This study investigates the metabolism and mode of action of galaxolide (HHCB) in the European sea bass -Dicentrarchus labrax- following a single intraperitoneal injection of 50 mg HHCB/kg body weight. In addition, a group of fish was injected with 50 mg/kg of ketoconazole (KCZ), a fungicide that is known to interfere with different Cyp isoenzymes. HHCB was actively metabolized by sea bass and acted as a weak inhibitor of the synthesis of oxyandrogens in gonads of male fish. Both, HHCB and a hydroxylated metabolite were detected in bile. The fungicide ketoconazole was a strong inhibitor of Cyp11beta and Cyp3a-catalyzed activities. The work contributes to the better understanding of the impact of synthetic musks on fish and proposes the determination of HHCB and/or its hydroxylated metabolite in bile as a tool to assess environmental exposure in wild fish.
The interactions of emerging contaminants with the xenobiotic and endogenous metabolizing system of deep-sea fish were compared. The drugs diclofenac, fluoxetine, and gemfibrozil belong to different pharmaceutical classes with diverse mechanistic actions, and the personal care products triclosan, galaxolide, and nonylphenol are representative of antibacterial agents, nitro-musks, and surfactants, respectively. The fish compared are representative of the middle and lower slope of deep-sea habitats. The species were adults of Trachyrynchus scabrus, Mora moro, Cataetix laticeps, and Alepocehalus rostratus. The hepatic metabolic system studied were the activities associated with several cytochrome P450 isoforms (CYPs): 7-ethoxyresorufin-O-deethylase (EROD), benzyloxy-4-[trifluoromethyl]-coumarin-O-debenzyloxylase (BFCOD), and 7-ethoxycoumarin-O-deethylase (ECOD). Results showed differences in baseline activities and sensitivity to chemicals which were species, chemical, and pathway dependent. T. scabrous was the most sensitive species to chemical interactions with the xenobiotic and endogenous metabolizing (EROD and BFCOD) systems, especially in the case of diclofenac interference with BFCOD activity (IC50 = 15.7 +/- 2.2 uM). Moreover, T. scabrous and A. rostratus possessed high basal ECOD activity, and this was greatly affected by in vitro exposure to diclofenac in T. scabrous also (IC50 = 6.86 +/- 1.4 uM). These results highlight the sensitivity of marine fish to emerging contaminants and propose T. scabrous (middle slope) and A. rostratus (lower slope) as sentinels and the inclusion of ECOD activity as a sensitive biomarker to these exposures.
IDENTIFICATION AND USE: Galaxolide (HHCB) is an almost colorless viscous liquid. It is a synthetic, artificial musk fragrance, which is used as a laundry detergent fragrance, as well as an ingredient in perfumes, soaps, and cosmetics. HUMAN STUDIES: No irritation was observed in any of the 42 subjects tested in human repeated insult patch test even after repeated occlusive applications of undiluted material. High concentrations of HHCB can affect steroidogenesis in vitro using the H295R cell line. HHCB was not genotoxic in the micronucleus test with human lymphocytes in vitro in the presence and absence of metabolic activation. ANIMAL STUDIES: HHCB was added to the diet of rats at levels calculated to result in mean daily doses of 5, 15, 50 or 150 mg HHCB/kg. On completion of the 90-day treatment period, three males and three females from the high dose and control groups were maintained for a treatment free period of 4 weeks. No adverse effects were revealed from clinical examination or following extensive histopathological examinations. There were no significant findings at any dose level. Developmental study in rats described axial skeletal malformations at 500 mg/kg per day. In rats chronically exposed to HHCB (35 mg/kg), reduced weight at birth at F1, induction of CYP2B and CYP3A and a slight increase in HDL-cholesterol in males was reported. In a Xenopus laevis metamorphosis study, developmental acceleration on day 14, together with hypertrophy of the thyroid follicular epithelium in tadpoles, suggested a possible agonistic effect of HHCB. When HHCB was injected i.p. into trout at a dose of 3.64 mg/kg, it caused inhibition of E2-induced vitellogenin production. The interaction of HHCB with the estrogen receptor (ER), androgen receptor (AR), and progesterone (PR) receptor, using sensitive and specific reporter gene cell lines was assessed. HHCB was found to be an antagonist toward the ERbeta, AR and PR. HHCB was not genotoxic when tested in Salmonella typhimurium strains TA97, TA98, TA100 and TA102 with or without metabolic activation. ECOTOXICITY STUDIES: In Dreissena polymorpha HHCB induced significant increases in lipid peroxidation and protein carbonyl levels. Moreover, significant increases in DNA strand breaks were caused by exposure to the highest concentrations HHCB, but no fixed genetic damage was observed. The mRNA expression levels of the four representative protein-coding genes (HSP70, CRT, cyPA, TCTP) were examined in earthworm Eisenia fetida exposed to HHCB. The results indicated that HSP70 and CRT genes expression patterns might be potential early molecular biomarkers for predicting the harmful exposure level and ecotoxicological effects of HHCB. In another study in earthworms, superoxide dismutase and catalase appeared to be the most responsive biomarkers of oxidative stress caused by HHCB.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
副作用
皮肤致敏剂 - 一种可以诱导皮肤产生过敏反应的制剂。
Skin Sensitizer - An agent that can induce an allergic reaction in the skin.
来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases
The accumulation of cadmium (Cd) in wheat seedlings under single and joint stress of galaxolide (HHCB) and Cd was investigated, and their phytotoxicity and oxidation stress including chlorophyll (CHL), malondialdehyde (MDA), superoxide dismutase, and perosidase were assessed. The results showed that the accumulation of Cd in wheat seedlings increased with an increase in the concentration of Cd in soil. The low concentration of HHCB inhibited the accumulation of Cd, while the high concentration of HHCB induced the accumulation of Cd. The content of CHL increased significantly in treatments with 1-50 mg/kg Cd. However, the content of CHL under joint stress of Cd and HHCB was significantly lower than that in the control. Besides, the content of MDA in wheat leaves and roots was also significantly affected by HHCB and Cd, particularly by their joint stress. Co-contamination of HHCB significantly affected the activity of antioxidant enzymes in wheat seedlings stressed by Cd. In a word, HHCB could aggravate the phytotoxicity of Cd to wheat seedlings.
Polycyclic musks and heavy metals are often present in natural aquatic environment. The aims of this study were to evaluate the toxic effects on Daphnia magna from exposure to the polycyclic musks and the heavy metals in combination with stress from suspended solids exposure. Galaxolide and lead were used as typical pollutants. The toxic effects on D. magna decreased with addition of suspended solids within the single experiments having galaxolide after 24 and 48 hr. A similar result was observed for the toxic effect of lead on the D. magna with adding suspended solids during exposure. Synergism on D. magna was found within the combined tests having galaxolide and lead during the 24 and 48 hr exposure based on additive index analysis. The combined toxic effect of galaxolide and lead was significantly decreased by adding suspended solids. The results could provide useful information for the toxic risks assessments of surface aquatic systems.
Using outdoor pot-culture experiment,biomasses of wheat seedlings and accumulation of HHCB and/or Cd in parts of wheat seedlings cultured in alluvial soil and cinnamon soil were investigated. The biomasses of wheat seedlings in different treatments followed the order as single HHCB treatment > HHCB and Cd treatment > single Cd treatment. The accumulation of HHCB in wheat seedlings cultured in alluvial soil was more than that in cinnamon soil, and effect of Cd on accumulation of HHCB in wheat seedlings cultured in alluvial soil was different to that in cinnamon soil. In alluvial soil, the accumulation of HHCB in different parts of wheat seedlings followed the sequence that root > stem > leaf. Cd significantly induced the accumulation of HHCB in wheat roots, but inhibited that of HHCB in wheat stems and leaves, and the highest inhibition rate was 44.07%. In cinnamon soil, the accumulation of HHCB in different parts of wheat seedlings followed the sequence that root > leaf > stem. The effect of Cd on accumulation of HHCB in wheat roots was not significant, but the median and high concentrations of Cd induced accumulation of HHCB in wheat stems and leaves significantly, and the highest induction rate was 35.95%. Besides, the accumulation of Cd in alluvial soil was lower than that in cinnamon soil, and HHCB could significantly induce the accumulation of Cd in wheat seedlings cultured in two different soils. The increasing rates of Cd accumulation in roots, stems and leaves in alluvial soil were 30.84%, 61.82% and 61.82%, and those in cinnamon soil were 41.53%, 184.16% and 206.18%, respectively. It is indicated that HHCB in cinnamon soil induced more accumulation of Cd in wheat seedlings than that in alluvial soil.
The systemic exposure to 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexa-methylcyclopenta-gamma-2-benzopyran (HHCB) was determined ... in humans under simulated conditions of exposure. Ring (14)C-labeled HHCB was applied in alcoholic solutions without occlusion to three male volunteers at concentrations approximating that which might be encountered in a typical cologne type product. After a 6-hr period, all material was removed from the surface of the skin. Blood, feces and urine were collected over a 5-day period. For both materials, levels in blood and plasma were below limits of detection at all times. Based on excretion, primarily in the urine, the total absorbed dose was approximately 0.1% for HHCB. However, over the 5-day period, 19.5% of HHCB was recovered from the skin in dressings over the site of application indicating that a 'reservoir' had formed in the skin but the material in the reservoir was lost, by desquamation and/or by reverse absorption, and not available systemically. A mean of 22% was shown to evaporate under the conditions of exposure.
... The systemic exposure to 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexa-methylcyclopenta-gamma-2-benzopyran (HHCB) was determined in rats under occlusion. Ring (14)C-labeled HHCB was applied dermally in alcoholic solutions to rats at doses of 4.5 mg/kg and occluded for 6 hr. Urine, feces and air were collected for up to 120 hr and analyzed for radioactivity. Pairs of rats were sacrificed periodically for analysis of tissues and organs. The total amount absorbed was approximately 14% for HHCB. Significant amounts diffused into the skin, most of which was further absorbed but a significant amount of which was lost to surface dressing by reverse diffusion and/or desquamation.
In the current study, the bioconcentration behavior and acute toxicity of ... galaxolide 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexa-methylcyclopenta[gamma]-2-benzopyran (HHCB), was studied in two benthic organisms ... Chironomus riparius exhibited bioconcentration factors (BCFs) for ... HHCB substantially lower than predicted for nontransformed organics. The BCF ... increased after coexposure of the organism to the cytochrome P450 inhibitor piperonyl butoxide. Thus, the low BCF values were the result of rapid biotransformation of HHCB in the midge larvae. Bioconcentration kinetics indicated that /HHCB/ induced its own cytochrome P450-mediated metabolism. Acute toxicity of /HHCB/ to midge larvae was reduced compared to predicted baseline toxicity. Bioconcentration of HHCB ... in the worm (Lumbriculus variegatus) is in agreement with predictions based on the octanol-water partition coefficients of this chemical. Acute toxicity was found to be similar to predicted values for baseline toxicity.
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
/MILK/ 合成麝香化合物被用作许多消费产品的添加剂，包括香水、除臭剂和洗涤剂。早期的研究报告了在美国收集的环境和野生动物样本中合成麝香的存在。在这项研究中，从马萨诸塞州收集的人乳样本被分析，以确定合成麝香如麝香二甲苯（1-叔丁基-3,5-二甲基-2,4,6-三硝基苯）、麝香酮（4-叔丁基-2,6-二甲基-3,5-二硝基乙酰苯）、HHCB（1,3,4,6,7,8-六氢-4,6,6,7,8,8-六甲基环戊[γ]-2-苯并吡喃）、AHTN（7-乙酰-1,1,3,4,4,6-六甲基-1,2,3,4-四氢萘）和HHCB-内酯（HHCB的氧化产物）的浓度。此外，我们还估计了婴儿基于摄入母乳的速率对合成麝香的日摄入量。在大多数被分析的样本中发现了合成麝香，浓度范围在<2至150 ng麝香二甲苯/g，<2至238 ng麝香酮/g，<5至917 ng HHCB/g，<5至144 ng AHTN/g，以及<10至88.0 ng HHCB-内酯/g（按脂质重量计算）。HHCB的浓度高于母乳样本中其他合成麝香的浓度。HHCB的平均浓度（220 ng/g，脂质重量）比10年前在德国和丹麦收集的母乳样本报告的浓度高出5倍。母亲年龄与麝香二甲苯、麝香酮、HHCB或AHTN的浓度没有相关性。随着之前哺乳的儿童数量的增加，麝香二甲苯、麝香酮、HHCB和AHTN的浓度呈现出下降趋势，尽管相关性不显著。基于平均每日摄入母乳的速率，估计婴儿每天摄入297 +/- 229 ng麝香二甲苯，780 +/- 805 ng麝香酮，1830 +/- 1170 ng HHCB，565 +/- 614 ng AHTN，以及649 +/- 598 ng HHCB-内酯。在美国，婴儿对合成麝香的摄入率低于对持久性有机污染物（POPs）如多氯联苯（PCBs）的估计。基于残留模式和积累特征，可以得出合成麝香的暴露特征与POPs不同，合成麝香的主要暴露源可能是通过皮肤吸收或吸入。
/MILK/ Synthetic musk compounds are used as additives in many consumer products, including perfumes, deodorants, and detergents. Earlier studies have reported the occurrence of synthetic musks in environmental and wildlife samples collected in the United States. In this study, human breast milk samples collected from Massachusetts, were analyzed for the determination of concentrations of synthetic musks such as musk xylene (1-tert-butyl-3,5-dimethyl-2,4,6-trinitrobenzene), musk ketone (4-tert-butyl-2,6-dimethyl-3,5-dinitroacetophenone), HHCB (1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta[gamma]-2-benzopyran), AHTN (7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene), and HHCB-lactone, the oxidation product of HHCB. In addition, we estimated the daily intake of synthetic musks by infants based on the ingestion rate of breast milk. Synthetic musks were found in most of the samples analyzed, and the concentrations ranged from < 2 to 150 ng musk xylene/g, < 2 to 238 ng musk ketone/ g, < 5 to 917 ng HHCB/g, < 5 to 144 ng AHTN/g, and < 10 to 88.0 ng HHCB-lactone/g, on a lipid weight basis. The concentrations of HHCB were higher than the concentrations of other synthetic musks in breast milk samples. The mean concentration of HHCB (220 ng/g, lipid weight) was 5 times greater than the concentrations reported 10 years ago for breast milk samples collected in Germany and Denmark. Maternal age was not correlated with the concentrations of musk xylene, musk ketone, HHCB, or AHTN. There was a trend of decreasing concentrations of musk xylene, musk ketone, HHCB, and AHTN, with the number of children previously breast-fed, although the correlation was not significant. Based on average daily ingestion rate of breast milk, an infant is estimated to ingest 297 +/- 229 ng musk xylene, 780 +/- 805 ng musk ketone, 1830 +/- 1170 ng HHCB, 565 +/- 614 ng AHTN, and 649 +/- 598 ng HHCB-lactone per day. The ingestion rate of synthetic musks by infants in the United States is lower than that estimated for persistent organic pollutants (POPs) such as polychlorinated biphenyls (PCBs). Based on the residue patterns and accumulation features, it can be concluded that the exposure characteristics for synthetic musks are different from those of POPs, and that the major source of exposure to synthetic musks is probably via dermal absorption or inhalation.
BITTER TASTE MODIFIERS INCLUDING SUBSTITUTED 1-BENZYL-3-(1-(ISOXAZOL-4-YLMETHYL)-1H-PYRAZOL-4-YL)IMIDAZOLIDINE-2,4-DIONES AND COMPOSITIONS THEREOF
申请人：SENOMYX, INC.
公开号：US20160376263A1
公开（公告）日：2016-12-29
The present invention includes compounds and compositions known to modify the perception of bitter taste, and combinations of said compositions and compounds with additional compositions, compounds, and products. Exemplary compositions comprise one or more of the following: cooling agents; inactive drug ingredients; active pharmaceutical ingredients; food additives or foodstuffs; flavorants, or flavor enhancers; food or beverage products; bitter compounds; sweeteners; bitterants; sour flavorants; salty flavorants; umami flavorants; plant or animal products; compounds known to be used in pet care products; compounds known to be used in personal care products; compounds known to be used in home products; pharmaceutical preparations; topical preparations; cannabis-derived or cannabis-related products; compounds known to be used in oral care products; beverages; scents, perfumes, or odorants; compounds known to be used in consumer products; silicone compounds; abrasives; surfactants; warming agents; smoking articles; fats, oils, or emulsions; and/or probiotic bacteria or supplements.
Perfuming Ingredients with Odor of the Pheromone Type
申请人：Chapuis Christian
公开号：US20080280809A1
公开（公告）日：2008-11-13
The present invention relates to certain β-decalone derivatives which can impart useful odor notes of the pheromone or costus type. The present invention concerns the use of the compounds in the perfumery industry to impart such odor notes as well as to the compositions or articles that contain these compounds.
[EN] 2,3,7-TRIMETHYLOCT-6-ENYL ACETATE AND 3,7-DIMETHYL-2-METHYLENE-OCT-6-ENYL ACETATE AND DERIVATIVES THEREOF AND THEIR USE AS AROMA CHEMICALS<br/>[FR] ACÉTATE DE 2,3,7-TRIMÉTHYLOCT-6-ÉNYLE ET DE 3,7-DIMÉTHYL-2-MÉTHYLÈNE-OCT-6-ÉNYLE, LEURS DÉRIVÉS ET LEUR UTILISATION EN TANT QUE PRODUITS CHIMIQUES AROMATIQUES
申请人：BASF SE
公开号：WO2018206415A1
公开（公告）日：2018-11-15
The present invention relates to 2,3,7-Trimethyloct-6-enyl acetate and 3,7-dimethyl-2-methylene-oct-6-enyl acetate and derivatives thereof and their use as aroma chemicals.
PERFUMING INGREDIENTS OF THE FLORAL AND/OR ANIS TYPE
申请人：Moretti Robert
公开号：US20110200546A1
公开（公告）日：2011-08-18
The present invention concerns a compound of formula wherein R represents a hydrogen atom or a C
1-2
alkyl or alkoxyl group; each R
1
, R
2
or R
3
represents a hydrogen atom or a methyl or ethyl group; and X represents a CHO, COOR
4
or CN group, R
4
being a methyl or ethyl group; and at least one of said R, R
1
or R
2
represents a group containing at least one carbon atom; and it use as perfuming ingredient, for instance to impart odor notes of the floral and/or anis type.
Novel norbornane and norbornene derivatives, use thereof and perfumed products containing same
申请人：Mane Jean
公开号：US20050004378A1
公开（公告）日：2005-01-06
The invention concerns a novel compounds of formula (I), wherein the dotted line bond is present or not, and wherein R
1
represents: when the dotted line bond is present —CHCH
3
OH or —CHCH
3
OCOR or —CHCH
3
XCH
2
CHOHR′ or —CHCH
3
OCHR′CH
2
OH or formula (II) when the dotted line bond is absent —CHCH
3
OH or —CHCH
3
OCOR or —COCH
3
or formula (II) or —CHCH
3
XCH
2
CHOHR′ or —CH
2
CH
2
XCH
2
CHOHR′ or —CHCH
3
OCHR′CH
2
OH or —CHCHCOR′ or —CH
2
CH
2
CHR′OH or —CH
2
CH
2
CHR′OCOR or CHCHCHOHR′ or —CHCHCHR′OCOR, wherein R represents H, Me, Et, Pr, isoPr, But, isoBut, CH
3
CH
2
)
4
, (CH
3
)
2
CHCH
2
, CH
2
CH, (CH3)
2
CCH, and R′ represents H, Me or Et, and X represents O, N or S, and their preparation method. Because of their fragrance, said compounds are highly interesting for the perfume industry, for cosmetic and care products.
