Human metabolism and excretion kinetics of the fragrance lysmeral after a single oral dosage.

2-(4-tert-Butylbenzyl)propionaldehyde, also known as lysmeral, lilial or lily-aldehyde (CAS No 80-54-6) is a synthetic fragrance used in a variety of consumer products like perfumes, after shave lotions, cosmetics and others. Due to its broad application, lysmeral was selected for the development of a biomonitoring method for the general population within the frame of the cooperation project of the Federal Ministry for the Environment (BMUB) and the German Chemical Industry Association (VCI). The project also comprises the identification of suitable biomarkers of exposure in human urine as well as basic toxicokinetic data after defined, experimental exposure. For this purpose, 5 healthy subjects were orally dosed once with 5.26mg lysmeral. Urine was collected immediately before and for 48h after administration of the fragrance. The lysmeral metabolites lysmerol, lysmerylic acid, hydroxylated lysmerylic acid and 4-tert-butylbenzoic acid (TBBA) were determined in all urine samples by a newly developed UPLC-MS/MS (ultra-high pressure liquid chromatography combined with tandem mass spectrometry) method. Peak excretion for all metabolites occurred between 2 and 5h after oral application, with the primary metabolites (lysmerol and lysmerylic acid) being excreted about 1h earlier than the secondary metabolites (hydroxylated lysmerylic acid and TBBA). More than 90% of all measured lysmeral metabolites were excreted after 12h, with the renal excretion being virtually complete after 48h. After this time period, TBBA, lysmerol, lysmerylic acid and hydroxyl-lysmerylic acid represent on average 14.3, 1.82, 0.20 and 0.16%, respectively, of the dose administered. In total, the 4 metabolites determined represent about 16.5% of the dose. With the conversion factors derived from the controlled human study, we estimated median exposure doses for lysmeral in a group of 40 human volunteers from the general population of approximately 140-220µg per day. In conclusion, the lysmeral metabolites lysmerol, lysmerylic acid, hydroxyl-lysmerylic acid and TBBA in urine are suitable biomarkers of exposure and can be applied, either single or in any combination, for biomonitoring of the general population.

Formation of harmful compounds in biotransformation of lilial by microorganisms isolated from human skin.

CONTEXT: The biotransformation of lilial results in an acid that is used in the dairy industry, in perfumery, as an intermediate in the manufacture of pharmaceuticals and cosmetics, and as a food additive for enhancing taste. OBJECTIVE: This study investigates the biotransformation of lilial by Staphylococcus aureus and Staphylococcus epidermidis, two bacterial species isolated from human skin. MATERIALS AND METHODS: Both species of Staphylococcus were isolated in samples taken from the skin of individuals living in a rural area of Iran. The pH of the culture medium was optimized, and after culturing the microorganisms, the bacteria were added to a flask containing a nutrient broth and incubated for several hours. The flasks of bacteria were combined with lilial, and various biochemical tests and diagnostics were performed, including Fourier transform infrared spectroscopy (FT-IR), ultraviolet-visible spectrophotometry (UV-Vis), and gas chromatography-mass spectroscopy (GC-MS). RESULTS: The S. aureus produced isobutyric acid (2-methylpropanoic acid) after 72 h (71% of the total products yielded during biotransformation), whereas the S. epidermidis produced terpenoid alcoholic media after 24 h (90% of total products obtained). DISCUSSION AND CONCLUSION: The results obtained indicate that biotransformation of lilial by S. aureus is more desirable than by S. epidermidis due to the highly efficient production of a single product. Bourgeonal and liliol were two toxic compounds produced during biotransformation, which indicates that the use of lilial in cosmetics can be harmful to the skin.

Occurrence and transport of synthetic musks in paired maternal blood, umbilical cord blood, and breast milk.

Although early exposure to environmental pollutants may have important toxicological consequences, the mechanisms of transplacental transfer of synthetic musks are still not well understood. The objective of the present study was to learn the musk contaminations in three matrices, including maternal blood, umbilical cord blood, and breast milk; and investigate their placental transfer mechanisms. The concentrations of eight commonly used synthetic musks were measured in 42 paired samples (126 individual samples in total) of maternal serum, umbilical cord serum, and breast milk from Chinese women living in Shanghai. Musks were ubiquitously detected, especially galaxolide (HHCB) and musk xylene (MX). The total lipid-based concentrations were higher in umbilical cord sera (87.3ng/g), but lower in breast milk (35.2ng/g), compared with maternal serum concentrations (71.2ng/g). There were significant correlations between maternal serum concentrations of HHCBs (HHCB and HHCB-lactone) and umbilical cord serum concentrations, and between maternal serum concentrations and breast milk concentrations (Spearman's rho=0.338-0.597, p<0.05), when outliers are excluded. The average transfer ratios of HHCB and HHCB-lactone between maternal sera and umbilical cord sera were >1. And the HHCB-lactone/HHCB ratio in maternal sera was higher compared with umbilical cord sera. Contamination levels were low compared with other regions and HHCBs were found to be the predominant constituents. No regional differences or age-related accumulations were observed. Our study suggests that prenatal exposure to HHCBs occurs and that transplacental transfer is the main route of exposure. Preferential accumulation in umbilical cord blood was observed. The results showed that transplacental transfer of HHCB did not correspond to passive diffusion since the transfer ratios were significantly different from 1. The transfer ratio for HHCB was also larger than that of HHCB-lactone, although HHCB has higher lipid solubility. Low fetal metabolism of HHCB was suggested by the HHCB-lactone/HHCB ratio in maternal and umbilical cord blood.

An in silico skin absorption model for fragrance materials.

Fragrance materials are widely used in cosmetics and other consumer products. The Research Institute for Fragrance Materials (RIFM) evaluates the safety of these ingredients and skin absorption is an important parameter in refining systemic exposure. Currently, RIFM's safety assessment process assumes 100% skin absorption when experimental data are lacking. This 100% absorption default is not supportable and alternate default values were proposed. This study aims to develop and validate a practical skin absorption model (SAM) specific for fragrance material. It estimates skin absorption based on the methodology proposed by Kroes et al. SAM uses three default absorption values based on the maximum flux (J(max)) - namely, 10%, 40%, and 80%. J(max) may be calculated by using QSAR models that determine octanol/water partition coefficient (K(ow)), water solubility (S) and permeability coefficient (K(p)). Each of these QSAR models was refined and a semi-quantitative mechanistic model workflow is presented. SAM was validated with a large fragrance-focused data set containing 131 materials. All resulted in predicted values fitting the three-tiered absorption scenario based on Jmax ranges. This conservative SAM may be applied when fragrance material lack skin absorption data.

Fate and effects of acetyl cedrene in sediments inhabited by different densities of the deposit feeder, Capitella teleta.

Fragrance materials, such as acetyl cedrene (AC), are of environmental concern because they are continuously released to aquatic systems down the drain. In the present study, Capitella teleta (formerly Capitella capitata species I) was exposed to AC-amended sediment at two population densities corresponding to 44,000 and 88,000 worms/m(2). The fate of AC in systems with worms was compared to that in identical systems without worms. We examined the toxicity of AC on worm survival, growth, and feeding rate, and quantified the fate of AC in exposure systems by mass balance. Worm survival was close to 100% in all treatments. Acetyl cedrene had some positive effects on worm growth, but not feeding, whereas density had negative effects on both growth and feeding rates. After 14 d, the sediment concentration of AC was reduced by 88 to 99% in the presence of worms, whereas sediment AC concentration was reduced by 13 to 31% or less in the absence of worms. Acetyl cedrene was detected in fecal pellets, at low concentrations compared to the initial concentration in the sediment, but not in worm tissue, suggesting that ingested AC is bioavailable to Capitella teleta and that worms can biotransform sediment-associated AC effectively.

In vitro skin penetration of fragrances: trapping the evaporated material can enhance the dermal absorption of volatile chemicals.

This study compared the evaporation and skin absorption profiles of four fragrance chemicals in in vitro skin penetration studies performed in conditions of airflows of low velocity with and without trapping of the evaporated volatiles. The presence of a trapping chamber above the skin surface slowed down the evaporation of the chemicals, possibly due to formation of a gaseous stagnant layer of greater thickness than the one existing at the skin surface in the real-life conditions of multidirectional and/or turbulent flows. In addition, the use of a trapping chamber considerably influenced the distribution of the fragrance chemicals in the skin layers and resulted in 2- to 8-fold increase of the doses available for systemic absorption. Such unrealistic overestimation of the percutaneous absorption can significantly impact the risk assessment of topically applied volatile chemicals and can lead to defining unrealistic margins of safety.

Fragrance material review on alpha-methylcyclohexylmethyl acetate.

A toxicologic and dermatologic review of alpha-methylcyclohexylmethyl acetate when used as a fragrance ingredient is presented.

Fragrance material review on 1-ethynylcyclohexyl acetate.

A toxicologic and dermatologic review of 1-ethynylcyclohexyl acetate when used as a fragrance ingredient is presented.

Fragrance material review on 1,7,7-trimethylbicyclo[4.4.0]dec-3-yl acetate.

A toxicologic and dermatologic review of 1,7,7-trimethylbicyclo[4.4.0]dec-3-yl acetate when used as a fragrance ingredient is presented.

Fragrance material review on myraldyl acetate.

A toxicologic and dermatologic review of myraldyl acetate when used as a fragrance ingredient is presented.

Fragrance material review on (3aalpha,4alpha,6alpha,7alpha,7aalpha)-3a,4,5,6,7,7a-hexahydro-3-methyl-5-methylene-4,7-methano-1H-inden-6-yl acetate.

A toxicologic and dermatologic review of (3aalpha,4alpha,6alpha,7alpha,7aalpha)-3a,4,5,6,7,7a-hexahydro-3-methyl-5-methylene-4,7-methano-1H-inden-6-yl acetate when used as a fragrance ingredient is presented.

Fragrance material review on 2-(1-methylpropyl)-1-vinylcyclohexyl acetate.

A toxicologic and dermatologic review of 2-(1-methylpropyl)-1-vinylcyclohexyl acetate when used as a fragrance ingredient is presented.

Fragrance material review on 4-methyl-8-methylenetricyclo[3.3.1.(3,7)]decan-2-yl acetate.

A toxicologic and dermatologic review of 4-methyl-8-methylenetricyclo[3.3.1.(3,7)]decan-2-yl acetate when used as a fragrance ingredient is presented.

A toxicologic and dermatologic assessment of cyclic acetates when used as fragrance ingredients.

An evaluation and review of a structurally related group of fragrance materials.

Fragrance material review on cyclohexyl cyclopent-2-ene-1-acetate.

A toxicologic and dermatologic review of Cyclohexyl cyclopent-2-ene-1-acetate when used as a fragrance ingredient is presented.

Fragrance material review on 3-tert-butylcyclohexyl acetate.

A toxicologic and dermatologic review of 3-tert-butylcyclohexyl acetate when used as a fragrance ingredient is presented.

Fragrance material review on d-cyclocitronellene acetate.

A toxicologic and dermatologic review of d-cyclocitronellene acetate when used as a fragrance material is presented.

Fragrance material review on 4-(isopropyl)-1-methylcyclohexyl acetate.

A toxicologic and dermatologic review of 4-(isopropyl)-1-methylcyclohexyl acetate when used as a fragrance ingredient is presented.

Fragrance material review on octahydro-4,7-methano-1H-indenemethyl acetate.

A toxicologic and dermatologic review of octahydro-4,7-methano-1H-indenemethyl acetate when used as a fragrance ingredient is presented.