Sodium 4-(methoxycarbonyl)phenolate

Carcinogenicity

Administrative data

Endpoint:

carcinogenicity

Remarks:

subcutaneous

Type of information:

experimental study

Adequacy of study:

weight of evidence

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

Reference

Reference 1

Reference Type:

publication

Title:

Unnamed

Year:

1971

Reference 2

Reference Type:

publication

Title:

Unnamed

Year:

1973

Materials and methods

Test guideline

Qualifier:

no guideline required

Guideline:

other: performed before guideline

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

Test material information

Constituent 1

Reference substance name:

Methyl 4-hydroxybenzoate

EC Number:

202-785-7

EC Name:

Methyl 4-hydroxybenzoate

Cas Number:

99-76-3

Molecular formula:

C8H8O3

IUPAC Name:

methyl 4-hydroxybenzoate

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 or test system 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 / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
0.6 mg/kg bw/application
Basis:
other: s.c., twice weekly

Doses / concentrations 2

Remarks:

Doses / Concentrations:
1.1 mg/kg bw/application
Basis:
other: s.c., twice weekly

Doses / concentrations 3

Remarks:

Doses / Concentrations:
2.0 mg/kg bw/application
Basis:
other: s.c., twice weekly

Doses / concentrations 4

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

1

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)

2

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.