4-(4-isopropoxyphenylsulfonyl)phenol

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2008-11-18 to 2009-03-10

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EU Method B.2 (Acute Toxicity (Inhalation))

Version / remarks:

2008-05-31

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

1981-05-12

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

Version / remarks:

August 1998

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

4-(4-isopropoxyphenylsulfonyl)phenol

EC Number:

405-520-5

EC Name:

4-(4-isopropoxyphenylsulfonyl)phenol

Cas Number:

95235-30-6

Molecular formula:

C15H16SO4

IUPAC Name:

4-[4-(propan-2-yloxy)benzenesulfonyl]phenol

Details on test material:

- Name of test material: D-8;
- Molecular formula: C15 H16 O4 S;
- Molecular weight: 292.3;
- Physical state: powder,
- Analytical purity: 99.5 %;
- Purity test date: 2008-09-17;
- Lot/batch No.: IHI-006;
- Expiration date of the lot/batch: 2011-09-12
- Stability under test conditions: 36 months;
- Storage condition of test material: Keep away from direct sunlight. Store in a cool dry place. Keep away from oxidizing agents, and high temperature.

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (Europe) Laboratories Inc.; TOXI COOP Ltd., 1003 Budapest Cserkesz u. 90;
- Age at study initiation: 8 - 12 weeks;
- Weight at study initiation: 218 - 321 g;
- Fasting period before study: no;
- Housing: 5 animals/cage in type III polypropylene/polycarbonate cages;
- Diet: ssniff SM R/M--Z+H "Autoclavable Complete Feed fro Rats and Mice; Supplier: ssniff Spezialdiäten GmbH, D-59494 Soest, Germany; ad libitum;
- Water: tap water ad libitum;
- Acclimation period: 16 days;

ENVIRONMENTAL CONDITIONS
- Temperature: 22 +/- 3 °C;
- Humidity: 30 - 70 % R.H.;
- Air changes: at least 15 air changes/h;
- Photoperiod: 12 hours daily, from 6:00 a.m. to 6:00 p.m.;

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

Each rat was individually held in a tapered, polycarbonate restraining tube fitted onto a single tier of the exposure chamber. Only the nose of each animal was exposed to the test atmosphere.
Following an equilibration period of at least the theoretical chamber equilibration time (T99) (Silver, 1946), a group of ten rats (five male and five female) was exposed to an atmosphere of the test material for a period of four hours. A target concentration of 5 mg/L was used for the exposure. As no deaths occurred and the mean achieved concentration was 101 % of target, no further data were required.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

Nominal: 44.99 mg/L;
Mean achieved: 5.04 mg/L;

No. of animals per sex per dose:

5 males/5 females;

Control animals:

no

Details on study design:

The animals were exposed, nose-only, to an atmosphere of the test item using a TSE Rodent Exposure System (TSE Systems GmbH, Bad Homburg, Germany). This system comprises of two, concentric anodised aluminium chambers and a computer control system incorporating pressure detectors and mass flow controllers.
Fresh aerosol from the generation system was constantly supplied to the inner plenum (distribution chamber) of the exposure system from where, under positive pressure, it was distributed to the individual exposure ports. The animals were held in polycarbonate restraint tubes located around the chamber which allowed only the animal’s nares to enter the exposure port. After passing through the animal’s breathing zone, spent aerosol entered the outer cylinder from where it was exhausted through a suitable filter system. Atmosphere generation was therefore dynamic.

Statistics:

NA

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.04 mg/L air (analytical)

Exp. duration:

4 h

Effect levels 2

Sex:

male/female

Dose descriptor:

LC0

Effect level:

5.04 mg/L air

Exp. duration:

4 h

Mortality:

No mortality was observed during the study.

Clinical signs:

other: Wet fur and fur staining on various occasions were commonly recorded on the day of exposure. These observations were considered to be related to the restraint and exposure procedures and, in isolation, were considered not to be biologically significant. S

Body weight:

There was no effect of treatment on body weight or body weight gain.

Gross pathology:

A single four hours nose-only exposure of D-8 to CRL: (WI) BR rat followed by a 14-day observation period at a dose level 5.04 mg/L was not associated with any test article-related macroscopic findings.

Other findings:

NA

Any other information on results incl. tables

Test Atmosphere Concentrations

 

Exposure Duration (minutes)	Sample Volume (L)	Atmospheric Concentration of D-8 (mg/L)
0	2.0	4.80
10	2.0	4.88
40	2.0	3.89
49	2.0	4.56
62	2.0	5.71
96	2.0	7.35
106	2.0	5.04
119	2.0	4.59
131	2.0	4.95
138	2.0	4.78
153	2.0	4.54
166	2.0	5.29
184	2.0	6.22
194	2.0	4.43
206	2.0	5.21
218	2.0	5.08
226	2.0	4.38
232	2.0	5.10

 

Mean Achieved Atmosphere Concentration = 5.04 mg/L

Standard Deviation = 0.78

 

Nominal Concentration:

Amount of Test Item Used (g): 397.71

Total Volume of Air Used (L): 8840

Nominal Concentration = 44.99 mg/L

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

D-8 was tested for inhalation toxicity in rats in a 4 h nose-only inhalation study according to EU Method B.2 Under the experimental conditions of this study, no deaths occurred in a group of ten rats exposed to a mean achieved atmosphere of 5.04 mg/L for four hours. The acute inhalation median lethal concentration (4hr LC50) of D-8, in Wistar Crl:(WI) BR rats, was therefore considered to be greater than 5.04 mg/L.

Executive summary:

This study was designed to assess the acute inhalation toxicity of D-8. A group of ten Wistar Crl:(WI) BR rats (five males and five females) was exposed to an aerosol atmosphere. The animals were exposed for four hours using a nose-only exposure system, followed by a fourteen day observation period. Under the experimental conditions of this study, no deaths occurred in a group of ten rats exposed to a mean achieved atmosphere of 5.04 mg/L for four hours. The acute inhalation median lethal concentration (4hr LC50) of D-8, in Wistar Crl:(WI) BR rats, was therefore considered to be greater than 5.04 mg/L.