reaction mass of isomers of: C7-9-alkyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Not specified

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted to GLP (taken from SNIF file). Registrant referring to studies >12 years old at the permission of ECHA.

Data source

Reference

Reference Type:

other: Body responsible for the test

Title:

Unnamed

Report date:

1991

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

not specified

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

406-040-9

EC Name:

-

Cas Number:

125643-61-0

Molecular formula:

C17 H25 O3 R, Where R = (C7 H15) or (C8 H17) or (C9 H19)

IUPAC Name:

Reaction mass of C7-9-alkyl 3-(3,5-di-trans-butyl-4-hydroxyphenyl)propionate

Test material form:

liquid: viscous

Details on test material:

Not specified.

Test animals

Species:

rat

Strain:

other: RAI (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

Not specified

Administration / exposure

Route of administration:

oral: unspecified

Vehicle:

other: Carboxymethyl-cellulose 0,5 % and Tween 80 0,1 %

Details on oral exposure:

Not specified

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

Not specified

Duration of treatment / exposure:

90-days

Frequency of treatment:

7 days/week

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
0 mg/kg bw/day
Basis:
actual ingested

Doses / concentrations 2

Remarks:

Doses / Concentrations:
3 mg/kg bw/day
Basis:
actual ingested

Doses / concentrations 3

Remarks:

Doses / Concentrations:
10 mg/kg bw/day
Basis:
actual ingested

Doses / concentrations 4

Remarks:

Doses / Concentrations:
30 mg/kg bw/day
Basis:
actual ingested

Doses / concentrations 5

Remarks:

Doses / Concentrations:
100 mg/kg bw/day
Basis:
actual ingested

No. of animals per sex per dose:

20

Control animals:

yes, concurrent no treatment

Details on study design:

Not specified, although presumably in accordance with OECD 408 guidelines.

Positive control:

No

Examinations

Observations and examinations performed and frequency:

Not specified

Sacrifice and pathology:

Not specified

Other examinations:

Not specified

Statistics:

Not specified

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

See below

Mortality:

mortality observed, treatment-related

Description (incidence):

See below

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

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

not specified

Ophthalmological findings:

not specified

Haematological findings:

effects observed, treatment-related

Description (incidence and severity):

See below

Clinical biochemistry findings:

effects observed, treatment-related

Description (incidence and severity):

See below

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Description (incidence and severity):

See below

Gross pathological findings:

not specified

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Histopathological findings: neoplastic:

not specified

Details on results:

Three animals died prematurely as a result of an application error.

The clinico-chemical investigations revealed elevated cholesterol values among the males from the 30 mg/kg and 100 mg/kg dosage groups.

The albumin/globulin relation was elevated at the high dosage. Elevated gamma-globulin values occurred among the males from the 30 mg/kg and 100 mg/kg dosage groups. Examination of the animal carcasses revealed elevated absolute and relative liver weights among both of the sexes at a dosage of 10 mg/kg and above.

Reduced absolute and relative adrenal weights were established for the females from the 30 mg/kg and 100 mg/kg dosage groups. The microscopic investigation revealed hepatocyte hypertrophy among both sexes at a dosage of 30 mg/kg and above. Foam cells occurred in the pulmonary alveoli among both sexes from the high-dosage group.

Effects in organs: The microscopic investigation revealed hepatocyte hypertrophy among both of the sexes from the high-dose group.

Effect levels

Dose descriptor:

NOEL

Effect level:

3 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: Not specified

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

The study was performed with the acidic parent substance and the main metabolite of the main component. The utilized substance is considered to be structurally related.

Applicant's summary and conclusion

Conclusions:

The conclusion in the provided dossier is that the effects noted resulted in non-classification, presumably as these were thought to be adaptive changes rather than definitive toxicity. On the basis of these, and not being privy to the entire study report, the substance is "not classified".

Executive summary:

The conclusion in the provided dossier is that the effects noted resulted in non-classification, presumably as these were thought to be adaptive changes rather than definitive toxicity. On the basis of these, and not being privy to the entire study report, the substance is "not classified".