Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
19 June - 11 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:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Version / remarks:
adopted 17 December 2001
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Version / remarks:
30 May 2008
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Hess. Ministerium für Umwelt, Klimaschutz, Landwirtschaft und Verbraucherschutz, Wiesbaden, Germany
Test type:
fixed dose procedure
Limit test:
no

Test material

Reference
Name:
Unnamed

Test animals

Species:
rat
Strain:
Wistar
Remarks:
Han TM
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Envigo RMS B.V., Inc, AD Horst, The Netherlands
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 9 - 11 weeks
- Weight at study initiation: 207.6 - 274.7 g (females)
- Fasting period before study: animals were fasted overnight prior to administration
- Housing: 1 - 5 animals of the same sex per cage in Makrolon Type IV cages, with wire mesh top, granulated soft wood bedding
- Diet: 2018C Teklad Global 18% protein rodent diet, ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 + 4
- Humidity (%): 28 -72
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION: DMPSA-K2 solution, dose calculation was adjusted to purity

- Rationale for the selection of the starting dose: Based on available information on the toxicity of the test item, 300 mg/kg bw was chosen as the initial starting dose, since a severe toxicity which may necessitate humane euthanasia was not expected at this dose level.
Doses:
300 and 2000 mg/kg bw
No. of animals per sex per dose:
1 (300 mg/kg bw)
5 (2000 mg/kg bw)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations and inspections for morbidity / mortality were performed at least three times within the first six hours after application (i.e., 30 minutes and 1 hour, 2 hours and 4 – 6 hours after dosing), thereafter at least once daily for 14 days. Bodyweights were determined Day 0 (prior to dosing), Day 7, and Day 14.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
At both doses 300 and 2000 mg/kg bw, there were no deaths observed during the study.
Clinical signs:
300 mg/kg bw: There were no clinical signs observed.
2000 mg/kg bw: One animal showed reduced activity. These signs were first noted approximately one hour after dosing. Recovery, as judged by external appearance and behavior, was complete by day 1 after dosing.
Body weight:
At both doses 300 and 2000 mg/kg bw, the animals showed expected gains in body weight over the observation period.
Gross pathology:
300 mg/kg bw: No abnormalities were noted at the macroscopic examination at study termination.
2000 mg/kg bw: One animal showed discoloration (red dots) in the thymus. No abnormalities were noted at necropsy in the remaining animals.

Any other information on results incl. tables

Table 1: Summary of results

 

Females

 

Animal number

Dose

[mg/kg bw]

Mortality

Clinical signs

Description

Necropsy finding

Description

 

 

 

number

number

 

number

 

Sighting study

1

300

0/1

0/1

-

0/1

-

2

2000

0/1

1/1

reduced activity within 6 h after treatment

0/1

-

Main study

3

2000

0/4

 

0/4

-

1/4

-

4

2000

-

 

-

5

2000

-

 

-

6

2000

-

 

discoloration thymus (red dots)

Applicant's summary and conclusion

Interpretation of results:
other: no classification required according to Regulation (EC) No. 1272/2008
Conclusions:
CLP: not classified