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Description of key information

The substance was tested in rats using OECD guideline protocols.  The acute oral LD50 was 1098 mg/kg bw, and the acute dermal LD50 was > 1000 mg/kg bw and < 2000 mg/kg bw.  An acute inhalation toxicity, showing no effect above 5000 mg/m3, is read-across from a category member, n-DDSA.

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:
Mar 2012 to May 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
GLP compliance:
yes (incl. QA statement)
Test type:
up-and-down procedure
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source:Harlan Labs, Inc.
- Age at study initiation: 8 to 10 weeks
- Weight at study initiation: 161 - 192 grams
- Fasting period before study: Overnight
- Housing:Single. In suspended stainless steel caging with mesh floors
- Diet (e.g. ad libitum): ad libitum Harlan Teklad Global 16% protein Rodent diet #2016.
- Water (e.g. ad libitum): Filtered tap water ad libitum
- Acclimation period: 6-15 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23 degrees C
- Humidity (%): 26-69
- Air changes (per hr): 14-15 per hour
- Photoperiod (hrs dark / hrs light): 12/ 12

IN-LIFE DATES: From: To: Feb 20 - Mar 27, 2012
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
Individual doses were calculated based on initial body weights, taking into account the density of the test substance as determined by PSL.
Doses:
Initially, a single animal received a limit dose of 2,000 mg/kg. Due to mortality of this animal, a main test was conducted. For the main test, the substance was administered in sequence to the animals, starting at 175 mg/Kg, progressing to 550 mg/Kg to a final dose of 2000 mg/Kg. The decision to proceed with the next animal was based on the survival of the previous animal following dosing.
No. of animals per sex per dose:
3 per dose.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observed once daily. Weighing on day 1, 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights: Particular attention was paid to tremors, convulsions, salivation, diarrhea and coma.
Statistics:
The Acute Oral toxicity ( Guideline 425) statistical program (Westat, version 1.0, May 2001) was used for all data analysis including: dose progression selections, stopping criteria determinations and/ or LD 50 and confidence limit calculations.
Preliminary study:
One animal given the limit dose of 2000 mg/ Kg did not survive.
Sex:
female
Dose descriptor:
LD50
Effect level:
1 098 mg/kg bw
Based on:
test mat.
95% CL:
> 550 - < 2 000
Mortality:
Three animals died after receiving 2000 mg/kg. Three animals survived after receiving 550 mg/kg.
Clinical signs:
other: All animals given 2000 mg/kg died within one day of test substance administration.
Gross pathology:
Toxic signs included: irregular respiration, hyperactivity, abnormal posture, piloerection and/ or reduced fecal volume. Gross necropsy of the decedents revealed discoloration of the lungs and/or stomach and intestines, a mottled liver and/ or distention of the intestines and/or stomach.
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Octenyl succinic anhydride (OSA) was tested in an up and down acute toxicity OECD 425 protocol in female rats. The LD50 was determined to be 1098 mg/kg bw. This is associated with CLP category IV for classification according to regulation EC No. 1272/ 2008.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 098 mg/kg bw
Quality of whole database:
adequate

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:
1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Assume guideline study, no information on GLP. No information is available on the method.
Qualifier:
according to guideline
Guideline:
other: no information
Principles of method if other than guideline:
No information on method, as found in a secondary source reported to the U.S. Environmental Protection Agency. It is assumed that the method was according to a current guideline.
GLP compliance:
no
Test type:
other:
Limit test:
yes
Species:
rat
Strain:
not specified
Sex:
male/female
Details on test animals or test system and environmental conditions:
The administered aerosol consisted of 90% dodecenyl succinic anhydride and 10% ethyl alcohol. No further information provided.
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
not specified
Vehicle:
not specified
Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
4 h
Concentrations:
nominal chamber concentration - 5300 mg/m3, time-weighted measured concentration - 1220 mg/m3. The geometric mean particle size was 1.3 microns.
No. of animals per sex per dose:
No information
Control animals:
not specified
Details on study design:
This appears to be an acute inhalation assay, of 4 hours duration, with an observation period of 14 days. Survival is reported on day 15.
Statistics:
No information
Sex:
male/female
Dose descriptor:
LC50
Effect level:
5 300 mg/m³ air (nominal)
Based on:
not specified
Exp. duration:
15 d
Remarks on result:
other: equivalent to 5.3 mg/l as a mist
Mortality:
2/5 female rats died by the 2nd day post-exposure, and 2/5 male rats died by the 5th day post-exposure.
Clinical signs:
other: No information
Body weight:
No information
Gross pathology:
No information
Interpretation of results:
GHS criteria not met
Conclusions:
A category member, n-dodecenyl succinic anhydride (nDDSA), as an aerosol, was tested in a four hour acute inhalation toxicity assay in rats. The LD50 was > 5.3 mg/L. This data suggests that nDDSA is not classified according to Regulation EC No. 1272/2008. Data can be read-across among members of the C8-12 Alkenyl Succinic Anhydrides Category, based on common functional groups, similar bread-down products and potency patterns among carbon-chain length. This is adequate to fulfill the information requirements, to be the basis for classification and labelling decisions, and for risk assessment.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
5 300 mg/m³ air
Quality of whole database:
minimal

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:
02-17-2012 to 04-19-2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
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
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.
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)
Sex:
male
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
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.
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.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 000 mg/kg bw
Quality of whole database:
adequate

Additional information

Octenyl succinic anhydride was tested for acute toxicity in rats using OECD guideline protocols. The acute oral LD50 using the OECD 425 procedure was 1098 mg/kg bw in males and females. The acute dermal LD50 was > 2000 mg/kg bw in males, but was slightly more toxic in females, with a LD50 value of > 1000 mg/kg bw. This is generally consistent with the values from other members of the C8 -12 Alkenyl Succinic Anhydride category. However, the values fall just under the threshold for classification of 2000 mg/kg bw. Compounds with a carbon chain length of eight are known to be more irritating than those of chain lengths which are longer. This may reflect the same biological activity as seen in the acute toxicity studies.

A category approach is used for the hazard assessment of several endpoints. The hypothesis for the category of C8-12 Alkenyl Succinic Anhydrides is that data can be read-across among members of the category because their properties and behaviours are similar, based on common functional groups and similar breakdown products, and based on a constant pattern in changing of the potency of properties of the various carbon chain lengths. Functional groups include a 2,5 -furanedione cyclic anhydride ring, a carbon chain of length 8 -12 carbons, and a single double-bond within the carbon chain. The primary functional group associated with toxicity is the succinic anhydride moiety, which quickly is hydrolysed to form a butanedioic acid. A constant pattern may also be displayed in acute toxicity, dermal irritancy and biodegradation, with the lowest carbon chain length (C8) displaying the highest activity. Irritation, toxicity and degradation potential diminish with increasing carbon chain length. Read-across among the category members is substantiated by the common behaviour in physico-chemical and toxicity behaviours, as provided in the Chemical Category Report Format (CCRF) attached to the IUCLID file. It is adequate to fulfill the information requirements of Annex IX, to be the basis for classification and labelling decisions, and for risk assessment. 


Justification for selection of acute toxicity – oral endpoint
guideline study under GLP

Justification for selection of acute toxicity – inhalation endpoint
experimental result reviewed by an authoritative regulatory body

Justification for selection of acute toxicity – dermal endpoint
Guideline study under GLP

Justification for classification or non-classification

The experimental LD50 values for the substance fall within category 4 of acute toxicity for the oral (300 mg/kg > LD50 > 2000 mg/kg) and the dermal (1000 mg/kg < LD50 < 2000 mg/kg) routes of exposure. An acute inhalation toxicity, showing no effect above 5 mg/L, is read-across from a category member, n-DDSA. The substance is classified for acute oral and dermal toxicity, according to Regulation EC No. 1272/2008.