This section of the FEDERAL REGISTER

contains notices to the public of the proposed

issuance of rules and regulations. The

purpose of these notices is to give interested

persons an opportunity to participate in the

rule making prior to the adoption of the final

rules.

Proposed Rules Federal Register

35275 

Vol. 81, No. 106 

Thursday, June 2, 2016 

DEPARTMENT OF THE TREASURY 

Internal Revenue Service 

26 CFR Part 1 

[REG–135734–14] 

RIN 1545–BM45 

Inversions and Related Transactions; 

Correction 

AGENCY: Internal Revenue Service (IRS), 

Treasury. 

ACTION: Correction to a notice of 

proposed rulemaking by cross-reference 

to temporary regulation. 

SUMMARY: This document contains 

corrections to a notice of proposed 

rulemaking by cross-reference to 

temporary regulations (REG–135734–14) 

that were published in the Federal 

Register on Friday, April 8, 2016 (81 FR 

20588). The proposed regulations relate 

to transactions that are structured to 

avoid the purposes of sections 7874 and 

367 of the Internal Revenue Code (the 

Code) and certain post-inversion tax 

avoidance transactions. 

DATES: Written or electronic comments 

and requests for a public hearing for the 

notice of proposed rulemaking 

published at 81 FR 20588, April 8, 2016 

are still being accepted and must be 

received by July 7, 2016. 

FOR FURTHER INFORMATION CONTACT: 

Concerning the proposed regulations 

under sections 304, 367, and 7874, 

Shane M. McCarrick or David A. Levine, 

(202) 317–6937; concerning the 

proposed regulations under sections 956 

and 770 (l), Rose E. Jenkins (202) 317– 

6934; concerning submissions or 

comments or requests for a public 

hearing, Regina Johnson 202–317–6901 

(not toll-free numbers). 

SUPPLEMENTARY INFORMATION: 

Background 

The notice of proposed rulemaking by 

cross-reference to temporary regulations 

(REG–135734–14) that is the subject of 

this correction is under sections 304, 

367, 956, 7701(l), and 7874 of the 

Internal Revenue Code. 

Need for Correction 

As published, the notice of proposed 

rulemaking by cross-reference to 

temporary regulations (REG–135734–14) 

contains errors that may prove to be 

misleading and are in need of 

clarification. 

Correction of Publication 

Accordingly, the notice of proposed 

rulemaking by cross-reference to 

temporary regulations (REG–135734–14) 

that was the subject of FR Doc. 2016– 

07299 is corrected as follows: 

■ 1. On page 20588, in the preamble, in 

the ‘‘Background’’ paragraph, in the fifth 

line, the language ‘‘954, 956, 7701(l), 

and 7874 of the’’ is corrected to read 

‘‘956, 7701(l), and 7874 of the’’. 

§ 1.7874–4 [Corrected] 

■ 2. On page 20590, second column, 

seventh line of paragraph (c)(1)(ii), the 

language ‘‘(ii) [Reserved].’’ is corrected 

to read ‘‘(ii) introductory text through 

(ii)(A) [Reserved].’’. 

■ 3. On page 20590, second column, 

second line of paragraph (i)(7), the 

language ‘‘(i)(7)(iii) introductory text 

[Reserved].’’ is corrected to read 

‘‘(i)(7)(iii)(B) [Reserved].’’. 

■ 4. On page 20590, third column, first 

and second line of paragraph (j), the 

language ‘‘(j) introductory text through 

(j)(6) [Reserved].’’ is corrected to read 

‘‘(i)(8) through (j)(6) [Reserved]’’. 

Martin V. Franks, 

Chief, Publications and Regulations Branch, 

Associate Chief Counsel, (Procedure and 

Administration). 

[FR Doc. 2016–13015 Filed 6–1–16; 8:45 am] 

BILLING CODE 4830–01–P 

ENVIRONMENTAL PROTECTION 

AGENCY 

40 CFR Part 372 

[EPA–HQ–TRI–2015–0607; FRL–9943–55] 

RIN 2025–AA42 

Addition of Hexabromocyclododecane 

(HBCD) Category; Community Rightto-Know Toxic Chemical Release 

Reporting 

AGENCY: Environmental Protection 

Agency (EPA). 

ACTION: Proposed rule. 

SUMMARY: EPA is proposing to add a 

hexabromocyclododecane (HBCD) 

category to the list of toxic chemicals 

subject to reporting under section 313 of 

the Emergency Planning and 

Community Right-to-Know Act (EPCRA) 

and section 6607 of the Pollution 

Prevention Act (PPA). EPA is proposing 

to add this chemical category to the 

EPCRA section 313 list because EPA 

believes HBCD meets the EPCRA section 

313(d)(2)(B) and (C) toxicity criteria. 

Specifically, EPA believes that HBCD 

can reasonably be anticipated to cause 

developmental and reproductive effects 

in humans and is highly toxic to aquatic 

and terrestrial organisms. In addition, 

based on the available bioaccumulation 

and persistence data, EPA believes that 

HBCD should be classified as a 

persistent, bioaccumulative, and toxic 

(PBT) chemical and assigned a 100- 

pound reporting threshold. Based on a 

review of the available production and 

use information, members of the HBCD 

category are expected to be 

manufactured, processed, or otherwise 

used in quantities that would exceed a 

100-pound EPCRA section 313 reporting 

threshold. 

DATES: Comments must be received on 

or before August 1, 2016. 

ADDRESSES: Submit your comments, 

identified by Docket ID No. EPA–HQ– 

TRI–2015–0607, by one of the following 

methods: 

• Federal eRulemaking Portal: http:// 

www.regulations.gov. Follow the online 

instructions for submitting comments. 

Do not submit electronically any 

information you consider to be 

Confidential Business Information (CBI) 

or other information whose disclosure is 

restricted by statute. 

• Mail: Document Control Office 

(7407M), Office of Pollution Prevention 

and Toxics (OPPT), Environmental 

Protection Agency, 1200 Pennsylvania 

Ave. NW., Washington, DC 20460–0001. 

• Hand Delivery: To make special 

arrangements for hand delivery or 

delivery of boxed information, please 

follow the instructions at http://

www.epa.gov/dockets/where-sendcomments-epa-dockets#hq. 

Additional instructions on commenting 

or visiting the docket, along with more 

information about dockets generally, is 

available at http://www.epa.gov/

dockets/commenting-epa-dockets. 


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35276 Federal Register / Vol. 81, No. 106 / Thursday, June 2, 2016 / Proposed Rules 

FOR FURTHER INFORMATION CONTACT:

For technical information contact: 

Daniel R. Bushman, Toxics Release 

Inventory Program Division (7409M), 

Office of Pollution Prevention and 

Toxics, Environmental Protection 

Agency, 1200 Pennsylvania Ave. NW., 

Washington, DC 20460–0001; telephone 

number: (202) 566–0743; email: 

bushman.daniel@epa.gov. 

For general information contact: The 

Emergency Planning and Community 

Right-to-Know Hotline; telephone 

numbers: toll free at (800) 424–9346 

(select menu option 3) or (703) 412– 

9810 in Virginia and Alaska; or toll free, 

TDD (800) 553–7672; or go to http://

www.epa.gov/superfund/contacts/

infocenter/. 

SUPPLEMENTARY INFORMATION: 

I. General Information 

A. Does this notice apply to me? 

You may be potentially affected by 

this action if you manufacture, process, 

or otherwise use HBCD. The following 

list of North American Industrial 

Classification System (NAICS) codes is 

not intended to be exhaustive, but rather 

provides a guide to help readers 

determine whether this document 

applies to them. Potentially affected 

entities may include: 

• Facilities included in the following 

NAICS manufacturing codes 

(corresponding to Standard Industrial 

Classification (SIC) codes 20 through 

39): 311*, 312*, 313*, 314*, 315*, 316, 

321, 322, 323*, 324, 325*, 326*, 327, 

331, 332, 333, 334*, 335*, 336, 337*, 

339*, 111998*, 211112*, 212324*, 

212325*, 212393*, 212399*, 488390*, 

511110, 511120, 511130, 511140*, 

511191, 511199, 512220, 512230*, 

519130*, 541712*, or 811490*. 

* Exceptions and/or limitations exist for 

these NAICS codes. 

• Facilities included in the following 

NAICS codes (corresponding to SIC 

codes other than SIC codes 20 through 

39): 212111, 212112, 212113 

(corresponds to SIC code 12, Coal 

Mining (except 1241)); or 212221, 

212222, 212231, 212234, 212299 

(corresponds to SIC code 10, Metal 

Mining (except 1011, 1081, and 1094)); 

or 221111, 221112, 221113, 221118, 

221121, 221122, 221330 (Limited to 

facilities that combust coal and/or oil 

for the purpose of generating power for 

distribution in commerce) (corresponds 

to SIC codes 4911, 4931, and 4939, 

Electric Utilities); or 424690, 425110, 

425120 (Limited to facilities previously 

classified in SIC code 5169, Chemicals 

and Allied Products, Not Elsewhere 

Classified); or 424710 (corresponds to 

SIC code 5171, Petroleum Bulk 

Terminals and Plants); or 562112 

(Limited to facilities primarily engaged 

in solvent recovery services on a 

contract or fee basis (previously 

classified under SIC code 7389, 

Business Services, NEC)); or 562211, 

562212, 562213, 562219, 562920 

(Limited to facilities regulated under the 

Resource Conservation and Recovery 

Act, subtitle C, 42 U.S.C. 6921 et seq.) 

(corresponds to SIC code 4953, Refuse 

Systems). 

• Federal facilities. 

To determine whether your facility 

would be affected by this action, you 

should carefully examine the 

applicability criteria in part 372, subpart 

B of Title 40 of the Code of Federal 

Regulations. If you have questions 

regarding the applicability of this action 

to a particular entity, consult the person 

listed under FOR FURTHER INFORMATION

CONTACT. 

B. What action is the Agency taking? 

EPA is proposing to add a 

hexabromocyclododecane (HBCD) 

category to the list of toxic chemicals 

subject to reporting under EPCRA 

section 313 and PPA section 6607. As 

discussed in more detail later in this 

document, EPA is proposing to add this 

chemical category to the EPCRA section 

313 list because EPA believes HBCD 

meets the EPCRA section 313(d)(2)(B) 

and (C) toxicity criteria. 

C. What is the Agency’s authority for 

taking this action? 

This action is issued under EPCRA 

sections 313(d) and 328, 42 U.S.C. 

11023 et seq., and PPA section 6607, 42 

U.S.C. 13106. EPCRA is also referred to 

as Title III of the Superfund 

Amendments and Reauthorization Act 

of 1986. 

Section 313 of EPCRA, 42 U.S.C. 

11023, requires certain facilities that 

manufacture, process, or otherwise use 

listed toxic chemicals in amounts above 

reporting threshold levels to report their 

environmental releases and other waste 

management quantities of such 

chemicals annually. These facilities 

must also report pollution prevention 

and recycling data for such chemicals, 

pursuant to section 6607 of the PPA, 42 

U.S.C. 13106. Congress established an 

initial list of toxic chemicals that 

comprised 308 individually listed 

chemicals and 20 chemical categories. 

EPCRA section 313(d) authorizes EPA 

to add or delete chemicals from the list 

and sets criteria for these actions. 

EPCRA section 313(d)(2) states that EPA 

may add a chemical to the list if any of 

the listing criteria in EPCRA section 

313(d)(2) are met. Therefore, to add a 

chemical, EPA must demonstrate that at 

least one criterion is met, but need not 

determine whether any other criterion is 

met. Conversely, to remove a chemical 

from the list, EPCRA section 313(d)(3) 

dictates that EPA must demonstrate that 

none of the following listing criteria in 

EPCRA section 313(d)(2)(A)–(C) are met: 

• The chemical is known to cause or 

can reasonably be anticipated to cause 

significant adverse acute human health 

effects at concentration levels that are 

reasonably likely to exist beyond facility 

site boundaries as a result of 

continuous, or frequently recurring, 

releases. 

• The chemical is known to cause or 

can reasonably be anticipated to cause 

in humans: Cancer or teratogenic effects, 

or serious or irreversible reproductive 

dysfunctions, neurological disorders, 

heritable genetic mutations, or other 

chronic health effects. 

• The chemical is known to cause or 

can be reasonably anticipated to cause, 

because of its toxicity, its toxicity and 

persistence in the environment, or its 

toxicity and tendency to bioaccumulate 

in the environment, a significant 

adverse effect on the environment of 

sufficient seriousness, in the judgment 

of the Administrator, to warrant 

reporting under this section. 

EPA often refers to the EPCRA section 

313(d)(2)(A) criterion as the ‘‘acute 

human health effects criterion;’’ the 

EPCRA section 313(d)(2)(B) criterion as 

the ‘‘chronic human health effects 

criterion;’’ and the EPCRA section 

313(d)(2)(C) criterion as the 

‘‘environmental effects criterion.’’ 

EPA published in the Federal 

Register of November 30, 1994 (59 FR 

61432) (FRL–4922–2), a statement 

clarifying its interpretation of the 

EPCRA section 313(d)(2) and (d)(3) 

criteria for modifying the EPCRA 

section 313 list of toxic chemicals. 

II. Background Information 

A. What is HBCD? 

HBCD is a cyclic aliphatic 

hydrocarbon consisting of a 12- 

membered carbon ring with 6 bromine 

atoms attached (molecular formula 

C12H18Br6). HBCD has 16 possible 

stereoisomers. Technical grades of 

HBCD consist predominantly of three 

diastereomers, a-, +- and g-HBCD (Ref. 

1). HBCD may be designated as a nonspecific mixture of all isomers 

(hexabromocyclododecane, Chemical 

Abstracts Service Registry Number 

(CASRN) 25637–99–4) or as a mixture of 

the three main diastereomers 

(1,2,5,6,9,10-hexabromocyclododecane, 

CASRN 3194–55–6) (Ref 1). The main 

use of HBCD is as a flame retardant in 

expanded polystyrene foam (EPS) and 


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extruded polystyrene foam (XPS) (Ref. 

2). EPS and XPS are used primarily for 

thermal insulation boards in the 

building and construction industry. 

HBCD may also be used as a flame 

retardant in textiles including: 

upholstered furniture, upholstery 

seating in transportation vehicles, 

draperies, wall coverings, mattress 

ticking, and interior textiles, such as 

roller blinds (Ref. 2). In addition, HBCD 

is used as a flame retardant in highimpact polystyrene for electrical and 

electronic appliances such as audiovisual equipment, as well as for some 

wire and cable applications (Ref. 2). 

Concerns for releases and uses of 

HBCD have been raised because it is 

found world-wide in the environment 

and wildlife and has also been found in 

human breast milk, adipose tissue and 

blood (Ref. 1). HBCD is known to 

bioaccumulate and biomagnify in the 

food chain and has been detected over 

large areas and in remote locations in 

environmental monitoring studies 

(Ref. 1). 

B. How is EPA proposing to list HBCD 

under EPCRA section 313? 

HBCD is identified through two 

primary CASRNs 3194–55–6 

(1,2,5,6,9,10-hexabromocyclododecane) 

and 25637–99–4 

(hexabromocyclododecane) (Ref. 1). 

EPA is proposing to create an HBCD 

category that would cover these two 

chemical names and CASRNs. The 

HBCD category would be defined as: 

Hexabromocyclododecane and would 

only include those chemicals covered 

by the following CAS numbers: 

• 3194–55–6; 1,2,5,6,9,10- 

Hexabromocyclododecane. 

• 25637–99–4; 

Hexabromocyclododecane. 

As a category, facilities that 

manufacture, process or otherwise use 

HBCD covered under both of these 

names and CASRNs would file just one 

report. 

In addition to listing HBCD as a 

category, EPA is proposing to add the 

HBCD category to the list of chemicals 

of special concern. There are several 

chemicals and chemical categories on 

the EPCRA section 313 chemical list 

that have been classified as chemicals of 

special concern because they are PBT 

chemicals (see 40 CFR 372.28(a)(2)). In 

a final rule published in the Federal 

Register of October 29, 1999 (64 FR 

58666) (FRL–6389–11), EPA established 

the PBT classification criteria for 

chemicals on the EPCRA section 313 

chemical list. For purposes of EPCRA 

section 313 reporting, EPA established 

persistence half-life criteria for PBT 

chemicals of 2 months in water/

sediment and soil and 2 days in air, and 

established bioaccumulation criteria for 

PBT chemicals as a bioconcentration 

factor (BCF) or bioaccumulation factor 

(BAF) of 1,000 or higher. Chemicals 

meeting the PBT criteria were assigned 

100-pound reporting thresholds. With 

regards to setting the EPCRA section 313 

reporting thresholds, EPA set lower 

reporting thresholds (10 pounds) for 

those PBT chemicals with persistence 

half-lives of 6 months or more in water/ 

sediment or soil and with BCF or BAF 

values of 5,000 or higher, these 

chemicals were considered highly PBT 

chemicals. The data presented in this 

proposed rule support classifying the 

HBCD category as a PBT chemical 

category with a 100-pound reporting 

threshold. 

III. What is EPA’s evaluation of the 

toxicity, bioaccumulation, and 

environmental persistence of HBCD? 

EPA evaluated the available literature 

on the human health toxicity, ecological 

toxicity, bioaccumulation potential, and 

environmental persistence of HBCD 

(Ref. 1). Unit III.A. provides a review of 

the human health toxicity studies and 

EPA’s conclusions regarding the human 

health hazard potential of HBCD. Unit 

III.B. discusses the ecological toxicity of 

HBCD, Unit III.C. contains information 

on the bioaccumulation potential of 

HBCD, and Unit III.D. provides 

information on the environmental 

persistence of HBCD. 

A. What is EPA’s review of the human 

health toxicity data for HBCD? 

1. Toxicokinetics. HBCD is absorbed 

via the gastrointestinal tract and 

metabolized in rodents (Refs. 3, 4, 5, 

and 6). Once absorbed, HBCD is 

distributed to a number of tissues, 

including fatty tissue, muscle, and the 

liver (Refs. 7, 8, 9, 10, 11, and 12). 

Elimination of HBCD is predominantly 

via feces (as the parent compound), but 

it is also eliminated in urine (as 

secondary metabolites) (Refs. 3, 4, and 

5). HBCD has been detected in human 

milk, adipose tissue, and blood (Refs. 

13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 

and 24). The composition of HBCD 

isomers in most rodent toxicity studies 

resembles that of industrial grade 

HBCD, which may differ from human 

exposure to certain foods that have been 

shown to contain elevated fractions of 

a-HBCD (Ref. 25). 

2. Effects of acute exposure. HBCD 

was not found to be highly toxic in 

acute oral, inhalation, and dermal 

studies in rodents. One study reported 

an oral median lethal dose (LD50) of 

>10,000 milligrams per kilogram (mg/

kg) in Charles River rats (Ref. 26). 

Another study by the same researchers, 

however, reported an LD50 of 680 mg/kg 

for females and 1,258 mg/kg for males 

in Charles River CD rats (Ref. 27). Two 

other studies reported an oral LD50 of 

>5,000 mg/kg in Sprague-Dawley rats 

and >10,000 mg/kg in NR rats (Refs. 28 

and 29). An oral study in NR mice 

reported an LD50 of >6,400 mg/kg (Ref. 

30). Acute inhalation studies in rats 

have generally concluded that HCBD is 

not highly toxic, with a median lethal 

concentration (LC50) reported by Gulf 

South Research Institute of >200 

milligrams per liter (mg/L) (Refs. 26, 27, 

29, 31). Acute dermal toxicity studies 

have generally shown HBCD not to be 

highly toxic in rabbits (Refs. 27, 29, 31, 

and 32). One dermal study reported an 

LD50 of 3,969 mg/kg (Ref. 27). 

Additionally, HBCD is not a dermal 

irritant in rabbits (Refs. 27, 29, and 31), 

but it is a mild skin allergen in guinea 

pigs (Ref. 32). Acute eye irritation 

studies have concluded that HBCD is a 

primary eye irritant (Ref. 27) and a mild, 

transient ocular irritant (Ref. 29). 

3. Effects of short-term and 

subchronic exposure. In subacute and 

subchronic studies, HBCD demonstrated 

effects on the thyroid and liver (Refs. 8, 

33, 34, and 35). In a subacute study, van 

der Ven et al. (Ref. 8) exposed Wistar 

rats (5/sex/dose) by gavage to a mixture 

of HBCD dissolved in corn oil at 

concentrations resulting in doses of 0.3, 

1.0, 3.0, 10, 30, 100, and 200 milligrams 

per kilogram per day (mg/kg/day) for 28 

days. The isomeric composition of the 

HBCD was 10.3% a, 8.7% b, and 81.0% 

g. The authors reported a benchmark 

dose lower bound confidence limit 

(BMDL) of 29.9 mg/kg/day for an 

increase in pituitary weight, a BMDL of 

1.6 mg/kg/day for an increase in thyroid 

weight, and a BMDL of 22.9 mg/kg/day 

for an increase in liver weight. The 

increase in thyroid weight was the most 

sensitive end point observed and, 

according to research by EPA, is 

considered relevant to humans (Ref. 36). 

Additionally, histopathology of the 

thyroid demonstrated that thyroid 

follicles were smaller, depleted, and had 

hypertrophied epithelium in female 

rats. 

In another subacute study, HBCD was 

administered orally by gavage in corn 

oil to Sprague-Dawley Crl:CD BR rats for 

28 days at doses of 0, 125, 350, or 1,000 

mg/kg/day (6 rats/sex/dose in 125 and 

350 mg/kg/day groups and 12 rats/sex/ 

dose in the control and 1,000 mg/kg/day 

groups) (Ref. 33). At the end of 28 days, 

6 rats/sex/dose were necropsied, while 

the remaining rats in the control and 

1,000 mg/kg/day groups were untreated 

for a 14-day recovery period prior to 

necropsy. The authors reported 


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increased absolute and liver to body 

weight ratios in females, but the authors 

considered the findings to be adaptive 

and not adverse. This study also 

identified a no-observed-adverse-effect 

level (NOAEL) of 1,000 mg/kg/day. 

In an older subacute study (Ref. 37), 

an HBCD product was administered to 

Sprague-Dawley rat (10/sex/group) at 

doses of 0, 1, 2.5, and 5% of the diet for 

28 days. Doses were calculated to be 0, 

940, 2,410, 4,820 mg/kg/day. Mean liver 

weight (both absolute and relative) was 

increased in all dose groups, but no 

microscopic pathology was detected. 

Thyroid hyperplasia was observed in 

some animals at all doses in addition to 

slight numerical development of the 

follicles and ripening follicles in the 

ovaries at the high dose. The authors 

concluded that these observed effects 

were not pathologic and reported a 

NOAEL of 940 mg/kg/day (Ref. 37). 

In a subchronic study, Chengelis 

(Refs. 34 and 35) administered HBCD by 

oral gavage in corn oil daily to 

Crl:CD(SD)IGS BR rats (15/sex/dose) at 

dose levels of 0, 100, 300, or 1,000 mg/ 

kg/day for 90 days. At the end of 90 

days, 10 rats/sex/dose were necropsied, 

while the remaining rats were untreated 

for a 28-day recovery period prior to 

necropsy. The authors reported 

significant treatment-related changes in 

rats, including decreased liver weight 

and histopathological changes, but the 

authors considered these changes mild, 

reversible, and adaptive. Decreased liver 

weight accompanied by the observed 

histopathological changes, however, can 

be considered an adverse effect. 

Therefore, EPA identified a lowestobserved-adverse-effect level (LOAEL) 

of 100 mg/kg/day based on these 

changes. 

In an older subchronic study (Ref. 38) 

an HBCD product was administered to 

Sprague-Dawley rats (10/sex/group) at 

doses of 0, 0.16, 0.32, 0.64, and 1.28% 

of the diet for 90 days. Doses were 

calculated to be 0, 120, 240, 470, and 

950 mg/kg/day. An increase in relative 

liver weight was observed and was 

accompanied by fatty accumulation. 

The pathology report concluded that 

although fat was visible microscopically 

in treated rats, the change was not 

accompanied by any pathology, and 

therefore could not be defined as ‘‘fatty 

liver.’’ No histological changes were 

found in any other organ. The authors 

concluded that the increased liver 

weight and the fat deposits, both of 

which were largely reversible when 

administration of HBCD was stopped, 

were the result of a temporary increase 

in the activity of the liver. They 

identified a NOAEL of 950 mg/kg/day. 

4. Carcinogenicity. No adequate 

studies were found evaluating the 

carcinogenicity of HBCD in animals or 

humans. One non-guideline study (Ref. 

39) was cited in the U.S. EPA’s Flame 

Retardant Alternatives for 

Hexabromocyclododecane (HBCD): 

Final Report (Ref. 40), but this study 

was not adequate to draw conclusions 

regarding carcinogenicity. 

5. Developmental and reproductive 

toxicity. The developmental and 

reproductive toxicity of HBCD have 

been investigated in several studies. In 

a 1-generation study that included 

additional immunological, endocrine 

and neurodevelopmental endpoints, van 

der Ven et al. (Ref. 9) exposed Wistar 

rats (10/sex/dose) to a composite 

mixture of technical-grade HBCD 

(10.3% a, 8.7% b, and 81.0% g) in the 

diet at concentrations resulting in doses 

of 0.1, 0.3, 1.0, 3.0, 10, 30, or 100 mg/ 

kg/day. In the highest dose group (100 

mg/kg/day) body weight decreases of 

7–36% in males and 10–20% in females 

were observed in first generation (F1) 

pups. The authors observed decreases in 

kidney and thymus weight in both F1 

males and females. Decreases in testes, 

adrenal, prostate, heart, and brain 

weights in F1 males were also observed. 

No histopathological changes, however, 

were observed in any of these organs. 

Other developmental effects were 

observed, including: Immune system 

effects, indications of liver toxicity, and 

decreases in bone mineral density at 

very low doses (i.e., <1.3 mg/kg/day). 

The authors noted that the vehicle used 

(corn oil) may have affected some 

observations at higher doses, including: 

Increased mortality during lactation, 

decreased liver weight in males, 

decreased adrenal weight in females, 

decreased plasma cholesterol in 

females, and other immunological 

markers of toxicity. Increased anogenital 

distance was observed in males at 100 

mg/kg on postnatal day (PND) 4, but not 

on PND 7 or 21. There was no effect on 

preputial separation. The time to 

vaginal opening was delayed in females 

at the 100 mg/kg dose. There were no 

effects of HBCD exposure on thyroid 

hormones triiodothyronine (T3) and 

thyroxine (T4) in either the parental or 

F1 animals. There were no effects on 

thyroid weight or thyroid pathology in 

the F1 animals (parents were not 

examined). The most sensitive 

endpoints with valid benchmark dose 

(BMD)/BMDL ratios for female rats were 

decreased bone mineral density with a 

BMDL of 0.056 mg/kg/day (BMD of 0.18 

mg/kg/day) at a benchmark response 

(BMR) of 10% and decreased 

concentrations of apolar retinoids in the 

liver with a BMDL of 1.3 mg/kg/day 

(BMD = 5.1 mg/kg/day) at a BMR of 

10%. The most sensitive endpoint with 

a valid BMD/BMDL ratio for male rats 

was an increased IgG response to sheep 

red blood cells with a BMDL of 0.46 mg/ 

kg/day (BMD = 1.45 mg/kg/day) at a 

BMR of 20%. There were no significant 

effects of HBCD exposure on any 

measure of reproduction, including: 

Mating success, time to gestation, 

duration of gestation, number of 

implantation sites, pup mortality (at 

birth and throughout lactation), or sex 

ratios within a litter. Therefore, a BMDL 

for reproductive toxicity could not be 

derived for this study. 

Saegusa et al. (Ref. 41) exposed 

pregnant Sprague-Dawley rats (10/sex/

dose) to HBCD from gestation day 10 

until PND 20 at dietary concentrations 

of 0, 100, 1,000, or 10,000 parts per 

million (ppm) in a soy-free diet. The 

authors observed increased relative 

thyroid weight and decreased T3 levels 

in F1 male Sprague-Dawley rats at 

postnatal week (PNW) 11 following 

dietary exposure to 1,000 ppm 

(approximately 146.3 mg/kg/day) HBCD. 

The authors also reported a significant 

reduction in the number of CNPasepositive oligodendrocytes at 10,000 ppm 

(approximately 1,504.8 mg/kg/day). EPA 

identified a maternal LOAEL of 10,000 

ppm (about 1,504.8 mg/kg/day) based 

on increased incidence of thyroid 

follicular cell hypertrophy, and a 

developmental LOAEL of 1,000 ppm 

(about 146.3 mg/kg/day) based on 

increased relative thyroid weight and 

decreased T3 levels in F1 males at PNW 

11. Changes in reproductive endpoints 

(e.g., the number of implantation sites, 

live offspring, sex ratio) were not 

observed. Therefore, a LOAEL for 

reproductive toxicity could not be 

determined for this study. 

Ema et al. (Ref. 42) administered 

HBCD to groups of male and female 

Crl:CD(SD) rats (24/sex/dose, as a 

mixture of a-HBCD, b -HBCD, and gHBCD with proportions of 8.5, 7.9, and 

83.7%, respectively) in the diet at 

concentrations of 0, 150, 1,500, or 

15,000 ppm from 10 weeks prior to 

mating through mating, gestation, and 

lactation. The authors reported a 

decrease in the number of primordial 

follicles in F1 female rats at 1,500 ppm 

(approximately 138 mg/kg/day) and a 

significant increase in the number of 

litters lost in the F1 generation at 15,000 

ppm (approximately 1,363 mg/kg/day). 

These authors reported no other 

significant treatment-related effects in 

any generation for indicators of 

reproductive health, including: Estrous 

cyclicity, sperm count and morphology, 

copulation index, fertility index, 


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gestation index, delivery index, 

gestation length, number of pups 

delivered, number of litters, or sex 

ratios. The authors reported a reduced 

viability index on day 4 and day 21 of 

lactation among second generation (F2) 

offspring at 15,000 ppm (approximately 

1,363 mg/kg/day). They observed 

additional developmental effects at 

doses as low as 1,500 ppm 

(approximately 115 and 138 mg/kg/day 

for F1 males and females, respectively), 

including: An increase in 

dihydrotestosterone (DHT) in F1 males 

and an increased incidence of animals 

with decreased thyroid follicle size in 

both sexes and generations. These 

authors reported no effects on sexual 

development indicated by anogenital 

distance, vaginal opening, or preputial 

separation among F1 or F2 generations. 

The percentage of pups with completed 

eye opening on PND 14 was 

significantly decreased compared to 

controls in F2 females at 1,500 ppm and 

in F2 males and females at 15,000 ppm. 

Fewer F2 females exposed to 15,000 

ppm HBCD completed the mid-air 

righting reflex (76.9%) than control F2 

females (100%). These findings were 

not consistent over generations or sexes 

and were not considered treatment 

related. No other effects of HBCD 

exposure on the development of reflexes 

were observed in either F1 or F2 

progeny. EPA identified a maternal 

LOAEL of 150 ppm (about 14 mg/kg/

day) based on increased thyroidstimulating hormone (TSH). A 

reproductive LOAEL of 1,500 ppm 

(about 138 mg/kg/day) was identified 

based on a decreased number of 

primordial follicles in the ovary 

observed in F1 females. A 

developmental LOAEL of 15,000 ppm 

(about 1,142 mg/kg/day for males and 

1,363 mg/kg/day for females) was 

identified based on increased pup 

mortality during lactation in the F2 

generation. 

Murai et al. (Ref. 43) fed female 

Wistar rats HBCD in the diet at 

concentrations of 0, 0.01, 0.1, or 1% 

throughout gestation (Days 0–20). Dams 

in the high-dose group demonstrated a 

statistically significant decrease (8.4%) 

in food consumption and increase in 

liver weight (13%) in comparison with 

controls. There were no treatmentrelated effects on maternal or fetal body 

weight. There were no effects on the 

number of implants; number of 

resorbed, dead, or live fetuses; body 

weight of live fetuses; or incidence of 

external or visceral abnormalities. A few 

skeletal variations were present but 

were also observed in controls and not 

considered significant. There were no 

effects on weaning or survival. The 

European Commission (Ref. 44) used the 

study’s data to calculate the doses to be 

0, 7.5, 75, and 750 mg/kg/day (based on 

the assumption of a mean animal weight 

of 200 grams (g) and food consumption 

of 15 g/day). They concluded that the 

offspring NOAEL was 750 mg/kg/day 

and the maternal LOAEL was 750 mg/ 

kg/day based on a 13% liver weight 

increase in the high dose group. 

Eriksson et al. (Ref. 45) conducted a 

study that examined behavior, learning, 

and memory in adult mice following 

exposure to HBCD on PND 10. The 

authors administered a single oral dose 

of HBCD (mixture of, a-, b-, and gdiastereoisomers) dissolved in a fat 

emulsion at 0, 0.9, or 13.5 mg/kg/day on 

PND 10 to male and female NMRI mice. 

The authors concluded that exposure on 

PND 10 affected spontaneous motor 

behavior, learning, and memory in adult 

mice in a dose-dependent manner. The 

authors identified the lowest exposure 

level, 0.9 mg/kg, as the LOAEL based on 

significantly reduced mean locomotor 

activity compared with controls during 

the first 20-minute interval of testing. 

EPA, however, identified a LOAEL of 

13.5 mg/kg/day based on decreased 

habituation, locomotion, and rearing 

during all intervals. This study was not 

conducted according to current 

guidelines (Ref. 46) and Good 

Laboratory Practices; therefore, EPA 

reserves judgment on the significance of 

these findings. 

6. Genotoxicity. A limited number of 

studies investigated the genotoxicity of 

HBCD. These studies indicate that 

HBCD is not likely to be genotoxic (Refs. 

47, 48, 49, 50, 51, 52, 53, and 54). 

7. Conclusions regarding the human 

hazard potential of HBCD. The available 

evidence indicates that HBCD has the 

potential to cause developmental and 

reproductive toxicity at moderately low 

to low doses. While there were some 

indications of liver toxicity in some 

short-term and subchronic studies, the 

evidence for these effects is not 

sufficient to support listing. The 

available evidence for developmental 

and reproductive toxicity, however, is 

sufficient to conclude that HBCD can be 

reasonably anticipated to cause 

moderately high to high chronic toxicity 

in humans based on the EPCRA section 

313 listing criteria published in the 

Federal Register of November 30, 1994 

(59 FR 61432) (FRL–4922–2). 

B. What is EPA’s review of the ecological 

toxicity of HBCD? 

HBCD can cause effects on survival, 

growth, reproduction, development, and 

behavior in aquatic and terrestrial 

species. Observed acute toxicity values 

as low as 0.009 mg/L for a 72-hour EC50

(i.e., the concentration that is effective 

in producing a sublethal response in 

50% of test organisms) based on 

reduced growth in the marine algae 

Skeletonema costatum (Ref. 55) indicate 

high acute aquatic toxicity. Observed 

chronic aquatic toxicity values as low as 

0.0042 mg/L (maximum acceptable 

toxicant concentration (MATC)) for 

reduced size (length) of surviving young 

in water fleas (Daphnia magna) (Ref. 56) 

indicate high chronic aquatic toxicity. 

Reduced chick survival in Japanese 

quails (Coturnix coturnix japonica) fed 

a 15 parts per million (ppm) HBCD diet 

(2.1 mg/kg/day) (Ref. 57 as cited in Ref. 

58) and altered reproductive behavior 

(reduced courtship and brood-rearing 

activity) and reduced egg size in 

American kestrels (Falco sparverius) fed 

0.51 mg/kg/day (Refs. 59, 60, 61, and 62) 

indicate high toxicity to terrestrial 

species as well. 

Assessment of HBCD’s aquatic 

toxicity is complicated by its low water 

solubility and differences in the 

solubility of the three main HBCD 

isomers, which makes testing difficult 

and interpretation uncertain for studies 

conducted above the water solubility. 

Studies conducted at concentrations 

above the water solubility of HBCD are 

essentially testing the effects at the 

maximum HBCD concentration 

possible. In some acute and chronic 

aquatic toxicity studies conducted using 

methods, test species, and endpoints 

recommended by EPA, no effects were 

reported at or near the limit of water 

solubility. However, water solubility is 

not considered a limiting factor for 

hazard determination for aquatic species 

since there are studies showing adverse 

effects at or below the water solubility 

of HBCD. In addition, the potential for 

HBCD to bioaccumulate, biomagnify, 

and persist in the environment, 

significantly increases concerns for 

effects on aquatic organisms. 

A wide range of effects of HBCD have 

been reported in fish (e.g., 

developmental toxicity, embryo 

malformations, reduced hatching 

success, reduced growth, hepatic 

enzyme and biomarker effects, thyroid 

effects, deoxyribonucleic acid (DNA) 

damage to erythrocytes, and oxidative 

damage) and in invertebrates (e.g., 

degenerative changes, morphological 

abnormalities, decreased hatching 

success, and altered enzyme activity) 

(Refs. 63, 64, 65, 66, 67, 68, 69, 70, 71, 

72, 73, and 74). Reduced thyroid 

hormone (triiodothyronine, T3, and 

thyroxine, T4) levels in rainbow trout 

(Oncorhynchus mykiss) (Refs. 68 and 

69), are similar to those observed in 

mammals. Reduced T4 levels were also 


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reported in birds exposed to HBCD 

(Ref. 61). 

1. Acute aquatic toxicity. Adverse 

effects observed following acute 

exposure were found in studies with 

marine algae, including EPArecommended estuarine/marine algae 

species Skeletonema costatum (Ref. 75 

as cited in Refs. 44 and 76, Refs. 55 and 

77), a series of short-term (72 to 120- 

hour) early life stage tests with zebrafish 

(Danio rerio) embryos (Refs. 64, 65, 67, 

and 72), and short-term (72-hour) results 

from an early life stage test with sea 

urchin embryos (Ref. 63). Effects in 

these studies, reported at concentrations 

as low as 0.009 mg/L (measured) in 

algae, 0.01 mg/L (nominal) in zebrafish 

embryos, and 0.064 mg/L (nominal) in 

sea urchin embryos, indicate high acute 

toxicity. Walsh et al. (Ref. 55) reported 

measured 72-hour EC50 values in 

Skeletonema costatum ranging from 

0.009 to 0.012 mg/L based on reduced 

growth rate in five different types of 

saltwater media (0.010 mg/L in seawater 

itself). The study tested two other 

marine algal species, Chlorella sp. and 

Thalassiosira pseudonana, that were 

also found to be inhibited by HBCD, 

albeit at higher concentrations than 

Skeletonema costatum. EC50 values for 

reduced growth in these species were 

0.05–0.37 mg/L (0.08 mg/L in seawater) 

for Thalassiosira pseudonana and >1.5 

mg/L for Chlorella sp. 

Subsequent studies by Desjardins et 

al. (Ref. 75) confirmed the high acute 

toxicity of HBCD to Skeletonema 

costatum. In these studies, single 

concentrations were tested, but the 

assays were conducted without solvent 

and the concentrations were measured. 

Desjardins et al. (Ref. 75) reported 

approximately 10% inhibition of growth 

in Skeletonema costatum exposed to 

0.041 mg/L for 72 hours. Desjardins et 

al. (Ref. 77) found that a saturated 

solution of 0.0545 mg/L resulted in 51% 

growth inhibition after 72 hours of 

exposure. The latter result corresponds 

to an approximate EC50 of 0.052 mg/L. 

Zebrafish embryo studies reported a 

variety of effects on embryos and larvae 

at low HBCD concentrations. In the 

Deng et al. (Ref. 64) study, 

developmental toxicity endpoints were 

assessed at 96 hours post-fertilization in 

embryos/larvae exposed to HBCD 

starting 4 hours post-fertilization. 

Survival of embryos/larvae was 

significantly reduced at all tested 

concentrations, making the low 

concentration of 0.05 mg/L the lowestobserved-effect-concentration (LOEC) in 

this study; a no-observed-effectconcentration (NOEC) was not 

established. Embryonic malformation 

rate was significantly increased and 

larval growth significantly decreased at 

≥0.1 mg/L. Malformations included 

epiboly deformities, yolk sac and 

pericardial edema, tail and heart 

malformations, swim bladder inflation, 

and spinal curvature. Embryo hatching 

rate was reduced only at the high 

concentration of 1 mg/L. Heart rate, a 

marker for cardiac developmental 

toxicity, was significantly decreased at 

all tested concentrations. Associated 

mechanistic studies suggest the 

mechanism for developmental toxicity 

involves the generation of reactive 

oxygen species (ROS) and the 

consequent triggering of apoptosis 

genes. Increased ROS formation 

(indicative of oxidative stress) was 

observed at a nominal concentration of 

0.1 mg/L. In the same study, zebrafish 

embryos exposed to HBCD exhibited 

increased expression of pro-apoptotic 

genes (Bax, P53, Puma, Apaf-1, caspase 

3, and caspase-9), decreased expression 

of anti-apoptotic genes (Mdm2 and 

Bcl-2), and increased activity of 

enzymes involved in apoptosis (caspase3 and caspase-9) with LOECs of 0.05–1 

mg/L. 

Hu et al. (Ref. 67) found that hatching 

of zebrafish embryos was delayed at 

0.002 mg/L, the lowest concentration 

tested, and other concentrations up to 

and including 0.5 mg/L, but not the two 

high concentrations of 2.5 and 10 

mg/L. The same authors observed an 

increase in heat shock protein (Hsp70) 

at 0.01 mg/L and an increase in 

malondialdehyde activity, used as a 

measure of lipid peroxidation, at 0.5 

mg/L. The activity of superoxide 

dismutase was increased at 0.1 mg/L, 

but decreased at 2.5 and 10 mg/L. The 

authors concluded that HBCD can cause 

oxidative stress and over expression of 

Hsp70 in acute exposures of zebrafish 

embryos. 

Du et al. (Ref. 65) exposed zebrafish 

embryos 4 hours post-fertilization to 

each of three diastereomers of HBCD 

(a-, b-, and g-HBCD) individually at 

nominal concentrations of 0.01, 0.1, and 

1.0 mg/L. Hatching success was reduced 

after 68 hours of exposure to g-HBCD at 

the lowest concentration (0.01 mg/L), 

but a higher concentration of a- or 

b-HBCD (0.1 mg/L) was necessary to 

reduce hatching success. After 92 hours, 

survival was reduced at concentrations 

of 0.01, 0.1, and 1 mg/L of g-, b-, and 

a-HBCD, respectively. Growth, 

measured as body length of larvae after 

92 hours of exposure, was reduced at 

0.1 mg/L of b- and g-HBCD and at 1 

mg/L of a-HBCD. After 116 hours of 

exposure, malformations were observed 

at all test concentrations of b- and 

g-HBCD and at 0.1 mg/L and above for 

a-HBCD. Effects on heart rate varied 

depending upon the length of exposure; 

reduced heart rate was observed at 0.1 

mg/L of b- and g-HBCD or 1 mg/L of 

a-HBCD at 44 hours and at 0.1 mg/L of 

a- and b-HBCD at 92 hours, whereas 

g-HBCD resulted in an increase in heart 

rate at 1 mg/L at 92 hours. An increase 

in generation of ROS was observed after 

116 hours at 0.1 mg/L of b- and g-HBCD 

and at 1 mg/L of a-HBCD. Activities of 

caspase-3 and caspase-9 enzymes, 

indicative of apoptosis, were increased 

after 116 hours at 0.1 mg/L of g-HBCD 

and at 1 mg/L of a- and b-HBCD. The 

authors ranked the HBCD diastereomers 

in the following order for 

developmental toxicity to zebrafish: 

g-HBCD > b HBCD > a-HBCD. 

Effects indicative of oxidative stress, 

as seen in the zebrafish embryo studies, 

were also found in clams. Zhang et al. 

(Ref. 74) measured parameters 

indicative of antioxidant defenses and 

oxidative stress after 1, 3, 6, 10, and 15 

days of exposure to low nominal 

concentrations of HBCD ranging from 

0.000086 to 0.0086 mg/L in the clam 

Venerupis philippinarum. Increases in 

ethyoxyresorufin-o-deethylase (EROD) 

activity, glutathione (GSH) content, and 

DNA damage were observed in clams 

exposed to 0.00086 mg/L, while 

increased lipid peroxidation (LPO) was 

observed at 0.0086 mg/L. These same 

effects were observed at lower 

concentrations as the length of exposure 

increased. 

Anselmo et al. (Ref. 63) exposed sea 

urchin (Psammechinus miliaris) 

embryos to HBCD in an early life stage 

test. Newly-fertilized embryos were 

exposed to HBCD at nominal 

concentrations of 0, 9, 25, 50, and 100 

nanomolar (nM) (0, 0.0058, 0.016, 0.032, 

and 0.064 mg/L, respectively) in 

dimethyl sulfoxide solvent and 

evaluated at 72 hours post-fertilization. 

A significant increase in morphological 

abnormalities was found at a nominal 

concentration of 100 nM HBCD (0.064 

mg/L), the highest concentration tested. 

Observed malformations included short 

or deformed larval arms and slight 

edema around the larval body. The 

NOEC for this effect at 72 hours was 

0.032 mg/L. 

2. Chronic aquatic toxicity. A 

measured MATC of 0.0042 mg/L, based 

on reduced size (length) of surviving 

young water fleas (Daphnia magna), 

indicates high chronic toxicity (Ref. 56). 

This study reported additional effects, 

including decreased reproductive rate 

and decreased mean weight of surviving 

young at 0.011 mg/L. Other effects 

reported following chronic exposure to 

HBCD included degenerative changes in 

the gills of clams (Macoma balthica), 

manifested by the increased frequency 


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of nuclear and nucleolar abnormalities 

and the occurrence of dead cells, at 

nominal concentrations of ≥0.1 mg/L 

(50-day LOEC) (Ref. 71), a nominal 

MATC of 0.045 mg/L for increased 

morphological abnormalities in sea 

urchin (P. miliaris) embryos exposed to 

HBCD for up to 16 days in an early life 

stage test (Ref. 63), and a nominal 

MATC of 0.03 mg/L for increased 

malformation rate in marine medaka 

(Oryzias melastigma) embryos exposed 

to HBCD for 17 days in an early life 

stage test (Ref. 66). The developmental 

abnormalities in medaka included yolk 

sac edema, pericardial edema, and 

spinal curvature (Ref. 66). Mechanistic 

findings in this study included 

increases in heart rate and sinus 

venosus-bulbus arteriosus (SV–BA) 

distance, which are markers for cardiac 

development, induction of oxidative 

stress and apoptosis, and suppression of 

nucleotide and protein synthesis. 

Thyroid effects were reported in 

juvenile rainbow trout (Oncorhynchus 

mykiss) following dietary exposure to 

HBCD (Refs. 68 and 69). Each of the 

diastereomers of HBCD (administered 

separately via diet at concentrations of 

5 ng/g of a-, b-, or g-HBCD for up to 56 

days) disrupted thyroid homeostasis, as 

indicated by lower free circulating T3 

and T4 levels. 

The mechanisms of the effects on fish 

and invertebrates following chronic 

exposure were similar to those found in 

acute studies. Effects observed in fish 

include increased formation of ROS 

resulting in oxidative damage to lipids, 

proteins, and DNA, decreased 

antioxidant capacities in fish tissue 

(e.g., brains, hepatocytes, or 

erythrocytes), and increasing levels of 

EROD (detoxification enzyme) and 

PentoxyResorufin-O-Deethylase (PROD, 

detoxification enzyme) levels in 

hepatocytes of fish exposed to the 

nominal concentration of ≥0.1 mg/L 

(corresponds to ∼0.2 mg/g whole fish 

(wet weight)) for 42 days (Ref. 73). 

Ronisz et al. (Ref. 70) found a significant 

increase in hepatic cytosolic catalase 

activity in rainbow trout (Oncorhynchus 

mykiss) 5 days after a single 

intraperitoneal injection of 50 mg/kg 

was administered. The same authors 

observed reductions in liver somatic 

index (LSI) and EROD activity in a 28- 

day study in which rainbow trout were 

injected intraperitoneally with HBCD on 

days 1 and 14 at a dose somewhat less 

than 500 mg/kg. Zhang et al. (Ref. 74) 

observed the following signs of 

oxidative stress in clams (V. 

philippinarum) after 15 days of 

exposure to HBCD: The activities of 

antioxidant enzymes (EROD, superoxide 

dismutase (SOD), and glutathione-Stransferase (GST)), as well as GSH 

content, were increased at 0.000086 

mg/L, the lowest concentration tested. 

In addition, LPO was increased at 

0.00086 mg/L and DNA damage was 

increased at 0.0086 mg/L. 

3. Terrestrial toxicity and 

phytotoxicity. Japanese quail (Coturnix 

coturnix japonica) exposed for 6 weeks 

to an isomeric mixture of HBCD in the 

diet experienced a reduction in 

hatchability at all tested concentrations 

(12–1,000 ppm) (Ref. 57). Additional 

effects included a significant reduction 

in egg shell thickness starting at 125 

ppm, decreases in egg weights and egg 

production rates starting at 500 ppm, 

increases in cracked eggs starting at 500 

ppm, and adult mortality at 1,000 ppm. 

A subsequent test, conducted at lower 

dietary concentrations, determined 

LOAEL and NOAEL values of 15 and 5 

ppm, respectively, based on significant 

reduction of survival of chicks hatched 

from eggs of quails fed HBCD (Ref. 57). 

Several studies have been conducted 

examining effects of HBCD on American 

kestrels (Falco sparverius). Kobiliris 

(Ref. 78) reported a reduced 

‘‘corticosterone response’’ (where 

‘‘corticosterone response’’ was defined 

as a stimulation of the adrenal cortex to 

produce and release corticosterone into 

the bloodstream), reduced flying 

activities of juvenile males during 

hunting behavior trials, and delayed 

response times of juvenile females 

during predator avoidance behavior 

trials in American kestrels exposed in 

ovo to 164.13 ng/g wet weight. Kestrels 

exposed via the diet to 0.51 mg/kg/day 

beginning 3 weeks prior to pairing and 

continuing until the first chick hatched 

began to lay eggs 6 days earlier than 

controls and laid larger clutches of 

smaller eggs (Ref. 59). Although the 

technical mixture of HBCD 

stereoisomers contained predominantly 

g-HBCD (80% of the mixture), the main 

isomer found in eggs was a-HBCD 

(>90% of the total HBCD in eggs). In a 

subsequent study, Marteinson et al. 

(Ref. 61) exposed kestrels to dietary 

HBCD at the same dose (0.51 mg/kg/

day) and found increased testes weight 

in unpaired males, a marginally 

significant effect on testis histology in 

unpaired males (increased number of 

seminiferous tubules containing 

elongated spermatids; p = 0.052), 

marginally increased testosterone levels 

in breeding males (increased at the time 

the first egg was laid; p = 0.054), and no 

significant effect on sperm counts. 

Plasma T4 levels were reduced in 

breeding males throughout the study, 

which the authors took to suggest that 

thyroid disruption that may have 

contributed to the observed increase in 

testes weight. Marteinson et al. (Ref. 62) 

found altered reproductive behavior in 

both sexes of kestrels fed 0.51 mg/kg/

day, including reduced activity in both 

sexes during courtship and in males 

during brood rearing, which may have 

contributed to the observed reduction in 

incubation nest temperature and also to 

the reduced egg size reported previously 

by Fernie et al. (Ref. 58). In a 22-day 

study of chickens (Gallus gallus 

domesticus) exposed to HBCD in ovo, 

reduced pipping success was observed 

at 100 ng/g egg (Ref. 79). 

The accumulation and toxicity of a-, 

b-, and g-HBCDs in maize have been 

studied (Ref. 80). The order of 

accumulation in roots was b-HBCD > 

a-HBCD > g-HBCD and in shoots it was 

b-HBCD > g-HBCD > a-HBCD. In maize 

exposed to 2 mg/L HBCD, the inhibitory 

effect of the diastereomers on the early 

development of maize as well as the 

intensities of hydroxyl radical and 

histone H2AX phosphorylation 

followed the order a-HBCD > b-HBCD > 

g-HBCD, which indicates diastereomerspecific oxidative stress and DNA 

damage in maize. The study confirmed 

that for maize exposed to HBCDs, the 

generation of reactive oxygen species 

was one, but not the only, mechanism 

for DNA damage. 

4. Conclusions regarding the 

ecological hazard potential of HBCD. 

HBCD has been shown to cause acute 

toxicity to aquatic organisms at 

concentrations as low as 0.009 mg/L and 

chronic toxicity at concentrations as low 

as 0.0042 mg/L. Toxicity to terrestrial 

species has been observed at doses as 

low as 0.51 mg/kg/day. The available 

evidence shows that HBCD is highly 

toxic to aquatic and terrestrial species. 

C. What is EPA’s review of the 

bioaccumulation data for HBCD? 

HBCD has been shown in numerous 

studies to bioaccumulate in aquatic 

species and biomagnify in aquatic and 

terrestrial food chains (Ref. 1). BCFs for 

HBCD in fish in the peer-reviewed 

literature range as high as 18,100 (Refs. 

81, 82, and 83). Some of the 

bioaccumulation values for fish species 

and a freshwater food web are shown in 

Table 1. The complete listing of the 

available bioaccumulation data and 

more details about the studies can be 

found in the ecological assessment 

(Ref. 1). 


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TABLE 1—HBCD BCF AND BAF DATA FOR FISH AND FRESHWATER FOOD WEB

Species Duration and test endpoint Value Reference 

Rainbow trout (Oncorhynchus mykiss) ................. 35-day BCF .................. 8,974 and 13,085 ............................................... Ref. 81. 

Fathead minnow (Pimephales promelas) ............. 32-day BCF .................. 18,100 ................................................................. Ref. 82. 

Mirror carp (Cyprinus carpio morpha noblis) ........ 30-day exposure and 

30-day depuration 

BCF.

a-HBCD: 5,570–11,500 ......................................

b-HBCD: 187–642 

g-HBCD: 221–584 

Ref. 83. 

Mud carp (Cirrhinus molitorella), nile tilapia 

(Tilapia nilotica), and suckermouth catfish 

(Hypostomus plecostomus).

Log BAF ....................... 4.8–7.7 for HBCD isomers (a-HBCD had higher 

BAFs than b- and g-HBCD) (BAFs ranged 

from ∼63,000 to 50,000,000).

Ref. 84. 

Freshwater food web ............................................ Log BAF ....................... a-HBCD: 2.58–6.01 ............................................

b-HBCD: 3.24–5.58 

g-HBCD: 3.44–5.98 

SHBCDs: 2.85–5.98 

(BAFs range from ∼700 to 950,000) ..................

Ref. 85. 

Drottar and Kruger (Ref. 81) provided 

strong evidence that HBCD 

bioaccumulates in a study conducted 

according to established guidelines 

(OECD Test Guideline (TG) 305 and 

Office of Prevention, Pesticides and 

Toxic Substances (OPPTS) 850.1730). In 

this study, BCFs of 13,085 and 8,974 

were reported in rainbow trout (O. 

mykiss) exposed to 0.18 and 1.8 mg/L, 

respectively. Concentrations of HBCD in 

tissue reached steady-state at day 14 for 

fish exposed to 1.8 mg/L and, during the 

subsequent depuration stage, a 50% 

reduction of HBCD from edible and nonedible tissue and whole fish was 

reported on days 19 and 20 postexposure. In fish exposed to 0.18 mg/L, 

an apparent steady-state was reached on 

day 21, but on day 35, the tissue 

concentration of HBCD in fish increased 

noticeably; thus, steady-state was not 

achieved according to study authors, 

and BCF values (for the exposure 

concentration of 0.18 mg/L) were 

calculated based on day 35 tissue 

concentrations. Clearance of 50% HBCD 

from tissue of 0.18 mg/L exposed fish 

occurred 30–35 days post-exposure. 

Veith et al. (Ref. 82) further supports 

the conclusion that HBCD 

bioaccumulates in a study conducted 

prior to the establishment of 

standardized testing guidelines for 

bioconcentration studies. The study 

reported a BCF of 18,100 following 

exposure of fathead minnows to 6.2 

mg/L; the BCF was identified as a steadystate BCF, but the report does not 

indicate the time when steady-state was 

reached. A depuration phase was not 

included in this study. Zhang et al. (Ref. 

83) calculated BCFs for each HBCD 

diastereomer in mirror carp and found 

strong evidence that a-HBCD (BCF of 

5,570–11,500) is much more 

bioaccumulative than b- and g-HBCD 

(BCF of 187–642); BCF values that were 

normalized to lipid content were much 

higher (30,700–45,200 for a-HBCD, 

1,030–1,900 for b-HBCD, and 950–1,730 

for g-HBCD) than non-normalized BCFs. 

BAFs, which capture accumulation of 

HBCD from diet as well as water and 

sediment, were calculated for freshwater 

food webs in industrialized areas of 

Southern China in two separate field 

studies. He et al. (Ref. 84) calculated log 

BAFs of 4.8–7.7 (corresponding to BAFs 

of 63,000–50,000,000) for HBCD isomers 

in carp, tilapia, and catfish, and found 

higher BAFs for a-HBCD than b- and 

g-HBCD. In a pond near an e-waste 

recycling site, Wu et al. (Ref. 85) 

calculated log BAFs of 2.85–5.98 for 

HBCD (corresponding to BAFs of 700– 

950,000) in a freshwater food web. Log 

BAFs for each diastereomer in this 

study were comparable to one another 

(see Table 1). La Guardia et al. (Ref. 86) 

calculated log BAFs in bivalves and 

gastropods collected downstream of a 

textile manufacturing outfall; these 

ranged from 4.2 to 5.3 for a- and bHBCD (BAFs of 16,000–200,000), and 

from 3.2 to 4.8 for g-HBCD (BAFs of 

1,600–63,000). 

In general, a-HBCD bioaccumulates in 

organisms and biomagnifies through 

food webs to a greater extent than the band g- diastereomers. Uncertainty 

remains as to the balance of 

diastereomer accumulation in various 

species and the extent to which 

bioisomerization and biotransformation 

rates for each isomer affect 

bioaccumulation potential. Some 

authors (e.g., Law et al., Ref. 87) have 

proposed that g-HBCD isomerizes to aHBCD under physiological conditions, 

rather than uptake being diastereisomerspecific. To test this theory, Esslinger et 

al. (Ref. 88) exposed mirror carp 

(Cyprinus carpio morpha noblis) to only 

g-HBCD and found no evidence of 

bioisomerization. In contrast, when Du 

et al. (Ref. 89) exposed zebrafish (Danio 

rerio) to only g-HBCD, they found 

detectable levels of a-HBCD in fish 

tissue, suggesting that bioisomerization 

occurred. Marvin et al. (Ref. 90) 

hypothesized that differences in 

accumulation could also be due in part 

to a combination of differences in 

solubility, bioavailability, and uptake 

and depuration kinetics. 

Zhang et al. (Ref. 91) calculated 

diastereomer-specific BCFs in algae and 

cyanobacteria ranging from 174 to 469. 

For the cyanobacteria (Spirulina 

subsalsa), the BCF for a-HBCD (350) 

was higher than the BCFs for b-HBCD 

(270) and g-HBCD (174). However, for 

the tested alga (Scenedesmus obliquus), 

the BCF for b-HBCD (469) was higher 

than that for the other isomers (390– 

407). 

In summary, HBCD has been shown 

in numerous studies to be highly 

bioaccumulative in aquatic species and 

biomagnify in aquatic and terrestrial 

food chains; however, diastereomer- and 

enantiomer-specific mechanisms of 

accumulation are still unclear. 

D. What is EPA’s review of the 

persistence data for HBCD? 

There are limited data available on 

the degradation rates of HBCD under 

environmental conditions. A short 

summary of the environmental fate and 

persistence data for HBCD is presented 

in Table 2; additional details about this 

data can be found in the HBCD hazard 

assessment (Ref. 1). 


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TABLE 2—ENVIRONMENTAL DEGRADATION OF HBCD 

Property Value Reference 

Air 

Photodegradation ............... Photo-induced isomerization of g-HBCD to a-HBCD in indoor dust with a measured decrease in 

HBCD concentration concurrent with an increase of pentabromocyclododecenes (PBCDs) in 

indoor dust.

Ref. 9.2. 

Indirect photolysis half-life: 26 hours AOPWIN v1.92 (estimated) .................................................. Ref. 93. 

Water 

Hydrolysis ........................... Not expected due to lack of functional groups that hydrolyze under environmental conditions 

and low water solubility (estimated).

Ref. 44. 

Sediment 

Aerobic conditions .............. No biodegradation observed in 28-day closed-bottle test .............................................................. Refs. 76 and 94. 

Half-life: 128, 92, and 72 days for a-, g-, and b-HBCD, respectively (estimated), based on a 

44% decrease in total initial radioactivity in viable freshwater sediment.

Ref. 95. 

Half-life: >120 days (estimated), based on a 15% decrease in total initial radioactivity in abiotic 

freshwater sediment.

Half-life: 11 and 32 days (estimated) in viable sediment collected from Schuylkill River and 

Neshaminy creek, respectively.

Ref. 96. 

Half-life: 190 and 30 days (estimated) in abiotic sediment collected from Schuylkill River and 

Neshaminy creek.

Anaerobic conditions .......... Half-life: 92 days (estimated), based on a 61% decrease in total initial radioactivity in viable 

freshwater sediment.

Ref. 95. 

Half-life: >120 days (estimated), based on a 33% decrease in total initial radioactivity in abiotic 

freshwater sediment.

Half-life: 1.5 and 1.1 days (estimated) in viable sediment collected from Schuylkill River and 

Neshaminy creek.

Ref. 96. 

Half-life: 10 and 9.9 days (estimated) in abiotic sediment collected from Schuylkill River and 

Neshaminy creek.

Soil 

Aerobic conditions .............. Half-life: >120 days (estimated), based on a 10% decrease in total initial radioactivity in viable 

soil.

Ref. 95. 

Half-life: >120 days (estimated), based on a 6% decrease in total initial radioactivity in abiotic 

soil.

Half-life: 63 days (estimated) in viable soil amended with activated sludge .................................. Ref. 96. 

Half-life: >120 days (estimated) in abiotic soil..

Anaerobic conditions .......... Half-life: 6.9 days (estimated) in viable soil amended with activated sludge ................................. Ref. 96. 

Half-life: 82 days (estimated) in abiotic soil using a nominal HBCD concentration of 0.025 mg/

kg dry weight.

1. Abiotic degradation. HBCD is not 

expected to undergo significant direct 

photolysis since it does not absorb 

radiation in the environmentally 

available region of the electromagnetic 

spectrum that has the potential to cause 

molecular degradation (Ref. 97). 

Although HBCD is expected to exist 

primarily in the particulate phase in the 

atmosphere, a small percentage may 

also exist in the vapor phase based on 

its vapor pressure (Refs. 22, 90, 98, and 

99). HBCD in the vapor phase will be 

degraded by reaction with 

photochemically produced hydroxyl 

radicals in the atmosphere. An 

estimated rate constant of 5.01 × 10¥12

cubic centimeters (cm3)/moleculessecond at 25 °C for this reaction 

corresponds to a half-life of 26 hours, 

assuming an atmospheric hydroxyl 

radical concentration of 1.5 × 106

molecules/cm3 and a 12-hour day (Refs. 

93 and 100). 

Photolytic isomerization of HBCD has 

been described in both indoor dust 

samples and in samples of HBCD 

standards dissolved in methanol using 

artificial light (Ref. 92). After 1 week in 

the presence of light, indoor dust 

containing predominantly g-HBCD was 

found to decrease in g-HBCD and 

increase in a-HBCD concentration. 

There was a measured decrease in 

HBCD concentration concurrent with an 

increase in PBCDs in the indoor dust 

exposed to artificial light. The three 

diastereomerically-pure HBCD 

standards (a-, b-, and g-HBCD) that were 

dissolved in methanol also began to 

interconvert within 1 week, resulting in 

a decrease in g-HBCD concentration and 

an increase in a-HBCD concentration. 

HBCD is not expected to undergo 

hydrolysis in environmental waters due 

to lack of functional groups that 

hydrolyze under environmental 

conditions and the low water solubility 

of HBCD (Ref. 44). 

Observed abiotic degradation of 

HBCD during simulation tests based on 

Organisation for Economic Cooperation 

and Development (OECD) methods 307 

and 308 was approximately 33% in 

anaerobic freshwater sediment, 15% in 

aerobic freshwater sediment, and 6% in 

aerobic soil after 112–113 days (Refs. 44 

and 95). The results from these studies 

correspond to estimated half-lives >120 

days in soil and sediment due to 

minimal degradation being observed. 

Initial concentrations of 14C 

radiolabeled HBCD (a-, b-, and g- 14C-HBCD in a ratio of 7.74:7.84:81.5) 

were 3.0–4.7 mg/kg dry weight in the 

sediment and soil systems. HBCD 

degradation observed under abiotic 

conditions was attributed to abiotic 

reductive dehalogenation (Refs. 44, 76, 

and 95). Degradation proceeded through 

a stepwise process to form 


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tetrabromocyclododecene, 

dibromocyclododecadiene (DBCD), and 

1,5,9-cyclododecatriene (Refs. 44 and 

95). Further degradation of 1,5,9- 

cyclododecatriene was not observed. In 

this study, HBCD degradation occurred 

faster in sediment than in soil and faster 

under anaerobic conditions compared to 

aerobic conditions (Refs. 44 and 95). 

Previous OECD 308 and 307 based 

simulation tests from the same authors 

(Davis et al. 2005, Ref. 96) presented 

results suggesting faster abiotic 

degradation, particularly in sediment 

under anaerobic conditions, but were 

performed at much lower HBCD 

concentrations and measured only 

g-HBCD (Refs. 44, 76, 90, 96, and 101). 

In this study, abiotic degradation halflives in freshwater sediments were 30– 

190 days under aerobic conditions and 

9.9–10 days under anaerobic conditions. 

Estimated half-lives in abiotic soil were 

>120 days under aerobic conditions and 

82 days under anaerobic conditions. 

This study evaluated g-HBCD only and 

did not address interconversion of 

HBCD isomers or a- and b-HBCD 

degradation. The initial concentrations 

of HBCD were 0.025–0.089 mg/kg dry 

weight in the sediment and soil systems, 

nearly 100 times less than the HBCD 

concentrations used in the subsequent 

Davis et al. 2006 study (Ref. 95). Higher 

concentrations of HBCD (3.0–4.7 mg/kg 

dry weight) in the Davis et al. 2006 

study (Ref. 95) allowed for 

quantification of individual isomers, 

metabolite identification and mass 

balance evaluation (Refs. 95 and 101). 

Additionally, the Davis et al. 2005 study 

(Ref. 96) was considered to be of 

uncertain reliability for quantifying 

HBCD persistence because of concerns 

regarding potential contamination of 

sediment samples, an interfering peak 

corresponding to g-HBCD in the liquid 

chromatography/mass spectrometry 

(LC/MS) chromatograms, and poor 

extraction of HBCD leading to HBCD 

recoveries of 33–125% (Refs. 44 and 

101). 

2. Biotic degradation. A few studies 

on the biodegradation of HBCD were 

located. A closed bottle screening-level 

test for ready biodegradability (OECD 

Guideline 301D, EPA OTS 796.3200) 

was performed using an initial HBCD 

concentration of 7.7 mg/L and an 

activated domestic sludge inoculum 

(Refs. 76 and 94). No biodegradation 

was observed (0% of the theoretical 

oxygen demand) over the test period of 

28 days under the stringent guideline 

conditions of this test. 

Degradation of HBCD during 

simulation tests with viable microbes, 

based on OECD methods 307 and 308, 

was approximately 61% in anaerobic 

freshwater sediment, 44% in aerobic 

freshwater sediment, and 10% in 

aerobic soil after 112–113 days (Refs. 44 

and 95). The results from this study 

correspond to estimated HBCD halflives of 92 days in anaerobic freshwater 

sediment, 128, 92, and 72 days for a-, 

g-, and b-HBCD, respectively in aerobic 

freshwater sediment, and >120 days in 

aerobic soil. An initial total 14C-HBCD 

concentration of 3.0–4.7 mg/kg dry 

weight in the sediment and soil systems 

was used, allowing for quantification of 

individual isomers, metabolite 

identification, and mass balance 

evaluation (Refs. 95 and 101). Although 

very high spiking rates can be toxic to 

microorganisms in biodegradation 

studies and lead to unrealistically long 

estimated half-lives, the results of this 

study did not suggest toxicity to 

microorganisms. Tests with viable 

microbes demonstrated increased HBCD 

degradation compared to the 

biologically-inhibited control studies. In 

combination, these studies suggest that 

HBCD will degrade slowly in the 

environment, although faster in 

sediment than in soil, faster under 

anaerobic conditions than aerobic 

conditions, faster with microbial action 

than without microbial action, and at 

different rates for individual HBCD 

diastereomers (slower for a-HBCD than 

for the g- and b-stereoisomers). 

The same researchers (Ref. 76) 

previously conducted a water-sediment 

simulation test for commercial HBCD 

based on OECD guideline 308 using 

nominal HBCD concentrations of 0.034– 

0.089 mg/kg dry weight (Refs. 44, 76, 

and 102). Aerobic and anaerobic 

microcosms were pre-incubated at 20 °C 

for 49 days and at 23 °C for 43–44 days, 

respectively. HBCD was then added to 

14–37 g dry weight freshwater sediment 

samples in 250 ml serum bottles 

(water:sediment ratio of 1.6–2.9) and the 

microcosms were sealed and incubated 

in the dark at 20 °C for up to 119 days. 

For the aerobic microcosms, the 

headspace oxygen concentration was 

kept above 10–15%. This study 

evaluated only g-HBCD and did not 

address interconversion of HBCD 

isomers or a- and b-HBCD degradation. 

Disappearance half-lives of HBCD with 

sediment collected from Schuylkill 

River and Neshaminy creek were 11 and 

32 days in viable aerobic sediments, 

respectively (compared to 190 and 30 

days in abiotic aerobic controls, 

respectively), and 1.5 and 1.1 days in 

viable anaerobic sediments, respectively 

(compared to 10 and 9.9 days in abiotic 

anaerobic controls). 

Data from these tests suggest that 

anaerobic degradation is faster than 

aerobic degradation of HBCD in viable 

and abiotic sediments and that 

degradation is faster in viable 

conditions than abiotic conditions. 

While these findings are consistent with 

Davis et al. 2006 (Ref. 95), the actual 

degradation rates in this study are much 

faster. However, results from this study 

do not provide a reliable indication of 

HBCD persistence. A mass balance 

could not be established because only 

g-HBCD was used to quantify HBCD 

concentrations, 14C-radiolabelled HBCD 

was not used, and degradation products 

were not identified; therefore, apparent 

disappearance of HBCD in this study 

may not reflect biodegradation. In 

addition, there were concerns that 

contaminated sediment may have been 

used, HBCD extraction was incomplete 

(HBCD recovery varied from 33 to 

125%), and an interfering peak was 

observed in the LC/MS chromatograms 

corresponding to g-HBCD (Refs. 44 and 

101). 

Similarly, a soil simulation test was 

conducted based on OECD guideline 

307 for commercial HBCD using 50 g 

dry weight sandy loam soil samples 

added to 250 ml serum bottles (Refs. 44, 

76, 96, and 103). The moisture content 

was 20% by weight. Aerobic and 

anaerobic microcosms were preincubated at 20 °C for 35 days and at 23 

°C for 43 days, respectively. Activated 

sludge was added to the soil at 5 mg/ 

g, and HBCD was added to the soil to 

achieve a nominal concentration of 

0.025 mg/kg dry weight. The 

microcosms were then incubated in the 

dark at 20 °C for up to 120 days. The 

disappearance half-lives were 63 days in 

viable aerobic soil (compared to >120 

days in abiotic aerobic controls) and 6.9 

days in viable anaerobic soil (compared 

to 82 days in abiotic anaerobic controls). 

As in the sediment studies, HBCD 

degradation in soil occurred faster 

under anaerobic conditions compared to 

aerobic conditions, and faster in viable 

conditions than abiotic conditions. The 

disappearance half-lives in soil were 

slower than those in sediment. 

Biological processes were suggested to 

be responsible for the increased 

degradation of HBCD in this study using 

viable conditions, relative to abiotic 

conditions; however, degradation was 

not adequately demonstrated in soil 

because no degradation products were 

detected and only g-HBCD was used to 

quantify HBCD concentrations, making 

it impossible to calculate a mass 

balance. HBCD recoveries on day 0 of 

the experiment were well below (0.011– 

0.018 mg/kg dry weight) the nominal 

test concentrations (0.025 mg/kg dry 

weight), suggesting rapid adsorption of 

HBCD to soil and poor extraction 

methods (Refs. 44 and 101). 


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In studies using 0.025–0.089 mg/kg 

HBCD (Davis et al. 2005, Ref. 96), the 

estimated half-life values were shorter 

than studies using 3.0–4.7 mg/kg HBCD 

(Davis et al. 2006, Ref. 95) by 

approximately one order of magnitude 

for aerobic viable sediment (11–32 days 

compared to72–128 days) and anaerobic 

viable sediment (1.1–1.5 days compared 

to 92 days). The viable aerobic soil halflife using lower concentrations of HBCD 

(Davis et al. 2005, Ref. 96) was less than 

half of the half-life based on the higher 

HBCD concentration (63 days compared 

to >120 days) (Davis et al. 2006, Ref. 95). 

Both Davis et al. studies (Refs. 95 and 

96) suggest that HBCD degrades faster in 

sediment than in soil, faster under 

anaerobic conditions than aerobic 

conditions, and faster with microbial 

action than without microbial action. 

HBCD is poorly soluble, and it was 

suggested that at higher concentrations 

of HBCD, degradation is limited by mass 

transfer of HBCD into microbes. 

However, results from the Davis et al. 

2005 study (Ref. 96) likely overestimate 

the rate of HBCD biodegradation, for the 

reasons noted previously (primarily, 

failure to use 14C-radiolabelled HBCD, 

quantify isomers other than g-HBCD, 

identify degradation products, or 

establish a mass balance, but also 

procedural problems with 

contamination of sediment, incomplete 

HBCD extraction, and occurrence of an 

interfering peak in the LC/MS 

chromatograms corresponding to gHBCD). 

It is important to note that the rapid 

biodegradation rates from Davis et al. 

2005 (Ref. 96) are not consistent with 

environmental observations. HBCD has 

been detected over large areas and in 

remote locations in environmental 

monitoring studies (Refs 1 and 104). 

Dated sediment core samples indicate 

slow environmental degradation rates 

(Refs. 44, 90, 96, and 101). For example, 

HBCD was found at concentrations 

ranging from 112 to 70,085 mg/kg dry 

weight in sediment samples collected at 

locations near a production site in 

Aycliffe, United Kingdom two years 

after the facility was closed down (Ref. 

44). Monitoring data do not provide a 

complete, quantitative determination of 

persistence because HBCD emission 

sources, rates, and quantities are 

typically unknown, and all 

environmental compartments are not 

considered. However, the monitoring 

data do provide evidence in support of 

environmental persistence. In addition, 

the widespread presence of HBCD in 

numerous terrestrial and aquatic species 

indicates persistence in the 

environment sufficient for 

bioaccumulation to occur (Ref. 1). 

IV. Rationale for Listing HBCD and 

Lowering the Reporting Threshold 

A. What is EPA’s rationale for listing the 

HBCD category? 

HBCD has been shown to cause 

developmental effects at doses as low as 

146.3 mg/kg/day (LOAEL) in male rats. 

Developmental effects have also been 

observed with a BMDL of 0.056 mg/kg/ 

day (BMD of 0.18 mg/kg/day) based on 

effects in female rats and a BMDL of 

0.46 mg/kg/day (BMD of 1.45 mg/kg/

day) based on effects in male rats. HBCD 

also causes reproductive toxicity at 

doses as low 138 mg/kg/day (LOAEL) in 

female rats. Based on the available 

developmental and reproductive 

toxicity, EPA believes that HBCD can be 

reasonably anticipated to cause 

moderately high to high chronic toxicity 

in humans. Therefore, EPA believes that 

the evidence is sufficient for listing the 

HBCD category on the EPCRA section 

313 toxic chemical list pursuant to 

EPCRA section 313(d)(2)(B) based on 

the available developmental and 

reproductive toxicity data. 

HBCD has been shown to be highly 

toxic to both aquatic and terrestrial 

species with acute aquatic toxicity 

values as low as 0.009 mg/L and chronic 

aquatic toxicity values as low as 0.0042 

mg/L. HBCD is highly toxic to terrestrial 

species as well with observed toxic 

doses as low as 0.51 and 2.1 mg/kg/day. 

In addition to being highly toxic, HBCD 

is also bioaccumulative and persistent 

in the environment, which further 

supports a high concern for the toxicity 

to aquatic and terrestrial species. EPA 

believes that HBCD meets the EPCRA 

section 313(d)(2)(C) listing criteria on 

toxicity alone but also based on toxicity 

and bioaccumulation as well as toxicity 

and persistence in the environment. 

Therefore, EPA believes that the 

evidence is sufficient for listing the 

HBCD category on the EPCRA section 

313 toxic chemical list pursuant to 

EPCRA section 313(d)(2)(C) based on 

the available ecological toxicity data as 

well as the bioaccumulation and 

persistence data. 

HBCD has the potential to cause 

developmental and reproductive 

toxicity at moderately low to low doses 

and is highly toxic to aquatic and 

terrestrial organisms; thus, EPA 

considers HBCD to have moderately 

high to high chronic human health 

toxicity and high ecological toxicity. 

EPA does not believe that it is 

appropriate to consider exposure for 

chemicals that are moderately high to 

highly toxic based on a hazard 

assessment when determining if a 

chemical can be added for chronic 

human health effects pursuant to 

EPCRA section 313(d)(2)(B) (see 59 FR 

61440–61442). EPA also does not 

believe that it is appropriate to consider 

exposure for chemicals that are highly 

toxic based on a hazard assessment 

when determining if a chemical can be 

added for environmental effects 

pursuant to EPCRA section 313(d)(2)(C) 

(see 59 FR 61440–61442). Therefore, in 

accordance with EPA’s standard policy 

on the use of exposure assessments (See 

November 30, 1994 (59 FR 61432, FRL– 

4922–2), EPA does not believe that an 

exposure assessment is necessary or 

appropriate for determining whether 

HBCD meets the criteria of EPCRA 

section 313(d)(2)(B) or (C). 

B. What is EPA’s rationale for lowering 

the reporting threshold for HBCD? 

EPA believes that the available 

bioaccumulation and persistence data 

for HBCD support a classification of 

HBCD as a PBT chemical. HBCD has 

been shown to be highly 

bioaccumulative in aquatic species and 

to also biomagnify in aquatic and 

terrestrial food chains. While there is 

limited data on the half-life of HBCD in 

soil and sediment, the best available 

data supports a determination that the 

half-life of HBCD in soil and sediment 

is at least 2 months. This determination 

is further supported by the data from 

environmental monitoring studies, 

which indicate that HBCD has 

significant persistence in the 

environment. The widespread presence 

of HBCD in numerous terrestrial and 

aquatic species also supports the 

conclusion that HBCD has significant 

persistence in the environment. 

Therefore, consistent with EPA’s 

established policy for PBT chemicals 

(See 64 FR 58666, October 29, 1999) 

(FRL–6389–11) EPA is proposing to 

establish a 100-pound reporting 

threshold for the HBCD category. 

V. References 

The following is a listing of the 

documents that are specifically 

referenced in this document. The docket 

includes these documents and other 

information considered by EPA, 

including documents that are referenced 

within the documents that are included 

in the docket, even if the referenced 

document is not itself physically located 

in the docket. For assistance in locating 

these other documents, please consult 

the person listed under FOR FURTHER

INFORMATION CONTACT. 

1. USEPA, OEI. 2016. Technical Review of 

Hexabromocyclododecane (HBCD) CAS 


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35286 Federal Register / Vol. 81, No. 106 / Thursday, June 2, 2016 / Proposed Rules 

Registry Numbers 3194–55–6 and 

25637–99–4. January 25, 2016. 

2. USEPA, OEI. 2014. Economic Analysis of 

the Proposed Rule to add HBCD to the 

List of TRI Reportable Chemicals. March 

28, 2014. 

3. Arita, R., Miyazaki, K., Mure, S. 1983. 

Metabolic test of HBCD. Test on 

chemical substances used in household 

items. Studies on pharmacodynamics of 

HBCD (unpublished). In: Toxicology 

summary: HBCD (HBCD), Albemarle, 

S.A. Department of Pharmacy, Hokkaido 

University Hospital, Japan. 

4. Yu, C.C., Atallah, Y.H. 1980. 

Pharmacokinetics of HBCD in rats 

(unpublished). Vesicol Chemical 

Corporation, Rosemont, IL. 

5. Szabo, D.T., Diliberto, J.J., Hakk, H. et al. 

2010. Toxicokinetics of the flame 

retardant HBCD gamma: Effect of dose, 

timing, route, repeated exposure, and 

metabolism. Toxicol. Sci. 117(2):282– 

293. 

6. Szabo, D.T., Diliberto, J.J., Hakk, H., Huwe, 

J.K., Birnbaum, L.S. 2011. Toxicokinetics 

of the flame retardant 

hexabromocyclododecane alpha: Effect 

of dose, timing, route, repeated 

Exposure, and metabolism. Toxicol. Sci. 

121(2):234–244. 

7. Reistad, T., Fonnum, F., Mariussen, E. 

2006. Neurotoxicity of the 

pentabrominated diphenyl ether 

mixture, DE–71, and HBCD (HBCD) in 

rat cerebellar granule cells in vitro. Arch. 

Toxicol. 80(11):785–796. 

8. van der Ven, L.T.M., Verhoef, A., van de 

Kuil, T., Slob, W., Leonards, P.E.G., 

Visser, T.J., Hamers, T., Herlin, M., 

Hakansson, H., Olausson, H., Piersma, 

A.H., Vos, J.G. 2006. A 28-day oral dose 

toxicity study enhanced to detect 

endocrine effects of 

hexabromocyclododecane in Wistar rats. 

Toxicological Sciences 94(2): 281–292. 

9. van der Ven, L.T.M., van de Kuil, T., 

Leonards, P.E., et al. 2009. Endocrine 

effects of HBCD (HBCD) in a onegeneration reproduction study in Wistar 

rats. Toxicol Lett 185:51–62. Including 

supplementary tables. 

10. Brandsma, S.H., van der Ven, L.T.M., De 

Boer, J. and Leonards, P.E. 2009. 

Identification of hydroxylated 

metabolites of hexabromocyclododecane 

in wildlife and 28-days exposed Wistar 

rats. Environ. Sci. Technol. 43, 6058– 

6063. 

11. Hakk, H., Szabo, D.T., Huwe, J., Diliberto, 

J. and Birnbaum, L.S. 2012. Novel and 

distinct metabolites identified following 

a single oral dose of a- or ghexabromocyclododecane in mice. 

Environ. Sci. Technol. 46:13494–13503. 

12. Sanders, J.M., Knudsen, G.A. and 

Birnbaum, L.S. 2013. The fate of bhexabromocyclododecane in female 

C57BL/6 mice. Toxicological Sciences 

134(2): 251–257. 

13. Antignac, J.P., Cariou, R., Maume, D., et 

al. 2008. Exposure assessment of fetus 

and newborn to brominated flame 

retardants in France: preliminary data. 

Mol. Nutr. Food Res. 52(2):258–265. 

14. Weiss, J., Wallin, E., Axmon, A., et al. 

2006. Hydroxy-PCBs, PBDEs, and 

HBCDDs in serum from an elderly 

population of Swedish fishermen’s wives 

and associations with bone density. 

Environ. Sci. Technol. 40(20):6282–6289. 

15. Kakimoto, K., Akutsu, K., Konishi, Y., et 

al. 2008. Time trend of HBCD in the 

breast milk of Japanese women. 

Chemosphere 71(6):1110–1114. 

16. Rawn, D.F.K., Ryan, J.J., Sadler, A.R. et 

al. 2014. Brominated flame retardant 

concentrations in sera from the Canadian 

Health Measures Survey (CHMS) from 

2007 to 2009. Environment International 

63: 26–34. 

17. Abdallah, M. and Harrad, S. 2011. 

Tetrabromobisphenol-A, 

hexabromocyclododecane and its 

degradation products in UK human milk: 

Relationship to external exposure. 

Environment International, 37: 443–448. 

18. Meijer, L., Weiss, J., Van Velzen, M., et 

al. 2008. Serum concentrations of neutral 

and phenolic organohalogens in 

pregnant women and some of their 

infants in The Netherlands. Environ. Sci. 

Technol. 42(9):3428–3433. 

19. Thomsen, C., Molander, P., Daae, H.L., et 

al. 2007. Occupational exposure to 

HBCD at an industrial plant. Environ. 

Sci. Technol. 41(15):5210–5216. 

20. Fangstrom, B., Strid, A., Bergman, A. 

2005. Temporal trends of brominated 

flame retardants in milk from Stockholm 

mothers, 1980–2004. Department of 

Environmental Chemistry, Stockholm 

University, Stockholm, Sweden. 

Available online at: http://

www.imm.ki.se/Datavard/PDF/

mj%C3%B6lk_poolade_NV%20

rapport%202005%20modersmjolk.pdf. 

21. Fangstrom, B., Athanassiadis, I., Odsjo, 

T., et al. 2008. Temporal trends of 

polybrominated diphenyl ethers and 

HBCD in milk from Stockholm mothers, 

1980–2004. Mol. Nutr. Food Res. 

52(2):187–193. 

22. Covaci, A., Gerecke, A.C., et al. 2006. 

Hexabromocyclododecanes (HBCDs) in 

the Environment and Humans: A 

Review. Environ. Sci. Technol. 40: 3679– 

3688. 

23. Johnson-Restrepo, B., Adams, D.H., et al. 

2008. Tetrabromobisphenol A (TBBPA) 

and Hexabromocyclododecanes (HBCDs) 

in tissues of humans, dolphins, and 

sharks from the United States. 

Chemosphere 70: 1935–1944. 

24. Toms, L-M.L., Guerra, P., Eljarrat, E., 

Barcelo ́, D., Harden, F.A., Hobson, P., et 

al. 2012. Brominated flame retardants in 

the Australian population: 1993–2009. 

Chemosphere 89:398–403. 

25. Schecter, A., Szabo, D.T., Miller, J., Gent, 

T.L., Malik-Bass, N., Petersen, M., 

Paepke, O., Colacino, J.A., Hynan L.S., 

Harris, T.R., Malla, S., Birnbaum, L.S. 

2012. Hexabromocyclododecane (HBCD) 

stereoisomers in U.S. food from Dallas, 

TX. Environmental Health Perspectives 

120(9): 1260–1264. 

26. IRDC (International Research and 

Development Corporation). 1977. Acute 

toxicity studies in rabbits and rats with 

HBCD with attachments. Submitted 

under TSCA Section 8E; EPA Document 

No. 88–7800065; NTIS No. OTS0200051. 

27. IRDC (International Research and 

Development Corporation). 1978. Acute 

toxicity studies in rabbits and rats with 

residue of HBCD with attachments and 

cover letter dated 030178. Submitted 

under TSCA Section 8E; EPA Document 

No. 88–7800088; NTIS No. OTS0200466. 

28. Pharmakon Research International Inc. 

1990. Acute exposure oral toxicity study 

in rats (83 EPA/OECD) with attachments 

and cover letter dated 030890. Submitted 

under TSCA Section 8D; EPA Document 

No. 86–900000166; NTIS No. 

OTS0522237. 

29. Gulf South Research Institute. 1988. 

Initial submission: Letter from Ethyl 

Corp to USEPA regarding technical and 

toxicity data on brominated flame 

retardants including HBCD. EPA 

Document No. FYI–OTS–0794–0947; 

NTIS No. OTS0000947. 

30. BASF. 1990. Report on the study of the 

acute oral toxicity of HBCD in the mouse 

with cover letter dated 03–12–90. 

Submitted under TSCA Section 8D; EPA 

Document No. 86–900000383; NTIS No. 

OTS0522946. 

31. Lewis, A.C., Palanker, A.L. 1978. A 

dermal LD50 study in albino rabbits and 

an inhalation LC50 study in albino rats. 

Test material GLS–S6–41A 

(unpublished). Consumer Product 

Testing, Fairfield, NJ; Experiment 

Reference No. 78385–2. Client: Saytech 

Inc. 

32. Momma, J., Kaniwa, M., Sekiguchi, H., 

Ohno, K., Kawasaki, Y., Tsuda, M., 

Nakamura, A., Kurokawa, Y. 1993. 

Dermatological evaluation of a flame 

retardant, hexabromocyclododecane 

(HBCD) on guinea pig by using the 

primary irritation, sensitization, 

phototoxicity, and photosensitization of 

skin. (Article in Japanese; English 

abstract). Eisei Shikenjo Hokoku 111:18– 

24. 

33. Chengelis, C. 1997. A 28-day repeated 

dose oral toxicity study of HBCD in rats. 

Study No. WIL–186004. WIL Research 

Laboratories, Inc. Ashland, OH. 

34. Chengelis, C. 2001. An oral (gavage) 90- 

day toxicity study of HBCD in rats. Study 

No. WIL–186012. WIL Research 

Laboratories, Inc. Ashland, Ohio. 

35. Chengelis, C. 2002. Amendment to the 

Final Report for: An oral (gavage) 90-day 

toxicity study of HBCD in rats. Study No. 

WIL–186012. WIL Research Laboratories, 

Inc. Ashland, Ohio. 

36. Hill, R.N., Crisp, T.M., Hurley, P.M., 

Rosenthal, S.L., and Singh, D.V. 1998. 

Risk assessment of thyroid follicular cell 

tumors. Environ. Health Perspect. 106, 

447–457. 

37. Zeller, H. and Kirsch, P. 1969. 

Hexabromocyclododecane: 28-day 

feeding trials with rats. BASF 

unpublished laboratory study. As cited 

in USEPA. 2001. High Production 

Volume (HPV) data summary and test 

plan for hexabromocyclododecane 

(HBCD) CAS No. 3194–55–6. Prepared 

by the American Chemistry Council’s 

Brominated Flame Retardant Industry 

Panel (BFRIP), Arlington, VA. 

38. Zeller, H. and Kirsch, P. 1970. 

Hexabromocyclododecane: 90-day 


asabaliauskas on DSK3SPTVN1PROD with PROPOSALS
Federal Register / Vol. 81, No. 106 / Thursday, June 2, 2016 / Proposed Rules 35287 

feeding trials with rats. BASF 

unpublished laboratory study. As cited 

in USEPA. 2001. High Production 

Volume (HPV) data summary and test 

plan for hexabromocyclododecane 

(HBCD) CAS No. 3194–55–6. Prepared 

by the American Chemistry Council’s 

Brominated Flame Retardant Industry 

Panel (BFRIP), Arlington, VA. 

39. Kurokawa, Y., Inoue, T., Uchida, Y., et al. 

1984. Carcinogenesis test of flame 

retarder hexabromocyclododecane in 

mice. Hardy, M.; Albemarle Corporation, 

personal communication, Department of 

Toxicology, National Public Health 

Research Institute, Biological Safety Test 

Research Center. Unpublished, 

translated from Japanese. As cited in 

reference 40. 

40. USEPA. 2014. Flame Retardant 

Alternatives for 

Hexabromocyclododecane (HBCD): Final 

Report. 

41. Saegusa, Y., Fujimoto, H., Woo, G., et al. 

2009. Developmental toxicity of 

brominated flame retardants, 

tetrabromobisphenol A and 1,2,5,6,9,10– 

HBCD, in rat offspring after maternal 

exposure from mid-gestation through 

lactation. Reprod. Toxicol. 28(4):456–67. 

42. Ema, M., Fujii, S., Hirata-Koizumi, M., et 

al. 2008. Two-generation reproductive 

toxicity study of the flame retardant 

HBCD in rats. Reprod. Toxicol. 

25(3):335–351. 

43. Murai, T., Kawasaki, H., Kanoh, S. 1985. 

Studies on the toxicity of insecticides 

and food additives in pregnant rats (7). 

Fetal toxicity of HBCD. Oyo Yakuri 

(Pharmacometrics) 29:981–986 (in 

Japanese with English abstract). 

44. European Commission. 2008. Risk 

Assessment: Hexabromocyclododecane 

CAS-No.: 25637–99–4 EINECS No.: 247– 

148–4, Final Report May 2008. 

Luxembourg: Office for Official 

Publications of the European 

Communities. 

45. Eriksson, P., Fischer, C., Wallin, M., et al. 

2006. Impaired behaviour, learning and 

memory, in adult mice neonatally 

exposed to HBCD (HBCDD). Environ. 

Toxicol. Pharmacol. 21(3):317–322. 

46. USEPA. 1998. Guidelines for 

neurotoxicity risk assessment. Risk 

Assessment Form. Federal Register. 63 

FR 26926, May 14, 1998 (FRL–6011–3). 

47. Industrial Bio-Test Labs. 1990. 

Mutagenicity of two lots of FM–100 lot 

53 and residue of lot 3322 in the absence 

and presence of metabolic activation 

with test data and cover letter. Submitted 

under TSCA Section 8D; EPA Document 

No. 86–900000267; NTIS No. 

OTS0523259. 

48. Litton Bionetics Inc. 1990. Mutagenicity 

evaluation of 421–32b (Final report) with 

test data and cover letter. Submitted 

under TSCA Section 8D; EPA Document 

No. 86–900000265; NTIS No. 

OTS0523257. 

49. SRI Research Institute. 1990. In vitro 

microbiological mutagenicity studies of 

four CIBA–GEIGY corporation 

compounds (Final report) with test data 

and cover letter. Submitted under TSCA 

Section 8D; EPA Document No. 86– 

900000262; NTIS No. OTS0523254. 

50. Zeiger, E., Anderson, B., Haworth, S., et 

al. 1987. Salmonella mutagenicity tests: 

III. Results from the testing of 255 

chemicals. Environ. Mutagen. 9 (Suppl. 

9):1–110. 

51. Huntingdon Research Center. 1978. Ames 

metabolic activation test to assess the 

potential mutagenic effect of compound 

no. 49 with cover letter dated 031290. 

Submitted under TSCA Section 8D; EPA 

Document No. 86–900000385; NTIS No. 

OTS0522948. 

52. Pharmakologisches Institute. 1978. Ames 

test with hexabromides with cover letter 

dated 031290. Submitted under TSCA 

Section 8D; EPA Document No. 86– 

900000379; NTIS No. OTS0522942. 

53. Ethyl Corporation. 1985. Genetic 

toxicology Salmonella/microsomal assay 

on HBCD with cover letter dated 030890. 

Submitted under TSCA Section 8D; EPA 

Document No. 86–900000164; NTIS No. 

OTS0522235. 

54. Microbiological Associates Inc. 1996. 

HBCD (HBCD): chromosome aberrations 

in human peripheral blood lymphocytes 

with cover letter dated 12/12/1996. 

Submitted under TSCA Section 8D; EPA 

Document No. 86970000358; NTIS No. 

OTS0573552. 

55. Walsh, G.E., Yoder, M.J., McLaughlin, 

L.L., et al. 1987. Responses of marine 

unicellular algae to brominated organic 

compounds in six growth media. 

Ecotoxicol. Environ. Saf. 14:215–222. 

56. Drottar, K.R., Krueger, H.O. 1998. 

Hexabromocyclododecane (HBCD): A 

flow-through life-cycle toxicity test with 

the cladoceran (Daphnia magna). Report 

#439A–108. Wildlife International Ltd, 

Easton, MD, pp 78. Submitted under 

TSCA Section 8D; EPA Document No. 

86980000152; OTS0559490. 

57. MOEJ (Ministry of the Environment, 

Japan). 2009. 6-Week administration 

study of 1,2,5,6,9,10- 

hexabromocyclododecane for avian 

reproduction toxicity under long-day 

conditions using Japanese quail. Report. 

Ministry of the Environment, Japan. 

Research Institute for Animal Science in 

Biochemistry & Toxicology (as cited in 

Ref. 58). 

58. UNEP (United Nations Environmental 

Program). 2010. 

Hexabromocyclododecane draft risk 

profile. United Nations Environmental 

Program, Stockholm Convention. 

59. Fernie, K.J., Marteinson, S.C., Bird, D.M., 

et al. 2011. Reproductive changes in 

American kestrels (Falco sparverius) in 

relation to exposure to technical 

hexabromocyclododecane flame 

retardant. Environ. Toxicol. Chem. 

30:2570–2575. 

60. Marteinson, S.C., Bird, D.M., Shutt, J.L., 

et al. 2010. Multi-generational effects of 

polybrominated diphenylethers 

exposure: Embryonic exposure of male 

American kestrels (Falco sparverius) to 

DE–71 alters reproductive success and 

behaviors. Environ. Toxicol. Chem. 29: 

1740–1747. 

61. Marteinson, S.C., Kimmins, S., Letcher, 

R.J., et al. 2011. Diet exposure to 

technical hexabromocyclododecane 

(HBCD) affects testes and circulating 

testosterone and thyroxine levels in 

American kestrels (Falco sparverius). 

Environ. Res. 111:1116–1123. 

62. Marteinson, S.C., Bird, D.M., Letcher, R.J., 

et al. 2012. Dietary exposure to technical 

hexabromocyclododecane (HBCD) alters 

courtship, incubation and parental 

behaviors in American kestrels (Falco 

sparverius). Chemosphere 89:1077–1083. 

63. Anselmo, H.M.R., Koerting, L., Devito, S., 

et al. 2011. Early life developmental 

effects of marine persistent organic 

pollutants on the sea urchin 

Psammechinus miliaris. Ecotox. Environ. 

Safe. 74:2182–2192. 

64. Deng, J., Yu, L., Liu, C., et al. 2009. 

Hexabromocyclododecane-induced 

developmental toxicity and apoptosis in 

zebrafish embryos. Aquat. Toxicol. 

93(1):29–36. 

65. Du, M., Zhang, D., Yan, C., et al. 2012. 

Developmental toxicity evaluation of 

three hexabromocyclododecane 

diastereoisomers on zebrafish embryos. 

Aquat. Toxicol. 112–113:1–10. 

66. Hong, H., Li, D., Shen, R., et al. 2014. 

Mechanisms of 

hexabromocyclododecanes induced 

developmental toxicity in marine 

medaka (Oryzias melastigma) embryos. 

Aquat. Toxicol. 152:173–185. 

67. Hu, J., Liang, Y., Chen, M., et al. 2009. 

Assessing the toxicity of TBBPA and 

HBCD by zebrafish embryo toxicity assay 

and biomarker analysis. Environ. 

Toxicol. 24:334–342. 

68. Palace, V.P., Pleskach, K., Halldorson, T., 

et al. 2008. Biotransformation enzymes 

and thyroid axis disruption in juvenile 

rainbow trout (Oncorhynchus mykiss) 

exposed to hexabromocyclododecane 

diastereoisomers. Environ. Sci. Technol. 

42(6):1967–1972. 

69. Palace, V., Park, B., Pleskach, K., et al. 

2010. Altered thyroxine metabolism in 

rainbow trout (Oncorhynchus mykiss) 

exposed to hexabromocyclododecane 

(HBCD). Chemosphere 80(2):165–169. 

70. Ronisz, D., Farmen Finne, E., Karlsson, 

H., et al. 2004. Effects of the brominated 

flame retardants 

hexabromocyclododecane (HBCDD), and 

tetrabromobisphenol A (TBBPA), on 

hepatic enzymes and other biomarkers in 

juvenile rainbow trout and feral eelpout. 

Aquat. Toxicol. 69:229–245. 

71. Smolarz, K. and Berger, A. 2009. Longterm toxicity of 

hexabromocyclododecane (HBCDD) to 

the benthic clam Macoma balthica (L.) 

from the Baltic Sea. Aquat. Toxicol. 

95(3):239–247. 

72. Wu, M., Zuo, Z., Li, B., et al. 2013. Effects 

of low-level hexabromocyclododecane 

(HBCD) exposure on cardiac 

development in zebrafish embryos. 

Ecotoxicology 22:1200–1207. 

73. Zhang, X., Yang, F., Zhang, X., et al. 

2008. Induction of hepatic enzymes and 

oxidative stress in Chinese rare minnow 

(Gobiocypris rarus) exposed to 

waterborne hexabromocyclododecane 

(HBCDD). Aquat. Toxicol. 86(1):4–11. 

74. Zhang, H., Pan, L., Tao, Y. 2014. 

Antioxidant responses in clam 


asabaliauskas on DSK3SPTVN1PROD with PROPOSALS
35288 Federal Register / Vol. 81, No. 106 / Thursday, June 2, 2016 / Proposed Rules 

Venerupis philippinarum exposed to 

environmental pollutant 

hexabromocyclododecane. Environ. Sci. 

Pollut. Res. 21:8206–8215. 

75. Desjardins, D., MacGregor, J.A., Krueger, 

H.O. 2004. Hexabromocyclododecane 

(HBCD): A 72 hour toxicity test with the 

marine diatom (Skeletonema costatum), 

Final report. Wildlife Internation Ltd, 

Easton, MD, pp 66. As cited in Refs. 44 

and 76. 

76. IUCLID. 2005. Hexabromocyclododecane 

IUCLID dataset. Submitted to U.S. EPA’s 

High Production Volume (HPV) 

Chemical Program. 

77. Desjardins, D., MacGregor, J.A., Krueger, 

H.O. 2005. Final report. Chapter 1, 

Hexabromocyclododecane (HBCD): A 72- 

hour toxicity test with the marine diatom 

(Skeletonema costatum) using a cosolvent. Chapter 2, 

Hexabromocyclododecane (HBCD): A 72- 

hour toxicity test with the marine diatom 

(Skeletonema costatum) using generator 

column saturated media. Wildlife 

International Ltd, Easton, MD, pp19. As 

cited in Ref. 44. 

78. Kobiliris, D. 2010. Influence of embryonic 

exposure to hexabromocyclododecane 

(HBCD) on the corticosterone response 

and ‘‘fight or flight’’ behaviors of captive 

American kestrels. Thesis submitted to 

McGill University in partial fulfilment of 

the requirements of the degree of Masters 

of Science. Department of Natural 

Resource Sciences, McGill University, 

Montreal, Canada. 

79. Crump, D., Egloff, C., Chiu, S., et al. 2010. 

Pipping success, isomer-specific 

accumulation, and hepatic mRNA 

expression in chicken embryos exposed 

to HBCD. Toxicol. Sci. 115:492–500. 

80. Wu, T., Wang, S., Huang, H., et al. 2012. 

Diastereomer-specific uptake, 

translocation, and toxicity of 

hexabromocyclododecane 

diastereoisomers to maize. J. Agr. Food 

Chem. 60:8528–8534. 

81. Drottar, K.R. and Krueger, H.O. 2000. 

Hexabromocyclododecane (HBCD): A 

flow-through bioconcentration test with 

the rainbow trout (Oncorhynchus 

mykiss). Report# 439A–111. Wildlife 

International Ltd, Easton, MD, pp 1–137. 

Submitted under TSCA Section FYI; EPA 

Document No. 84010000001; 

OTS0001392. 

82. Veith, G.D., Defoe, D.L., Bergstedt, B.V. 

1979. Measuring and estimating the 

bioconcentration factor of chemicals in 

fish. J. Fish Res. Board Can. 36:1040– 

1048. 

83. Zhang, Y., Sun, H., Ruan, Y. 2014. 

Enantiomer-specific accumulation, 

depuration, metabolization and 

isomerization of 

hexabromocyclododecane (HBCD) 

diastereomers in mirror carp from water. 

J. Haz. Mater. 264:8–15. 

84. He, M., Luo, X., Yu, L., et al. 2013. 

Diasteroisomer and enantiomer-specific 

profiles of hexabromocyclododecane and 

tetrabromobisphenol A in an aquatic 

environment in a highly industrialized 

area, South China: Vertical profile, phase 

partition, and bioaccumulation. Environ. 

Poll. 179:105–110. 

85. Wu, J., Guan, Y., Zhang, Y., et al. 2011. 

Several current-use, non-PBDE 

brominated flame retardants are highly 

bioaccumulative: Evidence from field 

determined bioaccumulation factors. 

Environ. Int. 37:210–215. 

86. La Guardia, M.J., Hale, R.C., Harvey, E., 

et al. 2012. In situ accumulation of 

HBCD, PBDEs, and several alternative 

flame-retardants in the bivalve 

(Corbicula fluminea) and gastropod 

(Elimia proxima). Environ. Sci. Technol. 

46:5798–5805. 

87. Law, K., Palace, V.P., Halldorson, T., et 

al. 2006. Dietary accumulation of 

hexabromocyclododecane 

diastereoisomers in juvenile rainbow 

trout (Oncorhynchus mykiss) I: 

Bioaccumulation parameters and 

evidence of bioisomerization. Environ. 

Toxicol. Chem. 25(7):1757–1761. 

88. Esslinger, S., Becker, R., Mu ̈ller-Belecke, 

A., et al. 2010. HBCD stereoisomer 

pattern in mirror carps following dietary 

exposure to pure g-HBCD enantiomers. J. 

Agric. Food Chem. 58:9705–9710. 

89. Du, M., Lin, L., Yan, C., et al. 2012. 

Diastereoisomer- and enantiomerspecific accumulation, depuration, and 

bioisomerization of 

hexabromocyclododecanes in zebrafish 

(Danio rerio). Environ. Sci. Technol. 

46:11040–11046. 

90. Marvin, C.H., Tomy, G.T., Armitage, J.M., 

et al. 2011. Hexabromocyclododecane: 

Current understanding of chemistry, 

environmental fate and toxicology and 

implications for global management. 

Environ. Sci. Technol. 45:8613–8623. 

Including supporting information 

document. 

91. Zhang, Y., Sun, H., Zhu, H., et al. 2014. 

Accumulation of 

hexabromocyclododecane diastereomers 

and enantiomers in two microalgae, 

Spirulina subsalsa and Scenedesmus 

obliquus. Ecotox. Environ. Safe. 

104:136–142. 

92. Harrad, S; Abdallah, MA; Covaci, A. 

(2009a) Causes of variability in 

concentrations and diastereomer patterns 

of Hexabromocyclododecanes in indoor 

dust. Environment International 35:573– 

579. 

93. USEPA. 2011. EPI Suite results for CAS 

003194–55–6. Download EPI SuiteTM 

v4.0. U.S. Environmental Protection 

Agency. Available online at http:// 

www.epa.gov/opptintr/exposure/pubs/ 

episuitedl.htm (see section 2, attachment 

A in Ref. 1). 

94. Schaefer, E.C. and Haberlein, D. 1996. 

Hexabromocyclododecane (HBCD): 

Closed bottle test. 439E–102, Wildlife 

International Ltd, Easton, MD, USA (as 

cited in Ref. 44). 

95. Davis, J.W., Gonsior, S.J., Markham, D.A., 

et al. 2006. Biodegradation and product 

identification of 

[14C]hexabromocyclododecane in 

wastewater sludge and freshwater 

aquatic sediment. Environ. Sci. Technol. 

40:5395–5401. Including supporting 

information document. 

96. Davis, J.W., Gonsior, S.J., Marty, G.T., et 

al. 2005. The transformation of 

hexabromocyclododecane in aerobic and 

anaerobic soils and aquatic sediments. 

Water Res. 39:1075–1084. 

97. Hazardous Substance Data Bank. 2011. 

1,2,5,6,9,10-Hexabromocyclododecane. 

Hazardous Substances Data Bank. Part of 

the National Library of Medicine’s 

Toxicology Data Network (TOXNET7). 

Bethesda, MD. Available online at http:// 

toxnet.nlm.nih.gov/cgi-bin/sis/ 

htmlgen?HSDB (accessed May 31, 2011). 

98. Bidleman, T.F. 1988. Atmospheric 

processes. Environ. Sci. Technol. 

22(4):361–367. 

99. Stenzel, J.I., Nixon, W.B. 1997. 

Hexabromocyclododecane (HBCD): 

Determination of the vapor pressure 

using a spinning rotor gauge with cover 

letter dated 08/15/1997. Chemical 

Manufacturers Association. Submitted 

under TSCA Section 8D. OTS0573702. 

100. USEPA. 1993. Determination of rates of 

reaction in the gas-phase in the 

troposphere. 5. Rate of indirect 

photoreaction: Evaluation of the 

atmospheric oxidation computer 

program of Syracuse Research 

Corporation for estimating the secondorder rate constant for the reaction of an 

organic chemical with hydroxyl radicals. 

Washington, DC: U.S. Environmental 

Protection Agency. EPA744R93001. 

101. National Industrial Chemicals 

Notification and Assessment Scheme. 

2012. Hexabromocyclododecane. Priority 

existing chemical assessment report. 

Volume 34. Commonwealth of Australia: 

Australia. National Industrial Chemicals 

Notification and Assessment Scheme. 

PEC34. 

102. Davis, J.W., Gonsior, S.J., Marty, G.T. 

2003. Evaluation of aerobic and 

anaerobic transformation of 

hexabromocyclododecane in aquatic 

sediment systems. Project Study ID 

021081, 87 pp. DOW Chemical 

Company: Midland, MI, USA. Submitted 

under TSCA Section FYI; EPA Document 

No. 84040000010; FYI–1103–01472, pg. 

440. 

103. Davis, J.W., Gonsior, S.J., Marty, G.T. 

2003. Evaluation of aerobic and 

anaerobic transformation of 

hexabromocyclododecane in soil. Project 

Study ID 021082, 61 pp. DOW Chemical 

Company: Midland, MI, USA. Submitted 

under TSCA Section FYI; EPA Document 

No. 84040000010; FYI–1103–01472, pg. 

379. 

104. USEPA. 2010. 

Hexabromocyclododecane (HBCD) action 

plan. U.S. Environmental Protection 

Agency. August 18, 2010. 

VI. What are the Statutory and 

Executive Orders reviews associated 

with this action? 

Additional information about these 

statutes and Executive Orders can be 

found at http://www2.epa.gov/lawsregulations/laws-and-executive-orders. 


asabaliauskas on DSK3SPTVN1PROD with PROPOSALS
Federal Register / Vol. 81, No. 106 / Thursday, June 2, 2016 / Proposed Rules 35289 

A. Executive Order 12866: Regulatory 

Planning and Review and Executive 

Order 13563: Improving Regulation and 

Regulatory Review 

This action is not a significant 

regulatory action and was therefore not 

submitted to the Office of Management 

and Budget (OMB) for review under 

Executive Orders 12866 (58 FR 51735, 

October 4, 1993) and 13563 (76 FR 3821, 

January 21, 2011). 

B. Paperwork Reduction Act (PRA) 

This action does not contain any new 

information collection requirements that 

require additional approval by OMB 

under the PRA, 44 U.S.C. 3501 et seq. 

OMB has previously approved the 

information collection activities 

contained in the existing regulations 

and has assigned OMB control numbers 

2025–0009 and 2050–0078. Currently, 

the facilities subject to the reporting 

requirements under EPCRA section 313 

and PPA section 6607 may use either 

EPA Toxic Chemicals Release Inventory 

Form R (EPA Form 1B9350–1), or EPA 

Toxic Chemicals Release Inventory 

Form A (EPA Form 1B9350- 2). The 

Form R must be completed if a facility 

manufactures, processes, or otherwise 

uses any listed chemical above 

threshold quantities and meets certain 

other criteria. For the Form A, EPA 

established an alternative threshold for 

facilities with low annual reportable 

amounts of a listed toxic chemical. A 

facility that meets the appropriate 

reporting thresholds, but estimates that 

the total annual reportable amount of 

the chemical does not exceed 500 

pounds per year, can take advantage of 

an alternative manufacture, process, or 

otherwise use threshold of 1 million 

pounds per year of the chemical, 

provided that certain conditions are 

met, and submit the Form A instead of 

the Form R. Since the HBCD category 

would be classified a PBT category, it is 

designated as a chemical of special 

concern, for which Form A reporting is 

not allowed. In addition, respondents 

may designate the specific chemical 

identity of a substance as a trade secret 

pursuant to EPCRA section 322, 42 

U.S.C. 11042, 40 CFR part 350. 

OMB has approved the reporting and 

recordkeeping requirements related to 

Forms A and R, supplier notification, 

and petitions under OMB Control 

number 2025–0009 (EPA Information 

Collection Request (ICR) No. 1363) and 

those related to trade secret designations 

under OMB Control 2050–0078 (EPA 

ICR No. 1428). As provided in 5 CFR 

1320.5(b) and 1320.6(a), an Agency may 

not conduct or sponsor, and a person is 

not required to respond to, a collection 

of information unless it displays a 

currently valid OMB control number. 

The OMB control numbers relevant to 

EPA’s regulations are listed in 40 CFR 

part 9 or 48 CFR chapter 15, and 

displayed on the information collection 

instruments (e.g., forms, instructions). 

C. Regulatory Flexibility Act (RFA) 

I certify that this action will not have 

a significant economic impact on a 

substantial number of small entities 

under the RFA, 5 U.S.C. 601 et seq. The 

small entities subject to the 

requirements of this action are small 

manufacturing facilities. The Agency 

has determined that of the 55 entities 

estimated to be impacted by this action, 

42 are small businesses; no small 

governments or small organizations are 

expected to be affected by this action. 

All 42 small businesses affected by this 

action are estimated to incur annualized 

cost impacts of less than 1%. Thus, this 

action is not expected to have a 

significant adverse economic impact on 

a substantial number of small entities. A 

more detailed analysis of the impacts on 

small entities is located in EPA’s 

economic analysis (Ref. 2). 

D. Unfunded Mandates Reform Act 

(UMRA) 

This action does not contain an 

unfunded mandate of $100 million or 

more as described in UMRA, 2 U.S.C. 

1531–1538, and does not significantly or 

uniquely affect small governments. This 

action is not subject to the requirements 

of UMRA because it contains no 

regulatory requirements that might 

significantly or uniquely affect small 

governments. Small governments are 

not subject to the EPCRA section 313 

reporting requirements. EPA’s economic 

analysis indicates that the total cost of 

this action is estimated to be $372,973 

in the first year of reporting (Ref. 2). 

E. Executive Order 13132: Federalism 

This action does not have federalism 

implications as specified in Executive 

Order 13132 (64 FR 43255, August 10, 

1999). It will not have substantial direct 

effects on the States, on the relationship 

between the national government and 

the States, or on the distribution of 

power and responsibilities among the 

various levels of government. 

F. Executive Order 13175: Consultation 

and Coordination With Indian Tribal 

Governments 

This action does not have tribal 

implications as specified in Executive 

Order 13175 (65 FR 67249, November 9, 

2000). This action relates to toxic 

chemical reporting under EPCRA 

section 313, which primarily affects 

private sector facilities. Thus, Executive 

Order 13175 does not apply to this 

action. 

G. Executive Order 13045: Protection of 

Children From Environmental Health 

Risks and Safety Risks 

EPA interprets Executive Order 13045 

(62 FR 19885, April 23, 1997) as 

applying only to those regulatory 

actions that concern environmental 

health or safety risks that EPA has 

reason to believe may 

disproportionately affect children, per 

the definition of ‘‘covered regulatory 

action’’ in section 2–202 of the 

Executive Order. This action is not 

subject to Executive Order 13045 

because it does not concern an 

environmental health risk or safety risk. 

H. Executive Order 13211: Actions 

Concerning Regulations That 

Significantly Affect Energy Supply, 

Distribution, or Use 

This action is not subject to Executive 

Order 13211 (66 FR 28355, May 22, 

2001), because it is not a significant 

regulatory action under Executive Order 

12866. 

I. National Technology Transfer and 

Advancement Act (NTTAA) 

This rulemaking does not involve 

technical standards and is therefore not 

subject to considerations under section 

12(d) of NTTAA, 15 U.S.C. 272 note. 

J. Executive Order 12898: Federal 

Actions To Address Environmental 

Justice in Minority Populations and 

Low-Income Populations 

EPA has determined that this action 

will not have disproportionately high 

and adverse human health or 

environmental effects on minority or 

low-income populations as specified in 

Executive Order 12898 (59 FR 7629, 

February 16, 1994). This action does not 

address any human health or 

environmental risks and does not affect 

the level of protection provided to 

human health or the environment. This 

action adds an additional chemical to 

the EPCRA section 313 reporting 

requirements. By adding a chemical to 

the list of toxic chemicals subject to 

reporting under section 313 of EPCRA, 

EPA would be providing communities 

across the United States (including 

minority populations and low income 

populations) with access to data which 

they may use to seek lower exposures 

and consequently reductions in 

chemical risks for themselves and their 

children. This information can also be 

used by government agencies and others 

to identify potential problems, set 

priorities, and take appropriate steps to 


asabaliauskas on DSK3SPTVN1PROD with PROPOSALS
35290 Federal Register / Vol. 81, No. 106 / Thursday, June 2, 2016 / Proposed Rules 

reduce any potential risks to human 

health and the environment. Therefore, 

the informational benefits of the action 

will have positive human health and 

environmental impacts on minority 

populations, low-income populations, 

and children. 

List of Subjects in 40 CFR Part 372 

Environmental protection, 

Community right-to-know, Reporting 

and recordkeeping requirements, and 

Toxic chemicals. 

Dated: May 16, 2016. 

Gina McCarthy, 

Administrator. 

Therefore, it is proposed that 40 CFR 

chapter I be amended as follows: 

PART 372—[AMENDED] 

■ 1. The authority citation for part 372 

continues to read as follows: 

Authority: 42 U.S.C. 11023 and 11048. 

■ 2. In § 372.28, amend the table in 

paragraph (a)(2) as follows: 

■ a. Revise the heading for the second 

column, and 

■ b. Alphabetically add the category 

‘‘Hexabromocyclododecane (This 

category includes only those chemicals 

covered by the CAS numbers listed 

here)’’ and list ‘‘3194–55–6 (1,2,5,6,9,10- 

Hexabromocyclododecane)’’ and 

‘‘25637–99–4 

(Hexabromocyclododecane)’’ 

The additions to read as follows: 

§ 372.28 Lower thresholds for chemicals 

of special concern. 

(a) * * * 

(2) * * * 

Category name 

Reporting 

threshold 

(in pounds unless otherwise 

noted) 

*******

Hexabromocyclododecane (This category includes only those chemicals covered by the CAS numbers listed here) ................. 100

3194–55–6 1,2,5,6,9,10-Hexabromocyclododecane ................................................................................................................... ............................

25637–99–4 Hexabromocyclododecane ....................................................................................................................................... ............................

*******

* * * * * 

■ 3. In § 372.65, paragraph (c) is 

amended by adding alphabetically an 

entry for ‘‘Hexabromocyclododecane 

(This category includes only those 

chemicals covered by the CAS numbers 

listed here)’’ to the table to read as 

follows: 

§ 372.65 Chemicals and chemical 

categories to which this part applies. 

* * * * * 

(c) * * * 

Category name Effective date 

*******

Hexabromocyclododecane (This category includes only those chemicals covered by the CAS numbers listed here) ................. 1/1/17 

3194–55–6 1,2,5,6,9,10-Hexabromocyclododecane ................................................................................................................... ............................

25637–99–4 Hexabromocyclododecane ....................................................................................................................................... ............................

*******

[FR Doc. 2016–12464 Filed 6–1–16; 8:45 am] 

BILLING CODE 6560–50–P 

DEPARTMENT OF COMMERCE 

National Oceanic and Atmospheric 

Administration 

50 CFR Part 660 

[Docket No. 150316270–5270–01] 

RIN 0648–XE520 

Fisheries Off West Coast States; 

Modifications of the West Coast 

Commercial Salmon Fisheries; 

Inseason Actions #1 Through #5 

AGENCY: National Marine Fisheries 

Service (NMFS), National Oceanic and 

Atmospheric Administration (NOAA), 

Commerce. 

ACTION: Modification of fishing seasons; 

request for comments. 

SUMMARY: NMFS announces five 

inseason actions in the ocean salmon 

fisheries. These inseason actions 

modified the commercial salmon 

fisheries in the area from Cape Falcon, 

OR to Point Arena, CA. 

DATES: The effective dates for the 

inseason actions are set out in this 

document under the heading Inseason 

Actions. Comments will be accepted 

through June 17, 2016. 

ADDRESSES: You may submit comments, 

identified by NOAA–NMFS–2016–0007, 

by any one of the following methods: 

• Electronic Submissions: Submit all 

electronic public comments via the 

Federal eRulemaking Portal. Go to 

www.regulations.gov/

#!docketDetail;D=NOAA-NMFS-2016- 

0007, click the ‘‘Comment Now!’’ icon, 

complete the required fields, and enter 

or attach your comments. 

• Mail: William W. Stelle, Jr., 

Regional Administrator, West Coast 

Region, NMFS, 7600 Sand Point Way 

NE., Seattle, WA. 98115–6349. 

Instructions: Comments sent by any 

other method, to any other address or 

individual, or received after the end of 

the comment period, may not be 

considered by NMFS. All comments 

received are a part of the public record 

and will generally be posted for public 

viewing on www.regulations.gov 

without change. All personal identifying 

information (e.g., name, address, etc.), 

confidential business information, or 

otherwise sensitive information 

submitted voluntarily by the sender will 

be publicly accessible. NMFS will 

accept anonymous comments (enter ‘‘N/ 

A’’ in the required fields if you wish to 

remain anonymous). 


asabaliauskas on DSK3SPTVN1PROD with PROPOSALS