188 Biomed Res Trace Elements 16(3) 188 197 2005

Review Articles

Recent prOgreSS in eXplOring the eSSentiality Of the nOn-metallic ultratrace element arsenic tO the nutritiOn Of animalS and man

Manfred Anke, Ralf Muller*), Ulrich Schafer

Institute of Nutrition and Environment, Faculty of Biology and Pharmacy, Friedrich Schiller University Jena, D-07743 Jena, Germany ; *) Society of Ecology and Environmental Chemistry Ltd., Zittauer Str. 27, 99091 Erfurt, Germany

Abstract Semisynthetic feeds with < 35 pg arsenic (As)/kg feed dry matter (DM) reduced the intrauterine growth rate, success of first insemination, conception rate and milk production, and increased the abortion rate and mortality of goats, minipigs, rats and chickens. None of the pregnant, As-deficient goats survived the second lactation. Death regularly occurred between the 17th and 35th day of lactation ; typically, animals suffered spasms and died shortly thereafter. The normative requirement of goats, minipigs, rats and chickens is < 50 ,lg As/kg diet DM, while that of human adults is < 10 pg/day.

Keywords : arsenic, essentiality for animals, geological inf luences, intake by man, foodstuf f s

Introduction of the arsenic-poor nutrition of the goats were The first suggestions of the essentiality of arsenic repeated 13 times with 81 control and 90 arsenic- were made in 1975 and 1976 by two laboratories, each deficient goats. A11 animals completed the trial of which was unaware of the other's investigations [1, throughout their natural life-span. 2]. The arsenic-deficiency experiments in growing, In their first year of life, control and arsenic- pregnant and lactating goats were repeated over 13 deficient goats consumed similar amounts of feed (687 generations. Likewise, the arsenic-deficiency trials and 680 g/day). On average, the surviving arsenic- with growing, pregnant and lactating miniature pigs deficient adult goats ate 7% more semisynthetic feed and their offspring after intrauterine development than did controls (629 and 674 g/day, respectively) were repeated twice L2, 3, 4]. The signs of arsenic L71 . deficiency in minipigs and goats were reviewed by On average, the arsenic-poor diet reduced intrauter- Anke et al. [5, 6, 7, 8, 9], and those for rats and ine growth by 6% or 182 g in 133 and 100 kids, respec- chickens by Nielsen LIOI and Uthus et al. L1l]. tively L12J . Similar effects of arsenic deficiency were Informations to material and methods are given by demonstrated in minipigs L2]. During the suckling Anke et al., Res. Trace Elements, 16 : 2005. period, arsenic-deficient kids gained less weight than control kids. Intrauterine arsenic-depleted kids grew Essentiality of arsenic for animals more slowly than did kids without intrauterine arsenic Semisynthetic feeds of the goats contained 35 pg depletion and control kids (9 and 17%, respectively) As/kg DM, while the control animals received 350 pg L14, 3]. As/kg DM (Table 1). The experiment on the influence Arsenic deficiency reduced significantly the success of the first service and the conception rate of the Address correspondence to : arsenic-deficient goats (11 and 29%, respectively, of M:anfred Anke, Am Steiger 12, the control and arsenic-deficient goats remained bar- D-07743 Jena, Germany ren). Arsenic deficiency increased the abortion rate E-mail : [email protected] and reduced milk production by 20%. The mortality TEL : + +49 3641 448536 of kids was 6% (control) and 32% (deficient kids). FAX : + +3641 448536 None of the pregnant arsenic-deficient goats survived Recent progress in exploring the essentiality of the non-metallic ultratrace element arsenic to the nutrition of animals and man 189

the second lactation L15, 16, 17, 18]. vomiting, diarrhea, marked depression, and dermatitis Barren arsenic-deficient goats achieved an age of 6 usually due to increased capillary permeability and years. Death regularly occurred between the 17th and cellular necrosis. 35th day of lactation ; typically, animals suffered The essential, beneficial and toxic effects of arsenic spasms and died shortly thereafter [19, 20, 21, 22J. are very important and similar to those of , Arsenic deficiency also led to a significantly as recorded in the past. Hence, in future it may be reduced ash content in the goat skeleton [2], and to necessary to examine the three aspects (essential, damage to the legs of chickens [1l]. A systematic beneficial and toxic effects) of this element L23, 24, 25, investigation of the skeleton and cardiac muscles and 26, 271. livers of arsenic-deficient goats shortly before death The normative arsenic requirement of the fauna showed ultrastructural changes with electron-dense was calculated to be < 50 pglkg feed DM L261. The material deposited in the mitochondrial membrane of arsenic demand of animals is satisfied by feedstuffs skeletal muscle, cardiac muscle and liver. At an and water in Central Europe L28]. advanced stage, this electron-dense substrate is released from the mitochondrial membrane and is Influence of the geological origin of the soil on the detectable in the cytoplasm. It has been suggested that arsenic content of the vegetation this material was insoluble phosphate, and The geological origin of the site has a significant that this change is a form of mitochondrial myopathy. effect on the arsenic concentration in plants. By It is possible that cardiomyopathy, in association with means of indicator plants, i.e, shooting wheat, rye in a derangement of the cardiac mitochondrial structure, blossom, field red clover in bud and meadow red may be caused by arsenic deficiency, though the fun- clover in blossom, it was possible to demonstrate the damental mode and site of action of the element are significant influence of the geological origin of the site yet to be identified L19, 20]. on the arsenic content of the flora. The arsenic con- Arsenic poisoning is commonly an acute clinical tents of rye and wheat grown together on an area of syndrome, and death usually occurs rapidly. Clinical 1 m2 correlated significantly (r = 0.79). The arsenic signs of acute arsenic toxicity include colicky pain, concentrations of two species grown on soils of the

Table 1 Influence of arsenic-poor nutrition on feed intake, growth, reproduction performance, mortality and tissue compositlon of goats

%1) = Control goats = 100 %, arsenic-deficient goats = x %; P2) = Significance level in the t-

test according to Student 190 Bromed Res Trace Elements 16(3) : 188-197, 2005

Table 2 Influence of the geological origin of the site on the relative arsenic contents of the flora and drinking water (Indicator plants n= 797 ; drinking water n= 120)

nl) = Number

~~.' ~ 25 oc:~ 20 =go 15 12 13 13 10 ~ 10 4 4 o 1 2 2 ~ 5 o 15a' O GZ <19 20- 40- 60- 80- 100- 120- 140- 160- 180- >200 39 59 79 99 1 1 9 1 39 1 59 1 79 1 99 Arsenle Intake pg/day laverage of a week)

Figure I Frequency distribution of the daily arsenic Figure 2 Frequency distribution of the daily arsenic intake by women intake by men same geological origin correlated (r = 0.72) for wheat of the vegetation, but also the arsenic content of the and rye, (r = 0.49) for wheat and field red clover, (r = drinking water (Table 2). The waters coming from 0.68) for wheat and meadow red clover, (r = 0.63) for gneiss, Rotliegende, alluvial riverside and loess soils rye and field red clover, (r = 0.47) for rye and meadow contain 2.3 pg/L of arsenic, whereas those from red clover, and (r = 0.44) for field and meadow red Bunter, Keuper, slate and phyllite soils contain only O. clover L29]. The vegetation richest in arsenic is 75 pg/L of arsenic L28]. produced on gneiss weathering soils in Central Eur- ope. Table 2 shows the arsenic levels of the flora from Arsenic intake by humans other soils relative to that from gneiss weathering The arsenic intake by women and men was inves- soils equaled to 100. The vegetation from the gneiss tigated by means of the duplicate portion technique and granite weathering soils of the arsenic province in over 7 subsequent days in 14 test populations in the Ore Mountains of Germany accumulated, on aver- Germany. Both sexes collected all foodstuffs, bever- age, six times the arsenic amount in comparison to the ages and sweets every day. On an average, men take plants grown on soils outside the arsenic province. in more arsenic than women (Table 3), and ovolacto- The indicator plants grown on phyllite weathering vegetarians eat significantly lower amounts of arsenic soils had only twice the amount of arsenic in compari- than people with mixed diets. The consumption of son to that in plants outside this region. The results marine fish, which deliver particularly much arsenic obtained are in accordance with arsenic amounts in in form of arsenobetain, influences the arsenic intake soil L30]. considerably L12]. Ovolacto-vegetarians do not eat The flora on the weathering soils of the Triassic fish. This is the reason for their lower arsenic intake formation (Muschelkalk, Bunter, Keuper), on slate in comparison to people with mixed diet. On the other and especially on phyllite weathering soils is relative hand, the mean dry matter intake by men with mixed poor in arsenic. The geological origin of the soil diet was 24% higher than that of women, and that of greatly influences not only the arsenic concentration vegetarians was approximately 26% higher than that Recent progress in exploring the essentlality of the non-metallic ultratrace element arsenic to the nutrltlon of animals and man 191

Table 3 Arsenic intake by German adults with mixed and ovolacto-vegetarian diets depending on time and gender (pg/day) (n= 1456)

1) Fp = Significance level in one-factorial or multifactorial variance analysis; 2) x = Arithme-

tic mean; 3) Standard deviation

Table 4 The arsenic contents of several cereals (llg/kg dry matter)

1) Wheat = 100%, Oat = x % of people with mixed diet [311. Due to their different women, 58% men). Animal foodstuffs and mainly dry matter intake, the arsenic consumption of women marine fish provide for only < 40% of the arsenic and men varies significantly (Table 3). On average, in intake by people with mixed diets. In Germany and Germany men with mixed diet consume 24%, male elsewhere in Central Europe, the contents of arsenic in ovolacto-vegetarians 40%, more arsenic than do drinking water and beverages are without importance women. Small amounts of sea fish increases the indl- for arsenic supplementation. vidual arsenic intake in Germany to four to six times the arsenic level in comparison to people eating no Arsenic contents of the foodstuffs marine fish Ll2]. Cereal products and pasta (Table 4) have a mean The total arsenic intake varies extremely with the arsenic content of 50 to 500 pglkg dry matter. Several consumption of sea-food (see standard deviation, foodstuffs of this group (flour for pancakes, macaroni, Table 3). Only Japanese and Spanish adults consume flour for dump]ings) get a certain proportion of their more arsenic L321. People in Germany and Central arsenic contents via additive substances. Others Europe take in more arsenic, because the combustion (white bread, rusk, wheat and rye bread etc.) contain of arsenic-rich lignite increases the arsenic emission significantly more arsenic than the original material and the arsenic concentration of locally grown food- for the production of flour-starch and cereal products, stuffs. The Provisional Tolerable Daily Intake (PTDI) i.e., than unprocessed cereals (Table 5). It is astonish- of 150 pg As/day or 2.1 pg/kg body weight L33] is, on ing that the processing of cereals increases their average, not exceeded by the test populations, but arsenic content very significantly. Worldwide, the three local teams of Greifswald near the Baltic Sea normal arsenic content in wheat, rye> barley and oat with a higher consumption of marine fish, and of Jena grains without pollution is < 50 pglkg dry matter L34] . in Thuringia, consumed > 150 pg/day (Greifswald 185 In Spain, the arsenic concentration in cereals was and 170 pg As/day ; Jena 170 and 188 and 205 and 254 found to be higher than 50 flg/kg dry matter L35J. pg As/day). The arsenic content of the drinking water Brown rice stores more arsenic than wheat and rye in Jena is normal, industrial arsenic emissions do not [36]. Generally, pulses (beans, Ientils, peas) accumu- occur. The reason for the high arsenic intake in Jena late a higher amount of arsenic than grains. The high is unknown. arsenic concentrations of peeled barley, oat flakes and For people with mixed diets in Germany, vegetable semolina in comparison to the whole grains is very foodstuffs supply the greatest share of arsenic (56% surprising. In Bangladesh, the concentration of arsenic 192 Biomed Res Trace Elements 16(3) 188 197 2005

Table 5 The arsenic contents of farinaceous products, flours and pulses (n 102)

1) DM = Dry matter 2) FS Fresh substance 3) s Standard devration 4) x Arrthmetrcal mean

Table 6 The arsenic contents of bread, cake and pastries (n 66)

Table 7 The arsenic contents of fruits (n 36)

in boiled rice was found higher than in the raw rice. about 190 and 690 pg of arsenic in dry matter, which The rice obviously absorbed part of the arsenic from is much more than the arsenic found in grains and the water used for boiling L36]. flours of wheat and rye. The reason for this phenome- Bread, cake and pastries are of special importance non is unknown. The investigated kinds of cake with regard to the food quantity consumed as well as showed arsenic concentrations of 350 to 580 pglkg of to energy and arsenic intake. Arsenic contents found arsenic in dry matter. This relatively high arsenic range from 200 to 700 pg/kg of arsenic in the dry content may result partly from the use of arsenic-rich matter (Table 6). Wheat and rye bread, toasted bread, additives (fat, eggs or cocoa) used in preparation. white bread rolls, which are the most frequently Fruits, same as grains, are poor in arsenic. Among consumed bread varieties in Germany, contained all fruits investigated, pineapple was found to store Recent progress in explorlng the essentiality of the non-metallic ultratrace element arsenic to the nutrition of animals and man 193

Table 8 The arsenic contents of vegetables and herbs (n 108)

Table 9 The arsenic contents of milk and dairy products (n 66)

the lowest arsenic concentrations, viz. 22 pglkg of Surprisingly, the main sources of arsenic are bread, arsenic in dry matter (Table 7). Oranges, bananas and cake and pastries. The arsenic concentration in cow's apples accumulate only 25 to 45 pglkg of arsenic in milk in Central Europe is relatively high. This is dry matter. With 150 pglkg dry matter, pears are caused by the high arsenic emissions of coal-burning relatively rich in arsenic. This is three times the power stations in the Czech Republic and Germany, amount of arsenic found in apples. which cause considerably increased levels of arsenic As expected, the arsenic concentrations of vegeta- in crops and water. Drinking water in the surrounding bles showed a relatively large variation (Table 8). countryside contained 70 pglL L39]. Most of the While the average arsenic contents of green dwarf several sorts of cheese are poorer in arsenic than milk. beans and potatoes are very low (approximately 20 Part of the milk's arsenic leaves the cheese with the pglkg dry matter), a maximum arsenic level of 350 whey. Butter and margarine are relatively rich in Itg/kg dry matter is found in mixed mushrooms. The arsenic. Yoghurt gets its high arsenic content through majority of vegetables investigated contained 50 to several supplements (Table 9). The arsenic content of 300 pglkg of arsenic in dry matter. Kohlrabi, Iettuce, cow's milk varies worldwide between 25 and 60 Ilglkg cultivated mushrooms (Agarius bisporus), asparagus, L40J or 200 to 500 pglkg dry matter. and cauliflower deliver 100 to 250 pg As/kg DM to the The arsenic content of the breast milk of women food chain of man. The highest arsenic intake is (11-57 pg/kg DM) corresponds to the arsenic level in through the consumption of edible seaweed (19 to 172 the milk of goats (colostral milk 10 pg As/kg DM, mg As/kg DM) L37, 38]. mature milk 24 pg/kg DM) with 350 pg As/kg DM 194 Biomed Res Trace Elements 16(3) : 188-197, 2005

Table 10 The arsenic contents of meat and offals (n 66)

Table 11 The arsenic contents of fish and tinned fish (n 42)

L41, 29] . The arsenic concentrations in German infant 60% of the total arsenic. Furthermore, when arsenic formulas corresponds to the higher arsenic levels in was determined in water-soluble and fat-soluble frac- cow's milk in Germany and varies between 160 and tions, the share of water-soluble arsenic reached 58 to 400 pglkg DM, which is relatively high. 97% of the total arsenic [45]. The arsenic contents of meat, offals and sausages The different preparations of herring (Table 11) vary greatly with the arsenic intake by the animals. contain, in good accordance with the literature, 1200 Generally, the arsenic content of sausage, with the to 1800 pg As/kg dry weight L46] . The level of arsenic exception of liver sausage, is lower than that of offals stored by herrings is low in comparison to several and meat (Table lO). Fat and blood dilute the arsenic other sea fishes. Rosefish, greenland cod and halibut, concentration in sausage. In Central Europe, the arse- and many other seafoods with the exception of whale nic level in the meat of chicken, pork, mutton and beef meat accumulate ten times more of arsenic in their varies between 250 and 560 pglkg dry matter, and edible tissues [47, 48]. Fresh water fish store much that in cow's liver and kidneys between 250 and 350 10wer arsenic concentrations than marine fish. Fresh- pglkg dry matter. These arsenic concentrations cor- water fish in lakes with higher arsenic concentration respond to the arsenic concentrations reported in the contribute correspondingly more arsenic to the food literature [42, 43]. Arsenic concentrations in the web. Planktivores have significantly more arsenic muscle, Iiver and kidneys of game (hare, wild boar, roe than omnivores L49]. deer, red deer, pheasant, duck) are lower than in farm In Central Europe, the arsenic concentration of animals L44J. drinking water varies between < 1.0 and > 10 pglL Most arsenic in the food web of man is delivered by (Table 2). In Germany, the limit of arsenic in drinking seafood (Table 11). Of the total arsenic stored by fish, water has been 10 pglL since 1996. More than 50% of ascidian, sea urchin, crustacean, shellfish, cephaloped, drinking water samples deliver < 1.0 pglL to the food polychaete and seaweed, only O to 7% is inorganic chain of farm animals and humans. Only 3% of the arsenic, which is more toxic than the organic variety. samples had > 10 pglL. Arsenic concentrations higher The only exception is a seaweed named Hisikia than 10 pglL usually have geological origins. fuszforme, in which inorganic arsenic accounted for Recent progress in exploring the essentiality of the non-metallic ultratrace element arsenic to the nutrition of animals and man 195

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