Hydrazine

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: reporting suffers from deficiencies e.g. individual animals are not presented

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1982

Reference 2

Reference Type:

other: abstract

Title:

Comparison of the Embryotoxicity of Hydrazine and Monomethylhydrazine.

Author:

Keller WC et al. (1980).

Year:

1980

Bibliographic source:

Abstr. Pap. Soc. Toxicol. 19, A21.

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Guide for the care and use of laboratory animals, Inst. Lab. Animals Resources, National Res. Council

Principles of method if other than guideline:

Pregnant female rats were intraperitoneal injected according to different shemes (see section adional informations on remarks and results) and fetuses were evaluated after delivering on gestation day 20 up to postpartal day 21.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Hydrazine

EC Number:

206-114-9

EC Name:

Hydrazine

Cas Number:

302-01-2

Molecular formula:

H4N2

IUPAC Name:

hydrazine

Details on test material:

IUCLID4 Test substance: other TS : hydrazine; purity = 95%

Test animals

Species:

rat

Strain:

Fischer 344

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Diet ad libitum
- Water ad libitu


ENVIRONMENTAL CONDITIONS
- Temperature (°F): 70-76
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

physiological saline

Details on exposure:

intraperitoneal injection

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

no data

Details on mating procedure:

- Impregnation procedure: cohoused
- If cohoused:
- Length of cohabitation: overnight

- Verification of same strain and source of both sexes: yes
- Proof of pregnancy: sperm in vaginal smear referred to as day 0 of pregnancy

Duration of treatment / exposure:

trial 1: gestation day 6-15
trial 2: gestation days 7-9; days 10-12; days 13-15
trial 3. gestadion days 7-9

Frequency of treatment:

once daily

Duration of test:

trial 1: until gd 20
trial 2: until gd 20
trial 3: until postnaltal day 21

No. of animals per sex per dose:

no data

Control animals:

yes, concurrent vehicle

Details on study design:

see section addition information on material and methods

Examinations

Maternal examinations:

see section addition information on material and methods

Ovaries and uterine content:

see section addition information on material and methods

Fetal examinations:

see section addition information on material and methods

Statistics:

student's t method, , Fisher's exact test, Newman Keulls post test

Indices:

not given

Historical control data:

not given

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Maternal toxic effects:yes

Details on maternal toxic effects:
see section remarks on results

Effect levels (maternal animals)

1

Dose descriptor:

NOAEL

Effect level:

2.5 mg/kg bw/day

Basis for effect level:

other: maternal toxicity

2

Dose descriptor:

NOAEL

Effect level:

2.5 mg/kg bw/day

Basis for effect level:

other: developmental toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:yes

Details on embryotoxic / teratogenic effects:
see section remarks on results

Effect levels (fetuses)

Dose descriptor:

NOAEL

Effect level:

2.5 mg/kg bw/day

Basis for effect level:

other: developmental toxicity

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Any other information on results incl. tables

RS-Freetext:
trial 1:(significant changes only)
maternal body weight gain significantly reduced at 5.0 mg/kg
or more (only as graphic); 
number of resorptions per litter significantly
increased at 5 mg/kg bw/d: 3.3 and 10 mg/kg bw/d: 6.0 versus 1.5 in controls; 
10 mg/kg bw/d: With the exception of one litter 
which had no resorptions and six viable fetuses,
 all litters were totally resorbed
fetal body weight sign.decreased at 5.0 mg/kg: 2.9 g versus 3.1 g of control ; 
no significant increase in fetal
abnormalities 

trial 2: 
 maternal body weight gain significantly reduced in dams treated 
gd7 -9(a), gd10 -12(b) and gd13 -15(c)(data not shown) during exposure period; 
   the most susceptible period for the effects of hydrazine  
was during gestation days 7 through 9 (a) 

number of resorptions per litter
significantly increased in (a)6.1 versus 1.5 of controls; fetal body weight significantly decreased in a)2.7 g and c) 2.9g versus 3.1 g in controls; significantly increase in fetal abnormalities in a) including supernumerary ribs, moderate
hydronphrosis and moderate hydrocephalus. trial 3: No significant effects
reported in postnatal evaluation.

Applicant's summary and conclusion

Executive summary:

Pregnant female rats were intraperitoneal injected with 0, 2.5, 5.0, 10.0 mg/kg/d once daily on gd 9 -16 and sacrificed on gd day 20. The NOAEL (maternal toxicity ) was determined 2.5 mg/kg bw/day based on reduced weight gain or weight loss during treatment from 5.0 mg/kg bw/d onwards; the NOAEL (developmental toxicity) was determined 2.5 mg/kg bw/day based on a dose-related embryolethality from 5.0 mg/kg bw/d onwards. Furthermore, treatmant of dams with 10 mg/kg bw on gd 7 -9 resulted in significantly increased number of resorptions per litter, significantly decreased fetal body weight and fetal abnormalities including supernumerary ribs, moderate hydronphrosis and moderate hydrocephalus (Keller 1982).