Mesenteric Lymph Nodes & Arteries & Lymphomas- Adverse Effects
Fluorinated and Fluoride Pesticides
 
 
Mesenteric artery, arteria mesenterica -- (one of two branches of the aorta that pass between the two layers of the mesentery to the intestines)

Regional Lymph Nodes
There are between 100 and 150 lymph nodes in the mesentery of the colon. Regional lymph nodes are the nodes along the colon, plus the nodes along the major arteries that supply blood to that particular colon segment.
Ref:
http://training.seer.cancer.gov/ss_module04_colon/unit02_sec02_reg_lymph_nodes.html

SEGMENT REGIONAL LYMPH NODES
Cecum Pericolic, anterior cecal, posterior cecal, ileocolic, right colic
Ascending colon Pericolic, ileocolic, right colic, middle colic
Hepatic flexure Pericolic, middle colic, right colic
Transverse colon Pericolic, middle colic
Splenic flexure Pericolic, middle colic, left colic, inferior mesenteric
Descending colon Pericolic, left colic, inferior mesenteric, sigmoid
Sigmoid colon Pericolic, inferior mesenteric, superior rectal, superior hemorrhoidal, sigmoidal, sigmoid mesenteric
Rectosigmoid Perirectal, left colic, sigmoid mesenteric, sigmoidal, inferior mesenteric, superior rectal, superior hemorrhoidal, middle hemorrhoidal
Rectum Perirectal, sigmoid mesenteric, inferior mesenteric, lateral sacral, presacral, internal iliac, sacral promontory (Gerota's) superior hemorrhoidal, inferior hemorrhoidal
Anus Perirectal, anorectal, superficial inguinal, internal iliac, hypogastric, femoral, lateral sacral
Lymph nodes along a "named vascular trunk" (as defined by the fourth edition of the AJCC staging manual) are those along a vein or artery that carries blood to a specific part of the colon, for example, the inferior and superior mesenteric arteries, sigmoidal artery, left or right colic artery. In the fifth and sixth editions, the location of the nodes does not affect assignment of the N category.

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

-- Food and Agricultural Organization of the United Nations

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

Fluazifop-butyl - Herbicide - CAS No. 69806-50-4

Fluazifop-butyl (CAS # 69806-50-4) was evaluated for subacute oral toxicity in Wistar albino rats (10/sex/group) administered 10 ml/kg doses in corn oil of 0, 4, 20, 100 and 500 mg/kg/day by oral gavage, 5 days/week for 2 weeks. Five-day weekly treatment periods were each followed by 2-day recovery. High-dose males only displayed overt toxicity and comprised the 2 study lethalities. These two 500 mg/kg/day males were sacrificed in extremis on Days 11 and 14 with severe pharmacotoxic signs including piloerection, reduced motor activity, retinal pallor, and a prone or hunched posture. One rat was bleeding from the penis ... The decedent animals were found with abnormal upper gastrointestinal contents, and one rat exhibited congestion of mesenteric lymph nodes with pallor of kidneys, liver and spleen... [ICI AMERS INC; 14 Day Subacute Oral Toxicity Study with PP009 in Rats; 07/11/80; EPA Doc No. 88-920007017; Fiche No. OTS0545392].
-- Fuazifop butyl was evaluated for reproductive and developmental effects in 2 successive generations of Charles River Wistar strain rats (30/sex/group) exposed continuously to 0, 10, 80 and 250 ppm in the diet. Each respective parent generation had received treatment for a minimum of 100 days (F0) and 120 days (F1) prior to mating. F0 and F1 dams weaned their progeny for 25 days postpartum to time of offspring selection for mating and continued study (F1) or sacrifice (F1, F2)... Upon histological investigation, increased incidence geriatric nephropathy (both sexes, 80 and 250 ppm), distension of mesenteric and/or cervical lymph nodes (250 ppm) and increased severity of nephrocalcinosis (females, 80 and 250 ppm), and an increased slight testicular tubular atrophy in males (250 ppm) were noted. F2 female progeny of 250 ppm exposed parents were found with significantly increased absolute and relative spleen weights. Histological changes were limited to marginal increases in hydronephrosis. [ICI AMERS INC; Fluazifop butyl: Effects Upon Reproductive Performance of Rats Treated Continuously Through 2 Generations (Final Report); 03/17/81; EPA Doc No. 88-920006849; Fiche No. OTS05543854]
Ref: TOXNET profile from Hazardous Substances Data Bank. FLUAZIFOP-BUTYL. CASRN: 69806-50-4.

http://www.fluoridealert.org/pesticides/fluazifop-butyl.toxnet.hsdb.htm

Flumioxazin - Herbicide - CAS No. 103361-09-7

SUBCHRONIC STUDIES 52894-046; 184614; "Three-Month Subacute Toxicity Study of S-53482 by Dietary Administration in Rats"; (Haruhiko Adachi; Sumitomo Chemical Co., Environmental Health Science Laboratory,, Ltd., Osaka, Japan; Study No. 1760; 4/26/91); Sixteen Crj:CD (SD) rats/sex/group were treated in the diet with 0, 30, 300, 1000 or 3000 ppm of S-53482 (lot no. PYG-89021-M, purity: 94.8%). Six of these animals/sex/group were treated for 5 weeks. The remaining 10 animals/sex/group were treated for 13 weeks ((M): 0, 1.94, 19.4, 65.2, 197.3 mg/kg/day, (F) 0, 2.22, 22.4, 72.8, 218.4 mg/kg/day). One female in the 3000 ppm group died during week 12. The mean body weights for the 3000 ppm males and females were 95.3 and 90.2% of the mean values for the control animals, respectively at the termination of the study. ... Other noted lesions for the 3000 ppm females were focal or generalized necrosis in the liver (0:0/10 vs. 3000: 4/10), extramedullary hematopoiesis in the liver (0: 0/10 vs. 3000: 5/10), myocardial fibrosis in the heart (0: 0/10 vs. 3000: 2/10), myelofibrosis and osteosis in the bone marrow (0: 0/10 vs. 3000: 3/10), atrophy of the thymus and the presence of thymal foam cells (0:0/10 vs. 3000: 3/10), sinus histiocytosis in the mesenteric lymph node (0:0/10 vs. 3000: 3/10), and cytoplasmic vacuolation in the adrenal cortex (0:0/10 vs. 3000: 3/10). Adverse effects indicated: anemia and hepatic necrosis. Subchronic NOEL (M/F): 300 ppm ((M) 19.4 mg/kg/day, (F) 22.4 mg/kg/day) (based upon hematologic effects noted for the 1000 ppm treated animals); Study acceptable. (Moore, 5/20/02)
Ref: January 2003 (revised) - Summary of Toxicological Data. California EPA, Department of Pesticides Regulation, Medical Toxicology Branch.

Fluometuron - Herbicide - CAS No. 2164-17-2

Group C -- Possible Human Carcinogen. Statistically significant increases in combined adenomas/carcinomas of the lung (M); Malignant lymphocytic lymphomas (F); CD-1 mice.
Ref:
April 26, 2006 . Chemicals Evaluated for Carcinogenic Potential by the Office of Pesticide Programs. From: Jess Rowland, Chief Science Information Management Branch Health Effect Division (7509C) Office of Pesticide Programs, USEPA.
http://www.fluorideaction.org/pesticides/pesticides.cancer.potential.2006.pdf

Fluroxypyr - Herbicide - CAS No. 69377-81-7

In the combined chronic toxicity/carcinogenicity study in rats, fluroxypyr 99.0% a.i. was administered to 50 Fischer 344 rats/sex/dose via the diet at dose levels of 0, 100, 500, and 1,000, females only,
mg/kg/day for 24 months 10 rats/sex/dose for 12 months. There was no apparent increase in the incidence of kidney tumors in either sex. With the exception of an increased incidence of parafollicular cell adenomas, single only, in males at 500 mg/kg/day, at the doses tested, there was no apparent treatment-related increase in any tumor type in either sex. The LOEL is 500 mg/kg/day, based on increased kidney weight in both sexes, increased incidence of atrophy, adipose tissue mesenteric tissues in males and an increase in the severity of chronic progressive glomerulonephropathy in the kidney in both sexes. The NOAEL is 100 mg/kg/day. Deaths occurred at 1,000 mg/kg/day in males within the first 90 days on test 2 by day 28 and 3 more by day 56.
Ref: Federal Register. Fluroxypyr (Dow Agro). September 30, 1998. Pesticide Tolerance. Final Rule.
http://www.fluoridealert.org/pesticides/fluroxypyr.fr.sept.30.1998.htm

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

An oncogenicity study in mice administered 0, 25, 500 and 7,000 ppm with a NOEL of 25 ppm based on a slight effect on liver weight and body weight gain at the LEL of 500 ppm. An increased incidence of hepatocellular adenomas and carcinomas was observed at 7,000 ppm in both sexes. Increased liver weight, non-neoplastic cellular changes in the liver, and amyloidosis in the duodenum, ileum, jejunum, kidneys, heart ventricle, mesenteric lymph node, and thyroid were also observed at 7,000 ppm.
Ref: Federal Register: February 26, 1997 (Volume 62, Number 38)] [Notices] [Page 8737-8740]. Rhone-Poulenc Ag Company; Pesticide Tolerance Petition Filing.

http://www.epa.gov/EPA-PEST/1997/February/Day-26/p4628.htm

PFOS - Insecticide, US EPA List 3 Inert

In the rat subchronic study, Goldenthal et al. (1978b) administered CD rats, 5/sex/group, dietary levels of 0, 30, 100, 300, 1000 or 3000 ppm PFOS (FC-95) for 90 days. The males weighed 196-232 g and the females weighed 165-206 g at study initiation. The dietary levels were equivalent to doses of 0, 2, 6, 18, 60 and 200 mg/kg/day... The rats were sacrificed after 90 days of treatment and a gross necrospy was conducted... All of the rats in the 300, 1000 and 3000 ppm groups died. Death occurred between days 13-25 and days 18-28 for the males and females, respectively, in the 300 ppm group...
The rats in all groups showed signs of toxicity including emaciation, convulsions following handling, hunched back, red material around the eyes, yellow material around the anogenital region, increased sensitivity to external stimuli, reduced activity and moist red material around the mouth or nose. Three males and two females in the 100 ppm group died prior to scheduled sacrifice. Two of the males and the two females died during week 5 and the third male died during week 11 of the study... All rats in the 30 ppm group survived until the end of the study... Histologic examination also showed lesions in all treated groups. Centrilobular to midzonal cytoplasmic hypertrophy of hepatocytes and focal necrosis was observed in the liver; the incidence and relative severity were greater in the males. In addition, especially among rats in the 300, 1000 and 3000 ppm groups, treatment related histologic lesions were noted in the primary (thymus, bone marrow) and secondary (spleen, mesenteric lymph nodes) lymphoid organs, stomach, intestines, muscle and skin. In the thymus, this consisted of depletion in the number and size of the lymphoid follicles and in the bone marrow hypocellularity was noted. The spleen was slightly atrophied with a corresponding decrease in the size and number of lymphoid follicles and cells and a similar depletion was noted in the mesenteric lymph nodes.
Ref: August 31, 2000. MEMORANDUM. SUBJECT: Hazard Assessment of PFOS. FROM: Jennifer Seed, Branch Chief, Existing Chemical Assessment Branch, Risk Assessment Division (7403). THRU: Oscar Hernandez , Division Director, Risk Assessment Division (7403). TO: Charlie Auer, Division Director, Chemical Control Division (7405).

Sodium fluoride - Insecticide, Wood preservative, US EPA List 4B Inert - CAS No. 7681-49-4

Abstract: The purpose of this study was to determine the mechanism responsible for alterations in NaF-induced contractions of blood vessels from streptozotocin-induced diabetic rats. In the presence of AlCl3, NaF (¥7.5 mM) produced significantly greater contractions in diabetic aorta and mesenteric artery compared with age-matched controls. Pretreatment with 1 microM nifedipine eliminated the enhanced contractile responses of diabetic vessels to NaF, resulting in no difference in the magnitude of NaF-induced contractions between control and diabetic vessels. In the presence of 100 microM deferoxamine, an Al 3+ chela-tor, NaF-induced contractions of diabetic vessels were markedly attenuated, whereas only the responses to lower concentrations of NaF were reduced in control vessels. No significant difference was found in the peak amplitude of transient contractions induced by 10 microM cyclopiazonic acid between control and diabetic vessels. The addition of 10 microM okadaic acid produced attenuated contractions in diabetic vessels. These findings indicate no involvement of the inhibitory effects of NaF on endoplasmic reticular Ca 2+ -pump ATPase and protein phosphatases in the genesis of the enhanced responsive-ness of diabetic vessels to NaF. Western blot analysis showed a 2.5-fold in-crease in the expression of G(qalpha) in diabetic aortic membranes. In contrast, the G(ialpha) level was modestly decreased and the G(salpha) and G(betagamma) levels were unchanged in diabetes. The present results suggest that enhanced vascular contractions to NaF in diabetes is attributed predominantly to a G protein-mediated Ca 2+ channel acti-vation that results from markedly increased G(qalpha) expression in vascular tissues under this pathological state.
Ref: Predominant contribution of the G protein-mediated mechanism to NaF-induced vascular contractions in diabetic rats: association with an increased level of G(qalpha) expression
Hattori Y, Matsuda N, Sato A, Watanuki S, Tomioka H, Kawasaki H, Kanno M. J Pharmacol Exp Ther 2000 Feb;292(2):761-8 - As cited and abstracted in Fluoride 2000; 33(2):97-98

Abstract:
1. Previous studies from this laboratory have demonstrated that alpha 1-adrenoceptor-mediated increases in tension and phosphoinositide metabolism are enhanced in the aorta and mesenteric arteries from diabetic rats. The purpose of the present investigation was to determine whether contractile responses to sodium fluoride (NaF), which directly stimulates GTP-binding proteins (G-proteins), are also enhanced in diabetic arteries.
2. NaF (1-20 mM) in the presence of 10 microM aluminium chloride produced slowly developing, concentration-dependent contractions in mesenteric arteries from three month streptozotocin-diabetic (60 mg kg-1, i.v.) male Wistar rats and age-matched control rats. The maximum contractile response but not the sensitivity to NaF was significantly greater in mesenteric arteries from diabetic than from control rats, as was the response to noradrenaline (NA). Maximum contractile responses of aorta and caudal artery from diabetic rats to NaF were also significantly enhanced.
3. Removal of the endothelium and denervation with 6-hydroxydopamine did not significantly alter the maximum contractile response of mesenteric arteries from either control or diabetic rats to NaF. Similarly, NaF had no effect on cyclic AMP levels in aorta, and no difference in cyclic AMP levels, either basally or in the presence of NaF, was detected between control and diabetic rat aorta.
4. Contractile responses of mesenteric arteries from both control and diabetic rats to NaF were diminished in calcium-free Krebs solution, but the NaF response remained significantly elevated in mesenteric arteries from diabetic rats compared to control.
5. Ryanodine (30 microM) which depletes intracellular calcium stores, nifedipine (3 microM) which blocks dihydropyridine-sensitive calcium channels and calphostin C (0.5 microM) which selectively inhibits protein kinase C, all significantly inhibited maximum contractile responses of mesenteric arteries from control and diabetic rats to NaF. There were no significant differences between control and diabetic arteries in the relative magnitude of the inhibition produce by the three antagonist.
6. These data suggest that there may be increased activation of the same signalling processes that mediate NA-stimulated vasoconstriction, perhaps contraction-associated G-proteins or the effectors coupled to these G-proteins, in response to NaF in mesenteric arteries from diabetic rats. This may also be responsible for the enhanced contractile responses of these arteries to alpha 1-adrenoceptor stimulation.
Ref: Br J Pharmacol 1996 May;118(1):115-22. Enhanced contractile responses of arteries from streptozotocin diabetic rats to sodium fluoride. Weber LP, Chow WL, Abebe W, MacLeod KM.

Teflubenzuron - Insecticide, Insect growth regulator - CAS No. 83121-18-0

-- In a 120-week long-term toxicity/carcinogenicity study, rats were fed diets containing 0, 20, 100 or 500 mg/kg feed, equal to 0, 1, 4.8 or 24.8 mg/kg bw/day in males and 0, 1.2, 5.9 and 29.9 mg/kg bw/day in females... Histopathological examination indicated an increased incidence of mesenteric lymph node haemangiomas in males in the high dose group (17%) in comparison with rats in concurrent controls (2%), but not when compared to the incidence in historical controls. A significantly increased incidence of pancreatic exocine carcinomas in male rats in the high dose group (4.3%), compared to concurrent controls (0 out of 50) and historical control groups (1.4% or 1 out of 69), was based on a low number of affected rats (2 out of 47) and was therefore not considered to be treatment related.
January 1999 - Summary Report. Committee for Veterinary Medicinal Products. The European Agency for the Evaluation of Medicinal Products.

http://www.fluoridealert.org/pesticides/Teflubenzuron.Review.1999.pdf

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

In the rat chronic/carcinogenicity study, the NOAEL of 11.0 mg/kg bw/day was set based on the reduction in body-weight gain in both sexes, decreased food consumption and slightly increased incidence of developmental cyst in pituitary gland and angiomatous hyperplasia of the mesenteric node in males. An effect on the liver (increased relative weight) was seen only in females at the highest dose level of 73 mg/kg bw/day.
Ref: January 30, 2004 - Regulatory Note REG2004-03. Canada Pest Management Regulatory Agency. Also available at:
http://www.hc-sc.gc.ca/pmra-arla/english/pdf/reg/reg2004-03-e.pdf

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

870.3150 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 myeloidhyperplasia in bone marrow, clinical chemistry changes suggesting hepatotoxicity, decrease thymus weight, thymic atrophy and hyaline tubular change in kidney.
Ref: Federal Register: September 1
7, 2003 (Volume 68, Number 180)]. Trifloxysulfuron; Pesticide Tolerance. Final Rule.
http://www.fluorideaction.org/pesticides/trifloxysulfuron.fr.sept.03.htm

Dogs were fed trifloxysulfuron at dietary concentrations of 0, 50, 500, 5000, 10 000 or 20 000 ppm for 90 days... Large mesenteric lymph nodes with suppuration and an increased severity of haemorrhage were observed in both sexes at 5000 ppm. Red popliteal lymph nodes were observed with haemorrhage and haemosiderosis in males at 20 000 ppm and chronic reactive hyperplasia in females at 20 000 ppm. Small testes was observed in one male at 10 000 ppm and testes weights were lower at 5000 and 10 000 ppm with reduced spermatogenesis observed in all males at 10 000 ppm and one at 5000 ppm. Prostatic atrophy was observed in one male at 5000 and 10 000 ppm and all males at 20 000 ppm. Masses on the heart, mottled lung and red small intestine were also observed at necropsy. The NOEL in this study was 500 ppm, equal to 19.8 mg/kg bw/day in males and 19.6 mg/kg bw/day in females.
Ref: Public Release Summary on Evaluation of the new active TRIFLOXYSULFURON SODIUM in the product ENVOKE HERBICIDE. National Registration Authority for Agricultural and Veterinary Chemicals. August 2002. Canberra Australia.
http://www.apvma.gov.au/publications/prstrif.pdf

 
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