Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 mg/m³
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
Value:
1 mg/m³
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
68.7 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
Value:
1 % in mixture (weight basis)
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Additional information - workers

- Acute dermal/inhalation systemic DNEL:

According to RIP 3.2.2, Chapter R8, R8.1.2.5, p. 16 no acute DNELs were derived since no acute toxicity hazard has been identified. The acute local DNEL also covers possible acute toxic effects.

- Acute dermal/inhalation local DNEL:
Diphosphorus pentaoxide is highly corrosive. Dilution with water is very exothermic and contributes to the corrosive activity of this material. The anion Phosphate is a naturally occurring dietary and body constituent.

The following DNELs were derived as default values:

-acute dermal exposure: the material is highly corrosive and dermal exposure must be avoided. According to the Dangerous Preparation Directive 1999/45/EC and Regulation 1272/2008/EC a formulation containing < 1% of a corrosive substance (R35, H314) has not to be labeled as corrosive or irritant. Therefore, the dermal acute DNEL for local effects is set at < 1%.

-acute inhalation exposure: the material is highly corrosive and exposure by inhalation must be avoided. According to EU OEL- Directive on indicative exposure limits (revision:07/02/2006) the time-weighted average – 8 hours value is 1 mg/m3.

- DNEL derivation

There is no systemic toxicity but corrosion and irritation at the port of entry expected to occur; the DNEL for local effects protects also from systemic toxicity.

However, in case of a very unlikely systemic exposure long-term systemic DNELs were derived as follows:

Diphosphorus pentaoxide is a hygroscopic solid which forms with moisture/water an aqueous solution of phosphorus oxyacids (primary hydrolysis) that are subject to further (secondary) hydrolysis to the end product phosphoric acid, H3PO4. The exposure to Diphosphorus pentaoxide under physiological conditions (aqueous system) will principally lead to local effects due to the strong corrosivity of the generated phosphoric acid. Consequently, the toxicity of Phosphoric acid/Diphosphorus pentaoxide, respectively is solely based on secondary effects of corrosivity. Due to the rapid and complete hydrolysis of Diphosphorus pentaoxide the only compound which will be available systemically after exposure is Phosphate.

Phosphate is known to be a food additive and an ADI(Acceptable Daily Intake) value for Phosphorus for the general population based on Phosphate toxicity data is available. According to the FAO/WHO (Food and Agriculture Organization of the United Nations/World Health Organization) it is set at 30-70 mg Phosphorus/kg bw (FAO Nutrition Meetings, Report Series No. 48A, WHO/FOODADD/70.39 June 1970 and Report Series No. 17, May 1998). In general, the ADI is a very conservative approach and applicable on the general population (incl. children, pregnant women and the elderly population). Therefore, it is justified to use this value instead of a long-term oral DNEL for humans (workers as well as consumers).

Long-term dermal systemic DNEL based on ADI(Phosphorus; derived by FAO/WHO Expert Commitee):
- DNEL(dermal) derived according to “Guidance on information requirements and chemical safety assessment”, Chapter R8-2, Example B.5 (p. 69).
corrected DNEL(dermal)             =ADI(Phosphorus; oral, human) x Absorption(oral-human)/Absorption(dermal-human)
                                                  = 30 mg/kg bw x 100%/100%
                                                  = 30 mg/kg bw
- since this DNEL(Phosphorus; dermal) is derived from an accepted ADI which includes valid toxicity data as well safety factors, the application of further assessment factors is not necessary.
=>30 mg Phosphorus/kg bw/d

As above mentioned Diphosphorus pentaoxide is hydrolysed to Phosphoric acid when it comes in contact with water (most common liquid in organisms) according to the following formula:

 

P2O5+ 3H2O → 2 H3PO4

This means that 2 mol Phosphate will be formed out of 1 mol Diphosphorus Pentaoxide. Diphosphorus Pentaoxide will be completely hydrolysed to Phosphate when dissolved in water. With reference to the chemical parameters mentioned below the

long-term dermal systemic DNEL for Diphosphorus pentaoxide is calculated to be: 68.7 mg/kg bw/d with

Molecular weight (P2O5): 142 g/mol

Molecular weight (P-): 31 g/mol 

30 mg Phosphorus/31 g/mol = 9.68 x 10-5mol Phosphorus

(9.68 x 10-5mol x 142 g P2O5/mol) / 2 = 68.7 mg/kg bw/d Diphosphorus pentaoxide

Long-term inhalatory DNEL based on ADI (Phosphorus; derived by FAO/WHO Expert Commitee):
- DNEL(inhalation) derived based on the following assumptions

ADI                             = 30 mg Phosphorus/kg bw/d

DNEL(P2O5; dermal)  = 68.7 mg/kg bw/d

Average body weight   = 70 kg (according to “Guidance on information requirements and chemical safety assessment”, Chapter R8.4.3.1, p. 30)

=>acceptable daily systemic dose= 68.7 mg/kg bw/d x 70 kg =4809 mg/d

 Respiratory volume (worker, 8h, light activity) = 10 m3/person (according to “Guidance on information requirements and chemical safety assessment”, Chapter R8.4.2, Table R8-2, p. 26)

 =>DNEL(inhalation)= 4809 mg / 10 m3=480.9 mg/m3

The calculated DNEL(inhalation) is very unlikely to occur. Working in an atmosphere containing 480.9 mg/m3 Diphosphorus pentaoxide dust is not possible due to the strong corrosive properties of this substance. Therefore, in order to follow the most conservative approach the acute inhalation DNEL for local effects, 1 mg/m3(please refer to DNEL derivation Acute dermal/inhalation local DNEL”), was chosen as DNEL(inhalation).

 

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 mg/m³
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
Value:
1 mg/m³
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
68.7 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
Value:
1 % in mixture (weight basis)
Most sensitive endpoint:
skin irritation/corrosion

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
68.7 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Acute/short term exposure
DNEL related information

General Population - Hazard for the eyes

Additional information - General Population

- Acute dermal/inhalation systemic DNEL:

According to RIP 3.2.2, Chapter R8, R8.1.2.5, p. 16 no acute DNELs were derived since no acute toxicity hazard has been identified. The acute local DNEL also covers possible acute toxic effects.

- Acute dermal/inhalation local DNEL:
Diphosphorus pentaoxide is highly corrosive. Dilution with water is very exothermic and contributes to the corrosive activity of this material. The anion Phosphate is a naturally occurring dietary and body constituent.

The following DNELs were derived as default values:

-acute dermal exposure: the material is highly corrosive and dermal exposure must be avoided. According to the Dangerous Preparation Directive 1999/45/EC and Regulation 1272/2008/EC a formulation containing < 1% of a corrosive substance (R35, H314) has not to be labelled as corrosive or irritant. Therefore, the dermal acute DNEL for local effects is set at < 1%.

-acute inhalation exposure: the material is highly corrosive and exposure by inhalation must be avoided. According to EU OEL- Directive on indicative exposure limits (revision:07/02/2006) the time-weighted average – 8 hours value is 1 mg/m3.

DNEL derivation

There is no systemic toxicity but corrosion and irritation at the port of entry expected to occur; the DNEL for local effects protects also from systemic toxicity.

 

However, in case of a very unlikely systemic exposure long-term systemic DNELs were derived as follows:

Diphosphorus pentaoxide is a hygroscopic solid which forms with moisture/water an aqueous solution of phosphorus oxyacids (primary hydrolysis) that are subject to further (secondary) hydrolysis to the end product phosphoric acid, H3PO4. The exposure to Diphosphorus pentaoxide under physiological conditions (aqueous system) will principally lead to local effects due to the strong corrosivity of the generated phosphoric acid. Consequently, the toxicity of Phosphoric acid/Diphosphorus pentaoxide, respectively is solely based on secondary effects of corrosivity. Due to the rapid and complete hydrolysis of Diphosphorus pentaoxide the only compound which will be available systemically after exposure is Phosphate.

Phosphate is known to be a food additive and an ADI(Acceptable Daily Intake) value for Phosphorus for the general population based on Phosphate toxicity data is available. According to the FAO/WHO (Food and Agriculture Organization of the United Nations/World Health Organization) it is set at 30-70 mg Phosphorus/kg bw (FAO Nutrition Meetings, Report Series No. 48A, WHO/FOODADD/70.39 June 1970 and Report Series No. 17, May 1998). In general, the ADI is a very conservative approach and applicable on the general population (incl. children, pregnant women and the elderly population). Therefore, it is justified to use this value instead of a long-term oral DNEL for humans (workers as well as consumers).

Long-term oral/ dermal systemic DNEL based on ADI(Phosphorus; derived by FAO/WHO Expert Commitee):
- DNEL(dermal) derived according to “Guidance on information requirements and chemical safety assessment”, Chapter R8-2, Example B.5 (p. 69).
corrected DNEL(dermal)            =ADI(Phosphorus; oral, human) x Absorption(oral

                                                   -human)/Absorption(dermal-human)
                                                  = 30 mg/kg bw x 100%/100%
                                                  = 30 mg/kg bw
- since this DNEL(Phosphorus; dermal) is derived from an accepted ADI which includes valid toxicity data as well safety factors, the application of further assessment factors is not necessary.
=>30 mg Phosphorus/kg bw/d

As above mentioned Diphosphorus pentaoxide is hydrolysed to Phosphoric acid when it comes in contact with water (most common liquid in organisms) according to the following formula:

 

P2O5+ 3H2O → 2 H3PO4

This means that 2 mol Phosphate will be formed out of 1 mol Diphosphorus Pentaoxide. Diphosphorus Pentaoxide will be completely hydrolysed to Phosphate when dissolved in water. With reference to the chemical parameters mentioned below the

long-term oral/dermal systemic DNEL for Diphosphorus pentaoxide is calculated to be: 68.7 mg/kg bw/d

Long-term inhalatory DNEL based on ADI(Phosphorus; derived by FAO/WHO Expert Commitee):
- DNEL(inhalation) derived based on the following assumptions

ADI                            = 30 mg Phosphorus/kg bw/d

DNEL(P2O5; dermal)  = 68.7 mg/kg bw/d

Average body weight   = 70 kg (according to “Guidance on information requirements and chemical safety assessment”, Chapter R8.4.3.1, p. 30)

 

=>acceptable daily systemic dose= 68.7 mg/kg bw/d x 70 kg = 4809 mg/d

 

Respiratory volume (24h) = 20 m3/person (according to “Guidance on information requirements and chemical safety assessment”, Chapter R8.4.2, Table R8-2, p. 26)

 

=>DNEL(inhalation)= 4809 mg / 20 m3= 240.5 mg/m3

The calculated DNEL(inhalation) is very unlikely to occur. The stay in an atmosphere containing 240.5 mg/m3Diphosphorus pentaoxide dust is not possible due to the strong corrosive properties of this substance. Therefore, in order to follow the most conservative approach the acute inhalation DNEL for local effects, 1 mg/m3(please refer to DNEL derivation Acute dermal/inhalation local DNEL”), was chosen as DNEL(inhalation).