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

Endpoint summary

Description of key information

A valid oral toxicity study according to OECD guideline 401 with Katalysator WAZ 5596 B  is on hand. For acute inhalation toxicity a study according OECD TG 403 was conducted. In this study groups of rats were exposed nose-only to an aerosol of Katalysator WAZ 5596-B. No studys for acute dermal toxicity is available. 

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: scientifically acceptable and well documented

Principles of method if other than guideline:

Four groups of 5 male and 5 groups of 5 female Wister rats (average weight 171-177 g) each received per gavage a single dose of 500 to 2300 mg/kg bw Katalysator WAZ 5596 B. The animals were observed for mortality, weight and clinical signs through day 14.

GLP compliance:

not specified

Test type:

standard acute method

Species:

rat

Strain:

Wistar

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

water

Doses:

male rats: 500, 1000, 2000, 2300 mg/kg bw
female rats: 500, 1000, 1300, 1600, 2000 mg/kg bw

No. of animals per sex per dose:

5 male and 5 female rats/dose

Control animals:

no

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 457 mg/kg bw

Based on:

test mat.

The corresponding mortality for male rats was 0% (500 mg/kg bw), 20% (1000 mg/kg bw), 40% (2000 ml/kg bw), 100% (2300 mg/kg bw), respectively.

The corresponding mortality for female rats was 0% (500 mg/kg bw), 0% (1000 mg/kg bw), 60% (1300 ml/kg bw), 60% (1600 mg/kg bw) and 100% (2000 ml/kg bw) respectively.

A single dose of 1000 to 2300 mg/kg bw Katalysator WAZ 5596 B caused on male and female rats the following signs of intoxication: reduction of general condition, sedation and rough fur. Surroundings of the eye was bloody in 1 male animals dosed with 2000 mg/kg bw and a bloody snout was visible on 2 female animale dosed with 1300 mg/kg bw. Gasping was observed 1 male and 1 female rats dosed with 1000 mg/kg bw. A swelled belly was observed in 1 male rat dosed with 1000 mg/kg bw and a increased diuresis on female animals dosed with 1600 mg/kg bw.A staggered gait was evident on females doses with 1300 or 1300 mg/kg bw.

Additional, with doses of 1000 to 2000 mg/kg bw (males) and 1000 to 1600 mg/kg bw (females) a weight reduction was observed.

Symptoms were evident 2 hour after application and continued until day 11 of the examination period.

Necropsy on animals dosed with 1000 to 2300 mg/kg bw, which died during post-observation period:

stomach mucosa was damaged, stomach and intestines were inflated, partly stomach was adhered with liver, spleen and diaphragm.

Animals dosed with 2300 mg/kg bw showed a strong reddened lung and in the chest cavity a clear reddish fluid was found

Necropsy of animals killed of post-observation period:

animals dosed wth 500 to 1000 mg/kg bw showed were without pathological findings

Interpretation of results:

harmful

Remarks:

Migrated information

Executive summary:

Four or five groups of 5 male and female Wister rats (average weight 171-177 g) each received per gavage a single dose of 500 to 2300 mg/kg bw Katalysator WAZ 5596 B. The animals were observed for mortality, weight and clinical signs through day 14.

As signs of intoxication reduction of general condition, sedation and rough fur, gasping and staggered gait were observed in the dose range of 1000 to 2300 mg/kg bw. body weight gain was retared in the first post-observation period.

A single dose of 500 mg/kg bw Katalysator WAZ 5596 B was tolerated by male and female rats without symptoms; LD50 = 1457 mg/kg bw.

Endpoint conclusion

Dose descriptor:

LD50

Value:

1 457 mg/kg bw

Quality of whole database:

The materials/methods and results are described in detail und are sufficient for evaluation

Acute toxicity: via inhalation route

Link to relevant study records

Reference

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

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

Species:

rat

Strain:

other: Wistar, strain HsdRCCHan

Sex:

male/female

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

Sex:

male/female

Dose descriptor:

LC50

Effect level:

280 mg/m³ air

Based on:

test mat.

Exp. duration:

4 h

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.

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.

Endpoint conclusion

Dose descriptor:

LC50

Value:

280 mg/m³ air

Quality of whole database:

The materials/methods and results are described in detail und are sufficient for evaluation

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

In a valid oral toxicity study a LD50 = 1457 mg/kg bw for male and female rats was found. A single dose of 500 mg/kg bw Katalysator WAZ 5596 B was tolerated by male and female rats without symptoms.

In a valid acute inhalation toxicity study a LC50 = 280 mg/m³ was determined. Mortality was caused by lung irritation and subsequent lung edema formation. The NOAEL was < 71 mg/m³ air.

Justification for selection of acute toxicity – oral endpoint
only available study

Justification for selection of acute toxicity – inhalation endpoint
only available study

Justification for classification or non-classification

Due to the results of the acute oral toxicity study and the acute inhalation toxicity study a classification with R 22 (harmful if swallowed) and R 23 (toxic by inhalation); GHS: Acute Tox. 4 (H302: Harmful if swallowed) and Acute tox. 2 (H330: Fatal if inhaled) is justified.