Registration Dossier

Administrative data

Description of key information

The substance 3-phenoxybenzyl alcohol is found to be non toxic by poral administration at doses upto 10 mg/kg/day in Sprague-Dawley rats in an Uterotrophic assay.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Data is from peer reviewed journal
Qualifier:
according to
Guideline:
other:
Principles of method if other than guideline:
Details of guideline not mentioned in publication. Uterotrophic assays was performed on rats using 3-phenoxybenzyl alcohol.
GLP compliance:
not specified
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Texas A&M University Department of Comparative Medicine
- Age at study initiation: 40–45 days old
- Weight at study initiation: No data available
- Fasting period before study: No data available
- Housing: in controlled conditions
- Use of restrainers for preventing ingestion (if dermal): Not applicable
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: No data available

ENVIRONMENTAL CONDITIONS
- Temperature (°C):23°C
- Humidity (%):No data available
- Air changes (per hr): No data available
- Photoperiod (hrs dark / hrs light): lights on, 06:00 h, lights off, 18:00 h

IN-LIFE DATES: From: To:
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
Gastric intubation
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
3 consecutive days
Frequency of treatment:
Daily
Remarks:
Doses / Concentrations:
1.0, 5.0, or 10.0 mg/kg/day
Basis:
no data
No. of animals per sex per dose:
randomly assigned to treatment groups
Control animals:
yes, concurrent vehicle
Details on study design:
No data available
Positive control:
a positive control group was subcutaneously injected with ethinyl estradiol (EE, CAS no. 57-63-6, purity 98%) at a dose of 0.6g/kg/day
Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: No data available
- Time schedule: No data available
- Cage side observations checked in table [No.?] were included. No data available

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

BODY WEIGHT: Yes
- Time schedule for examinations: No data available

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- 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:
- 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. No data available

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

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

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

OTHER:
Sacrifice and pathology:
Animals were euthanized 24 h after the final dose; and uteri, livers, and kidneys were carefully removed, cleaned of connective tissue, and weighed.
Other examinations:
No data available
Statistics:
No data available
Clinical signs:
not specified
Mortality:
not specified
Body weight and weight changes:
no effects observed
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
Organ weight findings including organ / body weight ratios:
no effects observed
Description (incidence and severity):
No change was observed in control and treated animals liver or kidney weights
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Details on results:
None of the doses affected uterine wet weight, while EE caused a significant increase in both absolute and relative wet weight (p < 0.001) as compared to animals receiving corn oil only. Additionally, test substance had no effect on liver or kidney weights
Dose descriptor:
NOEL
Effect level:
10 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
female
Basis for effect level:
other: No effect on uterine wet weight
Critical effects observed:
not specified
Conclusions:
The NOEL (No Observed Effect Level) for 3-phenoxybenzylic alcohol (13826-35-2) was found to be 10 mg/kg/day in a Uterotrophic assay.
Executive summary:

Repeated dose toxicity test was performed on pups of Sprague–Dawley rats at different concentrations. Adult female rats were bred and allowed to deliver pups normally.Fourteen days post-surgery vaginal lavage was performed daily for 3 consecutive days and cytology was observed to verify animals were not cycling. 3 consecutive days animals received 1.0, 5.0, or 10.0 mg/kg/day concentration of chemical .Animals were euthanized 24 h after the final dose; and uteri, livers, and kidneys were carefully removed, cleaned of connective tissue, and weighed. No change was observed in control and treated animals liver or kidney weights. And it was observed that 3PBAlc are not estrogenic in adult female Sprague–Dawley rats in vivo .

 

Therefore, the NOEL (No Observed Effect Level) for 3-phenoxybenzylic alcohol (13826-35-2) was found to be 10 mg/kg/day in the Uterotrophic assay.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
10 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
The data is K2 level as the data has been obtained from the experimental study published in peer reviewed journal.

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records
Reference
Endpoint:
repeated dose toxicity: inhalation
Data waiving:
exposure considerations
Justification for data waiving:
other:
Critical effects observed:
not specified
Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Link to relevant study records
Reference
Endpoint:
repeated dose toxicity: dermal
Data waiving:
other justification
Justification for data waiving:
other:
Critical effects observed:
not specified
Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Repeated Dose Toxicity - Oral:

Laffin et al (2010) conducted studies for 3-phenoxybenzyl alcohol to demonstrate effects on estrogenic activity of Sprague–Dawley rats. Adult female rats were bred and allowed to deliver pups normally. Fourteen days post-surgery vaginal lavage was performed daily for 3 consecutive days and cytology was observed to verify animals were not cycling. 3 consecutive days animals received 1.0, 5.0, or 10.0 mg/kg/day concentration of chemical .Animals were euthanized 24 h after the final dose; and uteri, livers, and kidneys were carefully removed, cleaned of connective tissue, and weighed. No change was observed in control and treated animals liver or kidney weights. The NOEL (No Observed Effect Level) for 3-phenoxybenzylic alcohol (13826-35-2) was found to be 10 mg/kg/day in a Uterotrophic assay.

In another test Laffin et al (2010), the effect of 3-phenoxybenzyl alcohol on the onset puberty was studied. Adult female rats were bred and allowed to deliver pups normally and pups were administered chemical on PND 22 and continuing until vaginal opening (VO) occurred. Control animals received an equal volume of corn oil. Once VO occurred, vaginal lavage was performed daily and cytology was observed until first diestrus (D1) indicating sexual maturity. The NOEL (No Observed Effect Level) for 3-phenoxybenzylic alcohol (13826-35-2) was found to be 10 mg/kg/day since no difference was found between treated and control animals and the smear on the day of VO was either proestrus or estrus in all animals.

Repeated Dose Toxicity - Inhalation:

The vapour pressure of test substance 3-Phenoxybenzyl alcohol was estimated to be 0.000313 Pa at 25°C by Modified Grain Method. Thus, the chemical is not considered to be volatile and thus repeated exposure by the inhaltion route seems unlikely. In addition, the chemical is used as a raw material for the manufacture of pesticides as well as pharmaceutical ingredient and hence repeated exposure by the inhalation route will be unlikely. Thus, this end point was considered for waiver.

Repeated Dose Toxicity - Dermal

In an acute study, the LD 50 value for the New Zealand white rabbits exposed to 3-Phenoxybenzylalcohol (CAS No: 13826-35-2) was found to be 10000 mg/kg. In addition, the chemical is used as a raw material for the manufacture of pesticides as well as pharmaceutical ingredient and hence repeated exposure by the dermal route will be unlikely. Thus, this end point was considered for waiver.


Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
The NOEL (No Observed Effect Level) for 3-phenoxybenzylic alcohol (13826-35-2) was found to be 10 mg/kg/day in a Uterotrophic assay.

Justification for selection of repeated dose toxicity inhalation - systemic effects endpoint:
The vapour pressure of test substance 3-Phenoxybenzyl alcohol was estimated to be 0.000313 Pa at 25°C by Modified Grain Method. Thus, the chemical is not considered to be volatile and thus repeated exposure by the inhaltion route seems unlikely. In addition, the chemical is used as a arw material for the manufacture of pesiticides as well as pharmaceutical ingredient and hence repeated exposure by the inhaltion route will be unlikely. Thus, this end point was considered for waiver.

Justification for selection of repeated dose toxicity dermal - systemic effects endpoint:
In an acute study, the LD 50 value for the New Zealand white rabbits exposed to 3-Phenoxybenzylalcohol (CAS No: 13826-35-2) was found to be 10000 mg/kg. In addition, the chemical is used as a raw material for the manufacture of pesticides as well as pharmaceutical ingredient and hence repeated exposure by the dermal route will be unlikely. Thus, this end point was considered for waiver.

Justification for classification or non-classification

On the basis of available data, the substance 3-phenoxybenzyl alcohol is likely to be non-toxic by repeated oral, inhalative or dermal administration.