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Diss Factsheets

Toxicological information

Repeated dose toxicity: dermal

Currently viewing:

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:
key study
Study period:
1974
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study predates official guidelines and GLP but is performed according to former scientific standards and is well documented. Animal species used had been rabbits.
Cross-reference
Reason / purpose for cross-reference:
read-across source
Reference
Endpoint:
short-term repeated dose toxicity: dermal
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
For details on endpoint specific justification please see read-across report in section 13 or find a link in cross-reference “assessment report”.
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
assessment report
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
Histopathological findings: neoplastic:
not examined
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.
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% )
Critical effects observed:
not specified
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:

The study used as source investigated repeated dermal toxicity.The study results of the source compound were considered applicable to the target compound. Justification and applicability of the read-across approach (structural analogue) is outlined in the read-across report in section 13 or find a link in cross reference “assessment report”.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1974
Report date:
1974

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

Constituent 1
Reference substance name:
Dihydrogenatedtallowalkyldimethylammonium chloride
IUPAC Name:
Dihydrogenatedtallowalkyldimethylammonium chloride
Details on test material:
- Name of test material (as cited in study report): Präpagen WK
- Physical state: pasty
- Analytical purity: 75 % active in isopropanol/water
- Impurities (identity and concentrations): < 2% tertiary amine
- Composition of test material, percentage of components: 75% active, isopropanol, water
- Isomers composition: no data
- Purity test date: no data
- Lot/batch No.: no data
- Expiration date of the lot/batch: 1976
- Radiochemical purity (if radiolabelling): n.a.
- Specific activity (if radiolabelling): n.a.
- Locations of the label (if radiolabelling): n.a.
- Expiration date of radiochemical substance (if radiolabelling): n.a.
- Stability under test conditions: stable
- Storage condition of test material: darkness at room temperature

Test animals

Species:
rabbit
Strain:
other: Gelbsilber
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Hoechst AG
- Weight at study initiation: 2.24 +/- 0.24 kg
- Fasting period before study: no
- Housing: single in metal cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24°C (medium temperature)
- Humidity (%): 60% (medium relative humidity)
- Air changes (per hr): approximately 12
- Photoperiod (hrs dark / hrs light): 12 hours periodically

Administration / exposure

Type of coverage:
occlusive
Vehicle:
water
Details on exposure:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- % coverage: 100
- Time intervals for shavings or clipplings: one day prior to start of treatment, thereafter once weekly

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no data

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
- For solids, paste formed: yes/no

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

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily each working day

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily each workin day

DERMAL IRRITATION (if dermal study): Yes
- Time schedule for examinations: daily each workin day

BODY WEIGHT: Yes
- Time schedule for examinations: weekly

FOOD CONSUMPTION:
- Food consumption: Yes (continuously)

WATER CONSUMPTION: Yes
- Time schedule for examinations: daily each workin day

OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: weekly
- Dose groups that were examined: all groups

HAEMATOLOGY: Yes
- Time schedule for collection of blood: prior to start of study and after study termination
- Anaesthetic used for blood collection: No
- Animals fasted: No data
- How many animals: all animals

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: at termination of study
- Animals fasted: No data
- How many animals: all animals

URINALYSIS: Yes / No / No data
- Time schedule for collection of urine:
- Metabolism cages used for collection of urine: Yes / No / No data
- Animals fasted: Yes / No / No data
- Parameters checked in table [No.?] were examined.

NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: prior to start of study and after termination
- Dose groups that were examined: all dose groups
- Battery of functions tested: no data

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
Histopathological findings: neoplastic:
not examined
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 dihydrogenatedtallowalkyldimethylammonium chloride (DHTDMAC; "Präpagen WK") containing approximately 77% in isopropanol/water was tested in a dermal repeated dose study in rabbits. The study predated official test guidelines and GLP but is of sufficient quality to give some information on the potential systemic toxicity of DHTDMAC 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. Additionally no neurological disturbances, tooth cognition or ophthalmologic investigations of the cornea showed no findings. Haematology, clinical chemistry and urinalysis revealed no significant findings. Gross pathology of the animals at study termination as well as histopathological investigations of heart, lung, liver, spleen, adrenals, testes and ovaries, pituitary gland, and thyroids 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 2% (v/v) aqueous DHTDMAC solution or greater 40 mg/kg body weight per day.