Registration Dossier

Administrative data

Endpoint:
short-term repeated dose toxicity: dermal
Type of information:
experimental study
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

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
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 / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0 %
Basis:
nominal per unit body weight
Remarks:
Doses / Concentrations:
0.2 %
Basis:
nominal per unit body weight
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

open allclose all
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% )
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:

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% DHTDMAC (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)