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Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information
Two non-standardised developmental toxicity tests observed foetotoxic effects after subcutaneous and intracoloemic injection in to the embryo with hydroxylammonium nitrate. These effects were thought to be in part a response of severe methaemoglobinaemia in the dams.
Link to relevant study records
Reference
Endpoint:
toxicity to reproduction
Remarks:
other: One generation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1995
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Study was not conducted to a standardised guideline or reproduction test. Insufficient controls.
Principles of method if other than guideline:
Male and female Sprague Dawley rats were exposed to a liquid propellant containing hydroxylammonium nitrate and triethanolammonium nitrate at doses of 20, 100 or 200 mg/100 ml in their drinking water. After 14 days, the animals were mated and treatment continued for a total of 90 days. Half of the male rats were sacrificed after mating, remaining animals were sacrificed at the end of the study period.
GLP compliance:
not specified
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
No data.
Route of administration:
oral: drinking water
Vehicle:
water
Details on exposure:
No data.
Details on mating procedure:
No data.
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No data.
Duration of treatment / exposure:
Animals were administered hydroxylammonium nitrate for 14 days prior to mating and maintained on the treatment for 90 days in total.
Frequency of treatment:
Ad libitum.
Details on study schedule:
No data.
Remarks:
Doses / Concentrations:
20, 100, 200 mg LP/100 ml
Basis:
nominal in water
Specific concentration of hydroxylammonium nitrate not determined.
No. of animals per sex per dose:
No data.
Control animals:
not specified
Details on study design:
No data.
Positive control:
No data.
Parental animals: Observations and examinations:
No data.
Oestrous cyclicity (parental animals):
No data
Sperm parameters (parental animals):
No data.
Litter observations:
No data.
Postmortem examinations (parental animals):
No data.
Postmortem examinations (offspring):
No data.
Statistics:
No data.
Reproductive indices:
No data.
Offspring viability indices:
No data.
Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
Male animals showed a treatment related decreases in RBC, HGB, MCV and MCH.
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Other effects:
effects observed, treatment-related
Description (incidence and severity):
Test substance intake: A treatment related decrease in water consumption was noted at the onset of the study and continued through to study termination.
Reproductive function: sperm measures:
effects observed, treatment-related
Description (incidence and severity):
A decrease in the concentration of motile sperm was observed in the high dose rats at sacrifice.
Reproductive performance:
no effects observed
A treatment related decrease in water consumption was observed from the onset of the study and continued through to study completion.

Male rats sacrificed after mating showed a treatment related splenomegaly and decreases in RBC, HGB, MCV and MCH. At the highest dose male rats had a decrease in the concentration of motile sperm.

There were no differences between the treated animals and control animals in gestation index, the length of gestation or male to female pup ratio.
Dose descriptor:
NOAEL
Remarks:
Specific dose of hydroxylammonium nitrate not determined
Effect level:
200 mg/L drinking water
Sex:
male/female
Remarks on result:
not determinable
Remarks:
no NOAEL identified
Mortality / viability:
no mortality observed
Body weight and weight changes:
no effects observed
There were no treatment related effects noted in the the live birth index or male to female pup ratio. During the 21 day lactation phase, mean pup weights were not statistically different between treated and control animals.
Reproductive effects observed:
not specified
Conclusions:
A liquid propellant containing hydroxylammonium nitrate and triethanolammonium nitrate caused splenomegaly in male rats after 14 days treatment. These animals also displayed treatment related decreases in RBC, HGB, MCV and MCH. At the highest dose, male rats showed a decrease in the concentration of motile sperm. There were no maternal or pup effects. A reproductive NOAEL of 20 mg LP/l can be derived based on male fertility. However as the specific concentration of of hydroxyammonium nitrate in the liquid propellant was not reported an specific NOAEL for the chemical can not be derived.
Executive summary:

Male and female Sprague Dawley rats were exposed to a liquid propellant containing hydroxylammonium nitrate and triethanolammonium nitrate at doses of 20, 100 or 200 mg/100 ml in their drinking water (specific concentration of hydroxylammonium nitrate in the liquid propellant was not stated). After 14 days, the animals were mated and treatment continued for a total of 90 days. Half of the male rats were sacrificed after mating, remaining animals were sacrificed at the end of the study period. There was a treatment related decrease in drinking water consumption over the study period, although there were no effects in either the dams or pups. Male rats sacrificed after mating displayed splenomegaly and alterations in blood parameters. At the highest dose, male rats showed lower concentrations of motile sperm. By this study design hydroxylammonium nitrate is considered to be a reproductive toxicant although the reliability of this study is considered to be not reliable.

Effect on fertility: via oral route
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
95 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
Only one study was located which was considered unreliable as the test chemical was administered in combination with another chemical, the exact concentration of the test chemical was not specified. Furthermore, sufficient control animals were not used to eliminate that possible effects on the test animals were not from the other chemical co-administered.
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

Male fertility was affected by the administration of hydroxylammonium nitrate. However the study was considered to be unreliable as only limited data was reported, furthermore the exact concentration of hydroxylammonium nitrate in the liquid propellant was not reported.


Short description of key information:
The fertility of female rats were not effected after the administration of a liquid propellant containing hydroxylammonium nitrate, however male animals displayed a decrease in the concentration of motile sperm at doses of 200 mg/L of a liquid propellant containing hydroxylammonium nitrate in drinking water.

Justification for selection of Effect on fertility via oral route:
Only one study was located, however it was considered unreliable. A NOAEL of 95 mg liquid propellant/kg bw/day can be identified, however the exact concentration of hydroxylammonium nitrate in the liquid propellant was not stated and therefore the exact dose can not be identified, the NOAEL is therefore likely to be conservative.

Effects on developmental toxicity

Description of key information
In a standardised OECD TG 414, hydroxylammonium sulphate did not cause developmental effects at the maximum concentration dosed to pregnant Wistar rats (20 mg/kg bw/day), maternal effects were observed at lower doses (maternal NOAEL: 10 mg/kg bw/day). A further study with hydroxylammonium nitrate did not cause developmental effects at doses of 640 mg/kg bw/day, this same study also derived a maternal NOAEL of 325 mg/kg bw/day. 
Link to relevant study records
Reference
Endpoint:
developmental toxicity
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
No data.
Reliability:
2 (reliable with restrictions)
Qualifier:
according to
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
GLP compliance:
not specified
Limit test:
yes
Species:
rat
Strain:
Wistar
Details on test animals and environmental conditions:
No data.
Route of administration:
oral: gavage
Vehicle:
water
Remarks:
at a standard dose volume of 5 ml/kg bw
Details on exposure:
No data.
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No data.
Details on mating procedure:
No data.
Duration of treatment / exposure:
Pregnant rats were treated on day 6 through to day 15 post coitum.
Frequency of treatment:
Daily
Duration of test:
Animals were dosed with the test chemical from day 6 through to day 15 post coitum and sacrificed on day 20.
Remarks:
Doses / Concentrations:
1, 3, 10, 20 mg/kg bw/day
Basis:
nominal in diet
No. of animals per sex per dose:
22 - 24 pregnant female/dose
Control animals:
yes, concurrent vehicle
Details on study design:
No data.
Maternal examinations:
Food consumption and body weights of the animals were recorded regularly throughout the study period. Animal health was checked daily.
Ovaries and uterine content:
After sacrifice, the number of corpora lutea, the number and distributions of implantation sites were counted.
Fetal examinations:
No data.
Statistics:
No data.
Indices:
No data.
Historical control data:
No data.
Details on maternal toxic effects:
Maternal toxic effects:yes. Remark: 10 mg/kg bw/day

Details on maternal toxic effects:
An enlargement of the spleen and a dose related statistically significant increase in absolute and relative spleen weights were observed in dams administered the two highest doses of bis(hydroxylammonium) sulfate.
Dose descriptor:
NOAEL
Effect level:
>= 10 mg/kg bw/day (nominal)
Based on:
test mat.
Basis for effect level:
other: maternal toxicity
Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects. Remark: at highest dose administered (20 mg/kg bw/day)

Details on embryotoxic / teratogenic effects:
There were no substance-related effects on conception rates, the mean number of corpora lutea, implantation sites, pre and post implantation losses, the number of resorptions and of viable foetuses. Examination of foetuses did not reveal any signs for substance related abnormalities.
Abnormalities:
not specified
Developmental effects observed:
not specified
Conclusions:
At the highest dose (20 mg/kg bw/day) administered to Wistar rats in this study, hydroxylammonium sulphate was not considered to cause embryo/foetotoxicity.
Executive summary:

In a developmental toxicity study according to OECD TG414, hydroxylammonium sulphate was administered to Wistar rats (22 -23/pregnant females/dose) via oral gavage at doses of 1, 3, 10 and 20 mg/kg bw/day on days 6 - 15 post coitum. Animals were sacrificed on day 20 and necropsied. At the two highest doses, dams displayed splenomegaly and a significant increase in absolute and relative spleen weights. No embryo/fetotoxicity was observed at the highest dose administered in this study. A maternal NOAEL of 3 mg/kg bw/day based on effects to the spleen and a NOAEL for embryo/fetotoxicity of 20 mg/kg bw/day can be derived. This study is considered to be reliable, therefore hydroxylammonium sulphate is not considered to be developmental toxicant at concentrations of 20 mg/kg bw/day in rats.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
20 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
Only two studies were located that addressed the reproductive and developmental toxicity of hydroxylammonium nitrate and assoicated analogues, only one of these studies folowed standardised guidelines for reporoductive toxicity testing.
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

Hydroxylammonium nitrate is thought to cause indirect foetotoxic effects as a result of severe methaemoglobinaemia in the dams. All effects observed in foetuses were associated with direct toxicity in the dams and foetoxic effects were observed at higher doses than maternal effects.


Justification for selection of Effect on developmental toxicity: via oral route:
The study was conducted to standardised guidelines.

Toxicity to reproduction: other studies

Additional information

Hydroxylammonium nitrate is thought to cause indirect foetotoxic effects as a result of severe methaemoglobinaemia in the dams. All effects observed in foetuses were associated with direct toxicity in the dams and foetoxic effects were observed at higher doses than maternal effects.

Justification for classification or non-classification

Hydroxylammonium nitrate is not classifiable as to its reproductive toxicity.