Reaction product of adipic acid and sebacic acid and isotridecan-1-ol

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Peer reviewed near guideline study; a study report on acute and (sub)chronic studies, read-across.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1982

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)

Deviations:

yes

Remarks:

no data on heamatology and clinical chemistry

GLP compliance:

no

Limit test:

no

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

IUPAC Name:

bis(2-ethylhexyl) adipate

Details on test material:

Supplier: W.R. Grace Co.(Fords, NJ)
- Name of test material (as cited in study report): di(2-ethylhexyl)adipate
- Substance type: a clear colourless liquid
- Analytical purity: 100.4% (ester titration)
- Lot/batch No.: GC-2-27-76
- Storage condition of test material: at 4 degrees Celcius

Test animals

Species:

mouse

Strain:

B6C3F1

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: NCI Frederick cancer institute
- Age at study initiation: 4 weeks
- Housing: 5 per cage
- Diet :e.g. ad libitum
- Water :e.g. ad libitum
- Acclimatisation period: 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-31
- Humidity (%): 10-88
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

Dietary preparation:
Test diets were prepared by mixing the chemical with an aliquot of powdered
Wayne® Lab Blox animal feed (Allied Mills, Chicago, IL), placing the
mixture in a Patterson-Kelly twin-shell intensifier bar V-blender with the
remainder of the feed, and mixing for 10 minutes . Test diets were sealed in
labelled plastic bags and stored at 4°C for no longer than 14 days.

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

The amounts of di(2-ethylhexyl)adipate in selected batches of feed were measured by vapor-phase chromatography of 50-ml methanol extracts of 2-g samples. At each dietary concentration, the mean of the analytical concentration was usually within +/-10% of the theoretical.

Duration of treatment / exposure:

Duration of treatment: 91 days

Frequency of treatment:

Frequency of treatment: daily (ad libitum)

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
1600, 3100, 6300, 12500, 25000 ppm
Basis:
nominal in diet

Doses / concentrations 2

Remarks:

Doses / Concentrations:
1600 ppm = approx. 200 mg/kg bw/day
Basis:
other: recalculated based on REACH guidance

No. of animals per sex per dose:

10 male and 10 female mice per dose.

Control animals:

yes, plain diet

Details on study design:

No further details were described.

Positive control:

No positive control was used.

Examinations

Observations and examinations performed and frequency:

Survival, body weight, histopathologic analysis and and feed consumption were assessed.
Clinical observations were
made twice daily and animals were weighed weekly.

Sacrifice and pathology:

At the end of the 91-day
study, survivors were killed, necropsies were performed on all animals, and
tissues were taken for histopathologic analysis .

Other examinations:

No other examinations were performed.

Statistics:

Statistical analyses for a possible dose-related effect on survival used the method of Cox (1972) for testing two groups for equality and Tarone's (1975) extension of Cox's methods for testing for a dose-related trend . One-tailed P values have been reported for all tests except the departure from linearity test, which is reported only when its two-tailed P value is less than 0 .05.

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Mortality:

mortality observed, treatment-related

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Food efficiency:

not specified

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

not examined

Histopathological findings: non-neoplastic:

not examined

Histopathological findings: neoplastic:

not examined

Details on results:

One female mouse died as a result of an accident . Weight gain
depression was 10% or more for male mice fed 3,100 ppm or more . Weight gain
depression was 10% or more for females fed 6,000 or 25,000 ppm . No compound-related
histopathologic effects or reduction in feed consumption were observed.
High and low doses selected for the chronic study with mice were 12,000
ppm and 25,000 ppm di(2-ethylhexyl)adipate in feed .

Effect levels

Dose descriptor:

NOAEL

Effect level:

1 600 ppm

Sex:

male/female

Basis for effect level:

other: Decreased body weight gain. Recalculated to be approx. 200 mg/kg bw/day.

Target system / organ toxicity

Critical effects observed:

not specified