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Toxicological information

Repeated dose toxicity: other routes

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Administrative data

Endpoint:
short-term repeated dose toxicity: other route
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:
4-Vinylphenol was administered intraperitoneally to mice for 14 consecutive days. After 14 days, the animals were necropsied and the liver and lungs were examined histopathologically.
GLP compliance:
yes
Limit test:
no

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:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River, Sulzfeld, Germany
- Age at study initiation: 11-12 weeks
- Weight at study initiation: 27-31 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:
not specified
Duration of treatment / exposure:
14 days
Frequency of treatment:
daily (doses are splitted into 3 daily doses; at intervals of 2 hours)
Doses / concentrations
Remarks:
Doses / Concentrations:
2, 6, 20, 60 mg/kg/day mouse
No. of animals per sex per dose:
5
Control animals:
yes

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: No data


DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily


BODY WEIGHT: Yes
- Time schedule for examinations: study days 0, 3, 7 and 14


OPHTHALMOSCOPIC EXAMINATION: No


HAEMATOLOGY: No


CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: on study days 1, 7 and 13
- Animals fasted: No data
- How many animals: 5
- Parameters checked: serum sorbitol dehydrogenase


URINALYSIS: No


NEUROBEHAVIOURAL EXAMINATION: No
Sacrifice and pathology:
GROSS PATHOLOGY: No data
HISTOPATHOLOGY: Yes, liver and lungs
Statistics:
body weight: Dunnett´s t-test with significant value of p< 0.05
serum sorbitol dehydrogenase: Kurskal-Wallis nonparametric test with significant value of p< 0.05

Results and discussion

Results of examinations

Details on results:
There were no effects on bodyweight and no clinical signs of toxicity. Also, there were no effects on SDH activity, or liver histology. Multifocal hyperplasia (minimal to slight) was seen in the medium and terminal bronchioles of 3/5 mice exposed to 6 or 20 mg/kg/day and of all mice at 60 mg/kg/day (slight to moderate).

Effect levels

open allclose all
Dose descriptor:
NOAEL
Remarks:
(4-VP)
Effect level:
2 mg/kg bw/day
Sex:
female
Dose descriptor:
LOAEL
Remarks:
(4-VP)
Effect level:
6 mg/kg bw/day
Sex:
female
Basis for effect level:
other: Multifocal hyperplasia (minimal to slight) in the medium and terminal bronchioles

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Dose [mg/kg/d] (a)

0

2

6

20

60

Number examined

5

5

5

5

5

Liver, fatty change

0

0

1

0

0

Lung, hyperplasia, bronchiolar

Grade 1(b)

Grade 2 (c)

Grade 3 (d)

0

0

1

1

1

0

0

2

1

0

0

0

0

1

4

(a)    Doses were administered as 3 equally partial doses at 0, 2, and 4 h for 14 consecutive days.

(b)   Grade 1 = minimal severity, very few in number and very small in size.

(c)    Grade 2 = slight severity, few in number and small in size.

(d)   Grade 3 = moderate severity, moderate in number and moderate in size.

Applicant's summary and conclusion