Adverse Effects
Florasulam
CAS No. 145701-23-1
 
 

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Activity: Herbicide
Structure:



Adverse Effects:
Anemia
Body Weight Decrease
Endocrine: Adrenal
Kidney
Liver
Environmental

Anemia (click on for all fluorinated pesticides)

Short term toxicity. Target / critical effect: Anemia, hepatotoxicity , renal hypertrophy epithelial cells, collecting ducts, adrenal vacuolation(dog ) Lowest relevant oral NOAEL / NOEL: 1 y & 90 d dog (oral feed) ; 5 mg/kg bw/d;...
Ref: September 18, 2002 - Review report for the active substance florasulam. European Commission Health & Consumer Protection Directorate-General.
http://www.fluoridealert.org/pesticides/Florasulam.EU.Sept.2002.pdf

Body Weight Decrease (click on for all fluorinated pesticides)

-- In the rat 90-d dietary study, other histopathological findings in the kidney included degeneration with regeneration in the descending portion of the proximal tubules (females at 500 mg/kg bw/d and above) which was considered to be typical of acute necrosis with regeneration rather than a 90-d old lesion and multi-focal mineralization in the papilla (females at 800 mg/kg bw/d). These lesions did not appear to be reversible. In the rat 2- year dietary study, other histopathological findings in the kidneys included a possible slight decreased incidence of age-related tubular degeneration/regeneration and a decreased severity of spontaneous geriatric renal degeneration (chronic progressive glomerularnephropathy) in males at 250 mg/kg bw/d and above, slight decreased incidence of spontaneous geriatric renal disease in females at 250 mg/kg bw/d and minimal reactive hyperplasia of the transitional epithelium and unilateral necrosis of the papilla in males at 500 mg/kg bw/d. The high-dose males also exhibited decreased proteinuria, which was considered to represent less severe chronic renal disease although the decreased specific gravity suggest that dilution may have also contributed to lower values. Body weight and body-weight gain were significantly lower in males at 1000 mg/kg bw/d and in females at 500 mg/kg bw/d and above in the 90-d dietary study and in males at 500 mg/kg bw/d (highest dose tested [HDT]) and in females at 250 mg/kg bw/d (HDT) in the 2-year dietary study. This was associated with concomitant lower food consumption in the high-dose animals in the both 90-d and 2-year dietary study.
-- In the dog, an increased incidence and severity of hypertrophy of the epithelial cells was observed in both sexes at 50 mg/kg bw/d and above in both the 90-d and 1-year dietary study. There were no treatment-related urinalysis findings in either the 90-d or 1-year dietary study. The severity (slight) of the hypertrophy did not appear to increase with prolonged exposure. In the 90-d dietary study treatment-related findings associated with the liver included increased alkaline phosphatase (ALP) activity in both sexes at 50 and 100 mg/kg bw/d, increased liver weights in both sexes at 100 mg/kg bw/d and a slight increased incidence or severity of hepatic vacuolation in both sexes at 50 and 100 mg/kg bw/d. Increased liver weights and hepatic vacuolation were not observed in the 1-year dietary study. In the 1-year dietary study, treatment-related findings associated with the liver, included increased alanine aminotransferase (ALAT) and ALP activity and decreased serum albumin and protein levels in both sexes at 100 mg/kg bw/d. After the high dose was reduced to 50 mg/kg bw/d (week 15), ALP activity remained elevated and serum albumin and protein levels remained lower in both sexes. In the 1-year dietary study, no histopathological findings were evident in the liver. In the 1-year dietary study, slight vacuolization of the zona reticularis and zona fasciculata in the adrenal glands was observed in the high-dose males and females; however, in the absence of any associated inflamation, necrosis or other changes, the toxicological significance of this finding was uncertain. The vacuolization was consistent with fatty changes. Body weight, body-weight gain and food consumption were significantly lower in both sexes at 100 mg/kg bw/d and remained lower in the high-dose females after the high dose was reduced in the 1-year dietary study. Body weight, body-weight gain and food consumption were unaffected by treatment in the 90-d dietary study.
Ref: Florasulam EF-1343 Suspension Concentrate Herbicide. REF2001-12. September 21, 2001. Canadian Pest Management Regulatory Agency. Health Canada.
http://www.hc-sc.gc.ca/pmra-arla/english/pdf/reg/reg2001-12-e.pdf

Endocrine: Adrenal (click on for all fluorinated pesticides)

Short term toxicity. Target / critical effect: Anemia, hepatotoxicity , renal hypertrophy epithelial cells, collecting ducts, adrenal vacuolation(dog ) Lowest relevant oral NOAEL / NOEL: 1 y & 90 d dog (oral feed) ; 5 mg/kg bw/d;...
Ref: September 18, 2002 - Review report for the active substance florasulam. European Commission Health & Consumer Protection Directorate-General.
http://www.fluoridealert.org/pesticides/Florasulam.EU.Sept.2002.pdf

-- The subchronic and chronic toxicity of florasulam was investigated in the mouse, rat and dog. A 28-d repeat dose dermal toxicity study was also carried out in rats. In the subchronic and chronic studies, treatment-related findings were observed in the kidney in all species and in the liver and adrenal glands in dogs. In the kidney, hypertrophy of the epithelial cells of the collecting ducts occurred in all species tested.
-- In subchronic and chronic dietary studies, treatment-related findings were observed in the kidneys in mice, rats and dogs and in the liver and adrenal glands in the dog. In the kidney, hypertrophy of the epithelial cells of the collecting duct was observed in all species tested. In rats, hypertrophy of the epithelial cells correlated with elevated serum bicarbonate levels, urinary acidification, decreased urinary specific gravity and increased kidney weights. In dogs, treatment-related findings associated with the liver included increased ALP activity, decreased serum albumin and protein levels, increased liver weights and increased incidence or severity of hepatic vacuolation. Dogs also exhibited slight vacuolization of the zona reticularis and zona fasciculata in the adrenal glands; however, in the absence of any associated inflammation, necrosis or other changes, the toxicological significance was uncertain. The most appropriate NOAEL for subchronic and chronic toxicity end points is 5.0 mg/kg bw/d in the 90-d and 1-year dietary studies in dogs. At the LOAEL, 50 mg/kg bw/d, treatment-related findings were observed in the kidneys and liver in the 90-d and 1-year dietary studies and in the adrenal glands in the 1-year dietary study.

Ref: Florasulam EF-1343 Suspension Concentrate Herbicide. REF2001-12. September 21, 2001. Canadian Pest Management Regulatory Agency. Health Canada.

http://www.hc-sc.gc.ca/pmra-arla/english/pdf/reg/reg2001-12-e.pdf

Kidney (click on for all fluorinated pesticides)

-- Short term toxicity. Target / critical effect: Anemia, hepatotoxicity , renal hypertrophy epithelial cells, collecting ducts, adrenal vacuolation(dog ) Lowest relevant oral NOAEL / NOEL: 1 y & 90 d dog (oral feed) ; 5 mg/kg bw/d;...
-- Long term toxicity and carcinogenicity. Target / critical effect: kidney collecting duct hypertrophy, papillary mineralisation, necrosis and inflammation (rat and/or mice) Lowest relevant NOAEL: 2 yr rat (oral feed): 10 mg/kg bw/d. no carcinogenic potential. Other toxicological studies Renal cells affected are probably Type A intercalated cells, involved in acid-base regulation.
Ref: September 18, 2002 - Review report for the active substance florasulam. European Commission Health & Consumer Protection Directorate-General.
http://www.fluoridealert.org/pesticides/Florasulam.EU.Sept.2002.pdf

-- In the rat 90-d dietary study, other histopathological findings in the kidney included degeneration with regeneration in the descending portion of the proximal tubules (females at 500 mg/kg bw/d and above) which was considered to be typical of acute necrosis with regeneration rather than a 90-d old lesion and multi-focal mineralization in the papilla (females at 800 mg/kg bw/d). These lesions did not appear to be reversible. In the rat 2- year dietary study, other histopathological findings in the kidneys included a possible slight decreased incidence of age-related tubular degeneration/regeneration and a decreased severity of spontaneous geriatric renal degeneration (chronic progressive glomerularnephropathy) in males at 250 mg/kg bw/d and above, slight decreased incidence of spontaneous geriatric renal disease in females at 250 mg/kg bw/d and minimal reactive hyperplasia of the transitional epithelium and unilateral necrosis of the papilla in males at 500 mg/kg bw/d. The high-dose males also exhibited decreased proteinuria, which was considered to represent less severe chronic renal disease although the decreased specific gravity suggest that dilution may have also contributed to lower values. Body weight and body-weight gain were significantly lower in males at 1000 mg/kg bw/d and in females at 500 mg/kg bw/d and above in the 90-d dietary study and in males at 500 mg/kg bw/d (highest dose tested [HDT]) and in females at 250 mg/kg bw/d (HDT) in the 2-year dietary study. This was associated with concomitant lower food consumption in the high-dose animals in the both 90-d and 2-year dietary study.
-- The subchronic and chronic toxicity of florasulam was investigated in the mouse, rat and dog. A 28-d repeat dose dermal toxicity study was also carried out in rats. In the subchronic and chronic studies, treatment-related findings were observed in the kidney in all species and in the liver and adrenal glands in dogs. In the kidney, hypertrophy of the epithelial cells of the collecting ducts occurred in all species tested.
-- In subchronic and chronic dietary studies, treatment-related findings were observed in the kidneys in mice, rats and dogs and in the liver and adrenal glands in the dog
. In the kidney, hypertrophy of the epithelial cells of the collecting duct was observed in all species tested. In rats, hypertrophy of the epithelial cells correlated with elevated serum bicarbonate levels, urinary acidification, decreased urinary specific gravity and increased kidney weights. In dogs, treatment-related findings associated with the liver included increased ALP activity, decreased serum albumin and protein levels, increased liver weights and increased incidence or severity of hepatic vacuolation. Dogs also exhibited slight vacuolization of the zona reticularis and zona fasciculata in the adrenal glands; however, in the absence of any associated inflammation, necrosis or other changes, the toxicological significance was uncertain. The most appropriate NOAEL for subchronic and chronic toxicity end points is 5.0 mg/kg bw/d in the 90-d and 1-year dietary studies in dogs. At the LOAEL, 50 mg/kg bw/d, treatment-related findings were observed in the kidneys and liver in the 90-d and 1-year dietary studies and in the adrenal glands in the 1-year dietary study.
Ref: Florasulam EF-1343 Suspension Concentrate Herbicide. REF2001-12. September 21, 2001. Canadian Pest Management Regulatory Agency. Health Canada.
http://www.hc-sc.gc.ca/pmra-arla/english/pdf/reg/reg2001-12-e.pdf

Liver (click on for all fluorinated pesticides)

Short term toxicity. Target / critical effect: Anemia, hepatotoxicity , renal hypertrophy epithelial cells, collecting ducts, adrenal vacuolation(dog ) Lowest relevant oral NOAEL / NOEL: 1 y & 90 d dog (oral feed) ; 5 mg/kg bw/d;...
Ref: September 18, 2002 - Review report for the active substance florasulam. European Commission Health & Consumer Protection Directorate-General.
http://www.fluoridealert.org/pesticides/Florasulam.EU.Sept.2002.pdf

-- The subchronic and chronic toxicity of florasulam was investigated in the mouse, rat and dog. A 28-d repeat dose dermal toxicity study was also carried out in rats. In the subchronic and chronic studies, treatment-related findings were observed in the kidney in all species and in the liver and adrenal glands in dogs. In the kidney, hypertrophy of the epithelial cells of the collecting ducts occurred in all species tested.
-- In subchronic and chronic dietary studies, treatment-related findings were observed in the kidneys in mice, rats and dogs and in the liver and adrenal glands in the dog. In the kidney, hypertrophy of the epithelial cells of the collecting duct was observed in all species tested. In rats, hypertrophy of the epithelial cells correlated with elevated serum bicarbonate levels, urinary acidification, decreased urinary specific gravity and increased kidney weights. In d
ogs, treatment-related findings associated with the liver included increased ALP activity, decreased serum albumin and protein levels, increased liver weights and increased incidence or severity of hepatic vacuolation. Dogs also exhibited slight vacuolization of the zona reticularis and zona fasciculata in the adrenal glands; however, in the absence of any associated inflammation, necrosis or other changes, the toxicological significance was uncertain. The most appropriate NOAEL for subchronic and chronic toxicity end points is 5.0 mg/kg bw/d in the 90-d and 1-year dietary studies in dogs. At the LOAEL, 50 mg/kg bw/d, treatment-related findings were observed in the kidneys and liver in the 90-d and 1-year dietary studies and in the adrenal glands in the 1-year dietary study.
-- In the dog, an increased incidence and severity of hypertrophy of the epithelial cells was observed in both sexes at 50 mg/kg bw/d and above in both the 90-d and 1-year dietary study. There were no treatment-related urinalysis findings in either the 90-d or 1-year dietary study. The severity (slight) of the hypertrophy did not appear to increase with prolonged exposure. In the 90-d dietary study treatment-related findings associated with the liver included increased alkaline phosphatase (ALP) activity in both sexes at 50 and 100 mg/kg bw/d, increased liver weights in both sexes at 100 mg/kg bw/d and a slight increased incidence or severity of hepatic vacuolation in both sexes at 50 and 100 mg/kg bw/d
. Increased liver weights and hepatic vacuolation were not observed in the 1-year dietary study. In the 1-year dietary study, treatment-related findings associated with the liver, included increased alanine aminotransferase (ALAT) and ALP activity and decreased serum albumin and protein levels in both sexes at 100 mg/kg bw/d. After the high dose was reduced to 50 mg/kg bw/d (week 15), ALP activity remained elevated and serum albumin and protein levels remained lower in both sexes. In the 1-year dietary study, no histopathological findings were evident in the liver. In the 1-year dietary study, slight vacuolization of the zona reticularis and zona fasciculata in the adrenal glands was observed in the high-dose males and females; however, in the absence of any associated inflamation, necrosis or other changes, the toxicological significance of this finding was uncertain. The vacuolization was consistent with fatty changes. Body weight, body-weight gain and food consumption were significantly lower in both sexes at 100 mg/kg bw/d and remained lower in the high-dose females after the high dose was reduced in the 1-year dietary study. Body weight, body-weight gain and food consumption were unaffected by treatment in the 90-d dietary study.
-- Ref: Florasulam EF-1343 Suspension Concentrate Herbicide. REF2001-12. September 21, 2001. Canadian Pest Management Regulatory Agency. Health Canada.

http://www.hc-sc.gc.ca/pmra-arla/english/pdf/reg/reg2001-12-e.pdf

Environmental (click on for all fluorinated pesticides)

European Union: Only uses as herbicide may be authorised. For the implementation of the uniform principles of Annex VI, the conclusions of the review report on florasulam, and in particular Appendices I and II thereof, as finalised in the Standing Committee on the Food Chain and Animal Health on 19 April 2002 shall be taken into account. In this overall assessment Member States: should pay particular attention to the potential for groundwater contamination, when the active substance is applied in regions with vulnerable soil and/or climatic conditions. Conditions of authorisation must include risk-mitigation measures, where appropriate.
Ref: COUNCIL DIRECTIVE of 15 July 1991 concerning the placing of plant protection products on the market 91/414/EEC - amended by 2003/5/EC (OJ No. L 8, 14.01.2003, p. 7)

http://www.uksup.sk/download/oso/20030409_smernica_rady_91_414_eec.pdf

 
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