Hydroxylamine

Endpoint summary

Additional information

CAS No. 10039-54-0:

Absorption

No data available.

No data available for the dermal uptake. In the EU risk assessment, it was stated that a default value for dermal absorption should be applied. Based on the physico-chemical properities of the substance (molecular weight: 164 g/mol; Log Pow -3.6; water solubility: 587000 mg/l) a low lipophilic character of the substance can be assumed, thus leading to conclude on a low absorption through the skin. Moreover, in aqueous solutions the substance will form quaternary ammonium ions limiting percutaneous absorption. Thus, according to the TGD (technical guidance document) a value of 10% would be derived. Experimental data on formation of methemoglobin and of Heinz bodies in erythrocytes of rabbits after dermal application onto the skin of rats and rabbits are indicative for an absoprtion. Depending on the time of exposure to the test material animal data demonstrate moderate to severe irritation properities which may explain a certain extent of dermal absorption despite the high hydrophilicity of the substance.

Distribution

No data available.

Metabolism and Excretion

i.v., rats: Approximately 99% of the i.v. administered hydroxylamine (in terms of hydroxylamine sulfate) disappeared from blood almost immediately and was partially converted in acid labile intermediates like acetohydroxamic acid in rats. In the urine, 1.1 – 1.5% of the dose given was excreted after the first 2 h. No attempt was made to identify the excretory products (Philips, 1967).

 

CAS No. 5470-11-1:

Absorption

No data available.

Distribution

No data available.

Metabolism

There are valid experimental data available to assess the metabolism of hydroxylamine hydrochloride.

Oral, rat: The rats were administered (per gavage) to¹⁵N-hydroxylamine hydrochloride (20 µmol) daily for 5 days,¹⁵N-hydroxylamine was oxidized in the rat to¹⁵N-nitrate in a yield of 4.7%. Most of the excess¹⁵N-nitrate was observed in the urines of day 4. Metabolic induction (500 mg/kg Arochlor) did not increase endogenous nitrate synthesis (Saul and Archer, 1984).

In vitro test with liver mitochondria from different warm-blooded animals (mammals and birds) as well as from fish, reptiles, and amphibians: Hydroxylamine reductase reduces hydroxylamine (stored as the hydrochloride) to ammonia. This study demonstrated that hydroxylamine reductase is present in mitochondria of the livers from mammals and birds, with mice and rats exhibiting the highest activity.Also the kidney of rats and cats contained some of the enzyme activity, whereas brain and serum have no expression. Preparations of human sources were not included (Bernheim, 1972).

A french article (only available as summary; therefore: Val. 4) of Valdiguie (1965) describes that hydroxylamine hydrochloride inhibited activities of glutamine synthetase, glutaminase, as well as glutamate dehydrogenase and transaminases. It seems to affect a broad spectrum of enzymes involved in the turnover of ammonia, which may partially explain intoxication caused by hydroxylamine.

Excretion

No data available.

 

CAS No. 7803-49-8 

Absorption

No data available but due to the results of acute oral (BASF AG, 1969) or acute dermal studies (Allied Corporation, 1983), hydroxylamine and its salts are absorbed after oral administration or topical application. The vapour pressure of hydroxylamine at 20°C is negligible, so that an inhalation of the hydroxylamine vapours is not possible. However, the formation of dust was seen, which will be absorbed through the respiratory tract (BASF AG 1974).

Distribution

No data available.

Metabolism

There are valid experimental data available to assess the metabolism of hydroxylamine.

In the publication of Neunhoeffer, 1973, the importance of the reduction of hydroxylamine to ammonia as a mechanism of detoxification was pointed out. Under physiological conditions however, hydroxylamine can react with different intermediates of the metabolism. Therefore, only small amounts of free or combined hydroxylamine occur in the organisms. The enzymes, which are responsible for the reduction of hydroxylamine, the hydroxylamine reductases, show a strong substrate inhibition, which means, that they only work in the presence of low hydroxylamine concentrations, increasing hydroxylamine concentrations lead to a strong decrease of the hydroxylamine reductase activity. Additionally, the oxidation of ammonia to hydroxylamine to a larger extent is prevented. Reactions which could take place physiologically are: hydroxylamine may react with esters, e.g. active acetyl-coenzyme A (thiol ester cleavage), with amides (amidases, transamidases), and with keto groups. Hydroxylamine may be a substrate of certain key metabolic enzymes (glutaminase: competing with NH₃, phosphopyruvate kinase: unspecific conversion of phosphoenolpyruvic acid into its pyruvic acid (alpha)oxime; aspartase: competing with NH₃). These side reactions may result in metabolic imbalances (e.g. at the expense of coenzyme A, pantothenic acid, and thiamine) and toxic intermediates at high hydroxylamine concentrations unless hydroxylamine cannot effectively be reduced to NH₃by hydroxylamine reductase, because of substrate inhibition.Thiamine (Vit. B6) was identified to be an effective hydroxylamine acceptor in vivo; Vit. B6 is supposed to be a limiting factor in cases of high hydroxylamine stress. A link to the purine metabolism was also drawn, thus giving some idea for hydroxylamine to exert mutagenic activity: aspartase (see above) may lead to incorporation of a modified building block for purine synthesis. Additionally, the reduction of carcinogenic activity of aromatic N-oxides was considered.

Also, Budowsky (1976) stated that hydroxylamine is a product of normal cell metabolism; it is formed as an intermediate in enzymatic reduction of nitrate and nitrite or oxidation of ammonia; the cells possess enzymic detoxification systems oxidizing hydroxylamines or reducing them to ammonia and water. Since the original report is not available, this study is not assignable (Val. 4).

In vitro study: Stolze and Nohl (1989) studied the reaction sequence for the hydroxylamine-induced methemoglobin formation with bovine oxyhemoglobin. Four distinct paramagnetic intermediates could be observed.The first step seems to be the formation of the hydronitroxide radical and methemoglobin. The second step was the rapid disappearance of the nitroxide radical. The main pathway is possibly the formation of nitrogen gas and water. The authors assume that in a third step methemoglobin reacts with excess hydroxylamine thereby forming the methemoglobin-hydroxylamine adduct. This complex would then be slowly oxidized to the hemoglobin-nitric oxide complex.

Excretion

No data available.