2-methylbutyl acrylate

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Read-across of data for an analogous chemical. The target chemical and the source chemical are very closely related alkyl acrylate compounds. They differ only by the addition of a methyl group in the butyl portion of the molecule. Both molecules are expected to be metabolized via the same hydrolysis and enzymatic pathways. The data from the source chemical are experimental results from well documented studies which meet basic scientific principles and are considered to be acceptable with restrictions.

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1978

Report date:

1978

Reference 2

Reference Type:

publication

Title:

n-Butyl Acrylate: Cytogenetic Investigations in the Bone Marrow of Chinese Hamsters and Rats, After 4-Day Inhalation.

Author:

Engelhardt G and Klimisch H-J

Year:

1983

Bibliographic source:

Fundamental and Applied Toxicology 3: 640-641

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)

GLP compliance:

no

Type of assay:

chromosome aberration assay

Test material

Test material information

Constituent 1

Reference substance name:

Butyl acrylate

EC Number:

205-480-7

EC Name:

Butyl acrylate

Cas Number:

141-32-2

IUPAC Name:

butyl acrylate

Details on test material:

- Name of test material (as cited in study report): Butyl acrylate
- Physical state: clear liquid
- Analytical purity: 99.5%
- Impurities (identity and concentrations): 0.0043% Acrylic acid, 0.01% Water, 0.01% Butane, 0.01% n-Butanol, 0.01% Butyl acetate, 0.01% Dibutyl ether, 0.03% isobutyl acrylate, 0.07% methylbutyl acrylate, 0.03% methacrylacidbutyl ether, 0.03% unknown.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: SPF-Breeding, WIGA, Sulzfeld
- Weight at study initiation: males-242 g (215-259 g) and females-190 g (171-215 g)
- Housing: 2-3 rats per cage
- Diet (e.g. ad libitum): Herilan-Mrh supplied by H. Eggersmann KG
- Water (e.g. ad libitum): tap water

Administration / exposure

Route of administration:

inhalation: vapour

Vehicle:

- Vehicle(s)/solvent(s) used: none

Details on exposure:

TYPE OF INHALATION EXPOSURE: whole body


GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION:
A constant amount of n-Butyl acrylate (14.4ml/hr) was delivered using a continuous infusion piston pump to a heated (110° C) glass evaporator. The n-butyl acrylate vapors were diluted with dust-free conditioned air (3200 l/hr; temperature = 22±2° C; humidity - 55±10 %) to deliver the desired concentration of test material to the test animals. The exposure chamber was 200 L. Control animals received fresh air only.

TEST ATMOSPHERE
- Brief description of analytical method used: The n-butyl acrylate air mixture was measured continuously using a flame ionization detector (FID). Apparatus used was a calibrated total hydrocarbons analyzer (CARLO ERBA, mod. 370).
- Samples taken from breathing zone: yes.

Duration of treatment / exposure:

6 hours/day for 4 days

Frequency of treatment:

6 hours/day

Post exposure period:

5 h

Doses / concentrations

Remarks:

Doses / Concentrations:
820 ppm (corresponding to aaprox. 4.3 mg/L) Calculation of concentrations (mg/L) based on Derelanko MJ (2000). Toxicologist's Pocket Handbook, CRC Press, conversion table, p. 57.
Basis:
analytical conc.

No. of animals per sex per dose:

10

Control animals:

yes, sham-exposed

Examinations

Tissues and cell types examined:

Bone marrow

Details of tissue and slide preparation:

CRITERIA FOR DOSE SELECTION: The dose was selected based on results of LC50 and subacute repeated dose studies. Dose of ca. 1/3 of LC50 was considered to be appropriate for this study. LC50/3 = 2145 ppm/3 = ca. 800 ppm. Analytical concentration was found to be 820 ppm.


DETAILS OF SLIDE PREPARATION: Three hours before sacrifice, the animals were injected ip with 3.3 mg/kg of colcemid in order to arrest mitosis in the metaphase. Two hours after the colcemid injection the animals were sacrificed and bone marrow prepared according to the method of Schmid and Staiger (1969). Fifty metaphases were analyzed per animal.

Schmid and Staiger, Mut. Res. 7 :99-108, 1969.

Statistics:

Statistical evaluations was performed using the chi2- test.

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

yes

Remarks:

The 4 days of exposure caused clinical signs of dyspnoea, bloody discharge from eyes and nose and decrease in body weight (6-7 %).

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

not applicable

Additional information on results:

There was no significant increase in the rate of chromosome aberrations in exposed rats with comparison to controls.
No mortality and pathological changes were observed in the exposed animals.

Any other information on results incl. tables

	No. of animals male/female^a	Metaphases Analyzed^b	Aberrant Metaphases						Mitotic index (%) male/female
			Incl. Gaps		Excl. Gaps^c		With Exchanges
			n	%	n	%	n	%
Fresh air control	10/10 (6/6)	1200	5	0.42	0	0	0	0	4.12/3.98
n-butyl acrylate	10/10 (8/8)	1600	2	0.13^d	1	0.06^d	0	0	3.16/3.43

a-       The figures given in parentheses correspond to the number of animals analyzed

b-       100 metaphases/animal

c-       Breaks, fragments, exchanges. No multiple aberrant metaphases (cells with ≥ 5 aberrations) or pulverizations observed.

d-       P>0.05

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative

Executive summary:

The results presented in this summary are experimental results for the source chemical n-butyl acrylate. The results are considered to be appropriate for read-across to the target chemical 2-methylbutyl acrylate.