Silicon orthophosphate

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

4.4 mg/m³

Most sensitive endpoint:

effect on fertility

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

100

Modified dose descriptor starting point:

NOAEC

Value:

440.8 mg/m³

Explanation for the modification of the dose descriptor starting point:

No study on long-term inhalation toxicity available.

AF for dose response relationship:

1

AF for differences in duration of exposure:

2

Justification:

DNEL is based on a oral subchronic study.

AF for interspecies differences (allometric scaling):

1

Justification:

AF not used for inhalation route.

AF for other interspecies differences:

2.5

AF for intraspecies differences:

5

AF for the quality of the whole database:

2

Justification:

Limited data quality (Klimisch score of 4).

AF for remaining uncertainties:

2

Justification:

Read-across substance was taken into consideration.

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.25 mg/kg bw/day

Most sensitive endpoint:

effect on fertility

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

400

Modified dose descriptor starting point:

NOAEL

Value:

500 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

No study on long-term dermal toxicity available.

AF for dose response relationship:

1

AF for differences in duration of exposure:

2

Justification:

DNEL is based on a oral subchronic study.

AF for interspecies differences (allometric scaling):

4

AF for other interspecies differences:

2.5

AF for intraspecies differences:

5

AF for the quality of the whole database:

2

Justification:

Limited data quality (Klimisch score of 4).

AF for remaining uncertainties:

2

Justification:

Read-across substance was taken into consideration.

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:

medium hazard (no threshold derived)

Additional information - workers

Systemic effects, long-term

For calculation of the DNEL for long-term inhalative systemic effects, the dose descriptor has to be converted into a corrected starting point by route-to-route extrapolation. Taking the high water solubility of silicon orthophosphate into consideration it is reasonable to assume a complete dissociation of silicon orthophosphate. Therefore, the NOAEL of 500 mg/kg bw/day from a one-generation study with the read-across substance silicon dioxide was taken into consideration for DNEL derivation. 50% absorption is assumed for oral absorption, and 100% for inhalation as recommended in ECHA-guidance Chapter R.8 and to follow a conservative approach: 500 mg/kg bw/day * (1/0.38 m³/kg bw/day) * (0.5/1) * 6.7 m³/ 10 m³) = 440.8 mg/m³.

The LOAEL of 800 mg/kg bw/day taken from the subchronic studies performed with dipotassium hydrogenorthophosphate in dogs (Schneider et al. 1980a/b) were also taken into consideration for DNEL derivation. The LOAEL was mainly based an on the changes that were observed in the kidneys at gross pathology and histopathology (nephrocalcinosis). Conversion of the oral LOAEL into a corrected inhalatory LOAEC would result in a value of 3999.99 mg/m³ (=800 mg/kg bw/day/1.4*70/10). Extrapolation of experimental data to the human situation revealed an DNEL of 13.3 mg/m³, taken the following assessment factors into consideration: dose-response relationship 3, duration of exposure 2, allometric scaling 1.4 (see correction), interspecies 2.5, intraspecies 5, quality of whole database 2, remaining 2. Hence, the worst case was taken into consideration and therefore the value of 4.4 mg/m³ based on the study on fertility was chosen as DNEL. The same is true for the dermal route. Based on the NOAEL of 500 mg/kg bw/day taken from the fertility study, a DNEL of 1.25 mg/kg bw/day was derived for systemic effects after long-term exposure. Taken the LOAEL of the study with dogs into consideration, the DNEL would be 1.9 mg/kg bw/day (=800 mg/kg bw/day / 420 (dose-response relationship 3, duration of exposure 2, allometric scaling 1.4, interspecies 2.5, intraspecies 5, quality of whole database 2, remaining 2)). Therefore, again the lower DNEL was chosen.

General Population - Hazard via inhalation route

Systemic effects

Acute/short term exposure

DNEL related information

Local effects

Acute/short term exposure

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Acute/short term exposure

DNEL related information

General Population - Hazard via oral route

Systemic effects

Acute/short term exposure

DNEL related information