Registration Dossier

Toxicological information

Developmental toxicity / teratogenicity

Currently viewing:

Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
Not reported
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study data from literature relating to non-standard test methods. The experiment was conducted in accordance with accepted scientific principles.

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Fetal Development Effects
Author:
Benson KA
Year:
1998
Bibliographic source:
AFRRI Special Publication 98(3): 17-21
Reference Type:
publication
Title:
Health Effects of Depleted Uranium Fragments
Author:
Armed Forces Radiobiology Research Institute
Year:
1998
Bibliographic source:
Livengood DR (ed) An Armed Forces Radiobiology Research Institute Workshop

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
A study was conducted to investigate the transfer of depleted uranium from mother to foetus to gain an understanding of the degree of foetal exposure and developmental effects from maternally implanted uranium. Tantalum was used in the study as a chemically inert control.
GLP compliance:
not specified
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: pellets

Test animals

Species:
rat
Strain:
Sprague-Dawley
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: (P) Females: 250 - 300 g
- Housing: Two females were housed with one untreated male during the breeding phase. From Gestation day 0 until gestation day 20 females were housed individually.

Administration / exposure

Route of administration:
implantation
Vehicle:
unchanged (no vehicle)
Details on exposure:
16 female rats were surgically implanted with 12 tantalum pellets, a non-surgical control was included.
Details on mating procedure:
- M/F ratio per cage: 1:2.
- Proof of pregnancy: Gestational Day (GD) 0 was determined by the presence of sperm in the vaginal washing.
- After successful mating each pregnant female was caged (how): individually.
Duration of treatment / exposure:
Animals were bred 7 - 14 days post-implantation; dams were euthanised on GD 20.
Frequency of treatment:
The test material was implanted during one surgical procedure. The implant remained in place until the animals were euthanised.
No. of animals per sex per dose:
16
Control animals:
yes, concurrent no treatment

Examinations

Maternal examinations:
Pregnant rats were monitored daily for weight gain, food intake and water intake.
Ovaries and uterine content:
Following euthanisation, dams were immediately subjected to caesarean-section and the uterine horns removed.
The uterine horns were examined for any resorption sites.
Fetal examinations:
Following euthanisation of the dams, foetuses were dissected out and all the placentae for that litter were collected. Litters were examined and a record made of:
-the total number of foetuses
-the number of viable foetuses
-the sex ratio
-any overt signs of teratological effects

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:no effects

Details on maternal toxic effects:
The maternal results are summarised in Table 1.
There was no effect on maternal food and water intake, weight gain during pregnancy and time-to-pregnancy.
Implanted pellets did not affect the ability of the rats breed or maintain the pregnancy until the day of euthanasia.

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
The litter data are summarised in Table 2
No effects were seen on the following litter parameters:
-the number of pups
-the number of males vs. females
-foetal weights

All litters were examined for overt signs of teratology and none were noted.

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Any other information on results incl. tables

Table 1 Effects of Implanted Tantalum on Maternal Parameters

Variable

No Surgery

12 Implanted Ta Pellets

# Dams bred

16

16

Days to pregnancy (SEM)

3.9 (± 1.76)

2.08 (± 0.23)

Mean weight gain (g)

133.79 (± 8.13)

138.32 (± 6.49)

Mean food intake (g)

23.44 (± 0.67)

24.51 (± 0.68)

Mean water intake (mL)

43.85 (± 2.59)

44.45 (± 2.60)

 

Table 2 Effects of Tantalum on Litter Data

Variable

No Surgery

12 Implanted Ta Pellets

Total # foetuses

13.8 (± 0.79)

13..5 (± 0.78)

# Males

6.6

6.3

# Females

7.2

7.2

# Non-viable

0

1

Average pup weight

3.56 (± 0.20)

3.164 (± 0.09)

Applicant's summary and conclusion

Conclusions:
The maternally implanted tantalum pellets had no developmental effects on offspring.
Executive summary:

A study was conducted to investigate the transfer of depleted uranium from mother to foetus to gain an understanding of the degree of foetal exposure from maternally implanted uranium. The impact of the depleted uranium on the dam’s ability to become pregnant and carry her litter to term was also investigated. Tantalum was used in the study as a chemically inert control.

Pregnant rats were monitored daily for weight gain, food intake and water intake. Following euthanisation, dams were immediately subjected to caesarean-section. The uterine horns were removed and foetuses were dissected out.

Litters were examined and a record made of the total number of foetuses, the number of viable foetuses, the sex ratio and any overt signs of teratological effects.

No effects were seen on the litters relating to the number of pups, the number of males vs. females and foetal weights. All litters were examined for overt signs of teratology and none were noted.

There were no effects reported in this study relating to maternal implantation of the test material.