Phosphoryl trichloride

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

“In water, phosphoryl trichloride hydrolyzes to phosphoric acid and hydrochloric acid with t1/2 < 10 seconds (Riess, 2002): POCl3+ 3 H2O→H3PO4+ 3 HCl” (OECD SIDS for phosphoryl trichloride, 2004).

 

“Phosphoryl trichloride as well as the hydrolysis product hydrochloric acid are not mutagenic in bacteria. As phosphoryl trichloride decomposes to acid in aqueous media the resulting acidity of the hydrolysis products may cause unspecific effects of low pH in in-vitro tests. The change in pH may induce chromosomal aberrations and other DNA damage. Specific effects of phosphoryl trichloride are not expected due to the rapid hydrolysis” (OECD SIDS for phosphoryl trichloride, 2004).

 

Phosphate and chloride are normal constituents of the body (OECD SIDS for hydrogen chloride, 2002; EFSA, 2005).

 

Chloride:

"Chloride is a normal constituent of the blood and the excess is expected to be excreted into the urine (Ganong, 2001). The uptake of sodium chloride via food is about 3.5-9 gram per person per day (Battarbee and Meneely, 1978; FASEB, 1979). It means 2.1-5.5 g chloride is taken into the body via food. The daily intake through inhalation during an 8-hour work shift is estimated to be only 108 mg/day under the worst case at the working place. The body pool of this anion (Cl-) is large, and the uptake of chloride via exposure to hydrogen chloride/ hydrochloric acid is much less than the uptake of chloride via food, it is therefore unlikely that occupational aerosol exposures significantly alter the normal body load. The uptake of protons via exposure to hydrogen chloride/ hydrochloric acid is not expected to change the pH in the blood under normal handling and use conditions (non-irritating). The pH of the extracellular fluid is regulated within a narrow range to maintain homeostasis. Via urinary excretion and exhalation of carbon dioxide, the pH is maintained at the normal pH of 7.4 (Ganong, 2001)" (OECD SIDS for hydrogen chloride, 2002).

 

Phosphate:

"Phosphorus (as phosphate) is an essential dietary constituent, involved in numerous physiological processes, such as the cell’s energy cycle (high-energy pyrophosphate bonds in adenosine triphosphate [ATP]), regulation of the whole body acid-base balance, as component of the cell structure (as phospholipids) and of nucleotides and nucleic acids in DNA and RNA, in cell regulation and signaling by phosphorylation of catalytic proteins and as second messenger (cAMP). Another important function is in the mineralization of bones and teeth (as part of the hydroxyapatite). Reviews and safety evaluations for phosphorus are available from the Joint FAO/WHO Expert Committee on Food additives (JECFA, 1982), the Food and Nutrition Board of the Institute of Medicine (FNB, 1997), and the UK Expert Group on Vitamins and Minerals (EGVM, 2003). JECFA has used the nephrocalcinosis, induced by excessive phosphate intake in rats, as the critical effect to set a maximum tolerable daily intake (MTDI) of 70 mg/kg for phosphoric acid and phosphate salts. The FNB set an upper level for phosphorus of 4.0 g/day for adults, based upon a NOAEL which represents the extrapolation of the phosphorus intake to serum phosphorus concentration curve in adults up to the intake of phosphorus which would result in serum phosphorus levels of infants, which are considered to be safe for tissues with respect to metastatic mineralization. The UK Expert Group on Vitamins and Minerals used the gastrointestinal effects due to high supplemental phosphate intake, to establish a NOAEL of 750 mg/day for supplemental phosphorus" (EFSA, 2005).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

“In water, phosphoryl trichloride hydrolyzes to phosphoric acid and hydrochloric acid with t1/2 < 10 seconds (Riess, 2002): POCl3+ 3 H2O→H3PO4+ 3 HCl” (OECD SIDS for phosphoryl trichloride, 2004).

“In vivo, the hydrolysis products, phosphoric and hydrochloric acid, will be neutralized immediately in the physiologic medium at low concentrations. The resulting anions chloride and phosphate are essential components of every living tissue. They are not expected to produce mutagenic effects. The reduced pH levels could lead to chromosomal changes and DNA damage at the portal-of-entry of phosphoryl trichloride. However, it is unlikely that systemic changes in pH would occur after exposure to phosphoryl trichloride, which are sufficient in magnitude to induce this effect in distant tissues or organs. Due to the corrosive nature of phosphoryl trichloride the performance of studies in animals is not warranted” (OECD SIDS for phosphoryl trichloride, 2004).

Additional information

No evidence of mutagenicity was seen in an Ames test performed with phosphoryl trichloride in the presence or absence of an exogenous metabolic activation system (Brusick, 1977).

“Phosphoryl trichloride as well as the hydrolysis product hydrochloric acid are not mutagenic in bacteria. As phosphoryl trichloride decomposes to acid in aqueous media the resulting acidity of the hydrolysis products may cause unspecific effects of low pH in in-vitro tests. The change in pH may induce chromosomal aberrations and other DNA damage. Specific effects of phosphoryl trichloride are not expected due to the rapid hydrolysis. In vivo, the hydrolysis products, phosphoric and hydrochloric acid, will be neutralized immediately in the physiologic medium at low concentrations. The resulting anions chloride and phosphate are essential components of every living tissue. They are not expected to produce mutagenic effects. The reduced pH levels could lead to chromosomal changes and DNA damage at the portal-of-entry of phosphoryl trichloride. However, it is unlikely that systemic changes in pH would occur after exposure to phosphoryl trichloride, which are sufficient in magnitude to induce this effect in distant tissues or organs. Due to the corrosive nature of phosphoryl trichloride the performance of studies in animals is not warranted” (OECD SIDS for phosphoryl trichloride, 2004).

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Phosphoryl trichloride is not classified for genotoxicity according to Annex VI of Regulation (EC) No 1272/2008. No classification for genotoxicity is proposed on the basis of a negative Ames test and the considerations for HCl and H3PO4.