L-arabinose

Endpoint summary

Link to relevant study record(s)

Reference

Endpoint:

basic toxicokinetics, other

Type of information:

other: Expert Statement

Adequacy of study:

key study

Study period:

15 May 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Expert Statement, no study available

Principles of method if other than guideline:

Expert Statement

GLP compliance:

no

Details on absorption:

Absorption is a property of a substance to diffuse across biological membranes. Generally, oral absorption is favored for molecular weights below 500 g/mol and log Pow values between -1 and 4. In the GI tract absorption of small water-soluble molecules (molecular weight up to around 200 g/mol) occurs through aqueous pores or carriage of such molecules across membranes with the bulk passage of water. As L-Arabinose is highly water soluble and has a molecular weight of 150 g/mol passive diffusion is expected. Absorption from the small intestine of rats has been reported (Davidson and Garry, 1940) but L-Arabinose is a much less absorbable pentose than D-Xylose when studied in Wistar rats (Seri et al., 1996). Zhang et al reported that L-Arabinose is transported into the blood circulation by passive uptake in the jejunum (Zhang et al., 2003). Seri et al showed that after oral administration via gavage of a single dose of 1000 mg/kg bw, plasma concentrations of L-arabinose were low, and 38.6 ± 2.0 µg/mL at 30 minutes was the highest value. In addition, in an acute oral toxicity study using L-Arabinose (99.6% purity) neither clinical effects nor mortality have been observed indicating low bioavailability.

Absorption via the respiratory route also depends on physico-chemical properties like vapor pressure, log Pow and water solubility. In general, highly volatile substances are those with a vapor pressure greater than 25 kPa or boiling point below 50°C. Due to its low vapor pressure of 1.89E-8 Pa at 20°C L-Arabinose is unlikely to be available as a vapor to a large extent. However, the substance is a needle-shaped crystalline solid and has a median particle size (D50) of 51 µm. Deposition pattern of dusts will depend on the particle size, shape and electrostatic properties. Particles with aerodynamic diameters below 100 µm have the potential to be inhaled. Absorption via the inhalation route might occur as dust due to median particle sizes of 51 µm. However, based on adequate data from an 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 L-Arabinose is evident and additional animal trials to study inhalation were not performed.

In general, dermal absorption is favored by small molecular weights and high water solubility of the substance. Log Pow values between 1 and 4 favor dermal absorption, particularly if water solubility is high. However, if water solubility is above 10 g/L and the log Pow value below 0 the substance may be too hydrophilic to cross the lipid rich stratum corneum and dermal uptake will be low. Therefore, for L-Arabinose low dermal absorption is predicted because of its high water solubility and log Pow value of -2.8. No cytotoxicity was reported in in vitro tests using reconstituted human epidermis in the EPISKIN model. Furthermore, no activation of keratinocytes was detected in the OECD TG 422D assay.

Details on distribution in tissues:

In general, the smaller the molecule the broader is its distribution. Small water-soluble molecules will diffuse through aqueous channels and pores in the membranes. After being absorbed into the body, L-Arabinose is expected to distribute through-out the body water. Due to its low log Pow the test item is unlikely to bioaccumulate in tissue, and there are no other physicochemical properties indicating bio-accumulating properties.

Details on excretion:

It is widely accepted that L-Arabinose resist metabolism and is mostly excreted unchanged via the urine (Pantophlet et al., 2017). In fact, L-Arabinose is used to measure intestinal permeability because urinary excretion is representative for the intestinal uptake (Lobley et al., 1990; Mishra and Makharia, 2012).
Furthermore, Seri et al reported that there was a significant difference between L-Arabinose -treated and D-Xylose-treated ingested rats for the ratio of urinary excretion to ingested dose (L-arabinose, 3.5% ± 0.13%; D-xylose, 22.8% ± 0.63%): This result suggested that L-arabinose is a much less absorbable pentose than D-Xylose (Seri et al., 1996).

Details on metabolites:

It is widely accepted that L-Arabinose resist metabolism and is mostly excreted unchanged via the urine (Pantophlet et al., 2017)

Conclusions:

Based on physico-chemical properties, oral and dermal absorption is expected to be low. This assumption is supported by the results of single dose oral toxicity studies in vivo. Absorption via the inhalation route might occur as dust due to median particle sizes of 51 µm. However, based on adequate data from an 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. Bioaccumulation of the substance is not expected after continuous exposure. Furthermore, the test substance is expected to be predominantly excreted unchanged via urine.

Description of key information

Based on physico-chemical properties, oral and dermal absorption is expected to be low. This assumption is supported by the results of a single dose oral toxicity study in vivo. Absorption via the inhalation route might occur as dust due to median particle sizes of 51 µm. However, based on adequate data from an 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. Bioaccumulation of the substance is not expected after continuous exposure. Furthermore, the test substance is expected to be predominantly excreted unchanged via urine.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

L-Arabinose is a white needle-shaped crystalline solid with no odor at 20°C and 1013.3 hPa and has a molecular weight of 150.13 g/mol. The test item is miscible with water at any ratio. The log Pow is determined to be -2.8 and the vapor pressure is 1.89E-8 Pa at 20°C. The test item has a median particle size (D50) of 51 µm. No boiling point of the test item was determined as the test item decomposes before boiling at 174.7 °C.

 

Absorption

Absorption is a property of a substance to diffuse across biological membranes. Generally, oral absorption is favored for molecular weights below 500 g/mol andlog Pow values between -1 and 4. In the GI tract absorption of small water-soluble molecules (molecular weight up to around 200 g/mol) occurs through aqueous pores or carriage of such molecules across membranes with the bulk passage of water. As L-Arabinose is highly water soluble and has a molecular weight of 150 g/mol passive diffusion is expected. Absorption from the small intestine of rats has been reported (Davidson and Garry, 1940) but L-Arabinose is a much less absorbable pentose than D-Xylose when studied in Wistar rats (Seri et al., 1996). Zhang et al reported that L-Arabinose is transported into the blood circulation by passive uptake in the jejunum (Zhang et al., 2003). Seri et al showed that after oral administration via gavage of a single dose of 1000 mg/kg bw, plasma concentrations of L-arabinose were low, and 38.6 ± 2.0 µg/mL at 30 minutes was the highest value. In addition, in an acute oral toxicity study using L-Arabinose (99.6% purity) neither clinical effects nor mortality have been observed indicating low bioavailability. 

 

Absorption via the respiratory route also depends on physico-chemical properties like vapor pressure, log Pow and water solubility. In general, highly volatile substances are those with a vapor pressure greater than 25 kPa or boiling point below 50°C. Due to its low vapor pressure of 1.89E-8 Pa at 20°C L-Arabinose is unlikely to be available as a vapor to a large extent. However, the substance is a needle-shaped crystalline solid and has a median particle size (D50) of 51 µm. Deposition pattern of dusts will depend on the particle size, shape and electrostatic properties. Particles with aerodynamic diameters below 100 µm have the potential to be inhaled. Absorption via the inhalation route might occur as dust due to median particle sizes of 51 µm. However, based on adequate data from an 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 L-Arabinose is evident and additional animal trials to study inhalation were not performed.

 

In general, dermal absorption is favored by small molecular weights and high water solubility of the substance. Log Pow values between 1 and 4 favor dermal absorption, particularly if water solubility is high. However, if water solubility is above 10 g/L and the log Pow value below 0 the substance may be too hydrophilic to cross the lipid rich stratum corneum and dermal uptake will be low. Therefore, for L-Arabinose low dermal absorption is predicted because of its high water solubility and log Pow value of -2.8. No cytotoxicity was reported in in vitro tests using reconstituted human epidermis in the EPISKIN model. Furthermore, no activation of keratinocytes was detected in the OECD TG 422D assay.

 

Distribution

In general, the smaller the molecule the broader is its distribution. Small water-soluble molecules will diffuse through aqueous channels and pores in the membranes. After being absorbed into the body, L-Arabinose is expected to distribute through-out the body water. Due to its low log Pow the test item is unlikely to bioaccumulate in tissue, and there are no other physicochemical properties indicating bio-accumulating properties.

 

Metabolism & Excretion

It is widely accepted that L-Arabinose resist metabolism and is mostly excreted unchanged via the urine (Pantophlet et al., 2017). In fact, L-Arabinose is used to measure intestinal permeability because urinary excretion is representative for the intestinal uptake (Lobley et al., 1990; Mishra and Makharia, 2012).

Furthermore, Seri et al reported that there was a significant difference between L-Arabinose-treated and D-Xylose-treated ingested rats for the ratio of urinary excretion to ingested dose (L-arabinose, 3.5% ± 0.13%; D-xylose, 22.8% ± 0.63%): This result suggested that L-Arabinose is a much less absorbable pentose than D-Xylose (Seri et al., 1996).