and 1,250 ppm for 80 weeks. Treatment-related non-neoplastic changes were also seen at 1,250 ppm in the lungs, kidneys, testes, epididymides, ovaries and bone, particularly the cranium; a compression of the brain was noted in a number of mice reflecting the extent of cranial bone changes and an increased thymic involution was seen in male mice that died on test. The 1,250 ppm dietary level for tetraconazole, because of the substantial bwt gain changes and increased mortality (more in males), appeared to be above the maximum tolerated dose (MTD). At 800 ppm, there were increases in non neoplastic changes in lungs, kidneys, testes, epididymides, ovaries and bone. In addition, there was substantial reduction in weight gain as compared with zero-dose control animals, but the mortality rate was unaffected. Eight hundred ppm appeared to be a reasonable estimate of the MTD for mouse.
Ref: Federal Register: October 14, 1999. Notice of Filing Pesticide Petitions to Establish a Tolerance for Certain Pesticide Chemicals in or on Food. PP 9F5066, 9F6023, and 7E4830. http://www.fluoridealert.org/pesticides/tetraconazole.fr.oct14.1999.htm

-- Chronic toxicity. EPA has established the RfD for tetraconazole at 0.005 mg/kg/day. This RfD is based on a 2-year chronic toxicity/ carcinogenicity study in rats with a NOAEL of 0.5 mg/kg/day 10 ppm and an uncertainty factor of 100 based on osseous hypertrophy of skull bones at the LOAEL of 3.9 mg/kg/day 80 ppm. Due to the severity of pup effects in the rat reproduction study, an additional FQPA safety factor of three has been applied to the acute and chronic RfD calculations. The percent of acute and chronic RfD utilized should not exceed 33%.
-- Developmental toxicity studies-- a. Rats. In the developmental study in rats, the maternal (systemic) NOAEL was 5 mg/kg/day, based on decreased body weight and decreased food consumption at the LOAEL of 22.5 mg/kg/day. The developmental (fetal) NOAEL was 22.5 mg/kg/day, based on visceral changes, supernumerary ribs, and delayed ossification at the LOAEL of 100 mg/kg/day.
-- Reproductive toxicity study-- Rats. In the 2-generation reproductive toxicity study in rats, the maternal (systemic) NOAEL was 0.7 mg/kg/day, based on dystocia, delayed vaginal opening, and increased liver weight at the LOAEL of 5.9 mg/kg/day. The developmental (pup) NOAEL was 0.7 mg/kg/day, based on increased time to observation of balanopreputial skin fold [foreskin] and liver weight at the LOAEL of 5.9 mg/ kg/day. At the high dose of 35.5 mg/kg/day, there was a decrease in the mean number of live pups per litter on lactation days 0 and 4 (precull) in the presence of significant maternal toxicity.
Ref: Federal Register: December 6, 1999. Tetraconazole; Pesticide Tolerances for Emergency Exemptions. Final Rule. http://www.fluoridealert.org/pesticides/tetraconazole.fr.dec.1999.htm
• Note from EC:
Dystocia. Literally, it means difficult labor and practically means abnormally slow progress of labor. The word comes from the Greek 'dys' meaning 'difficult, painful, disordered, abnormal' and 'tokos' meaning 'birth'. Four potential factors may cause difficult labor characterized by abnormally slow progress. They may occur separately or together. 1) Uterine contractions may be either too weak or too uncoordinated to open up the cervix. There may also be inadequate pushing with voluntary muscles during the second stage of labor. 2) The baby may be lined up wrong to easily pass through the birth canal. Alternatively, there may be other problems with the baby that also retard passage of the baby through the birth canal. 3) The maternal bony pelvis may be too narrow to allow the baby to pass through the birth canal. 4) Abnormalities of the birth canal other than those of the bony pelvis may obstruct fetal descent. The most common cause of dystocia is a small bony pelvis and/or insufficiently strong and coordinated uterine contractions. [drnathan/sitedex.htm]."
- Balanopreputial skin fold- see: http://www.cirp.org/library/history/hodges1/

1,1,1,2-Tetrafluoroethane (HFC-134a) - Propellant, US EPA List 4B Inert - CAS No. 811-97-2

-- In a developmental toxicity study, Lu and Staples (1981) exposed pregnant CD rats to HFC-134a at 30,000, 100,000, or 300,000 ppm for 6 h/d from days 6 to 15 of gestation. Following exposure of dams at 300,000 ppm, there was a significant reduction in fetal weight and significant increases in several skeletal variations. At 300,000 ppm, signs of maternal toxicity included reduced food consumption, reduced body weight gain, lack of response to noise stimuli, severe tremors, and uncoordinated movements. Dams exposed at 100,000 ppm showed reduced response to noise stimuli and uncoordinated movements. No terata or evidence for developmental toxicity were observed following exposure of dams at 30,000 or 100,000 ppm.
-- Hodge et al. (1979) exposed groups of 29 or 30 pregnant Wistar-derived rats to HFC-134a at 0, 1,000, 10,000, or 50,000 ppm for 6 h/d on days 6 to 15 of gestation. Abnormal clinical signs were observed in the animals, but there was no effect on maternal body weights. At 50,000 ppm, there was no evidence of terata, but fetal body weight was significantly reduced, and skeletal ossification was significantly delayed. There were no effects on any parameter at 10,000 ppm.
-- Groups of 28 pregnant New Zealand white rabbits were exposed at 0, 2,500, 10,000, or 40,000 ppm for 6 h/d on days 7 through 19 of pregnancy (Collins et al. 1995; Wickramaratne 1989 a,b). Doe were weighed during the study and sacrificed on day 29 of gestation... In the mid- and high-dose exposure groups, doe had reduced body weight gains compared with the control group; lower weight gains were partially associated with decreased food consumption. With the exception of a significantly increased incidence of unossified seventh-lumbar transverse process in fetuses in the 10,000- and 40,000-ppm groups, all other parameters were similar among control and treatment groups. This effect was also observed in the control group and was not considered treatment related. Therefore, there was no adverse developmental or teratogenic effect associated with exposure to FC-134a.
-- -- ... Fetotoxicity was ovserved in rats when dams were exposed at 50,000 ppm (Hodge et al. 1979). Slight maternal toxicity in rabbits, as indicated by lower body weight gains compared with the control group, were noted at 10,000 and 50,000 ppm (Collins et al. 1995). There was a slight delay in physical development of F1 rats following exposure of F0 females at 64,400 ppm (Alexander et al. 1996).
-- Alexander DJ, Libretto SE, Adams MJ, Hughes EW, Bannerman M. 1996. HFA-134a (1,1,1,2-tetrafluoroethane): effects of inhalation exposure upon reproductive performance, development and maturation of rats. Human Exp Toxicol 15:508-517.
-- Collins MA, Rusch GM, Sato F, Hext PM, Millischer RJ. 1995. 1,1,1,2-Tetrafluoroethane: repeat exposure inhalation toxicity in the rat, developmental toxicity in the rabbit, and genotoxicity in vitro and in vivo. Fundam Appl Toxicol 25:271-280.
-- Hodge MCE, Kilmartin M, Riley RA, Weight TM, Wilson J. 1979. Arcton 134a: teratogenicity study in the rat. ICI Report no. CTL/P/417. Central Toxicology Laboratory, Alderly Park, Macclesfield, Cheshire, U.K.
-- Lu M, Staples R. 1981. 1,1,1,2-tetrafkyirietgabe (FC-134a): embryo-fetal toxicity and teratogenicity study by inhalation in the rat. Report No. 317-81. Haskell Laboratory, Wilmington, DE. (Cited in NRC 1996).
-- Wickramaratne GA. 1989a. HCF-134a: Teratogenicity inhalation study in the rabbit. ICI Report No. CTL/P/2504. Central Toxicology Laboratory, Alderly Park, Macclesfield, Cheshire UK (Unpublished).
-- Wickramaratne GA. 1989b. HCF-134a: Embryotoxicity inhalation study in the rabbit. ICI Report No. CTL/P/2380. Central Toxicology Laboratory, Alderly Park, Macclesfield, Cheshire, UK. (Unpublished).
Ref: National Research Council. 2002. Acute Exposure Guideline Levels for Selected Airborne Chemicals. Volume 2. Subcommittee on Acute Exposure Guideline Levels, Committee on Toxicology, Board of Environmental Studies and Toxicology, Division of Earth and Life Studies. Available from: National Academy Press, 2101 Constitution Ave, NW, Box 285, Washington DC 20055. ISBN 0-309-08511-X. Online at:
http://books.nap.edu/books/030908511X/html/index.html

MUSCULOSKELETAL 0.2.15.1 ACUTE EXPOSURE - Rhabdomyolysis has been reported in a worker susceptible to malignant hyperthermia after exposure to fluorinated hydrocarbons and also following intentional freon inhalation. Compartment syndrome is a rare complication of severe exposure.
Ref: Hazardous Substances Data Bank for 1,1,1,2-TETRAFLUOROETHANE CASRN: 811-97-2.
http://www.fluorideaction.org/pesticides/1,1,1,2-tetrafluoroe.toxnet.htm
• Note from FAN: From online site on Rhabdomyolysis by DR PAUL A. BAGGALEY
Rhabdomyolysis is a common disorder which may result from a large variety of diseases, trauma, or toxic insults to skeletal muscle. It may be defined as a clinical and biochemical syndrome resulting from an injury which damages the integrity of the sarcolemma of skeletal muscle, leading to the release of potentially toxic muscle cell components into the circulation.(1,2,3) This may result in potential life-threatening complications including myoglobinuric acute renal failure, hyperkalaemia and cardiac arrest, disseminated intravascular coagulation, and more locally, compartment syndrome - see http://members.tripod.com/~baggas/rhabdo.html

Thiazopyr - Herbicide - CAS No. 117718-60-2

-- A developmental toxicity study in rats at 0, 10, 100 and 250 mg/kg/day with a maternal toxicity NOEL of 100 mg/kg/day. The effect were increased liver weight, increased salivation, significantly decreased body weight gain and decreased food consumption. The developmental NOEL was also 100 mg/kg/day. The effects at the high dose were increased incidence of unossified sternebrae and 7th cervical rib variation. No development effects were observed below the maternally toxic doses.
Ref: US EPA. Pesticide Fact Sheet. Thiazopyr Reason for Issuance: Registration of a New Chemical Date Issued: February 20, l997.
http://www.epa.gov/opprd001/factsheets/thiazopyr.pdf

Tolylfluanid - Fungicide - CAS No. 731-27-1

In all species tested, the concentrations of fluoride in the bone and teeth were increased in a dose-related manner. At high doses, this increase was associated with discolouration, particularly of the skull cap and incisors, in both sexes but starting at lower doses in male rats. In long-term studies, rats at 7500 ppm, equal to 500 mg/kg bw per day, required treatment for overgrown incisors more frequently than controls, presumably because fluoride deposition in the incisors had increased their strength and thus decreased the wear on these teeth. Hyperostosis of the skull and sternum was seen at high doses in mice and rats of either sex, and histopathological changes were seen in the bones of female mice at 300 ppm (equal to 120 mg/kg bw per day) and female rats at 1500 ppm (equal to 100 mg/kg bw per day). In both sexes, increased fluoride deposition was seen at 300 ppm, equal to 76 mg/kg bw per day, in mice and 18 mg/kg bw per day in rats. The NOAEL for fluoride deposition was 60 ppm, equal to 15 mg/kg bw per day, in mice, and 60 ppm, equal to 3.6 mg/kg bw per day, in rats. In dogs, the fluoride concentration in bone was increased in males at doses of 80 mg/kg bw per day and in females at 20 mg/kg bw per day and above, while the fluoride concentration in teeth was increased in males at 80 mg/kg bw per day and in females at all doses including the lowest one tested, 5 mg/kg bw per day, although not in a dose-related manner. The increase in fluoride deposition raises concern because mottling of dental enamel (or dental fluorosis) occurs in humans after exposure to high concentrations of fluoride, particularly where water has a high concentration of fluoride or has been inappropriately supplemented. While this is mainly a cosmetic defect, it is generally recognized as adverse. (page 254-255)
..........The Meeting established an ADI of 0–0.08 mg/kg bw on the basis of the NOAEL of 60 ppm, equal to 3.6 mg/kg bw per day, in the 2-year study in rats, in which increased fluoride deposition was seen at higher doses, and a safety factor of 50. This safety factor was used because of the limited differences noted between species in the deposition of fluoride in bones and teeth after administration of tolylfluanid. The NOAEL in the 2-year study in rats treated in the diet was used in preference to the LOAEL of 5 mg/kg bw per day in the 1-year study in dogs given tolylfluanid by capsule, as increased fluoride concentrations were seen only in the teeth and the low dose in the study in dogs, without a clear dose–response relationship... (page 256)
..........Metabolism involves cleavage of the fluorodichloromethylthio group from tolylfluanid to form N,N-dimethyl-N’-p-tolysulfamide (dimethylaminosulfotoluidine, DMST). The fluorodichloromethylsulfenyl side-chain undergoes further metabolism to form thiazolidine-2-thioxo-4-carboxylic acid, which is the main metabolite in the urine of rats and is of toxicological significance because of its potential anti-thyroid effects. Dimethyltolylsulfamide is also further metabolized, producing a range of metabolites that are not of toxicological significance. The release of the fluoride ion and its distribution in the body have not been clearly characterized. (page 254)
..........Studies that would provide information useful for continued evaluation of the compound (page 257)
• Further characterization of the distribution and excretion of fluoride and thiazolidine-2-thione4-carboxylic acid, particularly in milk
• Investigation of the cause of decreased pup survival during lactation
• Further observations in humans
Ref: Pesticide residues in food - 2002. Report of the Joint Meeting of the FAO Panel of Experts on Pesticide Residues in Food and the Environment and the WHO Core Assessment Group on Pesticide Residues. Rome, Italy. 16- 25 September 2002. ISBN 92-5-104858-4.
http://www.fluorideaction.org/pesticides/tolylfluanid.fao.2002.pdf

Toxicity - General: The skeletal system (bones and teeth), liver and thyroid were identified as target organs in the animal studies.
Ref: US EPA Pesticide Fact Sheet. Reason for Issuance: Import Tolerance. September 2002.
http://www.fluorideaction.org/pesticides/tolylfluanid.epa.facts.2002.pdf

Chronic toxicity studies on tolylfluanid were done in the rat, mouse and dog. Tolylfluanid was tested in two rat chronic dietary studies. Increased growth of the incisors of the upper jaw and skeletal changes (hyperostosis in the skull and ribs) resulted from the high fluorine content of the compound...
Ref: Federal Register: August 11, 1997 (Volume 62, Number 154). Page 42980-42986. Notice of Filing of Pesticide Petitions.
http://www.fluoridealert.org/pesticides/tolyfluanid.fr.august.1997.htm

-- Prenatal developmental in nonrodents (rabbit). Developmental NOAEL = 25 mg/kg/day LOAEL= 70 mg/kg/day, based on increased malformations (arthrogryposis [see definition below] of front extremities and small orbital cavity/folded retina) and variations (floating rib and accelerated ossification).
-- 2-Generation reproduction and fertility effects (rat). Parental/systemic NOAEL not established LOAEL = 15.9-21.5 mg/ kg/day, based on hardened crania of P generation animals Reproductive NOAEL not established LOAEL = 15.9-21.5 mg/ kg/day, based on increased clinical signs of toxicity Offspring NOAEL > 15.9-21.5 mg/kg/day (HDT) LOAEL not established
-- Combined chronic toxicity/carcinogenicity rodents (rat): NOAEL = 18.1/21.1 mg/ kg/day (M/F); LOAEL = 90.1/105.2 mg/ kg/day (M/F), based on skeletal changes. Evidence of thyroid follicular cell adenomas and/or carcinomas in high- dose males and females.
-- Combined chronic toxicity/carcinogenicity rodents (rat): NOAEL = 20/20 mg/kg/ day (M/F); LOAEL = 80/110 mg/kg/day (M/F), based on bone hyperostosis in males and females. Evidence of thyroid follicular cell adenomas and/or carcinomas in high- dose males and females.
-- -- Carcinogenicity rodents (mouse): NOAEL = 76.3/123.9 mg/kg/day (M/F) LOAEL = 375.8/610.8 mg/kg/day (M/F), based on skeletal, liver, and kidney changes. No evidence of carcinogenicity.
Ref: Federal Register: September 25, 2002. Tolylfluanid; Pesticide Tolerance. Final Rule. Federal Register. http://www.fluoridealert.org/pesticides/tolylfluanid.fr.sept25.2002.htm

WHAT IS ARTHROGRYPOSIS? Published by AVENUES A National Support Group for Arthrogryposis Multiplex Congenita - http://www.sonnet.com/avenues/pamphlet.html "Arthrogryposis" (Arthrogryposis Multiplex Congenita) is a term describing the presence of multiple joint contractures at birth. A contracture is a limitation in the range of motion of a joint. In some cases, few joints maybe affected and the range of motion may be nearly normal. In the "classic" case of Arthrogryposis, hands, wrists, elbows, shoulders, hips, feet, and knees are affected. In the most severe cases, nearly every body joint may be involved, including the jaw and back. Frequently, the joint contractures are accompanied by muscle weakness which further limits movement. Arthrogryposis is relatively rare, occurring in perhaps one in 3,000 births... There is a wide variation in the degree to which muscles and joints are affected in those with Arthrogryposis. In some cases, Arthrogryposis may be accompanied by other conditions, such as central nervous system disorders, which complicate the picture... In general, there are four causes for limitation of joint movement before birth: (1) Muscles do not develop properly (atrophy). In most cases, the specific cause for muscular atrophy cannot be identified. Suspected causes include muscle diseases (for example, congenital muscular dystrophies), maternal fever during pregnancy, and viruses which may damage cells which transmit nerve impulses to the muscles. (2) There is not sufficient room in the uterus for normal movement. For example, the mother may lack normal amount of amniotic fluid, or have an abnormally shaped uterus. (3) Central nervous system and spinal cord are malformed. In these cases, Arthrogryposis is usually accompanied by a wide range of other conditions. (4) Tendons, bones, joints or joint linings may develop abnormally. For example, tendons may not be connected to the proper place in a joint.

Transfluthrin - Insecticide - CAS No. 118712-89-3

-- The target organs were the liver (rat, mouse and dog) and kidney (rat)... In the rat, increases in fluoride content of teeth and bone were observed from 50 ppm in oral studies and at 200 mg m3 following inhalation exposure in 90 d studies.
-- Reproductive Toxicity. Developmental studies in both the rat and rabbit provided no evidence of teratogenicity when transfluthrin was administered at 125 and 150 mg kg d respectively. One death occurred at 125 mg kg d in the rat study and 2 deaths (1 each at 50 and 150 mg kg d) occurred in the rabbit study... The NOEl for parental toxicity was based on the following observations at 1000 ppm: - decreased body weight and body weight gain, increased absolute and relative liver and kidney weights, increased relative kidney weight, decreased hepatic triglyceride content, increased incidence of tubular pigmentation, tubular casts and pelvic calcinosis.
-- In a 90 d study Bor: WISW (SPF Cpb) rats (10 animals/sex/group) were administered diets containing 0, 10, 50, 500 or 5000 ppm transfluthrin (95% pure) in food moistened with peanut oil to avoid dust. The main study groups were treated for 13 w and 2 satellite groups had been intended as recovery groups from weeks 14-18 but were treated by accident. Animals were observed twice daily and clinical laboratory examinations carried out at 1 and 3 months... There was a dose-dependent increase in tooth fluoride content (significant above 50 ppm) reaching ~ 525% in males, ~350% in females at 14 w... The NOEL for this study was 10 ppm (0.85 mg kg d) based on the effects at and above 50 ppm (4.0 mg kg d) of significant increase in fluoride levels in teeth and bone in both sexes and evidence of kidney toxicity (based on absolute and relative weight increases in both sexes and urinary protein content increases in males). In addition liver and thyroid toxicity was noted at 500 and 5000 pm.
-- In a 90 d study Bor: WISW (SPF-Cpb) rats (10 animals/sex/group) were exposed via head and nose to an aerosol of transflutrin (95^ pure) in polyethylene glycol E400 and ethanol (1:1) for 6 h d and 5 d w. In addition 2 satellite groups were exposed to the vehicle or the top concentration and then observed for a further 4 w post-treatment. The measured exposure concentrations used were 0 (air and vehicle controls), 4.9, 46.7 or 220.2 mg m-3 (a top dose of 338.9 mg m-3 was used for 1 d. Due to a high mortality rate this was reduced to 220.2 mg m-3, the animals replaced and the study continued). ... Fluoride concentration measurements of bone ash showed a significant increase of approximately 30% in males at 220.2 mg m-3 both at the end of treatment and post treatment phases. Fluoride concentration teeth was significantly increased in females at 220.2 mg m-3 by approximately 50%. ... The NOEC for this study was 46.7 mg m=3. This is based on clinical signs of toxicity, increased fluoride incorportion into teeth and bone, and non-specific clinical chemistry changes at 220.2 mg m-3.
-- 3.3.3.4 Summary ... Following oral administratin the major target organ in the rat and dog was the liver, with evidence of kidney toxicity also seen in the rat. Fluoride determinations were undertaken in the rat only and showed evidence of accumulation in teeth and bone from 50 ppm (4 mg kg d)...
-- 3.2.3.2 In Vivo Studies. In a micronucleus study, Bor: NMRI (SPF Han) mice (5/sex) received a single gavage dose of 375 mg kg transfluthrin (95% pure) in Lutrol E 400. This dose was chosen following a range finding study in which mice received doses of between 250 and 2500 mg kg. In the range finding study, mortalities (1/5) and significant signs of toxicity (roughened fur, lateral position, twitching, spasm, salivation and shivering) were observed at 475 mg kg and above. In the main study similar signs of toxicity were observed for up to 24 h post dosing. It was reported that 7/40 animals died during this study and that a replacement group were treated in parallel to replace the animals which died. Sampling was undertaken at 24, 48 and 72 h post dosing. 1000 PCE's were scroed per animal and NCE's per 1000 PCE. Individual results were not reported. The PCE/NCE ratio as 1.06, 0.74 and 1.36 at 24, 48 and 72 h. Thus there is some indication of bone marrow toxicity at 48 h.
-- 3.2.4 Carcinogenicity Studies. ... In a combined chronic toxicity and carcinogenicity study, groups of 60 Wistar rats (strain Bor:WISW (SPF Cpb) of both sexes were administered transfluthrin (94.5-95% pure) in the diet at concentrations of 0, 20, 200 or 2000 ppm for 109 weeks. In addition, groups of 10 male and 10 female rats were treated identically for full interim necropsy at 52 weeks.... Fluoride accumulation occurred in both teeth and bone (femur) at 200 and 2000 ppm in males and females at 1 and 2 yr. The reported increases were approximately 2 and 5 fold for teeth (from 0.1 to 0.8 mg F/g ash) and 2 and 4 fold for bone (0.5-3 mg F/g ash). The main target organs were the liver and kidney...
-- B6C3F1 mice (60/group/sex) received 0, 10, 100 or 1000 ppm mg kg transfluthrin (94.8-95%) pure in the diet for up to 104 weeks with 10/sex/dose killed after one yar. Two additional groups(10/sex) received 0 or 1000 ppm for 13 weeks. ... Fluoride accumulation in bone and teeth of both sexes were observed (in the 13 week study at 1000 ppm) and at 53 and 104 weeks from 100 ppm (approximately 2 fold at 100 ppm and 4-5 fold at 1000 ppm with respect to controls). ... Based on the chronic toxicity, in males the NOEL is 10 ppm (2 mg kg d based on increases in liver weight and hepatocyte hypertrophy, at 1000 ppm and increased fluoride accumulation at 100 ppm). It is not possible to set a NOEL for females as increases in serum cholesterol, protein and albumin were reported at the lowest dose.
-- 3.2.4 Carcinogenicity Studies. The two available studies, in the rate and mouse both combine chronic toxicity and carcinogenicity... Single incidences of tumours occurring in treated groups but not controls were reported in the kidneys, ovaries, brain, parathyroid and skeletal muscle. Neither these, nor the occasional incidences of systemic tumors presented in Table 3.3 were considered to be treatment related (page 23).
-- 3.2.5 Reproductive Toxicology. 3.2.5.1 Developmental Studies. 3.2.5.1.1 Rat. In an adequately conducted developmental toxicology study, rats (28.group) were administered transfluthrin )95%) purity in 5% (v/v) aqueous Emulphor EL 719 vehicle by gavage at doses of 0, 25, 55 and 125 mg kg d during days 6-15 of gestation. Control animals received vehicle alone... Necropsy of the dams and examination of the foetuses were performed on day 20 of gestation. ... A significant increase in delayed ossification was observed for 3 skeletal elements (cervical arches, first and second sternebrae) at 55 mg kg d. However, this finding was not dose-dependent and there was no indication of delayed systemic ossificaiton. Therefore, this observation is considered incidental.. Transfluthrin was not teratogenic under the conditions of study. The NOEL for maternal toxicity was 25 mg kg d based upon tremors observed at 55 mg kg d and above.
Ref: Evaluation on: Transfluthrin Use as a Public Hygiene Insecticide. September 1997. Prepared by: the UK Health and Safety Executive, Biocides & Pesticides Assessment Unit, Magdalen House, Stanley Precinct, Bootle, Merseyside L20 3QZ. Available from: Department for Environment, Food and Rural Affairs, Pesticides Safety Directorate, Mallard House, Kings Pool, 3 Peasholme Green, York YO1 7PX. UK. Available at
http://www.pesticides.gov.uk/citizen/evaluations/165_confirm-box.htm
• Note: This was transcribed from the copy available on the web. While one can easily read this report on the web, the report is inaccessible, or locked, to any attempt to copy it. Any errors are mine. EC.

Trichlorofluoromethane - Insecticide, Fungicide, Propellant, EPA List 2 Inert - CAS No. 75-69-4

-- Aerosol sprays containing fluorocarbon propellants are another source of solvent intoxication. Prolonged exposure or daily use may result in damage to several organ systems. Clinical problems include cardiac arrhythmias, bone marrow depression, cerebral degeneration, and damage to liver, kidney, & peripheral nerves. Death occasionally has been attributed to inhalant abuse, probably via the mechanism of cardiac arrhythmias, especially accompanying exercise or upper airway obstruction. /fluorocarbon propellants/ [Hardman, J.G., L.E. Limbird, P.B. Molinoff, R.W. Ruddon, A.G. Goodman (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 9th ed. New York, NY: McGraw-Hill, 1996. 575]
-- MUSCULOSKELETAL 0.2.15.1 ACUTE EXPOSURE - Rhabdomyolysis has been reported in a worker susceptible to malignant hyperthermia after exposure to fluorinated hydrocarbons and also following intentional freon inhalation. Compartment syndrome is a rare complication of severe exposure.
Ref: Hazardous Substances Data Base for TRICHLOROFLUOROMETHANE.
http://www.fluoridealert.org/pesticides/trichlorofluorometha.toxnet.htm
• Definition
Rhabdomyolysis - The destruction of skeletal muscle cells. Often the result of electrical injury, alcoholism, injury (or laying in one position for an extended period of time), drug side effects or toxins.

Trifloxystrobin - Fungicide - CAS No. 141517-21-7

Subchronic toxicity. In subchronic studies, several mortality related changes were reported for the top dose in dogs (500 mg/kg) and rats (800 mg/kg). At these dose levels, excessive toxicity has resulted in body weight loss and mortality with the associated and non-specific changes in several organs (such as atrophy in the thymus, pancreas, bone marrow, lymph node, and spleen) which are not considered specific target organs for the test compound... In the rabbit teratology study, body weight loss and dramatically reduced food consumption were observed in the dam at 250 mg/ kg. No teratogenic effects or any other effects were seen on pregnancy or fetal parameters except for the increase in skeletal anomaly of fused sternebrae-3 and sternebrae-4 at the top dose level of 500 mg/kg. This finding is regarded as a marginal effect on skeletal development that could have resulted from the 40-65% lower food intake during treatment at this dose level. The developmental NOAEL was 250 mg/kg.
Ref: Federal Register. November 14, 2001. [PF-1048; FRL-6806-6]
http://www.fluoridealert.org/pesticides/trifloxystrobin.fr.nov14.01.htm

Reproductive toxicity Target / critical effect - Reproduction: Decreased bodyweight gain of pups and delayed eye opening at parental toxic doses. Lowest relevant reproductive NOAEL / NOEL: 50 ppm(2.3 mg/kg bw/day). Target / critical effect - Developmental toxicity: Enlarged thymus (rat) and skeletal effects (rabbit) at maternally toxic dose levels. Lowest relevant developmental NOAEL / NOEL: 50 mg/kg bw/day (rabbit)
Ref: Review report for the active substance trifloxystrobin. Trifloxystrobin. SANCO/4339/2000-Final. 7 April 2003. Finalised in the [European Commission] Standing Committee on the Food Chain and Animal Health at its meeting on 15 April 2003 in view of the inclusion of trifloxystrobin in Annex I of Directive 91/414/EEC.
http://www.fluorideaction.org/pesticides/trifloxystrobin.eu.april.03.pdf

Trifloxysulfuron-sodium - Herbicide - CAS No. 199119-58-9

-- In the rat teratology study, 300 and 1,000 mg/kg/day caused maternal toxicity consisting of reduced body weight and food consumption. Developmental toxicity was secondary to maternal toxicity and consisted of slightly reduced fetal body weights and an increase in minor skeletal anomalies and variations. The NOAELs for maternal and developmental toxicity were both 30 mg/kg/day...
Ref: Federal Register: March 21, 2003. Trifloxysulfuron-sodium; Notice of Filing a Pesticide Petition to Establish a Tolerance for a Certain Pesticide Chemical in or on Food.
http://www.fluoridealert.org/pesticides/Trifloxysulfuron-s.Mar21.03.htm

-- Prenatal developmental in rodents (rats). Maternal NOAEL: 300 mg/kg/day Maternal LOAEL: 1,000 mg/kg/day based on decreased food consumption during treatment, decreased body weight gain during post-treatment. Developmental NOAEL: 300 mg/kg/day Developmental LOAEL: 1,000 mg/kg/day based on slight decrease in fetal weight, increased skeletal anomalies, increased poor/absent skeletal ossification.
-- 90-Day oral toxicity in nonrodents (dogs). NOAEL: 19.8/19.6 mg/kg/day (M/F) LOAEL: 164.2/167.3 mg/kg/day (M/F): M = decreased body weight gain (20%), slight hematological effects, clinical chemistry changes suggesting hepatotoxicity, decreased thymus weight, thymic atrophy, increased glycogen in liver, hemorrhage in mesenteric lymph nodes; F = decreased body weight gain (44%), anemia with extramedullary hematopoiesis in liver/ spleen and myeloid hyperplasia in bone marrow, clinical chemistry changes suggesting hepatotoxicity, decrease thymus weight, thymic atrophy and hyaline tubular change in kidney.
Ref: Federal Register: September 17, 2003 (Volume 68, Number 180)] Rules and Regulations. Trifloxysulfuron; Pesticide Tolerance. Final Rule.
http://www.fluorideaction.org/pesticides/trifloxysulfuron.fr.sept.03.htm

Triflumizole - Fungicide - CAS No. 68694-11-1

-- Prenatal Maternal developmental in rodents (rat): Developmental NOAEL = 10 mg/kg/ day LOAEL = 35 mg/kg/ day based on decreased numbers of viable fetuses, increased dead or resorbed fetuses, increased numbers of late resorptions, decreased fetal body weight, and increased incidences of cervical ribs.
-- Prenatal Maternal developmental in nonrodents (rabbit): Developmental NOAEL = 50 mg/kg/ day LOAEL = 100 mg/kg/ day based on decreased 24-hour survival, decreased placental weights, and increased fetal and litter incidences of lumbar ribs.
Ref: Federal Register: June 12, 2002. Triflumizole; Pesticide Tolerance. Final Rule.
http://www.fluoridealert.org/pesticides/triflumizole.fr.june12.2002.htm

-- The teratology studies were conducted in the rabbit and rat. In the rat studies, incidences of dilatation of the renal pelvis and increased 14th rudimentary ribs were seen. In the rabbit, an increase in postimplantation losses was noted.
Ref: Ref: EPA Pesticide Fact Sheet September 1991. Triflumizole (Terraguard, Procure).
http://pmep.cce.cornell.edu/profiles/fung-nemat/tcmtb-ziram/triflumizole/fung-prof-triflumizole.html

Trifluralin - Herbicide - CAS No. 1582-09-8

5.2 RISK TO AQUATIC ORGANISMS.Trifluralin induces vertebral lesions in several fish species, and in some instances this effects is induced after short term exposure (24 hours for brown trout). (page 21-22).
Ref: March 14, 2005. European Food Safety Authority: Conclusion regarding the peer review of the pesticide risk assessment of the active substance trifluralin. EFSA Scientific Report (2005) 28, 1-77.
http://www.fluoridealert.org/pesticides/trifluralin.eu.long.2005.pdf

Sheepshead minnows, Cyprinodon variegatus Laeepede, exposed to 5 5 to 31 /xg/1 of the herbicide trifluralin, throughout their first 28 days of life, developed a heretofore undescribed vertebral dysplasia. This dysplasia consisted of semisymmetrical hypertrophy of vertebrae (three to 20 times normal), characterized by foci of osteoblast and fibroblasts actively laying down bone and bone precursors. Effects of the abnormal vertebral development were dorsal vertebral growth into the neural canal, ventral compression of renal ducts, and longitudinal fusion of vertebrae. Fish, exposed for 51 days to 16-6 /ng/1 trifluralin and thereafter depurated for 41 days, showed no increase in vertebral dysplasia during depuration; however, residual spinal column damage was evident. Serum calcium concentrations were elevated in adult fish exposed for 4 days to 16-6 /xg/1 trifluralin. Fluorosis or mimicry of hypervitaminosis A are considered possible mechanisms for the osseous effect, but are not considered to be the only possible causes. The highly predictable nature of this disorder in experimental exposures strengthens the probability that young flsh may serve as experimental models for determining effects of chemicals on early vertebrate ontogeny, particularly in regard to skeletal development.
Excerpt: Trifluralin (2, 6 dinitro-N, N-dipropyl-4-(trifluoromethyl) Benzamine) is a fluorine containing, pre-emergent herbicide widely used in the United States (Wiswesser 1976). Continuous laboratory exposure of early life stages of the sheepshead minnow Cyprinodon variegatus Laeepede to relatively low concentrations of trifluralin results in marked vertebral dysplasia...
Ref: Vertebral dysplasia in young fish exposed to the herbicide trifluralin. By JA COUCH, JT WINSTEAD, DJ HANSEN and LR GOODMAN. Journal of Fish Diseases 1979, 2, 35-42.
Full report at: http://www.fluorideaction.org/pesticides/trifluralin.1979.paper.pdf

Sheepshead minnows, Cyprinodon variegatus Laeepede, exposed to 5 5 to 31 /xg/1 of the herbicide trifluralin, throughout their first 28 days of life, developed a heretofore undescribed vertebral dysplasia. This dysplasia consisted of semisymmetrical hypertrophy of vertebrae (three to 20 times normal), characterized by foci of osteoblast and fibroblasts actively laying down bone and bone precursors. Effects of the abnormal vertebral development were dorsal vertebral growth into the neural canal, ventral compression of renal ducts, and longitudinal fusion of vertebrae. Fish, exposed for 51 days to 16-6 /ng/1 trifluralin and thereafter depurated for 41 days, showed no increase in vertebral dysplasia during depuration; however, residual spinal column damage was evident. Serum calcium concentrations were elevated in adult fish exposed for 4 days to 16-6 /xg/1 trifluralin. Fluorosis or mimicry of hypervitaminosis A are considered possible mechanisms for the osseous effect, but are not considered to be the only possible causes. The highly predictable nature of this disorder in experimental exposures strengthens the probability that young flsh may serve as experimental models for determining effects of chemicals on early vertebrate ontogeny, particularly in regard to skeletal development.
Excerpt: Trifluralin (2, 6 dinitro-N, N-dipropyl-4-(trifluoromethyl) Benzamine) is a fluorine containing, pre-emergent herbicide widely used in the United States (Wiswesser 1976). Continuous laboratory exposure of early life stages of the sheepshead minnow Cyprinodon variegatus Laeepede to relatively low concentrations of trifluralin results in marked vertebral dysplasia...
Ref: Vertebral dysplasia in young fish exposed to the herbicide trifluralin. By JA COUCH, JT WINSTEAD, DJ HANSEN and LR GOODMAN. Journal of Fish Diseases 1979, 2, 35-42.
Full report at: http://www.fluorideaction.org/pesticides/trifluralin.1979.paper.pdf

High doses of trifluralin are associated with increases in kidney, bladder, and thyroid tumors. Dogs chronically exposed to trifluralin in their diet showed decreased weight gain, changes in hematological parameters, and increased liver weight. Skeletal abnormalities were observed in the offspring of mice exposed via gavage (experimentally introducing trifluralin into the stomach). The RfD for trifluralin is based on increased liver weights and an increase in methemoglobinemia in dogs.
Ref: March 2000. Public Health Assessment Cenex Supply and Marketing, Inc. Quincy, Washington. CERCLIS # WAD058619255. Draft for Public Comment.. Prepared by: Washington State Department of Health Under Cooperative Agreement with the Agency for Toxic Substances and Disease Registry. Also available at http://www.doh.wa.gov/ehp/oehas/Cenex%20PHA%20Draft%20Public%20Review.pdf

-- ** 089 036915 "A Teratology Study (I) of Trifluralin (EL-152, Compound 36352) Administered Orally to Dutch Belted Rabbits." (Lilly Research Labs., 10/31/84, Study B02283 and Study BO1784) Trifluralin (96.7% pure), lot 00554AP2; 0, 100, 225, 500, or 800; oral gavage, days 6 - 18; 20/group; maternal NOEL = 225 mg/kg (maternal death and abortions), developmental toxicity NOEL = 225 mg/kg (decreased fetal weight); Complete and ACCEPTABLE WITH 036916. No adverse developmental toxicity reported. JAP, 11/18/85. EPA one-liner: Maternal NOEL = 225 mg/kg (abortions and anorexia), fetotoxic NOEL = 225 mg/kg (decreased percentage of live fetuses - cardiomegally and wavy ribs at 500 mg/kg/day); Core grade = Supplementary
Ref: SUMMARY OF TOXICOLOGY DATA TRIFLURALIN. California EPA, Department of Pesticides, Medical Toxicology Branch. Revised as of 11/29/95.
http://www.cdpr.ca.gov/docs/toxsums/pdfs/597.pdf

Teratology - rat: Maternal NOEL=100 mg/kg/day; Maternal LEL=500 mg/kg/day (decreased food consumption and increased liver and spleen weights); Developmental NOEL=none; LEL=20 mg/kg/day (reduced skeletal maturity and increased vascular fragility); core grade supplementary (Hoechst Aktiengesellschaft, 1983)
Ref: US EPA IRIS for Trifluralin CASRN: 1582-09-8.
http://www.epa.gov/iris/

Fish Vertebral Lesion Study: Based on the results from the field monitoring study, the Agency required a fish vertebral lesion study. The study submitted has been classified as invalid because of an inadequate control group, however, additional data are not required. Trifluralin contamination in both the acetone and water controls led to detectable concentrations in the fish at termination. Also, the stock fish that were used as a negative control were three to four weeks older than the test organisms at the time of radiographic exams. The stock fish had high incidence of wavy ribs (27.5%) and vertebral anomalies (23.8%). The Trifluralin Data Development Consortium (TDDC) has submitted a rebuttal to the review that classified this study as invalid. This rebuttal is currently being evaluated by the Agency. The Agency will explore with TDDC the appropriateness of a field monitoring study following the review of the rebuttal submission (MRID 42439601).
Ref: US EPA RED (Reregistration Eligibility Decision) for Trifluralin. EPA 738-R-95-040. April 1996.
http://www.fluorideaction.org/pesticides/trifluralin.red.1996.epa.pdf

Sheepshead minnows, Cyprinodon variegatus Lacepede, exposed to 5-5 to 31 micrograms/l of the herbicide trifluralin, throughout their first 28 days of life, developed a heretofore, undescribed vertebral dysplasia. This dysplasia consisted of semisymmetrical hypertrophy of vertebrae (three to 20 times normal), characterized by foci of osteoblast and fibroblasts actively laying down bone and bone precursors. Effects of the abnormal vertebral development were dorsal vertebral growth into the neural canal, ventral compression of renal ducts, and longitudinal fusion of vertebrae. Fish, exposed for 51 days to 16-6 micrograms/l trifluralin and thereafter depurated for 41 days, showed no increase in vertebral dysplasia during depuration; however, residual spinal column damage was evident. Serum calcium concentrations were elevated in adult fish exposed for 4 days to 16-6 micrograms/l trifluralin. Fluorosis or mimicry of hypervitaminosis A are considered possible mechanisms for the osseous effect, but are [abstract truncated].
Ref: 1981 - Vertebral Dysplasia in Young Fish Exposed to the Herbicide Trifluralin; by Couch J, Winstead JT, Hansen DJ, Goodman LR. Report available from The National Technical Information Service. Order No. NTIS/PB80-17775.

Pituitary glands of sheepshead minnows, Cyprinodon variegatus, exposed for 19 months to 1-5 micrograms/l trifluralin were significantly enlarged and possessed histopathologic characteristics (when compared to glands of controls) such as pseudocysts, congestion of blood vessels and edema. Most of the fish with enlarged pituitaries also had diffuse vertebral hyperostosis and other dysplastic vertebral changes. Several speculative mechanistic paths are suggested for the mode of the effect of trifluralin on the vertebral and pituitary tissues. Study of the form and function of pituitary glands of teleosts from natural populations might provide indications of chronic physiological stress, particularly in relation to chemical pollutant stress. Journal article, Pub. in the Jnl. of Fish Diseases, v7 p157-163, 1984.
Ref: 1984 - Histopathology and Enlargement of the Pituitary of a Teleost Exposed to the Herbicide Trifluralin; by Couch JA. Report available from The National Technical Information Service. Order No. NTIS/PB88-162375.

SKELETAL VARIANT ASSAY SYSTEM(SVAS) FOR DETECTION OF BIOLOGICAL EFFECTS OF ENVIRONMENTAL CONTAMINANTS
Author: BECK SL
Source: TOXICOL APPL PHARMACOL 37:149,1976
Name of Agent: 2,4,5-T ( 93-76-5 ) TRIFLURALIN ( 1582-09-8 ) CORN OIL ( 8001-30-7 )
No Abstract

POSTNATAL DETECTION OF PRENATAL EXPOSURE TO HERBICIDES IN MICE,USING NORMALLY OCCURRING VARIATIONS IN SKELETAL DEVELOPMENT
Author: BECK SL
Source: TERATOLOGY 15:15A,1977
Name of Agent (CAS RN): TRIFLURALIN ( 1582-09-8 ) 2,4,5-T ( 93-76-5 ) CORN OIL ( 8001-30-7 )
No Abstract

ASSESSMENT OF ADULT SKELETONS TO DETECT PRENATAL EXPOSURE TO 2,4,5-T OR TRIFLURALIN IN MICE
Author: BECK SL
Source: TERATOLOGY 23:33-55,1981
No Abstract

THE SKELETAL VARIANT ASSAY SYSTEM (SVAS): A POSTNATAL SCREEN FOR DETECTION OF PRENATAL INSULT
Author: BECK SL
Source: TERATOLOGY 29(2):17A-18A,1984 T
Test Object: MAMMAL, MOUSE Sex Treated: FEMALE
Name of Agent (CAS RN): 2,4,5-T ( 93-76-5 ) TRIFLURALIN ( 1582-09-8 ) CAPTAN ( 133-06-2 ) THALIDOMIDE ( 50-35-1 ) DIPHENYLHYDANTOIN ( 57-41-0 ) CORTISONE ( 53-06-5 ) DECAMETHRIN ( 52918-63-5 ) ACETAZOLAMIDE ( 59-66-5 ) TRYPAN BLUE ( 72-57-1 ) BROMODEOXYURIDINE ( 59-14-3 )
No Abstract

A COMPARISON OF THE SKELETAL VARIANT ASSAY SYSTEM (SVAS) ACROSS EXPERIMENTS: FREQUENT RESPONSES, HIGH MAGNITUDE EFFECTS, CLUSTERS, AND UNIQUE EFFECTS
Author: BECK SL
Source: TERATOLOGY 35(2):54A-55A,1987
Test Object: MAMMAL, MOUSE Sex Treated: FEMALE
Name of Agent (CAS RN): 2,4,5-T ( 93-76-5 ) TRIFLURALIN ( 1582-09-8 ) ACETAZOLAMIDE ( 59-66-5 ) TRYPAN BLUE ( 72-57-1 ) BUDR ( 59-14-3 )

Triflusulfuron-methyl - Herbicide - CAS No. 126535-15-7

In another 90-day subchronic study, dogs were fed dosages of 3.87, 146.1, or 267.6 mg/kg/day (males) or 3.72, 159.9, or 250.7 mg/kg/day (females). Triflusulfuron methyl was found to be hepatotoxic at 4,000 ppm (146.1 mg/kg/day males and 159.9 mg/kg/day females), and greater elevated hepatic enzyme levels and postmortem evidence, including elevation in liver weights and microscopic evidence of bile stasis. Other microscopic findings considered to be treatment related were testicular atrophy and decreased testicular weights and hypercellularity of the sternal and femoral bone marrow, with a corresponding increase in reticulocyte and leukocyte counts seen in the high-dose males and females. Based on the microscopic findings in the liver and testes of the 4,000 ppm and greater treated animals, the NOAEL was 3.87 mg/kg/day (males) and 3.72 mg/kg/day (females).
Ref: Federal Register. August 8, 2001. [PF-1036; FRL-6795-4]
http://www.fluoridealert.org/pesticides/triflusulfuron.m.fr.aug8.01.htm

In a rat reproduction study (2-generation, 1 litter/generation), the NOEL for systemic (parental) toxicity was 5.81 mg/kg bw/d based on lower body weights and food consumption. The NOEL for reproductive toxicity was 44 mg/kg bw/d (750 ppm) based on lower pup body weights and histopathological effects on the cerebellum consistent with undernutrition (decreased cellularity in the internal granular layer and increased cellularity in the external germinal layer) in the 2500 ppm group. In the rat developmental toxicity study, the NOEL for maternal toxicity was 120 mg/kg bw/d (based on reduced body-weight gain during dosing period at 350 and 1000 mg/kg bw/d) and for developmental toxicity was 120 mg/kg bw/d (based on delayed ossification). There was no evidence of teratogenicity...
Ref: Dec 3, 1999 - Report on Triflusulfuron methyl. Regulatory Note REG99-03. Pest Management Regulatory Agency, Health Canada, Ottawa.
http://www.fluorideaction.org/pesticides/triflusulfuron.methy.canada.pdf

51974-030; 119842; "Teratogenic Study of DPX-66037-24 in Rats" (Author: C.A. Mebus; E.I. du Pont de Nemours & Company, Inc., Newark, DE, Project No. HLR 525-91, 11/1/91); DPX-66037-24 (95.6% Triflusulfuron-methyl); 0, 30, 120, 350, 1000 mg/kg/day oral gavage; 25 Crl: CD BR female rats/dose; observations- maternal effects; five animals died due to dosing injuries; significant decreases in maternal weight changes and feed consumption were observed; fetal effects; significantly increased average number of malformed fetuses were observed, the majority of fetal malformations occurred in one fetus, when individual end points of developmental evaluation criteria were grouped a significant increase was noted in the 350 and 1000 mg/kg dose groups primarily due to retarded renal development and partial ossification of skulls, sternebra or vertebra; no adverse effect; Maternal NOEL = 120 mg/kg (based on decreased maternal weight gain and feed consumption), Developmental NOEL = 120 number of malformed fetuses, retarded fetal development).
Reference: Nov 18, 2005 - Summary of Toxicology Data. California Environmntal Protection Agency. Department of Pesticide Regulation. Medical Toxicology Branch.
http://www.fluoridealert.org/pesticides/triflusulfuron-m.ca.epa.2005.pdf