Ethylenediamine

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Study period:

before 1993

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1993

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Rabbits were dosed during gestation days 6 - 19. On day 21 uterine contents were examined, and the foetuses were evaluated for externally visible anomalies and for soft tissue and skeletal changes.

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Ethylenediamine

EC Number:

203-468-6

EC Name:

Ethylenediamine

Cas Number:

107-15-3

Molecular formula:

C2H8N2

IUPAC Name:

ethane-1,2-diamine

Details on test material:

- Name of test material (as cited in study report): Ethylendiamine
- Analytical purity: 99 %

Specific details on test material used for the study:

Due to corrosivity of EDA, ethylene diammonium dichloride (ECDA.2HCl) was used (CAS no. 333-18-6; EC no. 206-369-6). Ethylene diamine 99.7% pure, was used to prepare the corresponding ethylene diammonium dichloride water solutions.

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hazelton Research Products Inc., Denver, PA
- Age at study initiation: 6 months
- Weight at study initiation: 2500-3830 g
- Housing: Stainless steel cages with mesh flooring
- Diet : Purina Certified Rabbit Chow ad libitum
- Water : filtered water ad libitum
- Acclimation period: 14 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19
- Humidity (%): 52
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on exposure:

Artificaially inseminated New Zealand rabbits were fed EDA dihydrochloride salt solution by gavage during gestation day 6-19.

Details on analytical verification of doses or concentrations:

Analysed concentrations within 91-104% of theoretical concentration.

Duration of treatment / exposure:

gestation days 6-19

Frequency of treatment:

daily

Duration of test:

cesarean section on gestation day 30

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

10 mg/kg bw/day (actual dose received)

Remarks:

Measured as Ethylene diamine

Doses / concentrations 2

Dose / conc.:

40 mg/kg bw/day (actual dose received)

Remarks:

Measured as Ethylene diamine

Doses / concentrations 3

Dose / conc.:

80 mg/kg bw/day (actual dose received)

Remarks:

Measured as Ethylene diamine

No. of animals per sex per dose:

26

Control animals:

yes, concurrent vehicle

Details on study design:

Artificially-inseminated New Zealand White rabbits (26/group) were administered ethylenediamine (0, 10, 40 or 80 mg/kg/day) by gavage on gestational days (gd) 6 through 19. In order to avoid the irritant/corrosive properties of the EDA base, the test chemical was administered as the dihydrochloride salt. The doses administered were equivalent to 0, 22, 89 or 178 mg/kg/day of EDA 2HCI. At termination (gd 30), the uterus was removed and examined to determine pregnancy status and to evaluate the number of resorptions, and dead or live fetuses. Dead or live fetuses were weighed, and live fetuses examined for external, visceral and skeletal defects.

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

There were no treatment-related maternal deaths in this study, and no characteristic clinical signs of toxicity in EDA-treated does. At scheduled necropsy, 19-22 pregnancies per group were confirmed. There were no statistically significant effects of EDA on maternal food intake, body weight, weight gain, liver or kidney weight (absolute or relative), or gravid uterine weight. Higher doses were not evaluated in this study due to the observation of >=20% maternal mortality at >=100 mg/kg/day in a preliminary investigation (NTP, 1991).

Effect levels (maternal animals)

Dose descriptor:

NOAEL

Effect level:

>= 80 mg/kg bw/day (actual dose received)

Basis for effect level:

other: absence of maternal toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Uterine examination on gd 30 revealed no adverse effects of EDA upon prenatal viability, litter size, fetal weight or fetal morphology.

Effect levels (fetuses)

Dose descriptor:

NOAEL

Effect level:

>= 80 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: absence of embryotoxicity/teratogenicity

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

In conclusion, the maternal and developmental NOAEL for EDA in the New Zealand White rabbit exposed during major organogenesis is at least 80 mg/kg/day. Higher doses were not evaluated in this study due to the observation of >=20% maternal mortality at >=100 mg/kg/day in a preliminary investigation.

Executive summary:

New Zealand White rabbits were administered EDA*2HCl by gavage on gestation day 6-19. Doses were 0, 10, 40 or 80 mg/kg calculated as ethylene diamine. Number of resorptions, dead or alive fetuses, fetus weights and examination of live fetuses for external, skeletal or visceral effects was made. No characteristic clinical signs of toxicity were observed. No effect on maternal food intake, body weight or weight gain, liver or kidney weight. No adverse effects on prenatal viability, litter size, fetal weight or fetal morphology was observed.