Ethyl L-threoninate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Adequacy of study:

weight of evidence

Materials and methods

Objective of study:

other: Assessment of toxicokinetic behaviour

Test material

Test material information

Constituent 1

Applicant's summary and conclusion

Conclusions:

No studies are available. Based on the molecular structure, molecular weight, water solubility, and octanol-water partition coefficient of L-TEE, it can be expected that the oral and inhalational absorption rates maybe high and the dermal absorption rate is considered moderate. No data on distribution is available, but based on the effects seen in the 28-day study and physical/chemical data, L-TEE is expected to be distributed though the body.

L-TEE is an ester formed by L-threonine and ethanol, both of which are substances that are readily metabolized in the body. A high degree of endogenous hydrolysation into these substances is expected due to the activity of normally occurring esterases. However, no specific data on the hydrolysation rates are available

Based on the anticipated metabolic fate and the resulting formation of L-threonine and ethanol, it is considered relevant to consider data on these substances when evaluating L-TEE. Hence, no bioaccumulation is expected.

Executive summary:

In a 28 days oral toxicological study rats were exposed to L-TEE at 250, 500 or 1000 mg/kg bw/day.No adverse findings were observed, however, minimal/slight cortico-medullary mineralisation in the kidneys and increased lymphocyte counts were observed in females treated at all dose levels. From this, it can be deduced that L-TEE is absorbed from the gastro-intestinal tract. Due to lack of specific data on absorption rates, an oral absorption rat of 100% is therefore anticipated.

As no adequate data on inhalation is available, an absorption of 100% is anticipated.

L-TEE is a small molecule with a very high water solubilty so some dermal absorption may be expected. Having some liphophilic properties ethanol is considered to have a higher potential for dermal absorption as L-TEE and as an worst case assumption the same absorption rate for ethanol may be used for L-TEE. For dermal absorption of ehtanol, an absorption rate of 10 % has been found (Pendlington et al. 2001, Food and Chemical Toxicology 39 (2001) 169–174), thus the same abosrption rate is applied for L-TEE.

Based on the molecular structure, molecular weight, water solubility, and octanol-water partition coefficient of L-TEE it can be expected that the oral and inhalational absorption rates maybe high and the dermal absorption rate is considered moderate. No data on distribution is available, but based on the effects seen in the 28-day study and physical/chemical data, L-TEE is expected to be distrubuted thought the body. L-TEE is an ester formed by L-threonine and ethanol, both of which are substances that are readily metabolized in the body. A high degree of endogenous hydrolysation into these substances is expected due to the activity of normally occurring esterases. However, no specific data on the hydrolysation rates are available. Based on the antipicated metabolic fate and the resulting formation of L-threonine and ethanol, it is considered relevant to consider data on these substances when evaluating L-TEE. Hence, no bioaccumulation is expected.