Dihydro-3-(tetrapropenyl)furan-2,5-dione

Endpoint summary

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:

other: 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 hour

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 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

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.