p-methoxybenzyl acetate

Endpoint summary

Description of key information

Oral:  The acute oral toxicity study with 2000 mg/kg bw of the test substance caused no mortality in rats and therefore a LD0 of 2000 mg/kg bw and LD50 cut off >=5000 mg/kg bw were derived. 

Dermal:  The acute dermal LD50 was determined to be greater than 2000 mg/kg bw in rats.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2015-10-27 to 2015-11-30

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

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
- Age at study initiation: 8 weeks
- Weight at study initiation: 181.5−198.2 g
- Fasting period before study: overnight (16 h)
- Housing: Stainless wire mesh cage, 260W×350D×210H (mm), one animal/cage (during the study)
- Diet: ad libitum, Pelleted rodent chow (Teklad Certified Irradiated Global 18% Protein Rodent Diet 2918C), Lot: 2918C-051215MA, Harlan Laboratories, Inc., U.S.A.
- Water: ad libitum, public tap water in Cheongju-si was filtered and irradiated by ultraviolet light
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.2−23.4
- Humidity (%): 48.6−55.2
- Air changes (per hr): 10−15, fresh, filtered
- 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
- Amount of vehicle: 5 mL/kg
- Lot/batch no.: MKBS6944V

CLASS METHOD
- Rationale for the selection of the starting dose: Due to expected low toxicity of the test substance and based on the information supplied by the sponsor, 2000 mg/kg was selected as the starting dose for this study.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6, all females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All animals were observed for mortality, general condition and clinical signs at 30 minutes after dosing and at 1, 2, 4 and 6 h after dosing on Day 0 and once daily thereafter for 14 days (Day 1 to Day 14). The body weights were recorded prior to dosing on Day 0 and on Days 1, 3, 7 and on the day of necropsy, Day 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

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:

There were no effects on the mortality.

Clinical signs:

Decrease of fecal volume was evident in one animal at 2000 mg/kg on Day 1 after dosing, and then it normalized on Day 2 after 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 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.

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral toxicity study with 2000 mg/kg bw of the test substance caused no mortality in rats and therefore a LD0 of 2000 mg/kg bw and LD50 cut off >=5000 mg/kg bw were derived.

Executive summary:

In an orale acute toxicity study, six fasted Sprague-Dawley female rats, divided into two groups, were orally exposed once with the test substance at a concentration level of 2000 mg/kg bw and were observed for a period of 14 days (OECD 423). No deaths and abnormalities at necropsy were observed. Decrease of fecal volume was evident in one animal on Day 1, it normalized on Day 2. A tendency to suppressed body weight gain was evident in all animals at on Day 1. The body weight gain returned to be normal on Day 3 for all animals. The LD0 value of the test material was established to be 2000 mg/kg bw. The LD50cut off value of the test material was estimated to be greater 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-conform study according to OECD guideline.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

other justification

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

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

Study period:

2015-11-10 to 2015-12-14

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1987

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 8-9 weeks
- Weight at study initiation: male: 276.9 −294.0 g, female: 224.9 −246.8 g
- Housing: Stainless wire mesh cage, 260W×350D×210H (mm), one animal/cage (during the study)
- Diet: ad libitum, Pelleted rodent chow (Teklad Certified Irradiated Global 18% Protein Rodent Diet 2918C), Lot: 2918C-062215MA , 2918C-080315MA, Harlan Laboratories, Inc., U.S.A.
- Water: ad libitum, public tap water in Cheongju-si was filtered and irradiated by ultraviolet light

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.2−22.6
- Humidity (%): 47.7-57.6
- Air changes (per hr): 10−15, fresh, filtered
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: subscapular dorsal surface of back, 4 cm*5 cm
- Type of wrap if used: lint tape and plastic film, over-wrapped with Soft Cloth Tape with Liner and surgical tape

REMOVAL OF TEST SUBSTANCE
- Washing: absorbent cotton moistened with tepid water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount applied: 1.81 mL/kg bw corresponding to 2000 mg/kg bw
- Constant volume or concentration used: yes

Duration of exposure:

24 h

Doses:

1.81 mL/kg bw corresponding to 2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

yes, concurrent no treatment

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All animals were observed for mortality, general condition and clinical signs at 30 minutes after dosing and at 1, 2, 4 and 6 hours after dosing on Day 0 and once daily thereafter for 14 days (Day 1 to Day 14). The body weight was recorded recorded prior to dosing on Day 0 and on Days 3, 7 and on the day of necropsy, Day 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

Statistical analysis was performed using SAS Program (version 9.3, SAS Institute Inc., U.S.A.). Body weights were analyzed utilizing Folded-F test for homogeneity of variance (significance level: 0.05). Student t-test was employed on homogeneous data (significance levels: 0.05 and 0.01, two-tailed).

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed.

Clinical signs:

No clinical abnormalities was observed.

Body weight:

No statistical significant difference between control and treatment group was observed.

Gross pathology:

No grossly visible findings were evident in any animal.

Interpretation of results:

GHS criteria not met

Conclusions:

The acute dermal LD50 was determined to be greater than 2000 mg/kg bw in rats.

Executive summary:

An acute dermal toxicity study according to OECD 402 was conducted in rats. Test groups consisted of one dose group at a dose of 2000 mg/kg bw and a control group. Both groups consisted of 5 males and 5 females. All animals were monitored for clinical signs and body weight changes after dosing during the 14-day observation period. They were subjected to gross necropsy at the end of the observation period. All animals survived the duration of the study. No test substance-related effects were evident in clinical signs, body weight data or necropsy findings. Based on the results of this study, the LD50 value of the test substance was considered to be greater than 2000 mg/kg bw in male and female rats under the conditions of this study.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

GLP-conform study according to OECD guideline.

Additional information

Acute toxicity

Oral:

In an oral acute toxicity study (key study), six fasted Sprague-Dawley female rats, divided into two groups, were orally exposed once with the test substance at a concentration level of 2000 mg/kg bw and were observed for a period of 14 days (OECD 423). No deaths and abnormalities at necropsy were observed. Decrease of fecal volume was evident in one animal on Day 1, it normalized on Day 2. A tendency to suppressed body weight gain was evident in all animals on Day 1. The body weight gain returned to be normal on Day 3 for all animals. The LD0 value of the test material was established to be 2000 mg/kg bw. The LD50cut off value of the test material was estimated to be greater than 5000 mg/kg bw.

 

Dermal:

An acute dermal toxicity study according to OECD 402 was conducted in rats. Test groups consisted of one dose group at a dose of 2000 mg/kg bw and a control group. Both groups consisted of 5 males and 5 females. All animals were monitored for clinical signs and body weight changes after dosing during the 14-day observation period. They were subjected to gross necropsy at the end of the observation period. All animals survived the duration of the study. No test substance-related effects were evident in clinical signs, body weight data or necropsy findings. Based on the results of this study, the LD50 value of the test substance was considered to be greater than 2000 mg/kg bw in male and female rats under the conditions of this study.

Justification for classification or non-classification

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

The available experimental test data is reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on available data on acute toxicity via oral and dermal route, the test item is not classified according to Regulation (EC) No 1272/2008 (CLP), as amended for the ninth time in Regulation (EU) No 2016/1179.