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Toxicological information

Carcinogenicity

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Administrative data

Endpoint:
carcinogenicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
significant methodological deficiencies
Remarks:
insufficient for a reliable tumor analysis due to low number of animals (biostatistical limitations)
Cross-reference
Reason / purpose:
reference to same study

Data source

Referenceopen allclose all

Reference Type:
other company data
Title:
Unnamed
Year:
1953
Report Date:
1953
Reference Type:
study report
Title:
Unnamed
Year:
1956
Report Date:
1956

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
other: OECD Guideline 452 (Chronic Toxicity Studies)
Deviations:
yes
Remarks:
Group size 15 m+ 15 f, histopathology with 6 m + 6 f per group, smaller than the recommended 50 (note: Sufficient biostatistical power can never be achieved for substances that have no or a very low cancerogenic potential.)
Principles of method if other than guideline:
see 7.5.1: Columbia 1956_Silene(CS)_oral,24 mon,rat,key,RL2
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid

Test animals

Species:
rat
Strain:
other: albino
Sex:
male/female

Administration / exposure

Route of administration:
oral: feed
Vehicle:
other: gelatine (15 g/100 mL water)
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
2 years
Frequency of treatment:
daily, continuous
Doses / concentrations
Remarks:
Doses / Concentrations:
1.0, 5.0, 7.5 and 10 % (w/w) in feed
Basis:
nominal in diet
No. of animals per sex per dose:
15
Control animals:
yes, concurrent vehicle

Examinations

Observations and examinations performed and frequency:
see IUCLID section 7.5.1
Sacrifice and pathology:
GROSS PATHOLOGY: Yes

ORGAN WEIGHTS: Yes (see table 51)
liver, kidneys, and spleen (both sexes, each group)

HISTOPATHOLOGY: Yes (see table 50)
Tissues from 6 m and 6 f each dose level and control preserved in formalin:
thyroid, lung, heart, liver, kidney, stomach, large and small intestine, pancreas, spleen,
adrenal, urinary bladder, gonads, bone marrow, and skeletal muscle

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Food efficiency:
effects observed, treatment-related
Gross pathological findings:
effects observed, treatment-related
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Details on results:
Result (carcinogenicity): negative; for non-neoplastic and other effects see IUCLID section 7.5.1

Effect levels

Key result
Dose descriptor:
NOEL
Effect level:
ca. 2 500 - <= 3 200 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
not specified
Basis for effect level:
body weight and weight gain
Remarks on result:
other: corresponds to 5 % dietary level

Target system / organ toxicity

Key result
Critical effects observed:
no

Any other information on results incl. tables

No difference in survival from the control, and no gross signs of toxicity; highest dose group: growth suppression; slightly elevated pH of the urine; no tumors are observed. The NOEL is considered to be the 5% dietary level, which is estimated to correspond to about 2500 - 3200 mg/(kg bw*d), based on reduction in body-weight gain and isolated cases of calculi and brittle in kidney and urinary bladder, respectively, as well as a few cases of cholangitis-like lesions at the higher dose levels.

Applicant's summary and conclusion

Conclusions:
no evidence of carcinogenic potential