Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
09 July 2019 - 30 July 2019
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2019
Report date:
2019

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
2001
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
2002
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: EC No 440/2008, part B: "Acute Oral Toxicity, Acute Toxic Class Method".
Version / remarks:
2008
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: JMAFF Guidelines (2000), including the most recent revisions.
Version / remarks:
2000
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
(octan-2-yl)benzene
EC Number:
950-576-0
Cas Number:
31047-57-1
Molecular formula:
C14H22
IUPAC Name:
(octan-2-yl)benzene
Test material form:
liquid
Details on test material:
Identification: SHR 1396
Physical Description: Clear colorless liquid
Storage Conditions: At room temperature

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
- Females nulliparous and non-pregnant: yes
- Age at study initiation: approximately 8-9 weeks old
- Weight at study initiation: 146 to 174 g.
- Fasting period before study: Yes, for a maximum of 20 hours prior to dosing and until 3-4 hours after administration of the test item. Water was available.
- Housing: On arrival and following assignment to the study, animals were group housed (up to 3 animals of the same dosing group together) in polycarbonate cages (Makrolon MIV type; height 18 cm.) containing sterilized sawdust as bedding material (Lignocel S 8-15, JRS - J.Rettenmaier & Söhne GmbH + CO. KG, Rosenberg, Germany) equipped with water bottles. Animals were separated during designated procedures/activities.
- Diet: Pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany), ad libitum except during designated procedures.
- Water: Municipal tap-water was freely available to each animal via water bottles.
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 to 24
- Humidity (%): 47 to 73
- Air changes (per hr): 10 or more
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 10 July to 30 July 2019

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: The dose volume for each animal was based on the body weight measurement prior to dosing. Dose volume (mL/kg body weight) was calculated as follows: Dose level (g/kg) / spec.gravity or density (g/mL).

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 bw
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations were done twice, daily. Animals were weighed on Day 1 (predose), Day 8 and 15. A fasted weight was recorded on day of dosing.
- Necropsy of survivors performed: All animals were sacrificed by oxygen/carbon dioxide procedure at the end of the observation period. All animals assigned to the study were subjected to necropsy and descriptions of all internal macroscopic abnormalities were recorded.
- Other examinations performed: clinical signs, body weight,organ weights.
Statistics:
No statistical analysis was performed.

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:
other: Hunched posture and/or piloerection was noted for all animals between Days 1 and 5.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.

Applicant's summary and conclusion

Interpretation of results:
other: Not classified
Remarks:
According to Regulation (EC) No. 1272/2008
Conclusions:
In an acute oral toxicity study with female rats, performed according to OECD 423 and GLP principles, a LD50 >2000 mg/kg bw was determined.
Executive summary:

An acute oral toxicity study was performed according to OECD 423 test guideline and GLP principles. SHR 1396 was administered by oral gavage to two consecutive groups of three female Wistar Han rats at 2000 mg/kg body weight. No mortality occurred. Hunched posture and/or piloerection was noted for all animals between Days 1 and 5. The mean 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. No abnormalities were found at macroscopic post mortem examination of the animals. Based on these results, a LD50 >2000 mg/kg body weight was determined, and SHR 1396 does not have to be classified for acute oral toxicity according to Regulation (EC) No 1272/2008.