Adverse Effects
Diflufenican
CAS No. 83164-33-4
 
 

Return to Diflufenican Index Page

Activity: Herbicide (anilide)
Structure:

Adverse Effects:
Body Weight Decrease
Bone
Cholesterol
Endocrine: Testicular
Endocrine: Thymus
Liver
Environmental

"Diflufenican/isoproturon" ranked number 6 for "Most Widely used pesticides in the UK (by Area Treated)"

Rank Formulation Method Area treated (ha) Weight applied (kg ai)
6 Diflufenican/isoproturon Spray 1,057,086 662,735

Ref: April 29, 2000. UK Department for Environment, Food & Rural Affairs in the online report, "Design of a Tax or Charge Scheme for Pesticides. " Annex C3: Overview of Pesticide Industry
http://www.fluorideaction.org/pesticides/pesticides.ranks.uk.2000.htm


Body Weight Decrease (click on for all fluorinated pesticides)

--Subacute toxicity studies... In a 13-week oral study in the dog, the minimum effect level was 250 mg/kg bw based on enemis and increased cholesterol levels at the 250 mg/kg bw/day dose level. The observed effects at higher dose levels included impaired body weight gain, emesis, increased plasma cholesterol and increase in the relative thymus weights.
-- Subchronic/chronic toxicity studies... The NOAEL in the 104-week mouse study was 500 ppm (approximately 60 - 70 mg/kg bw/day) based on minimal reduction in body weight gain at the 500 ppm dose level and significant reduction in body weight gain and increase in the absolute and relative liver weight in females at the higher dose level. Diflufenican was not tumourigenic in the mouse. The NOEL in the 52-week oral study in the dog was 100 mg/kg bw/day based on significant increase in liver weight at the higher dose level.
-- Reproductive toxicity studies. In a teratogenicity study in the rat, the minimum effect level for maternal toxicity was 50 mg/kg bw/day based on reductions in weight gain at all dose levels...
-- Acceptable daily intake (ADI). The acceptable daily intake of 0.2 mg/kg bw/day is derived from the critial minimum effect level of 500 ppm (24 mg/kg bw/day), derived from the 24-month chronic dietary study in the rat or the multigeneration study in the rat and allows for a 100-fold safety factor. The observed effects included minimal reductions in body weight gain and a slight reduction in thymus weights at the 500 ppm dose level.
Ref: September 1995. Evaluation on Diflufenican. Evaluation of fully approved or provisionally approved products. 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/evallist_alphabet.htm

Bone (click on for all fluorinated pesticides)

-- Reproductive toxicity studies. In a teratogenicity study in the rat, the minimum effect level for maternal toxicity was 50 mg/kg bw/day based on reductions in weight gain at all dose levels. The NOEL for foetotoxicity and teratogenicity was 5000 mg/kg bw/day. In a teratogenicity study in the rabbit, the NOAEL for maternal toxicity was 50 mg/kg bw/day based on clinical signs of toxicity and the NOEl for foetotoxicity and teratogenicity 2500 mg/kg bw/day. A dose-related increase in the incidence of supernumerary ribs was considered to be within the historical control range. It was noted that the incidence in controls was low, whilst the statistical significance was marginal at the highest dose level.
Ref: September 1995. Evaluation on Diflufenican. Evaluation of fully approved or provisionally approved products. 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/evallist_alphabet.htm

Cholesterol (click on for all fluorinated pesticides)

--Subacute toxicity studies... In a 13-week oral study in the dog, the minimum effect level was 250 mg/kg bw based on enemis and increased cholesterol levels at the 250 mg/kg bw/day dose level. The observed effects at higher dose levels included impaired body weight gain, emesis, increased plasma cholesterol and increase in the relative thymus weights.
Ref: September 1995. Evaluation on Diflufenican. Evaluation of fully approved or provisionally approved products. 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/evallist_alphabet.htm

Endocrine: Testicular (click on for all fluorinated pesticides)

-- Subchronic and chronic toxicity studies. Rat. ... In a 24-month feeding study, groups of 50 male and 50 female F344 rats (main study groups, except the control group which consisted of 85 males and 85 females) were administered diflufenican (98.4% purity) in the diet, at concentrations of 0 (control), 500, 2500 or 12500 ppm. A further 30 male and 30 female rats per dose group (satellite study) were similarly treated to generate toxicity dta. An interim-kill was performed on 10 males and 10 females per dose group of the satellite study after 52-weeks... The organ weight changes noted after 104 weeks in the main group... There was an increase in the incidence of marked/severe degeneration of the tubular geminal epithelium of the testes at dose levels of 500 ppm (32/37), 2500 ppm (31/32) and 12500 (33/39) compared to controls (44/64). However, the incidence of slight/moderate degeneration of the geminal epithelium was greater in controls (20.64) compared to top dose males (6/39). Testicular geminal tubular degeneration was considered to be related to pressure atrophy arising from the high incidence of benign intestitial cell tumours (75 - 90%) in treated and control animals...
Ref: September 1995. Evaluation on Diflufenican. Evaluation of fully approved or provisionally approved products. 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/evallist_alphabet.htm

Endocrine: Thymus (click on for all fluorinated pesticides)

--Subacute toxicity studies... In a 13-week oral study in the dog, the minimum effect level was 250 mg/kg bw based on enemis and increased cholesterol levels at the 250 mg/kg bw/day dose level. The observed effects at higher dose levels included impaired body weight gain, emesis, increased plasma cholesterol and increase in the relative thymus weights.
-- Acceptable daily intake (ADI). The acceptable daily intake of 0.2 mg/kg bw/day is derived from the critial minimum effect level of 500 ppm (24 mg/kg bw/day), derived from the 24-month chronic dietary study in the rat or the multigeneration study in the rat and allows for a 100-fold safety factor. The observed effects included minimal reductions in body weight gain and a slight reduction in thymus weights at the 500 ppm dose level.
Ref: September 1995. Evaluation on Diflufenican. Evaluation of fully approved or provisionally approved products. Department for Environment, Food and Rural Affairs, Pesticides Safety Directorate, Mallard House, Kings Pool, 3 Peasholme Green, York YO1 7PX, UK.at:
http://www.pesticides.gov.uk/citizen/evaluations/evallist_alphabet.htm

Liver (click on for all fluorinated pesticides)

-- Subchronic/chronic toxicity studies... The NOAEL in the 104-week mouse study was 500 ppm (approximately 60 - 70 mg/kg bw/day) based on minimal reduction in body weight gain at the 500 ppm dose level and significant reduction in body weight gain and increase in the absolute and relative liver weight in females at the higher dose level. Diflufenican was not tumourigenic in the mouse. The NOEL in the 52-week oral study in the dog was 100 mg/kg bw/day based on significant increase in liver weight at the higher dose level.
Ref: September 1995. Evaluation on Diflufenican. Evaluation of fully approved or provisionally approved products. 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/evallist_alphabet.htm

Environmental (click on for all fluorinated pesticides)

-- Risk to mammals. Since new environmental fate and behaviour data have reported that diflufenican persists in the soil, there may be an increased risk of secondary poisoning to small mammals feeding on contaminated earthworms. Therefore, the risk of secondary poisoning to small earthworm eating mammals will be addressed using the available mammalian toxicity data.
... highly persistent in the soil with dissipation DT50 values of 311 to 733 days, as well as in the water body with little hydrolysis over a range of pH levels at 22C. This could lead to prolonged contamination of water due to run-off of soil containing residues and through direct contamination of water by overspray or spray drift (page 43).

Ref: September 1995. Evaluation on Diflufenican. Evaluation of fully approved or provisionally approved products. 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/evallist_alphab
et.htm


Note from FAN:
The following reports can be purchased from NTIS (National Technical Information Service) via phone at 703-605-6000. The cost for each report (generally on fiche) is approximately $25.00. If you have a copy of any of these reports please share them with us. - Thanks, EC.


Source: EPA/OTS; Doc #88-920009606

INITIAL SUBMISSION: LETTER FROM RHONE-POULENC INC TO USEPA REGARDING A ONCOGENICITY AND TOXICITY STUDY OF DIFLUFENICAN IN MICE WITH ATTACHMENTS AND COVER LETTER DATED 08-31-92

Corporate Name: LIFE SCI RESEARCH

Keywords: RHONE-POULENC INC
DIFLUFENICAN ; HEALTH EFFECTS ; CHRONIC TOXICITY ;
CARCINOGENICITY ; MAMMALS ; MICE ; ORAL ; DIET

Order Number: NTIS/OTS0571263


Source: EPA/OTS; Doc #88-920009402

INITIAL SUBMISSION: TERATOLOGICAL STUDY OF N-(2,4-DIFLUOROPHENYL)-2-[3-(TRIFLUOROMETHYL)PHENOXY]-3-PYRIDINECARBOXAMIDE IN RABBITS WITH COVER LETTER DATED 08/31/92

Keywords:
RHONE-POULENC INC ; [Diflufenican] ; HEALTH EFFECTS ; REPRODUCTION/FERTILITY EFFECTS ; TERATOGENICITY ; MAMMALS ; RABBITS ; ORAL ; GAVAGE ; SUBCHRONIC TOXICITY

Order Number: NTIS/OTS0555455


Source: EPA/OTS; Doc #88-920009414

INITIAL SUBMISSION: EFFECT OF N-(2,4-DIFLUOROPHENYL)-2-[3-(TRIFLUOROMETHYL)PHENOXY]-3-PYRIDINECARBOXAMIDE IN PREGNANT RATS WITH COVER LETTER DATED 08/31/92

Corporate Name: HUNTINGDON RESEARCH CTR

Keywords: RHONE-POULENC INC [Diflufenican] ; HEALTH EFFECTS ; REPRODUCTION/FERTILITY EFFECTS ; TERATOGENICITY ; MAMMALS ; RATS ; ORAL ; GAVAGE ; SUBCHRONIC TOXICITY

Order Number: NTIS/OTS0555467


Source: EPA/OTS; Doc #88-920009450

INITIAL SUBMISSION: COMBINED ONCOGENICITY AND TOXICITY STUDY OF N-(2,4-DIFLUOROPHENYL)-2-[3-(TRIFLUOROMETHYL)PHENOXY]-3-PYRIDINE-CARBOXIMIDE] IN RATS WITH COVER LETTER DATED 08-31-92

Source: EPA/OTS; Doc #88-920009450

Keywords: RHONE-POULENC INC ; [Diflufenican] ; HEALTH EFFECTS ; CHRONIC TOXICITY ; COMBINED CHRONIC TOXICITY/CARCINOGENICITY ; MAMMALS ; RATS ; ORAL ; DIET

Order Number: NTIS/OTS0571106


Source: EPA/OTS; Doc #88-920008945

INITIAL SUBMISSION: EFFECT OF M&B 38544 ON REPRODUCTIVE FUNCTION OF MULTIPLE GENERATIONS IN THE RAT WITH COVER LETTER DATED 08/31/92

Corporate Name: HUNTINGDON RESEARCH CENTRE LTD

Keywords: RHONE-POULENC INC ; M&G 38544 ; HEALTH EFFECTS ; REPRODUCTION/FERTILITY EFFECTS ; COMBINED TERATOGENICITY/REPRODUCTIVE EFFECTS ; MAMMALS ; RATS ; ORAL ; DIET ; CHRONIC TOXICITY ; COMBINED CHRONIC TOXICITY/CARCINOGENICITY

Order Number: NTIS/OTS0555262

 
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