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Activity: Herbicide (Aryloxyphenoxy propionic acid)
Structure:

Adverse Effects:
Blood
Endocrine: Thyroid
Kidney
Liver

Blood (click on for all fluorinated pesticides)

Abstract: 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.

Endocrine: Thyroid (click on for all fluorinated pesticides)

Abstract: 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.

Kidney (click on for all fluorinated pesticides)

Abstract: 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.

Liver (click on for all fluorinated pesticides)

Abstract: 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.

Abstract: The potential of haloxyfop [2-(4-((3-chloro-5-(trifluoromethyl)-2- pyridinyl)oxy)phenoxy)propanoic acid; HAL] to induce the proliferation of hepatocellular peroxisomes (PP) was examined in rats, mice, dogs, and monkeys. Chemically induced PP is associated with the development of liver tumors in rodents via an apparent species-dependent, nongenotoxic mechanism of action. HAL is nongenotoxic yet has been shown to cause liver tumors in female B6C3F1 mice. Ingestion of HAL by rats and/or mice (0.1-14 mg/kg/day for 2 to 4 weeks) resulted in significant dose-related PP as evidenced by hepatocellular hypertrophy, increased peroxisome volume density (VD), and induction of peroxisomal enzymes and CYP4A1. Only a relatively weak induction of PP was noted at a carcinogenic dosage in female mice...
Ref: Fundam Appl Toxicol 1995 Nov;28(1):71-9. Species-dependent induction of peroxisome proliferation by haloxyfop, an aryloxyphenoxy herbicide. Stott WT, Yano BL, Williams DM, Barnard SD, Hannah MA, Cieszlak FS, Herman JR.

PubMed Abstract: The CoA esters of diclofop, haloxyfop and fluazifop are up to 425-fold more potent than the corresponding unconjugated herbicides as inhibitors of rat liver acetyl-CoA carboxylase (EC 6.4.1.2); the most potent inhibitor is (R)-fluazifopyl-CoA2 (Ki = 0.03 microM).
Ref: Life Sci 1992;50(7):533-40. Coenzyme A esters of 2-aryloxyphenoxypropionate herbicides and 2-arylpropionate antiinflammatory drugs are potent and stereoselective inhibitors of rat liver acetyl-CoA carboxylase. Kemal C, Casida JE.