Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
13 Mar - 04 Apr 2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2018
Report Date:
2018

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
adopted Dec 2001
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
2002
Deviations:
not specified
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
2008
Deviations:
not specified
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:
2000
Deviations:
not specified
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid

Test animals

Species:
rat
Strain:
Wistar
Remarks:
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: approximately 8 - 9 weeks
- Weight at study initiation: 142 - 170 g
- Fasting period before study: Yes, the animals were deprived of food overnight (for a maximum of 20 h) prior to design and until 3 - 4 h after administration of the test item.
- Housing: Up to 3 animals of the same sex and same dosing group were housed 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). Animals were separated during designated procedures/activities.
- Diet: pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany), ad libitum
- Water: municipal tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 - 24
- Humidity (%): 40 - 70
- Air changes (per hr): 10 or more per h
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 13 Mar 2018 To: 04 Apr 2018

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
DOSAGE PREPARATION:
Dose volume (mL/kg body weight) was calculated as follows: Dose level (g/kg) / specific gravity or density (g/mL).
The test item was stirred continuously during dose administration.

CLASS METHOD:
- Rationale for the selection of the starting dose: The dose levels were based on the OECD test guideline. The toxicity of the test item was assessed by stepwise treatment of groups of 3 females. The absence or presence of mortality of animals dosed at one step determined the next step, based on the test procedure defined in the guidelines. The onset, duration and severity of the signs of toxicity were taken into account for determination of the time interval between the dose groups. The first group was treated at a dose level of 2000 mg/kg. Based on the results, two additional groups were dosed at 300 mg/kg.
Doses:
300 mg/kg bw (2 groups) and 2000 mg/kg bw (1 group)
No. of animals per sex per dose:
3 females in each group
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Throughout the study, animals were observed for general health/mortality and moribundity twice daily, in the morning and at the end of the working day. Postdose observations were performed at periodic intervals on the day of dosing (at least three times) and once daily thereafter. Animals were weighed individually on Day 1 (predose), 8 and 15.
- Necropsy of survivors performed: Yes, all animals assigned to the study were subjected to necropsy and descriptions of all internal macroscopic abnormalities were recorded.

Results and discussion

Effect levelsopen allclose all
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - < 2 000 mg/kg bw
Based on:
test mat.
Key result
Sex:
female
Dose descriptor:
LD50 cut-off
Effect level:
500 mg/kg bw
Based on:
test mat.
Mortality:
2000 mg/kg bw: 3/3 animals died on Day 1.
300 mg/kg bw: No mortality occurred.
Clinical signs:
2000 mg/kg bw: Tonic spasms, paddling movements, lateral recumbency, gasping, piloerection and hypersensitivity to touch were observed for all animals on Day 1.
300 mg/kg bw: Hunched posture was observed in 2/3 animals of the first group and in all animals of the second group on Day 1 and in 1/3 animals of the first group on Days 1 and 2. Piloerection and salivation were noted in all animals of both groups on Day 1.
Body weight:
No effect on body weight was noted.
Gross pathology:
Necropsy revealed no substance-related findings.

Applicant's summary and conclusion

Interpretation of results:
other: Acute Oral 4, H302 according to Regulation (EC) 1272/2008
Conclusions:
CLP: Acute Oral 4, H302 according to Regulation (EC) 1272/2008