Hydroxylammonium nitrate

Toxicity to reproduction: other studies

Administrative data

Endpoint:

toxicity to reproduction: other studies

Type of information:

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

Adequacy of study:

supporting study

Study period:

1990

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study was not conducted to standardised guidelines, however it was well reported.

Data source

Reference

Reference Type:

publication

Title:

Developmental toxicity of hydroxylamine: an example of a maternally mediated effect

Author:

DeSesso J.M., Goeringer G.C.

Year:

1990

Bibliographic source:

Teratology and Industrial Health. 6(1):109-21

Materials and methods

Principles of method if other than guideline:

Rabbits were injected subcutaneously or intravenously with hydroxylamine hydrochloride at doses between 50 - 650 mg/kg on day 12 of gestation. Animals that were still alive after 30 hours were sacrificed.
In a secondary experiment, hydroxylamine hydrochloride (25 - 200 µg in 5 - 40 µl of saline) was administered via intracoelomic injections into the chorionic cavity of developing rabbit embryos. Surviving embryos were allowed to develop to full gestation. A secondary group of animals (and embryos) were co-administered an antioxidant propyl gallate and again allowed to develop to full gestation.

GLP compliance:

not specified

Type of method:

in vivo

Test material

Test material information

Constituent 1

Reference substance name:

Hydroxylamine hydrochloride

IUPAC Name:

Hydroxylamine hydrochloride

Test material form:

not specified

Details on test material:

No data.

Test animals

Species:

rabbit

Strain:

not specified

Sex:

female

Details on test animals or test system and environmental conditions:

No data.

Administration / exposure

Route of administration:

other: Subcutaneous or intracoelomic injections into embryos

Vehicle:

not specified

Details on exposure:

No data

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

No data.

Duration of treatment / exposure:

A single treatment followed by sacrifice between 5 - 8 hours.

Frequency of treatment:

A single treatment by either subcutaneous or intravenous injection to pregnant dams

Duration of test:

5 - 8 hours

Doses / concentrations

Remarks:

Doses / Concentrations:
50 - 650
Basis:
nominal conc.

No. of animals per sex per dose:

No data.

Details on study design:

No data.

Statistics:

No data.

Results and discussion

Observed effects

All rabbits injected subcutanously exhibited sever cyanosis and at higher doses mortality occured (effect level not stated).

Applicant's summary and conclusion

Conclusions:

Pregnant rabbits administered hydroylamine hydrochloride via subcutaneous or intravenous injection caused maternal toxicity from methemoglobinemia which resulted in embryolethality. A maternal LOAEL of 50 mg/kg can be derived.
Hydroxylamine hydrochloride administered directly to embryos caused malformations, lethality and reabsorptions. A fetal LOAEL of 25 µg can be derived based on embryo reabsorption.

Executive summary:

In a non-standardised developmental toxicity test pregnant rabbits administered hydroxylamine hydrochloride via subcutaneous or intravenous injection (50 - 650 mg/kg) on gestational day 12 displayed severe cyanosis from methemoglobinemia resulting in embryolethality. Hydroxylamine hydrochloride injected into the chorionic cavity of embryos caused malformations, lethality and reabsorptions. A maternal LOAEL of 50 mg/kg based on methemoglobinemia and fetal LOAEL of 25 mg/kg based on reabsorptions can be derived. This study is considered reliable with restrictions and therefore by this study design hydroxylamine hydrochloride is considered a developmental toxicant.