Registration Dossier
Registration Dossier
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EC number: 231-714-2 | CAS number: 7697-37-2
Toxicological information
Basic toxicokinetics
Administrative data
- Endpoint:
- basic toxicokinetics
- Type of information:
- other: Qualitative judgement on the toxicokinetic behaviour based on physico-chemical characteristics.
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Nitric acid is an inorganic substance and thus some physico-chemical characteristics (like the octanol/water partition coefficient) are not defined. This limits the reliability of the qualitative judgement.
Data source
Materials and methods
- Objective of study:
- toxicokinetics
- Principles of method if other than guideline:
- This qualitative judgement on the toxicokinetic behaviour based on physico-chemical characteristics follows the recommendations of ECHA (ECHA Endpoint specific guidance, Chapter R.7c; section R.7.12.2.1).
- GLP compliance:
- no
Test material
- Reference substance name:
- Nitric acid
- EC Number:
- 231-714-2
- EC Name:
- Nitric acid
- Cas Number:
- 7697-37-2
- Molecular formula:
- HNO3
- IUPAC Name:
- nitric acid
- Test material form:
- other: liquid
Constituent 1
Results and discussion
Toxicokinetic / pharmacokinetic studies
- Details on absorption:
- Following the pKa of nitric acid (pKa = -1) the form in biological systems will be NO3(-), including the human intestine with pH in the range of 5 to 8. Predominant mechanism for absorption of small well water soluble molecules in the GI tract is passage through aqueous pores or carriage of such molecules across membranes with the bulk passage of water. Oral absorption might thus be as high as 100%. Dietary compounds might influence the rate and extend of nitrate absorption via the GI tract. An oral absorption factor of 100% is proposed while 50% is proposed as a worst-case assumption for route-to-route extrapolation when starting from an oral study. The high oral absorption of nitrate is also described by JECFA (WHO Food Additives Series No. 50, 2003).
Respiratory absorption: as nitric acid is a liquid at room temperature, exposures via the respiratory tract are possible. Based on its high water solubility, significant absorption via the respiratory tract is to expected. The substance must however also be sufficiently lipophilic to cross the alveolar and capillary membranes and as the octanol/water partition coefficient is not defined for inorganic substances, the relevance of this mechanism is difficult to assess for nitrate. Hydrophilic substances also have the tendency to be retained in the aqueous fluids (mucus) lining of the respiratory tract, limiting the systemic uptake as such substances may be transported out of the deposition region with the mucus and swallowed. As based on available physico/chemical data the systemic uptake of nitric acid is difficult to assess, a worst-case absorption factor of 100% is proposed for inhalation.
Dermal absorption will be significant as the substance has a low molecular weight and is very well water soluble. It may however be too hydrophilic to cross the lipid rich environment of the stratum corneum, but due to the absence of the octanol/water partition coefficient, this is difficult to predict. As nitric acid is corrosive to skin, any skin damage might enhance penetration of the substance. A default value of 100% skin absorption should be used for substances with molecular mass below 500. - Details on distribution in tissues:
- Wide distribution throughout the body is to be expected as small water-soluble molecules and ions will diffuse through aqueous channels and pores. In humans and most laboratory animal species except the rat, nitrate is actively secreted in saliva in a dose-dependent manner (JECFA nitrate evaluation, WHO Food Additives Series No. 50, 2003).
- Details on excretion:
- Excretion will be via urine as characteristics favourable for urinary excretion are low molecular weight (below 300 in the rat), good water solubility, and ionization of the molecule at the pH of urine.
Metabolite characterisation studies
- Details on metabolites:
- Nitrate can be reduced to nitrite by both enteric bacteria and mammalian nitrate reductase activity (quoted from JECFA nitrate evaluation, WHO Food Additives Series No. 50, 2003).
Applicant's summary and conclusion
- Conclusions:
- A qualitative judgement on the toxicokinetic behaviour was performed based on physico-chemical characteristics. Nitric acid is an inorganic substance and thus some physico-chemical characteristics (like the octanol/water partition coefficient) are not defined, limiting the possibilities of a qualitative assessment. Absorption factors of 100% are proposed for oral, inhalation and dermal absorption. For route-to-route extrapolation starting from oral data, an absorption factor of 50% is proposed as a worst-case assumption.
Nitrate can be reduced to nitrite by both enteric bacteria and mammalian nitrate reductase activity.
Nitric acid is not considered to have bioaccumulative potential as nitrate is highly soluble in water and rapidly excreted via the urine.
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