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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
repeated dose toxicity: oral
Remarks:
combined repeated dose and carcinogenicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Data from study report.

Data source

Reference
Reference Type:
publication
Title:
NTP TECHNICAL REPORT ON THE TOXICOLOGY AND CARCINOGENESIS STUDIES
Author:
U.S. National Toxicology Program (NTP)
Year:
1990
Bibliographic source:
U.S. National Toxicology Program (NTP) ,1990

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: As mention below
Principles of method if other than guideline:
Toxicological and carcinogenic study of α-methylbenzyl alcohol in B6C3F1 mice for sixteen days.
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
1-phenylethanol
EC Number:
202-707-1
EC Name:
1-phenylethanol
Cas Number:
98-85-1
Molecular formula:
C8H10O
IUPAC Name:
1-phenylethanol
Test material form:
other: Liquid
Details on test material:
- Name of test material (as cited in study report): alpha-METHYLBENZYL ALCOHOL
- Molecular formula (if other than submission substance): C8H10O
- Molecular weight (if other than submission substance): 122.2g/mol
- Substance type: Organic
- Physical state: Liquid
- Impurities (identity and concentrations): < 1%
Specific details on test material used for the study:
No data

Test animals

Species:
mouse
Strain:
B6C3F1
Details on species / strain selection:
No data
Sex:
male/female
Details on test animals or test system and environmental conditions:
Details on test animal and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories (Portage, MI)
- Age at study initiation: 6-8 weeks
- Weight at study initiation: No data available
- Fasting period before study: No data available
- Housing: Five animals per cage were housed in a controlled environment in polycarbonate cages with hardwood chips bedding and spun-bonded polyester as cage filter.
- Diet (e.g. ad libitum): NIH 07 Mouse ration, ad libitum
- Water (e.g. ad libitum): Water, ad libitum
- Acclimatization period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 52-89°F
- Humidity (%):40-70%
- Air changes (per hr): 12-15 room air changes/hour
- Photoperiod (hrs dark / hrs light): Fluorescent light 12 hours/day

IN-LIFE DATES: From: To: 2/6/80- 2/21/80

Administration / exposure

Route of administration:
oral: gavage
Details on route of administration:
No data
Vehicle:
corn oil
Details on oral exposure:
PREPARATION OF DOSING SOLUTIONS: α-Methylbenzyl alcohol was dissolved in corn oil.

DIET PREPARATION
- Rate of preparation of diet (frequency): No data available
- Mixing appropriate amounts with (Type of food): No data available
- Storage temperature of food: No data available

VEHICLE
- Justification for use and choice of vehicle (if other than water): Corn oil
- Concentration in vehicle: 0, 125, 250, 500, 1000 or 2000 mg/kg
- Amount of vehicle (if gavage): 10 ml/kg
- Lot/batch no. (if required): No data available
- Purity: No data available

Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No data
Duration of treatment / exposure:
16 days
Frequency of treatment:
5 days per week for 12 doses over 16 days.
Doses / concentrationsopen allclose all
Dose / conc.:
0 other: mg/kg
Remarks:
Basis:actual ingested
Dose / conc.:
125 other: mg/kg
Remarks:
Basis:actual ingested
Dose / conc.:
250 other: mg/kg
Remarks:
Basis:actual ingested
Dose / conc.:
500 other: mg/kg
Remarks:
Basis:actual ingested
Dose / conc.:
1 000 other: mg/kg
Remarks:
Basis:actual ingested
Dose / conc.:
2 000 other: mg/kg
Remarks:
Basis:actual ingested
No. of animals per sex per dose:
Total: 54-60 animals
Control: 4 or 5 males, 5 females
125 mg/kg: 4 or 5 males, 5 females
250 mg/kg: 4 or 5 males, 5 females
500 mg/kg: 4 or 5 males, 5 females
1000 mg/kg: 4 or 5 males, 5 females
2000 mg/kg:4 or 5 males, 5 females
Control animals:
yes, concurrent vehicle
Details on study design:
Details on study design
- Dose selection rationale: No data
- Rationale for animal assignment (if not random): Animals distributed to weight classes and then assigned to cages and to groups by a table of random numbers.
- Rationale for selecting satellite groups:No data
- Post-exposure recovery period in satellite groups:No data
- Section schedule rationale (if not random):No data
Positive control:
No data

Examinations

Observations and examinations performed and frequency:
Observations and examinations performed & frequency
Observed twice daily ; weighted initially and 1 week thereafter.
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Twice daily.

DETAILED CLINICAL OBSERVATIONS: No data available
- Time schedule: No data available

BODY WEIGHT: No data available
- Time schedule for examinations: No data avvailable.

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): No data available
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data available
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data available

FOOD EFFICIENCY: No data available
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data available

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data available
- Time schedule for examinations: No data available

OPHTHALMOSCOPIC EXAMINATION: No data available
- Time schedule for examinations: No data available
- Dose groups that were examined: No data available

HAEMATOLOGY: No data available
- Time schedule for collection of blood: No data available
- Anaesthetic used for blood collection: No data available
- Animals fasted: No data available
- How many animals: No data available
- Parameters checked in table [No.?] were examined.

CLINICAL CHEMISTRY: No data available
- Time schedule for collection of blood:
- Animals fasted: No data available
- How many animals: No data available
- Parameters checked in table [No.?] were examined.

URINALYSIS: No data available - Time schedule for collection of urine:
- Metabolism cages used for collection of urine: No data available
- Animals fasted: No data available
- Parameters checked in table [No.?] were examined.

NEUROBEHAVIOURAL EXAMINATION: No data available
- Time schedule for examinations:
- Dose groups that were examined:
- Battery of functions tested: sensory activity / grip strength / motor activity / other: No data available

OTHER: No data available
Sacrifice and pathology:
Gross pathology: Yes
Necropsy performed on all animals.

Histopathology: Yes
Histologic exams performed on 2 male and 2 female mice in the 500 mg/kg groups, and 1 male and 1 female mouse in the vehicle control groups.
Other examinations:
Not available
Statistics:
Not available

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
Data not available
Mortality:
mortality observed, treatment-related
Description (incidence):
Mortality: Sixteen of 18 mice that received 1000 or 2000 mg/kg died within 3 days.
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Depending on treatment, a 5-21% weight loss were observed in male and female mice.
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:
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:
effects observed, treatment-related
Description (incidence and severity):
No compound-related histopathologic lesions were observed.
Histopathological findings: neoplastic:
not specified
Other effects:
not examined
Details on results:
No data

Effect levels

Dose descriptor:
NOAEL
Effect level:
500 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: labored breathing & lethargic after dosing / histopathologic lesions
Remarks on result:
other: No toxic effect were observed

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
The No Observed Adverse Effect Level (NOAEL) of α-Methylbenzyl alcohol on male and female B6C3F1 mice in a 16 day study was observed at dose concentration of 500 mg/kg.
Executive summary:

In a combined repeated dose and carcinogenicity study, the toxic effects of α-Methylbenzyl alcohol was evaluated in B6C3F1 mice for sixteen days. The mice were orally (gavage) exposed to the test chemical in a dosage of 0, 125, 250, 500, 1000 or 2000 mg/kg.Sixteen of 18 mice that received 1000 or 2000 mg/kg died within 3 days. A decrease up to 21% in body weight were observed in male and female mice after treatment withα-methylbenzyl alcohol. The results also showed no compound-related histopathologic lesions were observed. Therefore, NOAEL was considered to be 500 mg/kg when male and female B6C3F1 were orally exposed to α-methylbenzyl alcohol for sixteen days.