L-arabinose

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

An Intake Assessment was performed to estimate the average daily intake of L-Arabinose (L-ARA) with a habitual diet. Three main foodstuffs were considered, complemented by the intake of L-Arabinose by gum arabic as food additive. A rough estimate of the dietary L-Arabinose consumption could be calculated. The highest contributor to the L-Arabinose intake in humans is gum arabic, which is widely used as food additive. The range of L-Arabinose intake by consumption of gum arabic as food additive varies from 0.61 to 25.1 g for adolescents and 0.37 g to 19.8 g for adults. Natural plant based foodstuffs contain L-ARA as a part of the NSP fraction, which at least to some extend are broken down to monomeric L-ARA in the GI-tract. Through the intake data of three main foodstuffs: apples, pears and beans, they provide evidence of a substantial L-ARA consumption with the habitual diet. Dried beans may contribute substantially to the L-arabinose intake. With this high daily intake of L-ARA in polysaccharide bound form and partial hydrolysis in the GI tract in human, thereof it can be concluded that safety of L-ARA is substantiated. As there is no evidence of any adverse effect of this ubiquitous pentose, which is part of the human food chain, no further animal safety testing is necessary for REACH registration of L-ARA.

According to REGULATION (EC) No 1907/2006, Annex VIII/IX, testing for reproduction/developmental toxicity (section 8.7) may be omitted, if testing does not appear scientifically necessary. According to Annex XI section 1.1.2, adequate data on human health properties should be considered to be equivalent to data generated by the corresponding test methods referred to in Article 13 (3) if the following conditions are met: 1) adequacy for the purpose of classification and labelling and/or risk assessment; 2) adequate and reliable coverage of the key parameters foreseen to be investigated in the corresponding test methods referred to in Article 13(3); 3) exposure duration comparable to or longer than the corresponding test methods referred to in Article 13(3); and 4) adequate and reliable documentation is provided. In addition and in accordance with Annex XI section 1.2, relevant independent sources of information are available, leading to the conclusion that the substance has not a particular dangerous property. Therefore, further testing on vertebrate animals for that property shall be omitted where adequate and reliable data for the absence of a particular dangerous property is available.

Based on adequate data from the Intake Assessment, a history of safe use of L-Arabinose in humans can be concluded. There is no evidence of any adverse effect of this ubiquitous pentose, which is part of the human food chain. In the light of this habitual exposure to L-Arabinose, the safety of orally ingested L-Arabinose is evident and additional animal trials to study repeated dose toxicity including reproductive and developmental toxicity is unjustified. Also from an animal welfare perspective, unnecessary animal trials should be avoided when there is no indication for toxicity.

Link to relevant study records

Reference

Reference 1

Endpoint:

reproductive toxicity, other

Type of information:

other: Intake Assessment

Adequacy of study:

key study

Study period:

July 2017

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Qualifier:

no guideline followed

Principles of method if other than guideline:

The goal of this report was to assess the daily intake of L-Arabinose from selected food stuffing and food additives to provide a scientific basis for the safe use of L-Arabinose to avoid performing further animal testing based on the strong rational that there is a history of safe use in humans.

GLP compliance:

no

Limit test:

no

Sex:

male/female

Route of administration:

oral: unspecified

Vehicle:

unchanged (no vehicle)

Key result

Dose descriptor:

NOAEL

Based on:

test mat.

Sex:

male/female

Remarks on result:

not determinable due to absence of adverse toxic effects

Key result

Critical effects observed:

no

Key result

Dose descriptor:

NOAEL

Remarks on result:

not determinable due to absence of adverse toxic effects

Key result

Critical effects observed:

no

Key result

Reproductive effects observed:

no

1 Proposed approach

In the absence of specific data on the intake of free L-Arabinose (L-ARA), it was decided to estimate the intake of L-ARA as structural element of polysaccharides like pectins and hemicelluloses that are abundant in plant based foodstuffs. Such a calculation would allow a rough comparison of the intake of free L-ARA with the overall dietary intake of L-ARA by plant NSPs. To estimate the typical daily intake of L-ARA with regular food, a research on the public domain with respect to L-ARA content of different foodstuff was conducted. Candidates of interest were fruits, vegetables, cereals and pulses known to be rich in pectin and hemicelluloses, and plant gums, more specifically gum arabic, which to our best knowledge has the highest L-ARA content of all food components. The idea was to calculate the anticipated intake of L-ARA from plant-based foodstuffs by combining the concentration of NSP in these foodstuffs with their ARA content and the consumption of the respective foodstuffs.

2 Results

A comprehensive literature (PUBMED) research on the L-ARA contents in foodstuff was performed, using the search terms listed in Table 1. Our research confirmed a previous observation that rather little is known about the arabinose content in whole foodstuffs. The substantial efforts spent into the characterization of complex plant carbohydrate structures were mainly dedicated to their structural elucidation, much less to the quantification of the monomers that constitute the structures. If the constituents were quantified, they were usually isolated from specific fractions, like in dried tomato cell walls (Pantophlet et al., 2017), or in potato hemicelluloses, pectins or celluloses (Dawson et al.,1987). Hardly any data exist on the overall quantitative carbohydrate composition of nutritionally relevant sources.

That is in part caused by the technical challenges to analyse highly complex NSPs. In addition, the structure and concentration of polysaccharides is defined by the expression of the glycosylating enzymes but does not follow an individual, genetically determined blueprint like proteins. The monomeric constituents are only accessible after total hydrolysis of the compounds using glycosylases that are specific for the respective type of glycosidic bond and/or a monosaccharide structure.

 

Table 1:  Hits obtained in PUBMED search

Search term	Obtained hits (total)	Relevant publications after title screening	Relevant publications after abstract screeninq
Arabinose [Title/Abstract] AND content [Title/Abstract] AND food [Title/Abstract]	24	10	4
Arabinose [Title/Abstract] AND pectin [Title/Abstract] AND food [Title/Abstract]	15	7	3
Arabinose [Title/Abstract] AND fruit [Title/Abstract]	99	23	9
Arabinose [Title/Abstract] AND composition [Title/Abstract] AND food [Title/Abstract]	38	5	1
Arabinose [Title/Abstract] AND cereals [Title/Abstract]	12	1	0
Arabinose  [Title/Abstract]  AND crops [Title/Abstract]	16	3	2
Arabinose      [Title/Abstract] AND consumption [Title/Abstract]	113	4	2
Arabinose      [Title/Abstract] AND polysaccharide [Title/Abstract] AND food [Title/Abstract]	44	5	1
Arabinose [Title/Abstract] AND pulses [Title/Abstract]	1	1	1

All relevant publications were taken into consideration for getting a comprehensive picture of arabinose content in foodstuff.

The L-ARA content of different foodstuff is tabulated below (Table 2)

Table 2:  Arabinose content in different foodstuff

Food Category	Foodstuff	L-ARA content	Reference
Food	Gum arabic E414	32 - 53%	(Lobley et al.. 1990)
additive	Pectin E440(i) and E440(ii)	1.5 -20%	(European    Parliament and Council, 2008)
Foodstuff	Pear	450 - 980 mg/ pear differs with maturity level	(Gross and Wallner, 1979)
	Whole apple	11% Arabinose in soluble fibre 20.8% in insoluble noncellulose poiyaccharides	(Salvador et al., 2000)
	Japanese plum	21 - 45% of neutral sugars of water retractable pectin	(EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS), 2017)
	Cherry	43 - 77 mg/g juice pressed from different cherry fruits	(Muller-Maatsch et al.. 2016)
	Rice (stem)	14 % of hemiceiiuiose	(Ahmed and Labavitch, 1980)
	Sorghum (Stem)	9 % of hemiceiiuiose	(Chang etal., 1998)
	Sweet lupines	54.3 g/kg	(Basantaet al., 2012)
	Chick pea	34.43 g/kg	(Kosmala et al., 2009)
	Faba beans	26.13 g/kg	(Arai-Sanoh et al , 2011)
	Field peas	35.68 g/kg	(Arai-Sanoh et al , 2011)
	Pea hulls	32.2 g/kg (dry matter)	(Perez-Maldonado et al., 1999)
	Fresh cabbage	12.5 % of pectin	(Perez-Maldonado et al., 1999)
	Cabbage	19.3 - 22.3 g/kg (dry matter)	(Perez-Maldonado et al., 1999)
	Sugar beet (stem)	9 % of hemiceiiuiose	(Perez-Maldonado et al., 1999)
	Sweet potato	9% of pectin 12% of hemiceiiuiose 2.1 % of cellulose	(Longstaff and McNab, 1989)
	Potato	7.8 % of pectin 9.3 % of hemiceiiuiose 1.5 % of cellulose	(Muller-Maatsch et al.. 2016)
	Cassava	5.7 % of pectin 6.3% of hemiceiiuiose 1.1% of cellulose	(Longstaff and McNab, 1989)
	Carrot	12.7 - 13.4 % g/kg {dry matter)	(Arai-Sanoh et al . 2011)
	Tomato	1.6 - 2.2% of alcohol insoluble substances 2 % of dried cell walls	(Salvador et al, 2000) (Salvador et al., 2000)
	Olives	3.4 -4.3 % of cell wall material	(Salvador et al., 2000)
	Wheat	Arabinoxylans 1.35-2.75 % in flour. ARA: XYL = 0.65	(Longstaff and McNab, 1989)

 

Table 3: Summary of dietary Intake by gum arabic (E 414) from its use as a food additive in the maximum level exposure assessment scenario, the brand loyal and non-brand- loyal refined estimated exposure assessment scenario for two population groups (minimum—maximum across the dietary surveys in [mg/kg BW per day] (Noreen et al.2017)

	maximum level exposure assessment scenario				brand-loyal refined estimated exposure assessment scenario				non-brand-loyal refined estimated exposure assessment scenario
Population Group	Adolescents (10-17 years)		Adults (18-64 years)		Adolescents (10-17 years)		Adults (18-64 years)		Adolescents (10-17 years)		Adults (18-64 years)
	min	max	min	max	min	max	min	max	min	max	min	max
Mean	196.2	671	87.8	350.9	101.1	423.9	50.8	201.9	35	146	15	65.2
95^thpercentile	458.1	1433.1	221.6	811.4	290	1055.3	124.9	566.5	88.6	419.1	43.7	175.9

 

Table 4:  Summary of L-ARA dietary intake by gum arabic (E 414) from its use as a food additive in [g/day]

	maximum level exposure assessment scenario				brand-loyal refined estimated exposure assessment scenario				non-brand-loyal refined estimated exposure assessment scenario
Population Group	Adolescents (10-17 years)		Adults (18-64 years)		Adolescents (10-17 years)		Adults (18-64 years)		Adolescents (10-17 years)		Adults (18-64 years)
	min	max	min	max	min	max	min	max	min	max	min	max
Mean	3.43	16.44	2.15	8.60	1.77	7.42	1.25	4.95	0.61	2 ee	0.37	1.60
95^th percentile	8.02	25.08	5.43	19.88	5.08	18.47	3.06	13.88	1.55	7.33	1.07	4.31

3.1 Arabinose intake from food additives

The most prominent NSP that contain L-ARA are gum arabic and pectin. About 35 - 50% of gum arabic and between 1.5 and 20% of pectin consist of arabinose (Campbell et al., 1990).

3.1.1 Pectin

Pectin is widely used as food additive as texture modifier, thickener, coating and gelling agent in different food categories and pharmaceutical products. It is authorized as E440(i) – for non-amidated pectins and E440(ii) - for amidated pectin in several food categories according to in the European Union (EU) according to Annex II and Annex III of Regulation(EC) No 1333/2008. Pectins used for technological purpose are mostly derived from apple and citrus peel (Gross and Wallner, 1979). Since use levels are not available, pectin as additive could not be considered in this exercise.

3.1.2 Gum arabic

Gum arabic, also known as acacia gum, is a dried exudation obtained from the stems and branches of natural strains of A. senegal(L.) Willdenow or closely related species of Acacia (family Leguminosae). It is an authorised food additive (E 414) in the European Union (EU) according to Annex II and Annex III of Regulation (EC) No 1333/2008. The product is used primarily as stabilizer and is authorised in a total of 76 food categories. The maximum uselevel as indicated is quantum satis (QS) as defined in regulation (EC) No. 241/2008 (Jimenez et al., 2001).In 2015, the import of gum arabic into the EU reached 76 000 tons, mainly from Sudan and Chad. It is unclear how much of this volume is consumed in the EU but it is evident that large amounts of gum arabic are used for the EU market and are consumed by European consumers.In March 2017, the European Food Safety Authority (EFSA) published a re-evaluation of gumarabic as food additive, including a refined exposure assessment. The exposure wascalculated based on products on the market and their actual content of gum arabic using the EFSA Comprehensive European Food Consumption Database and industry informationabout the use levels in the various food categories. The data set used for this calculation isprovided in the supplemental information to the re-evaluation of gum Arabic by EFSA (2017).The data resulting from the different European food consumption surveys cannot be directlycompared because the methodologies used to assess the intake differ from country tocountry. Therefore, the intake values from different surveys were not combined, but the minimum and maximum of all mean intake values were given. Hence, the individual values may originate from different surveys (countries).The panel came to the following conclusions:

•Gum arabic is unlikely to be absorbed intact and is slightly fermented by intestinal microbiota;

•sufficient toxicity data were available; there is no concern with respect to thegenotoxicity; no carcinogenic effects were reported in carcinogenicity studies in miceand rats at the doses up to 7,500 mg and 2,500 mg gum arabic/kg bw per day,

respectively, the highest doses tested;

•oral daily intake of a large amount of gum arabic up to 30,000 mg gum arabic/personper day (approximately equivalent 430 mg gum arabic/kg bw per day) for up to 30days was well tolerated in adults but some individuals experienced flatulence. A doseof 53,000 mg gum arabic/person per day (approximately equivalent 760 mg gumarabic/kg bw per day) induced mild flatulence, which was considered by the Panel asundesirable but not adverse,

The conclusion was drawn that there is no need for a numerical ADI for gum arabic (E 414),and that there is no safety concern at the refined exposure assessment for the reported usesof gum arabic (E 414) as a food additive.

This exposure assessment is the most reliable and systematic information available to date.We therefore consider it pivotal for the purpose of this assessment. The original EFSA evaluation includes gum arabic in infant nutrition and food for young children. EFSA assessed the intake of gum arabic for the maximum level exposure scenario and conducted a refined exposure assessment that differentiated between brand loyal and nonbrand loyal consumers. Use levels were derived from the industry. Only those categories were included in the calculation for which reliable use data were provided.

3.1.2.1 Maximum level exposure assessment scenario

As gum arabic (E 414) is authorized according to QS in almost all food categories, a ‘maximum level exposure assessment’ scenario was estimated based on the maximumreported use levels provided by industry. EFSA considered the exposure estimates derived following this scenario as the most conservative as it is assumed that that the population group will be exposed to gum Arabic (E 414) present in food at the maximum reported use levels over a longer period of time. Use levels for 61 food categories were provided by the industry, among others for confectionary, flavored milk drinks and sub-categories of bakery wares.

3.1.2.2 Refined exposure assessment scenario

The refined exposure assessment scenario is also based on use levels reported by industry but can consider only food categories for which the above data were available to the Panel.

The use levels taken into consideration for this calculation are provided in the supplemental information to the re-evaluation of gum Arabic by EFSA (2017). Based on the available dataset, the Panel calculated two refined exposure estimates based on different model populations:

-      The brand-loyal consumer scenario: It was assumed that a consumer is exposed longterm to gum arabic (E 414) present at the maximum reported use for one food category.

This exposure estimate is calculated as follows:

-      Combining food consumption with the maximum of the reported use levels for the main contributing food category at the individual level.

-      Using the mean of the typical reported use levels for the remaining food categories.

-      The non-brand-loyal consumer scenario: It was assumed that a consumer is exposed long-term to gum arabic (E 414) present at the mean reported use in food. This exposure estimate is calculated using the mean of the typical reported use levels for all food categories.

The data in Table 3 were extracted from the EFSA publication (Saini and Henry, 1989) and were transformed into the overall intake of gum arabic [g/day] by applying the average bodyweight of 70 kg for adults and 50 kg for adolescents (Additives et al., 2017; EFSA Panelon Food Additives and Nutrient Sources added to Food (ANS), 2017; Muller-Maatsch et al.,

2016). Assuming an average content of 35% arabinose in gum arabic, a total arabinose intake for the three intake scenarios mentioned above as presented in Table 4 results.

In adolescents, the anticipated mean L-ARA intake per day lies between 0.61 g (minimum values of the non-loyal brand exposure scenario and 16.4 g (maximum values of the maximum level exposure scenario). The L-ARA consumption in the 95thpercentile varies between 1.55 g and 25.1 g per day.

The mean arabinose intake by adults varies from 0.37 g (minimum values of the non-loyal brand exposure scenario to 8.59 g (maximum values of the maximum level exposure scenario), the arabinose consumption of the 95Thpercentile varies between 1.07 g and 19.88 g. In the maximum exposure scenario, flavoured drinks and unflavoured fermented milkproducts; confectionary and flavoured drinks were the main contributing food categories for adolescents and adults.

In the brand-loyal scenario, the main contributing food categories were confectionary for adolescents and flavoured drinks for adults. In the non-brand-loyal scenario, the maincontributing food categories were confectionary for adolescents and fine bakery wares for adults.

3.1.2.3 Summary: L-ARA intake by the food additive gum arabic

The analysis by EFSA reveals that gum arabic is widely used in processed foods in the EU,resulting in daily L-ARA intakes from below 0.5 g up to more than 20 g. The range of L-ARA intake by consumption of gum arabic as food additive varies from 0.6 to 25.1 g for adolescents and 0.4 g to 19.8 g for adults. Such intakes are considered as safe for the general population by EFSA.The intake is even higher for infants, toddlers and children younger than 9 years of age, but these data are not considered relevant for this calculation.Sensitive consumers may experience transient bloating but such effects were not considered pathological (Additives et al., 2017).

3.2 L-ARA intake via selected foodstuffs

Plant cell walls contain relatively high amounts of biopolymers such as pectin, cellulose and hemicellulose. Especially pectins and hemicelluloses contain substantial amounts of L-ARA.A comprehensive literature research was performed to gather information about the arabinose content of fruit, vegetables and food derived from vegetable origin (tabulated in Table 2). Reliable data on the arabinose content in food are rather limited. We identified threefoodstuffs for which the arabinose content was provided in a form suitable for the exposure assessment: dried beans, apples and pears. Data on whole tomato or citrus fruits, both rich sources of pectin, or while grain cereal products which contain arabinoxylans were not available. On average, wheat bran arabinoxylan makes up ca. 29% of the total dietary fiber content of wheat. In contrast, the arabinoxylan levels in flour were varied between 1.35 and 2.75% of the dry matter (EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS), 2017). The ARA:XYL ratio in wheat arabinoxylans is 0.65 (EFSA Scientific Committee, 2012) resulting in 0.8 – 1.8 % arabinose in the dry matter of wheat flour. A slice of wheat bread of 50 g could easily provide 0.3-0.6 g arabinose, whole grain breads even more. But it is hardly possible to determine the amount of wheat flour used for the manufacture of baked foods and other processed foodstuffs containing wheat flours.

The anticipated intake of arabinose was calculated using the Comprehensive European Food Consumption Database, which combines data obtained by various national food consumption surveys. The EFSA database was recently updated and is publicly available at (http://www.efsa.europa.eu/en/datexfoodcdb/datexfooddb.html). Only data from the recent NDNS survey in the UK were included in the calculation.

The exact methodologies of the national surveys and the compilation of the combined database are explained in (EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS), 2017). Since the methodologies of the surveys combined in the EFSA food consumption database are not the same, the applicant selected one survey – the National Diet and Nutrition Survey (NSDS) Years 1-3 from the UK, for this calculation. The survey was conducted between 2008 and 2011. The exact methodology is described in (EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS), 2017) .

3.2.1 Intake example dried beans

As mentioned in Table 2 the arabinose content of legumes differs from 26 – 36 g/kg. The intake is calculated based on consumption of dried beans, with an average arabinose content of 26 g/kg.

 

Table 5:  Consumption data of dried beans and the resulting intake of L-ARA in the total population and by consumers only

Daily Consumption of dried beans [g]
Population group	Total population		Consumers only		% Consumers
	mean	P95	mean	P95
Adolescents	19.5	90.0	45.8	125.0	42.5%
Adults	22.3	105.0	49.9	127.2	44.7%
Elderly	17.0	74.5	46.3	105.0	36.7%
Daily Consumption of L-ARA by dried beans [g]
Population group	Total population		Consumers only		% Consumers
	mean	P95	mean	P95
Adolescents	0.51	2.34	1.19	3.25	42.5%
Adults	0.58	2.73	1.30	3.31	44.7%
Elderly	0.44	1.94	1.20	2.73	36.7%

 

For adolescents, the L-ARA intake per day via consumption of beans lies between 0.51 g (mean intake, total population) and 3.25 g (95thpercentile consumers only).The L-ARA consumption for adults and elderly varies from 0.58 g and 0.44 g to 3.31 g and 2.73 g, respectively.

3.2.2 Intake example: pears

The average weight per pear is 168 g (8 pears weight about 1.3 -1.4 kg). The L-ARA content per pear differs from 450 and 980 mg per fruit. During maturation the arabinose content decreases (Gebruers et al., 2008), resulting in L-ARA contents of 0.27 g/100g fruit to 0.58 g/100 g fruit.

 

Table 6:  Consumption data of pear and the resulting intake of L-ARA

Daily Consumption of pear [g]
Population group	Total population		Consumers only		% Consumers
	mean	P95	mean	P95
Adolescents	2.95	15.00	51.72	127.50	13%
Adults	8.52	60.00	64.56	127.50	6%
Elderly	15.00	85.00	71.14	170.00	21%
Daily arabinose consumption with pear (very ripe; 450 mg L-ARA/fruit) [g/day]
Population group	Total population		Consumers only		% Consumers
	mean	P95	mean	P95
Adolescents	0.01	0.04	0.14	0.34	13%
Adults	0.02	0.16	0.17	0.34	6%
Elderly	0.01	0.23	0.17	0.46	21%
Daily arabinose consumption with pear (low maturity level; 980 mg L-ARA/fruit) [g/day]
Population group	Total population		Consumers only		% Consumers
	mean	P95	mean	P95
Adolescents	0.02	0.09	0.30	0.74	13%
Adults	0.05	0.35	0.38	0.74	6%
Elderly	0.09	0.50	0.41	0.99	21%

 

For British adolescents, the arabinose intake per day via consumption of pears lies between 0.01 g and 0.74 g.The arabinose consumption per day by adults and elderly varies from 0.02 g and 0.01 g to 0.74 g and 0.99 g, respectively.

3.2.3 Intake example: apple

The dry matter in apple is 15.1 % (Souci, Fachmann, Kraut; 2000).The arabinose content as reported by Chang et al. is 11% in soluble fibre and 20.8% in noncellulose polyaccharides, which themselves contribute to 8.9% and 5.8%, respectively, of the dry matter. Hence, the total amount of arabinose considering soluble fibre and non cellulose polysaccharides in apple is 0.33%.

 

Table 7:  Consumption data of apple and the resulting intake of L-ARA

Daily Consumption of apples (g)
Population group	Total population		Consumers only		Consumers
	mean	P95	mean	P95
Adolescents	20.04	75.00	45.56	112.50	44.0%
Adults	20.14	87.00	48.48	121.75	41.5%
Elderly	21.20	87.00	46.31	125.00	45.8%
Daily Consumption of L-ARA via apple consumption (g)
Population group	Total population		Consumers only		Consumers
	mean	P95	mean	P95
Adolescents	0.07	0.25	0.15	0.37	44.0%
Adults	0.07	0.29	0.16	0.40	41.5%
Elderly	0.07	0.29	0.15	0.41	45.8%

 

For adolescents, the L-ARA intake per day by consumption of apples lies between 0.07 g and 0.37 g.The L-ARA consumption for adults and elderly in the UK from apples varies from 0.07 g to 0.40 g and 0.41 g, respectively.

3.2.4 Summary L-ARA consumption with foodstuff

In the absence of comprehensive data on L-ARA content in foodstuffs, the intake assessment was conducted based on compositional data of only three by representative examples, namely beans, apples and pears. All three are a habitual element of the diet in the UK. The most recent NDNS food consumption survey (UK) was used for this calculation. Only adolescents, adults and elderly were included in the calculation.

The exercise demonstrated that substantial amounts of L-ARA are ingested via these foodstuffs. Estimating the overall intake based on these three items would provide a false number as substantial contributors to the arabinose intake could not be considered, e.g. cereals or other fruits and vegetables and products thereof.

Conclusions:

Based on those intake levels a history of safe use in humans can be concluded. As there is no evidence of any adverse effect of this ubiquitous pentose, which is part of the human food chain, no further animal safety testing is necessary for REACH registration of L-Arabinose. In the light of this habitual exposure to L-Arabinose, the safety of orally ingested L-Arabinose is evident and additional animal trials to study repeated dose toxicity including reproductive and developmental toxicity is unjustified. Also from an animal welfare perspective, unnecessary animal trials should be avoided when there is no indication for toxicity.

Executive summary:

L-Arabinose is commercially used in food supplements, as non-caloric sweetener and as precursor for the manufacture of flavourings. It is usually manufactured from waste streams of food manufacturing such as corn cobs by extensive hydrolysis. Plant polysaccharides contain substantial amounts of L-Arabinose, therefore it can be assumed that humans ingest relevant amounts of L-Arabinose with their habitual diet. The polysaccharides are degraded by colonic bacteria, resulting in the release of free L-Arabinose. In contrast to the pentose D-fructose, the intestinal absorption of L-Arabinose is low and the sugar is not metabolized. In nature, L-Arabinose is bound via glycosidic bonds to other sugar moieties, resulting in highly complex branched polysaccharide structures. Prominent examples are the non-starch polysaccharides (NSP) pectin and hemicelluloses such as arabinoglucans, arabinogalactans and arabinoxylans. These polymers can be found in fruits, vegetables and plant gums, cereals, and woods or woody parts of edible plant and are classified as dietary fibres. Based on available data, three main food items are included into the assessment: dried beans, apples and pears. The calculation was conducted based on the most recent British food consumption survey.

It is evident that substantial amounts of L-Arabinose are ingested via plant dietary fibers from fruits, vegetables and cereals. In addition, the intake of L-Arabinose via the arabinose-rich food additive gum arabic was taken into consideration, which was assessed in detail by EFSA in 2017. The range of LArabinose intake by consumption of gum arabic as food additive varies from 0.6 to 25.1 g for adolescents and 0.4 g to 19.8 g for adults. Such intakes are considered as safe for the general population.

Reference 2

Endpoint:

screening for reproductive / developmental toxicity

Type of information:

other: Expert Statement

Adequacy of study:

supporting study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Expert Statement

Justification for type of information:

An Intake Assessment was performed to estimate the average daily intake of L-Arabinose (L-ARA) with a habitual diet. Three main foodstuffs were considered, complemented by the intake of L-Arabinose by gum arabic as food additive. A rough estimate of the dietary L-Arabinose consumption could be calculated. The highest contributor to the L-Arabinose intake in humans is gum arabic, which is widely used as food additive. The range of L-Arabinose intake by consumption of gum arabic as food additive varies from 0.61 to 25.1 g for adolescents and 0.37 g to 19.8 g for adults. Natural plant based foodstuffs contain L-ARA as a part of the NSP fraction, which at least to some extend are broken down to monomeric L-ARA in the GI-tract. Through the intake data of three main foodstuffs: apples, pears and beans, they provide evidence of a substantial L-ARA consumption with the habitual diet. Dried beans may contribute substantially to the L-arabinose intake. With this high daily intake of L-ARA in polysaccharide bound form and partial hydrolysis in the GI tract in human, thereof it can be concluded that safety of L-ARA is substantiated. As there is no evidence of any adverse effect of this ubiquitous pentose, which is part of the human food chain, no further animal safety testing is necessary for REACH registration of L-ARA.
According to REGULATION (EC) No 1907/2006, Annex VIII/IX, testing for reproduction/developmental toxicity (section 8.7) may be omitted, if testing does not appear scientifically necessary. According to Annex XI section 1.1.2, adequate data on human health properties should be considered to be equivalent to data generated by the corresponding test methods referred to in Article 13 (3) if the following conditions are met: 1) adequacy for the purpose of classification and labelling and/or risk assessment; 2) adequate and reliable coverage of the key parameters foreseen to be investigated in the corresponding test methods referred to in Article 13(3); 3) exposure duration comparable to or longer than the corresponding test methods referred to in Article 13(3); and 4) adequate and reliable documentation is provided. In addition and in accordance with Annex XI section 1.2, relevant independent sources of information are available, leading to the conclusion that the substance has not a particular dangerous property. Therefore, further testing on vertebrate animals for that property shall be omitted where adequate and reliable data for the absence of a particular dangerous property is available.

Based on adequate data from the Intake Assessment, a history of safe use of L-Arabinose in humans can be concluded. There is no evidence of any adverse effect of this ubiquitous pentose, which is part of the human food chain. In the light of this habitual exposure to L-Arabinose, the safety of orally ingested L-Arabinose is evident and additional animal trials to study repeated dose toxicity including reproductive and developmental toxicity is unjustified. Also from an animal welfare perspective, unnecessary animal trials should be avoided when there is no indication for toxicity.

Principles of method if other than guideline:

Expert Statement

GLP compliance:

no

Key result

Remarks on result:

not determinable due to absence of adverse toxic effects

Key result

Critical effects observed:

no

Key result

Dose descriptor:

NOAEL

Sex:

male/female

Remarks on result:

not determinable due to absence of adverse toxic effects

Key result

Critical effects observed:

no

Reproductive effects observed:

no

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available information on the test item regarding toxicity to reproduction are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on available information, the test substance is not classified for reproductive or developmental toxicity according to Regulation (EC) No 1272/2008 (CLP), as amended for the eleventh time in Commission Regulation (EU) 2018/669.