Potassium sodium tartrate

Endpoint summary

Description of key information

Potassium Sodium Tartrate is an authorised food additive in the EU (E-337) used as a stabiliser and a sequestrant in cheese products, minced meat and susage casings (JEFCA report 17/24). Thereby there is extensive toxicological information regarding its safety and toxicokinetics. The US FDA lists Potassium Sodium Tartrate as a substance "Generally Regarded as Safe" (GRAS).  

Given the ionic nature of potassium sodium tartrate, its very high water solubility in excess of 100 mg/L and low Kow it is not expected that it will be significantly absorbed through the stratum corneum of the skin. Absorption is also predicted to be limited through biological membranes such as those in intestinal villus and in the lung alveoli, although as demonstrated by oral studies some 17 - 20% of tartaric acid / tartrates administered orally is absorbed. The amounts absorbed are rapidly distributed, partially metabolised and excreted unchanged in urine or as oxidised metabolites (CO2).

Animal and human studies performed upon laboratory animals and in humans indicate that tartaric acid and tartrates administered orally are to a large scale (80%) metabolised by bacteria in the intestines and excreted. Approximately 20% is absorbed and partially excreted via excreted via urine, exhaled air and faeces and part is metabolised in tissues, especially by the blood, liver, kidneys and bones. Maximum serum levels of tartrate are detected 1 h after intramuscular or oral dosing, with a subsequent biphasic decline with half-lifes of 3 and 53 h respectively. Labelled material can be detected in bone even 192 h after the last dose. Labelling experiments reveal that metabolised tartrate is oxidised and excreted as CO2.  

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

Review of Metabolism tartaric acid and its Na and K Salts JEFCCA

The following summary is reproduced from the Twenty-first Report of the Joint FAO/WHO Expert Committee on Food Additives, Geneva, 1977, WHO Technical Report Series No. 617: L(+) AND DL - TARTARIC ACID The information refers to Tartaric acid and its potassium, potassium-sodium and sodium salts.

 

L(+)-tartaric acid was reported to be inert in the human body (Finkle, 1933).

 

When taken by mouth, only about 20% of ingested tartrate is eliminated in the urine; the remainder is not absorbed as such since it is destroyed in the intestinal tract by bacterial action (Underhill et al., 1931; Finkle, 1933).

 

Contrary to the two above-mentioned studies a study has been published where the percentages of both L(+) and D(-)-tartrate acids eliminated in urine after intra-muscular injection to one man were only slightly greater than that after oral administration (Bauer and Pearson, 1957).

 

The excretion of L(+)-tartaric acid in the urine after p.o. administration was investigated in the rat, guinea-pig, dog and rabbit. In the rat 68% (61-85) of a 400 mg/kg bw dose was recovered.

 

In the guinea-pig 13-27% of the dose was recovered from doses ranging from 100 to 800 mg/kg bw. In the dog doses less than 600 mg/kg bw were totally excreted in the urine (83-100%), but with higher doses (600-1500 mg/kg) the recovery diminished to 50-60% and was associated with slight renal changes. In the rabbit 90-99% of a dose of 50 mg/kg bw was recovered. When the dose was raised to 100, 200 and 300 mg/kg bw 21-23%, 15-26% and 2-3% were found in urine, respectively.

 

Histological studies revealed an increasing degree of kidney damage in parallel with the decreasing excretion (Underhill et al., 1931). Sodium tartrate in daily doses of up to 10 or evenhas been used in medical practice as a laxative. It has been tested for this action in a clinical study involving the application of daily doses ofof sodium tartrate to 26 patients for an average of 11.8 doses, giving laxative responses in 66% of the subjects. The only side effects noticed were nausea or vomiting (1.6%) and abdominal cramps (2.1%) (Gold and Zahm, 1943).

 

 Following a single oral dose of 400 mg/kg monosodium () L(+) tartrate to rats, 70% of the radioactivity was excreted in urine, 16% in expired air and 14% in the faeces within 48 hours. Most of the labelled material was excreted by eight hours, the half-life for elimination from urine being 4.6 and 4.8 hours in male and female rats respectively.

 

Comparison with intravenous administration indicated that the portion of radioactivity expired resulted from metabolism of the tartrate salt to 14CO₂by the rat, about half of which occurred in the gut (HRC, 1975).

 

With monosodium () L(+) tartrate given at a daily dose of 2.73 g/kg for seven consecutive days, the concentration of label in blood and bone was maximal one hour after administration of the last dose. Half-lives for elimination were 5.9 and nine days respectively for blood and bone. By contrast, peak label concentrations in blood and bone following the same dose of monosodiom ()DL(-) tartrate occurred at three and 12 hours respectively while the half-lives were 6.5 and 2.5 days respectively for these organs. Labelled material in bone was not associated with the mineralized fraction.

 

Repeated doses of 2.73 g/kg for seven days of monosodium ()DL(-) tartrate to rats produced an increased kidney/body weight ratio compared to controls while monosodium ()L(+)-tartrate produced no such change. Autoradiographic studies demonstrated that after repeated oral administration of monosodium ()DL-tartrate, radioactivity was associated with the gastrointestinal tract, liver, kidneys and bone during 24 hours; after 48 hours and eight days radioactivity was associated only with bone and with granular deposits in the kidneys (HRC, 1975).

Literature cited:

Bauer, C. W. and Pearson, R. W. (1957) J. Amer. Pharm. Ass. Sci. Ed., 46, 575-578

Finkle, P. (1933) J. Biol. Chem., 100, 349

Gold, R. and Zahm, W. (1943) J. Amer. Pharm. Ass. Sci. Ed., 32, 173

Underhill, F. P., Leonard, C. S., Gross, E.G. and Joleski, T. C. (1931) J. Pharmacol. Exp. Ther., 43, 359

Unpublished report (1975) Huntingdon Research Centre Report CFT6/74427, 1974)

Note: The further research related to the Huntingdon report was subsequently published as:

"Renal and Bone Uptake of Tartaric Acid in Rats: Comparison of L(+) and DL-forms". Down, D.H., Sacharin, R.M., Chasseaud, L.F., Kirkpatrick, D and Franklin, E,R."

Review published by USFDA in

EVALUATION OF THE HEALTH ASPECTS OF POTASSIUM ACID TARTRATE, SODIUM POTASSIUM TARTRATE, SODIUM TARTRATE AND TARTARIC ACID AS FOOD INGREDIENTS (1979). Prepared for the USFDA by Life Sciences Research Office of the Federation of American Societies for Experimental Biology. Bethesda (Maryland). NTIS report - PB301403.

Absorption and metabolism

 

One of the first studies on tartrate metabolism was reported in 1896 by Pohl (18). Following the oral administration of 2.0 toof L(+) sodium tartrate to dogs, it was possible to recover 20 to 40 percent of the administered dose in the urine. Similar results were observed in rabbits, and Pohl (18) anecdotally reported that in man, after the ingestion of 4.0 orof sodium tartrate, tartaric acid could not be found in demonstrable amounts in the urine.

 

Brion (19) compared 24-hour excretion of the L(+), D(-), DL and meso forms of several tartrates after administration of 2.07 toof the substances by gavage to a single dog weighing. Recovery of tartrate in the urine was 25 to 29 percent after administration of L(+) sodium potassium tartrate; 3 to 6 percent after D(-) sodium ammonium tartrate; 25 to 42 percent after racemic (DL) tartaric acid; and 2 to 7 percent after mesotartaric acid or potassium acid meso-tartrate. Brion (19) concluded that D(-) tartaric acid and meso-tartaric acid are oxidized almost completely in dogs while the L(+) form is metabolized to a lesser extent

 

Studies by Neuberg and Saneyoshi (20) in 1911 indicated that when D( -), L(+), or DL-tartaric acid was administered by gavage (total) to each of two dogs, from 18 to 24 percent of the DC-), 7 to 31 percent of the L(+), and 21 to 43 percent of the DL tartrate was excreted in the urine during a 48-hour period. The isomeric form of the acid recovered from the urine was the same as that administered.

 

Simpson (21) demonstrated in rabbits, cats and dogs that from 45 to 88 percent of subcutaneously administered L(+)-tartaric acid was eliminated in the urine of the three species. However, following oral administration, only 0 to 6 percent was recovered from the urine of rabbits and 20 to 30 percent from dogs. Simpson concluded that tartaric acid is not readily oxidized in the tissues but is degraded by bacteria in the intestine.

 

In 1931, Underhill and associates (22) reported that the metabolic fate of tartrates varied in experimental animals Istereoisomeric form not stated but probably L(+)]. In the rabbit~ oral doses of less than 50 mg sodium potassium tartrate per kg body weight were recovered almost completely in the urine but only about 20 percent when 200 mg per kg was given.

 

In the dog, there was about 80 to 100 percent urinary recovery of up to 600 mg per kg doses of subcutansously injected sodium tartrate or orally administered sodium .potassium tartrate. Similar results were found in rats; 60 to 85 percent of an oral dose and 75 to 90 percent of a subcutaneous dose were recovered in the urine when 400 mg per kg sodium potassium tartrate was administered.

 

In guinea pigs, there was almost quantitative urinary recovery of parenterally administered sodium potassium tartrate, while only about 12 to 18 percent of the substance was recovered when administered by stomach tube.

 

The metabolism of sodium potassium tartrate in man was also studied by Underhill and his colleagues (23). Whether the tartrate was in stereoisomeric form not stated but probably L(+)] was administered by mouth in doses of 5.3 totartaric acid equivalents, about 20 percent was excreted in the urine; none was detected in the feces even after purgative doses. The urinary excretion of the substance was rapid and usually complete within 10 hours. The investigators concluded that in man, tartrate is apparently metabolized during its passage through the alimentary canal, most likely by bacterial action in the large intestine.

 

In 1933, Finkle (24) examined the metabolism of tartrates in male subjects. Following the oral administration ofof L(+) tartaric acid to 12 subjects, 11 to 24 percent was excreted in the urine (average 17 percent). When L(+) sodium tartrate was injected intramuscularly into 10 subjects in doses of 1.0 to, it was eliminated almost quantitatively (85 to 99 percent) within 12 hours. In no case were any traces of tartrates demonstrated in the feces. Finkle concluded the tartrates are not metabolized by the human body and suggested that the portion of tartrate given orally that failed to appear in the urine is destroyed in the intestinal tract by bacterial action.

 

Pratt and Swartout (25) demonstrated in a series of in vitro tests that sodium potassium tartrate, postassium acid tartrate and tartaric acid are readily degraded by intestinal bacteria.

 

In 1957, Bauer and Pearson (26) studied tartrate metabolism in man using more specific techniques for tartrate analysis than those of earlier investigators (18,19,22,24). Volunteer subjects (age, sex, or number of subjects not stated) were givenoral doses of either D-, L- or DL-tartaric acid. In four trials with the L(+) isomer, 12.2, 7.4, 6.4 and 0.4 percent of the dose

was recovered from the urine within 12 hours. One trial with the D(-) isomer gave no detectable urinary tartrate and four trials with the DL racemate gave 4.3, 2.0, 0.9 and 0.5 percent urinary recovery. Tartaric acid was also administered by intramuscular injection in about 750 mg doses. In four trials with the L(+) isomer, there was 16.5, 12.4, 11.7 and 6.35 percent urinary recovery of the injected dose. In two trials with the D(-) isomer, there was 1.86 and 0 percent urinary recovery.

 

Bauer and Pearson (26) concluded that, contrary to earlier reports (23,24), the different forms of tartrate are metabolized in human tissues when given in small amounts.