Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
664 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:
6 637 mg/m³
Explanation for the modification of the dose descriptor starting point:
assessment factor for route-to-route extrapolation: 1
AF for dose response relationship:
1
Justification:
default assessment factor
AF for differences in duration of exposure:
2
Justification:
default assessment factor
AF for interspecies differences (allometric scaling):
1
Justification:
allometric scaling is not applied in the case of systemic effects after inhalation
AF for other interspecies differences:
1
Justification:
L-tryptophan is an essential amino acid for all mammalian species
AF for intraspecies differences:
5
Justification:
default assessment factor
AF for the quality of the whole database:
1
Justification:
default assessment factor
AF for remaining uncertainties:
1
Justification:
L-tryptophan is an essential amino acid for all mammalian species
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:
941 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:
37 640 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
assessment factor route-to-route extrapolation 1, default assessment factor for oral to dermal exposure
AF for dose response relationship:
1
Justification:
default assessment factor
AF for differences in duration of exposure:
2
Justification:
default assessment factor
AF for interspecies differences (allometric scaling):
4
Justification:
default assessment factor
AF for other interspecies differences:
1
Justification:
L-tryptophan is an essential amino acid for all mammalian species
AF for intraspecies differences:
5
Justification:
default assessment factor
AF for the quality of the whole database:
1
Justification:
default assessment factor
AF for remaining uncertainties:
1
Justification:
L-tryptophan is an essential amino acid for all mammalian species
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

DNEL Long-term - inhalation, systemic effects

 

Relevant dose descriptor for the endpoint concerned: NOAEL of 3764 mg/kg bw/day in rats in a 90-day oral toxicity study with GLP compliance according to OECD Guideline 408

 

Correction of starting point:

Differences in respiratory volumes: respiratory volume of the rat in 8 h corresponds to 0.38 m3/kg bw, additional correction for the higher standard respiratory volumes of workers compared to resting persons: correction factor = (1 ÷ 0.38) * (6.7 ÷ 10) = 1.76

Overall correction factor: 1.76

Corrected starting point: 3764 * 1.76 = 6637 mg/m3

 

Assessment factors relating to the extrapolation procedure:

Interspecies: not considered, as an allometric scaling is not applied in the case of systemic effects after inhalation

Intraspecies: 5 (default assessment factor for workers)

Time extrapolation: 2 (default assessment factor for sub-chronic to chronic study)

Route to route extrapolation: 1 (as L-Tryptophan is an essential amino acid for humans and rats bioavailability following oral administration is considered to be high )

Dose-response: 1 (default assessment factor for a reliable NOAEL)

Quality of whole database: 1 (default assessment factor for completeness of the available data)

Overall assessment factor:5 * 2 * 1 * 1 * 1 = 10

 

DNEL Long-term - inhalation, systemic effects: 6637 mg/m3 ÷ 10 = 664 mg/m3

 

 

 

DNEL Long-term - dermal, systemic effects

 

Relevant dose descriptor for the endpoint concerned: NOAEL of 3764 mg/kg bw/day in rats in a 90-day oral toxicity study with GLP compliance according to OECD Guideline 408

 

Correction of starting point:

Differences in absorption: Oral absorption is assumed to be 100%, while dermal absorption is assumed to be 10% absorption.
Corrected starting point: 3764 * 100 / 10 = 37640 mg/m3

 

Assessment factors relating to the extrapolation procedure:

Interspecies: 4 (default assessment factor for allometric scaling; an additional assessment factor of 2.5 for “remaining differences” was not considered as L-tryptophan is an essential amino acid for all mammalian species)

Intraspecies: 5 (default assessment factor for workers)

Time extrapolation: 2 (default assessment factor for sub-chronic to chronic study)

Route to route extrapolation: 1 (default assessment factor for oral to dermal exposure)

Dose-response: 1 (default assessment factor for a reliable NOAEL)

Quality of whole database: 1 (default assessment factor for completeness of the available data)

Overall assessment factor: 4 * 5 * 2 * 1 * 1 * 1 = 40

 

DNEL Long-term - dermal, systemic effects: 37640 mg/kg bw/day ÷ 40 = 941 mg/kg bw/day

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
164 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):
20
Modified dose descriptor starting point:
NOAEC
Value:
3 273 mg/m³
Explanation for the modification of the dose descriptor starting point:
assessment factor route-to-route extrapolation 1
AF for dose response relationship:
1
Justification:
default assessment factor
AF for differences in duration of exposure:
2
Justification:
default assessment factor
AF for interspecies differences (allometric scaling):
1
Justification:
allometric scaling is not applied in the case of systemic effects after inhalation
AF for other interspecies differences:
1
Justification:
L-tryptophan is an essential amino acid for all mammalian species
AF for intraspecies differences:
10
Justification:
default assessment factor
AF for the quality of the whole database:
1
Justification:
default assessment factor
AF for remaining uncertainties:
1
Justification:
L-tryptophan is an essential amino acid for all mammalian species
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:
471 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):
80
Modified dose descriptor starting point:
NOAEL
Value:
37 640 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
assessment factor route-to-route extrapolation 1, default assessment factor for oral to dermal exposure
AF for dose response relationship:
1
Justification:
default assessment factor
AF for differences in duration of exposure:
2
Justification:
default assessment factor
AF for interspecies differences (allometric scaling):
4
Justification:
default assessment factor
AF for other interspecies differences:
1
Justification:
L-tryptophan is an essential amino acid for all mammalian species
AF for intraspecies differences:
10
Justification:
default assessment factor
AF for the quality of the whole database:
1
Justification:
default assessment factor
AF for remaining uncertainties:
1
Justification:
L-tryptophan is an essential amino acid for all mammalian species
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:
DNEL (Derived No Effect Level)
Value:
47 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):
80
Modified dose descriptor starting point:
NOAEL
Value:
3 764 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
assessment factor route-to-route extrapolation 1,
AF for dose response relationship:
1
Justification:
default assessment factor
AF for differences in duration of exposure:
2
Justification:
default assessment factor
AF for interspecies differences (allometric scaling):
4
Justification:
default assessment factor
AF for other interspecies differences:
1
Justification:
L-tryptophan is an essential amino acid for all mammalian species
AF for intraspecies differences:
10
Justification:
default assessment factor
AF for the quality of the whole database:
1
Justification:
default assessment factor
AF for remaining uncertainties:
1
Justification:
L-tryptophan is an essential amino acid for all mammalian species
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

DNEL Long-term - inhalation, systemic effects

 

Relevant dose descriptor for the endpoint concerned: NOAEL of 3764 mg/kg bw/day in rats in a 90-day oral toxicity study with GLP compliance according to OECD Guideline 408

 

Correction of starting point:

Differences in respiratory volumes: respiratory volume of the rat in 24 h corresponds to 1.15 m3/kg bw, correction factor 1 ÷ 1.15 = 0.87

Overall correction factor: 0.87

Corrected starting point: 3764 * 0.87 = 3273 mg/m3

 

Assessment factors relating to the extrapolation procedure:

Interspecies: not considered, as an allometric scaling is not applied in the case of systemic effects after inhalation

Intraspecies: 10 (default assessment factor for general population)

Time extrapolation: 2 (default assessment factor for sub-chronic to chronic study)

Route to route extrapolation: 1 (as L-Tryptophan is an essential amino acid for humans and rats bioavailability following oral administration is considered to be high)

Dose-response: 1 (default assessment factor for a reliable NOAEL)

Quality of whole database: 1 (default assessment factor for completeness of the available data)

Overall assessment factor:10 * 2 * 1 * 1 * 1 = 20

 

DNEL Long-term - inhalation, systemic effects: 3273 mg/m3 ÷ 20 = 164 mg/m3

 

 

 

DNEL Long-term - dermal, systemic effects

 

Relevant dose descriptor for the endpoint concerned: NOAEL of 3764 mg/kg bw/day in rats in a 90-day oral toxicity study with GLP compliance according to OECD Guideline 408

 

Correction of starting point:

Differences in absorption: Oral absorption is assumed to be 100%, while dermal absorption is assumed to be 10% absorption is.
Corrected starting point: 3764 * 100 / 10 = 37640 mg/m3

 

Assessment factors relating to the extrapolation procedure:

Interspecies: 4 (default assessment factor for allometric scaling; an additional assessment factor of 2.5 for “remaining differences” was not considered as l-tryptophan is an essential amino acid for all mammalian species)

Intraspecies: 10 (default assessment factor for general population)

Time extrapolation: 2 (default assessment factor for sub-chronic to chronic study)

Route to route extrapolation: 1 (default assessment factor for oral to dermal exposure)

Dose-response: 1 (default assessment factor for a reliable NOAEL)

Quality of whole database: 1 (default assessment factor for completeness of the available data)

Overall assessment factor: 4 * 10 * 2 * 1 * 1 * 1 = 80

 

DNEL Long-term - dermal, systemic effects: 37640 mg/kg bw/day ÷ 80 = 471 mg/kg bw/day

 

 

 

DNEL Long-term - oral, systemic effects

 

Relevant dose descriptor for the endpoint concerned: NOAEL of 3764 mg/kg bw/day in rats in a 90-day oral toxicity study with GLP compliance according to OECD Guideline 408

 

Starting point: 3764 mg/kg bw/day

 

Assessment factors relating to the extrapolation procedure:

Interspecies: 4 (default assessment factor for allometric scaling; an additional assessment factor of 2.5 for “remaining differences” was not considered as l-tryptophan is an essential amino acid for all mammalian species)

Intraspecies: 10 (default assessment factor for general population)

Time extrapolation: 2 (default assessment factor for sub-chronic to chronic study)

Route to route extrapolation: not considered, as same route

Dose-response: 1 (default assessment factor for a reliable NOAEL)

Quality of whole database: 1 (default assessment factor for completeness of the available data)

Overall assessment factor: 4 * 10 * 2 * 1 * 1 = 80

 

DNEL Long-term - oral, systemic effects: 3764 mg/kg bw/day ÷ 80 = 47 mg/kg bw/day