Reaction mass of 2-(3-{6-[3-(2-Hydroxyethyl)-3-methylureido]hexyl}-1-methylureido)ethanol and 6-[3-(2-Hydroxyethyl)-3-methylureido]hexylamino 3-(methylamino)propionate

Repeated dose toxicity: oral

Administrative data

Endpoint:

repeated dose toxicity: oral, other

Remarks:

range-finding study for the OECD TG 421 study

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

Jan.-Feb. 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Test guideline

Qualifier:

no guideline required

Principles of method if other than guideline:

- Principle of test: daily oral (gavage) administration to the rat for 7 days and to provide the basis for selection of dose levels for a subsequent OECD TG 421
- Parameters analysed / observed: Assessment of toxicity was based on clinical signs, body weight, food consumption and anatomic pathology evaluations. Full necropsies were performed on all animals with a recording of macroscopic observations and organ weights (kidney, liver, testis and epididymis).

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

N,N''-hexane-1,6-diylbis[N'-(2-hydroxyethyl)-N'-methylurea]

EC Number:

253-281-9

EC Name:

N,N''-hexane-1,6-diylbis[N'-(2-hydroxyethyl)-N'-methylurea]

Cas Number:

36938-15-5

Molecular formula:

C14H30N4O4

IUPAC Name:

2-(3-{6-[3-(2-Hydroxyethyl)-3-methylureido]hexyl}-1-methylureido)ethanol

Constituent 2

Reference substance name:

6-[3-(2-Hydroxyethyl)-3-methylureido]hexylamino 3-(methylamino)propionate

Molecular formula:

C14H30N4O4

IUPAC Name:

6-[3-(2-Hydroxyethyl)-3-methylureido]hexylamino 3-(methylamino)propionate

Test material form:

solid: bulk

Details on test material:

- Batch no.: EGGE 2806-1
- Currenta sample no.: 2187

Specific details on test material used for the study:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Solubility and stability of the test substance in the solvent/vehicle: Suspensions of 0.5 and 200 mg/mL were found to be stable and homogenous for seven days at room temperature

Test animals

Species:

rat

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: Kolliphor HS15/ethanol/water (40/10/50) (v/v/v)

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

7 days

Frequency of treatment:

once daily

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0 mg/kg bw/day (nominal)

Doses / concentrations 2

Dose / conc.:

100 mg/kg bw/day (nominal)

Doses / concentrations 3

Dose / conc.:

300 mg/kg bw/day (nominal)

Doses / concentrations 4

Dose / conc.:

1 000 mg/kg bw/day (nominal)

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

Examinations

Observations and examinations performed and frequency:

Assessment of toxicity was based on clinical signs, body weight, food consumption and anatomic pathology evaluations.

Sacrifice and pathology:

Full necropsies were performed on all animals with a recording of macroscopic observations and organ weights (kidney, liver, testis and epididymis).

Results and discussion

Effect levels

Dose descriptor:

NOEL

Effect level:

1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Any other information on results incl. tables

Daily administration of EGGE 2806-1 to rats at levels of 0, 100, 300 and 1000 mg/kg/day for 7 days resulted in no toxicological findings.

Applicant's summary and conclusion

Executive summary:

Groups of 5 rats per sex of the Crl:WI(Han) strain were dosed with 0, 100, 300, 1000 mg/kg bw and day for 7 consecutive days. Assessment of toxicity was based on clinical signs, body weight, food consumption and anatomic pathology evaluations. Full necropsies were performed on all animals with a recording of macroscopic observations and organ weights. Daily administration of EGGE 2806-1 to rats at levels of 0, 100, 300 and 1000 mg/kg/day for 7 days resulted in no toxicological findings. Based on this the No Observed Effect Level (NOEL) is considered to be 1000 mg/kg/day.