Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2019

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
Source: Slovak Academy of Sciences Dobrá Voda, Slovak Republic
Number of animals: 6 female
Age: 8-9 weeks; female animals were non-pregnant and nulliparous
Acclimation period: 5 days
Temperature: 22.31 ± 0.15 °C
Humidity: 53.60 ± 2.89 %
Light regimen: 12-hour light /12-hour dark cycle

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
olive oil
Details on oral exposure:
The required amount of the test item (according to the body weight and dose) was mixed with vehicle (Olive oil) shortly before administration. The dose of 2000 mg/kg was administered in a volume of 5 mL/kg body weight.
The test item was administered in a single dose by gavage using a metal stomach tube. Animals were fasted 10-12 h prior to dosing (food but not water was withheld over-night). Following a period of fasting, animals were weighed and the test item administered. After test item administration, food was withheld for further 3-4 hours.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
6 females per dose
Control animals:
not specified
Details on study design:
Clinical Observation:
Animals were observed individually immediately after administration of the test item and 0.5, 1, 2, and 4 hours later. Each animal was inspected daily for the next 14 days.
Observations included: changes in skin, fur, eyes, mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity, and behavioural pattern. Particular attention was given to potential neurologic endpoints such as tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.


Body Weight:
Individual weights of animals were measured immediately prior to administration of the test item and weekly thereafter. Weight differences after first and second weeks after administration were calculated and recorded.

Necropsy:
All test animals were subjected to gross necropsy and the results were recorded for each animal. Examinations included: external body surface and orifices, the appearance of tissues and organs in the thoracic cavity (trachea, esophagus, heart, aorta, lungs with main stem bronchi, thymus, tracheobronchial lymph node) and in the abdominal cavity (liver, spleen, adrenal glands, kidneys, ovaries, uterus including cervix, urinary bladder, small intestine, large intestine, pancreas, stomach, mesenteric lymph nodes).

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
All (6/6 females) animals survived the limit dose of 2000 mg/kg body weight.
Clinical signs:
No mortality was observed during the study. During the follow up period, no animals displayed signs of intoxication, change of health, nor any other adverse reaction.
Body weight:
The body weights of all animals increased during the study. No body weight losses were observed between the first and second week after administration.
Gross pathology:
All animals were necropsied. During necropsy, no macroscopic findings were observed.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 of the test item “L-Tyrosine, N-acetyl-3,5-dinitro-” is greater than 2000 mg/kg body weight after single oral administration to Wistar rats.
Based on Annex 2d Test Procedure with a Starting Dose of 2000 mg/kg body weight of OECD Guideline 423 it can be concluded that the test item “L-Tyrosine, N-acetyl-3,5-dinitro-” is according to GHS criteria classified in Category 5 or Unclassified with a LD50 cut off value equal to or greater than 5000 mg/kg body weight, after single oral administration to Wistar rats.
Executive summary:

The test item “L-Tyrosine, N-acetyl-3,5-dinitro-”administered to 6 females at a limit dose of 2000 mg/kg body weight did not cause death. Nosigns of toxicity were observed during the first 4 hours in females or the 14-day observation period thereafter. The body weights of all animals increased during the study. No body weight losses were observed between the first and second week after administration of the test item.During necropsy, no macroscopic findings were observed.