Hexahydro-2H-azepin-2-one, sodium salt

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1985

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Principles of method if other than guideline:

Groups of 10 Wistar rats/sex were exposed to a liquid aerosol of the test substance (50%, w/w) using a head-nose inhalation system.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

ε-caprolactam

EC Number:

203-313-2

EC Name:

ε-caprolactam

Cas Number:

105-60-2

Molecular formula:

C6H11NO

IUPAC Name:

azepan-2-one

Details on test material:

- Name of test material (as cited in study report): Caprolactam

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
- Age at study initiation: 8 weeks
- Mean weight at study initiation: male 250 g (224-268 g) female 178 g (161-192 g)
- Diet (e.g. ad libitum): Kliba labor diet
- Water (e.g. ad libitum): tap water

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

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose/head only

Vehicle:

other:

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Nose/head - inhalation system INA 20, BASF AG
- Exposure chamber volume: 55 l
- Method of holding animals in test chamber: animals were kept in the tube with muzzle projecting in the inhalation chamber
- System of generating particulates/aerosols: Generatorsystem- infusion pump INFU 362, membrane dose pump Duramat. The aerosol was generated using compressed air.
- Temperature in air chamber: 19-25 °C

TEST ATMOSPHERE
- Brief description of analytical method used: Quantitative determination of aerosol concentration was performed using gas chromatography. For this the aerosol probes were dissolved in 10ml Ethanol.
- Samples taken from breathing zone: yes
- Nominal concentrations were calculated using the substance consumption and the air volume.
- probes for particle size analysis were taken from 30 min after onset of exposure

VEHICLE
- Concentration of test material in vehicle: 50% (w/v) in water

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

5.25, 8.35 and 10.12 mg/l

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Body weight of individual animals was measured before treatment and after 7 and 14 days of treatment, daily clinical inspection
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology (anatomical/pathological)

Statistics:

According to the probit analysis of D.J. Finney, 1-150 (Syndics of the Cambridge University Press, 1971).

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LC50

Effect level:

8.16 mg/L air

95% CL:

7.2 - 9.23

Exp. duration:

4 h

Effect levels 2

Sex:

male

Dose descriptor:

LC50

Effect level:

ca. 9.6 mg/L air (analytical)

Exp. duration:

4 h

Effect levels 3

Sex:

female

Dose descriptor:

LC50

Effect level:

7.08 mg/L air (analytical)

95% CL:

5.87 - 8.1

Exp. duration:

4 h

Mortality:

see free text

Clinical signs:

other: Symptoms during exposure: closure of eyelid, irregular respiration, escape reaction Symptoms after exposure: dyspnoea, piloerection, intermittent respiration, bloody nose and eye discharge, tremor. Clinical signs were reversible after 5 days (low dose), 7

Body weight:

No effects on body weight gain were observed

Gross pathology:

Severe hyperemia in lungs and liver adiposis in some perished animals. No abnormalities in the sacrificed animals

Other findings:

- Histopathology: fatty degeneration in the liver and ischemic tubulonephrosis in the cortex of the kidney of 1 deceased animal. No lesions were observed in the sacrificed animals.

Any other information on results incl. tables

Dose (mg/l)	Sex	Mortality within
		4 h	1 day	14 days
5.25	M	0/10	1/10	1/10
	F	0/10	1/10	1/10
8.25	M	0/10	1/10	1/10
	F	0/10	7/10	7/10
10.12	M	2/10	7/10	7/10
	F	1/10	10/10	10/10

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The substance is considered to be classified as "may be harmful if inhaled" according to CLP (Cat.4) and EU (R20) standards.