RIFM fragrance ingredient safety assessment, 1-(2-methylprop-2-enoloxy)-2,2,4-trimethylpentan-3-ol, CAS Registry Number 526218-21-3.

The existing information supports the use of this material as described in this safety assessment. 1-(2-Methylprop-2-enoloxy)-2,2,4-trimethylpentan-3-ol was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data show that 1-(2-methylprop-2-enoloxy)-2,2,4-trimethylpentan-3-ol is not genotoxic. Data on 1-(2-methylprop-2-enoloxy)-2,2,4-trimethylpentan-3-ol provide a calculated margin of exposure (MOE) > 100 for the repeated dose toxicity endpoint. The reproductive and local respiratory toxicity endpoints were evaluated using the threshold of toxicological concern (TTC) for a Cramer Class III material, and the exposure to 1-(2-methylprop-2-enoloxy)-2,2,4-trimethylpentan-3-ol is below the TTC (0.0015 mg/kg/day and 0.47 mg/day, respectively). Data show that there are no safety concerns for 1-(2-methylprop-2-enoloxy)-2,2,4-trimethylpentan-3-ol for skin sensitization under the current declared levels of use. The phototoxicity/photoallergenicity endpoints were evaluated based on ultraviolet (UV) spectra; 1-(2-methylprop-2-enoloxy)-2,2,4-trimethylpentan-3-ol is not expected to be phototoxic/photoallergenic. The environmental endpoints were evaluated; for the hazard assessment based on the screening data, 1-(2-methylprop-2-enoloxy)-2,2,4-trimethylpentan-3-ol is not persistent, bioaccumulative, and toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards. For the risk assessment, 1-(2-methylprop-2-enoloxy)-2,2,4-trimethylpentan-3-ol was not able to be risk screened as there were no reported volumes of use for either North America or Europe in the 2015 IFRA Survey.

New insights into the impacts of huangjiu compontents on intoxication.

Although huangjiu is a popular alcoholic beverage in China, the occurrence of quick-intoxication suppresses huangjiu consumption and impedes development of the huangjiu industry. In this study, the Cryprinus carpio intoxication model was used to compare the differences in intoxication effect of alcoholic beverages and to assess the impacts of huangjiu components on intoxication for the first time. Exposure to huangjiu led to the most rapid physical imbalance of C. carpio, followed by red wine and Western liquor. Higher alcohols, biogenic amines and aldehydes could cause physical imbalance of fish by themselves, and synergistic effects were observed when combined with ethanol. 2-Phenylethanoland and isopentanol had the greatest positive effect on huangjiu intoxication, followed by histamine and phenethylamine. No synergistic effect was observed between individual aldehydes and ethanol. Identification of these impactful huangjiu components provides a new perspective on the establishment of more rigorous control on the quality and flavor of huangjiu.

Drinking "Vodka" or vodka - This is a question.

"Vodka" i.e. 2-methyl-2-butanol (2M2B) is growing in popularity as a substance of abuse, especially among East European youngsters. At present, there is not much data regarding its toxicity both in humans and animals. The direct effect of 2M2B on human tissue was evaluated and compared to that of two other alcohols (ethanol, 3-methyl-1-butanol). The used concentrations corresponded to those obtained from consumers of 2M2B. The experiments were carried out on HEK293 cell line with the use of the following techniques: MTT test, phase contrast and fluorescent microscopy. The MTT test indicated that the toxicity of 2M2B was comparable to that of ethanol, but it was much lower than that observed after 3-methyl-1-butanol (3M1B). The high toxicity of the latter alcohol was confirmed by the microscopy techniques. On the other hand, the toxicity of 2M2B - expressed by the reduction of the number of survived cells - was slightly higher compared to one induced by ethanol. Also, the values of pIC50 for each alcohol reflect its level of toxicity described above. On the basis of the literature data it is possible to argue that the toxicity of the tested alcohols results primarily from membrane damage induced by their solvent properties.

[Partynight outcome]. / Folgen einer Partynacht.

HISTORY AND CLINICAL FINDINGS: An 18 year old girl was admitted with progressive painful dysphagia and a severe hemorrhagic endoscopically impassable esophagitis. She reported to have consumed an unknown liquid from a small flask on a party three weeks ago. Later on, this liquid was identified as a party- and sex-drug known as "Poppers", designed to be consumed by sniffing. On admission she had difficulties in swallowing liquids and even saliva. She had lost 8 kg of weight during the last 3 weeks. Clinical examination revealed tachycardia, a moderate tenderness in the epigastrium and sparse bowel sounds. Investigation and treatment: On endoscopy, there was a severe corrosion injury of the esophagus with a consecutive stenosis at 40 cm ab ore. The stenosis could not be passed even with a 4.9 mm instrument. After initial placement of a feeding tube the stenosis was dilated with Savary-Bougies. In the following years, the patient suffered from recurrent stenosis due to excessive scar formation. Repeated treatment with longitudinal incisions by needle knife and steroid injections improved symptoms to a tolerable degree. 5 years after ingestion, the patient still carries a long segment esophageal scarring with mild to moderate stenosis. CONCLUSION: The party drug Poppers is an organic nitrogen compound that has increasingly come into use over the past years. It may cause severe and life threatening esophageal chemical burn injury. Symptoms of painful dysphagia after intake of an "unknown" liquid party drug should raise the suspicion of an accidental oral ingestion of Poppers.

RIFM fragrance ingredient safety assessment, 2-methyl-3-buten-2-ol, CAS Registry Number 115-18-4.

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, developmental, and reproductive toxicities were determined to have the most conservative systemic exposure derived NO[A]EL of 50 mg/kg/day, based on OECD gavage toxicity studies in rats, that resulted in a MOE of 4545455 after considering 100% absorption from skin contact and inhalation. A MOE of >100 is deemed acceptable.

Improving microbial biogasoline production in Escherichia coli using tolerance engineering.

UNLABELLED: Engineering microbial hosts for the production of fungible fuels requires mitigation of limitations posed on the production capacity. One such limitation arises from the inherent toxicity of solvent-like biofuel compounds to production strains, such as Escherichia coli. Here we show the importance of host engineering for the production of short-chain alcohols by studying the overexpression of genes upregulated in response to exogenous isopentenol. Using systems biology data, we selected 40 genes that were upregulated following isopentenol exposure and subsequently overexpressed them in E. coli. Overexpression of several of these candidates improved tolerance to exogenously added isopentenol. Genes conferring isopentenol tolerance phenotypes belonged to diverse functional groups, such as oxidative stress response (soxS, fpr, and nrdH), general stress response (metR, yqhD, and gidB), heat shock-related response (ibpA), and transport (mdlB). To determine if these genes could also improve isopentenol production, we coexpressed the tolerance-enhancing genes individually with an isopentenol production pathway. Our data show that expression of 6 of the 8 candidates improved the production of isopentenol in E. coli, with the methionine biosynthesis regulator MetR improving the titer for isopentenol production by 55%. Additionally, expression of MdlB, an ABC transporter, facilitated a 12% improvement in isopentenol production. To our knowledge, MdlB is the first example of a transporter that can be used to improve production of a short-chain alcohol and provides a valuable new avenue for host engineering in biogasoline production. IMPORTANCE: The use of microbial host platforms for the production of bulk commodities, such as chemicals and fuels, is now a focus of many biotechnology efforts. Many of these compounds are inherently toxic to the host microbe, which in turn places a limit on production despite efforts to optimize the bioconversion pathways. In order to achieve economically viable production levels, it is also necessary to engineer production strains with improved tolerance to these compounds. We demonstrate that microbial tolerance engineering using transcriptomics data can also identify targets that improve production. Our results include an exporter and a methionine biosynthesis regulator that improve isopentenol production, providing a starting point to further engineer the host for biogasoline production.

Acute effects of exposure to vapors of 3-methyl-1-butanol in humans.

UNLABELLED: The secondary alcohol 3-methyl-1-butanol (3MB, isoamyl alcohol) is used, for example, as a solvent in a variety of applications and as a fragrance ingredient. It is also one of the microbial volatile organic compounds (MVOCs) found in indoor air. There are little data on acute effects. The aim of the study was to assess the acute effects of 3MB in humans. Thirty healthy volunteers (16 men and 14 women) were exposed in random order to 1 mg/m(3) 3MB or clean air for 2 h at controlled conditions. Ratings with visual analogue scales revealed slightly increased perceptions of eye irritation (P = 0.048, Wilcoxon) and smell (P < 0.0001) compared with control exposure. The other ratings were not significantly affected (irritation in nose and throat, dyspnea, headache, fatigue, dizziness, nausea, and intoxication). No significant exposure-related effects were found in blinking frequency, tear film break-up time, vital staining of the eye, nasal lavage biomarkers, lung function, and nasal swelling. In conclusion, this study suggests that 3MB is not a causative factor for health effects in damp and moldy buildings. PRACTICAL IMPLICATIONS: 3-Methyl-1-butanol (3MB) is one of the most commonly reported MVOCs in damp and moldy buildings and in occupational settings related to agriculture and composting. Our study revealed no irritation effects at 1 mg/m3, a concentration higher than typically found in damp and moldy buildings. Our study thus suggests that 3MB is not a causative factor for health effects in damp and moldy buildings.

Pop goes the O2: a case of popper-induced methaemoglobinamia.

A 39-year-old man presented to the emergency department after falling downstairs after he consumed a large quantity of alcohol. On examination, he had altered mental state (GCS 14), central cyanosis and low oxygen saturation of 86%, despite 100% oxygen being administered. His arterial blood gas confirmed diagnosis of methaemoglobinaemia with a methaemoglobin percentage of 14.08. He was treated successfully with methylthioninium chloride. The patient later admitted to use of recreational poppers (amyl nitrates) the previous evening. The emergency physician is challenged by the presentation of a patient with altered mental state and unexplained low oxygen saturation with concurrent alcohol intoxication but must have a high index of suspicion for methaemoglobinaemia particularly with a history of recreational drug ingestion.

Fragrance material review on 1-phenyl-3-methyl-3-pentyl acetate.

A toxicologic and dermatologic review of 1-phenyl-3-methyl-3-pentyl acetate when used as a fragrance ingredient is presented. 1-Phenyl-3-methyl-3-pentyl acetate is a member of the fragrance structural group Aryl Alkyl Alcohol Simple Acid Esters (AAASAE). The AAASAE fragrance ingredients are prepared by reacting an aryl alkyl alcohol with a simple carboxylic acid (a chain of 1-4 carbons) to generate formate, acetate, propionate, butyrate, isobutyrate and carbonate esters. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for 1-phenyl-3-methyl-3-pentyl acetate were evaluated, then summarized, and includes physical properties, acute toxicity, skin irritation, and skin sensitization data. A safety assessment of the entire AAASAE will be published simultaneously with this document. Please refer to Belsito et al. (2012) for an overall assessment of the safe use of this material and all AAASAE in fragrances.

Fragrance material review on 2-methyl-4-phenylpentanol.

A toxicologic and dermatologic review of 2-methyl-4-phenylpentanol when used as a fragrance ingredient is presented. 2-Methyl-4-phenylpentanol is a member of the fragrance structural group Aryl Alkyl Alcohols and is a primary alcohol. The AAAs are a structurally diverse class of fragrance ingredients that includes primary, secondary, and tertiary alkyl alcohols covalently bonded to an aryl (Ar) group, which may be either a substituted or unsubstituted benzene ring. The common structural element for the AAA fragrance ingredients is an alcohol group -C-(R1)(R2)OH and generically the AAAs fragrances can be represented as an Ar-C-(R1)(R2)OH or Ar-Alkyl-C-(R1)(R2)OH group. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for 2-methyl-4-phenylpentanol were evaluated then summarized and includes physical properties, acute toxicity, skin irritation, mucous membrane (eye) irritation, skin sensitization, repeated dose, and genotoxicity data. A safety assessment of the entire Aryl Alkyl Alcohols will be published simultaneously with this document; please refer to Belsito et al. (2012) for an overall assessment of the safe use of this material and all Aryl Alkyl Alcohols in fragrances.

Fragrance material review on 1-phenyl-3-methyl-3-pentanol.

A toxicologic and dermatologic review of 1-phenyl-3-methyl-3-pentanol when used as a fragrance ingredient is presented. 1-Phenyl-3-methyl-3-pentanol is a member of the fragrance structural group Aryl Alkyl Alcohols and is a tertiary alcohol. The AAAs are a structurally diverse class of fragrance ingredients that includes primary, secondary, and tertiary alkyl alcohols covalently bonded to an aryl (Ar) group, which may be either a substituted or unsubstituted benzene ring. The common structural element for the AAA fragrance ingredients is an alcohol group -C-(R1)(R2)OH and generically the AAA fragrances can be represented as an Ar-Alkyl-C-(R1)(R2)OH group. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for 1-phenyl-3-methyl-3-pentanol were evaluated then summarized and includes physical properties, acute toxicity, skin irritation, mucous membrane (eye) irritation, skin sensitization, and genotoxicity data. A safety assessment of the entire Aryl Alkyl Alcohols will be published simultaneously with this document; please refer to Belsito et al. (2012) for an overall assessment of the safe use of this material and all Aryl Alkyl Alcohols in fragrances.