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Doubts about a phosphate understudy
Fd Cosmet. Toxicol. Vol. 9, pp. 887-901. Pergamon Press 1971. Printed in Great Britain
ARTICLES
OF
GENERAL
INTEREST
DOUBTS ABOUT A P H O S P H A T E U N D E R S T U D Y
Phosphates in the environment The Tenth Progress Report of the Standing Technical Committee on Synthetic Detergents (Ministry of Housing and Local Government, HMSO, London, 1969) discussed the effect of 'builders' in detergent formulations, remarking that the increased phosphate concentration in sewage effluents did not appear to have caused any increase in algal growth in reservoirs. The Eleventh Report of the same Committee (idem, HMSO, London, 1970) noted that no improvement in the concentration of detergents in sewage effluents and rivers had appeared, and that while the levels of phosphate residues were not considered critical at that time, the situation was being kept under review. Phosphates derived from household and other heavy-duty detergent formulations contribute substantially to the eutrophication of streams and lakes by encouraging the overgrowth of algae (Epstein, Environment 1970, 12 (7), 3). Most heavy-duty detergents usually contain at least 50% phosphates, while enzyme presoaks may contain as much as 80~o. Removal of phosphate from sewage, might well cause a substantial reduction in the rate of eutrophication. Tertiary treatment of municipal sewage could be relied upon to remove up to 95% of the phosphate present but would prove very costly. Moreover, there are many communities devoid of secondary, or sometimes even primary, sewage-treatment piants. Meanwhile, it has been estimated that phosphate detergents are currently responsible for some 50% of the phosphates in municipal sewage in Canada and about 70~o in the USA, where the average content of phosphate in sewage is 10 ppm (Epstein, loc. cit.). Several state and county authorities in the USA are in fact now taking steps to limit the amount of phosphates in detergents to levels of the order of only 8-12%, with promises of further restrictions to come (Burroughs, DES Envir. Bull. 1971, no. 2, p. 1)These moves are, however, being hotly contested. Halving the phosphate content of domestic detergents would probably render them ineffective only in localities where the water is exceptionally hard, and might be a worthwhile exercise, at least for marketing in soft-water areas. Another possibility is to add soaps to detergent formulations to compensate for a reduced phosphate content or to introduce discrimination by specifying low-phosphate detergents for ordinary light household purposes and persuading the housewife to reserve high-phosphate detergents for heavy duties only (Epstein, loc. tit.). The latter solution, however, would probably be ditficult to put into effect. Altogether the most obvious alternative to being mean with the existing phosphate detergents seems to be to find another compound to replace the phosphate. It is necessary, however, to select a compound which is equally hazard-free in terms of human and animal toxicology, and the very low toxicity of phosphates makes their replacement problematical. rc'r 9/6--rl
887
888
ARTICLES OF GENERAL INTEREST
In fact, the main hazard of detergent phosphates seems to be their occasionally high arsenic content, which can lead to a marked increase in levels of arsenic in river waters.
An alternative nitrogen-containh~g builder The search for a partial or complete replacement for phosphates in detergents led to nitrilotriacetic acid (NTA), salts of which have been subjected to a comprehensive evaluation of their effectiveness, toxicity and behaviour in sewage. NTA appears to be largely biodegradable in the presence of sufficient oxygen (Epstein, Ioc. cit.). At a concentration of 8 ppm, biodegradation in sewage plants accounts for 90~ of the NTA and at 16 ppm 7 5 ~ , and the biometabolism continues in streams and lakes afterwards. Nevertheless, the fate of NTA is somewhat erratic, depending in addition to oxygenation on several factors, including temperature, activity of sewage bacteria and liquid flow. Its metabolites are nitrate and nitrite, and it therefore still provides a limited scavenging crop for algae, though a much less nutritious one than that offered by phosphate. The increase in the nitrate content of sewage if NTA were to replace phosphate completely might be only some 5~o above the current municipal level (Epstein, loc. cit.).
Toxicology of NTA In studies on the fate and possible effects of NTA in animals and man, an important factor to consider has been the possibility that as a chelator of calcium ions it may accumulate in bone, particularly during periods of active growth. That this would be unlikely to occur to a degree that would have any demonstrable effect on bone development has, however, been indicated by studies on the fate of NTA following its oral administration to rats, rabbits, dogs and monkeys (Michael & Wakim, Toxic. appl. Pharmac. 1971, 18, 407). The equivalent of 10 mg NTA as the disodium salt, labelled with 14C in the carboxyl groups, was given to rats. Urinary excretion accounted for 70~o of the activity, and faecal excretion for 22~o, less than lyo appearing in exhaled carbon dioxide. Since a similar picture appeared after cannulation of the bile duct, it was supposed that NTA did not enter the enterohepatic system. Little absorption and transportation appeared to be effected by the lymphatic system. No more than 3 ~ of an orally administered dose (50 mg/kg) remained in the body of the rat, rabbit, dog or monkey after 72 hr, and most of this remaining activity was in bone. The amount of NTA incorporated into the rat tibia in conjunction with calcium ions was calculated as 8/zg/g bone, representing only 0"007~o of the total 24-hr calcium turnover by that tissue. A toxicity evaluation of NTA, mainly as its trisodium salt, has been reported by Nixon (ibid 1971, 18, 398). The oral LDso of trisodium NTA (20-50~o solution) was 1.1-1.68 g/kg in rats, about 750 mg/kg (as a 50~ solution) in monkeys, and more than 5 g/kg (as an 80~ solution) in dogs. In the latter species, emesis was stimulated at doses of 1 g/kg or more, both by solutions of trisodium NTA and by pastes of granular detergents containing NTA. No adverse histological effects were seen in a monkey given an oral dose of 0.5 g/kg. This animal survived the treatment, but one given a dose of 1 g/kg died after 70 min, death being preceded by a decrease in motor activity and then paralysis. Feeding of rats with more than 7500 ppm trisodium NTA in the diet for 90 days produced kidney lesions, including mild hydropic degeneration of the tubule cells and sometimes tubular atrophy and dilatation, but no lesions were found in other organs. Body-weight gain was retarded in rats given a feed containing 20,000 ppm NTA, but no adverse effects were reported in rats given 2000 ppm
ARTICLES OF GENERAL INTEREST
889
in the diet. No undue irritancy appeared in tests on the rabbit eye using a detergent formulation containing NTA. Repeated insult tests in man with a liquid detergent containing 2 0 ~ N T A produced no evidence of sensitization. In another study (Nolen et al. Fd Cosmet. Toxicol. 1971, 9, 509), trisodium N T A fed to two generations of rats, either continuously or from days 6 to 15 of pregnancy (that is, throughout the period of organogenesis) at dietary levels of 0.1 or 0"5~o produced no abnormalities in reproduction or in the foetuses. Moreover, doses of 2.5-250 mg/kg/day given by intubation to rabbits during organogenesis for one pregnancy had no detectable effects on reproduction or the foetuses (Nolen et al. loc. tit.). Thus the evidence so far available suggests that N T A at the levels at which it might be encountered as a result of even large-scale use as a detergent builder would not in itself present any significant hazard to health. Nevertheless there remain certain questions regarding the overall acceptability of NTA as a substitute for phosphates. These questions centre largely on the chelating capacity of NTA, to which we have already referred in connexion with its possible accumulation in bone, and led last December to a recommendation by the F D A that the use of NTA should be discontinued until more information could be obtained (Chemical and Engineering News, 4 January 1971, p. 15). The F D A move, with which industry agreed to comply, stemmed from a finding that N T A administered with cadmium and methylmercury to rats and mice caused more severe embryotoxic effects and a higher incidence of congenital malformations than did the metals administered alone. These effects were tentatively attributed to an NTA-dependent increase in placental transmission of the metals. The chelating properties of N T A are also suspect because of the possibility that detergent effluents could combine with industrial discharges or seepage from septic tanks to form toxic heavy-metal complexes, at least some of which are apparently resistant to biodegradation. Such heavy-metal chelates might also be formed by the action of N T A on deep-water deposits in lakes, a solubilization process which could increase the local distribution of metals such as lead and mercury (Epstein, loe. tit.). Finally, as a reflection of another current problem, attention has been drawn (Epstein, loc. cit.) to the possibility that under some conditions, the breakdown of N T A may be slow enough for secondary amines formed during the process, or even N T A itself, to react with any nitrite present to form nitrosamines. Obviously much more data on the environmental and toxicological implications of N T A will have to be available before decisions can be made on whether these possible problems would in fact constitute real hazards to man if N T A were to fulfil its technical potential as a major alternative to phosphate in the manufacture of industrial and domestic detergents.
ENZYME DETERGENTS, THE INDUSTRIAL WORKER AND YOU The controversy surrounding the safety-in-use of the biological enzyme detergents is continuing but sufficient data have accumulated to allow some positive conclusions to be reached (Cited in F.C.T. 1970, 8, 431). The hazards presented to the industrial worker still appear to be real, although there have been improvements in this sector. Under the less severe conditions of the home, untoward effects have been restricted to a few hypersensitive individuals.
ARTICLES
OF
GENERAL
INTEREST
DOUBTS ABOUT A P H O S P H A T E U N D E R S T U D Y
Phosphates in the environment The Tenth Progress Report of the Standing Technical Committee on Synthetic Detergents (Ministry of Housing and Local Government, HMSO, London, 1969) discussed the effect of 'builders' in detergent formulations, remarking that the increased phosphate concentration in sewage effluents did not appear to have caused any increase in algal growth in reservoirs. The Eleventh Report of the same Committee (idem, HMSO, London, 1970) noted that no improvement in the concentration of detergents in sewage effluents and rivers had appeared, and that while the levels of phosphate residues were not considered critical at that time, the situation was being kept under review. Phosphates derived from household and other heavy-duty detergent formulations contribute substantially to the eutrophication of streams and lakes by encouraging the overgrowth of algae (Epstein, Environment 1970, 12 (7), 3). Most heavy-duty detergents usually contain at least 50% phosphates, while enzyme presoaks may contain as much as 80~o. Removal of phosphate from sewage, might well cause a substantial reduction in the rate of eutrophication. Tertiary treatment of municipal sewage could be relied upon to remove up to 95% of the phosphate present but would prove very costly. Moreover, there are many communities devoid of secondary, or sometimes even primary, sewage-treatment piants. Meanwhile, it has been estimated that phosphate detergents are currently responsible for some 50% of the phosphates in municipal sewage in Canada and about 70~o in the USA, where the average content of phosphate in sewage is 10 ppm (Epstein, loc. cit.). Several state and county authorities in the USA are in fact now taking steps to limit the amount of phosphates in detergents to levels of the order of only 8-12%, with promises of further restrictions to come (Burroughs, DES Envir. Bull. 1971, no. 2, p. 1)These moves are, however, being hotly contested. Halving the phosphate content of domestic detergents would probably render them ineffective only in localities where the water is exceptionally hard, and might be a worthwhile exercise, at least for marketing in soft-water areas. Another possibility is to add soaps to detergent formulations to compensate for a reduced phosphate content or to introduce discrimination by specifying low-phosphate detergents for ordinary light household purposes and persuading the housewife to reserve high-phosphate detergents for heavy duties only (Epstein, loc. tit.). The latter solution, however, would probably be ditficult to put into effect. Altogether the most obvious alternative to being mean with the existing phosphate detergents seems to be to find another compound to replace the phosphate. It is necessary, however, to select a compound which is equally hazard-free in terms of human and animal toxicology, and the very low toxicity of phosphates makes their replacement problematical. rc'r 9/6--rl
887
888
ARTICLES OF GENERAL INTEREST
In fact, the main hazard of detergent phosphates seems to be their occasionally high arsenic content, which can lead to a marked increase in levels of arsenic in river waters.
An alternative nitrogen-containh~g builder The search for a partial or complete replacement for phosphates in detergents led to nitrilotriacetic acid (NTA), salts of which have been subjected to a comprehensive evaluation of their effectiveness, toxicity and behaviour in sewage. NTA appears to be largely biodegradable in the presence of sufficient oxygen (Epstein, Ioc. cit.). At a concentration of 8 ppm, biodegradation in sewage plants accounts for 90~ of the NTA and at 16 ppm 7 5 ~ , and the biometabolism continues in streams and lakes afterwards. Nevertheless, the fate of NTA is somewhat erratic, depending in addition to oxygenation on several factors, including temperature, activity of sewage bacteria and liquid flow. Its metabolites are nitrate and nitrite, and it therefore still provides a limited scavenging crop for algae, though a much less nutritious one than that offered by phosphate. The increase in the nitrate content of sewage if NTA were to replace phosphate completely might be only some 5~o above the current municipal level (Epstein, loc. cit.).
Toxicology of NTA In studies on the fate and possible effects of NTA in animals and man, an important factor to consider has been the possibility that as a chelator of calcium ions it may accumulate in bone, particularly during periods of active growth. That this would be unlikely to occur to a degree that would have any demonstrable effect on bone development has, however, been indicated by studies on the fate of NTA following its oral administration to rats, rabbits, dogs and monkeys (Michael & Wakim, Toxic. appl. Pharmac. 1971, 18, 407). The equivalent of 10 mg NTA as the disodium salt, labelled with 14C in the carboxyl groups, was given to rats. Urinary excretion accounted for 70~o of the activity, and faecal excretion for 22~o, less than lyo appearing in exhaled carbon dioxide. Since a similar picture appeared after cannulation of the bile duct, it was supposed that NTA did not enter the enterohepatic system. Little absorption and transportation appeared to be effected by the lymphatic system. No more than 3 ~ of an orally administered dose (50 mg/kg) remained in the body of the rat, rabbit, dog or monkey after 72 hr, and most of this remaining activity was in bone. The amount of NTA incorporated into the rat tibia in conjunction with calcium ions was calculated as 8/zg/g bone, representing only 0"007~o of the total 24-hr calcium turnover by that tissue. A toxicity evaluation of NTA, mainly as its trisodium salt, has been reported by Nixon (ibid 1971, 18, 398). The oral LDso of trisodium NTA (20-50~o solution) was 1.1-1.68 g/kg in rats, about 750 mg/kg (as a 50~ solution) in monkeys, and more than 5 g/kg (as an 80~ solution) in dogs. In the latter species, emesis was stimulated at doses of 1 g/kg or more, both by solutions of trisodium NTA and by pastes of granular detergents containing NTA. No adverse histological effects were seen in a monkey given an oral dose of 0.5 g/kg. This animal survived the treatment, but one given a dose of 1 g/kg died after 70 min, death being preceded by a decrease in motor activity and then paralysis. Feeding of rats with more than 7500 ppm trisodium NTA in the diet for 90 days produced kidney lesions, including mild hydropic degeneration of the tubule cells and sometimes tubular atrophy and dilatation, but no lesions were found in other organs. Body-weight gain was retarded in rats given a feed containing 20,000 ppm NTA, but no adverse effects were reported in rats given 2000 ppm
ARTICLES OF GENERAL INTEREST
889
in the diet. No undue irritancy appeared in tests on the rabbit eye using a detergent formulation containing NTA. Repeated insult tests in man with a liquid detergent containing 2 0 ~ N T A produced no evidence of sensitization. In another study (Nolen et al. Fd Cosmet. Toxicol. 1971, 9, 509), trisodium N T A fed to two generations of rats, either continuously or from days 6 to 15 of pregnancy (that is, throughout the period of organogenesis) at dietary levels of 0.1 or 0"5~o produced no abnormalities in reproduction or in the foetuses. Moreover, doses of 2.5-250 mg/kg/day given by intubation to rabbits during organogenesis for one pregnancy had no detectable effects on reproduction or the foetuses (Nolen et al. loc. tit.). Thus the evidence so far available suggests that N T A at the levels at which it might be encountered as a result of even large-scale use as a detergent builder would not in itself present any significant hazard to health. Nevertheless there remain certain questions regarding the overall acceptability of NTA as a substitute for phosphates. These questions centre largely on the chelating capacity of NTA, to which we have already referred in connexion with its possible accumulation in bone, and led last December to a recommendation by the F D A that the use of NTA should be discontinued until more information could be obtained (Chemical and Engineering News, 4 January 1971, p. 15). The F D A move, with which industry agreed to comply, stemmed from a finding that N T A administered with cadmium and methylmercury to rats and mice caused more severe embryotoxic effects and a higher incidence of congenital malformations than did the metals administered alone. These effects were tentatively attributed to an NTA-dependent increase in placental transmission of the metals. The chelating properties of N T A are also suspect because of the possibility that detergent effluents could combine with industrial discharges or seepage from septic tanks to form toxic heavy-metal complexes, at least some of which are apparently resistant to biodegradation. Such heavy-metal chelates might also be formed by the action of N T A on deep-water deposits in lakes, a solubilization process which could increase the local distribution of metals such as lead and mercury (Epstein, loe. tit.). Finally, as a reflection of another current problem, attention has been drawn (Epstein, loc. cit.) to the possibility that under some conditions, the breakdown of N T A may be slow enough for secondary amines formed during the process, or even N T A itself, to react with any nitrite present to form nitrosamines. Obviously much more data on the environmental and toxicological implications of N T A will have to be available before decisions can be made on whether these possible problems would in fact constitute real hazards to man if N T A were to fulfil its technical potential as a major alternative to phosphate in the manufacture of industrial and domestic detergents.
ENZYME DETERGENTS, THE INDUSTRIAL WORKER AND YOU The controversy surrounding the safety-in-use of the biological enzyme detergents is continuing but sufficient data have accumulated to allow some positive conclusions to be reached (Cited in F.C.T. 1970, 8, 431). The hazards presented to the industrial worker still appear to be real, although there have been improvements in this sector. Under the less severe conditions of the home, untoward effects have been restricted to a few hypersensitive individuals.