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Tartaric Acid

Date: 1991 (est.)
Length: 16 pages
87852379-87852394
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Packman
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Pohl
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Reid
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Saneyoshi
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Smith
Swartout
Underhill
Yoshida
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87852359/87852400/White Papers Lrc 910000
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Codex Alimentarius
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Independent Scientific Comm on Smoking +
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Joint Fao Who Expert Comm on Food Additi
Litton, Litton Labs
Nas, Natl Academy of Sciences
Select Comm on Gras Substances
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CONFIDENTIAL - PREPARED FOR COVINGTON & BURLING Tartaric Acid Background Tartaric acid (CAS No. 87-69-4/L- form; 133-37-9/racemic D,L- form) is the common name for the four-carbon dihydroxy dicarbo- xylic acid. Because it has two chiral centers, tartaric acid can exist in several stereoisomeric forms. The iaost common and com- mercially important form, and the primary focus of this report, is the L-form. Solutions of L-tartaric acid are dextrorotatory and so a more complete name is L(+)-tartaric acid. This material is often called natural tartaric acid (Arctander, 1969; Merck, 1983). The D-form is levorotatory and thus is properly called D(-)-tar- taric acid. The meso-form is optically inactive due to its molecular symmetry. Finally, there is a racemic form, or D,L- tartaric acid, which is a mixture of equal amounts of the D(-) and L(+)- forms and is optically neutral (Kirk-Othmer, 1978). Appen- dix I provides further information on the properties of tartaric acid. Unless specified otherwise, the term "tartaric acid" refers to the L (+) - form. Tartaric acid is a naturally occurring component of the fruit or other parts of several plants, most notably grapes. It exists both as the free acid and as salts of potassium, calcium, or mag- nesium. The mono-potassium salt, cream of tartar, was observed in antiquity as a finely crystalline deposit that formed during the fermentation of grape or tamarind juice and was called Faecula (little yeast) by the Romans. Free crystallized tartaric acid was first obtained from these fermentation residues by Scheele in 1769 and, in fact, by-products of the wine industry are still the only commercial source of the material. Although the wine industry is the source of the over- whelming majority of tartaric acid, other methods of preparation have been reported such as extraction from tamarind pulp and various chemical methods (Merck, 1983). The usual commercial process of synthesis yields the racemic (D,L) form (Lewis, 1977). D(-)-Tartaric acid has been found in nature in the fruit and leaves of Bauhinia reticulata, a tree native to Mali in western Africa. It may also be obtained by resolution of the racemate through the d-methylamphetamine salt (Kirk-Othmer, 1978; Merck, 1983). Racemic tartaric acid is not a product of plant processes but is formed readily from the natural, dextrorotatory acid by heating
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-2- alone or with a strong alkali or strong acid (Kirk-Othmer, 1978). Meso-tartaric acid is not naturally occurring but is obtained from other isomers by prolonged boiling with alkali. Tartaric acid oc- curs as colorless or translucent crystals or a white crystalline powder. Being odorless, it has no direct uses in the perfumery industry. It is, however, used as a sequestrant or, indirectly, as a bleaching agent for essential oils that are contaminated and colored by iron. Among these oils are patchouli, vetiver, copaiba, and clove leaf oil (Arctander, 1969). Tartaric acid has a strong, tart taste and an ability to augment the flavors of fruits in which it is a natural constituent. This is particularly true with natural and synthetic grape flavors. It is widely used in grape- and lime-flavored beverages because of its effect on the flavor. It is used as an acidulant for grape- flavored and for tart-tasting jams, jellies, and candies (Furia, 1972). Other uses of tartaric acid, primarily as an acidulant, include soft drinks, confectionery products, bakery products, and gelatins (Merck, 1983). Based on a 1970 FEMA/NAS survey, tartaric acid is reportedly used in foods at levels from 60-10,000 ppm; based on these levels, a possible average daily intake of 1703 mg was calculated. A survey made in 1975 indicated -440,000 kg was added annually to foods (FEMA, 1976; FASEB, 1979). Both tartaric acid and its monopotassium salt (cream of tartar) are common ingredients of baking powders and leavening systems. The acid serves to accelerate the leavening reactions during baking (Furia, 1972). Tartaric acid may be used as a synergist with antioxidants to prevent rancidity. It also acts to prevent discoloration in cheese and as a chelating agent in food containing animal or vegetable fats and oils (Furia, 1972). The diethyl and dibutyl esters are used in lacquers and in textile printing (Merck, 1983) Tartaric acid has been shown to impart an acrid note to both the smoke aroma and taste of flavored cigarettes (Leffingwell et al., 1972). - ~ Regulatory Status L(+)-Tartaric acid has been granted GRAS status by FEMA (Arctander, 1969). It has also been affirmed as GRAS as a general-purpose additive for food (21 CFR 184.1099) and animal feed (21 CFR 582.1099) by the Food and Drug Administration. It is also approved by the FDA for use in artificially sweetened fruit preserves and jams (21 CFR 150.161), margarine (21 CFR 166.110), antacids (21 CFR 331.10) and is a component of color additive,
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-3- grape skin extract (21 CFR 73.170). Tartaric acid is a permitted ingredient in over-the-counter antacid products (21 CFR 331.10) and vaginal drug products. L(+)Tartaric acid has been listed as an approved ingredient for tobacco products in the United Kingdom by the Independent Scientific Committee on Smoking and Health at levels not to exceed 2.0 percent in cigarette, cigar, or handrolling tobacco and 4.0 percent in pipe tobacco (Department of Health and Social Security, 1979). D- and DL-Tartaric acid are included in the list of Japanese Food Additives (1983). The Council of Europe (1981) included L(+)-tartaric acid in the list of flavoring substances which may be added to foodstuffs without hazard to public health. The Joint FAO/WHO Expert Committee on Food Additive (JECFA) allocated an average daily intake level of 30 mg/kg body weight for total L-tartaric acid and L-tartrates. L(+)-Tartaric acid is listed as an acidity regulator in the Codex Alimentarius (1983). It is permitted to be used in tomatoes, asparagus, pears, strawberries, and margarine at maximum levels limited by GMP (Good Manufacturing Practices). It is also per- mitted to be used in jams, jellies, and citrus marmalade (3 g/kg), cocoa powders (5 g/kg), and bouillons and consommes (250 mg/kg). Metabolism The metabolism of tartrates has been studied extensively. Very early studies (Pohl, 1896; Brion, 1898; Neuberg and Saneyoshi, 1911) with dogs and rabbits concluded that tartaric acid is par- tially oxidized by the-tissues and partially excreted in the urine (Informatics, 1974). Later work identified the gut flora as the major metabolic route for orally administered tartaric acid (Simp- son, 1925; Underhill, et al., 1931 a,b; Finkle, 1933; Pratt and Swartout, 1933; Dupuy, 1960). Bauer and Pearson (1957) concluded that tartrates are only in a small part eliminated in the urine after dosing a human subject orally and intramuscularly with 0.72 - 2.0 g of tartaric acid and recovering 0.4 - 16.5% of the dose from the urine. Several more recent studies have been conducted using radio- labelled tartrates. Chasseud et al. (1977) dosed adult rats Tially or by iv tail vein injection with 400 mg/kg monosodium C-L(+)-tartrate in aqueous solution14 At 48 hours after the oral dose, 70.1%, 13.6% and 15.6% of C had been excreted via the urine, feces and expired air, respectively. Following the iv dose, 81.8%, 0.9%, and 7.5% had been excreted via the urine, feces, and expired air, respectively.
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-4- Down, et al. (1977) studied the uptake of 14C-L(+)-tartrate in the kidneys andAone. Ten rats were dosed orally with 2.73 g/kg/day monosodium C-L(+)-tartrate for 7 days. Additional groups of 8 (2.57 g/kg/day) and 2 (2.73 g/kg/day) were included for whQie-body autoradiography and liver and kidney samples. Monosodium C- DL(+)-tartrate was tested simultaneously. Comparative results showed peak radioactivity concentrations in whole-blood and plasma at 1 and 3 hours (L(+)- and DL-tartaric acid, respectively) fol- lowing the final dosage. Whole-body autoradiography showed that radioactivity was present mainly in the bone, liver, kidneys, and gastrointestinal tract 3 hours after the last dose of both iso- mers. Examination of the bones revealed peak concentrations at 1 and 12 hours (L(+)- and DL-isomer, respectively) following the last dose. At 96 hours after the final dose, DL-tartrate concen- tration in the bone was twice that of L(+) tartrate. Radioactiv- ity retention in the rat kidney was much greater with DL-tartrate than with the L(+)-isomer. Kidney:body weight ratios showed DL- tartrate localization was accompanied by significantly increased kidney weight. Aggregated radioactive particles of DL-tartrate were present in the cortex and medulla of the kidneys and were de- tectable at 192 hours following the last dose. Histological exam- ination of the kidneys revealed crystalluria and focal chronic inflammation of the interstitium in the DL- tartrate-treated rats. Additionally, eosinophilic granulocytes and macrophages (con- taining birefringent crystalline material) were detected in the lumen of a few tubules. Kidneys from L(+)-tartrate treated animals were normal. Lewis (1977) studied the distribution of L(+) and1JL-tartaric acid by dosing rats orally at levels of 2.73 mg/kg of C-L(+) or DL- tartate. At three hours, most of the radioactivity was present in the kidneys, liver, bone and gastrointestinal tract. At 24, 48, and 192 hours DL-tartrate was still detectable in the kidneys; however, no L(+)-tartrate was detected at these time points. Lewis concluded that the poorly soluble calcium salt of DL-tar- trate resulted in renal retention of DL-tartrate; L(+)-tartrate which is more soluble, was not retained in the kidneys. Chadwick et al. (1978)latudied DL-tartrate metabolism in man and rats. Monosodium DL-[ C]-tartrate was given orally and iv to man; rats were dosed orally, ip and by diyict caecal injection. Rats were administered 20 uCi sodium DL-[ C] tartrate with 18.8 mg L(+)-tartrate as carrier by all three route14 In man, five subjects were given an oral dose of 5 pCi DL-[ C]-tartrate with 2.5, 5 or 10 g sodiuT4L(+)-tartrate as carrier and one subject received 10 pCi DL-[ C] tartrate with 125 mg sodium L(+)-tartrate as carrier by the iv route. In rats, 63% of the sodium DL-tar- trate dose was excreted unchanged in t~Z urine within 24 hr of ip administration and 9% was excreted as C02 within 6 hours. Fol- lowing oral administiition only 51% of the dose waslixcreted in the urine while 21% C appeared in expired air as CO2. After caecal injectio~, less than 2% was excreted in the urine and 67% was expired as CO2. In man only 12% of the dose was excreted
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-5- unchanged in the urine with 46% released in the breath. Following iv administration to one subject only, 64% of the dose was ex- creW in the urine over 22 hr and 18% was excreted in the breath as CO2 over 8 hr. The results of this study indicate that the major site of Wtrate metabolism is the intestine, although the liberation of CO2 following parental administration does indicate some metabolism by body tissues. Gry and Larsen (1978) compared the metabolic fate of L(+) and D(-)-tartaric acid in different species (rats, guinea pigs, and pigs) in vivo following oral administration and in vitro after incubation with caecal extracts. Rats treated with 1000 mg/kg of both isomers excreted 72.9% L(+)- and 52.1% D(-)-tartaric acid in urine after 48 hours with no reported kidney damage. In the guinea pig remarkable low urinary recoveries of both isomers (L(+)-3.6%) (D(-)-5.4%) were associated with marked kidney damage at 1000 mg/kg. In the pig, which exhibited an intermediate level of urinary excretion, (L(+)-isomer 26%; D(-)-isomer 33% of a 500 mg/kg dose), slight kidney effects were noted following oral administration of the L(+)-isomer. Caecal extracts incubated with the tartrate revealed no difference between the rat and the guinea pig in their ability to break down the tartrate. These results confirm earlier suggestions that rats and guinea pigs metabolize the compound differently and refute implications that gut flora destruction of tartaric acid is responsible for the observed dif- ferences between the two species. The investigators suggested that some correlation may exist between low recovery in the urine and kidney damage. They further reasoned that the guinea pig may be a more suitable model for assessing tartaric acid toxicity since the reported urinary recovery in humans following oral administration of tartaric acid is low, 17% (Finkle, 1933), the metabolic route is different in rats and humans, and the rat kidney exhibits an insensitivity to kidney damage. Acute, Subchronic, and Chronic Toxicity A thorough evaluation of the safety of tartrates, including tar- taric acid was made by the Select Committee of GRAS Substances (SCOGS) in 1979 (FASEB, 1979). Other reviews are also available (FEMA, 1976; Informatics, 1974). Information from these reviews and more recent data are included below: Acute toxicity values for tartaric acid are listed below (isomer not specified, but probably L(+)): Compound Test Route Species Value Na-Tartratea b LD50 Oral Rat 1290 mg/kg Tartaric Acid LD50 Oral Rat 920 mg/kg
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-6- Compound Test Route Species Value Na-tartratec d LD O Oral Mice 4370 mg/kg Na-tartrate d LDQ Oral Rabbit 3910 mg/kg Tartaric Acid LD50 IV Mice 485 mg/kg a(Merck, 1968) ; b(Litton, 1975a) ; c(Locke et al., 1942) ; d(Horn et al., 1957) Oral doses of 3.5-4.0 g/kg of L(+)-sodium tartrate to rabbits produced no effect, including no renal damage (Salant and Smith, 1914 in Informatics, 1974). Oral doses of > 5.0 g/kg were fatal. In animals dosed with 8-10 g/kg of L(+)-sodium tartrate, diarrhea was noted. Intravenously administered L(+)-sodium tartrate caused death at 4.2 g/kg and transient albuminuria was produced at sub-lethal injections of 400 mg/kg (Salant & Smith, 1914 in Informatics, 1974). Cats fed 10-16 g/kg of sodium tartrate (isomer not specified) developed vomiting and severe diarrhea (Salant and Smith, 1914 in Informatics, 1974). One of two cats that received 16 g/kg died. When given subcutaneously, 2.0 g/kg was fatal to 3 out of 4 cats, and 1.5 g/kg was fatal to 2 out of 3 cats. Two cats given 1 g/kg sodium tartrate subcutaneously developed albuminuria (Salant and Smith, 1914 in Informatics, 1974). Packman et al. (1963) performed a subchronic study with 15 male rabbits for 150 days. The rabbits were maintained on a diet containing 7.7% sodium tartrate (equivalent to 5% of tartaric acid) (isomer not specified). Examination of the adrenals, heart, kidneys, liver, lung, bladder, brain, prostate, stomach, spleen, testes, and thyroid were conducted at intervals during the study and at the conclusion of the study. There was no effect on growth, mortality, or food consumption, and no histopathological changes could be attributed to sodium tartrate. A two-year feeding study conducted by Fitzhugh and Nelson (1947) revealed no significant effects in growth rate (for the first year), mortality, gross pathology, or histopathology in rats fed diets containing 0.1-1.2% tartaric acid (isomer not specified). In a more recent study, Hunter et al. (1977) fed rats a diet containing 25,600, 42,240, 60,160 and 76,800 ppm monosodium L(+)-tartrate for two years. Survival was better in the three highest dose groups compared to control, likely due to a lower food intake and reduced body weight gain. No adverse clinical signs, and-no treatment-related changes in gross pathology or organ weights were observed. Histological examination of the tissues did not show evidence of toxicity or tumor induction attributable to treatment with monosodium L(+)-tartrate. Four dogs were orally dosed with 990 mg/kg tartaric acid (isomer not specified) for 90-114 days. Weight changes were varied from a
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-7- 30% increase to a 32% reduction in body weight relative to controls. Histological examination showed advanced renal tubular degeneration in one dog which died with azotemia after 90 days. The remaining dogs had casts in their urine and normal blood chemistry (Krop and Gold, 1945). The effect of occupational exposure to tartaric acid was investi- gated by Moscato et al., (1983). As reported in an abstract of this Italian study, 44 factory workers exposed to tartaric acid and a control group of 30 subjects (non-exposed) were evaluated by questionnaire , otorhinolaryngologic examination, spirometry, and a bronchodilatation test with salbutamol. Results of this study indicated that tartaric acid exposure caused increased incidences of oropharyngeal and cutaneous lesions, but no effect on dental, bronchial and gastric lesions was noted. Mochizuke et al., (1989) investigated how tartaric acid affects gastric secretion and pepsin activity. DL-Tartaric acid was oral- ly administered to five male Wistar rats in which the pylorus was ligated at a dose of -75 mg/kg. Control rats received distilled water. The stomachs were removed four hours after administration and their contents analyzed. DL-Tartaric acid had no effect on the volume or pH of the gastric juice as compared to control. Total gastric HC1 content (meq/L) was not altered, however, total acid content was significantly elevated above control (p <0.05). Pepsin activity expressed as pg/mL or pg/100 g body weight was not changed by the oral administration of tartaric acid. Carcinogenicity No information pertaining to the carcinogenicity of this compound was revealed in literature reviews conducted in 1989 and 1991 other than the aforementioned negative chronic rat study by Fitzhugh and Nelson (1947). Genotoxicity The mutagenic potential of L-tartaric acid was assessed in the Ames Salmonella/microsome reverse mutation assay using strains TA-1535, TA-1537, TA-1538, TA-98 and TA-100. No mutagenic activ- ity was detected in a range of doses from 100 to 1000 pg/plate both with and without a rat S9 microsomal activation system. This result provides evidence that neither L-tartaric acid nor its met- abolites are likely to pose a mutagenic or carcinogenic hazard. L(+)-potassium acid tartrate was not mutagenic to S. cerevisiae or strains TA 1535, TA 1537, and TA 1538 of S. typhimurium with and without activation (Litton, 1975b). Single oral doses of 1.25-125 mg/kg and single oral doses of 500-4000 mg/kg or 5 consecutive daily oral doses of 14.5 g/kg L(+)-tartaric acid were utilized in a series of host-mediated, dominant lethal and cytogenetic studies (Litton, 1975a). S.
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-8- cerevisiae and strains TA 1530 and G-46 of S. typhimurium were used with male ICR mice in the host-mediated assay. The dominant lethal assay utilized male rats. Both the dominant lethal assay and the host-mediated assay were negative, providing evidence that L(+)-tartaric acid is not mutagenic. Fifteen male albino rats per dosage level were utilized in the cytogenetic studies. No signif- icant increase in aberrations was seen in metaphase chromosome spreads at any dosage level from animals sacrificed at 6, 24, and 48 hours after dosing. Additional cytogenetic studies were performed in the human embryonic lung cell line WI-38. Twenty- four hour in vitro incubation at concentrations of 1, 10, and 100 pg/mL tartaric acid produced no excess chromosomal abnormalities (Litton, 1975a). An unscheduled DNA synthesis (UDS) assay in rat primary hepato- cytes was conducted to assess the potential of L-tartaric acid to produce DNA damage as indicated by increased DNA repair synthesis. Five treatments ranging from 25.0 to 1000.0 pg/ml were analyzed for UDS. L-tartaric acid did not cause a significant increase in UDS as measured by an increase in autoradiographic nuclear grain counts compared to untreated control hepatocytes. This material was therefore considered negative in this assay, suggesting DNA alterations were not produced. Developmental and Reproductive Effects Reid (1973) studied the teratogenic potential of L(+)-tartaric acid by the injection of L(+)-tartaric acid into the air cell or yolk of 96-hour chick embryos. Doses of 8 mg/kg and above were toxic; however, there were no statistically significant occur- rences of abnormalities that would indicate teratogenicity of L(+)-tartaric acid. A series of tests were conducted to determine the teratogenic potential of L(+)-tartaric acid (FDRL, 1973). Pregnant mice, rats, hamsters, and rabbits were orally administered doses of L(+)-tartaric acid ranging from 2.7-274 mg/kg for 10 days, 1.8-181 mg/kg for 10 days, 2.3-225 mgtkg for 5 days, and 2.2-215 mg/kg for 15 days, respectively. The mice, rats, hamsters, and rabbits were subjected to Cesarean section on days 17, 20, 14, and 29 of gestation, respectively. L(+)-tartaric acid exhibited no terato- genic activity in mice, rats, hamsters or rabbits under the given test conditions. Cardiovascular/Respiratory Toxicity An assessment of the potential of L-tartaric acid to affect the function of the cardiovascular and respiratory systems was con- ducted by its intravenous administration to two anesthetized young adult female beagle dogs. Ascending doses of 0.3, 1.0, 3.0, 10.0, 30.0, and 100.0 mg/kg were delivered in a 0.9% saline vehicle by
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-9- slow cephalic venous infusion as a battery of parameters were re- corded, including arterial blood pressure, heart rate, femoral blood flow, left ventricular systolic pressure, left ventricular dP/dt max., ECG (Lead II), respiration rate and tidal volume. A variety of parameters were calculated from the recorded values, including minute volume, mean blood pressure, peripheral resis- tance, isovolumic time, cardiac output index and cardiac effort index. With the exception of peripheral resistance, no changes were ob- served in any of the parameters of cardiovascular or respiratory function which were attributable to intravenous administration of L-tartaric acid at doses of 0.3 to 10 mg/kg. A large increase in peripheral resistance (usually a compensatory response to de- creases in blood pressure) was observed in one dog following administration of L-tartaric acid at a dose of 3.0 mg/kg. Most of this increase occurred after the initial 10-minute post dose period; however, similar large increases were observed following administration of L-tartaric acid at a dose of 30.0 mg/kg in this animal and at 100.0 mg/kg in the other animal, so this response was considered a test article-related effect. Intravenous administration of L-tartaric acid at doses of 30.0 mg/kg caused a drop in blood pressure, heart rate, left ventri- cular systolic pressure, dP/dt max., cardiac output index and cardiac effort index. Peripheral resistance fell after admini- stration of L-tartaric acid at a dose of 100.0 mg/kg. Increases were observed in respiration rate, isovolumic time, and femoral flow. Tidal volume and minute volume were increased in both dogs at a dose of 30.0 mg/kg, but in only one of the dogs at a dose of 100.0 mg/kg, so this effect could be test article related. No changes in the ECG (Lead II) were observed in either of the animals after administration of L-tartaric acid at doses between 0.3 and 10.0 mg/kg. At a dose of 30.0 mg/kg, an increase in the size of the T-wave was observed in one animal, and a decrease was observed in the other. After administration of L-tartaric acid at a dose of 100.0 mg/kg, an init'ral increase in the length of the S-T segment was observed in both animals; this was accompanied by an increase in the size of the T-wave in one dog, and a decrease in the height of the T-wave in the other. The length of the S-T segment rapidly returned to normal in both animals as did the de- crease in T-wave height in one dog. In the other dog, the T-wave was reduced in height for the remainder of the experiment. The no observable effect level (NOEL) for L-tartaric acid was determined to be 1.0 mg/kg in this study. These results indicate that L-tar- taric acid can effect the cardio-pulmonary system in dogs when ad- ministered at high dose levels. Effects of this type are not ~ anticipated under actual conditions of use. ~ ~ Cn
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-10- Hepatic Enzyme Induction An evaluation of the potential of L-tartaric acid to induce hepatic microsomal enzyme activity was performed in female Sprague-Dawley rats. Groups of seven animals were administered daily oral doses of 0 (vehicle, distilled water) 625, or 2000 mg/kg L-tartaric acid for four consecutive days. Three enzyme assays were employed to evaluate Cytochrome P-450 and P-448 activity: 1) p-nitroanisole-0-demethylase (PNAS), a marker for P-450 induction; 2) 7-ethoxycoumarin-0-deethylase (7EC), a marker for P-448 and P-450 induction; and 3) 7-ethoxyresorufin-0- deethylase (ETR), a marker for P-448 induction. No statistically significant changes were observed in liver weights or liver-tobody weight ratios at either dose level. PNAS and ETR activities at both dose levels were similar to those of the vehicle control. 7EC activity was significantly increased (approximately 3-fold) above control in the 2000 mg/kg group. These findings do not indicate a significant potential for L-tartaric acid to induce a broad spectrum of xenobiotic metabolizing enzyme activity at moderate or high doses. Immunotoxicity An evaluation of the immunosuppressive potential of L-tartaric acid was performed following its daily oral administration to female CD1 mice at dose levels of 0 (vehicle, distilled water) 750, 1500, and 3000 mg/kg for five consecutive days. This... screening test measured the ability of L-tartaric acid to modulate host resistance to infectious challenge with an LD10-30 dose of Listeria monocytogenes bacteria and to alter the numbers of antibody plaque-forming cells (PFC) produced following immun- ization with sheep red blood cells (SRBC). The effects on spleen and thymus weights,. spleen cellularity and spleen cell viability were also determined. L-Tartaric acid had no effects on host resistance at dost levels as high as 3000 mg/kg. Dose-related decreases in PFC/10 viable spleen cells and PFC/spleen were observed at the top dose, but these changes were not statistically significant. The most no- table changes occurred at dose levels associated with clinical observations and mortality and thus appeared to be effects second- ary to acute systemic toxicity. These findings demonstrate a lack of significant immunosuppressive potential attributable to L-tar- taric acid at subtoxic dose levels. Pyrolysis A literature search through April, 1991 revealed no information about the direct pyrolysis of tartaric acid.

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