4-methoxybenzyl alcohol

Endpoint summary

Description of key information

Based on the results of the acute oral toxicity study in rats, the LD (cut off) value of the test substance analogue was determined to be greater or equal than 5000 mg/kg bw and the discriminating dose was 2000 mg/kg bw.

The acute dermal LD50 value of the test item is 3000 mg/kg bw in rabbits based on this WoE approach

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

Please refer to attached "Read-across justification" in IUCLID section 13.

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

female

Dose descriptor:

LD0

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Key result

Sex:

female

Dose descriptor:

LD50 cut-off

Effect level:

>= 5 000 mg/kg bw

Based on:

test mat.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

28 October 2015 and 11 January 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

2001

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Orientbio Inc., Republic of Korea
- Age at study initiation: 8 weeks old
- Weight at study initiation: 181.5 - 198.2 g
- Fasting period before study: yes, overnight
- Housing: individually (during the study)
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.2 - 23.4
- Humidity (%): 48.6 - 55.2
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 400 mg/mL

MAXIMUM DOSE VOLUME APPLIED: 5 mL/kg

CLASS METHOD
- Rationale for the selection of the starting dose: Due to expected low toxicity of the test substance, 2000 mg/kg was selected as the starting dose.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6 (divided in two groups for step 1 and step 2)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of weighing: prior to dosing on day 0 and on days 1, 3, 7 and on the day of necropsy, day 14
- Frequency of observations (mortality, general conditions and clinical signs): at 30 min after dosing and at 1, 2, 4 and 6 hours after dosing on day 0 and once thereafter for 14 days (day 1 to day 14)
- Necropsy of survivors performed: yes (complete gross postmortem examinations were performed on all animals)

Statistics:

Statistical analysis was not performed. Mean scores and values are determined.

Key result

Sex:

female

Dose descriptor:

LD0

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Key result

Sex:

female

Dose descriptor:

LD50 cut-off

Effect level:

>= 5 000 mg/kg bw

Based on:

test mat.

Mortality:

none

Clinical signs:

Decrease of fecal volume was evident in one animal at 2000 mg/kg bw on day 1 after dosing, and then it normalized on day 2 afte dosing. Therefore, it was considered to be a test substance-related temporary change.

Body weight:

A tendency to suppressed body weight gain was evident in all animals at 2000 mg/kg bw on day 1 after dosing. Then, these animals returned to be normal on day 3. These changes were considered to be test substance-related effects.

Gross pathology:

No grossly visible evidence of morphological abnormalities was evident in any animal at 2000 mg/kg bw.

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results of the acute oral toxicity study in rats, the LD (cut off) value was determined to be greater or equal than 5000 mg/kg bw.

Executive summary:

The acute oral toxicity of the test substance analogue was examined in a GLP-conform study according to OECD 423. A single oral dose of the test substance analogue was administered to two groups of three female Sprague-Dawley rats. In the first step, a dose 2000 mg/kg bw was administered to the first group and no mortality was observed. In the second step, the same dose was administered to group 2. All animals were monitored for clinical signs and body weight changes during 14 -day observation period after administration. They were subjected to a gross necropsy at the end of the observation period. There were no deaths of animals at 2000 mg/kg bw. Decrease of fecal volume was evident in one animal at 2000 mg/kg bw on day 1 after dosing, and then it normalized on day 3. No substance-related effects were evident in any animal at 2000 mg/kg bw. Based on the results of the acute oral toxicity study in rats, the LD (cut off) value was determined to be greater or equal than 5000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

GLP and Guideline conform study

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Qualifier:

no guideline followed

Principles of method if other than guideline:

No details on materials and methods.

GLP compliance:

no

Species:

mouse

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

11 130 mg/kg bw

Based on:

test mat.

Interpretation of results:

GHS criteria not met

Conclusions:

The acute dermal LD50 value of the test substance was reported to be 11130 mg/kg bw in mice.

Executive summary:

The acute dermal LD50 value of the test substance was reported to be 11130 mg/kg bw in mice.

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

no data

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

3 000 mg/kg bw

Based on:

test mat.

95% CL:

>= 1 940 - <= 4 060

Mortality:

1250 mg/kg bw: 0/4
2500 mg/kg bw: 1/4
5000 mg/kg bw: 4/4

Clinical signs:

Loss of coordination and muscle tone in 2/4 at 5000 mg/kg and 1/4 at 2500 mg/kg.

The following skin irrtiation response was observed in the study:

	Redness		Edema
	Slight	Moderate	Slight	Moderate
1250 mg/kg	1/4	3/4	1/4	2/4
2500 mg/kg	0/3	3/3	1/3	2/3
5000 mg/kg	0/3	3/3	0/3	3/3

Interpretation of results:

GHS criteria not met

Conclusions:

A LD50 value of 3000 mg/kg bw was determined in a dermal toxicity in rabbits after treatment with the test item.

Executive summary:

To assess the acute dermal toxicity potential of the test item, a study equivalent to OECD TG 402 was performed. Four rabbits were each incubated with 1250 mg/kg bw, 2500 mg/kg bw and 5000 mg/kg bw, respectively. One rabbit died in the mid dose group (2500 mg/kg bw) and all rabbits died in the highest test group (5000 mg/kg bw). Clinical signs such as loss of coordination and muscle tone in 2/4 animals at 5000 mg/kg bw and 1/4 animals at 2500 mg/kg bw were observed.

Signs of skin irritation were observed in all animals.

Based on the results of this study, the LD50 value for acute dermal toxicity was determined to be 3000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

3 000 mg/kg bw

Quality of whole database:

Comparable to Guideline with acceptable restrictions.

Additional information

Acute oral toxicity

The acute oral toxicity of the test substance analogue, p-methoxybenzyl acetate, was examined in a GLP-conform study according to OECD 423. A single oral dose of the test substance analogue was administered to two groups of three female Sprague-Dawley rats. In the first step, a dose 2000 mg/kg bw was administered to the first group and no mortality was observed. In the second step, the same dose was administered to group 2. All animals were monitored for clinical signs and body weight changes during a 14 -day observation period after administration. They were subjected to a gross necropsy at the end of the observation period. There were no deaths of animals at 2000 mg/kg bw. Decrease of fecal volume was evident in one animal at 2000 mg/kg bw on day 1 after dosing, and then it normalized on day 3. No substance-related effects were evident in any animal at 2000 mg/kg bw. Based on the results of the acute oral toxicity study in rats, the LD (cut off) value was determined to be greater or equal than 5000 mg/kg bw.

 

Acute dermal toxicity

A weight of evidence approach is provided to assess the acute dermal toxicity potential of the test material. One study equivalent to OECD 402 was conducted with four rabbits which were treated with 1250, 2500 and 5000 mg/kg bw.Clinical signs such as loss of coordination and muscle tone in 2/4 animals at 5000 mg/kg bw and 1/4 animals at 2500 mg/kg bw were observed.Signs of skin irritation were observed in all animals. The acute LD50 value in this study was determined to be 3000 mg/kg bw.

A second LD50 value for acute dermal toxicity was published in the Journal of Pharmacology and Experimental Therapeutics. The LD50 value was reported to be 11130 mL/kg bw in mice.

Considering the worst case, the acute dermal LD50 value of the test item is 3000 mg/kg bw in rabbits based on this WoE approach. 

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

Based on the available experimental data, the test item is not considered to be classified for acute oral or dermal toxicity under Regulation (EC) No 1272/2008, as amended for the eighth time in Regulation (EC) No 2016/918.