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Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

Silicon orthophosphate is highly water soluble (1085 mg/L at 20°C). It completely dissociates into silicon and phosphate ions after systemic uptake (relevant pH ranges 2 -7). The tetravalent silicon ion and the phosphate ion will then react with the media to form different silicon and phosphate species depending on the pH and redox potential of the media. The dissociated silicon ion exists in water predominantly as H4SiO4/Si(OH)4, which is also the main species when silicon dioxide is dissolved in water. Therefore the silicon component of silicon orthophosphate can be covered by data from the read-across substance silicon dioxide, whereas the phosphate component has been assessed based on publically available data summaries from a study performed in Korea (no access granted for REACH Registration). No data for reproductive toxicity is available for the target substance silicon orthophosphate however the data from silicon dioxide is considered to be the worst-case and as such is acceptable for use.

An one-generation study with silicon dioxide was performed (Leuschner, 1963). 5 female rats and 1 male rat per group were fed the test substance or the control diet for 6 months at concentrations of 497 (males) and 509 (females) mg/kg bw/day. The animals were mated on a 1:5 basis after 4 1/2 month for an overall period of 14 days. No clinical signs, mortality, abnormalities in body-weight gain, feed consumption and haematology were observed. Effects on fertility were not described in the study. Therefore, the overall NOAEL was determined to be 497 mg/kg bw day. In pups, no behavioural, developmental or structural abnormalities were seen.

A publically available summary of an OECD 422 study on dipotassium hydrogenorthophosphate showed that reproductive performance of treated animals was similar to control animals considering mating/parturition rate, mating/gestation period and male/female fertility as reproductive indices. Therefore, the NOAEL of dipotassium hydrogenorthophosphate for fertility of male and female rats was determined to be1000 mg/kg bw/day. As this study was performed in Korea suitable access was not granted for REACH registration and as such no robust summary for this study is included in the dossier but the results are mentioned here for completeness.

The worst-case value derived from the silicon dioxide study will be used for the purpose of hazard classification and risk assessment.


Short description of key information:
Oral (one-generation study, silicon dioxide), subchronic, rat: NOAEL males= ≥500 mg/kg bw/day

Justification for selection of Effect on fertility via oral route:
Hazard assessment is conducted by means of read-across from silicon dioxide.

Effects on developmental toxicity

Description of key information
Oral (OECD 414, silicon dioxide), mouse: NOAEL (developmental), males/females = ≥1340 mg/kg bw/day
Oral (OECD 414, silicon dioxide), rabbit: NOAEL (developmental), males/females = ≥1600 mg/kg bw/day
Oral (OECD 414, silicon dioxide), hamster: NOAEL (developmental), males/females = ≥1600 mg/kg bw/day
Oral (OECD 414, silicon dioxide), rat: NOAEL (developmental), males/females = ≥1350 mg/kg bw/day
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

Silicon orthophosphate is highly water soluble (1085 mg/L at 20°C). It completely dissociates into silicon and phosphate ions after ingestion via the oral route (pH 2 -7). The tetravalent silicon ion and the phosphate ion will then react with the media to form different silicon and phosphate species depending on the pH and redox potential of the media. The dissociated silicon ion exists in water predominantly as H4SiO4/Si(OH)4, which is also the main species when silicon dioxide is dissolved in water. Therefore the silicon component of silicon orthophosphate can be covered by data from the read-across substance silicon dioxide, whereas the phosphate component has been assessed based on publically available data summaries from a study performed in Korea (no access granted for REACH Registration). No data for reproductive toxicity is available for the target substance silicon orthophosphate however the data from silicon dioxide is considered to be the worst-case and as such is acceptable for use.

Developmental toxicity of silicon dioxide was investigated by the FDA (1973) in rabbits, rats, mice and hamsters in studies performed equivalent to OECD 414. The animals (11 -26/group, depending on the species) were treated orally once a day with test substance concentrations between 13.4 and 1600 mg/kg bw/day during gestation. The administration of up to the highest doses tested had no clear discernible effect on nidation nor on maternal and fetal survival. The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ from the number occurring spontaneously in the sham-treated controls. Therefore, the NOAELs for developmental toxicity were determined to be1600 mg/kg bw/day for rabbits and hamster,1340 mg/kg bw/day for mice and1350 mg/kg bw/day for rats.

For dipotassium hydrogenorthophosphate an OECD 422 combined repeated dose toxicity study with reproduction / developmental toxicity screening conducted under GLP conditions was performed in male and female Sprague-Dawley rats (Shim, 2005).

16 animals/sex were treated once daily by gavage with 1000 mg/kg bw of the substance dissolved in water. The negative control group animals received the vehicle. The females were treated 2 weeks before mating until day 4 after parturition (~54 days) and the males for 42 days. 6 animals/sex were considered in satellite groups during a post-exposure recovery period of 2 weeks post administration.

A publically available summary of an OECD 422 study on dipotassium hydrogenorthophosphate showed that in the parental animals, there were no effects of systemic and fertile toxicity observed which were considered to be treatment related. In the offspring of the treated animals, no signs for developmental toxicity were observed considering corpus lutea, implantation sites, pre/post-implantation loss, litter size, birth rates, body weights and gross pathology as indices. Therefore, the NOAEL of dipotassium hydrogenorthophosphate for developmental toxicity of male and female rats was determined to be1000 mg/kg bw/day.

As this study was performed in Korea suitable access was not granted for REACH registration and as such no robust summary for this study is included in the dossier but the results are mentioned here for completeness.

The worst-case value derived from the silicon dioxide study will be used for the purpose of hazard classification and risk assessment.


Justification for selection of Effect on developmental toxicity: via oral route:
Hazard assessment is conducted by means of read-across from silicon dioxide.

Justification for classification or non-classification

The available data on toxicity to reproduction of the test substance do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.

No information is available on effects via lactation.

Additional information