Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
88 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:
1 760 mg/m³
Explanation for the modification of the dose descriptor starting point:
default assessment factor for route-to-route extrapolation: 2
AF for dose response relationship:
1
Justification:
default assessment factor
AF for differences in duration of exposure:
2
Justification:
default assessment factor
Justification:
not considered, as an allometric scaling is not applied in the case of systemic effects after inhalation
Justification:
not considered, as an allometric scaling is not applied in the case of systemic effects after inhalation
AF for intraspecies differences:
5
Justification:
default assessment factor
AF for the quality of the whole database:
1
Justification:
default assessment factor
Acute/short term exposure
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
100 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):
100
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Based on the physico-chemical properties of L-Threonine mother liquor (only partly soluble in water (396-490 g/L; calculated log P value below 0), a significant dermal uptake is not to be expected, i.e. the dermal absorption is assumed to be 10%. See also discussion below
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:
2.5
Justification:
default assessment factor
AF for intraspecies differences:
5
Justification:
default assessment factor
AF for the quality of the whole database:
1
Justification:
default assessment factor
Acute/short term exposure
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

DNELs for acute toxicity are not considered since long-term DNEL is sufficient to ensure that these effects do not occur.

 

Skin and eye irritation/corrosion: L-Threonine mother liquor was tested in GLP studies according to OECD guideline 404 and 405, which both gave no indications for skin and eye irritation.

 

Sensitization: For L-threonine mother liquor itself no studies are available. Therefore, data for the read-across substance Biofert Plusz are taken into further consideration. Biofert Plusz was not sensitizing in a valid study performed according to OECD Guideline 429.

 

Mutagenicity: For L-threonine mother liquor itself there are no studies available. Therefore, data for the read-across substance Biofert Plusz are taken into further consideration. Biofert Plusz was tested negative in different in vitro mutagenicity tests.

 

Reproductive toxicity: For L-threonine mother liquor itself there are no studies available. Therefore, data for the read-across substance Biofert Plusz are taken into further consideration. In rats no maternal and developmental toxicity was detected in a gavage study according to OECD Guideline 414 even at the high dose level of 1000 mg/kg bw/day.

 

 

DNEL Workers

 

DNEL Long-term - inhalation, systemic effects

 

For L-threonine mother liquor itself no studies with repeated dosing are available. Therefore, data for the read-across substance Biofert Plusz are taken into further consideration.

 

Relevant dose descriptor for the endpoint concerned: NOAEL of > 1000 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: 1000 * 1.76 = 1760 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)

Time extrapolation: 2 (default assessment factor)

Route to route extrapolation: 2 (default assessment factor)

Dose-response: 1 (default assessment factor [reliable NOAEL])

Quality of whole database: 1 (default assessment factor [completeness of available data])

Overall assessment factor: 5 * 2 * 2 * 1 * 1 = 20

 

DNEL Long-term - inhalation, systemic effects: 1760 mg/m3 ÷ 20 = 88 mg/m3

 

 

 

DNEL Long-term - dermal, systemic effects

 

For L-threonine mother liquor itself no studies with repeated dosing are available. Therefore, data for the read-across substance Biofert Plusz are taken into further consideration.

 

Relevant dose descriptor for the endpoint concerned: NOAEL of > 1000 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% (based on the physico-chemical properties of L-Threonine mother liquor (only partly soluble in water (396-490 g/L; calculated log P value below 0), a significant dermal uptake is not to be expected)

Corrected starting point: 1000 * 100 / 10 = 10000 mg/kg bw/day

 

Assessment factors relating to the extrapolation procedure:

Interspecies: 4 * 2.5 (default assessment factor for allometric scaling)

Intraspecies: 5 (default assessment factor)

Time extrapolation: 2 (default assessment factor)

Route to route extrapolation: 1 (default assessment factor)

Dose-response: 1 (default assessment factor [reliable NOAEL])

Quality of whole database: 1 (default assessment factor [completeness of available data])

Overall assessment factor: 4 * 2.5 * 5 * 2 * 1 * 1 * 1 = 100

 

DNEL Long-term - dermal, systemic effects: 10000 mg/kg bw/day ÷ 100 = 100 mg/kg bw/day

General Population - Hazard via inhalation 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

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
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

Only workers in the chemical or the agriculture industry might be exposed to L-threonine mother liquor in accidental cases. As L-threonine mother liquor is not a consumer product, an exposure for the general population is not to be expected. Therefore, there is no necessity to derive DNELs for the general population.