Ambient Water Quality Guidelines for Chlorophenols

Water Quality

Ambient Water Quality Guidelines for Chlorophenols

2. CHARACTERISTICS

2.1 Synonyms and Commercial Product Names

Table 2.1.1 gives the names of the chlorophenols as used in this report and as generally used by the Chemical Abstracting Service, CAS, the Registry of Toxic Effects of Chemical Substances, RTECS or the Ontario Municipal-Industrial Strategy for Abatement, MISA. Formulae and molecular weights are also given in this table. There are alternate naming protocols and many commercial product names for the various chlorophenols. One needs to be aware of these when searching the literature for data on specific active ingredients. Table 2.1.2 gives some of the alternate names by which chlorophenols may be found in the literature.

2.2 The Structure of Chlorophenols

There are 19 different chlorophenols, formed by replacing from one to five of the non-hydroxyl hydrogens of the phenol molecule with chlorine atoms. These include three monochlorophenols (MCPs), six dichlorophenols (DCPs), six trichlorophenols (TCPs), three tetrachlorophenols (TTCPs) and one pentachlorophenol (PCP). These compounds, and the parent phenol, are illustrated in Figure 2.2. Table 2.1.1 gives the names, formulae and molecular weights.

There are instances of confusion in the literature, mostly with TCPs and TTCPs, where the incorrect names or the wrong numbering systems are used. Different numbering systems are used which mask the identity of certain mirror image constructions resulting in the recognition of more distinct isomers, or congeners, than actually exist. Many of these incorrect numberings are listed in the synonym lists of section 2.1. For example, two literature sources give data for 2,4,5,6-TTCP which is identical to the properly named 2,3,4,6-TTCP. One reference lists ten DCPs and mentions that two other possible TTCP isomers are rarely mentioned in the literature. One must be aware that some good data may be reported under the wrong name due to carelessness or ignorance of organic chemistry naming protocols.

2.3 Properties and Effects of the Chlorophenols

Table 2.3 gives the CAS, MISA and RTECS registration numbers of the chlorophenols, whether or not they are in commercial use, and a number of physical characteristics which affect their environmental partitioning and biological effects. Only eight of the chlorophenol congeners are in commercial use, but all may be present as contaminants in many products, may be formed by chlorinating water or wastewater, or may result from the breakdown of higher chlorophenols in the environment.

All of the chlorophenols boil at temperatures well above the boiling point of water, most of them over 200C, or else they sublime. The melting points of all but four of the higher substituted congeners are below the boiling point of water. Vapor pressures are low, but not negligible, and tend to decrease as more chlorines are added. All specific gravities are greater than water and rise with increasing chlorine substitution to almost two in PCP. Only 2-MCP is a liquid at ambient temperatures, the others are generally needle-like crystalline solids. Solubility in water decreases with increasing chlorine substitution, as the Ko/w increases and the molecule becomes more hydrophobic. Due to their physical properties the chlorophenols will tend to accumulate in sediments.

Chlorophenols are weak acids; the dissociation constant generally increases with increasing chlorine substitution. The sodium and potassium salts are quite soluble at physiological temperatures and pH levels. PCP has an acid dissociation constant, pKa, of 4.8 and is largely dissociated at ambient levels of pH 7 to pH 8; thus most literature on Na-PCP is relevant for organisms in nature (7, 77, 258). The solubility of PCP is 14 mg/L at 20C, and of Na-PCP, 4 g/L at pH 8. At this pH, 99.9% of the PCP is dissociated and exists as Na-PCP in aqueous solutions (126). In alkaline solutions 2,4-DCP is very soluble (386, 442). Since the more hydrophobic undissociated chlorophenols can penetrate cell membranes and are more fat soluble than the dissociated forms, chlorophenols are more readily taken up by organisms, and are thus more toxic, at lower pH levels. The formulated products and oil-based solutions of chlorophenols are more toxic than aqueous solutions; they are also flammable. The chlorophenols do not actually burn, rather they decompose on heating to form toxic, volatile, chlorinated gases (199).

Chlorophenols are adsorbed very strongly by activated carbon at the µg/L level. Adsorption is a function of pH, and is affected by competition for adsorption sites by other chlorophenols and other organic compounds. Neutral species predominate below the pKa values and are adsorbed more strongly than anionic species. As the number of chlorine substituents increases, the solubility of the neutral species decreases and adsorption increases; however, as substitution increases, the pKa drops. In a mixture of chlorophenols, competition for adsorption sites will significantly reduce the adsorption of any congener over the value measured in an isolated test. At pH 5.2, fulvic acid from decomposing leaf litter out competes chlorophenols for adsorption sites, while humic and soil fulvic acids are about equal in adsorption competition with the chlorophenols. At pH 9.1, humic and leaf fulvic acids out compete 2,4,6-TCP for adsorption sites (472).

Temperature is not a critical factor in the toxicity of chlorophenols to homeotherms (warm-blooded animals), but is important in poikilotherms (cold-blooded animals), where respiration and metabolic rates are a function of ambient temperatures. Ionized chlorophenols are less lipophilic, and thus the uptake rates and toxicity are greater at low pH. Some chlorophenols, particularly PCP, ionize well below normal ambient pH; so animals generally make contact with ionized chlorophenols in aqueous solutions.

The half-life of most chlorophenols is quite short under most natural conditions: half lives range from days to weeks, or, on occasion months. Accumulation of high levels of chlorophenols in organisms, and the maintenance of such high levels is the result of constant input to the environment. If such input were to cease, the chlorophenol levels would be expected to drop quite quickly in sediments, water, and organisms. Bacteria break down chlorophenols by two different mechanisms: ring cleavage to yield aliphatics instead of aromatics, and dechlorination. Most of the data in the following descriptions of hazardous biological effects by chlorophenols are taken from CESARS (422). No data were found for the other chlorophenol congeners not discussed below.

2-MCP

The pure compound has an unpleasant and penetrating odor. It is a strong tissue irritant and is toxic by skin absorption, ingestion, or inhalation. When heated to decomposition, 2-MCP emits highly toxic fumes (445, 476).

3-MCP

The material is toxic when inhaled, ingested, or absorbed through the skin, and is strongly irritating to tissues. When heated to decomposition, 3-MCP emits highly toxic fumes (445, 526).

4-MCP

This chlorophenol is a strong tissue irritant and is toxic through skin absorption, ingestion or inhalation. The pure compound has an unpleasant, penetrating odor. When heated to decomposition, highly toxic fumes are emitted (426, 445).

2,4-DCP

There is a slight fire hazard with 2,4-DCP; it reacts strongly with oxidizing agents and also gives off hazardous fumes when heated or in contact with strong acids. The compound is a strong eye and tissue irritant, and inhaled dust irritates the respiratory tract. It is toxic if ingested and is readily absorbed through the skin in toxic amounts. Chloracne and porphyria have been reported in manufacturing personnel (315, 426, 442, 445).

2,4,5-TCP

This material is non-flammable and no serious health hazard occurs with normal industrial use. Ingesting large amounts would be harmful, and copious quantities of dust or fumes will irritate eye and nose membranes causing iritis, conjunctivitis, and corneal injury. Skin irritations, redness, and edema may occur, but there is no danger of poisoning by skin absorption. Prolonged skin contact may result in mild to moderate chemical burns (313, 445).

2,4,6-TCP

This material is non-flammable, but heating the salt to 280 C produces a number of dibenzo-p-dioxins in the 0.1 to 0.3 mg/kg range. Dusts cause eye, nose and pharynx irritation and may injure the cornea. The compound is readily absorbed through the skin and causes irritation ranging from redness and edema to chemical burns (445, 476).

2,3,4,5-TTCP and 2,3,5,6-TTCP

When heated to decomposition, these chlorophenols emit toxic chlorine gas fumes (426).

2,3,4,6-TTCP

The pure material has a pungent odor and is a strong skin irritant. It is non-flammable (445).

PCP

The pure material has a strong, pungent smell. It is non-flammable but generates toxic and irritating vapors when heated. Vapors and dusts irritate skin and mucous membranes. The vapors given off include CO, HCl and chlorinated phenols (483, 527).

2.4 QSAR Analyses of the Relative Toxicities of the Chlorophenols

Quantitative Structure-Activity Relationship Analyses of the results of an experiment testing some of the congeners or isomers in a series of related compounds, can often determine which active groups of the compounds have the most effect on the test organisms, and permit predictions of the toxicities of the remaining congeners or isomers. Table 2.4 and Figure 2.4 give the results of an experiment by Devillers et al. (57). The 24-h IC₅₀ values of 17 of the chlorophenols were determined for Daphnia magna. The ratios of the 24-h IC₅₀ of each congener relative to PCP were calculated and have been added to the table.

Figure 2.2 shows the substitution sites on the phenol molecule and their identification numbers; 2 and 6 are "ortho" sites, 3 and 5 are "meta" sites and 4 is the "para" site. Some observations and predictions can be made from the data in Table 2.4. These are depicted graphically in Figure 2.4 and discussed below.

All the substitution sites on the phenol molecule are not equal in their effect on toxicity to organisms. As discussed in section 4.2.1, the location of the chlorines affects the efficiency of microbial breakdown of chlorophenols. Meta-substituted or 3,5- compounds, are more resistant to microbial degradation than are ortho- substituted or 2,6- compounds. Of the monochlorophenols (MCPs) 4-MCP is much more toxic than either 2-MCP or 3-MCP. Within any isomeric group of congeners, those with a chlorine in the 4, or para position, are more toxic than the others. In addition, if chlorines are substituted at both the 3 and 5, or meta positions, toxicity is high. If both the meta and the para substitutions are made in the same molecule, toxicity is also high, as shown by 3,4,5-TCP.

Toxicity is reduced by simultaneous 2 and 6, or ortho substitutions. Such substitutions can reduce toxicities that might be expected from previous arguments about 3, 4, and 5 substitutions. The relatively low toxicity of 2,6-DCP compared to 3,5-DCP, and the lower toxicity of 2,4,6-TCP than would be expected from a para or 4 substitution are examples of reduced toxicity due to ortho substitutions. This trend is very evident in the data of Saito et al. (701); even better correlations are obtained if these ortho compounds are omitted from the correlation analyses. Since there is increasing toxicity as more chlorines are added, one would expect PCP to be much more toxic than 3,4,5-TCP; however, since the two extra chlorines are in the 2 and 6 positions, little of the expected extra toxicity is seen. Similar arguments are used by Liu et al. (691) on studies with bacteria.

The relatively low toxicity of the ortho substituted compounds 2-MCP, 2,6-DCP and 2,4,6-TCP has been confirmed by a number of in vivo experiments. Shigeoka et al. (702) used killifish, Daphnia, algae and activated sludge microorganisms; Kobayashi et al. (273) used goldfish; Saarikoski et al. (144) used guppies; Nendza et al. (703) used Escherichia coli; Ribo et al. ( 367) used bacteria; and Babich et al. (704) used BF-2 cells.

An experiment by Saito et al. (701) on the uptake of neutral red dye by GF-Scale cells, a fibroblastic cell line derived from goldfish scale cells, is also a good source of comparative QSAR data. In this experiment 15 of the chlorophenols were tested and a good table of physicochemical properties of the chlorophenols is given. This data set is not as complete as that of Devillers and Chambon (57), and it ranks the chlorophenols on uptake of a non toxic dye rather than on toxicity. The order of relative uptake in the Saito (701) experiment correlates well (r = 0.965) with pKa and log Ko/w (measures of ionization and lipophilicity, respectively, which together predict uptake) but not necessarily with functional toxicity. Uptake and toxicity are not necessarily the same.

Using these arguments one would expect the toxicity of 2,3,4,6-TTCP, which was not tested by Devillers and Chambon (57), to be less than that of the other TTCPs, though perhaps slightly more toxic than 3,4-DCP. An estimated 24-h IC₅₀ mean value for their experiment is about 2.70 mg/L with a congener to PCP ratio of 3.55. Similarly, the toxicity of 2,5-DCP is expected to be greater than that of 2,6-DCP, less than that of 3,5- or 2,4-DCP, and more toxic than 2,3-DCP. The estimated value for a 24-h IC50 mean value in their experiment is about 4.5 mg/L or a congener to PCP ratio of 5.92. See Table 2.4.

Since, for most species, there are generally abundant data on the effects of PCP, but few on the effects of other congeners, the ratios of the toxicities as calculated in Table 2.4, and inherent in the equations of reference 144, could be applied to the best PCP data to determine guidelines for the other congeners. This approach was tried and works well, but one can not apply pH corrections to the resulting guidelines. The guidelines resulting from this process are, however, comparable to those derived from a set of pH dependent equations based on fish toxicity studies, when the pH dependent guidelines are corrected to the same pH and temperature.

2.5 Summary of the Characteristics of the Chlorophenols

Table 2.1 gives the official names of the chlorophenols as used by CAS and in this report; formulae and molecular weights are also given. Table 2.1.2 gives alternate names for the chlorophenols, some based on illegitimate numbering of the substituted chlorines. There are three MCPs, six DCPs, six TCPs, three TTCPs and one PCP; these are all illustrated in Figure 2.2. Table 2.3 gives many physical characteristics of the chlorophenols which affect their biological action or environmental partitioning. Eight chlorophenols are in commercial use and the rest may be produced incidentally when organic material is chlorinated.

Chlorophenols are weak acids and some are fully dissociated at ambient pH levels and are thus available as the salt. Since for most organisms there are generally abundant data on the effects of PCP but few on the effects of other congeners, the ratios of the toxicities, as given in Table 2.4, can be applied to the best PCP data to determine guidelines for the other congeners; such guidelines can not, however, be readily adjusted for other pH levels. Temperature is an important variable for chlorophenol toxicity to poikilotherms where respiration and metabolism rates are functions of the ambient temperature, but is not important for homeotherms. Chlorophenols are notorious for causing taste and odor problems in water at levels below toxicity. The half-life of most chlorophenols in nature is short, rarely as long as months, so, once input to the environment stops, levels will drop rapidly. Bacterial breakdown proceeds by both ring cleavage and dechlorination, the former process occurring first and most readily.


	Water Quality Ambient Water Quality Guidelines for Chlorophenols 2. CHARACTERISTICS 2.1 Synonyms and Commercial Product Names Table 2.1.1 gives the names of the chlorophenols as used in this report and as generally used by the Chemical Abstracting Service, CAS, the Registry of Toxic Effects of Chemical Substances, RTECS or the Ontario Municipal-Industrial Strategy for Abatement, MISA. Formulae and molecular weights are also given in this table. There are alternate naming protocols and many commercial product names for the various chlorophenols. One needs to be aware of these when searching the literature for data on specific active ingredients. Table 2.1.2 gives some of the alternate names by which chlorophenols may be found in the literature. 2.2 The Structure of Chlorophenols There are 19 different chlorophenols, formed by replacing from one to five of the non-hydroxyl hydrogens of the phenol molecule with chlorine atoms. These include three monochlorophenols (MCPs), six dichlorophenols (DCPs), six trichlorophenols (TCPs), three tetrachlorophenols (TTCPs) and one pentachlorophenol (PCP). These compounds, and the parent phenol, are illustrated in Figure 2.2. Table 2.1.1 gives the names, formulae and molecular weights. There are instances of confusion in the literature, mostly with TCPs and TTCPs, where the incorrect names or the wrong numbering systems are used. Different numbering systems are used which mask the identity of certain mirror image constructions resulting in the recognition of more distinct isomers, or congeners, than actually exist. Many of these incorrect numberings are listed in the synonym lists of section 2.1. For example, two literature sources give data for 2,4,5,6-TTCP which is identical to the properly named 2,3,4,6-TTCP. One reference lists ten DCPs and mentions that two other possible TTCP isomers are rarely mentioned in the literature. One must be aware that some good data may be reported under the wrong name due to carelessness or ignorance of organic chemistry naming protocols. 2.3 Properties and Effects of the Chlorophenols Table 2.3 gives the CAS, MISA and RTECS registration numbers of the chlorophenols, whether or not they are in commercial use, and a number of physical characteristics which affect their environmental partitioning and biological effects. Only eight of the chlorophenol congeners are in commercial use, but all may be present as contaminants in many products, may be formed by chlorinating water or wastewater, or may result from the breakdown of higher chlorophenols in the environment. All of the chlorophenols boil at temperatures well above the boiling point of water, most of them over 200C, or else they sublime. The melting points of all but four of the higher substituted congeners are below the boiling point of water. Vapor pressures are low, but not negligible, and tend to decrease as more chlorines are added. All specific gravities are greater than water and rise with increasing chlorine substitution to almost two in PCP. Only 2-MCP is a liquid at ambient temperatures, the others are generally needle-like crystalline solids. Solubility in water decreases with increasing chlorine substitution, as the Ko/w increases and the molecule becomes more hydrophobic. Due to their physical properties the chlorophenols will tend to accumulate in sediments. Chlorophenols are weak acids; the dissociation constant generally increases with increasing chlorine substitution. The sodium and potassium salts are quite soluble at physiological temperatures and pH levels. PCP has an acid dissociation constant, pKa, of 4.8 and is largely dissociated at ambient levels of pH 7 to pH 8; thus most literature on Na-PCP is relevant for organisms in nature (7, 77, 258). The solubility of PCP is 14 mg/L at 20C, and of Na-PCP, 4 g/L at pH 8. At this pH, 99.9% of the PCP is dissociated and exists as Na-PCP in aqueous solutions (126). In alkaline solutions 2,4-DCP is very soluble (386, 442). Since the more hydrophobic undissociated chlorophenols can penetrate cell membranes and are more fat soluble than the dissociated forms, chlorophenols are more readily taken up by organisms, and are thus more toxic, at lower pH levels. The formulated products and oil-based solutions of chlorophenols are more toxic than aqueous solutions; they are also flammable. The chlorophenols do not actually burn, rather they decompose on heating to form toxic, volatile, chlorinated gases (199). Chlorophenols are adsorbed very strongly by activated carbon at the µg/L level. Adsorption is a function of pH, and is affected by competition for adsorption sites by other chlorophenols and other organic compounds. Neutral species predominate below the pKa values and are adsorbed more strongly than anionic species. As the number of chlorine substituents increases, the solubility of the neutral species decreases and adsorption increases; however, as substitution increases, the pKa drops. In a mixture of chlorophenols, competition for adsorption sites will significantly reduce the adsorption of any congener over the value measured in an isolated test. At pH 5.2, fulvic acid from decomposing leaf litter out competes chlorophenols for adsorption sites, while humic and soil fulvic acids are about equal in adsorption competition with the chlorophenols. At pH 9.1, humic and leaf fulvic acids out compete 2,4,6-TCP for adsorption sites (472). Temperature is not a critical factor in the toxicity of chlorophenols to homeotherms (warm-blooded animals), but is important in poikilotherms (cold-blooded animals), where respiration and metabolic rates are a function of ambient temperatures. Ionized chlorophenols are less lipophilic, and thus the uptake rates and toxicity are greater at low pH. Some chlorophenols, particularly PCP, ionize well below normal ambient pH; so animals generally make contact with ionized chlorophenols in aqueous solutions. The half-life of most chlorophenols is quite short under most natural conditions: half lives range from days to weeks, or, on occasion months. Accumulation of high levels of chlorophenols in organisms, and the maintenance of such high levels is the result of constant input to the environment. If such input were to cease, the chlorophenol levels would be expected to drop quite quickly in sediments, water, and organisms. Bacteria break down chlorophenols by two different mechanisms: ring cleavage to yield aliphatics instead of aromatics, and dechlorination. Most of the data in the following descriptions of hazardous biological effects by chlorophenols are taken from CESARS (422). No data were found for the other chlorophenol congeners not discussed below. 2-MCP The pure compound has an unpleasant and penetrating odor. It is a strong tissue irritant and is toxic by skin absorption, ingestion, or inhalation. When heated to decomposition, 2-MCP emits highly toxic fumes (445, 476). 3-MCP The material is toxic when inhaled, ingested, or absorbed through the skin, and is strongly irritating to tissues. When heated to decomposition, 3-MCP emits highly toxic fumes (445, 526). 4-MCP This chlorophenol is a strong tissue irritant and is toxic through skin absorption, ingestion or inhalation. The pure compound has an unpleasant, penetrating odor. When heated to decomposition, highly toxic fumes are emitted (426, 445). 2,4-DCP There is a slight fire hazard with 2,4-DCP; it reacts strongly with oxidizing agents and also gives off hazardous fumes when heated or in contact with strong acids. The compound is a strong eye and tissue irritant, and inhaled dust irritates the respiratory tract. It is toxic if ingested and is readily absorbed through the skin in toxic amounts. Chloracne and porphyria have been reported in manufacturing personnel (315, 426, 442, 445). 2,4,5-TCP This material is non-flammable and no serious health hazard occurs with normal industrial use. Ingesting large amounts would be harmful, and copious quantities of dust or fumes will irritate eye and nose membranes causing iritis, conjunctivitis, and corneal injury. Skin irritations, redness, and edema may occur, but there is no danger of poisoning by skin absorption. Prolonged skin contact may result in mild to moderate chemical burns (313, 445). 2,4,6-TCP This material is non-flammable, but heating the salt to 280 C produces a number of dibenzo-p-dioxins in the 0.1 to 0.3 mg/kg range. Dusts cause eye, nose and pharynx irritation and may injure the cornea. The compound is readily absorbed through the skin and causes irritation ranging from redness and edema to chemical burns (445, 476). 2,3,4,5-TTCP and 2,3,5,6-TTCP When heated to decomposition, these chlorophenols emit toxic chlorine gas fumes (426). 2,3,4,6-TTCP The pure material has a pungent odor and is a strong skin irritant. It is non-flammable (445). PCP The pure material has a strong, pungent smell. It is non-flammable but generates toxic and irritating vapors when heated. Vapors and dusts irritate skin and mucous membranes. The vapors given off include CO, HCl and chlorinated phenols (483, 527). 2.4 QSAR Analyses of the Relative Toxicities of the Chlorophenols Quantitative Structure-Activity Relationship Analyses of the results of an experiment testing some of the congeners or isomers in a series of related compounds, can often determine which active groups of the compounds have the most effect on the test organisms, and permit predictions of the toxicities of the remaining congeners or isomers. Table 2.4 and Figure 2.4 give the results of an experiment by Devillers et al. (57). The 24-h IC₅₀ values of 17 of the chlorophenols were determined for Daphnia magna. The ratios of the 24-h IC₅₀ of each congener relative to PCP were calculated and have been added to the table. Figure 2.2 shows the substitution sites on the phenol molecule and their identification numbers; 2 and 6 are "ortho" sites, 3 and 5 are "meta" sites and 4 is the "para" site. Some observations and predictions can be made from the data in Table 2.4. These are depicted graphically in Figure 2.4 and discussed below. All the substitution sites on the phenol molecule are not equal in their effect on toxicity to organisms. As discussed in section 4.2.1, the location of the chlorines affects the efficiency of microbial breakdown of chlorophenols. Meta-substituted or 3,5- compounds, are more resistant to microbial degradation than are ortho- substituted or 2,6- compounds. Of the monochlorophenols (MCPs) 4-MCP is much more toxic than either 2-MCP or 3-MCP. Within any isomeric group of congeners, those with a chlorine in the 4, or para position, are more toxic than the others. In addition, if chlorines are substituted at both the 3 and 5, or meta positions, toxicity is high. If both the meta and the para substitutions are made in the same molecule, toxicity is also high, as shown by 3,4,5-TCP. Toxicity is reduced by simultaneous 2 and 6, or ortho substitutions. Such substitutions can reduce toxicities that might be expected from previous arguments about 3, 4, and 5 substitutions. The relatively low toxicity of 2,6-DCP compared to 3,5-DCP, and the lower toxicity of 2,4,6-TCP than would be expected from a para or 4 substitution are examples of reduced toxicity due to ortho substitutions. This trend is very evident in the data of Saito et al. (701); even better correlations are obtained if these ortho compounds are omitted from the correlation analyses. Since there is increasing toxicity as more chlorines are added, one would expect PCP to be much more toxic than 3,4,5-TCP; however, since the two extra chlorines are in the 2 and 6 positions, little of the expected extra toxicity is seen. Similar arguments are used by Liu et al. (691) on studies with bacteria. The relatively low toxicity of the ortho substituted compounds 2-MCP, 2,6-DCP and 2,4,6-TCP has been confirmed by a number of in vivo experiments. Shigeoka et al. (702) used killifish, Daphnia, algae and activated sludge microorganisms; Kobayashi et al. (273) used goldfish; Saarikoski et al. (144) used guppies; Nendza et al. (703) used Escherichia coli; Ribo et al. ( 367) used bacteria; and Babich et al. (704) used BF-2 cells. An experiment by Saito et al. (701) on the uptake of neutral red dye by GF-Scale cells, a fibroblastic cell line derived from goldfish scale cells, is also a good source of comparative QSAR data. In this experiment 15 of the chlorophenols were tested and a good table of physicochemical properties of the chlorophenols is given. This data set is not as complete as that of Devillers and Chambon (57), and it ranks the chlorophenols on uptake of a non toxic dye rather than on toxicity. The order of relative uptake in the Saito (701) experiment correlates well (r = 0.965) with pKa and log Ko/w (measures of ionization and lipophilicity, respectively, which together predict uptake) but not necessarily with functional toxicity. Uptake and toxicity are not necessarily the same. Using these arguments one would expect the toxicity of 2,3,4,6-TTCP, which was not tested by Devillers and Chambon (57), to be less than that of the other TTCPs, though perhaps slightly more toxic than 3,4-DCP. An estimated 24-h IC₅₀ mean value for their experiment is about 2.70 mg/L with a congener to PCP ratio of 3.55. Similarly, the toxicity of 2,5-DCP is expected to be greater than that of 2,6-DCP, less than that of 3,5- or 2,4-DCP, and more toxic than 2,3-DCP. The estimated value for a 24-h IC50 mean value in their experiment is about 4.5 mg/L or a congener to PCP ratio of 5.92. See Table 2.4. Since, for most species, there are generally abundant data on the effects of PCP, but few on the effects of other congeners, the ratios of the toxicities as calculated in Table 2.4, and inherent in the equations of reference 144, could be applied to the best PCP data to determine guidelines for the other congeners. This approach was tried and works well, but one can not apply pH corrections to the resulting guidelines. The guidelines resulting from this process are, however, comparable to those derived from a set of pH dependent equations based on fish toxicity studies, when the pH dependent guidelines are corrected to the same pH and temperature. 2.5 Summary of the Characteristics of the Chlorophenols Table 2.1 gives the official names of the chlorophenols as used by CAS and in this report; formulae and molecular weights are also given. Table 2.1.2 gives alternate names for the chlorophenols, some based on illegitimate numbering of the substituted chlorines. There are three MCPs, six DCPs, six TCPs, three TTCPs and one PCP; these are all illustrated in Figure 2.2. Table 2.3 gives many physical characteristics of the chlorophenols which affect their biological action or environmental partitioning. Eight chlorophenols are in commercial use and the rest may be produced incidentally when organic material is chlorinated. Chlorophenols are weak acids and some are fully dissociated at ambient pH levels and are thus available as the salt. Since for most organisms there are generally abundant data on the effects of PCP but few on the effects of other congeners, the ratios of the toxicities, as given in Table 2.4, can be applied to the best PCP data to determine guidelines for the other congeners; such guidelines can not, however, be readily adjusted for other pH levels. Temperature is an important variable for chlorophenol toxicity to poikilotherms where respiration and metabolism rates are functions of the ambient temperature, but is not important for homeotherms. Chlorophenols are notorious for causing taste and odor problems in water at levels below toxicity. The half-life of most chlorophenols in nature is short, rarely as long as months, so, once input to the environment stops, levels will drop rapidly. Bacterial breakdown proceeds by both ring cleavage and dechlorination, the former process occurring first and most readily.