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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Study Initiation: 17 April 2019 Experiment Start: 24 April 2019 Experiment Termination: 10 May 2019
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Acute Oral Toxicity (OECD 423/EU B.1 tris)

Data source

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

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
Acute Oral Toxicity (OECD 423/EU B.1 tris)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Sodium phenylphosphinate
EC Number:
224-305-5
EC Name:
Sodium phenylphosphinate
Cas Number:
4297-95-4
Molecular formula:
C6H7O2P.Na
IUPAC Name:
sodium phenylphosphinate
Test material form:
solid: particulate/powder

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
Species: Wistar rats
Source: Slovak Academy of Sciences Dobrá Voda, Slovak Republic
Number and Sex of Animals: 6 females
Age at First Dose: 8-9 weeks; female animals were non-pregnant and nulliparous
Animal Health: Health condition of animals was examined by a veterinarian before initiation of the study.
Acclimation: The animals were acclimated under the conditions identical to the conditions during the experiment 5 days prior to the start of treatment. The acclimation was according to the standard operation procedure.

Housing Condition: The animals were housed in plastic cages suspended on stainless steel racks, 3 animals per cage in a room equipped with central air-conditioning. The average room temperature was maintained within the range of 22.30 ± 0.12 °C, relative humidity within 55.03 ± 1.37 %. The light regimen was set to a 12-hour light /12-hour dark cycle. Sanitation was performed according to the standard operation procedures.

Administration / exposure

Route of administration:
oral: drinking water
Vehicle:
water
Remarks:
Water for injection is a common vehicle in toxicity studies like OECD TG 423
Details on oral exposure:
The animals received tap water for human consumption. Supply of drinking was unlimited. The quality of drinking water is periodically analysed and recorded; certificate of analysis is included in the raw data.
Doses:
Number of Animals and Dose Levels
The starting dose could be selected from the fixed dose levels of 5, 50, 300, and 2000 mg/kg body weight. A limit dose of 2000 mg/kg body weight was used as a starting dose.
7.6 Dose Preparation
The required amount of the test item (according to the body weight and dose) was dissolved in vehicle (Water for injection) shortly before administration. The administration volume was 5 mL/kg body weight.
No. of animals per sex per dose:
One group of 3 females was dosed. Test item-related mortality was not observed during 24 hours and therefore, in a second step, another 3 females were treated at the same dose
Control animals:
no
Details on study design:
Dose Administration
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.
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
Dose descriptor:
LD50
Effect level:
> 200 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. In all 6/6 animals, lethargy was observed immediately after administration of the test item and in animal No 5, sleepiness was noted 30 minutes after administration.
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:
Category 5 based on GHS criteria
Remarks:
According to CLP Reglation - Unclassified with a LD50 cut off value equal to or greater than 5000 mg/kg body weight, after single oral administration to Wistar rats.
Conclusions:
The test item “Sodium phenylphosphinate” administered to 6 females at a limit dose of 2000 mg/kg body weight did not cause death. Lethargy and sleepiness were observed during observation period. The body weights of all animals increased during the study. No body weight losses were observed between the first and second week after administration. During necropsy, no macroscopic findings were observed.
The LD50 of the test item “Sodium phenylphosphinate” 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 “Sodium phenylphosphinate” 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.
In accordance with CLP Regulation criteria (LD50 > 2000 mg/kg bw) test item is not classified.
The LD50 of the test item “Sodium phenylphosphinate” 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 “Sodium phenylphosphinate” 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.
In accordance with CLP Regulation criteria (LD50 > 2000 mg/kg bw) test item is not classified.

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