Registration Dossier

Administrative data

Endpoint:
toxicity to reproduction: other studies
Type of information:
other: 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:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
Justification of Read Across is given in Section 13 of IUCLID.

Data source

Reference
Reference Type:
study report
Title:
Unnamed

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The test substance was tested for toxic and teratogenic effects to the developing chicken embryo.
GLP compliance:
not specified
Type of method:
in vivo

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
other: chicken egg
Strain:
not specified
Details on test animals and environmental conditions:
not applicable

Administration / exposure

Route of administration:
other: via air cell or via the yolk
Vehicle:
other: sesame oil
Details on exposure:
The test substance was administered in sesame oil by the two routes at two stages of embryonic development: via the air cell at pre-incubation (0 hours) and at 96 hours of incubation, and via the yolk at 0 hours and at 96 hours.
Duration of treatment / exposure:
0 or 96 hours
Frequency of treatment:
single treatment
Duration of test:
until the chicks hatched
Doses / concentrationsopen allclose all
Dose / conc.:
0.25 other: mg/egg (nominal)
Remarks:
corresponding to 5 mg/kg
Dose / conc.:
0.5 other: mg/egg (nominal)
Remarks:
corresponding to 10 mg/kg
Dose / conc.:
2.5 other: mg/egg (nominal)
Remarks:
corresponding to 50 mg/kg
Dose / conc.:
5 other: mg/egg (nominal)
Remarks:
corresponding to100 mg/kg
Dose / conc.:
10 other: mg/egg (nominal)
Remarks:
corresponding to 200 mg/kg
No. of animals per sex per dose:
10 or more (not further specified)
Control animals:
yes, concurrent vehicle
Details on study design:
The test substance was tested for toxic and teratogenic effects to the developing chicken embryo under four sets of conditions. It was administered in sesame oil as the solvent by the two routes at two stages of embryonic development: via the air cell at pre-incubation (0 hours) and at 96 hours of incubation, and via the yolk at 0 hours and at 96 hours using techniques that have been described previously*.
Groups of 10 or more eggs were treated under these four conditions at several dose levels until a total of ninety to one hundred eggs per level was reached for all levels allowing some to hatch. Groups of comparable size were treated with the solvent at corresponding volumes and untreated controls were also included in each experiment.
After treatment, all eggs were candled daily and non-viable embryos removed. Surviving embryos were allowed to hatch. All hatched chicks and non-viable embryos were examined carefully for abnormalities (internally and externally) as well as for toxic responses (such as oedema, haemorrhage, hypopigmentation of the down and other disorders such as feather abnormalities, significant groivth retardation, cachexia, ataxia or other nerve disorder; structural abnormality of the head, viscera, limbs, or body skeleton) and accidental deaths.
At hatchings, 3 chicks were removed at random from each level including control for skeletal clearing, weighing and fixing of bursa, spleen, liver and kidney. Tissues were processed, blocked in paraffin, sectioned, affixed to slides, and stained. Later these sections were examined for internal damage to the tissues.
* McLaughlin, J., Jr., Marliac, J.-P., Verrett, M. Jacqueline, Mutchler, Mary K., and Fitzhugh, O. G., (1963) Toxicol. Appl. Pharmacol. 5, 760-770; Verrett, M. J., Marliac, J.-P., and McLaughlin, J., Jr., (1964) JADAC 47, 1003-1006.
Statistics:
Chi Square Test.

Results and discussion

Effect levels

Remarks on result:
not determinable

Observed effects

Significantly higher mortality rates were observed when the test substance was administered via yolk at the two stages of embryonic development. Air cell treatment at 0 hours was more toxic than the air cell treatment at 96 hours of embryonic development. There were no teratogenic effects observed in all the four test conditions employed.

Applicant's summary and conclusion

Conclusions:
No teratogenic effects on the developing chicken embryo were observed in all the four test conditions.
Executive summary:

The test substance was evaluated for its toxic and teratogenic potential to the developing chicken embryo under four sets of conditions. It was administered in sesame oil as the solvent by the two routes at two stages of embryonic development: via the air cell at pre-incubation (0 hours) and at 96 hours of incubation, and via the yolk at 0 hours and at 96 hours. Groups of 10 or more eggs were treated under these 4 conditions at several dose levels until a total of 90 -100 eggs/level was reached for all levels allowing some to hatch. Groups of comparable size were treated with the solvent at corresponding volumes and untreated controls were also included in each experiment. After treatment, all eggs were candled daily and non-viable embryos were removed. Surviving embryos were allowed to hatch. All hatched chicks and non-viable embryos were examined carefully for abnormalities (internally and externally) as well as for toxic responses (such as oedema, haemorrhage, hypopigmentation of the down and other disorders such as feather abnormalities, significant groivth retardation, cachexia, ataxia or other nerve disorder; structural abnormality of the head, viscera, limbs, or body skeleton) and accidental deaths. At hatchings, 3 chicks were removed at random from each level including control for skeletal clearing, weighing and fixing of bursa, spleen, liver and kidney. Tissues were processed, blocked in paraffin, sectioned, affixed to slides, and stained. These sections were examined for internal damage to the tissues.

There were no teratogenic effects observed in all the four test conditions employed.