Phosphoryl trichloride

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

Phosphoryl trichloride (CAS no. 10025-87-3):

"Phosphoryl trichloride is quickly hydrolysed on contact with water. It is therefore very unlikely that phosphoryl trichloride will reach tissues distant from the portal of entry and become systemically available. The products of hydrolysis, hydrochloric acid and phosphorous acid, also act at the portal of entry. After absorption they will be neutralised immediately and the resulting anions are essential components of every living tissue. 

Therefore, it is very unlikely that phosphoryl trichloride could reach the reproductive organs or the embryo/fetus, and toxicity to reproduction or developmental toxicity in mammals are not likely to occur following exposure to phosphoryl trichloride by any route. 

Additionally, due to the corrosive properties of the substance, exposure is limited to a degree that avoids irritation and therefore a condition of general toxicity, which might cause secondary effects on reproductive performance, is not anticipated to be attained" (OECD SIDS for phosphoryl trichloride, 2004). 

 

"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). 

 

"Due to the corrosive nature of phosphoryl trichloride the performance of studies in animals is not warranted" (OECD SIDS for phosphoryl trichloride, 2004). 

 

Hydrogen chloride/hydrochloric acid and phosphoric acid are not toxic to reproduction.

 

 

Hydrogen chloride/hydrochloric acid (CAS no. 7647-01-0):

"No reliable studies have been reported regarding toxicity to reproduction and development in animals after oral, dermal or inhalation exposure to hydrogen chloride/hydrochloric acid. Because protons and chloride ions are normal constituents in the body fluid of animal species, low concentrations of hydrogen chloride gas/mist or solution do not seem to cause adverse effects to animals. In fact, the cells of gastric glands secrete hydrochloric acid into the cavity of the stomach and orally administered sulfuric acid, which results in pH change as well, did not cause developmental toxicity to laboratory animals. These facts indicate that hydrogen chloride/hydrochloric acid is not expected to have developmental toxicity. In addition, no effects on the gonads were observed in a good quality 90-day inhalation study up to 50 ppm" (OECD SIDS for hydrogen chloride, 2002).

 

 

Phosphoric acid (CAS no. 7664-38-2):

"The reproductive toxicity of phosphoric acid has been investigated in a reproductive and developmental toxicity screening test in rats [OECD TG 422]. In this study, phosphoric acid was administered via gavage to 13 of animals/sex/dose, concentration at 0, 125, 250 and 500 mg/kg bw/day, for 2 weeks. Based on results of reproductive and development toxicity, no treatment-related effects were observed. At 500 mg/kg bw/day, 2/13 adult females died, indicating parental toxicity at this dose. No effects of test substance were observed on mating, conception, parturition and external of neonates, neonate body weights, and survival rate. Therefore, NOAEL for reproductive and development toxicity was estimated to be 500 mg/kg bw/day, the highest dose tested"(OECD SIAP for phosphoric acid, 2011).

 

 

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).

Effect on fertility: via oral route

Endpoint conclusion:

no study available

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Effects on developmental toxicity

Description of key information

Phosphoryl trichloride (CAS no. 10025-87-3):

"Phosphoryl trichloride is quickly hydrolysed on contact with water. It is therefore very unlikely that phosphoryl trichloride will reach tissues distant from the portal of entry and become systemically available. The products of hydrolysis, hydrochloric acid and phosphorous acid, also act at the portal of entry. After absorption they will be neutralised immediately and the resulting anions are essential components of every living tissue. 

Therefore, it is very unlikely that phosphoryl trichloride could reach the reproductive organs or the embryo/fetus, and toxicity to reproduction or developmental toxicity in mammals are not likely to occur following exposure to phosphoryl trichloride by any route. 

Additionally, due to the corrosive properties of the substance, exposure is limited to a degree that avoids irritation and therefore a condition of general toxicity, which might cause secondary effects on reproductive performance, is not anticipated to be attained"(OECD SIDS for phosphoryl trichloride, 2004). 

 

"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). 

 

"Due to the corrosive nature of phosphoryl trichloride the performance of studies in animals is not warranted"(OECD SIDS for phosphoryl trichloride, 2004). 

 

Hydrogen chloride/hydrochloric acid and phosphoric acid are not toxic to reproduction.

 

 

Hydrogen chloride/hydrochloric acid (CAS no. 7647-01-0):

"No reliable studies have been reported regarding toxicity to reproduction and development in animals after oral, dermal or inhalation exposure to hydrogen chloride/hydrochloric acid. Because protons and chloride ions are normal constituents in the body fluid of animal species, low concentrations of hydrogen chloride gas/mist or solution do not seem to cause adverse effects to animals. In fact, the cells of gastric glands secrete hydrochloric acid into the cavity of the stomach and orally administered sulfuric acid, which results in pH change as well, did not cause developmental toxicity to laboratory animals. These facts indicate that hydrogen chloride/hydrochloric acid is not expected to have developmental toxicity. In addition, no effects on the gonads were observed in a good quality 90-day inhalation study up to 50 ppm"(OECD SIDS for hydrogen chloride, 2002).

 

 

Phosphoric acid (CAS no. 7664-38-2):

"The reproductive toxicity of phosphoric acid has been investigated in a reproductive and developmental toxicity screening test in rats [OECD TG 422]. In this study, phosphoric acid was administered via gavage to 13 of animals/sex/dose, concentration at 0, 125, 250 and 500 mg/kg bw/day, for 2 weeks. Based on results of reproductive and development toxicity, no treatment-related effects were observed. At 500 mg/kg bw/day, 2/13 adult females died, indicating parental toxicity at this dose. No effects of test substance were observed on mating, conception, parturition and external of neonates, neonate body weights, and survival rate. Therefore, NOAEL for reproductive and development toxicity was estimated to be 500 mg/kg bw/day, the highest dose tested"(OECD SIAP for phosphoric acid, 2011).

 

 

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).

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Toxicity to reproduction: other studies

Description of key information

No data available

Justification for classification or non-classification

Phosphorus oxychloride is not classified for reproductive or developmental toxicity according to Annex VI of Regulation (EC) No 1272/2008. No classification is proposed, based on the results of the data summarised.