1.0 Submitter/Company Information

2.0 Submission Information

8(e)/FYI ID Number: 8EHQ-1092-11952 A

Document Control Number: 88920010210

Microfiche Number: OTS0555613

3.0 Chemical Information
CAS Number: 80-62-6

Synonyms: METHYL METHACRYLATE

Other Chemicals in Submission:

4.0 Study Information
Study Title:
INITIAL SUBMISSION: THE TOXICITY AND POTENTIAL DANGERS OF METHYL METHACRYLATE AND METABOLITES WITH COVER LETTER DATED 10/15/92

Study Information:
Biochemical Interactions and/or Mechanism of Toxic Effects
Unknown Environmental Effects

Summary/Abstract:
ACUTE TOXICITY IN RATS IS OF UNDETERMINED CONCERN BECAUSE OF AN EXPOSURE ROUTE
OF INJECTION. THE QUANTITATIVE CRITERIA FOR THIS EXPOSURE HAS NOT BEEN SET.
RATS (NUMBER/SEX/DOSE NOT STATED) WERE ADMINISTERED 1000-3000 OR 7000 MG/KG
(0.001-0.003 OR 0.007 CC/G) OF METHYL METHACRYLATE MONOMER BY SUBCUTANEOUS
INJECTION. MODERATE DEPRESSION LASTING 1-4 HOURS RESULTED IN RATS DOSED AT
1000-3000 MG/KG. RATS DOSED AT 7000 MG/KG BECAME EXCITED AND HAD INCREASED
RESPIRATION; THIS WAS FOLLOWED 10 MINUTES LATER BY DEPRESSION, SLOW AND
IRREGULAR RESPIRATION, ASPHYXIA AND SLIGHT CYANOSIS. THESE ANIMALS DIED IN
COMA. NECROPSY REVEALED A LARGE AMOUNT OF URINE IN A VERY DISTENDED BLADDER IN
ANIMALS THAT DIED WITHIN 24 HOURS; BLOOD WAS OBSERVED IN THE URINE OF ANIMALS
THAT DIED 1-2 DAYS AFTER TREATMENT. THERE WAS NO INDICATION OF DESTRUCTION OF
RBCS OR ANY INFLUENCE ON BLOOD FORMING ORGANS. DIFFUSE HYPEREMIA OF THE
VISCERA, HEMORRHAGES, AND MODERATE NEPHROSIS IN THE KIDNEYS, AND MILD OR
MODERATE DEGENERATION O THE PARENCHYMA OF THE LIVER WERE OBSERVED. ACCORDING
TO THIS PAPER, 7500 MG/KG KILLS 80% OF THE RATS WITHIN 24 HOURS. WHEN
PORPHYRIN FROM THE URINE OF CATS TREATED WITH METHYL METHACRYLATE MONOMER WAS
DISSOLVED IN DILUTE HYDROCHLORIC ACID AND INJECTED SUBCUTANEOUSLY INTO RATS
(DOSE NOT STATED), THE RATS BECAME SENSITIZED TO STRONG LIGHT AND DEVELOPED
INFLAMMATORY REACTIONS OF THE MUCOUS MEMBRANES, EDEMA OF THE SKIN, AND NERVOUS
REACTIONS.

ACUTE TOXICITY IN RATS VIA ORAL ADMINISTRATION IS OF LOW CONCERN. DEATH IN 90%
OF THE ANIMALS OCCURRED 48 HOURS AFTER RATS RECEIVED 9000 OR 10,000 MG/KG
(0.009 OR 0.01 CC/G). THE ONSET OF DEPRESSION WAS SLOWER THAN FOR SUBCUTANEOUS
INJECTION BUT MORE LASTING AND DEVELOPED INTO COMA AND DEATH FOR ANIMALS THAT
WERE DEEPLY DEPRESSED. PATHOLOGICAL OBSERVATIONS INCLUDED CELLULAR
DEGENERATION IN THE LIVER (WITHOUT NECROSIS OR FIBROSIS), AND HYPEREMIA, FATTY
DEGENERATION OF THE TUBULAR EPITHELIUM, AND HEMORRHAGES IN THE TUBULES OF THE
KIDNEY.

ACUTE TOXICITY IN RATS VIA INHALATION IS OF LOW CONCERN. RATS WERE EXPOSED TO
11.2, 13.4, 16, 20.1, OR 25-35 MG/L OF METHYL METHACRYLATE MONOMER. IRRITATION
OF THE GASTROINTESTINAL TRACT, DEPRESSION, INCREASED URINARY EXCRETION, AND
SLIGHT DYSPNEA WERE OBSERVED IN RATS DOSED AT 16 OR 20.1 MG/L. DEPRESSION
BECAME MORE SEVERE AT 25-35 MG/L; THE ANIMALS SHOWED SIGNS OF DYSPNEA AND MILD
CYANOSIS, AND USUALLY DIED IN COMA.

REPEATED DOSE TOXICITY IN RATS AND MICE VIA INHALATION IS OF MEDIUM CONCERN.
RATS AND MICE (12 EACH) WERE EXPOSED TO 4.95 MG/L OF METHYL METHACRYLATE
MONOMER 6 HOURS/DAY FOR 18 DAYS. THERE WERE NO TOXICOLOGICAL SIGNS OTHER THAN
OCCASIONAL BLOOD IN THE URINE. RATS (40 TOTAL) AND MICE (24 TOTAL) WERE
EXPOSED TO THE SAME CONCENTRATION FOR 3 WEEKS; HALF OF THE SERIES WERE KEPT IN
DARK AND HALF WERE EXPOSED TO 2-3 HOURS DAILY OF DIRECT SUNLIGHT. MORTALITY
OCCURRED IN 8/20 RATS EXPOSED TO SUNLIGHT AND 2/20 RAT KEPT IN THE DARK.
MORTALITY OCCURRED IN 11/12 MICE EXPOSED TO SUNLIGHT AND 2/12 MICE KEPT IN THE
DARK. RATS KILLED AT THE END OF THE TEST SHOWED BLOOD IN THE URINE. RATS
EXPOSED TO LIGHT SHOWED IRREGULAR HYPEREMIA OF THE VISCERA AND MILD TO SEVERE
KIDNEY CHANGES (OCCASIONALLY NEPHROSIS WITH INTRATUBULAR HEMORRHAGES). BOTH
GROUPS OF MICE SHOWED MILD TO SEVERE NEPHROSIS AND BRONCHOPNEUMONIA. MICE
EXPOSED TO LIGHT SHOWED SOME CLOUDY SWELLING OF THE LIVER AND OCCASIONAL
MYOCARDIAL CHANGES.

ACUTE TOXICITY IN CATS IS OF UNDETERMINED CONCERN BECAUSE OF AN EXPOSURE ROUTE
OF INJECTION. THE QUANTITATIVE CRITERIA FOR THIS EXPOSURE HAS NOT BEEN SET.
RATS (NUMBER/SEX/DOSE NOT STATED) WERE ADMINISTERED 2500, 3000, 3200, 3500, OR
6000 MG/KG (0.0025, 0.003, 0.0032, 0.0035, OR 0.006 CC/G) OF METHYL
METHACRYLATE MONOMER BY SUBCUTANEOUS INJECTION. CATS DOSED AT 2500 OR 3000
MG/KG SHOWED SOME DEPRESSION BUT RECOVERED BY 16 HOURS. ONE CAT DOSED AT 3500
MG/KG BECAME DEEPLY DEPRESSED WITHIN 4 HOURS, DEVELOPED ASPHYXIA, AND DIED
AFTER 14 HOURS. CATS DOSED AT 3200 OR 6000 MG/KG EXHIBITED SALIVATION, MARKED
DEPRESSION, IRREGULAR RESPIRATION, DYSPNEA, AND DEATH 2 HOURS POST-DOSING. ALL
ANIMALS EXCRETED A MODERATE TO VERY LARGE AMOUNT OF RBCS. THE URINE AND BLOOD
OF SURVIVING CATS CONTAINED A LARGE AMOUNT OF PORPHYRIN PIGMENT. DIFFUSE
HYPEREMIA OF THE VISCERA, HEMORRHAGES, AND MODERATE NEPHROSIS IN THE KIDNEYS,
AND MILD OR MODERATE DEGENERATION OF THE PARENCHYMA OF THE LIVER WERE
OBSERVED. CATS WHICH RECEIVED 3000 MG/KG (0.003 CC/G) ORALLY EXHIBITED
DEPRESSION AND VOMITING FOR 6 HOURS. FOLLOWING A SECOND DOSE, ONE ANIMAL DIED
IN A COMA. PATHOLOGICAL OBSERVATIONS INCLUDED CELLULAR DEGENERATION IN THE
LIVER (WITHOUT NEPHROSIS OR FIBROSIS), AND HYPEREMIA, FATTY DEGENERATION OF THE
TUBULAR EPITHELIUM, AND HEMORRHAGES IN THE KIDNEY TUBULES.

ACUTE TOXICITY TO CATS AND RABBITS VIA INHALATION IS OF LOW CONCERN. 2 EACH
WERE EXPOSED TO 15 MG/L 7 HOURS/DAY FOR 5 CONSECUTIVE DAYS. MORTALITY OCCURRED
IN 1 CAT AFTER THE THIRD EXPOSURE. NONE OF THE ANIMALS EXCRETED BLOOD IN THE
URINE. RABBITS SHOWED A SLIGHT INCREASE OF THE PORPHYRIN LEVEL IN THE BLOOD
AND A MARKED INCREASE OR URINARY PORPHYRIN EXCRETIONS.

ACUTE TOXICITY VIA SUBCUTANEOUS INJECTION IN RABBITS IS OF UNDETERMINED CONCERN
BECAUSE OF AN EXPOSURE ROUTE OF INJECTION. THE QUANTITATIVE CRITERIA FOR THIS
EXPOSURE HAS NOT BEEN SET. DOSES WERE UNSTATED. THE TOXICITY IN RABBITS WAS A
LITTLE LESS THAN THAT FOR CATS ADMINISTERED THE TEST SUBSTANCE BY SUBCUTANEOUS
INJECTION. THE CLINICAL AND PATHOLOGICAL OBSERVATIONS WERE THE SAME, WITH THE
EXCEPTION OF 2 ANIMALS SHOWING SEVERE PARALYSIS IN ALL LIMBS.