Lanthanum
(endorsed 2017)
Guideline
Based on human health considerations, the concentration of lanthanum in drinking water should not exceed 0.002 mg/L.
General description
Lanthanum is an element in the rare earth group (also known as lanthanides group) that can enter water via run-off from agricultural soil where it has been used as fertiliser, from the weathering of rock, from specific discharges or use as a phosphate binder, and from leaching from the tailings of rare earth mining.
In water, lanthanum’s oxidation state is primarily trivalent and it may be present in varying amounts as dissolved lanthanum or as insoluble forms associated with particulates. The concentration of total lanthanum in raw drinking water sources in the Netherlands was reported to range between 0.0005 to 0.013 mg/L, although concentrations in surface waters within rare earth mining areas or downstream of some industrial activities may be much higher (de Boer et al 1996, Protano and Riccobono 2002, Kulaksiz and Bau 2011).
An assessment estimating the total daily intake of lanthanum in humans was not available.
Typical values in Australian drinking water
Australian drinking water supplies have not been routinely monitored for lanthanum. Limited analytical results from a small number of water sources in Australia indicate levels orders of magnitude lower than when lanthanum is applied for phosphate control.
The National Industrial Chemical Notification and Assessment Scheme (NICNAS) recommends regular monitoring of Australian drinking water reservoirs if they have been subject to the addition of a lanthanum-based water treatment product (NICNAS 2014). In this circumstance, as part of a drinking water supply system assessment, consideration should be given to the possibility of accumulation of lanthanum in the water or sediment following multiple applications of a lanthanum-based product.
Treatment of drinking water
It is expected that lanthanum levels in water will be reduced by the processes used to prepare water for drinking (e.g. coagulation, flocculation, sedimentation, filtration, pH correction, anti-scaling, or a combination of these) (NICNAS 2014).
Measurement
The concentration of lanthanum in water samples can be determined by inductively coupled plasma mass spectroscopy (ICP-MS) with a limit of reporting of less than 0.001 mg/L. The guideline value is for total lanthanum, so an analytical method should be used which measures both soluble and insoluble lanthanum.
Health considerations
In Australia, NICNAS reviewed the literature on lanthanum in its Secondary Notification Assessment for PhoslockTM (NICNAS 2014).
The health information for lanthanum is based on the data for soluble and insoluble lanthanum salts.
All lanthanum salts have very low oral bioavailability. The absorption and kinetics of lanthanum from lanthanum carbonate (a relatively insoluble salt) have been reasonably well studied in humans; it has an oral bioavailability of 0.00015–0.02%, but with a terminal half-life of 15–37 hours and only 1.7% of the absorbed dose excreted in urine (NICNAS 2014). The oral bioavailability of soluble forms of lanthanum may be one or two orders of magnitude higher than that of lanthanum carbonate (Pennick et al 2006, He et al 2007).
Several studies on the effects of human exposure to lanthanum carbonate, approved for medical use in non-pregnant adults with end-stage renal failure to prevent absorption of dietary phosphate, indicate that no adverse systemic effects were seen and the most frequently reported local effect following ingestion of the chemical is gastrointestinal in nature (Health Canada 2007, US FDA 2008, Swedish MPA 2006).
There is very little epidemiological data on lanthanum. The available published studies are poorly documented and inconclusive for determination of effects of lanthanum exposure due to the absence of direct exposure measurements and potential confounding factors, for example co-exposure to other chemicals in the environment (NICNAS 2014).
Lanthanum toxicity is caused by the free cation, with adverse systemic effects being observed in experimental animals from exposure to soluble lanthanum compounds. A number of oral repeat dose studies with lanthanum carbonate in a variety of animal species show no systemic toxicity relevant to humans; the observed local effect is gastric irritation due to high doses precipitating in the rodent stomach (NICNAS 2014). Repeated oral exposures of rodents to lanthanum chloride caused adverse systemic effects in the liver, and local irritation effects in the stomach (Cheng et al 2012, Cheng et al 2014, NICNAS 2014).
Studies in rodents of up to six months’ exposure to lanthanum chloride have reported that it can cause histopathological neurotoxicity, learning deficiency, small but measurable increases of lanthanum in the brain after high doses, and various changes in brain biochemistry (Briner et al 2000, Feng et al 2006a, Feng et al 2006b, He et al 2008, NICNAS 2014). The no-observed-adverse-effect-level (NOAEL) for lanthanum chloride established from the critical studies is 0.1 mg/kg bw/day, based on neurotoxicity (decreased numbers of brain cells) and learning decrements (NICNAS 2014). The equivalent amount of lanthanum ion is 0.06 mg La³+/kg bw/day.
There is no firm evidence that lanthanum is carcinogenic. The weight of evidence indicates that lanthanum is not mutagenic in tests with bacteria and that it does not damage DNA (NICNAS 2014).
Derivation of guideline
The guideline value for lanthanum in drinking water was derived as follows:
where:
0.06 mg/kg bw/day is the La³+ NOAEL for neurotoxic and neurobehavioural effects in rats.
70 kg is the average weight of an adult.
0.1 is a proportionality factor based on the assumption that 10% of daily intake is attributable to drinking water.
100 is the uncertainty factor to account for intra- and inter-species variations.
2 L/day is the estimated maximum amount of water consumed by an adult.
Factors for ‘less than lifetime’ exposure and/or uncertainty in the ‘toxicological database’ are not recommended because a comprehensive database for lanthanum carbonate, consisting of many repeat oral dose investigations in different species, including lifetime carcinogenicity studies, indicates only local effects at the site of application (stomach) and a NOAEL of 100 mg/kg bw/day. These toxicological studies have been performed using an insoluble lanthanum salt and such insoluble forms may be in drinking water sources to variable extents, and included in the total lanthanum analytical measurement. That is, some of the measured lanthanum may be in a form that has much less toxicity than the soluble lanthanum chloride upon which the drinking water guideline is based.
This guideline value is based on the effects of lanthanum from chronic exposure. As such, occasional detections of lanthanum above the guideline value would not normally be a human health concern.
References
Briner W, Rycek RF, Moellenberndt A, Dannull K (2000). Neurodevelopmental effects of lanthanum in mice. Neurotoxicology and Teratology, 22(4):573-581.
Cheng J, Cheng Z, Hu R, Cui Y, Cai J, Li N, Gui S, Sang X, Sun Q, Wang L, Hong F (2014). Immune dysfunction and liver damage of mice following exposure to lanthanoids. Environmental Toxicology, 29(1):64-73.
Cheng J, Li N, Cai J, Cheng Z, Hu R, Zhang Q, Wan F, Sun Q, Gui S, Sang X, Wang L, Hong F (2012). Organ histopathological changes and its function damage in mice following long-term exposure to lanthanides chloride. Biological Trace Element Research, 145(3):361–368.
de Boer JL, Verweij W, van der Velde-Koerts T, Mennes W (1996). Levels of rare earth elements in Dutch drinking water and its sources. Determination by inductively coupled plasma mass spectrometry and toxicological implications. A pilot study. Water Research, 30(1):190-198.
Feng LX, Xiao HQ, He X, Li ZJ, Li FL, Liu NQ, Zhao YL, Juang YY, Zhang ZY, Chai ZF (2006a). Long-term effects of lanthanum intake on the neurobehavioral development of the rat. Neurotoxicology and Teratology, 28:119-124.
Feng LX, Xiao HQ, He X, Li ZJ, Li FL, Liu NQ, Zhao YL, Huang YY, Zhang ZY, Chai ZF (2006b). Neurotoxicological consequence of long-term exposure to lanthanum. Toxicology Letters, 165(2):112–120.
He X, Zhang ZY, Feng LX, Li ZJ, Yang JH, Zhao YL, Chai ZF (2007). Effects of acute lanthanum exposure on calcium absorption in rats. Journal of Radioanalytical and Nuclear Chemistry, 272(3):557-559.
He X, Zhang ZY, Zhang H, Zhao YL, Chai ZF (2008). Neurotoxicological evaluation of long-term lanthanum chloride exposure in rats. Toxicological Sciences, 103(2):354–361.
Health Canada (2007). Summary basis of decision. Fosrenol Lanthanaum carbonate hydrate Submission Control No 102240.
Kulaksiz S and Bau M (2011). Rare earth elements in the Rhine River, Germany: first case of anthropogenic lanthanum as a dissolved microcontaminant in the hydrosphere. Environment International 37(5):973-979.
NICNAS (2014). Phoslock, Existing Chemical Secondary Notification Assessment Report NA/899S. NICNAS, Australian Government Department of Health.
Pennick M, Dennis K, Damment SJP (2006). Absolute bioavailability and disposition of lanthanum in healthy human subjects administered lanthanum carbonate. Journal of Clinical Pharmacology, 46(7):738-746.
Protano G and Riccobono F (2002). High contents of rare earth elements (RREs) in stream waters of a Cu-Pb-Zn mining area. Environmental Pollution, 117(3):499-514.
Swedish MPA (2006). Public Assessment Report, Scientific discussion, Fosrenol (lanthanum) SE/H/481/01-04/E01. Lakemedelsverket – Sweden’s Medical Product Agency.
USFDA (2008). Fosrenol product information sheet. Revision date April 2008.
NOTE: Important general information is contained in PART II, Chapter 6
NOTE: Important general information is contained in PART II, Chapter 8
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