Aluminium trilactate

Endpoint summary

Additional information

In accordance with the REACH Regulation (Annex XI, 1.5), read-across approaches are used to fullfil REACH information requirements short-term toxicity to fish, long-term toxicity to fish, Short-term toxicity to aquatic invertebrates, Long-term toxicity to aquatic invertebrates, Toxicity to aquatic algae and cyanobacteria and for derivation of PNECs.

Substances used for read across are Lactic acid and Aluminium substances with nontoxic counter ions. Aluminium trilactate is very soluble in water and dissociates toLactate and Aluminium in form of its cation.Thus, the read-across approachis justified in accordance with REACH Regulation (Annex XI, 1.5)by chemical structure and common physiological activity of the dissociation products.

Aluminium sulphate and Aluminium chloride as substances with Aluminium and nontoxic counter ion are used as relevant and adequate read-across substance to assess the intrinsic systemic activities of the Aluminium ion. Because, once dissociated, the individual source of the Aluminium ions is not longer relevant for its activity in the environment and e. g. Aluminium dissociated from Aluminium sulphate and Aluminium chloride will be indiscernible from an Aluminium ion dissociated from Aluminium trilactate. A full read-across of data and conclusions based on a molecular weight correction is considered. This approach has also been used in the comprehensive assessments on the toxicity of Aluminium, conducted by e. g. the World Health Organisation (WHO),Environment Canadaor the United States Agency for Toxic Substances and Disease Registry (US ATSDR). “When aluminum salts are added to water, they hydrolyse, and monomeric aluminum can be formed in the dissolved fraction. It is the monomeric aluminum, and not the salts, that can adversely affect organisms” (Environment Canada, 2010).

Bowmer et al. (1998) investigated the ecotoxicity of Lactic acid and Lactate salts to algae, Daphnia, and fish. Based on the experimental results with metal containing Lactates (Manganese lactate, Manganese chloride; Zinc lactate, Zinc chloride; Sodium lactate), the authors concluded that the toxicity of the metal Lactates to Daphnia magna is similar to that of their corresponding metal salts and the toxicity of Lactic acid in the tests with D. magna can be completely attributed to the low pH, which is confirmed by the lack of toxicity of Sodium lactate. According to the authors, the results indicate that the acute toxicity of metal Lactates can be attributed to the cationic part of the molecules. This conclusion was supported by a compilation of literature data indicating a significant higher toxicity of Aluminium than Lactate.

Several assessment reports on the ecotoxicity of Aluminium are available, which have been taken into account for environmental hazard assessment: Environment Canada (2010), WHO IPCS EHC(1997), US ATSDR(2008). The EU drinking water directive (98/83/EC) has established a limit concentration of 200 µd/L Aluminium. This is also considered in the hazard assessment.

Aluminium is described as the most abundant metallic element in the earth's crust comprising up to about 8% of the Earth’s surface where it is frequently found as alumino-silicates, hydroxides, phosphates, sulphates and cryolite. Aluminium is released by natural processes like soil erosion, weathering of rocks and volcanic activity and redistributed to other environmental compartments including water, air and biota. These natural sources have to be taken into account for hazard assessment as well: “Aluminum being a natural element, it is also useful to consider whether the PNEC is within the range of natural background concentrations. Although based on limited data, on an overall basis, the 90thpercentile value for dissolved aluminum at sampling stations located upstream of points of discharge of aluminum salts is 0.06 mg/L (Germain et al. 2000). It should be noted that only a portion of this dissolved aluminum is in inorganic monomeric forms (corresponding to the PNEC). Thus, the 90th-percentile value for inorganic monomeric aluminum in uncontaminated water is expected to be less than 0.06 mg/L.” (Environment Canada, 2010).

According to WHO IPCS EHC, 1997 “surface freshwater and soil water aluminium concentrations can vary substantially, being dependent on physico-chemical and geological factors. Aluminium can be suspended or dissolved. It can be bound with organic or inorganic ligands, or it can exist as a free aluminium ion. In natural waters aluminium exists in both monomeric and polymeric forms. Aluminium speciation is determined by pH and the concentrations of dissolved organic carbon (DOC), fluoride, sulfate, phosphate and suspended particulates. Dissolved aluminium concentrations for water in the circumneutral pH range are usually quite low, ranging from 1.0 to 50μg/litre. This rises to 500-1000μg/litre in more acidic water. At the extreme acidity of water affected by acid mine drainage, dissolved aluminium concentrations of up to 90 mg/litre have been measured.”

 

The toxicity of Aluminium is influenced by pH the presence of possible ligands as summarised by Environment Canada (2010): “Water pH is known to have a significant effect on the toxicity of dissolved aluminum. Under acidic conditions, aluminum is most toxic in the pH range 5.0–5.5. […]

The toxicity of dissolved aluminum is reduced in the presence of inorganic ligands, such as fluorides, sulphates and silicates, as well as organic ligands, such as fulvic and humic acids (Roy 1999a). It is well established thatDOMin particular influences the speciation and absorption of aluminum. In laboratory studies with fish, the toxicity of aluminum was reduced in the presence of organic acids, such as citric acid (Driscoll et al. 1980; Baker 1982), salicylic or oxalic acid (Peterson et al. 1989), humic acid (van Coillie et al. 1983; Parkhurstet al. 1990; Peuranen et al. 2002) and fulvic acid (Neville 1985; Lydersen et al. 1990a; Witters et al. 1990; Roy and Campbell 1997). In laboratory studies with amphibians (frog eggs and tadpoles), LC₅₀s for aluminum increased (i.e., toxicity was reduced) in the presence of DOM. However, in the field, the effects of DOM in attenuating aluminum toxicity are difficult to separate from the influences of pH and aluminum concentration (Clark and Hall 1985; Freda 1991).”

 

Dissolved inorganic monomeric Aluminium is considered to have the highest bioavailability to aquatic species and thus toxicity of Aluminium being related the concentration of dissolved inorganic monomeric Aluminium (Environment Canada, 2010;WHO IPCS EHC, 1997). Consequently, the most appropriate way to describe the toxicity of Aluminium is in terms of dissolved Aluminium. Many studies on Aluminium ecotoxicity are available, but only few provide dissolved Aluminium concentrations and so limiting their adequacy.

Short-term toxicity to fish

Two short term studies with Lactic acid as well as two studies with water soluble Aluminium salts (Aluminium sulphate and Aluminium chloride) are available:

The acute toxicity of Lactic acid to tilapia (Oreochromis mossambicus) was investigated in a study conducted according to the recommendations given by APHA (1995). Fish (in total 16) were exposed to nominal concentrations ranging from 60.5 to 423.5 mg/L for 96 h under semi-static conditions. In a further bioassay, the feeding rate of fish exposed to the Lactic acid for 96 h was determined. The 96 h LC50 was determined to be 257.73 mg/L (nominal). The study is regarded as reliable with restrictions although some information e.g. on test conditions are missing as the study was conducted according to the recommendations of APHA.

This result is supported by an acute toxicity study of Lactic acid to zebrafish:

The acute toxicity of Lactic acid toBrachydanio reriowas investigated in a study conducted according to OECD Guideline 203 (Fish, Acute Toxicity Test) and EPA Guideline No. EG-9 and Technical Support Document No. ES-6 under semi-static conditions. The test substance concentration was determined enzymatically. The 96 h LC50 was determined to be 320 mg/L (nominal). The authors explained the apparent toxicity of Lactic acid to B. rerio by the low pH values of the test substance solutions (4.1 and 3.5 at concentrations of 320 and 560 mg/L; pH according to guideline not adjusted).

In a 96-h acute toxicity study similar to OECD guideline 203, juvenileSalmo salar(Atlantic salmon) were exposed to Aluminium sulfate at the following measured concentrations:

The 96-h LC50 was 2.9 µM (95% CI 2.5–3.2 µM) without fulvic acid and 8.3 µM (95% CI 6.9–10.0 µM) with 5 mg/L fulvic acid. Recalculation to µg/L resulted in the following values: 96-h LC50: 78.2 µg Al/L (95% CI 67.5 - 86.3 µg/L) without fulvic acid and 107.9 µg Al/L (CI 94.4 - 121.4 µg/L) with fulvic acid. Al was less toxic in FA (fulvic acid) solutions than in the standard reconstituted soft water. As natural waters contain organic matter to some extent, the 96-LC50 obtained from the experiment with 5 mg/L fulvic acid is considered the more realistic value and thus used for hazard assessment.

In a 96-h acute toxicity study, juvenilerainbow trout (Oncorhynchusmykiss)were exposed to Aluminium chloride at nominal Al concentrations of 0, 1, 2, 4, and 8 mg/L. 

Variouscombinations of Al and hardness or Al andhumicacid concentrations were assessed. The lowest 96 h LC50 was 3.75 mg/L total Al or 0.36 mg/L dissolved Al (at low humic acid concentration of 1.4 mg/L). Higher humic acid concentrations reduced Al-related effects on mortality: at a humic acid concentration of 10.1 mg/L, the 96 h LC50 was 5.22 mg/L total Al or 0.79 mg/L dissolved Al.

InWHO IPCS EHC(1997) studies on acute toxicity to fish are reviewed; the values for 96 h LC50 range from 0.075 mg Al/L (in Salmo salar) to 235 mg Al/L (in Gambusia affinis). Varying test conditions (pH, hardness) make it difficult to compare. 

Based on the available data the most critical 96 h-LC50 was 107.9 µg Al/L; recalculated to Aluminium trilactate the 96 h-LC50 is 1.18 mg/L.

Long-term toxicity to fish

One long term study with Lactic acid as well as two studies with Aluminium are available:

The chronic toxicity of Lactic acid to juvenile tilapia (Oreochromis mossambicus) was investigated in a study conducted according to the recommendations of APHA (1995). The 90 d chronic toxicity tests were conducted in outdoor earthern vats. Behaviour and survival were examined twice daily. After a 90 d exposure period, no mortality of fish occurred and there was no apparent change in behaviour and colour of the exposed fish. The condition factor did not show any variation between the treatments. The maturity index of male fish significantly reduced in all concentrations tested whereas that of female fish decreased only in concentrations ranging from 5.08 to 25.41 mg/L. The minimum effective concentration of Lactic acid that caused a significant reduction in food conversion factor, specific growth rate, percent increase in weight, yield, and fecundity over control was determined to be 2.18 mg/L (nominal).

The study is regarded as reliable with restrictions although some information e.g. on test conditions are missing as the study was conducted according to the recommendations of APHA.

The 28/42-day chronic toxicity of Aluminium to early life stage (artificially implanted eggs, alevins and parr) of brown trout Salmo trutta (L.) was studied in natural streams of different acidity. 300 fertilized eggs of Salmo trutta were exposed to measured concentrations of 3, 5.2, 5.6, 12, 34, 56, 88, 377, 397 µg Al/L. Chemical analysis included detailed Aluminium speciation of surface and interstitial water samples, taken over the duration of intragravel life stages. Egg survival, from two minutes after fertilization to hatching, was usually above 71%, and was independent of the mean concentration of total monomeric aluminium over the range 3 - 397 µg/L.

The survival of alevins exposed for 28 days (before 'swim-up') or 42 days ('swim-up') was most strongly related to mean total monomeric Aluminium concentration and to pH. For 28- and 42-day exposures, LC50 values for Al were approximately 19 and 15 µg/L, respectively.

The 21-dayLC50 of parr (ca 3 months old) was > 84 µg Al/L.

The 60-day chronic toxicity of Aluminium sulfate hexadecahydrate to Salvelinus fontinalis (brook trout) was studied under static renewal conditions similar to OECD guideline 210. In the first exposure (exposure A), eyed eggs of brook trout and the resultant larvae and juveniles were exposed to nominal Al concentrations of 38, 75, 150, and 300 µg/L at pH5.5; controls (no Al added) were held at pH 5.5 and 7.2. In the second exposure (exposure B), eyed eggs and the resultant larvae and juveniles were exposed to nominal Al concentrations of 50, 100, 200, and 400 µg/L at pH 6.5; controls were held at pH 6.5 and 7.2. Because Al is less soluble under less acidic conditions and its toxicity to fish decreases, slightly higher Al exposure concentrations were used in exposure B than in A. The exposures were conducted in soft water containing about 3.0 mg/L Ca. The sublethal effects included were mortality in fry, weight, swimming capacity, and hatching. The most sensitive endpoint was hatching.The lowest NOEC was determined for incomplete hatching to be 13 µg/L dissolved Al.

Long term toxicity of Aluminium to fish has also been reviewed by Environment Canada (2010), LAWA (2010), WHO IPCS EHC (1997) and US ATSDR (2008). These reviews and the literature cited therein have also been taken into account for hazard assessment. WHO IPCS EHC (1997) summarises: ”Short- and long-term toxicity tests on fish have been carried out under a variety of conditions and, most importantly, at a range of pH values. The data show that significant effects have been observed at monomeric inorganic aluminium levels as low as 25μg/litre. However, the complex relationship between acidity and aluminium bioavailability makes interpretation of the toxicity data more difficult. At very low pH (not normally found in natural waters) the hydrogen ion concentration appears to be the toxic factor, with the addition of aluminium tending to reduce toxicity. In the pH range 4.5 to 6.0 aluminium in equilibrium exerts its maximum toxic effect.”

 

Some publications suggest lower NOECs being in the range of naturally occurring Aluminium concentrations (from 0.001 to 0.05 mg/L, and up to 0.5 - 1 mg/L in more acidic waters or water rich in organic matter, according to WHO, 1998). LAWA (2010) concluded that even though the studies are inherently valid, such data are not relevant for natural waters. The authors assume that the effective concentrations may be artefacts due to relating to incorrect Aluminium species.

 

LAWA (2010) and Environment Canada (2010) suggest a limit concentration (critical toxicity value, CTV) of 50 µg Al/L and 60 µg Al/L, respectively. Following this approach a NOEC of 50 µg Al/L corresponding to 0.55 mg/L Aluminium trilactate will be used.

Short-term toxicity to aquatic invertebrates

Three studies (in the oligochaete wormBranchiura sowerbyi, in the cladoceran crustaceanMoina micruraand inDaphnia magna) are available for Lactic acid. For Aluminium, two studies (inAsellus aquaticusand inDaphnia magna) with water soluble Aluminium salts are available.

The acute toxicity of Lactic acid to the oligochaete wormBranchiura sowerbyiwas investigated in a study conducted according to the recommendations given by APHA (1995). The organisms (in total 40) were exposed to nominal concentrations ranging from 38.72 to 67.76 mg/L for 96 h under semi-static conditions. The 96 h LC50 was determined to be 50.82 mg/L (nominal). Statistical analysis showed that the minimum doses that caused a significant mortality of worm was 38.72 mg/L (nominal). The study is regarded as valid with restrictions although some information e.g. on test conditions are missing as the study was conducted according to the recommendations of APHA.

The acute toxicity of Lactic acid to the cladoceran crustaceaMoina micrurawas investigated in a study conducted according to the recommendations given by APHA (1995). The organisms (in total 40) were exposed to nominal concentrations ranging from 266.2 to 411.4 mg/L for 96 h under semi-static conditions. The 96 h LC50 was determined to be 329.12 mg/L (nominal). Statistical analysis showed that the minimum doses that caused a significant mortality of cladoceran was 290.4 mg/L (nominal). The study is regarded as valid with restrictions although some information e.g. on test conditions are missing as the study was conducted according to the recommendations of APHA.

The acute toxicity of Lactic acid toDaphnia magnawas investigated in a study conducted according to OECD Guideline 202 (Daphnia sp. Acute Immobilisation Test) and EPA Guideline No. EG-1 and Technical Support Document No. ES-1 under static conditions. The test substance concentration was determined enzymatically. The 48 h EC50 was determined to be 240 mg/L (nominal). The authors explained the apparent toxicity of Lactic acid to D. magna by the low pH values of the test substance solutions (4.1 and 3.5 at concentrations of 320 and 560 mg/L).

The study is regarded as reliable with restrictions although the study was conducted according to guideline as the documentation is limited.

The acute toxicity of Aluminium sulfate hexadecahydrate toAsellus aquaticuswas studied under static renewal conditions.  Exposure concentrations were not given in this publication. Mortality/immobilization was observed at 24 h intervals. The 48 h LC50 was 6.57 mg/L (as Al), the 96-h LC50 was 4.37 mg/L (as Al). 

The 48 h LC50 for Aluminium (as Aluminium chloride) inDaphnia magnais reported to be 3.9 mg Al/L based on immobilisation and mortality.

According toWHO IPCS EHC(1997) LC50 values in aquatic invertebrates range from 0.48 mg/L in polychaete to 59.6 mg/L in Daphnia. “Responses to aluminium by macroinvertebrates are variable. In the normal pH range aluminium toxicity increases with decreasing pH; however, in very acidic waters aluminium can reduce the effects of acid stress. Some invertebrates are very resistant to acid stress and can be very numerous in acidic waters. Increased drift rate of invertebrates has been reported in streams suffering either pH or pH/aluminium stress; this is a common response to a variety of stressors. Lake invertebrates generally survived field exposure to aluminium but suffered as a result of phosphate reduction in oligotrophic conditions induced by precipitation with aluminium.”

The most critical 48 h LC50 in aquatic invertebrates was 3.9 mg Al/L or recalculated to Aluminium trilactate 42.53 mg/L.

 

Long-term toxicity to aquatic invertebrates

No data are available for long term effects of Lactic acid to aquatic invertebrates. From other aquatic toxicity studies it has become clear, that Aluminium is the more critical moiety. Thus, the lacking data for Lactic acid are not considered to be of great concern.

The 21-day-chronic toxicity of Aluminium chloride to Daphnia magna was studied under static renewal conditions (tested concentrations not given in the publication).  The 21 day LC50 and EC50 based on mortality and reproduction were 1400 and 680 µg Al/L(nominal), respectively.

The 21 day EC16 (based on reproduction) was 320 µg Al/L(nominal) or recalculated to Aluminium trilactate 3489.28 µg/L.

 

Toxicity to aquatic algae

One study in Selenastrum capricornutum is available for Lactic acid. For Aluminium chloride one study inChlorella pyrenoidosais available.

The toxicity of Lactic acid toSelenastrum capricornutumwas investigated in a study conducted according to OECD Guideline (1984) or EPA Guideline EG-8. The test duration of the static test was 72 or 96 h (not specified in respect to Lactic acid). The test substance concentrations were enzymatically determined. The 72/96 h EbC50, ErC50 and NOEC were determined to be >2800, 3500, and 1900 mg/L (nominal), respectively.

In a 96 hour acute toxicity study, the cultures ofChlorella pyrenoidosawere exposed to Aluminium chloride at nominal concentrations of 0, 25, 50, 100, 150 µg/L under static conditions at pH values from 4.8 to 6.0.

The EC30 was determined by the authors to be 70 nmol/L (at pH 6) and 1.8 µmol/L at pH 5 (measured concentrations). The EC10 and EC50 (at pH 5) were determined by linear regression by the submitter based on nominal concentrations, available in the article. These values are 95 and 158 µg Al/L (as dissolved Al), respectively.

According to WHO IPCS EHC(1997) “Aquatic unicellular algae showed increased toxic effect at low pH, where bioavailability of aluminium is increased. They are more sensitive than other icroorganisms, the majority of 19 lake species showing complete growth inhibition at 200μg/litre total aluminium (pH 5.5).“

The most critical EC50 in aquatic algae was158 µg Al/Lor recalculated to Aluminium trilactate1.72 mg/L.

 

Toxicity to microorganisms

The ready biodegradation of Aluminium trilactate (93.0% a.i.) was investigated in a study conducted according to EU Method C.4-C (Determination of the "Ready" Biodegradability - Carbon Dioxide Evolution Test; 30 May 2008) and OECD guideline 301 B adopted July 17, 1992 over a period of 28 days and using an inoculum obtained from activated sludge freshly obtained from a predominantly domestic municipal sewage treatment plant. The biodegradation rate was determined by measurement of carbon dioxide evolution. Inoculum blank, procedural/functional control with the reference substance Sodium acetate and 2 toxicity controls with reference substance and test substance (at 12 mg TOC/L = 35 mg/L test substance and 36 mg TOC/L = 100 mg/L test substance) were performed. The relative biodegradation was 79% (mean of 2 replicates). Furthermore, biodegradation of at least 60% was reached within a 10-day window. Thus, Aluminium trilactate was readily biodegradable in this modifies Sturm test. In both toxicity controls more than 25% biodegradation occurred within 14 days (55% at 12 mg TOC/L = 35 mg/L test substance and 54% at 36 mg TOC/L=100 mg/L test substance, based on ThCO2). Therefore, the test substance was assumed not to inhibit microbial activity at both concentrations tested.

Based on the available data, the NOEC (microorganisms) for Aluminium trilactate is 100 mg/L.

 

Conclusion for aquatic toxixicity

Based on the available data on aquatic toxicity, the most critical NOEC (for freshwater fish) is 13 µg Al/L (or 141.75 µg/L as Aluminium trilactate).

References:

Environment Canada (2010)Environment Canada Priority Substance List Assessment Report, Follow-up to the State of Science Report, 2000 Aluminium Salts (Final Content), available via internet: http://www.ec.gc.ca/lcpe-cepa/default.asp?lang=En&n=491F0099-1 and http://www.ec.gc.ca/lcpe-cepa/documents/substances/sa-as/final/al_salts-eng.pdf

European drinking water directive 98/83/EC, available via internet: http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=CELEX:31998L0083:EN:NOT

LAWA (Bund/Länder-Arbeitsgemeinschaft Wasser) (2010) Stoffdatenblatt Aluminium-Kation (14903-36-7), Available via internet: http://www.laenderfinanzierungsprogramm.de/cms/WaBoAb_prod/WaBoAb/Vorhaben/LAWA/Vorhaben_des_Ausschusses_Oberflaechengewaesser_und_Kuestengewaesser_%28AO%29/O_5.07/L4_db_Aluminium_Datenblatt_UQN-Vorschlag_100315.pdf

US ATSDR (United States Agency for Toxic Substances and Disease Registry)(2008) Toxicological profile for Aluminium, U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES, Public Health Service, Agency for Toxic Substances and Disease Registry, available via internet: http://www.atsdr.cdc.gov/toxprofiles/tp.asp?id=191&tid=34

WHO IPCS EHC (World Health Organistion International Programme on Chemical Safety Environmental Health Criteria)(1997) Aluminium (Environmental health criteria; 194), IPCS, World Health Organization, Geneva, available via internet: http://www.inchem.org/documents/ehc/ehc/ehc194.htm