Reaction mass of 1,8-diazabicyclo[5.4.0]undec-7-ene and 2H-Azepin-2-one, 1-(3-aminopropyl)hexahydro-

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

GLP compliance:

yes

Test type:

acute toxic class method

Test material

Test material information

Constituent 1

Reference substance name:

2H-Azepin-2-one, 1-(3-aminopropyl)hexahydro-

EC Number:

607-402-0

Cas Number:

24566-95-8

Molecular formula:

C9H18N2O

IUPAC Name:

2H-Azepin-2-one, 1-(3-aminopropyl)hexahydro-

Details on test material:

- Name of test material (as cited in study report): Aminopropylcaprolactam
- Physical state: liquid, yellow
- Homogeneity: homogeneous by visual inspection
- Analytical purity: 54.8% (main component, GC)
- Impurities (identity and concentrations): ca. 10% 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU; CAS 6674-22-2), ca. 6% epsilon-caprolactam (CAS 105-60-2), ca. 12% 3,3'-oxybis-1-propanamine (CAS 2157-24-6), ca. 3.5% 3-aminopropan-1-ol (CAS 156-87-6), water
- Lot/batch No.: K 99/2
- Date of manufacturing: June 13, 1996
- Stability under test conditions: The stability of the TS in aqua bidest. for a time period of 4 hours was confirmed by analysis. The stability of the TS over the study period has been proven by reanalysis.
- Storage condition of test material: refrigerator

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Dr. K. Thomae GmbH, Biberach, Germany
- Age at study initiation: young adults
- Weight at study initiation: animals of comparable weight (150 - 300 g; ± 20% of the mean weight)
- Fasting period before study: at least 16 hours befor administration
- Housing: single housing in stainless steel wire mesh cages , Type DK-III (Becker & Co., Castrop-Rauxel, Germany)
- Diet: ad libitum, Kliba-Labordiät 343 (Klingentalmühle AG, Kaiseraugst, Switzerland)
- Water: ad libitum, tap water
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 500 mg/kg bw dose group: 5 g/100 ml; 2000 mg/kg bw dose group: 20 g/100 ml
- Justification for choice of vehicle: aqueous formulation corresponds to the physiological medium

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg bw

CLASS METHOD
- Rationale for the selection of the starting dose: Based on the physical and chemical characteristics of the test substance and the composition a starting dose of 500 mg/kg bw has been chosen

Doses:

500 and 2000 mg/kg bw

No. of animals per sex per dose:

500 mg/kg bw dose group: 3 males, 3 females
2000 mg/kg bw dose group: 3 males

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: A check for any dead or moribund animal was made twice each workday and once on Saturdays, Sundays and on public holidays; recording of signs and symptoms several times on the day of administration, at least once each workday for the individual animals; individual body weights were determined shortly before application (day 0), weekly thereafter and at the end of the study
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 500 - <= 2 000 mg/kg bw

Based on:

test mat.

Mortality:

2 animals of the 2000 mg/kg bw group died within 4 hours after application. No mortality occured in the 500 mg/kg bw dose group.

Clinical signs:

other: 2000 mg/kg bw group: impaired or poor general state, dyspnoea, apathy, abdominal position, staggering, twitching, spastic gait, cyanosis and red clammy snout. The surviving animals appeared normal 5 days after application. 500 mg/kg bw dose group: the ani

Gross pathology:

Necropsy findings of the animals that died were agonal congestive hyperemia and red discoloration of the small intestine, large intestine and glandular stomach. No abnormalities were noted at necropsy of animals sacrificed at the end of the study.

Any other information on results incl. tables

Mortality:

Dose (mg/kg)	500	2000
Males: Number of animals	3	3
Dead animals after:
3 h	0	1
4 h	0	2
14 d	0	2
Females: Number of animals	3	n.d.
Dead animals after:
14 d	0

n.d.: not determined

 

Clinical signs and symptoms:

Dose (mg/kg)	500	2000
Males: Number of animals	3	3
Impaired general state		D1-D2, 1animal
Poor general state		H0-H4, 3 animals
Dyspnoea		H0-D2, 3 animals
Apathy		H0-H4, 3 animals
Abdominal position		H4, 1 animal
Staggering		H0-D2, 2 animals
Twitching		H4, 1 animal
Spastic gait		D2, 1 animal
Cyanosis		H4, 1 animal
Piloerection		H0-D2, 3 animals
Smeared fur		D2, 1 animal
Red clammy snout		D1-D2, 1 animal
Females: Number of animals	3	n.d.
	No abnormality

D: day; H: hour; n.d.: not determined

 

Mean body weight (g):

Dose (mg/kg)		500	2000
Males: Beginning of test		182	192
After	7 d	256	236
	13 d	291	285
Females: Beginning of test		174
After	7 d	202
	13 d	217

d: days

Applicant's summary and conclusion

Interpretation of results:

moderately toxic

Remarks:

Migrated information

Conclusions:

The LD50 after oral application was found to be > 500 ≤ 2000 mg/kg bw.