N-(hydroxymethyl)methacrylamide

Acute Toxicity: oral

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

Test material information

Constituent 1

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 levels

Effect levels 1

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

Effect levels 2

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

Effect levels 3

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.

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