DL-alanine

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

226.2 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

10

Modified dose descriptor starting point:

NOAEC

Value:

2 262 mg/m³

AF for dose response relationship:

1

Justification:

starting point NOAEC

AF for differences in duration of exposure:

2

Justification:

DNEL is based on a 90-day study

AF for interspecies differences (allometric scaling):

1

Justification:

AF not used for inhalation route

AF for other interspecies differences:

1

Justification:

AF not used, remaining differences in toxicolocial effects are not expected

AF for intraspecies differences:

5

Justification:

AF for workers

AF for the quality of the whole database:

1

AF for remaining uncertainties:

1

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

320.8 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

40

Modified dose descriptor starting point:

NOAEL

Value:

12 830 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

only study for oral route available

AF for dose response relationship:

1

Justification:

starting point NOAEL

AF for differences in duration of exposure:

2

Justification:

DNEL is based on a 90-day study

AF for interspecies differences (allometric scaling):

4

Justification:

test animal: rat

AF for other interspecies differences:

1

Justification:

AF not used, remaining differences in toxicolocial effects are not expected

AF for intraspecies differences:

5

Justification:

AF for workers

AF for the quality of the whole database:

1

AF for remaining uncertainties:

1

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - workers

Since only oral repeated dose studies are available, route-to-route extrapolation is considered necessary for the long-term systemic dermal and inhalation DNELs.

Due to lack of data, for both oral and inhalation exposure, 100% absorption is assumed. The particle size distribution has shown that only 0.64% of the particles is smaller than 5 micron, and only 1.2% smaller than 10 micron. This means that if particles would be inhaled they will deposit in the upper respiratory tract and swallowed, thus inhalation exposure will be identical to oral exposure.

For dermal exposure, 10% absorption is assumed. These absorption rates were assessed in a toxicokinetic assessment.

The DNELs for human exposure are derived according to the ECHA Guidance on information requirements and chemical safety assessment (Chapter R.8: Characterisation of dose-/concentration-response for human health, Version: 2, 2010).

The additional assessment factor 2.5 for "remaining interspecies differences" was not used for the following reasons:

The factor of 2.5 accounts for other interspecies differences in toxicokinetics (not related to metabolic rate) and toxicodynamics.
Absorption, Distribution, Metabolism as well as Excretion of proteinogenic amino acids are very similar between animals (mammals) and humans: These amino acids are taken up via the oral route by animals as well as humans by generally the same mechanisms (or/and are build endogenously). Regardless of whether they enter the intestinal cells as peptides or amino acids they enter the hepatic portal circulation as single amino acids. Absorbed amino acids leave the hepatic portal system and enter the peripheral blood. These amino acids are taken up by tissues for synthesis of cellular proteins and other physiologically active compounds in animals and humans. Degradation involves removal of the amino group, which in mammals is converted to urea and excreted in the urine. After removal of the amino group the rest of the acid is utilised as energy or used to synthesize other endogenous substances. Also with regard to toxicodynamics (however real toxic effects of amino acids in humans as well as in animals are hardly detectable even at high doses) there is no obvious difference between mammals and humans.

A subchronic (26 -wk) rat oral study with DL-alanine resulted in a NOAEL of 6800 mg/kg bw. Calculation of the DNEL longterm systemic results in: 6800 x 1/0.38 x 1/1 x 6.7/10 = 12000 mg/m3. Assessment factors: 1 (remaining differences), 5 (intraspecies), 2 (duration), 1 (NOAEL) = 12000/10 = 1200 mg/m3.

As DL-alanine is water soluble, the general nuisance dust limit of 10 mg/m3 for local effects does not apply.

 

Acute DNELs for local and systemic effects

Due to its very low systemic toxicity and the fact that DL-alanine (with high water solubility and a log P value well below 0) may be too hydrophilic to cross the lipid rich environment of the stratum corneum it is highly improbable that an acute dermal toxicity study would result in any toxicity. In absence of further information concerning route specific effects through dermal exposure, and absence of skin irritation, no acute dermal DNELs are considered applicable.

 

Long-term DNELs for local effects

The substance is not classified for local effects and therefore DNELs for local effects were not derived. As the substance is a highly water soluble dust the general nuisance dust limit of 10 mg/m3 should not be applied.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Explanation for the modification of the dose descriptor starting point:

As the chemical will only be transported and used as a starting chemical in an industrial process to produce chelates (in which it will be fully consumed), there will be no exposure of the general population possible.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Explanation for the modification of the dose descriptor starting point:

No exposure of the general population possible.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - General Population

There will be no exposure of the general population as the chemical will be used as a starting substance in an industrial process; it will be fully consumed in this process and not be present in the chemical finally produced.