(3E)-dec-3-en-2-one

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2009-04-16 to 2009-07-24

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:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (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:

(3E)-dec-3-en-2-one

Cas Number:

18402-84-1

Molecular formula:

C10H18O

IUPAC Name:

(3E)-dec-3-en-2-one

Details on test material:

- CAS: 18402-84-1
- Purity: 98.57% to 99.11% w/w
- Batch No.: Lot KB 147-36-1
- Physical state: liquid
- Colour: Colorless to pale yellow
- Storage conditions: room temperature

Test animals

Species:

rat

Strain:

Sprague-Dawley

Remarks:

albino

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Received from Ace Animals, Inc., Boyertown, PA on April 21, 2009.
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8-9 weeks
- Weight at study initiation: 217 - 238 g (males) and 182 - 208 (females)
- Housing: The animals were singly housed in suspended stainless steel caging with mesh floors, which conform to the size recommendations in the most recent Guide for the Care and Use of Laboratory Animals DHEW (NIH). Litter paper was placed
beneath the cage and was changed at least three times per week.
- Diet (e.g. ad libitum): Purina Rodent Chow #5012
- Water (e.g. ad libitum): Filtered tap water ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-23
- Humidity (%): 51-66
- 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: 2 x 3 inches
- % coverage: 10% of the body surface
- Type of wrap if used: 3-inch Durapore tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): not specified, but the test sites were gently cleansed of any residual test substance
- Time after start of exposure: 24 hrs

TEST MATERIAL
- Amount(s) applied : 5000 mg/kg bw

VEHICLE
- Amount(s) applied : none

Duration of exposure:

24 hours

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

Application of Test Substance:
Five thousand mg/kg of body weight of the test substance was applied evenly over a dose area of approximately 2 inches x 3 inches (approximately 10% of the body surface) and covered with a 2-inch x 3-inch, 4-ply gauze pad. The gauze pad and entire trunk of each animal were then wrapped with 3-inch Durapore tape to avoid dislocation of the pad and to minimize loss of the test substance. The rats were then returned to their designated cages. The day of application was considered Day 0 of the study.
After 24 hours of exposure to the test substance, the pads were removed and the test sites were gently cleansed of any residual test substance.

Body Weights:
Individual body weights of the animals were recorded prior to test substance application (initial) and again on Days 7 and 14 (termination) or after death.

Cage-Side Observations:
The animals were observed for mortality, signs of gross toxicity, and behavioral changes during the first several hours after application and at least once daily thereafter for up to 14 days or until death occurred. Observations included gross evaluation of skin and fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behavior pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhea, and coma.

Necropsy:
Surviving rats were euthanized via C02 inhalation at the end of the 14-day observation period. Gross necropsies were performed on decedent and euthanized animals. Tissues and organs of the thoracic and abdominal cavities were examined.

Statistics:

N.a.

Results and discussion

Preliminary study:

N.a.

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

One female died within two days of test substance application. Prior to death, this animal was hypoactive and exhibited prone posture.

Clinical signs:

other: The animal survivors were also hypoactive, but recovered by Day 2. Dermal irritation was noted at the dose site of all surviving animals between Days 1 and 14.

Gross pathology:

No abnormalities were observed at gross necropsy for the animals which survived until termination at day 14. Extremely red intestines were observed at gross necropsy for the animal which died during the study.

Other findings:

N.a.

Any other information on results incl. tables

Table 1: Mortality of tests animals

Dose (mg/kg bw)	Males	Females	Combined
5000	0/5	1/%	1/10

Table 2: Clinical observations

Observation	Males	Females
Mechanical damage due to unwrapping	5/5	5/5
Hypoactivity	4/5	4/5
Erythema	4/5	4/5
Light pink stain at dose site	5/5	5/5
Desquamation	5/5	3/5
Hyperkeratosis	0/5	1/5

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

In an acute dermal toxicity study in rats conducted according to OECD 402, one female died within two days at a dose of 5000 mg/kg bw. Based on the results and in accordance with OECD guideline 402 the LD50 value was determined to be greater than 5000 mg/kg bw in male and female rats. Thus, the substance does not warrant classification as being toxic or harmful based upon its acute dermal toxicity.

Executive summary:

An acute dermal toxicity test was conducted in accordance with OECD test guideline 402 to determine the potential of (3E)-dec-3-en-2-one to induce acute dermal toxicity in male and female Sprague-Dawley rats. 5000 mg/kg bw was applied to the skin of 5 rats per sex for 24 hours. The animals were observed for mortality, signs of gross toxicity, and behavioural changes at least once daily for up to 14 days. Body weights were recorded prior to application and again on Days 7 and 14 (termination) or after death. Necropsies were performed on all animals.

One female died within two days of test substance application. Prior to death, this animal was hypoactive and exhibited prone posture. Seven survivors were also hypoactive but recovered by Day 2. Dermal irritation was noted at the dose site of all surviving animals between Days 1 and 14. Gross necropsy of the decedent revealed extremely red intestines. No gross abnormalities were noted for the euthanized animals when necropsied at the conclusion of the 14-day observation period. Under the conditions of this study, the single dose acute dermal LD50 of the test item is greater than 5000 mg/kg bw in male and female rats.