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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

Repeated dose toxicity: Oral

In a combined repeated dose and carcinogenicity study, the toxic effects of 1-phenylethanol 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 femaleB6C3F1 were orally exposed toα-methylbenzyl alcohol for sixteen days.

Repeated dose toxicity: Inhalation

According to the quantitative structure activity relationship model prediction, the study NOEL of the substance by the inhalation route is estimated to be 2.8 mg/kg/day in F 344 rats.This indicates that 1-phenylethanol shall not exhibit toxic effect to rat by the inhalative route below the above mention dose.

Repeated dose toxicity: Dermal

The standard acute toxicity test gave an LD50 value of >2500 mg/kg body weight. It is therefore assumed that 1-phenylethanol shall not exhibit repeated dose toxicity (in a 28 day test) by the dermal route.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
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.
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
Specific details on test material used for the study:
No data
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
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.
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
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
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
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
Critical effects observed:
not specified
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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
500 mg/kg bw/day
Study duration:
subacute
Species:
mouse
Quality of whole database:
The data is K2 level as the data has been obtained from NTP Study report for the substance.

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Repeated dose toxicity: Oral

In different studies, 1-phenylethanol has been investigated to a greater or lesser extent. Often are the studies based on in vivo experiments in rats and mice.

In a combined repeated dose and carcinogenicity study by Michael P. Dieter (1990) for US NTP, the toxic effects of 1-phenylethanol 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 was observed in male and female mice after treatment with α-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 femaleB6C3F1 were orally exposed to α-methylbenzyl alcohol for sixteen days.

The same study has also been conducted in rats, the toxic effects of 1-phenylethanol was evaluated inF344/N rats for sixteen days. The rats were orally (gavage) exposed to the test chemical in a dosage of 0, 125, 250, 500, 1000 or 2000 mg/kg.One male and one female rat that received 2000 mg/kg exhibited labored breathing and were lethargic after dosing. The final mean body weights of rats that received 500, 1000, or 2000 mg/kg were 5%, 7%, or 21% lower than that of the vehicle controls for males and 8%, 7% or 15% lower for females. The results also showed evidence of hemorrhagic gastrointestinal tracts in one female and two male rats in the 2000 mg/kg dose group, and no compound-related histopathologic lesions were observed in two male and two female rats dosed at 1000 mg/kg. Therefore, NOAEL was considered to be 1000 mg/kg when male and femaleF344/N rats were orally exposed toα-methylbenzyl alcohol for sixteen days.

 

In a combined repeated dose and carcinogenicity sub-chronic study, the toxic effects of 1-phenylethanol was evaluated in male and femaleF344/N rats for thirteen weeks. The rats were orally (gavage) exposed to the test chemical in a dosage of0, 93, 187, 375, 750 or 1500 mg/kg.Deaths of 1/10 male rats and 3/10 female rats that received 1500 mg/kg were considered to be compound related. Throughout the studies, rats that received 750 or 1500 mg/kg exhibited ataxia, rapid breathing, and lethargy for up to 30 minutes after dosing, however, these clinical signs subsided after 30 minutes. The results showed that the final mean body weight of rats receiving 1500 mg/kg was 12% lower than that of vehicle controls for males and 7% lower for females. At termination and necropsy, the liver weight to body weight ratios for male rats in the 375, 750 and 1500 mg/kg groups and for all dosed female groups were significantly greater than those for vehicle controls. In addition, a minimal-to-mild increase in brown pigment, characteristic of hemosiderin, was seen in macrophages in the spleen of 10/10 males receiving 750 mg/kg and 9/10 males receiving 1500 mg/kg, but none was seen in males receiving 375 mg/kg. A similar pigment was seen in the spleen of 6/10 females receiving 1500 mg/kg, but none was seen in females receiving 750 mg/kg. Therefore, LOAEL was considered to be 187 mg/kg for maleF344/N rats and 93 mg/kg for female F344/N rats when they were orally exposed toα-methylbenzyl alcohol for thirteen weeks.

The same sub-chronic study is conducted inmale and female B6C3F1 mice for thirteen weeks. The rats were orally (gavage) exposed to the test chemical in a dosage of0, 46.9, 93.8, 187.5, 375 or 750 mg/kg.No compound-related deaths occurred, but mice that received 375 or 750 mg/kg exhibited labored breathing, ataxia, and lethargy for up to 30 minutes after they were dosed. Final mean body weights were not compound related, and liver weight to body weight ratios for dosed mice were not related to the dose administered. No compound-related histopathologic lesions were seen. Therefore, LOAEL was considered to be 187.5 mg/kg for maleB6C3F1 mice and 46.9 mg/kg for female B6C3F1 mice when they were orally exposed to α-methylbenzyl alcohol for thirteen weeks.

A combined repeated dose toxicity and carcinogenesis study on 1-phenylethanol was conducted in F344/N rats. 50 male & 50 female rats were orally administered with 1-phenylethanol for two years at dose levels 375 or 750 mg/kg. Significant reduction in body weight gain commenced at weeks 20-30 in high dose male and female rats, and body weights were 20%-30% below those of vehicle controls at study termination. In the low dose groups, body weight reduction occurred only in male rats c;iuring the last 10 weeks of the study. After 80 weeks, 60% of the high dose rats and 80%-100% of the low dose and vehicle control rats were alive; thereafter, the number of deaths in the chemicarly exposed groups increased sharply so that, at the end of 2 years, final survival for vehicle control, low dose, and high dose rats was 35/50, 8/50, and 1150 for males and 34/50, 25/50, and 11/50 for females.The No observed adverse effect level (NOAEL) of 1-phenylethanol in F344/N rat was considered to be 375 mg/kg in female rats, and the Lowest observed adverse effect level (LOAEL) was considered to be 375 mg/kg and 750 mg/kg in male & female rats, respectively.

Thus based on the above studies it can be concluded that substance is considered to be not toxic via repeated dose study and not classified as per the criteria of CLP regulation.

Repeated dose toxicity: Inhalation

According to Annex IX of the REACH regulation, testing by the inhalation route is appropriate only if exposure of humans via inhalation is likely. Taking into account the low vapour pressure and very low exposure limit of the substance 1-phenylethanol (98-85-1) ,which is reported as Inhalation Exposure*: 0.0000059 mg/kg/day or 0.00043 mg/day ,Total Systemic Exposure**: 0.00017 mg/kg/day (RIFM, 2017)( Reference; 95th percentile calculated exposure derived from concentration survey data in the Creme RIFM aggregate exposure model (Comiskey et al., 2015; Safford et al., 2015, 2017 and Comiskey et al., 2017).In addition acute toxicity value for 1-phenylethanol (98-85-1) (as provided in section 7.2.2) is >5 mg/L. There is no data available that suggests that 1-phenylethanol shall exhibit repeated dose toxicity by inhalation route. Hence this end point was considered for waiver.

 

Repeated dose toxicity: Dermal

The standard acute toxicity test gave an LD50 value of >2500 mg/kg body weight. It is therefore assumed that 1-phenylethanol shall not exhibit repeated dose toxicity (in a 28 day test) by the dermal route.

Based on the data available for the target chemical 1-phenylethanol (98-85-1) does not exhibit toxic nature upon repeated exposure by oral, inhalation and dermal route of exposure and hence is not likely to classify as per the criteria mentioned in CLP regulation.

Justification for classification or non-classification

Thus based on the above annotation for the target chemical 1-phenylethanol (98-85-1) does not exhibit toxic nature upon repeated exposure by oral, inhalation and dermal route of exposure and hence is not likely to classify as per the criteria mentioned in CLP regulation.