1-methylpiperidine

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions (non-GLP)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1979

Report date:

1979

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

1 hour exposure duration

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

1-methylpiperidine

EC Number:

210-959-9

EC Name:

1-methylpiperidine

Cas Number:

626-67-5

Molecular formula:

C6H13N

IUPAC Name:

1-methylpiperidine

Details on test material:

- Name of test material (as cited in study report): 1-Methylpiperidin
- Physical state: liquid, yellow
- Analytical purity: ≥ 98 %

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- animals: Wistar rat TNO 74
- Source: Winkelmann, Borchen, Germany
- Weight at study initiation: control: males: day 0: 214.9 ± 10.83 g, females: day 0: 182.3 ± 3.34 g, 13.8 mg/L: males: day 0: 215.7 ± 13.42 g, females: day 0: 177.1 ± 7.84 g, 15.4 mg/L: males: day 0: 217.1 ± 6.26 g, females: day 0: 183.5 ± 5.99 g.
- no further data

ENVIRONMENTAL CONDITIONS
- no data

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose/head only

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Using an infusion pump the aerosol was pressed into a diffuser nozzle, in which filtered compressed air is supplied additionally. The pressure at the diffuser nozzle is measured by a manometer. The mist from the diffuser nozzle enters the inhalation chamber.
- Exposure chamber volume: 36 L
- Method of holding animals in test chamber: glass tubes
- Source and rate of air: 10 L/min
- Method of conditioning air: The test substance was nebulised with dry compressed air. Thereby the test substance was mixed with water and the mixture was supplied to the nozzle.
- Method of particle size determination: Particle size distribution was determined with the concentration of 15.4 mg/L and as stray light diameter. For the concentration of 13.8 mg/L the same particle size distribution was assumed.
- Treatment of exhaust air: The condensate of the walls of the inhalation chamber is collected in a storage vessel. The aerosol is exhausted by an injection pump (8.6 L/min). 0.4 L/min are exhausted through a wash bottle to determine the concentration.
- Temperature, humidity, pressure in air chamber: 20 °C, 60 - 70 %

TEST ATMOSPHERE
- Brief description of analytical method used: Determination of the concentration was conducted during the whole inhalation duration. Withdrawal was done with 1.25 m/sec. The sample was passed through a wash bottle containing 100 mL HCl. Parts of the acid were neutralized by 1-methylpiperidine and the excess of acid was titrated back using 0.1 N NaOH. An indicator was used.
The concentration was calculated from the mass flow of liquid passing the nozzle compared to the volumetric air flow through the nozzle. The density of the substance was assumed as 1000 g/cm³.
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: < 5 µm (89.0 %); 0.5 - 1.0 µm (10.6 %); 1.0 - 3.0 µm (0.4 %)

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

1 h

Concentrations:

13.8 mg/L and 15.4 mg/L

No. of animals per sex per dose:

10

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: before initiating, during and after the observation period
- Necropsy of survivors performed: yes, animals were sacrifized using urethane anaesthesia
- Other examinations performed: mortality, clinical signs, behaviour, body weight, macroscopic changes.

Statistics:

Body weight: mean and standard deviation, U-Test Wilcoxon, Mann and Whitney.

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LC0

Effect level:

15.4 mg/L air

Based on:

test mat.

Exp. duration:

1 h

Remarks on result:

other: No mortality observed.

Effect levels 2

Sex:

male/female

Dose descriptor:

LC0

Effect level:

3.85 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: No mortality observed. LC0 value with 1h was converted by dividing by 4 (Haber’s rule/law, dusts and mists).

Mortality:

No mortality was observed with both concentrations.

Clinical signs:

other: 13.8 mg/mL: two min after exposure start slight restlessness, and 10 min after exposure start serous discharge at the nose, and intermittent respiration was observed in single male and female animals. 20 min after start of exposure all male and female ani

Body weight:

Control:
males: day 0: 214.9 ± 10.83 g; day 1: 206.9 ± 9.53 g; day 2: 216.4 ± 11.1 g; day 4: 221.7 ± 11.7 g; day 7: 231.5 ± 14 g; day 8: 236.3 ± 15.94 g; day 9: 237.6 ± 15.08 g; day 10: 239.1 ± 16.39 g; day 11: 241.6 ± 16.85 g; day 14: 252.6 ± 19.75 g.
females: day 0: 182.3 ± 3.34 g; day 1: 181.4 ± 2.99 g; day 2: 181.7 ± 3.71 g; day 4: 184.7 ± 4.08 g; day 7: 188.7 ± 5.25 g; day 8: 187.8 ± 4.71 g; day 9: 189.2 ± 5.12 g; day 10: 188.1 ± 5.22 g; day 11: 188.1 ± 5.54 g; day 14: 192.1 ± 5.59 g.

13.8 mg/L:
Body weight gain was significantly reduced for males from day 1 to 8 and for females from day 1 to 7 compared to the control.
males: day 0: 215.7 ± 13.42 g; day 1: 198.6 ± 16.77 g (-4 %); day 2: 201.4 ± 18.1 g (-7 %); day 4: 211.8 ± 19.0 g (-4.5 %); day 7: 216.5 ± 20.1 g (-6.5 %); day 8: 229.2 ± 20.93 g (-4 %); day 9: 231.3 ± 21.75 g; day 10: 233.8 ± 22.33 g; day 11: 236.3 ± 23.62 g; day 14: 248.8 ± 25.59 g.
females: day 0: 177.1 ± 7.84 g (-2.9 %); day 1: 163.0 ± 10.06 g (-10 %); day 2: 163.9 ± 8.06 g (-9.8 %); day 4: 174.4 ± 11.38 g (-5.6 %); day 7: 177.5 ± 13.58 g (-5.9 %); day 8: 178.9 ± 14.46 g (-4.7 %); day 9: 182.1 ± 14.91 g (-3.7 %); day 10: 182.0 ± 13.67 g (-3.2 %); day 11: 182.4 ± 13.89 g; day 14: 185.6 ± 13.38 g.

15.4 mg/L:
Body weight gain was significantly reduced for males and females from day 1 to 9 compared to the control.
males: day 0: 217.1 ± 6.26 g; day 1: 200.1 ± 8.09 g; day 2: 202.3 ± 10.2 g; day 4: 214.0 ± 8.69 g; day 7: 225.2 ± 9.38 g; day 8: 229.2 ± 9.24 g; day 9: 232.6 ± 8.34 g; day 10: 236.8 ± 8.43 g; day 11: 237.8 ± 8.80 g; day 14: 242.2 ± 9.68 g.
females: day 0: 183.5 ± 5.99 g; day 1: 166.2 ± 7.24 g; day 2: 167.1 ± 8.86 g; day 4: 174.7 ± 6.53 g; day 7: 182.0 ± 7.90 g; day 8: 182.3 ± 6.65 g; day 9: 185.3 ± 7.02 g; day 10: 188.3 ± 8.03 g; day 11: 189.0 ± 8.67 g; day 14: 191.5 ± 6.96 g.

Gross pathology:

No substance related abnormalities observed. Petechiae at the lung and pulmonary emphysema were observed in both, the control and the treatment group.