Triethyl O-acetylcitrate

Endocrine disrupter mammalian screening – in vivo (level 3)

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

Test material information

Constituent 1

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 / concentrations

Doses / concentrations 1

Dose / conc.:

40 mg/kg bw/day (nominal)

Doses / concentrations 2

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).