Registration Dossier

Toxicological information

Toxicity to reproduction: other studies

Currently viewing:

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

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.