β-Ionone is a close relative of β-carotenoids, which are found in a variety of fruits and vegetables[1]. β-ionone over 24 and 48 hours at 25, 50, 100, and 200 μM suppresses the proliferation of SGC-7901 cell line. 89 μM is the measured IC50 value[1].

Metabolism / Metabolites
A 3 kg male rabbit was orally administered a total of 23 g beta-ionone for 7 days (approx. 1000 mg/kg bw/day). Urine was collected daily and for 4 days after the final dose. Allylic ring oxidation and ketone reduction yielded 3-oxo-ionone, 3-oxo-beta-ionol, dihydro-3-oxo-beta-ionol, and 3-hydroxy-beta-ionol, which were detected in the urine. Unchanged beta-ionone and the glucuronic acid conjugates of 3-oxo-beta-ionol and dihydro-3-oxo-beta-ionol were also detected.
/Researchers/ fed beta-ionone to three rabbits in daily increasing doses of 2-5 g with a total dose of about 30 g in one week. In another test, feeding continued for two weeks in daily doses of 4 g, which increased to 5 g towards the end. In this schedule, the dose was not administered on some days. Urine was collected from all animals and analyzed for the presence of metabolites. The metabolites identified included 3-oxo-beta-ionone, bionol, dihydro-beta-ionol, oxy-beta-ionol, oxy-dihydro-beta-ionol, and oxy-dihydro-beta-ionone. Tetrahydro derivatives and multiple unsaturated products formed by dehydrogenation were not seen. Two separate feeding tests conducted in the spring and in the fall showed that conversion products of beta-ionone which are hydrogenated to the -hydroxyl and -carbonyl groups were excreted in the spring but not in the fall.

Toxicity Summary
IDENTIFICATION AND USE: Beta-ionone (BI) is a colorless to pale, straw-colored liquid. BI is of use, not only in perfumery, but also as a key intermediate in the synthesis of Vitamins A, E, and K. HUMAN EXPOSURE AND TOXICITY: At 1% BI produced no irritation or sensitization in patients. At 5% concentration, 2 patients showed questionable positive irritation reactions, but there was no sensitization. ANIMAL STUDIES: No evidence of sensitization was observed in guinea pigs. In rabbits application of neat beta-ionone produced very slight to well-defined erythema on the abraded and intact skin at 24 hr and well defined erythema at 72 hr. Very slight conjunctival irritation was observed in all three rabbits at 0, 1, 2, and 4 hr with neat BI. In 90 day feeding study in rats BI did not produce adverse effects. In development study in BI-treated pregnant rats compared to the untreated controls, the uterus weight, the ratio of resorptions per implantations and the percentage of resorptions per implantation per litter were substantially increased, and the ratio of live fetuses per implantations per litter was drastically decreased with 1000 mg/kg; with 250, 500 and 750 mg/kg, no effects were produced. BI exhibited no mutagenic activity in Salmonella typhimurium (strains TA98, TA100, TA1535 and TA1537) at concentrations up to approximately 180 ug/plate with and without metabolic activation. ECOTOXICITY STUDIES: Ultrastructural examination by transmission electron microscopy indicated that the thylakoids were distorted, and the thylakoid membrane stacks began to collapse when M. aeruginosa NIES-843 was exposed to BI at a concentration of 22.5 and 33.75 mg/L.

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Interactions
A possible role of metabolic activation by cytochrome P450 (P450) in thioacetamide-induced hepatotoxicity was investigated in male BALB/c mice. The mice were pretreated with the P450 inducer, beta-ionone, subcutaneously at 600 mg/kg, 72 and 48 hr prior to an intraperitoneal administration of either 100 or 200 mg/kg of thioacetamide. The elevated activities of serum alanine aminotransferase and serum aspartate aminotransferase by thioacetamide were greatly potentiated by the pretreatment with beta-ionone. Moreover, the potentiation of thioacetamide-induced hepatotoxicity was also observed in the histopathological examination of livers. The hepatic necrosis by thioacetamide was potentiated when mice were pretreated with beta-ionone. In liver microsomes, the activities of P450 2B-specific pentoxyresorufin O-depentylase and benzyloxyresorufin O-debenzylase were significantly induced by the treatment with beta-ionone. Beta-ionone also induced other P450-associated monooxygenases. Because the pretreatment with beta-ionone was not hepatotoxic at the dose inducing P450s. our present results suggest that beta-ionone may be a useful model inducer of P450 enzyme(s) in studying toxic mechanism of certain chemicals which require metabolic activation by P450s in mice.
Female ICR mice were treated with cocaine either alone or in combination with one of several cytochrome P450 (CYP) inducers, i.e. phenobarbital, beta-ionone, dexamethasone and beta-naphthoflavone. Cocaine-induced hepatotoxicity was first observed by pretreatment with phenobarbital, beta-ionone or dexamethasone in accordance with significant elevation of cocaine N-demethylation, the first step of cocaine bioactivation. The hepatic lesions occured in the periportal region (zone 1) by phenobarbital and beta-ionone and in the perivenular region (zone 3) by dexamethasone. The activities of the enzyme specific for CYP isozyme were determined to elucidate the effects of pretreatment with CYP inducers. Beta-naphthoflavone induced CYP1A and 2B but had no effects on hepatotoxicity by cocaine. On the other hand, beta-ionone enhanced hepatotoxicity without induction of CYP3A. Activities of cocaine N-demethylase correlated well with CYP2A (r=0.83) and CYP2B (r=0.81). Cocaine N-demethylation was inhibited particularly by addition of the CYP2A specific inhibitor, 8-methoxypsoralen. Moreover, pretreatment with 8-methoxypsoralen produced a marked inhibition of the hepatotoxicity induced by cocaine in phenobarbital-treated mice. These results suggest that cocaine-induced hepatotoxicity in female mice was mediated in part by CYP2A, participating in cocaine N-demethylation.
beta-Ionone demonstrates potent anticancer activity both in vitro and in vivo. We determined tumor incidence and the number of rats bearing tumors as well as cell proliferation and apoptosis in a rat mammary cancer model induced by 7, 12-dimethylbenz[a]anthracene (DMBA). Rats were fed an AIN-76A diet containing beta-ionone (0, 9, 18 or 36 mmol/kg), starting 2 weeks before DMBA administration and continuing for 24 weeks. A dose-dependent inhibition of mammary carcinogenesis by dietary beta-ionone was observed. Corresponding tumor incidence values were 82.1, 53.3, 25.9 and 10.0% (p < 0.01 or 0.05). Time to tumor appearance increased and tumor multiplicity decreased with increasing dietary beta-ionone. Histopathological and immunohistochemical evaluations of tumors were performed on the 64, 31, 15 and 3 tumors, respectively, identified in rats from the respective groups of 30. The proportions of adenocarcinomas, adenomas and benign masses were equally distributed in the latter group. In proportions within the other groups, the proportions of adenocarcinomas and benign masses decreased and increased with increasing dietary beta-ionone. Proliferating cell nuclear antigen (PCNA), cyclin D1 and Bcl-2 expression decreased, and Bax expression and nuclear fragmentation increased with increasing dietary beta-ionone. These results demonstrate the potent capacity of dietary beta-ionone to suppress DMBA-initiated mammary cancer in rats.
Beta-ionone (BI) is a degraded (C 13) sesquiterpene found in plant essential oils. It has been used in the synthesis of perfume chemicals and vitamin A. Recently, it was reported that BI is a rather potent in vitro inhibitor of CYP2B1-catalysed reactions in rat liver microsomes. The present study was performed to investigate whether inhibition of CYP2B1 reactions by BI could lead to an attenuation of cyclophosphamide (CP)-induced embryotoxicity in the rat. In a preliminary experiment, a dose-dependent prolongation of pentobarbital sleeping time in male and female Wistar rats suggested that BI inhibits CYP2B1 in vivo as well. In a second experiment, rats were treated by gavage with BI (0, 250, 500, 750 or 1000 mg/kg body wt) 45 min prior to a subcutaneous injection of either CP (7.5 mg/kg body wt) or its vehicle (saline) on day 11 of pregnancy. BI alone, at the highest dose tested, caused a high proportion of resorptions. Lower doses of BI, however, clearly attenuated CP-induced embryolethality and teratogenicity. These results seem to support the view that, as far as rats are concerned, CYP2B1 plays an important role in the conversion of CP into its embryolethal and teratogenic metabolites.

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Non-Human Toxicity Values
LD50 Rat oral 4590 mg/kg
LD50 Mouse ipr 2277 mg/kg

[1]. β-Ionone and Its Analogs as Promising Anticancer Agents. Eur J Med Chem. 2016 Nov 10;123:141-154.

Beta-ionone is a colorless to light yellow liquid with an odor of cedar wood. In very dilute alcoholic solution the odor resembles odor of violets. Used in perfumery.
Beta-ionone is an ionone that is but-3-en-2-one substituted by a 2,6,6-trimethylcyclohex-1-en-1-yl group at position 4. It has a role as an antioxidant and a fragrance.
beta-Ionone has been reported in Camellia sinensis, Perilla frutescens, and other organisms with data available.
beta-Ionone is a metabolite found in or produced by Saccharomyces cerevisiae.

C13H20O

192.30

192.151

14901-07-6

638014

Colorless to light yellow liquid

0.9±0.1 g/cm3

254.8±0.0 °C at 760 mmHg

-49ºC

121.3±11.9 °C

0.0±0.5 mmHg at 25°C

1.518

3.85

0

1

2

14

292

0

CC1=C(C=CC(=O)C)C(C)(C)CCC1

PSQYTAPXSHCGMF-BQYQJAHWSA-N

InChI=1S/C13H20O/c1-10-6-5-9-13(3,4)12(10)8-7-11(2)14/h7-8H,5-6,9H2,1-4H3/b8-7+

(E)-4-(2,6,6-trimethylcyclohexen-1-yl)but-3-en-2-one

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 (520.02 mM)
Ethanol: 100 mg/mL (520.02 mM)
H2O: < 0.1 mg/mL

Solubility in Formulation 1: ≥ 2.5 mg/mL (13.00 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 (13.00 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), 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 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 (13.00 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.)