Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
02 Nov 2016 to 08 Dec 2016
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 17, 2001
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
May 30, 2008
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
December 2002
Qualifier:
according to
Guideline:
other: Japan MAFF Testing Guideline of 12 Nousan No. 8147
Version / remarks:
November 24, 2000
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source: BASF SE
- Lot/batch No. of test material: Ra-He 2014-054
- Expiration date of the lot/batch: October, 2017
- Purity test date: 100% UVCB
- Appearance: solid / beige

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature

Test animals

Species:
rat
Strain:
Wistar
Remarks:
Crl:WI (Han) SPF
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Germany
- Females nulliparous and non-pregnant: yes
- Age at study initiation: approximately 10 weeks
- Weight at study initiation: between 170 - 180 g
- Fasting period before study: 16 hours
- Housing: caged individually in Makrolon cage, type III
- Bedding: H 15005-29; Ssniff, Spezialdiäten GmbH (Experimental Animal Diets Inc., 59494 Soest, Germany)
- Enrichment: Wooden gnawing blocks (Type NGM E-022) ; ABEDD® LAB & VET Service GmbH, Hasnerstraße 84/6; 1160 Wien – Austria
- Diet: VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany, ad libitum
- Water: Tap water, ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature(°C): 22 ± 3
- Humidity (%): 30 - 70
- Air changes (per hr): Approx. 10
- Photoperiod: 12 h / 12 h (6.00 a.m. – 6.00 p.m. / 6.00 p.m. – 6.00 a.m.)

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
deionized
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 2.5, 2.5 and 10 g/100 mL
- Amount of vehicle: 20 mL/kg bw
- Justification for choice of vehicle: Aqueous preparation corresponds to the physiological medium.

DOSAGE PREPARATION
The test item preparation for each test group was produced shortly before administration by stirring with a magnetic stirrer. The homogeneity of the test item preparation during administration was ensured by stirring with a magnetic stirrer.

TEST GROUPS
- Test group 1: 2000 mg/kg bw in 1 administration
- Test group 2: 500 mg/kg bw in 1 administration
- Test group 3: 500 mg/kg bw in 2 administrations
Doses:
500 and 2000 mg/kg bw
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Observation period: 14 days
- Body weight determination: Individual body weights shortly before administration (day 0), weekly thereafter, on the last day of observation and on the day of death starting with study day 1.
- Clinical observations: Clinical signs for each animal were recorded several times on the day of administration and at least once during each workday thereafter.
- Mortality: A check for any dead or moribund animals was made at least once each workday; these records are archived
- Pathology: Necropsy with gross-pathology examination was performed on the last day of the observation period after sacrifice by CO2-inhalation in a chamber with gradually increasing concentrations. Necropsy of all animals that died as early as possible after death.
- Histology: No histological examinations were performed.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 500 - < 2 000 mg/kg bw
Based on:
test mat.
Mortality:
- All animals of the single 2000 mg/kg bw test group died on study day 1 after administration.
- No mortality occurred in both 500 mg/kg bw test groups.
Clinical signs:
- Clinical signs in the single 2000 mg/kg test group revealed in all animals impaired general state and piloerection at hour 5 or from hour 4 until hour 5 after administration, while dyspnea and cowering position were seen at hour 5. All animals were found dead on day 1.
- Clinical signs in the first 500 mg/kg bw test group were in all animals impaired general state and piloerection from hour 2 until hour 5 or day 1 after administration.
- Clinical signs in the second 500 mg/kg bw test group revealed in all animals impaired general state and piloerection from hour 3 until hour 5 after administration, while one of these animals additionally showed dyspnea from hour 3 until hour 5.
Body weight:
The body weights of all surviving animals increased throughout the study period within the normal range.
Gross pathology:
- The following macroscopic pathologic findings were observed in the animals that died in the 2000 mg/kg bw test group (3 females): strong filled stomach, mustard discolored contents, strong red discoloration of the glandular stomach, strong red discoloration of the small intestine, congestion of the kidneys.
- There were no macroscopic pathological findings in the surviving animals sacrificed at the end of the observation period (both 500 mg/kg bw. groups, 6 females).

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria