1,3-Propanediol, 2,2-bis(hydroxymethyl)-, polymer with 2-(chloromethyl)oxirane, 2-propenoate

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

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:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to standard guidelines in compliance with GLP.

Data source

Reference

Reference Type:

publication

Title:

Toxicology Studies of Pentaerythritol Triacrylate in F344/N Rats, B6C3F1 Mice and Genetically Modifies (FVB tg.AC Hemizygous) Mice (Dermal Study)

Author:

NTP

Year:

2005

Bibliographic source:

US. Department of Health and Human Services

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Principles of method if other than guideline:

MacGregor JT et al (1990)

GLP compliance:

yes

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

Pentaerythritol triacrylate

IUPAC Name:

Pentaerythritol triacrylate

Constituent 2

Reference substance name:

2-(hydroxymethyl)-2-[[(1-oxoallyl)oxy]methyl]-1,3-propanediyl diacrylate

EC Number:

222-540-8

EC Name:

2-(hydroxymethyl)-2-[[(1-oxoallyl)oxy]methyl]-1,3-propanediyl diacrylate

Cas Number:

3524-68-3

IUPAC Name:

3-(acryloyloxy)-2-[(acryloyloxy)methyl]-2-(hydroxymethyl)propyl acrylate (non-preferred name)

Details on test material:

- Name of test material (as cited in study report): Pentaerythritol triacrylate
- Physical state: clear, viscous liquid
- Lot/batch No.: HCC0340 (Sartomer Co.)

Test animals

Species:

mouse

Strain:

B6C3F1

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Source: Taconic Laboratory Animals and Service (Germantown, NY)
- Age at study initiation: 6 weeks
- Assigned to test groups randomly: Yes
- Housing: Individually housed in polycarbonate cages
- Diet (e.g. ad libitum): NTP-2000 pelleted diet (Zeigler Brothers, Inc., Gardners, PA), ad libitum, changed weekly
- Water (e.g. ad libitum): Tap water (Columbus municipal supply), ad libitum
- Acclimation period: 11-15 d

Administration / exposure

Route of administration:

dermal

Vehicle:

- Vehicle(s)/solvent(s) used: acetone

Details on exposure:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2 ml/kg bw

Duration of treatment / exposure:

3 months

Frequency of treatment:

5 days per week for 14 weeks

Doses / concentrations

Remarks:

Doses / Concentrations:
0.75, 1.5, 3, 6 and 12 mg/kg bw
Basis:
nominal conc.

No. of animals per sex per dose:

10

Control animals:

yes, concurrent vehicle

Positive control(s):

No data

Examinations

Tissues and cell types examined:

Peripheral blood samples

Details of tissue and slide preparation:

TREATMENT AND SAMPLING TIMES: Peripheral blood samples were obtained from male and female mice at the end of the study.
DETAILS OF SLIDE PREPARATION: Smears were immediately prepared and fixed in absolute methanol. The methanol fixed slides were stained with acridine orange and coded.
METHOD OF ANALYSIS: Slides were scanned to determine the frequency of micronuclei in 2,000 normochromatic erythrocytes (NCEs) per animal. In addition, the normochromatic/polychromatic erythrocyte (NCE/PCE) ratio in 1,000 total erythrocytes per animal was determined to provide a measure of chemical-induced bone marrow toxicity.

Statistics:

- Results were analyzed by a statistical software package

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

no effects

Any other information on results incl. tables

Frequency of micronuclei in peripheral blood normochromatic erythrocytes of B6C3F1 mice following dermal application of pentaerythritol triacrylate for 3 months^a

 

Compound	Dose (mg/kg)	Number of Mice with Erythrocytes Scored	Micronucleated NCEs/ 1,000 NCEs^b	P Value^c	NCEs^b(%)
Male
Acetone^d		10	1.20 ± 0.21		98.2 ± 0.1
Pentaerythritol triacrylate	0.75	10	0.75 ± 0.15	0.9253	98.1 ± 0.1
	1.5	10	1.00 ± 0.15	0.7269	98.4 ± 0.1
	3	10	0.90 ± 0.19	0.8229	98.3 ± 0.1
	6	10	1.05 ± 0.22	0.6727	98.4 ± 0.1
	12	10	1.05 ± 0.16	0.6727	98.2 ± 0.1
			P=0.394^e
Female
Acetone		9	0.72 ± 0.15		98.2 ± 0.1
Pentaerythritol triacrylate	0.75	10	0.65 ± 0.15	0.606	98.1 ± 0.1
	1.5	9	0.78 ± 0.19	0.4237	98.3 ± 0.1
	3	10	0.65 ± 0.17	0.606	98.3 ± 0.1
	6	10	0.90 ± 0.18	0.2722	98.3 ± 0.1
	12	10	0.85 ± 0.11	0.329	98.4 ± 0.1
			P=0.210

 ^aStudy was performed at SITEK Research Laboratories, Inc.

NCE=normochromatic erythrocyte

^bMean ± standard error

^cPairwise comparison with the vehicle controls, significant at P ≤ 0.005

^dVehicle control

^eSignificance of micronucleated NCEs/1,000 NCEs tested by the one-tailed Cochran-Armitage trend test, significant at P ≤ 0.025