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Toxicological information

Repeated dose toxicity: dermal

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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

Constituent 1
Chemical structure
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 / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0, 5, 50 (12 weeks)
Basis:

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

open allclose all
Dose descriptor:
NOAEL
Effect level:
50 other: mg/kg
Sex:
male/female
Basis for effect level:
other: neurobehaviour
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.