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Administrative data

Description of key information

The oral LD50 in rats was 2.9 g/kg, and the dermal LD100 was > 6.2 g/kg in rabbits.  The dermal LD50 is less than 6.2 g/kg, and is estimated to be > 2.0 g/kg.  An acute inhalation toxicity study, LC50 > 5.3 mg/L, is read-across from a category member, nDDSA.

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: guideline study by GLP
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Remarks:
Preceeds GLP guidance, but QA signature is available.
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
other: Sherman-Wistar
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS

- Weight at study initiation: weighing between 200 and 300 gm
- Fasting period before study: The rats were deprived of food but not water for 24 hours prior to dosing.

- Housing:
- Diet : ad libitum
- Water: ad libitum
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
1.0 gm/kg
2.0 gm/kg
4.0 gm/kg
8.0 gm/kg
16.0 gm/kg
No. of animals per sex per dose:
Five groups of 5 males
Control animals:
no
Sex:
male
Dose descriptor:
LD50
Effect level:
2.9 other: g/kg
Based on:
test mat.
95% CL:
> 2 - < 4
Mortality:
Group (g/kg) Motality
1.0 0/5
2.0 0/5
4.0 5/5
8.0 5/5
16.0 5/5
Clinical signs:
No untoward symptoms were observed at 1.0 gm/kg.
At 2.0 gm/kg the animals were lethargic and oily looking for up to 48 hours.
At 4.0 gm/kg the animals were severely depressed after 4 hours and semi-comatose within 12 hours. Death occurred within 72 hours.
At 8.0 gm/kg and 16.0 gm/kg the animals were semi-comatose after 4 hours and subsequently died within 12-48 hours.
Body weight:
Dose Level (g/kg) Initial Weight (g) Final Weight (g)
1 215 250
2 235 255
4 240
8 240
16 200
Gross pathology:
Gross pathologic examination revealed nothing remarkable.

Test Results

Dose Level (g/kg)

# of animals dosed

Motalities

Total dead 14 days

Total survived 14 days

Initial weight (g)

Final weight (g)

1

2

3

4

5

6

7

8

9

10

11

12

13

14

1

5

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

5

215

250

2

5

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

5

235

255

4

5

0

2

3

 

 

 

 

 

 

 

 

 

 

5

5

0

240

 

8

5

4

 

 

 

 

 

 

 

 

 

 

 

 

5

5

0

240

 

16

5

5

 

 

 

 

 

 

 

 

 

 

 

 

5

5

0

200

 

 

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Tetrapropenyl succinic anhydride (TPSA) was tested in rats for acute oral toxicity according to an OECD 423 protocol. THe LD50 was 2.9 g/kg bw or 2900 mg/kg bw. The substance is not classified according to Regulation EC No. 1272/2008.
Executive summary:

In an acute oral toxicity study, 5 groups fasted Sherman-Wistar strain Albino rats (five male/group) were given a single oral dose of test material at a dose level of  1.0, 2.0, 4.0, 8.0 and 16.0  g/kg bw and observed for14 days.

No untoward symptoms were observed at 1.0 gm/kg. At 2.0 gm/kg the animals were lethargic and oily looking for up to 48 hours. At 4.0 gm/kg the animals were severely depressed after 4 hours and semi-comatose within 12 hours. Death occurred within 72 hours. At 8.0 gm/kg and 16.0 gm/kg the animals were semi-comatose after 4 hours and subsequently died within 12-48 hours. All survived animals showed expected bodyweight gain during the study period.

The oral LD50 value of test material in male Sherman-Wistar rats has been determined to be 2.9 g/kg bodyweight, with 95% confidence intervals of 2.0-4.0 g/kg bodyweight.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
2 900 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:
migrated information: read-across based on grouping of substances (category approach)
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:
not classified
Remarks:
Migrated information The criteria for classification as Acute Toxicity Category 4 is ≤ 5.0 mg/L. Criteria used for interpretation of results: EU
Conclusions:
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
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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: No information on method used. Precedes establishment of guidelines and GLP
Qualifier:
no guideline available
Principles of method if other than guideline:
No internationally harmonized guideline available in 1969. Data obtained froma reliable textbook of toxicology. Practical handling experience has not resulted in the questioning of the overall accuracy of this data.
GLP compliance:
no
Test type:
other: standard method at the time
Species:
rabbit
Strain:
not specified
Sex:
not specified
Details on dermal exposure:
no data provided
Sex:
not specified
Dose descriptor:
LD100
Effect level:
> 6 200 - < 7 500 mg/kg bw
Based on:
test mat.

The publication states that, although TPSA is not readily absorbed through the skin, the percutaneous lethal dose ranges from 6.2 to 7.5 grams/kg in rabbits.

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The dermal lethal dose of Tetrapropenyl succinic anhydride (TPSA) in rabbits was reported to be 6200 to 7500 mg/kg. The substance is not classified.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
adequate

Additional information

Acute toxicity values for tetrapropenyl succinic anhydride (TPSA) were reported in a reliable textbook. The oral LD50 in rats was 2.9 g/kg, and this was found to be consistent with another C8 -12 Alkenyl Succinic Anhydride category member, linear C12 n-dodecenyl succinic anhydride (nDDSA), though less toxic than octenyl succinic anhydride (OSA). Read-across among the category members is substantiated by the fact that they have common functional groups and similar behaviour in physico-chemical and toxicity tests, as provided in the Chemical Category Report Format (CCRF) attached to the IUCLID file. The dermal toxicity values are not clear from the text: "the percutaneous lethal dose ranges from 6.2 to 7.5 grams/kg in rabbits." This could be interpreted to mean that the LD50 is between these values, or that the LD100 is between these values. If the LD50 is > 6.2 g/kg or 6200 mg/kg bw, then the substance is not toxic dermally. If the values are conservatively considered to be LD100 values, then the LD50 is less than 6.2 g/kg, and is estimated to be > 2.0 g/kg. This is consistent with nDDSA, and again slightly less toxic than OSA. Carbon chain compounds of a length of eight have been found to have higher dermal irritation effects than carbon chains of other lengths in dermal irritation tests (Sato, et al., 1999, Stillman, et al., 1975). This has been observed here with newly generated skin irritation data for OSA and nDDSA. Thus, the category data for the C8 -12 Alkenyl Succinic Anhydrides support the conclusion that the C12-TPSA has a low order of acute toxicity.


Justification for selection of acute toxicity – oral endpoint
experimental study in a reputable laboratory

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

Justification for selection of acute toxicity – dermal endpoint
Data reported in a reliable textbook. The data are interpreted to indicate that the LD100 was > 6.2 g/kg in rabbits. The LD50 is estimated to be > 2000 mg/kg bw.

Justification for classification or non-classification

Oral and dermal LD50 values for tetrapropenyl succinic anhydride are less than 2000 mg/kg bw, and the inhalation LD50 is less than 5 mg/L. These do not meet the criteria in Regulation EC No. 1272/2008 for classification for acute toxicity.