Methacrylic anhydride

Neurotoxicity

Administrative data

Endpoint:

neurotoxicity: sub-chronic inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: FOB segment in full guideline inhalation study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Guideline:

other: FOB in subchronic inhalation study

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Methacrylic acid

EC Number:

201-204-4

EC Name:

Methacrylic acid

Cas Number:

79-41-4

Molecular formula:

C4H6O2

IUPAC Name:

2-methylprop-2-enoic acid

Details on test material:

Test substance No.: 06/0581-2
Batch-Identification: 011835eda0
Purity: 99.8 area-%
Homogeneity: Homogeneous
Storage stability: Expiry day: 13 Apr 2008Date of production: 12 Apr 2007
Physical state/Appearance:Liquid / colorless, clear
Storage conditions: Room temperature, no direct sunlight, under light exclusion,
protect against heat, storage between 18-25°C, under atmospheric oxygen

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Age when supplied; sex: about 7 weeks, male and female
Supplier: Charles River Laboratories, Research Models and Services, Germany GmbH; Sandhofer Weg 7, 97633 Sulzfeld
During the period when the rats were not exposed they were housed singly in wire cages (type DK III, Becker & Co., Castrop-Rauxel, FRG (floor area about 800 cm²)). Underneath the cages, waste trays were fixed containing bedding material (Type Lignocel FS14 fibres,
dustfree bedding supplied by SSNIFF, Soest, Germany)
The motor activity measurements were conducted in Polycarbonate cages with wire covers from Ehret, Emmendingen, FRG (floor area about 800 cm²) and bedding.
The animals were kept in fully air-conditioned rooms in which a temperature in the range of 20 - 24°C and relative humidity in the range of 30 - 70% were ensured by means of a central air-conditioning system.
A light/dark rhythm of 12 hours was maintained.
The room was completely disinfected using a disinfector ("AUTEX", fully automatic, formalinammonia-based terminal disinfector) before the start of the study. Usually, each week the floor and the walls were cleaned with water containing about 1 % Mikroquat®.
The animals were maintained on milled mouse/rat laboratory diet “GLP”, (Provimi Kliba SA, Kaiseraugst, Basel Switzerland) and tap water ad libitum.

Administration / exposure

Route of administration:

inhalation: vapour

Vehicle:

air

Details on exposure:

For each concentration, the test substance was supplied to the two-component atomizer of a thermostated vaporizer at a constant rate by means of the piston metering pump. The vapor was generated by spraying the substance with compressed air into a counter current of conditioned supply air (about 50% ± 20% relative humidity, 22°C ± 2°C). Thereafter it was further mixed with conditioned supply air and passed into the inhalation system.

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

The concentrations of the inhalation atmospheres in test groups 1 - 4 were analyzed by HPLC.

Duration of treatment / exposure:

90 d

Frequency of treatment:

6 hours/day, 5 days/week

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 70 mg/m³ (20 ppm), 141 mg/m³ (40 ppm), 352 mg/m³ (100 ppm ), 1232 mg/m³ (350 ppm )
Basis:

No. of animals per sex per dose:

10/sex/dose

Control animals:

yes, sham-exposed

Details on study design:

Ten male and ten female Sprague Dawley rats per test group were whole body exposed to a vapor of the test substance on 6 hours per working day for 90 days (65 exposures). The target concentrations were 20, 40, 100 and 350 ppm (corresponding to 70, 141, 352 and 1232 mg/m3). A concurrent control group was exposed to conditioned air.

Examinations

Observations and clinical examinations performed and frequency:

Functional observation battery (FOB) was carried out on the assigned animals once before the exposure period and once against the end of the exposure period. Motor activity was measured on the same day and with the same animals as FOB was performed.

Results and discussion

Results of examinations

Behaviour (functional findings):

no effects observed

Details on results:

Up to the highest dose tested (350 ppm) there were no effects in the functional observational battery and no effects on motor activity.

Effect levels

Dose descriptor:

NOAEC

Effect level:

350 ppm

Sex:

male/female

Basis for effect level:

other: = 1232 mg/m³

Remarks on result:

other:

Any other information on results incl. tables

Up to the highest dose tested (350 ppm) there were no effects in the functional observational battery and no effects on motor activity.

Applicant's summary and conclusion

Conclusions:

Up to the highest dose tested (350 ppm) there were no effects in the functional observational battery and no effects on motor activity.

Executive summary:

Methacrylic acid was tested for subchronic inhalation toxicity. Up to the highest dose tested (350 ppm) there were no effects in the functional observational battery and no effects on motor activity.