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Description of key information

The substance 3-Phenoxybenzylalcohol is expected to show acute toxicity effect by the oral route. And other available data indicates that the substance is not likley to exhibit acute toxicity by the inhalation & dermal route of exposure.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
(Q)SAR
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Data is from QSAR Toolbox Version 3.3
Justification for type of information:
QSAR prediction: migrated from IUCLID 5.6
Qualifier:
according to
Guideline:
other: The prediction is done using QSAR Toolbox version 3.3
Principles of method if other than guideline:
The prediction is done using QSAR Toolbox version 3.3
GLP compliance:
not specified
Limit test:
no
Species:
rat
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
no data
Route of administration:
oral: unspecified
Vehicle:
not specified
Details on oral exposure:
no data
Doses:
no data
No. of animals per sex per dose:
no data
Control animals:
not specified
Details on study design:
no data
Statistics:
no data
Sex:
not specified
Dose descriptor:
LD50
Effect level:
1 369.803 mg/kg bw
Based on:
test mat.
Mortality:
no data
Clinical signs:
no data
Body weight:
no data
Gross pathology:
no data
Other findings:
no data





The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

(((((((("a" and ("b" and ( not "c") )  )  and ("d" and ( not "e") )  )  and ("f" and ( not "g") )  )  and "h" )  and ("i" and ( not "j") )  )  and ("k" and ( not "l") )  )  and "m" )  and ("n" and "o" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Benzyl Alcohols by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules by DPRA Cysteine peptide depletion

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as High reactive OR High reactive >> Activated haloarenes by DPRA Cysteine peptide depletion

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.3

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Michael-type addition on alpha, beta-unsaturated carbonyl compounds OR AN2 >> Michael-type addition on alpha, beta-unsaturated carbonyl compounds >> Four- and Five-Membered Lactones OR SN2 OR SN2 >> Alkylation, ring opening SN2 reaction OR SN2 >> Alkylation, ring opening SN2 reaction >> Four- and Five-Membered Lactones by DNA binding by OASIS v.1.3

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OASIS v1.3

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Nucleophilic addition OR Nucleophilic addition >> Addition to carbon-hetero double bonds OR Nucleophilic addition >> Addition to carbon-hetero double bonds >> Ketones by Protein binding by OASIS v1.3

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Not categorized by Repeated dose (HESS)

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Thiocarbamates/Sulfides (Hepatotoxicity) No rank by Repeated dose (HESS)

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Non binder, impaired OH or NH2 group OR Non binder, non cyclic structure OR Strong binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Discrete chemical by Substance Type ONLY

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is >= 2.31

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.45

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The median lethal dose (LD50) value of the test substance 3-Phenoxybenzyl alcohol in rats was estimated to be 1369.8034 mg/kg bw.
Executive summary:

The acute toxicity of 3-Phenoxybenzyl alcohol by oral route was estimated using QSAR Toolboox version 3.3

The median lethal dose (LD50) value of the test substance 3-Phenoxybenzyl alcohol in rats was estimated to be 1369.8034 mg/kg bw. Considering the CLP Criteria for classification of the substance, it is concluded that 3-Phenoxybenzyl alcohol is classified for acute oral toxicity Category IV to rat.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 658 mg/kg bw
Quality of whole database:
The predicted data is K2 level obtained from the QSAR 3.3 prediction results.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Data is from online Chemical Repository Database
Qualifier:
according to
Guideline:
other:
Principles of method if other than guideline:
To observed acute inhalation toxicity given Inhalation exposure of rats for 1 hour to an aerosol and vapor atmosphere of 3 Phenoxybenzyl Alcohol at a concentration of 2.0 mg/l.
GLP compliance:
not specified
Test type:
acute toxic class method
Species:
rat
Strain:
other: Charles River CD rats
Sex:
male/female
Details on test animals and environmental conditions:
- Source: the Ethyl Corporation, Ferndale,Michigan
- Age at study initiation: No data available
- Weight at study initiation:
Male rats :200 to 254 grams
Females rats: 200 to 220 grams
- Fasting period before study: No data available
- Housing: The rats were housed individually in wire-mesh cages and were kept throughout the pre- and post exposure periods in a temperature and humidity controlled room in accordance with standards outlined in the "Guide For the Care and Use of Laboratory Animals; DREW No. (N.LH. 74-23) 1974".

- Diet (e.g. ad libitum): Purina Laboratory Chow(ad libitum)
- Water (e.g. ad libitum): Water ( ad libitum)
- Acclimation period: No data available

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no temperature mention , only temperature control room given
- Humidity (%):no humidity mention , only humidity control room given
- Air changes (per hr):Not data available
- Photoperiod (hrs dark / hrs light): Not data available

IN-LIFE DATES: From: To: Not data available
Route of administration:
inhalation
Type of inhalation exposure:
not specified
Vehicle:
not specified
Details on inhalation exposure:
No data available
Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
1 h
Concentrations:
2 mg/l
No. of animals per sex per dose:
5 male/ 5 female
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 48 hours

- Frequency of observations and weighing:
Frequency of observations: immediately following the 1 hour exposure period and twice daily after for 48 hours.

Frequency of weighing: Individual body weights were recorded prior to the 1 hour exposure and at 24 and 48 hours in order to detect any latent effects following the exposure.

- Necropsy of survivors performed: No necropsy was conducted because all of the rats survived the exposure and observation period.

- Other examinations performed: clinical signs, body weight

- other: The vapors and aerosols of the compound were generated by metering the liquid at the rate of 0.0494 ml/min with a Harvard® Infusion Pump into a positive pressure atomizer located near the chamber air inlet at the top of the exposure chamber. The "metered" concentration of the compound (2.0 mg/I) in the chamber atmosphere was calculated from the ratio of the rate of liquid dissemination (55.3 mg/min*) to the rate of total chamber airflow (27 l/min). The total chamber airflow represents the volume of air ejected from the atomizer plus the volume of make-up air.
Statistics:
No data available
Sex:
male/female
Dose descriptor:
LC0
Effect level:
> 2 other: mg/l
Based on:
test mat.
Exp. duration:
1 h
Mortality:
None of the rats died in the experiment
Clinical signs:
other: The immediate response of the rats to the experimental atmosphere was an increase of activity in preening. After several minutes of exposure, this activity decreased. The rats appeared normal during the experimental period.
Body weight:
Details given in table below
Gross pathology:
No necropsy was conducted because all of the rats survived the exposure and observation period and were sacrificed and discarded.

Body weight gain appeared normal during the 48 hour observation period

   

Individual Body Weights, Grams

Group,

Rat No.

Sex

Pre-exposure

Post-exposure (Days)

2.0 mg/l

 

 

 

16770

M

205

214

228

16771

M

254

260

270

16772

M

200

208

222

16773

M

203

211

212

16774

M

225

244

252

16775

F

220

226

232

16776

F

210

212

212

16777

F

208

215

220

16778

F

200

208

214

16779

F

218

232

233

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LC0 value for the Charles River CD rat for 3-Phenoxybenzylalcohol (CAS No :13826-35-2) was found to be > 2 mg/l.
Executive summary:

Acute inhalation study was performed on Charles River CD rats at 2 mg/l concentration. 5 male of weight from 200 to 254 grams and 5 female from 200 to 220 grams were used. The rats were housed individually in wire-mesh cages and were kept throughout the pre- and post-exposure periods in a temperature and humidity controlled room in accordance with standards outlined in the "Guide For the Care and Use of Laboratory Animals; DREW No. (N.LH. 74-23) 1974".

During exposure, the rats were caged individually in compartmented,Wire-mesh exposure cages. The cages were placed in a 160- liter cubical. Stainless steel and glass chamber. Constant chamber airflow was maintained by means of a rotary centrifugal air pump located at the exhaust side of the chamber. The chamber exhaust was filtered with an activated charcoal filter and a Cambridge Absolute filter before being discharged outside of the laboratory.

 

Observations for pharmacotoxic signs and mortality were made during and immediately following the 1 hour exposure period and twice daily thereafter for 48 hours.

None of the rats died in the experiment. No necropsy was conducted because all of the rats survived the exposure and observation period and were sacrificed and discarded.

Therefore, the LC0 value of 3-Phenoxybenzylalcohol (CAS No: 13826-35-2) for Charles River CD rat was found to be >than 2 mg/l.

 

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Value:
2 mg/m³
Quality of whole database:
The data is K4 level as the data has been obtained from the experimental study results.

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Data is from online Chemical Repository Database
Qualifier:
according to
Guideline:
other:
Principles of method if other than guideline:
Acute Dermal Toxicity (LD50) Study in the Albino Rabbit assess for 14 days.
GLP compliance:
not specified
Test type:
other: Acute toxic class method
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Kuiper's Rabbit Ranch, Gary, Indiana
- Age at study initiation: No data available
- Weight at study initiation: 2318 to 2925 grams
- Fasting period before study: No data available
- Housing: housed in hanging wire-mesh cages in temperature and humidity controlled quarters
- Diet (e.g. ad libitum): Purina Rabbit Chow(ad libitum)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: No data available

ENVIRONMENTAL CONDITIONS
- Temperature (°C): temperature controlled quarters(°C not mention)
- Humidity (%): humidity controlled quarters (% not mention)
- Air changes (per hr): No data available
- Photoperiod (hrs dark / hrs light): No data available

IN-LIFE DATES: From: To: No data available
Type of coverage:
not specified
Vehicle:
not specified
Details on dermal exposure:
MAXIMUM DOSE VOLUME APPLIED: 20000 mg/kg.
Doses:
2500, 5000, 10000 and 20000 mg/kg.
No. of animals per sex per dose:
8 male and 8 female
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Frequency: They were observed at 24 hours and daily thereafter for a total of 14 days for pharmacotoxic signs and dermal irritation

Weighing: Body weights were measured initially and at 7 and 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: body weight, gross necropsy.

Statistics:
No data available
Sex:
male/female
Dose descriptor:
LD50
Effect level:
10 000 mg/kg bw
Based on:
test mat.
95% CL:
6 702 - 14 921
Sex:
male
Dose descriptor:
LD50
Effect level:
10 000 mg/kg bw
Based on:
test mat.
95% CL:
5 000 - 20 000
Sex:
female
Dose descriptor:
LD50
Effect level:
10 000 mg/kg bw
Based on:
test mat.
95% CL:
5 000 - 20 000
Other findings:
Pharmacotoxic signs were observed during the 14-day observation period as hypo activity, decrease limb tone, ataxia, dehydration, emaciation etc.

Mortality:

Dosage level(mg/kg)

                        Total Mortalities

Male

Female

Total

2500

0/2

0/2

0/4

5000

0/2

0/2

0/4

10000

1/2

1/2

2/4

20000

2/2

2/2

4/4

Clinical signs:

Days

Erythema

Edema

Atonia

Desquamation

None

Very slight

slight

moderate

None

Very slight

slight

None

Very slight

slight

None

Very slight

slight

1-3

 

 

2/4

2/4

2/4

 

2/4

4/4

 

 

4/4

 

 

4*

 

 

3/3

 

 

2/3

1/3

1/3

 

2/3

3/3

 

 

5

1/3

 

2/3

 

2/3

 

1/3

1/3

 

2/3

3/3

 

 

6**

1/2

 

1/2

 

2/2

 

 

1/2

 

1/2

1/2

 

1/2

7

1/2

1/2

 

 

2/2

 

 

 

1/2

1/2

 

 

2/2

8

2/2

 

 

 

2/2

 

 

1/2

 

1/2

 

 

2/2

9

2/2

 

 

 

2/2

 

 

1/2

 

1/2

 

1/2

1/2

10

2/2

 

 

 

2/2

 

 

1/2

1/2

 

 

1/2

1/2

11-14

2/2

 

 

 

2/2

 

 

2/2

 

 

 

 

2/2

*1 of 4 rabbits dead.

**2 of 4 rabbits dead.

 

Body weight:

The following body weights were obtained during the 14-day observation period:

Dosage level(mg/kg)

Individual

Rabbit no.

Sex

Control

Weight

7 day weights

14 day weights

10000

31683

Male

2642

2050

2427

 

31685

Male

2583

Died

Died

 

31710

Female

2731

2363

2612

 

31714

Female

2768

Died

Died

Gross pathology:

Rabbits which were scarified following 14 days of observations.

Number Exhibiting Sign/Number necropsied

Dosage Level (mg/kg)

 

2500

          5000

           10000

Male

Female

Male

Female

Male

Female

No gross lesions

2/2

1/2

2/2

1/2

1/1

1/1

Stomach, green fluid contents

 

1/2

 

 

 

 

Stomach mucosa, dark red foci

 

1/2

 

 

 

 

Spleen, pale coloration

 

 

 

1/2

 

 

Sub-lumbar region, two areas of necrotic fat

 

1/2

 

 

 

 

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LD 50 value for the New Zealand white rabbits by 3-Phenoxybenzylalcohol (CAS No: 13826-35-2) was found to be 10000 mg/kg.
Executive summary:

Acute toxicity test (Dermal) inNew Zealand white rabbits by 3-Phenoxybenzylalcohol (CAS No: 13826-35-2) was performed.

8 Male and 8 female animals were used for the study at 2500, 5000, 10000 and 20000 mg/kg.They were individually housed in hanging wire-mesh cages in temperature and humidity controlled quarters.The rabbits weighed from 2318 to 2925 grams at the beginning of the study.Body weights were measured initially and at 7 and 14 days.They were maintained in accordance with the recommendations contained in H.E.W. Publication No. 74-23 (N.L.H.) entitled "Guide for the Care and Use of Laboratory Animals.

The hair was removed from the back of each rabbit. The skin of one male and one female in each group was abraded with a scalpel blade.The test material was applied once only to the backs of the rabbits. The area wrapped with gauze bandaging and occluded with Saran Wrap and observed for 14 days. Gross necropsy was done if some rabbits were died during 14 days and at the end of 14 days.

 

From the above study and observations, the LD 50 value for the New Zealand white rabbits by 3-Phenoxybenzylalcohol (CAS No: 13826-35-2) was found to be 10000 mg/kg.

 

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
10 000 mg/kg bw
Quality of whole database:
The data is K4 level as the data has been obtained from the experimental study results.

Additional information

Acute toxicity: oral:

The acute toxicity of 3-Phenoxybenzyl alcohol by oral route was estimated using QSAR Toolboox version 3.3

The median lethal dose (LD50) value of the test substance 3-Phenoxybenzyl alcohol in rats was estimated to be 1369.8034 mg/kg bw. Considering the CLP Criteria for classification of the substance, it is concluded that 3-Phenoxybenzyl alcohol is classified for acute oral toxicity Category IV to rat.

Acute toxicity: inhalation:

Acute inhalation study was performed onCharles River CD rats at 2 mg/l concentration. 5 male of weight from 200 to 254 grams and 5 female from 200 to 220 grams were used. The rats were housed individually in wire-mesh cages and were kept throughout the pre- and post-exposure periods in a temperature and humidity controlled room in accordance with standards outlined in the "Guide For the Care and Use of Laboratory Animals; DREW No. (N.LH. 74-23) 1974".

During exposure, the rats were caged individually in compartmented,Wire-mesh exposure cages. The cages were placed in a 160- liter cubical. Stainless steel and glass chamber. Constant chamber airflow was maintained by means of a rotary centrifugal air pump located at the exhaust side of the chamber. The chamber exhaust was filtered with an activated charcoal filter and a Cambridge Absolute filter before being discharged outside of the laboratory.

 

Observations for pharmacotoxic signs and mortality were made during and immediately following the 1 hour exposure period and twice daily thereafter for 48 hours.

None of the rats died in the experiment. No necropsy was conducted because all of the rats survived the exposure and observation period and were sacrificed and discarded.

Therefore,the LC0 value of3-Phenoxybenzylalcohol (CAS No: 13826-35-2) for Charles River CD rat was found to be >than 2 mg/l.

 

Acute toxicity: dermal:

Acute toxicity test (Dermal) inNew Zealand white rabbits by 3-Phenoxybenzylalcohol (CAS No: 13826-35-2) was performed.

8 Male and 8 female animals were used for the study at 2500, 5000, 10000 and 20000 mg/kg.They were individually housed in hanging wire-mesh cages in temperature and humidity controlled quarters.The rabbits weighed from 2318 to 2925 grams at the beginning of the study.Body weights were measured initially and at 7 and 14 days.They were maintained in accordance with the recommendations contained in H.E.W. Publication No. 74-23 (N.L.H.) entitled "Guide for the Care and Use of Laboratory Animals.

The hair was removed from the back of each rabbit. The skin of one male and one female in each group was abraded with a scalpel blade.The test material was applied once only to the backs of the rabbits. The area wrapped with gauze bandaging and occluded with Saran Wrap and observed for 14 days. Gross necropsy was done if some rabbits were died during 14 days and at the end of 14 days.

 

From the above study and observations, the LD 50 value for the New Zealand white rabbits by 3-Phenoxybenzylalcohol (CAS No: 13826-35-2) was found to be 10000 mg/kg.

 


Justification for selection of acute toxicity – oral endpoint
The median lethal dose (LD50) value of the test substance 3-Phenoxybenzyl alcohol in rats was estimated to be 1369.8034 mg/kg bw.

Justification for selection of acute toxicity – inhalation endpoint
The LC0 value for the Charles River CD rat for 3-Phenoxybenzylalcohol (CAS No :13826-35-2) was found to be > 2 mg/l.

Justification for selection of acute toxicity – dermal endpoint
The LD 50 value for the New Zealand white rabbits by 3-Phenoxybenzylalcohol (CAS No: 13826-35-2) was found to be 10000 mg/kg.

Justification for classification or non-classification

Based upon the study results and available information, the substance 3-Phenoxybenzylalcohol is expected to show acute toxicity effect by the oral route in category 4 and thus will be considered for further classification. Available data indicates that the substance is not likely to exhibit acute toxicity by the inhalation and dermal route of exposure.