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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
17.63 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):
25
Dose descriptor starting point:
NOAEL
DNEL value:
500 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL 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 ratio of 1:2 was used as a worst-case scenario.

The equation in Figure R. 8-3 of the guidance on information requirements

AF for dose response relationship:
1
Justification:
When the starting point for the DNEL calculation is a NOAEL, the default assessment factor, as a standard procedure, is 1
AF for differences in duration of exposure:
1
Justification:
As work place data are available to show that long-term inhalation exposure of humans does not result in adverse effects, a reduced factor of 1 was applied.
Justification:
No assessment factor. An allometric scaling factor of 4 was not applied as differences between human and rat breathing rates and body weights were taken into account when correcting the NOEC.
AF for other interspecies differences:
2.5
Justification:
Default assessment factor to take into account 'other differences'
AF for intraspecies differences:
5
Justification:
Intraspecies factor for workers
AF for the quality of the whole database:
2
Justification:
An additional assessment factor to take into account the deviations from the OECD guideline and uncertainties arising from the dataset was applied.
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:
low hazard (no threshold derived)

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.35 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):
50
Dose descriptor starting point:
NOAEL
DNEL value:
500 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
217.39 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 ratio of 1:2 was used as a worst-case scenario.  
AF for dose response relationship:
1
Justification:
When the starting point for the DNEL calculation is a NOAEL, the default assessment factor, as a standard procedure, is 1
AF for differences in duration of exposure:
1
Justification:
As work place data are available to show that long-term inhalation exposure of humans does not result in adverse effects, a reduced factor of 1 was applied.
Justification:
An allometric scaling factor of 4 was not applied as differences between human and rat breathing rates and body weights were taken into account when correcting the NOEC.
AF for other interspecies differences:
2.5
Justification:
Default assessment factor to take into account 'other differences' .
AF for intraspecies differences:
10
Justification:
Intraspecies factor for the general population.
AF for the quality of the whole database:
2
Justification:
An additional assessment factor to take into account the deviations from the OECD guideline and uncertainties arising from the dataset was applied.
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:
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:
low hazard (no threshold derived)

Additional information - General Population

Inorganic Phosphate Group 2i Derived No Effect Level (DNEL) derivation

 

Inorganic phosphate group 2i(sodium and potassium pyrophosphates):

 

IP No

Substance name

CAS No

EINECS No

Classification (EU CLP)

5

Disodium dihydrogenpyrophosphate

7758-16-9

231-835-0

- Irritating to eyes , category 2

6

Trisodium hydrogen diphosphate

14691-80-6

238-735-6

 - Corrosive to eyes, Category 1

-Acute toxicity - Category 4

7

Tetrasodium pyrophosphate

7722-88-5

231-767-1

- Corrosive to eyes, category 1

- Acute toxicity via the oral route, category 4

15

Tetrapotassium pyrophosphate

7320-34-5

230-785-7

- Irritating to eyes , category 2

 

All members of the group are structurally similar ionic inorganic compounds with the anion only changing by the number of hydrogen atoms to account for changes in charge due to increase in cation numbers.

Progression through the group sees an increase in cation number from two to four followed by a change in cation from sodium to potassium. Both cations are group 1 alkali metals with the same ionic charge, similar chemical behaviour and both sodium and potassium are essential biological elements.

 

 

Available tests

 

Key study is a 90-day repeated dose toxicity oral study performed according to OECD 408 (deviations noted include: 5 day dosing regimen and no individual data reported). No indication of GLP compliance is reported but the study is considered to be of sufficient adequacy and reliability to be considered a reliability 2. Additional supporting data are available but lack data are not considered suitable for use in the derivation of DNELs.

Additionally, six teratology studies are also available, four on disodium dihydrogenpyrophosphate and two on tetrasodium pyrophosphate.

 

Table1: Overview of available sub toxicity studies with pyrophosphates

Study length

Animal

N(L)OAEL [mg/kg bw/day]

Reference

Reliability

13 Week

SD Rat

500 mg/ kg bw/day (NOAEL)

Seo DS et al, 2011

2 (KEY STUDY)

13 week

Rat

0.6% in feed (LOEL)

Shimoji Net al.1988

2

6/12 months

Mouse

1% in feed (LOEL)

Omoto Met al.1986

4

16 weeks

Rat

1% in feed (LOEL)

Datta PKet al.1962

2

72 hr

Rat

10% in feed (one dose only)

CraigJM 1957

4

10 d

Mouse

335

Morgareidge K 1973

2

10 d

Rat

169

Morgareidge K 1973

2

5 d

Hamster

166

Morgareidge K 1973

2

13 d

Rabbit

128

Morgareidge K 1973

2

10 d

Mouse

130

Bailey DE and Morgareidge K 1974

2

10 d

Rat

138

Bailey DE and Morgareidge K 1974

2

    

Choice of endpoint

The Derived No Effect Level will use the NOAEL of 500 mg/kg bw/day from the key study in rats (Seo DS, 2011). See above for DNEL justifications.  The starting point was not corrested for differences in molecular formula since the NOAEL is based on the effects of pyrophosphate.

 

References

SCF (1990). Reports of the Scientific Committee for Food (Twenty-fifth series), First series of food additives of various technological functions, Opinion expressed on 18 May 1990,: Commission of the European Communities

 

[1]Guidance on information requirements and chemical safety assessment Chapter R.8 Appendix R. 8-8

[2]Guidance on information requirements and chemical safety assessment Chapter R.8 Appendix R. 8-8