Boron orthophosphate

Endpoint summary

Description of key information

In the absence of specific data on the ADME of boron orthophosphate (BOP),

its physicochemical properties and relevant toxicity data (where available) were assessed for insights into likely ADME characteristics. Although BOP has a MW>100 and <500, its low water solubility suggests that absorption via the inhalation and oral routes is likely to be low. Signs of systemic toxicity observed following a single oral administration in rats indicates that absorption can occur via this route, and therefore is also considered likely following inhalation. Very low dermal absorption is expected. Based on a precautionary approach, a default of 100% is considered appropriate for oral and inhalation routes and 1% for dermal route. Wide tissue distribution of absorbed BOP could occur due to its low MW. The suggested metabolism involves hydrolysis to the more soluble and polar products, borate and phosphate ions. Due to these factors and their low MW, urinary excretion is the most probable route of elimination and bioaccumulation is unlikely.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

ABSORPTION

Oral

No specific data regarding oral absorption of boron orthophosphate (BOP) were found. ECHA guidance suggests that absorption is considered favourable for substances with a molecular weight (MW) below 500 Daltons (ECHA, 2017). It is unclear whether this guidance is intended to cover inorganic as well as organic substances. If it is, then the MW (106 Daltons) might be indicative of absorption. For a substance to be absorbed efficiently from the gastrointestinal tract it must be in solution. A recent study report (O’Conner & Woolley, 2010) determined the water solubility of boron orthophosphate to be 0.143 g/L [143 mg/L], whereas it was more soluble (although still only to a low degree) in simulated gastric fluid (O’Conner, 2012). Whilst boron orthophosphate is not expected to readily dissolve in the gastrointestinal fluids, the substance may (since the MW is below 200) pass through aqueous pores or be carried through the epithelial barrier by the bulk passage of water (ECHA, 2012). Signs of systemic toxicity observed in rats following a single oral dose of boron orthophosphate (Bradshaw, 2013) are an indicator of absorption via this route. In the absence of specific data to the contrary, a default value of 100% is suggested.

Dermal

No data is available regarding dermal absorption of boron orthophosphate. ECHA guidance suggests that absorption is considered favourable for substances with a MW below 100 Daltons (ECHA, 2017). Therefore, the MW (106 Daltons) suggests dermal absorption is likely. For a compound to penetrate the stratum corneum, it must be sufficiently water soluble i. e. above 1 mg/L (ECHA, 2017). The aqueous solubility of boron orthophosphate (143 mg/L) indicates that dermal absorption will be moderate (ECHA, 2017). A default value of 100% skin absorption is recommended, since the substance has a MW below 500 (ECHA, 2017). However, boron orthophosphate is an inorganic solid substance similar to boric acid. Boron orthophosphate has a higher molecular weight and a lower water solubility compared to boric acid (106 g/mol vs. 61.8 g/mol and 0.143 g/L vs. 49.2 g/L). Those physical-chemical parameter for boric acid would lead according to ECHA guidance also to a moderate dermal absorption. Even though no dermal absorption studies have been performed according to modern guidelines with boric acid, during Meetings of the Commission Working Group on the Classification and Labelling of Dangerous Substances it has been stated several times that human skin absorption for boric acid is less than 0.3%. In the SCCNFP Opinion concerning boric acid, borates and tetraborates adopted 23 September 1998 (SCCNFP/0024/98) the percutaneous absorption was considered to be about 0.2%.The SCCS considers that the available measurements of dermal absorption have a significant degree of uncertainty. Therefore absorption of 0.5% will be used in the safety evaluation for the boric compounds discussed in this Opinion on boron compounds (SCCS/1249/09). This is in agreement with other recent risk assessment of borates in EU (EU, 2009, ECHA, 2010). It should be noted that skin absorption is probably higher in case of damaged skin. QSAR estimation (DERMWIN) result in a permeability constant of 7.89 -E06 cm/h and a flux rate of 0.00115 µg/cm²/h which lead to a very low dermal absorption potential of 1%. For the estimation a calculated (EpiSuite) log Pow of -2.59 was considered. This estimated value for boron orthophosphate is very close to the agreed dermal absorption value for boric acid therefore, a dermal absorption rate of 1% is assumed for boron orthophosphate as a worst case.

 

Inhalation

According to ECHA (2017) guidance, particles with aerodynamic diameters below 100 µm have the potential to be inhaled. In a recent study report (Griffiths, 2013), the mean mass median aerodynamic diameter of boron orthophosphate was measured at 2.72 µm. Therefore BOP particles can be inhaled and, since they are below 15 µm, may reach the alveolar region of the respiratory tract (ECHA, 2017). Very hydrophilic substances might be absorbed through aqueous pores (MW <200) or be retained in the mucous and transported out of the respiratory tract, and subsequently swallowed. However, due to boron orthophosphate’s low solubility, the rate at which the particles dissolve into the mucous fluid will limit the amount that can be absorbed directly (ECHA, 2017). As signs of systemic toxicity observed in an oral rat study (Bradshaw, 2012) indicate absorption following ingestion, it is likely that the substance will also be absorbed if inhaled (ECHA, 2017). On this basis, a default of 100% is proposed.

 

DISTRIBUTION/METABOLISM

No data were found regarding the distribution and metabolism for boron orthophosphate. As a small molecule, a wide tissue distribution is possible (ECHA, 2017). Since the substance is of low solubility, it will not be able to diffuse through aqueous channels and pores (ECHA, 2017). The structure suggests that boron orthophosphate will slowly ionise to phosphate anions and boron species. The boron is likely to be converted to borate anions which would either exist as “free” ions or become associated with normal body cations (e. g. sodium). Boron and phosphorous are essential elements; presumably any borate and phosphate formed would not affect the body’s normal content and would be handled in the same way.

 

EXCRETION

Based on the low MW and the probable hydrolysis, any absorbed boron orthophosphate would most likely be excreted in the urine. Biliary excretion tends to be limited to compounds of higher MWs (around 300 in the rat) (ECHA, 2017) and is likely not to be a significant excretion route for boron orthophosphate.

 

References

Bradshaw J (2013). Boron orthophosphate: Acute oral toxicity in the rat - fixed dose method. Project number: 41204125. Harlan Laboratories Ltd, Derbyshire.

 

ECHA (2017). Guidance on information requirements and chemical safety assessment. Chapter R.7c: Endpoint specific guidance. November 2012 (version 1.1).

EU (2009). European Union Draft Risk Assessment Report on Disodium Tetraborate, Anhydrous Boric Acid, Boric Acid, Boric Acid, Crude Natural. (https://echa.europa.eu/documents/10162/ea3533df-1457-4664-98d6-51b2f904af36)

ECHA (2010) Committee for Risk Assessment (RAC). Opinion on new scientific evidence on the use of boric acid and borates in photographic applications by consumers. ECHA/RAC/A77-O-0000001273-82-05/F. Helsinki 29 April 2010.

 

Griffiths DR (2013). Boron orthophosphate: Acute inhalation toxicity (nose only) study in the rat. Project number: 41204126. Harlan Laboratories Ltd, Derbyshire.

 

O’Conner BJ (2012). Boron orthophosphate: Determination of Solubility in Simulated Gastric Fluid. Harlan study number: 41203846. Harlan Laboratories Ltd, Derbyshire.

 

O’Conner BJ & Woolley SM (2010). Boron orthophosphate: Determination of melting/freezing temperature and water solubility. Project number: 2920/0028. Harlan Laboratories Ltd, Derbyshire.

SCCS/1249/09: https://ec.europa.eu/health/scientific_committees/consumer_safety/docs/sccs_o_027.pdf