Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
20 February 2017 - 16 March 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:
2001
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
2002
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
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:
2000
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
Remarks:
paste
Details on test material:
Name as cited in report: DDDA TEA salt
Physical appearance: beige to pale yellow paste
Storage conditions: at room temperature
Specific details on test material used for the study:
- Correction factor: 1.25 based on the manufacturing water content
- Stability at higher temperatures: not stable; maximum temperature is 25°C
- Solubility in vehicle (water): partially
- Stability in vehicle (water): stable

Test animals

Species:
rat
Strain:
other: Crl: WI(Han)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River France, L’Arbresle, France
- Animals: 6 young adult females (nulliparous and non-pregnant) of approximately 9 weeks old
- Weight at study initiation: 170-185 g
- Fasting period before study: Animals were deprived of food overnight (for a maximum of 20 hours) prior to dosing and until 3-4 hours after administration of the test item. Water was available.
- Housing: up to 5 animals of the same sex and same dosing group were housed together in in polycarbonate cages (Makrolon MIV type; height 18 cm.) containing sterilized sawdust as bedding material equipped with water bottles. For psychological/environmental enrichment, animals were provided with paper, except when interrupted by study prcedures/activities.
- Diet: Pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany) was provided ad libitum throughout the study, except during designated procedures.
- Water: municipal tap-water was available ad libitum.
- Acclimation period: at least 5 days before the commencement of dosing.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 10 to 21°C
- Humidity (%): 40-50
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 20 February 2017 - 16 March 2017

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
- 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. The vehicle is accepted by international guidelines.
- A single dose of test item was administered to the appropriate animals by oral gavage on Day 1, using a syringe with a plastic gavage cannula attached. The dosing formulations were stirred continuously during dose administration.
- Justifiction for dose level: the dose level was based on the OECD guidelines.
Doses:
2000 mg test item (10 mL) /kg bodyweight
No. of animals per sex per dose:
3 females/group
Control animals:
no
Details on study design:
- Method: The test was performed in a stepwise treatment of 3 females, starting with a dose level of 2000 mg/kg bw. Based on the results, an additional group was dosed at 2000 mg/kg bw.
- Duration of observation period following administration: 14 days
- Frequency of observations:
Mortality and moribundity: twice daily
Weighing: individually on day 1, day 8 and day 15.
Other examinations: at least three times on the day of dosing and once daily thereafter.
- Necropsy: yes, all moribund animals and animals surviving to the end of the observation period were sacrificed by oxygen/carbon dioxide procedure. All animals assigned to the study were subjected to necropsy and descriptions of all internal macroscopic abnormalities were recorded.
Statistics:
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:
Hunched posture, piloerection, quick breathing, ptosis and/or chromodacryorrhoea (snout) were noted for all animals on Days 1 and/or 2.
Body weight:
The mean 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
Conclusions:
The oral LD50 of DDDA TEA salt was established in an acute oral toxicity study in rats (Acute Toxic Class Method), to exceed 2000 mg/kg bw. Based on these results, DDDA TEA salt does not have to be classified and has no obligatory labelling requirement for acute oral toxicity according to the GHS.