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Diss Factsheets

Toxicological information

Toxicity to reproduction

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Administrative data

fertility, other
based on test type (migrated information)
Type of information:
experimental study
Adequacy of study:
supporting study
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: basic information given

Data source

Reference Type:
Effects of imipramine, nitrite and dimethylnitrosamine on reproduction in mice.
Anderson, L.M., Goner-Sorolla, A., Ebeling, D.
Bibliographic source:
Research Communications in Chemical Pathology and Pharmacology Vo. 19 (2), 311 ff

Materials and methods

Principles of method if other than guideline:
Determination of effects on reproductive parameters, including rates of fertility and perinatal survival, litter sizes, and weanling weights.
GLP compliance:

Test material

Constituent 1
Chemical structure
Reference substance name:
Sodium nitrite
EC Number:
EC Name:
Sodium nitrite
Cas Number:
Molecular formula:
sodium nitrate
Details on test material:
sodium nitrite

Test animals

Details on test animals or test system and environmental conditions:
CD-1 female mice (5-6 weeks old, Charles River Breeding Farms) were housed in groups of 10 and treated as follows. Group 1 received imipramine (Bio-Craft Laboratories) thoroughly mixed (100 mg/kg) with powdered Purina Laboratory Chow. Group 2 received 1 g/l NaNO2 in their drinking water.
Group 3 received both imipramine and nitrite. Group 4 received in their water 0.1 ppm DMN diluted twice weekly from a stock solution kept cold and dark and prepared fresh monthly . All mice were housed in plastic cages with hardwood shavings and filter bonnets, in a room at 24 ± 2°C, 40% relative
humidity and a 14/10 hr light/dark cycle.

Administration / exposure

Route of administration:
oral: drinking water
Details on mating procedure:
After 10 wk males were added. The females were separated to individual cages when a vaginal plug was found and treatment was continued. Near term they were inspected for births once daily, except weekends . Females showing no signs of pregnancy were returned to the males for a second fertilization.
The reproductive success of each group was measured by the number of females with surviving litters and the total number of offspring at weaning. Only in the control group did each of the 10 females have surviving offspring. Fewer offspring were weaned in the DMN-, imipramine-, and nitrite-treatment groups, compared with the controls. This effect was of statistical significance for the imipramine group and the nitrite group. However, imipramine and nitrite administered together did not have an additive adverse effect of reproduction; indeed the progeny yield in this group was not significantly different
from that in the control group, even though 1 female had no litter.
After Exp . 1 indicated potentially interesting effects of the chemicals on reproductive success, Exp. 2 was carried out to study these effects in more detail.
Duration of treatment / exposure:
Exposure period: During mating and pregnancy
Premating exposure period (males): no data
Premating exposure period (females): 20 weanling female mice were given tap water for 1 week and then drinking water with NaNO2 at a concentration of 1000 mg/l for the next 75 days (pretreatment period).
Duration of test: about 100 days
Frequency of treatment:
Doses / concentrations
Doses / Concentrations:
190 mg/kg b.w.
nominal in water
No. of animals per sex per dose:
Control animals:
yes, concurrent no treatment


Parental animals: Observations and examinations:
preconception water consumption and weight gain, conception time, litter size, rates of stillbirth and neonatal death, histopathology of the major organs of dead pups
Litter observations:
histopathology of the major organs of dead pups, weaning weights and sex ratios of the offspring

Results and discussion

Results: P0 (first parental generation)

Details on results (P0)

Compared to control values, average conception time was 5 days longer, and more females littered more than 30 days after the males were added. Litters were on the average slightly smaller than control. Perinatal death was more common than among the controls; most of the dead young were stillborn. At weaning the offspring were somewhat smaller than controls, a difference which was statistically significant for males.

Effect levels (P0)

Dose descriptor:
Remarks on result:
not determinable
no NOAEL identified Generation not specified (migrated information)

Overall reproductive toxicity

Reproductive effects observed:
not specified

Applicant's summary and conclusion