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Toxicological information

Carcinogenicity

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Administrative data

Endpoint:
carcinogenicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Basic data given: comparable to guidelines/standards. Justification for read-across see chemical safety report chapter 1.
Cross-reference
Reason / purpose:
reference to same study

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Toxicological Evaluation of Commercial Alkyldimethylamine oxides: Two-Year Chronic Feeding and Dermal Studies
Author:
Cardin, C.W.; Domeyer, B.E. and Bjorkquist, L.
Year:
1985
Bibliographic source:
Fundamental and Applied Toxicology 5, 869-878
Reference Type:
secondary source
Title:
SIDS Initial Assessment Report
Author:
OECD
Year:
2006
Bibliographic source:
OECD Existing Chemicals Database

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 453 (Combined Chronic Toxicity / Carcinogenicity Studies)
GLP compliance:
no
Remarks:
original study performed in 1979, prior to the adoption of GLP compliance standards. However, it was reviewed and found acceptable by the laboratory´s Quality Assurance Department in accordance with US FDA´s GLP Regulation of June 20, 1979.

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
other: Charles River
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding laboratories Inc., Portage, Michigan, USA
- Age at study initiation: 4 weeks
- Housing: individually
- Diet: Zeigler NIH-07diet containing test substance, ad libitum
- Water: ad libitum
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-24
- Humidity (%): 46-70
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: feed
Vehicle:
water
Details on exposure:
PREPARATION OF DOSING SOLUTIONS:

DIET PREPARATION
- Rate of preparation of diet (frequency): weekly
- Mixing appropriate amounts with (Type of food): Zeigler NIH-07
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
not indicated
Duration of treatment / exposure:
104 weeks
Frequency of treatment:
daily with the food
Post exposure period:
none
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 0.01, 0.1 and 0.2 % of the test compound (100% (w/v) active basis, corresponds to 0, 4.24, 42.3, or 87.4 mg/kg bw/day for males and 0, 5.23, 52.6, or 107 mg/kg bw/day for females.
Basis:
nominal in diet
No. of animals per sex per dose:
60
Control animals:
yes, concurrent vehicle
Details on study design:
- Dose selection rationale: Doses were selected based on the results from a 13 week study which showed the high dose causing about a 5 to 8 % reduction in body weight.
- Dose calculation according to SIDS.
Positive control:
none

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: weekly

BODY WEIGHT: Yes
- Time schedule for examinations: weekly for the first 14 weeks of study, biweekly for the next 12 weeks and monthly thereafter.

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/week: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: yes

OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: once during pretest and at 3,6,12,16,19,22 and 24 months
- Dose groups that were examined: all

HAEMATOLOGY: Yes
- Time schedule for collection of blood: all rats to be sacrificed at 52 weeks of the study and all rats at study termination
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: all

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: all rats to be sacrificed at 52 weeks of the study and all rats at study termination
- Animals fasted: No data
- How many animals: all

URINALYSIS: Yes
- Time schedule for collection of urine: all rats to be sacrificed at 52 weeks of the study and all rats at study termination
- Metabolism cages used for collection of urine: No data
- Animals fasted: No data
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes
Statistics:
Body weights, feed consumption, efficiency of feed utilization, clinical chemistry parameters and absolute and relative organ weights were compared by analysis of variance (one way classification), Bartlett´s test for homogeneity of variances, and at least significant differences criterion. If Bartlett´s test were significant, then pairwise comparisons were made by the Mann-Whitney U test. All statistical analyses were conducted at a 5 %, two-sided risk level, and each treatment group was compared with the main control group by sex.

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
details see below
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
no effects observed
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
no effects observed
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Behaviour (functional findings):
not examined
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:
no effects observed
Details on results:
CLINICAL SIGNS AND MORTALITY
There were no significant differences in survival at 104 weeks. There were no significant, compound-related differences in mean feed consumption, clinical chemistry or ophthalmology.

BODY WEIGHT AND WEIGHT GAIN
The high dose animals demonstrated >10% decreases in mean body weight.

HISTOLOGY
There were no compound-related effects on histopathic examination. There was no evidence of a carcinogenic response after chronic dietary administration of the test substance.
Relevance of carcinogenic effects / potential:
No carcinogenity observed.

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
42.3 mg/kg bw/day
Based on:
test mat.
Sex:
male
Basis for effect level:
other: 42.3 mg /kg bw is the NOAEL for systemic effects. No carcinogenicity was observed in the highest dose tested.
Remarks on result:
other: Effect type: toxicity (migrated information)
Dose descriptor:
NOAEL
Effect level:
52.6 mg/kg bw/day
Based on:
test mat.
Sex:
female
Basis for effect level:
other: 52.6 mg /kg bw is the NOAEL for systemic effects. No carcinogenicity was observed in the highest dose tested.
Remarks on result:
other: Effect type: toxicity (migrated information)

Applicant's summary and conclusion

Conclusions:
Under the conditions of the test, the test substance is not carcinogenic to male and female rats after oral exposure for 104 weeks. The NOAEL is 42.3 (male) or 52.6 (female) mg/kg bw/day for toxic effects. .
Executive summary:

Male and female Charles River rats were given a diet containing 0, 0.01, 0.1 or 0.2 % test substance ad libitum for 104 weeks. This corresponds to 0, 4.24, 42.3, or 87.4 mg/kg bw/day for males and 0, 5.23, 52.6, or 107 mg/kg bw/day for females.

No substance related carcinogenic effects were observed in any organ. NOAEL-values were established based on general signs of general toxicity. For males the NOAEL is 42.3 for females it is 52.6 mg/kg bw/day.