α,α-dimethylphenethyl acetate

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

α,α-dimethylphenethyl acetate

EC Number:

205-781-3

EC Name:

α,α-dimethylphenethyl acetate

Cas Number:

151-05-3

Molecular formula:

C12H16O2

IUPAC Name:

1,1-dimethyl-2-phenylethyl acetate

Test material form:

solid

Test animals

Species:

rat

Strain:

Wistar

Details on species / strain selection:

This strain has been used for non-clinical safety studies, recommended by regulatory agencies.

Sex:

male/female

Details on test animals or test system and environmental conditions:

10 males and 13 females
Total 40 males and 52 females

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Duration of treatment / exposure:

Males: Premating -two weeks, during the mating period, post mating – till total dosing period of 28 days.
Females: Premating - two weeks, during mating period (variable time to conception), duration of pregnancy and 13 days after delivery.

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

250 mg/kg bw/day (nominal)

Doses / concentrations 2

Dose / conc.:

500 mg/kg bw/day (nominal)

Doses / concentrations 3

Dose / conc.:

1 000 mg/kg bw/day (nominal)

Control animals:

yes, concurrent vehicle

Examinations

Observations and examinations performed and frequency:

CLINICAL SIGNS AND MORTALITY; FUNCTIONAL OBSERVATION BATTERY; BODY WEIGHT; FOOD CONSUMPTION; DURATION OF GESTATION AND LITTER EXAMINATION; HAEMATOLOGY AND CLINICAL CHEMISTRY

Sacrifice and pathology:

GROSS NECROPSY; ORGAN WEIGHTS; HISTOPATHOLOGY;

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

effects observed, non-treatment-related

Description (incidence and severity):

Slight lowering of body weight gain during premating period (for both males and females) and mating period (for males)

Food consumption and compound intake (if feeding study):

no effects observed

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Organ weight findings including organ / body weight ratios:

effects observed, non-treatment-related

Description (incidence and severity):

A solitary incidence of statistically significant decrease was noticed in absolute weight of epididymides in male rat (in G4 dose group) which was not considered to be a treatment related change due to lack of change in relative weight of epididymides, hence not considered to be of toxicological significance.

Gross pathological findings:

effects observed, non-treatment-related

Description (incidence and severity):

Few incidental findings were observed in lungs and mediastinal lymph nodes and these comprised of reddening and abscess in lungs and enlargement of mediastinal lymph nodes. As these findings were not dose dependent and present in animals from control group as well, were therefore considered to be unrelated to treatment.

Neuropathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Effect levels

Key result

Dose descriptor:

NOAEL

Effect level:

ca. 500 mg/kg bw/day (nominal)

Sex:

male/female

Basis for effect level:

body weight and weight gain

Target system / organ toxicity

Key result

Critical effects observed:

no