L-Glutamic acid, N-[4-(4-oxobutyl)benzoyl]-, 1,5-diethyl ester

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

10 December 2009 to 12 January 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP, guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

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

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

1,5-diethyl (2S)-2-{[4-(4-oxobutyl)phenyl]formamido}pentanedioate

EC Number:

700-603-5

Cas Number:

908145-87-9

Molecular formula:

C20 H27 N O6

IUPAC Name:

1,5-diethyl (2S)-2-{[4-(4-oxobutyl)phenyl]formamido}pentanedioate

Details on test material:

Pure active sample of Compound 2945989 was used to perform the testing.
Lot Number: Z84-H70580-095
Potency: Assume 100%

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

The animals were housed in suspended wire cages, 5/sex/cage prior to dosing and 3/sex/cage following dosing.
Paper bedding was placed beneath the cages and changed at least three times/week.
Fresh PMI Rat Chow (Diet #5012) was freely available except for 16-20 hours prior to dosing.
Water was available ad libitum.
The animal room, reserved exclusively for rats on acute tests, was temperature controlled, had a 12-hour light/dark cycle, and was kept clean and vermin free.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

The test article was administered oraly by syringe and a dosing needle on an mg/kg basis.

Doses:

The dose was based on the dry weight of the test article.
A single dose was administered orally by syringe and dosing needle at a dose level of 300 mg/kg or 2000 mg/kg.

No. of animals per sex per dose:

Initially, three healthy male and three healthy female rats were dosed orally with Compound 2945989, at 300 mg/kg. Since there was no toxicity
noted at this level, an additional three healthy male and three healthy female rats were dosed orally at 2000 mg/kg.

Control animals:

no

Details on study design:

Type and frequency of observations made after dosing:
In Vivo - Animals were observed ½, 1, 2, 3 and 4 hours postdose and once daily for 14 days for mortality, toxicity and pharmacological effects. Body weights were recorded immediately pretest, weekly and at termination.
Post Mortem – All animals were humanely sacrificed using CO2 and were examined for gross pathology following study termination.

The test article was assigned to a toxic category based on the mortality response noted.

Statistics:

An estimate of the LD50 was made based on mortality that occurred during the study.

Results and discussion

Preliminary study:

not a fixed dose study

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

discriminating dose

Effect level:

ca. 300 mg/kg bw

Based on:

test mat.

Remarks on result:

other: All six animals survived

Effect levels 2

Sex:

male/female

Dose descriptor:

discriminating dose

Effect level:

ca. 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: All six animals survived

Mortality:

300mg/kg - no mortality observed
2000mg/kg - no mortality observed

Clinical signs:

other: 300mg/kg: No physical signs were observed. Body weight changes were normal in 5/6 animals. One animal lost weight. 2000mg/kg: No physical signs were observed. Body weight changes were normal for both sexes. Necropsy results were normal

Gross pathology:

300mg/kg - Necropsy results were normal in 5/6 animals. One animal was noted with a larger than normal thymus.
2000mg/kg - Necropsy results were normal

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Compound 2945989, Lot# Z84 -H70580 is considered to be in GHS Acute Toxic Category 5 or unclassified under the EU CLP Regulations.

Executive summary:

Initially, three healthy male and three healthy female Sprague Dawley rats were dosed orally with Compound 2945989, Lot# Z84-H70580-095 at 300 mg/kg. Since there was no toxicity noted at this level, an additional three healthy male and three healthy female Sprague Dawley rats were dosed orally at 2000 mg/kg. The rats were observed ½, 1, 2, 3 and 4 hours postdose and once daily for 14 days for mortality, toxicity and pharmacological effects. Body weights were recorded immediately pretest, weekly and at termination. All animals were examined for gross pathology. The test article was assigned to a toxic category based on the mortality response noted.

Summary:

300 mg/kg: All six animals survived the single 300 mg/kg oral dose. No physical signs were observed. Body weight changes were normal in 5/6 animals. One animal lost weight. Necropsy results were normal in 5/6 animals. One animal was noted with a larger than normal thymus.

2000 mg/kg: All six animals survived the single 2000 mg/kg oral dose. No physical signs were observed. Body weight changes were normal for both sexes. Necropsy results were normal.

Conclusion: The LD50 is greater than 2000 mg/kg. Compound 2945989, Lot# Z84-H70580-095 is considered to be in Acute Toxic Category 5 or unclassified under EU CLP Regulations.