E17-194T, (P,P-diethyl, monoester with 1,2 propanediol)_

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

December 12, 2017 -January 17,2018

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 guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

2002

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)

Version / remarks:

2008

Deviations:

no

GLP compliance:

yes

Test type:

up-and-down procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of 1-hydroxypropan-2-yl diethylphosphinate and 2-hydroxypropyl diethylphosphinate

Cas Number:

2230512-72-6

Molecular formula:

C7H17O3P

IUPAC Name:

Reaction mass of 1-hydroxypropan-2-yl diethylphosphinate and 2-hydroxypropyl diethylphosphinate

Test material form:

liquid

Details on test material:

R&D level

Specific details on test material used for the study:

COA attached

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

Number of Animals: 5
Sex: Female, nulliparous and non-pregnant.
Species/Strain: Rat/Sprague-Dawley derived, albino.
Age/Body Weight: Young adult (8-11 weeks)/1 45-187 grams at experimental start.
Source: Received from SAGE® Labs on December 7 and 20,2017.

Husbandry
Housing: The animals were singly housed in suspended stainless steel caging, which
confonns to the size recommendations in the most recent Guide for the Care and Use
of Laboratory Animals (Natl. Res. Council, 20 II). Enrichment (e.g., toy) was placed
in each cage. Litter paper was placed beneath the cage and was changed at least
three times per week.
Animal Room Temperature and Relative Humidity Ranges: 19-23°C and 36-60%,
respectively.
Animal Room Air Changes/Hour: 12. Airflow measurements are evaluated regularly
and the records are kept on file at Product Safety Labs.
Photoperiod: 12-hour light/dark cycle
Acclimation Period: 5-19 days
Food: Envigo Teklad Global 16% Protein Rodent Diet® #2016. The diet was
available ad libitum, except during fasting.
Water: Filtered tap water was supplied ad libitum.
Contaminants: There were no known contaminants reasonably expected to be found
in the food or water at levels which would have interfered with the results of this
study. Analyses of the food and water are conducted regularly and the records are
kept on file at Product Safety Labs.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

The test substance was administered to the stomach using a stainless steel ball-tipped gavage
needle attached to an appropriate syringe. Following administration, each animal was returned to
its designated cage. Feed was replaced approximately 3-4 hours after dosing.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 females received the limit dose 2000 mg/kg bw

Control animals:

no

Details on study design:

Selection of Animals:
Prior to each dosing, experimentally naive rats were fasted overnight by removing the feed from
their cages. During the fasting period, the rats were examined for health and weighed (initial).
Five healthy, naive female rats (not previously tested) were selected for test.
Preparation of Test Substance:
The test substance was administered as received and mixed well prior to use.
Dose Calculations:
Individual doses were calculated based on the initial body weights, taking into account the
density (detennined by PSL) of the test substance.
Dosing:
The test substance was administered to the stomach using a stainless steel ball-tipped gavage
needle attached to an appropriate syringe. Following administration, each animal was returned to
its designated cage. Feed was replaced approximately 3-4 hours after dosing.
Cage-Side Observations
The animals were observed for mortality, signs of gross toxicity, and behavioral changes
approximately 30 minutes post-dosing, during the first several hours post-dosing and at least once
daily thereafter for 14 days after dosing. Observations included gross evaluation of skin and fur,
eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems,
somatomotor activity and behavior pattern. Particular attention was directed to observation of
tremors, convulsions, salivation, diarrhea, and coma.
Body Weights
Individual body weights of the animals were recorded prior to test substance administration
(initial) and again on Days 7 and 14 (terminal) following dosing.
Necropsy
All rats were euthanized via CO, inhalation at the end of the 14-day observation period. Gross
necropsies were performed on all animals. Tissues and organs of the thoracic and abdominal
cavities were examined.

Statistics:

Statistical analysis was limited to the calculation of the mean density value for dosing.

Results and discussion

Preliminary study:

An initial limit dose of 2000 mg/kg bw was administered to one healthy female rat by oral gavage

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no effects observed

Mortality:

none

Clinical signs:

other: none

Gross pathology:

No gross abnormalities. see attached table.

Other findings:

none

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study, the acute oral LD50 of E17 -194T is greater than 2000 mg/kg/ body weight in female rats.
E17-194T is not subject to GHS classification

Executive summary:

An acute oral toxicity test was conducted with rats to determine the potential for E17-194T to

produce toxicity from a single dose via the oral route. Under the conditions of this study, the

acute oral LDso of the test substance is greater than 2000 mg/kg of body weight in female rats.

An initial limit dose of 2000 mg/kg was administered to one healthy female rat by oral gavage.

Due to the absence of mortality in this animal, four additional females received the same dose

level, sequentially. Since these animals survived, no additional animals were tested. Females

were selected for the test because they are frequently more sensitive to the toxicity of test

compounds than males. All animals were observed for mortality, signs of gross toxicity, and

behavioral changes at least once daily for 14 days after dosing. Body weights were recorded

prior to administration (initial) and again on Days 7 and 14 (terminal) following dosing.

Necropsies were performed on all animals at terminal sacrifice.

All animals survived test substance administration, gained body weight, and appeared active and

healthy during the study. There were no signs of gross toxicity, adverse clinical effects, or

abnormal behavior. No gross abnormalities were noted for any of the animals when necropsied at

the conclusion of the 14-day observation period.