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Administrative data

Description of key information

No concern for acute toxicity

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:
1991-07-03 to 1991-07-17
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study; well-performed and well documented
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
Mean body weight at start of study: males 182 ± 2g, females 180 ± 4g
Age at the start of the study: males approx. 7 weeks, females approx. 8 weeks.
Route of administration:
oral: gavage
Vehicle:
water
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Sex:
male/female
Dose descriptor:
discriminating dose
Effect level:
2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no effect

No mortality, no clinical sign and no body weight was observed.

The animals killed at the end of the observation period showed no macroscopically visible changes.

 

Table: Body weight development [g]

 

Day 1

Day 8

Day 15

males (n=5)

181.8± 1.5

241.4± 4.0

284.4± 6.7

females (n=5)

180.2± 4.4

203.2± 7.5

219.8± 7.8

 

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Pentapropylensuccinic anhydride, reaction products with ethanolamine, sodium and triethanolamine salts was investigated for tis acute oral toxicity according to the OECD Gudieline 401. No effect was found at the limit dose of 2000 mg/kg bw. No classification is warranted.
Executive summary:

Pentapropylensuccinic anhydride, reaction products with ethanolamine, sodium and triethanolamine salts was investigated for tis acute oral toxicity according to the OECD Gudieline 401. Five male and five female rats received Pentapropylensuccinic anhydride, reaction products with ethanolamine, sodium and triethanolamine salts as a 20% solution in water, the administration volume being 10 ml/kg body weight. No mortality, no clinical signs and no body weight effect was observed. The animals killed at the end of the observation period showed no macroscopically visible changes.

No classification is warranted.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
sufficiently robust; the low acute oral toxicity is in line with the observed low dermal toxicity and low repeated dose oral toxicity

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:
2011
Reliability:
1 (reliable without restriction)
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
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
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

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.

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:
The nasal discharge was observed on day 1 post-dose in male animal number 1.
Body weight:
Weight loss was recorded for all animals during the first week of observation, but all animals showed weight gain during the second week.
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

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

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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
sufficiently robust; the low acute dermal toxicity is in line with the observed low oral toxicity and low repeated dose oral toxicity

Additional information

Pentapropylensuccinic anhydride, reaction products with ethanolamine, sodium and triethanolamine salts was investigated for its oral and dermal acute toxicity according to the OECD Guideline 401 and 402 respectively. No significant effect was found for limit dose of 2000 mg/kg bw both for oral and dermal routes. Clear irritation effect was observed upon dermal application, possibly also related to transient body weight effect in dermal acute toxicity study.


Justification for selection of acute toxicity – oral endpoint
Guideline study; well-performed and well-documented

Justification for selection of acute toxicity – dermal endpoint
Guideline study; well-performed and well-documented

Justification for classification or non-classification

No significant toxic effect was found at limit dose of 2000 mg/kg bw both for oral and dermal routes.

No classification is warranted.