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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well documented publication which meets basic scientific principles. Non-standard treatment regimen.
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
publication
Title:
Long-term effects of lanthanum intake on the neurobehavioral development of the rat
Author:
Feng, L. et al.
Year:
2006
Bibliographic source:
Neurotoxicology and Teratology 28(1): 119-124

Materials and methods

Principles of method if other than guideline:
Maternal rats were exposed to lanthanum from gestation day 0 through postnatal day 20. From postnatal day 20, pups were exposed to Lanthanum until postnatal day 150. Physical and neurobehavioural development of the pups was recorded, the DNA and protein/DNA concentrations were determined at postnatal day 30 and the Morris water mate test was conducted at postnatal day 150.
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Lanthanum Chloride
- Molecular formula (if other than submission substance): LaCl3
- Analytical purity: no data

Test animals

Species:
rat
Strain:
Wistar
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Animal Center of Beijing Medical University
- age: 7-9 weeks
- Housing: 5 in a polycarbonate cage

ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
other: oral: probably gavage
Vehicle:
not specified
Analytical verification of doses or concentrations:
no
Details on mating procedure:
- Female rats were mated with males of the same age and strain
- Proof of pregnancy: vaginal plug [day 0] of pregnancy
- No information about: length of cohabitation, success of copulation
- After successful mating each pregnant female was caged individually
Duration of treatment / exposure:
Dams: from gestation day 0 through postnatal day 20
Pups: from postnatal day 20 until they were killed (postnatal day 150)
Frequency of treatment:
probably daily during treatment period
Duration of test:
150 days
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 0.1, 2 and 40 mg/kg/day
Basis:
nominal conc.
No. of animals per sex per dose:
15 maternal rats/dose
a total of 30 pups (equal numbers of males and females when possible) per dose
Litters were randomly culled to 4 male, 4 female pups when possible on PND 0
Control animals:
yes, concurrent no treatment

Examinations

Maternal examinations:
no maternal examinations were reported
Ovaries and uterine content:
not examined
Statistics:
Before weaning data were evaluated at a litter base. The postweaning data however were not related to the litter and thus may contain a litter bias.
Group differences were determined by ANOVA followed by Student's t-test for body weight, surface righting, swimming time.
Historical control data:
not included

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:not examined

Effect levels (maternal animals)

Dose descriptor:
NOAEL
Effect level:
40 mg/kg bw/day (nominal)
Basis for effect level:
other: developmental toxicity

Results (fetuses)

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

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Any other information on results incl. tables

- No differences in litter size between groups.

- No differences in pinna detachment and eye opening between groups.

- Body weights showed no significant differences among all groups on the 0 day. Compared to other groups, although no significant difference was observed, the body weight of the 2 mg/kg group was elevated on PND0 and PND30, with a significant difference on PND90. However, the weight gain of the 40 mg/kg group was decreased at all ages, with a significant difference at 5 months. This was not regarded a biologicallly significant effect. All weight data were also in the range of the controls.

All other effects reported cannot be considered related to developmental/postnatal toxicity as they result from direct dosing of the young animals and litter bias wa snot considered in the study design. These are reported in section 7.9.

Applicant's summary and conclusion