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Toxicological information

Toxicity to reproduction

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Administrative data

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.

Data source

Reference
Reference Type:
publication
Title:
A reproductive toxicity screen of a liquid propellant (LP) formulation administered in the drinking water of Sprague-Dawley rats.
Author:
Kinkead E.R., Wolfe R.E., Salins S.A., Latendresse J.R., Caldwell D.J., Miller C.R.
Year:
1995
Bibliographic source:
Journal of the American College of Toxicology. 14(2):173

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
not specified
Details on test material:
The test material was a liquid propellant containing hydroxylammonium nitrate and trethanolammonium nitrate (specific percentage of each chemical not stated).

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
No data.

Administration / exposure

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.
Doses / concentrations
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.

Examinations

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.

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

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 / performance (P0)

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

Details on results (P0)

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.

Effect levels (P0)

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

Results: F1 generation

General toxicity (F1)

Mortality / viability:
no mortality observed
Body weight and weight changes:
no effects observed

Details on results (F1)

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.

Overall reproductive toxicity

Reproductive effects observed:
not specified

Applicant's summary and conclusion

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.