Subject(s)
Norisoprenoids/chemistry , Norisoprenoids/toxicity , Perfume/chemistry , Perfume/toxicity , Animals , Databases, Chemical , Humans , Risk AssessmentABSTRACT
ß-ionone (BIO) is used in fragrances, toiletries and non-cosmetic products, and as a flavor food additive. Notwithstanding the widespread human exposure, there are limited data on the reproductive toxicity of BIO. This study evaluated the developmental toxicity of BIO (0, 125, 250, 500 and 1000â¯mg/kg body weight/day) given orally to rats on days 6-15 of gestation (GD6-15). C-section was on GD21 and implantations, living and dead fetuses and resorptions were recorded. Fetuses were weighed, and examined for external abnormalities and skeleton and visceral anomalies. The embryotoxicity of a single oral dose of BIO (1000â¯mg/kg body wt) given on GD11 was evaluated as well. At the highest dose, BIO reduced weight gain and produced chromodacryorrhea and other signs of toxicity. BIO did not increase the frequency of malformations nor did it retard fetal growth. Nonetheless, BIO decreased the pregnancy rate in the group of females exposed on GD6-15, and increased the resorption rate in those treated on GD11 only. In conclusion, except for a higher embryolethality at a maternally toxic dose, BIO caused no embryotoxic effect over the dose range tested and the study NOAEL for maternal and developmental toxicity was 500â¯mg of BIO/ kg of body weight/day.
Subject(s)
Norisoprenoids/toxicity , Weight Gain/drug effects , Abnormalities, Drug-Induced/pathology , Animals , Dose-Response Relationship, Drug , Female , Male , Norisoprenoids/administration & dosage , Norisoprenoids/chemistry , Rats , Rats, WistarABSTRACT
The use of this material under current use conditions is supported by the existing information. This material was evaluated for genotoxicity, repeated dose toxicity, developmental toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity, skin sensitization potential, as well as, environmental safety. Repeated dose toxicity was determined to have the most conservative systemic exposure derived NO[A]EL of 10 mg/kg/day. A dietary 90-day subchronic toxicity study conducted in rats resulted in a MOE of 182 while assuming 100% absorption from skin contact and inhalation. A MOE of >100 is deemed acceptable.
Subject(s)
Norisoprenoids/toxicity , Perfume/toxicity , Toxicity Tests/methods , Animals , Consumer Product Safety , DNA Damage/drug effects , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Endpoint Determination , No-Observed-Adverse-Effect Level , Norisoprenoids/chemistry , Perfume/chemistry , Rats , Risk AssessmentSubject(s)
Consumer Product Safety , Norisoprenoids/toxicity , Perfume/toxicity , Animals , DNA Damage/drug effects , Dose-Response Relationship, Drug , Endpoint Determination , Female , Humans , Male , Mice , No-Observed-Adverse-Effect Level , Norisoprenoids/chemistry , Perfume/chemistry , Rats , Risk Assessment , Toxicity TestsABSTRACT
A series of endoperoxides (3a-j) were synthesized and evaluated for cytotoxic activity against four human cancer cell lines by using SRB dye assay. All the compounds displayed moderate to high cytotoxic effect against almost all investigational cancer cells. Particularly, compounds bearing electron withdrawing groups such as nitro substituted compound 3j (IC50 = 0.001 µM) and fluoro substituted compound 3i (IC50 = 0.003 µM) showed comparatively more cytotoxic potential than standard drugs against lung cancer cell line (A549). All synthesized endoperoxides (3a-j) were further evaluated for their apoptotic potential through various parameters such as flow-cytometric analysis of nuclear DNA, flow-cytometric determination of mitochondrial membrane potential (ΔΨm), spectrofluorimetric estimation of intracellular ROS level and caspase-3 & 9 assays in treated lung cancer cells (A549); results reveal that endoperoxides induce apoptosis in cancer cells via mitochondrial pathway.
Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Drug Design , Norisoprenoids/chemistry , Norisoprenoids/pharmacology , Peroxides/chemistry , Animals , Antineoplastic Agents/toxicity , CHO Cells , Caspase 3/metabolism , Caspase 9/metabolism , Cell Line, Tumor , Cell Survival/drug effects , Cricetinae , Cricetulus , DNA/metabolism , Humans , Intracellular Space/drug effects , Intracellular Space/metabolism , L-Lactate Dehydrogenase/metabolism , Membrane Potential, Mitochondrial/drug effects , Norisoprenoids/toxicity , Reactive Oxygen Species/metabolismABSTRACT
Alpha-iso-methylionone (AIM), a fragrance ingredient, was evaluated for systemic toxicity in rats. Male and female Sprague Dawley rats were administered 0, 5, 30, or 500 mg/kg/d AIM via gavage for 90 days. Statistically significant changes in blood chemistry parameters (reduced aspartate aminotransferase [AST], and increased cholesterol, creatinine, and total protein) were observed in both sexes at 500 mg/kg/d. There were statistically significant increases in liver and kidney weights in both sexes and in spleen weights in males at 500 mg/kg/d. Adaptive hepatocyte enlargement was observed in both sexes at 500 mg/kg/d. Globular accumulations of eosinophilic material were observed in the renal tubular epithelium in males at ≥30 mg/kg/d. Thyroid and bone marrow histopathological changes were observed in males at 500 mg/kg/d. The no-observed-effect level was 5 mg/kg/d for males and 30 mg/kg/d for females. Based on histopathological changes in the kidney in males, the no-observed-adverse-effect level was 30 mg/kg/d.
Subject(s)
Norisoprenoids/toxicity , Perfume/toxicity , Administration, Oral , Animals , Blood Chemical Analysis , Bone Marrow Cells/drug effects , Bone Marrow Cells/pathology , Dose-Response Relationship, Drug , Female , Kidney/drug effects , Kidney/pathology , Kidney Tubules/drug effects , Kidney Tubules/pathology , Liver/drug effects , Male , No-Observed-Adverse-Effect Level , Organ Size/drug effects , Rats , Rats, Sprague-Dawley , Spleen/drug effects , Thyroid Gland/drug effects , Thyroid Gland/pathology , Toxicity Tests, SubchronicABSTRACT
Three new megastigmane glucopyranosides, komaroveside A [(3S,4R,5Z,7E)-3,4-dihydroxy-5,7-megastigmadien-9-one-3-O-ß-D-glucopyranoside] (1), komaroveside B [(3S,4S,5S,6R,7E)-5,6-epoxy-3,4-dihydroxy-7-megastigmen-9-one-3-O-ß-D-glucopyranoside] (2) and komaroveside C [(3S,4S,5S,6R,7E,9S)-5,6-epoxy-3,4,9-trihydroxy-7-megastigmen-3-O-ß-D-glucopyranoside] (3) were isolated, together with eight known compounds, from Cardamine komarovii. The identification of these compounds and the elucidation of their structures were based on 1D- and 2D-NMR spectral data analysis. The isolated compounds were tested for their cytotoxicity against four human tumor cell lines (A549, SK-OV-3, SK-MEL-2, HCT15) in vitro using the sulforhodamine B bioassay.
Subject(s)
Antineoplastic Agents, Phytogenic/chemistry , Cardamine/chemistry , Cyclohexanones/chemistry , Glucosides/chemistry , Norisoprenoids/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Antineoplastic Agents, Phytogenic/toxicity , Cell Line, Tumor , Drug Screening Assays, Antitumor , Glucosides/isolation & purification , Glucosides/toxicity , Humans , Magnetic Resonance Spectroscopy , Molecular Conformation , Norisoprenoids/isolation & purification , Norisoprenoids/toxicityABSTRACT
In order to explore the potential targets of toxicity of ß-ionone on the photosynthetic system of Microcystis aeruginosa, the polyphasic rise in chlorophyll a (Chl a) fluorescence transient and transcript expression for key genes in photosystem II (PSII) of M. aeruginosa NIES-843 were studied. The EC50 value of ß-ionone on M. aeruginosa NIES-843 was found to be 21.23±1.87 mg/L. It was shown that ß-Ionone stress can lead to a decrease in pigment content of M. aeruginosa NIES-843 cells, and that carotenoids were more sensitive to ß-ionone stress than Chl a. The normalized Chl a fluorescence transients were slightly decreased at 6.67 and 10 mg/L ß-ionone, but significantly increased at 15, 22.5 and 33.75 mg/L. There was no significant variation on transcript expression of psbA and psbO at a concentration of 6.67 mg/L ß-ionone, but they were down-regulated at 22.5 mg/L. 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 ß-ionone at a concentration of 22.5 and 33.75 mg/L. Our results indicate that the reaction centre of PS II and the electron transport at the acceptor side of PS II are the targets responsible for the toxicity of ß-ionone on the PS II of M. aeruginosa NIES-843.
Subject(s)
Microcystis/drug effects , Norisoprenoids/toxicity , Photosynthesis/drug effects , Water Pollutants, Chemical/toxicity , Chlorophyll/metabolism , Chlorophyll A , Gene Expression/drug effects , Microcystis/physiology , Microcystis/ultrastructure , Photosynthesis/geneticsABSTRACT
A toxicologic and dermatologic review of methyl-alpha-ionone when used as a fragrance ingredient is presented.
Subject(s)
Norisoprenoids/toxicity , Perfume/toxicity , Animals , Consumer Product Safety , Dose-Response Relationship, Drug , Humans , Mutagenicity Tests , Mutagens/classification , Mutagens/pharmacokinetics , Mutagens/toxicity , Norisoprenoids/classification , Norisoprenoids/pharmacokinetics , Perfume/classification , Perfume/pharmacokinetics , Risk Assessment , Skin/drug effects , Skin/metabolism , Skin Absorption , Skin Irritancy Tests , Skin TestsABSTRACT
A toxicologic and dermatologic review of alpha-iso-methylionone when used as a fragrance ingredient is presented.
Subject(s)
Norisoprenoids/toxicity , Perfume/toxicity , Allergens/classification , Allergens/pharmacokinetics , Allergens/toxicity , Animals , Consumer Product Safety , Dose-Response Relationship, Drug , Humans , Norisoprenoids/classification , Norisoprenoids/pharmacokinetics , Noxae/classification , Noxae/pharmacokinetics , Noxae/toxicity , Perfume/classification , Perfume/pharmacokinetics , Reproduction/drug effects , Risk Assessment , Skin/drug effects , Skin/metabolism , Skin Absorption , Skin Irritancy Tests , Skin Tests , Toxicity TestsABSTRACT
A toxicologic and dermatologic review of alpha-ionone when used as a fragrance ingredient is presented.
Subject(s)
Norisoprenoids/toxicity , Perfume/toxicity , Animals , Consumer Product Safety , Dose-Response Relationship, Drug , Humans , Irritants/classification , Irritants/pharmacokinetics , Irritants/toxicity , Mutagenicity Tests , Mutagens/classification , Mutagens/pharmacokinetics , Mutagens/toxicity , Norisoprenoids/pharmacokinetics , Perfume/pharmacokinetics , Risk Assessment , Skin/drug effects , Skin/metabolism , Skin/pathology , Skin Absorption , Skin Irritancy Tests , Skin TestsABSTRACT
A toxicologic and dermatologic review of cis-beta-damascone when used as a fragrance ingredient is presented.
Subject(s)
Norisoprenoids/toxicity , Perfume/toxicity , Allergens/classification , Allergens/pharmacokinetics , Allergens/toxicity , Animals , Consumer Product Safety , Humans , Irritants/classification , Irritants/pharmacology , Irritants/toxicity , Norisoprenoids/classification , Norisoprenoids/pharmacokinetics , Perfume/classification , Perfume/pharmacokinetics , Risk Assessment , Skin/drug effects , Skin/metabolism , Skin/pathology , Skin Absorption , Skin Irritancy Tests , Skin Tests , Stereoisomerism , Toxicity TestsABSTRACT
An evaluation and review of a structurally related group of fragrance materials.
Subject(s)
Norisoprenoids/toxicity , Perfume/toxicity , Skin/drug effects , Administration, Cutaneous , Administration, Oral , Allergens/classification , Allergens/pharmacokinetics , Allergens/toxicity , Animals , Consumer Product Safety , Dose-Response Relationship, Drug , Expert Testimony , Female , Humans , Male , Norisoprenoids/chemistry , Norisoprenoids/pharmacokinetics , Noxae/classification , Noxae/pharmacokinetics , Noxae/toxicity , Perfume/classification , Perfume/pharmacokinetics , Risk Assessment , Skin/metabolism , Skin/pathology , Skin Absorption , Skin Irritancy Tests , Toxicity TestsABSTRACT
A toxicologic and dermatologic review of trans,trans-delta-damascone when used as a fragrance ingredient is presented.
Subject(s)
Norisoprenoids/toxicity , Perfume/toxicity , Allergens/classification , Allergens/pharmacokinetics , Allergens/toxicity , Animals , Consumer Product Safety , Dose-Response Relationship, Drug , Humans , Norisoprenoids/classification , Norisoprenoids/pharmacokinetics , Perfume/classification , Perfume/pharmacokinetics , Risk Assessment , Skin/drug effects , Skin/metabolism , Skin Absorption , Skin Tests , Stereoisomerism , Toxicity TestsABSTRACT
A toxicologic and dermatologic review of isodamascone when used as a fragrance ingredient is presented.
Subject(s)
Norisoprenoids/toxicity , Perfume/toxicity , Administration, Cutaneous , Consumer Product Safety , Humans , Norisoprenoids/classification , Norisoprenoids/pharmacokinetics , Perfume/classification , Perfume/pharmacokinetics , Risk Assessment , Skin/metabolism , Skin Absorption , StereoisomerismABSTRACT
A toxicologic and dermatologic review of 6-methyl-beta-ionone when used as a fragrance ingredient is presented.
Subject(s)
Norisoprenoids/toxicity , Perfume/toxicity , Administration, Cutaneous , Animals , Consumer Product Safety , Humans , Norisoprenoids/classification , Norisoprenoids/pharmacokinetics , Perfume/pharmacokinetics , Risk Assessment , Skin/metabolism , Skin AbsorptionABSTRACT
A toxicologic and dermatologic review of beta-ionone when used as a fragrance ingredient is presented.
Subject(s)
Norisoprenoids/toxicity , Perfume/toxicity , Animals , Consumer Product Safety , Dose-Response Relationship, Drug , Humans , Irritants/classification , Irritants/pharmacokinetics , Irritants/toxicity , Norisoprenoids/classification , Norisoprenoids/pharmacokinetics , Perfume/classification , Perfume/pharmacokinetics , Risk Assessment , Skin/drug effects , Skin/metabolism , Skin/pathology , Skin Irritancy Tests , Skin Tests , Teratogens/classification , Teratogens/pharmacokinetics , Teratogens/toxicity , Toxicity TestsABSTRACT
A toxicologic and dermatologic review of iso-methyl-beta-ionone when used as a fragrance ingredient is presented.
Subject(s)
Norisoprenoids/toxicity , Perfume/toxicity , Administration, Cutaneous , Animals , Consumer Product Safety , Humans , Norisoprenoids/classification , Norisoprenoids/pharmacokinetics , Perfume/pharmacokinetics , Risk Assessment , Skin/metabolism , Skin AbsorptionABSTRACT
A toxicologic and dermatologic review of trans-beta-damascone when used as a fragrance ingredient is presented.
Subject(s)
Norisoprenoids/toxicity , Perfume/toxicity , Allergens/classification , Allergens/pharmacokinetics , Allergens/toxicity , Animals , Consumer Product Safety , Dose-Response Relationship, Drug , Humans , Lymph Nodes/drug effects , Lymph Nodes/pathology , Norisoprenoids/classification , Norisoprenoids/pharmacokinetics , Perfume/classification , Perfume/pharmacokinetics , Risk Assessment , Skin/drug effects , Skin/metabolism , Skin/pathology , Skin Absorption , Skin Irritancy Tests , Skin Tests , Stereoisomerism , Toxicity TestsABSTRACT
A toxicologic and dermatologic review of ionone when used as a fragrance ingredient is presented.
