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

Endpoint summary

Description of key information

Acute oral toxicity in Rats

Acute dermal toxicity in Rats

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

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

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

2002

Deviations:

no

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

Specific details on test material used for the study:

COA attached

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.

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.

Preliminary study:

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

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

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Klimisch score 1: guidelines study and according to GLP

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

December 26, 2017 - January 10, 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Version / remarks:

1998

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: JMAFF 12-Nousan-8147

Version / remarks:

2000

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Housing: The animals were singly housed in suspended stainless steel caging, which
conforms to the size recommendations in the most recent Guide for the Care and Use
of Laboratory Animals (Natl. Res. Council, 2011). 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: 20-23°C and 31-56%,
respectively.
Animal Room Air ChangeslHour: 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: 19 or 20 days
Food: Envigo Teklad Global 16% Protein Rodent Diet® #2016. The diet was
available ad libitum.
Water: Filtered tap water was supplied ad libitum.

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

Two thousand milligrams of the test substance per kilogram of body weight was applied evenly
over a dose area of approximately 2 inches x 3 inches (approximately 10% of the body surface)
and covered with a 2-inch x 3-inch, 4-ply gauze pad. The gauze pad and entire trunk of each
animal were then wrapped with 3-inch Durapore tape to avoid dislocation of the pad and to
minimize loss of the test substance. The rats were then returned to their designated cages. The day
of application was considered Day 0 ofthe study.
After 24 hours of exposure to the test substance, the pads were removed and the test sites were
gently cleansed with a 3% soap solution followed by tap water and a clean paper towel to remove
any residual test substance.

Duration of exposure:

24 hours

Doses:

2000 mg /kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

Two thousand milligrams of the test substance per kilogram of body weight was applied to the
skin of ten healthy rats for 24 hours. The animals were observed for mortality, signs of gross
toxicity, and behavioral changes at least once daily for 14 days. Body weights were recorded
prior to application (initial) and again on Days 7 and 14 (terminal). Necropsies were performed
on all animals at terminal sacrifice.

Statistics:

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

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

no indication of skin irritation up to the relevant limit dose level

Mortality:

No

Clinical signs:

other: All animals survived test substance administration and gained body weight during the study. Apart from one animal exhibiting erythema on Day I, there were no other adverse clinical findings recorded for any animals over the course of the study. No gross a

Gross pathology:

No gross abnormalities were
noted for any of the animals when necropsied at the conclusion of the l4-day observation period See attached table 3

Other findings:

None

Interpretation of results:

other: Not subject to classification under GHS

Conclusions:

Under the conditions of this study, the single dose acute dermal LD50 ofE17-194T is greater than
2000 mg/kg of body weight in male and female rats.

Executive summary:

SUMMARY

An acute dermal toxicity test was conducted with rats to determine the potential for

E17-194T to produce toxicity from a single topical application. Under the conditions of this

study, the single dose acute dermal LDso of the test substance is greater than 2000 mg/kg of body

weight in male and female rats.

Two thousand milligrams of the test substance per kilogram of body weight was applied to the

skin of ten healthy rats for 24 hours. The animals were observed for mortality, signs of gross

toxicity, and behavioral changes at least once daily for 14 days. Body weights were recorded

prior to application (initial) and again on Days 7 and 14 (terminal). Necropsies were performed

on all animals at terminal sacrifice.

All animals survived test substance administration and gained body weight during the study.

Apart from one animal exhibiting erythema on Day I, there were no other adverse clinical

findings recorded for any animals over the course of the study. No gross abnormalities were

noted for any of the animals when necropsied at the conclusion of the l4-day observation period.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Klimisch score 1: guidelines study and according to GLP

Justification for classification or non-classification

Not subject to GHS classification