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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:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Published public domain study, non-standard method

Data source

Reference
Reference Type:
publication
Title:
Toxicological model investigation of chicken embryo
Author:
Mora, S., Simon, F. & Kapp, P.
Year:
1991
Bibliographic source:
Acta Veterinaria Scandinavica, Suppl. 87: 197-198

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Screening assay: test substance injected into the air sac of chicken eggs during incubation
GLP compliance:
not specified
Remarks:
: published study
Limit test:
no

Test material

Constituent 1
Reference substance name:
Urea
EC Number:
200-315-5
EC Name:
Urea
Cas Number:
57-13-6
IUPAC Name:
urea
Details on test material:
Purity grade: analytical

Test animals

Species:
other: chick embryo
Strain:
not specified
Details on test animals or test system and environmental conditions:
Chick embryo, at days 16, 17 and 18 of incubation

Administration / exposure

Route of administration:
other: injection into egg air sac
Vehicle:
water
Details on exposure:
Urea dissolved in distilled water was injected into the air sac of the chick eggs on day 16, 17, and 18 of incubation.
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No information available
Details on mating procedure:
Not relevant
Duration of treatment / exposure:
Exposure to substance occurred at day 16, 17, and 18 of incubation
Frequency of treatment:
Exposure to substance occurred at day 16, 17, and 18 of incubation
Doses / concentrations
Remarks:
Doses / Concentrations:
200, 400, 800, and 1200 mg/kg egg
Basis:
nominal in water
No. of animals per sex per dose:
No information available
Control animals:
yes
Details on study design:
Blood samples were taken on Day 19; AST and LDH activities were assessed. T3 and T4 were measured by RIA

Examinations

Maternal examinations:
Not relevant
Ovaries and uterine content:
Not relevant
Fetal examinations:
Electron microscopy and plasma biochemistry

Results and discussion

Results: maternal animals

Maternal developmental toxicity

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

Details on maternal toxic effects:
Not relevant

Effect levels (maternal animals)

Dose descriptor:
other: mortality varied between 8.8 and 38.9%, dose dependently

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:yes

Details on embryotoxic / teratogenic effects:
Mortality of the embryos varied between 8.8 and 38.9%, dose-dependently. Plasma T3 level increased and plasma T4 level decreased. Electron microscopy revealed cytoplasmic oedema, mitochondrial swelling and membrane damage in thyroid cells.

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Any other information on results incl. tables

The mortality in the control group was 6.1%.

Applicant's summary and conclusion

Conclusions:
Mortality of the embryos varied between 8.8 and 38.9%, dose-dependently. The mortality in the control group was 6.1%. Plasma T3 level increased and plasma T4 level decreased. Electron microscopy revealed cytoplasmic oedema, mitochondrial swelling and membrane damage in thyroid cells.
Executive summary:

Urea in 0.05 ml water was injected into incubated fertilised chick eggs on Days 16, 17 and 18 at dose levels of 200, 400, 800 or 1200 mg/kg egg weight. AST and LDH activities were assessed in Day 19 blood samples. T3 and T4 levels were measured by RIA. The thyroid was investigated by electron microscopy. Mortality of the embryos varied between 8.8 and 38.9%, dose-dependently. The mortality in the control group was 6.1%.

Plasma T3 level increased and plasma T4 level decreased. Electron microscopy revealed cytoplasmic oedema, mitochondrial swelling and membrane damage in thyroid cells. The authors indicate that urea causes thyroid damage, however this conclusion is not considered to be reliable given the absence of other investigations and the level of general toxicity seen in this study.