N-benzyl-N-C16-18 (even numbered)-alkyl-N-methyl-C16-18 (even numbered)-alkyl-1-aminium chloride

Repeated dose toxicity: dermal

Administrative data

Endpoint:

short-term repeated dose toxicity: dermal

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Study period:

1974

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Secondary literature extracted from the EU Risk Assessment Report on Dioctadecyldimethylammonium chloride- Study predates official guidelines and GLP but is performed according to former scientific standards. Animal species used are rabbits.

Data source

Reference

Reference Type:

secondary source

Title:

Unnamed

Year:

2002

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

20 dermal applications to rabbits (one per day, 5 days per week, 4 weeks) of 2 mL per kg body weight of 0, 0.2 and 2% aqueous test substance solution.

GLP compliance:

no

Remarks:

study predates GLP

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Dimethyldioctadecylammonium chloride

EC Number:

203-508-2

EC Name:

Dimethyldioctadecylammonium chloride

Cas Number:

107-64-2

Molecular formula:

C38H80N.Cl

IUPAC Name:

N,N-dimethyl-N-octadecyloctadecan-1-aminium chloride

Constituent 2

Reference substance name:

1-octadecanamium,N,N-dimethyl-N-octadecyl-,chloride

IUPAC Name:

1-octadecanamium,N,N-dimethyl-N-octadecyl-,chloride

Constituent 3

Reference substance name:

Dimethyldioctadecylammonium choride

IUPAC Name:

Dimethyldioctadecylammonium choride

Details on test material:

- Name of test material: Präpagen WK (dioctadecyldimethylammonium chloride)
- Physical state: pasty
- Analytical purity: 75 %
- Composition of test material, percentage of components: 75% active in isopropanol/water
no other data available

Test animals

Species:

rabbit

Strain:

other: Gelbsilber

Sex:

male/female

Administration / exposure

Type of coverage:

occlusive

Vehicle:

water

Details on exposure:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2 mL
- Concentration (if solution): 0, 0.2, 2% (v/v)
- Constant volume or concentration used: yes


VEHICLE
- Justification for use and choice of vehicle (if other than water): water

USE OF RESTRAINERS FOR PREVENTING INGESTION: no

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

20 dermal applications (5 per week for 4 weeks)

Frequency of treatment:

single treatment per day

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
0 %
Basis:
nominal per unit body weight

Doses / concentrations 2

Remarks:

Doses / Concentrations:
0.2 %
Basis:
nominal per unit body weight

Doses / concentrations 3

Remarks:

Doses / Concentrations:
2 %
Basis:
nominal per unit body weight

No. of animals per sex per dose:

3 male and 3 female rabbits per group

Control animals:

yes, concurrent vehicle

Details on study design:

- Dose selection rationale: expert judgement
- Rationale for animal assignment (if not random): random
- Rationale for selecting satellite groups: no satellite groups
- Post-exposure recovery period in satellite groups: n.a.
- Section schedule rationale (if not random): random

Positive control:

not required

Examinations

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

Statistics:

Yes

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Dermal irritation:

effects observed, treatment-related

Description (incidence and severity):

in majority mild redness in high dose group

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

no effects observed

Ophthalmological findings:

no effects observed

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

no effects observed

Behaviour (functional findings):

no effects observed

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Details on results:

The dermal treatment resulted in some slight irritative responses mainly in high dose animals. No clinical or morphological sign of substance-induced systemic toxicity.

Effect levels

1

Dose descriptor:

NOAEL

Effect level:

40 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: based on systemic effects ( NOAEC = 2% )

2

Dose descriptor:

NOAEL

Effect level:

4 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: based on local skin effects ( NOAEC = 0.2% )

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

Based on the results of this study, the NOAEL for systemic effects was 40 mg/kg body weight per day (or 2% v/v) and the NOAEL for local skin effects was 4 mg/kg body weight per day (or 0.2 % v/v).

Executive summary:

Justification for cross reading of Benzyl-dihydrogenated-methyl ammonium chloride (BDHTMAC) to dihydrogenated-dimethyl-ammonium chloride (DHTDMAC) or its major active component,dimethyldioctadecylammonium chloride (DODMAC):

An overview of available data existing on common toxicological endpoints for the two substances demonstrates their similar toxicological behaviour: Both substances have a low acute toxicity but strong skin and eye corrosive properties. They are not sensitising and not mutagenic. The 28-day repeated dose toxicity studies performed by oral route in rats conclude to the same NOAEL of 100 mg/kg bw /day. The same biochemical changes (increase in ALAT enzyme) and the same target organ (adrenals) have been identified by these studies. Based on these results, the two substances display a similar toxic profile and it is scientifically appropriate to use cross-reading.

Technical grade dioctadecyldimethylammonium chloride containing approximately 75% active in isopropanol/water was tested in a dermal repeated dose study in rabbits.

The study predated official test guidelines and GLP but give some information on the potential systemic toxicity of quaternary ammonium compound, di-C16 -18 -alkyldimethyl, chloride via the dermal route of exposure.

Groups of 3 male and 3 female rabbits (strain "Gelbsilber") received 20 dermal applications (5 days per week for 4 consecutive weeks) of aqueous solutions containing 0, 0.2 and 2% DODMAC (corresponding to about 0, 4 and 40 mg/kg body weight per day). General behaviour, general health condition, food consumption were not influenced by the treatment. Haematology, clinical chemistry and urinalysis revealed no significant findings. Gross pathology of the animals at study termination as well as histopathological investigations revealed no substance related changes. Local skin effects in form of slight redness and foldings were observed in some of the high dose animals.

Based on the results of this study the NOAEL for systemic dermal effects was greater 40 mg/kg body weight per day (2% (v/v) aqueous test substance solution)