Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
7.27 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
Dose descriptor starting point:
NOAEL
Value:
82.5 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
72.7 mg/m³
Explanation for the modification of the dose descriptor starting point:

The following correction was made to the NOAEL (oral): Correction respiratory volume rat (8 hour) 1/0.38 m³/kg bw/day, Correction for respiratory volume (worker): 6.7 m³/10 m³. Correction for oral to inhaled 1/2. Therefore the corrected NOAEC for repeated-dose systemic effects via the inhalation route is: oral 82.5*(1/0.38) *(6.7 m³/10 m³)*(1/2) = 72.7 mg/m³.

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
2
Justification:
Default (subchronic to chronic)
AF for interspecies differences (allometric scaling):
1
Justification:
Default (oral rat to inhaled human)
AF for other interspecies differences:
1
Justification:
The effects observed in the oral study were indicative of the iron binding capacity of the test substance and its influence on calcium homeostasis, however, without causing any changes in calcium plasma levels, therefore no intraspecies differenced apply.
AF for intraspecies differences:
5
Justification:
Default (worker)
AF for the quality of the whole database:
1
Justification:
Default
AF for remaining uncertainties:
1
Justification:
Default
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:
8.25 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):
20
Dose descriptor starting point:
NOAEL
Value:
82.5 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
165 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Measured data are available for DTPMP-H, which indicate that oral absorption is around 2% and dermal absorption is <1%. The following correction was made for the NOAEL (oral): Correction for absorption 2/1. Therefore, the corrected NOAEL for repeated-dose systemic effects via the dermal route is: 82.5*(2/1) = 165 mg/kg bw/day.

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
2
Justification:
Default (subchronic to chronic)
AF for interspecies differences (allometric scaling):
2
Justification:
The effects observed in the oral study were indicative of the iron binding capacity of the test substance and its influence on calcium homeostasis, however, without causing any changes in calcium plasma levels. Therefore, the proposed assessment factor for interspecies differences is 2.
AF for other interspecies differences:
1
Justification:
The effects observed in the oral study were indicative of the iron binding capacity of the test substance and its influence on calcium homeostasis, however, without causing any changes in calcium plasma levels, therefore no intraspecies differenced apply.
AF for intraspecies differences:
5
Justification:
Default (worker)
AF for the quality of the whole database:
1
Justification:
Default
AF for remaining uncertainties:
1
Justification:
Default
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

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.8 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
Dose descriptor starting point:
NOAEL
Value:
82.5 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
35.9 mg/m³
Explanation for the modification of the dose descriptor starting point:

The following correction was made to the NOAEL (oral): Correction respiratory volume rat (24 hour) 1/1.15 m³/kg bw. Correction for oral to inhaled 1/2. Therefore the corrected NOAEC for repeated-dose systemic effects via the inhalation route is: 82.5*(1/1.15)*(1/2) = 35.9 mg/m³.


AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
2
Justification:
Default (subchronic to chronic)
AF for interspecies differences (allometric scaling):
1
Justification:
Default (oral rat to inhaled human)
AF for other interspecies differences:
1
Justification:
The effects observed in the oral study were indicative of the iron binding capacity of the test substance and its influence on calcium homeostasis, however, without causing any changes in calcium plasma levels, therefore no intraspecies differenced apply.
AF for intraspecies differences:
10
Justification:
Default (general population)
AF for the quality of the whole database:
1
Justification:
Default
AF for remaining uncertainties:
1
Justification:
Default
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:
4.1 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
Dose descriptor starting point:
NOAEL
Value:
82.5 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
165 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Measured data are available for DTPMP acid, which indicate that oral absorption is around 2% and dermal absorption is < 1%. The following correction was made for the NOAEL (oral): Correction for absorption 2/1. Therefore, the corrected NOAEL for repeated -dose systemic effects via the dermal route is: 82.5*(2/1) = 165 mg/kg bw/day.

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
2
Justification:
Default (subchronic to chronic)
AF for interspecies differences (allometric scaling):
2
Justification:
The effects observed in the oral study were indicative of the iron binding capacity of the test substance and its influence on calcium homeostasis, however, without causing any changes in calcium plasma levels. Therefore the proposed assessment factor for interspecies differences is 2.
AF for other interspecies differences:
1
Justification:
The effects observed in the oral study were indicative of the iron binding capacity of the test substance and its influence on calcium homeostasis, however, without causing any changes in calcium plasma levels, therefore no intraspecies differenced apply.
AF for intraspecies differences:
10
Justification:
Default (general population)
AF for the quality of the whole database:
1
Justification:
Default
AF for remaining uncertainties:
1
Justification:
Default
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:
2.1 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
Dose descriptor starting point:
NOAEL
Value:
82.5 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No correction was applied to the dose descriptor starting point.

The DNEL long-term systemic effects via the oral route are based on anaemia observed in repeated dose toxicity studies. The starting NOAEL is 82.5 mg active acid/kg bw/day with an assessment factor of 2 applied for duration and 10 for intraspecies. Since the effect was most likely to have been caused by inhibition of iron uptake in the gastrointestinal tract (i.e. a local physicochemical effect in the gut), no allometric scaling or assessment factor for interspecies differences were included in the DNEL calculation. This is justified by the fact that test species used (rats) are more susceptible to iron deficiencies than humans and other standard laboratory species.

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
2
Justification:
Default (subchronic to chronic)
AF for interspecies differences (allometric scaling):
2
Justification:
The effects observed in the oral study were indicative of the iron binding capacity of the test substance and its influence on calcium homeostasis, however, without causing any changes in calcium plasma levels. Therefore the proposed assessment factor for interspecies differences is 2.
AF for other interspecies differences:
1
Justification:
Since the effect was most likely to have been caused by inhibition of iron uptake in the gastrointestinal tract (i.e. a local physicochemical effect in the gut), no allometric scaling or assessment factor for interspecies differences were included in the DNEL calculation. This is justified by the fact that test species used (rats) are more susceptible to iron deficiencies than humans and other standard laboratory species.
AF for intraspecies differences:
10
Justification:
Default (general population)
AF for the quality of the whole database:
1
Justification:
Default
AF for remaining uncertainties:
1
Justification:
Default
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