N-(hydroxymethyl)acrylamide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1981

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well documented report of a guideline study conducted to GLP.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: NTP 16-day oral toxicity study by gavage in rodents

Principles of method if other than guideline:

Dose range-finding study prior to chronic studies in rodents.

GLP compliance:

yes

Test type:

other: 16 day gavage

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

N-(hydroxymethyl)acrylamide

EC Number:

213-103-2

EC Name:

N-(hydroxymethyl)acrylamide

Cas Number:

924-42-5

Molecular formula:

C4H7NO2

IUPAC Name:

N-(hydroxymethyl)acrylamide

Details on test material:

- Name of test material (as cited in study report): N-Methylolacrylamide
- Substance type: Non-volatile, organic
- Physical state: Solid
- Analytical purity: approximately >98%
- Impurities (identity and concentrations): unkown but evidence indicates that 1% may have been a polymer of Nmethylolacrylamide,
which would not have been detected by the analytical methods used
- Composition of test material, percentage of components: 100%
- Isomers composition: not applicable
- Purity test date: no data
- Lot/batch No.: 1-45-000
- Expiration date of the lot/batch: no data
- Stability under test conditions: stable
- Storage condition of test material: storage at 5°C

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Industries
- Age at study initiation: approximately 7 weeks old
- Weight at study initiation: 147 ± 4 g for males ; 115 ± 5 g for females
- Fasting period before study: no data
- Housing: 5 per cage
- Bedding: Absorb-Dri, Inc., Garfield, NJ
- Diet: ad libitum
- Feed: NIH 07 Rat and Mouse Ration (Zeigler Bros., Inc., Gardners, PA)
- Water: ad libitum (automatic watering system)
- Acclimation period: 20 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 40-60
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: 07/04/1981 To: 23/07/1981

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Amount of vehicle (if gavage): 5
- Justification for choice of vehicle: substance is totally water soluble
- Purity: deionised
MAXIMUM DOSE VOLUME APPLIED: 5 ml/kg
- Rationale for the selection of the starting dose: Based on acute toxicity of acrylamide

Doses:

0,25, 50, 100,200, or 400 mg/kg

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: none (16 day study)
- Frequency of observations and weighing: observation two times per day and weighing on days 1 and 7 and at necropsy
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology

Statistics:

None

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 200 - < 400 mg/kg bw

Based on:

test mat.

Mortality:

All rats that received 400 mg/kg died within 4 days, and 3/5 male rats and 2/5 female rats that received 200 mg/kg also died before the end of the study.

Clinical signs:

other: No abnormal clinical observations were noted in the study.

Gross pathology:

Compound related lesions in rats included hyperplasia of the bronchiolar and tracheal epithelium, dysplasia of the nasal and tracheal epithelium, centrilobular hepatocellular necrosis, lymphoid depletion of the spleen, and myelin degeneration of the lumbar ventral spinal nerve. Bronchial epithelial hyperplasia (mild) appeared to be dose related in males and females. Sinusoidal congestion of the liver and vacuolar degeneration of myocardial fibers were seen in males and females given 400 mg/kg.

Applicant's summary and conclusion

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of the test, the acute oral LD50 of N-methylolacrylamide in the Fischer rat is between 200 and 400 mg/kg bw.

Executive summary:

Test condition :Groups of 5 rats per sex were dosed with 50, 100, 200, 400 or 800 mg/kg.

Male rats ranged form 101-128 g starting body weight, females weighed

from 84-102 g at the study initiation. Animals received a single dose in a

concentration 5.0 ml/kg. Animals were observed twice a day for clinical

signs. After 14 days observation, surviving animals were terminated

without necropsy or histopathology. No clinical pathology was performed.

Result :All rats in the 800 mg./kg group died on or before Day 2. In the 400 mg/kg

group, four males and three females died during the first week of

observation. No abnormal clinical signs were noted.

Conclusion :LD50 = 400 mg/kg