ε-caprolactam

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:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1987

Report date:

1987

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

Cited as Directive 84/449/EEC, B.1

GLP compliance:

yes

Remarks:

Bayer AG, Institute of Toxicology

Test type:

standard acute method

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

Specific details on test material used for the study:

- Name of test material (as cited in study report): epsilon-Caprolactam
- Physical state: solid
- Analytical purity: 99.9%

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Winkelmann, Borchen
- Age at study initiation: male 9 weeks, female 14 weeks
- Mean weight at study initiation: male 182 g, female 170 g
- Fasting period before study: 16 h before dosing
- Housing: 5 per cage
- Diet (e.g. ad libitum): Altromin 1324 pellets
- Water (e.g. ad libitum): tap water
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±2
- Humidity (%): 50±10
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Amount of vehicle (if gavage): 10 ml/kg bw

Doses:

male: 0, 312, 1000, 1250, 1600, 2000, 2250 mg/kg bw
female: 0, 312, 1000, 1250, 1600, 2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: several times on the day of application and daily thereafter. Body weights were recorded before application, 7 d post application and at the end of the observation period.
- Necropsy of survivors performed: yes

Statistics:

Rosiello et al., J. Tox. Environ. Health 3, 797, 1977.

Results and discussion

Effect levels

Effect levels 1

Sex:

female

Dose descriptor:

LD50

Effect level:

1 475 mg/kg bw

95% CL:

1 216 - 1 789

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

1 876 mg/kg bw

95% CL:

1 359 - 2 590

Mortality:

Mortality was observed (see table 1 and 2).

Clinical signs:

other: 1250 - 2250 mg/kg bw: clonic convulsion, piloerection, salivation, dyspnoea, tremor, high stepping gait, nose discharge, hollow flanks. The signs were observed till 7 days of the observation period. In the females of 1000 mg/kg bw dose group, slight gasp

Gross pathology:

Deceased animals: redness in the lungs and gastro-intestinal tract, enlarged liver
Sacrificed animals: no abnormalities were detected

Any other information on results incl. tables

Table 1: Mortality rate in males

Dose (mg/kg bw)	Mortality rate	Died within
312	0/5	-
1000	0/5	-
1250	0/5	-
1600	3/5	6 h
2000	2/5	4 h
2250	4/5	5 h

Table 2: Mortality rates in females

Dose (mg/kg bw)	Mortality rate	Died within
312	0/5	-
1000	1/5	3 h
1250	0/5	-
1600	4/5	6 h
2000	4/5	4 h

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The LD50 for male and female rats was reported to be 1876 and 1475 mg/kg bw, respectively.

Executive summary:

This study was performed according to guideline and GLP. The LD50 for male and female rats was reported to be 1876 and 1475 mg/kg bw, respectively. Significant mortality was observed from the dose level of 1600 mg/kg bw within 6 h after exposure. Clinical signs were clonic convulsion, piloerection, salivation, dyspnoea, tremor, high stepping gait, nose discharge, hollow flanks. The signs were persistent until the end of the 7 days observation period. At necropsy, redness in the lungs and gastro-intestinal tract, and enlarged liver were described.