2-hydroxy-1-(4-(4-(2-hydroxy-2-methylpropionyl)benzyl)phenyl)-2-methylpropan-1-one

Endpoint summary

Description of key information

Studies conducted to recognised testing guidelines with GLP certification.

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:

2002-09-17 to 2002-10-10

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

adopted 17. December 2001

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

adopted 30. September 1996

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd, Laboratory Animal Services; CH-4414 Füllinsdorf / Switzerland
- Age at study initiation: Males: 9 weeks; Females: 13 weeks
- Weight at study initiation (mean): Males: 245.1 g; Females: 183.7 g
- Fasting period before study: fasted for approximately 17 hours before treatment; food was provided again approximately 3 hours after dosing.
- Housing: In groups of 3 rats/sex in Makrrolon type-4 cages
- Diet: Pelleted standard Provimi Kliba 3433 rat maintenance diet, ad libitum
- Water: Community tap water from Fullinsdorf ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Humidity: 30-70 %
- Air changes : 10-15 air changes per hour
- Photoperiod: 12 hours fluorescent light/ 12 hours dark, music during the light period

IN-LIFE DATES: From: 17-Sept-2002 To: 10-Oct-2002

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Remarks:

(PEG 300)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL, based on dose volume
- Amount of vehicle (if gavage): a dose volume of 10 mL/kg bw was used
- Justification for choice of vehicle: The vehicle was chosen after a non-GLP solubility trial, which was performed before the study initiation date.
- Lot/batch no. (if required): 433337/1 20602


MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:

2000 mg/kg bw/d

No. of animals per sex per dose:

3 rats

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: Mortality and viability: twice daily during days 1-15; body weights: On test days 1 (prior to administration), 8 and 15; clinical signs: daily during acclimatization and at approximately 1, 2, 3 and 5 hours after administration on test day 1. Once daily during
days 2-15.
- Necropsy of survivors performed: yes

Statistics:

No statistical analysis was used.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occurred during the study.

Clinical signs:

other: A slight hunched posture was observed in all females at the 2-, 3- and 5-hour examinations on day 1 and was present again in one female on days 2 and 3 and in all females from day 8 to 15. The coats of all females were slightly ruffled at the 2-, 3- and

Gross pathology:

No macroscopic findings were recorded at necropsy.

The median lethal dose of the test item after single oral administration to rats of both sexes, observed over a period of 15 days is:

LD50 (rat) > 2000 mg/kg bw/d.

Interpretation of results:

practically nontoxic

Conclusions:

The oral LD50 of the test material in the Rat was found to be >2000 mg/kg bw.

Executive summary:

In this guideline (OECD 423) study conducted with GLP certification, the acute oral LD50 of the test material (EC 444-860-9) to rats was determined to be >2000 mg/kg bw (both sexes). The test material was administered via gavage at a dose of 2000 mg/kg bw. The result of the test was not sufficient to trigger classification and labelling of the test material for acute toxicity under the EU Classification, Labelling, and Packaging (CLP) regulation (1272/2008).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

other justification

Justification for data waiving:

the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size

Endpoint conclusion

Endpoint conclusion:

no study available

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:

2002-09-19 to 2002-10-10

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

adopted 1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

adopted 1992

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd, Biotechnology and Animal Breeding Division; CH-4414 Füllinsdorf / Switzerland
- Age at study initiation: Males: 9 weeks; Females: 10 weeks
- Weight at study initiation (mean): Males: 257.9 g; Females: 202.18 g
- Fasting period before study: no
- Housing: In groups of 5 rats/sex in Makrolon type 4 cage.
- Diet: Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, batch no. 34/02
- Water: Community tap water from Füllinsdorf ad libitum.
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Humidity: 30-70 %
- Air changes: 10-15 air changes per hour
- Photoperiod: 12 hours fluorescent light/ 12 hours dark, music during the light period


IN-LIFE DATES: From: 19-Sept-2002 To: 10-Oct-2002

Type of coverage:

semiocclusive

Vehicle:

polyethylene glycol

Remarks:

(PEG 300)

Details on dermal exposure:

TEST SITE
- Area of exposure: approximately 10 % of the total body surface
- % coverage: no data
- Type of wrap if used: The dressing was wrapped around the abdomen and fixed with an elastic adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the skin was flushed with lukewarm tap water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): no data
- Concentration (if solution): 500 mg/mL per kg bw, based on dose volume
- Constant volume or concentration used: yes
- For solids, paste formed: no

VEHICLE
- Amount(s) applied (volume or weight with unit): 4 mL/kg bw
- Concentration (if solution): no data
- Lot/batch no. (if required): 4333371/1 20602
- Purity: no data

Duration of exposure:

single dose

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 rats

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: Mortality / Viability: daily during acclimatization and twice daily during days 1 -15; body weights:on test days 1 (prior to administration), 8 and 15; clinical signs: daily during acclimatization and at approximately 1, 2, 3 and 5 hours after administration on test day 1. Once daily during days 2-15. All abnormalities were recorded.
- Necropsy of survivors performed: yes

Statistics:

No statistical analysis was used.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occurred during the study.

Clinical signs:

other: No systemic or local signs of toxicity were observed during the study period.

Gross pathology:

No macroscopic findings were observed at necropsy.

The median lethal dose of the test item after single dermal administration to rats of both sexes, observed over a period of 15 days is: LD50 (rat): greater than 2000 mg/kg bw.

Interpretation of results:

practically nontoxic

Conclusions:

The dermal acute LD50 of the test material is >2000 mg/kg bw in Rats (both sexes).

Executive summary:

In this guideline (OECD 402) study conducted with GLP certification, the acute dermal LD50 of the test material (EC 444-860-9) to the rat was determined to be >2000 mg/kg bw (both sexes). The test material was administered under occlusive conditions as a limit test (2000 mg/kg bw) to male and female for 24 hours, with a post application observation period of 15 days. The result of the test does not trigger classification of the test material as acutely toxic according to the EU Classification, Labelling, and Packaging (CLP) regulation (1272/2008).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

A single dose of the test item was administered by gavage to male and female rats at concentrations of 2000 mg/kg bw. The animals were observed for 14 days. Mortality, body weight and clinical signs were recorded continuously. Organ weighing and gross necropsy was performed after scheduled sacrifice.

A single dose of the test item was applied onto skin of male and female Wistar rats at concentrations of 2000 mg/kg bw. The animals were observed for 14 days. Mortality, body weight and clinical signs were recorded continuously. Organ weighing and gross necropsy was performed after scheduled sacrifice.

No mortality occurred in any of the two studies. Clinical signs of toxicity, i.e. hunched posture, ruffled fur and emaciation were observed after oral administration in male and female animals. Gross necropsy did not reveal any findings. The LD50 is therefore considered to be > 2000 mg/kg bw.

Justification for classification or non-classification

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

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. A single dose of the test item was administered orally or dermally to Wistar rats at concentrations of 2000 mg/kg bw. No mortality occurred. Clinical signs of toxicity, i.e. hunched posture, ruffled fur and emaciation were observed after oral administration in male and female animals. Gross necropsy did not reveal any findings. The LD50 is therefore considered to be > 2000 mg/kg bw. As a result the substance is not considered to be classified for acute toxicity under Regulation (EC) No. 1272/2008.