Styrene

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

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:

- Name of test material (as cited in study report): Styrene
- Physical state: liquid
- Analytical purity: 99.86 % (w/w)
- Impurities (identity and concentrations): ethylbenzene 0.040 % (w/w), α-methylstyrene 0.030 % (w/w)
- Lot/batch No.: 20041209
- Stability under test conditions: Polymerized in air, light, heat and peroxyacid. Polymerization inhibitor is added (approx. 20 ppm). Test substance was stable during the dosing period.
- Storage condition of test material: cold and dark (refrigerator)
- Other: Supplier: Asahi Kasei Chemicals Corporation

Test animals

Species:

rat

Strain:

other: Crj: CD (SD) IGS

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Japan (Hino Breeding Center)
- Age at study initiation: males 7 wks, females 8 wks
- Weight at study initiation: males 252.3 - 277.3 g, females 217.9 - 233.6 g
- Fasting period before study:
- Housing: individually in stainless steel cages with wire mesh floors in a barrier-system animal room
- Diet (e.g. ad libitum): autoclaved MF pelleted diet (lot no. 041102, Oriental Yeast) ad libitum
- Water (e.g. ad libitum): clorinated water from the Hita City supply ad libitum
- Acclimation period:1 wk


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.6 - 23.9
- Humidity (%): 51.8 - 56.6
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: clipped dorsal area of the trunk (5x4 cm)
- % coverage: approx. 10 % of the total body surface area
- Type of wrap if used: test site covered with a cotton lint (4x4 cm, Nankei Sangyo) and adhesive bandage (ALCARE)


REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, with Otsuka distilled water, lot no. 3G79N, Otsuka Pharmaceutical Factory
- Time after start of exposure: 24 h


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.21 ml/kg
- Concentration (if solution): undiluted
- Constant volume or concentration used: yes

Duration of exposure:

24 h

Doses:

2000 mg/kg

No. of animals per sex per dose:

5

Control animals:

other: yes, sham-exposed

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical signs were recorded just after dosing and 5, 10 and 30 min and 1, 2, 3 and 4 hr after dosing, twice daily from day 1 to 3 after dosing, and thereafter once daily by day 14. Body weights were measured just before dosing and on days 1, 7 and 14 post-dosing.
- Necropsy of survivors performed: yes, all animals were euthanized at the termination of the observation period by exsanguination under ether anesthesia, and subjected to a detailed gross necropsy.
- Other examinations performed: clinical signs, body weight

Statistics:

The mean and standard deviation in each group were calculated in the body weights.

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Remarks on result:

other: Limit test

Effect levels 2

Sex:

male/female

Dose descriptor:

LD0

Effect level:

2 000 mg/kg bw

Remarks on result:

other: Limit test

Mortality:

No deaths occurred in males and females.

Clinical signs:

other: Control: Decreased spontaneous locomotion was observed in the control group from 30 min to 4 hr (males) and 1 hr to 4 hr (females) after dosing, and disappeared on day 1. 2000 mg/kg: Decreased spontaneous locomotion from 5 min to 4 hr after dosing in 5/

Gross pathology:

No abnormalities were observed.

Any other information on results incl. tables

Summary of body weights (mean ± S.D.):

	Male		Female
Observation period (day)	Control	2000 mg/kg	Control	2000 mg/kg
0	261.3 ± 10.0	265.0 ± 5.4	222.9 ± 4.3	227.4 ± 4.7
1	262.1 ± 11.9	268.0 ± 7.5	220.4 ± 8.6	216.0 ± 9.6
7	318.3 ± 20.9	319.0 ± 11.8	254.6 ± 16.5	251.6 ± 6.7
14	368.3 ± 26.2	363.4 ± 20.3	274.5 ± 19.3	274.7 ± 11.7

Decreased spontaneous locomotion was considered to be not test substance-related, since the same sign was also noted in the control group and considered due to compression by the adhesive bandage. Incomplete eyelid opening, writhing and vocalization were considered related to irritation, as the test substance is classified as eye and skin irritant in the List of Dangerous Substances in EU (JETOC: No. 97; ECETOC: Technical Report No. 66), however, all of them disappeared on the next day after dosing. Decreased body weights observed in females were considered due to compression of the bandage, as it occurred in the control group, as well.