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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:
experimental study
Adequacy of study:
key study
Study period:
1996 to 1999
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to standard guidelines in compliance with GLP. Pentaerythritol triacrylate is a constituent of PETIA.
Cross-reference
Reason / purpose for cross-reference:
reference to other study

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
2005

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Deviations:
no
Principles of method if other than guideline:
Method: MacGregor JT et al (1990)
GLP compliance:
yes
Type of assay:
micronucleus assay

Test material

Constituent 1
Reference substance name:
2-Propenoic acid, reaction products with pentaerythritol
EC Number:
629-850-6
Cas Number:
1245638-61-2
Molecular formula:
Not available for this UVCB.
IUPAC Name:
2-Propenoic acid, reaction products with pentaerythritol
Test material form:
other: Colorless or light amber nonvolatile liquid
Details on test material:
- Name of test material: Pentaerythritol triacrylate
- Molecular formula (if other than submission substance): C14H18O7
- Molecular weight (if other than submission substance): 298.3
- Physical state: Liquid (also occurs as a semisolid or crystalline solid at temperatures up to 40°C)
- Analytical purity: 45% (for lot HCC0340)
- Impurities: HPLC indicated a major peak, seven impurity components with areas greater than 1% of the major peak area, and nine impurity components with relative areas between 0.5% and 1%. The impurities were tentatively identified as structurally related adducts, dimers, and acrylates as well as trimethylolpropane triacrylate and its related esters and adducts.
- Lot/batch No.: HCC0340
- Stability under test conditions: No degradation of the bulk chemical was detected
- Storage condition of test material: Stored at room temperature, protected from light in amber glass bottles with Teflon®-lined lids.

Test animals

Species:
mouse
Strain:
B6C3F1
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS:
- 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


ENVIRONMENTAL CONDITIONS
- Temperature (°F): 72 ± 3 °F
- Humidity (%): 50 ± 15 %
- Air changes (per h): 10/h
- Photoperiod (h dark / h light): 12 h dark / 12 h fluorescent light

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
Post exposure period:
No data
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.
Evaluation criteria:
No data
Statistics:
- Results were analyzed by a statistical software package
- Significance of micronucleated NCEs/1,000 NCEs tested by the one-tailed Cochran-Armitage trend test (significant at P ≤ 0.025), followed by Pairwise comparison with the vehicle controls (significant at P ≤ 0.005)

Results and discussion

Test results
Key result
Sex:
male/female
Genotoxicity:
negative
Toxicity:
no effects
Additional information on results:
RESULTS OF DEFINITIVE STUDY
- Induction of micronuclei (for Micronucleus assay): See Table 1
- Ratio of NCE/PCE (for Micronucleus assay): See Table 1

Any other information on results incl. tables

Table 1: 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

Conclusions:
Interpretation of results (migrated information): negative
Under the conditions of this mouse micronucleus assay, the test substance was negative for mutagenic activity.
Executive summary:

A study was conducted to determine the mutagenicity potential of PETIA in the mouse peripheral blood micronucleus test.

The substance (0.75 - 12 mg/kg bw) was administered dermally to male and female B6C3F1 mice for 3 months. Peripheral blood samples were obtained at the end of the study and smears slides were immediately prepared and scanned to determine the frequency of micronuclei in 2,000 normochromatic erythrocytes (NCEs) per animal. In addition, the normochromatic erythrocytes/polychromatic erythrocyte (NCE/PCE) ratio in 1,000 total erythrocytes per animal was determined to provide a measure of chemical-induced bone marrow toxicity.

 

No increase in the frequency of micronucleated NCEs and NCE/PCE ratios were observed in peripheral blood samples from the male or female B6C3F1 mice.

Under the conditions of the study, the test substance was considered to be negative for mutagenic activity.