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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
411.4 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):
150
Dose descriptor starting point:
NOAEL
Value:
2 500 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
61 710 mg/m³
Explanation for the modification of the dose descriptor starting point:

The calculation of the DNEL is based on an oral NOAEL observed in a developmental toxicity study in rats with the source substance (N-acetyl-L-tryptophan) (Kadota, 1980).

To take into account the interspecies difference between the rat and human the no observed adverse effect level (NOAEL) has to be corrected as follows:

Corrected starting point for the inhalative route for workers:

= NOAEL(oral) * (1/0.38 m³/kg bw/day) * (ABSoral-rat/ABSinh-human) * 6.7 m³ (8h) /10 m³ (8h) * (days of exposure per week in rats / days of exposure per week worker)

= 2500 mg/kg bw/day * (1/0.38 m³/kg bw/day) * (1/0.1) * 0.67 m³ * (7/5) = 61710 mg/m³.

 

(ABSoral-rat = oral absorption in rats, ABSinh-human = inhalation absorption rate in humans)

The inhalation absorption is assumed to be 10% based on granulometry data, which shows, D10: 14.1 µm, that a very low fraction of the particles are likely to reach the alveoli of the lungs. The D50: 94.0 µm and the D90: 292.7 µm, indicating that a fraction of the particles may be inhaled and are likely to be deposited before reaching the alveolar region. Particles deposited in the nasopharyngeal/thoracic region will mainly be cleared from the airways by the mucocilliary mechanism and swallowed or coughed out.

Therefore, the corrected starting point for workers was 61710 mg/m³ for inhalation.

AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a NOAEL
AF for differences in duration of exposure:
6
Justification:
The DNEL is based on a subacute (10-day) study
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for the inhalation route
AF for other interspecies differences:
2.5
Justification:
Default value
AF for intraspecies differences:
5
Justification:
Default value for workers according to ECHA REACh Guidance
AF for the quality of the whole database:
2
Justification:
The DNEL is based on a study with some limitations
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
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:
41.7 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):
600
Dose descriptor starting point:
NOAEL
Value:
2 500 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
25 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The calculation of the DNEL is based on an oral NOAEL observed in a developmental toxicity study in rats with the source substance (N-acetyl-L-tryptophan) (Kadota, 1980).

Corrected starting point for the dermal route for workers:

Dermal NOAEL = oral NOAEL*ABS(oral)/ABS(dermal)

= 2500 mg/kg bw/day * (1/0.1) = 25000 mg/kg bw/day.

The dermal absorption potential is assumed to be 10%, based on the prediction of low dermal absorption potential (please refer to the toxicokinetic statement).

AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a NOAEL
AF for differences in duration of exposure:
6
Justification:
The DNEL is based on a subacute (10-day) study
AF for interspecies differences (allometric scaling):
4
Justification:
Default AF for rats
AF for other interspecies differences:
2.5
Justification:
Default value
AF for intraspecies differences:
5
Justification:
Default value for workers
AF for the quality of the whole database:
2
Justification:
The DNEL is based on a study with some limitations
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
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

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
72.5 µg/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):
300
Dose descriptor starting point:
NOAEL
Value:
2 500 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
21 739.1 mg/m³
Explanation for the modification of the dose descriptor starting point:

The calculation of the DNEL is based on an oral NOAEL observed in a developmental toxicity study in rats with the source substance (N-Acetyl-L-tryptophan) (Kadota, 1980).

To take into account the interspecies difference between the rat and human the no observed adverse effect level (NOAEL) has to be corrected as follows:

Corrected starting point for the inhalative route for the general population:

= NOAEL(oral) * (1/1.15 m³/kg bw/day) * (ABSoral-rat/ABSinh-human)

= 2500 mg/kg bw/day * (1/1.15 m³/kg bw/day) * (1/0.1) = 21739.1 mg/m³

(ABSoral-rat = oral absorption in rats, ABSinh-human = inhalation absorption rate in humans)

The inhalation absorption is assumed to be 10% based on granulometry data, which shows, D10: 14.1 µm, that a very low fraction of the particles are likely to reach the alveoli of the lungs. The D50: 94.0 µm and the D90: 292.7 µm, indicating that a fraction of the particles may be inhaled and are likely to be deposited before reaching the alveolar region. Particles deposited in the nasopharyngeal/thoracic region will mainly be cleared from the airways by the mucocilliary mechanism and swallowed or coughed out.

The corrected starting point for workers was 21739.1 mg/m³ for inhalation.

AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a NOAEL
AF for differences in duration of exposure:
6
Justification:
The DNEL is based on a subacute (10-day) study
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for the inhalation route
AF for other interspecies differences:
2.5
Justification:
Default AF
AF for intraspecies differences:
10
Justification:
Default AF for general population
AF for the quality of the whole database:
2
Justification:
The DNEL is based on a study with some limitations
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
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:
DNEL (Derived No Effect Level)
Value:
20.8 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):
1 200
Dose descriptor starting point:
NOAEL
Value:
2 500 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
25 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The calculation of the DNEL is based on an oral NOAEL observed in a developmental toxicity study in rats with the source substance (N-acetyl-L-tryptophan) (Kadota, 1980).

Corrected starting point for the dermal route for the general population:

Dermal NOAEL = oral NOAEL*ABS(oral)/ABS(dermal)

= 2500 mg/kg bw/day * (1/0.1) = 25000 mg/kg bw/day.

The dermal absorption potential is assumed to be 10%, based on the prediction of low dermal absorption potential (please refer to the toxicokinetik statement).

AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a NOAEL
AF for differences in duration of exposure:
6
Justification:
The DNEL is based on a subacute study
AF for interspecies differences (allometric scaling):
4
Justification:
Default AF for rats
AF for other interspecies differences:
2.5
Justification:
Default AF
AF for intraspecies differences:
10
Justification:
Default AF for general population
AF for the quality of the whole database:
2
Justification:
The DNEL is based on a study with some limitations
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.08 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
1 200
Dose descriptor starting point:
NOAEL
Value:
2 500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No route-to-route extrapolation necessary.

AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a NOAEL
AF for differences in duration of exposure:
6
Justification:
The DNEL is based on a subacute study
AF for interspecies differences (allometric scaling):
4
Justification:
Default AF for rats
AF for other interspecies differences:
2.5
Justification:
Default AF
AF for intraspecies differences:
10
Justification:
Default AF for general population
AF for the quality of the whole database:
2
Justification:
The DNEL is based on a study with some limitations
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
repeated dose toxicity
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population