Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
20 June 2017 - 07 July 2017
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 guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
December 2001
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
December 2002
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
May 2008
Deviations:
no
Qualifier:
according to
Guideline:
other: Appendix to Director General Notification, No. 12-Nousan-8147. Agricultural Production Bureau, Ministry of Agriculture, Forestry and Fisheries of Japan (JMAFF)
Version / remarks:
November 2000, including the most recent revisions
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Details on test material:
- Physical appearance: white powder with lumps
- Test item storage: at room temperature protected from light
Specific details on test material used for the study:
- pH (1% in water, indicative range): 5.12 - 4.78

Test animals

Species:
rat
Strain:
other: Crl: WI(Han)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Females nulliparous and non-pregnant: yes
- Age at study initiation: approx. 8 weeks
- Weight at study initiation: 143 - 158 g
- Fasting period before study: yes, animals were deprived of food for a maximum of 20 hours prior to dosing and until 3-4 hours after administration of the test item. Water was available.
- Housing: group housing in polycarbonate cages containing sterilized sawdust as bedding material (up to 5 animals per cage).
- Diet: pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany), ad libitum
- Water: municipal tap-water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 21 - 22°C
- Humidity: 43-72%
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 21 June 2017 To: 07 July 2017

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Remarks:
specific gravity: 1.125
Details on oral exposure:
VEHICLE
- 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.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg body weight

DOSAGE PREPARATION: Test item dosing formulations (w/w) were homogenized to visually acceptable levels at appropriate concentrations to meet dose level requirements. The dosing formulations were stirred until and during dosing. Adjustment was made for specific gravity of the vehicle. A factor of 1.064 was used to correct for the purity/composition of the test item.

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. The study was conducted in a stepwise manner with two groups of 3 females. The first group was treated at a dose level of 2000 mg/kg bw. Based on the results, one additional group was dosed at 2000 mg/kg bw.
No. of animals per sex per dose:
6 females/dose (2 groups of three females in a stepwise manner)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality/Viability: twice daily; Body weights: on the day of dosing (fasted weight) and on days 1 (pre-administration), 8 and 15; Clinical signs: at periodic intervals on the day of dosing (day 1) and once daily thereafter
- Necropsy of survivors performed: yes
- Other examinations performed: no
Statistics:
The LD50 cut-off value was established based on OECD guideline 423. No statistical analysis was performed (the method used is not intended to allow the calculation of a precise LD50 value).

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:
Piloerection and/or hunched posture were noted for the animals on Days 1 and/or 2.
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
Remarks:
Not classified according to Regulation (EC) No. 1272/2008
Conclusions:
In an acute oral toxicity study with female rats, performed according to OECD 423 test guidelines, the LD50 value of ROC-118 was established to exceed 2000 mg/kg bw. Based on the result obtained in this study, ROC-118 does not need to be classified for acute toxicity under GHS and under Regulation (EC) No. 1272/2008.
Executive summary:

An acute toxicity study was performed according to OECD guideline 423 and GLP principles to determine the toxicity of ROC-118 when administered to female rats at a single dose. Two consecutive groups of three female Wistar rats were dosed by oral gavage at a dose of 2000 mg/kg body weight. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice. After 14 days, no mortality occured, body weight gain was normal and no abnormalities were found at macroscopic post mortem examination of the animals. Piloerection and/or hunched posture were noted for the animals on Days 1 and/or 2. Based on these results, the LD50 value of ROC-118 was established to exceed 2000 mg/kg bw and the substance is not classified under GHS and Regulation (EC) No. 1272/2008.