Absorption, Distribution and Excretion
Male and female rats were given a single oral dose of ((14)C)pyriproxyphenyl (phenoxyphenyl-labeled) <4-phenoxyphenyl(R,S)-2-(2-pyridinoxy)propyl ether> at doses of 2 (low dose) or 1000 (high dose) mg/kg. (14)C was rapidly excreted in feces and urine, with the fecal route being the dominant route (approximately 90% of the dose). Peak concentrations of (14)C in blood, kidneys, liver, and other tissues (excluding adipose tissue) were 0.4, 0.4, 2.5, and <0.2 g pyriproxyphenyl equivalents/g tissue (ppm) at 2–8 hours post-administration. Peak concentrations of (14)C in adipose tissue occurred at 12–24 hours post-administration, ranging from 0.3 to 0.5 ppm. On day 7, the residual 14C in tissues of the low-dose and high-dose groups were less than 0.02 ppm and 10 ppm, respectively. No significant sex differences were observed in 14C excretion or residual 14C in tissues. However, slight sex differences were observed in the extent of metabolic response. Rats were orally administered 2 mg/kg or 1000 mg/kg of 14C-labeled pyriproxyfen, or 2 mg/kg of unlabeled pyriproxyfen for 14 consecutive days, followed by a single oral dose of 2 mg/kg of labeled pyriproxyfen. During the 7-day collection period, most of the radioactive material was excreted in feces (81-92%) and urine (5-12%). No radioactive material was detected in exhaled breath. Tissue radioactivity levels were extremely low (< 0.3%), except for fat. The detection of metabolites in urine, feces, liver, kidneys, bile, and blood identified multiple (>20) metabolites compared to synthetic standards.

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Metabolism/Metabolites
This study investigated the metabolism of pyridyl ether (4-phenoxyphenyl(RS)-2-(2-pyridinoxy)propyl ether, Sumilarv) in rats and mice. Rats and mice were given single oral doses of 2 mg/kg and 1000 mg/kg of (pyridyl-2,6-(14)C)- or (phenoxyphenyl-(14)C)pyridyl ether, respectively. Within 7 days of administration, carbon-14 was almost completely excreted in urine and feces, with fecal excretion being the dominant form in both animals. The excretion of carbon-14 in rat feces and urine was 84-97% and 4-12% of the administered dose, respectively, and in mice, it was 64-91% and 9-38%, respectively. The main metabolic reactions of pyriproxyfen include: (1) hydroxylation at the 4-position of the terminal benzene ring; (2) hydroxylation at the 2-position of the terminal benzene ring; (3) hydroxylation at the 5-position of the pyridine ring; (4) dephenylation; (5) ether bond cleavage; and (6) the formation of phenolic compounds that bind to sulfates or glucuronic acids. Although the overall metabolic profiles of pyriproxyfen between the two species did not differ significantly, significant sex differences were found in metabolic reactions 1, 3, and 6 in rats, while no such differences were found in mice. This study examined the levels of cytochrome P450 and b5 in the gut and fat body microsomes of third-instar larvae from a pyriproxyfen-resistant strain (YPPF) and two pyriproxyfen-sensitive strains (YS and SRS). Compared with the YS and SRS strains, the YPPF strain larvae had higher levels of total cytochrome P450 in the gut and fat body microsomes. Furthermore, the hydroxylation capacity of aniline in the gut and fat body microsomes of YPPF larvae was significantly higher than that of YS larvae. In vitro metabolic studies of pyriproxyfen showed that the metabolic rate in the gut and fat body of YPPF larvae was much higher than that in YS and SRS larvae. In houseflies, the major metabolites of pyriproxyfen were identified as 4'-hydroxypyriproxyfen and 5''-hydroxypyriproxyfen. Cytochrome P450 inhibitors, such as piperonylbutyl ether (PB) and 2-propynyl-2,3,6-trichlorophenyl ether (PTPE), significantly reduced the metabolic rate in all three strains. This study confirms that microsomal cytochrome P450 monooxygenases play an important role in pyriproxyfen resistance in houseflies. Furthermore, the study also showed that the fat body is just as important as the gut for pyriproxyfen metabolism in resistant housefly larvae. Rats were orally administered 2 or 1000 mg/kg of 14C-labeled pyriproxyfen, or 2 mg/kg of unlabeled pyriproxyfen for 14 consecutive days, followed by a single oral dose. Pyriproxyfen was labeled at a dose of 2 mg/kg. ...Detection of metabolites in urine, feces, liver, kidneys, bile, and blood revealed multiple (>20) metabolites compared to synthetic standards. The main biotransformation reactions of pyriproxyfen include: (i) oxidation at the 4' position of the terminal phenyl group; (ii) oxidation at the 5' position of the pyridine group; (iii) ether bond cleavage and the conjugation of the resulting phenols with sulfuric acid.

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Biological half-life
...Under refrigeration conditions, the biological half-life of pyriproxyfen in pepper fruit is 918 days. ...

Toxicity Summary
Identification and Uses: Pyriproxyfen may be a solid or liquid. Pyriproxyfen is a potent insect growth regulator that affects the hormonal balance of insects, thereby strongly inhibiting embryogenesis, metamorphosis, and adult formation. It is used to control agricultural, veterinary, and human pests such as whiteflies and scale insects; flies, mosquitoes, and fleas. It is also used as a veterinary drug. Human Exposure and Toxicity: This substance may have effects on the blood and liver. This may lead to anemia, dysfunction, and tissue damage. Pyriproxyfen has been reported to have some estrogenic activity against human ovarian cancer cells. In genotoxicity studies, HeLa cells exposed to concentrations up to 6.4 μg/mL (unactivated) and 51.2 μg/mL (activated) of insoluble pyriproxyfen did not induce an increase in unplanned DNA synthesis, regardless of activation. Animal studies: Twenty-one male and twenty-one female rats were fed diets containing pyriproxyfen at concentrations of 0, 80, 400, 2000, and 10000 ppm, respectively, for six months. No deaths occurred in any group. Both male and female rats fed 10000 ppm pyriproxyfen developed hair loss on the neck and/or back, as well as soft stools. Throughout the treatment period, both male and female rats fed 10000 ppm pyriproxyfen showed significantly decreased body weight gain, along with reduced food intake and increased water consumption at the beginning of treatment. Regarding organ weight, increased liver (male mice fed 2,000 ppm and 10,000 ppm, female mice fed 10,000 ppm), kidney (both male and female mice fed 10,000 ppm), and thyroid (female mice fed 10,000 ppm) weights were observed, while decreased pituitary (female mice fed 2,000 ppm and 10,000 ppm) weights were observed. Gross pathological examination revealed a higher incidence of dark brown livers and a lower incidence of well-defined lobular textures (male mice fed 10,000 ppm). Hepatomegaly was observed in a small number of male and female mice fed the 10,000 ppm group. Mice were immunized three times with ovalbumin (dissolved in 5% ethanol), with or without pyriproxyfen or alum. High doses of pyriproxyfen (9 or 15 mM) significantly enhanced the specific total IgG immune response. This enhancing effect disappeared 24 hours after pyriproxyfen treatment. Furthermore, pyriproxyfen induced higher titers of IgG2a and enhanced tumor necrosis factor-α and gamma-interferon responses. In gene mutation assays (Ames assay)/reverse mutation assays, gene mutation induction experiments were performed on five strains of Salmonella typhimurium and WP2 uvra Escherichia coli. The results showed that pyriproxyfen did not induce gene mutations in the dose range of 10 to 5,000 μg/plate, regardless of metabolic activation. The highest dose was insoluble. Gene mutation assays in mammalian cells showed that pyriproxyfen did not induce mutagenesis in CHO (Chinese hamster ovary) V79 cells at up to a cytotoxic dose (300 μg/mL), regardless of metabolic activation. In vitro structural chromosome aberration assays showed that pyriproxyfen did not induce chromosome breakage in CHO cells at a cytotoxic dose (300 μg/mL), regardless of metabolic activation. Ecotoxicity Study: This study investigated the effects of pyriproxyfen on the reproduction of Daphnia magna using a series of male reproductive screening tests. Results showed that pyriproxyfen increased male fertility in a concentration-dependent manner, with an EC50 of 156 pM (50.24 ng/L). Furthermore, pyriproxyfen reduced the overall fertility of parthenogenetic Daphnia magna across all tested age groups (7 days, 14 days, and 21 days). To compare the effects of short- and long-term exposure and determine the likelihood of recovery, juvenile (3 days old) and sexually mature (10 days old) female Daphnia magna were exposed to 155 pM pyriproxyfen for 2–12 days, and their reproductive activity was measured for 16 days. Results indicated that longer pyriproxyfen exposure (8–12 days) prolonged the reproductive period of male Daphnia magna and reduced their reproductive rate; however, Daphnia exposed for only 2–4 days recovered and produced relatively normal numbers of larvae. Furthermore, juvenile Daphnia are also highly sensitive to pyriproxyfen, but its main effect is to reduce reproductive rate and prolong development, rather than reduce male Daphnia reproduction. Researchers also investigated the effects of pyriproxyfen on early ovarian synthesis in land crabs (Gecarcoidea natalis). Pyriproxyfen may cause endocrine disorders by mimicking methyl farnesate to stimulate early ovarian development and induce vitellin synthesis. This study investigated the effects of the juvenile hormone analog pyriproxyfen on bee larvae and adults in bee colonies. Bees in the pyriproxyfen-treated group emerged earlier than those in the control group, and the highest dose resulted in a significantly increased rate of adult deformities (wing atrophy). Larvae were more easily rejected by their hive companions, leading to a shorter lifespan. This may be related to the difference in the cutaneous hydrocarbon profiles of bees in the control and pyriproxyfen-treated groups. In addition, bees in the pyriproxyfen-treated group exhibited fewer social behaviors (ventilation, brooding, contact with hive companions or food reserves) than those in the control group. Larval exposure to sublethal doses of pyriproxyfen affects multiple life history traits in bees.

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Toxicity Data
LC50 (Rat)> 1,300 mg/m3/4h

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Interactions
Many pesticides are used in agricultural production, some of which have estrogenic activity, such as endocrine disruptors that may affect wildlife and humans. This study aimed to investigate the estrogenic effects of some pesticide mixtures in agricultural production. We assessed estrogenic activity by detecting the proliferative activity of MtT/Se cells that respond well to estrogen. To assess MtT/Se cells, we delved into the molecular level of estrogen receptor (ER)-α and ER-β. The ER-α to ER-β ratio was 3.55:1 as determined by semi-quantitative real-time PCR. These results indicate that ER-α is dominant in MtT/Se cells at the transcriptional level, thus suggesting that the estrogenic activity detected in these cells may be primarily mediated by ER-α. Pyriproxyfen has been found to have estrogenic activity. Many pesticides are commonly found in agricultural products. Therefore, we evaluated the estrogenic activity of a mixture of two pesticides. The REC(10) levels of phoxim/pyriproxyfen and thiabendazole/o-phenylphenol were increased 10-fold. We conclude that the combination of these two pesticides exhibits a significantly higher estrogenic effect compared to the results of testing each pesticide individually.

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Non-human toxicity values
Oral LD50 in rats >5000 mg/kg
Dermal LD50 in rats >2000 mg/kg
Inhalation LC50 in rats >1300 mg/m³/4 hr
Dermal LD50 in rabbits >2000 mg/kg

Pyriproxyfen is an aromatic ether composed of a propylene glycol molecule with a 2-pyridyl group at the O-1 position and a 4-phenoxyphenyl group at the O-3 position. It is a juvenile hormone analog. Pyriproxyfen belongs to the aromatic ether class of compounds and has a functional correlation with 4-phenoxyphenol. Pyriproxyfen is a pyridine insecticide effective against a variety of arthropods. It was introduced to the United States in 1996 to protect cotton crops from whiteflies. It has also been found to be effective in protecting other crops. Additionally, it is used to prevent fleas on domestic pets. Mechanism of Action: Pyriproxyfen mimics insect juvenile hormones, inhibiting metamorphosis and larval development. It also accumulates in the ovaries of female fleas, preventing egg hatching. When used in combination with adult insecticides (e.g., permethrin, fipronil), it kills all stages of the parasite, thus reducing the likelihood of reinfection.

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Therapeutic Use
(Veterinary): ...We report two cases of head lice infestation in ponies from random sources. No infection or clinical signs were observed during a 4-week quarantine period and for 3 to 9 months thereafter, but symptoms of infection began to appear when the ponies were moved from pasture to indoor pen. Both geldings presented with itchy and scratching lesions on their necks and were diagnosed with head lice (Werneckiella equi Denny, 1842). Both ponies were successfully treated with standard wound care and a spray containing 2.0% permethrin and 0.05% pyriproxyfen. These cases highlight the importance of recognizing the possibility of lice infestation, even in healthy, well-cared-for animals, and the need for staff to be aware of early behavioral signs of infection, such as rubbing and restlessness.

C20H19NO3

321.37

321.136

95737-68-1

Pyriproxyfen-d6;2673269-99-1;Pyriproxyfen-d4;2446366-95-4

91753

White to off-white solid powder

1.2±0.1 g/cm3

462.0±35.0 °C at 760 mmHg

45-47°C

165.4±16.2 °C

0.0±1.1 mmHg at 25°C

1.581

4.84

0

4

7

24

338

0

NHDHVHZZCFYRSB-UHFFFAOYSA-N

InChI=1S/C20H19NO3/c1-16(23-20-9-5-6-14-21-20)15-22-17-10-12-19(13-11-17)24-18-7-3-2-4-8-18/h2-14,16H,15H2,1H3

2-[1-(4-phenoxyphenoxy)propan-2-yloxy]pyridine

Tiger 10EC; Sumilarv; Pyriproxyfen

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ≥ 100 mg/mL (~311.17 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (7.78 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (7.78 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)