Reaction mass of benzyldodecylbis(2-hydroxypropyl)ammonium chloride and benzylbis(2-hydroxypropyl)tetradecylammonium chloride

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP conform guidelinestudy

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Principles of method if other than guideline:

Four groups of rats were nose-only exposed to actual concentrations of 71.8, 168.5, 280.4, and 394.4 mg/m³. The aerosol was generated neat without any vehicle. The animals were observed for mortality, weight and clinical signs through day 14. A gross necropsy was performed.

GLP compliance:

yes

Test type:

standard acute method

Test material

Test material information

Constituent 1

Reference substance name:

Benzyldodecylbis(2-hydroxypropyl)ammonium chloride

EC Number:

265-345-3

EC Name:

Benzyldodecylbis(2-hydroxypropyl)ammonium chloride

Cas Number:

65059-91-8

Molecular formula:

C25H46NO2.Cl

IUPAC Name:

N-benzyl-N,N-bis(2-hydroxypropyl)dodecan-1-aminium chloride

Details on test material:

Content of quaternary propoxylated fatty amine: 59.0 %
Content of propoxylated fatty amine: 2.8%
Content of hydrochloride propoxylated fatty amine: 12.0 %
propane-1 ,2-diol: 6.6%
a-chlorotoluene: 13.9%
Water content: 8.1 %

Test animals

Species:

rat

Strain:

other: Wistar, strain HsdRCCHan

Sex:

male/female

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

air

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

Group 1 Group 2 Group 3 Group 4 Group 5
Target Conc. (mg/m³) 0 75 200 340 500
Nominal Conc. (mg/m³) (Control Air) 158.3 455.6 519.4 838.9
Gravimetric Conc. (mg/m³) -- 71.8 168.5 280.4 394.4

No. of animals per sex per dose:

Three male and three female rats were simultaneously exposed to the starting concentration under nose-only conditions for 4 h (start of study with group 5). All other concentrations utilize five animals/sex/group. This procedure is in compliance with OECD GD#39 (2009).

Control animals:

other: historical control

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

280 mg/m³ air

Based on:

test mat.

Exp. duration:

4 h

Any other information on results incl. tables

Mortality occurred at 280.4 and 394.4 mg/m³ and most rats succumbed within one day postexposure. The following clinical signs were observed: bradypnea, dyspnea, labored breathing patterns, breathing sounds, irregular breathing patterns, motility reduced, atony, high-legged gait, hair-coat ungroomed, piloerection, cyanosis, emaciation, nasal discharge (serous), nose: red encrustations, muzzle: red discoloration, prostration, tremor, gait squatted, urine: reddish discoloration, eyes: red encrustations, abdomen enlarged, bloated abdomen, salivation, decreased reflexes, hypothermia, and transient decrease in body weights. Gross necropsy demonstrated frank acute lung edema which is taken as cause of death. The lead pathodiagnostic effects were related to respiratory tract irritation which was not reversible within the 2-week exposure period.

Applicant's summary and conclusion

Executive summary:

A study on the acute inhalation toxicity of KATALYSATOR WAZ 5596-B (henceforward referred to as test substance) on rats has been conducted in accordance with OECD TG#403 (2009). Test procedures were adapted so as to comply also with the EU Directive 92/69/EEC, and especially OECD GD#39 (2009). Four groups of rats were nose-only exposed to actual concentrations of 71.8, 168.5, 280.4, and 394.4 mg/m³. The aerosol was generated neat without any vehicle. The results can be summarized as follows:

LC50 inhalation (liquid aerosol, 4 h): LC50-males&females: 280 mg/m³)

NO(A)EL: Males&females: <71.8 mg/m³air)

Mortality occurred at 280.4 and 394.4 mg/m³ and most rats succumbed within one day postexposure. The following clinical signs were observed: bradypnea, dyspnea, labored breathing patterns, breathing sounds, irregular breathing patterns, motility reduced,atony, high-legged gait, hair-coat ungroomed, piloerection, cyanosis, emaciation, nasal discharge (serous), nose: red encrustations, muzzle: red discoloration, prostration, tremor, gait squatted, urine: reddish discoloration, eyes: red encrustations, abdomen enlarged, bloated abdomen, salivation, decreased reflexes, hypothermia, and transient decrease in body weights. Gross necropsy demonstrated frank acute lung edema which is taken as cause of death. The lead pathodiagnostic effects were related to respiratory tract irritation which was not reversible within the 2-week exposure period.

The respirability of the aerosol was adequate to achieve the objective of study, i.e. the average mass median aerodynamic diameter (MMAD) was ~ 1.4 μm, the average geometric standard deviation (GSD) was ~2.3.

In summary, the aerosolized test substance proved to have a high acute inhalation toxicity in rats. Mortality was caused by lung irritation and subsequent lung edema formation.