Styrene

Repeated dose toxicity: other routes

Administrative data

Endpoint:

short-term repeated dose toxicity: other route

Type of information:

experimental study

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

Reference

Reference 1

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 2

Reference Type:

review article or handbook

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

Bibliographic source:

Styrene CAS No. 100-42-5, EINECS No. 202-851-5, Draft for submission to SCHER, November 2007

Materials and methods

Principles of method if other than guideline:

4-Vinylphenol was administered intraperitoneally to rats 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

Test material information

Constituent 1

Reference substance name:

Styrene

EC Number:

202-851-5

EC Name:

Styrene

Cas Number:

100-42-5

Molecular formula:

C8H8

IUPAC Name:

ethenylbenzene

Specific details on test material used for the study:

The substance tested is a metabolite of styrene.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: female: Charles River, Sulzfeld, Germany
- Age at study initiation: 5-6 weeks
- Weight at study initiation: 129-160 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 rat

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

Effect levels

Dose descriptor:

NOAEL

Remarks:

(4-VP)

Effect level:

> 60 mg/kg bw/day

Sex:

female

Basis for effect level:

other: no adverse effects observed at doses up to 60 mg/kg bw/day administered ip for 14 consecutive days.

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

No data about the effects of 4 -VP on body weight, clinical signs and serum sorbitol dehydrogenase were given.

No histopathological effects of 4 -VP were found in the lungs or liver of the rats (see table.)

Histopathological lesions

	Dose [mg/kg/d] (a)
	0	2	6	20	60
Number examined	5	5	5	5	5
Liver, fatty change, portal	2	0	4	2	1
Lung, foam cells	0	1	0	0	0

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