1-phenylethanol

Repeated dose toxicity: oral

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

Test material information

Constituent 1

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-phenylethan-1-ol

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 / concentrations

Doses / concentrations 1

Dose / conc.:

0 other: mg/kg

Remarks:

Basis:actual ingested

Doses / concentrations 2

Dose / conc.:

125 other: mg/kg

Remarks:

Basis:actual ingested

Doses / concentrations 3

Dose / conc.:

250 other: mg/kg

Remarks:

Basis:actual ingested

Doses / concentrations 4

Dose / conc.:

500 other: mg/kg

Remarks:

Basis:actual ingested

Doses / concentrations 5

Dose / conc.:

1 000 other: mg/kg

Remarks:

Basis:actual ingested

Doses / concentrations 6

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.