Screening Assessment for the Challenge Phenol, 4,4'- (3H-2,1-benzoxathiol-3-ylidene)bis[2-bromo-6-methyl-,S,S-dioxide (Bromcresol Purple) (2024)

Environment Canada
Health Canada

August 2009

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. Conclusion
12. References
13. Appendix 1 - Robust Study Summaries

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 of Phenol, 4,4'- (3H-2,1-benzoxathiol-3-ylidene)bis[2-bromo-6-methyl-,S,S-dioxide (Bromcresol Purple), Chemical Abstracts Service Registry Number 115-40-2. This substance was identified as a high priority for screening assessment and included in the Challenge because it had originally been 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 bromcresol purple 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.

Bromcresol purple is an organic substance used mainly as an analytical reagent in laboratories. This substance was not in commerce in significant quantities in Canada in 2006, indicating that its release to the Canadian environment is likely very low. Based on possible uses of this substance, if released, it would most likely be to water bodies or landfills. Since bromcresol purple is expected to be soluble in water, is not volatile and does not have a tendency to bind to particles (based on data for an analogue chemical), it could be found in surface water and possibly in groundwater following leaching through soil.

Based on its physical and chemical properties, bromcresol purple does not degrade quickly in the environment and is expected to be persistent in water and soil. Based on currently available information, bromcresol purple does not have the potential to accumulate in organisms. This substance has been determined to meet the persistence criteria but not the bioaccumulation criteria as set out in the Persistence and Bioaccumulation Regulations. In addition, it is not highly hazardous to aquatic organisms (LC₅₀/EC₅₀ greater than 1 mg/L).

For this screening assessment, a highly conservative exposure scenario was selected in which a facility (user of the substance) discharges bromcresol purple into the aquatic environment. The predicted environmental concentration (PEC) in water was many orders of magnitude below predicted no-effect concentrations (PNECs) calculated for fish, daphnids and algae. Thus, this substance is not believed to cause ecological harm in the aquatic environment.

This substance will be included in the upcoming Domestic Substances List inventory update initiative. In addition and where relevant, research and monitoring will support verification of assumptions used during the screening assessment.

Based on the information available, it is concluded that Bromcresol Purple does not meet any of the criteria set out in section 64 of CEPA 1999.

Top of Page

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 results of a screening assessment, the Ministers can propose to take no further action with respect to the substance, to add the substance to the Priority Substances List (PSL) for further assessment, or to recommend that the substance be added to the List of Toxic Substances in Schedule 1 of the Act and, where applicable, the implementation of virtual elimination.

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, 4,4'- (3H-2,1-benzoxathiol-3-ylidene)bis[2-bromo-6-methyl-,S,S-dioxide was identified as a high priority for assessment of ecological risk as it had been found to be persistent, bioaccumulative and inherently toxic to aquatic organisms and is believed to be in commerce in Canada. The Challenge for this substance was published in the Canada Gazette on November 17, 2007 (Canada 2007). 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, information pertaining to the quantity in commerce of the substance was received.

Although Phenol, 4,4'- (3H-2,1-benzoxathiol-3-ylidene)bis[2-bromo-6-methyl-,S,S-dioxide 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 was not 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. Therefore, this assessment focuses principally on information relevant to the evaluation of ecological risks.

Under CEPA 1999, screening assessments focus on information critical to determining whether a substance meets the criteria for defining a chemical as toxic as set out in section 64 of the Act, where

"64. [...] a substance is toxic if it is entering or may enter the environment in a quantity or concentration or under conditions that

1. have or may have an immediate or long-term harmful effect on the environment or its biological diversity;
2. constitute or may constitute a danger to the environment on which life depends; or
3. constitute or may constitute a danger in Canada to human life or health."

Screening assessments examine scientific information and develop conclusions by incorporating a weight-of-evidence approach and precaution.

This 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 May 2008. Key studies were critically evaluated; modelling results may have been used to reach conclusions. When available and relevant, information presented in hazard assessments from other jurisdictions was considered. The 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 screening assessment was prepared by staff in the Existing Substances Program at Health Canada and Environment Canada and it incorporates input from other programs within these departments. This assessment has undergone external written peer review/consultation. Additionally, a draft of this screening assessment was subject to a 60-day public comment period. While external comments were taken into consideration, the final content and outcome of the screening risk assessment remain the responsibility of Health Canada and Environment Canada. The critical information and considerations upon which the assessment is based are summarized below.

Top of Page

Top of Page

Table 2 contains experimental and modelled physical and chemical properties of bromcresol purple that are relevant to its environmental fate. Given the scarcity of experimental data for this substance, a search was conducted and a few close structural analogues were identified. The only analogue for which some experimental data could be found is bromophenol blue (CAS RN 115-39-9), a substance that is also assessed as part of the Challenge. Information on the chemical identity of bromophenol blue is provided in Table 3.

Key studies reporting experimental data for some physical and chemical properties of both bromcresol purple and its analogue, bromophenol blue, were critically reviewed for validity. These reviews (Robust Study Summary) are found in Appendix 1. The studies were found as a result of recent literature searches.

When available, experimental data from analogues are preferred to modelled data for the substance being assessed, especially if the models do not provide accurate predictions. Given the scarcity of experimental data for both bromcresol purple and its analogue, bromophenol blue, quantitative structure-activity relationship (QSAR) models were used to generate data for physical and chemical properties of bromcresol purple. These models (except WSKOWWIN 2000) are mainly based on fragment addition methods, i.e., they rely on the structure of a chemical. Since these models only accept the neutral form of a chemical as input (in SMILES form), the modelled values shown in Table 2 are for the neutral form of bromcresol purple.

Based on the experimental pK_a values found, more than half of bromcresol purple will be in its ionized form at pH greater than 6.3-6.5. Since environmentally relevant pH values fall in the range of 6 to 9, this means that most (between 50 and 100%) of bromcresol purple will be ionized (present in anionic form) in the environment. These experimental pK_a values are consistent with the reported use of bromcresol purple as a pH indicator (see Uses section) in the pH range 5.2 to 6.8 (pH-meter.Info 2005). The ionization of bromcresol purple is not only due to the dissociation of the hydroxyl groups, but also to the hydrolysis of the ester link between the central carbon and the oxygen atom in the benzoxathiole ring. Following this reaction, a sulfonic acid group is formed, which is expected to greatly increase the water solubility of this substance. These pK_a values for bromcresol purple were recently identified and were not considered during categorization.

Regarding solubility, there is a discrepancy in the information provided in Table2 for this property. Indeed, the qualitative statement from O'Neil (2001) points to a low water solubility for bromcresol purple whereas the modelled value, which is based on experimental values for melting point and log K_ow from an analogue, indicates a very high solubility. O'Neil (2001) does not provide an indication of what range of solubility values correspond to the statement "practically insoluble." From an ecotoxicological point of view, a substance having water solubility as low as 1 mg/L can be of concern, depending on its toxicity (Environment Canada 2003). Based on the empirical solubility value available for a structural analogue (4000 mg/L; bromophenol blue) which is completely ionized at ambient pH, and given the fact that bromcresol purple will mostly be ionized in the environment, it is believed that bromcresol purple is also highly soluble in water. In addition, the comparison of functional groups in bromophenol blue and bromcresol purple suggests that the latter could be more soluble than the former, since solubility generally increases as the number of bromide atoms in a substance decreases. The modelled solubility value for bromcresol purple may be overestimated since it is based on the log K_ow for the ionized form of the analogue bromophenol blue. The latter is expected to be fully ionized under environmental pH (6-9), which would not be the case for bromcresol purple.

Regarding other physical and chemical properties, the experimental and analogue values shown in Table 2 suggest that at ambient pH most bromcresol purple is present in anionic form, it does not bioaccumulate in organisms, it does not bind to particles and it is highly mobile in soil. It is, however, recognized that the analogue log K_ow and log K_oc values may underestimate partitioning of bromcresol purple since this compound may not be completely ionized, depending on the ambient pH. The volatility of bromcresol purple cannot be assessed because the modelled values for vapour pressure and Henry's Law constant are probably not reliable (see below). However, given its ionized state under environmental pH, this substance will likely have a low volatility. A more detailed discussion of how physical and chemical properties influence the environmental fate of this substance is presented later in this report.

As seen from Table 2, several models do not perform well in estimating some of the physical and chemical properties of bromcresol purple. In particular, the modelled log K_ow and log K_oc values differ from the experimental values measured for an analogue by a few orders of magnitude. This is most likely because the chemical structures of ionisable substances like bromcresol purple are poorly represented in the training set of some the models used. Because modelled data are not reliable, the analogue data presented in Table 2 for bromophenol blue were used as appropriate in this assessment.

Top of Page

Bromcresol purple is not reported to be naturally produced in the environment.

Information gathered through a CEPA section 71 notice for the 2006 calendar year indicates that bromcresol purple was not manufactured in, imported into or used in Canada in a quantity exceeding the prescribed thresholds (i.e., 100kg for manufacture/import and 1000kg for use). However, two companies reported using the substance below the reporting threshold. A total of eight Canadian companies identified themselves as stakeholders, i.e., as having an interest in this substance (Environment Canada 2007). A similar CEPA section 71 notice for the 2005 calendar year also indicated that bromcresol purple was not in commerce at the reporting threshold (i.e., 100kg for manufacture/import). For that year, five Canadian companies had identified themselves as stakeholders (Canada 2006b).

The quantity reported to be manufactured, imported or in commerce in Canada during the 1986 calendar year was 500kg. The number of notifiers for the 1984 to 1986 calendar years was fewer than four. The data gathered from the CEPA section 71 notices suggest that the use of this substance has decreased over the last two decades.

Top of Page

Top of Page

Top of Page

Based on its physical and chemical properties (Table 2) and potential mode of entry into the environment, bromcresol purple is expected to mainly be found in surface water, and possibly in soil and groundwater.

The acid dissociation constant (pK_a) of 6.3-6.5 for bromcresol purple indicates that half of this chemical will be dissociated at these pH values. In water bodies at environmentally relevant pH (6-9), most (between 50 and 100%) of the chemical will thus be ionized as a result of the following two reactions: 1) the release of one proton from each of the two hydroxyl groups; or 2) the hydrolysis of the ester link between the central carbon and the oxygen atom in the benzoxathiole ring, resulting in the oxygen atom bearing a net negative charge. As such, the partitioning behaviour of this chemical will be better predicted using the log K_ow and log K_oc values available for the ionized rather than neutral form (Table 2; analogue data).

If bromcresol purple is used as an analytical reagent in laboratories (e.g., as liquid pH indicator) or for any other use that would result in its disposal down the drain, it will reach sewage treatment plants (STPs). Assuming no degradation in these plants, it would stay in wastewater and would not partition to sewage sludge based on its expected high water solubility (Table 2; analogue data) and low log K_ow and log K_ocvalues for its ionized forms (Table 2; less than 1, analogue data). Similarly, once released to receiving water, bromcresol purple would mainly remain in the water column rather than partition into the sediments, given its expected high solubility in water and low log K_ow and log K_oc values for the ionized form. Bromcresol purple would not volatilize to air from water based on its tendency to ionize at ambient pH in water.

If bromcresol purple is used as a paper form pH indicator or for any other use that would generate solid wastes, it will end up in landfills through waste disposal. Assuming little or no degradation once in these sites, bromcresol purple would likely leach through soil layers or undergo surface run-off given its expected high solubility in water and low affinity for soil constituents, as indicated by the very low log K_oc value for the ionized form of the analogue. The substance could eventually reach groundwater and/or local surface waters. Again, bromcresol purple would not volatilize to air from soil as indicated by its tendency to ionize at ambient pH. This substance is not expected to be released directly into air. The assumptions of no degradation in water and soil for this substance are supported by the assessment of its persistence in these media, as presented below.

Top of Page

The preceding information on the likely pattern of release and subsequent environmental fate of bromcresol purple suggests that it will mostly be found in surface water and possibly in and groundwater, but not in sediments. This substance is also not expected to be present in air.

There are no empirical degradation data available for bromcresol purple or for a structural analogue. ETAD (1995) states that, with some exceptions, dyes may be considered essentially non-biodegradable under aerobic conditions. Repeated evaluation of ready- and inherent-biodegradability using accepted screening tests (e.g., OECD tests) have confirmed this characteristic (Pagga and Brown 1986, ETAD 1992). Based on the chemical structure of bromcresol purple, there is no reason to suspect that its biodegradation would be significantly different from that of other dyes described in ETAD (1995).

Due to the lack of experimental data, the persistence of bromcresol purple was examined using the predictive QSAR models for biodegradation shown in Table 4 below. Given the ecological importance of the water compartment, the fact that most of the available models apply to water and the fact that bromcresol purple is expected to be released and remain in this compartment, biodegradation in water was primarily examined. Although the degradation models are structure-based and only consider the neutral form of bromcresol purple, most of the modelled values (Table 4) are considered to be reliable, as some chemicals of structural comparability to bromcresol purple are contained in their training sets.

The results from Table 4 show that all of the probability models (BIOWIN1, 2, 5, 6 and 7) suggest that bromcresol purple does not biodegrade rapidly. In fact, most of the probability results are less than 0.3, the cut-off suggested by Aronson et al. (2006) to identify substances as having a half-life greater than 60 days (based on the MITI probability models), and they are all less than 0.5, the cut-off suggested by the model developers for slow biodegradation. The US EPA (2002) and Aronson et al. (2006) suggest that the half-life result from the primary survey model (BIOWIN 4) of "weeks-months" corresponds to a half-life of approximately 37.5 days. It is suggested by the US EPA (2002) that the ultimate survey model (BIOWIN 3) result, "recalcitrant," corresponds to a half-life of approximately 180days and by Aronson et al. (2006) that it corresponds to a half-life of 240 days. The substance is also not expected to degrade rapidly under anaerobic conditions. The overall conclusion from BIOWIN is "not ready-biodegradable." Other ultimate degradation models (CATABOL and TOPKAT) did not produce any acceptable results, as the substance was out of their respective domain of applicability.

When the results of the probability models and the overall BIOWIN conclusion are considered, there is model consensus, suggesting that the biodegradation half-life of bromcresol purple in water is greater than 182 days.

Using an extrapolation ratio of 1:1 for a water: soil biodegradation half-life (Boethling et al. 1995), the biodegradation half-life in soil is also greater than 182 days. This indicates that bromcresol purple is expected to be persistent in soil.

Overall, the empirical data on dyes from ETAD (1992, 1995) as well as the modelled data (Table 4) demonstrate that bromcresol purple meets the persistence criteria in water and soil (half-lives greater than or equal to 182 days) as set out in the Persistence and Bioaccumulation Regulations (Canada 2000). This substance is not expected to be found in air or sediments.

There are no experimental bioaccumulation factor (BAF) or bioconcentration factor (BCF) data available for bromcresol purple or for a structural analogue. Since the experimental pK_aof bromcresol purple is 6.3-6.5 (Table 2), it is expected that this substance will exist mostly under its ionized form at environmentally relevant pH (6-9). The experimental log K_ow value for the ionized form of the analogue bromophenol blue is -3.07 (Table 2), indicating a low potential for bioaccumulation. It is recognized that the analogue log K_ow value may underestimate the partitioning of bromcresol purple since this substance will not be fully ionized at pH 6-7. However, its log K_ow is still expected to be low. Ionization was not considered during categorization with respect to bioaccumulation potential.

Since no experimental BAF or BCF data for bromcresol purple were available, a predictive approach was applied using available BAF and BCF models as shown in Table5 below. The experimental log K_ow value for the ionized form of the analogue bromophenol blue was used as input for the models. The modelled bioaccumulation values do not take into account the metabolic potential of the substance; therefore these bioaccumulation values may be over-estimated. However, as the predicted bioconcentration and bioaccumulation factors for bromcresol purple were low, this would not influence the bioaccumulation conclusion.

The modified Gobas BAF middle trophic-level model for fish predicted a BAF of less than 1L/kg, indicating that bromcresol purple has a low potential to bioconcentrate and biomagnify in the environment. Again, this is based on the log K_ow value for the analogue which is fully ionized at environmental pH. Even if the model underestimates the bioaccumulation potential of bromcresol purple when not completely ionized (e.g. pH 6-7), the BAF value would still be expected to be low.

The results of BCF model calculations provide additional evidence to support the low bioconcentration potential of this substance. The very low BCF value of 3.16 is a default value recommended by the BCFWIN model for compounds having a log K_ow less than 1; therefore, this result is not a model-generated BCF calculated specifically for bromcresol purple.

Top of Page

As mentioned earlier, bromcresol purple would tend to remain in water if it was released in this environmental compartment. In addition, it is expected to be persistent in this compartment. Therefore, this substance could be of concern for ecological effects in aquatic ecosystems.

Considering a pH range of 6 to 9 as being environmentally relevant, bromcresol purple will mostly be found under its ionized form in aquatic ecosystems. Given its expected high water solubility, aquatic organisms could be exposed. However, since it is believed to have low affinity for lipids (see Table 5), it should not accumulate to a significant extent in tissues of exposed organisms.

There are no acceptable experimental aquatic toxicity data available for bromcresol purple or for a structural analogue. Therefore, modelled data were used to estimate its potential for aquatic toxicity (Table 6). The ECOSAR model was run using the experimental analogue values shown in Table 2 for water solubility and log K_ow (ionized form). It was not possible to enter these values in the other models used (OASIS Forecast and AIEPS) as these models only accept chemical structure as input data. OASIS Forecast predicts a log K_ow value based on the structure entered (neutral form) and uses it to estimate toxicity. AIEPS is a probabilistic neural network based predictive model that uses structural fragments and presence or absence of atoms to determine similarity between the substance being modeled and those in the training set. It then calculates a prediction for three acute endpoints (fathead minnow, Daphnia magna and Pseudokirchneriella subcapitata).

The aquatic toxicity predictions obtained from the ECOSAR model are reliable to some extent. Indeed, both the log K_ow (analogue data) and molecular weight of bromcresol purple are covered by the domain of this model (cut-off of 7.0 for log K_ow and 1000g/mol for molecular weight). However, the closest analogues contained in the training set of ECOSAR are chlorophenols, suggesting that the values predicted for the toxicity of bromcresol purple are uncertain. Nevertheless, these modelled results suggest that bromcresol purple is not highly hazardous to aquatic organisms (acute LC/EC₅₀ greater than 1.0 mg/L), as observed for numerous substances having a very low log K_ow.

The result from the OASIS Forecast model suggests that bromcresol purple is highly hazardous (LC₅₀ less than or equal to 1.0 mg/L); however, this value is not considered reliable. Indeed, the discrepancy between this value and the ECOSAR predictions is partly due to the fact that a modelled log K_ow value for the neutral molecule is used by OASIS Forecast in calculations. As it can be seen in Table 2, this value is not representative of the partitioning behaviour of the ionized form of the molecule. In addition, the chemical structure of bromcresol purple is not well covered by the training set used by OASIS. Similarly, the AIEPS model did not provide reliable predictions as the similarity index indicated that most of chemicals in the training set were less than 60% similar to bromcresol purple.

Given the high persistence of bromcresol purple in the environment (see Table 4), chronic exposure is likely to occur. However, considering the likely low acute toxicity of this substance and its low bioaccumulation potential, its chronic aquatic toxicity is also expected to be low.

There are no environmental monitoring data available for this substance. Based on the submissions received in response to the CEPA section 71 notice (Environment Canada 2007), releases of bromcresol purple to the Canadian environment are believed to be very low. Accordingly, concentrations of this substance in environmental media are also expected to be very low.

Even though bromcresol purple does not meet the bioaccumulation potential criteria prescribed by the Persistence and Bioaccumulation Regulations (Canada 2000), it can persist in the environment and, depending on the level of exposure, could potentially cause harm to the environment. To investigate this, a quantitative evaluation of exposure associated with the release of this chemical to aquatic ecosystems was conducted.

Environmental concentrations were estimated from available information, including estimated substance quantities, potential release rates, and characteristics of possible receiving water bodies. Environment Canada's Industrial Generic Exposure Tool - Aquatic (IGETA) was employed to estimate the substance concentration in a generic watercourse receiving industrial effluents (Environment Canada 2008a). This tool represents a highly conservative scenario in which the substance is released by a single facility at a single point in a watercourse. The generic scenario is designed to provide estimates of concentrations based on conservative assumptions regarding the amount of chemical processed and released, the number of processing days, the sewage treatment plant removal rate, and the size of the receiving watercourse. The tool models an industrial-release scenario using loading data based on information from sources such as industrial surveys and knowledge of the distribution of industrial discharges across the country. It calculates a predicted environmental concentration (PEC) assuming instantaneous dilution in a small receiving water. The equation and inputs used to calculate the PEC in the receiving watercourse are described in Environment Canada (2008b). There were no reports of uses for this substance above the reporting threshold (1000kg) in response to the CEPA section 71 notice (Environment Canada 2007). The reporting threshold of 100kg for manufacture and import was used as a highly conservative estimate of the quantity of bromcresol purple released to sewers from an industrial facility. Other key parameter values were as follows: 261 processing days (working days only, based on expected uses), no removal at sewage treatment plants (worst-case scenario) and 0.65m³/s as the flow of the receiving watercourse (15th percentile of the distribution of receiving watercourse flows in the country). The resulting PEC was calculated to be 0.0064 mg/L.

The approach taken in this ecological screening assessment was to examine various supporting information and develop conclusions based on a weight-of-evidence approach and using precaution as required under CEPA 1999. Lines of evidence considered include results from a conservative risk quotient calculation, as well as information on persistence, bioaccumulation, inherent toxicity, sources and fate of the substance.

A risk quotient analysis, integrating conservative estimates of exposures with ecological effects information, was performed for the aquatic medium to determine whether there is potential for ecological harm in Canada. For this, a conservative predicted no-effect concentration (PNEC) was derived by selecting the lowest critical toxicity value (CTV) for aquatic organisms from the reliable model results (ECOSAR). In this case, the CTV was predicted to be above the water solubility limit of 4000 mg/L (see Table 6). This value was divided by an assessment factor of 1000 to account for uncertainties associated with interspecies and intraspecies variability in sensitivity, extrapolation from acute toxicity endpoints to chronic toxicity and use of modelled toxicity data to represent field conditions. This yielded a PNEC value of 4 mg/L. The PEC calculated with IGETA was then used together with the PNEC to calculate the risk quotient, i.e. PEC/PNEC = 0.0016.

Given that IGETA provides a conservative estimate of exposure and in view of the large assessment factor used to estimate chronic effect thresholds (PNECs), the results indicate a very low potential for ecological harm resulting from local exposure to a point-source industrial release of bromcresol purple to the aquatic environment.

In summary, the information gathered suggests that bromcresol purple would not be causing ecological harm if it were to be released into the Canadian environment. Information on importation, manufacture and use of bromcresol purple in Canada suggests very low releases of this chemical into the Canadian environment. Data collected for calendar years 1986, 2005 and 2006 do not indicate an increasing trend in usage.

If it was released into the environment, this substance would mainly be found in water and possibly in soil. It would persist in these environmental compartments but it would not bioaccumulate in organisms. This substance has low acute toxicity to aquatic organisms. A risk quotient analysis based on a highly conservative industrial scenario shows that aquatic organisms would not be at risk if they were exposed to bromcresol purple. The lack of toxicity data for terrestrial organisms prevented the calculation of risk quotients for the soil compartment. However, given the very low releases expected for this chemical, it is believed that it would not adversely affect terrestrial organisms.

Top of Page

Based on the information presented in this screening assessment, it is concluded that bromcresol purple is not 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 or that constitute or may constitute a danger to the environment on which life depends.

It is therefore concluded that bromcresol purple does not meet the definition of toxic as set out in section 64 of CEPA 1999. Additionally, bromcresol purple meets the criteria for persistence as set out in the Persistence and Bioaccumulation Regulations (Canada 2000) but does not meet the criteria for bioaccumulation potential as set out in the same regulations.

Top of Page

[ACD] Advanced Chemistry Development, Inc. 2005. ACD/pK_a DB. ACD/Labs Release 9.00. Product Version 9.0. Copyright 1994-2005. http://www.acdlabs.com/

[AIEPS] Artificial Intelligence Expert Predictive System. 2003-2007. Version 2.05. Ottawa (ON): Environment Canada, Existing Substances Division, New Substances Division. Model developed by Stephen Niculescu. Available from: Environment Canada, Existing Substances Division, New Substances Division.

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.

Aronson D, Boethling B, Howard P, W Stiteler W. 2006. Estimating biodegradation half-lives for use in chemical screening. Chemosphere 63: 1953-1960.

[BCFBAF] BioConcentration Factor Program for Windows [Estimation Model]. 2000. Version 3.00. Washington (DC): US Environmental Protection Agency, Office of Pollution Prevention and Toxics; Syracuse (NY): Syracuse Research Corporation. [cited 2008 May]. http://www.epa.gov/oppt/exposure/pubs/episuite.htm

[BIOWIN] Biodegradation Probability Program for Windows [Estimation Model]. 2000. Version 4.10. Washington (DC): US Environmental Protection Agency, Office of Pollution Prevention and Toxics; Syracuse (NY): Syracuse Research Corporation. [cited 2009 May]. http://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, part 5, s. 77. Canada Gazette. Part III. vol. 22, no. 3. http://canadagazette.gc.ca/partIII/1999/g3-02203.pdf

Canada. 2000. Canadian Environmental Protection Act: 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. http://canadagazette.gc.ca/partII/2000/20000329/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. http://canadagazette.gc.ca/partI/2006/20061209/pdf/g1-14049.pdf

Canada, Dept. of the Environment, Dept. of Health. 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. http://canadagazette.gc.ca/partI/2006/20060304/pdf/g1-14009.pdf

Canada, Dept. of the Environment, Dept. of Health. 2007. Canadian Environmental Protection Act, 1999: Notice of fourth release of technical information relevant to substances identified in the Challenge. Canada Gazette, Part I, vol. 141. no. 46, p. 3192-3197.

CATABOL. [Computer Model]. c2004-2008. Version 5.10.2. Bourgas (BG): Bourgas Prof. Assen Zlatarov University, Laboratory of Mathematical Chemistry. http://oasis-lmc.org/?section=software&swid=1

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.

[ECOSAR] Ecological Structural Activity Relationships [Internet]. 2004. Version 1.00. Washington (DC): US Environmental Protection Agency, Office of Pollution Prevention and Toxics; Syracuse (NY): Syracuse Research Corporation. [cited 2009 May]. http://www.epa.gov/oppt/exposure/pubs/episuite.htm

Environment Canada. 2003. Guidance Manual for the Ecological Categorization of Organic and Inorganic Substances on Canada's Domestic Substances List (DSL): determining persistence, bioaccumulation potential, and inherent toxicity to non-human organisms. Gatineau (QC): Environment Canada, Existing Substances Division. [released 2004 April on CD-ROM, entitled Existing Substances Program]. Available upon request from: Existing Substances Division, Environment Canada, Ottawa, K1A 0H3.

Environment Canada. 2007. Data for Batch 4 substances collected undertheCanadian Environmental Protection Act, 1999, Section71:Notice with respect to certain Batch 4 Challenge substances. Data prepared by: Environment Canada, Existing Substances Program.

Environment Canada. 2008a. Guidance for conducting ecological assessments under CEPA 1999, Science Resource Technical Series, Technical Guidance Module: The Industrial Generic Exposure Tool - Aquatic (IGETA), Working document, Gatineau (QC): Environment Canada, Existing Substances Division.

Environment Canada. 2008b. Industrial Generic Exposure Tool - Aquatic (IGETA) report (115-40-2 IGETA report 2008-05-29). Draft. Gatineau (QC): Environment Canada, Existing Substances Division.

ETAD (Ecological and Toxicological Association of Dyes and Organic Pigments Manufacturers). 1992. Draft Guidelines for the Assessment of Environmental Exposure to Dyestuffs.

ETAD (Ecological and Toxicological Association of Dyes and Organic Pigments Manufacturers). 1995. Health & Environmental Information on Dyes Used in Canada. An overview to assist in the implementation of the New Substances Notification Regulation under the Canadian Environmental Protection Act. Prepared by the ETAD Canadian Affiliates. July 1995. Report 7/21/95

Franco, I, Leita, L, Vischetti, C, de Nobili, M. 1999. Adsoprtion of five model organic compounds on a peat at different stages of drying. J. Soil Contamination 8(4): 423-440.

[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. [cited 2008 May]. http://www.epa.gov/oppt/exposure/pubs/episuite.htm

Kollig, HP 1988. Criteria for evaluating the reliability of literature data on environmental process constants. Toxicol. Environ. Chem. 17: 287-311.

[KOCWIN] Organic Carbon Partition Coefficient Program for Windows [Estimation Model]. 2000. Version 2.00. Washington (DC): US Environmental Protection Agency, Office of Pollution Prevention and Toxics; Syracuse (NY): Syracuse Research Corporation. [cited 2009 May]. http://www.epa.gov/oppt/exposure/pubs/episuite.htm

[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. [cited 2009 May]. http://www.epa.gov/oppt/exposure/pubs/episuite.htm

Kulichenko, SA, Fesenko, SA, Fesenko, NI. 2001. Color indicator system for acid-base titration in aqueous micellar solutions of the cationic surfactant tridecylpyridinium. J. Anal. Chem. 56(11): 1002-1006.

[MPBPWIN] Melting Point Boiling Point Program for Microsoft Windows [Estimation Model]. 2000. Version 1.43. Washington (DC): US Environmental Protection Agency, Office of Pollution Prevention and Toxics; Syracuse (NY): Syracuse Research Corporation. [cited 2009 May]. http://www.epa.gov/oppt/exposure/pubs/episuite.htm

[MSDS] Material Safety Data Sheet [Internet]. 2006. Solon (OH): MP Biomedicals, LCC (United States) Bromocresol purple, CAS RN 115-40-2. [cited 2008 Apr 30]. Restricted access. http://www.msdsonline.com/

[NCI] National Chemical Inventories [database on CD-ROM]. 2006. Columbus (OH): American Chemical Society. [cited 2008 May]. http://www.cas.org/products/cd/nci/index.html

[OASIS Forecast] Optimized Approach based on Structural Indices Set [Internet]. 2005. Version 1.20. Bourgas, Bulgaria: Laboratory of Mathematical Chemistry. [cited 2009 May]. http://oasis-lmc.org/?section=software

[OECD] Organisation for Economic Co-operation and Development. 1995. OECD Guideline for Testing of Chemicals. Test No. 107 Partition Coefficient (n-octanol/water): Shake Flask Method [Internet]. Guideline adopted 27 July 1995. Paris (FR): OECD, Environment Directorate. http://oberon.sourceoecd.org/vl=1533603/cl=13/nw=1/rpsv/ij/oecdjournals/1607310x/v1n1/s7/p1

[OECD] Organisation for Economic Co-operation and Development. 2000. OECD Guideline for Testing of Chemicals. Test No. 106 - Adsorption - Desorption Using a Batch Equilibrium Method [Internet]. Guideline adopted 21st January 2000. Paris (FR): OECD, Environment Directorate. http://oberon.sourceoecd.org/vl=1627150/cl=27/nw=1/rpsv/ij/oecdjournals/1607310x/v1n1/s6/p1

O'Neil, M.J. (ed.). 2001. The Merck Index - An encyclopaedia of chemicals, drugs, and biologicals. 13th Edition, Whitehouse Station, NJ. Merck and Co., Inc. p. 1447.

Pagga, U, Brown, D. 1986. The degradation of dyestuffs: Part II Behaviour of dyestuffs in aerobic biodegradation tests. Chemosphere, 15(4): 478-491.

pH-meter.Info [Internet]. c2005. Marki, Poland: ChemBuddy; [cited 2008 July 24]. Available from: http://www.ph-meter.info/pH-measurements-indicators

[PhysProp] Interactive PhysProp Database [database on the Internet]. 2006. Syracuse (NY): Syracuse Research Corporation. [cited 2008 May] http://www.syrres.com/esc/physdemo.htm

[TOPKAT] Toxicity Prediction Program [Internet]. 2004. Version 6.2. San Diego (CA): Accelrys Software Inc. [cited 2008 May]. http://www.accelrys.com/products/topkat/index.html

[US EPA] US Environmental Protection Agency. 2002. PBT Profiler Methodology [Internet]. Washington (DC): US EPA, Office of Pollution Prevention and Toxics. http://www.pbtprofiler.net/methodology.asp

[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. [cited 2009 May]. http://www.epa.gov/oppt/exposure/pubs/episuite.htm

Yao, W, Byrne, RH. 2001. Spectrophotometric determination of freshwater pH using bromocresol purple and phenol red. Environ. Sci. Thecnol. 35: 1197-1201.

Zeroual, Y, Kim, BS, Kim, CS, Blaghen, M, Lee, KM. 2006. Biosorption of bromophenol blue from aqueous solutions by Rhizopus stolonifer biomass. Water, Air, Soil Poll. 177: 135-146.

Top of Page

Reference: Franco I, Leita L, Vischetti C, de Nobili M. 1999. Adsorption of five model organic compounds on a peat at different stages of drying. J. Soil Contamination 8(4):423-440.

Test substance: CAS RN 115-39-9;Bromophenol blue.

Physical and chemical properties measured: pK_a, K_ow, K_oc.

• The sorbent material used in this batch equilibrium experiment was peat rather than soil. Since adsorption-desorption characteristics are usually useful for assessing the behaviour of a substance in soils, soil samples would have ideally been used in this experiment. Indeed, the sorptive capacity of peat is expected to be much higher than for soils, given its high organic carbon content. However, given that adsorption could be described by Freundlich isotherms (as indicated by the 1/n values in Table 3) and given that %OC for each sample was provided, the assessor was able to calculate K_oc values based on the K_fmeasured by the authors.
• The fact that the K_oc values for bromophenol blue were very low, even when dried peat was used (very high sorptive capacity), indicates that the hydrophobicity of bromophenol blue is very low.
• For the batch equilibrium experiment, the test substances should have been dissolved in 0.01 M CaCl₂ rather than distilled water in order to improve centrifugation and minimize cation exchange (OECD TG No 106; 2000).
• The optimal sorbent/solute ratio was determined in preliminary experiments.
• The pH of the aqueous phase before and/or after adsorption was not reported. This factor has an important influence on adsorption for ionizable substances. One of the study authors was contacted to clarify this aspect. The clarification is as follows: Batch equilibrium experiments were conducted in peat/water suspensions whose pH was that imposed by the buffering action of the peat's functional groups (pH = 4.5), as it actually happens in the field where xenobiotics are present at low concentration and the pH is imposed by the soil. To ensure that pH did not vary, the compounds were dissolved in distilled water and the pH of the solution was adjusted to that of a compound free suspension of peat in water. The adsorption isotherm therefore refers to a situation where the compound was for the most part ionized.
• Although the authors mention that they measured the water solubility of the test compounds, it does not seem that they measured it for bromophenol blue because they cite the value from O'Neil (2001) for this property (Table 2).
• The authors did not mention how they were able to measure a K_ow for both non-ionized and ionized forms of bromophenol blue (e.g., use of a buffer). Also, they did not mention the value of the pH of the aqueous phase during the measurements. The OECD TG 107 - Partition Coefficient (n-octanol/water): Shake Flask Method states that "Dissociation or association of the dissolved molecules results in deviations from the partition law (OECD TG 107; 1995). Such deviations are indicated by the fact that the partition coefficient becomes dependent upon the concentration. Measurements should be made on ionizable substances only in their non-ionized form (free acid or free base) produced by the use of an appropriate buffer with a pH of at least one unit below (free acid) or above (free base) the pK." One of the study authors was contacted to clarify this methodological aspect. The clarification is as follows: The K_ow of the non-ionized form of bromophenol blue was determined in an unbuffered water solution acidified to pH 1-1.5 with 0.020 mL of concentrated HCl, while the K_ow of the ionized form was determined in a solution made alkaline with a similar amount of 0.5 M NaOH. The study author who was contacted recognized that this is not a standard procedure. However, this person mentioned that measurements of K_ow in buffers could be misleading because of possible formation of ionic couples, intermolecular associations at high ionic strength, etc. This person also mentioned that the environmental behavior of substances such as bromophenol blue, which can be expected to be present in their ionized form in the environment, cannot be predicted on the basis of the K_ow of the non-ionized molecule.
• UV-Vis seems like an appropriate method to measure the concentration of the chemicals in this study given their absorption maximum and chemical structure (numerous double bonds).
• Because reference chemicals of known constant were not tested in this study, the Environment Canadaevaluator conducted a search for published data in order to validate (or not) the results measured in this study. Experimental data were found in the literature for bromophenol blue and for other substances tested in this study. They show that the values found in this study for water solubility, pK_a and K_ow are within the same order of magnitude as those published (see table below). No data were found to validate the K_oc values measured; however, there are sufficient methodological details provided in the paper and in the author's response to consider the value for the ionized form of bromophenol blue as reliable. In addition, although an actual K_oc value was not provided, a paper by Zeroual et al. 2006 indicated that bromophenol blue does not adsorb to organic matter (fungal biomass) at pH 6, i.e., when under an ionized form.

Reference: Kulichenko SA, Fesenko SA, Fesenko NI. 2001. Color indicator system for acid-base titration in aqueous micellar solutions of the cationic surfactant tridecylpyridinium. J. Anal. Chem. 56(11):1002-1006.

Test substance: CAS RN 115-39-9 (Bromophenol blue), CAS RN 115-40-2 (Bromcresol purple) and CAS RN 125-31-5 (Xylenol blue).

Physical and chemical properties measured: pK_a.

• The authors measured the pK_a of test substances in aqueous solutions. They also measured the so-called pK_eff for the same substances in aqueous micellar solutions containing the ionic surfactant tridecylpyridinium. The pK_a values for the aqueous solutions are the ones used for the risk assessment.
• Even though the CAS RNs were not provided to check the identity of the test substances, a verification in the NCI confirms that there is only one CAS RN associated with the names bromcresol purple and xylenol blue. For bromophenol blue, there is only one CAS RN associated with the non-salt form.
• A comparison between the pK_a values measured in this study with other published data for the same substances indicates that all data are similar. Therefore, the values from this study are considered reliable.
  • 6.49 for bromcresol purple (Yao and Byrne 2001)
    vs
    6.40 (this study)
  • 8.03 and 8.08 for phenol red (Yao and Byrne 2001, PhysProp 2006)
    vs
    8.00 (this study)
  • 7.0 for bromothymol blue (O'Neil 2001)
    vs
    7.30 (this study)

Reference: Yao W, Byrne RH. 2001. Spectrophotometric determination of freshwater pH using bromocresol purple and phenol red. Environ. Sci. Technol. 35:1197-1201.

Test substances: CAS RN 115-40-2 (Bromcresol purple).

Physical chemical property measured: pK_a.

Additional comments (by the Environment Canada evaluator):

• Even though the CAS RNs were not provided to check the identity of the test substances, a verification in the NCI confirms that there is only one CAS RN associated with the names bromcresol purple and phenol red. The salts of these substances were used in the experiment.
• A comparison between the pK_a values measured in this study with other published data for the same substances indicates that all data are similar. Therefore, the values from this study are considered reliable.
  • 6.40 for bromcresol purple (Kulichenko et al. 2001)
    vs
    6.49 (this study)
  • 8.00 and 8.08 for phenol red (Kulichenko et al. 2001, PhysProp 2006)
    vs
    8.03 (this study)