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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Toxicological information

Repeated dose toxicity: oral

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Administrative data

chronic toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Japanese reference, only abstract and tables in English available. Japanese government peer-reviewed the documents, audited selected studies.

Data source

Reference Type:
Chronic effects of methacrylamide - 12 month study of administration in drinking water to rats and mice.
Aratani J
Bibliographic source:
Kanazawa Daigaku Juzen Igakkai Zasshi 102(6): 720 - 727; Secondary literature from SIDS

Materials and methods

Principles of method if other than guideline:
Method: no data.
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
EC Number:
EC Name:
Cas Number:
Molecular formula:
Details on test material:
Purity of the test substance: no data

Test animals


Administration / exposure

Route of administration:
oral: drinking water
Duration of treatment / exposure:
4, 8, and 12 months
Doses / concentrations
Doses / Concentrations:
0, 200, 400, 800 and 1200 ppm (equivalent to ca. 0, 4.6, 9.1, 19.5, and 31.6 mg/kd/day)
other: The equivalent doses mentioned above are re-calculated because the original doses in the literature by Aritani were apparently incorrect.
No. of animals per sex per dose:
Number of animals in each dose group was 18 to 20
Control animals:
Details on study design:
Post-exposure period: 12 month in the longest case


For comparison of 3 or more groups, the differences between group means were first examined by one-way ANOVA and then by Dunnett’s
multiple comparison test. Differences were considered significant at p<0.05.
For comparison of 2 groups, Fisher’s exact probability test were used.

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
mortality observed, treatment-related
Body weight and weight changes:
effects observed, treatment-related
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
no effects observed
Ophthalmological findings:
not specified
Haematological findings:
no effects observed
Clinical biochemistry findings:
effects observed, treatment-related
Urinalysis findings:
no effects observed
Behaviour (functional findings):
effects observed, treatment-related
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
effects observed, treatment-related
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Details on results:
1200 ppm: Body weight gain was slightly but insignificantly suppressed compared to control during the treatment period.
Symptoms of peripheral neuropathy including hindlimb weakness and abnormal gait were detected.
800 and 1200 ppm: Walking performance on a rotating rod decreased significantly.
More than 800 ppm: shrinkage and loss of myelinated fibers of the sciatic nerve and atropy of the gastrocnemius muscle was detected.
Some rats showed a distension of the urinary bladder. Water and food consumption were not different among control and treatment groups during
the treatment period. Hemogram did not change significantly.
Dose-related increases in serum total cholesterol and phospholipid content and y-glutamyl transpeptidase activity were seen after 12 months,
although the increase in the last item was not statistically significant. Rat urine after 12 months did not show any significant biochemical change.
During post-administration period, pigmentation of body fur due to urinary incotinence, and symptoms of neuropathy were advanced,
especially in rats receiving the two higher doses. No significant differences in absolute or relative organ weights were seen among either treatment or post treatment periods.

Effect levels

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Dose descriptor:
Effect level:
ca. 9.1 mg/kg bw/day (nominal)
Dose descriptor:
Effect level:
ca. 19.5 mg/kg bw/day (nominal)

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Neurotoxic effects were observed. The NOAEL for male rats in this drinking water study was considered to be ca. 9.1 mg/kg/day (400 ppm).
Executive summary:

In a chronic toxicity study Methacrylamide  was administered to male Wistar rats in drinking water at dose levels of 0, 4.6, 9.1, 19.5 and 31.6 mg/kg bw/day for 4, 8 and 12 month.

Histopathological observations related to neurotoxicity such as shrinkage and loss of myelinated fiber of sciatic nerve were observed at 800 ppm (ca. 19.5 mg/kg/day) and higher.

The NOAEL is 9.1 mg/kg/day

Original study in Japanese. Only abstract in English available