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Toxicological information

Specific investigations: other studies

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Administrative data

Endpoint:
specific investigations: other studies
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: GLP guideline study.
Cross-reference
Reason / purpose for cross-reference:
reference to same study

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Ring-oxidized metabolites of styrene contribute to styrene-induced Clara-cell toxicity in mice.
Author:
Cruzan G, Carlson GP, Turner M, Mellert W.
Year:
2005
Bibliographic source:
J Toxicol Environ Health, Part A 68(3): 229-237
Reference Type:
secondary source
Title:
European risk assessment report, Styrene CAS No. 100-42-5, EINECS No. 202-851-5, Draft for submission to SCHER, November 2007.
Author:
European Union
Year:
2007

Materials and methods

Principles of method if other than guideline:
In a study conducted to investigate the role of the ring-oxidized metabolite of styrene, 4-VP, in mouse lung toxicity, groups of 4-5 male CD-1 mice received a single ip injection of 0 or 100 mg/kg 4-VP.
GLP compliance:
yes
Type of method:
in vivo
Endpoint addressed:
not applicable

Test material

Constituent 1
Chemical structure
Reference substance name:
p-vinylphenol
EC Number:
220-103-6
EC Name:
p-vinylphenol
Cas Number:
2628-17-3
Molecular formula:
C8H8O
IUPAC Name:
4-vinylphenol
Details on test material:
- Name of test material (as cited in study report): 4-vinylphenol (Sigma-Aldrich or Lancaster Synthesis, Windham, NH)
- Analytical purity: no data
- Storage condition of test material: 10% 4-vinylphenol in propylene glycol

Test animals

Species:
mouse
Strain:
CD-1
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River, Wilmington, MA
- Weight at study initiation: 22-24 g
- Housing: in air conditioned rooms
- Diet (e.g. ad libitum): standard rodent diet (Purina 5001, Purina Milss, St. Louis, MO) or pellets (Provimi KLIBA SA, Kaiseraugst, Switzerland)
- Water (e.g. ad libitum): from water bottles


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24 °C
- Humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
physiological saline
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
single injection
Frequency of treatment:
once
Post exposure period:
12, 24, 48 and 72 h, 4 and 6 d
Doses / concentrations
Remarks:
Doses / Concentrations:
100 mg/kg bodyweight
Basis:
nominal conc.
No. of animals per sex per dose:
4-5
Control animals:
yes
Details on study design:
Groups of 4 to 5 male CD-1 control mice or mice administered 100 mg/kg 4-vinylphenol ip (weighing 22-24 g) were sacrificed after 12, 24, 48 or 72 h or 4 or 6 d. Mice were anesthetized with diethyl ether; the trachea was exposed, where a small nick was made and an oral feeding needle inserted and tied in place. The lungs were lavaged twice with 0.8 ml of room-temperature lavage fluid (total 1.6 ml); recovery was about 85%. The fluid consisted of NaCl (145 mM), KCl (5 mm), NaH 2PO 4 (1.9 mm), Na2HPO4 (9.4 mM), and glucose (5.5 mm) at a pH of 7.4.

The difference from control was evaluated using Student's test (Instat by GraphPad Software, San Diego, CA) with a significance value of p < 0.05. Serum sorbitol dehydrogenase was evaluated by the Kruskal-Wallis nonparametric test (Siegel, 1956) with a significance value of p < 0.05.

Examinations

Examinations:
The number of cells in 100 µl bronchoalveolar lavage fluid (BALF) was counted using a hemocytometer. The remaining BALF from each mouse was centrifuged at low speed, the amount of protein was determined using the bicinchoninic method (Redinbaugh & Turley, 1986), and lactate dehydrogenase (LDH) activity was measured by the spectrophotometric method of Vassault (1983).

Results and discussion

Details on results:
4-Vinylphenol administration resulted in lung damage as measured by increased lactate dehydrogenase (LDH) activity (approx. 2-fold compared to controls), and cells in bronchoalveolar lavage fluid (BALF) 12 h after a single 100-mg/kg ip administration to CD-1 mice. LDH activity remained elevated until d 4; the number of cells remained elevated until d 6 (approx. 7- to 20-fold compared to controls). Protein was significantly elevated only on d3.

Any other information on results incl. tables

Lactate dehydrogenase (a)

Cells (b)

Protein (c)

Time after application

Control

4-VP

Control

4-VP

Control

4-VP

12 h

125.6 ± 26.3

200.2 ± 12.8 (d)

109 ± 37

795 ± 116 (d)

524 ± 59

452 ± 67

24 h

92.5 ± 23.1

254.2 ± 26.0 (d)

40 ± 14

1104 ± 89 (d)

408 ± 48

454 ± 52

48 h

97.5 ± 21.0

210.1 ± 25.7 (d)

44 ± 13

753 ± 230 (d)

360 ± 40

486 ± 63

72 h

73.0 ± 14.1

156.6 ± 14.7 (d)

76 ± 14

1415 ± 41 (d)

360 ± 28

598 ± 68 (d)

4 d

89.2 ± 16.9

86.1 ± 4.5

67 ± 16

345 ± 200 (d)

368 ± 25

478 ± 51

6 d

77.8 ± 9.1

104.5 ± 11.8

76 ± 21

51 ± 15

442 ± 10

520 ± 33

(a)   µmol/min/L of bronchoalveolar lavage fluid

(b)  cells/µL bronchoalveolar lavage fluid

(c)   µg protein/ µL bronchoalveolar lavage fluid

(d)  significantly different from control p<0.05

Applicant's summary and conclusion