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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Study period:
No information
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1994
Report Date:
1994

Materials and methods

Principles of method if other than guideline:
Short-term reproductive and developmental toxicity screen (28days). Males (group 1) are, prior to chemical exposure, cohabited with a group of females (group3) for the first 3 days of the study. The animals are separated at the end of cohabitation. The females are housed until they are dosed from gestation day 6-15. They are allowed to give birth, and rear their young until postnatal day 4. Meanwhile, the males are dosed from study day 3 until 27. These males are again mated with another group of females (group2) from study day 12 until 16. During this time, both sexes are treated with the compound.
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
-Name of test material-cadmium telluride

Test animals

Species:
rat
Strain:
Sprague-Dawley
Details on test animals and environmental conditions:
no information

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 0.5% hemimethylcellulose
Details on exposure:
The test substance was suspended in 0.5% hemimethylcellulose and administred to adult male and female Spragley-Dawley rats daily by oral gavage.
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
none
Details on mating procedure:
M/F ratio per cage: 1:1
- Length of cohabitation: 3 days and afterwards 5 days with respective females groups
- Proof of pregnancy: Sperm in vaginal smear or plug during cohabitation

Duration of treatment / exposure:
-day 6 until day 15 of gestation (females: group 3)
-continuously exposed: day 0 until day 27 (females: group 2)
Frequency of treatment:
Daily
Duration of test:
28 days
Doses / concentrationsopen allclose all
Dose / conc.:
10 mg/kg bw/day
Dose / conc.:
30 mg/kg bw/day
Dose / conc.:
100 mg/kg bw/day
No. of animals per sex per dose:
10
Control animals:
yes, concurrent no treatment
Details on study design:
Dose selection rationale:
A 28-day dose-range-finding (DRF) study was conducted to set doses for the main study. This DRF study involved no mating, just dosing to group-housed adult rats. 8 animals/ sex/dose. Doses tested were: 1000, 500, 250, 100 and 0 mg/kg/d. Hematological, clinical chemistry and body/organ weight effects were found at the lowest level (100mg/kg/d). Main study doses were set at 10,30, 100 mgCdTe/kg/d

Examinations

Maternal examinations:
BODY WEIGHT: Yes
- Time schedule for examinations: group 3: gestation day 0,6,10, 15 and post natal day 1, 4, group 2: day 0,4,8,12,16,20,24,28

FOOD CONSUMPTION :
- Food consumption for each animal determined and calculated as mean daily g food/kg body weight/day: Yes
Ovaries and uterine content:
- Number of live implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes
- Other: Total implants/ corpora lutea
Fetal examinations:
no
Statistics:
none
Indices:
no information
Historical control data:
no information

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Mortality:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
females: group 3: dose related inhibtion of weight gain that started at the lowest dose group, and animals in both middle and high dose groups gained significantly less weight during the experiment and finished lighter than controls

females (group 2): animals in the top dose (100 mg/kg bw) gained less than half the weight that controls gained over the course of the study

Maternal developmental toxicity

Number of abortions:
no effects observed
Pre- and post-implantation loss:
no effects observed
Early or late resorptions:
no effects observed
Dead fetuses:
no effects observed
Details on maternal toxic effects:

Details on maternal toxic effects:
- Mortality and time to death: no death occurred
- Body weight gain: dose-related inhibition of weight gain that started at the lowest dose group, and animals in the both middle and high dose groups gained significantly less weight
- Food consumption: the females dosed during fetal organogenesis with the high dose level consumed less food than controls, and animals in the middle dose group consumed less food from gestational day 8-12.

Effect levels (maternal animals)

open allclose all
Dose descriptor:
NOAEL
Basis for effect level:
other: maternal toxicity
Remarks on result:
not determinable
Remarks:
no NOAEL identified
Dose descriptor:
LOAEL
Effect level:
10 mg/kg bw/day
Basis for effect level:
other: maternal toxicity
Dose descriptor:
NOAEL
Effect level:
100 mg/kg bw/day
Basis for effect level:
other: developmental toxicity

Results (fetuses)

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

Details on embryotoxic / teratogenic effects:
- mortality: no increase in fetal loss before or after birth
- Weight: no adverse effect on birth weight or weight gain of the pups after birth

Effect levels (fetuses)

Dose descriptor:
NOAEL
Effect level:
100 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
reduction in number of live offspring
fetal/pup body weight changes
changes in postnatal survival

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Any other information on results incl. tables

none

Applicant's summary and conclusion

Conclusions:
Oral CdTe exposure in the pregnant rat is associated with a dose related decrease in dam body weight in all CdTe groups but no change in life pups delivered, post-natal deaths or pup weight at or after birth are observed.
Executive summary:

A Short-term reproductive and developmental toxicity screen test (28days)with 10 Sprague-Dawley rats/sex/dose was conducted. A pilot dose-range-finding study found hematology, clin chem, and body/organ weight effects at the lowest level (100 mg/kg/d); main study doses were set at 10, 30, and 100 mg CdTe/kg/d, p.o. in 0.5% methylcellulose. Food consumption was variably decreased (less than or equal to 18%) at 30 and 100 mg/kg. All dosed males gained less weight; the high dose group lost 23 gr (3.7% body wt). Relative kidney weight was increased; male liver and spleen wts and all reproductive indices (fertility, sperm #, motility) were unchanged. CdTe did not alter the number of live implants, resorptions or corpora lutea in females treated before/during/after cohabiting with treated males, although body wt gain was inhibited by CdTe (less than or equal to 50%). Another group of females was dosed GD 6-15 only, and delivered their litters; all were killed pnd4. There was a dose-related decrease in dam body wt in all CdTe groups (on pnd1, less than or equal to 15%), with no change in the number of live pups delivered, postnatal deaths or pup wt at or after birth.

These data show that, despite effects on body wt gain, this duration of CdTe dosing had no detectable effects on male or female rat reproduction or early embryo development.