7-hydroxy-3-(4-methoxyphenyl)-4-benzopyrone

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

6 February - 3 June 2008

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

7-hydroxy-3-(4-methoxyphenyl)-4-benzopyrone

EC Number:

207-623-9

EC Name:

7-hydroxy-3-(4-methoxyphenyl)-4-benzopyrone

Cas Number:

485-72-3

Molecular formula:

C16H12O4

IUPAC Name:

7-hydroxy-3-(4-methoxyphenyl)-4H-chromen-4-one

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

- Lot No. of test material: 07-170-FIL-2/3
- Appearance: White powder
- Expiration date: May 2010
- Purity: 98.4%
- Storage condition of test material: Room temperature

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Texas Animal Specialties, Humble, TX
- Females nulliparous and non-pregnant: yes
- Age at study initiation: Approx. 9 weeks old
- Weight at study initiation: Males 239 - 304 g; Females 165 - 219 g
- Fasting period before study: No
- Housing: Suspended, wire bottom, stainless steel cage; 1 animal per cage
- Diet: PMI Feeds Inc. Formulab #5008 available ad libitum
- Water: Municipal water supply available ad libitum from automatic water system
- Acclimation period: Not specified

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C
- Humidity (%): 30 - 70%
- Air changes (per hr): 10 - 12 air changes/ hour
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle

IN-LIFE DATES: From: 27 February 2008 To: 13 March 2008

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

water

Details on dermal exposure:

TEST SITE
- Area of exposure: The test material was applied to the dorsal surface of the trunk in a thin uniform layer.
- % coverage: Not less than 10% of the total body surface area was clipped
- Type of wrap if used: The area of application was covered with a 5 x 10 cm surgical gauze patch and secured with non-irritating adhesive tape. The trunk of each animal was then wrapped with vet wrap which was secured in place with non-irritating adhesive tape to prevent possible ingestion of the test substance.

REMOVAL OF TEST SUBSTANCE
- Washing: The test sites were gently washed with room temperature tap water and a clean cloth to remove as much residual test material as possible.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): The dose amount was 1.21 - 1.54 g in males and 0.823 - 1.01 g in females.
- Concentration (if solution): An individual dose was calculated for each animal based on its Day 0 bodyweight just before exposure.
- Constant volume or concentration used: no
- For solids, paste formed: The test material was moistened with water.

VEHICLE
- Concentration (if solution): Each dose was moistened with a sufficient amount of deionised water at a concentration of 1.0 mL/g of test substance.

Duration of exposure:

24 hours exposure to test material

Doses:

5050 mg/kg

No. of animals per sex per dose:

5 animals/ sex

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations for mortality and clinical/ behavioural signs of toxicity: 2-3 times on the day of exposure (Day 0) and at least once daily thereafter for 14 days
- Frequency of weighing: Individual body weights were recorded just prior to dosing and on days 7 and 14.
- Frequency of dermal irritation observations: approximately 60 minutes after removal of wrappings and on Days 4, 7, 11 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross necropsy

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 050 mg/kg bw

Based on:

test mat.

Remarks on result:

no indication of skin irritation up to the relevant limit dose level

Mortality:

There was no mortality during the study.

Clinical signs:

other: All animals appeared normal for the duration of the study. Irritation included very slight erythema in one animal on Day 1.

Gross pathology:

The gross necropsy conducted at termination of the study revealed no observable abnormalities.

Other findings:

- Actual temperature: 20 - 24°C
- Actual relative humidity: 27 - 90% (Humidity was outside of the protocol range but did not affect the study outcome)

Any other information on results incl. tables

Table 1: Body weights, time of death and gross necropsy (Dose level 5050 mg/kg)

Animal No.	Dose amount (g)	Body weights (g)			Time of death*	Gross necropsy findings
		Day 0	Day 7	Final
251-M	1.21	239	269	284	Day 14	No observable abnormalities
252-M	1.42	282	311	337	Day 14	No observable abnormalities
253-M	1.45	288	318	342	Day 14	No observable abnormalities
254-M	1.41	279	315	346	Day 14	No observable abnormalities
255-M	1.54	304	336	349	Day 14	No observable abnormalities
256-F	0.944	187	198	207	Day 14	No observable abnormalities
257-F	0.914	181	196	212	Day 14	No observable abnormalities
258-F	1.01	200	215	227	Day 14	No observable abnormalities
259-F	1.01	219	237	249	Day 14	No observable abnormalities
260-F	0.823	165	177	189	Day 14	No observable abnormalities

* Day of dosing is Day 0; Day 14 is terminal sacrifice

M – Male

F – Female

Note: Animal 259 dose amount should have been 1.11 g

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute dermal LD50 of the test substance, Formononetin, is estimated to be greater than 5050 mg/kg in males and females.