Screening Assessment for the Challenge

Phenol, 2,6-bis(1,1-dimethylethyl)-4-(1-methylpropyl)-

Chemical Abstracts Service Registry Number
17540-75-9

Environment Canada
Health Canada

July 2010

(PDF Version - 571 KB)

1. Synopsis
2. Introduction
3. Substance Identity
4. Physical and Chemical Properties
5. Sources
6. Uses
7. Releases to the Environment
8. Environmental Fate
9. Persistence and Bioaccumulation Potential
10. Potential to Cause Ecological Harm
11. Potential to Cause Harm to Human Health
12. Conclusions
13. References
14. Appendix 1: Robust Study Summaries for Aquatic Toxicity of 2,4,6-tri-tert-butylphenol
15. Appendix 2: PBT Model Inputs Summary Table for DTBSBP
16. Appendix 3: Exposure Estimations
17. Appendix 4: Structures and data for DTBSBP analogues considered in this assessment
18. Appendix 5: Summary of (Q)SAR Predictions

Synopsis

Pursuant to section 74 of the Canadian Environmental Protection Act, 1999 (CEPA 1999), the Ministers of the Environment and of Health have conducted a screening assessment on Phenol, 2,6-bis(1,1-dimethylethyl)-4-(1-methylpropyl)- (DTBSBP), Chemical Abstracts Service Registry Number 17540-75-9. This substance was identified as a high priority for screening assessment and included in the Challenge because it was found to meet the ecological categorization criteria for persistence, bioaccumulation potential and inherent toxicity to non-human organisms and is believed to be in commerce in Canada .

The substance DTBSBP was not considered to be a high priority for assessment of potential risks to human health, based upon application of the simple exposure and hazard tools developed by Health Canada for categorization of substances on the Domestic Substances List. Therefore, this assessment focuses on information relevant to the evaluation of ecological risks.

DTBSBP is an organic substance that is used in Canada and elsewhere as an antioxidant and liquid stabilizer in plastics such as PVC and polyurethane foam, as well as in brake fluids, ink resins and mineral/vegetable oils used in industrial applications.  It is also used as an antioxidant in the petrochemical sector.  This substance is not naturally produced in the environment.  A quantity of 16 686 kg of DTBSBP was reported to be imported into Canada in 2006, for use mainly in plastics manufacturing. The quantity of DTBSBP imported into Canada , along with the potentially dispersive uses of this substance, indicates that it may be released into the Canadian environment.

Based on reported use patterns and certain assumptions, 54% of DTBSBP is estimated to end up in waste disposal sites. Small proportions are estimated to be released to water (3.7%), paved/unpaved surfaces (0.2%) and air (0.4%). DTBSBP has a low solubility in water, is moderately volatile and has a tendency to partition to particles and lipids (fat) of organisms because of its hydrophobic nature. DTBSBP will be likely found equally in sediments (51%) and water (48%) when released to water.  It is not expected to be subject to long-range atmospheric transport.

Based on its physical and chemical properties as well as empirical biodegradation data, DTBSBP is not expected to degrade quickly in the environment. It is persistent in water, soil and sediments. DTBSBP also has the potential to accumulate in organisms and may biomagnify in food chains. The substance has been determined to meet the persistence and bioaccumulation criteria as set out in the Persistence and Bioaccumulation Regulations. In addition, modelled and analogue aquatic toxicity data indicate that the substance is potentially highly hazardous to aquatic organisms.  It is therefore concluded that DTBSBP is entering the environment in a quantity or concentration or under conditions that have or may have an immediate or long-term harmful effect on the environment or its biological diversity.

There was no empirical data identified regarding measured concentrations of DTBSBP in environmental media in Canada or elsewhere. DTBSBP may be used in plasticized PVC for food packaging applications. A conservative human exposure estimate derived from the potential use of plasticized PVC films in food packaging was considered. Overall, it is expected that exposure to DTBSBP through dietary intake, if any, in Canada would be minimal. Exposure to DTBSBP by the general population in Canada was examined by considering polyol and polyurethane foam products in mattresses, furniture, and automotive trim materials. Due to the lack of experimental data on DTBSBP, exposure estimates were derived based on the structurally similar but more volatile antioxidant, butylated hydroxytoluene. This likely resulted in overestimates which can be considered as conservative upper-bounding estimates.

The health effects database for DTBSBP is limited, however it was not genotoxic in vitro assays and one study suggests low acute toxicity.  Information on analogues indicates that liver and haematological effects are common endpoints which are observed across this group of compounds.

Based on the information available, the margins between upper-bounding estimates of exposure through food (i.e. migration from food packaging) and consumer products and levels associated with effects in experimental animals are considered to be adequately protective of human life and health.  It is therefore concluded that DTBSBP is not entering the environment in a quantity or concentration or under conditions that constitute or may constitute a danger in Canada to human life or health. 

Based on the information available, it is concluded that DTBSBP meets one or more of the criteria set out in section 64 of the Canadian Environmental Protection Act, 1999.  DTBSBP is persistent and bioaccumulative in accordance with the regulations, and its presence in the environment results primarily from human activity.

This substance will be considered for inclusion in the Domestic Substances List inventory update initiative. In addition and where relevant, research and monitoring will support verification of assumptions used during the screening assessment and, where appropriate, the performance of potential control measures identified during the risk management phase.

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Introduction

The Canadian Environmental Protection Act, 1999 (CEPA 1999) (Canada 1999) requires the Minister of the Environment and the Minister of Health to conduct screening assessments of substances that have met the categorization criteria set out in the Act to determine whether these substances present or may present a risk to the environment or human health.

Based on the information obtained through the categorization process, the Ministers identified a number of substances as high priorities for action. These include substances that

• met all of the ecological categorization criteria, including persistence (P), bioaccumulation potential (B) and inherent toxicity to aquatic organisms (iT), and were believed to be in commerce in Canada ; and/or
• met the categorization criteria for greatest potential for exposure (GPE) or presented an intermediate potential for exposure (IPE), and had been identified as posing a high hazard to human health based on classifications by other national or international agencies for carcinogenicity, genotoxicity, developmental toxicity or reproductive toxicity.

The Ministers therefore published a notice of intent in the Canada Gazette, Part I, on December 9, 2006 (Canada 2006a), that challenged industry and other interested stakeholders to submit, within specified timelines, specific information that may be used to inform risk assessment, and to develop and benchmark best practices for the risk management and product stewardship of those substances identified as high priorities.

The substance Phenol, 2,6-bis(1,1-dimethylethyl)-4-(1-methylpropyl)- was identified as a high priority for assessment of ecological risk as it was found to meet the ecological categorization criteria for persistence, bioaccumulation potential and inherent toxicity to aquatic organisms and was believed to be in commerce in Canada. The Challenge for this substance was published in the Canada Gazette on January 31, 2009 ( Canada 2009a, 2009b). A substance profile was released at the same time. The substance profile presented the technical information available prior to December 2005 that formed the basis for categorization of this substance. As a result of the Challenge, submissions of information pertaining to the uses and exposure of the substance were received.

Although Phenol, 2,6-bis(1,1-dimethylethyl)-4-(1-methylpropyl)- was determined to be a high priority for assessment with respect to the environment, it did not meet the criteria for GPE or IPE, and neither did it meet the criteria for high hazard to human health based on classifications by other national or international agencies for carcinogenicity, genotoxicity, developmental toxicity or reproductive toxicity. Therefore, this assessment focuses principally on information relevant to the evaluation of ecological risks

Screening assessments focus on information critical to determining whether a substance meets the criteria as set out in section 64 of CEPA 1999. Screening assessments examine scientific information and develop conclusions by incorporating a weight-of-evidence approach and precaution.^[1]

This final  screening assessment includes consideration of information on chemical properties, hazards, uses and exposure, including the additional information submitted under the Challenge. Data relevant to the screening assessment of this substance were identified in original literature, review and assessment documents, stakeholder research reports and from recent literature searches, up to August 2009 for the ecological sections of the document and November 2009 for human health–related sections. Key studies were critically evaluated; results from in silico modelling were used to reach conclusions.

When available and relevant, information presented in hazard assessments from other jurisdictions was considered. The final screening assessment does not represent an exhaustive or critical review of all available data. Rather, it presents the most critical studies and lines of evidence pertinent to the conclusion.

This final screening assessment was prepared by staff in the Existing Substances Programs at Health Canada and Environment Canada and incorporates input from other programs within these departments. The ecological portions of this assessment have undergone external peer review/consultation. Additionally, the draft of this screening assessment was subject to a 60-day public comment period. While external comments were taken into consideration, the  content and outcome of the final screening assessment remain the responsibility of Health Canada and Environment Canada.  Approaches used in the screening assessments under the Challenge have been reviewed by an independent Challenge Advisory Panel.

The critical information and considerations upon which the assessment is based are summarized below.

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Substance Identity

For the purposes of this document, this substance will be referred to as DTBSBP, an acronym based on the common name.

Table 1 . Substance identity for DTBSBP

Chemical Abstracts Service Registry Number (CAS RN)	17540-75-9
DSL name	Phenol, 2,6-bis(1,1-dimethylethyl)-4-(1-methylpropyl)-
National Chemical Inventories(NCI) names1	Phenol, 2,6-bis(1,1-dimethylethyl)-4-(1-methylpropyl)-(TSCA, ENCS, AICS, PICCS, ASIA-PAC) 4-sec-Butyl-2,6-di-tert-butylphenol (DSL, EINECS, ECL) PHENOL, 2,6-DI-TERT-BUTYL-4-SEC-BUTYL- (PICCS)
Other names	2,6-Di-tert-butyl-4-sec-butylphenol; Isonox 132; NSC 14460; Phenol, 4-sec-butyl-2,6-di-tert-butyl-; Vanox 1320
Chemical group (DSL Stream)	Discrete organics
Major chemical class or use	Phenols
Major chemical sub-class	Alkylphenols, hindered phenols
Chemical formula	C18H30O
Chemical structure
SMILES2	Oc1c(cc(cc1C(C)(C)C)C(CC)C)C(C)(C)C
Molecular mass	262.44 g/mol
1 National Chemical Inventories (NCI). 2007: AICS (Australian Inventory of Chemical Substances); ASIA-PAC (Asia-Pacific Substances Lists); DSL (Canada’s Domestic Substances List); ECL (Korean Existing Chemicals List); EINECS (European Inventory of Existing Commercial Chemical Substances); ENCS (Japanese Existing and New Chemical Substances); PICCS (Philippine Inventory of Chemicals and Chemical Substances); and TSCA (Toxic Substances Control Act Chemical Substance Inventory). 2 Simplified Molecular Input Line Entry System

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Physical and Chemical Properties

Table 2a below contains experimental and modelled physical and chemical properties of DTBSBP that are relevant to its environmental fate.

DTBSBP is a liquid under ambient conditions (SI Group 2009a). Since DTBSBP is not expected to ionize at a relevant environmental pH, ionization of this substance was not considered for prediction of its physical and chemical properties.

Table 2a. Physical and chemical properties of DTBSBP

As noted in Table 2a, the modelled log K_ow for DTBSBP was obtained by using the experimental value adjustment feature in KOWWIN (2000), using the measured log Kow of 6.06 of analogue substance 2,4,6-tri-tert-butylphenol (CAS RN 732-26-3) (NITE 2002a). This was done because of the very close structural similarity of these two substances, which also have the same molecular weights, and also because the log K_ows of these two substances estimated using KOWWIN (2000) were very close (6.43 for DTBSBP; 6.39 for 2,4,6-tri-tert-butylphenol).  Therefore, it was felt that adjusting the predicted Kow for DTBSBP with the experimental value for 2,4,6-tri-tert-butylphenol would yield a more accurate result than using the KOWWIN (2000) predicted value on its own.

To fill data gaps for biodegradation, bioaccumulation and ecotoxicity endpoints, a literature search was performed and the database ChemIDplus® (NLM 2009) was used to identify appropriate analogue substances of DTBSBP. The substances 2,4,6-tri-tert-butylphenol (CAS RN 732-26-3) and 2,6-di-tert-butyl-4-ethylphenol (CAS RN 4130-42-1) were found to be appropriate analogues for DTBSBP as they are similar in molecular mass and have similar structure and functional groups to DTBSBP. The structures and molecular masses of these analogue substances are shown in Appendix IV, along with those of other analogue substances used in the health portion of this assessment (see Potential to Cause Harm to Human Health section).  Estimated physical-chemical property data for these substances, as well as for DTBSBP, for comparison purposes, are presented in Table 2b below.  To permit a level comparison between the substances, the estimated data was obtained by running EPI Suite (2008) without the input of any available measured physical-chemical properties.  Empirical data found for the analogue substances are also given in Table 2b, along with the source of the data.

Table 2b. Predicted and experimental physical-chemical properties of DTBSBP and analogue substances1

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Sources

DTBSBP is not known to be naturally produced in the environment.

Information was collected through surveys conducted for the years 2005 and 2006 under Canada Gazette notices issued pursuant to section 71 of CEPA 1999 (Canada 2006b, 2009b). These notices requested data on the Canadian manufacture and import of DTBSBP.

In Canada , no manufacture of DTBSBP was reported in 2005 or 2006. Currently there is just one known global manufacturer of this substance, the SI Group in the United States (SI Group 2009b). Three companies reported total importations of between 1000 kg and 100 000 kg of the substance into Canada in 2005 (Environment Canada 2006). In 2006, a total of 16 686 kg of DTBSBP was reported to be imported into Canada by five companies, including one company that imported quantities below the reporting threshold of 100 kg/year (Environment Canada 2009a). Six companies identified themselves as “stakeholders” in 2006. 

DTBSBP is a High Production Volume (HPV) chemical in the United States . In 2006, between 10 million and 50 million pounds (4.5 million to 23 million kg) were produced and/or imported by only one company, SI Group, Inc. (US EPA 2006). No commercial or consumer usage data in the United States were available, as these were considered to be confidential (US EPA 2006). This substance is also on the Organisation for Economic Co-operation and Development’s list of HPV chemicals (OECD 2004a). This substance is included on the Oslo-Paris (OSPAR) Commission’s list of substances of possible concern and has been identified as a Low Production Volume (LPV) chemical in the European Union (ESIS 2009).

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Uses

In response to the CEPA section 71 notices for the 2005 and 2006 calendar years ( Canada 2006b, 2009b), the following business activities were identified as not confidential: plastics product manufacturing, and antioxidant/corrosion inhibitor used in brake fluid.

This information is consistent with the DSL nomination data (1984–1986), which identified the use of DTBSBP as antioxidant/corrosion inhibitor/scavenger/antiscaling agent in the manufacture of plastics products. It is also used as an antioxidant in other manufactured products. Information on the other uses of DTBSBP reported to Environment Canada is not provided here as it is considered to be confidential business information. However, this information was considered in this risk assessment of DTBSBP.

The additional information below on potential uses of DTBSBP was found through searches of the available scientific and technical literature, although potential uses in Canada were not specifically identified.

DTBSBP is listed by the U.S. Food and Drug Administration as an effective food contact substance, which is any substance that is intended for use as a component of materials used in manufacturing, packing, packaging, transporting or holding food (US FDA 2008). It is specifically used as an antioxidant in food contact applications in plasticized vinyl chloride homo- and co-polymers (PVC) (SII 2001). For example, it may be used in PVC films for wrapping meat and produce (personal communication with Health Products and Food Branch, Food Directorate, Health Canada, 2009-03-23; unreferenced).

DTBSBP is used as an antioxidant and liquid stabilizer in polyols used in polyurethane, PVC, adhesives and functional fluids (SII 2001). Although OSPAR lists the functional use category for DTBSBP as a pesticide, it is further stated in their fact sheet that there is no authorized use in the European Union in plant protection products (OSPAR 2006). It is not registered for use as a pesticide active ingredient (PMRA 2009) or formulant in Canada (PMRA 2007). 

According to the North American manufacturer of DTBSBP, it is used in the following industries (SI Group 2009b, 2010b):

• PVC, both rigid and flexible grades – polymerization chain terminator and PVC stabilizer
• thermoplastics, such as low-density polyethylene (LDPE)
• polyols/flexible foams – stabilizer/antioxidant
• brake fluids – stabilizer/antioxidant/corrosion inhibitor
• ink resins – stabilizer/antioxidant
• peroxide inhibitor for petrochemical and refinery streams – stabilizer/antioxidant
• mineral/vegetable oils, such as turbine oil, hydraulic oil, chainsaw oil – stabilizer/antioxidant

When used as an antioxidant, the concentration of DTBSBP ranges from 300 to 1000 ppm (0.03–0.10 weight %) (SI Group 2009b). The purity of DTBSBP is typically 98.6%. DTBSBP is used at a concentration of 0.1% wt in brake fluid (SI Group 2009b).

Because DTBSBP has certain advantages as compared to the antioxidant butylated hydroxytoluene (BHT), such as it being a liquid at ambient temperatures, and therefore easier to handle, DTBSBP is being used as a replacement for  BHT in many of the applications listed above (SI Group 2009b).

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Releases to the Environment

The following information on releases for the year 2006 was obtained from a Canada Gazette notice issued pursuant to section 71 of CEPA 1999 (Canada 2009b). Some companies reported transfers of small quantities of the substance (less than 100 kg in total) in non-hazardous waste to an off-site waste management facility (Environment Canada 2009a). No companies reported releases of this substance to air, water or soil.

Additionally, the losses of DTBSBP via various routes during its life cycle are estimated based on regulatory survey data, industry data and data published by different organizations. The losses are grouped into seven types: (1) discharge to wastewater; (2) emission to air; (3) loss to land; (4) chemical transformation; (5) disposal to landfill; (6) disposal by recycling; and (7) disposal by incineration. Losses may occur at one or more of the substance’s life cycle stages that include manufacture, industrial use, consumer/commercial use, and disposal. To assist in estimating these losses, a spreadsheet (Mass Flow Tool) was used that incorporates all data and assumptions required for the estimation (Environment Canada 2009b). Unless specific information on the rate or potential for release of the substance from landfills and incinerators is available, the Mass Flow Tool does not quantitatively account for releases to the environment from waste disposal sites.

The losses estimated for DTBSBP over its life cycle for worst-case scenario applications (i.e., maximum potential releases) are presented in Table 3. These losses are based on the total amount of 16 686 kg of DTBSBP reported to be in Canadian commerce in 2006 (Environment Canada 2009c). In this scenario, loss to wastewater pertains to the discharge prior to any treatment, either on-site industrial wastewater treatment or off-site municipal sewage treatment. Loss via chemical transformation refers to changes in substance identity that occur within the manufacture, industrial use or consumer/commercial use stages, but excludes those during waste management operations such as incineration and wastewater treatment. Loss to recycling refers to the quantity sent to recycling facilities. The substance can further be released from the recycling facilities to the environment. The quantity exported is included in Table 3 in order to present a complete mass balance for the substance.

Of the total quantity of DTBSBP used in Canadian commerce, 3.9% (644 kg) is expected to be released to wastewater (see Table 3). In general, wastewater is a common source for releases to water and soil (via biosludge application) through wastewater treatment facilities. Industrial formulation and container handling accounts for the largest proportion (81%) of the releases to wastewater, while consumer uses account for 19 % of the releases to wastewater, mainly from use of brake fluid (Environment Canada 2009c). The plastics products industry sector is estimated to account for the largest total losses, as this is the sector that uses the greatest mass of DTBSBP in Canada (Environment Canada 2009a). The consumer releases from brake fluid would be widely dispersive (e.g., a large number of very small sources), while the industrial releases would be point sources.

DTBSBP is also expected to be released to the environment via routes other than wastewater. Emissions to air can lead to atmospheric exposure if the substance remains in air, or to exposures in soil and water if the substance is subject to atmospheric deposition. Losses to land accounts for 0.2% of the total mass of DTBSBP. Mechanisms for losses to land include consumer use of brake fluid and leaks and spills during industrial use. The substance lost to land can be washed onto soil or into a nearby sewer, resulting in soil or aquatic exposure. DTBSBP is not expected to leach from waste into landfill leachate.   Due to its high sorptivity (Koc = 4.47), it is expected to sorb strongly to soil and sediments.  As well, based on laboratory testing, DTBSBP is not extractable from rigid PVC into the solvent heptane (SI Group 2009b).

This substance is expected to be used in some manufactured items and consumer products. Although no information is available on the quantity of manufactured items or consumer products containing DTBSBP that are imported into Canada, it is anticipated that the loss proportions from these goods would be similar to those estimated here (see Table 3). However, the quantities sent for waste management and losses to wastewater from use of brake fluid and other consumer/commercial products could be significantly higher if importation of these items were taken into consideration.

Table 3. Estimated losses of DTBSBP during its life cycle   

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Environmental Fate

Based on its physical and chemical properties (Table 2a), the results of Level III fugacity modelling (Table 4) suggest that DTBSBP is expected to predominantly reside in sediment and air if released to air, in sediment if released to water, and in soil if released to soil.

The relatively high acid dissociation constant (pK_a) of 11.85 for the hydroxyl group of DTBSBP indicates that, in water bodies at environmentally relevant pH (6–9), nearly 100% of the substance will be undissociated. This indicates that biotic exposure in water will be from the neutral form of the substance. The relatively low proportion of dissociated chemical also indicates that partitioning behaviour predicted using the log K_ow and log K_oc is appropriate.

Based on the Mass Flow Tool results discussed in the Releases to the Environment section above, significant releases from industry and consumer uses to water are expected, with the air and soil compartments receiving small proportionate releases.

Table 4. Results of the Level III fugacity modelling (EQC 2003)

If released solely to air, 36.4% of the substance will remain in air, and the greatest proportion of the substance is predicted to partition to sediment from atmospheric deposition to water bodies (~54%; Table 4), with small amounts partitioning to soil and water. The moderate estimated vapour pressure of 0.35 Pa and Henry’s Law constant (3.70 Pa·m³/mol) indicate that DTBSBP is slightly volatile.

Based on its high estimated log K_oc value of  4.47, if released into water, DTBSBP is expected to adsorb strongly to suspended solids and sediment. Volatilization from water surfaces is expected to be a relatively unimportant fate process, based upon this compound’s estimated Henry’s Law constant. Thus, if water is a receiving medium, DTBSBP is expected to partition mainly into sediment (~96%).

Based on its high estimated log K_oc, if released to soil, DTBSBP will have high adsorptivity to soil (i.e., is expected to be immobile)_. Volatilization from moist soil surfaces will be a relatively unimportant fate process, based upon the substance’s estimated Henry’s Law constant. This chemical will slightly volatilize from dry soil surfaces, based upon its vapour pressure. Therefore, if released to soil, DTBSBP will remain there (~99.9%; Table 4).

If DTBSBP is released equally to air, water and soil, it will reside primarily in sediment and soil (Table 4).

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Persistence and Bioaccumulation Potential

Environmental Persistence

Table 5a presents the empirical biodegradation data for DTBSBP. Since only one experimental study on the biodegradation of DTBSBP was available, a quantitative structure-activity relationship (QSAR) and analogue-based weight-of-evidence approach (Environment Canada 2007) was applied using the data shown in Tables 5b, 5c and 5d below. 

Table 5a. Empirical data for degradation of DTBSBP

Modelled data for degradation of DTBSBP are presented in Table 5b. In air, a predicted atmospheric oxidation half-life value of 0.52 days demonstrates that DTBSBP is likely to be rapidly oxidized. The substance is not expected to react with other photo-oxidative species in the atmosphere, such as O_3.Therefore, it is expected that reactions with hydroxyl radicals will be the most important fate process in the atmosphere for DTBSBP. With a half-life of 0.52 days via reactions with hydroxyl radicals, DTBSBP is considered not persistent in air.

Empirical biodegradation data were identified for the analogue substances 2,4,6-tri-tert-butylphenol (CAS RN 732-26-3) and 2,6-di-tert-butyl-4-ethylphenol (CAS RN 4130-42-1) and are presented in Tables 5c and 5d below, respectively.

All models predicting ultimate biodegradation agree that DTBSBP will not biodegrade rapidly and is expected to have a half-life > 182 days (Table 5b) in water. These ultimate degradation results are consistent with the properties associated with the functional groups in the chemical structure of DTBSBP (tert-butyl). These results, predicting an ultimate degradation half-life of ³ 182 days, are supported by the empirical data for the substance itself (Table 5a) and the analogue data (Tables 5c, d), which indicate that the analogue substances 2,4,6-tri-tert-butylphenol and 2,6-di-tert-butyl-4-ethylphenol do not readily biodegrade. Also, DTBSBP does not contain functional groups expected to undergo hydrolysis in water, and this substance contains structural features associated with chemicals that are persistent (i.e., – tert-butyl branches, benzene ring with more than two substituents and K_ow >3). Therefore, the substance’s degradation half-life in water is expected to be ³ 182 days. Thus, DTBSBP is considered to be persistent in water. 

Using an extrapolation ratio of 1:1:4 for a water:soil:sediment biodegradation half-life (Boethling et al. 1995), the ultimate degradation half-life in soil is also > 182 days and the half-life in sediments is > 365 days. Therefore, DTBSBP is expected to be persistent in soil and sediment.

Table 5b. Estimated data for degradation of DTBSBP  

Table 5c. Empirical data for biodegradation of 2,4,6-tri-tert-butylphenol

Table 5d. Empirical data for biodegradation of 2,6-di-tert-butyl-4-ethylphenol

Long-range Transport Potential

The Transport and Persistence Level III Model (TaPL3) (TaPL3 2000) was used to estimate the characteristic travel distance (CTD), defined as the maximum distance traveled in air by 63% of the substance. Beyer et al. (2000) have proposed CTDs of > 2000 km as representing high long-range atmospheric transport potential (LRATP), 700–2000 km as moderate LRATP, and < 700 km as low LRATP. Based on the CTD estimate of 259 km, the long-range atmospheric transport potential of DTBSBP is considered to be low. This means that DTBSBP is not expected to be transported through the atmosphere a significant distance from its emission sources.

The OECD Persistent Organic Pollutants (POPs) Screening Model can also be used to help identify chemicals with high persistence and long-range transport potential (Scheringer et al. 2006). The OECD model is a global model that compartmentalizes the earth into air, water and soil phases. This model is “transport-oriented” rather than “target-oriented,” as it simply identifies the CTD without indicating specifically where a substance may be transported to (Fenner et al. 2005). Klasmeier et al. (2006) have suggested that a threshold of 5098 km, based on the model’s CTD estimate for PCB-180, can be used to identify substances with high long-range transport potential. PCB-180 is empirically known to be found in remote regions. The CTD calculated for DTBSBP using the OECD model is 280 km, indicating that DTBSBP has low long-range-transport potential. The OECD POPs Screening Model also calculates the transfer efficiency (TE), which is the percentage of emission flux to air that is deposited to the surface (water and soil) in a remote region (TE % = D/E x 100, where E is the emission flux to air and D = the deposition flux to surface media in a target region). The TE for DTBSBP was calculated to be 3.9E-06%, which is well below the boundary of 4.65E-04% (PCB-28) established based on the model’s reference substances empirically known to be deposited from air to soil or water. The low TE means that DTBSBP is unlikely to be deposited to Earth’s surface in any remote region.

It is therefore concluded that DTBSBP does not have the potential to be transported over long distances in the atmosphere. It is expected that airborne DTBSBP that is not transferred to water or soil will be degraded by hydroxyl radicals in air.

Thus, the empirical, analogue and modelled data (Tables 5a, 5b, 5c and 5d) demonstrate that DTBSBP meets the persistence criteria in water, soil and sediment (half-lives in soil and water = 182 days and half-life in sediment = 365 days), but does not meet the criteria for persistence in air (half-life criteria of ³ 2 days) as set out in the Persistence and Bioaccumulation Regulations (Canada 2000).

Potential for Bioaccumulation

When considered alone, the log K_ow value of 6.1 (Table 2a) suggests that DTBSBP could have the potential to be highly bioaccumulated in the environment. However, log Kow on its own does not take into account factors that mitigate bioaccumulation (e.g., metabolism). These factors are considered further in the evaluation of bioaccumulation potential below.

Since no experimental bioaccumulation data for DTBSBP were available, a QSAR and analogue weight-of-evidence approach (Environment Canada 2007) was applied using available analogue data and bioaccumulation factor (BAF) and bioconcentration factor (BCF) models as shown in Tables 6a, 6b, 6c and 6d below. Table 6a presents the empirical bioconcentration factor (BCF) for the analogue substances. No other empirical BCF data were found for these substances.

Table 6a. Empirical data for bioconcentration of analogue substances

The empirical data in Table 6a indicate that the analogue substances 2,4,6-tri-tert-butylphenol and 2,6-di-tert-butyl-4-ethylphenol bioconcentrate in fish tissues to a high degree, with 2,4,6-tri-tert-butylphenol appearing to be more bioaccumulative than 2,6-di-tert-butyl-4-ethylphenol. This is expected, given that 2,4,6-tri-tert-butylphenol has a higher measured log K_ow value of 6.06 (NITE 2002a) than the predicted logK_ow value of 5.52 for 2,6-di-tert-butyl-4-ethylphenol (no measured K_ow value was found for this substance) and both are expected to have similar rates of biotransformation and elimination.

Mass balance BCF and BAF estimates for the analogue substances, corrected for potential biotransformation, were generated using the BCFBAF model (EPI Suite 2008), and are shown in Table 6b.  The mean BCF values from Table 6a were used to derive the in vivo-based metabolic rate constants (k_M) according to the method of Arnot et al. (2008a). Since metabolic potential can be related to body weight and temperature (Hu and Layton 2001, Nichols et al. 2007), the BCFBAF (2008) model further normalizes the k_M for a 10g fish at 15^oC to the body weight of the middle trophic level fish in the Arnot-Gobas model (184 g) (Arnot et al. 2008b). The middle trophic level fish was used to represent overall model output as suggested by the model developer and is most representative of fish weight likely to be consumed by an avian or terrestrial piscivore.

Table 6b. Mass-Balance BAF and BCF predictions for analogue substances using the BCFBAF (2008) model

The Arnot-Gobas (2003) modelled BCF values for the analogue substances shown in Table 6b, which are corrected for metabolism, are in good agreement with the empirical data (Table 6a). Therefore, this model seems to produce good results for this type of substance (hindered phenol).

It should be noted that the structure and molecular weight of 2,4,6-tri-tert-butylphenol are more similar to DTBSBP than those of 2,6-di-tert-butyl-4-ethylphenol. As well, the measured log K_ow value of 2,4,6-tri-tert-butylphenol is more similar to the KOWWIN predicted log K_ow value of 6.43 (non-adjusted) for DTBSBP (see Table 2a) than that of 2,6-di-tert-butyl-4-ethylphenol. Therefore, 2,4,6-tri-tert-butylphenol seems to be the better analogue of the two substances discussed here, and therefore, DTBSBP would be expected to bioconcentrate in fish tissues to a similar extent as 2,4,6-tri-tert-butylphenol.

According to the Persistence and Bioaccumulation Regulations (Canada 2000) a substance is bioaccumulative if its BCF or BAF is > 5000; however measures of BAF are the preferred metric for assessing bioaccumulation potential of substances. This is because BCF may not adequately account for the bioaccumulation potential of substances via the diet, which predominates for substances with log K_ow> ~4.0 (Arnot and Gobas 2003). Kinetic mass-balance modelling is in principle considered to provide the most reliable prediction method for determining the bioaccumulation potential because it allows for correction for metabolic transformation as long as the log K_ow of the substance is within the log K_ow domain of the model, which is the case for DTBSBP and the analogue substances.

The geometric mean of the highest BCF range (4320–23 200 L/kg)  for analogue substance 2,4,6-tri-tert-butylphenol from Table 6a, which is equal to 10 011 L/kg, was used to derive the median in vivo-based metabolic rate constant (k_M) according to the method of Arnot et al. (2008a). This metabolic rate constant, as well as the predicted adjusted log K_ow value for DTBSBP of 6.1 (Table 2a), was used to estimate metabolism-corrected BCF and BAF values for DTBSBP, as shown in Table 6c.

Because metabolic potential can be related to body weight and temperature (e.g., Hu and Layton 2001; Nichols et al. 2007), the k_M was further normalized to 15^oC and then corrected for the body weight of the middle trophic level fish in the Arnot-Gobas model (184 g) as explained previously (Arnot et al. 2008b). After normalization routines, the median k_M was calculated to be 0.001 (Table 6c).

Table 6c. Middle Trophic Level Fish Mass-Balance BAF and BCF predictions for DTBSBP using the 2003 Arnot-Gobas kinetic model corrected for metabolic rate

The median metabolism-corrected BCF value for DTBSBP is 15 135 L/kg (Table 6c). The geometric mean of the steady-state BCF range reported in Japan’s National Institute of Technology and Evaluation (NITE) database for 2,4,6-tri-tert-butylphenol is 10 011 L/kg, which is consistent with the above value for DTBSBP. The BAF for DTBSBP calculated using this metabolism value is 407 380 L/kg (Table 6c).  This value is also in good agreement with the predicted BAF of 2,4,6-tri-tert-butylphenol of 324 700 L/kg (Table 6b).

Additional modelled BCF data for DTBSBP are given in Table 6d. The models employed in Table 6d use linear regression methods based on log K_OW to derive the BCFs.  All of the modelled data are considered valid, as the model output indicates that DTBSBP is within the domains of the models. In the Dimitrov model, DTBSBP is modelled as part of the “phenols and anilines” class, and in BCFBAF model, it is modelled as a “tert-butyl ortho-phenol type.”  The OECD (2008) prediction was obtained using the OECD QSAR Application Toolbox (v. 1.1.02).  Chemicals from the phenols class with =90% similarity to DTBSBP, and that had BCF studies of 28 days in length or greater were used to generate the QSAR.  Eleven substances from the phenols class met the above criteria.  The resulting BCF prediction equation is: BCF[log(L/kg wet)] = -0.979 + 0.768*log K_OW (EPI Suite).  There was no BAF data for similar substances within the OECD (2008) Toolbox, so a prediction for BAF was not possible. 

Table 6d. Additional predicted BCF data for DTBSBP

A weight-of-evidence approach was used to determine whether DTBSBP meets the bioaccumulation criteria (BCF, BAF = 5000) as set out in the Persistence and Bioaccumulation Regulations(Canada 2000). The high K_ow value of DTBSBP (log K_ow = 6.1) indicates that bioaccumulation in fish is expected to be primarily through the diet rather than through uptake through the gills. Therefore, more weight was given to the bioaccumulation (BAF) data than the bioconcentration (BCF) data. The modelled BAF data indicate that DTBSBP is likely to be highly bioaccumulative (see Table 6b). The BCF values obtained with the Arnot-Gobas model (Tables 6b and 6c), as well as the empirical analogue BCF data (Table 6a) also indicate that DTBSBP is highly bioaccumulative. The Arnot-Gobas (2003) model (Table 6b) was shown to be a good predictor of the empirical BCF data for the analogue substances (Table 6a). Therefore, more weight is given to the results of the Arnot-Gobas model than to the results of the other BCF models in Table 6d), which produced lower BCF values (< 5000).  The OECD (2008) QSAR Application Toolbox also produced a BCF result for DTBSBP of greater than 5000. This prediction takes into account the inherent biotransformation potential of this class of substances under experimental tests conditions.

Considering the above data, it is concluded that DTBSBP meets the bioaccumulation criteria (BCF, BAF = 5000) as set out in the Persistence and Bioaccumulation Regulations (Canada 2000).

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Potential to Cause Ecological Harm

Ecological Effects Assessment

A – In the Aquatic Compartment

There are no experimental data available for the aquatic toxicity of DTBSBP; therefore, modelled and analogue data were used to estimate the potential for aquatic toxicity using a weight-of evidence-approach (Environment Canada 2007). Table 7a contains predicted ecotoxicity values, and Table 7b contains empirical data for the analogue 2,4,6-tri-tert-butylphenol that were considered reliable. No empirical aquatic toxicity data were found for the analogue 2,6-di-tert-butyl-4-ethylphenol. The reliability of the empirical toxicity data is based on the quality of the studies as determined by robust study summaries, which are included in Appendix I.

Table 7a contains toxicity predictions for DTBSBP modelled as a phenol rather than as a neutral organic. However, the predictions for DTBSBP modelled as a neutral organic in ECOSAR are very similar to the ECOSAR values modelled as a phenol found in Table 7a.  All of the modelled toxicity predictions are within the applicability domains of the models , as none of the maximum K_ow and molecular weight cut-off values specified in ECOSAR (2004) were exceeded.  In addition, the predictions are all below the estimated water solubility of the substance, with the  exception of the earthworm prediction. Therefore, no effects at saturation are predicted for the earthworm (ECOSAR 2004).

The OECD (2008) fish toxicity prediction in Table 7a was obtained using the OECD QSAR Application Toolbox (v. 1.1.02).  To generate this prediction, fathead minnow 96 hour toxicity data for substances from the Phenols and Anilines class were considered, which was further refined to just include phenols.   This class was again refined to only consider substances not predicted to be protein or estrogen receptor (ER) binders, since DTBSBP was also predicted not to be a protein or ER binder, based on its structure (OECD 2008).  Twenty-eight substances met the above criteria.  The resulting LC₅₀ prediction equation is:  LC50 [log(1/mol/L)] = 2.44 + 0.666*Log K_OW (EPI Suite).

Table 7a. Modelled data for aquatic toxicity of DTBSBP

Table 7b. Empirical data for aquatic toxicity of 2,4,6-tri-tert-butylphenol

The measured analogue toxicity values (Table 7b) seem to generally support the modelled toxicity values for DTBSBP (Table 7a).

Based on the above modelled and analogue data, there is evidence that DTBSBP has the potential to cause harm to aquatic organisms following short-term (acute) and longer-term (chronic) exposure at relatively low concentrations (i.e., acute LC/EC₅₀ = 1.0 mg/L and/or chronic LC/EC₅₀or NOEC  = 0.1 mg/L).

B - In Other Environmental Compartments

No ecological effects studies were found for DTBSBP in any media. Mammalian data were found and considered in the Potential to Cause Harm to Human Health section of this report.  One model prediction for earthworm was available, and is included in Table 7a, which indicates no effects at saturation.  As such, effect levels for this substance have not been estimated for soil and sediment. However, DTBSBP could end up in these media as a result of releases to the aquatic environment, landfill disposal of sludge from wastewater treatment plants, disposal of products containing these substances, or sludge application to soils.

Ecological Exposure Assessment

No environmental monitoring data from Canada or elsewhere were found for DTBSBP. 

Characterization of Ecological Risk

The approach taken in this ecological screening assessment was to examine all of the available information and develop conclusions based on a weight-of-evidence approach and using precaution as required under CEPA 1999. Lines of evidence considered included information on persistence, bioaccumulation, toxicity, sources and fate of this substance.

Based on empirical, modelled and analogue data, DTBSBP is expected to be persistent in water, soil and sediment. It is also expected to have a high bioaccumulation potential and high potential for toxicity to aquatic organisms based on analogue and modelled data.

The importation volume of DTBSBP into Canada (16 686 kg in 2006), along with information on its industrial and consumer uses, indicates the potential for widespread and point-source releases into the Canadian environment, including an estimated 623 kg to wastewater (see Releases to the Environment section). DTBSBP is expected to be released mainly to water (Table 3), though it is expected to reside in sediment as well (Table 4).

Evidence that a substance is highly persistent and bioaccumulative as defined in the Persistence and Bioaccumulation Regulations of CEPA 1999 (Canada 2000), when taken together with potential for environmental release or formation and potential for toxicity to organisms, provides a significant indication that it may be entering the environment under conditions that may have harmful long-term ecological effects. Substances that are persistent remain in the environment for a long time after being released, increasing the potential magnitude and duration of exposure. Substances that have long half-lives in mobile media (air and water) and partition into these media in significant proportions have the potential to cause widespread contamination. Releases of small amounts of bioaccumulative substances may lead to high internal concentrations in exposed organisms. Highly bioaccumulative and persistent substances are of special concern, since they may biomagnify in food webs, resulting in very high internal exposures, especially for top predators. 

Given the information on the amount of DTBSBP that is imported into Canada and on the nature of its reported industrial and consumer uses, there is potential for release of this substance into the Canadian environment. Once released in the environment, because of its resistance to degradation, it will remain in water, sediment and soil for long times. As it persists in the environment, and because of its lipophilic character, it will likely bioaccumulate and may be biomagnified in trophic food chains. It has also demonstrated potential for relatively high toxicity. This information indicates that DTBSBP has the potential to cause ecological harm in Canada .

Uncertainties in Evaluation of Ecological Risk

In general, DTBSBP is a data-poor substance. There are very few measured physical and chemical property data, and no measured data on its bioaccumulation or toxicity were found. However, a close analogue substance with measured data was found (2,4,6-tri-tert-butylphenol), and these data were found to agree well with the predicted data for DTBSBP. DTBSBP as a neutral organic phenol is also well covered in the training sets of models (neutral organics), and thus predictions of persistence, bioaccumulation and ecotoxicity are considered reliable.

There is uncertainty regarding the risk that DTBSBP may pose now or in the future. Typically quantitative risk estimates (i.e., risk quotients or probabilistic analyses) are important lines of evidence when evaluating a substance’s potential to cause environmental harm. However, when risks for persistent and bioaccumulative substances such as DTBSBP are estimated using such quantitative methods, they are highly uncertain and are likely to be underestimated. Given that long-term risks associated with persistent and bioaccumulative substances cannot at present be reliably predicted, quantitative risk estimates have limited relevance. Furthermore, since accumulations of such substances may be widespread and are difficult to reverse, a conservative response to uncertainty is justified.

Also, regarding ecotoxicity, based on the predicted partitioning behaviour of this chemical, the significance of soil and sediment as important media of exposure is not well addressed by the effects data available. Indeed, the only effects data identified apply to pelagic aquatic exposures, although the water column is not the only medium of concern based on partitioning estimates.

Given the use of DTBSBP in other countries such as the U.S. , it is possible that this substance is entering the Canadian market as a component of manufactured items and consumer products. Therefore, quantities of DTBSBP released to the various environmental media are likely higher than those estimated here. It is also recognized that releases from recycling and waste disposal sites may be possible and may contribute to the overall environmental concentration. However, available information is currently not sufficient to derive a quantitative estimate for these releases.

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Potential to Cause Harm to Human Health

Exposure Assessment

In the published literature, there were no empirical data identified regarding measured concentrations of DTBSBP in environmental media in Canada (air, water, soil and sediment) or elsewhere. In responses to a notice issued under section 71 of CEPA 1999, there were no reported releases of DTBSBP to air, water or soil (Environment Canada 2009a).

No studies were identified reporting the presence of DTBSBP in food. DTBSBP has been approved by the U.S. Food and Drug Administration for use as an antioxidant in plasticized PVC for food packaging (US FDA 2008). Plasticized PVC may be used in films for wrapping fresh and frozen meat and produce. A conservative DTBSBP probable daily intake (PDI) of 0.0581 µg/kg-bw was estimated assuming that some plasticized PVC films may be used for wrapping meat (March 2009 email from Food Directorate, Health Canada, to Risk Management Bureau, Health Canada; unreferenced). In the case of using PVC films for wrapping produce, a PDI was not considered because its value is expected to be much lower in comparison (about 10 000 times lower) to that for the use of PVC films for wrapping meat.

DTBSBP is also used as an antioxidant in plastic hoses used in the Canadian food industry (March 2009 email from Food Directorate, Health Canada , to Risk Management Bureau, Health Canada ; unreferenced). These plastic hoses are employed to transfer food during processing and packaging and are intended to be used in contact with all kinds of foods. A PDI for DTBSBP of 0.36 × 10^-6 ng/kg-bw was derived, taking into consideration that the hose was a repeated-use article (March 2009 email from Food Directorate, Health Canada, to Risk Management Bureau, Health Canada; unreferenced). The contribution of this source to the total intake is considered to be negligible.

Overall confidence in the exposure characterization for environmental media and dietary intake is considered to be low. There is uncertainty in the exposure to DTBSBP from environmental media in Canada, as no information is available; however, based on the conservative assumptions modelled for exposure from the potential use of plasticized PVC films in food packaging, it is expected that exposure to DTBSBP through dietary intake, if any, in Canada is very low.

In Canada , DTBSBP is used in the manufacture of plastics foam products (not including polystyrene), such as flexible polyurethane foams ( Canada 2006b; Canada 2009b). It is also used in the manufacture of PVC (SI Group 2009b).  According to laboratory testing, DTBSBP is not extractable from rigid PVC (SI Group 2009b); therefore exposure to this substance in rigid PVC-associated applications is expected to be negligible. Flexible PVC containing DTBSBP may be used in plastic hoses in the food industry, and exposure to this substance in this application was also shown to be negligible (see previous section). Thus, exposure to DTBSBP via usage of consumer items was examined by considering its presence in foam products.

Canadian consumer use of flexible foams lies in three major markets: bedding, furniture and transportation (Chinn et al. 2006). Flexible foam is used for cushioning in these applications, and in interior trim materials in transportation vehicles (Meyer-Ahrens 2005). DTBSBP is a substitute in the foam industry for BHT, a solid-form antioxidant that is structurally similar (see Figure 1), because DTBSBP is a liquid and less volatile, making it easier to handle in industrial applications (SI Group 2009b). No data were identified with regard to the loss of DTBSBP from mattresses, furniture foam and automotive interiors. Since the volatility of DTBSBP is lower than that of BHT, studies that investigated the volatilization loss of BHT from foam mattresses and auto interior trim were considered in this assessment to screen the upper level of potential inhalation exposure to DTBSBP. Direct skin contact with the actual foam material inside mattresses, furniture and automotive interior foam is rare for the general population; therefore dermal exposure, if any, was considered to be negligible.

Figure 1. Comparison of structurally similar antioxidants, DTBSBP and BHT

An investigation into volatile emissions from foam mattresses found BHT emissions from one of five fresh foam mattress samples (Hillier et al. 2003). The authors did not state if DTBSBP was screened in this study. Since DTBSBP is a less volatile substitute than BHT, as a conservative approach, the extrapolated concentration of BHT is taken as the upper limit of DTBSBP atmospheric concentration from foam mattress emissions. Considering an upper-bound-scenario whereby the maximum potential atmospheric concentration of DTBSBP (2.02 µg/m³) persists continually, the maximum potential inhalation chronic dose was calculated to be 0.178 µg/kg-bw per day for the 0.5–4 years age group (refer to Appendix III).

Potential volatile emissions from foam-filled furniture were also estimated and resulted in a mean event concentration of 2.69 µg DTBSBP/m³ and a maximum potential inhalation chronic dose of 0.872 µg DTBSBP/kg-bw per day (0.5–4 years age group) as an upper-bounding scenario (refer to Appendix III). While the representativeness of a “standardised mattress” for the quantity of foam in household furniture is unknown, the extrapolated BHT exposure values can still be expected to overestimate the maximum potential exposure to DTBSBP from household furniture because DTBSBP is less volatile than BHT.

Flexible polyurethane foam is used for headlining and auto seat cushioning in transportation vehicles (ISOPA 2005). A study of volatile emissions from polymeric materials used as automotive interior trim (Loock et al. 1993) detected BHT, and the emission rate was derived at 90ºC to be 12.8 µg per gram of polyurethane foam per hour. The authors did not state if they screened for DTBSBP.  Considering this emission rate of BHT, the fact that emission rates would be lower at temperatures below the experimental temperature, a quantity of 15 kg of polyurethane in a typical medium-sized car (ISOPA 2005) and the lower volatility of DTBSBP compared to that of BHT, potential inhalation exposure to DTBSBP emissions from automotive interior trim is reasoned to be minimal (refer to Appendix III).

Although direct skin contact with the actual foam materials (e.g., inside mattresses) is rare for the general population, a conservative approach was used when considering exposure for infants and toddlers. In fact, oral exposure may result from mouthing activities on foam objects, such as toys, packaging and children’s furniture (Norris and Smith 2002). While it is uncertain whether DTBSBP is contained in common foam objects mouthed by toddlers and infants, a conservative approach to consider possible oral exposure is necessary in order to ensure consideration of this younger demographic, since foam is a common material for toys and packaging. Since the mouthing behaviour of infants on soft furnishings and other foam objects is well documented (Norris and Smith 2002), an exposure scenario of infants and toddlers mouthing foam objects was considered. Following the method used in VCCEP (Voluntary Children’s Chemical Evaluation Program) assessments to estimate oral exposure via mouthing of foam (Environ 2003a, 2003b), the maximum potential intake was estimated to be 6.52 × 10^-4 mg/kg-bw per day for infants and 3.16 × 10^-4 mg/kg-bw per day for toddlers (refer to Appendix III). Another method was considered to approximate oral exposure from mouthing foam objects and yielded similar estimated exposure values: 2.17 × 10^-4 mg/kg-bw per day for infants and 1.05 × 10^-4 mg/kg-bw per day for toddlers (refer to Appendix III).

Confidence in the numerical results of the exposure estimations is low in the absence of experimental data for DTBSBP. The estimations presented are likely to be overestimates, as they are based on conservative assumptions and derived from experimental data on the structurally similar and more volatile antioxidant, BHT, to screen the upper level of exposure. As a result, there is confidence that the exposure estimates are conservative upper-bounding estimates.

Health Effects Assessment

DTBSBP was negative in in vitro mutagenicity assays in E. coli strain WP2 uvrA or S. typhimurium strains TA98, TA100, TA1535, TA1537 and TA1538, with or without metabolic activation, and was negative for chromosomal aberrations in Chinese hamster ovary cells with or without metabolic activation (SII 2002).The available toxicity data indicate low acute toxicity for DTBSBP, with an oral LD₅₀ of 4800 mg/kg bw in rats (Springborn Laboratories, Inc. 1980). The outputs of predictive models, as summarized in Appendix V, were also considered using four different QSAR models--DEREK, TOPKAT, CASETOX and Leadscope Model Applier--for which the predictions for carcinogenicity, genotoxicity, and developmental and reproductive toxicity were predominately negative (DEREK 2008; TOPKAT 2008; CASETOX 2008; Leadscope 2009). 

For this assessment, data on several analogue substances (Appendix IV) were examined to inform the understanding of the potential health effects associated with exposures to DTBSBP.

Data were available from several analogues for toxicological endpoints including carcinogenicity; genotoxicity; reproductive and developmental toxicity; and chronic, sub-chronic and acute toxicity as shown in Appendix IV. Genotoxicity data for CAS 4130-42-1, phenol, 2,6-bis(1,1-dimethylethyl)-4-ethyl-, was negative in E. coli strain WP2 pkm101 and S. typhimurium strains TA97, TA98, TA100 and TA102, with or without metabolic activation (Hachiya and Takizawa 1994). Similarly, CAS 2416-94-6 and CAS 128-39-2 were also negative for gene mutations in S. typhimurium strains TA98, TA100, TA1535, TA1537 and TA1538 with or without metabolic activation. Additionally, CAS 128-39-2 was also negative in E. coli with and without metabolic activation and did not induce chromosomal aberrations in Chinese hamster V79 cells with and without activation (US EPA 2009a).

Chronic toxicity data for analogue CAS 732-26-3, TTBP, showed no statistically significant increased incidence of tumours compared to controls in a 24-month feeding study in male and female rats exposed to 0, 30, 100, 300 or 1000 ppm of TTBP. In the same study, no non-neoplastic effects were observed at 30 ppm (equivalent to 1.5 mg/kg-bw/day; based on Health Canada 1994) (Matsumoto et al. 1991). Effects included increased liver weights and increased platelet count, phospholipids and total cholesterol at 100 ppm and higher.

In a 28-day study administering the analogue CAS 128-39-2, 2,6-di-tert-butylphenol, to Wistar rats via gavage at 0, 15, 100 or 600 mg/kg-bw/day, no effects were observed at 100 mg/kg bw/day; however at 600 mg/kg-bw/day, increased liver weight in males and females was observed with  a slight increase in the incidence of hepatocellular hypertrophy in the centrilobular area in both sexes and eosinophilic inclusions in the renal cortex of males (US EPA 2009a). 

In a combined reproductive and developmental toxicity screening test conducted with analogue CAS 128-39-2, 2,6-di-tert-butylphenol, Wistar rats were administered 0, 30, 150 or 750 mg/kg-bw/day of the substance by gavage. At 150 mg/kg-bw/day no adult systemic and developmental toxicity were observed. At 750 mg/kg-bw/day, there were marginal effects on body weight in adults and reduced viability and weight gain in the pups. No reproductive effects were observed at the exposure levels tested (US EPA 2009a). 

In a short-term study, male beagle dogs were fed 0, 49.2, 173 or 454 mg/kg-bw/day of TTBP (CAS 732-26-3) for 11 days. At the highest dose tested (454 mg/kg-bw/day), the dogs showed signs of behavioural abnormalities and increased glutamic-oxalacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT) and alkaline phosphatase (ALP). The lowest-observed-effect level (LOEL) of 173 mg/kg-bw/day was established based on diarrhea, and blood in the feces was observed at both the mid and low doses of 173 and 454 mg/kg-bw/day respectively (Anonymous 1987). In addition, a dermal LD₅₀ of greater than 1000 mg/kg-bw/day in rats was reported for analogue, 2,6-di-tert-butylphenol,CAS 128-39-2.

Another analogue identified, CAS 128-37-0 BHT, has been considered by the Organisation for Economic Co-operation and Development’s HPV Chemicals Programme (2002) and was determined not to be a genotoxic carcinogen, and a threshold level of 100 mg/kg-bw/day was established for the possible carcinogenic and tumour-promoting effects of BHT (OECD 2004c).

Characterization of Risk to Human Health

Inhalation of DTBSBP from consumer products is the main estimated route of exposure for the general population.  However, health effects data available for DTBSBP and its analogue substances were conducted via the oral route.  Therefore daily intake was estimated from predicted air concentrations for the characterization of risk. Comparison of the chronic no-observed-effects level (NOEL) of 30 ppm (1.5 mg/kg-bw per day) for the TTBP analogue (CAS RN 732-26-3) via oral exposure with the upper-bounding estimate of daily intake of DTBSBP by toddlers through inhalation exposure of volatile emissions from foam-filled furniture (8.72 × 10^-4 mg/kg-bw per day) results in a margin of exposure of approximately 1720.  No health effects studies via a similar comparison using the chronic NOEL of 30 ppm for the TTBP analogue (CAS RN 732-26-3) with the estimated probable daily intake (PDI = 0.0581 µg/kg-bw) due to potential migration of DTBSBP from meat and produce plastic packaging yields a margin of exposure of approximately 25 800. Based on the information available, it is considered that the estimated margins of exposure are considered adequate to protect human health.

Uncertainties in Evaluation of Risk to Human Health

Due to the limited data available for DTBSBP, the confidence in the toxicological dataset is considered to be low; however, data from analogue substances were available to address data gaps. However, there is uncertainty surrounding the extrapolation of data on analogous substances to predict the health effects of DTBSBP, as it is possible that other characteristics specific to each substance may influence their toxic potential.  In addition, no studies conducted via the inhalation route of exposure were available.

There is uncertainty in the exposure estimation of DTBSBP from environmental media, dietary intake (i.e. migration from food packaging) and consumer products due to the limited information available. However, estimations are based on conservative assumptions and thus considered to be conservative upper-bounding estimates.

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Conclusion

Based on the information presented in this final screening assessment, it is concluded that DTBSBP is entering or may be entering the environment in a quantity or concentration or under conditions that have or may have an immediate or long-term harmful effect on the environment or its biological diversity. 

Based on the information presented in this final screening assessment, it is concluded that DTBSBP is not entering the environment in a quantity or concentration or under conditions that constitute or may constitute a danger in Canada to human life or health. 

It is therefore concluded that DTBSBP meets one or more criteria under section 64 of CEPA 1999.  Additionally, DTBSBP meets the criteria for persistence and bioaccumulation as set out in the Persistence and Bioaccumulation Regulations (Canada 2000).

This substance will be considered for inclusion in the Domestic Substances List inventory update initiative. In addition and where relevant, research and monitoring will support verification of assumptions used during the screening assessment and, where appropriate, the performance of potential control measures identified during the risk management phase.

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References

ACD/pK_aDB [Prediction Module]. 2005. Version 9.04. Toronto (ON): Advanced Chemistry Development. [cited 2009 Feb 27]. Available from: http://www.acdlabs.com/products/phys_chem_lab/pka/[restricted access]

[AIEPS] Artificial Intelligence Expert Predictive System. 2003–2007. Version 2.05. Ottawa (ON): Environment Canada . Model developed by Stephen Niculescu. Available from: Environment Canada , Ecological Assessment Division, New Chemicals Evaluation Section.

Anonymous. 1987. Toxicity of 2,4,6-tri-tert-butylphenol in beagle dogs, Tokyo Metrop. Res. Lab. Public Health, Tokyo. 32-2, 67-68. [cited in US EPA 2009b]

[AOPWIN] Atmospheric Oxidation Program for Windows [Estimation Model]. 2000. Version 1.92. Washington (DC): US Environmental Protection Agency, Office of Pollution Prevention and Toxics; Syracuse (NY): Syracuse Research Corporation. Available from: www.epa.gov/oppt/exposure/pubs/episuite.htm

Arnot JA, Gobas FAPC. 2003. A generic QSAR for assessing the bioaccumulation potential of organic chemicals in aquatic food webs. QSAR Comb Sci 22(3):337–345.

Arnot JA, Mackay D, Bonnell M. 2008a. Estimating metabolic biotransformation rates in fish from laboratory data. Environ Toxicol Chem 27(2):341–351.

Arnot JA, MacKay D, Parkerton T, Bonnell M. 2008b. A database of fish biotransformation rate constants. Environ Sci Technol (In press).

[BCFBAF] Bioaccumulation Program for Windows [Estimation Model]. 2008. Version 3.00. Washington (DC): US Environmental Protection Agency, Office of Pollution Prevention and Toxics; Syracuse (NY): Syracuse Research Corporation. Available from: www.epa.gov/oppt/exposure/pubs/episuite.htm

Beyer A, Mackay D, Matthies M, Wania F, Webster E. 2000. Assessing long-range transport potential of persistent organic pollutants. Environ Sci Technol 34(4):699–703.

[BIOWIN] Biodegradation Probability Program for Windows [Estimation Model]. 2000. Version 4.02. Washington (DC): US Environmental Protection Agency, Office of Pollution Prevention and Toxics; Syracuse (NY): Syracuse Research Corporation. Available from: www.epa.gov/oppt/exposure/pubs/episuite.htm

Boethling RS, Howard PH, Beauman JA, Larosche ME. 1995. Factors for intermedia extrapolations in biodegradability assessment. Chemosphere 30(4):741-752.

Canada . 1999. Canadian Environmental Protection Act, 1999. S.C., 1999, c. 33, Canada Gazette, Part III, vol. 22, no.3. Available from: http://www.gazette.gc.ca/archives/p3/1999/g3-02203.pdf

Canada . 2000. Canadian Environmental Protection Act, 1999: Persistence and Bioaccumulation Regulations. P.C. 2000-348, 23 March, 2000, SOR/2000-107, Canada Gazette, Part II, vol. 134, no. 7, p. 607-612. Available from: http://www.gazette.gc.ca/archives/p2/2000/2000-03-29/pdf/g2-13407.pdf

Canada , Dept. of the Environment, Dept. of Health. 2006a. Canadian Environmental Protection Act, 1999: Notice of intent to develop and implement measures to assess and manage the risks posed by certain substances to the health of Canadians and their environment. Canada Gazette, Part I, vol. 140, no. 49, p. 4109–4117. Available from: http://www.gazette.gc.ca/archives/p1/2006/2006-12-09/pdf/g1-14049.pdf

Canada , Dept. of the Environment. 2006b. Canadian Environmental Protection Act, 1999: Notice with respect to selected substances identified as priority for action. Canada Gazette, Part I, vol. 140, no. 9, p. 435–459. Available from: http://www.gazette.gc.ca/archives/p1/2006/2006-03-04/pdf/g1-14009.pdf

Canada , Dept. of the Environment, Dept. of Health. 2009a. Canadian Environmental Protection Act, 1999: Notice of eighth release of technical information relevant to substances identified in the Challenge. Canada Gazette, Part I, vol. 143, no. 5, p. 192–196. Available from: http://www.gazette.gc.ca/rp-pr/p1/2009/2009-01-31/pdf/g1-14305.pdf 

Canada , Dept. of the Environment. 2009b. Canadian Environmental Protection Act, 1999: Notice with respect to Batch 8 Challenge substances.   Canada Gazette, Part I, vol. 143, no. 5, p. 196–213. Available from: http://www.gazette.gc.ca/rp-pr/p1/2009/2009-01-31/pdf/g1-14305.pdf

CASETOX [Prediction module]. 2008. Version 2.0. Beachwood (OH): MultiCASE. [cited 2009 September 30]. Available from: http://www.multicase.com/products/prod03.htm  [restricted access].

Chinn H, Löchner U, Kishi A. 2006. CEH marketing research report: Polyurethane Foams. Menlo Park (CA): SRI Consulting. Available from: http://www.sriconsulting.com/CEH/Public/Reports/index.html[restricted access]

[CERI] Chemicals Evaluation and Research Institute [database on the Internet]. 2009a. Biodegradation and bioaccumulation data of existing chemicals based on the Chemical Substances Control Law, Japan . Tokyo (JP). Japan Chemical Industry Ecology-Toxicology and Information Centre (JETOC). Record for CAS RN 732-26-3. [cited 2009 July]. Available from: http://qsar.cerij.or.jp/cgi-bin/QSAR/e_r_text_query.cgi 

[CERI] Chemicals Evaluation and Research Institute [database on the Internet]. 2009b. Biodegradation and bioaccumulation data of existing chemicals based on the Chemical Substances Control Law, Japan . Tokyo (JP). Japan Chemical Industry Ecology-Toxicology and Information Centre (JETOC). Record for CAS RN 4130-42-1. [cited 2009 Sept.]. Available from: http://qsar.cerij.or.jp/cgi-bin/QSAR/e_r_text_query.cgi 

[CITI] Chemicals Inspection and Testing Institute, Japan. 1992. Biodegradation and bioaccumulation data of existing chemicals based on the Chemical Substances Control Law, Japan . Tokyo (JP). Oct. 1992.  Japan Chemical Industry Ecology-Toxicology and Information Centre (JETOC).

[ConsExpo] Consumer Exposure Model [Internet]. 2006. Version 4.1. Bilthoven (NL): Rijksinstituut voor Volksgezondheid en Milieu (National Institute for Public Health and the Environment). Available from: http://www.rivm.nl/en/healthanddisease/productsafety/ConsExpo.jsp#tcm:13–42840

[CPOPs] Canadian POPs Model. 2008. Gatineau (QC): Environment Canada , Ecological Assessment Division; Bourgas (BG): Bourgas Prof. Assen Zlatarov University, Laboratory of Mathematical Chemistry. [Model developed based on Mekenyan et al. 2005]. Available upon request.

[DEREK] Deducting Estimation from Existing Knowledge [Prediction module on CD ROM]. 2008. Version 10.0.2. Cambridge (MA): Harvard University, LHASA Group. [cited 2009 September 30]. Available from: http://lhasa.harvard.edu/?page=toxicology.htm[restricted access].

Dimitrov S, Dimitrova N, Parkerton T, Comber M, Bonnell M, Mekenyan O. 2005. Base-line model for identifying the bioaccumulation potential of chemicals. SAR QSAR Environ Res 16(6):531–554.  In the CPOPs Model Suite.

[ECOSAR] Ecological Structural Activity Relationships [Internet]. 2004. Version 0.99h. Washington (DC): US Environmental Protection Agency, Office of Pollution Prevention and Toxics; Syracuse (NY): Syracuse Research Corporation. Available from: www.epa.gov/oppt/exposure/pubs/episuite.htm

[Environ] ENVIRON International Corporation. 2003a. Voluntary Children’s Chemical Evaluation Program Pilot (VCCEPP)–Tier 1 assessment of the potential health risks to children associated with exposure to the commercial pentabromodiphenyl ether product and appendices [Internet]. Emerville (CA): ENVIRON International Corporation. Available from: http://www.epa.gov/oppt/vccep/pubs/chem22a.html

[Environ] ENVIRON International Corporation. 2003b. Voluntary Children’s Chemical Evaluation Program Pilot (VCCEPP)–Tier 1 assessment of the potential health risks to children associated with exposure to the commercial octabromodiphenyl ether product and appendices [Internet]. Emerville (CA): ENVIRON International Corporation. Available from: http://www.epa.gov/oppt/vccep/pubs/chem23a.h

Environment Canada . 2006. Data for selected substances collected under the Canadian Environmental Protection Act, 1999, Section 71: Notice with respect to selected substances identified as priority for action. Data compiled by: Environment Canada , Program Development and Engagement Division.

Environment Canada . 2007. Guidance for Conducting Ecological Assessments under CEPA, 1999: Science Resource Technical Series: Technical Guidance Module: QSARs. Reviewed Draft Working Document. Gatineau (QC): Environment Canada , Ecological Assessment Division.

Environment Canada . 2009a. Data for Batch 8 substances collected under the Canadian Environmental Protection Act, 1999, Section 71: Notice with respect to certain Batch 8 Challenge substance, Canada Gazette Part I, vol. 143, no. 5, p. 196–213.  Data compiled by: Environment Canada , Program Development and Engagement Division.

Environment Canada . 2009b. Guidance for Conducting Ecological Assessments under CEPA, 1999: Science Resource Technical Series, Technical Guidance Module: Mass Flow Tool. Working Document. Gatineau (QC): Environment Canada , Ecological Assessment Division.

Environment Canada . 2009c. Mass Flow Tool for Phenol, 2,6-bis(1,1-dimethylethyl)-4-(1-methylpropyl) or DTBSBP, CAS RN 17540-75-9. Internal draft document. Gatineau (QC): Environment Canada , Ecological Assessment Division. 

[EPI Suite] Estimation Programs Interface Suite for Microsoft Windows [Estimation Model]. 2008. Version 4.0. Washington (DC): US Environmental Protection Agency, Office of Pollution Prevention and Toxics; Syracuse (NY): Syracuse Research Corporation. Available from: www.epa.gov/oppt/exposure/pubs/episuitedl.htm

[EQC] Equilibrium Crieterion Model. 2003. Version 2.02. Peterborough (ON): Trent University, Canadian Environmental Modelling Centre. Available from: http://www.trentu.ca/academic/aminss/envmodel/models/EQC2.html

[ESIS] European Chemical Substances Information System. 2009. Information for CAS RN 17540-75-9. Ispra [IT]: European Commission, Joint Research Centre, Institute for Health and Consumer Protection, European Chemicals Bureau. [cited 2009 June 9]. Available from: http://ecb.jrc.ec.europa.eu/esis/

Fenner K, Scheringer M, MacLeod M, Matthies M, McKone TE, Stroebe M, Beyer A, Bonnell M, Le Gall A, Klasmeier J, Mackay D, Pennington DW, Scharenberg B, Wania F. 2005. Comparing estimates of persistence and long-range transport potential among multimedia models. Environ Sci Technol 39:1932–1942.

Geiger DL, Brooke LT, Call DJ. 1990. Acute Toxicities of Organic Chemicals to Fathead Minnows (Pimephales promelas). Vol. 5. Center for Lake Superior Environmental Studies, University of Wisconsin-Superior, Superior, Wisconsin. 332 p.

Hachiya, N and Takizawa, Y.  1994.  Mutagenicity of plastic additives.  Hen'igensei Shiken 3(3): 147-154 [cited in Chemical Carcinogenesis Research Information System 2001]

Health Canada . 1994. Human health risk assessment for priority substances: Appendix E Reference values for intakes and body weights of laboratory animals.[Internet]. Ottawa (ON): Health Canada , Environmental Health Directorate, Environmental Substances Division. [cited 2009 October 8]. 35 p. Available from: http://www.hc-sc.gc.ca/ewh-semt/pubs/contaminants/approach/index-eng.php

Health Canada . 1998. Exposure factors for assessing total daily intake of priority substances by the general population of Canada . Unpublished report. Ottawa (ON): Health Canada . Environmental Health Directorate.

[HENRYWIN] Henry’s Law Constant Program for Microsoft Windows [Estimation Model]. 2000. Version 3.10. Washington (DC): US Environmental Protection Agency, Office of Pollution Prevention and Toxics; Syracuse (NY): Syracuse Research Corporation. Available from: www.epa.gov/oppt/exposure/pubs/episuite.htm

Hillier K, Schupp T, Carney I. 2003. An investigation into VOC emissions from polyurethane flexible foam mattresses. Cell Polym 22(4):237–259.

Hu TM,  Layton WL. 2001. Allometric scaling of xenobiotic clearance: uncertainty versus universality. AAPS PharmSci [Internet]. Vol. 3(4): Article 29. Available from: http://www.aapsj.org/view.asp?art=ps030429

[HYDROWIN] Hydrolysis Rates Program for Microsoft Windows [Estimation Model]. 2000. Version 1.67. Washington (DC): US Environmental Protection Agency, Office of Pollution Prevention and Toxics; Syracuse (NY): Syracuse Research Corporation. Available from: www.epa.gov/oppt/exposure/pubs/episuite.htm

Iida-Kondo C, Yoshino N, Kurabayashi T, Mataki S, Hasegawa M, Kurosaki N. 2006. Comparison of Tongue Volume/Oral Cavity Volume Ratio between Obstructive Sleep Apnea Syndrome Patients and Normal Adults Using Magentic Resonance Imaging. J Med Dent Sci 53:119–126.

[ISOPA] European Diisocyanate & Polyol Producers Association. 2005. Factsheet: the benefits of polyurethanes in transportation [Internet]. [cited 2009 Oct 6]. Available from: http://www.isopa.org/isopa/uploads/Documents/documents/Transportation.pdf

Klasmeier J, Matthies M, MacLeod M, Fenner K, Scheringer M, Stroebe M, Le Gall AC, McKone TE, van de Meent D, Wania F. 2006. Application of multimedia models for screening assessment of long-range transport potential and overall persistence. Environ Sci Technol 40:53–60.

Klempner DR, Sendijarevic V, editors. 2004. Handbook of polymeric foams and foam technology. Portland (OR): Book News, Inc.

[KOWWIN] Octanol-Water Partition Coefficient Program for Microsoft Windows [Estimation Model]. 2000. Version 1.67. Washington (DC): US Environmental Protection Agency, Office of Pollution Prevention and Toxics; Syracuse (NY): Syracuse Research Corporation. Available from: www.epa.gov/oppt/exposure/pubs/episuite.htm

Leadscope [Prediction module]. 2009. Leadscope Model Applier Version 1.2.0-3.  Columbus, OH: Leadscope, Inc. [cited 2009 September 30]. Available from: http://www.leadscope.com/all_products.php[restricted access].

Lide, D.R., ed.  2003.  CRC Handbook of Chemistry and Physics, 84^th ed.  CRC Press, USA .

Loock F, Lampe T, Bahadir M. 1993. Examination of the emission of (semi-)volatile organic compounds from polymer materials used as interior trim materials in automobiles. Fresenius J Anal Chem 347:280–285.

Matsumoto K, Ochiai T, Sekita K, Uchida O, Furuya T, Kurukawa Y. 1991 Chronic toxicity of 2, 4, 6-Tri-tert-butylphenol in rats. Journal of Toxicological Sciences 16: 167-179.  [cited in  US EPA 2009]. Available from: http://iaspub.epa.gov/oppthpv/Public_Search.PublicTabs?SECTION=1&epcount=2&v_rs_list=25034978,25034972

Mekenyan G, Dimitrov SD, Pavlov TS, Veith GD. 2005. POPs: a QSAR system for creating PBT profiles of chemicals and their metabolites. SAR QSAR Environ Res 16(1-2):103-133.

Meyer-Ahrens S. 2005. Chapter 7.1 in Polyurethanes [Internet]. Ullmann’s Encyclopedia of Industrial Chemistry, online version. Available from: http://mrw.interscience.wiley.com/emrw/9783527306732/ueic/article/a21_665/current/pdf[restricted access].

[MPBPWIN] Melting Point Boiling Point Program for Microsoft Windows [Estimation Model]. 2000. Version 1.41. Washington (DC): US Environmental Protection Agency, Office of Pollution Prevention and Toxics; Syracuse (NY): Syracuse Research Corporation. Available from: www.epa.gov/oppt/exposure/pubs/episuite.htm

[NCI] National Chemical Inventories [database on CD-ROM]. 2007. Issue 1. Columbus (OH): American Chemical Society. [cited 2009 June]. Available from: http://www.cas.org/products/cd/nci/index.html

Nichols JW, Fitzsimmons PN, Burkhard LP. 2007. In vitro – in vivo extrapolation of quantitative hepatic biotransformation data for fish. II. modeled effects on chemical bioaccumulation. Environ Toxicol Chem 26: 1304-1319.

[NITE] National Institute of Technology and Evaluation [database on the Internet]. 2002a. Comprehensive Information for CAS RN 732-26-3. Tokyo [JP]: NITE. [cited 2009 July 13]. Available from: http://www.safe.nite.go.jp/english/Haz_start.html

[NITE] National Institute of Technology and Evaluation [database on the Internet]. 2002b. Comprehensive Information for CAS RN 17540-75-9. Tokyo [JP]: NITE. [cited 2009 July 13]. Available from: http://www.safe.nite.go.jp/english/Haz_start.html

 [NITE] National Institute of Technology and Evaluation [database on the Internet]. 2002c. Biodegradation and Bioconcentration data.  Data for CAS RN 4130-42-1. [cited 2009 Oct 19].  Available from: http://www.safe.nite.go.jp/data/hazkizon/pk_e_kizon_input_second.home_object

[NLM] U.S. National Library of Medecine [database on the Internet].  2009.  ChemIDplus Advanced.  Data for CAS RN 732-26-3 and CAS RN 4130-42-1. [cited 2009 July 13].  Available from: http://chem.sis.nlm.nih.gov/chemidplus/chemidheavy.jsp

Norris B, Smith S (Institute for Occupational Ergonomics, School of Mechanical, Materials, Manufacturing Engineering and Management, University of Nottingham, University Park, Nottingham NG7 2RD). 2002. Research into the mouthing behaviour of children up to 5 years old. Executive summary. London ( UK ): Department of Trade and Industry. Report No.: URN 02/748. Available on request.

[OASIS Forecast] Optimized Approach based on Structural Indices Set [Internet]. 2005. Version 1.20. Bourgas (BG): Bourgas Prof. Assen Zlatarov University, Laboratory of Mathematical Chemistry. Available from: http://oasis-lmc.org/?section=software

[OECD] Organisation for Economic Co-operation and Development. 2004a. The 2004 OECD list of high production volume chemicals [Internet]. Paris (FR): OECD, Environment Directorate. [cited 2009 June 29]. Available from: http://www.oecd.org/dataoecd/55/38/33883530.pdf

[OECD] Organisation for Economic Co-operation and Development. 2004b. Emission scenario document on plastics additives [Internet]. Paris (FR): OECD, Environment Directorate. (Series on Emission Scenario Documents No. 3). Report No.: ENV/JM/MONO(2004)8, JT00166678. [cited yr mon date]. Available from: http://www.olis.oecd.org/olis/2004doc.nsf/LinkTo/NT0000451A/$FILE/JT00166678.PDF

[OECD] Organisation for Economic Co-operation and Development. 2004c. The Screening Information Data Set (SIDS) Initial Assessment Report for 2,6-di-tert-butyl-p-cresol (BHT). Discussed at SIDS Initial Assessment Meeting 14; March 2002.  Paris (FR): OECD, Environment Directorate. [cited 2009 October 27]. Available from: http://www.chem.unep.ch/irptc/sids/OECDSIDS/128370.pdf

OECD POPs Screening Tool – see Scheringer et al. (2006)

[OECD] Organisation for Economic Co-operation and Development, Environment Directorate. 2008.  QSAR Application Toolbox. Version 1.1.0.2.  Developed by: Bourgas (BG): Bourgas Prof. Assen Zlatarov University, Laboratory of Mathematical Chemistry.  Available for download at : http://www.oecd.org/document/54/0,3343,en_2649_34379_42923638_1_1_1_1,00.html

[OSPAR] OSPAR Commission. 2006. OSPAR List of Substances of Possible Concern [Internet]. Reykjavik (IS): OSPAR Convention for the Protection of the Marine Environment of the North-East Atlantic, Hazardous Substances, The OSPAR List of Substances of Possible Concern, (last updated August 2006), Reference No. 2002-17. [cited 2009 June 29]. Available from: http://www.ospar.org/eng/html/welcome.htmlor http://www.ospar.org/v_substances/get_page.asp?v0=17540759.xls

[PCKOCWIN] Organic Carbon Partition Coefficient Program for Windows [Estimation Model]. 2000. Version 1.66. Washington (DC): US Environmental Protection Agency, Office of Pollution Prevention and Toxics; Syracuse (NY): Syracuse Research Corporation. Available from: www.epa.gov/oppt/exposure/pubs/episuite.htm

[PMRA] Pest Management Regulatory Agency. 2007. Memorandum to Pesticide Registrants. Post-categorization of substances on the Domestic Substances List: Impacts of the Challenge for Pesticide Registrants. Attachment 1: Actives, Formulants and Formulant Impurities on the Challenge List Resulting from Categorization of the DSL [Internet]. Ottawa (ON): Health Canada , Pest Management Regulatory Agency. [cited 2009-10-26].

[PMRA] Pest Management Regulatory Agency. 2009. Pest Management Regulatory Agency's Public Registry: Product Information, Label Search [Internet]. Ottawa (ON): Health Canada , Pest Management Regulatory Agency. [cited 2009-10-26]. Available from: http://pr-rp.pmra-arla.gc.ca/portal/page?_pageid=34,17551&_dad=portal&_schema=PORTAL

[RIVM] Rijksinstituut voor Volksgezondheid en Milieu. 2006. General Fact Sheet: Limiting conditions and reliability, ventilation, room size, body surface area. Updated version for ConsExpo 4 [Internet]. Report No.: 320104002/2006. Bilthoven (NL): RIVM (National Institute for Public Health and the Environment). [cited 2009 Aug 31]. Available from: http://www.rivm.nl/bibliotheek/rapporten/320104002.pdf

Scheringer M, MacLeod M, Wegmann F. 2006. The OECD P_OV and LRTP Screening Tool [Internet]. Version 2.0. Organization for Economic Cooperation and Development; Zurich (CH): Swiss Federal Institute of Technology. Distributed at OECD/UNEP Workshops on Application of Multimedia Models for Identification of Persistent Organic Pollutants, Ottawa, Canada , May 31 – June 2, 2006. Available from: http://www.oecd.org/document/17/0,3343,en_2649_34373_40754961_1_1_1_1,00.html

Sigma-Aldrich.  2009.  Material Safety Data Sheet for 4-sec-Butyl-2,6-di-tert-butylphenol.  Revised 08/28/2009.  Available from: http://www.sigmaaldrich.com/MSDS/MSDS/DisplayMSDSPage.do

SI Group. 2009a. Material Safety Data Sheet for ISONOX® 132 (CAS RN 17540-75-9). Dated January 22, 2009. Available at: http://www.siigroup.com/productinfo.asp?product=24

SI Group. 2009b. Information submitted to Environment Canada, Program Development and Engagement Division under the Chemicals Management Plan Challenge initiative. Gatineau, QC.

SI Grouop 2010a.  Submission to Environment Canada , Ecological Assessment Division.  Letter entitled: “Freeze Point Data for 2, 6-di-tert-butyl-4-sec-butylphenol; CAS No. 17540-75-9 (DTBSBP)”.  May 24, 2010.

SI Group. 2010b.  Submission to Environment Canada , Program Development and Engagement Division. Letter entitled: “Response to Batch 8 Challenge Risk Management Scope document for 2, 6-di-tert-butyl-4-sec-butylphenol; CAS No. 17540-75-9 (DTBSBP)”.  March 31, 2010.

[SII] Schenectady International, Inc. (now called SI Group) 2001. Alkylphenols Category. Section One, Development of Categories and Test Plans, Chemical Right to Know Initiative, HPV Challenge Program. Report submitted to US Environmental Protection Agency, Office of Pollution Prevention and Toxics, HPV Challenge Program, Washington, D.C. 40 pp. Available from: http://www.epa.gov/hpv/pubs/summaries/alkylphn/c13007rt.pdf

[SII] Schenectady International, Inc. (now called SI Group). 2002. Alkylphenols Category. Section Two, Ortho-substituted Mono-alkylphenols, Chemical Right to Know Initiative, HPV Challenge Program. Report submitted to US Environmental Protection Agency, Office of Pollution Prevention and Toxics, HPV Challenge Program, Washington, D.C. Received 3 Apr. 2002.  565 pp. Available from: http://www.epa.gov/oppt/chemrtk/pubs/summaries/alkylphn/c13007rr.pdf

Springborn Laboratories, Inc. 1980. Acute Oral LD50 Toxicity Study in Rats Robust Study Summary for CAS RN 17540-75-9, US EPA, High Production Volume Information System (HPVIS). [cited in US EPA 2009] . Available from: http://iaspub.epa.gov/oppthpv/Public_Search.PublicTabs?SECTION=1&epcount=1&v_rs_list=25034442

[TaPL3] Long Range Transport and Persistence Level III model [Internet]. 2000. Version 2.10. Peterborough (ON): Trent University, Canadian Environmental Modelling Centre. Available from: ttp://www.trentu.ca/academic/aminss/envmodel/models/TaPL3.html

[TOPKAT] Toxicity Prediction by Komputer Assisted Technology [Internet]. 2008. Version 6.2.  San Diego (CA): Accelrys Software Inc. [cited 2009 September 30].  Available from: http://www.accelrys.com/products/topkat/index.html

[ US EPA] United States Environmental Protection Agency. 2006. Non-confidential 2006 Inventory Update Reporting (IUR) records by chemical. Search results for CAS RN 17540-75-9.  Washington (DC): US EPA, Office of Pollution Prevention and Toxics. [cited 2009 Aug 13].  Available from: http://cfpub.epa.gov/iursearch/index.cfm?s=chem

[ US EPA] United States Environmental Protection Agency. 2009a.  Screening-Level Hazard Characterization [Internet]. Washington (DC): US EPA, Office of Pollution Prevention and Toxics. [cited 2009 September] Available from: http://www.epa.gov/champ/pubs/hazchar/Category_Alkylphenols_Sept2009.pdf

[ US EPA] United States Environmental Protection Agency. 2009b. High Production Volume Information System (HPVIS) [Internet]. Washington (DC): US EPA, Office of Pollution Prevention and Toxics. [cited 2009 July] Available from: http://www.epa.gov/hpvis/index.html

[ US FDA] United States Food and Drug Administration. 2008. Inventory of Effective Food Contact Substance (FCS) Notifications: FCN No. 80. [Internet]. Washington (DC): US Food and Drug Administration, Center for Food Safety and Applied Nutrition, Office of Food Additive Safety. [cited 2008 April]. Available from: http://www.cfsan.fda.gov/~dms/opa-fcn.html

[ US NLM] United States National Library of Medicine. 2008. ChemIDplus program. Division of Specialized Services.  Updated May 2008.  [cited 2009 August].  Available from: http://chem.sis.nlm.nih.gov/chemidplus/chemidheavy.jsp

Versar Inc. 1986. Standard Scenarios for Estimating Exposure to Chemical Substances During Use of Consumer Products, Vol. I. Prepared for U.S. Environmental Protection Agency

 [WSKOWWIN] Water Solubility for Organic Compounds Program for Microsoft Windows [Estimation Model]. 2000. Version 1.41. Washington (DC): US Environmental Protection Agency, Office of Pollution Prevention and Toxics; Syracuse (NY): Syracuse Research Corporation. Available from: www.epa.gov/oppt/exposure/pubs/episuite.htm

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Appendix 1: Robust Study Summaries for Aquatic Toxicity of 2,4,6-tri-tert-butylphenol

Robust Study Summary Form: Aquatic iT

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Appendix 2: PBT Model Inputs Summary Table for DTBSBP

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Appendix 3: Exposure Estimations

In the following exposure estimations, it was assumed that Canadians spend, on average, 8 hours sleeping (Hillier et al. 2003), and through professional judgement, 3 hours driving. Canadians are assumed to spend 21 hours indoors each day (Health Canada 1998), taking into account the assumption of 8 hours sleeping, it was assumed that the remaining 13 hours were spent indoors, out of the bedroom.

Inhalation chronic doses due to DTBSBP emissions from foam mattresses and foam-filled furniture were estimated for all age groups, and are shown in the Table 1 below. The calculations for these estimations are illustrated in Table 2 using adult exposure as an example. Oral exposures of infants and toddlers from mouthing foam were also estimated (refer to Table 1); details are shown in Table 2.

Table 1. Upper-bounding estimates of intake of DTBSBP from consumer products by the general population of Canada

Table 2. Exposure estimates from the use of consumer products

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Appendix 4: Structures and data for DTBSBP analogues considered in this assessment

Name / CAS RN	Structure	Molecular weight (g/mol)	Analogue identification method (%similar)	Health effects toxicity data available
Note: Other CAS numbers were included in the U.S. EPA Hazard Characterization Document (2772-45-4; 120-95-6; 96-76-4); however, they were not included, as the data did not further contribute to the overall health effects assessment.
Phenol, 2,6-bis(1,1-dimethylethyl)-4-ethyl- 4130-42-1		234.4	Tanimoto coeff. (79) Chemid (88.16)	Genetox: Negative in TA97, TA98, TA100, TA102, WP2 p with/without activation  (Hachiya and Takizawa 1994)
Phenol, 2,4,6-tris(1,1-dimethylethyl)- (TTBP) 732-26-3		262.4	Chemid (93.36)	Chronic: Negative for carcinogenicity; Non-neoplastic effects NOEL=30ppm (Matsumoto et al. 1991) Short-term: LOEL= 173 mg/kg bw/day based on diarrhea, and blood in the feces (Anonymous 1987)
Butylated hydroxytoluene (BHT) 128-37-0		220.4	Tanimoto coeff. (75) Chemid (83.3)	Considered by the OECD SIDS programme and determined not to be a genotoxic carcinogen and a threshold of 100 mg/kg-bw/day was established for the possible carcinogenic and tumour-promoting effects of BHT (OECD 2004c)
2,6-Di-tert-butylphenol 128-39-2		206.3	US EPA Hazard Characterization Category Di and Tri-Substituted Mixed Alkylphenols	Genetox: Negative in S. typhimurium (TA98, TA100, TA 1535, TA1537 and TA1538) with and without activation  (US EPA 2009a) Negative for chromosomal aberrations in Chinese hamster V79 cells with and without activation (US EPA 2009a).  Repeated-dose (28 day) (US EPA 2009a): LOAEL=600 mg/kg-bw/day based on increase liver weight and a slight increase in the incidence of hepatocellular hypertrophy in the centrilobular area in both sexes and eosinophilic inclusions in the renal cortex of males NOAEL=100 mg/kg-bw/day Combined repro/devo study: (US EPA 2009a) Reproductive toxicity: LOAEL= None established NOAEL= 750 mg/kg-bw/day Adult systemic and developmental oxicity: LOAEL= 750 mg/kg-bw/day NOAEL=150 mg/kg-bw/day Acute: LD50 (dermal)> 1000 mg/kg-bw/day in rats
2,3,6-Trimethylphenol 2416-94-6		136.2	U.S. EPA Hazard Characterization Category Di and Tri-Substituted Mixed Alkylphenols	Genetox: In vitro: Negative in S. typhimurium (TA98, TA100, TA 1535, TA1537 and TA1538) with and without activation (US EPA 2009a)

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Appendix 5: Summary of (Q)SAR Predictions

(Q)SAR Predictions on Carcinogenicity

(Q)SAR Predictions on Genotoxicity

(Q)SAR Predictions on Developmental Toxicity

Model Applier

Multicase Casetox

(Q)SAR Predictions on Reproductive Toxicity

Model Applier

Multicase Casetox

Footnote

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Date modified:

2013-06-20