Methyl methacrylate

Repeated dose toxicity: other routes

Administrative data

Endpoint:

chronic toxicity: other route

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study well documented, meets generally accepted scientific principles, acceptable for assessment. With regard to carcinogenicity testing, the number of animals used in this test is below current guideline requirements. The power of this study and the negative finding have to be placed into perspective with the other three negative in vivo studies, the absence of genotoxicity and the lack of positive evidence in the cancer mortality studies on MMA.

Data source

Reference

Reference Type:

publication

Title:

Studies on the Chronic Oral Toxicity of Monomeric Ethyl Acrylate and Methyl Methacrylate.

Author:

Borzelleca JF, Larson PS, Hennigar GR, Huf EG, Crawford EM, Blackwell, Smith R

Year:

1964

Bibliographic source:

Toxicol. Appl. Pharmacol. 6: 29-36

Materials and methods

Principles of method if other than guideline:

other: not applicable

GLP compliance:

no

Test material

Test material information

Constituent 1

Details on test material:

Methylmethacrylate; purity not reported. The undiluted stock was inhibited from polymerization with 10 ppm of monomethyl ether of t-butylhydroquinone.

Test animals

Species:

dog

Strain:

other: purebred Beagle dog

Sex:

male/female

Administration / exposure

Route of administration:

other: oral, dietary equivalents as Gelatine capsule containing MMA solution in corn oil

Vehicle:

corn oil

Details on exposure:

Methyl methacrylate was dissolved in corn oil and administered  to beagle dogs in gelatin capsules at doses equivalent to that achieved  by dietary concentrations of 0,  100, 100 or 1000 - 1500 ppm on a daily  basis. 

Duration of treatment / exposure:

104 weeks (2 years)

Frequency of treatment:

Daily

Doses / concentrations

Remarks:

Doses / Concentrations:
10, 100 and 1000 - 1500 ppm
 In the  high-dose group, the initial concentration administered was 1000 ppm and  was then increased to 1200 ppm at week 5, to 1400 ppm at week 7 and to  1500 ppm at week 9, continuing through the end of the study. The animals  were individually housed and provided feed ad libitum.  

No. of animals per sex per dose:

Two males and two females were tested at each dose.

Control animals:

yes, concurrent no treatment

Details on study design:

Post-exposure period: Not applicable

Examinations

Observations and examinations performed and frequency:

Body weights were measured prior to study initiation, and at weeks 13,  26, 39, 52, 65, 78, 91 and 104. Hematological measurements, including  hematocrit, hemoglobin, total white and differential white cell counts,  were obtained from each animal prior to study initiation, and at 2, 4 and  13 weeks and at three month intervals thereafter. Urine samples were  collected to evaluate urinary concentrations of reducing substances and  proteins at the same time periods.  

Sacrifice and pathology:

At sacrifice organ to bodyweight ratios were determined for the  heart, spleen, kidney, liver and testes.  Select tissues collected and  preserved from all survivors and decedents included: heart, lung, liver,  kidney, urinary bladder, spleen, gastroenteric, skeletal muscle, bone  marrow, skin, brain, thyroid, adrenal, pancreas, pituitary and gonads.  Histopathological examinations were made on all tissues from each dog.

Results and discussion

Results of examinations

Body weight and weight changes:

effects observed, treatment-related

Haematological findings:

no effects observed

Urinalysis findings:

no effects observed

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Histopathological findings: non-neoplastic:

no effects observed

Details on results:

A decrease in body weight gain was observed in the dogs administered  methyl methacrylate at a concentration of 1000 - 1500 ppm. Hematological  values and urine concentrations of reducing substances and proteins were  within the normal ranges for all groups tested. Organ to body weight  ratios were similar between the treated animals and those of the control  animals, except a statistically significant decrease in spleen ratios was  observed in dogs receiving 100 ppm methyl methacrylate. The biological  significance of this finding was not apparent. No abnormal  histopathological findings were noted.

Effect levels

Dose descriptor:

NOAEL

Effect level:

100 ppm

Sex:

male/female

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

The authors did not state a NOAEL but it is considered to be 100 ppm.