Registration Dossier

Diss Factsheets

Toxicological information

Acute Toxicity: oral

Currently viewing:

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1985-11-04 - 1985-12-17
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study OECD 401, GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report date:
1986

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
adopted May 12, 1981
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
N-(hydroxymethyl)methacrylamide
EC Number:
213-086-1
EC Name:
N-(hydroxymethyl)methacrylamide
Cas Number:
923-02-4
Molecular formula:
C5H9NO2
IUPAC Name:
N-(hydroxymethyl)-2-methylacrylamide
Test material form:
other: liquid
Details on test material:
Approximately 60 % aqueous solution (commercial product)

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, Füllinsdorf, Switzerland
- Age at study initiation: 9 - 14 weeks
- Weight at study initiation: males: 199 - 286 g; females: 172 - 227 g
- Fasting period before study: yes, 12 - 18 hours
- Housing: Groups of five in Makrolon type-3 cages, standard softwood bedding ("Lignocel", Schill AG, Muttenz, Switzerland)
- Diet (e.g. ad libitum): Ad libitum, Pelleted standard Kliba 343, Batch 33/85 rat maintenance diet (Klingentalmühle AG, Kaiseraugst, Switzerland
- Water (e.g. ad libitum): Ad libitum, Community tap water from Itingen, Switzerland
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2 °C
- Humidity (%): 55 ± 10 %
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 20 ml at 5000 mg/kg; 0therwise 10ml

Doses:
200, 600, 1000 and 5000 mg/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: Four time during test day 1 and daily during days 2 - 15
- Weighing: days 1 (pre-administration), 8 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, necropsy
Statistics:
LOGIT-Model, (COX, analysis of Binary Data, London 1977)

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
959 mg/kg bw
Based on:
test mat.
95% CL:
631 - 1 556
Remarks on result:
other: 60 % aqueous solution
Sex:
male
Dose descriptor:
LD50
Effect level:
1 153 mg/kg bw
Based on:
test mat.
95% CL:
574 - 3 613
Remarks on result:
other: 60 % aqueous solution
Sex:
female
Dose descriptor:
LD50
Effect level:
853 mg/kg bw
Based on:
test mat.
95% CL:
377 - 1 929
Remarks on result:
other: 60 % aqueous solution
Mortality:
At 200 mg/kg: no mortalities
At 600 mg/kg: 1 male after 24 hrs, 1 female after 3 days
At 1000 mg/kg: 2 males after 24 hrs, 1 female after 3 hrs, 1 female after 5 hrs, 2 females after 24 hrs
At 5000 mg/kg: 1 male after 5hrs, 4 males after 24 hrs, 3 females after 3 hrs, 2 females after 5 hrs
Clinical signs:
At 200 mg/kg: no signs or symtoms
At 600 mg/kg: sedation, dyspnea, ataxia (females), curved body position (females), ruffled fur (females), spasms (females)
At 1000 mg/kg: sedation, dyspnea, ataxia, curved body position, diarrhea (females), ruffled fur
At 5000 mg/kg: sedation, dyspnea, lacrimation, ataxia, curved body position, spasms, ruffled fur
Body weight:
MALES

Dose (mg/kg) Day 1 Day 8 Day 15
200 272±12 308±13 321±15
600 249±3.5 287 312
1000 237±3.9 264 306
5000 213±13 DEAD ---

FEMALES

Dose (mg/kg) Day 1 Day 8 Day 15
200 200±4.3 215±5.1 222±5.4
600 212±14 233 242
1000 202±5.1 230 240
5000 185±9.1 DEAD ---
Gross pathology:
At 200 mg/kg: killed - no pathologic changes
At 600 mg/kg: dead - stomach: filled, severe (1 animal) ;intestines :filled with orange to red contents (2 animals); urinary bladder :filled with dark-red contents (1 animal);
killed - no pathologic changes (8 animals)
At 1000 mg/kg: dead - stomach/intestines: filled with test article (6 animals)
killed - lung: mottled (3 animals); no pathologic changes (1 animal)
At 5000 mg/kg: dead - lung: mottled (1 animal); dark-red discolored (1 animal) ;intestines: reddend (3 animals), slightly reddend (6 animals); no pathologic changes: 1 animal
Other findings:
no

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
According to the test result: LD50(rat, acute oral): 959 mg/kg the test substance N-methylol methacrylamide (60% in aqueous solution) has to be
classified as acute oral toxic category 4 (EU GHS and UN GHS criteria).
Executive summary:

In an acute oral toxicity study according to OECD 401 conducted with GLP, groups of fasted male and female Wistar rats were given a single oral dose of N-methylol methacrylamide (60 % aqueous solution) at a dose levels of  200, 600, 1000 and 5000 mg/kg for both sexes.

The LD50 for males was 1153 mg/kg and for females 853 mg/kg.

 

Oral LD50Combined = 959 mg/kg bw

 

Based on the results N-methylol methacrylamide is allocated to EU GHS and UN GHS acute oral category 4.

NOTE: Any of data in this dataset are disseminated by the European Union on a right-to-know basis and this is not a publication in the same sense as a book or an article in a journal. The right of ownership in any part of this information is reserved by the data owner(s). The use of this information for any other, e.g. commercial purpose is strictly reserved to the data owners and those persons or legal entities having paid the respective access fee for the intended purpose.

Categories Display