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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 2017-08-31 to 2017-09-22
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report date:
2017

Materials and methods

Test guideline
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:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
2-[4-(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)phenyl]butyric acid
EC Number:
303-995-2
EC Name:
2-[4-(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)phenyl]butyric acid
Cas Number:
94232-67-4
Molecular formula:
C18H15NO4
IUPAC Name:
2-[4-(1,3-dioxo-2,3-dihydro-1H-isoindol-2-yl)phenyl]butanoic acid
Specific details on test material used for the study:
Batch: 17001R73A
Purity: 102%

Test animals

Species:
rat
Strain:
other: Crl: WI(Han)
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
Source: Charles River Deutschland, Sulzfeld, Germany.
Age at study initiation: Young adult animals (approximately 8 weeks old) were selected.
Weight at study initiation: 147 to 171 g.
Housing: On arrival and following assignment to the study, animals were group housed (up to 5 animals of the same sex and same dosing group together) in polycarbonate cages containing sterili zed sawdust as bedding material equipped with water bottles.
Diet: Pelleted rodent diet was provided ad libitum throughout the study.
Water: Municipal tap-water was freely available to each animal via water bottles.
Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
Temperature (°C): 18°C to 24°C (Target), 21°C to 22°C (Actual)
Humidity (%): 40% to 70% (Target), 46% to 72% (Actual)
Air changes (per hr): Ten or greater
Photoperiod (hrs dark / hrs light): 12-hour light/12-hour dark cycle

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
Amount of vehicle: 10 mL/kg body weight was used for each dose.
Justification for choice of vehicle: Trial preparations were performed at the Test Facility to select the suitable vehicle and to establish a suitable formulation procedure.

CLASS METHOD
Rationale for the selection of the starting dose:The dose levels were based on the OECD test guidelines and were selected from the series 5 (lowest dose level), 50, 300 and 2000 (highest dose level) mg/kg body weight. The starting dose level should be the one that is likely to produce mortality in at least some of the animals and was selected based on available toxicity data of the test item.
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
Three female
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality/Moribundity Checks: twice daily. Body weights: A fasted weight was recorded on the day of dosing. Terminal body weights were collected from animals found dead or euthanized moribund after Day 1 (predose), 8 and 15. Clinical signs: at periodic intervals on the day of dosing (at least three times) and once daily thereafter.
- Necropsy of survivors performed: yes, at the end of observation period, all animals were sacrificed by oxygen/carbon dioxide procedure and subjected to necropsy.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
Hunched posture and piloerection were noted for all animals between Days 1 and 4. Abnormal gait was noted for three animals on Day 1.
Body weight:
The body weight gain shown by the animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The oral LD50 value of test item in Wistar rats was established to to exceed 2000 mg/kg body weight.
Executive summary:

The objective of this study was to determine the potential toxicity of test item, when given by oral gavage at a single dose to rats of a single sex at one or more defined doses to evaluate the potential reversibility of any findings.

 

The study was carried out in compliance with the OECD No.423 (2001) guidelines.

 

The test item was administered by oral gavage to two consecutive groups of three female Wistar rats at 2000 mg/kg body weight. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15).

 

No mortality occurred.

 

Hunched posture and piloerection were noted for all animals between Days 1 and 4. Abnormal gait was noted for three animals on Day 1.

 

The body weight gain shown by the animals over the study period was considered to be normal.

 

No abnormalities were found at macroscopic post mortem examination of the animals.

 

The oral LD50 value of Phtalimido butyric acid in Wistar rats was established to exceed 2000 mg/kg body weight.

 

According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.