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

Endpoint summary

Description of key information

Acute oral toxicity LD50 > 2500 mg/kg bw in the Sprague-Dawley CD strain rat; OECD guideline 423; Allen DJ, 2000.

Acute dermal toxicity LD50 > 2000 mg/kg bw in the Sprague-Dawley rat (HdsHan:WIST); OECD guideline 402; Sanders A, 2010.

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:

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.

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

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

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.

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

Preliminary study:

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

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 500 mg/kg bw

Based on:

test mat.

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

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

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The study was conducted in accordance with OECD 423 guidance and to GLP standards in a GLP certified laboratory. The reliablity score for the study was 1.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Quality of whole database:

N/A

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:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

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

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

UK GLP Monitoring authority

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Five male and five female Wistar (HSdlHAN:WIST) strain rats were supplied by Harlan Laboratories UK Ltd, Oxon, 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 study by indelible ink marking on the tail and a number written on the cage card. At the start of the study the animals weighed at least 200 g, and were eight to twelve weeks of age.

The animals were housed in suspended solid floor polypropylene cages furnished with woodflakes. The animals were housed individually during the 24 hour exposure period and gang housed up to four per sex for the remainder of the study. 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 (06:00 am to 18:00 pm) dark cycle.

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

On the day before treatment the back and flanks of each animal were clipped free of hair. Initially one male and one female were treated at a dose level of 2,000 mg/kg in the absence of data suggesting any toxicity.

The calculated volume of test material as received was applied evenly to an area of shorn skin (approximately 10% of the total body surface area using a graduated syringe. A piece of surgical gauze was placed over the treatment area and semi occluded with a piece of self-adhesive tape. The animals were caged individually for the 24 hour exposure period . Shortly after dosing the dressings were examined to ensure that they were securely in place.

After the 24 hour contact period, the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with distilled water to remove ant residual test material.

As no mortalities were noted a further group of animals (four male and four females) was similiarly treated with the test material at a dose of 2,000 mg/kg body weight to give a total of five male and five females. After the 24-hour contact period the bandages were carefully removed, the skin and surrounding hair cleaned with cotton wool moistened with distilled water. These animals were gang housed for the remainder of the study.

Duration of exposure:

24 hour exposure period with fourteen day post exposure period.

Doses:

2,000 mg/kg

No. of animals per sex per dose:

Five

Control animals:

not required

Details on study design:

The animals were observed for death or overt signs of toxicity 30 minutes, one hour, two hours and four hours after dosing and subsequently once daily for fourteen days.

After removal of the dressings and subsequently once daily for fourteen days, the test sites were examined for evidence of primary irritation and scored according to the Draize scale (Draize JH (1977) Dermal and eye toxicity tests). Any other skin reactions if present were also recorded.

Individual body weights were recorded prior to the application of the test material on Day 0, Day 7 and 14.

A the end of the study the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoraic cavities. The appearance of any macroscopic abnormalities was recorded. No tissue samples were retained.

Statistics:

None

Preliminary study:

LD50 > 2,000 mgKg

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths in either sex

Clinical signs:

other: There were no signs of systemic toxicity in either sex

Gross pathology:

Individual examinations were made
No abnormalities were noted

Other findings:

Individual dermal reactions were measured.
Very slight to well defined erythema was noted at the test sites of four males and four females. Other dermal reactions noted at the test site of one female was haemorrhage of dermal capillaries, small superfical scattered scabs and crust formation. Treated skin sites of one male and one female appeared normal throughout the study. The remaining treated skin sites of all other animals appeared normal 3 to 9 days after dosing.

Individual Clinical observations and mortality data

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

Individual Bodyweights and weekly bodyweight changes

Dose mg/kg	Animal & Sex	BW day 0 gm	BW day 7 gm	BW day 14 gm	BW Change gm during week 1	BW Change gm during week 2
2000	1-0 Male	245	263	280	18	17
2000	3-0 Male	237	254	302	17	48
2000	3-1 Male	238	269	298	31	29
2000	3-2 Male	231	252	281	21	29
2000	3 -3 Male	231	252	281	21	29
2000	2-0 Female	211	212	220	1	8
2000	4-0 Female	216	218	222	2	4
2000	4-1 Female	216	215	218	-1	3
2000	4-2 Female	219	220	221	1	1
2000	4-3 Female	203	203	206	0	3

Where BW = Bodyweight

Individual necropsy findings

Dose Mg/kg	Animal & Sex	Time of death	Macroscopic observations
2000	1-0 Male	Killed day 14	No abnormalities detected
2000	3-0 Male	Killed day 14	No abnormalities detected
2000	3-1 Male	Killed day 14	No abnormalities detected
2000	3-2 Male	Killed day 14	No abnormalities detected
2000	3-3 Male	Killed day 14	No abnormalities detected
2000	2-0 Female	Killed day 14	No abnormalities detected
2000	4-0 Female	Killed day 14	No abnormalities detected
2000	4-1 Female	Killed day 14	No abnormalities detected
2000	4-2 Female	Killed day 14	No abnormalities detected
2000	4-3 Female	Killed day 14	No abnormalities detected

Individual Dermal reactions

Dose mg/kg	Animal & Sex	Observation	D1	D2	D3	D4	D5	D6	D7	D8	D9	D10	D11	D12	D13	D14
2000	1-0 Male	Erythema Oedema Other	0 0 0	1 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0
2000	3-0 Male	Erythema Oedema Other	0 0 0	1 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0
2000	3-1 Male	Erythema Oedema Other	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0
2000	3-2 Male	Erythema Oedema Other	0 0 0	1 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0
2000	3-3 Male	Erythema Oedema Other	0 0 0	1 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0
2000	2-0 Female	Erythema Oedema Other	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0
2000	4-0 Female	Erythema Oedema Other	1 0 0	1 0 0	1 0 0	1 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0  0 0	0 0 0	0 0 0	0 0 0
2000	4-1 Female	Erythema Oedema Other	2 0 0	2 0 0	2 0 Hd	1 0 Hd	0 0 Hd	0 0 Hd	0 0 Ss	0 0 Cf	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0
2000	4-2 Female	Erythema Oedema Other	1 0 0	1 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0
2000	4-3 Female	Erythema Oedema Other	1 0 0	1 0 0	1 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0

Where 0= No reactions, Hd = haemorrhage of dermal capillaries, Ss = Small superfical scabs, Cf = Crust formation

Interpretation of results:

GHS criteria not met

Conclusions:

The acute dermal median lethal dose (LD50) of the test material in the Wistar strain rat was found to be greater than 2,000 mg/kg

Executive summary:

An Acute dermal limit test (project # 3180/006) was commissioned by Nalco Ltd, UK and performed by Harlan Laboratories Ltd, UK in accorance with Method B4 of commision regulation 440/2008. The study was performed in the Wistar rat on PR-4758 technical grade (batch # FA0A0049). The study was performed in strict accordance with GLP. Standard protocols for animal husbandy and test method were followed and no deviations from the husbandy conditions or method recorded. Results indicate that the Acute dermal LD50 in the Wistar rat is > 2,000 mg/kg. No deaths were recorded, there were no clinical signs of systemic toxicity. Bodyweight gain was within normal parameters, no significant dermal irritation effects were recorded and no gross abnormalities noted at necrospy.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The study was conducted in accordance with OECD 402 guidance and to GLP standards in a GLP certified laboratory. The reliablity score for the study was 1.

Additional information

Test material is not acutely toxic based upon acute oral and dermal studies in the rat. An acute inhalation study is not deemed necessary based upon an extremely low vapour pressure (13 pa at 25 deg C) furthermore the potential for aerosol generation during manufacture, formulation or end use is minimal. As such an acute inhalation study has been waived as scientifically unnecessary.

Justification for selection of acute toxicity – oral endpoint

Only one key study available, was conducted in accordance with OECD 423 guidance and to GLP standards in a GLP certified laboratory.

Justification for selection of acute toxicity – inhalation endpoint

N/A

Justification for selection of acute toxicity – dermal endpoint

Only one key study available, was conducted in accordance with OECD 402 guidance and to GLP standards in a GLP certified laboratory.

Justification for classification or non-classification

Test material is not acutely toxic based upon acute oral and dermal studies in the rat and as such does not meet classification criteria.