sodium/triethanolamine- 6-(2,5-dioxo-3-C12-18-alkenyl(even and odd, branched, unsaturated)-pyrrolidin-1-yl)hexanoate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

2011-05-05 to 2011-05-25

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Rationale for reliability of 2: Guideline study, well-performed and well-documented, read-across Justification of read-across: The acid form of the registration substance and proposed supporting substance (Tetrapropylensuccinimido)-capronic acid are homolog series of (Polypropylensuccinimido)-caproid acid.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

(Tetrapropylensuccinimido)-caproic acid

IUPAC Name:

(Tetrapropylensuccinimido)-caproic acid

Constituent 2

Reference substance name:

6-(3-tetrapropenyl-2,5-dioxopyrrolidin-1-yl)hexanoic acid

EC Number:

800-770-5

Cas Number:

1424148-99-1

Molecular formula:

C22H39NO4

IUPAC Name:

6-(3-tetrapropenyl-2,5-dioxopyrrolidin-1-yl)hexanoic acid

Test material form:

gas under pressure: refrigerated liquefied gas

Details on test material:

Batch Nr: ESD0009058

Test animals

Species:

rat

Strain:

other: RccHanTM: WIST(SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories B.V.
- Age at study initiation: 9 or 11 weeks
- Weight at study initiation: 183.8 g – 193.5 g (females); 228.2 g – 245.7g (males)
- Fasting period before study:
- Housing: Standard Laboratory Conditions.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: Six days under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Vehicle:

corn oil

Details on dermal exposure:

TEST SITE
- Area of exposure: 5 x 5 cm
- % coverage: 10% of the total body surface
- Type of wrap if used: surgical gauze pad

REMOVAL OF TEST SUBSTANCE
- Washing (if done): After the 24-hour application period, the dressing was removed and the skin was flushed with
lukewarm water and drapped off with disposable paper towels.
- Time after start of exposure: 24-hour

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 4 mL/kg
- Concentration (if solution): 2000 mg/kg
- Constant volume or concentration used: yes

VEHICLE
- Amount(s) applied (volume or weight with unit): 4 mL/kg
- Lot/batch no. (if required): 400 159 216

Duration of exposure:

24 Hour

Doses:

2000 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: Daily during acclimatization. Once before treatment and within the first 30 minutes and approximately 1, 2, 3 and 5 hours after treatment on test day 1 (in common with the clinical signs). Twice daily during test days 2 – 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, macroscopic examination

Statistics:

No statistical analysis was performed

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No intercurrent deaths occurred during the course of the study.

Clinical signs:

No clinical signs were observed throughout the entire observation period.

Body weight:

The body weight of the animals was within the range commonly recorded for this strain and age.

Gross pathology:

No macroscopic findings were recorded at necropsy.

Other findings:

All animals showed slight erythema from the beginning of the observation until days three or five and six. Additionally, all animals had slight focal crusts and slight desquamation on several days, in most cases during the six last days of the observation period.

Any other information on results incl. tables

Justification for the read-across approach using (Tetrapropylensuccinimido)-capronic acid as supporting substance:

The acid form of the registration substance and proposed supporting substance (Tetrapropylensuccinimido)-caproic acid are homolog series of (Polypropylensuccinimido)-caproic acid. These substances are produced by reaction of 6-aminocaproic acid with corresponding polypropylensuccinic anhydride. The only structural difference is that the alkyl moiety of the registratoin substance is composed of five propylen unit, whereas that of the supporting substance is composed of four propylen unit. The given structural difference is not likely to be associated with significantly deviating acute dermal toxicity, because neither the skin penetration property nor the chemical reactivity is likely to be significantly influenced by the given structural difference.

Evaluation of the acute dermal toxicity of the registration substance

The read-across supporting substance did not induce any systemic effect in the acute dermal toxicity study. Likewise no significant acute dermal toxicity for the registration substance can be derived.

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

The median lethal dose of (Tetrapropylenesuccinimido)-caproic acid after single dermal administration to male and female rats, observed over a period of 14 days, is: LD50(dermal) (Wistar rat): greater than 2000 mg/kg body weight

Executive summary:

The acute dermal toxicity of the registration substance was assessed based on the read-across approach using (Tetrapropylensuccinimido)-caproic acid as read-across supporting substance.

The acute dermal toxicity of (Tetrapropylensuccinimido)-caproic acid was investigated according to the OECD Guideline 402. At dose level of 2000 mg/kg bw no systemic effect was observed.