Methacrylamide

Repeated dose toxicity: dermal

Administrative data

Endpoint:

short-term repeated dose toxicity: dermal

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

abstract

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1976

Materials and methods

Principles of method if other than guideline:

Method: no data

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Methacrylamide

EC Number:

201-202-3

EC Name:

Methacrylamide

Cas Number:

79-39-0

Molecular formula:

C4H7NO

IUPAC Name:

methacrylamide

Test material form:

solid

Test animals

Species:

other: newborn rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:
- Age at study initiation: newborn
- Weight at study initiation:
- Fasting period before study:
- Housing:
- Diet (e.g. ad libitum):
- Water (e.g. ad libitum):
- Acclimation period:


ENVIRONMENTAL CONDITIONS
- Temperature (°C):
- Humidity (%):
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light):


IN-LIFE DATES: From: To:

Administration / exposure

Type of coverage:

not specified

Vehicle:

other: not specified

Details on exposure:

Route of Administration: percutaneously, as a solution
TEST SITE
- Area of exposure:
- % coverage: no data
- Type of wrap if used: no data
- Time intervals for shavings or clipplings:


REMOVAL OF TEST SUBSTANCE
- Washing (if done): no data
- Time after start of exposure: no data


TEST MATERIAL
- Amount(s) applied (volume or weight with unit):
- Concentration (if solution):
- Constant volume or concentration used:
- For solids, paste formed: yes/no


VEHICLE
- Justification for use and choice of vehicle (if other than water):
- Amount(s) applied (volume or weight with unit):
- Concentration (if solution):
- Lot/batch no. (if required):
- Purity:

USE OF RESTRAINERS FOR PREVENTING INGESTION: no data

Duration of treatment / exposure:

2 groups for each dose - 5 weeks or 12 weeks
In the high dose group (500 mg/kg) the 7 weeks from week 6-12 served as a recovery period, in the other two dose groups dosing was contimued until week 12.

Frequency of treatment:

no data

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
0, 5, 50 (12 weeks)
Basis:

Doses / concentrations 2

Remarks:

Doses / Concentrations:
0, 5, 50, 500 mg/kg/d (5 weeks)
Basis:

No. of animals per sex per dose:

no data

Control animals:

yes

Details on study design:

Post-exposure period: 7 weeks (500 mg/kg/d group only)

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: No

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule:
no data
DERMAL IRRITATION (if dermal study): No data

BODY WEIGHT: no data
- Time schedule for examinations:


FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight
gain data: No

WATER CONSUMPTION: No

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: Yes
- Time schedule for collection of blood: no data
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: no data
- Parameters checked in table [No.?] were examined.

CLINICAL CHEMISTRY: Yes
- Animals fasted: No data


URINALYSIS: No

NEUROBEHAVIOURAL EXAMINATION: Yes

Sacrifice and pathology:

GROSS PATHOLOGY AND ORGAN WEIGHTS
yes, but no details reported
Histopathology:
yes, but no details reported

Statistics:

no data

Results and discussion

Results of examinations

Dermal irritation:

not examined

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

not specified

Behaviour (functional findings):

effects observed, treatment-related

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

not examined

Details on results:

Results: Clincal signs of neurotoxicity in 15/23 animals at 500 mg/kd/d. First observed at day 23. The incidence and severity of the toxic signs steadily increased (5 weeks). The effects were reversible within 20 days after the last administration. No adverse effects were noted at 5 and 50 mg/kg/d.
No abnormalities were observed in haematology, clinical chemistry, gross and microscopic pathology of the treated animals.

Effect levels

1

Dose descriptor:

NOAEL

Effect level:

50 other: mg/kg

Sex:

male/female

Basis for effect level:

other: neurobehaviour

2

Dose descriptor:

other: LDL0

Effect level:

> 500 other: mg/kg

Sex:

male/female

Basis for effect level:

other: mortality

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

Neurotoxic effects were observed. The NOAEL for male rabbits in this dermal study was considered to be 50 mg/kg.