Daphnia growth rate is slowed down by methoprene, and a single concentration response line with a threshold of 12.6 nM is shown. A 2-segment line with thresholds of 4.2 and 0.21 nM, respectively, was shown by the response curve for mephenyl, which reduced molting frequency in a concentration-dependent manner. Methoprene also had an apparent concentration-dependent effect on the endpoint associated with reproductive maturity, the time to first oviposition, with a NOEC of 32 nM. Fecundity is decreased by methoprene based on a 2-segment line threshold of 24 and

Absorption, Distribution and Excretion
When (14)C methoprene was administered orally to rats, slightly less than 20% was excreted within 5 days in the urine and a similar amount in feces and almost 40% was excreted as (14)C02. About 17% was retained in the body. Highest concentrations were in liver (84.5 ppm), kidneys (29 ppm), lungs (26 ppm), fat (36.5 ppm), and the adrenal cortex (12-13 ppm). About 12 labeled compounds were detected in the urine but no unchanged methoprene was observed.
Distribution and elimination of (14)C given to chickens as methoprene (14)C (isopropyl (2E,4E)-11-methoxy-3,7,11-trimethyl-2,4-dodecadienate 5 (14)C were investigated. When about 4 mg of methoprene was given in a single oral dose to colostomized chickens, elimination of (14)C was greatest in exhaled air; however, when 105 or 107 mg of methoprene was given, elimination of (14)C was greatest in urine. Up to 19% of the (14)C from a single dose of methoprene was eliminated over a 14 day period in the eggs of laying hens, and (14)C was detected in all tissues and organs examined.
When the metabolic fate of methoprene (isopropyl (2E,4E)-11-methoxy-3,7,11-trimethyl- 2,4-dodecadienoate) was studied in a guinea pig, a steer, and a cow, a rather large percentage of the radiolabel was incorporated in the tissues and respired by the animals. In the urine and feces, a small amount of radiolabel was metabolized into free primary metabolites, somewhat more was incorporated into simple glucuronides, and a considerable quantity of radiolabel was found in polar compounds, possibly complex conjugates or polar biochemicals. No methoprene was found in the urine, but approximately 40% of the radiolabel in feces was contributed by unmetabolized methoprene. The formation of conjugates and the metabolism of methoprene was more extensive in the steer than in the guinea pig.
Treatment of Leghorn chickens with a single oral dose of (5-14C)methoprene (isopropyl (2E,4E)-11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate) resulted in residual radioactivity in tissues and eggs. The chemical nature of the residual radiolabel in tissue (muscle, fat, liver), eggs, and excrement was thoroughly examined at several doses (0.6 to 77 mg/kg). Although a high initial dose (59 mg/kg) resulted in methoprene residues in muscle (0.01 ppm), fat (2.13 ppm), and egg yolk (8.03 ppm), these residues of methoprene represented only 39 and 2% of the total (14)C label in fat and egg yolk, respectively. Radiolabeled natural products from extensive degradation of methoprene were by far the most important 14C residues in tissues and eggs, particularly at the lower dose of 0.6 mg/kg where (14)C cholesterol and normal (14)C fatty acids (as triglyceride) contributed 8 and 71% of the total radiolabel in egg yolk. Novel minor metabolites of methoprene were observed in lipid depots, resulting from saturation of the dienoate system. These minor metabolites were conjugated to glycerol and/or cholesterol. radioactivity were found in the bile, liver, skin, fetus, and udder. In all species, approximately 40 percent of the radioactivity in the feces was due to unchanged methoprene. No methoprene was found in the urine.
For more Absorption, Distribution and Excretion (Complete) data for METHOPRENE (6 total), please visit the HSDB record page.

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Metabolism / Metabolites
About 4 mg (14)C methoprene was administered orally to colostomized chickens. (14)C02 was the main (14)C product detected. When large doses were given, elimination was greatest in urine and (14)C was also found in the eggs and all tissues and organs examined ... . In addition to natural (14)C cholesterol and (14)C fatty acid triglycerides, there were metabolites conjugated to glycerol and/or cholesterol. Urine ... and ... feces contained compounds ... and each had undergone considerable isomerization. About 19% of the (14)C appeared in the eggs. Most of this was associated with egg proteins. The egg yolks also had radiolabeled fatty acid glycerides and cholesterol. Blood contained radiolabeled cholesterol and traces of cholesteryl esters. Tissue residues were similar to those found in eggs.
A Hereford steer received a single oral dose of 5-(14)C-methoprene and sacrificed 2 weeks later. No primary metabolites were observed in fat, muscle, liver, lung, blood and bile. However, the majority of the tissue radioactivity was present as (14)C cholesterol. About 72% of the activity in bile appeared in cholesterol, cholic acid, and deoxycholic acid. Protein and cholesteryl esters of fatty acids also contained some radioactivity.
When administered to a lactating cow, 5-(14)C-methoprene gave rise to randomly labeled acetate. This was incorporated into milk fat which was degraded to saturated and mono and di- enoic fatty acids. Labeled lactose, lactalbumin, casein, and free and esterified cholesterol was also observed ... . Similar qualitative results were observed in urine of a guinea pig orally dosed with methoprene. Quantitative differences were observed.
Studies with housefly microsomal enzymes showed that the Beta-esterases present did not appreciably hydrolyze methoprene whereas other analogs were metabolized. Microsomal oxidase activity against juvenile hormone analogs was greater in resistant fly strains. ... Branched chain esters of methoprene analogs did not show significant difference in hydrolysis by housefly microsomal esterases. Methoprene was effective at 0.1 ug/pupa while others were ineffective at 10 ug/pupa.
For more Metabolism/Metabolites (Complete) data for METHOPRENE (15 total), please visit the HSDB record page.

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Biological Half-Life
The degradation of methoprene by unidentified pond organisms was studied. The half-life in the pond water was about 30 h at 0.001 ppm and 40 h at 0.01 ppm.
In wheat, the half-life of methoprene was estimated to be 3 to 7 weeks, depending on moisture content. The only metabolite observed was the free acid.

Toxicity Summary
IDENTIFICATION AND USE: Methoprene is a clear amber liquid. It is used for control of many insect pests in public health, stored commodities (including tobacco), food handling, processing and storage establishments, on animals, and on plants (including glasshouse plants). Particular uses include control of mosquito larvae; sciarid flies in mushroom houses; cigarette beetles and tobacco moths in stored tobacco; Pharaoh's ants; leaf miners on glasshouse chrysanthemums; stored product pests in food and tobacco processing plants and warehouses. HUMAN EXPOSURE AND TOXICITY: There are no data available. ANIMAL STUDIES: Non-irritating to skin and eyes (rabbits). In 2 year feeding trials, rats receiving 5000 mg/kg diet and mice receiving 2500 mg/kg diet showed no ill-effects. No teratogenic effects on rats at 1000 mg/kg and on rabbits at 500 mg/kg. No mutagenic effects on rats at 2000 mg/kg. No reproductive adverse effects in 3-generation reproduction studies on rats at 2500 mg/kg diet. Methoprene applied at a concentration of 0.2 ppm did not significantly affect the locomotor activities of mosquitofish or goldfish. This application rate is ten times the suggested rates. Methoprene-membrane interaction and perturbation of cell bioenergetics may underlie the mechanism of toxicity of this compound in non-target organisms. Methoprene induces a weak mutagenic effect in the Drosophila wing spot test. ECOTOXICITY STUDIES: Xenopus laevis embryos (stage 8) were exposed to the test chemicals for 96 hr. Assays were conducted under static renewal (24 hr) conditions and chemical concentrations in water were measured at the beginning and end of the renewal periods. Methoprene exposure did not result in developmental toxicity at concentrations up to 2 mg/L. Applications of amethoprene enhanced the levels of dopamine in the brains of 4-day-old male honey bees.

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Toxicity Data
LC50 (rat) > 210,000 mg/m3

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Interactions
Exposure to multiple stressors from natural and anthropogenic sources poses risk to sensitive crustacean growth and developmental processes. Applications of synthetic pyrethroids and insect growth regulators near shallow coastal waters may result in harmful mixture effects depending on the salinity regime. The potential for nonadditive effects of a permethrin (0.01-2 ug/L), methoprene (0.03-10 ug/L ), and salinity (10-40 ppt) exposure on male and female Uca pugnax limb regeneration and molting processes was evaluated by employing a central composite rotatable design with multifactorial regression. Crabs underwent single-limb autotomy followed by a molting challenge under 1 of 16 different mixture treatments. During the exposure (21-66 d), individual limb growth, major molt stage duration, abnormal limb regeneration, and respiration were monitored. At 6 d postmolt, changes in body mass, carapace width, and body condition factor were evaluated. Dorsal carapace tissue was collected, and protein and chitin were extracted to determine the composition of newly synthesized exoskeleton. The present results suggest chronic, low-dose exposures to multiple pesticide stressors cause less-than-additive effects on U. pugnax growth processes. Under increasing concentrations of methoprene and permethrin, males had more protein in their exoskeletons and less gain in body mass, carapace width, and body condition compared to females. Females exhibited less gain in carapace width than controls in response to methoprene and permethrin. Females also displayed elevated respiration rates at all stages of molt, suggesting a high metabolic rate. Divergent growth and fitness between the sexes over the long term could influence crustacean population resilience.

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Non-Human Toxicity Values
LD50 Rat oral >34600 mg/kg
LD50 Dog oral >5000 mg/kg
LD50 Rabbit percutaneous 3500 mg/kg
LD50 Non-toxic to adult bees (oral and topical) >1000 ug/l/bee
For more Non-Human Toxicity Values (Complete) data for METHOPRENE (7 total), please visit the HSDB record page.

[1]. Olmstead AW, LeBlanc GL. Low exposure concentration effects of methoprene on endocrine-regulated processes in the crustacean Daphnia magna. Toxicol Sci. 2001;62(2):268-273.

[2]. Toxicity of methoprene as assessed by the use of a model microorganism. Toxicol In Vitro. 2005;19(7):951-956.

Therapeutic Uses
/EXPL THER/ The effects of methoprene, a juvenile hormone analogue (JHA), on Trypanosoma cruzi bloodstream trypomastigotes (Tulahuen strain, Tul 2 stock) were studied. It was observed that 150 uM of methoprene in in vitro experiments cause cellular death of T. cruzi. In contrast, methoprene was not able to clear bloodstream trypomastigotes in in vivo experiments, but it was observed a decrease of parasitemia levels of infected mice treated with 200 ug of methoprene/mouse/day during 5 days. According to these results and the low toxicity of methoprene, we suggest that this compound will serve as an effective agent to sterilize blood for transfusions.
/EXPL THER/ Drug therapy for the treatment of African sleeping sickness is limited by toxicity and resistance and in the last 50 years only one new drug has been introduced for the treatment of the human disease. We report that the juvenile hormone analog, methoprene, and several structurally related isoprenoid compounds kill Trypanosoma brucei in culture. Of the other isoprenoids tested, juvenile hormone III and mammalian retinoid X receptor ligands were the most potent trypanocides. Both the procyclic forms and the bloodstream trypomastigotes are killed by these compounds with LD50 values of 5-30 uM. Of the two methoprene stereoisomers, the EE form was the most active, suggesting that a protein target may be involved in mediating effects of these analogues against the parasite. Methoprene was not, however, able to clear trypanosomes from the blood of infected mice. Methoprene acid, the immediate downstream metabolite of methoprene, is not an effective anti-trypanosomal agent, suggesting that in the mice methoprene is converted to an inactive compound. Since methoprene and its analogues have low and well characterized toxicity in mammals these studies stress the importance of further exploring these isoprenoids as lead compounds for the treatment of African sleeping sickness.

C19H34O3

310.478

310.25

40596-69-8

S-Methoprene;65733-16-6;Methoprene-d7;2673270-24-9

5366546

Colorless to light yellow liquid

0.9±0.1 g/cm3

385.7±25.0 °C at 760 mmHg

164ºC

162.4±17.8 °C

0.0±0.9 mmHg at 25°C

1.462

5.63

0

3

11

22

378

0

CC(OC(/C=C(/C=C/CC(CCCC(OC)(C)C)C)\C)=O)C

NFGXHKASABOEEW-LDRANXPESA-N

InChI=1S/C19H34O3/c1-15(2)22-18(20)14-17(4)11-8-10-16(3)12-9-13-19(5,6)21-7/h8,11,14-16H,9-10,12-13H2,1-7H3/b11-8+,17-14+

propan-2-yl (2E,4E)-11-methoxy-3,7,11-trimethyldodeca-2,4-dienoate

ZPA-1019; ZPA 1019; Methoprene

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)

Ethanol : ~100 mg/mL (~322.09 mM)
Acetone :≥ 50 mg/mL (~161.05 mM)
DMSO : ~25 mg/mL (~80.52 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (8.05 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 (8.05 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
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 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (8.05 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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Solubility in Formulation 4: ≥ 2.5 mg/mL (8.05 mM) (saturation unknown) in 10% EtOH + 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 EtOH stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of 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 5: ≥ 2.5 mg/mL (8.05 mM) (saturation unknown) in 10% EtOH + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear EtOH stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 6: ≥ 2.5 mg/mL (8.05 mM) (saturation unknown) in 10% EtOH + 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 EtOH 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.)