4-(4-isopropoxyphenylsulfonyl)phenol

Endpoint summary

Description of key information

D-8 was tested for acute toxicity by oral and dermal application in fixed dose studies in the rat. These studies showed a LD50 > 2000 mg/kg bw via both application routes. D-8 was tested for inhalation toxicity in rats in a 4 h nose-only inhalation study according to EU Method B.2. 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.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1986-04-30 to 1986-07-25

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OTS 798.1175 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Interfauna UK Ltd.; Huntingdon; Cambridgeshire; England;
- Age at study initiation: four to six weeks;
- Weight at study initiation: 90 to 134 g;
- Fasting period before study: overnight prior to dosing;
- Housing: metal cages with wire-mesh plates;
- Diet: Labsure LAD 1 standard laboratory rodent diet ad libitum;
- Water: municipial tap water ad libitum;
- Acclimation period: 6 days;

ENVIRONMENTAL CONDITIONS
- Temperature: 21 to 23 °C;
- Humidity: mean 57 % R.H. daily;
- Air changes: 15 air changes per hour;
- Photoperiod: 12 hours dark/12 hours light per day;

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

D-8 was prepared at 50 % w/v in 1 % aqueous methylcellulose and administerd at a volume of 10.0 mL/kg.
The appropriate dose volume of the test substance was administered to each rat using a syringe and a plastic catheter.

Doses:

5.0 g/kg

No. of animals per sex per dose:

five males/five females

Control animals:

no

Details on study design:

Preliminary study:
A trial test was carried out by dosing two male and two female rats at 5.0 g/kg bw.
Main study:
A group of ten rats (five males and five females) was treated at 5.0 g/kg bw.

Preliminary study:

No mortalities were observed during the preliminary study.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Mortality:

No mortality was observed neither during the preliminary study nor the main study.

Clinical signs:

other: Pilo-erection, abnormal body carriage (hunched posture), abnormal gait (waddling), lethargy, pallor of extremities, increased salivation and diarrhoea were observed in all rats shortly after dosing. There were no other clinical signs and recovery, as judg

Gross pathology:

Terminal autopsy findings wrere normal.

Other findings:

No other findings

The acute lethal oral dose to rats of D-8 was found to be greater than 5.0 g/kg bw.

No mortalities were found during the observation period. No significant signs of toxic effects could be detected during necropsy.

Table: Results of toxicity testing of D-8

Study	Dose (g/kg)	Mortality ratio (no. of deaths/no. dosed)
		males	females	combined
Preliminary	5.0	0/2	0/2	0/4
Main	5.0	0/5	0/5	0/10

 

Interpretation of results:

GHS criteria not met

Conclusions:

D-8 was tested for acute oral toxicity in rats according to EU Test Guideline B.1. The acute lethal oral dose to rats of D-8 was found to be greater than 5000 mg/kg bw.

Executive summary:

D-8 was tested for acute oral toxicity in rats. The substance was administered by gavage to male and female rats in a single dose of 5.0 g/kg bw. No mortalities occured during the observation period. No clinical signs of toxicity could be observed during necropsy after termination of the the study. It was concluded that the acute lethal oral dose for D-8 in rats was greater 5000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

OECD TG 401

Acute toxicity: via inhalation route

Link to relevant study records

Reference

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

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2008-05-31

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

1981-05-12

Deviations:

no

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

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.;

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

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.04 mg/L air (analytical)

Exp. duration:

4 h

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

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

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

5 000 mg/m³ air

Quality of whole database:

OECD TG 403

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1990-04-10 to 1990-05-10

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Limited; Margate, Kent;
- Age at study initiation: approximately 7 to 9 weeks;
- Weight at study initiation: approximately 200 g;
- Fasting period before study: not indicated;
- Housing: individually in grid bottomed polypropylene cages;
- Diet: SQC R and M No. 1 expanded pelleted rodent diet ad libitum; Supplier: Special Diet Services; Witham, Essex;
- Water: mains drinking water from polypropylene bottles ad libitum;
- Acclimation period: eleven days before dosing

ENVIRONMENTAL CONDITIONS
- Temperature: 18 to 21 °C;
- Humidity: 41 - 58 % R.H.;
- Air changes: not stated;
- Photoperiod: 12 hrs dark/12 hrs light;

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

Weighed aliquots of the test materials were applied to the clipped skin of the test animals in a dose level of 2000 mg/kg bw. The test material was moistened with water to assure intense contact with the skin of the animals. After spreading of the test material as even as possible on the skin of the test animals, the pplication site was covered with surgical gauze. The trunk of the test animals was then encircled by a length of elastic adhesive bandage to keep the material in contact withthe skin.

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 males; 5 females

Control animals:

no

Details on study design:

All animals were examined at approximately 30 minutes and 1, 2 and 4 hours after dosing and then daily for fourteen consecutive days. Any signs of toxicity or other effects were noted along with the time of onset and duration. Animals were weighed at weekly intervals.

Statistics:

NA

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Remarks on result:

other: no

Sex:

male/female

Dose descriptor:

LD0

Effect level:

2 000 mg/kg bw

Mortality:

No mortalities were observed throughout the study.

Clinical signs:

other: No effects of treatment were observed throughout the study.

Gross pathology:

No significant abnormalities were found at necropsy.

Other findings:

No other findings were observed.

D-8 caused no apparent toxic effect and no mortality following the dermal administration to rats as a single dose of 2000 mg/kg. bw. No effects of treatment were observed throughout the study and no significant abnormalities were found at necropsy.

Interpretation of results:

GHS criteria not met

Conclusions:

D-8 was tested for acute dermal toxicity in the rat by occlusive application of a single dose of 2000 mg/kg bw. No effects of treatment were observed throughout the study and no significant abnormalities were found at necropsy. It was concluded that the LD50 of the dermal toxicity is greater than 2000 mg/kg bw.

Executive summary:

D-8 was tested for dermal toxicity in five male and five female rats. The test substance was applied in a single dose of 2000 mg/kg bw to the clipped skin of the animals under an occlusive dressing for 24 hours. After removing of the test article, animals were observed fourteen days for signs of treatment. No signs of toxicity were observed throughout the duration of the study. No significant abnormalities were detected at necropsy. The lethal dose on dermal application was determined to be greater than 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

EU method B.3

Additional information

Oral

D-8 was tested for acute oral toxicity in a fixed dose study in the rat according to EU Method B.1 / OECD Guideline 401. The LD50 for male and female rats was found to be > 5000 mg/kg bw.

Dermal

D-8 was tested for acute dermal toxicity in a fixed dose study in the rat according to EU Method B.3 / OECD Guideline 402. The LD50 for male and female rats was found to be > 2000 mg/kg bw. Under the conditions of the applied tests, D-8 was considered practically non-toxic following dermal application.

Inhalation

D-8 was tested for inhalation toxicity in rats in a 4 h nose-only inhalation study according to EU Method B.2 / OECD Guideline 403. 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. Under the conditions of the applied test, D-8 was considered practically non-toxic.

Justification for classification or non-classification

Classification, Labeling, and Packaging Regulation (EC) No 1272/2008

The available data for acute toxicity are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on this data, the substance is not considered to be classified for acute toxicity under Regulation (EC) No 1272/2008, as amended for the twelfth time in Regulation (EU) No 2019/521.