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Endocrine disrupter mammalian screening – in vivo (level 3)

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Administrative data

Endpoint:
endocrine disrupter mammalian screening – in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
publication
Title:
Assessment of endocrine-disrupting activities of alternative chemicals for bis(2-ethylhexyl)phthalate.
Author:
Park J, Park C, Gye MC, Lee Y
Year:
2019
Bibliographic source:
Environ Res 172: 10-17

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 440 (Uterotrophic Bioassay in Rodents: A Short-term Screening Test for Oestrogenic Properties)
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Triethyl O-acetylcitrate
EC Number:
201-066-5
EC Name:
Triethyl O-acetylcitrate
Cas Number:
77-89-4
Molecular formula:
C14H22O8
IUPAC Name:
triethyl 2-acetoxypropane-1,2,3-tricarboxylate
Details on test material:
ATEC purchased from Sigma-Aldrich St. Louis, MO, USA

Test animals

Species:
mouse
Strain:
ICR
Sex:
female
State:
ovariectomized female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
7 days
Frequency of treatment:
daily
Doses / concentrationsopen allclose all
Dose / conc.:
40 mg/kg bw/day (nominal)
Dose / conc.:
400 mg/kg bw/day (nominal)
No. of animals per sex per dose:
6
Control animals:
yes
yes, concurrent vehicle
Positive control:
E2: ß-estradiol 0.4 mg/kg/day.

Examinations

Statistics:
The data were expressed as mean ± SD using GraphPad Prism 7.0 (Graph Pad Software, La Jolla, CA, USA). Statistical analysis of the data was determined by 2-tailed student's t-test andp < 0.01 (*) was considered as statistically significance.

Results and discussion

Endocrine disrupting potential:
negative

Results of examinations

Clinical signs:
not specified
Mortality:
not specified
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Water consumption and compound intake (if drinking water study):
not specified
Clinical biochemistry findings:
not specified
Endocrine findings:
no effects observed
Description (incidence and severity):
No significant increase in uterine weight compared with the negative control group (OVX control).
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified

Effect levels

Dose descriptor:
NOAEL
Effect level:
>= 400 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
female
Basis for effect level:
organ weights
Remarks on result:
not determinable due to absence of adverse toxic effects

Applicant's summary and conclusion

Conclusions:
ATEC treatment produced no significant differences compared with ß-estradiol in estrogen-dependent tissues weights (e.g. uterus).
Executive summary:

Estrogenic effects were assessed using ovariectomized female ICR mice employing the in vivo uterotrophic assay. Mice were administered ATEC at 40 and 400 mg/kg b.w./day. Control animals received ß-estradiol (positive control) or corn oil only (vehicle control).