Blood - Adverse Effects
Fluorinated and Fluoride Pesticides

beginning with
A-E F • G-P Q-Z

Some Definitions:

Anisocytosis: Variation in red cell size. Normal red blood cells are 7 to 8 micrometers, and have an average volume of 90 fl, with a normal range of 80-100 fl. RBCs which are smaller than normal are termed microcytic (MCV 100). Macrocytic anemia has many causes, including folate/vitamin B12 deficiency and some drugs (e.g., methotrexate, Zidovudine (AZT), and hydroxyurea).

Erythrocyte: A mature red blood cell. SYN. haemacyte, hemacyte, red blood cell, red corpuscle.

Erythropoiesis is the process of red blood cell production (which occurs in red bone marrow).•

Haemangioma (also known as a strawberry birthmark) is a type of birthmark caused by an abnormal collection of abnormal blood vessels just below the skin.

Heinz' bodies Small irregular, deep purple granules in red blood cells due to damage of the haemoglobin molecules. Seen in premature infants, in certain forms of drug sensitivity, characteristically in glucose-6-phosphate dehydrogenase deficiency following administration of oxidant drugs, e.g. primaquin. Also in certain type of hereditary haemolytic anaemia, especially in patients with thalassaemia. The bodies are best seen when the blood is stained with crystal violet. Heinz reported these bodies in the blood of guinea pigs treated with acetylphenylhydrazine. Also known as: Ehrlich's bodies Ehrlich Innenkörper (German) Ehrlich hĢmoglobinĢmische Innenkörper (German) Heinz-Ehrlich bodies

Hematopoietic. SYN hemopoietic (see below).

Hemopoietic. Pertaining to or relted to the formation of blood cells. SYN haemoplastic, hematogenic (1), hematogenous, hematoplastic, hematopoietic, hemogenic,hemoplastic, sanguifacient.•

Hematopoietic system. the blood making organs; in the embryo at different ages these are the yolk sac, liver, thymus, spleen, lymph nodes, and bone marrow; after birth they are principally the bone marrow, spleen, thymus, and lymph nodes.•

Hypochromasia: Decrease in hemoglobin concentration per red cell. Morphologically, this is reflected by increased size of the central pallor of the RBC when observed on a peripheral blood smear.

Leukocyte Histology • a white or colorless cell of the blood, having a nucleus and either granular or nongranular cytoplasm; leukocytes function as bacterial or viral phagocytes, as detoxifiers of toxic proteins, and in the development of immunities. Also, WHITE BLOOD CELL.

Lipofuscin. This brownish pigment is left over from the breakdown and absorption of damaged blood cells. Lipofuscin is found in heart muscle and smooth muscles and is also called the "aging" pigment.

Methemoglobinemia. A condition in which the iron in the hemoglobin molecule (the red blood pigment) is defective, making it unable to carry oxygen effectively to the tissues.

Microcytic Anemia These are associated with an inability to produce hemoglobin. Hemoglobin consists of iron inserted into the prtoporphyrin ring complex to form heme which in turn is inserted into the globin chain. Hence these anemias are seen in: iron deficiency - absence of iron chronic disease - iron unavailable thalassemia - inability to produce globin chains sideroblastic anemia- inability to produce heme.

Polychromasia: Blue-gray coloration of young (anucleate) red cells when observed on a Wright-stained peripheral smear, due to the presence of residual RNA in the cytosol of the immature red cell. Polychromatic cells which are macrocytic suggest that this cell is a reticulocyte. Increased polychromasia occurs when the bone marrow releases immature RBC's into the peripheral blood in response to stress such as a hemolytic crisis.

Sulfhemoglobinemia. A morbid condition due to the presence of sulfmethemoglobin in the blood; it is marked by a persistent cyanosis, but the blood count does not reveal any special abnormality in blood cells; it is thought to be caused by the action of hydrogen sulfide absorbed from the intestine.•

Stedman's Concise Medical Dictionary for the Health Professions. Illustrated, 4th ed

The use of high doses increases the likelihood that potentially significant toxic effects will be identified. Findings of adverse effects in any one species do not necessarily indicate such effects might be generated in humans. From a conservative risk assessment perspective however, adverse findings in animal species are assumed to represent potential effects in humans, unless convincing evidence of species specificity is available.

-- Food and Agricultural Organization of the United Nations

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

Gliftor - Rodenticide - Rodenticide - CAS No. 8065-71-2

Abstract. Rats were subjected to chronic inhalation of gliftor (I; 110, 64, 13, and 1 mg/m-3). A dose of 110 mg/m-3 beginning with the 30th day of poisoning caused pronounced leukocytosis (maximum on the 72nd day), eosinophilia, and lymphopenia. The contents of Hb, erythrocytes, and monocytes were close to the control values. A dose of 64 mg/m-3 caused less leukocytosis and insignificant changes of the content of neutrophils and lymphocytes. With a dose of 1 mg/m-3 there was a significant increase of the relative number of eosinophils and decrease of the number of lymphocytes. This dose was considered the threshold. With single cutaneous applications the LD5- for rabbits was 66 plus or minus 10 mg/kg. The recommended maximum allowable concentration of I for worker exposure in the air of production rooms in 0.05 mg/m-3 (1/20 of the threshold value).
Ref: Change of the morphological composition of the peripheral blood in gliftor poisoning; by TKACH NZ, MILOVANOVA VI, KNYSH VS. TR INST KRAEV PATOL AKAD NAUK KAZ SSR; 22 1971 12-16. [Abstract from Toxline at Toxnet.]

• Definition: Leukocytosis is a condition characterized by an elevated number of white cells in the blood.

Abstract. Under conditions of the acute inhalation effect of the vapors of gliftor (I) the LD50 for rats was 580 plus or minus 65 and for mice 1260 plus or minus 15 mg/m-3. The threshold concentration (TC) for rats with respect to brief disturbance of the functional state of the CNS was 50 and the subthreshold 10 mg/m-3; for mice the TC was 190 mg/m-3. Chronic (4 mo.) inhalation by rats of I in a concentration of 110 and 64 mg/m-3 disturbed the functional state of the CNS and antitoxic and protein-forming functions of the liver and reduced oxidation-reduction processes. I in a concentration of 1.0 mg/m-3 increased the concent of eosinophils and reduced the number of lymphocytes by the end of the poisoning period. I is a hazardous compound. A maximum allowable concentration of I of 0.05 mg/m-3 in the air of production shops is recommended for worker exposure.
Ref: Effect of gliftor on certain metabolic processes of experimental animals under inhalation poisoning conditions; by TKACH NZ, KNYSH VS, MILOVANOVA VI, SHISHKOVA NK, SLEPOVA LI. TR INST KRAEV PATOL AKAD NAUK KAZ SSR; 22 1971 5-12. [Abstract from Toxline at Toxnet.]

Abstract. The threshold concentration with respect to the effect of gliftor (I) on the organoleptic properties of water is at the 1 mg/l level. I has feeble cumulative properties. Rabbits tolerated the chronic oral administration with water of 1/10 and 1/20 LD50 of I, receiving in all 11.2-5.6 LD50. In this case leukocytosis, an increase of the quantity of coproporphyrin excreted in the urine, and an increase of the blood nucleic acid level were noted. The threshold dose is close to 0.15 mg/mg (3.0 mg/l). The organoleptic sign is the limiting factor in establishing the maximum allowable concentration of I in water.
Ref: Effect of gliftor on rabbits under conditions of chronic oral poisoning; by ALIEV KA, TKACH NZ, SHISHKOVA NK, KOLOD'KO TP. TR INST KRAEV PATOL AKAD NAUK KAZ SSR; 22 1971 17-23. [Abstract from Toxline at Toxnet.]

Haloxyfop - Herbicide - CAS No. 69806-34-4

The subchronic toxicity of haloxyfop (2-(4-((3-chloro-5-(trifluoromethyl)-2- pyridinyl)oxy)phenoxy)propanoic acid) herbicide, a peroxisome proliferator, was evaluated in rats, mice, dogs and monkeys. Male rats given 0.2 or 2.0 mg/kg/day and female rats given 2.0 mg/kg/day in feed for 16 weeks had peroxisome associated hepatocellular hypertrophy. Male and female rats given 2.0 mg/kg/day for 37 weeks also had increased renal tubular pigment. Mice given 2.0 mg/kg/day in feed for 13 weeks had peroxisome associated hepatocellular hypertrophy. Dogs fed 20 mg/kg/day and monkeys gavaged with 30 mg/kg/day for 13 weeks had hepatocellular hypertrophy, decreased size of thyroid follicles, and decreased red blood cell counts and serum cholesterol. Hepatocellular effects in dogs and monkeys were not associated with peroxisome proliferation. No-observed effect levels were between 0.02 and 0.2 mg/kg/day for rats, 0.2 mg/kg/day for mice, and 2 mg/kg/day for dogs and monkeys. There were no effects on reproduction in rats at dose levels up to 1.0 mg/kg/day or evidence of teratogenicity in rats or rabbits at dose levels up to 7.5 or 20 mg/kg/day, respectively.
Ref: Subchronic and reproductive toxicity and teratology of haloxyfop herbicide. Authors: Quast JF Yano BL Dietz FK Marler RM Hayes WC. Source: Toxicologist 1990 Feb;10(1):175. As cited at Toxnet.

Hexaflumuron - Insecticide; Plant Growth Regulator - CAS No. 86479-06-3

Abstract: A toxicological evaluation of a new insecticide Sonet was realized. It was established that by its toxicity Sonet belongs to hazardous substances of class III. The main manifestations of its toxic effect on the body warm-blooded animals is its influence on the erythropoiesis and functional state of the liver.
Ref: Sviatnyi IM et al. (1992). [A hygienic evaluation of the insecticide Sonet and the characteristics of the mechanism of its toxic action in an experiment] [Article in Russian]. Lik Sprava. Jan;(1):84-7.
• Definition: Erythropoiesis is the process of red blood cell production (which occurs in red bone marrow).

Hydramethylnon - Insecticide - CAS No. 67485-29-4

PubMed abstract: Holstein calves (3 to 5 months of age) were used to develop an animal model sensitive to environmental toxicants. In the present study, the fire ant toxicant AMDRO was fed (113.5 g/day/calf) to weanling castrated calves (9 test and 9 controls) for 7 weeks. As early as 14 days after the start of the AMDRO feeding, leukopenia was observed. Differential counts revealed significant non-transient decreases in lymphocytes and eosinophils. Eosinopenia was observed from days 21 to 49 of AMDRO treatment. Variability in hematocrit and hemoglobin values in treated and control calves precluded making a determination of trends due to toxicant exposure...
Ref: Am J Vet Res 1984 May;45(5):1023-7;
Hematologic and immunologic responses of Holstein calves to a fire ant toxicant, by Evans DL, Jacobsen KL, Miller DM.

In a 21-day dermal toxicity study in rabbits, MRID 00101559, groups of 10 male and 10 female New Zealand White rabbits received a total of 15 repeated dermal applications of hydramethylnon at doses of 0 (control), 10, 50, or 250 mg/kg/day, 6 hours/day, 5 days/week over a three week period... Toxicity observed at the highest dose tested (250 mg/kg/day) included decreased food consumption in males and females as well as thrombocytopenia (a persistent decrease in the number of blood platelets that is usually associated with hemorrhagic conditions) in females. Although thrombocytopenia was observed at this dose (250 mg/kg/day), it was not considered to be an adverse, or biologically significant effect because it was seen in the presence of skin irritation in animals having abraded skins. In addition, alterations in hematological parameters are often seen in dermal toxicity studies in the presence of skin irritation. Therefore, the 250 mg/kg/day (the highest dose tested), in spite of the presence of this effect, is considered to be the NOAEL for dermal and systemic toxicity; a LOAEL was not established. MRID 00101559 is classified as acceptable and satisfies guideline requirement 82-2 for a 21-dermal toxicity study in rats.
Ref: US EPA. Reregistration Eligibility Decision (RED) Hydramethylnon. EPA 738-R-98-023. December 1998.

Indoxacarb - Insecticide - CAS No. 173584-44-6

-- The substance causes damage to haemoglobin, resulting in an increased turn over of red blood cells. At low exposure levels, some fluctuations in isolated red blood cell parameters were observed, which are of unclear biological significance and may be incidental. Based on a weight of evidence consideration of all available short and long term studies an overall NOEL of 10 ppm or 0.6 mg/kg was proposed for the effects on blood parameters in rats. The U.S. EPA has recently reached a similar conclusion and selected 40 ppm as a NOEL.
-- The haemosiderin deposits in spleen and liver, and spleen and bone marrow hyperplastic response should be considered to be secondary physiological responses to the increased RBC turn over. The very shallow dose-response curve also indicates that the compensatory mechanism of the haemopoietic system was not overcome (except at high doses in the dog) and the effect of indoxacarb in rats and dogs can be described as a compensated haemolytic effect.

July 18, 2002: Opinion of the Scientific Committee on Plants on specific questions from the Commission concerning the evaluation of Indoxacarb. European Commission. Health & Consumer Protection Directorate-General.

-- 90-Day oral toxicity in nonrodents. DPX-JW062 NOAEL = 5.0 mg/kg/day LOAEL = 19 mg/kg/ day based on hemolytic anemia, as indicated by decrease in HGB, RBCs; increases in platelets, increased reticulocytes; and secondary histopathologic findings indicative of blood breakdown (pigment in Kupffer cells, renal tubular epithelium, and spleen and bone marrow macrophages); increase in splenic EMH; and RBC hyperplasia in bone marrow in dogs
-- 21/28-Day dermal toxicity. DPX-MP062 NOAEL = 2,000 mg/kg/ day LOAEL = < 2,000 mg/ kg/day in rats DPX-MP062 NOAEL = 50 mg/kg/ day LOAEL = 500 mg/kg/ day based on decreased body weights, body weight gains, food consumption, and food efficiency in F, and changes in hematology parameters (increased reticulocytes), the spleen (increased absolute and relative weight M only, gross discoloration),
clinical signs of toxicity in both sexes in rats.
-- Chronic toxicity rodents
. DPX-JW062 NOAEL = M 5, F 2.1 mg/kg/day LOAEL = M 10, F 3.6 mg/kg/day based on decreased body weight, body weight gain, and food consumption and food efficiency; decreased HCT, HGB and RBC at 6 months in F only No evidence of carcinogenic potential
-- Chronic toxicity dogs
. DPX-JW062 NOAEL = M 2.3, F 2.4 mg/kg/day LOAEL = M 18, F 19 mg/kg/day based on decreased HCT, HGB nd RBC; increased Heinz bodies and reticulocytes and associated secondary microscopic changes in the liver, kidneys, spleen, and bone marrow; increased absolute and relative liver weights
Ref: Federal Register: July 18, 2002. Indoxacarb; Pesticide Tolerance. Final Rule. Federal Register.

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

Short term toxicity. Target / critical effect: Periacinar hypertrophy in liver, ocular lesions, haematological effects. Lowest relevant oral NOAEL / NOEL: 3 mg/kg bw/d, rat. Lowest relevant dermal NOAEL / NOEL: 100 mg/kg bw/d, 21d rat. Lowest relevant inhalation NOAEL / NOEL: no data available, not required.
April 2003 - Review report for the active substance isoxaflutole. Isoxaflutole Sanco/3136/99-Final. 7 April 2003. Finalised in the Standing Committee on the Food Chain and Animal Health at its meeting on 15 April 2003 in view of the inclusion of isoxaflutole in Annex I of Directive 91/414/EEC.

Nissol (also known as MNFA) - Acaricide, Insecticide - CAS NO. 5903-13-9

A health survey was carried out on 181 farmers before and after the pesticidal application of Nissol (MNFA). Questionnaires on general health, determination of blood pressure and body weight, examination of urine and liver functions, physical examinations, indirect chest roentgenography, blood picture, blood sugar level, and ECG were recorded for some farmers. Forty-five percent of the farmers complained of subjective symptoms at the second examination (4 days after the application), unrelated to the duration of working hours. The major subjective symptoms were general malaise, headache, nausea, loss of appetite, diarrhea, insomnia, abdominal pain, and tachypnea in that order. On the average, body weight loss appeared in 33.6% of the farmers three weeks after the application. Hemoglobin increased in 4.6%, decreased in 18.7%, and did not change in 77% of the farmers. Red cell count decreased in about 52% of the farmers. Leukocyte count increased in less than fifty percent of the farmers with a noticeable increase of neutrophils. Some increase of urobilinogen and glycosuria were noticed while proteinuria remained stable. Clinically questionable findings were not obtained in liver functions. The findings on ECG were a slight decrease of heart rate and a slight elongation of PQ; however, no arrhythmia was found.
Ref: Studies of organofluorine pesticide intoxication. II. Results of health examinations of farmers using an organofluorine pesticide; by Hashida K. Okayama Igakkai Zasshi (J. Okayama Med. So; 83(7-8): 295-310; 1971. [Abstract from Toxnet.]

Abstract. The selective toxicity of N-methyl-N- ( 1-naphthyl ) monofluoroacetamide ( MNFA ) in various species of animals and the effects of the compound on the central action, the peripheral action and the fluctuations in the cardiovascular and respiratory systems were investigated. Tabulated data present the physiological function or activity investigated, the test animal, the dosage of MNFA administered and the route of administration. Results showed that below the toxic level, MNFA had little or no general pharmacologic effect and only a minute effect on the central and peripheral nervous systems and various peripheral organs of the differenct animals tested. When a toxic dose of MNFA was administered, respiratory depression, a fall of blood pressure and body temperature and a decrease in heart rate were generally observed. Both the rat and cat developed convulsions. Just prior to death, a flat wave was observed in the electrical activity of the brain which was indicative of a serious impediment. A drop in blood pressure of about 30% was observed at 24 hr in rats that received 50 mg/kg of MNFA orally. Cardiac response revealed the characteristic feature of this compound to be cardiac depression in every species tested. In addition, among animals that have a high sensitivity to MNFA, such as the guinea pig, dog and cat, bigeminal or trigeminal ventricular premature beats were observed. An enhancement of epinephrine activity by MNFA was also noted. MNFA had a slight effect on the red cell count, but the white cell count in rabbits decreased markedly accompanied by a decrease of pseudoeosinophils and an increase of lymphocytes. The blood sugar level in mice showed an initial increase prior to a final decrease, while in rats and guinea pigs there was a decrease and the value remained unchanged in rabbits and dogs. Ketone bodies were only detected in the mouse.
Ref. Some pharmacologic properties of a new fluorine pesticide, N-methyl- N- ( 1-Naphthyl ) monofluoroacetamide; by Hasimoto Y, Noguchi T, Mori T, Kitagawa H. Toxicol. Appl. Pharmacol.; 13(2), 174-88, 1968.

Lactofen - Herbicide - CAS No. 77501-63-4

Renal dysfunction and decreased hemoglobin and hematocrit levels and red blood cell counts (the LOEL was 25/75 mg/ kg/day; the NOEL was 5 mg/kg/day) were observed in a 1-year feeding study in dogs. Increased renal and hepatic pigmentation (the LOEL was 50 mg/kg/day; the NOEL was 25 mg/kg/day) were noted in a 2-year feeding study in rats. In a 90-day mouse study, increased alkaline phosphatase, serum glutamate oxaloacetate transaminase (SGOT), and serum gleutanic pyruvic transaminase (SGPT) activities, increased liver weight, hepatic necrosis, biliary hyperplasia, decreased hematocrit and hemoglobin levels and red blood cell counts, extramedullary hematopoiesis, and kidney nephrosis and fibrosis (the LOEL was 26 mg/kg/day; the NOEL was not determined) were seen. Decreased hemoglobin and hematocrit levels, decreased red blood cell counts, and brown pigment in the kidney and liver (the LOEL was 50 mg/kg/day) were noted in a 90-day feeding study in rats. EPA believes that there is sufficient evidence for listing lactofen on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on the available carcinogenicity data and hepatic, renal, and hematological 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.

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

-- Based on the findings of the 90-day subchronic toxicity study, it appears that LPOS suppresses the formation of blood in males. This endpoint is not of concern because subchronic or chronic exposure is not expected from this use. Based on the results of the developmental studies, there does not appear to be any increased sensitivity of the pups in comparison to the maternal parents.
-- In an unacceptable subchronic oral toxicity study in rats, the LOAEL was found to be 0.60 mg/kg/day in females, based on increased liver weight and 0.30 mg/kg/day in males, based on decreased triglycerides and hepatocytic vacuolization. The NOAEL is 0.20 mg/kg/day in females. No NOAEL was determined in males.
It appears that LPOS suppresses hematopoiesis (blood production) in males as indicated by significant decreases in RBCs, hemoglobin, hematocrit, and the finding of extramedullary hematopoiesis. This study was classified as unacceptable for the following reasons: 1) a NOAEL was not determined in males; 2) an analysis of blood coagulation factors which is required for a subchronic study was not measured in the animals; 3) the mean food and water consumption calculated as g/week is not correct in the study (it is actually g/day) which raises the possibilities of potential errors in compound consumption, since the test substance was administered in drinking water; and 4) a range finding study was not performed in order to develop a rationale for the appropriate selection of doses in males and females.
Ref: US EPA. New Pesticide Fact Sheet. Lithium perfluorooctane sulfonate (LPOs). August 1999.

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

-- In the beagle dog, treatment by oral gavage with BAS 320 I for a subchronic duration (90-day timepoint in the chronic toxicity study) resulted in reduced body weight gain and/or decreased food consumption in several dogs at 30 mg/kg b.w./day and slightly decreased mean cell
hemoglobin concentration (MCHC) at 30 mg/kg b.w./day. Under the conditions of the study, the NOAEL for oral administration of BAS 320 I for 90 days was 12 mg/kg b.w./day.
-- In the beagle dog, treatment via gelatin capsules with BAS 320 I for a 12-month chronic duration resulted in reduced body weight gain and/or decreased food consumption in several dogs at 30 mg/kg b.w./day and slightly decreased mean MCHC at 30 mg/kg b.w./day. Under the conditions of the study, the NOAEL for oral administration of BAS 320 I for 12 months was 12 mg/kg b.w./day.
Ref: October 27, 2004. Federal Register.
Pesticide tolerance petition.

Methanesulfonyl fluoride - Fumigant, Insecticide - CAS No. 558-25-8

Range of Toxicity:
-- Minimum lethal human exposure is unknown. In rats exposed by inhalation to a concentration of 2.2 ppm for 1 hour, only minimal salivation was seen; at 5 ppm for the same duration, copious salivation, eye and nose exudates, diarrhea, depression, ataxia, and tremors were observed.
-- Only subclinical alterations of blood glucose, serum creatinine, total bilirubin, and depression of acetylcholinesterase were noted in rats exposed by inhalation to 19 or 91 ppb of methanesulfonyl fluoride for 61 exposures, each lasting 7 hours.
-- ACUTE EXPOSURE. Methanesulfonyl fluoride is an irreversible inhibitor of acetylcholinesterase in vitro. It also inhibits butyrylcholinesterase and trypsinogen in vitro.
Ref: TOXNET profile from Hazardous Substances Data Base.

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

--Chronic Toxicity and Carcinogenicity. In a 6-month toxicity study, norflurazon technical was administered in the diet to male and female beagle dogs (4/sex/group) at dose levels of 0, 50, 150, or 450 ppm (0, 1.53, 5.02, and 14.27 mg/kg for males; 0, 1.58, 4.77, and 17.75 mg/kg for females). At the 150 ppm dose level, liver weight was increased by 38% in male dogs and by 23% in female dogs. Thyroid weight was increased by 33% in male dogs and 37% in female dogs at this dose level. Also noted at the 150 ppm dose level were increases in cholesterol in both sexes (23-40% in males, 6-34% in females), a decrease in SGPT (36-38% in males, 13-20% in females) and SGOT (4-23% in males, 13-23% in females). At the 450 ppm dose level, similar changes were observed in male and female dogs, with the additional observation of a decrease in red cell count in female dogs (79-92% of control). The systemic NOEL was determined to be 50 ppm (1.53 mg/kg/day [males]; 1.58 mg/kg/day [females] )...

Novaluron - Insecticide - CAS No. 116714-46-6

Toxicology Summary... The main toxicological effect noted in the animal database was oxidative stress and destruction of red blood cells (RBCs), most likely due to the action of an aniline metabolite (3-chloro-4-(1,1,2-trifluoromethoxy) aniline). As a result of erythrocyte destruction, secondary effects were observed in associated blood tissues/organs and included pigmentation in Kupffer cells in the liver as well as macrophages in the spleen. At higher doses, the effect on red blood cell parameters was of a sufficient magnitude to result in hemolytic anaemia and provoke a regenerative response as evidenced by an increase in reticulocytes, Howell-Jolly Bodies and/or Heinz bodies, with accompanying hyperplastic response in the bone marrow and spleen... (pages 10-11)
Ref: Proposed Registration Decision. PRD2006-05. Health Canada Pest Management Regulatory Agency. December 22, 2006.

-- SUBCHRONIC STUDIES (Oral) 52846-002; 174427; "Rimon" Technical: Toxicity Study by Dietary Administration to CD Rats for 13 Weeks Followed by a 4 Week Reversibility Period”; (P.W. East; Huntingdon Life Sciences Ltd, Eye, Suffolk, England; Report No. MAK399/972319; 4/2/98); Ten CD rats/sex/group were fed 0, 50, 100, 10000 or 20000 ppm of Rimon Technical (Novaluron Technical) (batch no. 031068069, purity: 99.8% (pre-study analysis)) in the diet for 13 weeks ((M): 0, 4.2, 8.3, 818.5, 1666.9 mg/kg/day, (F): 0, 4.7, 8.9, 871.0, 1820.6 mg/kg/day). An additional 5 animals/sex/group in the 0, 50 and 20000 ppm groups were maintained for 4 more weeks after the termination of dosing in order to assess the reversibility of treatment-related effects. No treatment-related mortality resulted. No treatment-related effects on clinical signs, food consumption or body weight were evident. The red blood cell was the target of toxicity. The mean red blood cell count was decreased in a dose-related manner ((M) 10000 ppm and above, p<0.001 at 10000 ppm), (F) 50 ppm and above, p<0.05 at 50 ppm). Likewise, hemoglobin content was decreased in a dose-related manner ((M) 10000 ppm and above, p<0.01 at 10000 ppm, (F) 100 ppm and above, p<0.001 at 100 ppm). For the females the packed cell volume was lower for the 100 ppm treatment group and above (p<0.001). In conjunction with these effects on the red blood cells, the % of methemoglobin was increased in the 10000 and 20000 ppm groups (p<0.001). As a response to this effect, the % of reticulocytes was increased in these two groups (p<0.05 or p<0.001)...
-- DERMAL: 52846-038; 178971; ““Rimon” Technical: Toxicity Study by Dermal Administration to CD Rats for 4 Weeks”; (P.B. Rees; Huntingdon Life Sciences Ltd, Eye, Suffolk, England; Project ID. MAK/478; 9/14/98); The skin of 5 CD rats/sex/group was treated with 0, 75, 400 or 1000 mg/kg/day of RIMON Technical (batch no. 970211/4, purity: 99.7%) for 6 hours/day for 28 days. The test material was suspended in 1.0% (w/v) aqueous methylcellulose. No mortality resulted from the treatment. The mean body weight and food consumption values for the 1000 mg/kg group males were less than those of the control animals. The methemoglobin concentration was greater for the 1000 mg/kg males (p<0.05) and the 400 (p<0.01) and 1000 mg/kg (p<0.001) females. No treatment-related effects were noted in the ophthalmology, clinical chemistry, or urinalysis. There were no treatment-related lesions in either the gross or microscopic examinations. No adverse effect indicated. NOEL: (Systemic) (M) 400 mg/kg/day (based upon the lower mean body weight and food consumption and increased methemoglobin level noted for the 1000 mg/kg males) (F) 75 mg/kg/day (based upon increased methemoglobin level noted for the 400 mg/kg females); (Dermal) 1000 mg/kg/day (no effect evident at the highest dose tested). Study acceptable. (Moore, 3/20/01)
Ref: 2001. Summary of Toxicology Data for Novaluron. California Environmental Protection Agency, Department of Pesticide Regulation, Medical Toxicology Branch. Chemical Code # 5754, Tolerance # 52846 3/23/01.

-- Short-term incidental oral (1-30 days); Intermediate-term incidental oral (1-6 months); and Intermediate-term inhalation (1 to 6 months): 90-day feeding study in rat. LOAEL = 8.64 mg/kg/day based on clinical chemistry (decreased hemoglobin, hematocrit and RBC counts) and histopathology (increased hematopoiesis and hemosiderosis in spleen and liver).
Re: June 2, 2004. Novaluron; Pesticide Tolerance. Final Rule. Federal Register.

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

-- “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.

-- 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.

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

Human Health Assessment. Toxicity, Oxyfluorfen is of low acute oral, dermal, and inhalation toxicity. The primary toxic effects are alterations in blood parameters (anemia) and in the liver. Oxyfluorfen is classified as a possible human carcinogen based on combined hepatocellular adenomas/carcinomas in the mouse carcinogenicity study. A cancer potency factor (Q1*) was used to estimate human risk. The FQPA Safety Factor for protection of infants and children was reduced to 1X for all population subgroups as there was no increased susceptibility in animals due to pre- or post-natal exposure to oxyfluorfen.
-- Toxicity was similar for subchronic and chronic rat, mouse, and dog studies in both sexes. Oxyfluorfen inhibits heme production, which results in a variety of anemias. Heme is the part of the hemoglobin molecule that contains iron and binds oxygen. In the 1997 subchronic rat study which used the current 98% a.i. formulation, the red blood cell count was normal, but the red blood cell mass was decreased due to the small size of the red blood cells, presumably because of inhibition of the protoporphyrinogen oxidase enzyme. The anemia was generally mild in other studies, with varying hematologic abnormalities described in the rat, mouse, and dog studies.
-- It should be noted that older toxicity studies with oxyfluorfen used technical material of approximately 71% or 85% purity. The newer toxicity studies used a technical material of approximately 98% purity, which is the basis for the current registrations of oxyfluorfen. The newer technical material has similar impurities to the older technical material, but in reduced concentrations. Toxicity was less severe for studies with the 98% product than for the 71% product; however, one mammal developmental study with the 98% technical was submitted in which animals experienced the most severe anemia and related hematologic effects of any of the mammalian studies. When there were studies with both the new and old technical material, preference for an endpoint for risk assessment purposes was generally given to the newer, 98% technical material (current registrations).
Ref: US EPA Reregistration Eligibility Decision (RED) OXYFLUORFEN. EPA738-R-02-014 October 2002.

-- Phototoxicity. Oxyfluorfen may pose risks to animals not conveyed by standard guideline toxicity studies because oxyfluorfen's mode of action suggests it may be more toxic in the presence of light (phototoxic). Oxyfluorfen, and other light-dependent peroxidizing herbicides, act in plants by producing phototoxic compounds. Toxicity studies with oxyfluorfen and other similar herbicides suggest the same phototoxic compounds may occur in animals as a result of herbicide exposure. Because guideline toxicity studies are normally conducted under relatively low, artificial light conditions, the effects of being exposed simultaneously to oxyfluorfen and sunlight are not known. To provide information on the magnitude of this effect, EFED is currently requesting fish phototoxicity studies be conducted for light-dependent peroxidizing herbicides (Appendix D).
-- Phototoxicity is a concern for terrestrial organisms as well. Although oxyfluorfen inhibits heme synthesis, the anemia described in all but one of the mammalian sub-chronic studies was generally mild, with varying hematologic abnormalities. The anemia described one subchronic study with rats (MRID 449331-01) was more severe. The red blood cell count was normal, but the red blood cell mass was decreased because of the small size of the red blood cells, presumably because of inhibition of the protoporphyrinogen oxidase enzyme. In wild mammal populations, these hematologic effects have the potential to magnify since the lack of natural sunlight in the laboratory does reduce the likelihood of activating the phototoxic effects of oxyfluorfen.
-- US EPA identified the herbicides Acifluorfen, Azafenidin, Carfentrazone-ethyl, Flumiclorac-penty, Flumioxazin, Fluthiacet-methyl, Fomesafen, Lactofen, Oxadiargyl, Oxadiazon, Oxyfluorfen, Sulfentrazone, Thidiazimin as phototoxic pesticides [10 out of the 13 pesticides that EPA identified are organofluorines].
Ref: December 11, 2001 - US EPA. Revised Environmental Fate and Effects Division Preliminary Risk Assessment for the Oxyfluorfen Reregistration Eligibility Decision Document (also at: ).

Penoxsulam - Herbicide - CAS No. 219714-96-2

-- Chronic toxicity. Chronic exposure in the dog indicated that the renal effects were not exacerbated with long-term exposure. Following long-term exposure in rats, the kidneys and urinary bladder were the primary target organs. Histologic changes seen at the end of 2 years of exposure consisted of inflammation and hyperplasia of the renal pelvic transitional epithelium, crystal deposition in the kidneys and urinary bladder, and hyperplasia of the mucosa of the urinary bladder. In the mouse, the liver was the primary target organ, and histologic changes consisted of hepatocellular hypertrophy. There were no treatment-related increases in tumors in either rats or mice. The incidence of mononuclear cell leukemia (Fischer rat leukemia) was increased in all groups of treated male rats compared to the concurrent controls. However, the incidences in the treated groups were identical across a 50-fold increase in dosage, and well within the range of control values reported in the literature.
Ref: August 6, 2003. Federal Register: August 6, 2003 (Volume 68, Number 151)] [Notices] [Page 46609-46613]. Penoxsulam; Notice of Filing a Pesticide Petition To Establish a Tolerance for a Certain Pesticide Chemical in or on Food.


PFOS - PFOS - Insecticide, US EPA List 3 Inert

Due to length, click here for effects page


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

-- In the rat 2-generation reproduction study, reproduction function, reproductive parameters and litter parameters were not influenced by treatment in the first and second generation (P1/P2) parental animals at any dose level up to and including 500 ppm (equal to 39 and 42 mg/kg bw/d in males and females, respectively), the highest dose tested. Hematological findings, increased spleen weights, and histopathological findings indicative of regenerative hemolytic anemia were noted for P1/P2 males and females at 250 ppm (equal to 19 and 21 mg/kg bw/d for males and females, respectively) and above. Hematological findings including lower red blood cell count, hemoglobin, and hematocrit were also noted for male and female second generation (F2) pups at 250 ppm and above on lactation day 21 (only time point evaluated). Although the hematological findings noted in the F2 offspring may be secondary to maternal toxicity, a direct treatment-related effect cannot be dismissed; therefore, these findings were considered to be toxicologically relevant. The NOAEL for parental and offspring toxicity was 50 ppm (equal to 3.7 and 4.0 mg/kg bw/d in males and females, respectively). On the basis of the parental and offspring NOAELs in the rat 2-generation reproductive toxicity study (one litter/generation), there was no indication that neonates were quantitatively more sensitive than adults to the toxic effects of picolinafen.
-- Hematological and histopathological findings indicative of regenerative hemolytic anemia were noted in all species tested. The most sensitive species appears to be the rat. The most appropriate NOAEL for regenerative hemolytic anemia is 50 ppm (equal to 2.4 and 3.0 mg/kg bw/d for males and females, respectively), as determined in the 2-year rat dietary study. The MOE for regenerative hemolytic anemia is 171 compared to the ADI.

Ref: February 17, 2003 - Canada. Picolinafen. Regulatory Note REG2003-02. Alternative Strategies and Regulatory Affairs Division, Pest Management Regulatory Agency.

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

LD50 ranges of sodium, potassium, or ammonium fluorosilicates administered intragastrically in rats and mice were 89-128 and 45-64 mg fluoride ion/kg, respectively. Severe cornea damage was observed 3 hr after the administration of 50 mg of any of the salts into rabbits' eyes. Min toxic dose (intragastric) of fluorosilicic acid in rats was 8 mg/kg. Min toxic concn in 4 hr inhalation of the salt aerosols were 7.4-9.6 mg/cu m; nontoxic concn was 0.8 mg/cu m. Main toxic effects were decreased activities of cholinesterase and lactate dehydrogenase in blood serum. The intragastric effects of the fluorosilicates were similar to and additive with those of sodium fluoride. [Rumyantser GI et al; Oig Sanit (11): 80-2 (1988)]
Ref: TOXNET profile from Hazardous Substances Data Bank for AMMONIUM SILICOFLUORIDE.

Primisulfuron-methyl - Fungicide, Herbicide- CAS No. 86209-51-0

In a 90-day dog feeding study, reduced thyroid weights accompanied by colloid depletion and parafollicular hyperplasia and anemia were observed at the LOEL of 25 mg/kg/day. The NOEL was 0.625 mg/kg/day. In a 1-year dog study, dietary administration of 250/125 mg/kg/day (LOEL: the dose was changed after week 10 in the study) produced thyroid hyperplasia, anemia, increased platelet levels, vacuolar changes, and increased absolute and relative liver weights. The NOEL was 25 mg/kg/day. In an 18-month study in mice, dietary administration of 1.7 mg/kg/day produced increased absolute and relative liver weights in females. No NOEL was established...
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.

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

-- Short term toxicity Target / critical effect: Liver (hepatocyte hypertrophy), heart (myocardial degeneration), hematopoietic system (red blood cells decreased) Lowest relevant oral NOAEL / NOEL: NOAEL = 6 mg/kg b.w./day (90-day, dog)
Ref: July 2, 2002 - Review report for the active substance prosulfuron. Finalised in the Standing Committee on the Food Chain and Animal Health at its meeting on 26 February 2002 in view of the inclusion of prosulfuron in Annex I of Directive 91/414/EEC.European Commission Health & Consumer Protection Directorate-General.

Chronic toxicity. In the 1-year dog chronic dosing study, the NOAEL was 1.84 mg/kg/day based on hematologic and clinical chemistry effects and incidence of lipofuscin accumulation in the liver at 18.6 mg/kg/day.
Ref: Federal Register: December 31, 2002. Prosulfuron; Notice of Filing Pesticide Petitions to Establish Tolerances for a Certain Pesticide Chemical in or on Food.

-- A 2-year chronic feeding/carcinogenicity study in rats fed dosages of 0, 0.4, 7.9, 79.9 or 160.9 (males), and 0, 0.5, 9.2, 95.7 or 205.8 mg/kg/day (females) was conducted. There was uncertain evidence of carcinogenicity with slight increases in the incidence of mammary gland adenocarcinomas in females at 95.7 and 205.8 mg/kg/day, slight increase in incidence of benign testicular interstitial cell tumors at 79.9 and 160.9 mg/kg/day (significant trend only). A systemic NOAEL of 7.9 mg/kg/day was based on decreased body weight and body weight gain, hematopoietic effects (males), and possibly increased serum GGT and decreased liver, kidney and adrenal weights (females) at 79.9 mg/kg/ day.
Ref: Federal Register: August 25, 1999. [PF-882; FRL-6093-7]. Notice of Filing a Pesticide Petition to Establish a Tolerance for Certain Pesticide Chemicals in or on Food.

Pyraflufen-ethyl - Herbicide - CAS No. 129630-19-9

-- Short term toxicity Target / critical effect: Liver, kidney, red blood cells. Lowest relevant oral NOAEL / NOEL: 200 ppm (20 mg/kg bw/d) 90 day mouse (satellite group in 78 wk study)
-- Long term toxicity and carcinogenicity Target / critical effect: Red blood cells and liver in mice, urinary and biliary tract in rats.
Ref: July 2, 2002 - Review report for the active substance pyraflufen-ethyl. Finalised in the Standing Committee on Plant Health at its meeting on 29 June 2001 in view of the inclusion of Pyraflufen-ethyl in Annex I of Directive 91/414/EEC. SANCO/3039/99-FINAL. European Commission Health & Consumer Protection Directorate-General.

Pyridalyl - Insecticide - CAS No. 179101-81-6

Subchronic toxicity.
-- Pyridalyl technical was tested in rats in a 3-month feeding study. Effects included decreased body weight gain,
altered blood biochemistry, increased relative liver weight and histopathological changes in the liver, ovary, adrenal and lung. The NOAEL is 100 ppm (5.56 mg/kg/day in males and 6.45 mg/kg/day in females).
-- A 13-week feeding study in mice was conducted. Effects included decreased body weight gain, hematological and blood biochemical effects,increased liver weight, decreased kidney and ovary weights and histopathological changes in liver, kidney, ovary and adrenal. The NOAEL is 70 ppm in males (8.169 mg/kg/day) and 700 ppm in females (86.78 mg/kg/day).
-- A 13-week oral (capsule) toxicity study was conducted in dogs. Effects included decreased body weight gain, clinical signs indicative of respiratory distress, hematological and blood biochemistry effects, increased liver, lung and kidney weights and histopathological alterations of the lung, kidney, adrenal and liver. The NOAEL was 10 mg/kg/day.
Chronic toxicity.
In a 104-week combined chronic/oncogenicity study in rats,
effects included decreased body weight gain, increased frequency of rearing (high dose females only), hematological alterations and histopathological alterations of the spleen. No oncogenicity was found. The NOAEL for this study is 100 ppm (3.4 mg/kg/day in males and 4.1 mg/kg/day in females).
-- Pyridalyl was administered for 12-months by capsule to dogs. There were alterations in blood biochemistry (alkaline phosphatase and alanine aminotransaminase) and increased liver weights. The NOAEL of the study was 20 mg/kg/day.
Ref: Federal Register: December 5, 2003. Pyridalyl; Notice of Filing a Pesticide Petition.

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