1,2-디브로모-4-(1,2-디브로모에틸)사이클로헥산

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

SMALL SPILLS AND LEAKAGE: If a spill of this chemical occurs, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with acetone and transfer the dampened material to a suitable container. Use absorbent paper dampened with acetone to pick up any remaining material. Seal your contaminated clothing and the absorbent paper in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with acetone followed by washing with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

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.

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. (NTP, 1992)

Endocrine disrupting compounds can interfere with androgen receptor (AR) signaling and disrupt steroidogenesis leading to reproductive failure. The brominated flame-retardant (BFR) 1, 2-dibromo-4-(1, 2-dibromoethyl) cyclohexane (TBECH), is an agonist to human, chicken and zebrafish AR. Recently another group of alternative BFRs, allyl 2, 4, 6-tribromophenyl ether (ATE), and 2, 3-dibromopropyl 2, 4, 6-tribromophenyl ether (DPTE) along with its metabolite 2-bromoallyl 2, 4, 6-tribromophenyl ether (BATE) were identified as potent human AR antagonists. These alternative BFRs are present in the environment. The aim of the present study was to determine the effect of mixed exposures to the AR agonist and the AR antagonists at environmentally relevant concentrations. In vitro reporter luciferase assay showed that the AR antagonists, when present at concentration higher than TBECH, were able to inhibit TBECH-mediated AR activity. These AR antagonists also promoted AR nuclear translocation. In vitro gene expression analysis in the non-tumorigenic human prostate epithelial cell RWPE1 showed that TBECH induced AR target genes whereas DPTE repressed these genes. Further analysis of steroidogenic genes showed that TBECH up-regulated most of the genes while DPTE down-regulated the same genes. The results indicate that when TBECH and DPTE are present together they will antagonize each other, thereby reducing their individual effects.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 3500(SRC), determined from a structure estimation method(2), indicates that 1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane is expected to have slight mobility in soil(SRC). Volatilization of 1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 5.7X10-8 atm-cu m/mole(SRC), developed using a fragment constant estimation method(3). 1,2-Dibromo-4-(1,2-dibromoethyl)cyclohexane is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.1X10-4 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Half lives of 617 and 614 days for alpha- and beta-1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane, respectively, following incubation of 165 ng/g for 52+ weeks using a low organic carbon urban soil(4) suggests 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 3500(SRC), determined from a structure estimation method(2), indicates that 1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 5.7X10-8 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(6), an estimated BCF of 1300(SRC), from an estimated log Kow of 5.24(2) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is very high(SRC). Half-lives of 617 and 614 days for alpha- and beta-1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane, respectively, following incubation of 165 ng/g for 52+ weeks using a low organic carbon urban soil(6) suggests 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), 1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane, which has an estimated vapor pressure of 1.1X10-4 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase 1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane 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 79 hrs(SRC), calculated from its rate constant of 4.9X10-12 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(2). 1,2-Dibromo-4-(1,2-dibromoethyl)cyclohexane does not contain chromophores that absorb at wavelengths >290 nm(3) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC).

IDENTIFICATION AND USE: 1,2-Dibromo-4-(1,2-dibromoethyl)cyclohexane (BCH) is a white powder. It is used as a fire-retardant additive (polystyrene, polyurethane, polyvinyl chloride). HUMAN STUDIES: BCH is an agonist to human androgen receptor (AR). Cells with AR mutations were more susceptible to androgenic endocrine disrupters. Combining theoretical modeling with in vitro ligand-binding and receptor-activation assays demonstrated that BCH binds to and activates the human AR, indicating that it is a potential endocrine disruptor. ANIMAL STUDIES: In birds and fish there is some evidence of disruption in endocrine and reproductive parameters due to BCH. In vitro studies indicate that BCH is an androgen receptor agonist. Rats were exposed to 0, 0.9, 4.2, 21.3, 98.0 or 328.9 mg BCH/kg bw/d in males and 0, 0.8, 3.9, 19.4, 91.7 or 321.4 mg BCH/kg bw/d in females for 28 days in diet. Some evidence of hormone disruption was observed, including changes in serum testosterone levels in males and changes in serum T3 and T4 levels in females. BCH activated AR in chicken LMH cell line. Further quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) analysis showed that BCH interacted with and altered the expression of both thyroid receptors and estrogen receptors. In addition, the qRT-PCR analysis showed that BCH altered the transcription pattern of genes involved in inflammatory, apoptotic, proliferative, DNA methylation, and drug-metabolizing pathways. BCH was negative in mutagenicity assay when tested in four Salmonella typhimurium strains (TA98, TA100, TA1535, and TA1537) in the presence and absence of metabolic activation. ECOTOXICITY STUDIES: Captive American kestrels (Falco sparverius) were exposed via diet during reproduction to an environmentally relevant concentration of beta- BCH. Reductions in egg production and fertility resulted in decreased hatchling success. Androgen-dependent behaviors were also significantly increased in beta-BCH-exposed birds. In zebra finch embryos, analysis of tissue samples at various developmental stages suggests that alpha-/beta-BCH was metabolized rapidly, and thus was unlikely to cause any direct, long-term effects on the development of zebra finch embryos or offspring.

/BIRDS and MAMMALS/ Captive American kestrels (Falco sparverius) were exposed via diet during reproduction to an environmentally relevant concentration of beta-1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane (beta-TBECH). The beta-TBECH isomer was injected into the food source at a daily dosing concentration of 0.239 ng/g kestrel/day (22 pairs); control birds were exposed via diet to the safflower oil vehicle only (24 pairs). Eight pairs in each group were exposed for four weeks and sacrificed for tissue analysis; the remaining pairs completed their breeding cycle, with exposure ceasing at the end of incubation (82 days). alpha- and beta-TBECH appeared to be rapidly metabolized and/or eliminated from fat, liver, and plasma; both isomers and potential hydroxylated metabolites of beta-TBECH (plasma) were undetected. Notwithstanding, compared to controls, pairs exposed to beta-TBECH laid fewer eggs (p = 0.019) and laid lighter eggs (successful eggs: p = 0.009). Exposed pairs also demonstrated poorer egg fertility (p = 0.035) although testis mass and histology were similar among males. Reductions in egg production and fertility resulted in decreased hatchling success (p = 0.023). The beta-TBECH-exposed pairs also produced fewer males overall (p = 0.009), which occurred concurrently with increased estradiols maternally deposited in eggs (p = 0.039). These findings demonstrate that beta-TBECH may be detrimental for breeding in wild birds receiving similar exposure levels.

/BIRDS and MAMMALS/ Detected in environmental samples, 1,2-dibromo-4-(1,2-dibromoethyl) cyclohexane (DBE-DBCH) is a bioaccumulative isomer of a current-use brominated flame retardant. All 4 structural isomers are androgen agonists; however, little toxicological information exists for this compound. The objective of the present study was to determine if beta-DBE-DBCH, the isomer found most prominently in animal tissue, affects androgen-dependent behavior of breeding American kestrels (Falco sparverius). The authors hypothesized that if beta-DBE-DBCH acts as an androgen agonist in kestrels, androgen-dependent behaviors (i.e., copulation, courtship, aggression) would increase and behaviors inhibited by androgens (i.e., parental care behaviors) would decrease. Sixteen captive experimental kestrel pairs were exposed to 0.239 ng beta-DBE-DBCH/g kestrel/day by diet from 4 wk prior to pairing until their nestlings hatched (mean 82 days) and compared with vehicle only-exposed control pairs (n=15). Androgen-dependent behaviors were significantly increased in beta-DBE-DBCH-exposed birds, consistent with the authors' hypothesis. These behavioral changes included copulation and other sexual behaviors in males and females and aggression in males, suggesting that beta-DBE-DBCH may have acted like an androgen agonist in these birds. Parental behaviors were not reduced in exposed birds as predicted, although dietary exposure had ceased before chicks hatched. Further assessment of beta-DBE-DBCH is recommended given these behavioral changes and the previously reported reproductive changes in the same birds.

A concentration range of 0.04 to 3.44 ng/g wet weight was reported for 1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane in the eggs of colonial populations of Great Lakes herring gulls (Larus argentatus), collected in 1982 to 2006(1). A concentration range for alpa-1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane of not detected to 0.20 ng/g wet weight was reported in 3 of 28 liver samples from urban-feeding ring-billed gulls (L. delawarensis) from Ile Deslauries on the St. Lawrence River, downstream from Montreal, Quebec, Canada. It was not detected in 30 plasma samples; sampling was conducted from April-June 2010(2). A concentration range of not detected to 11.3 ng/g lipid weight was reported in blubber from Canadian Arctic beluga (Delphinapterus leucas) collected from 23 male animals taken 2003-2006(3).

Wastewater treatment plants (WWTPs) are an important source of anthropogenic chemicals, including organic flame retardants (FRs). Limited studies indicate birds can be exposed to FRs by feeding from waters receiving WWTP effluent or in fields receiving biosolids. Expanding on our earlier study, 47 legacy and 18 new FR contaminants were characterized in the eggs of insectivorous tree swallows (Tachycineta bicolor) feeding in water bodies receiving effluent from two WWTPs and compared to those from a reference site 19 km downstream of the nearest WWTP. Of the FRs measured, polybrominated diphenyl ethers (PBDEs) dominated the FR profile, specifically BDE-47, -99, -100, -153, -154, with considerably lower concentrations of hexabromocyclododecane (HBCDD), BDE-183 and BDE-209; each detected in 96-100% of the eggs overall except HBCDD (83%). FR concentrations were usually significantly greater in eggs from the secondary WWTP versus the tertiary WWTP and/or reference site. Despite low detection rates, concentrations of new FRs, specifically pentabromobenzyl acrylate (PBBA), 1,2,-bis-(2,4,6-tribromophenoxy)ethane (BTBPE), bis(2-ethylhexyl)-tetrabromophthalate (BEHTBP), tetrabromo-o-chlorotoluene (TBCT), hexabromobenzene (HBB), alpha- and beta-1,2-dibromo-4-(1,2-dibromoethyl)-cyclohexane (DBE-DBCH), were greater than HBCDD or BDE-209. Additional evidence that WWTPs are an important source of exposure to new FR contaminants for birds utilizing associated water bodies is that only the WTTP eggs, not the reference eggs, had measureable concentrations of PBBA, TBCT, BEHTBP, HBB, alpha-DBE-DBCH, 2,2',4,5,5'-pentabromobiphenyl (BB-101), pentabromoethyl benzene (PBEB), 2,4,6-tribromophenyl allyl ether (TBPAE), and tetrabromo-p-xylene (pTBX). Our study suggests that WWTPs are an important source of legacy and new FR contaminants for birds consuming prey that are associated with WWTP out-flows.

1,2-Dibromo-4-(1,2-dibromoethyl)cyclohexane concentrations in blubber from Finless porpoises (Neophocaena phocaenoides) and Indo-Pacific humpback dolphins (Sousa chinensis) from the South China Sea between 2005 and 2015(1).[Table#5720]

EPA has released the Interactive Chemical Safety for Sustainability (iCSS) Dashboard. The iCSS Dashboard provides an interactive tool to explore rapid, automated (or in vitro high-throughput) chemical screening data generated by the Toxicity Forecaster (ToxCast) project and the federal Toxicity Testing in the 21st century (Tox21) collaboration. /The title compound was tested by ToxCast and/or Tox21 assays/[USEPA; ICSS Dashboard Application; Available from, as of August 9, 2018: http://actor.epa.gov/dashboard/]

The following link will take the user to the National Toxicology Program (NTP) Test Status of Agents Search page, which tabulates the results and current status of tests such as "Short-Term Toxicity Studies", "Long-term Carcinogenicity Studies", "Developmental Studies", "Genetic Toxicology Studies", etc., performed with this chemical. Testing status for 1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane is available.[Available from, as of August 9, 2018: https://ntpsearch.niehs.nih.gov/?e=True&ContentType=Testing+Status]

Using a structure estimation method based on molecular connectivity indices(1), the Koc of 1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane can be estimated to be 3500(SRC). According to a classification scheme(2), this estimated Koc value suggests that 1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane is expected to have slight mobility in soil(SRC).

The mutagenicity of 1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane (DDC) was evaluated in Salmonella tester strains TA98, TA100, TA1535, TA1537 and TA1538 (Ames Test), both in the presence and absence of added metabolic activation by Aroclor-induced rat liver S9 fraction. Based on preliminary bacterial toxicity determinations, DDC, diluted in DMSO, was tested for mutagenicity at concentrations up to 500 ug/plate using the overlay plate test method. DDC did not cause a positive response in any of the bacterial tester strains, either with or without metabolic activation.

The mutagenicity of 1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane (DDC) was evaluated in Salmonella tester strains TA98, TA100, TA1535, TA1537 and TA1538 (Ames Test), both in the presence and absence of added metabolic activation by Aroclor-induced rat liver S9 fraction. Based on preliminary bacterial toxicity determinations, DDC, diluted in DMSO, was tested for mutagenicity at concentrations up to 1000 ug/plate using the plate incorporation method. DDC did not cause a positive response in any of the bacterial tester strains, either with or without metabolic activation.

URBAN/SUBURBAN: 1,2-Dibromo-4-(1,2-dibromoethyl)cyclohexane was present at a median concentration of 0.46 pg/cu m (0.18-2.4 pg/cu m) in air from seven locations in and around Stockholm, Sweden, collected from April 30 to June 4, 2012(1).

INDOOR: 1,2-Dibromo-4-(1,2-dibromoethyl)cyclohexane concentrations ranged from <6.3-780 pg/cu m (42 pg/cu m median) in ventilation air samples from five offices, four apartments, four stores and two schools in Stockholm, Sweden, collected from February to May 2012(1).

RURAL/REMOTE: Bimonthly bulk atmospheric deposition samples (precipitation + dry particle) were taken for one year at an arctic (Abisko, 68 deg 20' N, 19deg 03' E) and a sub-arctic (Krycklan 64 deg 14' N, 19 deg 46' E) location in northern Sweden using Amberlite IRA-743 as an absorbent for hydrophobic pollutants. The samples were analyzed by gas chromatography-high resolution mass spectrometry (GC-HRMS) for polychlorinated biphenyls (PCBs), legacy organochlorine pesticides (OCPs = hexachlorocyclohexanes and chlordane-related compounds), polybrominated diphenyl ethers (PBDEs) and emerging chemicals. Higher deposition rates of most compounds were observed at the more northern site despite its receiving less precipitation and being more remote. HCHs and PCBs made up the bulk of the total deposition at both sites. Five emerging chemicals were detected: the current-use pesticides trifluralin and chlorothalonil; and non-BDE flame retardants 1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane (TBECH), 1,2-bis(2,4,6-tribromophenoxy) ethane (BTBPE), and Dechlorane Plus (DP). A decrease in the fraction of the anti isomer of DP was observed at the arctic site, indicating isomer-selective degradation or isomerization during long range transport. Air parcel back trajectories revealed a greater influence from air originating over the ocean at the more northern site. The differences in these air sources were reflected in higher total HCH to total PCB ratios compared to the more southern site, as HCHs are related to volatilization from the ocean and Abisko is located <100 km from the Norwegian coast, while PCBs are emitted from continental sources.

/ENDOCRINE MODULATION/ Reported incidences of prostate cancer and masculinization of animals indicate a release of compounds with androgenic properties into the environment. Large numbers of environmental pollutants have been screened to identify such compounds; however, not until recently was 1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane (TBECH) identified as the first potent activator of the human androgen receptor (hAR). TBECH has been found in beluga whales and bird eggs and has also been found to be maternally transferred in zebrafish. In the present study we investigated interaction energies between TBECH diastereomers (alpha, beta, gamma, and delta) and the hAR, and their ability to activate the receptor and induce prostate-specific antigen (PSA) expression in vitro. We performed computational modeling to determine interaction energies between the ligand and the AR ligand-binding site, and measured in vitro competitive binding assays for AR by polarization fluorometry analysis. We used enzyme-linked immunosorbent assays to determine PSA activity in LNCaP and HepG2 cells. We found the gamma and delta diastereomers to be more potent activators of hAR than the alpha and beta diastereomers, which was confirmed in receptor binding studies. All TBECH diastereomers induced PSA expression in LNCaP cells even though the AR present in these cells is mutated (T877A). Modeling studies of LNCaP AR revealed that TBECH diastereomers bound to the receptor with a closer distance to the key amino acids in the ligand-binding domain, indicating stronger binding to the mutated receptor. The present study demonstrates the ability of TBECH to activate the hAR, indicating that it is a potential endocrine disruptor.

/ENDOCRINE MODULATION/ Endocrine disrupting compounds can interfere with androgen receptor (AR) signaling and disrupt steroidogenesis leading to reproductive failure. The brominated flame-retardant (BFR) 1, 2-dibromo-4-(1, 2-dibromoethyl) cyclohexane (TBECH), is an agonist to human, chicken and zebrafish AR. Recently another group of alternative BFRs, allyl 2, 4, 6-tribromophenyl ether (ATE), and 2, 3-dibromopropyl 2, 4, 6-tribromophenyl ether (DPTE) along with its metabolite 2-bromoallyl 2, 4, 6-tribromophenyl ether (BATE) were identified as potent human AR antagonists. These alternative BFRs are present in the environment. The aim of the present study was to determine the effect of mixed exposures to the AR agonist and the AR antagonists at environmentally relevant concentrations. In vitro reporter luciferase assay showed that the AR antagonists, when present at concentration higher than TBECH, were able to inhibit TBECH-mediated AR activity. These AR antagonists also promoted AR nuclear translocation. In vitro gene expression analysis in the non-tumorigenic human prostate epithelial cell RWPE1 showed that TBECH induced AR target genes whereas DPTE repressed these genes. Further analysis of steroidogenic genes showed that TBECH up-regulated most of the genes while DPTE down-regulated the same genes. The results indicate that when TBECH and DPTE are present together they will antagonize each other, thereby reducing their individual effects.

beta-1,2-Dibromo-4-(1,2-dibromoethyl)cyclohexane concentrations in plankton, invertebrates and fish from Lake Taihu, South China, collected in August 2014 and May 2015. The method detection limits (MDL) were 1.6 and 48 pg/g wet weight (ww), respectively. alpha-1,2-Dibromo-4-(1,2-dibromoethyl)cyclohexane was only detected in silver fish, concentration range of 134-208 pg/g ww(1).[Table#5722]

Pursuant to section 8(d) of TSCA, EPA promulgated a model Health and Safety Data Reporting Rule. The section 8(d) model rule requires manufacturers, importers, and processors of listed chemical substances and mixtures to submit to EPA copies and lists of unpublished health and safety studies. 1,2-Dibromo-4-(1,2-dibromoethyl)cyclohexane is included on this list. Effective date: 6/28/84; Sunset date: 12/29/88.

Used as a fire-retardant additive (polystyrene, polyurethane, polyvinyl chloride); [HSDB]

Additive flame retardant. /From table/

Low-density polystyrene foam: A total of 1-2 parts of hexabromocyclododecane, pentabromomonochlorocyclohexane (Dow Chemical 651P), and dibromoethyldibromocyclohexane (Ethyl Saytex BCL-462 flame retardant) are adequate to produce foam that meets building code requirements in the United States.

Fire-retardant additive (polystyrene, polyurethane, polyvinyl chloride)

Cyclohexane, 1,2-dibromo-4-(1,2-dibromoethyl)-: INACTIVE

Additive brominated flame retardant used in domestic and industrial applications ... was used to investigate the biodegradation kinetics in aerobic and anaerobic soil