Bis(2-ethylhexyl) sebacate

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1980

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Data source

Reference

Reference Type:

publication

Title:

Carcinogenesis Bioassay of Di(2-ethylhexyl) Adipate

Author:

National Toxicology Program

Year:

1980

Bibliographic source:

Technical Report No. 212

Materials and methods

Principles of method if other than guideline:

Ten animals per sex per group were fed diets containing the test substance for 13 weeks. Clinical observations were performed twice daily. Body weights and feed consumption were measured weekly. At termination, selected tissues (not specified) were preserved and evaluated histologically.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Bis(2-ethylhexyl) adipate

EC Number:

203-090-1

EC Name:

Bis(2-ethylhexyl) adipate

Cas Number:

103-23-1

Molecular formula:

C22H42O4

IUPAC Name:

bis(2-ethylhexyl) adipate

Details on test material:

CAS no: 103-23-1
Lot no: LDJ4348
Purity: 99.8%
Supplier: Wako Pure Chemical Industries (Tokyo, Japan)

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Administration / exposure

Route of administration:

oral: feed

Duration of treatment / exposure:

13 weeks

Frequency of treatment:

daily

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

1 600 ppm

Remarks:

0.16%

Doses / concentrations 2

Dose / conc.:

3 100 ppm

Remarks:

0.31%

Doses / concentrations 3

Dose / conc.:

6 300 ppm

Remarks:

0.63%

Doses / concentrations 4

Dose / conc.:

12 500 ppm

Remarks:

1.25%

Doses / concentrations 5

Dose / conc.:

25 000 ppm

Remarks:

2.5%

Control animals:

yes, concurrent vehicle

Examinations

Observations and examinations performed and frequency:

Clinical observations were performed twice daily. Body weights and feed consumption were measured weekly.

Sacrifice and pathology:

At termination, selected tissues (not specified) were preserved and evaluated histologically

Results and discussion

Results of examinations

Clinical signs:

not specified

Mortality:

mortality observed, non-treatment-related

Description (incidence):

One female rat died at 0.16%. This was not considered to be compound-related.

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

Weight gain in male and female rats was decreased by at least 11% at the 2.5% dose level, and by at least 11% in male rats at the 0.63 and 1.25% dose levels.

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

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:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Other effects:

not specified

Effect levels

1

Dose descriptor:

NOAEL

Effect level:

315 mg/kg bw/day (nominal)

Based on:

test mat.

Remarks:

0.63% in feed

Sex:

male/female

Basis for effect level:

body weight and weight gain

2

Dose descriptor:

LOAEL

Effect level:

625 mg/kg bw/day (nominal)

Based on:

test mat.

Remarks:

1.25% in feed

Sex:

male/female

Basis for effect level:

body weight and weight gain

Target system / organ toxicity

Critical effects observed:

no

Applicant's summary and conclusion

Conclusions:

Ten animals per sex per group were fed diets containing the test substance for 13 weeks. Clinical observations were performed twice daily. Body weights and feed consumption were measured weekly. At termination, selected tissues (not specified) were preserved and evaluated histologically.
Results: One female rat died at 0.16% (~80 mg/kg bw/day). This was not considered to be compound-related. Weight gain in male and female rats was decreased by at least 11% at the 2.5% dose level (~1250 mg/kg bw/day), and by at least 11% in male rats at the 0.63 (~315 mg/kg bw/day) and 1.25% (~ 625 mg/kg bw/day) dose levels. Neither compound-related histopathology nor reduction in feed consumption were noted.
NOEL = 0.63 .. % (~315 mg/kg bw/day)
LOEL = 1.25 .. % (~625 mg/kg bw/day)