Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Toxicological information

Developmental toxicity / teratogenicity

Currently viewing:

Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1965
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1965
Report date:
1965

Materials and methods

Principles of method if other than guideline:
Rats:
Pregnant rats were devided into 3 groups of 29-31 animals and exposed from day 3-15 of gestation.
Dosing: 0, 20, 100, 200 mg/kg bw/day (control 59 pregnant rats, reciving water by oral tube)
On day 21 half the animals were killed and examined. Remaining animals were allowed to continue until term.
Endpoints examined: average number of foetus and average weight, average length of pregnancy, average number of young, average weight of young, average no. of mothers with dead foetus, number of dead foetus, number of still-born, no. ofyoung with subcutaneous haematomas at birth, average no. of weanlings, mortality during lactation period,average weight at weaning

Mice:
Pregnant mice were devided into 3 groups of 16-19 animals and exposed from day 6-15 of gestation.
Dosing: 0, 20, 100, 200 mg/kg bw/day (control 23 pregnant mice, reciving water by oral tube)
On day 18 half the animals were killed and examined. Remaining animals were allowed to continue until term.
Endpoints examined: average number of foetus and average weight, average no. of mothers with dead foetus, number of dead foetus, average length of pregnancy, average litter size, average weight, average number of weanlings,mortality during lactation period, average weight at weaning

Rabbits:
Pregnant rabbits were exposed from day 6-18 of gestation.
Dosing: 0, 125 mg/kg bw/day (control 11 pregnant rabbits, reciving placebo tablets)
On day 30 half the animals were killed and examined .Remaining animals were allowed to continue until term.
Endpoints examined: average number of foetus and average weight, average number of young and average weight of young
GLP compliance:
no
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Fusidic acid
EC Number:
230-256-0
EC Name:
Fusidic acid
Cas Number:
6990-06-3
Molecular formula:
C31H48O6
IUPAC Name:
2-[(1Z,2S,3aS,3bS,5aS,6S,7R,9aS,9bS,10R,11aR)-2-(acetyloxy)-7,10-dihydroxy-3a,3b,6,9a-tetramethyl-hexadecahydro-1H-cyclopenta[a]phenanthren-1-ylidene]-6-methylhept-5-enoic acid
Test material form:
solid: crystalline
Details on test material:
Details are given for each individual study
Specific details on test material used for the study:
Sodium fusidate

Test animals

Species:
other:
Strain:
other: albino rats; albino mice, rabbits (Danish white breed)

Administration / exposure

Route of administration:
other: Rats and mice: oral drinking water. Rabbits: tablets
Vehicle:
not specified
Details on exposure:
Rats:
Pregnant rats were devided into 3 groups of 29-31 animals and exposed from day 3-15 of gestation.
Dosing: 0, 20, 100, 200 mg/kg bw/day (control 59 pregnant rats, reciving water by oral tube)

Mice:
Pregnant mice were devided into 3 groups of 16-19 animals and exposed from day 6-15 of gestation.
Dosing: 0, 20, 100, 200 mg/kg bw/day (control 23 pregnant mice, reciving water by oral tube)


Rabbits:
Pregnant rabbits were exposed from day 6-18 of gestation.
Dosing: 0, 125 mg/kg bw/day (control 11 pregnant rabbits, reciving placebo tablets)
Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
animals pregnant at initiation of the study
Duration of treatment / exposure:
rat: 12d (3-15 of gestation)
mice: 9d (day 6-15 of gestation.)
rabbits: 12d (day 6-18 of gestation)
Frequency of treatment:
daily dose of either 0, 20, 100 or 200 mg/kg bw.
Duration of test:
rat: 21d
mice: 18d
rabbits: 30d
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/kg bw/day (nominal)
Dose / conc.:
20 mg/kg bw/day (nominal)
Dose / conc.:
100 mg/kg bw/day (nominal)
Dose / conc.:
200 mg/kg bw/day (nominal)
No. of animals per sex per dose:
only pregnant females were exposed:
rat: 29-31
mice: 16-19
rabbits: 18
Control animals:
yes, concurrent no treatment
Details on study design:
please refer to above section: principles of method if other than guideline

Examinations

Maternal examinations:
duration of pregnancy (mice and rat)
number of mothers with dead foetuses/ number of dead foetus (mice and rat)
number of mothers with stillborn (rat)
Fetal examinations:
average number
average weight
subcutaneous haematomas
Statistics:
NA
Indices:
NA
Historical control data:
NA

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Clinical signs:
not examined
Dermal irritation (if dermal study):
not examined
Mortality:
not examined
Body weight and weight changes:
not examined
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
not examined
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
not examined
Histopathological findings: neoplastic:
not examined
Other effects:
not examined

Maternal developmental toxicity

Number of abortions:
not examined
Pre- and post-implantation loss:
not examined
Total litter losses by resorption:
effects observed, non-treatment-related
Description (incidence and severity):
Mice: The rather large number of partially absorbed foetuses seen in all groups at autopsy, is probably due to mothers discomfort from the daily oral administration
Early or late resorptions:
not examined
Dead fetuses:
no effects observed
Description (incidence and severity):
rat: number of stillborn examined: No effects observed
Changes in pregnancy duration:
no effects observed
Changes in number of pregnant:
not examined
Other effects:
no effects observed
Description (incidence and severity):
Rats: Number of stillborn
Mice, rabbit: Litter size
All: average number of young, distribution male/female
Details on maternal toxic effects:
no effects

Effect levels (maternal animals)

Key result
Dose descriptor:
NOAEL
Remarks:
rat, mice and rabbit
Effect level:
>= 200 mg/kg bw/day (nominal)
Based on:
test mat.

Maternal abnormalities

Abnormalities:
not examined

Results (fetuses)

Fetal body weight changes:
no effects observed
Reduction in number of live offspring:
no effects observed
Changes in sex ratio:
no effects observed
Changes in litter size and weights:
effects observed, treatment-related
Description (incidence and severity):
Rabbit: Litter size was rather low in the fusidin treatment group. Findings might be explained by the fact that intestinal disturbances (loose stool, decreased appetite) were encountered more often among mothers treated with the antibiotic and could be ascribed to an alternation in the intestinal flora.
Changes in postnatal survival:
effects observed, non-treatment-related
Description (incidence and severity):
Rats: rather high mortality is believed to be caused by manipulative procedures with mother and young
External malformations:
not examined
Skeletal malformations:
not examined
Visceral malformations:
not examined
Other effects:
not specified

Effect levels (fetuses)

Key result
Dose descriptor:
NOAEL
Effect level:
>= 200 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
reduction in number of live offspring
changes in sex ratio
fetal/pup body weight changes
changes in litter size and weights
changes in postnatal survival
Remarks on result:
other: Rats: high ratio of mortality in all groups during gestation and lactation period, not treatment related

Fetal abnormalities

Abnormalities:
not examined

Any other information on results incl. tables

Data show that 634 foetuses and young from 89 treated rats do not deviate from 447 foetuses and young from 59 control rats.

Data show that 352 foetuses and young from 52 treated mice do not deviate from 179 foetuses and young from 23 control mice.

Data show that 91 foetuses and young from 18 treated rabbits do not deviate from 86 foetuses and young from 11 control rabbits.

Applicant's summary and conclusion

Conclusions:
A prenatal non-GLP developmental toxicity study was performed in pregnant rats, mice and rabbits to examine the possible teratogenic effects of fusidin acid.

No test-item related toxicity and adverse effects observed using dose levels of 0, 20, 100, 200 mg/kg bw/d (rats/mice) or 0, 125 mg/kg bw/d (rabbits). Thus, based on the results of this study using three species (mice/rats/rabbits), the dose level of 200 mg fusidin acid/kg/ bw/d can be considered as the No Observed Adverse Effect Level (NOAEL) for maternel toxicity as well as for developmental effects.
Executive summary:

A prenatal non-GLP developmental toxicity study was performed in pregnant rats, mice and rabbits to examine the possible teratogenic effects of fusidin acid.

Rats and mice were dosed orally with 0, 20, 100, 200 mg/kg bw/d for 12 days (rats, day 3-15 of gestation) or 9 days (mice, day 6-15 of gestation). Rabbits were dosed orally with 0, 125 mg/kg bw/d for 12 days

(day 6-18 of gestation).

No test-item related toxicity and adverse effects observed. Thus, based on the results of this study using three species (mice/rats/rabbits), the dose level of 200 mg fusidin acid/kg/ bw/d can be considered as the No Observed Adverse Effect Level (NOAEL) for maternel toxicity as well as for developmental effects.