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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
other: publication
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Justification for type of information:
Please see Analogue justification

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
2002

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Groups of animals were provided feed containing a milk solution of the Source substance at doses of 50
and 250 mg/kg for 12 months.
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
not mentioned

Test animals

Species:
rat
Strain:
not specified

Administration / exposure

Route of administration:
oral: feed
Type of inhalation exposure (if applicable):
other: milk solution
Details on exposure:
Groups of animals were provided feed containing a milk solution of the source substance 3 at doses of 50
and 250 mg/kg for 12 months
Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
In the 9th month of the study, a cross-mating of the animals was performed.
Duration of treatment / exposure:
1 year
Frequency of treatment:
not mentioned
Duration of test:
not mentioned
Doses / concentrationsopen allclose all
Dose / conc.:
250 mg/kg diet
Dose / conc.:
50 mg/kg diet
No. of animals per sex per dose:
not mentioned
Control animals:
yes
Details on study design:
during the ninth month of the study, the animals were cross mated and a new generation of animals bred.
Male gonads were evaluated and embryotoxic effects were examined. Early and late embryonic death
seved as indicators of embryotoxicity. These indicators were determined by calculating the numbers of
yellow bodies, places of implantation, and the number of normal, resorptive, and deformed tissues. The
length of newborns and the size and weight of placenta were also determined.

Examinations

Maternal examinations:
behaviour and body weight, cerebral perfusion pressure, morphological composition of the blood, content of blood sulphhydryl groups, catalytic activity, activity of cholinesterases and blood peroxidases, secretory functions of the liver, weight coefficient of the organs and their pathomorphological changes were studied
Ovaries and uterine content:
not mentioned
Fetal examinations:
Early and late embryonic death served as indicators of embryotoxicity; length of newborns, body weight
Statistics:
not specified

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified

Maternal developmental toxicity

Number of abortions:
no effects observed
Pre- and post-implantation loss:
no effects observed
Total litter losses by resorption:
no effects observed
Early or late resorptions:
no effects observed
Dead fetuses:
no effects observed
Changes in pregnancy duration:
not specified
Description (incidence and severity):
Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): no effects observed
Changes in number of pregnant:
not specified
Other effects:
not examined

Effect levels (maternal animals)

Key result
Dose descriptor:
NOAEL
Remarks:
no remark
Effect level:
250 mg/kg diet
Based on:
test mat.
Remarks:
no remark
Basis for effect level:
other: no effects observed
Remarks on result:
other: no remark

Results (fetuses)

Fetal body weight changes:
no effects observed
Description (incidence and severity):
increase in body weight
Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): not specified
Reduction in number of live offspring:
no effects observed
Changes in sex ratio:
not specified
Changes in litter size and weights:
no effects observed
Description (incidence and severity):
increase in size of progeny
Changes in postnatal survival:
not specified
External malformations:
not specified
Skeletal malformations:
not specified
Visceral malformations:
not specified
Other effects:
not examined

Effect levels (fetuses)

Key result
Dose descriptor:
NOAEL
Effect level:
250 mg/kg diet
Based on:
test mat.
Remarks:
no remarks
Sex:
not specified
Basis for effect level:
other: no difference in number of animals vorn per pregant female were noted, no difference in physiological development of the progeny, no induction of embryotoxicity
Remarks on result:
other: no remarks

Applicant's summary and conclusion

Conclusions:
It was concluded that the test substance did not induce embryotoxicity, and did not affect the growth and development of the progeny. No difference in number of animals born per pregant female were noted.
Executive summary:

Compared to controls, substantial changes in certain dynamic factors evaluated (body weight, cerebral perfusion pressure, and hematological parameters early in the study in 250 mg/kg dose groups. However, toward the end of the study, practically none of the differences between test and control animals were considered substantial. Dosing with 50 mg/kg did not result in remarkable changes in any of the dynamic factors studied.

It was concluded that the test substance did not induce embryotoxicity, and did not affect the growth and development of the progeny.  No difference in number of animals born per pregant female were noted.