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Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
12 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):
5
Dose descriptor starting point:
NOAEL
DNEL value:
34 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
60 mg/m³
Explanation for the modification of the dose descriptor starting point:

No data were available for HEDP potassium salts. Therefore, DNELs were based on data for HEDP sodium salts.

A corrected inhalatory NOAEC rat was calculated on the basis of the oral NOAEL rat (34 mg/kg bw/day) by using a default respiratory volume for the rat corresponding to the daily duration of human exposure (sRVrat; see ECHA Guidance R.8. 2012).

The NOAEL for HEDP-2Na (41 mg/kg bw/d) is equivalent to 34 mg active acid/kg bw/day.

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) is not required as there are toxicokinetic data for absorption following oral and inhalation exposure, which support a conservative absortion of 5%. Therefore the corrected NOAEC for repeated-dose systemic effects via the inhalation route is: 34*(1/0.38) *(6.7 m³/10 m³) = 60.0 mg/m³.

AF for dose response relationship:
1
AF for differences in duration of exposure:
1
Justification:
Chronic oral study
AF for interspecies differences (allometric scaling):
1
Justification:
Default assessment factor for interspecies local/systemic effects by inhalation
AF for other interspecies differences:
1
Justification:
Based on anaemia observed in repeated dose toxicity studies. The DNELs derived are precautionary and the AF used may be overcautious. Based on that the AF for other interspecies differences is reduced to 1.
AF for intraspecies differences:
5
Justification:
ECHA REACH Guidance (R.8, 2012), worker
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
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:
34 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):
10
Dose descriptor starting point:
NOAEL
DNEL value:
34 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
340 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No data were available for HEDP potassium salts. Therefore, DNELs were based on data for HEDP sodium salts.

The NOAEL for HEDP-2Na (41 mg/kg bw/d) is equivalent to 34 mg active acid/kg bw/day.

The NOAEL (oral) for HEDP-2Na (41 mg/kg bw/d) is equivalent to 34 mg active acid/kg bw/day. For oral exposure, an absorption of 5% was assumed (see chapter toxicokinetics). For dermal exposure, an absorption of 0.5% was assumed (see chapter toxicokinetics). The starting point is therefore increased by a factor of 10 for the dermal route.

AF for dose response relationship:
1
AF for differences in duration of exposure:
1
Justification:
Chronic oral study
AF for interspecies differences (allometric scaling):
2
Justification:
The mode of action is physicochemical (complexation of metals) and should be irrespective of species. Therefore the proposed assessment factor for interspecies differences is only 2.
AF for other interspecies differences:
1
Justification:
Based on anaemia observed in repeated dose toxicity studies. The DNELs derived are precautionary and the AF used may be overcautious. Based on that the AF for other interspecies differences is reduced to 1.
AF for intraspecies differences:
5
Justification:
ECHA REACH Guidance (R.8, 2012), worker
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Route of original study:
Dermal
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:
2.95 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
DNEL value:
34 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
29.56 mg/m³
Explanation for the modification of the dose descriptor starting point:

No data were available for HEDP potassium salts. Therefore, DNELs were based on data for HEDP sodium salts.

A corrected inhalatory NOAEC rat was calculated on the basis of the oral NOAEL rat (34 mg/kg bw/day) by using a default respiratory volume for the rat corresponding to the daily duration of human exposure (sRVrat; see ECHA Guidance R.8. 2012).

The NOAEL for HEDP-2Na (41 mg/kg bw/d) is equivalent to 34 mg active acid/kg bw/day.

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) is not required as there are toxicokinetic data for absorption following oral and inhalation exposure, which support a conservative absorption of 5%.

Therefore the corrected NOAEC for repeated-dose systemic effects via the inhalation route is: 34*(1/1.15) = 29.56 mg/m³.

AF for dose response relationship:
1
AF for differences in duration of exposure:
1
Justification:
Chronic oral study
AF for interspecies differences (allometric scaling):
1
Justification:
Default assessment factor for interspecies local/systemic effects by inhalation
AF for other interspecies differences:
1
Justification:
Based on anaemia observed in repeated dose toxicity studies. The DNELs derived are precautionary and the AF used may be overcautious. Based on that the AF for other interspecies differences is reduced to 1.
AF for intraspecies differences:
10
Justification:
ECHA REACH Guidance (R.8, 2008), consumer
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
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:
17 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
DNEL value:
34 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
340 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No data were available for HEDP potassium salts. Therefore, DNELs were based on data for HEDP sodium salts.

The NOAEL for HEDP-2Na (41 mg/kg bw/d) is equivalent to 34 mg active acid/kg bw/day. For oral exposure, an absorption of 5% was assumed (see chapter toxicokinetics). For dermal exposure, an absorption of 0.5% was assumed (see chapter toxicokinetics). The starting point is therefore increased by a factor of 10 for the dermal route.

AF for dose response relationship:
1
AF for differences in duration of exposure:
1
Justification:
Chronic oral study
AF for interspecies differences (allometric scaling):
2
Justification:
The mode of action is physicochemical (complexation of metals) and should be irrespective of species. Therefore the proposed assessment factor for interspecies differences is only 2.
AF for other interspecies differences:
1
Justification:
Based on anaemia observed in repeated dose toxicity studies. The DNELs derived are precautionary and the AF used may be overcautious. Based on that the AF for other interspecies differences is reduced to 1.
AF for intraspecies differences:
10
Justification:
ECHA REACH Guidance (R.8, 2012), consumer
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Route of original study:
Dermal
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:
1.7 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):
20
Dose descriptor starting point:
NOAEL
DNEL value:
34 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
34 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No data were available for HEDP potassium salts. Therefore, DNELs were based on data for HEDP sodium salts.

No route to route extrapolation (oral study). The NOAEL for HEDP-2Na (41 mg/kg bw/d) is equivalent to 34 mg active acid/kg bw/d.

AF for dose response relationship:
1
AF for differences in duration of exposure:
1
Justification:
Chronic oral study
AF for interspecies differences (allometric scaling):
2
Justification:
The mode of action is physicochemical (complexation of metals) and should be irrespective of species. Therefore, the proposed assessment factor for interspecies differences is only 2.
AF for other interspecies differences:
1
Justification:
Based on anaemia observed in repeated dose toxicity studies. The DNELs derived are precautionary and the AF used may be overcautious. Based on that the AF for other interspecies differences is reduced to 1.
AF for intraspecies differences:
10
Justification:
ECHA REACH Guidance (R.8, 2012), consumer
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.7 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
20
DNEL extrapolated from long term DNEL

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population