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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: guidelie study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report date:
1991

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
EPA OTS 798.4900 (Prenatal Developmental Toxicity Study)
Principles of method if other than guideline:
Tributyl phosphate was administered by gastric intubation to rats during the day 6-15 gestation interval. Dose levels were 188, 375 and 750 mg/kg/day. Each study group was comprised of 24 mated female CD rats. Animals were sacrificed on day 20 of gestation and given a gross postmortem evaluation.
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Tributyl phosphate
EC Number:
204-800-2
EC Name:
Tributyl phosphate
Cas Number:
126-73-8
Molecular formula:
C12H27O4P
IUPAC Name:
tributyl phosphate
Constituent 2
Reference substance name:
200-800-2
IUPAC Name:
200-800-2
Details on test material:
purity 100 %

Test animals

Species:
rat
Strain:
Sprague-Dawley

Administration / exposure

Route of administration:
other: oral
Vehicle:
corn oil
Analytical verification of doses or concentrations:
yes
Details on mating procedure:
Females were placed with male rats nightly in a 1:1 ratio. Vaginal smears were taken early in the morning following intervals of nightly co-habitation and females were considered to have mated if sperm was noted at microscopic evaluation or a vaginal plug was observed.
Duration of treatment / exposure:
day 6 to 15 of gestation
Frequency of treatment:
daily
Duration of test:
until day 20 of gestation
Doses / concentrations
Remarks:
Doses / Concentrations:
188, 375, or 750 mg/kg bw
Basis:

No. of animals per sex per dose:
24 animals
Control animals:
yes
Details on study design:
Sex: female
Duration of test: up to day 20 of gestation

Results and discussion

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Effect levels (fetuses)

open allclose all
Dose descriptor:
NOAEL
Effect level:
750 mg/kg bw/day (actual dose received)
Basis for effect level:
other: teratogenicity
Dose descriptor:
NOAEL
Effect level:
750 mg/kg bw/day (actual dose received)
Basis for effect level:
other: embryotoxicity

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Any other information on results incl. tables

In all treatment groups toxicity to dams was produced as
evidenced by decrease in absolute body weights and
cumulative body weight gains. 29.2 % mortality in the
highest dosage group. Treatment related increase in the
incidence of delayed skeletal ossification (equivocal
biological significance), reduced mean fetal weight in the
highest dose group, no teratogenic effects.

Applicant's summary and conclusion

Executive summary:

Tributyl phosphate was administered by gastric intubation to rats during the day 6-15 gestation interval. Dose levels were 188, 375 and 750 mg/kg/day. Each study group was comprised of 24 mated female CD rats. Animals were sacrifieced on day 20 of gestation and given a gross postmortem evaluation.Tributyl phosphate was administered by gastric intubation to rats during the day 6-15 gestation interval. Dose levels were 188, 375 and 750 mg/kg/day. Each study group was comprised of 24 mated female CD rats. Animals were sacrifieced on day 20 of gestation and given a gross postmortem evaluation.

No embryotoxic effects were seen at any of the dose levels evaluated and only at the 750 mg/kg/day dose level was a reduction in mean fetal weight seen.

In groups treated at the 188 and 375 mg/kg/day dose levels, only mild developmental delays were seen in regard to both concurrent control data and historical control data.

No embryotoxic effects were seen at any of the dose levels evaluated and only at the 750 mg/kg/day dose level was a reduction in mean fetal weight seen.

External, visceral and skeletal examination of the fetuses recovered from females in the treatment groups at day 20 of gestation revealed no teratogenic response at any of the dose levels evaluated.

The NOAEL = 750 mg/kg bw for teratogenicity and embryotoxicty

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