1,3,4,6,7,8-Hexahydro-4,6,6,7,8,8-hexamethylindeno[5,6-c]pyran

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide. Advice for firefighters: Wear self-contained breathing apparatus for firefighting if necessary.[Sigma-Aldrich; Safety Data Sheet for 1,3,4,6,7,8-Hexahydro-4,6,6,7,8,8- hexamethylcyclopenta

Keep container tightly closed in a dry and well-ventilated place. Containers which are opened must be carefully resealed and kept upright to prevent leakage. Store under inert gas. Storage class (TRGS 510): Combustible liquids.[Sigma-Aldrich; Safety Data Sheet for 1,3,4,6,7,8-Hexahydro-4,6,6,7,8,8- hexamethylcyclopenta

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into the environment must be avoided. Methods and materials for containment and cleaning up: Keep in suitable, closed containers for disposal.[Sigma-Aldrich; Safety Data Sheet for 1,3,4,6,7,8-Hexahydro-4,6,6,7,8,8- hexamethylcyclopenta

SRP: Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in air, soil or water; effects on animal, aquatic and plant life; and conformance with environmental and public health regulations. If it is possible or reasonable use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination.

Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contaminated packaging: Dispose of as unused product.[Sigma-Aldrich; Safety Data Sheet for 1,3,4,6,7,8-Hexahydro-4,6,6,7,8,8- hexamethylcyclopenta

Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.[Sigma-Aldrich; Safety Data Sheet for 1,3,4,6,7,8-Hexahydro-4,6,6,7,8,8- hexamethylcyclopenta

Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday.[Sigma-Aldrich; Safety Data Sheet for 1,3,4,6,7,8-Hexahydro-4,6,6,7,8,8- hexamethylcyclopenta

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into the environment must be avoided.[Sigma-Aldrich; Safety Data Sheet for 1,3,4,6,7,8-Hexahydro-4,6,6,7,8,8- hexamethylcyclopenta

SRP: The scientific literature for the use of contact lenses by industrial workers is inconsistent. The benefits or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place.

Eye/face protection: Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).[Sigma-Aldrich; Safety Data Sheet for 1,3,4,6,7,8-Hexahydro-4,6,6,7,8,8- hexamethylcyclopenta

Skin protection: Handle with gloves.[Sigma-Aldrich; Safety Data Sheet for 1,3,4,6,7,8-Hexahydro-4,6,6,7,8,8- hexamethylcyclopenta

Body Protection: Impervious clothing. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.[Sigma-Aldrich; Safety Data Sheet for 1,3,4,6,7,8-Hexahydro-4,6,6,7,8,8- hexamethylcyclopenta

Respiratory protection: Respiratory protection not required. For nuisance exposures use type OV/AG (US) or type ABEK (EU EN 14387) respirator cartridges. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).[Sigma-Aldrich; Safety Data Sheet for 1,3,4,6,7,8-Hexahydro-4,6,6,7,8,8- hexamethylcyclopenta

Galaxolide residue levels in 14 human adipose tissue samples and 5 human milk samples from indiduals residing in Keil, Schleswig-Holstein, Germany, 1993-1995, ranged from 16 to 189 ug/kg fat(1). Adipose tissue levels were (ug/kg fat (age of donor)): females: 83 (43), 41 (51), 44 (60), 56 (68), 118 (41), 133 (60), 39 (70), 64 (70); males: 28 (48), 189 (30), 83 (48), 112 (74), 77 (59), 80 (84)(1). Levels in breast milk were: 16 (32), 28 (38), 108 (28), 57 (31), 37 (31), all in ug/kg fat(1). Galaxolide was present in 1005 of adipose tissues of Korean females collected in 2007 and 2008; the mean concentration was 81 ng/g lipid wt, range of 28-211 ng/g lipid wt(2). The median blood concentration of galaxolide in 110 healthy young adults, Vienna, Austria, was reported as 420 ng/L(3). Galaxolide median concentration was 63.9 ng/g lipid (max 268 ng/g lipid) mother's milk from 101 women living in Uppsala County, Sweden. Samples were collected from 1996-2003(4).

... This study examined the concentrations of six polycyclic musks in blood samples from healthy volunteers. Blood was taken from hundred healthy students. The lipophilic fraction was extracted and after purification analyzed by GC-MS. Study participants also completed a questionnaire on the use of cosmetics, about nutrition and other life-style aspects. Two compounds -- galaxolide and tonalide -- were identified in higher percentages of the blood plasma samples. Maximum plasma levels over 100 ng/L were also only found for galaxolide (4100 ng/L) and tonalide (800 ng/L). Women showed significantly higher levels than men.

... /HHCB was/ determined in a total of 14 human adipose tissue samples and 5 human milk samples by GC/EI/MS in the SIM mode. The residue levels ranged from 16 to 189 ug/kg fat for HHCB.

Galaxolide ... was analyzed in 15 human adipose tissue samples from Switzerland by gas chromatography/high resolution mass spectrometry. The levels of Galaxolide were up to 171 ng/g lipids.

Concentrations of HHCB and AHTN in human adipose fat collected from New York City were measured. Concentrations of HHCB and AHTN in human adipose fat samples ranged from 12 to 798 and from <5 to 134 ng/g, on a lipid weight basis, respectively. A significant correlation existed between the concentrations of HHCB and AHTN in human adipose fat. Concentrations of HHCB and AHTN were not positively correlated with age or gender of the donors.

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.

Single and joint toxic effects of polycyclic musks including 1,3,4,6,7,8-hexahydro-4,6,6,6,7,8,8-hexamethylcyclopenta[g]-2-benzopyran (HHCB) and 7-acetyl-1,1,3,4,4,6-hexamethyl-l,2,3,4-tetrahydronapthalene (AHTN) and cadmium (Cd) on seed germination and seedling growth of wheat (Triticum aestivum) were investigated. The results showed that the toxicity sequence of HHCB toxic to wheat seed germination and seedling growth was similar to that of AHTN, that is, germination rate > shoot elongation > root elongation, while the toxicity of Cd was in the sequence of root elongation > shoot elongation > germination rate, according to the LC50 and EC50 values. It is suggested that polycyclic musks and Cd had different toxicological mechanisms. Root and shoot elongation of wheat might be good bioindicators for the contamination of polycyclic musks and Cd in soil. The mixture of polycyclic musks and Cd had synergistic effects on T. aestivum according to the equi-toxic mixture approach when root elongation was selected as the toxicological endpoint. Thus, the joint toxicity of HHCB and Cd was significantly higher than the single toxicity of HHCB or Cd, which was also confirmed by the EC50 mix value of the mixture (EC50 mix = 0.530 TUmix). The EC(50mix) value of the mixture of AHTN and Cd was 0.614 TUmix, which indicated that the mixture toxicity was strengthened when AHTN coexisted with Cd.

LC50; Species: Pimephales promelas (Fathead minnow) 32 days post-hatching; Concentration: 0.140 mg/L for 36 days /Conditions of bioassay not specified in source examined/

LC50; Species: Oryzias latipes (Japanese Medaka) age 24 hr larva; Conditions: freshwater, renewal, 25 °C; Concentration: 950 ug/L for 96 hr (95% confidence interval: 910-1010 ug/L) /formulation/

EC50; Species: Daphnia magna (Water Flea); Conditions: freshwater, renewal; Concentration: 282 ug/L for 21 days (95% confidence interval: 260-312 ug/L); Effect: decreased reproduction

LC50; Species: Daphnia magna (Water Flea) age 6-24 hr, parthenogenetic; Conditions: freshwater, static, no suspended solids, pH 7.0, dissolved oxygen 7.0 mg/L; Concentration: 568 ug/L for 24 hr (95% confidence interval: 440-754 ug/L) /77.45% purity/

For more Ecotoxicity Values (Complete) data for Galaxolide (20 total), please visit the HSDB record page.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 2.0X10+4(SRC), determined from a structure estimation method(2), indicates that galaxolide is expected to be immobile in soil(SRC). Volatilization of galaxolide from moist soil surfaces is expected to be an important fate process(SRC) given an estimated Henry's Law constant of 1.1X10-4 atm-cu m/mole(SRC), based upon its vapor pressure, 5.45X10-4 mm Hg(3), and water solubility, 1.75 mg/L(3). However, adsorption to soil is expected to attenuate volatilization(SRC).) Galaxolide is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(4). A biodegradation half-life in soil of 4 months(3) indicates that biodegradation is not an important environmental fate process in soil(SRC).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 2.0X10+4(SRC), determined from a structure estimation method(2), indicates that galaxolide is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is expected(3) based upon an estimated Henry's Law constant of 1.1X10-4 atm-cu m/mole(SRC), derived from its vapor pressure, 5.45X10-4 mm Hg(4), and water solubility, 1.75 mg/L(4). Using this Henry's Law constant and an estimation method(3), volatilization half-lives for a model river and model lake are 18 hrs and 10 days, respectively(SRC). However, volatilization from water surfaces is expected to be attenuated by adsorption to suspended solids and sediment in the water column. The estimated volatilization half-life from a model pond is 31 months if adsorption is considered(5). According to a classification scheme(6), a BCF of 1584(4) suggests the potential for bioconcentration in aquatic organisms is very high(SRC). A release of 0% CO2 in four weeks using an effluent from a semi-continuous activated sludge (SCAS) in the OECD 302 test(4) indicates that biodegradation is not an important environmental fate process in water(SRC).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), galaxolide, which has a vapor pressure of 5.45X10-4 mm Hg at 25 °C((SRC), determined from a fragment constant method(2)), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase galaxolide is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be approximately 10 hrs(SRC), calculated from its rate constant of 2.60X10-11 cu cm/molecule-sec at 25 °C(3). Particulate-phase galaxolide may be removed from the air by wet and dry deposition(SRC). Galaxolide does not contain chromophores that absorb at wavelengths >290 nm(4) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC).

Galaxolide residue levels in 5 human milk samples from individuals residing in Keil, Schleswig-Holstein, Germany, 1993-1995, ranged from 16 to 108 ug/kg fat(1). Levels in breast milk samples were (age of donor): 16 (32), 28 (38), 108 (28), 57 (31), 37 (31), all in ug/kg fat(1). Galaxolide median concentration was 63.9 ng/g lipid (max 268 ng/g lipid) mother's milk from 101 women living in Uppsala County, Sweden. Samples were collected from 1996-2003(2).

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.

HHCB dominated in Danish human milk samples collected in 1999 with a median concentration of 147 ug/kg fat (38.0-422 ug/kg fat).

The average level/ of HHCB was/ 2.9 ppb with a maximum of 48 ppb in human milk samples

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.

The percentage of 82 sampled personal care products containing galaxolide was as follows: body lotions, 64; perfumes, 42: deodorants, 100; hair care products, 31; shower products 41; sanitation, 54. The maximum concentration of galaxolide in personal care and sanitation products, was reported at 22 mg/g. This corresponds to an average daily exposure range of 18 to 23,700 ug/day(1).

The occurrence of ten synthetic musks in samples of 10 widely consumed fish and shellfish species from Tarragona (Catalonia, Spain) was determined. The most used nitro and polycyclic musks, as well as a well-known transformation product in tissues, were analyzed. Furthermore, the human health risks derived from the musk exposure through seafood consumption were characterized. None of the nitro musks were detected in any of the analyzed samples. In contrast, most of the polycyclic musks were found, being galaxolide (HHCB) and tonalide (AHTN) present in all the samples. HHCB was the greatest contributor, with maximum levels in sardine and mackerel (367 and 304 ng g(-1) (d.w.) (dry weight), respectively). The highest exposure to individual musks was estimated for HHCB and HHCB-Lactone, with average values of 19.7 and 6.8 ng kg(-1)bw day(-1), respectively, in adults. A notably lower mean exposure was calculated for AHTN, cashmeran (DPMI) and traseolide (ATII), being ranged between 1.1 and 3.7 ng kg(-1)bw day(-1). The current concentrations of musks in fish and shellfish should not mean human health risks for the adult population living in Tarragona. However, a continuous monitoring would be desirable to assure that the exposure does not follow increasing temporal trends.

/AQUATIC SPECIES/ In 72-hr studies with algae (Pseudokirchneriella subcapitata), NOEC was 0.201 mg/L for HHCB. In 21-day reproductive tests with daphnia (Daphnia magna) NOEC was 0.111 mg/L. In 21-day growth tests with bluegill sunfish (Lepomis macrochirus), NOEC was 0.068 mg/L. And, finally 35-day early life stage tests with fathead minnows (Pimephales promelas) resulted in a NOEC of 0.068 mg/L. These results lead to Predicted No Effect Concentrations (PNEC) of 6.8 ug/L HHCB for aquatic organisms ... Comparing PNECs with the measured or predicted environmental exposures leads to risk characterisation ratios as follows: aquatic species: ... HHCB 0.074; sediment organisms: ... HHCB 0.064.

/AQUATIC SPECIES/ ... Galaxolide ... /was/ tested for acute and subchronic effects on a marine crustacean, the calanoid copepod Acartia tonsa. Sublethal effects on A. tonsa larvae were investigated with a rapid and cost effective bioassay, which is based on the easily detectable morphological change from the last nauplius to the first copepodite stage during copepod larval development. The inhibition of larval development after 5 days exposure was a very sensitive endpoint, with 5-day EC50 values as low as ... 0.059 mg/L ... This value was more than one order of magnitude below the 48-hr LC50 value found for adults, which was 0.47 mg/L ... .

/AQUATIC SPECIES/ ... This study reports on the lethal and sublethal toxicity of the polycyclic musks AHTN (Tonalide) and HHCB (Galaxolide) to glochidial (larval) and juvenile life stages of the freshwater mussel Lampsilis cardium. In glochidia, 24-hr median lethal concentrations (LC50s) ranged ... from 1000 to >1750 ug HHCB/L (water solubility). Results for 48-hr tests were similar to the 24-hr tests. In 96-hr tests with juveniles, a dose-response relation between mortality and musk /was not observed/. However, the growth rate was reduced by musk exposure. The median effective concentration (EC50, based on growth) ... ranged from 153 to 831 ug HHCB/L.

/AQUATIC SPECIES/ 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.

Galaxolide concentrations in shallow water marine organisms from the Ariake Sea, Japan, collected in 2004. The concentration of galaxolide in the blubber of finless porpoises and striped dolphins collected from Japanese coastal waters from 1977 through 2005 ranged from 3.7 to 28 ng/g wet wt; min concentration of <0.8 in striped dolphin in 1980 and a max of 52 ng/g wet wt in finless porpoise reported in 2003. Other marine mammal concentrations were (species; location; year; concn (ng/g wet wt)(1):[Table#7195]

Galaxolide concentration in effluents from sewage treatment plants located in various countries were: Germany was 1.9 ug/L; maximum concentrations from The Netherlands were 1.6 and 0.29 ug/L; median concentration in Switzerland was 2.3 ug/L; samples from Sweden ranged from 1-6 ug/L; median concentration in a sample from the US was 1.2 ug/L(1). Concentrations in sewage sludge from various sewage treatment plants were: The Netherlands, primary, 5.4-27 mg/kg dw, activated 0-63 mg/kg dw, digested 9.0-31 mg/kg dw; Germany, sludge 4.3-13.4 mg/kg dw, activated 0.1-5.2 mg/kg dw. Galaxolide concentrations in sewer slime collected from German urban, industrial and rural areas ranged from 9.1-21.8 mg/kg dw(1). Mean effluent concentration from a municipal sewage treatment plant in Berlin, Germany was 7.8 ug/L(2). The level in the raw water of five Berlin waterworks was 0.036 ug/L(2). Galaxolide levels were measured in twelve US and five European wastewater treatment plants monitored between 1997 and 2000; the average influent was 16.6 and 9.71 ug/L for US and European plants, respectively(3). Effluent concentrations following various treatment operations were as follows (ng/L): primary gravitational settling plus activated sludge, US - 2053, Europe - 4620; primary gravitational settling plus carousel, Europe - 1065; oxidation ditch, US - 1496; primary gravitational settling plus trickling filter, US - 2056, Europe - 2400; primary gravitational settling plus rotating biological contactor, US - 2210; lagoon, US - 53(3).

Galaxolide was detected at concentrations up to 1,300 ng/L in all samples of effluents tested from Canadian (Nova Scotia and New Brunswick, Jan 2002) and Swedish (Uppsala, Vastra, and Gavleborg, Jun-Dec, 1999) sewage treatment plants(1). Specific concentrations reported were: Canada - Strawberry Marsh sewage treatment plant, Miramichi, New Brunswick, population 20,000, 480 n/L; Lancaster, Saint John, New Brunswick, population 90,000, 205 ng/L; Mill Cove Plant, Bedford, Nova Scotia, population 350,000, 1,300 ng/L(1). Sweden - Enkoping, population 21,000, 336 ng/L; Skene, population 17,280, 218 ng/L; Gasslosa, population 79,000, 423ng/L; Nolbaga, population 39,500, 157 ng/L; Ljusne, population 2,596 407 ng/L(1). Galaxolide concentrations in the influent and effluent of a sewage plant were 4,200 and 3,700 ng/L and the influent and effluent levels in the associated sewage pond were 3,600 and 1,700 ng/L(2).

The typical effluent concentration into Lake Michigan for galaxolide was 1640 ng/L in the dissolved phase(1). Average influent/effluent concentrations where 549.68/32.06 ug/L for a cosmetic plant located in HuangPu industrial park in GuangZhou, China, sampled from Nov 15-22, 2004. The average concentrations in primary and secondary sludge from the plant were 512.45 and 565.67 mg/kg dry weight, respectively(2). Galaxolide was present in influent at concentration range of 7800-16,900 ng/L six UK sewage treatment works surveyed in late autumn and early winter 2001(3). Galaxolide was detected at a concentration range of 4,772-13,399 ng/L in influent samples and 2,960-10,525 ng/L in effluents samples of two waste water treatment plants in Lubbock, TX. Samples collected from winter 2009 to winter 2010; detection limit = 4 ng/L(4).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of galaxolide can be estimated to be 2.9X10+4(SRC). A log Koc of 4.86 has also been reported, test conditions not available(2). According to a classification scheme(3), these Koc values suggest that galaxolide is expected to be immobile in soil(SRC). In soil column experiments, galaxolide was added at 0.330 ug/L to a 2.4 m soil column employing a Mohall-Laveen sandy loam soil from northwest of Phoenix, AZ(4). After percolating through the soil column over 23 days, the concentration in the column effluent was below the detection limit of 0.500 ug/L(4). Galaxolide has been found in association with suspended particulate matter collected from the Elbe River at Magdeburg, Germany during June 1996-May 1997(5).

Used as fragrance agent in perfumes, soaps, cosmetics, and detergents; [Merck Index]

Synthetic, artificial musk fragrance.

Fragrance ingredient in perfumes, soaps, cosmetics, and detergents.

HHCB is used to make a fragrance long lasting and have a positive technical effect on its balance bringing the initial and residual smell into harmony.

2023: 4,000,000 - <5,500,000 lb

Production volumes for non-confidential chemicals reported under the Inventory Update Rule. [Table#7204]

This chemical is listed as a High Production Volume (HPV) (65FR81686). Chemicals listed as HPV were produced in or imported into the U.S. in >1 million pounds in 1990 and/or 1994. The HPV list is based on the 1990 Inventory Update Rule. (IUR) (40 CFR part 710 subpart B; 51FR21438).

Non-confidential 2016 Chemical Data Reporting (CDR) information on the production and use of chemicals manufactured or imported into the United States. Chemical: Cyclopenta[g]-2-benzopyran, 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethyl-:

The starting material for its synthesis is 1,1,2,3,3-pentamethylindane, which is prepared by cycloaddition of tert-amylene to alpha-methylstyrene. The pentamethylindane is hydroxyalkylated with propylene oxide in a Friedel-Crafts reaction using aluminum chloride as a catalyst (analogous to the synthesis of 2-phenethyl alcohol from benzene and ethylene oxide). Ring closure of the resulting 1,1,2,3,3-pentamethyl-5-(beta-hydroxyisopropyl)indane to /4,6,6,7,8,8-Hexamethyl-1,3,4,6,7,8-hexahydrocyclopenta[g]benzopyran/ is accomplished with paraformaldehyde and a lower aliphatic alcohol via the acetal or with paraformaldehyde and a carboxylic acid anhydride via the acylate.

... Synthesized as following: There is a condensation-cyclization stage of tert-amyl alcohol and a-methyl styrene in acidic conditions to obtain the indane system, followed by a Friedel-Crafts reaction with propylene oxide to get the side chain. The side chain is finally closed to the isochromanic system using formaldehyde.

Preparation: L. G. Heeringa, M. G. J. Beets, United Kingdom patent 991146; eidem, United States of America patent 3360530 (1965, 1967 both to International Flavors & Frangrances).

Cosmetics product ingredient: 1,3,4,6,7,8-Hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-?-2-benzopyran (Hexamethylindanopyran)

Information on 218 consumer products that contain Hexamethylindanopyran in the following categories is provided:

Information on 2 consumer products that contain Hexahydrohexamethyl cyclopentabenzopyran in the following categories is provided:

Fragrance Ingredients

Cosmetics -> Antifoaming

Soap, Cleaning Compound, and Toilet Preparation Manufacturing

Cyclopenta[g]-2-benzopyran, 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethyl-: ACTIVE

The commercial product is diluted with solvents (e.g., diethyl phthalate, isopropyl myristate, benzyl benzoate) to make it less viscous.

Concentrations of HHCB (Galaxolide), AHTN (Tonalide), and HHCB-lactone (Galaxolidone) from a variety of consumer products, including perfumes, body lotions, and deodorants were measured. Concentrations of HHCB, AHTN, and HHCB-lactone in consumer products ranged from <5 ng/g to over 4000 ug/g, <5 ng/g to 451 ug/g, and <5 ng/g to 217 ug/g, respectively. The highest concentrations were found in perfumes, body creams and lotions, and deodorants. The results suggest that a wide variety of source materials exist for HHCB and AHTN, and that these materials are used on a daily basis.