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Key value for chemical safety assessment

Effects on fertility

Description of key information
Please refer to "Justification for classification or non-classification"
Additional information

Please refer to "Justification for classification or non-classification"


Short description of key information:
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.

Effects on developmental toxicity

Description of key information
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.
Additional information

Please refer to "Justification for classification or non-classification"

Justification for classification or non-classification

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 reproductive and developmental toxicity of Phosphoric acid/Diphosphorus pentaoxide, respectively is solely based on secondary effects of corrosivity. Therefore, the concentration of Diphosphorus pentaoxide has to be adjusted to a pH level which is tolerated in order to avoid local effects and focus on systemic impacts of the test substance. In an acute fish toxicity study (study no. FAZ13451; for details please refer to IUCLID Chapter 6.1.1) a pH of 3.19 was determined for a solution of 100 mg Diphosphorus pentaoxide/L. This concentration might be locally tolerated by the stomach tissue concerning irritating effects when given to rats via gavage repeatedly.

Taking into account the above mentioned facts, higher tier studies applying dosages greater than 100 mg Diphosphorus pentaoxide/L are scientifically and for animal welfare reasons not justified due to due to foreseeable caustic effects. Beyond this, for local irritation the concentration is in most cases the relevant parameter, and prolongation of exposure is expected to influence the severity of effect and morphology of changes, but not the NOAEC/NOAEL.

With reference to the recent OECD Guidelines for the testing of chemicals the dose volume should not exceed 20 mL/kg bw in case of aqueous solutions which leads to a maximum of 2 mg Diphosphorus pentaoxide/kg bw/d (maximum dose level of 100 mg/L). As above mentioned Diphosphorus pentaoxide is hydrolysed to Phosphoric acid when it comes in contact with water (most common vehicle in animal studies) 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 hydrolised to Phosphate when dissolved in water. With reference to the chemical parameters mentioned below the daily Phosphate uptake by a study animal (highest dose 2 mg Diphosphorus pentaoxide/kg bw/d at a maximum dose level of 100 mg/L) is calculated to be 2.7 mg Phosphate/kg bw/d.

with

Molecular weight (P2O5): 142 g/mol

Molecular weight (PO43-): 95 g/mol

Max. daily dosage: 2 mg Diphosphorus pentaoxide/kg bw/d

=> (0.002g / 142 g/mol) = 1.4 x 10-5 mol Diphosphorus pentaoxide/kg bw/d

=> 2 x 1.4 x 10-5 mol = 2.8 x 10-5 mol Phosphate/kg bw/d

=> (2.8 x 10-5 mol x 95 g/mol) = 2.7 x 10-3 g/kg bw/d

=> 2.7 mg Phosphate/kg bw/d.

Furthermore, the mean food consumption of a rat is 100 g/kg bw/d and a rhodent standard diet contains 0.7 0.8 % Phosphorus, the mean daily Phosphorus uptake is calculated to be 0.8 g/kg bw/d:

Mean food consumption (rat): 100 g/kg bw/d

Mean phosphorus content in rhodent diet: 0.8 %

=> (0.8 % x 100 g/kg bw/d) / 100 % = 0.8 g Phosphorus/kg bw/d

Compared to the daily uptake of 800 mg Phosphorus/kg bw/d via diet the calculated additional amount of Phosphate (2.7 mg/kg bw/d) is negligible and systemic effects are very unlikely to occur. Furthermore, no risk is arising from the Phosphate which is part of the daily diet.

Considering the above mentioned calculations/arguments a reproductive/developmental toxicity study is scientifically not justified since the systemic exposure to Diphosphorus Pentaoxide itself is not expected to occur due to complete dissolution to Phosphoric acid and exposure to the resulting Phosphate is negligible compared to the normal daily Phosphorus uptake via diet.

Furthermore, Phosphate is known to be a food additive and endogenous compound with widespread functions within biochemical (inter)actions. It is also a key component of numerous bio-macromolecules, bones, teeth etc.

Although no sufficient data for classification of Diphosphorus pentaoxide is available, the substance is not expected to exert reproductive/developmental toxic effects due to the unlikelihood of systemic exposure (strict application of risk management measures concerning the corrosivity) and the widespread occurence in organisms of mammalians.