Hydroxylammonium chloride

Endpoint summary

Description of key information

Based on the physico-chemical properties and the available toxicological data with hydroxylammonium chloride, oral and dermal absorption potential is very likely. Absorption by inhalation is assumed to be low based on granulometry data. Taking into account the physico-chemical properties and the dermal and oral absorption potential, distribution within the body can be considered as very likely. After absorption, hydroxylammonium chloride (CAS 5470-11-1) will enter the blood circulating system through which it will be distributed within the body. Since the test substance is an inorganic compound, dissociation into the hydroxylammonium and the chloride ion are expected under aqueous conditions. Consequently, urinary excretion of the dissociation products is very likely.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

Basic toxicokinetics:

There are no studies available in which the toxicokinetic behaviour of hydroxylammonium chloride (CAS 5470-11-1) has been investigated.

Therefore, in accordance with Annex VIII, Column 1, Section 8.8.1, of Regulation (EC) No 1907/2006 and with Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance (ECHA, 2017), assessment of the toxicokinetic behaviour of hydroxylammonium chloride (CAS 5470-11-1) is conducted to the extent that can be derived from the relevant available information. This comprises a qualitative assessment of the available substance specific data on physico-chemical and toxicological properties according to Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance (ECHA, 2017).

Hydroxylammonium chloride (CAS 5470-11-1) is a solid at 20 °C with a molecular weight of 69.49 g/mol, a water solubility of 470 g/L and the determined vapour pressure is <1E-3 Pa at 20 °C. The log Pow was not determined as the test substance is inorganic.

 

Absorption

Absorption is a function of the potential for a substance to diffuse across biological membranes. The most useful parameters providing information on this potential are the molecular weight, the octanol/water partition coefficient (log Pow) value and the water solubility. The log Pow value provides information on the relative solubility of the substance in water and lipids (ECHA, 2017).

Oral

Mechanisms by which substances can be absorbed in the GI tract include the passage of small water-soluble molecules (molecular weight up to around 200) through aqueous pores or carriage of such molecules across membranes with the bulk passage of water. Water-soluble substances will readily dissolve into the gastrointestinal fluids. Absorption of very hydrophilic substances by passive diffusion may be limited by the rate at which the substance partitions out of the gastrointestinal fluid. However, if the molecular weight is low (less than 200) the substance may pass through aqueous pores or be carried through the epithelial barrier by the bulk passage of water (ECHA, 2017).

The high water solubility (470 g/L) and the very low molecular weight of 69.49 g/mol indicate that absorption is very likely.

In addition, acute oral toxicity data resulted in a LD50 value of 642 mg/kg bw (reference 7.2.1-1). Furthermore, clinical signs such as intermittent breath and dyspnoe, apathy, cynosis, agitated behaviour, stretching and slight tremor were observed at doses of 400 – 800 mg/kg bw. Dark blue to violet or black discolouration and enlargement of the spleen was seen in the survivors that were sacrificed 7 days after administration of the test material. The findings of the acute oral toxicity study are indicating systemic toxicity. If signs of systemic toxicity are present, then absorption has occurred (ECHA, 2017).

Overall, taking into account the physico-chemical properties and the available toxicological data of hydroxylammonium chloride (CAS 5470-11-1) indicating systemic toxicity, the potential for oral absorption of the substance is very high.

Dermal

There are no data available on dermal absorption or on acute dermal toxicity of hydroxylammonium chloride (CAS 5470-11-1). On the basis of the following considerations, the dermal absorption of the substance is considered to be likely.

The dermal absorption rate was not calculated by QSAR analysis (Dermwin v2.02, EpiSuite 4.1) as the entered structure is an inorganic compound, which are in general not included in the training data set for the methodology utilized in that program. Therefore, inorganic compounds are outside the estimation domain.

To partition from the stratum corneum into the epidermis, a substance must be sufficiently soluble in water (ECHA, 2017). Thus, based on a water solubility of 470 g/L, dermal uptake of the substance is considered to be very likely. In addition, the low molecular weight of 69.49 g/mol is favourable for dermal uptake. If the substance is a skin irritant or corrosive, damage to the skin surface may enhance penetration (ECHA, 2017). Hydroxylammonium chloride (CAS 5470-11-1) is classified as skin irritant according to Annex VI of the CLP Regulation. Moreover, the available in vitro irritation study with hydroxylammonium chloride (CAS 5470-11-1) revealed a positive result (reference 7.3.1-1).

Overall, taking into account the physico-chemical properties and available toxicological data of hydroxylammonium chloride (CAS 5470-11-1), the dermal absorption potential of the substance is anticipated to be likely.

Inhalation

In humans, particles with aerodynamic diameters below 100μm have the potential to be inhaled. Particles with aerodynamic diameters below 50μm may reach the thoracic region and those below 15μm the alveolar region of the respiratory tract (ECHA, 2017).

Inhalation of hydroxylammonium chloride (CAS 5470-11-1) is considered as negligible as the inhalation of the test substance is unlikely with regard to the particle size (median particle size L50: 377.8 µm). Thus, the contained particles are far above the inhalable size. Moreover, the test substance has a low determined vapour pressure of 2.1E-03 Pa thus being of low volatility (ECHA, 2017). Therefore, under normal use and handling conditions, inhalation exposure and thus availability for respiratory absorption of the substance in the form of vapours, gases, or mists is not significant.

Based on the physical state and the physico-chemical properties of hydroxylammonium chloride (CAS 5470-11-1), absorption via the lung is considered to be negligible.

Distribution and accumulation

Distribution of a compound within the body depends on the rates of the absorption and the physico-chemical properties of the substance; especially the molecular weight, the lipophilic character and the water solubility. In general, the smaller the molecule, the wider is the distribution. Small water-soluble molecules and ions will diffuse through aqueous channels and pores. The rate at which very hydrophilic molecules diffuse across membranes could limit their distribution (ECHA, 2017).

Hydroxylammonium chloride (CAS 5470-11-1) has a low molecular weight and high water solubility. Based on the physico-chemical properties and the absorption potential, distribution within the body can be considered as very likely. After absorption, hydroxylammonium chloride (CAS 5470-11-1) will enter the blood circulating system through which it will be distributed within the body. This assumption is based on the systemic toxicity findings observed in the acute oral toxicity study.

Highly lipophilic substances in general tend to concentrate in adipose tissue, and depending on the conditions of exposure may accumulate. Although there is no direct correlation between the lipophilicity of a substance and its biological half-life, it is generally the case that substances with high log Pow values have long biological half-lives. The test substance hydroxylammonium chloride (CAS 5470-11-1) is inorganic and may have no potential to accumulate in adipose tissue (ECHA, 2017).

Metabolism

Hydroxylammonium chloride (CAS 5470-11-1) is an inorganic substance and hence, will not undergo metabolic transformation. Dissociation into the hydroxylammonium and the chloride ion are expected under aqueous conditions.

Excretion

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. In contrast, molecules that are excreted in the bile have a high molecular weight (ECHA, 2017). Taken these aspects into account, urinary excretion of the dissociation products is assumed.

 

References

ECHA (2017). Guidance on information requirements and chemical safety assessment, Chapter R.7c: Endpoint specific guidance.Version 3.0, June 2017