Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
40 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
30
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
40 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
30
Modified dose descriptor starting point:
NOAEC

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4 mg/m³
Most sensitive endpoint:
acute toxicity
DNEL related information
Overall assessment factor (AF):
1 000
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
40 mg/m³
Most sensitive endpoint:
acute toxicity
DNEL related information
Overall assessment factor (AF):
100

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
170 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
1
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2 000 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
DNEL related information
Overall assessment factor (AF):
1
Modified dose descriptor starting point:
NOAEL

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2 000 mg/cm²
Most sensitive endpoint:
acute toxicity
DNEL related information
Overall assessment factor (AF):
1
Dose descriptor starting point:
other: NOAEL

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

The acute dermal DNEL (systemic effects) has been taken from an acute dermal toxicity study. At 2000 mg/kg bw no adverse effects were observed in rats. Moreover, it is known that MGDA has a very low penetration rate through skin.

 

The acute inhalative DNELs (systemic effects) has been derived from the long-term DNEL (40 mg/m3) and considered to be identical due to the early onset of potential kidney effects.

 

The acute DNELs for local effects stem from an RD50 experiment with NTA. RD50 in rats was 4.25 g/m3 (30 min), no effects were recorded at 0.91 g/m3 (NOAEL). A time extrapolation factor of 20 is employed and a factor of 5 between RD50 and NOAEL for sensory irritation.

 

The chronic dermal DNEL (systemic effects) is based on the NOAEL of an oral repeated dose study (90 days). It is also pointed out that there is practically no skin penetration.

 

The chronic inhalative DNEL (systemic effets) employes the NOAEL from the oral 90-day study (170 mg/kg bw/d) and the following assessment factors: 5 for route to route extrapolation (20% intestinal absorption), 2 for allometry and 3 for intraspecies variance. The example of NTA has shown that intestinal resorption and translocation into the kidney (target organ) is slower in humans than in rats, which means that peak concentrations in the renal tubules (which determine the target organ cytotoxicity) are higher in rats than in humans. In that case, the allometric relation should just be the reverse, namely humans should be 4-fold less sensitive than rats. Therefore, the default factor of 4 for allometric relations is reduced to 2. Also the intraspecies factor is reduced from 5 to 3 since the material undergoes no metabolic transformation or other enzyme-linked chemical reactions. A time extrapolation factor is not needed (28-day and 2-year study available. This results in a safe dose of 5.6 mg/kg/day which means 400 mg/person and a workplace exposure of 40 mg/m3.

 

The local chronic DNEL for inhalation has been derived from an acute inhalation study (RD50) with NTA and the acute DNEL. A further time extrapolation of 10 has been employed.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
20 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
60
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
20 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
60
Modified dose descriptor starting point:
NOAEC

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2 mg/m³
Most sensitive endpoint:
acute toxicity
DNEL related information
Overall assessment factor (AF):
2 000
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
20 mg/m³
Most sensitive endpoint:
acute toxicity
DNEL related information
Overall assessment factor (AF):
200

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
25 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
2
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
400 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
DNEL related information
Overall assessment factor (AF):
5
Modified dose descriptor starting point:
NOAEL

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
400 mg/cm²
Most sensitive endpoint:
acute toxicity
DNEL related information
Overall assessment factor (AF):
5
Dose descriptor starting point:
other: NOAEL

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
17 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
10
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
85 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
2
Modified dose descriptor starting point:
NOAEL

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

Basically, similar endpoints and dose descriptors were used as for workers but 2-fold higher assessment factors accounting for intraspecies variation.

 

For the acute oral DNEL, the NOAEL in an oral rat 90-day study (170 mg/kg bw/d) has been combined with an allometric factor of 2. With the example NTA it has been shown that the kidney toxicity is not much dependent from the length of exposure.

 

For the chronic oral DNEL the NOAEL of 170 mg/kg bw/day in the same 90-day study was combined with an overall assessment factor of 10. A chronic oral study is also available showing a somewhat higher NOAEL which, however, in terms of kidney toxicity is less reliable.