Persistence, Bioaccumulation, Environmental Hazard and Human Health Hazard Ratings for Alternatives to PBT Chemicals Proposed for Regulation


Section 6(c)(2)(C) of the Toxics Substances Control Act (TSCA) directs EPA to consider, to the extent practicable, whether technically and economically feasible alternatives that benefit health or the environment will be reasonably available as a substitute to chemicals proposed to be regulated under section 6(a). To this end, EPA analyzed the persistence, bioaccumulation, human hazard, and environmental hazard of possible alternatives to three of the five PBT chemicals (phenol, isopropylated phosphate (3:1) (PIP (3:1)), Pentachlorothiophenol (PCTP), and 2,4,6-tris(tert-butyl)phenol (2,4,6-TTBP)) proposed for regulation under section 6(a). A review of the data on the alternatives for PIP(3:1), PCTP, and 2,4,6-TTBP are provided in Table 1. For DecaBDE, EPA conducted an alternatives assessment in 2014 under EPA's Design for the Environment (DfE). DfE alternatives assessment partnerships bring together environmental organizations, industry leaders, academia, and others to evaluate the environmental and health impacts of potential safer alternative chemicals. The DfE alternatives assessment represents the best available information on alternatives for DecaBDE and the results are summarized below in Table 2.
One of the five chemicals, Hexachlorobutadiene (HCBD), is not included in this document. For HCBD, EPA is proposing no regulatory action under section 6(h); consequently, no potential substitutes have been identified, and it is not repeated in this document.  
Knowledge of the persistence, bioaccumulation, human hazard, and environmental hazard for possible alternatives aids EPA in describing the qualitative benefits of reducing exposure to the PBT chemicals should they be replaced with the alternative chemicals. The methodology for determining persistence, bioaccumulation, and hazard scores is described below.
 EPA identified substitutes for each chemical regulated under the proposed rule through various sources, including technical documents (e.g., EPA's Design for the Environment Alternatives Assessment, product patents), docket comments (for EPA's initial request for information from the public on the uses of the chemicals) conversations with industry, and general internet research (e.g., Google or other targeted searches).











Methodology for determining persistence and bioaccumulation scores for PCTP, isopropylated PIP (3:1) and 2,4,6-TTBP alternatives:

The persistence and bioaccumulation reviews were completed based on the results of EPISuite modeling and summaries of measured data available in ECHA, JCHECK and Physprop for the potential alternatives. It should be noted that EPISuite[TM]  should not be used to calculate pchem properties for Zinc Pentachlorothiophenol and Pentafluorothiophenol as salts and highly fluorinated compounds are outside the domains of EPISuite. 

Persistence:
P1 Environmental half-life < 2 months
P2 Environmental half-life > 2 months and < 6 months
P3 Environmental half-life > 6 months

A search was performed to identify data in the JCHECK or ECHA databases. If hydrolysis or biodegradation data were found, it was generally used to estimate a chemical's persistence score.

If no data were found in those databases, the chemical was run in EPISuite if the chemical was judged to be within the domains of the EPISuite models. BIOWIN models #5 and #6 were given priority in estimating persistence as they are QSARs based on measured data from OECD 301 C.

For chemicals without measured data and outside the domain of EPISuite, persistence was estimated based on EPA's experience from other chemicals having a similar structure.

Bioaccumulation:
B1 BCF < 1000
B2 BCF > 1000 & < 5000
B3 BCF > 5000
BU  "Unknown" - Insufficient information to establish bioaccumulation score

A search was performed to identify data in the JCHECK or ECHA databases. If bioconcentration data were found (e.g., OECD 305), it was generally used to estimate a chemical's bioaccumulation score.

If no data were found in those databases, the chemical was run in EPISuite if the chemical was judged to be within the domains of the EPISuite models. Both the regression model's estimated BCF and the Arnot Gobas BCF and BAF estimates were considered in determining the bioaccumulation score. In general, the highest model output was used to determine the bioaccumulation score. It was also considered whether the chemical's BCF and BAF were lower for higher trophic level organisms as a potential indicator of trophic magnification or dilution.

Some of the alternative chemicals were outside of EPISuite's domain and had no available measured data in the two chosen databases to estimate a BCF value. These chemicals were given a score of BU to indicate that it could not be determined the bioaccumulation score.


Methodology for determining environmental hazard scores for PBT alternatives:

For the identified alternative chemicals for three of the PBT chemicals, ECOSAR v.2.0  was used to predict environmental hazard. The ECOSAR Class Program estimates water solubility and the log of the octanol/water partition coefficient (log Kow) using methodology developed by the EPA and used in the EPA/OPPT EPISuite model for evaluation of physical-chemical properties and environmental fate of chemicals (the WSKOWWIN Program). Although the chemical class category of Neutral Organics within ECOSAR v.2.0 includes many discrete chemicals, if the log Kow is greater than 5 (acute fish and invertebrate), 6.4 (acute algae), 8 (fish and invertebrate Chronic Value (ChV)), or 5 (algae ChV), and the LC50 exceeds the water solubility by 10X, no effects at saturation are predicted. The difference in log Kow cutoffs between acute and chronic tests is expected as the hydrophobic nature of a test substance might not allow equilibrium to be achieved within the standard exposure durations for acute tests but may ultimately be achieved during chronic studies. The environmental hazard of Zinc Pentachlorothiophenol was not identified using ECOSAR v2.0 because the chemical structure is outside the model domains. Additionally, a possible chemical structure was selected to represent the Triaryl Phosphates isobutylenated (Phenol, isobutylenated, phosphate (3:1)) substance in order to use the modeling methods described for determining hazard. The ultimate environmental hazard score was determined using the methods from the TSCA Work Plan Chemicals: Methods Document (https://www.epa.gov/sites/production/files /2014-03/documents/work_plan_methods_document_web_final.pdf).


Methodology for determining structure to evaluate for chemicals requiring modeling

Triaryl Phosphates isobutylenated (Phenol, isobutylenated, phosphate (3:1)), 68937-40-6 is a mixture of chemical structures with varying numbers of butyl groups subsitituted on the phenyl groups. The composition may be composed of molecules that range from 0 to 15 substituted butyl groups. For the initial workplan assignment of fate and eco scores EPA used the SMILES string that EPISuite[TM] recommended for the CAS #. The same methodology is employed for determining the PBT scores for Triaryl Phosphates isobutylenated (Phenol, isobutylenated, phosphate (3:1)), 68937-40-6. This structure has one butyl group per phenyl group, but it is not necessarily the predominant structure in commercial mixtures and was chosen to allow for model evaluation of a single structure in EPISuite[TM] and ECOSAR. Selecting other structures within the CAS # may lead to other PBT evaluations.


Methodology for determining human health hazard scores for PBT alternatives:

For the identified alternative chemicals for three of the PBT chemicals, a search of authoritative sources was conducted for each alternative. The sources searched included:
 Health Canada Assessments
 European Union assessments
 ECHA data
 Australian Government Department of Health National Industrial Chemicals Notification and Assessment Scheme (NICNAS)
 Organisation for Economic Co-operation and Development (OECD) Screening Information Dataset (SIDS)
 United Nations Environment Programme (UNEP) Stockholm Convention on Persistent Organic Pollutants
 USEPA HPV Chemical Challenge Program
 Hazardous Substances Data Bank (HSDB)
 Agency for Toxic Substances and Disease Registry (ATSDR)
 The International Agency for Research on Cancer (IARC) 
 World Health Organization International Programme on Chemical Safety (IPCS) 
 National Institute for Public Health and the Environment (RIVM), 
 Texas Commission on Environmental Quality (TCEQ)
 U.S. EPA Integrated Risk Information System (IRIS)
 U.S. EPA Provisional Peer Review Toxicity Values for Superfund (PPRTV)
 EPA chemistry Dashboard https://comptox.epa.gov/dashboard
The ultimate human health hazard score was determined using the methods from the TSCA Work Plan Chemicals: Methods Document (https://www.epa.gov/sites/production/files/2014-03/documents/work_plan_methods_document_web_final.pdf).

The final hazard score encompasses both human health and environmental toxicity concerns, where the highest (i.e., most conservative) environmental or human health score is used.


Methodology for determining persistence, bioaccumulative and environmental and human health hazard scores for DecaBDE:

Table 2 summarizes the potential health, bioaccumulation, persistence and environmental risks for each pertinent alternative from EPA's alternatives assessment for DecaBDE, as well as potential uses in industry. As shown in the table, there are alternatives for a range of potential industry uses that have low ratings for human and environmental toxicity across all endpoints. However, there are also alternatives that are associated with similar or more severe health effects than DecaBDE. For example, the only known direct chemical substitute, decabromodiphenyl ethane (DBDPE), is similar in structure and toxicity to DecaBDE; it also poses high risk for developmental toxicity. When industry considers potential substitutes, the toxicity of substitutes should thus be taken into account to help realize the benefits of reduced exposures to DecaBDE. 


Table 1: Persistence, Bioaccumulation and Hazard Ratings for Potential Chemical Substitutes for PIP(3:1), PCTP, and 2,4,6-TTBP

                                      PBT
                                PBT Alternative
                             PBT Alternative CASRN
                              Persistence Rating
                            Bioaccumulation Rating
                          Environmental hazard Rating
                          Human health hazard Rating
                              Final Hazard Rating
                                   PIP(3:1)
                     2-ethylhexyl diphenyl phosphate ester
                                   1241-94-7
                                       1
                                       1
                                       3
                                       2
                                       3
                                   PIP(3:1)
  Triaryl Phosphates isobutylenated (Phenol, isobutylenated, phosphate (3:1))
                                  68937-40-6
                                       3
                                       3
                                       1
                                       2
                                       2
                                   PIP(3:1)
                         Isodecyl, diphenyl phosphate
                                  29761-21-5
                                       1
                                       1
                                       3
                                       2
                                       3
                                     PCTP
                               Diphenyldisulfide
                                   882-33-7
                                       3
                                       1
                                       3
                                       3
                                       3
                                     PCTP
                             Pentafluorothiophenol
                                   771-62-0
                                       3
                                       U
                                       3
                                      N/A
                                       3
                                     PCTP
                           2,2'-Dithiobisbenzanilide
                                   135-57-9
                                       1
                                       1
                                       3
                                       1
                                       3
                                     PCTP
                          Zinc Pentachlorothiophenol
                                   117-97-5
                                       3
                                       U
                                       U
                                       1
                                       1
                                  2,4,6-TTBP
                        c,4-Dimethyl-6-tert-butylphenol
                                   1879-09-0
                                       3
                                       1
                                       3
                                       3
                                       3
                                  2,4,6-TTBP
                       2,6-Di-tert-butyl-p-cresol (BHT)
                                   128-37-0
                                       3
                                       2
                                       3
                                       2
                                       3
Unknown (U) indicates that EpiSuite and ECOSAR (v2.0) could not be used to predict the chemical's persistence and bioaccumulative properties and environmental hazard, respectively.
Not Available (N/A) indicates the inability to find human health hazard information per methodology outlined above in "Methodology for determining human health hazard scores for PBT alternatives".




Table 2: Persistence, Bioaccumulation and Hazard Ratings for Potential Chemical Substitutes for DecaBDE (see Alternatives Assessment for the Flame Retardant Decabromodiphenyl Ether (DecaBDE)


Substance Name and CAS Number
Human Health Effects[1]
Aquatic Toxicity[1]
Persistence[1]
Bioaccumulation[1]
Potential Industry Uses

Acute Toxicity
Carcinogenicity
Genotoxicity
Reproductive
Developmental
Neurological
Repeated Dose
Skin Sensitization
Respiratory Sensitization
Eye Irritation
Dermal Irritation
Acute 
Chronic 
 
 
 
VL = Very Low hazard L = Low hazard M = Moderate hazard H = High hazard VH = Very High hazard  Endpoints in colored text (VL, L, M, H, and VH) were assigned based on empirical data. Endpoints in black italics (VL, L, M, H, and VH) were assigned using values from estimation software and professional judgment. 
DecaBDE 
1163-19-5
L
M
L
L
H
L
M
L
-
L
L
L
L
VH
H
See section 4.1 for detailed use profile 
Known Direct Chemical Substitutes
Decabromodiphenyl ethane2 
84852-53-9
L
M
L
L
H
L
L
L
-
VL
VL
L
L
VH
H
Electronics; Wire and Cable; Public Buildings; Construction Materials; Automotive; Storage and Distribution; Products; Textiles; Waterborne emissions & coatings
Unconfirmed Potential Substitutes
Aluminum diethylphosphinate 225789-38-8
L
L
L
VL
M
M
M
L
-
L
VL
M
M
H
L
Electronics; Wire and Cable; Automotive; Aviation; Textiles
Aluminum hydroxide 21645-51-2
L
L
L
L
L
M
M
L
-
VL
VL
M
M
H
L
Electronics; Wire and Cable; Public Buildings; Construction Materials; Automotive; Aviation; Textiles; Waterborne emissions & coatings
Ammonium polyphosphate
68333-79-9
L
L
L
L
L
L
L
L
-
VL
L
L
L
VH
L
Electronics; Wire and Cable; Public Buildings; Construction Materials; Automotive; Aviation; Storage and Distribution; Products; Textiles; Waterborne emissions & coatings
Bis (hexachlorocyclopentadieno) cyclooctane
13560-89-9
L
M
M
VL
VL
L
M
L
-
VL
L
L
L
VH
H
Electronics; Wire and Cable; Public Buildings; Construction Materials; Waterborne emissions & coatings
Bisphenol A bis-(diphenyl phosphate)
181028-79-5
L
M
L
L
L
L
L
L
-
L
L
L
L
H
H
Electronics
Brominated Epoxy Polymer(s)[3]
68928-70-1
L
L
L
L
L
L
L
L
-
L
L
L
L
VH
L
Electronics; Public Buildings; Construction Materials; Automotive; Storage and Distribution Products
Mixture of Brominated Epoxy Polymer(s) and Bromobenzyl Acrylate[4]
                                       L
                                       L
                                       L
                                       L
                                       L
                                       L
                                       L
                                       L
                                       -
                                       L
                                       L
                                       L
                                       L
                                      VH
                                       L
Electronics; Storage and Distribution Products
Brominated epoxy resin endcapped with tribromophenol
135229-48-0
L
L
L
L
L
L
L
L
-
L
VL
L
L
VH
L
Electronics; Public Buildings; Construction Materials; Automotive
Brominated polyacrylate
59447-57-3
L
L
L
L
L
L
L
L
-
L
L
L
L
VH
L
Electronics; Automotive; Storage and Distribution Products
Brominated poly(phenylether)[4]
L
L
L
VL
M
L
L
L
-
L
VL
L
L
VH
H
Electronics; Wire and Cable; Public Buildings; Construction Materials; Automotive; Storage and Distribution Products; Textiles; Waterborne emissions & coatings
Brominated polystyrene[3]
88497-56-7
L
L
L
L
L
L
L
L
-
L
L
L
L
VH
L
Electronics; Automotive
Ethylene bistetrabromophthalimide
32588-76-4
L
M
L
L
M
L
L
L
-
VL
VL
L
L
VH
H
Electronics; Wire and Cable; Public Buildings; Construction Materials; Automotive; Storage and Distribution Products; Waterborne emissions & coatings
Magnesium hydroxide
1309-42-8
L
L
L
L
L
L
L
L
-
M
L
L
L
H
H
Electronics; Wire and Cable; Public Buildings; Construction Materials; Automotive; Aviation; Storage and Distribution Products; Waterborne emissions & coatings
Melamine cyanurate
37640-57-6
L
M
M
M
M
L
H
L
-
L
L
L
L
VH
L
Electronics; Wire and Cable; Public Buildings; Construction Materials; Automotive; Aviation; Textiles; Waterborne emissions & coatings
Melamine polyphosphate
15541-60-3
L
M
M
L
L
L
M
L
-
L
VL
L
L
H
L
Electronics; Wire and Cable; Public Buildings; Construction Materials; Automotive; Aviation; Storage and Distribution Products; Waterborne emissions & coatings
N-alkoxy hindered amine reaction products
191680-81-6
L
M
L
H
H
L
H
L
-
L
VL
H
H
H
H
Construction Materials; Textiles
Phosphonate oligomer
68664-06-2
L
M
L
L
L
M
L
L
-
M
M
L
H
VH
H
Electronics; Public Buildings; Construction Materials
Phosphoric acid, mixed esters with [1,1‟-bisphenol-4,4‟-diol] and phenol
1003300-73-9
L
M
L
L
L
L
L
L
-
VL
VL
H
H
H
M
Electronics; Automotive; Aviation
Polyphosphonate
68664-06-2
L
L
L
L
L
L
L
L
-
M
M
L
H
VH
H
Electronics; Wire and Cable; Public Buildings; Construction Materials; Automotive; Aviation; Textiles
Poly[phosphonate-cocarbonate] 
77226-90-5
L
L
L
L
L
L
L
L
-
L
L
L
L
VH
L
Electronics; Wire and Cable; Public Buildings; Construction Materials; Automotive; Aviation
Red phosphorus
7723-14-0
L
L
M
L
L
L
L
L
-
M
M
L
L
H
L
Electronics; Wire and Cable; Automotive; Aviation; Waterborne emissions & coatings
Resorcinol bisdiphenylphosphate
125997-21-9
L
M
L
L
M
M
M
L
-
L
VL
VH
VH
M
H
Electronics
Substituted amine phosphate mixture[4]
H
M
M
M
M
L
M
L
M
M
VL
M
L
H
L
Electronics; Wire and Cable; Public Buildings; Construction Materials; Automotive; Aviation; Storage and Distribution Products
Tetrabromobisphenol A bis (2,3-dibromopropyl ether)[3]
21850-44-2
L
M
M
M
M
L
M
L
-
L
L
L
L
VH
H
Electronics; Public Buildings; Construction Materials; Automotive
Triphenyl phosphate
115-86-6
L
M
L
L
L
L
H
L
-
L
VL
VH
VH
L
M
Electronics
Tris(tribromoneopentyl) phosphate[3]
19186-97-1
M
M
L
M
M
H
L
L
-
L
L
L
L
H
M
Electronics; Public Buildings; Construction Materials; Textiles
Tris(tribromophenoxy) triazine[3]
25713-60-4
L
L
L
L
L
L
L
L
-
L
VL
L
L
VH
H
Electronics
Source(s):
ILEPA (2007); EPA, (2014a; 2014a)
Note(s):
[1] Hazard classifications (e.g., high, moderate) are based on the Design for the Environment (DfE) criteria for alternatives assessment.
[2] Decabromodiphenyl ethane (DBDPE) is structurally very similar to decaBDE and is known to already have substituted decaBDE in some products and uses, though it may not be an appropriate substitute for all potential uses listed.
[3] Based on structure, chemical is considered a likely potential substitute for decaBDE.
[4] CAS number for potential alternative is confidential.


