substance year week species NOEL LOEL target organs symptoms at LOEL appl. Fungicides

Transcription

1 1 F dog liver AST, a.ph. F rat adrenal, kidney weight; BUN F rat liver fatty infiltration, weight F mouse body weight F dog 8 80 liver, kidney mortality; liver + kidney w.; anemia, ALAT, a.ph.,album., salivation F rat urinary bladder urothelial hyperplasia; cholest. F mouse 4 12 liver vacuolation, rel. weight F dog urinary bladder, mucosal hyperplasia ALAT albumin F rat liver hypertrophy, weight F dog liver, thyroid hyperplasia in liver + thyroid F mouse urinary bladder mucosal hyperplasia F dog thyroid hyperplasia F rat < thyroid hyperplasia F dog vomiting; food intake F rat < blood, kidney, adrenal MCV, MCH, cholest., kidney + adrenal w., tubular dilatation + necrosis in kidney; body w. + food F mouse adrenal abs. + rel. weight; body w.+ food intake F dog vomiting, water consumpt. F rat liver, kidney hypertrophy; colored urine F mouse liver glycogen depletion F dog blood, gastrointestine WBC, clotting time, diarrhoea body w. + food + water intake F mouse urinary bladder mortality; urinary tract lesions, urogenital tract lesions; food F rat liver, thyroid hypertrophy, eosinoph. foci, weight; GGT, a.ph., hypertrophy and hyperplasia of thyroidal epithelia; follicular cell tumors; b.w. + food intake F dog 3 15 liver hepatitis-like lesions, weight F mouse prostate, adrenal, weights; GGT, BUN kidney F rat liver, blood weight; leucocyt. F dog 5 20 testes atrophy of semineferous tubules LDH F rat 5 50 blood, heart LDH, eosinoph.; weight F rat forestomach, blood hyperkeratosis and proliferation of endothelium; leucocytes, prot. F dog 4 24 ALAT, globul. album. F rat 7 35 thyroid, gastrointestine TG, T4, hyperkeratosis of oesophagus, Ca2+, body w. F dog liver, kidney, blood, eye, skin ALAT, GLDH, a.ph., 0-demeth. PNOD, P450, liver weight, portal inflammat. ph and urinary vol, excret. of protein platel.+neutroph., alopecia, dermatitis, cataract, degenerat. of lens F mouse gastrointestine hyperkerat. of mucosa food int. crouching posture F dog skin, liver dermatitsis, bilateral cataracts, alopecia; ALAT, GLDH F rat body weight F rat thyroid hyperplasia; body w. + food F mouse liver weight; body w. F dog < water consumpt. appl., application design, with asterisks () application via capsule or stomach intubation,

2 F dog blood anemia, reticulocytosis; b.w. F mouse body w. + food intake F rat muscle skeletar muscular atrophy F rat kidney, prostate urinary incontinence; enlargement and edema of prostate F dog body weight F mouse 75 no effect F dog body weight F rat kidney urinary incontinence F rat < blood, liver T.G., glucose, prot., Hb; rel. weight F dog 5 10 ALAT, a.ph.; body w. F rat liver, ChE weight plasma-che F dog 5 10 ALAT, a.ph. F dog a.ph., ALAT F rat ChE, liver brain-che; liver w.; b.w. F mouse 3 15 ChE RBC-ChE F rat body weight gain F mouse liver centrilob. enlargement F dog liver, kidney, blood rel. liver rel. kidney w.; albumin protein, MCV, platelets F dog liver weight F mouse liver granulomatous inflamm. in liver weight; body weight F rat body weight + food intake F rat liver weight, prot.,album., Ca2+ K+ F dog a.ph. body w. gain + food F mouse liver, adrenal hypertrophy, weight; adrenal w.; globulins album./glob. F rat liver AST, a.ph. body w.+ food int. F dog liver, kidney AST, a.ph.; urine vol. + ph gravity, IgG, body w. + food F mouse liver, skin mortality; hyperplasia, adenoma + carcinoma, weight; acanthosis, hyperkeratosis b.w. F rat pituitary, liver mortality; pituitary adenoma; bile duct prolif.+ portal sclerosis F dog 0.6 no effect F rat 7 10 liver pnod, weight F dog 20 no effect F mouse liver, blood weight bilirubin F dog blood activated partial thromblast.time F rat glucose F mouse body weight F rat blood, gastrointestine (forestomach), kidney anemia; ulceration, mucosal hyperplasia, inflammat., erosion BUN bilirub., album.; body w.+food F dog blood anemia, prot., album., body w. F dog liver, weight; cholest., protein F mouse eye, urinary bladder retinal atrophy; protein-like bodies in urinary bladder; b.w. + food F rat blood, lpancreas, kidney anemia; hematopoiesis in liver; acinar atrophy in pancreas, steatosis/fatty infiltration of pancreas; kidney w.; b.w. F mouse lung weight, protein F dog liver, thyroid cyt.p-450, liver + thyroid w. food intake appl., application design, with asterisks () application via capsule or stomach intubation, 2

3 F rat a.ph. F rat ChE RBC + plasma-che, ALAT F dog ChE RBC + plasma-che F mouse ChE RBC + plasma-che F /81 52 dog ChE, kidney RBC + plasma-che, spec. gravity F rat ChE, kidney RBC + plasma-che, LDH, gravity F dog < gastrointestine infiltration with round cells, emesis, diarrhoea F rat < gastrointestine, skin lesions, hyperkerat. of tail skin body weight gain + food intake F dog emesis F mouse liver weight F rat 100 no effect F rat liver GGT in liver + blood, weight F dog < liver, adrenal rel.liver + adrenal w. F mouse 2 5 cholest., TG F rat 8 21 liver GGT, cholest., hypertrophy, weight, fat deposition F dog 2 7 kidney hypertrophy of prox. tubular cells F dog blood anemia, platelets F mouse liver hypertrophy, weight F rat 2 8 blood platelets F dog a.ph. adrenal swelling and discolorat. of glandul. F rat 15 (7.5) 50 (25) F dog liver, blood, bladder, adrenal F (< 1992) F /92 (< 1992) 99 mouse 23 (180) 104 rat 7.5 (50) cells and fat droplets; body w. swollen livers,hepatic cord atrophy macrophages; a.ph., anemia; small granulomata in mucosa of urinary bladder; adrenal w. 115 liver, testes, hypertrophy; vacuolat. + hypertrophy gastrointestine of testicular interst. cells; hyperkeratosis of non-gland liver, testes,blood weight; interstitial testicul. cell hyperplasia, spermatozoa in epididymides; hemosiderin in spleen; vacuol. in adrenals F rat body weight gain F dog liver a.ph., AST; weight 3 F rat liver weight F dog gastrointestine vomiting, diarrhoea, body w. F mouse liver weight F dog blood platelets body w. + food F mouse body w. + food intake F rat GGT ALAT body w. F dog CNS, thymus prostate a.ph., tremor, thymus + prostate weight F rat liver, heart, blood liver + heart w., anemia F mouse liver, weight; a.ph., ALAT F dog liver, prostate a.ph.; liver weight, lipidosis; prostate weight F rat food intake F /93 13 rat eye statiations of the lens (1993) (13) (15) (22) F dog blood thromocytes, Jolly bodies appl., application design, with asterisks () application via capsule or stomach intubation,

4 F mouse liver, testes, adrenal liver weight; focal hyperplasia in Leydig cells; lipogenic pigments in adrenal gland; TG, cholest., album. F (1982) 52 (26) dog 2.5 (7) 5 adrenal, testes, prostate, blood hemosiderin; adrenal + testes w. prostate atrophy F rat < 2.3 (28) 2.3 liver, adrenal, prostate, ovary, eye foci; lipidosis of adrenal cortex; interstit. fibrosis of prostate; lipidosis of ovarial interstit. cells; lenticular degeneration F dog liver, bile duct proliferat.; ALAT, a.ph gastrointestine salivation,vomiting, diarrhoea body w. F mouse 9 36 liver, heart, testes weights F rat liver, thyroid hypertrophy, weight; follicular neoplasia; body w. F rat blood, liver, spleen, kidney RBC, reticul. liver, spleen + kidney w. F dog blood, gall bladder erythropoiesis in spleen,hematopoi. in bone marrow, hemosid. in Kupffer cells;thickening of mucosa F dog blood RBC, Heinz bodies; hemosiderosis in cortical renal tubules; erythropoiesis in bone marrow F mouse spleen, kidney weight; creatinine; b.w. F rat kidney, blood hemosiderosis in spleen, spleen + kidney w.; Heinz bodies,bilirub. F dog liver pnod, cyt.p450, cholest. body weight + food F rat 8 40 liver enlargement, weight F rat 7 28 liver, kidney AST, ALAT, GLDH, BUN, creatinine F mouse body weight F dog 15 (> 2.5) 60 liver pnod; a.ph. F rat 5 25 ALAT F dog 3 5 blood, kidney RBC-parameters, ketonuria F mouse liver rel.weight, body weight 4 F rat 5 10 liver AST, a.ph.; body w. F dog 1 5 skin, thymus, prostate ALAT, a.ph.; inflamm. and conjunctivities prost. and thym.w. F / dog adrenal ALAT, a.ph.; adrenal effects F rat 5 25 body weight F mouse liver eosinophil. foci, weight body w. F rat kidney vacuolar swelling of tubular epithelial cells F dog cholest. F dog blood MCV; body weight F / rat thyroid weight (1969) (< 5) (5) F mouse liver hypertrophy F /85 78 rat 5 15 liver, kidney weights; body w. F mouse 40 no effect F / dog liver ground glass of cytoplasm; b.w. F dog blood anemia, iron; bilirubin F rat 4 20 kidney granular pigments in renal cortex appl., application design, with asterisks () application via capsule or stomach intubation,

5 F rat liver, testes,kidney cholest.,hypertrophy liver + testes w., urobilinogen body w F dog liver a.ph., weight, albumin, emesis body weight gain F dog liver, blood weight, brown pigment; a.ph. anemia; body w. + food F rat liver, thyroid weight, cholest.; thyroid neoplasia; acanthosis, b.w. F dog liver, blood cholest., ALAT, a.ph., weight; leucocyt., neutroph., platelets F rat liver, blood fatty vacuol., a.ph., weight Hb, body weight gain F dog kidney, adrenal, liver, blood cytoplasm. pigments in cortical tubul. epithel.; cortical fatty vacuol. in adrenals; liver w. a.ph., globuline, Hb, album. F mouse body w. + food intake F rat liver periacinar fatty vacuol. F dog < thyroid protein-bound iodine F rat kidney weight,glomerulonephr. ALAT F / dog liver, kidney, bile duct prolif., pigmentation, gastrointestine pericholangitis, portal fibrosis; glomerulcytosis, degenerative changein epithel. cells of prox. tubulus; chronic gastritis F mouse forestomach squamous hyperplasia/hyperkerat. F rat stomach, fore-stomach, kidney, adrenal squamous hyperplasia, hyperkeratosis, erosion, ulcer; papilloma in forestomach; nephrosis, renal epithelial hyperplasia in prox. tubules kidney + adrenal w. F /71 (1972) 13 (26) rat 24 (6) 120 (30) blood anemia; hemosiderin deposition in liver, spleen, lung, kidney, heart F dog blood hemosiderin deposition in liver, spleen and bone marrow F dog blood hemosiderin in Kupffer cells and in bone marrow F (1972) 104 (26) rat 9.6 (6) 96 (30) blood hemosiderin in spleen and Kupffer cells, Hb; body w. F mouse mortality; body w. F rat blood, liver, kidney thyroid anemia; hepatocell. lipofuscin chol., album., weight; glomerulonephritis, weight; follicular thyroid hyperplasia, weight F (1991) 13 (13) dog < 50 (< 1.25) 50 (1.25) liver, thyroid ALAT, vacuolat. of cytoplasm; follic. cell hypertrophy in thyroid F dog 8 40 liver, thyroid weight; hyperplasia of follicul. epithelium, weight; cholest., T4, BUN F mouse liver hypertrophy, adenomas F rat liver, thyroid, kidney, adrenal mortality; hypertrophy + lipofuscin; thyorid follicular cell hyperplasia, weight; nephro-pathy, weight, urinary protein; lipidosis of adrenal cortex; cholest., BUN, creatinine, TSH, T3, T4 F dog liver ALAT, a.ph., bile duct proliferat. F mouse liver hypertrophy, weight F dog 620 no effect appl., application design, with asterisks () application via capsule or stomach intubation, 5

6 F rat liver,kidney weight; creatinine F rat thyroid, uterus thyroid + uterus w., leukopenia body weight gain + food intake F dog body weight + food intake F rat thyroid, kidney T3, kidney w. F dog 3 15 kidney, thymus weight; a.ph.; thymus w. F dog 1 5 kidney, liver blood urine, pigments, kidney + liver w., hepatocell. hypertrophy F mouse 3 15 kidney chronic nephrosis of cortical tubules, weight F rat 1 6 kidney neoplasia, proteinuria, urinary blood; GGT F dog liver ALAT, AST; bad condition (1.25) F rat liver, heart liver and heart weight F rat liver, kidney liver + kidney w.; body w. F dog adrenal, testes vacuol. + degenerative changes in cells of zona fascicul.; failure in spermatogenesis, Œweight Œbody w. + food intake F dog < liver weight F rat testes spermatogenesis F /78 13 rat liver hepatomegaly F dog liver weight F dog cholest. F mouse liver foci, neoplastic nodules, hepatoblastoma, weight F rat blood Hb, HT; body w. F dog body weight F rat liver ALAT, AST F mouse 5 12 liver weight; body w. F dog 1 50 liver APND, weight F rat 1 10 liver APND, fatty changes, prolif. of SER, weight F dog 1 5 adrenal cortical vacuolation of zona fasciculata; a.ph. F rat 1 10 liver, kidney fatty changes, clear cell foci, weight; urine ph F mouse 1 5 liver, blood fatty changes; WBC F dog a.ph.; body weight F mouse liver hypertrophy, fatty changes, necrosis + bile stasis; ALAT, SDH; body w. F rat 1 24 liver, blood hypertrophy; platelets, leucocyt body w. + food F rat body weight F dog 26 no effect F dog liver, kidney hypertrophy; a.ph., ALAT, TG BUN F mouse 5 20 body weight F rat a.ph. F /83 13 rat 3 6 liver, blood, weight, bilirubin, Hb gastrointestine leuco salivation, diarrhoea F dog liver, blood, prostate ALAT, a.ph., weight; RBC,Hb prostate weight F mouse 6 25 liver weight F48 78 mouse liver adenomas, fatty vacuol., weight F / rat liver swollen livers; food intake F dog liver swollen livers, hypertrophy, a.ph appl., application design, with asterisks () application via capsule or stomach intubation, 6

7 F dog liver pnod F rat 100 no effect (4) (3) (10) F mouse < liver hypertrophy F /76 (1976) 104 rat 15 (2.5) 25 (25) blood RBC, Hb; body w. F dog liver aminopyrine-n-dem., cyt.p-450 weight; a.ph. F rat adrenal, liver vacuolated adrenal cells in zona fascicul.; cyt. P450; body w. F dog liver pnod, a.ph.; body w. F dog adrenal hypertrophy of zona fascicul. cells F mouse liver periportal vacuolation F rat liver, blood pnod, pigments in Kupffer cells; hemosiderin in spleen; body w., food intake F rat liver hypertrophy, vacuolation F dog liver a.ph., weight, hypertrophy F mouse liver cell necrosis, hypertrophy AST F dog body weight F mouse liver hypertrophy + vacuol., weight F rat 3 30 liver, thyroid hypertrophy and vacuolation, weight; cholest.; focal cystic hyperplasia in thyroid + follicular cell neoplasia, adenoma + carcinoma, weight; body w. F dog liver, blood karyomegaly, pigmentation, hematopoietic nodules F (1971) 104 rat 2 (0.6) 7.5 adrenal, kidney weight; renal tubular cell hyperplasia; BUN, glucose cholest., TG; body w. F rat liver weight (230) F dog ALAT, a.ph.; album./glob. F dog liver, testes cirrhosis; cholest., a.ph., ALAT testicul. degeneration; anorexia body w. +food intake F mouse < liver, thymus, brain carcinoma + adenoma, weight thymus + brain w. F rat 125 no effect F rat liver weight, food intake F dog liver, eye bile duct hyperplasia, weight; retinal changes F rat liver, pancreas altered hepatocytes, weight; exocrine degranulat; cholest. F dog 1 10 nose, bone marrow, liver, blood nasal dryness; myeloid/erythroid ratio in bone marrow; liver w. cholest., leucocyt. F mouse 1 10 liver granulomatous hepatitis, weight F rat liver, kidney, cholest., hypertrophy, weight BUN, colored urine, regenerative tubular epithel. and granular casts F dog gastrointestine dark and soft stool F dog gastrointestine dark and soft stool F rat kidney, liver blue urine; liver weight F mouse kidney, liver, urinary bladder blue urine; centrilob. hypertrophy; epithelial hyperplasia F / rat liver, adrenal, blood weight; fatty degeneration of zona fasc. leucocyt.,. body weight gain appl., application design, with asterisks () application via capsule or stomach intubation, 7

8 F dog liver, gastrointestine weight; salivat., vomiting, fluid feces, body w. F /84 52 dog 3 15 liver weight, cholest. + triglyc. F mouse adrenal, liver adrenal +liver w., degenerat. and hypertrophy of hepatocytes F rat a.ph., ALAT F rat < thyroi cholest., phospholip.; hypertr. of thyroid follicle epithelia F dog body weight + food intake F mouse liver cell necrosis, depletion of glycogen F mouse liver, thyroid MFO; follicul. cell hyperplasia F rat thyroid T4, TSH F dog 3 26 thyroid,blood, enlarged/dark thyroids; anemia; thymus cholest.,bilirub.; lymphoid deplet hematopoiesis in bone marrow F dog 5 20 blood, testes, liver Hb, RBC, PCV, testes w. liver w. body w. + food F mouse body w. F / rat thyroid increased height of follic. epithel. T4; body w. F rat blood, kidney anemia; weight; hematopoiesis F dog K+ in serum F rat urinary bladder, urinary tract F dog testes degeneration calculi and mineralisation, epithelial hyperplasia and neo-plasia; hyperplasia and inflammat. in urinary tract F rat liver rel. liver w. body w. F dog blood Hb, PCV, WBC F dog blood RBC, PCV F rat blood, kidney anemia, BUN F rat liver hypertrophy F dog 5 50 gastrointestine diarrhoea F mouse liver rel. weight, blue stain of pelvis 8 F dog Œbody w. F mouse liver, thymus, spleen, lymph node weight; enlarged thymus, spleen + lymph nodes; food + water int. F rat liver, kidney, blood gastrointestine hepatocell. tumors, necrosis, atrophy, degeneration; nephro-pathy, cysts, urobilinogen; anemia; diarrhoea, body w. F62 13 rat liver, thyroid hypertrophy; thyroid follicular cell (10) (40) hypertrophy; body weight + food F62 13 dog gastrointestine emesis, saliv.; body w. + food F rat blood, thyroid Hb, HT; thyroid w.; b.w. F dog liver, kidney, adrenal liver, kidney, adrenal w. F mouse heart, liver, kidney mortality; atrial thrombosis of myocard; liver + kidney w. body w. + food intake F rat body weight + food intake F dog 80 no effect observed F /76 (1976) 13 (13) rat 20 (7.5) 25 (25) thymus, adrenal thymus w. adrenal w. F (1986) 13 (52) dog 25 (12.5) 75 (62.5) appl., application design, with asterisks () application via capsule or stomach intubation, liver a.ph., PAS-react.; apathy, b.w. F dog kidney, liver alterations of cortical tubuli; a.ph., ALAT, GLDH, BUN, creatinine, glucose in urine; b.w.

9 F rat bone alterations F rat body weight gain F dog food intake F mouse 2 50 liver hypertrophy, weight, cholest. 2 < F dog 6.25 no effect F mouse liver hypertrophy, weight F rat adrenal weight; glucose; body w. F rat 1 4 piloerection body weight gain F dog liver, kidney a.ph., GGT, TG, album., hepatomegaly, weight; creatin. F mouse liver cell necrosis, eosinophilia, vacuol. F dog liver a.ph., cholest., bilirubin, albumin; hepatocytic pigment, intrahepatocytic bodies F mouse liver nodules + tumors, inflammation, single cell necrosis, hypertrophy body weight F rat liver GGT, cholest., protein, globul. TG; liver w. F rat liver hepatic MFO F dog liver hypertrophy F dog liver hypertrophy, weight; a.ph. F rat testes atrophy, weight F mouse liver MFO-activity F rat blood anemia, Na+, Cl- F dog blood, liver, anemia, emesis, diarrhoea gastrointestinal a.ph., TG, weight F dog a.ph. F rat liver hepatocell. hypertrophy F /79 52 rat liver, kidney vacuolation, weight, nitrosoanisole metabolism; creatinine F dog < liver, gastrointestine cholestasis; diarrhoea F mouse liver, blood hyperplasia,vacuol. ALAT,BUN 9 F dog spleen weight F rat sorbitol-dh (1980) 9 (0.75) (3) F dog liver a.ph., cholest., ALAT, GLDH, SDH; food intake F rat liver ALAT, AST F mouse 120 appl., application design, with asterisks () application via capsule or stomach intubation,