EPA Document# EPA-740-R1-8001
June 2018
United States	Office of Chemical Safety and
¦¦¦¦ Jfm Environmental Protection Agency	Pollution Prevention
Environmental and Human Health Hazards
of Five Persistent, Bioaccumulative and
Toxic Chemicals
Peer Review Draft
June 2018

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Contents
1.	EXECUTIVE SUMMARY	4
2.	BACKGROUND	5
3.	APPROACH FOR SURVEYING THE CHEMICAL-SPECIFIC HAZARD DATA	6
3.1.	Environmental Hazard Data	6
3.2.	Human Health Hazard Data	7
4.	DECABROMODIPHENYL ETHER	8
4.1.	Environmental Hazard Summary	8
4.2.	Human Health Hazard Summary	12
5.	HEXACHLOROBUTADIENE	15
5.1.	Environmental Hazard Summary	15
5.2.	Human Health Hazard Summary	17
6.	PHENOL, ISOPROPYLATED, PHOSPHATE (3:1)	20
6.1.	Environmental Hazard Summary	20
6.2.	Human Health Hazard Summary	24
7.	2,4,6-TRIS(TERT-BUTYL) PHENOL	26
7.1.	Environmental Hazard Summary	26
7.2.	Human Health Hazard Summary	28
8.	PENTACHLOROTHIOPHENOL	30
8.1.	Environmental Hazard Summary	30
8.2.	Human Health Hazard Summary	32
9.	REFERENCES	34
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Tables
Table 4-1. Summary of Surveyed Environmental Hazard Data for Decabromodiphenyl Ether	9
Table 4-2. Summary of Surveyed Human Health Hazard Data for Decabromodiphenyl Ether	13
Table 5-1. Summary of Surveyed Environmental Hazard Data for Hexachlorobutadiene	16
Table 5-2. Summary of Surveyed Human Hazard Data for Hexachlorobutadiene	18
Table 6-1. Summary of Surveyed Environmental Hazard Data for Phenol, Isopropylated, Phosphate
(3:1)	21
Table 6-2. Summary of Surveyed Human Health Hazard Data for Phenol, Isopropylated, Phosphate
(3:1)	25
Table 7-1. Summary of Surveyed Environmental Hazard Data for 2,4,6-Tris(tert-butyl) phenol	27
Table 7-2. Summary of Surveyed Human Health Hazard Data for 2,4,6-Tris(tert-butyl) phenol	29
Table 8-1. Summary of Surveyed Environmental Hazard Data for Pentachlorothiophenol (PCTP)	31
Table 8-2. Summary of Surveyed Human Health Hazard Data for Pentachlorothiophenol (PCTP)	33
Acknowledgement
This report was developed by the United States Environmental Protection Agency (U.S. EPA),
Office of Chemical Safety and Pollution Prevention (OCSPP), Office of Pollution Prevention and
Toxics (OPPT). The OPPTTeam acknowledges support and assistance from EPA contractor ICF
(Contract No. EP-C-14-001).
Disclaimer
Reference herein to any specific commercial products, process or service by trade name,
trademark, manufacturer or otherwise does not constitute or imply its endorsement,
recommendation or favoring by the U.S. Government.
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1. Executive Summary
Section 6(h) of the Toxic Substance Control Act (TSCA), as amended by the Frank R. Lautenberg
Chemical Safety for the 21st Century Act, directs U.S. Environmental Protection Agency (EPA) to
take expedited action to propose rules under TSCA with respect to chemicals identified in EPA's
2014 Update of the TSCA Work Plan for Chemical Assessments and meeting criteria relating to
persistence, bioaccumulation and toxicity (PBT) and other factors. EPA must issue a proposed
rule no later than June 22, 2019, with a final rule to follow no more than 18 months later.
EPA has developed this hazard summary document for five PBT chemical substances it has
identified for proposed action under TSCA section 6(h "PBT chemicals"). This document and the
data cited for each PBT will support the development of a proposed rule that addresses the
risks of injury to the environment and health that the EPA determines are presented by the
subject PBT chemicals.
To create this hazard summary, environmental and human health hazard data were compiled
from various primary and secondary sources of both confidential and publicly-available
information. The hazard summaries relevant to environmental hazard include acute and chronic
toxicological information for both aquatic and terrestrial wildlife. Due to a general lack of data
found for 2,4,6-Tris(tert-butyl) phenol (2,4,6 TTBP) and pentachlorothiophenol (PCTP) in the
primary and secondary sources initially searched, additional literature searches were conducted
for environmental hazard data for these chemicals by searching for the chemical name and
CASRN in Web of Science and Science Direct. Generally, more acute than chronic aquatic
toxicity data are available for all five PBT chemicals. However, data were available for
organisms spanning three trophic levels for all the PBT chemicals, except for PCTP.
The hazard summaries relevant to human health focus on repeated-dose studies given the PBT
nature of the chemicals of interest. Available published and unpublished repeated-dose toxicity
data are tabulated according to health endpoints and the identified studies are briefly
summarized. Human health hazard data are presented in the context of existing toxicological
assessments, when available.
Available hazard information is tabulated and briefly summarized within this document. The
purpose of the environmental and human health summary is to identify known hazards of the
PBT chemicals; the information in this document is not meant to represent an exhaustive
literature review nor an analysis of relative importance or comparative dose-response among
hazards. EPA leveraged previous data compilations and existing information, wherever possible,
as the initial data gathering approach and to survey the environmental and human health
hazard data and information.
The document is intended to provide an overview of the nature and extent of hazards for use in
making risk-based regulatory decisions. However, some qualitative interpretation is provided in
discussing the reported data. Similarly, the document summarizes points of departure (e.g.,
NOAEL/LOAEL) or other hazard benchmarks as reported in the data source, rather than the
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'selection' of particular studies for use in conjunction with any particular exposure pathway(s)
or risk assessment scenarios, or a dose-response analysis conducted by EPA.
2. Background
Under the Toxic Substances Control Act (TSCA), as amended by the Frank R. Lautenberg
Chemical Safety for the 21st Century Act, EPA has new authorities to regulate existing chemical
substances. Section 6(h) of TSCA directs EPA to take expedited regulatory action under section
6(a), for certain PBT chemicals.
The chemical substances subject to TSCA section 6(h) are those:
•	Identified in the 2014 update of the TSCA Work Plan for Chemical Assessments;
•	That the Administrator has a reasonable basis to conclude are toxic and that with
respect to persistence and bioaccumulation, score high for one and either high or
moderate for the other, under the 2012 TSCA Work Plan Chemicals Methods Document
(or a successor scoring system);
•	That, are not a metal or a metal compound;
•	For which the Administrator has not completed a Work Plan Problem Formulation,
initiated a review under section 5 (new chemicals), or entered into a consent agreement
under section 4 (testing), prior to June 22, 2016;
•	Exposure to which under the conditions of use is likely to the general population, to a
potentially exposed or susceptible subpopulation, or the environment, on the basis of
an exposure and use assessment; and
•	That are not designated as a high priority substance by EPA and are not the subject of a
manufacturer request for a risk evaluation.
Taking the above criteria into account, EPA has identified the following five PBT chemicals for
proposed action under TSCA section 6(h):
•	Decabromodiphenyl ether (DecaBDE) (CASRN 1163-19-5)
o Scored high for hazard, high for persistence, and high for bioaccumulation on the
2014 update
•	Hexachlorobutadiene (HCBD) (CASRN 87-68-3)
o Scored high for hazard, high for persistence, and high for bioaccumulation on the
2014 update
•	Phenol, isopropylated, phosphate (3:1) (PIP 3:1) (CASRN 68937-41-7)
o Scored high for hazard, high for persistence, and high for bioaccumulation on the
2014 update
•	2,4,6-Tris(tert-butyl) phenol (2,4,6 TTBP) (CASRN 732-26-3)
o Scored high for hazard, moderate for persistence, and high for bioaccumulation on
the 2014 update
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•	Pentachlorothiophenol (PCTP) (CASRN 133-49-3)
o Scored high for hazard, high for persistence, and high for bioaccumulation on the
2014 update
3. Approach for Surveying the Chemical-Specific Hazard Data
The purpose of this document is to identify known hazards of the PBT chemicals; the
information in this document is not meant to represent an exhaustive literature review nor an
analysis of relative importance or comparative dose-response among hazards. Under TSCA
section 6(h), EPA is required to take expedited regulatory action for PBT chemicals meeting the
abovementioned criteria.
EPA conducted chemical-specific searches for information on the following five PBT chemicals
to conduct a survey of available data: decabromodiphenyl ether (CASRN 1163-19-5),
hexachlorobutadiene (CASRN 87-68-3), phenol, isopropylated, phosphate (3:1) (CASRN 68937-
41-7), 2,4,6-Tris(tert-butyl) phenol (CASRN 732-26-3), and pentachlorothiophenol (CASRN 133-
49-3).
3.1. Environmental Hazard Data
EPA leveraged previous data compilations, wherever possible, as the initial data gathering
approach. Literature already available from various governmental jurisdictions were relied on
to summarize potential environmental hazards. Database searches from the European
Chemicals Agency (ECHA) Database and EPA's ECOTOXicology knowledgebase (ECOTOX) were
utilized to identify environmental hazard data for the PBT chemicals. Additionally, EPA searched
for chemical assessments conducted by the following sources:
•	Environment Canada Health Canada,
•	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, and
•	USEPA HPV Chemical Challenge Program.
The above-mentioned databases and sources of chemical assessments did not include data on
every chemical. When applicable, literature already gathered from other jurisdiction
assessments were relied upon to examine potential environmental hazard. Identified data in
these sources are summarized below.
EPA conducted a high-level literature search and leveraged existing information, wherever
possible, to facilitate the data gathering effort supporting potential risk management practices.
Environmental literature was searched for and screened following well accepted methods,
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approaches and procedures established for the ECOTOX knowledge base. The ECOTOX standard
operating procedures (SOPs) provide details about the information needs driving the
environmental literature searches1. Due to the lack of data initially identified for 2,4,6-Tris(tert-
butyl) phenol and pentachlorothiophenol (PCTP) in the various sources cited above and in
ECOTOX, additional searches on the Web of Science and Science Direct were conducted.
For all literature searches, both the chemical name and the CAS registry number (CASRN) were
used as key words. There was no date limit used for any of the literature searches. If there was
a date limit option included for any of the databases, the whole range was used (i.e., ECOTOX's
publication year range is 1915 to 2018).
3.2. Human Health Hazard Data
EPA leveraged previous data compilations and existing information, wherever possible, as the
initial data gathering approach and to survey the human health hazard data and information.
Using the CASRN for each PBT chemical, EPA searched the International Toxicity Estimates for
Risk (ITER; https://toxnet.nlm.nih.gov/newtoxnet/iter.htm) database for available human
health assessments for the five PBT chemicals. This database searches for assessments was
from the following organizations:
•	Agency for Toxic Substances and Disease Registry (ATSDR),
•	Health Canada,
•	The International Agency for Research on Cancer (IARC),
•	World Health Organization International Programme on Chemical Safety (IPCS),
•	National Science Foundation (NSF) International,
•	National Institute for Public Health and the Environment (RIVM),
•	Texas Commission on Environmental Quality (TCEQ), and
•	U.S. EPA Integrated Risk Information System (IRIS).
In addition, toxicological assessments from California EPA (CalEPA), U.S. EPA Provisional Peer
Review Toxicity Values for Superfund (PPRTV), U.S. EPA Alternative Assessments, and the
Organisation for Economic Co-operation and Development (OECD) Screening Information
Dataset (SIDS) were separately searched for hazard information on the PBT chemicals. Several
human health assessments were identified from this search for DecaBDE and HCBD. For the
remaining three chemicals, EPA searched the European Chemicals Agency (ECHA) database,
EPA's ChemView, and the Hazardous Substances Data Bank (HSDB) on TOXNET. The databases
were searched by chemical CASRN to gather additional human health data/information from
unpublished studies. For PCTP, no relevant repeated dose animal toxicity studies or human data
were available for the chemical. Thus, a search was conducted for analogous chemicals that are
known to metabolize or degrade into PCTP using the expanded results feature in the HSDB.
1ECOTOX and related SOPs (https://cfpub.epa.gov/ecotox/help.cfm?helptabs=tab4).
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The summaries were constructed from the hazards identified in the toxicological assessments,
when available. For chemicals without existing assessments, all repeated-dose studies
identified in the additional literature searches were provided in the evidence tables and
summarized in the text.
The following chapters provide a summary of the hazard data for each of the chemicals subject
to TSCA section 6(h) identified using the methods provided in Chapter 3. The hazards are
provided as brief summaries and in tables.
4. Decabromodiphenyl Ether
4.1. Environmental Hazard Summary
The available information indicates that DecaBDE is acutely toxic to aquatic invertebrates
(daphnia) at concentration as low as 0.02 mg/L (Nakari and Huhtala. 2010). Acute toxicity to fish
varies among species, with acute effects reported in the range of 0.01 to >500 mg/L (Nakari and
Huhtala. 2010; Chemicals Inspection and Testing Institute. 1992). No effect on growth of a
sediment invertebrate (midge) was observed up to 5,000 mg/kg sediment dry weight (Hardy et
al.. 2012). Chronic exposures of DecaBDE to various species of vertebrates also show the
potential to cause both growth and reproductive toxicity as well as an array of other
toxicological endpoints (e.g., neurotoxicity, behavioral changes) (He et al.. 2011; Noyes et al..
2011; Kuo et al.. 2010; Kierkegaard et al.. 1999). Data on the effects of DecaBDE on aquatic
vegetation was not identified, however, one study demonstrated that at exposure
concentrations up to 1 mg/L, DecaBDE did not inhibit the growth of three species of marine
algae (Walsh et al.. 1987). In terms of terrestrial toxicological data on DecaBDE, there are three
chronic earthworm studies that have exposures spanning between 14 and 56 days that indicate
DecaBDE is toxic at high concentrations (>2,000 mg/kg soil dry weight) (ECHA. 2018a; Hardy et
al.. 2011; Great Lakes Chemical Corp. 2000). Similarly, with a variety of commonly grown
vegetables, even at the highest exposure concentration (5,349 mg/kg soil dry weight), no
mortality was documented and there was no reduction in growth (Wildlife Intl LTD. 2001).
Most of the available hazard information on DecaBDE are for a product containing DecaBDE,
therefore it is important to note that many of the studies cited in Table 4-1 examined effects
from the exposure to a mixture containing DecaBDE. Commercial mixtures containing DecaBDE
(77-98%) also consist of smaller amounts of congeners of nona- and octa-brominated diphenyl
ether, although the product composition can vary greatly (ECHA. 2012; U.S. EPA. 2008).
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Table 4-1. Summary of Surveyed Environmental Hazard Data for Decabromodiphenyl Ether
Media J*""*
Duration
—
Endpoint
ILJIM
Unit
Chemical and Study
Specification
Reference


Rainbow trout
96-hr LLRso
(lethality)
>110
mg/L
Water accommodated
fraction (WAF) exposure;
nominal
Hardv et al. (2012)


Zebrafish embryo
<8-d LOAEL
(neurological
pathway
expression and
abnormal
behavior)
12.5
mg/kg
Sediment to embryo
bioavailability test with BDE-
209. Positive bioaccumulation
of BDE-209.
Garcia-Revero et al.
(2014)a
Aquatic
Acute
Zebrafish
96-hr LOEC
(hatching)
0.0125
mg/L
Non-good laboratory practice
(GLP) International
Organization for
Standardization ((ISO) 12890,
1999); BDE-209 exposure
above the water solubility
(0.72 Mg/L)
Nakari and Huhtala
(2010)a


Killifish
48-hr LCso
(lethality)
>500
mg/L
Non-GLP Japanese Industrial
Standards ((JIS) K 0102-1986-
71); only one concentration
(500 mg/L- nominal) used; no
information on purity
Chemicals Inspection
and Testing Institute
(1992)


Daphnid
48-hr ECso
(immobilization)
0.019
mg/L
GLP (ISO 6341, 1997); BDE-209
exposure above the water
solubility (0.72 ng/L)
Nakari and Huhtala
(2010)a


Algae
96-hr ECso
(growth)
>1
mg/L
Only 0 and 1 mg/L exposures
Walsh et al. (1987)

Chronic
Rainbow trout
120-d LOAEL
(uptake)
>10
mg/kg
bw/d
Non-GLP 49-d feeding study
with 71-d depuration; Dow
FR-300-BA
Kierkegaard et al. (1999)
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Study
Media „ Organism
Duration
Endpoint
Hazard Value
Unit
Chemical and Study
Specification

Reference


Lake whitefish
30-d LOAEL
(growth)
2
Hg/g food
BDE-209
Kuoetal. (2010)a


Zebrafish
LOAEL
(delayed hatching,
reduction in motor
neuron
development and
growth)
0.001-1
HM
Multigenerational exposure to
BDE-209 (exposure period
n/a).
Heetal. (2011)a


Fathead minnow
28-d LOAEL
(thyroid hormone
regulation)
9.8
Hg/g food
Followed by 14-d depuration;
BDE-209
Noves etal. (2011)a


Goldfish
21-d LOEC
(oxidative stress)
10
mg/kg bw
Intraperitoneal exposure
Feng et al. (2013)


African clawed frog
45-d LOEC
(thyroid system
disruption; growth)
1; 1000
ng/L
BDE-83R
Qin etal. (2010)a


Midge
28-d LOEC
(growth)
>5,000
mg/kg
sediment
dw
GLP
Hardv et al. (2012)
Terrestrial
Chronic
Earthworm
14-d LOEL
(body chemistry
changes)
2000
Hg/cm2
n/a
Great Lakes Chemical
Corp (2000)
Earthworm
28-d LOEC
(mortality and
reproduction)
NOEC: 1,910;
LOEC: 3,720
mg/kg soil
dw
Organisation for Economic Co-
operation and Development
(OECD) GLP study (OECD TG-
222)
Hardv et al. (2011)
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Study
Media „ Organism
Duration
Endpoint
Hazard Value
Unit
Chemical and Study
Specification
Reference


Earthworm
56-d ECso
(survival and
reproduction)
>4910
mg/kg soil
dw
GLP (EPAOPPTS 850.6200;
OECD 207); equal proportions
of three different products
ECHA (2018a);
(unnamed 2001 and
2002 report)3
Onion, Cucumber,
Soybean, Ryegrass,
Tomatoes and Corn
21-d NOEC
(growth)
5349; >6250
(nominal)
mg/kg soil
dw
GLP (OECD 208; EPAOPPTS
850.4100; EPAOPPTS
850.4225); equal proportions
of three different products
Wildlife Intl LTD (2001)a
aUse of a commercial product or mixture (containing the target chemical) in the study.
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4.2. Human Health Hazard Summary
Toxicological assessments have been conducted by EPA's IRIS program (U.S. EPA. 2008). Health
Canada (Health Canada. 2012). ATSDR, and IARC (IARC. 1999a). Oral repeated dose animal data
for DecaBDE indicate developmental neurological effects, developmental immunological
effects, general developmental toxicity, and liver effects.
Several published oral studies have been conducted and range from short-term developmental
studies to 2-year carcinogenicity studies in rats and mice (Table 4-2). Limited information is
available on the effects from inhalation and dermal routes of exposure so no conclusion was
made regarding these exposure routes. The available toxicological assessments identified
developmental neurotoxicity in several developmental studies with dose-related effects such as
altered behavior, reduced strength and reflexes, reduced locomotor activity, and impaired
learning (Health Canada. 2012; U.S. EPA. 2008). Dose-related brain effects were reported in
adult rats as well, which was demonstrated by a decrease in brain weight following 28-days of
oral gavage (Van der Ven et al.. 2008).
Developmental immunotoxicity was indicated by reduced IgM levels and reduced natural killer
cell numbers in F1 female mice that were dose-related (Teshima et al.. 2008). The toxicological
assessment also found that general developmental effects were also observed in mice as
indicated by reduced DNA integrity in the sperm and reduced serum T3 levels (Tseng et al..
2013; Tseng et al.. 2008; Hsu et al.. 2006) and increased liver weights, centrilobular hypertrophy
and increased cytoplasmic eosinophilia in renal proximal tubules in rat pups (Fujimoto et al..
2011). Noncancer liver effects were observed in a 2-year dietary study in rats which reported
degeneration and thrombosis in the liver (NTP. 1986).
In addition, animal data indicates that there is suggestive evidence for carcinogenic potential
based on increased liver granulomas, centrilobular hypertrophy, and adenomas and carcinomas
as well as increased thyroid follicular cell hyperplasia in mice (NTP. 1986). NOAELs for
developmental effects ranged from 1.34 mg/kg-day to 10 mg/kg-day in mice and rats. The
cancer slope factor for liver neoplasms and carcinomas is 7 x 10"4 per mg/kg-day (U.S. EPA.
2008).
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Table 4-2. Summary of Surveyed Human Health Hazard Data for Decabromodiphenyl Ether
Organ/System
Study Type
Doses
POD
Health Effect
Reference
Developmental
neurotoxicity
Neurodevelopmental oral
study to neonatal mice
0, 1.34, 2.22, 13.4,
20.1 mg/kg-day
NOAEL: 1.34 mg/kg-day
LOAEL: 2.22 mg/kg-day
Change in behavior,
decreased activity, poor
habituation
Johansson et al. (2008)
Developmental
neurotoxicity
Oral gavage study in
pregnant mice from PND
2-15
0, 6, 20 mg/kg-day
LOAEL: 6 mg/kg-day
Effects on palpebral
reflex, grip strength,
locomotor activity,
struggling behavior in F1
pups
Rice et al. (2007)
Developmental
neurotoxicity
Oral gavage study in
pregnant mice from PNDs
2-15
0, 6, 20 mg/kg-day
NOAEL: 6 mg/kg-day
LOAEL: 20 mg/kg-day
Altered performance in
neurological and visual
tests suggesting impaired
learning in F1 offspring
Rice et al. (2009)
Developmental
neurotoxicity
OECDTG 426; Oral study
in pregnant rats from GD
6 to lactation day 21
0,1,10,100,1000
mg/kg-day
NOAEL: 10 mg/kg-day
LOAEL: 100 mg/kg-day
Increase in pup deaths,
reduced motor activity
Biesemeier et al. (2011)
Developmental
neurotoxicity
Single dose gavage in
Sprague-Dawley male rats
on PND3
0, 6.7, 20.1 mg/kg-
day
NOAEL: none identified
LOAEL: 6.7 mg/kg-day
Changes in locomotion,
activity, and rearing
Viberg et al. (2007)
Developmental
neurotoxicity
Single dose gavage in
NMRL male mice on PND
3 and 19
0,2.22, 20.1 mg/kg-
day
NOAEL: 2.22 mg/kg-day
LOAEL: 20.1 mg/kg-day
Changes in locomotion,
activity, and rearing
Viberg et al. (2003)
Developmental
immunotoxicity
Oral gavage of mice dams
from day 10 of gestation
to PND 21
0,10,100,1000
ppm
NOAEL: not reported
LOAEL: 5 mg/kg-day
Reduced IgM and reduced
NK cell counts in F1
females
Teshima et al. (2008)
Developmental
Oral gavage of mice dams
on days 0-17 of
pregnancy
0, 10, 500, 1500
mg/kg-day
LOAEL: 10 mg/kg-day
Reduced sperm DNA
integrity, decrease T3,
and sperm H2O2 in F1
males,
(2013); Tseng et al.
(2008); Hsu et al. (2006)
Developmental
Oral dietary study in
pregnant rats from GD 10
to PND 20
0, 10, 100, 1000
ppm
LOAEL: 0.7-2.4 mg/kg-day
Liver and kidney
histopathological effects
in F1 pups
Fuiimoto et al. (2011)
Oxidative stress
60-day oral gavage mouse
study
0, 0.1, 40, 80, 160
mg/kg-day
NOAEL: 0.1 mg/kg-day
LOAEL: 40 mg/kg-day
Decreased superoxide
dismutase; increased
malonyldialdehyde
Liang et al. (2010)
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Organ/System
Study Type
Doses
POD
Health Effect
Reference
Brain
28-day oral gavage Wistar
rat study
0, 1.87, 3.75, 7.5,
15, 30, 60 mg/kg-
day
NOAEL: 30 mg/kg-day
LOAEL: 60 mg/kg-day
Decreased brain weight
Van der Ven et al. (2008)
Liver
2-year dietary study in
Males: 0,1120,
NOAEL: 1120 mg/kg-day in
Degeneration and
NTP (1986)

F344 rats
2240 mg/kg-day
males
LOAEL:
2240 mg/kg-day in females
thrombosis of the liver

Liver
2-year dietary study in
Males: 0, 3200,
NOAEL: none identified
Increased granulomas,
NTP (1986)

B6C3F1 mice
6650 mg/kg-day
LOAEL: 3200 mg/kg-day
hypertrophy, adenomas
and carcinomas in the
liver

Thyroid
2-year dietary study in
Males: 0, 3200,
NOAEL: none identified
Increased follicular cell
NTP (1986)

B6C3F1 mice
6650 mg/kg-day
LOAEL: 3200 mg/kg-day
hyperplasia

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5. Hexachlorobutadiene
5.1. Environmental Hazard Summary
HCBD is acutely toxic to aquatic invertebrates at concentrations ranging from 0.032 to 0.5 mg/L
(Knie et al.. 1983; U.S. EPA. 1980). Acute LCsos in two species offish were both 0.09 mg/L
(Geiger et al.. 1985; Leeuwangh et al.. 1975). Algae appear to be less sensitive to HCBD, as
compared to aquatic invertebrates and fish, with a reported NOAEL of 25 mg/L (Bringmann and
Kuhn. 1977). There is only chronic HCBD aquatic toxicity data available for fish. HCBD is toxic to
fish at exposure levels ranging from 0.0096 to 0.16 mg/L, where the effects ranges from
reductions in growth, increases in mortality, and liver damage (Hermens et al.. 1985; Benoit et
al.. 1982; Laseter et al.. 1976). HCBD is both acutely and chronically toxic to aquatic life at very
low concentrations. A single toxicity test was identified for terrestrial organisms. A 90-d chronic
exposure of HCBD to quail revealed a significant reduction in chick survival when parents were
fed 10 mg HCBD/kg food-day (Schwetz et al.. 1974).
EPA used information from toxicological assessments of hexachlorobutadiene (HCBD) from
Health Canada, data from the ECHA database, data from ECOTOX. As seen in Table 5-1, all
surveyed data except for one study focuses on the aquatic toxicological effects of HCBD.
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Table 5-1. Summary of Surveyed Environmental Hazard Data for Hexachlorobutadiene
Media
Study duration

Organism

Hazard value

Chemical and Study
Specification
Reference


Fathead minnow
96-hr LCso
(lethality)
0.09
mg/L
n/a
Geiger et al. (1985)


Goldfish
96-hr LCso
(lethality)
90
Hg/L
n/a
Leeuwangh et al.
(1975)


Mysid shrimp
96-hr LCso
(lethality)
32
Hg/L
n/a
U.S. EPA (1980)

Acute
Sowbug
96-hr LCso
(lethality)
130
Hg/L
n/a
Leeuwangh et al.
(1975)


Daphnia
24-hr ECso
(endpoint n/a)
0.5
mg/L
n/a
Knie et al. (1983)
Aquatic

Algae
8-d NOAEL
25
mg/L
exposure
concentration over
water solubility
Bringmann and Kuhn
(1977)

Fathead minnow
28-d LOAEL
(lethality and growth)
0.013
mg/L
n/a
Benoit et al. (1982)


Guppy
14-d LCso
(lethality)
0.16
mg/L
n/a
Hermens et al. (1985)

Chronic
Goldfish
49-d LOAEL
(body weight; liver
weight and erratic
behavior)
0.0096; 0.03
mg/L
n/a
Leeuwangh et al.
(1975)


Largemouth bass
10-d LOAEL
(kidney and liver
damage)
0.03195
mg/L
n/a
Laseter et al. (1976)
Terrestrial
Chronic
Quail
90-d LOAEL
(chick survival)
10
mg/kg food
n/a
Schwetz et al. (1974)
Page 16 of 39

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5.2. Human Health Hazard Summary
Toxicological assessments have been conducted by California EPA (Rabovsky. 2000). EPA's
PPRTV (U.S. EPA. 2007) and IRIS (U.S. EPA. 1988) programs, Health Canada (Health Canada.
2012). the International Agency for Research on Cancer (IARC. 1999b) and the Agency for Toxic
Substances and Disease Registry (ATSDR. 1994). Inhalation and oral animal data for HCBD
indicate renal, reproductive, and developmental effects.
Numerous published oral studies ranging from 2 weeks to 2 years in rats and mice
demonstrated renal effects (Table 5-2). The available toxicological assessments found that
dose-related increases in histopathological lesions in the kidneys were observed such as renal
tubule regeneration, degeneration of the renal tubules corresponding to biochemical changes
in the urine, and kidney weight increases (U.S. EPA. 2007). Renal adenomas and carcinomas
were observed after 2 years and HCBD was considered to be a possible human carcinogen (U.S.
EPA. 1988).
Reproductive effects were observed in an inhalation developmental study in rats and was
characterized by reduced body weight gains in maternal adults (Saillenfait et al.. 1989).
Developmental effects characterized by reduced fetal body weights in the F1 generation were
observed following either oral or inhalation exposures in rats (Field et al.. 1990; Saillenfait et al..
1989; Harleman and Seinen. 1979). NOAELS for kidney effects ranged from 0.2 to 10 mg/kg-d
for oral exposures. LOAELs for developmental effects ranged from 0.5 mg/kg-day to 11 mg/kg-
day for oral exposures and inhalation exposures for reproductive and developmental effects
yielded NOAECs between 2 and 10 ppm.
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Table 5-2. Summary of Surveyed Human Hazard Data for Hexachlorobutadiene
Organ/System
Study type
Doses
POD
Health Effect
Reference
Kidney
Oral dietary study for 4 weeks in
male and female Wistar rats
0, 25, 100, 400 ppm
NOAEL: 25 ppm (2.6
mg/kg-day)
LOAEL: 100 ppm (10.2
mg/kg-day)
Increased kidney weights,
histopathological effects,
blood and urine
biochemistry effects
Jonker et al. (1993)
Kidney
13-week oral dietary study in
0, 1, 3, 10, 30, 100 ppm
NOAEL: 1 ppm (0.2
Increased renal tubule
NTP (1991); Yang Retal.

male and female B6C3F1 mice

mg/kg-d)
LOAEL: 3 ppm (0.5
mg/kg-d)
regeneration
(1989)
Kidney
Oral gavage study for 21
consecutive days in male
Sprague-Dawley rats
0, 0.2, 20 mg/kg-day
NOAEL: 0.2 mg/kg-day
LOAEL: 20 mg/kg-day
Increased DNA repair in
kidneys and increased
kidney weights
Stott et al. (1981)
Kidney
Oral dietary study for 2 weeks in
Wistar rats
0, 50, 150, 450 ppm
LOAEL: 50 ppm (8
mg/kg-day)
Degeneration of renal
tubules
Harleman and Seinen (1979)
Kidney
Oral developmental study in
female Wistar rats for 18 weeks
0, 150, 1500 ppm
LOAEL: 150 ppm (11
mg/kg-day)
Decreased body weight
gain, increased kidney
weights, and altered
kidney histopathology in
F0 dams
Harleman and Seinen (1979)
Kidney
Oral 13-week study in male and
0, 0.4, 1.0, 2.5, 6.3, 15.6
NOAEL: 1.0 mg/kg-day
Histopathological effects
Harleman and Seinen (1979)

female Wistar rats
mg/kg-day
LOAEL: 2.5 mg/kg-day
in kidneys

Kidney
Oral 2-year dietary study in male
and female Sprague-Dawley rats
0, 0.2, 2, 20 mg/kg-day
NOAEL: 0.2 mg/kg-day
LOAEL: 2 mg/kg-day
Kidney histopathological
lesions, changes in urine
biochemistry
Kociba et al. (1977)
Kidney
Oral 2-year dietary study in male
0, 0.2, 2, 20 mg/kg-day
Oral slope factor: 7.8
Increased renal tubular
Kociba et al. (1977); U.S.

and female Sprague-Dawley rats

xlO"2 mg/kg-day;
Inhalation unit risk:
2.2 x 10"5 mg/kg-day
adenomas and carcinomas
EPA (1987)
Kidney
Oral dietary developmental study
through lactation in male and
female Sprague-Dawley rats
0, 0.2, 2, 20 mg/kg-day
NOAEL: 0.2 mg/kg-day
LOAEL: 2 mg/kg-day
Kidney histopathological
lesions in F0 adults
Schwetz et al. (1977)
Kidney
Oral 30 dietary study in female
Sprague-Dawley rats
0, 1, 3, 10, 30, 65,100
mg/kg-day
NOAEL: 10 mg/kg-day
LOAEL: 30 mg/kg-day
Increase in renal lesions
Kociba et al. (1977)
Page 18 of 39

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Organ/System
Study type
Doses
POD
Health Effect
Reference
Developmental
Oral dietary developmental study
in pregnant CD rats through PND
10
0, 100, 200, 400, 750,
1100, 1500 ppm
NOAEL: 200 ppm
(22.5 mg/kg-day)
LOAEL: 400 ppm (35.3
mg/kg-day)
Reduced pup body weight
and increased kidney
weights in F1
Field etal. (1990)
Developmental
Inhalation developmental toxicity
study in Sprague-Dawley rats to
PND 21
0, 2, 5, 10, 15 ppm
NOAEC: 10 ppm
LOAEC: 15 ppm
Reduced fetal body
weight in F1
Saillenfait et al. (1989)
Developmental
Oral developmental study in
female Wistar rats for 18 weeks
0, 150, 1500 ppm
LOAEL: 150 ppm (11
mg/kg-day)
Decreased fetal body
weight in F1 generation
Harleman and Seinen (1979)
Reproductive
Inhalation developmental toxicity
study in Sprague-Dawley rats to
PND 21
0, 2, 5, 10, 15 ppm
NOAEC: 2 ppm
LOAEC: 5 ppm
Reduced maternal weight
gain in F0 adults
Saillenfait et al. (1989)
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6. Phenol, isopropylated, phosphate (3:1)
6.1. Environmental Hazard Summary
The CASRN 68937-41-7 does not represent a discrete chemical, thereby making it difficult to
know the degree of propylation that results in the hazardous effects summarized in Table 6-1.
Most of the studies cited in Table 6-1 represent exposures to whole commercial products and
the amount of PIP (3:1) varies greatly in content and propylation configurations; the exposure
to other chemicals within the product (e.g., triphenyl phosphate) may have influenced the
effects observed.
The majority of the toxicity tests where PIP (3:1) is evaluated used whole product mixtures, and
if reported, the table provides the percentage of PIP (3:1) present in the tested product. Acute
toxicity tests with a variety of products or formulations, most also containing 5% triphenyl
phosphate, indicate acute toxicity (96-hr LC50s) ranging from 1.6 in rainbow trout to >1000
mg/L in zebrafish (ECHA. 2018b: U.S. EPA. 2010). Similarly, 5% triphenyl phosphate preparations
were acutely toxic to daphnids over a range from 0.83 to >100 mg/L (ECHA. 2018b: U.S. EPA.
2012). The algal toxicity tests available do not provide a threshold for toxicity, but the exposure
concentrations used in the studies suggest that PIP (3:1) is not acutely toxic to algae at
concentrations below 1,000 mg/L (ECHA. 2018b). Fathead minnows chronically exposed to
Kronitex 200 and Reofos 35, two products containing PIP (3:1), as well as triphenyl phosphate
which is aquatically toxic, resulted NOECs of 0.088 and 0.0031 mg/L, respectively (ECHA.
2018b). Daphnids and chironomids (sediment exposure) chronically exposed to the commercial
product Reofos 35 for 21 and 28 days, respectively, showed toxicity, with LOECs of 106 |ag/L,
and 37 mg/kg sediment dry weight, respectively (ECHA. 2018b). At the highest concentration
tested, the commercial product 310M did not have effect on various vegetables (e.g., wheat,
radish, mung bean) (ECHA. 2018b). The 14-d NOEC for growth in earthworms exposed to the
commercial product Reofos was 500 mg/kg soil dry weight, whereas the 56-day NOEC for
reproduction was 250 mg/kg soil dry weight (ECHA. 2018a).
Page 20 of 39

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Table 6-1. Summary of Surveyed Environmental Hazard Data for Phenol, Isopropylated, Phosphate (3:1)
Media
Study
Duration


¦	J

Aquatic
Acute
Fathead minnow
96-hr LCso
(lethality); LOEC;
NOEC
(hemorrhaging,
and abnormal
surfacing behavior)
10.8; 5.6; 3.2
mg/L
Non-GLP; Triphenyl
phosphate >5%
ECHA (2018b); (unnamed
1978 report)
Fathead minnow
96-hr LCso
(lethality)
50.1
mg/L
Non-GLP; Kronitex 200
(Triphenyl phosphate >5%)
ECHA (2018b); (unnamed
1978 report)3
Zebrafish
96-hr NOEC
>1000
mg/L
GLP (OECD203); Durad
310M (Triphenyl
phosphate <5%)
ECHA (2018b); (unnamed
1997 report)3
Rainbow trout
96-hr LCso
(lethality);
LOEC (twitching
behavior and
labored
respiration)
1.6; 1
mg/L
Non-GLP; Triphenyl
phosphate >5%
U.S. EPA (2010); ECHA
(2018b) (ununamed 1979
report)
Rainbow trout
96-hr LCso; NOEC
(mortality)
4.46; <0.56
mg/L
Non-GLP; Kronitex 200
(Triphenyl phosphate >5%)
ECHA (2018b); (unnamed
1979 report)3
Daphnid
48-hr LCso; NOEC
(lethality)
1.5; 1.0
mg/L
Non-GLP; Kronitex 200
(Triphenyl phosphate >5%)
ECHA (2018b); named 1979
report)3
Daphnid
48-hr NOEC
(immobilization)
>1000
mg/L
GLP (OECD 202-
immobilization); Curad
310M; prepared as WAFs
ECHA (2018b); (unnamed
2001 report)3
Daphnid
48-hr LCso
(lethality)
2.44
mg/L
non-GLP; Triphenyl
phosphate >5%
ECHA (2018b); (unnamed
1979 report)3
Daphnid
48-hr ECso
(immobilization)
0.83
mg/L
n/a
U.S. EPA (2012) (not
referenced)
Algae
96-hr ECso
(growth)
>2.5
mg/L
GLP (OECD 201; OPPTS
850.5400; EU Method C.3);
Reofos 65 (Triphenyl
phosphate >5%)
ECHA (2018b); (unnamed
2005 report)3
Page 21 of 39

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Media
Study
Duration
Organism
Endpoint
Hazard Value
Unit
Chemical and Study
Specification
Reference


Algae
72-hr ECso
(growth)
>1000
mg/L
GLP (OECD201); Durad
310M. Prepared asWAF
(Triphenyl phosphate <5%)
ECHA (2018b); (unnamed
2001 report)3
Chronic
Fathead minnow
33-d NOEC; LOEC
(growth and
development
abnormalities)
3.1; 8.2
M-g/L; mg/L
GLP (OECD210; EPAOPPTS
850.1400); Reofos 35
ECHA (2018b); (unnamed
2014 report)3
Fathead minnow
90-d NOEC
0.088 (Kronitex
200); 0.029
(Phosflex 31P)
mg/L
Non-GLP; Kronitex 200
(four to six per cent
triphenyl phosphate, seven
to 10 per cent 2-
isopropylphenyl diphenyl
phosphate, 20-25 per cent
4-isopropylphenyl diphenyl
phosphate, along with bis-
(2-isopropylphenyl) phenyl
phosphate and minor
amounts of di-, tri- and
tetraisopropyl-substituted
triphenyl phosphates) or
Phosflex 31P (28-30 per
cent triphenyl phosphate,
along with isomers of
isopropylphenyl diphenyl
phosphate, isomers of
diisopropylphenyl diphenyl
phosphate and tri-
substituted phenol
phosphates. The study was
carried out using a flow-
through test system).
Effects based on growth
(just Kronitex) and
mortality (Phosflex- both
endpoints).
ECHA (2018b); (unnamed
1986 report)3
Page 22 of 39

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Media
Study
Duration
Organism
Endpoint
Hazard Value
Unit
Chemical and Study
Specification
Reference


Daphnid
21-d NOEC; LOEC
(growth,
reproduction)
41.5; 106;
Hg/L
GLP (OECD211; EPAOPPT
850.1300); Reofos 35
ECHA (2018b); (unnamed
2014 report)3
Chironomid
28-d EC50
(emergence); LOEC
(developmental
rate); NOEC
87; 37; <37
mg/kg
sediment dw
GLP (OECD 218; ASTM E
1706-05). EC50
(emergence rate); LOEC
(development rate); NOEC
(development rate);
Reofos 35
ECHA (2018b); (unnamed
2015 report)3
Algae
14-d LOEC
(growth)
0.1
mg/L
Phosflex 31P (Triphenyl
phosphate 28-30%)
Sanders et al. (1985)
Terrestrial
Sub-chronic
Earthworm
14-d NOEC
(growth)
500
mg/kg soil dw
GLP (OECD 207); Reofos 35
ECHA (2018b)(unnamed
2014 report)3
Wheat, radish,
mung bean
19; 18; 19-d EC50
(seedling
emergence)
>100
mg/kg soil dw
GLP (OECD 208); Durad
310M
ECHA (2018b)(unnamed
2001 report)3
Chronic
Earthworm
56-d NOEC
(reproduction)
250
mg/kg soil dw
GLP (OECD 222; ISO 11268-
2); Reofos 35
ECHA (2018a) (unnamed
2017 report)3
aUse of a commercial product or mixture (containing CAS# 68937-41-7) in the study.
Page 23 of 39

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6.2. Human Health Hazard Summary
Surveyed inhalation and oral animal data for Isopropylated, phosphate (3:1) indicate
reproductive and developmental effects, increased mortality, neurological effects and effects
on systemic organs, specifically adrenals, liver, ovary, heart, and lungs (U.S. EPA. 2015). All
available repeated-dose studies were unpublished study reports available on the ECHA
database for various molecular compositions of isopropylated phenol phosphate (Table 6-2).
An OECD 422 guideline oral gavage study in Sprague-Dawley rats reported dose-dependently
reduced copulation and reduced conception indices (ECHA. 2018a). In addition, postnatal
survival and early postnatal development were reduced in this study. Various systemic organ
effects were noted by increased ovarian, adrenal, and liver weights with reduced epididymal
weights in the parental generation.
A 90-day oral gavage OECD 408 guideline study observed dose-dependently increased adrenal
weights with corresponding macroscopic changes in both male and female rats as well as
increased liver weights with centrilobular or pablobular hypertrophy, increased ovary weights
with interstitial cell vacuolation, and increased thyroid weights with follicular cell hypertrophy
(ECHA. 2018b).
A 90-day inhalation study in Fischer rats, golden hamsters, and rabbits found that all rabbits
died in the highest dose group while the exposed rats were reported to have inflammation in
the heart and lung and hypertrophy in the ovaries. Finally, hens orally gavaged for 91 days had
increased ataxia and correlating neural degenerative changes (ECHA. 2018a). Altogether, the
surveyed data indicate evidence for systemic effects on several organs, reproductive,
developmental and neurological effects. The NOAEL for reproductive and developmental
effects was 25 mg/kg-d for oral exposures. LOAELs for reproductive and developmental effects
were 100 mg/kg-d ay for oral exposures. Systemic and neurological effect LOAELs were 25-100
mg/kg-day. An inhalation NOAEC of 10 mg/m3 and LOAEC of 100 mg/m3 was identified for
systemic effects.
Page 24 of 39

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Table 6-2. Summary of Surveyed Human Health Hazard Data for Phenol, Isopropylated, Phosphate (3:1)
Organ/System
Study type
Doses
POD
Health Effect
Reference
Adrenals
90-day oral gavage toxicity
study in Sprague-Dawley rats
(OECD408)
0, 25, 100, 325
mg/kg-day
NOAEL: none identified
LOAEL: 25 mg/kg-d
Macroscopic effects and
increased organ weights
ECHA (2018b)
Systemic organs
90-day oral gavage toxicity
study in Sprague-Dawley rats
(OECD408)
0, 25, 100, 325
mg/kg-day
NOAEL: 25 mg/kg-d
LOAEL: 100 mg/kg-d
Liver, thyroid and ovary
weight increases with
corresponding pathology
ECHA (2018b)
Systemic organs
OECD 422 oral gavage study
in Sprague-Dawley rats
0, 25, 100, 400
mg/kg-day
NOAEL: not identified
LOAEL: 25 mg/kg-day
Increased ovary/oviduct,
adrenal glands, and liver
weights; decreased
epididymal weights in F0
ECHA (2018b)
Reproductive
OECD 422 oral gavage study
in Sprague-Dawley rats
0, 25, 100, 400
mg/kg-day
NOAEL: 25 mg/kg/day
LOAEL: 100 mg/kg-day
Reduced copulation/
conception indices in FO
ECHA (2018b)
Developmental
OECD 422 oral gavage study
in Sprague-Dawley rats
0, 25, 100, 400
mg/kg-day
NOAEL: 25 mg/kg/day
LOAEL: 100 mg/kg-day
Postnatal development
affected in F1
ECHA (2018b)
Mortality, Systemic
90-day inhalation study in
Fischer 344 rats, Golden
hamsters, and rabbits
0,10,100 mg/m3
NOAEC: 10 mg/m3
LOAEC: 100 mg/m3
All rabbits died in high
dose group; pulmonary
and heart inflammation,
ovarian hypertrophy in
rats
ECHA (2018b)
Neurological
91-evday oral gavage study in
hens
0, 10, 20, 90, 270
mg/kg/day
NOAEL: 20 mg/kg/day
LOAEL: 90 mg/kg-day
Ataxia and neural
degeneration
ECHA (2018a)
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7. 2,4,6-Tris(tert-butyl) phenol
7.1. Environmental Hazard Summary
The information in Table 7-1 demonstrates that 2,4,6-Tris(tert-butyl) phenol (2,4,6 TTBP) is
acutely toxic to fish and algae at exposure concentrations as low as 0.061 and 0.04 mg/L,
respectively (ECHA. 2018a; Geiger et al.. 1990). Fathead minnows exposed to 0.061 mg/L also
experienced significant mortality during a 31-day depuration period (Geiger et al.. 1990).
Although the acute daphnid exposure did not result in any effects at the highest exposure
concentration tested (0.072 mg/L), a chronic exposure to 2,4,6 TTBP resulted in a EC50 of 2.2
mg/L (ECHA. 2018a). Unfortunately, there are no further details on the chronic daphnid
exposure due to the lack of detail from a summary of the Japanese report. The data presented
in Table 7-1 suggests that 2,4,6 TTBP is both acutely and chronically toxic to aquatic organisms.
No toxicity data for terrestrial species were identified.
Page 26 of 39

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Table 7-1. Summary of Surveyed Environmental Hazard Data for 2,4,6-Tris(tert-butyl) phenol
1	l^uaJI	
m i
Hazard
Value
Unit
Chemical and Study
Specification
Reference


Carp
96-hr LCso
(lethality)
>0.048
mg/L
GLP (OECD203; EU Method
CI). Exposures prepared as
water soluble fraction (WSF).
ECHA (2018a); (unnamed
2015 report)


Rainbow trout
96-hr LCso
(lethality)
>0.1
mg/L
GLP (OECD203)
ECHA (2018a); (unnamed
1992 report)

Acute
Fathead
minnow
96-hr LCso
(lethality)
0.061
mg/L
97% purity; exposure to only
one concentration (60.9 ng/L)
Geiger et al. (1990)
Aquatic

Daphnid
48-hr ECso
(immobilization)
>0.072
mg/L
GLP (OECD202; EU C2).
Exposure prepared as WSF.
Effect based on mobility.
ECHA (2018a); (unnamed
2015 report)


Algae
72-hr NOEC
0.04
mg/L
GLP (OECD201; EU C3).
Exposure prepared as WSF.
Effect based on growth
ECHA (2018a); (unnamed
2015 report)

Chronic
Fathead
minnow
96-hr post-
exposure/depuration
mortality
0.061
mg/L
97% purity; fish depurated for
31 days after 96-hr exposure
Geiger et al. (1990)

Daphnid
21-d ECso; NOEC
2.2; 0.36
mg/L
GLP (OECD221)
ECHA (2018a); (Japanese
report not referenced)
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7.2. Human Health Hazard Summary
Surveyed animal data for 2,4,6-Tris(tert-butyl) phenol (2,4,6 TTBP) indicate liver and
developmental effects based on oral animal studies. No inhalation data were identified.
Repeated dose studies are limited to two OECD 422 guideline studies in Wistar rats and a 2-year
oral carcinogenicity study in Wistar rats (Table 7-2).
Maternal liver weights were dose-dependently increased in one of the OECD 422 guideline
studies and was accompanied with hepatocellular hypertrophy and necrosis (ECHA. 2018a). A
two-year oral carcinogenicity study observed increased liver weights, focal necrosis, and
corresponding changes in blood biochemistry that were dose-related which is indicative of liver
effects in both male and female rats with more severe effects occurring in females (Matsumoto
et al.. 1991). One unpublished OECD 422 guideline study report observed reduced body weights
in the offspring and increased postnatal (ECHA. 2018a). Another unpublished OECD 422
guideline study observed reduced pup viability index and reduced weight gain (ECHA. 2018a).
The LOAEL for the observed effects were 10-750 mg/kg-day and the reported NOAELs were 3-
150 mg/kg-day.
Page 28 of 39

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Table 7-2. Summary of Surveyed Human Health Hazard Data for 2,4,6-Tris(tert-butyl) phenol
Organ/System
Study Type
Doses
POD
Health Effect
Reference
Liver
OECD 422 in Wistar Rats
Males: 29 days
Females: 41-56 days
0, 3,10, 30 mg/kg-day
NOAEL: 3 mg/kg-d
LOAEL: 10 mg/kg-d
Increased liver weights;
Hepatocellular
hypertrophy with
necrosis in females
ECHA (2018a)
Liver
2-year oral carcinogenicity
study in Wistar rats
0, 30, 100, 300, 1000 ppm
NOAEL: 30 ppm (approx. 5
mg/kg-d)
LOAEL:100ppm (approx. 15
mg/kg-d)
Increased liver weights
and blood biochemistry;
focal necrosis
Matsumoto et al.
(1991)
Developmental
OECD 422 in Wistar Rats
Males: 29 days
Females: 41-56 days
0, 3,10, 30 mg/kg-day
NOAEL: 3 mg/kg-d
LOAEL: 10 mg/kg-d
Reduced pup body
weight and increased
postnatal loss
ECHA (2018a)
Developmental
OECD 422 in Wistar rats
Males: 43 days
Females: up to PND 4
0, 30,150, 750 mg/kg-d
NOAEL: 150 mg/kg-d
LOAEL: 750 mg/kg-d
Reduced pup viability
ECHA (2018a)
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8. Pentachlorothiophenol
8.1. Environmental Hazard Summary
Pentachlorothiophenol (PCTP) is acutely toxic to aquatic organisms, where mortality was
observed in zebrafish and protozoa exposed to 2.8 and 3.1 mg/L, respectively (U.S. EPA. 2018;
HSDB. 2015). Terrestrial toxicity data is limited for PCTP, but 50% mortality was observed within
24 hours when chicken eggs were injected with 1 mg/egg (U.S. EPA. 2018).
Aquatic and terrestrial plant data are available for PCTP. Radishes and sudangrass exposed to
PCTP resulted in a 5-day and 6-day EC50 of 0.762 and 0.479 mM, respectively (Sund and
Nomura. 1963). A study with giant kelp was available but missing details. Two studies listed in
Table 8-1 (CalEPA. 1964; Sund and Nomura. 1963) are not yet available on the public version of
ECOTOX but should be available soon.
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Table 8-1. Summary of Surveyed Environmental Hazard Data for Pentachlorothiophenol (PCTP)
1
Study
Duration
r~ i
R 1
Hazard Value
mg/L
Chemical and Study Specification
—Bi I
Aquatic
Acute
Zebrafish
96-hr LCioo
(lethality)
2.8
mortality
IUCLID HSDB (2015)
N/A
Golden orfe
LCioo
(lethality)
1
mg/L
unknown: study duration; 88%
PCTP (2% tetrachlorodithiol,and
pentachlorphenol, and 10%
pentachlorbenzoldisulfide)
IUCUD HSDB (2015)
Acute
Giant kelp
4-d
(endpoint n/a)
10,000
Hg/L
n/a
CalEPA (1964)
Acute
Ciliate Protozoa
(growth)
48-hr ECso;
LC50 (lethality)
4.8; 3.1
Al mg/L
100% purity; no doses reported
ECOTOX U.S. EPA (2018)
Terrestrial
Acute
Chicken
24-hr LCso
(lethality)
1
mg/egg
100% purity; injection: 0,1, or 5
mg/egg)
ECOTOX U.S. EPA (2018)
Radish;
Sudangrass
5-d	EC50;
6-d	ECso
(growth)
0.000762;
0.000479
M
n/a
Sund and Nomura (1963)
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8.2. Human Health Hazard Summary
PCPT is both a metabolite and biodegradation product of pentachloronitrobenzene (PCNB)
(Khan et al.. 2011) and a metabolite of hexachlorobenzene (WHO. 1997). EPA has completed
IRIS toxicological reviews for both parent compounds (pentachloronitrobenzene and
hexachlorobenzene) and identified liver and reproductive effects associated exposure to the
analogous chemicals Table 8-2. No repeat dose animal or human epidemiological data were
identified in the surveyed literature for pentachlorothiophenol (PCPT).
A two-year dietary study in dogs found that pentachloronitrobenzene increased liver weight,
elevated serum biochemistry levels associated with liver dysfunction and induced cholestatic
hepatosis with secondary bile nephrosis (U.S. EPA. 1987).
A two-year feeding study in Sprague-Dawley rats reported that hexachlorobenzene exposure
increased hepatic centrilobular basophilic chromogenesis and increased pup loss (U.S. EPA.
1988). The NOAEL range for the observed effects ranged from 0.08- 0.29 mg/kg-day for
hexachlorobenzene and was 0.75 mg/kg-day for PCNB.
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Table 8-2. Summary of Surveyed Human Health Hazard Data for Pentachlorothiophenol (PCTP)
Organ/System
Study Type
Doses
POD
Health Effect
Reference
Liver
2-year feeding dog
study
0, 30, 180, 1080 ppm
Pentachloronitrobenzene
RfD: 3E-3 mg/kg-d
NOEL: 30 ppm (0.75 mg/kg-d)
Increased liver weight,
ALP, and cholestatic
hepatosis
U.S. EPA (1987)
Liver
2 year feeding
Sprague-Dawley rats
0, 0.32, 1.6, 8.0, 40 ppm
Hexachlorobenzene
RfD: 8E-4 mg/kg-d
NOEL: 1.6 ppm (0.08 mg/kg-d)
Increased hepatic
centrilobular basophilic
chromogenesis
U.S. EPA (1988)
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