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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
17-01-2012 to 21-02-2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study performed under GLP. All relevant validity criteria were met.
Justification for type of information:
Information as to the availability of the in vivo study is provided in 'attached justification'.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
inspected: July 2011; signature: August 2011
Test type:
fixed dose procedure
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
2-methoxy-4-methylphenyl methyl carbonate
EC Number:
700-673-7
Cas Number:
132638-45-0
Molecular formula:
C10H12O4
IUPAC Name:
2-methoxy-4-methylphenyl methyl carbonate
Test material form:
solid
Details on test material:
- Physical state: Extremely pale yellow crystalline solid
- Storage condition of test material: Approximately 4°C in the dark, under nitrogen

Test animals

Species:
rat
Strain:
Wistar
Remarks:
RccHan:WIST
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Recognised Supplier
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: 157 to 170g
- Fasting period before study: Overnight before dosing and four hours after dosing.
- Housing: up to 4 in solid-floor propylene cages with woodflakes
- Diet (ad libitum): 2014C Teklad Global Rodent Diet (Recognised Supplier); provided ad libitum (except for overnight fasting period and four hours post doing).
- Water (ad libitum): ad libitum (except for fasting period)
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25
- Humidity (%): 30 to 70
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12 h light / 12 h dark

IN-LIFE DATES: From: 17-01-2012 To: 21-02-2012

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 30 or 200 mg/mL in the vehicle and administered at a volume of 10 mL/kg body weight
- Amount of vehicle (if gavage): Administered at a volume of 10 mL/kg body weight
- Justification for choice of vehicle: Test item did not dissolve/suspend in water

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bodyweight

DOSAGE PREPARATION (if unusual): Not applicable.
Doses:
300 and 2000 mg/kg
No. of animals per sex per dose:
1 female at 300 mg/kg
5 females at 2000 mg/kg
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Cages were checked at least twice daily for any mortalities. Clinical observations were made ½, 1, 2, and 4 hours after dosing and then daily for fourteen days. Individual body weights were recorded on Day 0 (prior to dosing) and on Days 7 and 14 or at mortality. Individual weekly body weight changes and group mean body weights were calculated.
- Necropsy of survivors performed: yes

Results and discussion

Preliminary study:
No signs of systemic toxicity or effect on body weight were recorded in the female dosed at 300 mg/kg
Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
300 mg/kg bw: No mortality.
2000 mg/kg bw: No mortality.
Clinical signs:
300 mg/kg bw: No signs of systemic toxicity were noted during the observation period.
2000 mg/kg bw: Signs of systemic toxicity noted were hunched posture, lethargy, ataxia, pilo-erection, ptosis, prostration and increased lachrimation. All females appeared normal one or three days after dosing. Hunched posture continued to day 2 in 1/5 females.
Body weight:
300 mg/kg bw: Expected gains in bodyweight were observed in the observation period.
2000 mg/kg bw: Expected gains in bodyweight were observed in the observation period.
Gross pathology:
300 mg/kg bw: No abnormalities were noted at necropsy.
2000 mg/kg bw: No abnormalities were noted at necropsy.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study the oral LD50 was established to exceed 2000 mg/kg bw in female Wistar (RccHan™: WIST) rats. Applicant assessment indicates, under the conditions of this study and according to the OECD TG 420 criteria, the LD50 cut-off value was considered to be greater than 2000 mg/kg body weight and less than 5000 mg/kg body weight.
Executive summary:

The study was performed according to OECD TG 420 and EU Method B.1 bis guidelines for Acute Toxicity Oral: fixed dose method and in accordance with GLP. The objective of the study was to assess the acute oral toxicity of the test material following a single oral administration in the female Wistar (RccHan™: WIST) strain rat by the fixed dose method. The test item was formulated in arachis oil BP vehicle at 30 mg/mL and then administered by single oral gavage in a sighting test to one fasted female at 300 mg/kg bw. In the absence of toxicity, an additional fasted female was treated with 30 mg/mL test item in arachis oil BP at 2000 mg/kg bw. In the absence of mortality, a further four fasted females were treated. Clinical signs and bodyweight development were monitored during the study and were subsequently subjected to gross necropsy. There were no mortalities. Clinical observations were absent at 300 mg/kg bw. Clinical observations at 2000 mg/kg bw included hunched posture, lethargy, ataxia, pilo-erection, ptosis, prostration and increased lachrimation. All signs ceased by day 3. All females showed expected gains in bodyweight during the study period and there was no abnormal necropsy findings. Under the conditions of this study the oral LD50 was established to exceed 2000 mg/kg bw in female Wistar (RccHan™: WIST) strain rat. Applicant assessment indicates, under the conditions of this study and according to the OECD TG 420 criteria, the LD50 cut-off value was considered to be greater than 2000 mg/kg body weight and less than 5000 mg/kg body weight.

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