Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
28 May 2018 - 14 June 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 2001
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
May 2008
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
December 2002
Deviations:
no
Qualifier:
according to
Guideline:
other: JMAFF Guidelines
Version / remarks:
November 2000, including the most recent revisions.
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Remarks:
aqueous solution
Details on test material:
Sodium hydrogen substituted amino acid, FC-C 13403
Apppearance: Clear Colorless solution
Specific details on test material used for the study:
The test item was stored in the freezer and was allowed to warm to room temperature for at least 30 minutes before dosing.
Adjustment was made for specific gravity of the test item; specific gravity: 1.17 g/cm3

Test animals

Species:
rat
Strain:
other: Crl:WI (Han)
Sex:
female
Details on test animals and environmental conditions:
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: Young adult animals (approx. 8-11 weeks old)
- Nulliparous and non-pregnant: Yes
- Weight at study initiation: 154 to 222 g.
- Fasting period before study: yes
- Housing: Group housing of 3 animals per cage in labeled polycarbonate Makrolon cages (type: MIV) containing sterilized sawdust as bedding material.
- Diet: Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water: Free access to municipal tap water.
- Acclimation period: At least 5 days

The feed was analyzed by the supplier for nutritional components and environmental contaminants, there were no known contaminants in the feed that would interfere with the objectives of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 -22 (daily mean; set conditions: 18-24)
- Humidity (%): 44 - 74%
- Air changes (per hr): Ten or more
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 29 May 2018 to 14 June 2018

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
GAVAGE METHOD: syringe with a plastic gavage cannula

Frequency: single dosage, on day 1.

MAXIMUM DOSE VOLUME APPLIED:
The dose volume for each animal was based on the body weight measurement prior to dosing.
Dose volume (mL/kg body weight) was calculated as follows: Dose level (g/kg) / specific gravity (g/mL).

- Rationale for the selection of the starting dose: maximum recommended dose according to OECD 423.
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
6 (2 groups of three females in a stepwise manner).
Control animals:
no
Details on study design:
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, one additional group was dosed at 2000 mg/kg.

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.

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Postdose observations were performed at periodic intervals on the day of dosing (at least three times) and once daily thereafter.

Mortality/Viability: 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.

Body weights: Animals were weighed individually on day 1 (predose), 8 and 15.

- Necropsy of survivors performed: yes
- Other examinations performed: none.
Statistics:
Not applicable

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, lateral recumbency, piloerection, abnormal gait, quick breathing and/or ptosis were noted for the animals on day 1.
Piloerection was observed in two animals on day 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.
A incidence of slight body weight loss on day 15 in one animal was considered not indicative of toxicity, based on the absence of any corroborative findings in the animals.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of these animals.

Any other information on results incl. tables

According to the OECD 423 test guideline, the LD50 cut-off value was considered to be 5000 mg/kg body weight.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
In an acute oral toxicity test, performed according to OECD guideline 423 and GLP principles, the oral LD50 of sodium hydrogen substituted amino acid solution was found to be > 2000 mg/kg body weight. Based on the results, sodium hydrogen substituted amino acid solution does not need to be classified for acute oral toxicity according to GHS and CLP criteria.