Butanoic acid, 4-[(2-hydroxyethyl)amino]-4-oxo-2-(pentapropenyl)-, sodium salt, compd. with 2,2',2''-nitrilotris[ethanol] (1:?:?)

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2011

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2012

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

other: Limit Test

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Pentapropylensuccinic anhydride, reaction products with ethanolamine, sodium and triethanolamine salts

IUPAC Name:

Pentapropylensuccinic anhydride, reaction products with ethanolamine, sodium and triethanolamine salts

Details on test material:

Batch No.: ESD0010887
Expiry Date: 13.12.2012
Physical state at RT: Liquid
Colour: Brown
Active Components (%): 82.4% (17.6 % Water)
Density: 1.087 g/cm3
pH: 9.0 (1 % in water)
Boiling Point (C): 107 C
Stability: Stable
Storage Conditions:Room Temperature

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Species/strain: healthy rats, WISTAR rats Crl: WI(Han) (full barrier)
Source: Charles River, 97633 Sulzfeld, Germany
Sex: male and female
The female animals were non-pregnant and nulliparous.
Number of animals: 5 male and 5 female
Age at the beginning of the study: males: 11 - 12 weeks old
females: 16 - 17 weeks old
 Body weight on the day of administration: males: 273 – 304 g;
females: 208 – 232
The animals were derived from a controlled full-barrier maintained breeding system (SPF). According to Art. 9.2, No. 7 of the German Act on Animal Welfare the animals were bred for experimental purposes.
Environmental Conditions:
Full barrier in an air-conditioned room
Temperature: 22 +/- 3 °C
Relative humidity: 55 +/-10%
Artificial light, sequence being 12 hours light, 12 hours dark
Air change: 10 x / hour
Free access to Altromin 1324 maintenance diet for rats and mice (lot no. 1018)
Free access to tap water, sulphur acidified to a pH value of approximately 2.8 (drinking water, municipal residue control, microbiological controls at regular intervals)
The animals were kept individually in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding (lot no. 030511)
Certificates of food, water and bedding are filed at BSL BIOSERVICE
Adequate acclimatisation period (at least five days) under laboratory conditions

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

Preparation of Animals:
The animals were marked for individual identification by tail painting.
Approximately 24 hours before the test, the fur was removed from the dorsal area of the trunk using an electric clipper. Care was taken to avoid abrading the skin, and only animals with healthy intact skin were used.

Application:
The test item was applied at a single dose, uniformly over an area which was approximately 10% of the total body surface.
The test item was held in contact with the skin by a dressing throughout a 24-hour period except for 2 animals which had unwrapped themselves overnight. The dressing consisted of a gauze-dressing and non-irritating tape and was fixed with an additional dressing in a suitable manner.

No less than 10% of the body surface was cleared for the application.
Prior to the application a detailed clinical observation was made of all animals.

Duration of exposure:

24 hours (except for 2 animals which had unwrapped themselves overnight). At the end of the exposure period the residual test item was removed using tap water.

Doses:

2000mg/kg Body weight

No. of animals per sex per dose:

5/sex (one dose- Limit test)

Control animals:

no

Details on study design:

Observation Period: All animals were observed for 14 days after dosing.
Primary Skin Irritation:
Signs of erythema and oedema were assessed using the scoring system laid down in OECD Guideline 404 .
Scoring System:
No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beef-redness) to eschar formation preventing grading of erythema 4
No oedema 0
Very slight oedema (barely perceptible) 1
Slight oedema (edges of area well defined by definite raising) 2
Moderate oedema (raised approximately 1 mm ) 3
Severe oedema (raised more than 1 mm and extending beyond exposure area) 4


Body Weight Assessment: The animals were weighed on day 1 (prior to the application) and on days 8 and 15.

Clinical Examinations:
A careful clinical examination was made several times on the day of dosing (at least once during the first 30 minutes and with special attention given during the first 4 hours post-dose). As soon as symptoms were noticed they were recorded. Thereafter, the animals were observed for clinical signs once daily until the end of the observation period. All abnormalities were recorded.
Cageside observations included changes in the skin and fur, eyes and mucous membranes. Also respiratory, circulatory, autonomic and central nervous systems and somatomotor activity and behaviour pattern were examined. Attention was directed to observations of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.

Pathology: At the end of the observation period the animals were sacrificed with an overdosage of pentobarbital injected intraperitoneally (Narcoren®, Merial; lot no. 212041; expiry date: 04/2014) at the dosage of approximately 8 mL/kg bw.
All animals were subjected to gross necropsy. All gross pathological changes were recorded and in case of findings the tissues were preserved for a possible histopathological evaluation. The preserved tissues of which no histopathological evaluation was made will be discarded 3 months after the release of the final report unless otherwise agreed upon with the sponsor.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

discriminating dose

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortality

Mortality:

No Mortality was observed in this study

Clinical signs:

other: The nasal discharge was observed on day 1 post-dose in male animal number 1.

Gross pathology:

With the exception of acute injection of blood vessels in the abdominal region, which is due to the euthanasia injection, no specific gross pathological changes were recorded for any animal

Any other information on results incl. tables

Clinical Signs: no effect for males and females

Skin Irritation -Individual Data-Males

Day after Start of Application	Animal No. 21		Animal No. 22		Animal No. 23		Animal No. 24		Animal No. 25
	E/O	Comments	E/O	Comments	E/O	Comments	E/O	Comments	E/O	Comments
day 2	3/0	*	3/0	*	3/0	*	2/2	*, **	3/1	*
day 3	2/0	*	2/0	*	2/0	*	2/2	*	2/0	*
day 4	2/0	*	2/0	*	2/0	*	2/1	*	2/0	*
day 5	2/0	*	2/0	*	1/0	*	2/1	*	2/1	*
day 6	1/0	*	1/0	*	1/0	*	2/1	*	2/0	*
day 7	1/0	*	1/0	*	1/0	nsf	1/1	*	2/0	*
day 8	0/0	nsf	1/0	small s	1/0	nsf	1/0	es	1/0	es
day 9	0/0	nsf	0/0	es	0/0	nsf	0/0	es	0/0	es
day 10	0/0	nsf	0/0	es	0/0	nsf	0/0	es	0/0	es
day 11	0/0	nsf	0/0	es	0/0	nsf	0/0	es	0/0	es
day 12	0/0	nsf	0/0	es	0/0	nsf	0/0	es	0/0	es
day 13	0/0	nsf	0/0	es	0/0	nsf	0/0	es	0/0	es
day 14	0/0	nsf	0/0	es	0/0	nsf	0/0	nsf	0/0	es
day 15	0/0	nsf	0/0	es	0/0	nsf	0/0	s	0/0	es
Comments: E = erythema; O = oedema; 1, 2, 3, 4 = scoring system laid down in OECD Guideline 404 es = eschar; s = scratches; nsf = no specific findings * = remains of the test item ** = animal was found unwrapped

Skin Irritation -Individual Data-Females

Day after Start of Application	Animal No. 26		Animal No. 27		Animal No. 28		Animal No. 29		Animal No. 30
	E/O	Comments	E/O	Comments	E/O	Comments	E/O	Comments	E/O	Comments
day 2	2/1	**, w (2 mm)	3/1	*	2/1	*	3/1	*	1/0	*,**
day 3	2/0	w (1 mm)	2/0	*	2/0	*	2/0	*	1/0	*
day 4	2/0	w (1 mm)	2/0	*	2/0	*	2/0	*	1/0	*
day 5	2/0	w (1 mm)	2/1	*	1/0	*	2/0	*	1/0	*
day 6	2/0	w (1 mm)	2/0	*	1/0	*	2/0	*	1/0	*
day 7	1/0	w (1 mm)	2/0	*	1/0	*	1/0	*	1/0	*
day 8	1/0	w (1 mm)	1/0	es	1/0	es	1/0	es	0/0	es
day 9	0/0	es	0/0	es	0/0	es	0/0	es	0/0	nsf
day 10	0/0	es	0/0	es	0/0	es	0/0	es	0/0	nsf
day 11	0/0	es	0/0	es	0/0	es	0/0	es	0/0	nsf
day 12	0/0	es	0/0	es	0/0	es	0/0	es	0/0	nsf
day 13	0/0	es	0/0	es	0/0	es	0/0	es	0/0	nsf
day 14	0/0	nsf	0/0	nsf	0/0	nsf	0/0	es	0/0	nsf
day 15	0/0	nsf	0/0	nsf	0/0	nsf	0/0	es	0/0	s
Comments: E = erythema; O = oedema; 1, 2, 3, 4 = scoring system laid down in OECD Guideline 404 es = eschar; s = scratches; nsf = no specific findings; w = wound * = remains of the test item ** = animal was found unwrapped

Body Weight Development:

Dose: 2000 mg/kg body weight
Animal No. / Sex	g Day 1	g Day 8	g Day 15	% Day 1-15
21 / male	273	258	271	-1
22 / male	275	265	276	0
23 / male	300	285	296	-1
24 / male	304	295	312	3
25 / male	289	279	291	1
26 / female	208	201	203	-2
27 / female	232	225	233	0
28 / female	224	218	227	1
29 / female	209	204	212	1
30 / female	217	215	219	1

Macroscopic Findings no effect for males and no effect for females

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: other: GHS

Conclusions:

Under the conditions of the present study, single dermal application of the test item Pentapropylensuccinic anhydride, reaction products with ethanolamine, sodium and triethanolamine salts to rats at a dose of 2000 mg/kg body weight was associated with neither mortality nor signs of toxicity.
No classification is warranted.

Executive summary:

Pentapropylensuccinic anhydride, reaction products with ethanolamine, sodium and triethanolamine salts was investigated for its acute dermal toxicity in rats according to the OECD Guideline 402. No effect was found at dose of 2000 mg/kg bw but irritation effect was evident.

No classification is warranted.