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Administrative data

Endpoint:
short-term repeated dose toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
The subacute inhalation toxicity of 109 industrial chemicals
Author:
Gage JC
Year:
1970
Bibliographic source:
Brit. J. Industr. Med., 27, 1-18
Reference Type:
publication
Title:
Gage J.C., Brit. J. Industr. Med., 27, 1-18, 1970
Author:
Gage JC
Year:
2003
Bibliographic source:
cited in: OECD SIDS, 2-Dimethylaminoethylmethacrylate, CAS No: 2867-47-2, 07/2003

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Short-term vapor inhalation toxicity was studied in rats with a constant flow pump for 3 wks, 5 d/w, 6 h/d.
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
2-dimethylaminoethyl methacrylate
EC Number:
220-688-8
EC Name:
2-dimethylaminoethyl methacrylate
Cas Number:
2867-47-2
Molecular formula:
C8H15NO2
IUPAC Name:
2-(dimethylamino)ethyl methacrylate
Details on test material:
Purity not specified, but commercial grade assumed.
Specific details on test material used for the study:
TEST MATERIAL:
- Name of test material: 2-Dimethylaminoethyl methacrylate

Test animals

Species:
rat
Strain:
other: Alderly Park SPF
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 700 g
- Diet: ad libitum except during exposures
- Water: ad libitum except during exposures

Administration / exposure

Route of administration:
other: inhalation: vapour at 100 ppm, possibly mist at 250 ppm
Type of inhalation exposure:
whole body
Vehicle:
other: air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Rats were exposed in a chamber described elsewhere (Gage, 1959); usually the inner Perspex chamber of that design was replaced by a glass cylinder, 30 cm diameter and 25 cm high.
- Method of conditioning air: The air used for the atmospheres was filtered, dried to a relative humidity of less than 10%, and supplied at a line pressure of 1 atm (1.013x10E+5 NmE-2).
- Method of atmosphere generation: A vapour concentration by injecting a liquid at a known rate into a metered stream of air by means of a controlled fluid-feed atomizer (Gage, 1953).
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
3 weeks
Frequency of treatment:
6 hrs/day, 5 days/week
Doses / concentrationsopen allclose all
Dose / conc.:
100 ppm (nominal)
Dose / conc.:
250 ppm (nominal)
No. of animals per sex per dose:
4
Control animals:
other: At intervals of about two months, batches of control rats were maintained in a chamber for the exposure period, in order to check the characteristics of the colony.
Details on study design:
- Design of the experiments: Alderley Park specific-pathogen-free rats with an average weight of 700 g were used in nlost of these experirnents. They were maintained in the exposure chamber for periods of up to 6 hours, and between repeated daily exposures they were returned to their cages where food and water were freely available. In the initial experiments the concentrations were selected to produce, if possible, acute effects after short exposures. Thereafter the exposure period was extended and the concentration lowered until the animals could survive 6-hour exposures, five days a week for up to four weeks. With liquids, the vapour pressure limited the range of concentrations which could be tested in these acute and subacute
experiments.
If at any stage effects were observed which could be attributed to the exposure, the experiment was repeated with progressively lower concentrations until a concentration was reached which was without effects on the animals.

Examinations

Observations and examinations performed and frequency:
The rats were weighed each morning, and their conditions and behaviour were recorded throughout the exposure period. Urine was collected overnight after the last exposure day for biochemical tests. The animals were left overnight with food and drink. On the following day the rats were anaesthetized with halothane and partially exsanguinated by heart puncture for haematological tests.
Sacrifice and pathology:
One day after the last exposure day rats were anaesthetized with halothane and partially exsanguinated by heart puncture for haematological tests. After a gross examination of the organs, the lungs were inflated with formol-saline and immersed in the same fixative. The following organs were also taken for microscopical examination after fixation in formol-corrosive: lungs, liver,kidneys, spleen, and adrenals; and occasionally heart, jejunum, ileum, and thymus.

Results and discussion

Results of examinations

Details on results:
At 250 ppm: Nose and eye irritation, rapid breathing, weight gain low and irregular. No change of haematological and clinical parameters in blood and urine. No pathological (macroscopical and microscopical) effects on organs were observed.

At 100 ppm: No toxic effects were observed.

Effect levels

open allclose all
Dose descriptor:
NOAEC
Effect level:
100 ppm
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: nose and eye irritation
Dose descriptor:
LOAEC
Effect level:
250 ppm
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: nose and eye irritation

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
The NOAEC for repeated inhalation toxicity is considered to be 100 ppm (643 mg/m³).
Executive summary:

Short-term vapor inhalation toxicity was studied in rats with a constant flow pump for 3 wks, 5 d/w, 6 h/d. At 250 ppm (1608 mg/m³), nose and eye irritation and labored breathing were observed. The body weight gain was slow. There were no changes in the hematological parameters. No pathological (macroscopical and microscopical) effects on organs were observed. At 100 ppm (643 mg/m³), no toxic effects were observed.

Conclusion: The NOAEC for repeated inhalation toxicity is considered to be 100 ppm (643 mg/m³).