Registration Dossier

Toxicological information

Carcinogenicity

Currently viewing:

Administrative data

Endpoint:
carcinogenicity
Remarks:
subcutaneous
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
other information
Study period:
published: June 1971
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptably documented study which meets basic scientific principles and contains sufficient detail to be able to judge the results reliable as a contribution to the understanding of the carcinogenicty of this substance.

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Unnamed
Year:
1971
Reference Type:
publication
Title:
Unnamed
Year:
1973

Materials and methods

Test guideline
Qualifier:
no guideline required
Guideline:
other: performed before guideline
Deviations:
not applicable
Principles of method if other than guideline:
To determine the carcinogenic potential of Methylparaben the substance was injected twice weekly at different dosages for 1 year. Each animal was sacrificed and autopsied at 12 or 18 months on test period.
GLP compliance:
no
Remarks:
performed before GLP guidelines

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
The test compound was provided by the Division of Biologic Standards, National Institutes of Health

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals and environmental conditions:
- Caesarean derived 4-weeks-old weanlings
- weight: approx. 60 g on arrival
- placed on test within 2 weeks after arrival
- housing: 2 in a cage in air-conditioned quarters
- maintained on Purina Rat Chow and water ad libitum

Administration / exposure

Route of administration:
subcutaneous
Vehicle:
physiological saline
Details on exposure:
The treatment consisted of twice-weekly injections for 52 weeks, with the dose level maintained on the mg/kg bw basis by adjusting the injection volumes to the animal weights.
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
Methylparaben was formulated every 2 weeks and only used for 2 weeks.
Duration of treatment / exposure:
52 weeks
Frequency of treatment:
Twice weekly
Post exposure period:
6 months
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0.6 mg/kg bw/application
Basis:
other: s.c., twice weekly
Remarks:
Doses / Concentrations:
1.1 mg/kg bw/application
Basis:
other: s.c., twice weekly
Remarks:
Doses / Concentrations:
2.0 mg/kg bw/application
Basis:
other: s.c., twice weekly
Remarks:
Doses / Concentrations:
3.5 mg/kg bw/application
Basis:
other: s.c., twice weekly
No. of animals per sex per dose:
- 0.6 mg/kg bw/application: 20 animals
- 1.1 mg/kg bw/application: 40 animals
- 2.0 mg/kg bw/application: 60 animals
- 3.5 mg/kg bw/application: 80 animals
Control animals:
yes, concurrent no treatment
yes, concurrent vehicle
yes, historical
Details on study design:
- The treatment consisted of twice-weekly injections for 52 weeks, with the dose level maintained on the mg/kg bw basis by adjusting the injection volumes to the animal weights.
- After 52 weeks of treatment the animals were kept for observation an additional 6 months.
- 3 types of controls were used: a) vehicle control (60 males, 60 females) received twice weekly injections of saline at 0.25 mL per injection; b) negative controls (60 males and 60 females) received no treatment; c) positive controls (Ni3S2,4 groups of 40 animals each)
Positive control:
Positive controls (80 males and 80 females) received predetermined fixed doses of Nickel sulfide, the positve controls were divided into subgroups: A, B, C, and D of 40 animals each (20 males, 20 females). Each animal in the A and B groups received a single subcutaneous injcetion of 10.0 and 3.3 mg, respectively. Groups C and D were given the same doses of Nickel sulfide by a single intramuscular injection in the thigh.

Examinations

Observations and examinations performed and frequency:
Animals were examined each day, all abnormalities were reported immediately.
A weekly record was kept of animal weights, injection volumes and gross observations.
Sacrifice and pathology:
All experimental animals were necropsied after they died or were sacrificed (after 18 months). Organ weights were obtained and selected tissue was preserved for histopathologic studies.
Other examinations:
All spontaneous deaths, moribund animals, and those showing gross pathology or abnormal organ weights were examined histopathologically in addition to those chosen for routine examination.
Statistics:
no data

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
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:
Mortality:
At the end of one year, the mortality of the treated groups did not exceed that of the negative and vehicle controls. This was confirmed after 18 months at study termination.

Histopathology:
No remarkable effects.
Relevance of carcinogenic effects / potential:
No significant carcinogenic effects observed.

Effect levels

open allclose all
Dose descriptor:
NOEL
Effect level:
3.5 other: mg/kg bw/application
Sex:
male/female
Basis for effect level:
other: No evidence for carcinogencity.
Remarks on result:
other: Effect type: carcinogenicity (migrated information)
Dose descriptor:
NOEL
Effect level:
3.5 other: mg/kg bw/application
Sex:
male/female
Basis for effect level:
other: No obvious toxicity
Remarks on result:
other: Effect type: toxicity (migrated information)

Any other information on results incl. tables

None

Applicant's summary and conclusion

Conclusions:
Methylparaben did not show any carcinogenic properties under the conditions described.
Executive summary:

The toxic and carcinogenic potential of Methylparaben was studied in rats. Methylparaben application up to 1 year and 3.5 mg/kg bw/application did not show any increase in tumor inicidence. The concurrent positive control (Nickel sulfide) induced tumors.