Registration Dossier

Administrative data

Endpoint:
carcinogenicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study, well described.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 451 (Carcinogenicity Studies)
Deviations:
yes
Principles of method if other than guideline:
Method: other: skin painting study; 0.2 ml/animal in ethanol; application to the shaven dorsal skin; animals: 50m/50f
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Test substance: 65.79 % Quab 188 and 32.36 % water

Test animals

Species:
mouse
Strain:
other: Bor: NMRI, SPF
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Winkelmann Versuchstierzucht GmbH, Borchen, GERMANY
- Age at study initiation: 31-33 days
- Weight at study initiation: 17-28 g (m); 15-24 g (f)
- Housing: 1/Macrolon type II cage
- Diet: standard diet ad libitum
- Water: drinking water ad libitum
- Acclimation period: 2 wk

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 40-70
- Air changes (per hr): 18-20
- Photoperiod (hrs dark / hrs light): 12 h/12 h

IN-LIFE DATES: From: 1985-10-28 To: 1987-10-28

Administration / exposure

Route of administration:
dermal
Vehicle:
ethanol
Details on exposure:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit):
- Concentration (if solution): 0, 0.018, 0.18 ml QYUAB 118/animal dissolved in 10% aqueous ethanol
- Constant volume or concentration used: 0.20 ml

Duration of treatment / exposure:
life-time: 89 weeks (females); 105 weeks (males)
Frequency of treatment:
2 times/week
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 0.018 and 0.18 ml/animal (= 0, 13.8 and 138 mg/animal)
Basis:

No. of animals per sex per dose:
50
Control animals:
yes, concurrent vehicle
Positive control:
no

Results and discussion

Results of examinations

Details on results:
CLINICAL SIGNS AND MORTALITY, BODY WEIGHT AND WEIGHT GAIN
no effects

ORGAN WEIGHTS
No treatment-related effects

GROSS PATHOLOGY
No treatment related effects.


HISTOPATHOLOGY: NEOPLASTIC (if applicable)
Microscopic examination of the application site showed a minimal increase in hyperceratosis and acanthosis probably reflecting a minimal irritation potential of the test substance after repeated application. No tumors were observed at the site of application. An statistically significantly increased incidence of the number of animals with bronchio/alveolar tumors (56/100) and/or bronchio-alveolar hyperplasia (22/100) was observed in the high dose group compared to the control group (tumors: 27/100, hyperplasia: 7/100). In the low dose group the numerical incidence of those changes was also increased (tumors: 44/100, hyperplasia: 16/100), but the difference from the controls was not statistically significant. A higher incidence of focal glandular hyperplasia of the stomach was observed in the high dose females only. This finding was mostly due to an increased incidence of minimal to slight hyperplasia. No other treatment related changes were observed in the study.




OTHER FINDINGS

Any other information on results incl. tables

In conclusion 2-Chloro-2-hydroxypropyl-trimethylammonium chloride caused minimal hyperkeratosis and acanthosis, but no local tumors at the site of application. However, an increased incidence of tumors and hyperplasia in the lungs of the animals seems to be a treatment related effect. The interpretation of these findings is difficult because the duration of the current study was considerably longer than the average study duration in published historic data of the same mouse strain. Additionally, even if the slightly increased tumor incidence represents a real effect, its biological significance is unclear and may represent a promoting effect rather than a tumor inducing phenomenon. The slight increased incidence of glandular hyperplasia of the stomach seen in high dose group may be due to unintended oral uptake of the test substance

Applicant's summary and conclusion