Uronium hydrogen sulphate

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

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

Test material information

Constituent 1

Reference substance name:

Urea

EC Number:

200-315-5

EC Name:

Urea

Cas Number:

57-13-6

Molecular formula:

CH4N2O

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

Effect level:

>= 200 - <= 1 200 mg/kg bw/day (nominal)

Based on:

test mat. (dissolved fraction)

Basis for effect level:

mortality

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.

Effect levels (fetuses)

Dose descriptor:

NOAEL

Effect level:

500 mg/kg bw/day

Based on:

test mat.

Basis for effect level:

other: teratogenicity

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.