6,6'-(Ethane-1,2-diylbis(azanediyl))bis(dibenzo[c,e][1,2]oxaphosphinine-6-oxide)“

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2017-08-14 - 2017-10-10

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 guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

6,6'-(Ethane-1,2-diylbis(azanediyl))bis(dibenzo[c,e][1,2]oxaphosphinine-6-oxide)“

EC Number:

815-096-7

Cas Number:

1421927-53-8

Molecular formula:

C26H22N2O4P

IUPAC Name:

6,6'-(Ethane-1,2-diylbis(azanediyl))bis(dibenzo[c,e][1,2]oxaphosphinine-6-oxide)“

Test material form:

solid: particulate/powder

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Source: Dobrá Voda, Slovak Republic
Number and Sex of Animals: 6 females
Age at First Dose: 8-12 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, up to 3 animals per cage in a room equipped with central airconditioning. The average room temperature was maintained within the range of 23.2 ± 0.3° C, relative humidity within 55.3 ± 2.5 %. The
light regimen was set to a 12-hour light /12-hour dark cycle. Sanitation was performed according to the standard operation procedures.
Diet: The laboratory food ssniff (Spezialdiäten GmbH, Germany) was offered at recommended doses each day approximately at the same
time. The certificate of analysis is included in the raw data.
Water: The animals received tap water for human consumption. Drinking water was supplied ad libitum. The quality of drinking water is
periodical analysed and recorded; certificate of analysis is included in the raw data.
Bedding: Lignocel S3/4, Lufa - ITL GmbH, Germany
Animals Identification: The animals in the cage were marked by a line (I-III) on the tail with a waterproof marker. Each cage was marked with the study code, ID of animals and date of administration of the test item.
Justification for the Choice of Species: Normally females are used for testing OECD TG 423 because females are typically the more sensitive gender.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

The test item was administered in a single dose by gavage using a metal stomach tube. Animals were fasted prior to dosing (food but not water were withheld over-night). Following a period of fasting, animals were weighed and the test item administered. After test article administration, food was
withheld for further 3-4 hours.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6

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 prior to dosing (food but not water were withheld over-night). Following a period of fasting, animals were weighed and the test item administered. After test article 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 test item was administration 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.

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 was observed during the study.

Clinical signs:

other: During the follow up period, no animals displayed signs of intoxication, change of health, nor any other adverse reactions.

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 EDA-DOPO is greater than 2000 mg/kg body weight after single oral administration to Wistar rats.

Executive summary:

The purpose of the study was to evaluate the potential toxic effect of the test item EDA-DOPO when administered as a single oral dose to Wistar rats.

The procedure according to OECD Guideline 423 Acute Toxic Class (ATC) method was used. Available information indicated that the test item is likely to be non-toxic; therefore, a limit dose of 2000 mg/kg body weight was used as a starting dose. One group of 3 females was dosed. Test itemrelated mortality was not observed during 24 hours and therefore in a next steps 3 females were treated with the same dose. All 6 females survived the limit dose. No signs of toxicity were observed at the dosage of 2000 mg/kg during the first 4 hours in females or the 14-days observation period thereafter.

The body weights of all animals increased during the study. During necropsy, no macroscopic findings were observed.

The LD50 of the test item EDA-DOPO is greater than 2000 mg/kg body weight after single oral administration to Wistar rats.