Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
11.75 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):
37.5
Dose descriptor starting point:
NOAEL
Value:
500 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
440.79 mg/m³
Explanation for the modification of the dose descriptor starting point:

The equation in Figure R. 8-3 of the guidance on information requirements and chemical safety assessment, Chapter R.8 was used to convert the chronic oral NOAEL into a chronic inhalation NOAEC (an absorption value of ratio of 1:2 was used as a worst-case scenario).

AF for dose response relationship:
1
Justification:
Default value
Justification:
No assessment factor as a chronic study was used to derive the DNEL
Justification:
No assessment factor. The allometric scaling factor of 4 was not applied because differences in breathing rate and rat to human body sizes were considered in the conversion from an oral to inhalation threshold data
AF for other interspecies differences:
2.5
Justification:
Default assessment factor to take into account 'other differences'
AF for intraspecies differences:
5
Justification:
Default assessment factor for workers
AF for the quality of the whole database:
3
Justification:
Additional assessment factor applied to take into account any uncertainties which might arise from the poor quality of the study from which the NOAEL is derived
AF for remaining uncertainties:
1
Justification:
Default value
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:
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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

Data available for the derivation of DNELs is from studies on analogous substance pentasodium triphosphate.

The most relevant NOAEC for the long-term DNELs is from the chronic study (Hodge 1959) which has the highest NOAEC below the lowest LOAEC and is therefore considered the most sensitive endpoint -

An assessment factor was applied in the derivation of long term systemic DNELS to take into account:

"Poor quality of study from which the NOAEL is derived (e.g. few animals and inconsistent spacing between doses) also give uncertainty about the statistically derived NOAEL". Hodge dosed at intervals of 0.05%, 0.5% and 5%, the large spacing provides uncertainty about where the true NOAEL might lie.

Conversion from % in diet to mg/kg bw was calculated in accordance with Appendix F of the guidelines for the preparation of toxicological working papers for the joint FAO/WHO expert committee on food additives, December 2000.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.83 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):
75
Dose descriptor starting point:
NOAEL
Value:
500 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
287.5 mg/m³
Explanation for the modification of the dose descriptor starting point:

The equation in Figure R. 8-3 of the guidance on information requirements and chemical safety assessment, Chapter R.8was used to convert the chronic oral NOAEL into a chronic inhalation NOAEC (an absorption value of ratio of 1:2 was used as a worst-case scenario).

AF for dose response relationship:
1
Justification:
Default value
Justification:
No assessment factor as a chronic study was used to derive the DNEL
Justification:
No assessment factor. The allometric scaling factor of 4 was not applied because differences in breathing rate and rat to human body sizes were considered in the conversion from an oral to inhalation threshold data
AF for other interspecies differences:
2.5
Justification:
Default assessment factor to take into account 'other differences'
AF for intraspecies differences:
10
Justification:
Default assessment factor for the general population
AF for the quality of the whole database:
3
Justification:
Additional assessment factor applied to take into account any uncertainties which might arise from the poor quality of the study from which the NOAEL is derived (poorly spaced dose intervals)
AF for remaining uncertainties:
1
Justification:
Default value
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:
other toxicological threshold
Value:
70 mg/kg bw/day
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

Data available for the derivation of DNELs is from studies on analogous substance pentasodium triphosphate.

The most relevant NOAEC for the derivation of the long term DNELs is from the chronic study (Hodge 1959) which has the highest NOAEC below the lowest LOAEC and is therefore considered the most sensitive endpoint -

An assessment factor was applied in the derivation of long term systemic DNELS to take into account:

"Poor quality of study from which the NOAEL is derived (e.g. few animals and inconsistent spacing between doses) also give uncertainty about the statistically derived NOAEL". Hodge dosed at intervals of 0.05%, 0.5% and 5%. The large spacing provides uncertainty about where the true NOAEL might lie.

Conversion from % in diet to mg/kg bw was calculated in accordance with Appendix F of the guidelines for the preparation of toxicological working papers for the joint FAO/WHO expert committee on food additives, December 2000.