2-Octen-1-ylsuccinic anhydride, mixture of cis and trans

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

02-17-2012 to 04-19-2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

3-(oct-2-en-1-yl)dihydrofuran-2,5-dione

EC Number:

629-679-7

Cas Number:

42482-06-4

Molecular formula:

C12H18O3

IUPAC Name:

3-(oct-2-en-1-yl)dihydrofuran-2,5-dione

Test material form:

other: Liquid

Details on test material:

- Name of test material: Octenyl succinic anhydride (CAS #26680-54-6). Source: Gulf Bayport Chemicals LP., Pasadena, TX.
- Physical state: Liquid at room temperature
- Analytical purity: 99.0%
- Lot/batch No.:44514821
- Expiration date of the lot/batch: December 21, 2012
- Stability under test conditions: Test substance was expected to be stable for the duration of testing.
- Storage condition of test material: The substance was stored at room temperature.
- Other: Slightly acidic pH
Solubility: Soluble in acetone.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS: 20 rats 5 males and 15 females (non pregnant, nulliparous).
- Age/Body weight: Young adult (9-10 weeks)/males 244-257 grams and females 173-231 grams at experimental start.
- Source: Harlan Laboratories, Inc. on February 14 and 28, and March 20, 2012.
- Age at study initiation: Young adult (9-10 weeks)
- Weight at study initiation: males 244-257 grams and females 173-231 grams
- Housing: The animals were singly housed in suspended stainless steel caging with mesh floors. Litter paper was placed beneath the cage and was changed at least three times per week.
- Diet (e.g. ad libitum): 16% Protein Rodent Diets. The diet was available ad libitum,
- Water (e.g. ad libitum): Filtered tap water was supplied ad libitum by an automatic water dispensing system.
- Acclimation period: 7 or 16 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Room temperature
- Humidity (%): 19-22°C and 30-67%,
- Air changes (per hr): 16
- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle

IN-LIFE DATES: From: To: February 14 to Feb 28, Feb 28 to March 14, and March 20 to April 4th, 2012.

Administration / exposure

Type of coverage:

other:

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: % coverage: 10
- Type of wrap if used: 3-inch Durapore tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Gently cleansed to remove residual substance
- Time after start of exposure: 24 hrs

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 200, 1,000 or 2,000 mg/kg of body weight
- Concentration (if solution): Neat, as received
- Constant volume or concentration used: yes
- For solids, paste formed: yes/no N/A

VEHICLE
- Amount(s) applied (volume or weight with unit): The appropriate amount of test substance (200, 1,000 or 2,000 mg/kg of body weight) 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
- Concentration (if solution): As supplied
- Lot/batch no. (if required): Lot #: 44514821
- Purity: 99.0%

Duration of exposure:

24 hrs

Doses:

Individual doses were calculated based on the initial body weights, taking into account the density (as determined by PSL) of the test
substance

No. of animals per sex per dose:

No. of Animals/Dose Level: 5 Females (200 and 1,000 mg/kg)
5 Males and 5 Females (2,000 mg/kg)

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 0, 7 and 14 days or after death
- Necropsy of survivors performed: Yes- Surviving rats were euthanized via CO2 inhalation on Day 14. Gross necropsies were performed on all decedents and euthanized animals.
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: Body weights at start, day 7 and day 14. 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. On all decedents and euthanized animals, tissues and organs of the thoracic and abdominal cavities were examined.

Statistics:

Number of Animals: 20
Sex: 5 Males and 15 Females. The females assigned to test were nulliparous and nonpregnant.
Number of Animals/Dose Level: 5 Females (200 and 1,000 mg/kg) and 5 Males and 5 Females (2,000 mg/kg)

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

> 1 000 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

SUMMARY OF MORTALITY DATA
Dose (mg/kg) Number Dead/Number Tested
Males Females Total
200 0/5 0/5 0/5
1,000 0/5 0/5 0/5
2,000 1/5 4/5 5/10

Clinical signs:

other: All 5 females with 1000 mg/kg exposure to the test substance survived the study period with no gross abnormalities. Other than mechanical damage due to unwrapping around the dose site of four rats between Days 1 and 4, and dermal irritation noted at the d

Gross pathology:

Other than dermal irritation noted at the dose site of all animals between Days 1 and 9, there were no other adverse clinical findings recorded for any of the animals over the course of the study.

Other findings:

No gross abnormalities were observed for any of the animals when necropsied at the conclusion of the 14-day observation period.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Under the conditions of this study, the single dose acute dermal LD50 of octenyl succinic anhydride (OSA) is greater than 2,000 mg/kg in male rats and is between 1,000 and 2,000 mg/kg of body weight in female rats.