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Toxicological information

Genetic toxicity: in vivo

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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:
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

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
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 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 monthsa

 

Compound

Dose (mg/kg)

Number of Mice with Erythrocytes Scored

Micronucleated NCEs/ 1,000 NCEsb

P Valuec

NCEsb(%)

Male

Acetoned

 

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=0.394e

 

 

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

Applicant's summary and conclusion