Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Mar - 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:
December 17, 2001
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
2002
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
(from the competent authority) Landesanstalt für Umwelt Baden-Württemberg
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: solid, waxy, white to yellowish
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Batch No.of test material: 0017319511
- Expiration date of the batch: December 18, 2018
- Purity: > 99 %
- Physical state / color: Solid, waxy / white to yellowish

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature
- Stability under test conditions: The homogeneity of the test item preparation during administration was ensured by stirring with a magnetic stirrer.
- Solubility and stability of the test substance in the solvent/vehicle: good homogeneity in corn oil Ph.Eur.

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: For better handling the test item was heated at approx. 50 °C. The test item preparation was prduced for each administration group shortly before administration with a spatula and by stirring with a magnetic stirrer. The test item preparation was administere lukewarm.

FORM AS APPLIED IN THE TEST (if different from that of starting material) : suspension

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 (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: young adult animals (female animals approx. 10 weeks)
- Weight at study initiation: animals of comparable weight (± 20 % of the mean weight)
- Fasting period before study: Feed was withdrawn from the animals at least 16 hours before administration, but water was available ad libitum.
- Housing: single housing in fully air-conditioned rooms
- Diet (e.g. ad libitum): VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany, ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: At least 5 days before the beginning of the experimental phase

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 °C ± 3 °C
- Humidity (%): 30 - 70 %
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12 h / 12 h

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Remarks:
Ph.Eur.
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 40 g/100 mL
- Amount of vehicle (if gavage): 5.00 mL/kg bw
- Justification for choice of vehicle: Good homogeneity in corn oil Ph.Eur.

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg bw

DOSAGE PREPARATION (if unusual): For better handling the test item was heated at approx. 50 °C. The test item preparation was produced for each administration group shortly before administration with a spatula and by stirring with a magnetic stirrer. The test item preparation was administered lukewarm.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: By request of the sponsor a starting dose of 2000 mg/kg bw was chosen in the first step with 3 female animals. Because no mortality occurred, a further dose of 2000 mg/kg bw was administered to another group of 3 female animals in the second step.
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: Individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation. Clinical signs for each animal were recorded several times on the day of administration and at least once during each workday thereafter. A check for any dead or moribund animals was made at least once each workday.
- Necropsy of survivors performed: yes
Statistics:
Calculations were performed using Microsoft Excel 2010 and checked with a calculator.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no mortality occurred
Mortality:
No mortality occurred in both 2000 mg/kg bw test groups.
Clinical signs:
No clinical signs were observed during clinical examination in both 2000 mg/kg bw test groups.
Body weight:
All animals gained weight in a normal range throughout the study period.
Gross pathology:
There were no macroscopic pathological findings in any animal sacrificed at the end of the observation period (6 females).

Any other information on results incl. tables

Table 1: Mortality

Dose [mg/kg bw]

2000

2000

Sex

Female

Female

Administration

1

2

No. of animals

3

3

Mortality (animals)

No mortality

No mortality

Table 2: Maximum incidence of clinical signs

Dose [mg/kg bw]

2000

2000

Sex

Female

Female

Administration

1

2

No. of animals

3

3

Animal No.

R 151

R 152

R 153

R 154

R 155

 R 156

Abnormalities

-

-

-

-

-

-

Table 3: Body weights

Dose [mg/kg bw]

2000

2000

Administration

1

2

Animal No.

R 151

R 152

R 153

Mean weight

Standard deviation

R 154

R 155

R 156

Mean weight

Standard deviation

Body weight at study day [g]

 

0

178

176

168

174.0

5.29

179

173

169

173.7

5.03

7

200

193

183

192.0

8.54

200

189

191

193.3

5.86

14

215

195

189

199.7

13.61

207

198

207

204.0

5.20

Table 4: Gross pathology

Dose [mg/kg bw]

2000

2000

Administration

1

2

No. of animals

3

3

Animal No.

R 151

R 152

R 153

R 154

R 155

 R 156

Macroscopic pathologic abnormalities

-

-

-

-

-

-

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this study the median lethal dose of the test substance after oral administration was found to be greater than 2000 mg/kg bw in rats.
Executive summary:

In an acute oral toxicity study performed according to the Acute Toxic Class Method, a dose of 2000 mg/kg bw of the test item (preparations in corn oil Ph.Eur.) was administered by gavage to two test groups of three fasted Wistar rats each.

2000 mg/kg (both test groups):

- No mortality occurred

- No clinical signs were observed

- All animals gained weight in a normal range throughout the study period

- There were no macroscopic pathological findings in any animal sacrificed at the end of the observation period (6 females)

The acute oral LD50 was calculated to be greater than 2000 mg/kg bw in rats.