Methoxyammonium chloride

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

other information

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Oxidation of ammonia and hydroxylamine to nitrate in the rat and in vitro

Author:

Saul, R.L., and Archer, M.C.

Year:

1984

Bibliographic source:

Carcinog. 5 (1), 77-81

Reference 2

Reference Type:

publication

Title:

Oxidation of ammonia and hydroxylamine to nitrate in the rat and in vitro

Author:

Saul, R.L., and Archer, M.C.

Year:

1984

Bibliographic source:

IARC Sci. Publ. (ONeill, I.K. et al., ed.), 57, 241-246

Materials and methods

Objective of study:

metabolism

Test material

Test material information

Constituent 1

Reference substance name:

Hydroxylammonium chloride

EC Number:

226-798-2

EC Name:

Hydroxylammonium chloride

Cas Number:

5470-11-1

Molecular formula:

ClH.H3NO

IUPAC Name:

hydroxyammonium chloride

Details on test material:

Hydrochloride [5470-11-1], not further specified

Radiolabelling:

yes

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Administration / exposure

Route of administration:

oral: unspecified

Duration and frequency of treatment / exposure:

once

Doses / concentrations

Remarks:

Doses / Concentrations:
Ca. 4.7 % of 20 µmol 15N-labelled HA.HCl (= ca. 3.5 mg base/kg)

Results and discussion

Any other information on results incl. tables

It was recovered as nitrate in urine with the maximum at day 4. Metabolic 
induction (500 mg/kg Arochlor) did not increase endogenous nitrate synthesis.
Since it could be shown that ammonia is converted into nitrate in very low 
amounts (ca. 0.008 %), the authors speculate that ammonia may be oxidized to 
nitrate via HA with reactive oxygen species involved.

Applicant's summary and conclusion

Executive summary:

The study findings indicate that ammonia is oxidized to nitrate in the rat. Male Sprague-Dawley rats gavaged with 1000 μmol N-15ammonium chloride each day for 5 days were found to excrete low, but significant amounts of excess N-15-nitrate in their urines on the five days of treatment and on the five subsequent days. A total of 0.28 ± 0.03 μmol excess N-15-nitrate (mean ± SE) per rat was recovered, which indicates that ammonia is converted to nitrate in a yield of ̃0.0080%. The oxidation of N-15-labeled glycine and L-glutamic acid to N-15-nitrate could not be detected. N-15-Hydroxylamine was oxidized in the rat to N-15-nitrate in a yield of 4.7%, which shows that hydroxylamine is a possible intermediate in tbe ammonia oxidation process. Injection of rats with Arochlor 1254, an Inducer of several isozymes of cytochrome P-450, did not significantly affect the rate of endogenous nitrate synthesis. Carbon tetrachloride, which causes hepatic lipid peroxidation, produced a small but significaot increase in nitrate synthesk. We confirmed the observation that a bacterial endotoxin can greatly stimulate nitrate synthesis, and we showed that concument treabnent with superoxide dhsmutase does not modify the effect of the endotoxin. An in vitro chemical model system was used to demonstrate that oxidation of ammonia to nitrate by the hydmxyl radical at physiological pH is chemically feasible. Our results are consistent with the hypothesk that ammonia is oxidhed to nitrate in vivo by a ooneqmatic process which invohes active oxygen species such as the hydroxyl radical. We estimate that a 215 g rat produces 3.0 μmol of nitrate per day via ammonia oxidation