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Water Quality Ambient Water Quality Guidelines for Chlorophenols 7. TERRESTRIAL LIFE Data on non-mammalian, non-aquatic animals is virtually non-existent. Chlorophenols prevent the transfer of non-persistent viruses by repelling the aphid vector (474). PCP in the blood is bound to protein which reduces tissue plasma ratios, but slows the clearance rate by the kidneys (277). Once absorbed, PCP is distributed throughout the body and accumulates in the liver, kidneys, brain, fat and spleen (407, 408, 409, 199). Most reported exposures to PCP are to technical grade material which is contaminated with dioxins and many other compounds (Section 3.3) and the reported effects of PCP may be wholly or partly attributable to these contaminants. As PCP concentrations increase, effects progress from sweating to thirst, fever, rapid pulse and finally to respiratory and cardiac arrest (225). Other effects include systemic effects in the kidney and liver (227), chloracne in rabbits, kidney and liver damage in animals (225, 161), lung damage (161), increased blood pressure, nausea, increased respiration rates, bleeding, hyperglycemia, weak eye-reflex and motor activity, glycosuria, lung congestion, convulsions, vascular system damage, eye irritations, histological changes in liver, kidneys, spleen and skin, skin irritation, respiratory disorders, neurological changes, headaches, weakness, drowsiness, irritability, hyperpyrexia and coma, mucous membrane irritation, reduced organ weights and altered organ functions, and death in severe cases. Growth rates are reduced (289, 294, 312, 313, 314, 315, 199).
Table 7.1 gives the levels of some commercial chlorophenol preparations necessary to control fungi and bacteria which cause problems in the pulp and paper industry (658). These are quite resistant organisms and the levels of active ingredients required for complete control are well into the mg/L range; this is in contrast to the levels at which fish are affected which are in the µg/L range. This illustrates the potential toxicity of pulp and paper wastes in aquatic habitats.
Table 7.1 gives the levels of some commercial preparations of chlorophenols needed to inhibit two fungi common in the pulp and paper industry, Aspergillis niger and Penicillium expansum (658). Table 7.1.1 gives some EC50 and EC100 values for growth effects on various fungi by a number of chlorophenols. Fungi are quite resistant and mg/L levels are required for control. Sapstain fungi in unseasoned wood include Trichoderma virgatum and Penicillium sp. which are controlled by 0.46% v/v of TTCP and Aureobasidium controlled by 0.92% v/v of TTCP. PCP controls Trichoderma harzianum at 0.25% v/v and Phialophora sp. at 0.125% v/v. Neither PCP nor TTCP are effective against the brown mold, Cephalosus fragrans, when used at commercial rates. It requires 1.84% v/v of TTCP and 1.0% v/v PCP for control (657). 4-MCP; 2,4-DCP; 2,4,6-TCP; 2,3,4,6-TTCP Tests were carried out with the fungus Trichoderma viride at 25C for 40 hours, to determine the EC50 for control of growth (381). The results were 47.6 mg/L, 8.6 mg/L, 6.9 mg/L, and 0.8 mg/L for 4-MCP, 2,4-DCP, 2,4,6-TCP and 2,3,4,6-TTCP, respectively. As is evident from these results, increasing the number of chlorines increases the toxicity and the degree of growth suppression. 2,3,4-TCP; 2,3,5-TCP; 2,3,4,5-TTCP; 2,3,4,6-TTCP; 2,3,5,6-TTCP Tests with 16 fungal species were carried out to determine what concentration would completely inhibit growth on agar. For 2,3,4-TCP the range was 5.9 to 24.7 mg/L, for 2,3,5-TCP it was 2.96 to 11.8 mg/L, for 2,3,4,5-TTCP the range was 1.74 to 13.9 mg/L, for 2,3,4,6-TTCP it was 6.96 to 23.2 mg/L, and for 2,3,5,6-TTCP the range was 29 to 464 mg/L (432). 2,3,5-TCP When Aspergillis niger mycelia were incubated at 22C on agar plates containing 25 mg/L of 2,3,5-TCP, growth was suppressed (431). 2,3,4,5-TTCP; 2,3,4,6-TTCP; 2,3,5,6-TTCP Five fungi were tested to determine the concentrations of TTCPs which completely inhibited growth. For the five species, grown at 20C for 7 days, Candida albicans, Aspergillis fumigatus, Trichophyton rubrum, Trichophyton mentagrophytes and Microsporon canis, the lowest EC100, in mg/L of medium was, respectively: 23.2, 6.96, 23.2, 2.32 and 0.696 for 2,3,4,5-TTCP; PCP The metabolism of glucose by the citric acid (Kreb) cycle in Aspergillis niger, is blocked by 1.3 mg/L PCP. Direct oxidation occurs and no ATP formation results (569).
Table 7.1 gives the levels of some commercial preparations of chlorophenols needed to inhibit two bacteria common in the pulp and paper industry, Bacillus mycoides and Aerobacter aerogenes (658). Table 7.1.2 gives the effects of chlorophenols on bacteria, including the microtox assay using Photobacterium phosphoreum. The EC50 values determined for some natural water sources correlated positively with the humic concentration of the water (435) when a Microtox assay was conducted. The microtox assay is relatively sensitive for a bacterial test compared to the more robust sewage culture bacteria. The major difference is likely that the sewage bacteria have been acclimated to chlorophenols for some time and populations relatively efficient at breaking down chlorophenols have been established. In any case, sensitivity levels are still lower than those of more responsive organisms like fish and amphibians. Bacteria are part of the solution to organic pollution problems since they actively break down most compounds. Due to the short life cycle, rapid growth, and very effective gene transfer mechanisms in bacteria, adaptations of populations occur quite quickly in long-term experiments. Also, if previously exposed cultures are re-used in subsequent tests, the EC50 values will get progressively higher with time. Consequently, tests done on bacterial mixtures like sewage sludges will give quite variable results, which are not likely to be reproducible. For most of the different standard bacterial assay tests which have been developed, there is at least one order-of-magnitude greater toxicity to chlorinated phenols than to the parent phenol. As indicated in Section 5.8.1 increasing chlorination tends to produce higher toxicity. 2,4-DCP The growth of pseudomonads in the presence of 2,4-DCP at 25 and pH 7.1 to pH 7.8 was strongly inhibited above 25 mg/L. The log phase of growth is dependent upon both concentration and prior adaptation of the culture (511). The TTC dehydrogenase method for determining bacterial toxicity, using activated sludge as the bacterial source, indicated a sensitivity level of 50 mg/L and an EC50 of 500 mg/L for 2,4-DCP (512). 2,4,6-TCP In strain 018 of Bacillus
subtilis, 2,4,6-TCP inhibited proline
and glycine transport mechanisms (468). The bacteria in dairy cultures responsible for yogurt, kefir, butter and cheese are inhibited at 100 mg/L of either 2,4,5-TCP or PCP (486). 2,3,4,5-TTCP Pseudomonas fluorescens suspensions were treated with 2,3,4,5-TTCP and PCP in two sets of tests. In the first test series, the cells were first exposed to 0, 10, 25 or 35 mg/L of 2,3,4,5-TTCP, then subsequently exposed to 0 or 5 mg/L of 2,3,4,5-TTCP, or 5 mg/L of PCP, after a recovery period during which the initial dose was removed. The second test series began with 10 mg/L of PCP as the initial dose, followed by 1, 5 and 10 mg/L of 2,3,4,5-TTCP. When the first and second doses were both 2,3,4,5-TTCP, no mortality occurred either with an initial dose of 10 mg/L, or a subsequent 5 mg/L dose of 2,3,4,5-TTCP. An initial dose of 25 mg/L caused 86.6% death and the subsequent 5 mg/L dose, 64.2% death. An initial dose of 35 mg/L caused 99.9% mortality, and the subsequent 5 mg/L dose, 55.7% death. When the first dose was 2,3,4,5-TTCP and second dose PCP, the initial doses of 10, 25 and 35 mg/L caused 0%, 87.2% and 99.4% mortality; subsequent PCP doses of 5 mg/L caused 96.4% to 99.9% deaths. Cells first treated with PCP at 1 mg/L and then 2,3,4,5-TTCP at 5 or 10 mg/L, had mortalities of 17.7% and 32.1% respectively (519). It is presumed that first exposing the cells to 2,3,4,5-TTCP sensitizes them to further chlorophenol exposures. A concentration of 10 mg/L of 2,3,4,5-TTCP is a no-effect level and the LC50 is between 10 and 25 mg/L PCP In in-vitro assays, Pseudomonas fluorescens was less sensitive to PCP at 20C and more sensitive at 4C or 30C. Cells were most sensitive at maximum stationary phase (8.6 mg/L), less sensitive at early log phase of growth (18 mg/L) and least sensitive at mid log phase (29 mg/L). After 1-hour exposures, mortality reached 100% at 70 mg/L; there was no mortality at 10 mg/L. No further mortalities occurred after a 16-hour recovery period (557). The light output of luminescent bacteria exposed to PCP for 2 to 5 minutes decreased in proportion to the PCP dose. Sensitivity was measured at 5 µg/L (585). The uptake of proline and glycine by Bacillus subtilis is inhibited by as little as 1.3 mg/L of PCP (568).
There are no data documenting the effects of chlorophenols in irrigation water on the growth of crops or other terrestrial plant life. Since plants share the same mitochondrial terminal oxidation system with other eukaryotic life, one would expect similar reactions at similar concentrations of chlorophenols delivered to the mitochondria. Under normal aerobic, non-flooded soil conditions, chlorophenols would be in the ionized salt form, poorly dissolved in water, and strongly bound to soil particles, especially organics. Irrigation water, which is otherwise suitable for human consumption or which supports aquatic life, should be quite acceptable for crop irrigation. The effects of chlorophenols in water on seed germination in radishes, Raphanus sativus, and sudan grass, Sorghum sudanense, are shown in Table 7.2 (651). Radish is somewhat more sensitive to most chlorophenols than sorghum, but both plants are far less sensitive than fish and amphibians. Due to a lack of data, no guidelines are set for chlorophenols in irrigation water, but levels below the 100 µg/L range are not expected to have any noticeable effect on most crops. 2-MCP Tomato plants convert 2-MCP to the glycoside, Beta-0-chlorophenyl-gentiobiocide, which is isolated from the roots but not the shoots (364). 4-MCP When the roots of the broad bean, Vicia faba, are exposed to 250 mg/L of 4-MCP, mitosis is affected with lagging chromosomes, stickiness, fragmentation, cytomixis, and general disturbance of mitotic stages (448). 2,4-DCP Soaking seeds of Gossypium barbadense and Triticum vulgare in a 1 g/L solution of 2,4-DCP for 24 hours completely inhibits germination and also inhibits the emergence of Vicia faba seedlings (499). 2,4,5-TCP When "Woedar", 45% 2,4,5-TCP, was applied to rice at 2,3 or 5 kg/ha there was no difference noted in starch, protein, or ash levels, at any treatment level, compared to controls (481).
There are few data on wildlife. However, due to the ubiquitous nature of the effects of chlorophenols on mammals, what data there are on livestock and laboratory animals should be applicable. The acute oral LD50 for northern bobwhite quail given a single dose of PCP was 627 mg/kg and the NOEL was 175 mg/kg (749). The dietary LC50 for bobwhite quail was 5.581 mg/g and the NOEL was 562 µg/g (750); for mallard ducks the respective values were 4.184 mg/g and 562 µg/g (751). The oral LD50 was determined to be 380 mg/kg in mallards and 504 mg/kg in pheasants (753).
PCP is repellent to livestock, which avoid grazing on heavily treated pastures (162); similar avoidance is to be expected by wild ungulates. Animals with well-developed urinary systems are most likely to recover from PCP poisoning, but baby pigs are deficient when still young, and acute, lethal poisoning has occurred when farrowing occurs in newly constructed and excessively treated pens. Used crankcase oil was often used as a carrier for the PCP and the combination is lethal if it is not thoroughly dried (660). Two Hereford cows died after drinking 5% PCP in kerosene. Extreme necrosis of the liver and kidneys occurred (661). Wood preservative containing PCP may be very toxic while still wet on freshly treated wood, but, properly applied and well dried, the wood has little toxicity (659). 2,4-DCP Sheep and cattle were fed 2,4-DCP at 9, 30 and 60 mg/kg body weight, daily, for 28 days. Muscle and fat tissues had no 2,4-DCP, but concentrations in liver and kidney tissues were high. If the diet was stopped 1 week before analyses, the kidney levels were much reduced, but liver levels were still high (315). 2,4,5-TCP Cows were fed rations containing 2,4,5-TCP at levels from 10
to 1000 mg/kg for 2 to 3 weeks. No residue of 2,4,5-TCP greater
than 0.05 mg/kg was found in milk or cream at diet levels up
to 30 mg/kg. At the 1000 mg/kg dose, mean residues in milk were
0.24 mg/kg and in cream 0.19 mg/kg (464). The wood from which farrowing pens were constructed was treated with 4.4% PCP, 0.63% other chlorophenols, and 81.6% petroleum distillates, only days before pregnant sows were introduced. Contact with the still wet lumber resulted in enough skin absorption to cause fetal mortality and the birth of weak pigs. PCP on the teats and mammary glands discouraged nursing. Piglets had pathological lesions in kidneys, bladder, liver, spleen, stomach, and intestinal and respiratory tracts (315). A calf given a single dose of 3200 mg of PCP in 40 gallons of water (17 mg/L) did not show any effects in 4 days. When their drinking water was spiked with 51 mg/L of CaPCP or 60 mg/L of KPCP, calves showed some effects in 5 weeks and 7 weeks, respectively (167). Some LD50s for calves are 140 mg/kg given orally (323), and 35 to 50 mg/kg in an 11-day trial (323). The oral LD50 for sheep was 120 mg/kg (323).
Tables 7.5.1 and 7.5.2 give the effects of PCP and other chlorophenols on mammals and birds, mostly laboratory animals, on a mg/kg, mg/L and mg/animal basis. In a 2,4,5-TCP feeding experiment with rats (313), the concentration of TCP was expressed as mg/kg of diet. In this instance the concentration was converted to an estimate of the mg/kg dose using 250 g as the estimated mean weight of the rats and 25 g as their estimated mean food consumption per day. Both these estimates are at the high end of the possible range. Mixtures Rats were fed a mixture of 90:10, PCP:TTCPs at zero, 1, 3, 10 and 30 mg/kg/day in a 2-year feeding study. The acute LD50 was estimated to be 150 mg/kg. At the highest dose of 30 mg/kg/day there was slightly reduced weight gain in females, decreased litter survival and progeny growth rates, increased serum glutamic pyruvate transaminase activity in males and females, increased urine specific gravity in females, and increased pigment in the liver and kidney of males. Liver and kidney pigmentation occurred in females at 10 mg/kg. The NOELs were 10 mg/kg/day in males and 3 mg/kg/day in females (38). 2-MCP The lowest intravenous dose causing a lethal effect was 120 mg/kg in rabbits (364). The lowest LD50 for rats was 230 mg/kg given intraperitoneally (229), 670 mg/kg given orally, and 950 mg/kg given subcutaneously (364). There were no oral NOEL doses recorded for 2-MCP, but the estimated level would be about 0.01 of the LD50 or 7 mg/kg. Some other LD50 data for 2-MCP include 440 mg/kg for the blue fox, 950 mg/kg given subcutaneously to rabbits (364), and 2230 mg/kg given orally in olive oil and 3160 mg/kg given subcutaneously to rats (652). The lethal dose given intraperitoneally to rats is reported as 230 mg/kg and given subcutaneously to guinea pigs is 800 mg/kg (364). 3-MCP The lowest intraperitoneal dose causing an LD50effect was 335 mg/kg in male rats (229, 372); the equivalent oral dose was 697 mg/kg and subcutaneously it was 1.73 g/kg, both also in rats (372). There were no references to oral NOEL doses, but an estimated value would be about 7 mg/kg in rats. Other LD50 data include treating male rats with 1865 mg/kg orally or 4360 mg/kg subcutaneously, both in olive oil (652). 4-MCP In rats the lowest LD50 intraperitoneal dose was 250 mg/kg (372); the equivalent oral dose was 500 mg/kg (372, 653) and it was 1.03 g/kg given subcutaneously in olive oil (372, 652). There were no references to oral NOEL doses, but an estimated value would be 5 mg/kg in rats. Other LD50 data for rats are 281 mg/kg intraperitoneally (229), 660 mg/kg orally in olive oil (372, 652), and 1.5 g/kg dermally (372, 653). The oral LD50 for mice is given as 800 mg/kg orally (372).
MCPs In rats 250 mg/kg is given as the LD50 for MCPs as a group (315, 232). 2,4-DCP An oral dose of 150 mg/kg to pigeons caused no deaths and 87 to 95% was eliminated in 5 days (497). In mice NOEL doses found were 25 and 100 mg/kg for 6 month periods; the lowest effect level for these mice was 230 mg/kg, and the LD50 for mice was 1600 to 1630 mg/kg (312). For rats the oral LD50s were 3670 mg/kg for males and 4500 mg/kg for females (312). The LD50s for rats were found to be 430 mg/kg given intraperitoneally (229), 1720 mg/kg given in fuel oil (652) and 1730 mg/kg given subcutaneously (496). 2,6-DCP In rats there are sub-lethal effects on mitochondrial enzymes in the liver at 5.5 mg/kg (425), while oral LD50 effects do not occur until 2940 mg/kg (426). This is a ratio of sub-lethal effects: LD50 of 5.5 : 2940 or 0.00187 which is considerably less than the standard factor of 0.01 for many compounds. Perhaps one needs to use a greater safety factor in estimating NOEL levels from LD50 levels where chlorophenols are concerned. The LD50s for rats, where the 2,6-DCP was given intraperitoneally, were 390 mg/kg (229, 372) and where given subcutaneously the value was 1730 mg/kg (426). DCPs In rats the LD50 for DCPs as a group is reported as 250 mg/kg (315, 232). 2,3,6-TCP There are few data for this compound in mammals, with only one intraperitoneal LD50 value of 308 mg/kg in rats (229) being found and no oral dose data. Data from references 364 and 372, which show the ratio of oral to intraperitoneal doses to be about 2.29, would indicate that an appropriate oral dose is 705 mg/kg for an LD50 and thus a NOEL dose should be about 7 mg/kg. 2,4,5-TCP There was no percutaneous absorption of 2,4,5-TCP from the intact skin of rabbits or guinea pigs (476). When rats are fed alpha-hexachlorocyclohexane, 2,4,5-TCP is found as a metabolite in the urine (490). Feeding rats 30 to 1000 mg/kg/day for up to 17 weeks caused little, if any, liver damage (478). Rabbits received 20 oral doses of 2,4,5-TCP over 28 days. No changes were seen in kidney or liver at 1 to 10 mg/kg and only slight effects were noted at 100 and 500 mg/kg (313). Rats received 18 oral doses of 2,4,5-TCP over 24 days. At 1000 mg/kg they lost 10 g in the first 10 days, but later regained the weight. Livers were enlarged at autopsy but no other obvious effects were noted. No effects were seen at 30, 100, or 300 mg/kg (313). In a 98-day experiment, male and female rats were fed 10, 30, 100, 300, or 1000 mg/kg of diet as 2,4,5-TCP. Only mild reversible effects were seen at the 300 or 1000 mg/kg dose, no effects were observed at lower rates of exposure. At 1000 mg/kg there were diuretic and growth retarding effects (313). Oral LD50 values for rats are reported as 2800 mg/kg (476), 2960 mg/kg (313), 3000 mg/kg (464), and 4000 mg/kg (475); oral LD50 values are 2560 mg/kg and 3160 mg/kg (313), and an oral LD100 value is 3980 mg/kg (313). Other responses to doses of 2,4,5-TCP are an LD50 of 2260 mg/kg for a subcutaneous dose in fuel oil to rats, an LD50 of 820 mg/kg given orally in fuel oil to rats, and an LD50 of 355 mg/kg given intraperitoneally to male rats.
2,4,6-TCP In male rats the intraperitoneal LD50 dose of 2,4,6-TCP is 276 mg/kg (229). 3,4,5-TCP The LD50 for male rats of 3,4,5-TCP given intraperitoneally is reported as 372 mg/kg (229, 418). TCPs In male rats 250 mg/kg is reported as the LD50 dose for TCPs as a group (315, 232). 2,3,4,5-TTCP Male, 250 to 300 g, and female, 220 to 270 g, rats were treated with 2,3,4,5-TTCP at 2 g/kg. It was dissolved in ethanol and applied to an 8 cm2 shaved area of the skin. After 14 days dermatosis consisting of large, hard, scar tissue occurred, but only one male rat died. The dermal LD50 is greater than 2 g/kg (106). Five days after 200 g rats were given intraperitoneal injections of 498.5 or 1507 mg/kg of 2,3,4,5-TTCP, the livers were removed and microsome fractions prepared. The higher dose rate induces twice as many revertants in the Salmonella mutagenicity test and doubles aryl hydrocarbon hydroxylase activity. The lower dose increased AHH activity only 1.6 times and mutagenicity 1.2 to 1.4 times. Cytochrome P-450 levels were slightly elevated at either dose rate (520). Injecting 5 mg/egg of 2,3,4,5-TTCP into the fluids around a 17-day chick embryo causes an increase in porphyrin in chick liver cells after 24 hours incubation at 38C (453). Similar effects are found with identical doses of 2,3,4,6-TTCP and 2,3,5,6-TTCP; in the latter case, porphyrin production is increased four-fold (453). Some LD50 values for female mice are 97 mg/kg given intraperitoneally in 40% ethanol, 133 mg/kg given intraperitoneally in propylene glycol, 400 mg/kg given orally in 40% ethanol, and 677 mg/kg given orally in propylene glycol; for male mice a value of 572 mg/kg is given for ingestion in 40% ethanol; and for female gerbils the value is 533 mg/kg when given orally in propylene glycol (450). 2,3,4,6-TTCP Male rats were given 2,3,4,6-TTCP orally in olive oil. In one test series on 300-g rats they received 10, 50 or 100 mg/kg daily for 55 days. Intestinal necroses occurred in three animals from the 100 mg dose rate, liver necroses occurred in one rat on 50 mg/kg and two rats on 100 mg/kg. There was no effect at 10 mg/kg and no effect on other tissues at any dose. A short-term, 24 -hour, high dose trial was carried out at 0, 300, 360, 410, 432, 518, and 632 mg/kg. There were no effects on brain, kidneys, and muscles. Stomach, spleen, and small intestine effects were seen in some animals; generally livers were affected, one rat at 432 mg/kg, one rat at 518 mg/kg and seven rats at 622 mg/kg (324). Some LD50 values for 2,3,4,6-TTCP are 698 mg/kg when given orally in propylene glycol to female gerbils; for female mice 735 mg/kg given orally in propylene glycol, 82 mg/kg given intraperitoneally in propylene glycol, and 131 mg/kg given orally in 40% ethanol; for male mice 163 mg/kg given orally in 40% ethanol (450), and for male rats 130 mg/kg given intraperitoneally in olive oil (229).
2,3,5,6-TTCP The LD50s for 2,3,5,6-TTCP were determined to be 979 mg/kg for female gerbils when given orally in propylene glycol, 89 mg/kg given orally in 40% ethanol to male mice and, when given to female mice, 48 mg/kg when given intraperitoneally in 40% ethanol, 109 mg/kg when given orally in 40% ethanol, 109 mg/kg when given intraperitoneally in propylene glycol, and 543 mg/kg when given orally in propylene glycol (450). PCP Rats injected with 20 mg PCP increased their body temperature 1.5 to 2.0C (544). Male and female rats were fed technical grade PCP for 62 days before, during, and following mating until the 24th month. Dose rates were 0, 3, or 30 mg/kg. No maternal effects were noted during gestation but by 21 days post-partum, maternal body weight differed for those on the 30 mg/kg rate. The number of liveborn pups and their survival at 7, 14, and 21 days post-partum, decreased on the 30 mg/kg dose. Skeletal deformations were evident in pups subjected to 30 mg/kg. No effects were seen at 3 mg/kg (539). Rats were given technical grade PCP at 0, 0.4, 4, and 40 mg/kg. No fetal deaths occurred but fetal weight decreased up to 20% at 40 mg/L. In dams treated with 0.4 mg/kg, there was 20% mortality of new-born pups. Implantation of the ovum appears to have been prevented by 0.4 mg/kg in the dams; food consumption was not affected (558). Pure PCP was given rats at 0, 0.34, 3.4, or 34 mg/kg. Food intake was not affected; no fetal deaths were noted. Fetal weight decreased 20% in 34 mg/kg dosed rats. Deaths of newborn pups was 12 to 13% in the first 2 weeks when dams received 3.4 or 34 mg/kg (558). Pregnant Sprague-Dawley rats received pure or commercial PCP in corn oil at 0, 5, 15, 30, or 50 mg/kg. Maternal weight gain decreased at 30 and 50 mg/kg dose rates when treated from days 6 to 15. No fetuses survived 50 mg/kg pure PCP. The no effect level was 5 mg/kg/day for pure PCP (288). Among cats that slept on sawdust bedding containing 1 to 600 mg/kg PCP, two 5-year old pregnant cats and nine 1 to 6 month old cats died. They had enlarged kidneys, liver degeneration, poor blood clotting, hemorrhaging, lung lesions, and enlarged lymph nodes (559). Beagle dogs were given technical PCP orally for a year at dose rates of 0, 1.5, 3.5 and 6.5 mg/kg/d. The LOAEL was 6.5 and the NOAEL was 3.5 mg/kg/day (752). In a series of experiments reported by Jones et al. 1968 (541) on rabbits, the LD100 varied from 22 to 300 mg/kg for periods ranging from 1.5 to 10 hours, when the method of application included intravenous, dermal, oral, and subcutaneous in pine, fuel, olive, and Dione oils. The most sensitive treatment was a 1.5-h LD100 administered intravenously. There are too many experiments, reported in Table 7.5.1, to repeat here; they are mostly on rats, documenting the effects of PCP. The lowest effect level was an LD20 for ovum implantation in rats of 0.4 mg/kg (558).
4-MCP Human skin, obtained at autopsy, was shown to be permeable to, and damaged by, 4-MCP at 0.75% w/v (372). 2,4,5-TCP When 1 mg/kg 2,4,5-TCP was fed to eight people, none was detected in urine or feces (489). 2,4,6-TCP Human spermatozoa lose the cytoplasmic sheath around the central nuclear material and tail fibres, at a dose of 0.2 ng/cell (467). PCP and TTCPs For 1 year a 21-year old man handled wet wood treated with 3% PCP and 1.5 % TTCP. He bled from gums, skin, bowel, and urinary tract, suffered from anemia, and died 5 months later from systemic hemorrhaging, including cerebral bleeding (560). PCP and other Chlorophenols Five men worked in a plant where wood was dipped in a preservative containing 4.1% PCP and 0.9% other chlorophenols in 83% petroleum distillate. All were hospitalized with sweating, fever, anorexia, and weight loss. The oldest, 58, died of cardiac dilation, pulmonary congestion, and liver and kidney cell degeneration. All showed PCP in their urine (561). PCP A 10 minute immersion of the hands in a 0.4% PCP solution, 106.5 mg/L, by a man produced red, painful hands for 2 hours. After 2 days a 24-hour urine specimen contained 236 µg/L PCP; elimination of the remaining PCP was gradual. Levels did not drop to normal for 4 weeks and 27% was still present after 3 weeks (545). Four families drank and bathed in well water containing 12.5 mg/L PCP for some time. Symptoms included irritated throats, red faces, and hand and leg weakness. Health improved in 2 to 3 days after stopping use of the water (545). Studies of woodworkers with long-term exposure to PCP fail to show consistent, significant effects on organs, nerves, blood, reproduction or immunology (199). In a wood-working plant in Winnipeg, Manitoba, five industrial PCP poisonings, one fatal, occurred in 1963. Inadequate precautions in handling and using the toxic material were the reasons and once proper precautions were initiated and adhered to, no further incidents occurred (561). Other literature reports of fatalities were also traced to ignorance or negligence by the workforce (561, 662). In Germany, 10 cases of PCP intoxication occurred at one PCP manufacturing plant. Symptoms were irritation of the mucosa and upper respiratory tract, neuralgic pain and generalized acne (663). In St. Louis, MO, in 1967, 6 to 14-day old infants were severely affected by PCP poisoning which led to two deaths. Over the next 5 months, 11 more were affected but blood transfusions resulted in immediate recovery from the profuse diaphoresis. The PCP was absorbed from diapers and bed linen laundered in PCP. Serum PCP dropped from 11.8 to 3.1 mg/100 mL in 24 hours following the exchange blood transfusions. An autopsy on one infant that died in 3 hours showed PCP levels of 2.1 to 3.4 mg/100 g of tissue in kidney, adrenal, heart, blood vessels, fat, and connective tissue. PCP levels in diapers were from 2.64 to 17.20 mg/100 g and in crib pads from 4.89 to 178.7 mg/100 g. At the same time, PCP levels in the serum and urine of adults attending prenatal clinics averaged 4 µg/100 mL and in infants at unaffected hospitals serum levels were 11 µg/100 mL and urine levels 2 µg/100 mL (664, 665). In a case control study on workers in Hawaii there was no significant difference in the general medical health between currently PCP exposed workers and former wood treatment operators. There was no evidence of increased deaths or cases of cancer in the Hawaiian timber treatment operators (754). Most of the preceding anecdotal material on people serves simply to indicate the various sources of poisonings and the effects; there is no concentration or dose data useful in setting guidelines. This is not unusual for effects on people since controlled tests are rarely carried out. A dermal application of 10 g/L is reported to have an effect and an 18 g dose to a 70-kg person, 257 mg/kg, is reported as an LD100 level (163).
Table 7.7 gives some recommended chlorophenol intake limits for humans; there are no guidelines for animals. The given limits have been converted to an equivalent µg/kg based on an adult 70-kg person. The lowest PCP limit listed is 3 µg/kg/day for people (224). In Table 7.5.1 the lowest PCP dose rate which has an effect, an LD20 for ovum implantation in rats, is 0.4 mg/kg; at 0.34 mg/kg no effects were recorded (558).
ORGANOLEPTIC GUIDELINES The recommended guidelines based on organoleptic effects are the human drinking water guidelines as presented in Chapter 6. These values assume no other source of chlorophenols in the diet or in the inhaled air.
Based on toxicity calculations the following guidelines are recommended with the proviso that such levels, while not toxic, may prove unpalatable to some species and thus restrict water intake or force animals to search for alternate sources of drinking water. Under drought or similar conditions these toxicity based guidelines may be appropriate, but generally the human drinking water guidelines are recommended. These values assume no other source of chlorophenols in the diet or in the inhaled air. For lactating animals under high temperatures and high water intake rates (up to 200 mL/kg): In drinking water the combined concentrations of all the: monochlorophenols, MCPs, should not exceed 185 mg/L, The concentration of pentachlorophenol, PCP, should not exceed 17.5 mg/L. For non-lactating animals under normal temperatures and low water intake rates (about 20 mL/kg): In drinking water the combined concentrations of all the: monochlorophenols, MCPs, should not exceed 1854 mg/L, The concentration of pentachlorophenol, PCP, should not exceed 175 mg/L.
There is another study which gives an NOEL value of 3.0 mg PCP/kg (38, 539) which would result in a value of 15.0 mg/L for lactating animals in hot weather and 150 mg/L for normal conditions. This is a marginally different result from the newer dog studies which are accepted as the best available data. Assuming that 3500 µg PCP/kg or 3.5 mg PCP/kg, the lowest acceptable and most recent NOEL level from table 7.5.1 (752), is a safe dose level for animals, one can calculate water concentrations knowing the mean weight of the animal and its daily water requirements. The calculated numbers would be based on toxicity, not on organoleptic effects, and may well be too high to be palatable to wildlife and livestock, thus restricting their water intake. This would also assume that the water was the only source of PCP for the animal and that no PCP came from the diet or from inhalation. An extreme water intake rate for lactating animals in hot weather would be 200 mL/kg; this translates to 3.5 X (1000/200)= 17.5 mg/L of PCP in the water, as an upper limit based on toxicity. A more normal water consumption rate is 20 mL/kg under average temperature conditions and for non-lactating animals gives a PCP drinking water guideline of 175 mg/L. In people, where water consumption rates are lower, a value of 20 mg/L was calculated in Chapter 6 for a 70-kg person drinking 1.5 L /day. Using the toxicity ratios shown in Table 2.4, since the effects of chlorophenols are ubiquitous to eukaryotes, and choosing the most toxic isomer in each group of isomers, the appropriate level, in mg/L, when PCP is 17.5, would be 41 for TTCPs, 21 for TCPs, 46 for DCPs and 185 for MCPs. The appropriate level, in mg/L, when PCP is 175, would be 410 for TTCPs, 210 for TCPs, 460 for DCPs and 1854 for MCPs. These are toxicity guidelines and may prove to be unpalatable to some animals. Using the human drinking water guidelines, based on organoleptic effects, is probably more appropriate, since most animals can smell and taste much lower concentrations than humans.
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