Fatty acids, C18-unsatd., reaction products with acrylic acid and polyethylenepolyamines

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted in accordance with international guidelines and in accordance with GLP. All relevant validity criteria were fulfilled.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

UK GLP Monitoring authority

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Fatty acids, C18-unsatd., reaction products with acrylic acid and polyethylenepolyamines

EC Number:

287-820-4

EC Name:

Fatty acids, C18-unsatd., reaction products with acrylic acid and polyethylenepolyamines

Cas Number:

85586-18-1

Molecular formula:

Not applicable (a generic molecular formula cannot be provided for this specific UVCB substance)

IUPAC Name:

(Z,9Z)-N-(2-{2-[(8Z)-heptadec-8-en-1-yl]-4,5-dihydro-1H-imidazol-1-yl}ethyl)octadec-9-enimidic acid; 3-[(2-carboxyethyl)({2-[3-(2-carboxyethyl)-2-[(8Z)-heptadec-8-en-1-yl]imidazolidin-1-yl]ethyl})amino]propanoic acid; 3-{2-[(8Z)-heptadec-8-en-1-yl]-3-{2-[(E)-[(9Z)-1-hydroxyoctadec-9-en-1-ylidene]amino]ethyl}imidazolidin-1-yl}propanoic acid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Three male and three female Sprague-Dawley CD strain rats were supplied by Charles River Lyd, Margate, UK. On receipt the animals were randomly allocated to cages. The females were nulliparous and non-pregnant. After an acclimatisation period of at least five days, the animals were selected at random and given a number unique within the cage by indelible ink marking on the tail. At the start of the study the animals weighed at least 200g, and were eight to twelve weeks of age.

The animals were housed in suspended solid floor polypropylene cages furnished with woodflakes. The animals were gang housed by sex during the exposure period and and for the remainder of the study. With the exception of an overnight fast immediately bbefore dosing and for apprxomately three to four hours afterward, free access to mains water and food was allowed thoughout the study. Food, water and bedding are routinely anlaysed by the laboratory and were considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study.

The temperature and humidity were set to within limits of 19 to 25 degrees centigrade and 30 to 70 percent relative humidity respectively. The rate of air exchange was at least fifteeen changes per hour. Lighting was controlled to a twelve hour light ; dark cycle.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

All animals were dosed once only by gavage using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to the fasted bodyweight at the time of dosing. Treatment of animals was sequential. Sufficient time was allowed between each sex to confimr the survival of the previously dosed anima

Doses:

2000 mg/kg (limit test) administered at a dose volume of 1.91 ml/kg undiluted.

No. of animals per sex per dose:

Three

Control animals:

no

Details on study design:

The animals were observed for deaths or overt signs of toxicity, 30 minutes, 1 hour, 2 hours and 4 hours after dosing and subsequently once daily for fourteen days. Individual bodyweights were recorded prior to dosing and at days 7 and 14.

At the end of the study period, all animals were killed by cervical dislocation. All animals were subjected to gross pathological examination. This consisted of an external examination and opening of the thoraic and abdominal cavities for examination of major organs. The appearance of macroscopic abnormalities was recorded . No tissues were retained.

Statistics:

None

Results and discussion

Preliminary study:

The median LD50 was estimated to be > 2,500 mg.Kg bodyweight

Effect levels

Effect levels 1

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 500 mg/kg bw

Based on:

test mat.

Effect levels 2

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

> 2 500 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths recorded in the study.

Clinical signs:

other: There were no signs of systemic toxicity recorded in the study.

Gross pathology:

No abnormalitites were noted at necropsy.

Other findings:

None

Any other information on results incl. tables

Mortality data

Sex	# animals	1/2 hr	1 hr	2hr	4hr	Day 1	Day 2	Day 3	Day 4	Day 5	Day 6	Day 7	Day 8	Day 9	Day 10	Day 11	Day 12	Day 13	Day 14
Male	3	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Female	3	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

Individual clinical observations

Dose	Animal & Sex	# animals	1/2 hr	1 hr	2hr	4hr	Day 1	Day 2	Day 3	Day 4	Day 5	Day 6	Day 7	Day 8	Day 9	Day 10	Day 11	Day 12	Day 13	Day 14
2000	1-0 Female	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
2000	1-1 Female	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
2000	1-2 Female	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
2000	2-0 Male	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
2000	2-1 Male	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
2000	2-2 Male	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

0 = No signs of systemic toxicity

Individual Bodyweights and weekly bodyweight changes

Dose	Animal & Sex	BW gm Day 0	BW gm Day 7	BW gm Day 14	BW Change in Gm Week 1	BW Change in Gm Week 2
2000	1-0 Female	218	250	273	32	23
2000	1-1 Female	209	236	255	27	19
2000	1-2 Female	208	239	255	31	16
2000	2-0 Male	209	282	332	73	50
2000	2-1 Male	216	298	352	82	54
2000	2-2 Male	212	283	330	71	47

Where BW = Bodyweight

Individual necropsy findings

Dose	Animal & Sex	Time of death	Macroscopic observations
2000	1-0 Female	Killed day 14	No abnormalities noted
2000	1-1 Female	Killed day 14	No abnormalities noted
2000	1-2 Female	Killed day 14	No abnormalities noted
2000	2-0 Male	Killed day 14	No abnormalities noted
2000	2-1 Male	Killed day 14	No abnormalities noted
2000	2-2 Male	Killed day 14	No abnormalities noted

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral median lethal dose (LD50) of the test material PR-4758 in the Sprague-Dawley CD Strain rat was estimated to be greater than 2,500 mg/kg bodyweight.

Executive summary:

An Acute oral limit test (project # 1376/003) was commissioned by Nalco Exxon Ltd, UK and performed by Safepharm Laboratories Ltd, UK in accordance with Method B1 Tris of commission directive 96/54/EC. The study was performed in the Sprague Dawley CD rat on PR-4758 grade. The study was performed in strict accordance with GLP. Standard protocols for animal husbandry and test method were followed and no deviations from the husbandry conditions or method recorded. Results indicate that the Acute dermal LD50 in the Sprague Dawley CD rat is > 2,500 mg/kg body weight. No deaths were recorded, there were no clinical signs of systemic toxicity, Bodyweight gain was within normal parameters and no gross abnormalities noted at necropsy.