2-tert-butyl-4-methoxyphenol

Repeated dose toxicity: other routes

Administrative data

Endpoint:

short-term repeated dose toxicity: other route

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Data is from peer reviewed journal

Data source

Reference

Reference Type:

publication

Title:

Repeated dose toxicity study of the test chemical

Author:

Kanga et al

Year:

2005

Bibliographic source:

Toxicology

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: refer below principle

Principles of method if other than guideline:

Repeated dose toxicity study was performed to determine the mutagenic nature of the test chemical

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-tert-butyl-4-methoxyphenol

EC Number:

204-442-7

EC Name:

2-tert-butyl-4-methoxyphenol

Cas Number:

121-00-6

Molecular formula:

C11H16O2

IUPAC Name:

2-tert-butyl-4-methoxyphenol

Test material form:

solid: bulk

Details on test material:

- Name of test material: tert-butyl-4-methoxyphenol
- Common name: Phenol, (1,1-dimethylethyl)-4-methoxy-
- Molecular formula: C11H16O2
- Molecular weight: 180.2454 g/mol
- Smiles notation: COc1ccc(O)c(c1)C(C)(C)C
- InChI=1S/C11H16O2/c1-11(2,3)9-7-8(13-4)5-6-10(9)12/h5-7,12H,1-4H3
- Substance type: Organic

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: National Veterinary Research and Quarantine Service (Anyang, Korea).
- Age at study initiation: 20-days-old immature female
Housing: All animals were cared according to the guidelines for good animal laboratory practices prepared by National Veterinary Research and Quarantine Services.
- Diet (e.g. ad libitum): Commercial diet, ad libitum
- Water (e.g. ad libitum): Tap water, ad libitum
Temperature (°C): 24±2 ◦C
- Humidity (%): 50±20%
- Air changes (per hr): No data available
- Photoperiod (hrs dark / hrs light): 12-h
light/dark cycle

Administration / exposure

Route of administration:

subcutaneous

Vehicle:

corn oil

Details on exposure:

BHA was dissolved in corn oil and diluted to dosages of 50, 100, 250 and 500 mg/kg
Area of exposure: dorsal surface, caudal to the nape of neck

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

3 days

Frequency of treatment:

Daily

Doses / concentrations

Remarks:

Doses / Concentrations:
50, 100, 250 and 500 mg/kg

No. of animals per sex per dose:

Total : 76
0 mg/kg/body weight/day: 11 female
50 mg/kg/body weight/day: 11 female
100 0 mg/kg/body weight/day: 11 female
250 mg/kg/body weight/day: 11 female
500 mg/kg/body weight/day: 11 female
2 µg/kg + 50 mg/kg ( E2 +BHA): 7 female
2 µg/kg + 500 mg/kg ( E2 +BHA): 7 female
2 µg/kg (E2): 7 female

Control animals:

yes, concurrent no treatment

Details on study design:

Dose selection rationale: Doses were referenced from NOEL (No observed effect level, 250 mg/kg) of BHA (WHO, 1989; Vorhees et al., 1981). Animals were assigned on the basis of age.

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Daily
BODY WEIGHT: Yes
- Time schedule for examinations: Daily
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes
- Time schedule for examinations: Daily
CLINICAL CHEMISTRY: Yes
All 76 rat were examined

Statistics:

Body weight gain, organ weights, consumption of feed and water, uterine epithelial cell height and hormone contents were analyzed by one-way analysis of variance with post hoc comparison between the vehicle control or positive control group and each treatment group, followed by Duncan’s multiple comparison using Statistica program (Version 5.5). A p value < 0.05 was taken as a statistically significant difference between two groups.

Results and discussion

Results of examinations

Clinical signs:

not specified

Mortality:

not specified

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

When treated with 250 and 500 mg/kg/day significant decreased in body weight gain were observed as compare to control. 17 β-estradiol with BHA 500 mg/kg/day: Significant decreased were observed as compare to control in female rat.

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:

not specified

Clinical biochemistry findings:

effects observed, treatment-related

Description (incidence and severity):

No change was observed in Estradiol level of treated rat

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Description (incidence and severity):

Absolute and Relative Uterine weight was significantly decreased in 50, 100,250 and 500 mg/kg/day dose group. 17 β-estradiol with BHA 500 mg/kg/day: Significant decreased were observed in relative liver weight as compare to control

Gross pathological findings:

not specified

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

No effect was observed in Uterine epithelial cell height of trested female rat as compare to control Also,BHA 50 or 500 mg/kg/day did not affect on 17β-estradiol induced increase of uterine epithelial cell height

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Effect levels

Dose descriptor:

LOAEL

Effect level:

50 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

female

Basis for effect level:

other: Effect on body weight gain and organ weight

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

Low observed adverse effect level (LOAEL) was considered to be 50 mg/kg/body weight/day when female rat were sub-cutaneously exposed to the test chemical.

Executive summary:

In a repeated dose subcutaneous toxicity study, female Crj:CD (SD) rats were exposed to the test chemical by subcutaneous injection into dorsal surface, caudal to the nape of neck in the concentration of 0, 50, 100, 250 and 500 mg/kg/body weight/day. Toxic changes were observed as decrease in body weight gain of 250 and 500 mg/kg/day treated female rat. Changes were also observd in uterine weight of female rat at 50 mg/kg/day. Therefore, Low observed adverse effect level (LOAEL) is considered to be 50 mg/kg/body weight/day when female rats are exposed to the test chemical by subcutaneous injection for 3 days.