Abstract  The slow, non-mediated transmembrane movement of the lipid probes lysophosphatidylcholine, NBD-phosphatidylcholine and NBD-phosphatidylserine in human erythrocytes becomes highly enhanced in the presence of 1-alkanols (C2-C8) and 1,2-alkane diols (C4-C8). Above a threshold concentration characteristic for each alcohol, flip rates increase exponentially with the alcohol concentration. The equieffective concentrations of the alcohols decrease about 3-fold per methylene added. All 1-alkanols studied are equieffective at comparable calculated membrane concentrations. This is also observed or the 1,2-alkane diols, albeit at a 5-fold lower membrane concentration. At low alcohol concentrations, flip enhancement is reversible to a major extent upon removal of the alcohol. In contrast, a residual irreversible flip acceleration is observed following removal of the alcohol after a treatment at higher concentrations. The threshold concentrations to produce irreversible flip acceleration by 1-alkanols and 1,2-alkane diols are 1.5- and 3-fold higher than those for flip acceleration in the presence of the corresponding alcohols. A causal role in reversible flip-acceleration of a global increase of membrane fluidity or membrane polarity seems to be unlikely. Alcohols may act by increasing the probability of formation of transient structural defects in the hydrophobic barrier that already occur in the native membrane. Membrane defects responsible for irreversible flip-acceleration may result from alterations of membrane skeletal proteins by alcohols.

Abstract  Parabens are used as antimicrobial preservatives in consumer products. Exposure to methylparaben (MP) has been associated with adverse health outcomes, therefore, an alternative compound, 1,2-hexanediol (1,2-H), has been applied for cosmetics. In the present study, the phototoxicity of MP and 1,2-H, as well as the toxic effect caused by chronic exposure, were investigated using Daphnia magna. The 48 h acute toxicity tests with D. magna were conducted under indoor or ultraviolet (UV) light irradiation conditions, i.e., exposure to 4 h/d sunlight. Changes in the transcription of genes related to oxidative stress were determined in D. magna juveniles, to investigate the underlying mechanism of phototoxicity. The 21 d chronic toxicity tests of MP and 1,2-H were performed under indoor light irradiation. Exposure to MP under environmental level of UV light was more detrimental to D. magna. Transcripts of catalase and glutathione-S-transferase genes in D. magna was significantly increased by co-exposure to MP and UV light. After 21 d of chronic exposure to MP and 1,2-H, the reproduction no-observed effect concentrations for D. magna were 1 and >10 mg/L, respectively. The present study showed that exposure to UV could magnify the toxicity of MP on daphnids. Although acute and chronic toxicities of 1,2-H were generally lower than those of MP, its effects on other aquatic organisms should not be ignored. Further studies are needed to identify other mechanisms of MP phototoxicity.

Abstract  Caprylyl glycol and related 1,2-glycols are used mostly as skin and hair conditioning agents and viscosity agents in cosmetic products, and caprylyl glycol and pentylene glycol also function as cosmetic preservatives. The Cosmetic Ingredient Review (CIR) Expert Panel noted that, while these ingredients are dermally absorbed, modeling data predicted decreased skin penetration of longer chain 1,2-glycols. Because the negative oral toxicity data on shorter chain 1,2-glycols and genotoxicity data support the safety of the 1,2-glycols reviewed in this safety assessment, the Panel concluded that these ingredients are safe in the present practices of use and concentration described in this safety assessment.

Abstract  n-Alkanol inhibition of N-methyl-D-aspartate (NMDA) receptors exhibits a "cutoff" effect: alcohols with up to eight to nine carbon atoms inhibit the receptor, whereas larger alcohols do not. This phenomenon was originally proposed to result from size exclusion; i.e., alcohols above the cutoff are too large to bind to an amphiphilic site on the receptor. In the present study, 1,Omega-diols with 3 to 14 carbon atoms inhibited NMDA-activated current in Chinese hamster ovary and human embryonic kidney 293 cells transiently expressing NR1 and NR2B NMDA receptor subunits. Results of fluctuation analysis experiments were consistent with a similar mechanism of inhibition of NMDA-activated current by alcohols and diols. The average change in apparent energy of binding of the diols caused by addition of a methylene group was 2.1 kJ/mol, which is consistent with an important role of hydrophobic interactions. Because 1,Omega-diols with 9 to 14 carbons inhibited NMDA-activated current, despite having molecular volumes exceeding that at the cutoff point for 1-alkanols, a size exclusion mechanism seems inadequate to explain the cutoff effect. A disparity in hydrophobicity values at the cutoff for alcohols and diols, however, revealed that hydrophobicity could also not entirely explain the cutoff phenomenon. From these results, it seems that the cutoff effect on NMDA receptors results primarily from the inability of long-chain alcohols to achieve adequate concentrations at their site of action due to low aqueous solubility, although other factors may also contribute to the effect.

Abstract  Several studies have reported that 1,2-alkanediols show increasing anti-microbial activity as their alkane chain length increases. However, there are no reports on the influence of alkane chain length on the skin irritation potential of 1,2-alkanediols. To investigate the influence of alkane chain length on the skin irritation potential of 1,2-alkanediols. The objective and subjective (sensory) skin irritation potentials of five 1,2-alkanediols - 1,2-butanediol, 1,2-pentanediol, 1,2-hexanediol, 1,2-octanediol and 1,2-decanediol - were evaluated. We also estimated percutaneous absorption by measuring in vitro skin penetration using a Franz diffusion cell system. Like anti-microbial activity, sensory irritation potential increased as alkane chain length increased, most likely due to increasing membrane interference and/or intrinsic toxicity of 1,2-alkanediols. 1,2-Hexanediol showed the lowest objective skin irritation potential, which increased when the alkane chain length decreased or increased. Furthermore, percutaneous absorption negatively correlated with the alkane chain length of 1,2-alkanediols. These results show that a lower skin absorption potential is not indicative of a low skin irritation potential. Our results suggest that the factors and processes involved in skin irritation potential are complex and that skin irritation potential is influenced by intrinsic toxicity and the potential for penetration or integration in the lipid bilayer.