Buprofezin has a half-life of 3.43 to 3.59 days and dissipates easily in strawberries [1]. Tetranychus uritcae and Panonychus ulmi larvae are poisonous to hexythiazox, having LC50 values of 0.15-0.58 mg AI/L and 0.23-0.62 mg AI/L, respectively [2].

Absorption, Distribution and Excretion
Three groups of five male and five female Fischer F344 rats (age 10 weeks) rats were given a single oral dose of [thiazolidine-5-(14)C]hexythiazox (specific activity, 6.6 mCi/mmol; purity, > 99%). The three different treatment protocols included a single oral dose at a lower dose (10 mg/kg bw), a single oral dose at the lower dose after fourteen oral doses of unlabeled hexythiazox and a single oral dose at a higher dose (880 mg/kg bw). The lower dose equated to approximately 50 uCi/kg bw and the higher dose, approximately 90 uCi/kg bw. The vehicle chosen for administration of the lower dose was dimethyl sulfoxide (DMSO), while the vehicle chosen for the higher dose was olive oil, because of the solubility limitations of hexythiazox in DMSO. ... The maximum concentrations of radioactivity in plasma were observed about 3-4 hr after administration in the groups at 10 mg/kg bw groups (groups B & C) and 12 hr after dosing at at 880 mg/kg bw (group D). At those times the mean plasma concentrations of radioactivity in groups B and C were 1.8-2.2 ppm for males and 2.3-2.6 ppm for females, and in group D, 37 ppm for males and 27 ppm for females; indicating saturation of absorption at the higher dose. At 72 or 96 hr after administration approximately 0.1 ppm of the radioactivity remained in the plasma in groups B and C; the concentrations of radioactivity in plasma in group D had decreased to approximately 2 ppm. The plasma absorption and elimination followed first-order kinetics, with rate constants of 0.53/hr and approximately 0.075/hr respectively, at 10 mg/kg bw in males. The elimination rate constant corresponded to a half-life of approximately 9 hr. In females, the half-life was slightly longer at 11.4 hr and the half-life was also prolonged in males and females at the higher dose, at 17.3 and 21.7 hr, respectively. In groups B and C approximately 30% of the administered radioactivity was excreted in the urine and approximately 60-70% of the administered radioactivity was recovered in the feces. In group D, 9.5% of the radioactivity was found in the urine and 89.1% in the feces. Of the administered dose, 1.1-10.1% was associated with tissues at 96 hr. The highest concentrations of radioactivity were found in fat, adrenal, liver, ovary and digestive organs and their contents. The highest concentrations of radioactivity in tissues were observed in fat 96 hr after dosing, reaching approximately 2.3, 1.2 and 76 ppm in males and 5.4, 3.3 and 129 ppm in females, in groups B, C and D, respectively. Approximately 36-71% of the radioactivity in the liver and less than 2% of the radioactivity in fat remained as bound (14)C after extraction. Residue concentrations in fat were generally twice as high in females as in males. Concentrations of radioactivity in fat at the end of the studies were low, but more than 20-fold those in plasma, indicating some potential for bioaccumulation. There were no remarkable differences in patterns of absorption and excretory patterns between males and females or after repeated doses.

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Metabolism / Metabolites
Three groups of five male and five female Fischer F344 rats (age 10 weeks) rats were given a single oral dose of [thiazolidine-5-(14)C]hexythiazox (specific activity, 6.6 mCi/mmol; purity, > 99%). The three different treatment protocols included a single oral dose at a lower dose (10 mg/kg bw), a single oral dose at the lower dose after fourteen oral doses of unlabeled hexythiazox and a single oral dose at a higher dose (880 mg/kg bw). The lower dose equated to approximately 50 uCi/kg bw and the higher dose, approximately 90 uCi/kg bw. The vehicle chosen for administration of the lower dosedimethyl sulfoxide (DMSO), while the vehicle chosen for the higher dose was olive oil, because of the solubility limitations of hexythiazox in DMSO. ... Samples from /these/ studies ... were extracted and analyzed for metabolites. In the groups at the lower dose, the primary identified compound was hexythiazox, present in the urine at approximately 2% of the administered radioactivity and in feces at approximately 40% of the administered radioactivity. Unidentified compounds extracting into methanol represented approximately 80% of the radioactivity in urine and 30% of the fecal radioactivity. The primary, identified metabolic reactions were hydroxylation of the cyclohexane ring and cleavage of the amide-cyclohexane bond. The major identified radiolabelled metabolite in excreta was PT-1-8 (cis), which comprised 8-12% of the administered radioactivity in excreta in the groups at the lower dose. The remaining identified metabolites were present at low concentrations (each < 2% of the administered radioactivity): PT-1-2, PT-1-3, PT-1-4, PT-1-8 (trans), PT-1-9, PT-1-10 and PC-1-1. The major identified radiolabelled component in fat was the parent compound; the predominant metabolite in liver and kidney was PT-1-4.

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Biological Half-Life
Three groups of five male and five female Fischer F344 rats (age 10 weeks) rats were given a single oral dose of [thiazolidine-5-(14)C]hexythiazox (specific activity, 6.6 mCi/mmol; purity, > 99%). The three different treatment protocols included a single oral dose at a lower dose (10 mg/kg bw), a single oral dose at the lower dose after fourteen oral doses of unlabeled hexythiazox and a single oral dose at a higher dose (880 mg/kg bw). ... The elimination rate constant corresponded to a half-life of approximately 9 hr. In females, the half-life was slightly longer at 11.4 hr and the half-life was also prolonged in males and females at the higher dose, at 17.3 and 21.7 hr, respectively.

Toxicity Summary
IDENTIFICATION AND USE: Hexythiazox is a solid. Hexythiazox is an acaricide that acts against egg, larval and nymph stages. HUMAN EXPOSURE AND TOXICITY: Hexythiazox has not been linked to adverse effects in any epidemiological reports. A single poisoning incident has been reported in the Philippines. ANIMAL STUDIES: Hexythiazox was not irritating to the skin of rabbits; was a slight, transient eye irritant and produced no evidence of skin sensitizing potential in maximization tests. 90-day feeding study in rats demonstrated increased liver weights in both sexes; increased relative ovary and female kidney weights at 500 and 3500 ppm; increased blood total protein and albumin levels at 500 ppm after 2-months of feeding; fatty degeneration of the zona fasciculta of the adrenal cortex of both sexes at 500 and 3500 ppm. Overall rates of tumor incidence (benign and malignant) were similar in rats receiving hexythiazox and in the control group. Developmental studies in rabbits and rats did not indicate any teratogenic potential for hexythiazox. Hexythiazox has been tested for genotoxicity in a wide range of assays. The weight of evidence is that hexythiazox has no significant genotoxic potential. ECOTOXICITY STUDIES: Hexythiazox is practically nontoxic to birds on an acute basis. The bobwhite acute LD50 is >2,510 mg/Kg while the mallard and bobwhite LC50's were >5,620 ppm. However, no avian reproduction studies were reviewed. Hexythiazox is also practically nontoxic to small mammals (LD50 >5000 mg/kg, reproductive NOAEL >/= 2400 ppm laboratory rat, acute and two generation). Hexythiazox is acutely highly toxic to freshwater species. The LC50 for bluegill is 0.53 ppm and the EC50 for Daphnia is 0.74 ppm. In a supplemental chronic life-cycle test, exposure to technical hexythiazox adversely affected survival in daphnia (NOAEC = 6.1 ppb and LOAEC = 12.7 ppb).

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Toxicity Data
LC50 (rat) > 2,000 mg/m3
Oral LD50 (rat) > 5000 mg/kg bw
Dermal LD50 (rat) > 5000 mg/kg bw
Inhalation > 2.0 mg/l/4 h (whole body exposure)

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Non-Human Toxicity Values
LD50 Quail oral >5 g/kg
LD50 Mouse (male and femals) dermal >5000 mg/kg
LD50 Mouse (male and female) oral >5000 mg/kg
LD50 Rat (male and female) oral >5,000 mg/kg
For more Non-Human Toxicity Values (Complete) data for Hexythiazox (7 total), please visit the HSDB record page.

[1]. Ayman N Saber, et al. Dissipation Dynamic, Residue Distribution and Processing Factor of Hexythiazox in Strawberry Fruits Under Open Field Condition. Food Chem. 2016 Apr 1;196:1108-16.
[2]. R Nauen, et al. Acaricide Toxicity and Resistance in Larvae of Different Strains of Tetranychus Urticae and Panonychus Ulmi (Acari: Tetranychidae). Pest Manag Sci. 2001 Mar;57(3):253-61.

(S,S)-hexythiazox is a hexythiazox.
Hexythiazox is an acaricide used for the control of eggs and larvae of many phytophagous mites and functions as a mite growth regulator. It is also considered as a thiazolidine based acaricide that has long-lasting effects against many kinds of mites and is applied at any stage of the plant growth from budding to fruiting. Its mode of action is non-systemic with contact and stomach action.

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Mechanism of Action
... A mutation in chitin synthase 1 (CHS1) /has been/ linked to etoxazole resistance. In this study, we identified and investigated a Tetranychus urticae strain (HexR) harboring recessive, monogenic resistance to each of hexythiazox, clofentezine, and etoxazole. To elucidate if there is a common genetic basis for the observed cross-resistance, we adapted a previously developed bulk segregant analysis method to map with high resolution a single, shared resistance locus for all three compounds. This finding indicates that the underlying molecular basis for resistance to all three compounds is identical. This locus is centered on the CHS1 gene, and as supported by additional genetic and biochemical studies, a non-synonymous variant (I1017F) in CHS1 associates with resistance to each of the tested acaricides in HexR. Our findings thus demonstrate a shared molecular mode of action for the chemically diverse mite growth inhibitors clofentezine, hexythiazox and etoxazole as inhibitors of an essential, non-catalytic activity of CHS1.

C17H21CLN2O2S

352.88

352.101

78587-05-0

Hexythiazox-d11;2714418-33-2

13218777

White crystals
Colorless crystals

1.3±0.1 g/cm3

108-108.5°C

100 °C

1.621

3.41

1

3

2

23

448

2

C[C@H]1[C@@H](SC(N1C(NC2CCCCC2)=O)=O)C3=CC=C(Cl)C=C3

XGWIJUOSCAQSSV-XHDPSFHLSA-N

InChI=1S/C17H21ClN2O2S/c1-11-15(12-7-9-13(18)10-8-12)23-17(22)20(11)16(21)19-14-5-3-2-4-6-14/h7-11,14-15H,2-6H2,1H3,(H,19,21)/t11-,15+/m0/s1

(4S,5S)-5-(4-chlorophenyl)-N-cyclohexyl-4-methyl-2-oxo-1,3-thiazolidine-3-carboxamide

Hexythizox Cesar Calibre

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 (~283.38 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (7.08 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.)